Aetiology
Acanthosis nigricans (AN) is associated with numerous underlying diseases, both acquired and inherited, but most commonly with obesity and hyperinsulinaemia.[2][5][6] It is thought that these conditions may lead to the release of various growth factors that then cause epidermal hyperplasia.[2][20][21][22] In some cases, there is no identifiable family history or associated medical condition and the cause is unknown.
Pathophysiology
While the detailed molecular pathogenesis of AN remains to be discovered, various endocrine and tumour-produced growth factors are postulated to play a role in AN development due to their effects on receptors present on epidermal cells.[2][20][21][22] In particular, epidermal growth factor and transforming growth factor alpha may be produced by tumours associated with AN.[2][21] In obesity and diabetes-related AN, increased levels of various endocrine products, including insulin-like growth factor-1 (IGF-1) and insulin itself, may play a role as their receptors are present on epidermal keratinocytes.[2][21][22]
Classification
Classification according to type[2]
Benign AN
Unilateral or generalised lesions present at birth or early childhood
Familial with autosomal-dominant trait with variable penetrance
Some affected families have an autosomal-dominant mutation in fibroblast growth factor receptor 3 gene (FGFR3)
May be classified as a variant of epidermal naevus
Usually not associated with obesity or endocrine abnormalities
May be mosaic condition with an increased risk of developing generalised AN in the right setting, such as obesity or hyperinsulinaemia
Obesity-associated AN
Weight-dependent and correlates with increasing body mass index
Resolves with weight loss
Associated with insulin resistance, which often accompanies obesity
Clinical marker for identifying patients at risk for developing diabetes mellitus
Syndromic AN
Associated with genetic syndromes, particularly those in which insulin resistance, obesity, or fibroblastic growth factor defects are present
Malignant AN
Characterised by sudden onset and rapid spread
Described in all age groups, although most common onset in adulthood
Most common locations are flexures and posterior neck, although there is involvement of oral and genital mucosa in 35% of patients. Acral surfaces and skin overlying cutaneous metastases may also be involved
May co-exist with sign of Leser-Trelat, 'tripe palms', florid cutaneous papillomatosis, and generalised pruritus
Most commonly associated with intra-abdominal carcinomas, typically gastric adenocarcinoma. Carcinomas of the liver, uterus, breast, lung, pancreas and bowel are detected less frequently[10]
Activated by the tumour, and parallels the course of the cancer, often regressing with treatment and returning with tumour recurrence
Acral AN
Also known as acral acanthotic anomaly
Hyperpigmented, acanthotic plaques on extensor surfaces, such as elbows, knees, dorsal hands and feet
Usually seen in healthy individuals with darkly pigmented skin
Unilateral AN
May be the unilateral form of benign acanthosis nigricans
Not associated with endocrinopathy, obesity, or malignancy
Drug-induced AN
Rarely induced by systemic corticosteroids, nicotinic acids, oestrogens, oral contraceptives, insulin, methyltestosterone, topical fusidic acid, and pituitary extract
Mixed-type AN
Two of the above types of AN appearing in the same patient
Usually malignant AN in concurrence with another type
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