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.
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.
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 |
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