Acanthosis nigricans

Published on 19/03/2015 by admin

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Acanthosis nigricans

Kevin F. Kia and Ponciano D. Cruz, Jr

Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports

image

Acanthosis nigricans is characterized by hyperpigmented, verrucous or velvety plaques that usually appear on flexural surfaces and in intertriginous regions. It is most commonly seen in individuals with insulin resistance states, especially obesity, and less frequently in association with other metabolic disorders, drugs, and malignancy. Although hyperinsulinemia, hyperandrogenemia, circulating anti-insulin receptor antibodies, and activating mutations in fibroblast growth factor receptor (especially for syndromes associated with skeletal dysplasia) have been implicated as causal factors, the precise pathogenesis is not yet known.

Management strategy

The management of patients with acanthosis nigricans depends on the underlying cause, the identification of which requires a salient history, a targeted physical examination, and a finite set of laboratory tests.

Relevant historical information includes age at onset, presence or absence of a family history, medications, and presence or absence of symptoms related to hyperinsulinemia (with or without diabetes mellitus), hyperandrogenemia (with or without virilism), and internal malignancy (with or without weight loss).

Drugs reported in association with acanthosis nigricans include nicotinic acid, corticosteroids, estrogens, insulin, fusidic acid, protease inhibitors, triazinate, diethylstilbestrol, palifermin, niacin, and recombinant growth hormone.

Physical examination should document obesity, masculinization, lymphadenopathy, and organomegaly. Initial laboratory screening should include fasting blood glucose and insulin tested concurrently to confirm or exclude insulin resistance (insulin value inappropriately high for the glucose level).

As obesity is the most common cause of both insulin resistance and acanthosis nigricans, it is reasonable to assume that it is the cause of acanthosis nigricans in obese patients with no historical or physical examination evidence of malignancy or of suspect drugs.

Rare causes of insulin resistance and acanthosis nigricans include the type A and B syndromes, the former characterized by defective insulin receptors and manifested typically in young girls with masculinized features, and the latter reported mostly in women with circulating anti-insulin receptor antibodies in association with autoimmune disorders such as lupus erythematosus. Other causes of insulin resistance and acanthosis nigricans are polycystic ovarian disease, HAIR-AN syndrome (hyperandrogenism, insulin resistance, and acanthosis nigricans), familial lipodystrophies, and various endocrinopathies. If insulin resistance is present, then the possibility of malignancy becomes unlikely.

The most common malignancy associated with acanthosis nigricans is gastric adenocarcinoma. Less frequently reported are endocrine, genitourinary and lung carcinomas, and melanoma. Malignant acanthosis nigricans may coexist with other cutaneous markers of internal malignancy, such as tripe palms, the sign of Leser–Trelat, florid cutaneous papillomatosis, and hyperkeratosis of the palms and soles (tylosis). If malignancy-associated acanthosis nigricans is suspected, the initial laboratory screen may include a complete blood count, stool test for occult blood, chest and gastrointestinal radiographs, as well as gastrointestinal endoscopy. Pelvic and rectal examinations, including pelvic ultrasonography, may be warranted in women and men depending on their age.

In the absence of objective evidence for a specific cause, the acanthosis nigricans may be labeled as idiopathic, which may or may not be familial. Treatment of the underlying cause often leads to resolution of the acanthosis nigricans. Otherwise, most published modes of treatment are symptomatic and/or cosmetic, and testimony to their efficacy has been anecdotal.

Specific investigations

First-line therapy

image Treat the underlying cause D

Second-line therapy

image Topical tretinoin and ammonium lactate D
image Oral metformin E and topical vitamin A E
image Topical tazarotene E
image Topical calcipotriol E
image Topical trichloroacetic acid C

Third-line therapy

image Oral isotretinoin E
image Oral ketoconazole E
image Palliative chemotherapy E
image Cyproheptadine E
image Dietary fish oil E
image Oral contraceptives E
image Dermabrasion E
image Long-pulsed alexandrite laser E
image Continuous wave carbon dioxide laser E

[/level-membership-for-dermatology-category][not-level-membership-for-dermatology-category]

Acanthosis nigricans

Kevin F. Kia and Ponciano D. Cruz, Jr

Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports

image

Acanthosis nigricans is characterized by hyperpigmented, verrucous or velvety plaques that usually appear on flexural surfaces and in intertriginous regions. It is most commonly seen in individuals with insulin resistance states, especially obesity, and less frequently in association with other metabolic disorders, drugs, and malignancy. Although hyperinsulinemia, hyperandrogenemia, circulating anti-insulin receptor antibodies, and activating mutations in fibroblast growth factor receptor (especially for syndromes associated with skeletal dysplasia) have been implicated as causal factors, the precise pathogenesis is not yet known.

Management strategy

The management of patients with acanthosis nigricans depends on the underlying cause, the identification of which requires a salient history, a targeted physical examination, and a finite set of laboratory tests.

Relevant historical information includes age at onset, presence or absence of a family history, medications, and presence or absence of symptoms related to hyperinsulinemia (with or without diabetes mellitus), hyperandrogenemia (with or without virilism), and internal malignancy (with or without weight loss).

Drugs reported in association with acanthosis nigricans include nicotinic acid, corticosteroids, estrogens, insulin, fusidic acid, protease inhibitors, triazinate, diethylstilbestrol, palifermin, niacin, and recombinant growth hormone.

Physical examination should document obesity, masculinization, lymphadenopathy, and organomegaly. Initial laboratory screening should include fasting blood glucose and insulin tested concurrently to confirm or exclude insulin resistance (insulin value inappropriately high for the glucose level).

As obesity is the most common cause of both insulin resistance and acanthosis nigricans, it is reasonable to assume that it is the cause of acanthosis nigricans in obese patients with no historical or physical examination evidence of malignancy or of suspect drugs.

Rare causes of insulin resistance and acanthosis nigricans include the type A and B syndromes, the former characterized by defective insulin receptors and manifested typically in young girls with masculinized features, and the latter reported mostly in women with circulating anti-insulin receptor antibodies in association with autoimmune disorders such as lupus erythematosus. Other causes of insulin resistance and acanthosis nigricans are polycystic ovarian disease, HAIR-AN syndrome (hyperandrogenism, insulin resistance, and acanthosis nigricans), familial lipodystrophies, and various endocrinopathies. If insulin resistance is present, then the possibility of malignancy becomes unlikely.

The most common malignancy associated with acanthosis nigricans is gastric adenocarcinoma. Less frequently reported are endocrine, genitourinary and lung carcinomas, and melanoma. Malignant acanthosis nigricans may coexist with other cutaneous markers of internal malignancy, such as tripe palms, the sign of Leser–Trelat, florid cutaneous papillomatosis, and hyperkeratosis of the palms and soles (tylosis). If malignancy-associated acanthosis nigricans is suspected, the initial laboratory screen may include a complete blood count, stool test for occult blood, chest and gastrointestinal radiographs, as well as gastrointestinal endoscopy. Pelvic and rectal examinations, including pelvic ultrasonography, may be warranted in women and men depending on their age.

In the absence of objective evidence for a specific cause, the acanthosis nigricans may be labeled as idiopathic, which may or may not be familial. Treatment of the underlying cause often leads to resolution of the acanthosis nigricans. Otherwise, most published modes of treatment are symptomatic and/or cosmetic, and testimony to their efficacy has been anecdotal.

Specific investigations

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