Acanthosis Nigricans

Description

• Acanthosis nigricans (AN) is a benign dermatosis characterized by velvety, hyperpigmented, hyperkeratotic plaques, which
  • Are usually symmetric
  • Most often occur on the posterior neck, flexural and intertriginous surfaces (axilla, elbow, inframammary areas, groin and anogenital regions), and sometimes in mucocutaneous areas
  • Are most often asymptomatic but may cause pruritus
• Typically a sign of hyperinsulinemia and insulin resistance but can be a marker of malignancy
• Individuals with AN are at risk of developing metabolic syndrome.
• Etiologies include obesity, insulin resistance, genetic syndromes, familial AN, malignant AN, and drug reactions (1).

Epidemiology

• AN is more common between the ages of 11 and 40 years and in those with body mass index (BMI) ≥30.
• It is more common in individuals with diabetes or risk factors for diabetes.
• It may be a useful indicator of risk of diabetes mellitus (2) and subclinical atherosclerosis (3).

Prevalence

• Prevalence of AN in unselected populations varies from 7% to 74% according to age, race, frequency of type, degree of obesity, and concomitant endocrinopathies (2).
• It is more prevalent in Hispanic, African American, and Native American individuals compared to white or Asian individuals (1).
• In a study of 89 African Americans with AN, there was a 21.3% frequency of DM2 (2).

Etiology and Pathophysiology

• Obesity induced (pseudo-AN) and insulin resistance (2)
  • Are the most common etiologies of AN
  • More prevalent in individuals with BMI >30. It is weight dependent and may regress with weight loss.
  • Higher prevalence of AN in individuals with more risk factors for diabetes and those with type 2 diabetes
  • Other endocrinopathies associated with AN include polycystic ovarian syndrome (PCOS), acromegaly, and Cushing syndrome; thyroid diseases; hirsutism; and Addison disease.
• Syndromic AN (1)
  • Genetic disorders characterized by insulin resistance can also present with AN. Examples include Down syndrome, leprechaunism, congenital generalized lipodystrophy, and familial partial lipodystrophy.
• Familial AN (1)
  • Autosomal dominant mutation of the fibroblast growth factor receptor 3 gene
  • Lesions are usually seen in early childhood.
• Malignant AN (1)
  • A rare cause of AN characterized by
    • Sudden onset, rapid progression, and more extensive lesions
    • Presents in atypical locations such as in the mucosa, palms, and soles
    • It usually presents in older adults who are often not obese.
    • 90–95% are associated with abdominal cavity adenocarcinomas.
• May also present with other cutaneous disorders representing internal malignancy such as Leser-Trélat sign (sudden onset of multiple seborrheic keratosis) or tripe palms (ridged velvety lesions of the palms)
• Drug-induced AN (1)
  • A rare cause that can be seen with drugs that promote hyperinsulinemia such as systemic glucocorticoids, insulin, oral contraceptives (OCPs), niacin, testosterone, and protease inhibitors
  • Lesions usually regress after discontinuation of these drugs.

Genetics
High levels of insulin stimulate epidermal keratocytes and dermal fibroblasts via insulin-like growth factor receptors (IGF-1). The keratocyte proliferation leads to skin changes like papillomatosis and hyperkeratosis (4).

Risk Factors

• Obesity (3)
• Insulin resistance (3)
• Race and ethnicity (3)
• Family history of DM2 (3)

General Prevention

Encourage diet and exercise to all age groups to reduce likelihood of insulin resistance syndrome.