Acanthosis Nigricans: Symptoms, Causes & Treatment

Acanthosis nigricans (AN) is a dermatological condition characterized by symmetric, hyperpigmented (brown-to-black), velvety, thickened plaques appearing in skin folds and flexural areas — most commonly the axillae, posterior neck, groin, inframammary folds, and umbilicus; less commonly the knuckles, elbows, and perioral region. AN is fundamentally a cutaneous marker of systemic disease rather than a primary skin disorder.

The pathophysiology involves stimulation of insulin receptors or IGF-1 receptors on keratinocytes by elevated circulating insulin (in insulin resistance states) or by circulating growth factors from tumors, triggering keratinocyte and fibroblast proliferation — producing the characteristic hyperkeratosis and papillomatosis of the skin. This explains why AN is so strongly associated with insulin resistance, metabolic syndrome, obesity, and polycystic ovary syndrome (PCOS): hyperinsulinemia drives the skin changes. Type 2 diabetes risk is substantially elevated in patients presenting with AN.

AN is clinically classified into several types: (1) Obesity/insulin resistance-associated (the most common by far); (2) Endocrine-associated: PCOS, Cushing's syndrome, acromegaly, hypothyroidism; (3) Drug-induced: niacin, systemic corticosteroids, OCP, insulin therapy, protease inhibitors; (4) Malignant AN: associated with internal malignancy (usually gastric or colon adenocarcinoma) — rapid onset, extensive, involves mucous membranes and palms/soles; (5) Genetic/familial; (6) Benign idiopathic. Distinguishing malignant AN is critical — it may precede cancer diagnosis.

• Symmetric hyperpigmented velvety plaques in flexural areas: axillae (most common), posterior and lateral neck, groin, inframammary folds, umbilicus
• Thickened skin with papillomatous texture — like dirty or unwashed skin that doesn't wash off
• Mild pruritus in some patients
• Acrochordons (skin tags) commonly co-occur in affected areas
• Malignant AN: rapidly progressive, extensive distribution including oral mucosa, palms, soles, and eyelids; poor cosmetic appearance; associated weight loss and constitutional symptoms suggesting underlying malignancy

• Insulin resistance and obesity: the most common cause — hyperinsulinemia stimulates keratinocyte IGF-1 receptors
• Polycystic ovary syndrome (PCOS): hyperinsulinemia and androgen excess
• Type 2 diabetes and prediabetes
• Endocrine disorders: acromegaly (GH excess), Cushing's syndrome, hypothyroidism, Addison's disease
• Drug-induced: nicotinic acid (niacin), systemic corticosteroids, combined OCP, insulin therapy, protease inhibitors (HIV therapy), fusidic acid
• Malignant AN: adenocarcinoma of the stomach (most common), colon, lung, liver, breast — tumor secretes transforming growth factors that stimulate keratinocytes
• Genetic/familial syndromes: HAIR-AN syndrome (hyperandrogenism, insulin resistance, AN), lipodystrophy syndromes

Clinical diagnosis: characteristic morphology and distribution. Investigation of underlying cause: fasting glucose and insulin (HOMA-IR for insulin resistance), HbA1c, TSH (thyroid disease), testosterone/androgen panel (PCOS in women), prolactin (pituitary disease). Skin biopsy: rarely needed — shows papillomatosis, hyperkeratosis, and slight acanthosis without significant inflammation. Malignancy workup for rapid-onset or atypical AN: endoscopy (gastric and colonoscopy), CT chest/abdomen/pelvis, tumor markers (CEA, CA-125); the skin change may precede cancer diagnosis by months.

Treatment targets the underlying cause — there is no primary dermatological treatment for AN itself. Weight loss and insulin sensitization: the most effective intervention for obesity-associated AN — weight loss of 5–10% body weight noticeably improves skin changes; metformin (for insulin resistance or PCOS) reduces hyperinsulinemia and frequently improves AN. Treating endocrine disorders (PCOS, Cushing's, hypothyroidism) resolves drug-induced AN when the offending drug is stopped. Topical cosmetic treatments (not curative): topical retinoids (tretinoin), salicylic acid, urea-based moisturizers, kojic acid — reduce thickening and discoloration modestly. Laser and intense pulsed light (IPL): cosmetic improvement for residual pigmentation. Malignancy-associated AN: regresses only if the underlying cancer is treated successfully.

• Complications are primarily from the underlying cause: type 2 diabetes, cardiovascular disease from metabolic syndrome, PCOS-related infertility
• Psychological impact: cosmetic distress and social stigma — dark neck skin is often incorrectly attributed to poor hygiene by patients and peers
• Missed malignancy in malignant AN: untreated underlying cancer remains the true life-threatening complication

• Primary prevention of insulin resistance through healthy weight maintenance, regular physical activity, and Mediterranean-type diet
• Early treatment of PCOS, hypothyroidism, and other associated endocrine conditions
• Avoidance of causative medications when alternatives exist (niacin, high-dose systemic corticosteroids)