Acanthosis nigricans (AN) is a condition described as dark, velvety, thickened skin in a symmetric distribution more commonly located in intertriginous areas including the axillary (Fig. E1), neck (Fig. E2), and groin regions. It is generally associated with insulin resistance due to diabetes and/or obesity; however, it can less frequently occur in the setting of an underlying malignancy (Fig. E3), medications, or congenital syndromes.¹

AN

Individuals with AN are generally asymptomatic but may experience pruritus. Physical features include symmetric, thickened areas of skin that are hyperpigmented in nature and with a velvety texture. Initially, the areas of skin affected have a grey-brown/black pigmentation and are dry and rough. The most commonly affected areas include the axillae, groin, back and sides of the neck, and popliteal areas, also known as the intertriginous areas. In extensive cases of AN, the lips, conjunctiva, areola, and buccal mucosa may also be involved.^1,2

AN is a result of high insulin levels leading to both direct and indirect activation of insulin-like growth factor (IGF) receptors on fibroblasts and keratinocytes, thus stimulating growth and proliferation that results in AN. Tyrosine kinase receptors like epidermal growth factor receptor (EGFR) and fibroblast growth factor receptor (FGFR) are also thought to be mediators. While hyperinsulinemia is thought to promote AN, it is also hypothesized that friction and perspiration contribute given the location of the typical areas of AN. Different classifications of AN have been proposed, though most classifications share the categories of benign versus malignant/paraneoplastic.^1,4,5

The following diagnoses should be considered from the cutaneous standpoint of AN:²

• Intertriginous granular parakeratosis
• Confluent and reticulated papillomatosis
• Haber syndrome
• Dowling-Degos disease
• Reticulate acropigmentation of Kitamura

The following diagnoses should be considered as potentially underlying or co-existing with AN:

• Prediabetes
• Diabetes
• Obesity
• Metabolic syndrome
• Polycystic ovary syndrome (PCOS)
• Nonalcoholic fatty liver disease (NAFLD)
• Chronic glucocorticoid exposure
• Hypertension
• Hyperlipidemia
• Malignancy

A complete history and physical exam should be taken to diagnose AN. Labwork should be obtained to evaluate for any underlying causes leading to AN.^3,6

• Fasting blood glucose and hemoglobin A1c should be obtained as these tests will aid in evaluating for prediabetes or diabetes.
• A fasting lipid panel may reveal hyperlipidemia.
• Liver function tests (aspartate transaminase [AST], alanine transaminase [ALT], alkaline phosphatase [ALP]) can be obtained to screen for fatty liver disease.
• If PCOS is suspected and the individual has hyperandrogenic symptoms such as excessive hair growth, serum total testosterone can be checked. If irregular menses are also present, early morning 17-hydroxyprogesterone should also be evaluated.

• Based on the Rotterdam Criteria for PCOS, if there is a high clinical suspicion for PCOS and the individual meets 1/3 of the criteria based on ovulation or hyperandrogenism, a transvaginal ultrasound should be performed to evaluate for polycystic ovaries (the diagnosis of PCOS requires 2/3 of the Rotterdam Criteria).
• If malignancy is suspected, appropriate imaging studies based on the clinical scenario should be pursued, computed tomography (CT) versus magnetic resonance imaging (MRI).

If AN is present in the setting of obesity leading to hyperinsulinemia, exercise, a healthy diet, and weight loss are nonpharmacologic options.

If AN is thought to be secondary to a medication, the medication in question should be discontinued.

In general, treatment of the underlying cause leading to AN is the mainstay of treatment for AN. This includes appropriate management of diabetes, PCOS, hyperlipidemia, malignancy, medications, etc. Conditions commonly occurring with hyperinsulinemia including hypertension and hyperlipidemia should also be treated. AN should recede with proper treatment of the underlying disease process.

If AN is refractory to the treatment described above, both topical and oral retinoids may be used. Laser treatment, vitamin D analo-gues (like calcipotriol) are also options for treatment.

• Referral to Endocrinology should be considered and can help to manage underlying conditions including diabetes, hyperlipidemia, and PCOS.
• Referral to a nutritionist can help with healthy dietary choices for weight loss.

• AN is a condition that occurs in the setting of another underlying disease process. It is important to timely and appropriately evaluate, diagnose, and treat this underlying process.
• Lifestyle changes are important in management of AN; however, medications may be necessary depending on what evaluation reveals is contributing to AN.

• Healthy habits such as a balanced diet and exercise can help to avoid hyperinsulinemia, metabolic syndrome, diabetes and subsequently AN.
• Regular follow-up with Primary Care for routine cancer screenings can help to avoid AN in the setting of malignancy.

Diabetes Mellitus (Related Key Topic)

Metabolic Syndrome (Related Key Topic)

Polycystic Ovarian Syndrome (Related Key Topic)