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An adolescent girl with obesity and recently diagnosed type II diabetes mellitus (DM) presents to her family physician with concerns about a “dirty area” under her arms and on her neck that “couldn't be cleaned” (Figure 220-1). She has irregular periods that often skip several months at a time. The physician makes the diagnosis of acanthosis nigricans.

Figure 220-1

Acanthosis nigricans in the left axilla of an overweight Hispanic 10-year-old girl. Note areas of dark velvety discoloration and pink filiform hypertrophy. (Courtesy of Richard P. Usatine, MD.)

  • Acanthosis nigricans (AN) is a localized form of hyperpigmentation that involves epidermal alteration. AN is usually associated with insulin resistance and is seen in patients with endocrine disorders (e.g., type II DM, Cushing syndrome, acromegaly), obesity, and polycystic ovary syndrome.

  • In a cross-sectional study conducted in a southwestern practice-based research network (N = 1133), AN was found in 17% of children and 21% of adults.1
  • In 2 studies, AN was present in 36% of patients with newly diagnosed DM and 39% of children with obesity.2,3
  • AN is sometimes associated with malignancy, primarily adenocarcinoma (60%) of the stomach, gallbladder, colon, ovary, pancreas, rectum, and uterus.4,5
  • Although most cases are idiopathic, there are also genetic causes of AN.5
  • A condition of hyperandrogenism (HA), insulin resistance (IR), and AN called HAIR-AN syndrome occurs in approximately 1% to 3% of women with HA.6 This syndrome may also be seen in patients with autoimmune disorders like Hashimoto thyroiditis.
  • AN can be an adverse effect from hormonal therapies.7

  • AN results from of long-term exposure of keratinocytes to insulin.
  • Keratinocytes have insulin and insulin-like growth receptors on their surface and the pathogenesis of this condition may be linked to insulin binding to insulin-like growth receptors in the epidermis.
  • Fibroblast growth factor receptor 3 (FGFR3) gene mutations should be considered in patients with coexistent AN and skeletal dysplasia.8

The diagnosis of AN is made clinically in a patient with or at risk for IR who has the characteristic lesions.

Clinical Features

  • AN ranges in appearance from diffuse streaky thickened brown velvety lesions to leathery verrucous papillomatous lesions (Figures 220-1, 220-2, 220-3, 220-4, 220-5, 220-6, 220-7, 220-8, and 220-9).
  • Women with HAIR-AN syndrome have evidence of virilization (e.g., increased body hair in male distribution, enlarged clitoris) in addition to AN.6

Figure 220-2

Acanthosis nigricans in the right axilla of a 25-year-old woman with type 2 diabetes. The skin appears velvety. (Courtesy of Richard P. Usatine, MD.)

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