Acanthosis nigricans (AN) is a localized skin disorder manifesting with hyperpigmented, velvety plaques typically located in flexural and intertriginous regions. The precise pathogenesis is unknown but is speculated to involve the stimulation of insulin-like growth factor receptors and tyrosine kinase receptors on keratinocytes and fibroblasts. In the United States, Americans of African descent are 25 times more likely to have acanthosis nigricans than Americans of European descent. The condition is reported to be most common in Native Americans.

AN can be classified into 8 types:

I. Obesity-associated – Most common; linked to diabetes, insulin resistance, high body mass index (BMI), metabolic syndrome, and polycystic ovarian syndrome (PCOS).

II. Malignancy-associated / cutaneous paraneoplastic syndrome – Most commonly associated with gastric carcinoma, but numerous other malignancies have been reported. Elderly nonobese patients with new AN should have malignancy considered as a cause. Atypical (palmar, perioral, or mucosal) distributions or acute-onset AN may be more associated with malignancy.

III. Drug-induced – Niacin (nicotinic acid) is the most closely associated medication, but AN can also be caused by oral contraceptives, corticosteroids, diethylstilbestrol, heroin, fusidic acid, methyltestosterone, protease inhibitors, and folate.

IV. Syndromic – Type A refers to patients with HAIR-AN (hyperandrogenism, insulin resistance, and acanthosis nigricans) syndrome and acromegaly. Type B is typically seen in women who have uncontrolled diabetes mellitus and autoimmune diseases (systemic lupus erythematosus, scleroderma, Sjögren syndrome, and Hashimoto thyroiditis). This type is associated with the formation of antibodies against insulin receptors.

V. Acral – Affects elbows, knees, and knuckles. Typically seen in healthy sub-Saharan Africans.

VI. Unilateral – Also called nevoid. Usually represents an epidermal nevus in childhood.

VII. Benign – Rare autosomal dominant type developing at birth or during childhood.

VIII. Mixed – Any 2 or more of the above types combined.

Other related endocrinopathies include pituitary hypogonadism, thyroid disease, Addison disease, and acromegaly.