Acanthosis nigricans (AN) is a localized skin disorder manifesting with hyperpigmented, velvety plaques typically located in flexural and intertriginous regions. The precise pathogenesis is unknown but is thought to involve insulin resistance-mediated overstimulation of insulin-like growth factor receptors and tyrosine kinase receptors on keratinocytes and fibroblasts, resulting in epidermal thickening and hyperpigmentation. In the United States, AN is most prevalent among Black, Hispanic, and American Indian populations.

Key associations are grouped as follows:

• Insulin-resistant states – Most common; linked to diabetes, high body mass index (BMI), metabolic syndrome, polycystic ovarian syndrome (PCOS), endocrinopathies (acromegaly and gigantism, pseudoacromegaly, Cushing syndrome, and Addison disease; rarer associated syndromes include Prader-Willi syndrome, Alström syndrome, MORFAN syndrome [mental retardation, pre- and postnatal overgrowth, remarkable face, and AN], ataxia-telangiectasia, hyperandrogenic states, hypogonadal syndromes), and insulin-resistant states (type A/B syndromes, leprechaunism [Donohue syndrome], lipoatrophic diabetes, Rabson-Mendenhall syndrome, pineal hypertrophic syndrome, and acral hypertrophy syndrome). Type A refers to patients with HAIR-AN (hyperandrogenism, insulin resistance, and AN). Type B is typically seen in women who have uncontrolled diabetes mellitus and autoimmune diseases (systemic lupus erythematosus, scleroderma, Sjögren syndrome, and Hashimoto thyroiditis) and is associated with the formation of anti-insulin receptor antibodies.
• Malignancy-associated / cutaneous paraneoplastic syndrome – Most commonly associated with gastric carcinoma and other adenocarcinomas, such as those arising elsewhere in the gastrointestinal (GI) tract, lung, breast, and less frequently the rectum, gallbladder, liver, pancreas, and prostate, among other organs. Older adult nonobese patients with new AN should have malignancy considered as a cause. Atypical (palmar, perioral, or mucosal) distributions or acute-onset AN may be more associated with malignancy.
• Drug-induced – Niacin (nicotinic acid) is the most closely associated medication, but AN can also be caused by oral contraceptives, insulin, somatotrophin, triazinate, corticosteroids, diethylstilbestrol, heroin, fusidic acid, methyltestosterone, protease inhibitors, and folate. Localized AN can rarely develop at insulin injection sites.
• Familial / syndromic – These include FGFR2- or FGFR3-related syndromes such as Crouzon syndrome with AN, Beare-Stevenson cutis gyrata syndrome, severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN), thanatophoric dysplasia, and RAVEN syndrome (epidermal nevus mimicking AN), as well as HRAS-related Costello syndrome. Patients with FGFR-related syndromes often have craniosynostosis and characteristic skeletal or facial features, while Costello syndrome is associated with redundant velvety skin, periorificial papillomas, deep palmoplantar creases, and cardiac abnormalities.