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KembaraXtra-Medicine: Acanthosis Nigricans
Acanthosis nigricans (AN) is a dermatologic condition characterized by dark, velvety, thickened skin that appears in a symmetric distribution, most commonly affecting intertriginous areas such as the axillae, neck, and groin. The condition is most often associated with insulin resistance, particularly in the setting of obesity and diabetes mellitus, but it can also occur less commonly due to underlying malignancy, medication effects, or congenital syndromes. AN itself is not dangerous, but it is an important cutaneous marker of systemic disease and warrants further evaluation.
AN is coded under ICD-10-CM L83. The reported prevalence varies widely across studies, but available data suggest that AN is more commonly observed among Black Americans, Native Americans, and Hispanic Americans compared with White or Asian Americans. This condition can affect individuals of all ages. Major risk factors include obesity, insulin resistance, type 2 diabetes, and malignancy, particularly gastrointestinal adenocarcinomas in cases of malignant or paraneoplastic AN.
Clinically, individuals with AN are often asymptomatic, though some may report pruritus or irritation. On examination, the affected skin appears hyperpigmented, thickened, and velvety, initially presenting as dry, rough, gray-brown to black patches. The most commonly involved sites include the axillae, groin, posterior and lateral neck, and popliteal fossae. In more extensive or severe cases, involvement of mucosal surfaces such as the lips, buccal mucosa, conjunctiva, and areolae may be seen. Rapid onset, extensive involvement, or mucosal disease should raise concern for an underlying malignancy.
The pathogenesis of AN is primarily related to hyperinsulinemia, which leads to direct and indirect stimulation of insulin-like growth factor (IGF) receptors on keratinocytes and fibroblasts. This stimulation promotes epidermal proliferation and dermal thickening. Other growth factor pathways, including epidermal growth factor receptor (EGFR) and fibroblast growth factor receptor (FGFR) signaling, may also play contributory roles. Mechanical factors such as friction and perspiration are thought to exacerbate AN, which helps explain its predilection for intertriginous regions. Clinically, AN is often categorized as benign (metabolic-related) or malignant/paraneoplastic, though additional subclassifications exist.
The diagnosis of AN is typically clinical, based on history and physical examination. From a dermatologic standpoint, conditions that may resemble AN include intertriginous granular parakeratosis, confluent and reticulated papillomatosis, Haber syndrome, Dowling–Degos disease, and reticulate acropigmentation of Kitamura. Because AN is frequently a manifestation of systemic disease, evaluation should also consider associated or underlying conditions such as prediabetes, diabetes, obesity, metabolic syndrome, polycystic ovary syndrome (PCOS), nonalcoholic fatty liver disease (NAFLD), chronic glucocorticoid exposure, hypertension, hyperlipidemia, and malignancy.
The workup of AN should be guided by clinical context and focuses on identifying underlying causes. Recommended laboratory tests include fasting blood glucose and hemoglobin A1c to assess for prediabetes or diabetes, fasting lipid panel for hyperlipidemia, and liver function tests to screen for fatty liver disease. In patients with features of hyperandrogenism or menstrual irregularities suggestive of PCOS, serum total testosterone and early morning 17-hydroxyprogesterone may be indicated. Imaging studies are not routinely required but may include transvaginal ultrasound when PCOS is suspected or CT/MRI if there is concern for malignancy based on clinical features such as sudden onset or rapid progression.
Management of AN centers on treating the underlying condition, which is the most effective approach. In cases related to obesity and insulin resistance, weight loss through diet and exercise is the cornerstone of therapy and often leads to gradual improvement or resolution of skin findings. If AN is medication-induced, discontinuation of the offending agent is recommended when feasible. Associated conditions such as diabetes, PCOS, hypertension, hyperlipidemia, or malignancy should be managed according to standard guidelines.
When AN persists despite optimal management of the underlying cause, adjunctive dermatologic treatments may be used for cosmetic or symptomatic relief. These include topical retinoids, vitamin D analogues, keratolytic agents, and, in more refractory cases, systemic retinoids or laser therapy. Referral to endocrinology is often helpful for management of metabolic disorders, and referral to a nutritionist can support sustainable lifestyle changes.
A key clinical pearl is that acanthosis nigricans is a sign, not a diagnosis. Its presence should prompt clinicians to search for and address the underlying disease process. Preventive strategies focus on maintaining healthy lifestyle habits, including balanced nutrition, regular physical activity, and routine primary care follow-up with appropriate metabolic and cancer screening, which can reduce the risk of developing AN and its associated conditions.
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