Endocrinology · Metabolic Disorders
The facts most likely to be tested
Acanthosis nigricans presents as hyperpigmented, velvety plaques typically located in intertriginous areas like the axilla, neck, and groin.
The most common underlying etiology is insulin resistance, frequently associated with obesity, type 2 diabetes mellitus, and metabolic syndrome.
Rapid onset of extensive acanthosis nigricans, especially in non-obese patients, is a classic paraneoplastic sign of underlying malignancy, most commonly gastric adenocarcinoma.
Pathophysiologically, the condition results from hyperinsulinemia stimulating insulin-like growth factor-1 (IGF-1) receptors on keratinocytes and fibroblasts.
Endocrine disorders such as Cushing syndrome, polycystic ovary syndrome (PCOS), and acromegaly are frequent secondary causes due to their impact on insulin signaling.
Drug-induced acanthosis nigricans is a known side effect of medications including nicotinic acid, glucocorticoids, and protease inhibitors.
The primary management strategy is to identify and treat the underlying metabolic or malignant condition rather than treating the skin lesion directly.
Vignette unlocked
A 58-year-old male presents to the clinic complaining of unintentional weight loss and fatigue over the past three months. Physical examination reveals dark, velvety, hyperpigmented plaques in the axillary folds and on the back of the neck. The patient has no history of diabetes or obesity. Laboratory studies show a normocytic anemia and elevated liver enzymes. A CT scan of the abdomen reveals a large mass in the gastric antrum.
Which of the following is the most likely mechanism for the patient's dermatologic findings?
Paraneoplastic stimulation of keratinocyte growth via TGF-alpha
The patient's rapid onset of acanthosis nigricans in the absence of metabolic syndrome is highly suggestive of a paraneoplastic process, specifically gastric adenocarcinoma, which secretes growth factors that stimulate skin proliferation.
Full handout
High yield triage
Etiology / Epidemiology
Strongly associated with insulin resistance and obesity; also a paraneoplastic marker for gastric adenocarcinoma.
Clinical Manifestations
Symmetric, velvety, hyperpigmented plaques in intertriginous areas like the posterior neck and axillae.
Diagnosis
Primarily a clinical diagnosis; screen for underlying hyperinsulinemia or malignancy if rapid onset.
Treatment
Treat the underlying cause (e.g., weight loss, metformin); avoid topical steroids as they are ineffective.
Prognosis
Lesions typically fade with metabolic control; rapid onset warrants urgent malignancy workup.
Full handout
Epidemiology & Etiology
Most common in patients with Type 2 Diabetes or Metabolic Syndrome. Rapid onset in non-obese adults is a classic paraneoplastic sign of malignant acanthosis nigricans, most commonly gastric adenocarcinoma. Other causes include Cushing syndrome, PCOS, and drug-induced states.
Pertinent Anatomy
Predominantly affects intertriginous zones where skin-on-skin friction occurs. Common sites include the posterior neck, axillae, groin, and inframammary regions. Involvement of the mucous membranes or palms is highly suggestive of a paraneoplastic process.
Pathophysiology
Hyperinsulinemia leads to activation of IGF-1 receptors on keratinocytes and fibroblasts. This stimulation causes epidermal hyperplasia and hyperkeratosis. In malignancy, TGF-alpha is often overexpressed by tumor cells, driving similar rapid proliferation.
Clinical Manifestations
Presents as symmetric, velvety, hyperpigmented plaques with a dirty appearance. Red flags include rapid progression, weight loss, or involvement of palms/soles (tripe palms), which mandate an immediate search for internal malignancy.
Diagnosis
Diagnosis is clinical. In suspected metabolic cases, order fasting glucose and HbA1c to assess for diabetes. If malignancy is suspected, a full body CT scan or endoscopy is the gold standard for identifying the primary tumor.
Treatment
Management focuses on weight loss and metformin to improve insulin sensitivity. Topical retinoids or salicylic acid may improve cosmetic appearance but do not treat the root cause. Do not use systemic steroids as they worsen the underlying metabolic dysregulation.
Prognosis
Lesions often regress significantly with weight reduction and glycemic control. Failure to improve despite metabolic correction requires re-evaluation for occult malignancy.
Differential Diagnosis
Confluent and reticulated papillomatosis: lacks the velvety texture and insulin association
Erythrasma: shows coral-red fluorescence under Wood's lamp
Seborrheic keratosis: discrete, 'stuck-on' appearance rather than diffuse plaques
Tinea corporis: peripheral scaling and positive KOH prep
Addison's disease: hyperpigmentation occurs in non-intertriginous areas and mucous membranes