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A 13-year-old Hispanic girl presents to her family physician with concerns about "dirty areas" under her arms and on her neck that "can't be cleaned" (Figure 229-1). Her periods have stopped and she is getting new hair growth on her face. She is overweight and has a family history of diabetes. The physician makes the diagnosis of acanthosis nigricans.

FIGURE 229-1

Acanthosis nigricans on the neck and in the axilla of an overweight 13-year-old Hispanic girl. She also has hirsutism, secondary amenorrhea, and a family history of diabetes. (Reproduced with permission from Richard P. Usatine, MD.)


  • Acanthosis nigricans (AN) is a localized form of hyperpigmentation that involves epidermal alteration. AN is usually associated with insulin resistance or hyperinsulinemia and is seen in patients with endocrine disorders (e.g., type 2 diabetes mellitus [DM], Cushing syndrome, acromegaly), obesity, and polycystic ovary syndrome.1-3


  • In a cross-sectional study of prevalence conducted in a nationwide underserved practice-based research network (N = 1730), AN was found in 18.2% of children and 19.5% of adults. Those with AN were twice as likely to have DM as those without AN (35.4% vs. 17.6%, p < 0.001).4

  • Several studies have used AN as a predictor of metabolic syndrome5,6; AN observed on the knuckles of Latin American youth had been reported as an early clinical indicator.7

  • AN is sometimes associated with malignancy, primarily adenocarcinoma (60%) of the stomach, gallbladder, colon, ovary, pancreas, rectum, and uterus.2,8,9

  • Although most cases are idiopathic, there are also genetic causes of AN.2,8

  • A condition of hyperandrogenism (HA), insulin resistance (IR), and AN called HAIR-AN syndrome occurs in approximately 1% to 3% of women with HA.10 This syndrome may also be seen in patients with autoimmune disorders such as Hashimoto thyroiditis.

  • AN can be an adverse effect from hormonal therapies.11


  • AN results from long-term exposure of keratinocytes to insulin.2

  • Keratinocytes have insulin and insulin-like growth receptors on their surface. The pathogenesis of this condition is linked to insulin binding to insulin-like growth receptors in the epidermis stimulating keratinocyte proliferation.2

  • Fibroblast growth factor receptor 3 (FGFR3) gene mutations should be considered in patients with coexistent AN and skeletal dysplasia.12


The diagnosis of AN is made clinically, with histopathology only when confirmation is needed, and can be classified by severity on a scale of 0–4. Increased scores correlate with increased BMI and fasting insulin levels.2


  • AN ranges in appearance from diffuse streaky thickened brown velvety lesions to leathery verrucous papillomatous lesions (...

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