Acanthosis nigricans (AN) is a localized skin disorder typically characterized by symmetric, hyperpigmented, velvety plaques in intertriginous areas like the posterior neck and axilla. It is due to overstimulation of fibroblasts and keratinocytes via insulin-like growth factor receptors and tyrosine kinase receptors. AN is most commonly associated with obesity, with the prevalence of AN in obese pediatric populations ranging from 49.2% to 67.6%. AN is furthermore a visible marker of insulin resistance, a precursor to the development of type 2 diabetes. One pilot study of 507 children found that the combination of AN and an increased body mass index (BMI) was linked to an 80% incidence rate of insulin resistance.

Key associations are grouped as follows:

• Insulin-resistant states – Most common; linked to diabetes, high BMI, metabolic syndrome, and 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.
• 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 metabolic syndrome, 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. These syndromes often present in childhood.
• 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.
• Malignancy-associated / cutaneous paraneoplastic syndrome – Very rare in children but has been documented with juvenile gastric adenocarcinoma (most common), Wilms tumor, and osteogenic sarcomas.