Acanthosis nigricans is a commonly encountered skin dermatosis that can be seen in various clinical scenarios. It is overwhelmingly associated with obesity but can occur secondary to medications, endocrine disorders such as the HAIR-AN syndrome (hyperandrogenism, insulin resistance, and acanthosis nigricans), diabetes, and internal malignancies. This last type is clinically distinctive and manifests in a unique manner.
Clinical Findings: Classic cases of acanthosis nigricans affect the nape of the neck, the axillae, and the groin regions. Native Americans and African Americans are at a significantly increased risk for development of acanthosis nigricans. The slow, insidious onset of patches and plaques with a velvety, hyperpigmented, thickened, rough surface is characteristic of acanthosis nigricans. Maceration with a malodorous smell is often noted. The patients are for the most part asymptomatic, although some complain of intermittent pruritus. The clinical findings in association with obesity are enough to make the diagnosis. A thorough history should be taken to rule out a medication-induced form of acanthosis nigricans. The only routine laboratory testing performed is screening for occult diabetes. Patients with obesity are at higher risk for diabetes later in life, and lifelong follow-up and screening by their primary care physician is required.
Many medications have been shown to induce acanthosis nigricans. They include niacinamide, glucocorticoids, insulin, and some birth control pills. The medication most commonly associated with acanthosis nigricans is niacinamide. Most cases resolve or improve greatly with discontinuation of the medication. The appearance is often identical to that of classic acanthosis nigricans, but the history is suggestive, with the timing of rash onset related to the introduction of the causative medication.
Malignancy-associated acanthosis nigricans is often widespread and involves unique areas, including the mucous membranes, palms, and soles. This form has a rapid onset and affects different areas of the body than the classic form of acanthosis nigricans does. The palms and soles are often involved, and the face can be involved. Any case in which there is rapid onset of acanthosis nigricans in a widespread distribution, often in a nonobese individual, warrants proper evaluation to rule out an internal malignancy. Referral to a gastroenterologist and an internist for cancer screening is of utmost importance.
A few endocrine disorders can be associated with acanthosis nigricans, most frequently diabetes mellitus and the HAIR-AN syndrome It is associated with insulin resistance and also with hyperandrogenism.
Rare causes of acanthosis nigricans include the familial forms, which are inherited in an autosomal dominant fashion.
Pathogenesis: The skin thickening and clinical findings are possibly caused by an increase in insulin-like growth factor receptor, fibroblast growth factor receptor, and epidermal growth factor receptor and their subsequent effects on the skin. The reason it affects certain regions preferentially is unknown. Malignancyassociated acanthosis nigricans is believed to be caused by some cytokine or growth factor directly secreted by the tumor, possibly in the fibroblast growth factor receptor class of molecules. The tumor causes the clinical findings by secreting these substances. Acanthosis nigricans is believed to be a paraneoplastic process in these cases. Medication-induced acanthosis nigricans is poorly understood but is possibly related to the medication’s local effects on the skin in genetically predisposed individuals.
Histology: Epidermal hyperplasia, acanthosis, and papillomatosis are present. There is minimal to no inflammatory infiltrate, and the dermis is essentially normal in appearance. Extensive hyperkeratosis with a mild excess of melanin production likely explains the hyperpigmentation seen in acanthosis nigricans.
Treatment: Treatment is often difficult unless the afflicted individual makes a conscious effort to get to an ideal body weight and to get his or her diabetes under excellent control. This is the only likely scenario in which the skin findings of acanthosis nigricans will resolve. Temporizing methods of therapy include the use of keratolytic agents such as lactic acid to help thin the plaques and make them less noticeable. These agents are difficult to use in the axillae because of stinging. The topical use of tretinoin cream has also been successful. Destructive laser therapies have been used with varying success.
Treatment of malignancy-associated acanthosis nigricans is directed at the underlying malignancy. Removal of the tumor ay result in complete resolution of the skin disease.