A 10-year-old girl with obesity and recently diagnosed type II diabetes mellitus (DM) presents to her pediatrician with concerns about a “dirty area” under her arms and on her neck that “couldn’t be cleaned” (Figure 190-1). The pediatrician makes the diagnosis of acanthosis nigricans and explains to the mother the importance of weight loss, good diet, and exercise. She uses this as a teachable moment to explain how the obesity and diabetes are adversely affecting the daughter and how this is visible on the skin. The role of genetics is discussed too but there is emphasis on the risk factors that can be altered.

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  Acanthosis nigricans (AN) is a localized form of hyperpigmentation that involves epidermal alteration. AN is associated with insulin resistance and usually seen in patients with endocrine disorders (e.g., type 2 DM, Cushing syndrome, acromegaly), obesity, and polycystic ovary syndrome.

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  In a cross-sectional study conducted in a southwestern practice-based research network (N = 1133), AN was found in 17 percent of children and 21 percent of adults.¹

  
  
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  In two studies, AN was present in 36 percent of patients with newly diagnosed DM and 39 percent of children with obesity.^2,3 AN prevalence rates have been reported to be as high as 60 to 92 percent of black and Hispanic children with diabetes.⁴

  
  
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  AN has been reported in children with Wilms’ tumor and osteogenic sarcoma.⁴

  
  
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  A condition of hyperandrogenism (HA), insulin resistance (IR), and acanthosis nigricans (AN) called HAIR-AN syndrome is a subphenotype of the polycystic ovary syndrome (Figure 190-2).^5–7 It is one of the most common causes of menstrual problems, hyperandrogenic symptoms, and insulin resistance among adolescent patients.⁶ In one series of patients with HAIR-AN in an adolescent clinic, the mean age of affected patients was 15.5, initial mean weight at diagnosis was 94.5 kg, and the mean BMI was 33 kg/2.6 m.

  
  
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  AN can be an adverse effect from hormonal therapies.⁸

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  AN results from long-term exposure of keratinocytes to insulin and is an indicator of insulin sensitivity independent of body mass index (BMI).⁴

  
  
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  Type A IR appears responsible for producing AN in patients who are obese and Type B resistance, mediated by antibody formation against insulin receptors, appears to cause AN in patients with other autoimmune diseases.⁴

  
  
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  Keratinocytes have insulin and insulin-like growth receptors on their surface and the pathogenesis of this condition is linked to insulin binding to insulin-like growth receptors in the epidermis.

  
  
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  Fibroblast growth factor receptor 3 (FGFR3) gene mutations should be considered in patients with coexistent AN and skeletal dysplasia (e.g., thanatophoric dysplasia, severe achondroplasia with developmental delay and AN [SADDAN syndrome], and Crouzon syndrome with AN);^9,10 in these patients, IR does not appear to be the mechanism in producing AN.¹⁰ Insulin receptor mutations have also been described.⁴

  
  
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  Malignant AN likely occurs as a result of tumor cell expression of peptides that enhance proliferation of transforming growth factor-a and epidermal growth factor.⁴

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

Clinical Features

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  AN ranges in appearance from diffuse streaky thickened brown velvety lesions to leathery verrucous papillomatous lesions (Figures 190-1 to 190-6).

  
  
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  Women with HAIR-AN syndrome have evidence of virilization (e.g., increased body hair in male distribution, enlarged clitoris) in addition to AN.⁶

  
  
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  There is a significant correlation between AN and obesity (Figures 190-3 and 190-4) and hypertension.¹¹