Published on 19/03/2015 by admin
Filed under Dermatology
Last modified 22/04/2025
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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
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.
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.
Document obesity based on ideal body weight
Determine fasting blood glucose and insulin levels in parallel
Depending on historical clues, screen for other endocrine disease
Consider malignancy; if suspected refer to appropriate specialist for the best diagnostic procedure
Consider drugs as a cause
Hud J, Cohen J, Wagner J, Cruz P. Arch Dermatol 1992; 128: 941–4.
Up to 74% of obese adult patients seen at the Parkland Memorial Hospital Adult Obesity Clinic in Dallas, Texas, had acanthosis nigricans. The skin disorder predicted the existence of hyperinsulinemia.
Bolding J, Wratchford T, Perkins K, Ogershok P. WV Med J 2005; 101: 112–15.
The prevalence of obesity (37%) and acanthosis nigricans (17%) was established in this adolescent population of West Virginia.
Sinha S, Schwartz RA. J Am Acad Dermatol 2007; 57: 502–8.
A review of the evaluation of children presenting with acanthosis nigricans.
Hermanns-Le T, Scheen A, Pierard G. Am J Clin Dermatol 2004; 5: 199–203.
A review of the pathogenesis and treatment of acanthosis nigricans.
Torleyu D, Bellus G, Munro C. Br J Dermatol 2002; 147: 1096–101.
Craniosynostosis and skeletal dysplasia syndromes with acanthosis nigricans are associated with activating mutations in fibroblast growth factor receptors, particularly FGFR3.
Dunaif A, Graf M, Mandeli J, Laumas V, Dobrjansky A. J Clin Endocrinol Metab 1987; 65: 499–507.
Among obese women with polycystic ovaries, 50% had acanthosis nigricans.
Rigel D, Jacobe M. J Dermatol Surg Oncol 1980; 6: 923–7.
Gastric carcinoma was reported in 55% of 227 cases of acanthosis nigricans associated with an internal malignancy. Other intra-abdominal malignancies accounted for 18% of cases, and the remaining 27% had extra-abdominal sites of malignancy.
Mellor-Pita S, Yebra-Bango M, Alfaro-Martinez J, Suarez E. Clin Infect Dis 2002; 34: 716–17.
A man with HIV infection developed insulin resistance, diabetes mellitus, and acanthosis nigricans soon after starting treatment with protease inhibitors.
Tromovitch T, Jacobs P, Kern S. Arch Dermatol 1964; 89: 222–3.
A man treated with nicotinic acid (4 g/day) developed acanthosis nigricans, which cleared after discontinuation of the drug.
Downs A, Kennedy C. Br J Dermatol 1999; 141: 390–1.
A boy with achondroplasia treated long-term with recombinant growth hormone (3–4 units of subcutaneous somatotropin weekly for 7 years) developed acanthosis nigricans in the groin and axilla.
Rendon M, Cruz P, Sontheimer R, Bergstresser P. J Am Acad Dermatol 1989; 21: 461–9.
In a woman with systemic lupus erythematosus and the type B syndrome of insulin resistance, the acanthosis nigricans cleared after treatment with oral corticosteroids and subcutaneous injection of insulin. Her circulating anti-insulin antibodies also disappeared with treatment of the autoimmune disease.
Pfeifer SL, Wilson RM, Gawkrodger DJ. Postgrad Med J 1999; 75: 421–2.
An obese woman with HAIR-AN syndrome was diagnosed a year later with insulinoma. One year after resection of the tumor the patient’s virilism resolved, and 9 years after the surgery the acanthosis nigricans was much improved.
Kurtoglu S, Atabek ME, Keskin M, Canöz O. Turk J Pediatr 2005; 47: 183–7.
A 3-day-old girl with the salt-wasting type of 21-hydroxylase deficient congenital adrenal hyperplasia presented with acanthosis nigricans of both axillae. Following corticosteroid and mineralocorticoid therapy for disease, the acanthosis nigricans resolved.
Blobstein SH. Cutis 2003; 71: 33–4.
Five obese patients with acanthosis nigricans were successfully treated with 12% ammonium lactate cream twice daily and tretinoin 0.05% cream nightly to one side of the neck (the other side serving as control).
There was no mention of whether the obese patients lost weight during the treatment period, which could have contributed to the improvement.
Montes L, Hirschowitz B, Krumdieck C. J Cutan Pathol 1974; 1: 88–94.
A teenage girl had acanthosis nigricans, deafness, steatorrhea, peripheral sensory nerve demyelination, and hypovitaminosis A. The skin condition improved within 2 weeks of applying retinoic acid ointment 0.1% twice daily.
Weisshaar E, Bonnekoh B, Franke I, Gollnick H. Hautarzt 2001; 52: 499–503 [in German].
A single report of a boy suffering from morbid obesity since infancy. In a right–left comparison the affected skin of one body side was treated with tazarotene 0.05% vs urea 10%, once daily each. A great benefit for the tazarotene-treated side was seen after 3 weeks.
Bohm M, Luger T, Metze D. Br J Dermatol 1998; 139: 932–3.
An obese patient with metastatic transitional cell carcinoma of the bladder, insulin resistance, and acanthosis nigricans was treated with topical calcipotriol 0.005% twice daily for 3 months, which led to improvement of her skin condition.
Tankova T, Koev D, Dakovska L, Kirilov G. Int J Clin Pract 2002; 56: 578–81.
Five obese patients (two children and three adults with diabetes mellitus) were treated with metformin daily for 6 months, resulting in significant reduction in plasma insulin, body weight, and body fat mass. Both children and one adult showed improvement of acanthosis nigricans.
Zayed A, Sobhi R, Abdel Halim DM. J Dermatolog Treat 2012 [epub ahead of print].
Topical trichloroacetic acid used as a superficial chemical peel, once weekly for 4 weeks, showed improvement in appearance of the acanthosis in the six females studied.
Katz R. Arch Dermatol 1980; 116: 110–11.
An obese, hirsute, diabetic woman with acanthosis nigricans was treated with oral isotretinoin (2–3 mg/kg/day for 4 months), producing clearance of the skin problem. However, long-term treatment was required to maintain clearance because the acanthosis nigricans recurred when the retinoid was discontinued.
Because of the side effects of isotretinoin, long-term use for a benign condition may not be practical.
Walling HW, Messingham M, Myers LM, Mason CL, Strauss JS. J Drugs Dermatol 2003; 2: 677–81.
An obese man developed acanthosis nigricans, tripe palms, and laryngeal papillomatosis, with no evidence of malignancy after 6 years of follow-up. Isotretinoin (80 mg/day) led to improvement after 2 months of therapy. The addition of metformin produced extra improvement.
Tercedor J, Rodenas JM. J Am Acad Dermatol 1992; 27: 786.
Ketoconazole improved acanthosis nigricans in a patient with HAIR-AN syndrome. Due to its hepatotoxic effects, oral ketoconazole, which has anti-androgenic effects, is largely avoided nowadays.
Anderson SH, Hudson-Peacock M, Muller AF. Br J Dermatol 1999; 141: 714–16.
A man with metastatic gastric adenocarcinoma and disseminated acanthosis nigricans was treated with palliative chemotherapy, leading to significant improvement.
Greenwood R, Tring F. Br J Dermatol 1982; 106: 697–8.
A man with gastric adenocarcinoma and acanthosis nigricans showed clearance of the skin disease following treatment with cyproheptadine (4 mg three times daily for 3 weeks).
As the patient had undergone palliative gastrectomy 4 months earlier, it is not clear whether removal of the adenocarcinoma or the cyproheptadine was responsible for clearing the acanthosis nigricans.
Schwartz RA. J Am Acad Dermatol 1994; 31: 1.
A white woman with lipodystrophic diabetes mellitus and acanthosis nigricans was treated with dietary fish oil supplementation, leading to improvement of the skin condition despite continued elevation of triglyceride levels.
Andersen RN, Coleman SA, Fish SA. J Clin Endocrinol Metab 1974; 38: 347–55.
A girl with acanthosis nigricans and polycystic ovaries showed complete clearance of acanthosis nigricans and hyperandrogenism after treatment with Ortho-Novum 2 mg/day.
Rosenback A, Ram R. Dermatol Surg 2004; 30: 1158–60.
A woman with axillary acanthosis nigricans was treated with long-pulsed alexandrite laser (5 ms) on one axilla, with the other as an untreated control. The treated axilla showed significant improvement.
Bredlich R, Krahn G, Kunzi-Rapp K, Wortmann S, Peter RU. Br J Dermatol 1998; 139: 937–8.
An obese man with acanthosis nigricans who had failed previous treatments with topical retinoids and salicylic acid was then treated with continuous-wave carbon dioxide laser (three sessions at 4- to 6-week intervals). His acanthosis nigricans improved after 6 months of treatment.
Treatment of Skin Disease Comprehensive Therapeutic Strategies 4e
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