Approach

Clinical history and distinctive examination findings usually make the diagnosis of acanthosis nigricans (AN) readily apparent.[1]​ A skin biopsy may be helpful in atypical cases or to exclude other entities in the differential diagnosis.

Identification of risk factors

Risk factors that are strongly associated with AN include obesity, insulin resistance, the presence of a positive family history of AN, diabetes mellitus, certain genetic syndromes (particularly those associated with insulin resistance, obesity or fibroblastic growth factor defects), and malignancy.[2][4][5][6][7]​​​[8][9][18][20]​​​

History

The first sign noted by patients is hyperpigmentation, with the affected skin having a darker or dirty appearance. This is followed by thickening of the epidermis and intensified skin markings.[2] These changes often occur first on the posterior neck. Acrochordons (skin tags) frequently appear in affected areas.[23]​​

Obesity-related AN may follow weight gain. Malignant AN often occurs abruptly, rapidly spreads, and may be accompanied by weight loss.[2][8][9] A positive family history may be present in those with benign or unilateral AN.[2][4][20] Onset may rarely correlate with commencement of a new medication.[2]​​

Physical examination

Symmetric, hyperpigmented plaques ranging in colour from yellow to dark brown are most commonly found on flexural surfaces. The posterior neck, axilla, vulva, umbilicus, inner thighs, and groin are the most frequently affected sites.[1]​ Skin tags may be present. The patient may have overweight or obesity. Mucosal involvement and hyperkeratosis of the palms and soles should alert the clinician to the possibility of malignant AN.[2][8][9][12]​ Generalised involvement may be seen in benign (familial) or malignant AN. AN may also have an acral distribution on the extensor surfaces of extremities without involvement of intertriginous areas.[2][24][Figure caption and citation for the preceding image starts]: Acanthosis nigricans involving the axilla of an obese Caucasian womanFrom the collection of Melvin Chiu, MD [Citation ends].com.bmj.content.model.Caption@fec47ef[Figure caption and citation for the preceding image starts]: Acanthosis nigricans involving the back and arms of an obese black womanFrom the collection of Miguel Gutierrez, MD [Citation ends].com.bmj.content.model.Caption@7a2bcc96

Malignancy screening

If no other cause is readily identifiable and there is rapid, widespread onset with involvement of mucosal surfaces and palms, malignancy screening for an intra-abdominal malignancy is warranted (e.g., abdominal CT scan following thorough clinical examination).[2][24]​ Malignant AN may be accompanied by the sudden appearance of multiple seborrhoeic keratoses or generalised pruritus.[8] Patients with malignant AN may be underweight and are typically over the age of 40 years.[2][8][9]

Testing for insulin resistance

Fasting glucose and insulin tests (e.g., fasting blood insulin) are performed if the patient has obesity to screen for insulin resistance.[18]​​

Skin biopsy with histological examination

Skin biopsy is unnecessary in most cases, but can be helpful in atypical presentations or to rule out other differential diagnoses.[1]

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