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ACANTHOSIS NIGRICANS (AN) ICD-10: L 83

  • Asymmetric velvety thickening and hyperpigmentation of the skin, seen chiefly on the neck, axilla, groins, and other body folds.

  • May be hyperkeratotic and associated with skin tags.

  • A cutaneous marker related to heredity, obesity, endocrine disorders (particularly diabetes), drug administration, and malignancy.

  • Insidious onset; in malignancy, rapid.

CLASSIFICATION

  • Type 1: Hereditary Benign AN. No associated endocrine disorder.

  • Type 2: Benign AN. Endocrine disorders associated with insulin resistance: insulin-resistant type II diabetes mellitus, hyperandrogenic states, acromegaly/gigantism, Cushing disease, hypogonadal syndromes with insulin resistance, Addison disease, and hypothyroidism.

  • Type 3: Pseudo-AN. Associated with obesity; more common in patients with darker pigmentation. Common in metabolic syndrome. Obesity produces insulin resistance.

  • Type 4: Drug-Induced AN. Nicotinic acid in high dosage, stilbestrol in young males, glucocorticoid therapy, diethylstilbestrol/oral contraceptive, and growth hormone therapy.

  • Type 5: Malignant AN. Paraneoplastic, usually adenocarcinoma of gastrointestinal or genitourinary tract; less commonly, bronchial carcinoma and lymphoma.

EPIDEMIOLOGY

AGE OF ONSET Type 1: Occurs during childhood or puberty; other types dependent on associated conditions.

ETIOLOGY AND PATHOGENESIS

Dependent on associated disorder. In a subset of women with hyperandrogenism and insulin intolerance and AN, loss-of-function mutation in the insulin receptor or anti-insulin receptor antibodies can be found (types A and B). It is postulated that excess growth factor stimulation in the skin leads to proliferation of keratinocytes and fibroblasts. In hyperinsulinemia AN, excess insulin binding to insulin-like growth factor 1 receptor and fibroblast growth factor receptor has also been implicated. In malignancy-associated AN, transforming growth factor β released from tumor cells may stimulate keratinocyte proliferation via epidermal growth factor receptors.

CLINICAL MANIFESTATION

Insidious onset; in type 5 rapid. The first visible change is darkening of pigmentation.

SKIN LESIONS All types of AN: Darkening of pigmentation, skin appears dirty (Fig. 5-1). As skin thickens, it appears velvety; skin lines accentuated; surface becomes rugose, mammillated. Type 3: Velvety patch on inner, upper thigh at site of chafing; often has many skin tags in body folds and neck. Type 5: Hyperkeratosis and hyperpigmentation more pronounced (Fig. 5-2A). Involvement of oral mucosa and vermilion border of lips (Fig. 5-2B). Hyperkeratosis of the palms/soles, with accentuation of papillary markings, "Tripe hands" (Fig. 5-2C).

Figure 5-1

Acanthosis nigricans Velvety, dark-brown to gray thickening of the armpits with prominent skin folds and feathered edges in a 30-year-old obese woman from the Middle East. There were similar changes on the neck, the antecubital fossae, and on the knuckles.

Figure 5-2

Acanthosis nigricans, type 5 (malignant) (A) Verrucous, papillomatous grayish-brown plaques in groins, medial aspects of the thigh, and scrotum. Similar lesions were found on neck and all other ...

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