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ACANTHOSIS NIGRICANS

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Acanthosis nigricans (AN) is a diffuse, velvety thickening and hyperpigmentation of the skin, chiefly in axillae and other body folds, which may be related to hereditary factors, associated endocrine disorders, obesity, drug administration, and, in one rare form, malignancy.

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CLASSIFICATION

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

  • Type 2—Benign AN: Associated with insulin resistance (IR), impaired glucose tolerance, IR diabetes mellitus (DM), hyperandrogenism, acromegaly, gigantism, Cushing's disease, growth hormone, hypogonadism, Addison's disease, hypothyroidism, polycystic ovary syndrome, or total lipodystrophy.

  • Type 3—Pseudo-AN: Obesity-induced IR, darker skin types.

  • Type 4—Drug-induced AN: Nicotinic acid, oral contraceptives, insulin, or other exogenous hormone treatments.

  • Type 5—Malignant AN Paraneoplastic, usually adenocarcinoma; less commonly, lymphoma.

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EPIDEMIOLOGY

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AGE Any age. Peak: puberty to adulthood.

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GENDER M = F.

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INCIDENCE Up to 19% of the population. Incidence thought to be rising with increased obesity and diabetes in both pediatric and adult populations.

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RACE African Americans > Hispanics, Native Americans > Caucasians, Asians.

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PATHOPHYSIOLOGY

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Epidermal changes of AN are likely caused by triggers that stimulate keratinocyte and fibroblast proliferation. In benign AN, the trigger is likely insulin or an insulin-like growth factor. In malignant AN, the trigger is likely the tumor or tumor secretions. Growth receptors that have been implicated in the development of AN include fibroblast growth factor receptor (FGFR), insulin-like growth factor receptor-1 (IGFR1), and epidermal growth factor receptor (EGFR).

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HISTORY

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AN has an asymptomatic, insidious onset. The first visible change is darkening of pigmentation which gradually progresses to velvety plaques that may be pruritic.

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PHYSICAL EXAMINATION

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Skin Findings
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TYPE Plaque.

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COLOR Dark brown to black, hyperpigmented, skin appears dirty. Longstanding lesions may show hyperlinearity of skin markings.

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PALPATION Velvety, rugose, mammillated.

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DISTRIBUTION Posterior neck > axillae (Fig. 18-1), groin > antecubital, knuckles, submammary, umbilicus, areola. Usually symmetric.

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FIGURE 18-1
Acanthosis nigricans

Hyperpigmented velvety plaque in the axilla of an adolescent.

Graphic Jump Location
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MUCOUS MEMBRANES Oral, nasal, laryngeal, and esophagus: velvety texture with delicate furrows.

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NAILS Leukonychia, hyperkeratosis.

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OTHER Skin tags in same areas, likely due to similar growth-factor stimulation.

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General Findings
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OCULAR Papillomatous lesions on the eyelids and conjunctiva.

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BENIGN AN Obesity or underlying endocrine disorder.

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MALIGNANT AN Underlying malignancy most commonly gastric adenocarcinoma (70%).

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DIFFERENTIAL DIAGNOSIS

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AN can be confused with confluent and reticulated papillomatosis of Gougerot and Carteaud (CARP), terra firma-forme dermatosis, hypertrichosis, Becker's nevus, epidermal nevus, hemochromatosis, Addison's disease, or pellagra.

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LABORATORY EXAMINATIONS

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