Dermatology

2008-04-07T00:17:00.000-07:00

News Release Bloggerwave

News Release

Copenhagen , May 4, 2007

Gaining popularity, growing strong- Bloggerwave is
Bloggerwave.com has proven to be the desired destination for bloggers from around the world. A multi tier offering for bloggers, advertisers and agencies has caused this site to create an explosion of e-activity in this sector. Their concept of commercial blogging to enhance brand image, product sales and public relations, has really paid off! The site has done IQ Division Company proud by bringing together hundreds of bloggers who are keen to get their opinions on screen while getting paid to do so.

Here info Link
bloggerwave

JOIN US, YOU WILL BE FIND HOW TO BE A GREAT WEBMASTER

1. What should we do

Contact Us

Office Location
Contact With : Bloggerwave
Fruebjergvej 3
2100-Copenhagen
Denmark
Tel : +45 3696 4530
So .. dont worry about your PRIVATION we will kept to protect it

2. Join us

You have time to join us with Bloggers or advertisers

a. Click ">Bloggers or advertisers">

b. Login With Blogger or advertisers

3 . How about advertisers

Advertiser is Pathner with blogger. Thy have twin bussines from bloggerwave to make money on internet market.
Be Bloggerwave Pathner

Since their effective launch, Bloggerwave.com has certainly caused waves in the industry. Having seen exponential growth and concept acceptance from the word ‘go’, they are now revving up their operations to sustain the premature success. To start with, they have set up a dedicated server to handle the traffic and to strengthen the back office.
Ulrik S. Thomsen, Managing Director with Bloggerwave Ltd. was quoted saying “Since we now have proven the concept and have already recruited several thousands of bloggers, we have decided to focus even more on clients, partnerships and getting more opportunities and assignments to our bloggers”.
With more effective servers and improvement to other finer details the site is back with a vengeance. Next on the agenda, they intend to tag each commercial blog to give it a ring of authenticity. So don’t be surprised if you see ‘Sponsored by Bloggerwave’ next to a posting. As pioneers in commercially sponsored blogs, the website hopes to reign in top clients and maintain their loyalty for years to come.

you wil be find sponsor link here

There’s also good news for bloggers. The site commits to making payment at the end of every month for successful blog postings even on the first assignment. They understand that credibility is key in this business. A safe and dedicated site, bloggerwave.com honours their payment commitments.
With better offerings, improved services and a passionate game plan, bloggerwave.com will be something to watch out for. Propelled by success they aim to push ahead to offer best-in-class services to both bloggers and organisations alike. This drive will certainly take them places.

Pepperdine University

2008-03-05T23:02:00.000-08:00

Pepperdine University

Pepperdine University has given opportunity to all students in the world who want to join in MBA programs.

MBA Programs

Pepperdine's Graziadio School of Business and Management offers MBA programs for working professionals, full-time students and leaders. See the list below and decide which of our MBA programs best suit your needs.

For those employed full-time / part-time students

* Fully Employed MBA - part-time, evening program, for students who wish to work
full-time while pursuing their education. Offered in West Los Angeles, Irvine, Encino,
Westlake Village, and Pasadena.
* Joint BA and MBA (MBAJ) - part-time, evening just for the graduates of Pepperdine
completion of the undergraduate program in management. Offered in West Los Angeles,
Irvine, Encino, Westlake Village, and Pasadena.

For full-time students

* Full-time MBA - Program for students who wish to pursue their degree full time. Available
in Malibu, CA.
* International MBA - Full-time program for students who wish to obtain an MBA with an
emphasis on international affairs. Available in Malibu, CA.
* JD / MBA - Full-time, a joint Juris Doctor / MBA from Pepperdine, in conjunction with the
Faculty of Law. Available in Malibu, CA.
* MBA / MPP - Full-time, joint MBA / Master 's of Public Policy, in conjunction with the
program Pepperdine's School of Public Policy. Available in Malibu, CA.
* 5-year BS / MBA - Full-time, co-holder of a BA and an MA in conjunction with the program's
first cycle Seaver Pepperdine College.

For Executives

* Executive MBA - Part-time MBA program for experienced business managers. Offered in
northern and southern California.
* Presidential and Key Executive MBA - Part-time MBA program for senior executives.
Available in Southern California.

Here Link Popular Pathership

2008-01-29T21:13:00.000-08:00

http://www.healtycenter.com/	100%	Daily	2008-02-20 07:37
http://www.healtycenter.com/01/anterior-cruciate-ligament-injury/	100%	Daily	2008-02-20 07:37
http://www.healtycenter.com/01/achilles-tendon-rupture/	100%	Daily	2008-02-20 07:33
http://www.healtycenter.com/01/achilles-tendonitis/	100%	Daily	2008-02-20 07:32
http://www.healtycenter.com/01/acromioclavicular-joint-injury/	100%	Daily	2008-02-20 07:30
http://www.healtycenter.com/01/ankle-fracture/	100%	Daily	2008-02-20 07:29
http://www.healtycenter.com/01/ankle-impingement-syndrome/	100%	Daily	2008-02-20 07:28
http://www.healtycenter.com/01/ankle-sprain-2/	100%	Daily	2008-02-20 07:26
http://www.healtycenter.com/01/ankle-taping-and-bracing/	100%	Daily	2008-02-20 07:24
http://www.healtycenter.com/01/athletes-with-disabilities/	100%	Daily	2008-02-20 07:23
http://www.healtycenter.com/01/athletic-foot-injuries/	100%	Daily	2008-02-20 07:20
http://www.healtycenter.com/01/acute-rheumatic-fever/	100%	Daily	2008-02-20 07:17
http://www.healtycenter.com/01/amyloidosis-aa-inflammatory/	100%	Daily	2008-02-20 07:15
http://www.healtycenter.com/01/amyloidosis-overview/	100%	Daily	2008-02-20 07:13
http://www.healtycenter.com/01/amyloidosis-transthyretin-related/	100%	Daily	2008-02-20 07:11
http://www.healtycenter.com/01/ankylosing-spondylitis-and-undifferentiated-spondyloarthropathy/	100%	Daily	2008-02-20 07:09
http://www.healtycenter.com/01/antiphospholipid-syndrome/	100%	Daily	2008-02-20 07:03
http://www.healtycenter.com/01/arthritis-as-a-manifestation-of-systemic-disease/	100%	Daily	2008-02-20 07:00
http://www.healtycenter.com/01/adenoma-bronchial/	100%	Daily	2008-02-18 05:02
http://www.healtycenter.com/01/alpha1-antitrypsin-deficiency/	100%	Daily	2008-02-18 05:00
http://www.healtycenter.com/01/altitude-related-disorders/	100%	Daily	2008-02-18 04:59
http://www.healtycenter.com/01/asbestosis/	100%	Daily	2008-02-18 04:53
http://www.healtycenter.com/01/aspergillosis/	100%	Daily	2008-02-18 04:51
http://www.healtycenter.com/01/asthma/	100%	Daily	2008-02-18 04:48
http://www.healtycenter.com/01/atelectasis/	100%	Daily	2008-02-18 04:44
http://www.healtycenter.com/01/acute-treatment-of-disaster-survivors/	100%	Daily	2008-02-18 04:40
http://www.healtycenter.com/01/adjustment-disorders/	100%	Daily	2008-02-18 04:38
http://www.healtycenter.com/01/introduction-adjustment-disorder-ad-is-related-to-stress-in-the-short-term-nonpsychotic-disturbance-people-with-alzheimers-disease-are-often-regarded-as-outdated-or-disproportionately-too-inten/	100%	Daily	2008-02-18 04:36
http://www.healtycenter.com/01/adhesive-capsulitis/	100%	Daily	2008-02-18 04:32
http://www.healtycenter.com/02/the-ruptured-achilles-tendon/	100%	Daily	2008-02-18 04:30
http://www.healtycenter.com/01/achilles-tendon-injuries-and-tendonitis/	100%	Daily	2008-02-18 04:26
http://www.healtycenter.com/01/acid-maltase-deficiency-myopathy/	100%	Daily	2008-02-18 04:22
http://www.healtycenter.com/01/126/	100%	Daily	2008-02-18 04:19
http://www.healtycenter.com/01/adductor-strain/	100%	Daily	2008-02-18 04:17
http://www.healtycenter.com/01/adult-physiatric-history-and-examination/	100%	Daily	2008-02-18 04:11
http://www.healtycenter.com/01/alcoholic-neuropathy/	100%	Daily	2008-02-18 04:09
http://www.healtycenter.com/01/131/	100%	Daily	2008-02-18 04:06
http://www.healtycenter.com/01/ankle-sprain/	100%	Daily	2008-02-18 04:04
http://www.healtycenter.com/01/acute-poliomyelitis/	100%	Daily	2008-02-18 04:02
http://www.healtycenter.com/01/perioperative-anticoagulation-management-2/	100%	Daily	2008-02-18 03:58
http://www.healtycenter.com/01/perioperative-dvt-prophylaxis/	100%	Daily	2008-02-18 03:55
http://www.healtycenter.com/01/perioperative-dvt-prophylaxis-2/	100%	Daily	2008-02-18 03:52
http://www.healtycenter.com/01/perioperative-management-of-the-diabetic-patient/	100%	Daily	2008-02-18 03:50
http://www.healtycenter.com/01/perioperative-management-of-the-female-patient/	100%	Daily	2008-02-18 03:48
http://www.healtycenter.com/02/mesothelioma/	100%	Daily	2008-02-18 03:38
http://www.healtycenter.com/01/abdominal-incisions-and-sutures-in-gynecologic-oncological-surgery/	100%	Daily	2008-02-18 03:22
http://www.healtycenter.com/01/abruptio-placentae/	100%	Daily	2008-02-18 03:19
http://www.healtycenter.com/01/adnexal-tumors/	100%	Daily	2008-02-18 02:58
http://www.healtycenter.com/01/amenorrhea/	100%	Daily	2008-02-18 02:54
http://www.healtycenter.com/01/amniotic-fluid-embolism/	100%	Daily	2008-02-18 02:48
http://www.healtycenter.com/01/gynecologic-myomectomy/	100%	Daily	2008-02-18 02:46
http://www.healtycenter.com/01/abnormal-neonatal-eeg/	100%	Daily	2008-02-18 02:36
http://www.healtycenter.com/01/absence-seizures/	100%	Daily	2008-02-18 02:01
http://www.healtycenter.com/01/acute-disseminated-encephalomyelitis/	100%	Daily	2008-02-18 01:58
http://www.healtycenter.com/01/acute-inflammatory-demyelinating-polyradiculoneuropathy/	100%	Daily	2008-02-18 01:57
http://www.healtycenter.com/01/acquired-cystic-kidney-disease/	100%	Daily	2008-02-18 01:52
http://www.healtycenter.com/01/acute-renal-failure/	100%	Daily	2008-02-18 01:51
http://www.healtycenter.com/01/acute-tubular-necrosis/	100%	Daily	2008-02-18 01:48
http://www.healtycenter.com/01/alport-syndrome/	100%	Daily	2008-02-18 01:46
http://www.healtycenter.com/01/amyloidosis-beta2m-dialysis-related/	100%	Daily	2008-02-18 01:44
http://www.healtycenter.com/01/acanthamoeba/	100%	Daily	2008-02-15 07:16
http://www.healtycenter.com/01/acinetobacter/	100%	Daily	2008-02-15 07:12
http://www.healtycenter.com/01/ala-dehydratase-deficiency-porphyria/	100%	Daily	2008-02-15 07:07
http://www.healtycenter.com/01/acute-lymphoblastic-leukemia/	100%	Daily	2008-02-15 07:06
http://www.healtycenter.com/01/acute-myelogenous-leukemia/	100%	Daily	2008-02-15 06:55
http://www.healtycenter.com/01/agnogenic-myeloid-metaplasia-with-myelofibrosis/	100%	Daily	2008-02-15 06:52
http://www.healtycenter.com/01/acalculous-cholecystitis/	100%	Daily	2008-02-15 06:45
http://www.healtycenter.com/01/acalculous-cholecystopathy/	100%	Daily	2008-02-15 06:42
http://www.healtycenter.com/01/achalasia/	100%	Daily	2008-02-15 06:40
http://www.healtycenter.com/01/achlorhydria/	100%	Daily	2008-02-15 06:35
http://www.healtycenter.com/01/adrenal-adenoma/	100%	Daily	2008-02-15 06:29
http://www.healtycenter.com/01/acromegaly/	100%	Daily	2008-02-15 06:28
http://www.healtycenter.com/01/addison-disease/	100%	Daily	2008-02-15 06:27
http://www.healtycenter.com/01/adrenal-crisis/	100%	Daily	2008-02-15 06:24
http://www.healtycenter.com/01/adrenal-disease-and-pregnancy/	100%	Daily	2008-02-15 06:22
http://www.healtycenter.com/01/abdominal-pain-in-elderly-persons/	100%	Daily	2008-02-15 06:12
http://www.healtycenter.com/01/abdominal-trauma-blunt/	100%	Daily	2008-02-15 06:10
http://www.healtycenter.com/01/abdominal-trauma-penetrating/	100%	Daily	2008-02-15 06:08
http://www.healtycenter.com/01/abortion-complete/	100%	Daily	2008-02-15 06:06
http://www.healtycenter.com/01/abortion-complications/	100%	Daily	2008-02-15 06:04
http://www.healtycenter.com/01/abortion-incomplete/	100%	Daily	2008-02-15 06:02
http://www.healtycenter.com/01/abortion-inevitable/	100%	Daily	2008-02-15 06:00
http://www.healtycenter.com/01/abortion-missed/	100%	Daily	2008-02-15 05:59
http://www.healtycenter.com/01/abortion-septic/	100%	Daily	2008-02-15 05:56
http://www.healtycenter.com/01/acanthosis-nigricans/	100%	Daily	2008-02-13 05:55
http://www.healtycenter.com/01/angioedema-hereditary/	100%	Daily	2008-02-13 05:53
http://www.healtycenter.com/01/atopic-dermatitis/	100%	Daily	2008-02-13 05:50
http://www.healtycenter.com/01/aortopulmonary-septal-defect/	100%	Daily	2008-02-13 05:40
http://www.healtycenter.com/01/53/	100%	Daily	2008-02-13 05:40
http://www.healtycenter.com/01/angina-pectoris-2/	100%	Daily	2008-02-13 05:38
http://www.healtycenter.com/01/aortic-coarctation-2/	100%	Daily	2008-02-13 05:37
http://www.healtycenter.com/01/aortic-regurgitation-2/	100%	Daily	2008-02-13 05:35
http://www.healtycenter.com/01/aortic-stenosis-2/	100%	Daily	2008-02-13 05:32
http://www.healtycenter.com/01/ashman-phenomenon-2/	100%	Daily	2008-02-13 05:30
http://www.healtycenter.com/01/atherosclerosis-2/	100%	Daily	2008-02-13 05:28
http://www.healtycenter.com/01/atrial-fibrillation-2/	100%	Daily	2008-02-13 05:26
http://www.healtycenter.com/01/atrial-flutter-2/	100%	Daily	2008-02-13 05:23
http://www.healtycenter.com/01/atrial-myxoma-2/	100%	Daily	2008-02-13 05:19
http://www.healtycenter.com/01/atrial-septal-defect-2/	100%	Daily	2008-02-13 05:11
http://www.healtycenter.com/01/atrial-tachycardia-2/	100%	Daily	2008-02-13 05:06
http://www.healtycenter.com/01/atrioventricular-block-2/	100%	Daily	2008-02-13 05:03
http://www.healtycenter.com/01/atrioventricular-dissociation/	100%	Daily	2008-02-13 05:01
http://www.healtycenter.com/01/atrioventricular-nodal-reentry-tachycardia-avnrt/	100%	Daily	2008-02-13 05:00
http://www.healtycenter.com/01/benign-cardiac-tumors/	100%	Daily	2008-02-13 04:58
http://www.healtycenter.com/01/brugada-syndrome/	100%	Daily	2008-02-13 04:51
http://www.healtycenter.com/01/cardiac-catheterization-left-heart/	100%	Daily	2008-02-13 04:48
http://www.healtycenter.com/01/cardiac-cirrhosis/	100%	Daily	2008-02-13 04:44
http://www.healtycenter.com/01/cardiac-tamponade/	100%	Daily	2008-02-13 04:42
http://www.healtycenter.com/01/cardiogenic-shock/	100%	Daily	2008-02-13 04:40
http://www.healtycenter.com/01/cardiomyopathy-alcoholic/	100%	Daily	2008-02-13 04:39
http://www.healtycenter.com/02/carotid-sinus-hypersensitivity/	100%	Daily	2008-02-13 04:37
http://www.healtycenter.com/02/cor-pulmonale/	100%	Daily	2008-02-13 04:37
http://www.healtycenter.com/02/coronary-artery-atherosclerosis/	100%	Daily	2008-02-13 04:36
http://www.healtycenter.com/01/cardiomyopathy-cocaine/	100%	Daily	2008-02-13 04:36
http://www.healtycenter.com/02/cardiomyopathy-dilated/	100%	Daily	2008-02-13 04:34
http://www.healtycenter.com/02/cardiomyopathy-restrictive/	100%	Daily	2008-02-13 04:34
http://www.healtycenter.com/02/cardiomyopathy-hypertrophic/	100%	Daily	2008-02-13 04:33
http://www.healtycenter.com/02/cardiomyopathy-peripartum/	100%	Daily	2008-02-13 04:33
http://www.healtycenter.com/02/carney-complex/	100%	Daily	2008-02-13 04:32
http://www.healtycenter.com/02/complications-of-myocardial-infarction/	100%	Daily	2008-02-13 04:31
http://www.healtycenter.com/02/cor-triatriatum/	100%	Daily	2008-02-13 04:31
http://www.healtycenter.com/02/coronary-artery-atherosclerosis-2/	100%	Daily	2008-02-13 04:30
http://www.healtycenter.com/01/acidosis-metabolic/	100%	Daily	2008-02-13 04:24
http://www.healtycenter.com/01/acidosis-respiratory/	100%	Daily	2008-02-13 04:22
http://www.healtycenter.com/01/acute-respiratory-distress-syndrome/	100%	Daily	2008-02-13 04:20
http://www.healtycenter.com/01/anomalous-left-coronary-artery-from-the-pulmonary-artery-surgical-perspective/	100%	Daily	2008-02-13 04:16
http://www.healtycenter.com/01/aortic-valve-disease-and-the-ross-operation/	100%	Daily	2008-02-13 04:13
http://www.healtycenter.com/01/alkalosis-metabolic/	100%	Daily	2008-02-13 04:11
http://www.healtycenter.com/01/alkalosis-respiratory/	100%	Daily	2008-02-13 04:09
http://www.healtycenter.com/01/anemia-of-prematurity/	100%	Daily	2008-02-13 04:06
http://www.healtycenter.com/01/anomalous-left-coronary-artery-from-the-pulmonary-artery/	100%	Daily	2008-02-13 04:04
http://www.healtycenter.com/01/aortic-stenosis-supravalvar/	100%	Daily	2008-02-13 04:00
http://www.healtycenter.com/01/aortic-stenosis-valvar/	100%	Daily	2008-02-13 03:51
http://www.healtycenter.com/01/aortic-valve-insufficiency/	100%	Daily	2008-02-12 05:52
http://www.healtycenter.com/01/aortic-valve-bicuspid/	100%	Daily	2008-02-12 05:47
http://www.healtycenter.com/01/reticular-dysgenesis/	100%	Daily	2008-02-04 08:14
http://www.healtycenter.com/01/hypogammaglobulinemia/	100%	Daily	2008-02-04 08:13
http://www.healtycenter.com/01/hypocomplementemia/	100%	Daily	2008-02-04 08:11
http://www.healtycenter.com/12/hereditary-angioedema/	100%	Daily	2008-02-04 08:10
http://www.healtycenter.com/12/food-allergies/	100%	Daily	2008-02-04 08:09
http://www.healtycenter.com/12/digeorge-syndrome/	100%	Daily	2008-02-04 08:08
http://www.healtycenter.com/12/complement-deficiencies/	100%	Daily	2008-02-04 08:08
http://www.healtycenter.com/12/anaphylaxis/	100%	Daily	2008-02-04 08:06
http://www.healtycenter.com/12/angioedema/	100%	Daily	2008-02-04 08:02
http://www.healtycenter.com/12/alloimmunization-from-transfusions/	100%	Daily	2008-02-04 07:59
http://www.healtycenter.com/12/allergic-and-environmental-asthma/	100%	Daily	2008-02-04 07:54
http://www.healtycenter.com/01/perioperative-cardiac-management/	100%	Daily	2008-01-28 06:23
http://www.healtycenter.com/01/acromegaly-2/	100%	Daily	2008-01-11 07:17
http://www.healtycenter.com/01/hypersensitivity-reactions-delayed/	100%	Daily	2008-01-11 06:58
http://www.healtycenter.com/01/urticaria/	100%	Daily	2008-01-11 06:46
http://www.healtycenter.com/01/angina-pectoris/	100%	Daily	2008-01-11 06:42
http://www.healtycenter.com/01/wiskott-aldrich-syndrome/	100%	Daily	2008-01-11 06:42
http://www.healtycenter.com/01/vocal-cord-dysfunction/	100%	Daily	2008-01-11 06:40
http://www.healtycenter.com/01/aortic-coarctation/	100%	Daily	2008-01-11 06:29
http://www.healtycenter.com/01/aortic-regurgitation/	100%	Daily	2008-01-11 06:28
http://www.healtycenter.com/01/aortic-stenosis/	100%	Daily	2008-01-11 06:27
http://www.healtycenter.com/01/aortitis/	100%	Daily	2008-01-11 06:27
http://www.healtycenter.com/01/ashman-phenomenon/	100%	Daily	2008-01-11 06:26
http://www.healtycenter.com/01/atherosclerosis/	100%	Daily	2008-01-11 06:26
http://www.healtycenter.com/01/atrial-fibrillation/	100%	Daily	2008-01-11 06:24
http://www.healtycenter.com/01/atrial-septal-defect/	100%	Daily	2008-01-11 06:21
http://www.healtycenter.com/01/atrial-myxoma/	100%	Daily	2008-01-11 06:21
http://www.healtycenter.com/01/atrial-flutter/	100%	Daily	2008-01-11 06:21
http://www.healtycenter.com/01/atrial-tachycardia/	100%	Daily	2008-01-11 06:05
http://www.healtycenter.com/01/atrioventricular-block/	100%	Daily	2008-01-11 06:02
http://www.healtycenter.com/01/aortitis-2/	100%	Daily	2008-01-11 05:59
http://www.healtycenter.com/01/accelerated-idioventricular-rhythm/	100%	Daily	2008-01-07 03:37
http://www.healtycenter.com/01/severe-combined-immunodeficiency/	100%	Daily	2008-01-05 20:32
http://www.healtycenter.com/01/rhinitis-allergic/	100%	Daily	2008-01-05 20:30
http://www.healtycenter.com/panhypogammaglobulinemia/	100%	Daily	2008-01-05 20:23
http://www.healtycenter.com/indoor-aeroallergens/	100%	Daily	2008-01-05 20:21
http://www.healtycenter.com/immunoglobulin-m-deficiency/	100%	Daily	2008-01-05 20:18
http://www.healtycenter.com/immunoglobulin-g-deficiency/	100%	Daily	2008-01-05 20:16
http://www.healtycenter.com/immunoglobulin-a-deficiency/	100%	Daily	2008-01-05 20:13
http://www.healtycenter.com/about/	100%	Daily	2007-10-25 07:54
http://www.healtycenter.com/2008/02/	100%	Daily	2008-02-18 04:30
http://www.healtycenter.com/2008/01/	100%	Daily	2008-01-30 07:15
http://www.healtycenter.com/2007/12/

Actinomycosis

2007-11-29T20:52:00.000-08:00

Background: Many infectious and inflammatory diseases affect the skin and the oral mucosa. Actinomycosis is one such characteristic and persistent infection. It is a subacute, chronic, cellulitic invasion of the soft tissues that causes the formation of external sinus tracts that discharge sulfur granules. This process spreads unimpeded by traditional anatomic barriers after the endogenous oral commensal organisms invade the tissues of the face and neck. The infection may spread to the pulmonary and GI systems as well (Schaal, 1984).

Actinomycosis is caused by various bacterial species of the actinomycete group. Usually, the disease is caused by Actinomyces israelii, an anaerobic gram-positive organisms that enters the tissue through a break in the mucosa (Eastridge, 1972). The Actinomyces genus of bacteria includes other species that normally inhabit the oral cavity but are seldom pathogenic. The infection begins as an inflammatory soft tissue mass, which can enlarge into an abscesslike swelling, with penetration of the overlying skin and the development of recognizable draining fistulae.

The term actinomycosis is misleading. Because of the derivative term mycosis (from the Greek mykes), some believe that actinomycosis is a fungal infection, although it is not a fungal infection. Aktino referred to the radiating organism in the sulfur granule as ray fungus. Human actinomycosis was first described in the medical literature in 1857, although a similar disease in cattle had been described in 1826. In 1877, Bollinger found Actinomyces bovis in granules from cattle with a condition called lumpy jaw. In 1878, Israel discovered granules in human autopsy material and described actinomycosis in humans in 1885 (Richtsmeier, 1979). Israel further discovered that Actinomyces species do not survive outside mammalian hosts and that they are not found exogenously in plants or soil.

Prior to the antibiotic era, actinomycosis was a common illness and easily recognized at clinical examination. However, the microbiologic features of the etiologic organisms were not fully clarified until the 1940s (Erikson, 1940). The therapeutic outcome of surgical management was variable, and even if healing occurred, sequelae and complications were common (Waksman, 1943; Georg, 1974). The disease often became lifelong, and death was not unusual. At the dawn of the antibiotic era, morbidity resulting from actinomycosis decreased, and a general lack of familiarity with the disease process resulted (Brock, 1973). Subsequently, diagnoses of actinomycosis were often delayed because of a lack of microbiologic techniques.

strong>Pathophysiology: The pathogen is a filamentous bacterium. Historically, actinomycosis has been confused with a fungal disease because of its appearance and the slowly progressive nature of the lesions, which mimics mycotic illness. Confusion was so great that, for many years, some investigators placed Actinomyces species in an intermediate status between fungi and bacteria (Eastridge, 1972). The unique nature of the organism is the absence of a nuclear membrane, which places Actinomyces species among the higher prokaryotic bacteria. The lack of chitin and gluten, coupled with the presence of muramic acid in the cell walls and the absence of mitochondria, is another distinct feature (Behbehani, 1983).

All species of Actinomyces are normal commensal inhabitants of the oral and buccal cavities in humans and certain other mammals. They cannot be classified as symbiotic organisms because they do not have a mutually beneficial relationship with their host. They are not true parasites because they usually do not cause harm to the host; however, they definitely assume a parasitic role when they result in an infection with an inflammatory tissue response. Similar to Mycobacterium tuberculosis, actinomycetes survive phagocytosis by host cells, and they may be characterized as facultative intracellular parasites.

Actinomycosis does not appear to be an opportunistic infection because it is not common in patients who are immunosuppressed or in patients with AIDS. One of the authors has experience in producing a bone infection in animals that leads to osteomyelitis; however, actinomycosis could not be induced in the tibias and mandibles of rabbits. This outcome may have been the result of the avirulent nature of the organisms. Perhaps the presence of other infectious bacteria is required in addition to the Actinomyces species to initiate the infection in experimental models (Najjar, 1980).

Frequency:

In the US: The incidence of human actinomycosis has been decreasing in the United States. Weese and Smith reported prevalences of 1 case per 12,000 admissions in the 1930s and 1 case per 21,000 admissions in the 1950s. Bennhoff reported a prevalence of only 1 case per 63,000 admissions in the 1970s. Actinomycosis can still be found in inner-city populations of the United States.

Internationally: Actinomycosis remains a problem in underdeveloped countries (Coleman, 1969).

Mortality/Morbidity: No evidence of long-term morbidity is observed in patients treated with antibiotics and surgical excision of the necrotic tissue.

Race: Actinomycosis affects persons of all socioeconomic levels and all races, and the disease is not limited to any single segment of the population.

Sex: A male-to-female predominance in a ratio of approximately 3:1 has been observed (Eng, 1981). This predominance is postulated to reflect the greater likelihood for facial and oral trauma and the lack of oral hygiene in males compared with females.

Age: The incidence of actinomycosis is higher in persons aged 30-60 years than in others, and the disease is rare in children. This difference may reflect the increased incidence of periodontal disease in elderly individuals.

Treatment
Medical Care: The presence of associated bacteria appears to be fundamental to the development of clinical infection. Therefore, antibiotic coverage should be aimed at all associated organisms in patients with actinomycosis. An aerobic environment is an unfavorable condition for the growth of Actinomyces species and thus halts the infection (Schaal, 1983; Lewis, 1978; Hennrikus, 1987; Lerner, 1974; Deshpande, 1985).

With the combined use of penicillin and surgery, cure has become the rule rather than the exception.

The treatment of choice includes large doses of antibiotics and prolonged therapy coupled with drainage of the abscesses or radical excision of the sinus tracts. High penicillin concentrations are necessary to penetrate areas of fibrosis and suppuration and possibly the granules themselves. Occasionally, extensive disease may respond to intravenous penicillin alone, rendering surgery unnecessary.

If recognized early, cervicofacial infection has an excellent prognosis with the use of antibiotics alone. In the treatment of this infection, tetracyclines are as effective as penicillin. Intravenous penicillin G (10-20 million U/d for 2-6 wk) followed by oral penicillin (2-4 g/d for an additional 3-12 mo) is the typical therapy for the most deep-seated infections (Holmberg, 1977).

Actinomyces organisms are also susceptible to chloramphenicol, erythromycin, tetracyclines, and clindamycin but not to metronidazole or aminoglycosides.

When tuberculosis is suspected, the effects of rifampin therapy can mask the signs of undiagnosed pulmonary actinomycosis.

Because the bacterial species do not vary in terms of their susceptibility to first-line drugs (eg, penicillin, tetracyclines, erythromycin, first-generation parenteral cephalosporins, clindamycin), infection with strains other than A israelii should also respond to adequate courses of treatment with penicillin G or any of its alternatives. Serum concentrations of sulfonamides (4-8 mg/dL) inhibit some strains of A israelii; therefore, proven cases of actinomycosis (that are not mistaken instances of nocardiosis) may occasionally respond to sulfonamides. Oral cephalosporins and semisynthetic penicillins (eg, oxacillin, dicloxacillin) are less active in vitro and are best avoided (Boand, 1949).

The acquired resistance of Actinomyces species to antimicrobials, particularly to penicillin G, has not been confirmed in vivo. When the response to penicillin is poor, consider an undrained abscess or an associated infection with a resistant bacterium. European investigators favor the use of ampicillin for initial therapy because associated bacteria are less susceptible to penicillin G in vitro, and they use metronidazole or clindamycin as a secondary agent when Bacteroides fragilis or Bacteroides thetaiotaomicron is present. Imipenem produces an impressive response in extensive, complicated, and relapsing abdominothoracic infections that fail to respond to several surgical procedures and trials of penicillin G (Edelmann, 1987).

Surgical Care: Surgical management has consisted of various treatment modalities, including excision of sinus tracts, drainage of the abscess cavities, removal of the bulky infected masses, and irrigation and curettage of the osteomyelitic bony lesions.

The abscesses should be drained, or sinus tracts should be radically excised. With the combined use of penicillin and surgery, cure has become the rule rather than the exception.

Consultations: An oral and maxillofacial surgeon should be consulted because the jaws are involved.

Medication
The goals of pharmacotherapy in the treatment of actinomycosis are to eradicate the infection, reduce morbidity, and prevent complications.
Drug Category: Antibiotics -- Therapy must cover all likely pathogens in the context of this clinical setting. Antibiotic selection should be guided by blood culture sensitivity whenever feasible.

Drug Name	Penicillin G (Pfizerpen) -- Interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms. Prolonged therapy, including >1 year, may be necessary.
Adult Dose	Cervicofacial: 1-6 million U/d IV for 2-6 wk Thoracic and abdominal: 10-20 million U/d IV (administer slowly) for 2-6 wk; administer penicillin VK thereafter
Pediatric Dose	<1> 1-4 weeks: 25,000 U q8h IV (1.2-2 kg) or q6h (>2 kg) <12>1 month: for mild/mod disease use 25,000-50,000 U/kg/d IV divided qid; for severe disease use 250,000-400,000 U/kg/d IV in 4-6 divided doses >12 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Effects are increased by coadministration with probenecid and decreased by coadministration with tetracyclines and other bacteriostatic antibiotics
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in impaired renal function and newborns; rash; anaphylaxis; opportunistic infections with prolonged use; electrolyte imbalances with high doses (above 10 million U/d) if not administered slowly, frequently check electrolytes, renal function, and hematopoietic function (risk of positive Coombs' hemolytic anemia); black hairy tongue; Warner Chillcott's penicillin VK powder contains aspartame (if patient has PKU)

Drug Name	Penicillin VK (Beepen-VK, Betapen-VK, Pen-Vee K, Robicillin VK, Veetids) -- Interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms. Has better GI absorption than penicillin G
Adult Dose	2-4 g/d PO in 4-6 divided doses (best if 1 h before or 2 h after meals) for 6-12 mo
Pediatric Dose	<1> >1 month: 15-62.5 mg/kg/d PO in 3-6 divided doses for 6-12 mo; not to exceed adult doses
Contraindications	Documented hypersensitivity
Interactions	Probenecid may increase effectiveness by decreasing clearance; tetracyclines are bacteriostatic, causing a decrease in the effectiveness of penicillins when administered concurrently
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in renal impairment

Actinic Purpura

2007-11-29T20:49:00.000-08:00

Background

Actinic purpura is a benign clinical entity resulting from sun-induced damage to the connective tissue of the dermis. Actinic purpura is characterized by ecchymoses on the extensor surfaces of the forearms and the dorsa of the hands that usually last 1-3 weeks.

Bateman first described the condition in 1818 when he noted dark purple blotches and determined that they were due to the extravasation of blood into the dermal tissue. Hence, it is sometimes called Bateman purpura.

It is common in elderly individuals and usually occurs after unrecognized minor trauma to the respective areas.

Pathophysiology

The purple macules and patches of this condition occur because red blood cells leak into the dermal tissue. This extravasation is secondary to the fragility of the blood vessel walls caused by ultraviolet radiation–induced dermal tissue atrophy. This atrophy renders the skin and microvasculature more susceptible to the effects of minor trauma and shearing forces. The insult to the skin is typically so minor that isolating it as a cause of the ecchymoses can be difficult.

Notably, no inflammatory component is found in the dermal tissue. The absence of a phagocytic response to the extravascular blood has been postulated to be responsible for delaying resorption for as long as 3 weeks.

Actinic purpura may be, along with osteoporosis, a sign of collagen loss in skin and bone.² This causal loss of skin collagen has been confirmed when collagen was expressed absolutely, instead of as a percentage or ratio. That is, women have less collagen than men and it decreases by 1% a year in exposed and unexposed skin. These changes in skin collagen may correspond to changes in bone density. The hypothesis is that the changes in skin collagen also occur in bone collagen, leading to the associated changes in bone density.

Frequency

United States

Actinic purpura is an extremely common finding in elderly individuals, occurring in approximately 11.9% of those older than 50 years. Its prevalence markedly increases with years of exposure to the sun.

International

Data are not available.

Mortality/Morbidity

The ecchymoses may be cosmetically distressing and may leave dyspigmentation or scarring, but the lesions are not associated with any serious complications.

Race

The effects of chronic sun exposure with the resultant ultraviolet radiation–induced skin changes occur more often and are more pronounced in fair-skinned individuals than in others.

Sex

Both sexes are equally affected.

Age

Actinic purpura occurs almost exclusively in the elderly population, though it may sporadically occur in younger people.
The incidence varies with respect to age.
Approximately 2% of those aged 60-70 years and as many as 25% of those aged 90-100 years can have the purpuric lesions.

Treatment

Medical Care

Actinic purpura does not require extensive medical care.
- To prevent further ultraviolet-induced damage to the skin, sunscreens that provide both UV-A and UV-B protection should be applied daily, especially to areas affected by the purpuric lesions.
- Patients should also use barrier protection (eg, clothing).
- Inform patients that sunscreens help prevent but do not reverse the photodamage.
Tretinoin has been observed to reverse many changes that occur with photodamage.
- The use of tretinoin may be beneficial in actinic purpura because photodamage is ultimately responsible for this disorder.
- Tretinoin increases the amount of dermal collagen and decreases the amount of abnormal elastin when applied topically. However, to the authors' knowledge, no results demonstrate that actinic purpura lesions improve with the topical application of tretinoin.

Activity

Advise patients with actinic purpura to limit their sun exposure by applying sunscreen daily or by avoiding sun exposure altogether.
Instruct patients to minimize any trauma to the skin where the purpuric lesions are present.

Actinic Prurigo

2007-11-29T20:45:00.000-08:00

Background

Actinic prurigo (AP) is a chronic, pruritic skin disease caused by an abnormal reaction to sunlight. In 1954, Escalona first described it in Mexico. Lesions appear hours or days following sun exposure, contrary to what happens in solar urticaria where skin lesions appear minutes after UV exposure. It is commonly associated with cheilitis and conjunctivitis.

Pathophysiology

No systemic or local photosensitizer is known in patients with AP, and a hypersensitivity implicating immunoglobulin E (IgE) has not been demonstrated.

AP has many features of a type IV hypersensitivity reaction. Skin lesions associated with AP are infiltrated with T lymphocytes, mostly CD4⁺, and some of the T-cells express activation markers.AP falls in the category of autoimmune diseases because lymphocytes from patients have been proven to be stimulated in a thymidine incorporation assay when confronted with their own UV-irradiated keratinocytes or UV-irradiated epidermal homogenates.

At this point, the antigen that provokes the inflammatory reaction is not clear, but an epidermal protein is believed to be transformed by UV exposure. In the series by Santos-Martinez et al, the presence of transforming growth factor-beta interleukin 13, and interleukin 10 was demonstrated in a non–type-TH1, non–type-TH2 pattern, similar to what has been shown in lesions of psoriasis and in the synovial fluid of rheumatoid arthritis.

Another potentially important finding in the pathogenesis of AP may be the fact that Langerhans cells in persons with AP show resistance to UV exposure when compared with those in healthy individuals.This same finding has been shown in patients with a similar disease, polymorphous light eruption (PLE). Because these cells are resistant to their demise after UV exposure, they might handle and deliver UV-modified cutaneous antigens to T cells in larger amounts or in a more persistent way; this process could cause or augment the inflammatory phenomenon that is observed in the skin of patients with AP. The apoptotic mechanism in these cells may be somewhat altered, facilitating their survival.

On the other hand, the polyclonal cellular immune response found in biopsy samples from Mexican patients through Southern blot analysis may involve an imbalance linked to a specific hyperimmunity, in which the proportion of autoimmune cells is increased and the proportion of other cells is decreased.

Although different series are searching for a specific HLA, studies have shown associations with B40 and CW3 alleles in some populations, especially Amerindians. For instance, in the Chimila Indians from Colombia,a high frequency of HLA-Cw4 was found. However, in Cree Indians from Saskatchewan, Canada, the most common antigens were HLA-A24 and HLA-Cw4.

Other studies have shown a strong association with HLA-DR4. The more precise finding appears to be in the Mexican series, in which HLA-DR4 DRB1*0407 is found in more than 90% of patients with AP.Another series also found HLA-DR4 DRB1*0407 in Colombian patients. Related alleles such as DRB*0407 have been found in British populations,and DRB1*14 has been found in the Inuit Indians of Canada.

English patients with polymorphic light eruption (PMLE) have not shown an association with any HLA, which suggests that HLA-DR4 (DRB1*0407) could be used as a marker to distinguish PMLE from AP. Therefore, the association with HLA in AP but not in PLE suggests that AP represents an immunologically mediated disease with strong genetic determinants for its expression.

Frequency

United States

AP occurs in persons of all skin types, but its prevalence in the general population is unknown. It probably represents less than 5% of referrals to photodermatologic clinics.AP is well known in the United States among Native Americans.

International

In Mexico, AP represents 1.34% of consultations with pediatric dermatologists and 4% of consultations with general dermatologists. AP is common in Mexico, Central America, and South America, and it is well known in Canada among Native Americans.AP rarely occurs in Europe and Asia, where PLE (a disease with pathogenetic features similar to AP) is more regularly seen. Isolated cases have been reported in France,Germany, Japan, Singapore, Thailand,and Australia. However, the prevalence rate of AP in photodermatology clinics around the world varies from 0-5%.

Mortality/Morbidity

AP is not associated with mortality.

Race

AP frequently affects mestizos of Latin America and American Indians with skin phototypes IV or V.

Sex

In children and adolescents, no differences in prevalence exist between the sexes. However, in adults, women are more frequently affected than men, with a female-to-male ratio of 2:1.

Age

AP can occur at any age; however, one third of patients are children.

Treatment

Medical Care

The cornerstone of pharmacologic treatment is 100 mg/d of thalidomide. Studies have shown that this drug modulates its effect on PA through suppression of tumor necrosis factor-alpha synthesis and modulation of interferon-gamma–producing CD3⁺ cells.Thalidomide can be gradually reduced and then reinstituted in cases of relapse. Women in their childbearing years must use contraceptives because of the teratogenic potential of thalidomide. On some occasions, topical steroids or immunosuppressors are indicated, especially in acute exacerbated cases. Once the skin lesions remit, sunscreens should be used.

Other medications frequently used with moderate results, because of their anti-inflammatory action, are antimalarials and pentoxyphilline,although these drugs are more useful as topical corticosteroid-sparing agents.

Less favorable results are obtained with antihistaminics, beta-carotenes, and psoralen plus UV-A light.

If complications (eg, secondary infection, eczema) occur, patients can be treated with oral antibiotics or topical Burow solution.

Activity

Patients affected by AP should not have restrictions in any areas, such as employment and education. However, changing from outdoor to indoor occupations is important if the patient is not improving with treatment.

Medication

Treatment is mainly aimed at avoiding sun exposure. However, oral and topical corticosteroids are frequently used for short periods. Thalidomide is used, either alone or with topical corticosteroids, for resistant or multiple relapse cases.

Drug Category: Immunosuppressant agents

These agents inhibit key steps responsible for initiating immune activity.

Drug Name	Thalidomide (Thalomid)
Description	Immunomodulatory agent that may suppress activated lymphocytes or prevent their activation. Also down-regulates excessive production of tumor necrosis factor-alpha and selected cell-surface adhesion molecules involved in leukocyte migration.
Adult Dose	100-300 mg/d PO qd with water, preferably hs and at least 1 h pc <50>
Pediatric Dose	0.5-2.5 mg/kg/d PO qd with water
Contraindications	Documented hypersensitivity
Interactions	May increase sedation of alcohol, barbiturates, chlorpromazine, and reserpine; because of teratogenic effects, women must use 2 additional methods of contraceptives or abstain from intercourse
Pregnancy	X - Contraindicated in pregnancy
Precautions	Perform pregnancy test within 24 h prior to initiating therapy (weekly during the first month, followed by monthly tests in women with regular menstrual cycles or q2wk in women with irregular menstrual cycles); bradycardia may occur; use protective measures (eg, sunscreens, protective clothing) against exposure to sunlight or UV light (eg, tanning beds); prescribing physician must enter STEPS program established by manufacturer

Drug Category: Corticosteroids

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.

Drug Name	Prednisone (Orasone, Meticorten, Sterapred, Deltasone)
Description	Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and also suppresses lymphocytes.
Adult Dose	0.5-2 mg/kg/d PO; taper as condition improves; single morning dose is safer for long-term use, but divided doses have more anti-inflammatory effect
Pediatric Dose	4-5 mg/m²/d PO; alternatively, 0.05-2 mg/kg PO divided bid/qid; taper over 2 wk as symptoms resolve
Contraindications	Documented hypersensitivity; viral, fungal, connective tissue, or tubercular skin infections; peptic ulcer disease; hepatic dysfunction; GI bleeding or ulceration
Interactions	Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use

Drug Name	Betamethasone (Diprolene, Maxivate, Alphatrex)
Description	For inflammatory dermatoses responsive to steroids. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing capillary permeability. Affects production of lymphokines and has inhibitory effect on Langerhans cells.
Adult Dose	Apply thin film bid/qid until response
Pediatric Dose	Apply as in adults with caution
Contraindications	Documented hypersensitivity; paronychia; cellulitis; impetigo; angular cheilitis; erythrasma; erysipelas; rosacea; perioral dermatitis; acne
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Do not use in skin with decreased circulation; can cause atrophy of groin, face, and axillae; may cause striae distensae or rosacealike eruption; may increase skin fragility; rarely may suppress HPA axis; if infection develops and is not responsive to antibiotic treatment, discontinue until infection is under control; do not use monotherapy to treat widespread plaque psoriasis

Drug Category: Antimalarial agents

These agents are used for their anti-inflammatory and photoprotective effects.

Drug Name	Hydroxychloroquine (Plaquenil)
Description	Exerts anti-inflammatory activity by suppressing lymphocyte transformation and may have photoprotective effect. Use in AP requires small doses once a day for long periods.
Adult Dose	200 mg/d PO qd to bid
Pediatric Dose	4 mg/kg/d PO once
Contraindications	Documented hypersensitivity to 4-aminoquinoline derivatives; psoriasis; retinal and visual field changes attributable to 4-aminoquinolines
Interactions	Cimetidine may increase serum levels of chloroquine (possibly other 4-aminoquinolones); magnesium trisilicate may decrease absorption of 4-aminoquinolones
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in hepatic disease, G-6-PD deficiency, psoriasis, or porphyria; not recommended for long-term use in children; perform periodic ophthalmologic examinations; test for muscle weakness; retinopathy, tinnitus, nerve deafness, skin eruption, headache, anorexia, nausea, vomiting, and diarrhea may occur

Drug Name	Chloroquine phosphate (Aralen Phosphate)
Description	Inhibits chemotaxis of eosinophils and locomotion of neutrophils, and impairs complement-dependent antigen-antibody reactions. May also have photoprotective effect.
Adult Dose	250-600 mg PO qd
Pediatric Dose	Not established; 4 mg/kg/d PO can be used
Contraindications	Documented hypersensitivity; psoriasis; retinal and visual field changes attributable to 4-aminoquinolones
Interactions	Cimetidine may increase serum levels of chloroquine (possibly other 4-aminoquinolones); magnesium trisilicate may decrease absorption of 4-aminoquinolones
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in hepatic disease, G-6-PD deficiency, psoriasis, or porphyria; not recommended for long-term use in children; perform periodic ophthalmologic examinations; test for muscle weakness; retinopathy, tinnitus, nerve deafness, skin eruption, headache, anorexia, nausea, vomiting, and diarrhea may occur

Actinic Keratosis

2007-11-29T20:43:00.000-08:00

Background: Actinic keratosis (AK) is a UV light–induced lesion of the skin that may progress to invasive squamous cell carcinoma. It is by far the most common lesion with malignant potential to arise on the skin. AK is seen in fair-skinned persons in areas of long-term sun exposure, with an estimated frequency of 40-50% of the adult population older than 40 years in Australia, the country with the highest skin cancer rate in the world.

Although the premalignant nature of AK was recognized almost 100 years ago, the name AK was not introduced until 1958. The name literally means thickened scaly growth (keratosis) caused by sunlight (actinic). These lesions are common in white populations. In the United States, AK represents the second most frequent reason for patients to visit a dermatologist. Although most do not, some of these lesions may progress to invasive squamous cell carcinoma with metastatic potential. They can be safely and effectively eradicated, and therefore therapy is warranted.

Pathophysiology: AKs arise on fair-skinned people in areas of long-term sun exposure, such as the face, ears, bald scalp, forearms, and backs of the hands. However, they may occur on any area that is repeatedly exposed to the sun, such as the back, the chest, and the legs. Long-term UV light exposure is implicated as the cause from both epidemiologic observations and molecular analysis of tumor cells. AK frequency correlates with cumulative UV exposure. Therefore, AK frequency increases with each decade of life, is greater in residents of sunny countries closer to the equator, and is greater in persons with outdoor occupations. DNA analysis of the cells within AKs shows characteristic UV-induced mutations in key genes.

Clinically, AKs range from barely perceptible rough spots of skin to elevated, hyperkeratotic plaques several centimeters in diameter. Most often, they appear as multiple discrete, flat or elevated, keratotic lesions. Lesions typically have an erythematous base covered by scale (hyperkeratosis). They are usually 3-10 mm in diameter and gradually enlarge into broader, more elevated lesions. With time, actinic keratoses may develop into invasive squamous cell carcinoma. Development of actinic keratoses may occur as early as the third or fourth decade of life in patients who live in areas of high solar radiation, are fair-skinned, and do not use sunscreen for photoprotection. Usually, patients demonstrate a background of solar-damaged skin with telangiectasias, elastosis, and pigmented lentigines.

In both histologic and molecular parameters, AKs share features with squamous cell carcinoma. AK is an epidermal lesion characterized by aggregates of atypical, pleomorphic keratinocytes at the basal layer that may extend upwards to involve the granular and cornified layers. The epidermis itself shows an abnormal architecture, with acanthosis, parakeratosis, and dyskeratoses. Cellular atypia is present, and the keratinocytes vary in size and shape. Mitotic figures are present.

This presentation may resemble Bowen disease or carcinoma in situ, and the distinction between the 2 is a matter of degree (extent of the lesion) rather than differences in individual cells. Often, marked hyperkeratosis and areas of parakeratosis with loss of the granular layer are present. A dense inflammatory infiltrate is usually present. The case has been made that AK is the earliest manifestation of squamous cell carcinoma and should be regarded as such rather than as a precancerous lesion. Others have argued that calling AK a carcinoma unduly alarms patients. Cockerell has proposed renaming the lesion keratinocytic intraepidermal neoplasia, in a nomenclature analogous to cervical and vulvar intraepithelial neoplasia.

Frequency:

In the US: AK occurs primarily in whites, the frequency of which correlates with cumulative UV exposure. Therefore, frequency increases with age, proximity to the equator, and outdoor occupation. AKs are seen more in men than in women and have also been correlated with a high-fat diet. Overall, the rate in the United States is estimated to range from 11-26%.

Internationally: The prevalence is highest in Australia, where a light-skinned population is common and outdoor sports are very popular activities. Overall, AK is estimated to be present in 40-50% of the Australian population older than 40 years.

Mortality/Morbidity: Lesions begin as barely perceivable rough spots of skin, better felt than seen. The early lesions feel like sandpaper. Later lesions become erythematous, scaly plaques that may enlarge to several centimeters. Lesions may remain unchanged for years, may spontaneously regress, or may progress to invasive squamous cell carcinoma. Most AKs do not progress to invasive squamous cell carcinoma; however, most invasive squamous cell carcinomas have evidence of a preexisting AK. Invasive squamous cell carcinoma may produce significant morbidity by direct extension into facial structures. In less than 10% of cases, invasive squamous cell carcinoma may metastasize, with a low 5-year survival rate.

Race: The prevalence is much higher in individuals with fair skin and blue eyes and is lower in individuals with darker skin types. It is relatively nonexistent in black skin. Patients with AKs tend to have Fitzpatrick type I or II skin, which burns and does not tan. The prevalence is reduced precipitously in persons with Fitzpatrick types III, IV, and V skin and is nonexistent in those with Fitzpatrick type VI skin.

Sex: The prevalence of AK is higher in men than in women. This is theorized to result from a greater likelihood that men have an outdoor occupation and thus have greater cumulative UV exposure.

Age: The frequency of AK is directly related to cumulative sun exposure. The age of occurrence is related to the skin type and the amount of sun damage. AKs can occur in patients aged 20-30 years, but they are more common in patients aged 50 years and older.

Treatment
/a>Medical Care: AKs may remain unchanged, spontaneously resolve, or progress to invasive squamous cell carcinoma. The fate of any one AK is impossible to predict. Although the risk of progression of any one AK to invasive squamous cell carcinoma is small, a patient may have many lesions, and thus the risk of progression becomes significant. Therapy is generally well tolerated and simple; therefore, treatment is warranted.

Medical management begins with educating the patient to limit sun exposure. Patients should be cautioned to avoid sun exposure from 10:00 AM to 3:00 PM as much as possible. They also must wear adequate sunscreens and protective clothing daily. One study suggested that a low-fat diet leads to fewer new AKs and greater resolution of old ones.

Treatment consists of 2 broad categories: surgical destruction of the lesion and medical therapy. Medical therapy has the advantage of being able to treat large areas with many lesions. The disadvantages of medical therapies include lengthy courses of treatment with irritation and discomfort. Currently, the US Food and Drug Administration has approved 4 medications for the treatment of AKs. These are topical 5-fluorouracil (5-FU), 5% imiquimod cream, topical diclofenac gel, and photodynamic therapy (PDT) with topical delta-aminolevulinic acid.

The most experience in topical therapy for AKs is with 5-FU. Several formulations are available, including a 5% cream or solution, a 2% solution, a 1% cream or solution, and, most recently, a micronized 0.5% cream. Although not well studied, efficacy among the various formulations does not seem to differ significantly.
- The most popular formulation is the 5% cream, which is applied twice daily for 1 month. During the treatment phase, the lesions become increasingly erythematous and cause discomfort; small subclinical lesions become visible. This treatment can be temporarily disfiguring, with erythematous ulcerations and crust formation. However, if the patient completes the treatment, the lesions usually heal within 2 weeks of stopping treatment, the complexion is smooth, and the AKs are improved.
- The 0.5% micronized cream was developed to increase tolerability because inflammation and discomfort can be a limiting factor in the use of topical 5-FU. The 0.5% micronized cream is applied once daily for 1 month.

Imiquimod is a topical medication that up-regulates a variety of cytokines, which, in turn, invoke a nonspecific immune response (interferons, natural killer cells) and an specific immune response (T cells). It is applied 2-3 times a week for up to 4 months, although generally 1 month is sufficient. Reaction to the drug is idiosyncratic, with some patients barely reacting and others developing marked inflammation. Subclinical lesions previously not appreciated may become inflamed during therapy. In patients with a brisk inflammatory response, dosing is reduced to twice or even once a week, with preservation of therapeutic efficacy but increased tolerability. Experimental evidence suggests patients may develop T-cell memory after treatment with this drug and thus may be less likely to develop new AKs in the future.

Topical diclofenac is a nonsteroidal anti-inflammatory drug. Its mechanism of action against AKs is unknown. It is effective therapy when applied twice a day for 3 months. A shorter course of therapy is dramatically less effective. Its chief advantage is that it produces little-to-no inflammation and thus is very well tolerated.

PDT uses a light-sensitizing compound that preferentially accumulates in AK cells, where it can be activated by the appropriate wavelength of light. Delta-aminolevulinic acid is a component of the heme biosynthetic pathway that accumulates preferentially in dysplastic cells. Once inside these cells, it is enzymatically converted to protoporphyrin IX, a potent photosensitizer. With exposure to light of an appropriate wavelength, oxygen free radicals are generated and cell death results.
- Patients experience pain in the areas treated, which is similar in scope to the pain resulting from topical 5-FU. The treated lesions may become erythematous and crusted. One treatment with PDT appears to be as effective as topical 5-FU therapy.
- When used with light sources that have a cosmetic benefit by themselves, such as the pulsed dye laser of intense pulsed light devices, a cosmetic benefit may be seen from the use of topical PDT beyond that of AK eradication.
- An unknown parameter in the use of topical PDT is the optimal incubation time following application of the topical aminolevulinic acid before light exposure. A second unknown parameter is the optimal light source to use for this treatment. Ongoing studies are addressing these issues.

Surgical Care: The goal of surgical therapy is complete eradication of the AKs, usually by physical destruction, with limited-to-no damage to surrounding normal tissue. When the diagnosis is unclear and invasive tumor is possible, biopsy is indicated. However, biopsy generally leaves a scar.

Cryosurgery refers to use of a cryogen to lower the temperature of the skin and produce cell death. The most common cryogen used is liquid nitrogen, with a temperature of -195.8°C. Keratinocytes die when exposed to approximately -40 to -50°C. Other structures in the skin, such as collagen, blood vessels, and nerves, are more resistant to the lethal effects of cold than keratinocytes. Melanocytes are more sensitive than keratinocytes; thus, cryosurgery often leaves white spots. This technique has not been studied in a scientific fashion until recently, when it was demonstrated to produce an overall clearance rate of 67%.

Lesions suggestive of invasive cancer may be treated with curettage, shave excision, or conventional excision, all of which provide a sample for histologic evaluation. These treatments require local anesthesia, produce a wound that requires time to heal, and are likely to scar.

Cosmetic resurfacing procedures, in which the entire epidermis is removed, sometimes with some portion of the dermis, are effective for AK eradication. Cosmetic resurfacing procedures include medium and deep chemical peels, dermabrasion, and ablative laser resurfacing. All of these are cosmetic procedures unlikely to be covered by insurance, all carry the risk of scarring and infection, and all require experience and expertise on the part of the dermatologic surgeon. They are highly unlikely to be performed solely for AK therapy.

Diet: One study suggested that a low-fat diet in humans leads to greater resolution of existent AKs and the development of fewer new ones during the study period.

Activity: Instruct patients to practice sun safety, such as the use of sunscreen and protective clothing, and to limit outdoor activity from 10:00 AM to 3:00 PM.

Medication
The goals of pharmacotherapy are to reduce morbidity and to prevent complications.
Drug Category: Antineoplastic agents -- DOC is topical 5-FU lotion or cream, which inhibits cell growth and proliferation.

Drug Name	Fluorouracil (Fluoroplex, Carac, Efudex) -- Used topically for management of AKs. Interferes with DNA synthesis by blocking methylation of deoxyuridylic acid via inhibition of thymidylate synthetase and, subsequently, cell proliferation. For lesions on bald scalp or extremities, longer treatment is often necessary.
Adult Dose	Apply topically to affected areas bid for approximately 2-6 wk (has been used as long as 12 wk in some cases)
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; pregnancy
Interactions	None reported
Pregnancy	X - Contraindicated in pregnancy
Precautions	Inflammatory reactions may occur with occlusive dressings; porous gauze dressing may be applied for cosmetic reasons, without an increase in reaction; patients should expect inflammatory reaction with crusting; application to mucous membranes may cause increased inflammation and ulceration; exposure to UV rays (ie, sunlight) may increase intensity of the reaction

Drug Category: Immunomodulators, topical -- Investigation of imiquimod demonstrates it induces interferons alpha and gamma, TNF-alpha, and interleukin 12, among other cytokines. Studies using 5% cream in mice showed significant induction of interferon alpha at the site of application, occurring as early as 2 h after treatment. At 4 h after application, increases in interferon alpha mRNA levels were found, indicating an increase in transcription. Cytokine up-regulation is thought to be activated by imiquimod binding to toll-like receptor VII.

Drug Name	Imiquimod (Aldara) -- Immune response modifier thought to produce a nonspecific anti-AK response (interferon, natural killer cells) and a specific immune response (cytotoxic T cells). Indicated to treat clinically typical, nonhyperkeratotic, nonhypertrophic AKs on the face or scalp.
Adult Dose	Apply no more than 1 packet to defined area of face or scalp 2 times/wk hs for 16 wk; apply to dry skin (at least 10 min after washing face) and leave on for approximately 8 h; then, wash area with mild soap and water
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Avoid exposure to sunlight or artificial tanning devices; regular use of sunscreen is encouraged; avoid contact with lips, eyes, or nostrils; common adverse effects include erythema, edema, vesicles, erosion or ulceration, weeping, exudate, flaking, scaling, dryness, and scabbing, or crusting

/a>
a>

Acropustulosis of Infancy

2007-11-29T20:42:00.000-08:00

Background: Infantile acropustulosis is a recurrent, self-limited, pruritic, vesicopustular eruption of the palms and the soles occurring in young children during the first 2-3 years of life. Newly described in 1979, it is probably much more common than the scarcity of reports would imply.

Pathophysiology: The pathophysiology of infantile acropustulosis is unknown. Many cases are preceded by well-documented or suspected scabies infestation, and a scabies id reaction has been suggested. More often, cases occur despite scabies having been thoroughly ruled out. Bacterial and viral culture results are consistently negative, and negative immunofluorescence results suggest that infantile acropustulosis is not an antibody-mediated autoimmune process.

Frequency:

In the US: The exact incidence is unknown.

Internationally: The exact incidence is unknown. One study from Israel reported 25 cases in a 9-year period, suggesting that this is not as uncommon as once thought.

Mortality/Morbidity: All cases spontaneously resolve in a few months to 3 years.

Race: Early reports suggested a predominance of African Americans. Now, acropustulosis is believed to affect all races equally.

Sex: Early reports suggested a male predominance. Larger series have since shown an equal distribution between males and females.

Age: Although children as old as 9 years have been reported, acropustulosis typically begins between the first 2-12 months of life. Resolution by age 3 years is the norm.

Treatment
Medical Care: Treatment is often unnecessary because of the self-limited nature of this condition.

Topical steroids and oral dapsone have been used successfully, if justified in more difficult cases.

Topical pramoxine preparations are available without prescription for the treatment of pruritus.

Oral antihistamines may be useful.

Consultations: Consult a dermatologist or a pediatric dermatologist.

Activity: Isolation is not warranted.

Medication
High-potency topical steroids (classes 1 and 2) have been used successfully for control of pruritus. Children who are extremely symptomatic may be treated with dapsone.
Drug Category: Topical steroids -- These agents provide symptomatic relief of pruritus.

Drug Name	Betamethasone (Diprolene, Betatrex) -- For inflammatory dermatoses responsive to steroids. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing capillary permeability. Use fluorinated topical steroids with caution in children.
Pediatric Dose	Apply thin film to affected areas bid; occlusion increases effectiveness; avoid wraps that may present choking hazard
Contraindications	Documented hypersensitivity; paronychia; cellulitis; impetigo; angular cheilitis; erythrasma; erysipelas; rosacea; perioral dermatitis; acne
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Application over large surface areas may cause systemic absorption and adrenal suppression; do not use on skin with decreased circulation; can cause atrophy of groin, face, and axillae; if infection develops and is not responsive to antibiotic treatment, discontinue until infection is under control

<Drug Category: Antibiotics -- Diaminodiphenylsulfone antibiotics have been used as anti-inflammatory agents.

Drug Name	Dapsone (Avlosulfon) -- Bactericidal and bacteriostatic against mycobacteria; mechanism of action is similar to that of sulfonamides where competitive antagonists of PABA prevent formation of folic acid, inhibiting bacterial growth. Used mainly to treat leprosy and dermatitis herpetiformis. Has antineutrophil and anti-inflammatory properties.
Pediatric Dose	1-2 mg/kg/d PO; not to exceed 100 mg
Contraindications	Documented hypersensitivity; known G-6-PD deficiency (assay for G-6-PD activity prior to initiation of therapy)
Interactions	May inhibit anti-inflammatory effects of clofazimine; hematologic reactions may increase with folic acid antagonists, eg, pyrimethamine (monitor for agranulocytosis during second and third months of therapy); probenecid increases toxicity; trimethoprim with dapsone may increase toxicity of both drugs; because of increased renal clearance, levels may significantly decrease when administered concurrently with rifampin
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Associated with a variety of systemic toxicities, including agranulocytosis, anemia, methemoglobinemia, hepatitis, and neuropathy; patients may experience headache and/or GI distress on initiation of therapy; perform weekly blood counts (first mo), then monthly WBC counts (6 mo), then semiannual WBC counts; discontinue if a significant reduction in platelets, leukocytes, or hematopoiesis occurs; caution in methemoglobin reductase deficiency, G-6-PD deficiency, or hemoglobin M because of high risk for hemolysis and Heinz body formation Caution in patients exposed to other agents or conditions (eg, infection, diabetic ketosis) capable of producing hemolysis; peripheral neuropathy can occur (rare); phototoxicity may occur when exposed to UV light; pancreatitis may occur; various forms of renal complications including acute renal failure, acute tubular necrosis, and oliguria have occurred with dapsone use

<Drug Category: Antipruritics -- These agents may relieve associated itching.

Drug Name	Pramoxine (Tronothane, Prax) -- Blocks nerve conduction and impulses by inhibiting depolarization of neurons. Use 1% lotion or cream.
Pediatric Dose	Apply to affected area prn; not to exceed 200 mg
Contraindications	Documented hypersensitivity; do not apply over large areas; avoid contact with eyes and nose
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in patients with trauma in area to be treated

Acromegaly

2007-11-29T20:38:00.000-08:00

Background

Excess secretion of growth hormone (GH) induces gigantism in prepubertal children and acromegaly in adults. Acromegaly arises from GH-secreting pituitary adenomas. GH is necessary for normal linear growth. GH is not the principal stimulator of growth, but it acts indirectly by stimulating the formation of other hormones. These hormones are termed somatomedins (SMs, ie, somatotropin-mediating hormones) or insulinlike growth factors (IGFs).

Somatomedin C (SM-C; insulinlike growth factor I [IGF-I]), the most important SM in postnatal growth, is produced in the liver, chondrocytes, kidney, muscle, pituitary, and gastrointestinal tract.

Pathophysiology

GH secretion from the pituitary gland is controlled by a combined hypothalamic regulation. Secretion is stimulated by growth hormone–releasing hormone (GHRH) and inhibited by GH release–inhibitory hormone or somatostatin (also termed somatotropin release–inhibitory factor or SRIF).

Syndromes of excessive secretion of GH or acromegaly are caused 95% of the time by a pituitary adenoma of the somatotrophs. A few cases of ectopic GHRH-producing tumors, usually seen in the lung or pancreas, also have been described.

Isolated familial somatotropinoma is a rare disease; at least 2 cases of acromegaly or gigantism has been reported in a family that does not exhibit features of Carney complex or multiple endocrine neoplasia type 1.¹ It appears to be inherited as an autosomal dominant disease with incomplete penetrance. Although an association exists between the disease and loss of heterozygosity on 11q13, the responsible gene remains unknown.

Approximately 40% of somatotroph tumors have a mutation in the alpha subunit of a stimulatory G protein. Activation of this G protein is associated with binding of guanosine triphosphate (GTP) to the alpha subunit, which allows the alpha subunit to stimulate cyclic adenosine monophosphate (AMP) production. The normal free subunit has intrinsic GTPase activity, which inactivates GTP, preventing continued cyclic AMP stimulation. The mutant alpha subunit in acromegalic patients does not possess GTPase activity; therefore, continued cyclic AMP stimulation results.

GHRH-induced acromegaly is rare but is clinically indistinguishable from acromegaly caused by pituitary adenomas.

High levels of IGF-I are found in acromegaly, and low levels are found in children with GH deficiency. Insulin and IGF-I are similar peptides, and either can bind to IGF-I receptors.

Activation of this receptor leads to the growth and differentiation of many different cell lines, including keratinocytes, fibroblast, and the pilar unit of the skin.

Epidermal growth factor (EGF) and its homologs, transforming growth factor-alpha and amphiregulin, play a pivotal role in the regulation of keratinocyte growth and differentiation. All 3 growth factors stimulate cell growth by activating the epidermal growth factor receptor (EGF-R) that is expressed on keratinocytes in culture and in situ. Active proliferation of keratinocytes is associated with increased expression of the EGF-R and of its ligands (ie, transforming growth factor-alpha and amphiregulin) in the epidermis.

IGF-I and insulin, both of which stimulate keratinocyte growth through the IGF-I receptor, have been identified as primary keratinocyte mitogens. Proliferation induced by insulin and IGF-I requires the presence of other growth factors (notably EGF), and IGF-I stimulates keratinocyte proliferation in the absence of any other polypeptide growth factor at physiologic concentrations, through the IGF-I receptor. Thus, IGF-I is 1 of the factors inducing the growth factor component of the EGF-R–dependent autocrine loop in keratinocytes.

Frequency

United States

Acromegaly is uncommon, with an incidence of 3-4 cases per million per year. This figure easily may be an underestimation because of the insidiousness of this disease.

Mortality/Morbidity

Acromegaly is a severe disease often diagnosed late. Morbidity and mortality rates are high, in particular, because of associated cardiovascular, cerebrovascular, and respiratory disorders and malignancies.

Acromegaly is associated with an increase in left ventricular mass, even in the absence of systemic hypertension. Pathologic studies on acromegalic hearts have shown extensive interstitial fibrosis, suggesting the existence of a specific acromegalic cardiomyopathy.

Alveolar hypertrophy or hyperplasia is the mechanism for lung growth in this condition.

Increased colon and breast cancers have been associated with acromegaly.

Sex

Male-to-female ratio is equal.

Age

Acromegaly occurs most frequently in middle age. The mean age of diagnosis is 40 years in men and 45 years in women.

Treatment

Medical Care

No single treatment modality consistently achieves control of the disease. A multimodality approach usually requires surgery as the first line of treatment, followed by medical therapy for residual disease. Radiation treatment usually is reserved for recalcitrant cases. The most effective and practical drugs currently in use include somatostatin analogs and dopamine agonists such as bromocriptine.

This chronic debilitating disorder caused by a GH-producing pituitary adenomas is usually treated with transsphenoidal surgery as the treatment of choice; however, radiotherapy and medical treatment are important because surgery cures only approximately 60% in long-term studies.Slow-release formulations of somatostatin are now widely used, also as primary treatment, and appear to be safe and effective in 50-60% of the patients. A GH-receptor blocking agent, pegvisomant, appears to normalize IGF-1 levels in almost all patients

Somatostatin is a natural inhibitor of GH secretion. Octreotide is used most extensively.
- Octreotide binds to the somatostatin receptor subtypes II and V and inhibits GH secretion.

- Treatment with octreotide reduces GH concentration to less than 5 ng/mL in 65% of patients and less than 2 ng/mL in 40%.

- Octreotide normalizes the IGF-I concentration in 60% of patients.

- Tumor shrinkage is seen in 20-50% of patients.

- Primary treatment with depot octreotide and lanreotide has been found to induce tumor shrinkage in newly diagnosed acromegaly.The best predictor of tumor shrinkage was after treatment with IGF-l.

Bromocriptine lowers serum GH in as many as 75% of patients, but in only 20% are the levels reduced to normal.

- Patients in whom prolactin is elevated are more likely to have a favorable response.
- GH-secreting tumors usually do not decrease in size with bromocriptine.
- Bromocriptine has an adjunctive role in patients who fail to achieve a cure by surgical treatment or who are to be treated with radiation.

Periodic reassessment of GH production is advisable after treatment.

Criteria for cure include a normal basal GH level and normal GH dynamic responses.

SM-C levels appear to correlate better with clinical activity than do GH levels; therefore, SM-C levels should be monitored.

Radiotherapy takes years to become effective. Approximately 60% of patients have GH concentration of less than 5 ng/mL 10 years after radiotherapy. A similar number develop panhypopituitarism as a result of treatment. Because of the disappointing results and adverse effects, radiotherapy is used as an adjunct treatment for large invasive tumors and when surgery is contraindicated. Some studies suggest that radiation is associated with the development of secondary tumors.

Surgical Care

Surgery is performed as first-line therapy.

Transsphenoidal hypophysectomy has the dual advantage of rapidly improving symptoms caused by mass effect of the tumor and significantly reducing or normalizing GH/IGF-I concentrations.

Remission rates of 80-85% can be expected for microadenomas and 50-65% for macroadenomas.

Carefully monitor patients for enlargement or recurrence of a pituitary mass lesion.

The biochemical activity of disease after pituitary surgery in persons with acromegaly has been evaluated. By definition, biochemical cure in acromegaly involves both the normalization of IGF-1 levels and a glucose-suppressed GH level of less than 1 ng/mL. A significant proportion of acromegalic patients were found have a change in biochemical status upon long-term follow-up after surgery. Most of these changes occurred within the first postoperative year and were more likely to occur if the initial GH postglucose and IGF-1 levels were discordant.

Medication

The goal of pharmacotherapy is to reduce morbidity and to prevent complications.

Drug Category: Somatostatin analogs

Reduce blood levels of GH and IGF-I in patients with an inadequate response to surgery, radiation, and bromocriptine.

Drug Name	Octreotide (Sandostatin)
Description	Acts primarily on somatostatin receptor subtypes II and V. Inhibits GH secretion. Also has a multitude of other endocrine and nonendocrine effects, including inhibition of glucagon, VIP, and GI peptides.
Adult Dose	Initial: 50 mcg SC tid; may increase to 500 mcg tid Doses of 300-600 mcg/d or higher seldom result in additional benefit
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	May reduce cyclosporine effects; patients on insulin, oral hypoglycemics, beta-blockers, and calcium channel blockers may need dose adjustments
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adverse effects primarily are related to effect on GI motility and include nausea, abdominal pain, diarrhea, increased incidence of gallstones and biliary sludge; hypoglycemia or hyperglycemia may be seen because of alteration in counter-regulatory hormones, insulin, glucagon, and GH; bradycardia, cardiac conduction abnormalities, and arrhythmias reported; hypothyroidism also may occur because of inhibition of TSH secretion; caution in renal impairment

Drug Name	Octreotide LAR (Sandostatin LAR)
Description	Long-acting somatostatin analog given q4wk. Similar improvements in GH/IGF-I concentration compared to octreotide, but associated with fewer adverse effects. A trial of short-acting somatostatin analog is necessary to confirm patient's ability to tolerate the compound. Do not administer in deltoid area because of significant discomfort at injection site. Gluteal injection sites should be alternated.
Adult Dose	10-30 mg IM q28d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	May reduce cyclosporine effects; patients on insulin, oral hypoglycemics, beta-blockers, and calcium channel blockers may need dose adjustments
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Adverse effects primarily are related to effect on GI motility and include nausea, abdominal pain, diarrhea, and increased incidence of gallstones and biliary sludge; hypoglycemia or hyperglycemia may be seen because of alteration in counter-regulatory hormones, insulin, glucagon, and GH; bradycardia, cardiac conduction abnormalities, and arrhythmias reported; hypothyroidism may occur because of inhibition of TSH secretion; caution in renal impairment; cholelithiasis may occur

Drug Category: Dopamine agonists

Usually added to somatostatin analogs if complete remission is not achieved. Have modest effects if used as single agent.

Drug Name	Bromocriptine (Parlodel)
Description	Acts on central dopamine receptors. More effective in tumors that co-secrete prolactin. Dose used to treat acromegaly usually is much higher than for hyperprolactinemia.
Adult Dose	1.25 mg PO hs qd initial; increase gradually to 20-30 mg PO qd in divided doses Safety not demonstrated with dosages >100 mg/d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; uncontrolled hypertension; ischemic heart disease; peripheral vascular disorders
Interactions	Other ergot alkaloids increase toxicity of bromocriptine; amitriptyline, butyrophenones, imipramine, methyldopa, phenothiazines, and reserpine may decrease bromocriptine effects
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adverse effects include nausea, vomiting, headaches, nasal congestion, orthostatic hypotension, and digital vasospasm; patients tend to develop tolerance to adverse effects; caution in renal or hepatic disease

Drug Category: Growth hormone antagonists

The newest class of drugs used to decrease excessive GH effect. Blocks GH binding to receptors, thus, decreases IGF-I, IGF binding protein-3 (IGFBP-3), and acid-labile subunit (ALS).

Drug Name	Pegvisomant (Somavert)
Description	Recombinant DNA analog of human GH structurally altered to act as GH receptor antagonist. Selectively binds to GH receptors on cell surfaces, thereby blocking endogenous GH binding. This action interferes with GH signal transduction, resulting in decreased levels of IGF-I, IGFBP-3, and ALS.
Adult Dose	Loading dose: 40 mg SC Maintenance dose: 10 mg SC qd initially; may increase or decrease q4-6wk by 5-mg increments as determined by IGF-I levels; not to exceed 30 mg/d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	May decrease insulin or oral hypoglycemic effects; patients receiving opioid analgesics may require higher doses to suppress IGF-I production to recommended levels
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Vial stopper contains latex; may cause GH-secreting tumors to grow; may increase insulin sensitivity; may induce GH deficiency; may increase liver enzyme levels

Acrokeratosis Verruciformis of Hopf

2007-11-29T20:37:00.000-08:00

Background: Acrokeratosis verruciformis is an autosomal dominant genodermatosis characterized by multiple warty lesions resembling plane warts typically observed on the dorsum of the hands and feet. Hopf first suggested the name acrokeratosis verruciformis in 1931. In 1947, Niedleman first published the largest series describing an Italian American family in which acrokeratosis verruciformis of Hopf occurred in 14 members. In the follow-up study in 1962, Niedleman and McKusick further described 24 cases in 4 generations of the same family. The number and distribution of cases in the latter report suggested an autosomal dominant mode of transmission.

Lesions identical to those of acrokeratosis verruciformis are also observed in many patients with acral Darier disease (also termed keratosis follicularis). To complicate matters further, lesions of acrokeratosis verruciformis have been reported in relatives of individuals with Darier disease. Considerable controversy surrounds the nature and relationship of acrokeratosis and Darier disease and whether they are manifestations of one genetic abnormality. Acrokeratosis verruciformis and acral Darier disease have been distinguished as 2 distinct entities in the literature. Although clinically similar, acrokeratosis verruciformis is thought to remain nondyskeratotic throughout life, whereas acral lesions of Darier disease show, upon careful histologic examination, various gradations of benign acantholytic dyskeratosis.

Darier disease (keratosis follicularis) is the most important disorder to be distinguished from acrokeratosis. Darier disease, acrokeratosis verruciformis, epidermodysplasia verruciformis, plane warts, and seborrheic keratoses can be differentiated by histologic examination of biopsy samples from individual lesions. The hard nevus of Unna can be differentiated clinically by its late onset.

Pathophysiology: The close similarity of Hopf disease to the acral warty lesion of keratosis follicularis has been noted by Hopf and Darier themselves. The similarities led later observers to postulate a relationship between the two diseases. The exact relationship between acrokeratosis verruciformis and Darier disease has not yet been satisfactorily resolved. A classic case of Darier disease poses no diagnostic problem. However, deciding whether a forme fruste of Darier disease (with atypical acral papules) is identical to acrokeratosis verruciformis remains difficult.

Frequency:

Internationally: Unknown

Race: Acrokeratosis verruciformis has been described in individuals of many races.

Age: Acrokeratosis verruciformis is usually present at birth or in early childhood. Onset may be delayed until the fifth decade of life.

Treatment
Medical Care: The only effective treatment is superficial ablation. Treatment is not generally recommended, but medical and surgical treatments have been tried. Applications of retinoic acid have been helpful in some individuals. Destruction of the lesions with cryotherapy or laser, especially destructive lasers such as a carbon dioxide or Nd:YAG laser, may be used. Untreated lesions persist and become more noticeable after prolonged sun exposure because of darkening.

Medication
Drug Category: Retinoids -- Tretinoin has been reported to be successful in some individuals with these lesions.

Drug Name	Tretinoin (Avita, Retin-A) -- Developed to treat acne vulgaris. Alters maturation and differentiation of keratinocytes. Has been used for a variety of conditions, including flat warts, abnormalities of keratinization, and other keratoses. Available in 0.025%, 0.05%, and 0.1% concentrations in a variety of vehicles, including gels, solutions, and creams.
Adult Dose	Begin with lowest tretinoin formulation and increase as tolerated; apply hs or qod; lower frequency of application if irritation develops
Pediatric Dose	<12> >12 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Toxicity increases with coadministration of benzoyl peroxide, salicylic acid, and resorcinol; avoid topical sulfur, resorcinol, salicylic acid, other keratolytics, abrasives, astringents, spices, and lime
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Photosensitivity may occur with excessive sunlight exposure; caution in eczema; do not apply to mucous membranes, mouth, and angles of nose; pruritus, erythema, and a burning sensation may be noted, especially with higher strengths; hypopigmentation and, rarely, hyperpigmentation, may be noted locally

Acrokeratosis Neoplastica

2007-11-29T20:34:00.000-08:00

Background: Acrokeratosis neoplastica (AN) is a rare psoriasiform dermatosis that is associated consistently with internal malignancy, usually squamous cell carcinoma (SCC) of the upper aerodigestive tract. Skin manifestations include acute onset of onychodystrophy and violaceous scaly patches on the helices, nose, and malar and acral surfaces. Usually, skin manifestations precede diagnosis of the malignancy.

The term Bazex syndrome describes 2 different entities: AN and the genetic syndrome of basal cell carcinomas, follicular atrophoderma, hypotrichosis, and hypohidrosis or hyperhidrosis.

Pathophysiology: The skin manifestations of AN parallel the disease course, suggesting the presence of circulating antibodies to tumor antigens. Cytokines may play a role.

Frequency:

In the US: Approximately 125 cases have been reported in the literature.

Mortality/Morbidity:

Mortality and morbidity are related directly to the available treatment options for the underlying neoplasm.

In most reported cases, cervical lymph node metastases are present at the time of diagnosis, usually indicating a poor prognosis.

Sex: In one review, 105 of 113 cases were in males.

Age: Mean age of onset is 61 years.

Treatment
Medical Care:

Treatment depends on the type and stage of the underlying neoplasm. Often, treating the neoplasm improves the cutaneous disease. If the neoplasm is cured, skin signs abate.

While specific treatment of the skin improves the eruption, this usually is not curative.

Topical corticosteroids may improve scaly lesions.

Therapy with cholecalciferol also has been reported to be of benefit.

Consultations:

Consultation with an internal medicine specialist for malignancy workup is appropriate.

Consultation with a hematologist, oncologist, otolaryngologist and/or gastroenterologist also can assist with focused evaluations.

Medication
The goal of pharmacotherapy is to improve scaly lesions, reduce morbidity, and prevent complications.
Drug Category: Corticosteroids -- These agents have anti-inflammatory properties and cause profound and varied metabolic effects. In addition, these agents modify the body's immune response to diverse stimuli.

Drug Name	Betamethasone (Diprolene, Betatrex) -- For inflammatory dermatosis responsive to steroids. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing capillary permeability.
Adult Dose	Apply thin film bid/qid until response
Pediatric Dose	Administer as in adults with caution
Contraindications	Documented hypersensitivity; paronychia; cellulitis; impetigo; angular cheilitis; erythrasma; erysipelas; rosacea; perioral dermatitis; and acne
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Do not use in skin with decreased circulation; can cause atrophy of groin, face, and axillae; if infection develops and is not responsive to antibiotic treatment, discontinue until infection is under control; do not use monotherapy to treat widespread plaque psoriasis

Drug Category: Dietary Supplements -- For treatment of vitamin D deficiency or prophylaxis of vitamin D deficiency. Vitamin D and its analogs have profound effects on cellular proliferation and differentiation in addition to immunomodulatory effects. Calcipotriene, a vitamin D analog, is a well-accepted treatment for psoriasis, which is a condition that shares some similarities with AN. However, the reports of efficacy in the treatment of AN with vitamin D are anecdotal.

Drug Name	Cholecalciferol (Delta-D, Vitamin D-3) -- Stimulates absorption of calcium and phosphate from small intestine and promotes release of calcium from bone into blood. Antiproliferative and anti-inflammatory effects on skin.
Adult Dose	Delta-D: 400 IU PO qd Vitamin D-3: 1000 IU PO qd Calcitriol: 0.25-1 mcg PO qd
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; hypercalcemia; malabsorption syndrome
Interactions	Colestipol, mineral oil, and cholestyramine may decrease absorption of ergocalciferol from small intestine; thiazide diuretics may increase effects of vitamin D; may interfere with calcium channel blockers
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in impaired renal function, renal stones, heart disease, or arteriosclerosis

Acrokeratoelastoidosis

2007-11-29T20:32:00.001-08:00

Background: Acrokeratoelastoidosis (AKE) is a rare genodermatosis characterized by small, firm papules or plaques on the sides of the hands and feet. These nodules may result from an abnormality in the secretion or excretion of elastic material by fibroblasts in the dermis. AKE was first described in 1953 by Costa.

Both autosomal dominant and sporadic forms have been observed. AKE is not congenital; it slowly arises at puberty, or sometimes later, and then remains stable. Usually, no treatment is necessary. AKE is similar to 2 other diseases: keratoelastoidosis marginalis and focal acral hyperkeratosis. The clinical and histologic differences among these diseases allow their distinction.

Pathophysiology: The cause of AKE is not known. Autosomal dominant transmission is common, but the clinical expressions vary widely. AKE-like lesions on the palms of patients have recently been noted in association with systemic or localized scleroderma, possibly due to an altered pattern of connective tissue metabolism similar to that of systemic scleroderma. In 2003, Yoshinaga et al reported on a patient with AKE in association with localized scleroderma. In 2002, Tajima et al found a high rate of AKE in patients with systemic scleroderma (7 in 26 systemic sclerodermas). No other reports have confirmed these findings, and the relationship between these 2 diseases is not conclusive. A possible linkage to chromosome 2 has also been proposed (Greiner, 1983), but further studies are needed to confirm this hypothesis.

Frequency:

In the US: AKE is rare.

Internationally: The eruption is rare, and when the lesions are few, AKE often remains unnoticed.

Mortality/Morbidity: Once present, the eruption is stable, with no adverse effects.

Sex: Women appear to be affected more frequently than men.

Age: AKE is not congenital. It arises at puberty or sometimes later. Some cases have been described in the pediatric dermatologic literature (Hu, 2002).

Treatment
Medical Care:

Treatment is not indicated in most patients.

Mild keratolytics occasionally help, but recurrences are common.

Topical retinoids are not effective.

Acrokeratoelastoidosis

2007-11-29T20:32:00.000-08:00

Frequency:

In the US: AKE is rare.

Internationally: The eruption is rare, and when the lesions are few, AKE often remains unnoticed.

Mortality/Morbidity: Once present, the eruption is stable, with no adverse effects.

Sex: Women appear to be affected more frequently than men.

Age: AKE is not congenital. It arises at puberty or sometimes later. Some cases have been described in the pediatric dermatologic literature (Hu, 2002).

Treatment
Medical Care:

Treatment is not indicated in most patients.

Mild keratolytics occasionally help, but recurrences are common.

Topical retinoids are not effective.

Acrodynia

2007-11-29T20:30:00.000-08:00

Background: Now a rare disease, acrodynia (painful extremities) primarily affects young children. The symptoms of irritability, photophobia, pink discoloration of the hands and feet, and polyneuritis can be attributed to chronic exposure to mercury.

Pathophysiology: The most frequent sources of mercury prior to the legislated removal of the heavy metal from these preparations were calomel-containing anthelminthics, laxatives, diaper rinses, teething powders, fungicides in paint, repeated gamma-globulin injections, termite-protected wood (mercury bichloride), watch batteries (ie, via ingestion), mercurial antibacterial ointments, mercurial skin-lightening creams, and dental amalgam. This legislation corresponded to the virtual disappearance of acrodynia. Present-day cases reveal more novel exposure, such as mercuric oxide used to treat eyelid mites. Some have suggested the disease may represent a delayed allergic or hypersensitivity reaction because not all persons exposed to mercurial compounds develop the disease.

Because the metal can be stored in the body to some extent and intolerance may develop long after exposure, morbid symptoms may appear weeks or months after the drug administration (ie, exposure), with its cause escaping recognition. The deleterious effects of relatively small doses of mercury on the nervous system that are sometimes seen in the course of acrodynia add to the acrodynic reaction. In acrodynia, no reflex dilatation of the peripheral vessels occurs in response to heat. Vasoconstriction is abolished only when the nerve supply to the arterioles is interrupted.

Frequency:

In the US: Acrodynia was once widely prevalent; however, it is rare today, owing to the discontinued use of mercury in different preparations.

Internationally: Acrodynia was especially common in Australia. Epidemics of mercury poisoning have followed the release of mercury into the environment from industrial activity, with uptake of methyl mercury from eating fish from Minamata Bay, Japan, and uptake of both inorganic and methyl mercury following the release of mercury vapor and its subsequent deposition in waterways from gold recovery procedures in the Amazon basin. The ingestion of wheat and barley seed treated with an alkyl mercury fungicide for sowing, by a largely illiterate population in Iraq, led to a major outbreak of poisoning with a high fatality rate.

Mortality/Morbidity: Older children tend to have less morbidity. Death can result in 10% of cases.

Age: Acrodynia most often occurs in infants and young children. The age of onset is between 4 months and 8 years. Newborns and adults appear to be less susceptible to the disease.

Treatment
Medical Care: Removal of the inciting agent is the goal of treatment. Correcting fluid and electrolyte losses and rectifying any nutritional imbalances (vitamin-rich diets, vitamin-B complex) are of utmost importance in the treatment of the disease.

Recently, the chelating agent meso 2,3-dimercaptosuccinic acid has been shown to be the preferred treatment modality. It can almost completely prevent methylmercury uptake by erythrocytes and hepatocytes.

In the past, dimercaprol (British antilewisite; 2,3-dimer-capto-l-propanol) and D-penicillamine were the most popular treatment modalities. Disodium edetate (Versene) was also used.

Neither disodium edetate nor British antilewisite has proven reliable. British antilewisite has now been shown to increase CNS levels and exacerbate toxicity.

N-acetyl-penicillamine has been successfully given to patients with mercury-induced neuropathies and chronic toxicity, although it is not approved for such uses. It has a less favorable adverse effect profile than meso 2,3-dimercaptosuccinic acid.

Hemodialysis with and without the addition of L-cysteine as a chelating agent has been used in some patients experiencing acute renal failure from mercury toxicity.

Peritoneal dialysis and plasma exchange also may be of benefit.
Tolazoline (Priscoline) has been shown to offer symptomatic relief from sympathetic overactivity.
Antibiotics are necessary when massive hyperhidrosis, which may rapidly lead to miliaria rubra, is present. This can easily progress to bacterial secondary infection with a tendency for ulcerating pyoderma.

Medication
The goals of pharmacotherapy are to remove the causing agent, to reduce morbidity, and to prevent complications.
Drug Category: Chelating agents -- Succimer almost completely prevents methylmercury uptake by erythrocytes and hepatocytes.

Drug Name	Succimer (Chemet) -- Metal chelating agent, analog of dimercaprol, used in lead poisoning. Recommended treatment course is 19 d. Blood mercury levels should be monitored at least qwk after therapy to determine if a repeat course is indicated. A minimum of 2 wk between courses is recommended.
Adult Dose	10 mg/kg IV q8h for 5 d; then q12h for 2 wk
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Do not administer concomitantly with edetate calcium disodium or penicillamine
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in renal or hepatic impairment; to prevent toxicity, patient should be well hydrated; adverse effects include rash, GI symptoms (eg, nausea, vomiting, diarrhea, appetite loss, metallic taste in mouth), and increases in serum transaminases

Drug Category: Vasodilators -- Offer symptomatic relief from sympathetic overactivity.

Drug Name	Tolazoline (Priscoline) -- Alpha-adrenoliticum, vasodilatins peripherica. IV medication used only in hospital. Directly dilates blood vessels and is a competitive antagonist of alpha-receptors.
Adult Dose	3-5 mg IV q4h
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; renal failure, low blood pressure, or endocranial bleeding
Interactions	Do not coadminister with epinephrine because hypotensive effect may be potentiated from unopposed beta-adrenoceptor stimulation; may cause disulfiramlike reaction if given with ethanol
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Stimulates gastric acid secretion and should not be used in peptic ulcer disease; caution in mitral stenosis

Acrodermatitis Enteropathica

2007-11-29T20:27:00.000-08:00

Background: Acrodermatitis enteropathica (AE) is an autosomal recessive disorder characterized by periorificial and acral dermatitis, alopecia, and diarrhea.

Pathophysiology: The genetic mutation of SLC39A4 on 8q24.3 appears to be the cause.

AE can only be accurately diagnosed after attempts to remove zinc supplementation have failed. Therefore, patients with AE must remain on zinc supplementation for life. Differentiating AE from acquired zinc deficiencies can be difficult because both conditions present in the same manner. Some studies have shown that low zinc levels in the mother's milk may produce an acquired zinc deficiency in full-term, breastfed infants. Zimmerman et al has proposed that some acquired zinc deficiencies may be due to a defect in mammary zinc secretion. These studies tend to dispute the claim that human breast milk has a protective effect against zinc deficiency. Acquired zinc deficiency may also occur in premature infants, whether or not maternal zinc levels are low or normal, because of the infants' greater bodily demand or lower bodily stores of zinc.

Frequency:

In the US: The frequency is unknown.

Internationally: An estimated 1 in 500,000 people in Denmark are affected.

Mortality/Morbidity: AE is lethal, usually within the first few years of life, if left untreated. However, Graves et al reported an untreated adult survivor.

Race: No racial predilection exists.

Sex: No sexual preference exists.

Age: AE appears in the first few months after birth or after cessation of breastfeeding

Treatment
Medical Care: Treatment of AE involves greater than 1-2 mg/kg of oral zinc supplementation per day for life.

Diet: No special diet is necessary as long as zinc supplementation is continued.

Activity: No activity restrictions are necessary.

Medication
Zinc dietary supplementation of 1 mg/kg/d for life is essential. Secondary bacterial and/or candidal infections need to be addressed as necessary.
Drug Category: Mineral supplements -- These agents are used to reduce morbidity and to prevent complications.

Drug Name	Zinc gluconate (Verazinc, Zinca-Pak, Orazinc) -- Cofactor for more than 70 types of enzymes. Plays a role in many metabolic processes. One 10-mg tab contains 1.4 mg of elemental zinc.
Adult Dose	1 mg/kg/d PO for life
Pediatric Dose	0.5-1 mg elemental zinc/kg PO qd, divided 1-3 times/d
Contraindications	Documented hypersensitivity
Interactions	May reduce effect of penicillamine, tetracycline, and quinolones; concomitant administration of copper or iron with zinc may decrease their gastrointestinal absorption
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in renal impairment; very high dosages can result in sideroblastic anemia and microcytic anemia, secondary to zinc-induced copper deficiency (latter can be associated with neurologic defects

Acrodermatitis Chronica Atrophicans

2007-11-29T01:34:00.001-08:00

Background: Acrodermatitis chronica atrophicans (ACA) is the third or late stage of European Lyme borreliosis (LB). This unusual, progressive, fibrosing skin process is due to the effect of continuing active infection with Borrelia afzelii. Buchwald first delineated it in 1883; Herxheimer and Hartmann described it in 1902 as a tissue paper–like cutaneous atrophy. It is evident on the extremities, particularly on the extensor surfaces, beginning with an inflammatory stage with bluish red discoloration and cutaneous swelling and concluding several months or years later with an atrophic phase. Sclerotic skin plaques may also develop. Physicians should use serologic and histologic examination to confirm this diagnosis.

Pathophysiology: B afzelii is the predominant, but may not be the exclusive, etiologic agent of ACA. Another genospecies of the Borrelia burgdorferi sensu lato complex, Borrelia garinii, has also been detected.

ACA is the only form of LB in which no spontaneous remission occurs. Its pathophysiology is not yet fully understood. ACA appears to be associated with long-term persistence of Borrelia organisms in the skin; several nonspecific reactions together with a specific immune response may contribute to its manifestations.

The persistence of the spirochetes despite a marked cutaneous T-cell infiltration and high serum antibody titers may be connected with resistance of the pathogen to the complement system; the ability to escape to immunologically protected sites (eg, endothelial cells, fibroblasts); and the ability to change antigens, which may lead to an inappropriate immune response. Lack of protective antibodies, with a narrow antibody spectrum and a weak cellular response with down-regulation of major histocompatibility system class II molecules on Langerhans cells, has been observed in patients with LB.

A restricted pattern of cytokine expression in ACA, including the lack of interferon-gamma, may contribute to its chronicity. Cross-reactive antibody responses could take part in autoimmune damage, but whether autoimmune reactions play any role in the pathogenesis of the disease is unclear. The pathogenic mechanism of atrophic skin changes has also not been clarified. Perhaps periarticular regions are favorite sites because of reduced acral skin temperatures or reduced oxygen pressure.

Frequency:

In the US: The occurrence of ACA is connected with the ecology of LB, which varies in different geographical regions of the world.
Despite a high incidence of LB in the United States (varying from 95 cases per 100,000 population in Connecticut to 1250 cases per 100,000 population in Nantucket County, Massachusetts [1996 data]), ACA is not seen in the United States, except in a few European immigrants.

Internationally: The occurrence of ACA is connected with the ecology of LB, which varies in different geographical regions of the world.
Ixodes scapularis, Ixodes pacificus, and 4 other tick species distributed in North America transmit B burgdorferi sensu stricto, causing EM and LB arthritis.
Tick vectors of B afzelii, the main etiologic agent of ACA (and erythema migrans [EM]), are Ixodes ricinus, Ixodes hexagonus, and Ixodes persulcatus distributed in western and central Europe and in far eastern Europe and Asia. Almost all of these hard tick species may also transmit B garinii, a causative agent of EM and neurologic symptoms of LB.
In Europe, LB with all its dermatologic manifestations occurs in almost all countries, predominantly in the central part of the continent. The annual incidence per 100,000 population varies from 16 cases in France to 120 cases in northeastern Poland and Slovenia and to 130 cases in Austria (1995 data).
The frequency of ACA is about 1-10% of all European patients with LB, varying according to the region of the population sampled. Among the group of patients with skin manifestations of LB observed in Vienna, the ratio of the number of EM cases to ACA cases and to Borrelia lymphocytoma (BL) cases was 30:3:1. This ratio is 170:5:1 in the authors' as-yet-unpublished studies (provided in the group of patients with LB in northeastern Poland).
Because the clinical diagnosis of ACA is much more difficult than that of EM or BL, the condition is often underdiagnosed, and, in fact, the ratio of EM cases to ACA cases may be higher. The total number of cases could increase with increasing frequency of untreated European LB. ACA is probably the most common late and chronic manifestation of the borreliosis in European patients with Lyme disease.
A Bulgarian survey found that borrelial lymphocytoma and ACA were rare (0.3%) (Christova, 2004).

Mortality/Morbidity: The course of ACA is long-standing, lasting from a few to several years, and it leads to extensive flaccid atrophy of the skin and, in some patients, to the limitation of upper and lower limb joint mobility.

Chronic, difficult-to-treat ulcerations of atrophic skin may develop after minor trauma. Malignant degeneration has rarely been observed; one should not consider ACA to be a precancerous disorder.

The general status of patients with ACA remains good, though they may experience neurologic and/or rheumatologic signs and symptoms.

Race: ACA is not limited to any one nationality or race. It is much more frequent in whites than in other races, probably because of a far higher exposure to ticks transmitting B afzelii.

Sex: More than two thirds of patients with ACA are women. Among the authors' 19 patients, only 5 were men (Flisiak, 1999).

Age: The disease can occur in any age group, but it is most frequent in adults, usually in their 40s or 50s.

The youngest of the authors' patients was 26 years; the oldest was 73 years (Flisiak, 1999).

The mean age of the female group was 54.3 ± 12.8 years; the mean age of the male group was 46.2 ± 6.5 years.

ACA is rare in adolescents; however, it has been observed in children. A case in a 15-year-old girl was reported by Zalaudek et al in 2005.

Treatment
Medical Care: The choice of treatment depends on the coexistence of other signs or symptoms of LB with ACA. The authors also consider the value of the titer of serologic tests.

If the extracutaneous LB signs are absent and the level of specific antibodies is low, the authors usually recommend oral doxycycline or oral amoxicillin, over 3 weeks.

If organic or systemic physical or laboratory signs of LB are present or if the antibody titer is high, the appropriate treatment should be introduced mainly with ceftriaxone or cefotaxime or aqueous penicillin G given intravenously for 21-28 days.

Consultations: Seek the appropriate consultations (ie, neurologist, ophthalmologist, rheumatologist, cardiologist) if extracutaneous signs and symptoms exist.

Medication
The goals of pharmacotherapy are to eradicate the infection, to reduce morbidity, and to prevent complications.
Drug Category: Antibiotics -- Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of this clinical setting.

Drug Name	Amoxicillin (Amoxil, Trimox) -- Bactericidal against Borrelia species. Semisynthetic penicillin of aminopenicillins group demonstrating wide spectrum of bactericidal activity related to gram-positive and gram-negative bacteria. Mechanism of action involves bacterial cell wall synthesis inhibition.
Adult Dose	500 mg PO q6h or 1000 mg PO q12h for 21-28 d
Pediatric Dose	2-3 years: 40-60 mg/kg/d PO bid/tid >4 years: 375-750 mg/d PO tid
Contraindications	Documented hypersensitivity; infectious mononucleosis; lymphatic leukemia
Interactions	Neomycin decreases its absorption; allopurinol increases rash development; reduces efficacy of oral contraceptives
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in renal impairment; may cause dyspepsia or rash

Drug Name	Doxycycline (Vibramycin) -- Tetracycline antibiotic that inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. Used for antibacterial and anti-inflammatory effect and for concern about possible coexistent infection.
Adult Dose	100-200 mg PO qd for 21-28 d
Pediatric Dose	<8> >8 years: Administer as in adults
Contraindications	Documented hypersensitivity; severe hepatic dysfunction
Interactions	Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy
Pregnancy	D - Unsafe in pregnancy
Precautions	Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last one half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines

Drug Name	Ceftriaxone (Rocephin) -- Bactericidal against Borrelia species. Third-generation cephalosporin with broad-spectrum, gram-negative activity. Lower efficacy against gram-positive organisms and higher efficacy against resistant organisms. Arrests bacterial growth by binding to 1 or more penicillin-binding proteins.
Adult Dose	2 g IV q24h for 14-21 d 1-2 g IV/IM q12-24h
Pediatric Dose	50-100 mg/kg IV/IM; not to exceed 4 g/d
Contraindications	Documented hypersensitivity
Interactions	High doses of probenecid may increase clearance by blocking biliary secretion and displacement of ceftriaxone; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in renal impairment; caution in women who are breastfeeding and allergy to penicillin; caution in children who are hyperbilirubinemic because of its ability to displace bilirubin; adverse effects include headaches, dizziness, pseudomembranous colitis, nausea, vomiting, and diarrhea

Drug Name	Cefotaxime (Claforan) -- Third-generation of semisynthetic cephalosporin with board-spectrum bactericidal activity against gram-negative bacteria and Staphylococcus and Streptococcus species. Resistant to beta-lactamases. Mechanism of action is related to inhibition of bacteria cellular wall component synthesis.
Adult Dose	1-2 g IV q8h for 14-21d
Pediatric Dose	<12> >12 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Synergic with aminoglycosides, vancomycin, and anticoagulants; may cause false-positive Coombs reaction
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	May cause hypersensitivity reaction, headaches, dizziness, pseudomembranous colitis, nausea, and vomiting; neutropenia and biochemical signs of liver injury are seldom

Drug Name	Penicillin G (Pfizerpen) -- Beta-lactam antibiotic. The mechanism of action is related to bacterial cell wall synthesis inhibition in the growth phase as a result of penicillin and bacterial transpeptidase binding.
Adult Dose	4.5-6 million U IV q6h or 3-4 million U IV q4h (18-24 million U/d) for 21 d
Pediatric Dose	50,000-80,000 U/kg/d IV divided q6h
Contraindications	Documented hypersensitivity; caution in patients with bronchial asthma, renal insufficiency, or circulatory insufficiency; caution in those receiving potassium and diuretics
Interactions	Probenecid and NSAIDs increase blood concentration and extend time of action; penicillin benzathine demonstrates in vivo synergism with aminoglycoside antibiotics, but, in vitro, it causes their inactivation; not to be administered in the same syringe with vancomycin, cephalothin, amphotericin B, or metronidazole; antagonism toward tetracycline, chloramphenicol, and mucolytic drugs; high doses given with digoxin increase toxicity; combination with beta-adrenergic blocking drugs increases risk of anaphylaxis
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Not contraindicated in pregnancy but can lead to fetal hypersensitization, particularly in the second or third trimester; can induce anaphylactic shock, hypersensitivity reactions, arthralgia, fever, eosinophilia, lymphadenopathy, and kidney interstitial inflammation; high doses can lead to hemolytic anemia, leukopenia, and electrolytic disturbances; neurotoxicity; can induce Jarisch-Herxheimer reaction in patients with spirochetosis

Acrodermatitis Chronica Atrophicans

2007-11-29T01:34:00.000-08:00

Frequency:

In the US: The occurrence of ACA is connected with the ecology of LB, which varies in different geographical regions of the world.
Despite a high incidence of LB in the United States (varying from 95 cases per 100,000 population in Connecticut to 1250 cases per 100,000 population in Nantucket County, Massachusetts [1996 data]), ACA is not seen in the United States, except in a few European immigrants.

Internationally: The occurrence of ACA is connected with the ecology of LB, which varies in different geographical regions of the world.
Ixodes scapularis, Ixodes pacificus, and 4 other tick species distributed in North America transmit B burgdorferi sensu stricto, causing EM and LB arthritis.
Tick vectors of B afzelii, the main etiologic agent of ACA (and erythema migrans [EM]), are Ixodes ricinus, Ixodes hexagonus, and Ixodes persulcatus distributed in western and central Europe and in far eastern Europe and Asia. Almost all of these hard tick species may also transmit B garinii, a causative agent of EM and neurologic symptoms of LB.
In Europe, LB with all its dermatologic manifestations occurs in almost all countries, predominantly in the central part of the continent. The annual incidence per 100,000 population varies from 16 cases in France to 120 cases in northeastern Poland and Slovenia and to 130 cases in Austria (1995 data).
The frequency of ACA is about 1-10% of all European patients with LB, varying according to the region of the population sampled. Among the group of patients with skin manifestations of LB observed in Vienna, the ratio of the number of EM cases to ACA cases and to Borrelia lymphocytoma (BL) cases was 30:3:1. This ratio is 170:5:1 in the authors' as-yet-unpublished studies (provided in the group of patients with LB in northeastern Poland).
Because the clinical diagnosis of ACA is much more difficult than that of EM or BL, the condition is often underdiagnosed, and, in fact, the ratio of EM cases to ACA cases may be higher. The total number of cases could increase with increasing frequency of untreated European LB. ACA is probably the most common late and chronic manifestation of the borreliosis in European patients with Lyme disease.
A Bulgarian survey found that borrelial lymphocytoma and ACA were rare (0.3%) (Christova, 2004).

Chronic, difficult-to-treat ulcerations of atrophic skin may develop after minor trauma. Malignant degeneration has rarely been observed; one should not consider ACA to be a precancerous disorder.

The general status of patients with ACA remains good, though they may experience neurologic and/or rheumatologic signs and symptoms.

Race: ACA is not limited to any one nationality or race. It is much more frequent in whites than in other races, probably because of a far higher exposure to ticks transmitting B afzelii.

Sex: More than two thirds of patients with ACA are women. Among the authors' 19 patients, only 5 were men (Flisiak, 1999).

Age: The disease can occur in any age group, but it is most frequent in adults, usually in their 40s or 50s.

The youngest of the authors' patients was 26 years; the oldest was 73 years (Flisiak, 1999).

The mean age of the female group was 54.3 ± 12.8 years; the mean age of the male group was 46.2 ± 6.5 years.

ACA is rare in adolescents; however, it has been observed in children. A case in a 15-year-old girl was reported by Zalaudek et al in 2005.

Treatment
Medical Care: The choice of treatment depends on the coexistence of other signs or symptoms of LB with ACA. The authors also consider the value of the titer of serologic tests.

If the extracutaneous LB signs are absent and the level of specific antibodies is low, the authors usually recommend oral doxycycline or oral amoxicillin, over 3 weeks.

If organic or systemic physical or laboratory signs of LB are present or if the antibody titer is high, the appropriate treatment should be introduced mainly with ceftriaxone or cefotaxime or aqueous penicillin G given intravenously for 21-28 days.

Drug Name	Amoxicillin (Amoxil, Trimox) -- Bactericidal against Borrelia species. Semisynthetic penicillin of aminopenicillins group demonstrating wide spectrum of bactericidal activity related to gram-positive and gram-negative bacteria. Mechanism of action involves bacterial cell wall synthesis inhibition.
Adult Dose	500 mg PO q6h or 1000 mg PO q12h for 21-28 d
Pediatric Dose	2-3 years: 40-60 mg/kg/d PO bid/tid >4 years: 375-750 mg/d PO tid
Contraindications	Documented hypersensitivity; infectious mononucleosis; lymphatic leukemia
Interactions	Neomycin decreases its absorption; allopurinol increases rash development; reduces efficacy of oral contraceptives
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in renal impairment; may cause dyspepsia or rash

Drug Name	Doxycycline (Vibramycin) -- Tetracycline antibiotic that inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. Used for antibacterial and anti-inflammatory effect and for concern about possible coexistent infection.
Adult Dose	100-200 mg PO qd for 21-28 d
Pediatric Dose	<8> >8 years: Administer as in adults
Contraindications	Documented hypersensitivity; severe hepatic dysfunction
Interactions	Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy
Pregnancy	D - Unsafe in pregnancy
Precautions	Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last one half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines

Drug Name	Ceftriaxone (Rocephin) -- Bactericidal against Borrelia species. Third-generation cephalosporin with broad-spectrum, gram-negative activity. Lower efficacy against gram-positive organisms and higher efficacy against resistant organisms. Arrests bacterial growth by binding to 1 or more penicillin-binding proteins.
Adult Dose	2 g IV q24h for 14-21 d 1-2 g IV/IM q12-24h
Pediatric Dose	50-100 mg/kg IV/IM; not to exceed 4 g/d
Contraindications	Documented hypersensitivity
Interactions	High doses of probenecid may increase clearance by blocking biliary secretion and displacement of ceftriaxone; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in renal impairment; caution in women who are breastfeeding and allergy to penicillin; caution in children who are hyperbilirubinemic because of its ability to displace bilirubin; adverse effects include headaches, dizziness, pseudomembranous colitis, nausea, vomiting, and diarrhea

Drug Name	Cefotaxime (Claforan) -- Third-generation of semisynthetic cephalosporin with board-spectrum bactericidal activity against gram-negative bacteria and Staphylococcus and Streptococcus species. Resistant to beta-lactamases. Mechanism of action is related to inhibition of bacteria cellular wall component synthesis.
Adult Dose	1-2 g IV q8h for 14-21d
Pediatric Dose	<12> >12 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Synergic with aminoglycosides, vancomycin, and anticoagulants; may cause false-positive Coombs reaction
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	May cause hypersensitivity reaction, headaches, dizziness, pseudomembranous colitis, nausea, and vomiting; neutropenia and biochemical signs of liver injury are seldom

Drug Name	Penicillin G (Pfizerpen) -- Beta-lactam antibiotic. The mechanism of action is related to bacterial cell wall synthesis inhibition in the growth phase as a result of penicillin and bacterial transpeptidase binding.
Adult Dose	4.5-6 million U IV q6h or 3-4 million U IV q4h (18-24 million U/d) for 21 d
Pediatric Dose	50,000-80,000 U/kg/d IV divided q6h
Contraindications	Documented hypersensitivity; caution in patients with bronchial asthma, renal insufficiency, or circulatory insufficiency; caution in those receiving potassium and diuretics
Interactions	Probenecid and NSAIDs increase blood concentration and extend time of action; penicillin benzathine demonstrates in vivo synergism with aminoglycoside antibiotics, but, in vitro, it causes their inactivation; not to be administered in the same syringe with vancomycin, cephalothin, amphotericin B, or metronidazole; antagonism toward tetracycline, chloramphenicol, and mucolytic drugs; high doses given with digoxin increase toxicity; combination with beta-adrenergic blocking drugs increases risk of anaphylaxis
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Not contraindicated in pregnancy but can lead to fetal hypersensitization, particularly in the second or third trimester; can induce anaphylactic shock, hypersensitivity reactions, arthralgia, fever, eosinophilia, lymphadenopathy, and kidney interstitial inflammation; high doses can lead to hemolytic anemia, leukopenia, and electrolytic disturbances; neurotoxicity; can induce Jarisch-Herxheimer reaction in patients with spirochetosis

Acrochordon

2007-11-20T20:41:00.000-08:00

Background

An acrochordon is a small, soft, common, benign, usually pedunculated neoplasm that is found particularly in persons who are obese. It is usually skin colored or hyperpigmented, and it may appear as surface nodules or papillomas on healthy skin. Most acrochordons vary in size from 2-5 mm in diameter, although larger acrochordons up to 5 cm in diameter are sometimes evident. The most frequent localizations are the neck and the axillae, but any skin fold, including the groin, may be affected.

Birt-Hogg-Dube (BHD) syndrome is a rare autosomal dominant genodermatosis characterized by skin tumors, including multiple fibrofolliculomas, trichodiscomas, and acrochordons.¹ These patients tend to develop renal and colonic carcinomas. The defective gene in BHD syndrome has been identified and is suspected of being a tumor suppressor gene. Several mutations of the BHD gene have been reported. All skin lesions in the syndrome may actually represent fibrofolliculomas cut in various planes of section.

Pathophysiology

Previous theories have suggested that a localized paucity of elastic tissue may result in sessile or atrophic lesions. It is also thought that pendulous variations may be caused by losses of large confluent areas of elastin; however, a recent study of elastic tissue in fibroepithelial polyps (FEPs) showed no significant abnormalities.

Frequency

International

Acrochordons have been reported to have an incidence of 46% in the general population.

Mortality/Morbidity

Acrochordons are benign tumors. On rare occasions, histologic examination of a clinically diagnosed FEP reveals a basal or squamous cell carcinoma. In a recent study, 5 of 1335 clinically diagnosed FEP specimens were malignant. Four were basal cell carcinomas, and one was a squamous cell carcinoma in situ. None of these specimens was submitted by a dermatologist. This study concluded that clinically diagnosed FEPs have a low probability of having malignant characteristics on histologic examination.

Sex

An equal prevalence of acrochordons exists in males and females.

Age

When present, acrochordons increase in frequency up through the fifth decade. As many as 59% of persons may have acrochordons by the time they are aged 70 years.

Treatment

Surgical Care

Skin tags are generally treated for noncosmetic reasons.

Small, pedunculated acrochordons may be removed with curved or serrated blade scissors, while larger skin tags may simply require excision. For small acrochordons, application of aluminum chloride prior to removal will decrease the amount of minor bleeding.
Anesthesia prior to electrodesiccation is another option.
Other methods of removal include cryotherapy and ligation with a suture or a copper wire; however, freezing of the surrounding skin during liquid nitrogen cryotherapy may result in dyschromic lesions. Taking hold of the acrochordon with forceps and applying cryotherapy to the forceps may provide superior results.

Acquired Progressive Lymphangioma

2007-11-20T20:40:00.000-08:00

Background: Acquired progressive lymphangioma (APL) is an uncommon vascular tumor that is of importance primarily because it can be confused histologically with Kaposi sarcoma (KS) or angiosarcoma. Wilson-Jones first described the tumor as APL and later as benign lymphangioendothelioma.

Pathophysiology: APL has long been suspected of being a lymphatic proliferation. Recently, stains for lymphatic endothelium (ie, podoplanin [D2-40], LYVE-1, and PORX-1) have become available. They will make it possible to unequivocally identify and categorize APL, although no studies have been published to date.

APL is not associated with preexisting vascular malformations or lymphedema. Although the lesion rarely is identified during infancy, some suggest it is a hamartoma that first becomes apparent during adolescence or young adult life; the development of APL is possibly triggered by hormonal changes. In contrast to KS, APL should not trigger a workup for HIV infection.

Frequency:

In the US: APL is rare; fewer than 30 cases have been reported.

Mortality/Morbidity: APL is a benign process with no mortality and minimal morbidity.

Race: No racial predisposition is reported.

Sex: Males and females are affected equally.

Age: APL affects adolescents and young adults.

Treatment
Medical Care: No medical care is required.

Surgical Care:

Once the diagnosis is established, no treatment is necessary.

Solitary nodules can be excised; occasionally, local recurrence is observed.

If more extensive patches and plaques are cosmetically disturbing but too large to excise, they can be treated with a laser.

Because APL is relatively free of blood, the usual absorption characteristics that are importance in hemangiomas and vascular malformations are less important, and an individually tailored approach with test areas is recommended.

Consultations: Consultations with appropriate surgical specialists may be necessary, depending on the location of the APL.

Acquired Digital Fibrokeratoma

2007-11-20T20:38:00.001-08:00

Background

In 1968, Bart et al described 10 cases of an uncommon acquired growth that was located on the fingers. Although it clinically resembled a cutaneous horn or rudimentary supernumerary digit, it had distinct histopathological findings. The authors named this growth acquired digital fibrokeratoma (ADFK). Subsequently, Pinkus reported 28 more cases; however, because the lesions Pinkus described also occurred on the proximal hand, toes, soles, and one in the prepatellar region, he suggested the entity might be more appropriately called acquired acral fibrokeratoma.

Pathophysiology

Despite the fact that most patients deny a history of precedent trauma, the major hypothesis is that subclinical injury contributes to the development of these lesions.

Frequency

United States

Currently, no means of tracking nonmelanoma skin cancer, much less various benign dermatological conditions, is in place in the United States; therefore, the actual incidence of acquired acral fibrokeratoma is unknown. Most cases reported in the literature involve individual case reports presented because of the lesions' unusual size, location, histological features, or association with other conditions. Only a few reports describe a series of patients, with 129 patients being the most reported from any one institution. Therefore, whether this condition is rare or rarely reported remains unknown.

Mortality/Morbidity

ADFKs are benign stationary lesions that are more cosmetically bothersome than they are problematic. However, patients who have been reported to have giant acral digital fibromas on the dorsum or plantar surface of the foot may report some discomfort.

Race

ADFKs have been reported in persons of all races.

Sex

ADFKs seem to have a slight male predominance; however, too few cases have been described to adequately assess the significance of any sexual predilection.

Age

The patients reported with ADFKs range in age from 12-70 years, with most cases occurring in middle-aged adults. Clinically similar lesions that occur in young children are more likely to represent rudimentary supernumerary digits.

Treatment

Surgical Care

Simple excision is curative, recurrence is rare.

Acneiform Eruptions

2007-11-20T20:33:00.000-08:00

Background

Acneiform eruptions may consist of comedones, papulopustules, cysts, or nodules that resemble acne vulgaris. Occasionally, this may lead to their initial misdiagnoses. Acnelike disorders occur from a wide variety of diseases, including infections, growth anomalies, and drug reactions. Those entities included in this discussion are nevus comedonicus, eruptive hair cysts, tuberous sclerosis, amineptine acne, steroid acne, chloracne, acneiform drug eruptions, gram-negative folliculitis, eosinophilic pustular folliculitis, Pityrosporum folliculitis, coccidioidomycosis, secondary syphilis, sporotrichosis, rosacea, and perioral dermatitis.

Treatment

History

Patients with acneiform diseases present with acnelike lesions such as papulonodules, pustules, comedones, and cysts. The physical locations, which commonly include the face, trunk, and extremities, usually vary between the diseases. For example, steroid acne and the various folliculitis disorders usually manifest more prominently on the trunk and extremities, whereas perioral dermatitis and rosacea locate to the face. The evolution of the lesions may provide additional clues to the etiology. The infectious disorders can form ulcerated and crusted nodules. Systemic signs and symptoms may also narrow the differential diagnosis; for example, certain drug eruptions are associated with febrile illness and peripheral blood leukocytosis. Occupational and medication exposures, including over-the-counter and herbal remedies, should be recorded.

Physical

Nevus comedonicus (NC) is an infrequent developmental anomaly manifesting as aggregated open comedones. It consists of dilated follicular or eccrine orifices plugged with keratin. Also known as comedone nevus and nevus acneiformis unilateralis, it may be solitary, congenital, or occur later in life as a result of occupational exposure. The differential diagnosis of NC includes familial dyskeratotic comedones and linear comedone formations usually linked with acne vulgaris or chronically sun-damaged skin (Favre-Racouchot disease). Infrequently, multiple comedones in other unusual contexts may raise NC as a possible consideration. Treatment of NC is generally surgical, through excision or carbon dioxide laser ablation of the involved skin. Medical therapy with topical retinoids may be of some benefit. For more information.

The eruptive vellus hair cysts manifest as flesh-colored papules found usually on the face, chest, neck, thighs, groin, buttocks, and axillae. They represent an anomaly of the vellus hair follicles and may be hereditary. Histopathology reveals a mid dermal epithelial cyst containing vellus hairs and keratinous material. These cysts may undergo spontaneous regression, form a connection to the epidermis, or undergo degradation with a resultant foreign body granulomatous formation. Treatment is often difficult. Incision and drainage of individual lesions carries the risk of subsequent scarring, and modalities such as carbon dioxide laser ablation are difficult to use over large surface areas. Topical retinoids and 12% lactic acid preparations have proven useful in some instances. For more information.

Steroid acne is observed as monomorphous papulopustules located predominantly on the trunk and extremities, with less involvement of the face. Characteristically, it appears after the administration of topical or systemic corticosteroids, including intravenous and inhaled therapy. The eruption usually resolves after discontinuation of the steroid and, in addition, may respond to the usual treatments of acne vulgaris. For more information.

Exposure to halogenated aromatic hydrocarbon compounds, such as chlorinated dioxins and dibenzofuranes, by inhalation, ingestion, or direct contact of contaminated compounds or foods induces a cutaneous eruption of polymorphous comedones and cysts referred to as chloracne. Other associated skin findings may include xerosis and pigmentary changes. Internal changes involving the ophthalmic, nervous, and hepatic systems may also occur, and some chloracnegens can be oncogenic. Treatment is difficult because chloracne may persist for years, even without further exposure. Chemicals that contain iodides, bromides, and other halogens can also induce an acneiform eruption similar to that of steroid acne; however, the iodide-induced eruption may be more extreme.

Antibiotics may induce an acute generalized pustular eruption. Penicillins and macrolides are the greatest offenders. Patients usually are febrile with leukocytosis, and the eruption does not usually involve comedones. Other implicated antibiotics include co-trimoxazole, doxycycline, ofloxacin, and chloramphenicol. Other types of medications can also produce an acnelike eruption, including corticotropin, nystatin, isoniazid, itraconazole, hydroxychloroquine, naproxen, mercury, amineptine, the antipsychotics olanzapine and lithium, and chemotherapy drugs. For more information.

Various infections may also display an acneiform pattern. Gram-negative folliculitis, a persistent papulopustular eruption, may be a complication in patients on prolonged antibiotic treatment for acne vulgaris or rosacea. It is more common in male patients. Culture of the papulopustules grows gram-negative bacilli and gram-negative rods, including Escherichia coli and Klebsiella, Enterobacter, and Proteus species. Treatment consists of the appropriate antibiotic coverage for the causative organism. Isotretinoin may sometimes be an effective alternative or adjunctive treatment.

Pityrosporum folliculitis is another infectious folliculitis that is presumably caused by a host reaction to the yeast Malassezia furfur, previously named Pityrosporum ovale, a normal human skin commensal. It appears primarily on the trunk and upper extremities of late adolescents and young adults. Unlike acne vulgaris, it is pruritic, does not contain comedones, and responds to appropriate antifungal therapy rather than antibiotics. The yeast and hyphae can be observed in biopsy specimens in the widened follicular ostia along with keratinous material, and occasionally, rupture of the follicular wall may occur. Treatment typically involves topical or systemic antifungal therapy.

Eosinophilic pustular folliculitis (EPF) is another disease of unknown etiology that usually manifests as a recurrent pruritic papulopustular eruption on the face, trunk, and extremities. Histopathology reveals a predominantly perifollicular infiltration of eosinophils with some mononuclear cells and subcorneal pustules composed of eosinophils. EPF has been described in infants and in immunocompromised patients with HIV, and the classic immunocompetent type is known as Ofuji disease (first described by Ofuji in the adult Japanese population). Patients may also demonstrate blood eosinophilia and leukocytosis. Treatment modalities and results vary greatly. Options include topical and systemic corticosteroids, oral antibiotics, indomethacin, dapsone, isotretinoin, and pulsed ultraviolet phototherapy (PUVA).

Other infectious diseases may also induce an acnelike pattern.

In secondary syphilis, papulopustules and nodules, some crusted, may occur on the face, trunk, and extremities. The causative agent, the spirochete Treponema pallidum, may be easily observed in biopsy specimens with the Warthin-Starry stain. In addition, serologic tests and the presence of spirochetes on darkfield microscopy may reveal the diagnosis.

Mycotic infections may also manifest cutaneously with papules and nodules that may ulcerate and crust.

Sporothrix schenckii, the responsible agent of sporotrichosis, commonly induces a lymphocutaneous reaction, but it can also produce a persistent fixed localized cutaneous papulonodular eruption that may involve the face. The organism can be demonstrated histologically, by peripheral blood smear, and by fungal culture.
Cutaneous coccidioidomycosis usually caused by inhalation and dissemination of Coccidioides immitis, may rarely occur by primary inoculation and appear as papulopustules, nodules, or plaques that can eventually ulcerate and crust.

Rosacea appears similarly to acne vulgaris with papulopustules on the face, but in addition, patients may also have facial flushing and telangiectases.

- Rosacea is more common in the white population and in women in the third and fourth decades of life. Men, however, are more commonly affected by sebaceous and connective tissue hyperplasia of the nose (rhinophyma), a complication of chronic rosacea. Associated eye findings are variable but include blepharitis, conjunctivitis, iritis, iridocyclitis, hypopyon iritis, and even keratitis.

- Although biopsies are not usually performed, histopathology may reveal lymphohistiocytic perivascular and perifollicular inflammation, ectatic vascular channels, elastosis, and hypertrophy of the connective tissue and sebaceous follicles. Treatment primarily includes sunscreens and topical antibiotics such as metronidazole, retinoids, and oral tetracyclines

Perioral dermatitis, also a disorder of unknown etiology, is mainly observed in the young, white, female population as papulopustules with erythematous bases. The eruption is predominantly perioral in location, characteristically sparing the vermilion border of the lip, but it may also include the perinasal and periorbital areas. Biopsies are rarely performed but would show some changes similar to rosacea. The etiology is unknown, as in rosacea, and suggested causative agents include Demodex, topical or inhaled corticosteroids, moisturizers, fluorinated compounds, and contact irritants or allergens. Therapy typical includes cessation of halogenated topical steroids and initiation of topical antibiotic therapies such as metronidazole. Proper use of a spacer or inhalation device may help when the dermatitis occurs with inhaled steroids.

Treatment

Medical Care

Treatment varies with the particular disease suspected and consists of a wide range of methods, including excision, laser ablation, topical/oral antibiotics, topical/oral retinoids, and drug withdrawal. Please review individual topics in physical for greater detail.

Acne Vulgaris

2007-11-20T20:30:00.000-08:00

Background

Acne vulgaris is a common skin disease that affects 85-100% of people at some time during their lives. It is characterized by noninflammatory follicular papules or comedones and by inflammatory papules, pustules, and nodules in its more severe forms. Acne vulgaris affects the areas of skin with the densest population of sebaceous follicles; these areas include the face, the upper part of the chest, and the back.

Pathophysiology

The pathogenesis of acne vulgaris is multifactorial. Four key factors are responsible for the development of an acne lesion. These factors are follicular epidermal hyperproliferation with subsequent plugging of the follicle, excess sebum, the presence and activity of Propionibacterium acnes, and inflammation.

Follicular epidermal hyperproliferation is the first recognized event in the development of acne. The exact underlying cause of this hyperproliferation is not known. Currently, the 3 leading hypotheses have been proposed to explain why the follicular epithelium is hyperproliferative in individuals with acne.

First, androgen hormones have been implicated as the initial trigger. Comedones, the clinical lesion that results from follicular plugging, begin to appear around adrenarche in persons with acne. Furthermore, the degree of comedonal acne in prepubertal girls correlates with circulating levels of the adrenal androgen dehydroepiandrosterone sulfate (DHEA-S). Additionally, androgen hormone receptors are present in the portion of the follicle where the comedone forms; individuals with malfunctioning androgen receptors do not develop acne.

Second, changes in lipid composition have been implicated in the development of acne vulgaris. Persons with acne frequently have excess sebum production and oily skin. This excess sebum may dilute the normal epidermal lipids and result in a change in the relative concentrations of the various lipids. Diminished concentrations of linoleic acid have been demonstrated in individuals with acne and, interestingly, these levels normalize after successful treatment with isotretinoin. This relative decrease in linoleic acid may be what initiates comedone formation.

Inflammation is the third hypothesized factor incriminated in comedone formation. Interleukin (IL)–1–alpha is a proinflammatory cytokine. It has been used in a tissue model to induce follicular epidermal hyperproliferation and comedone formation. Although inflammation is not apparent microscopically or clinically in early lesions of acne, it may still play a pivotal role in the development of acne vulgaris and the comedones.

Excess sebum is another key factor in the development of acne vulgaris. Sebum production and excretion are regulated by a number of different hormones and mediators. Androgen hormones, in particular, promote sebum production and release. Still, most men and women with acne have normal circulating levels of androgen hormones. An end-organ hyperresponsiveness to androgen hormones has been hypothesized. Androgen hormones are not the only regulators of the human sebaceous gland. Numerous other agents, including growth hormone and insulinlike growth factor, also regulate the sebaceous gland and may contribute to the development of acne.

P acnes is a microaerophilic organism present in many acne lesions. Although, it has not been shown to be present in the earliest lesions of acne, the microcomedo, its presence in later lesions is almost certain. The presence of P acnes promotes inflammation through a variety of mechanisms. P acnes stimulates inflammation by producing proinflammatory mediators that diffuse through the follicle wall. Recent studies have shown that P acnes activates the toll-like receptor 2 on monocytes and neutrophils. Activation of the toll-like receptor 2 then leads to the production of multiple proinflammatory cytokines, including IL-12, IL-8, and tumor necrosis factor. Hypersensitivity to P acnes may also explain why some individuals develop inflammatory acne vulgaris while others do not.

Inflammation may be a primary phenomenon or a secondary phenomenon. Most of the evidence to date suggests a secondary inflammatory response to P acnes as mentioned above. However, IL-1-alpha expression has been identified in the microcomedone, and it may play a role in the development of acne.

Frequency

United States

Acne vulgaris affects 85-100% of people at some time during their lives.

Mortality/Morbidity

Acne can cause physical pain and psychosocial suffering.

Acne can lead to scarring.

A severe inflammatory variant of acne, acne fulminans, can be associated with fever, arthritis, and other systemic symptoms.

Race

The prevalence of acne in North Americans of African ancestry and whites is similar.

Sex

Acne vulgaris is more common in males than in females during adolescence.

It is more common in women than in men during adulthood.

Age

Acne vulgaris may be present in the first few weeks and months of life when a newborn is still under the influence of maternal hormones and when the androgen-producing portion of the adrenal gland is disproportionately large. This neonatal acne resolves spontaneously.

Adolescent acne usually begins prior to the onset of puberty, when the adrenal gland begins to produce and release more androgen hormone.

Acne is not limited to adolescence. Twelve percent of women and 5% of men at age 25 years have acne. By age 45 years, 5% of both men and women still have acne.

Treatment

Background

Pathophysiology

Frequency

United States

Acne vulgaris affects 85-100% of people at some time during their lives.

Mortality/Morbidity

Acne can cause physical pain and psychosocial suffering.

Acne can lead to scarring.

A severe inflammatory variant of acne, acne fulminans, can be associated with fever, arthritis, and other systemic symptoms.

Race

The prevalence of acne in North Americans of African ancestry and whites is similar.

Sex

Acne vulgaris is more common in males than in females during adolescence.

It is more common in women than in men during adulthood.

Age

Acne vulgaris may be present in the first few weeks and months of life when a newborn is still under the influence of maternal hormones and when the androgen-producing portion of the adrenal gland is disproportionately large. This neonatal acne resolves spontaneously.

Adolescent acne usually begins prior to the onset of puberty, when the adrenal gland begins to produce and release more androgen hormone.

Acne is not limited to adolescence. Twelve percent of women and 5% of men at age 25 years have acne. By age 45 years, 5% of both men and women still have acne.

Medication

The goal of pharmacotherapy is to reduce morbidity and to prevent complications.

Drug Category: Retinoids

These agents decrease the cohesiveness of abnormal hyperproliferative keratinocytes, and they may reduce the potential for malignant degeneration. They also modulate keratinocyte differentiation.

Drug Name	Isotretinoin (Accutane)
Description	Most effective oral medication. Oral agent that treats serious dermatologic conditions. Isotretinoin is synthetic 13-cis isomer of naturally occurring tretinoin (trans-retinoic acid). Both agents are structurally related to vitamin A. Decreases sebaceous gland size and sebum production. May inhibit sebaceous gland differentiation and abnormal keratinization. Effective March 1, 2006 the FDA requires that prescribers of isotretinoin, patients who take isotretinoin, and pharmacists who dispense isotretinoin all must register with the iPLEDGE system. Female patients must sign an informed consent that they will use contraceptives during the treatment course and for 30 d after discontinuing therapy.
Adult Dose	Total cumulative dose of 120-150 mg/kg recommended; starting dose should be <0.5>
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Toxicity may occur with vitamin A coadministration; pseudotumor cerebri or papilledema may occur when coadministered with tetracyclines; may reduce plasma levels of carbamazepine
Pregnancy	X - Contraindicated in pregnancy
Precautions	Obtain 2 negative pregnancy test results in patients of childbearing potential prior to initiating therapy; pregnancy must be avoided during and for 1 mo after treatment, and monthly pregnancy test results must be documented; hyperlipidemia may develop; pseudotumor cerebri, vision impairment, headaches, myalgias, arthralgias, and depression have been reported; dry skin and cheilitis are nearly universal adverse effects

Drug Name	Tretinoin (Retin-A, Retin-A Micro, Avita)
Description	Inhibits microcomedo formation. Normalizes follicular epidermal differentiation and exhibits anti-inflammatory properties. Available as 0.025%, 0.05%, and 0.1% creams. Also available as 0.01% and 0.025% gels.
Adult Dose	Begin with lowest tretinoin formulation and increase as tolerated; apply hs or qod; lower the frequency of application if irritation develops
Pediatric Dose	<12 years: Not established >12 years: Apply as in adults
Contraindications	Documented hypersensitivity
Interactions	Coadministration with benzoyl peroxide may lessen effectiveness
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Photosensitivity may occur with excessive sunlight exposure; erythema and peeling may occur (most prominent within first few wk of treatment)

Drug Name	Adapalene (Differin)
Description	A naphthoic acid derivative that binds the retinoic acid receptor. Normalizes follicular epidermal differentiation and exhibits anti-inflammatory properties. Available in cream, gel, solution, and pledget formulations.
Adult Dose	Apply a small amount to involved skin qd
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Erythema and peeling may occur in some individuals; avoid contact with mucous membranes, eyes, mouth, and nostrils; avoid exposure to sunlight and sunlamps; dryness of skin, scaling, erythema, burning, and pruritus may occur

Drug Name	Tazarotene (Tazorac, AVAGE)
Description	Retinoid prodrug whose active metabolite modulates differentiation and proliferation of epithelial tissue; may also have anti-inflammatory and immunomodulatory properties. Available in 0.05% and 0.1% cream and gel formulations.
Adult Dose	Apply sparingly to affected area qd
Pediatric Dose	Children: Not established Adolescents: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Do not use concomitantly with dermatologic drugs or cosmetics that have a strong drying effect on the skin (eg, salicylic acid, benzoyl peroxide, astringents)
Pregnancy	X - Contraindicated in pregnancy
Precautions	Erythema and peeling may occur at application site

Drug Category: Antibiotics

Topical and systemic antibiotics used in the treatment of acne vulgaris are directed at P acnes. They also have anti-inflammatory properties.

Drug Name	Minocycline (Dynacin, Minocin)
Description	Treats infections caused by susceptible gram-negative and gram-positive organisms, in addition to infections caused by susceptible chlamydial, rickettsial, and mycoplasmal organisms. Available in 50-, 75-, and 100-mg preparations.
Adult Dose	50-100 mg PO bid
Pediatric Dose	<8 years: Not recommended >8 years: 4 mg/kg PO initially, followed with 2 mg/kg q12h
Contraindications	Documented hypersensitivity; severe hepatic dysfunction
Interactions	Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy; tetracyclines can increase hypoprothrombinemic effects of anticoagulants
Pregnancy	D - Unsafe in pregnancy
Precautions	Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last one half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines; hepatitis or lupuslike syndromes may occur

Drug Name	Doxycycline (Bio-Tab, Doryx, Vibramycin)
Description	Antibacterial agent effective against gram-positive and gram-negative organisms. Available in 20-, 50-, and 100-mg preparations.
Adult Dose	100 mg PO bid
Pediatric Dose	<8 years: Not recommended >8 years: 2-5 mg/kg/d PO/IV in 1-2 divided doses; not to exceed 200 mg/d
Contraindications	Documented hypersensitivity; severe hepatic dysfunction
Interactions	Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy
Pregnancy	D - Unsafe in pregnancy
Precautions	Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last one half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines

Drug Name	Tetracycline (Sumycin)
Description	Antibacterial agent effective against gram-positive and gram-negative organisms.
Adult Dose	250-500 mg PO q6h Mild-to-moderate infections: 500 mg PO bid or 250 mg PO qid for 7-14 d
Pediatric Dose	<8 years: Not recommended >8 years: 25-50 mg/kg/d (10-20 mg/lb) PO divided qid
Contraindications	Documented hypersensitivity
Interactions	Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy; tetracyclines can increase hypoprothrombinemic effects of anticoagulants
Pregnancy	D - Unsafe in pregnancy
Precautions	Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last one half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines

Drug Name	Trimethoprim/sulfamethoxazole (Bactrim, Bactrim DS, Septra, Septra DS)
Description	Antibiotic with activity against many gram-positive and gram-negative organisms. Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. Available as 80 mg trimethoprim and 400 mg sulfamethoxazole or as 160 mg trimethoprim and 800 mg sulfamethoxazole (double strength).
Adult Dose	160 mg TMP/800 mg SMZ PO q12h
Pediatric Dose	8 mg/kg/d TMP/40 mg/kg/d SMZ PO/IV divided q12h
Contraindications	Documented hypersensitivity; megaloblastic anemia due to folate deficiency
Interactions	May increase PT when used with warfarin (perform coagulation tests and adjust dose accordingly); coadministration with dapsone may increase blood levels of both drugs; coadministration of diuretics increases incidence of thrombocytopenia purpura in elderly persons; phenytoin levels may increase with coadministration; may potentiate effects of methotrexate in bone marrow depression; hypoglycemic response to sulfonylureas may increase with coadministration; may increase levels of zidovudine
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	For adults, adjust dosage accordingly: CrCl (mL/min) 80-50, IV dose q18h recommended; CrCl 50-10, IV dose qd recommended; CrCl <10, not recommended; HD, 4-5 mg/kg after HD; and during peritoneal dialysis, 0.16-0.8 g q48h Discontinue at first appearance of skin rash or sign of adverse reaction; obtain CBC counts frequently; discontinue therapy if significant hematologic changes occur; goiter, diuresis, and hypoglycemia may occur with sulfonamides; prolonged IV infusions or high doses may cause bone marrow depression (if signs occur, give 5-15 mg/d leucovorin); caution in folate deficiency (eg, persons with chronic alcoholism, elderly persons, those receiving anticonvulsant therapy, those with malabsorption syndrome); hemolysis may occur in individuals with G-6-PD deficiency; in patients with AIDS, TMP-SMZ may not be tolerated or cause a response; caution in renal or hepatic impairment (perform urinalyses and renal function tests during therapy); give fluids to prevent crystalluria and stone formation

Acne Keloidalis Nuchae

2007-11-20T20:28:00.001-08:00

Background: Acne keloidalis nuchae (AKN) refers to the occurrence of keloidlike papules and plaques on the occipital scalp and the posterior part of the neck, almost exclusively in African American men. Initially, patients usually develop a chronic folliculitis and perifolliculitis of the occipital part of the scalp and the posterior part of the neck, which heal with keloidlike lesions, sometimes with discharging sinuses. They often coalesce to form one or several large plaques, which gradually enlarge for years. The lesions are often painful and cosmetically disfiguring.

Kaposi first described acne keloidalis in 1869 as dermatitis papillaris capillitii. The disease had previously been known in Hebra's clinic and is described and pictured in Hebra's atlas under the name sycosis framboesiformis. Three years after Kaposi's publication, Bazin named the condition acne keloidalis. Since then, the disease has appeared in the literature under a variety of names.

Little can be added clinically to Adamson's description of AKN in 1914. The eruption occurs on the upper posterior neck in the form of a raised transverse band at the lower margin of the hairy scalp. The band is usually dusky red in color, smooth and firm to the touch, and of keloidal consistency. It is hairless except at its upper margin, which is abrupt, broken into nodules and fringed with hair in tufts, like aigrettes, or the bunches of bristles in a brush. There may be pustules or crusted nodules here and there along the upper border. The lower margin slopes gradually to the normal skin. Usually there are no comedones or follicular pustules of acne when the patient comes under observation, and there may or may not be a history of acne of the face in youth. Often the patient complains of itching at the site of the eruption.

Pathophysiology: The exact cause of AKN is still speculative. Injury produced by short haircuts (especially when the posterior hairline is shaved with a razor, a practice common in African American men) and curved hair follicles (analogous to pseudofolliculitis of the beard in African Americans) may be the precipitating factors. Other frequently suggested etiologic possibilities are constant irritation from shirt collars, chronic low-grade bacterial infections, and an autoimmune process (AKN usually responds to systemic steroid therapy). The use of antiepileptic drugs and an increased number of mast cells in the occipital region have also been indicated as causes.

The recent findings of Sperling et al indicate that AKN is a primary form of scarring alopecia. Many of the histologic findings closely resemble those found in certain other forms of scarring alopecia. They claim that overgrowth of microorganisms does not play an important role in the pathogenesis of AKN. They also found no association between pseudofolliculitis barbae and AKN.

Herzberg et al provided another explanation based on extensive transverse microscopy, histochemistry, and electron microscopy. Herzberg et al described the following hypothetical sequence of inflammatory events that take place in AKN:

The acute inflammation, whether it begins in the sebaceous gland or elsewhere in the region of the deep infundibular or isthmus levels, is a cause or the result of a weakened follicular wall at these levels. This enables the release of hair shafts into the surrounding dermis. The "foreign" hairs incite further acute and chronic granulomatous inflammation. The localized granulomatous inflammation manifests itself clinically as a papular lesion. Fibroblasts lay down collagen and scars form in the region of the inflammation. Distortion and occlusion of the follicular lumen by fibrosis leads to hair retention in the inferior follicle and further smoldering granulomatous inflammation and scarring. The scarring and granulomatous inflammation manifest themselves clinically as keloidlike scars and plaques.

They also found that the follicular lymphocytic infiltrate contained a mixed B- and T-cell population and that the plasma cell immunoglobulins are of a polyclonal nature.

Frequency:

In the US: AKN is said to represent 0.45% of all dermatoses affecting black persons.

Mortality/Morbidity: AKN is a medically benign but often psychologically devastating dermatosis. Squamous cell carcinoma has developed secondary to radiation therapy in rare cases. Chronic pruritus, scarring, and drainage may occur. Without therapy, the lesions may continue to enlarge and sometimes coalesce, and new ones may appear. Scarring alopecia of the involved scalp is a common finding.

Race: AKN most often occurs in African Americans. Hispanics are the next most common group, followed by Asians and (least often) whites.

Sex: Although the early literature inferred that AKN occurred only in males, it is now known to occur in females. The male-to-female ratio is approximately 20:1.

Age: Onset usually occurs in early adulthood, but some cases do develop during adolescence. Onset prior to puberty or after age 50 years is extremely rare.

Treatment
Medical Care: After a thorough history, obtain a specimen for bacterial culture and sensitivity. A biopsy should be performed if the presentation is not typical.

The first line of defense against AKN is prevention (as with many other cutaneous disorders). People who have this problem should not get the occipital part of their hairline edged with a razor or wear tight fitting shirts or other clothing that will cause mechanical irritation of the posterior part of their hairline. Initiating therapy quickly lowers the patient's chances of developing large lesions.

Twice-a-day treatment with a combined retinoic acid (Retin-A) and a class 2 or 3 corticosteroid cream or gel may be sufficient to relieve all symptomatology and flatten the existing lesions. This mixture seems to be somewhat more effective than class 1 or 2 steroids alone.

When pustules, crust formation, or drainage is present, use topical clindamycin on a twice-daily basis until the pustules abate and the inflammation subsides. If the patient does not have significant improvement in 4-5 days, take a bacterial culture of the involved area, and start the appropriate systemic antibiotic. In the rare cases where large abscesses or draining sinuses are present, give patients a 7- to 10-day course of prednisone after starting appropriate systemic antibiotics.

Intralesional steroid injections (10-40 mg/mL) are another method of therapy. Injections are easier if the papules are electrodesiccated and curetted first. Application of a lidocaine-prilocaine cream mixture under plastic film occlusion 2 hours prior to injection decreases the pain of injections. Warn patients that the area injected might become hypopigmented, which may remain for 6-12 months.

Laser therapy (carbon dioxide or Nd:YAG) has been successful for some patients. Postoperative intralesional triamcinolone injections (10 mg/mL q2-3wk) help prevent recurrence. Cryotherapy has also proven to be successful in some cases. The area is frozen for 20 seconds, allowed to thaw and is then frozen again a minute later. The morbidity (discomfort and drainage) is greater than other modalities, and the treated site often becomes hypopigmented and may remain so for 12-18 months (when the thaw time is >25 seconds, melanocytes are destroyed and the treated area often becomes hypopigmented, especially in patients with dark skin).

Once healing has taken place, apply a tretinoin-fluorinated steroid mixture to the occipital part of the scalp twice daily to help prevent recurrence.

Surgical Care:

Removing each papule with a hair transplant punch is the next therapeutic option if combined retinoic acid/corticosteroid treatment is not successful. The punch should extend deep (past the deepest level of the hair follicle) into the subcutaneous tissue, as superficial removal seems to have a much higher incidence of recurrence. After removal, inject the wound edges with a bolus of Kenalog 40 mg, and, then, it should be closed with 4-0 sutures. Or, use an equal amount of 2% lidocaine with epinephrine and triamcinolone acetonide at 40 mg/mL to anesthetize the surgical site.

The preferred method of removal for larger linear lesions (1 cm or less in diameter) is a horizontal ellipse for excision with primary closure. The base of the excision should extend below the hair follicles. Close the postoperative site with 4-0 silk sutures.

Postoperative care is the same as with punch grafts.
The postoperative site often splays to the diameter of the initial excision. Always remember when closing primarily not to close when the posterior part of the neck is flexed or patients will spend a week or more having to look upward. Under this amount of tension, the resultant scar splays and will be the same size as the amount of area removed, often creating an area of alopecia as large as the initial defect.

For large lesions that cannot be excised and closed primarily, the area of AKN is excised to the fascia or to the deep subcutaneous tissue and left to heal secondarily.

Prior to performing surgery, tell both the patient and the caregiver providing the postoperative care (clean postoperative site twice a day with alcohol or sodium chloride solution, and apply an antibiotic ointment) that the postoperative site will be cosmetically unacceptable initially, and the patient will experience pain and discomfort for the first few days.
Complete wound healing takes 8-12 weeks. Give patients explicit verbal and written postoperative care instructions.
If possible, show patients and postoperative caregivers a set of photographs showing the before; immediate postoperative, 1-week postoperative, and monthly postoperative healing progression; and final healing.
Initiate a broad-spectrum antibiotic (eg, erythromycin) on the day of surgery and continue for 10 days because sterilizing the scalp is impossible.
Tie off or coagulate all bleeders after excision. Then, apply pressure to the postoperative site for 10 minutes, and check for bleeding again. If most of the oozing has stopped, apply an antibiotic ointment to minimize bacterial colonization, and place a nonadherent dressing (eg, Telfa, Vaseline gauze, adaptic) over the defect. Wrap gauze over the dressing to help secure it and absorb the exudate. Use paper tape to secure the gauze.
Pain medication may be necessary for the first 48 hours.
Have patients return in 24-36 hours (preferably with the person responsible for changing dressings) for removal of the initial dressing. Soak the area with sodium chloride solution not only to facilitate the removal of the dressing but also to clean the postoperative site.
Instruct patients to start cleaning the site twice a day (following the regimen above) once the dressing is removed.
Instruct patients to return for follow-up visits in 1 and 3 weeks or sooner if any complications occur. Visits thereafter are necessary only on an as-needed basis.
Instruct patients to return for follow-up care for possible initiation of topical steroid/retinoic acid therapy once the area has healed, usually in 2-3 months.
A follicular papule or pustule occasionally develops along the border of the linear scar. Treat all inflammatory lesions with topical clindamycin until the infection subsides and then remove the lesions with the hair transplant punch method.

Excision with grafting is not as cosmetically acceptable because it results in a large depressed non–hair-bearing area.
Optimal healing with second intention healing is achieved when the excision is a horizontal ellipse of the posterior part of the scalp, including the posterior part of the hairline, and extends to the level of the muscle fascia or the deep subcutaneous tissue.

Healed second intention scars are almost imperceptible, especially when the occipital region of hair is allowed to grow long.

Do not give corticosteroid injections prior to complete wound closure because they prevent wound contraction.

Medication
The goals of pharmacotherapy are to reduce morbidity and to prevent complications.
Drug Category: Corticosteroids -- These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli. Class 2 or 3 topical steroid creams or gels (eg, Elocon cream, topical cream or gel, Lidex cream or gel) may be mixed with equal parts of retinoic acid; this should be applied bid.

Drug Name	Triamcinolone acetonide (Kenalog, Amcort) -- For inflammatory reactions responsive to steroids; decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing capillary permeability.
Adult Dose	10-40 mg/mL injected in postoperative sites q2-3wk for 4wk
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; fungal, viral, and bacterial skin infections
Interactions	Coadministration with barbiturates, phenytoin, and rifampin decreases effects
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Multiple complications (eg, severe infections, hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression) may occur; abrupt discontinuation of glucocorticoids may cause adrenal crisis

Drug Name	Prednisone (Deltasone, Meticorten, Orasone) -- May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Used when patient has acute flare.
Adult Dose	40-80 mg PO every morning
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; viral, fungal, tubercular skin, or connective tissue infections; peptic ulcer disease; hepatic dysfunction; GI disease
Interactions	Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use

Drug Name	Clobetasol propionate (Olux foam) or Mometasone (Elocon) -- May depress formation, release, and activity of endogenous chemical mediators of inflammation. Available as 0.025%, 0.05%, and 0.1% cream (Elocon) and as a 0.05% foam (Olux).
Adult Dose	Mix with equal parts of retinoic acid and apply bid sparingly to affected areas; do not use occlusive dressing
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; fungal, viral, or tubercular skin lesions; herpes simplex or herpes zoster
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Use over large or denuded areas of the body for prolonged periods of time with an occlusive dressing or on infants may produce adverse systemic effects

Drug Name	Fluocinonide (Lidex, Fluonex) -- High-potency topical corticosteroid that inhibits cell proliferation; has immunosuppressive and anti-inflammatory properties.
Adult Dose	Mix with equal parts of retinoic acid and apply bid sparingly to affected areas; do not use occlusive dressing
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; herpes simplex infection; fungal, viral, or tubercular skin lesions
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	May cause adverse systemic effects if used over large areas, denuded areas, on occlusive dressings, or during prolonged treatment periods

Drug Category: Retinoids -- These agents decrease the cohesiveness of abnormal hyperproliferative keratinocytes, and they may reduce the potential for malignant degeneration. They modulate keratinocyte differentiation. They have been shown to reduce the risk of skin cancer formation in patients who underwent renal transplantation.

Drug Name	Tretinoin (Retin-A) -- Inhibits microcomedo formation and eliminates existing lesions. Makes keratinocytes in sebaceous follicles less adherent and easier to remove. Available as 0.025%, 0.05%, and 0.1% creams. Also available as 0.01% and 0.025% gels.
Adult Dose	Mix with equal parts of a class 2 or 3 corticosteroid cream or gel and apply bid
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Toxicity increases with coadministration of benzoyl peroxide, salicylic acid, and resorcinol; avoid topical sulfur, resorcinol, salicylic acid, other keratolytics, abrasives, astringents, spices, and lime
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Photosensitivity may occur with excessive sunlight exposure; caution in eczema; do not apply to mucous membranes, mouth, and angles of nose

Drug Category: Antibiotics -- Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of this clinical setting.

Drug Name	Erythromycin (E-Mycin, Erythrocin) -- Inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest. For treatment of staphylococcal and streptococcal infections. Age, weight, and severity of infection determine proper dosage in children. When bid dosing is desired, half-total daily dose may be taken q12h. Double the dose for more severe infections.
Adult Dose	250 mg PO qid taken for 10 d postoperatively to prevent infection
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; hepatic impairment
Interactions	Coadministration may increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; coadministration with lovastatin and simvastatin increases risk of rhabdomyolysis
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in liver disease; estolate formulation may cause cholestatic jaundice; GI adverse effects are common (give doses pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occur

Drug Name	Mupirocin (Bactroban) -- Topical antibiotic; inhibits bacterial growth by inhibiting RNA and protein synthesis.
Adult Dose	Apply topically bid
Pediatric Dose	Apply as in adults
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Prolonged use may result in the growth of nonsusceptible organisms

Acne Fulminans

2007-11-20T20:25:00.000-08:00

Background

Acne fulminans (AF), also known as acne maligna, was originally described as acute febrile ulcerative acne conglobata (AC). In 1958, at a meeting of the Detroit Dermatological Society, Burns and Colville presented a 16-year-old white boy with acute febrile disease and AC. Many similar cases have been reported since then. The primary features of this disease include sudden onset, severe and often ulcerating acne, fever, polyarthritis, and failure to respond to antibacterial therapy; the response to debridement in combination with steroid therapy is good. It can be the dermatologic manifestation of the synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome. AF is a syndrome of fulminant, necrotizing acne associated with bone lesions, constitutional symptoms, and laboratory abnormalities.

Pathophysiology

AF is an uncommon, immunologically induced, systemic disease in which the triggering antigen is believed to be from Propionibacterium acnes. Some authors note that elevated blood levels of testosterone may play an important role in the pathogenesis of AF. High levels of testosterone and anabolic steroids cause an increase in sebum excretion and in the population density of P acnes. The increase in the amount of P acnes or related antigens may trigger the immunologic reaction in some individuals and lead to an occurrence of AF. In addition to testosterone, isotretinoin may also precipitate AF, possibly related to highly increased levels of P acnes antigens in the patient's immune system.

Another theory postulates that AF may be an autoimmune complex disease because circulating immune complexes have been demonstrated in some patients with AF. Immunologically, the reaction is a type III or IV hypersensitivity reaction.

Genetic factors may play an important role in some patients; 3 sets of identical twins who developed an identical pattern of AF have been documented.

Acne may be the only clinical sign of androgen excess in men, and one report is available about a boy with AF and androgen excess due to late-onset congenital adrenal hyperplasia.

Frequency

United States

AF is a rare disease. Over the past several years, fewer cases of this disease have occurred, possibly because of earlier and better treatment of acne.

Age

The disease predominantly affects young males with a history of acne.

Treatment

Medical Care

The recommended treatment for AF is a combination of oral steroids and isotretinoin.

Oral steroids should be started and gradually reduced over 6 weeks to avoid adverse effects of a prolonged course of systemic steroids.
Isotretinoin should be started at 4 weeks, initially at 0.25 mg/kg daily and gradually increased to achieve complete clearance. Isotretinoin with a minimum total dose of 120 mg/kg is recommended. Relapses are rare. If required, a repeat course of isotretinoin (150 mg/kg) may be used.
Some authors suggest treating patients with spontaneous development of AF with oral steroids and supplemental intralesional therapy.
The response to broad-spectrum antibiotic treatment is poor. Oral antibiotics are responsible for a slow response in the resolution of acne and systemic symptoms. The combination of oral isotretinoin and systemic steroids is better than the combination of oral isotretinoin and antibiotics.
Infliximab, a recently developed monoclonal antibody against tumor necrosis factor-alpha, also may be a treatment option for patients with AF that is unresponsive to conventional therapies.

Medication

Begin treatment with oral prednisone 1 mg/kg/d and taper over 6 weeks. By the fourth week, initiate isotretinoin at 0.25 mg/kg/d. If isotretinoin cannot be used, dapsone may be substituted for the retinoid, beginning at 50 mg/d and increasing to 100-150 mg/d.

Drug Category: Corticosteroids

These agents have profound and varied metabolic effects. They possess anti-inflammatory and immunosuppressive properties.

Drug Name	Prednisone (Delta-Cortef, Econopred)
Description	Synthetic adrenocortical steroid with predominantly glucocorticoid properties. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reducing capillary permeability. Stabilizes lysosomal membranes and suppresses lymphocyte and antibody production.
Adult Dose	0.5-1 mg/kg/d PO for 6 wk; taper as condition improves Single morning dose is safer for long-term use, but divided doses have greater anti-inflammatory effects
Pediatric Dose	0.14-2 mg/kg/d initial PO divided tid/qid (4-60 mg/m²/d)
Contraindications	Documented hypersensitivity; viral, fungal, connective tissue, and tubercular skin infections; peptic ulcer disease; hepatic dysfunction; GI tract disease
Interactions	Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Abrupt discontinuation may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur

Drug Category: Retinoids

Vitamin A derivatives have many roles. They encourage cellular differentiation, are antiproliferative, and serve as immunomodulators.

Drug Name	Isotretinoin (Accutane)
Description	Oral agent that treats serious dermatologic conditions. Isotretinoin is the synthetic 13-cis isomer of the naturally occurring tretinoin (trans-retinoic acid). Both agents are structurally related to beta-carotene. Decreases sebaceous gland size and sebum production. May inhibit sebaceous gland differentiation and abnormal keratinization. Effective March 1, 2006 the FDA requires that prescribers of isotretinoin, patients who take isotretinoin, and pharmacists who dispense isotretinoin all must register with the iPLEDGE system.
Adult Dose	Initial: 0.25 mg/kg/d PO; increase gradually (usually 1 mg/kg/d) for 20 wk or a total dose of 120-150 mg/kg
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Toxicity may occur with beta carotene coadministration; pseudotumor cerebri or papilledema may occur when coadministered with tetracyclines; may reduce plasma levels of carbamazepine
Pregnancy	X - Contraindicated in pregnancy
Precautions	May decrease night vision; inflammatory bowel disease may occur; may be associated with development of hepatitis; occasionally exaggerated healing response of acne lesions (ie, excessive granulation with crusting) may occur; patients with diabetes may experience problems controlling blood glucose levels while on isotretinoin; avoid exposure to UV light or sunlight until tolerance is achieved; discontinue if rectal bleeding, abdominal pain, or severe diarrhea occurs; mood swings or depression may occur; caution in history of depression.

Drug Name	Tretinoin (Avita, Retin-A, Retin-A Micro)
Description	Structurally related to vitamin A. May be helpful for recalcitrant disease, but recurrence is common. Long-term, low-dose therapy may be suitable for selected patients. May cause skin irritation in some patients. Also, has been linked to promotion of angiogenesis; however, has not demonstrated increased telangiectasias. Also inhibits microcomedo formation and eliminates lesions. Makes keratinocytes in sebaceous follicles less adherent and easier to remove. Available as 0.025%, 0.05%, and 0.1% creams. Available also as 0.01% and 0.025% gels.
Adult Dose	Begin with lowest concentration of tretinoin formulation and increase as tolerated; apply hs or qod; lower frequency of application if irritation develops
Pediatric Dose	<12 years: Not established >12 years: Apply as in adults
Contraindications	Documented hypersensitivity
Interactions	Toxicity may occur with vitamin A coadministration; toxicity increased when coadministered with sulfur, benzoyl peroxide, resorcinol, or any product with strong drying effects; phototoxicity increased when coadministered with tetracyclines, fluoroquinolones, or thiazides
Pregnancy	C - Safety for use during pregnancy has not been established
Precautions	Photosensitivity may occur with excessive sunlight exposure; burning, stinging, peeling, pruritus, or erythema has been reported at site of application; caution with eczema (may cause severe irritation); avoid contact with mucous membranes, mouth, and angles of nose

Drug Category: Sulfone antibiotics

These agents may inhibit bacterial growth by preventing the formation of folic acid.

Drug Name	Dapsone (Avlosulfon)
Description	Bactericidal and bacteriostatic against Mycobacteria species; mechanism of action is similar to that of sulfonamides in which competitive antagonists of PABA prevent formation of folic acid, inhibiting bacterial growth. Anti-inflammatory mechanism of action may involve suppression of neutrophil function by inhibition of the halide-myeloperoxidase system. Excretion is primarily in urine; half-life is 28 h.
Adult Dose	50-150 mg PO qd
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; G-6-PD deficiency
Interactions	May inhibit anti-inflammatory effects of clofazimine; hematologic reactions may increase with folic acid antagonists (eg, pyrimethamine); monitor for agranulocytosis during second and third mo of therapy; probenecid increases toxicity; trimethoprim with dapsone may increase toxicity of both drugs; because of increase in renal clearance, levels may decrease significantly when administered concurrently with rifampin; avoid use with zalcitabine because of increased risk of peripheral neuropathy (additive effects)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Perform weekly blood counts (first mo), then WBC counts monthly (6 mo), then semiannually; discontinue if significant reduction in platelets, leukocytes, or hematopoiesis occurs; caution in patients with methemoglobin reductase deficiency, G-6-PD deficiency (patients receiving >200 mg/d), or hemoglobin M because of high risk for hemolysis and Heinz body formation; caution in patients exposed to other agents or conditions (eg, infection, diabetic ketosis) capable of producing hemolysis; peripheral neuropathy can occur (rare); phototoxicity may occur when exposed to UV light

Acne Conglobata

2007-11-20T20:24:00.000-08:00

Background

Acne conglobata (AC) is an uncommon and unusually severe form of acne characterized by burrowing and interconnecting abscesses and irregular scars (both keloidal and atrophic), often producing pronounced disfigurement. The comedones often occur in a group of 2 or 3, and cysts contain foul-smelling seropurulent material that returns after drainage. The nodules are usually found on the chest, the shoulders, the back, the buttocks, the upper arms, the thighs, and the face. AC may develop as a result of a sudden deterioration of existing active papular or pustular acne, or it may occur as the recrudescence of acne that has been quiescent for many years.

Pyoderma gangrenosum, AC, and aseptic arthritis are clinically distinct inflammatory disorders. Although this triad of symptoms rarely occurs in an individual patient, it was reported in a 3-generation kindred with autosomal dominant transmission of the 3 disorders; this condition is called familial pyoderma gangrenosum, AC, and aseptic arthritis (PAPA) syndrome.

Pathophysiology

The primary causes of AC remain unknown. Chromosomal defects in the XXY karyotype may be responsible for severe forms of AC. In contrast, the XXY karyotype of Klinefelter syndrome is believed to exclude severe acne; however, 1 patient with the unusual combination of Klinefelter syndrome and AC has been reported.

The association of this disease with specific human leukocyte antigen (HLA) phenotypes has not been proven. The HLA-A and HLA-B phenotypes were evaluated in 65 patients with AC, in whom antigen frequencies were found to be normal. Other patients with AC and hidradenitis suppurativa were studied; 4 of 6 patients had HLA-B7 cross-reacting antigens (ie, HLA-B7, HLA-Bw22, HLA-B27, HLA-Bw40, HLA-Bw42), and all had HLA-DRw4.

PAPA syndrome has been mapped to a locus on the long arm of chromosome 15 (maximum 2-point logarithm of odds score 5.83; recombination fraction [straight theta] 0 at locus D15S206).¹ Assuming complete penetrance, haplotype analysis of recombination events defined an interval of 10 centimorgans between loci D15S1023 and D15S979. This finding suggests that these clinically distinct disorders may share a genetic etiology.

Frequency

International

AC is an uncommon disease.

Mortality/Morbidity

AC can produce pronounced disfigurement. Severe scarring produces psychological impairment; individuals with AC are often ostracized, or they may feel excluded. AC has also been responsible for anxiety and depression in many patients.

Sex

The disease affects males more frequently than females.

Age

The onset of AC usually occurs in young adults aged 18-30 years, but infants may develop this condition as well.

Treatment

Medical Care

The therapy of choice for AC is isotretinoin 0.5-1 mg/kg for 4-6 months.

Simultaneous use of systemic steroids, such as prednisone 1 mg/kg/d for 2-4 weeks, may also prove beneficial, particularly if systemic symptoms are evident.
Alternatives include oral tetracycline 2 g/d or erythromycin 2 g/d, either alone or with isotretinoin or prednisone.
For treatment-resistant cases, dapsone 50-150 mg/d is recommended; this treatment should be carefully monitored.
Along with vigorous medical therapy, emotional support is essential.
Treatment of AC with infliximab has been tried; the authors do not recommend this therapy.

Surgical Care

Large hemorrhagic nodules may be aspirated.
Intralesional triamcinolone or cryotherapy may also be valuable.
Occasionally, surgical excision of interconnecting large nodules may be beneficial.

Medication

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Corticosteroids

Have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.

Drug Name	Prednisolone (Delta-Cortef, Econopred, Articulose-50)
Description	Synthetic adrenocortical steroid with predominantly glucocorticoid properties. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reducing capillary permeability. Stabilizes lysosomal membranes and also suppresses lymphocyte and antibody production.
Adult Dose	0.5-1 mg/kg/d PO for 6 wk; taper as condition improves Single morning dose is safer for long-term use, but divided doses have more anti-inflammatory effect
Pediatric Dose	Initial: 0.14-2 mg/kg/d PO divided tid/qid (4-60 mg/m²/d)
Contraindications	Documented hypersensitivity; viral, fungal, connective tissue, or tubercular infection; peptic ulcer disease; hepatic dysfunction; GI tract disease
Interactions	Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Abrupt discontinuation may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur

Drug Category: Retinoids

Vitamin A derivatives have many roles. They encourage cellular differentiation, they are antiproliferative, and they serve as immunomodulators.

Drug Name	Isotretinoin (Accutane)
Description	Oral agent that treats serious dermatologic conditions. Isotretinoin is the synthetic 13-cis isomer of the naturally occurring tretinoin (trans-retinoic acid). Both agents are structurally related to beta-carotene. Decreases sebaceous gland size and sebum production. May inhibit sebaceous gland differentiation and abnormal keratinization. Effective March 1, 2006, FDA requires that prescribers of isotretinoin, patients who take isotretinoin, and pharmacists who dispense isotretinoin all must register with the iPLEDGE system.
Adult Dose	Initial: 0.5 mg/kg/d PO, increase gradually (usually 1 mg/kg/d) for 20 wk
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Toxicity may occur with beta carotene coadministration; pseudotumor cerebri or papilledema may occur when coadministered with tetracyclines; may reduce plasma levels of carbamazepine
Pregnancy	X - Contraindicated in pregnancy
Precautions	May decrease night vision; inflammatory bowel disease may occur; may be associated with development of hepatitis; exaggerated healing response of acne lesions (ie, excessive granulation with crusting) may occur; patients with diabetes may experience problems in controlling blood glucose levels while on isotretinoin; avoid exposure to UV light or sunlight until tolerance is achieved; discontinue if rectal bleeding, abdominal pain, or severe diarrhea occurs; mood swings or depression may occur; caution in history of depression

Drug Name	Tretinoin (Avita, Retin-A, Retin-A Micro)
Description	Structurally related to vitamin A. May be helpful for recalcitrant disease, but recurrence is common. Long-term, low-dose therapy may be suitable for selected patients. May cause skin irritation in some patients. Also, has been linked to promotion of angiogenesis; however, has not demonstrated increased telangiectasias. Also inhibits microcomedo formation and eliminates lesions. Makes keratinocytes in sebaceous follicles less adherent and easier to remove. Available as 0.025%, 0.05%, and 0.1% creams. Available also as 0.01% and 0.025% gels.
Adult Dose	Begin with lowest concentration of tretinoin formulation and increase as tolerated; apply hs or qod; lower frequency of application if irritation develops
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Toxicity may occur with vitamin A coadministration; toxicity increased when coadministered with sulfur, benzoyl peroxide, resorcinol, or any product with strong drying effects; phototoxicity increased when coadministered with tetracyclines, fluoroquinolones, or thiazides
Pregnancy	C - Safety for use during pregnancy has not been established
Precautions	Photosensitivity may occur with excessive sunlight exposure; burning, stinging, peeling, pruritus, or erythema has been reported at site of application; caution with eczema (may cause severe irritation); avoid contact with mucous membranes, mouth, and angles of nose

Drug Category: Antibiotics

Therapy must be comprehensive and cover all likely pathogens in the context of the clinical setting. Antibiotic selection should be guided by blood culture sensitivity whenever feasible.

Drug Name	Roxithromycin (Rulid, Oxoid)
Description	Not available in the United States. Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, thereby arresting RNA-dependent protein synthesis.
Adult Dose	150-300 mg PO bid for 4-6 wk, continue if response is favorable
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; coadministration with pimozide
Interactions	Toxicity increases with coadministration of fluconazole and pimozide; plasma levels of certain benzodiazepines may increase, prolonging CNS depression; arrhythmias and increase in QTc intervals occur with disopyramide; coadministration with omeprazole may increase plasma levels of both agents
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in liver disease; GI tract adverse effects are common (administer doses pc); discontinue if nausea, vomiting, malaise, abdominal colic, or fever occur

Drug Name	Clarithromycin (Biaxin)
Description	6-methoxy erythromycin. Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, thereby arresting RNA-dependent protein synthesis.
Adult Dose	250-500 mg PO bid for 4-6 wk, continue if response is favorable
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; coadministration with pimozide
Interactions	Toxicity increases with coadministration of fluconazole and pimozide; effects decrease and GI tract adverse effects may increase with coadministration of rifabutin or rifampin; may increase toxicity of anticoagulants, cyclosporine, tacrolimus, digoxin, omeprazole, carbamazepine, ergot alkaloids, triazolam, and HMG-CoA reductase inhibitors; plasma levels of certain benzodiazepines may increase, prolonging CNS depression; arrhythmias and increase in QTc intervals occur with disopyramide; coadministration with omeprazole may increase plasma levels of both agents
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Coadministration with ranitidine or bismuth citrate is not recommended with CrCl <25>

Acanthosis Nigricans

2007-11-20T20:22:00.001-08:00

Background: Although Addison may have seen a case of acanthosis nigricans (AN) before 1885 and misdiagnosed it as Addison disease, the first documented case of AN was in 1889. By 1909, this dermatosis had been described in approximately 50 patients and was suspected to be associated with internal malignancy. In 1976, Kahn et al published their landmark study in which the association between AN and insulin resistance was first described.

Pathophysiology: AN most likely is caused by factors that stimulate epidermal keratinocyte and dermal fibroblast proliferation. In the benign form of AN, the factor is probably insulin or an insulinlike growth factor that incites the epidermal cell propagation. In malignant AN, the stimulating factor is hypothesized to be a substance secreted either by the tumor or in response to the tumor. Transforming growth factor-alpha is structurally similar to epidermal growth factor and is a likely candidate. Exogenous medications also have been implicated as etiologic factors.

Frequency:

In the US: The exact incidence of AN is unknown. In an unselected population of 1412 children, the changes of AN were present in 7.1%. Obesity is closely associated with AN, and more than one half of the adults who weigh greater than 200% of their ideal body weight have lesions consistent with AN. The malignant form of AN is far less common, and, in one study, only 2 of 12,000 patients with cancer had signs of AN.

Mortality/Morbidity: AN is divided into 2 broad categories, benign and malignant.

Patients with the benign form of AN experience very few, if any, complications of their skin lesions. However, many of these patients have an underlying insulin-resistant state that is the cause of their AN. The severity of the insulin resistance is highly variable and ranges from an incidental finding on routine blood studies to overt diabetes mellitus. The severity of skin findings may parallel the degree of insulin resistance, and a partial resolution may occur with treatment of the insulin-resistant state. Insulin resistance is the most common association of AN in the younger age population.

Malignant AN is associated with significant complications because the underlying malignancy is often an aggressive tumor. Average survival time of patients with signs of malignant AN is 2 years, although cases in which patients have survived for up to 12 years have been reported. In older patients with new onset AN, most have an associated internal malignancy.

Race: AN is much more common in people with darker skin pigmentation. The prevalence in whites is less than 1%. In Hispanics, the prevalence is 5.5%, and, in African Americans, the prevalence is the highest at 13.3%. The incidence is also increased in the Native American population. In contrast to the benign form, there is no racial propensity with malignant AN.

Sex: The incidence of AN is equal for men and women.

Age: Lesions of benign AN may be present at any age, including at birth, although it is found more commonly in the adult population. Malignant AN occurs more frequently in elderly persons; however, cases have been reported in children with Wilms tumor.

Treatment
Medical Care:

The goal of therapy is to correct the underlying disease process. Treatment of the lesions of AN is for cosmetic reasons only. Correction of hyperinsulinemia often reduces the burden of hyperkeratotic lesions. Likewise, weight reduction in obesity-associated AN may result in resolution of the dermatosis.

No treatment of choice exists for AN. Topical medications that have been effective in some cases include keratolytics (eg, topical tretinoin). Oral agents that have shown some benefit include etretinate, isotretinoin, metformin, and dietary fish oils. Cyproheptadine has been used in cases of malignant AN because it may inhibit the release of tumor products. Dermabrasion and long-pulsed alexandrite laser therapy may also be used to reduce the bulk of the lesion.

Medication
The goal of pharmacotherapy is to improve cosmetic appearance.
Drug Category: Topical retinoids -- These agents promote shedding of hyperkeratotic skin. They are modifiers of keratinocyte adhesion, differentiation, and proliferation.

Drug Name	Tretinoin (Avita, Retin-A) -- Promotes detachment of cornified cells and enhances shedding of corneocytes. Inhibits microcomedo formation and eliminates lesions that are present. Makes keratinocytes in sebaceous follicles less adherent and easier to remove. Available as 0.025%, 0.05%, and 0.1% creams. Available also as 0.01% and 0.025% gels.
Adult Dose	Begin with lowest tretinoin formulation and increase as tolerated; apply hs or qod; lower frequency of application if irritation develops
Pediatric Dose	<12> >12 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Toxicity increases with coadministration of benzoyl peroxide, salicylic acid, and resorcinol; avoid topical sulfur, resorcinol, salicylic acid, other keratolytics, abrasives, astringents, spices, and lime
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Photosensitivity may occur with excessive sunlight exposure; caution in eczema; avoid mucous membranes, mouth, and angles of nose