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How Acanthosis Nigricans Can Indicate Insulin Resistance Or Diabetes

Acanthosis nigricans is a skin disorder characterized by velvety, papillomatous, hyperkeratotic, darkly pigmented skin lesions found in body folds such as the axilla and neck. In obese patients, the presence of acanthosis nigricans is an indicator of insulin resistance or diabetes mellitus.1 Kahn and colleagues first identified the link between acanthosis nigricans and insulin resistance in 1976.2 In 2000, the American Diabetes Association formally established acanthosis nigricans as an indicator of the development of diabetes.3

The theory is that acanthosis nigricans results from factors that stimulate epidermal keratinocyte and dermal fibroblast proliferation. High concentrations of insulin can stimulate keratinocyte and fibroblast proliferation through high affinity binding to insulin-like growth factor 1 (IGF-1) receptors.4 Additionally, elevated IGF-1 levels in obese patients can contribute to keratinocyte and fibroblast proliferation.4

Acanthosis nigricans is often an incidental finding in the physical exam, presenting as asymptomatic areas of dark, thickened skin. Occasionally the lesions may become pruritic. Acanthosis nigricans lesions are characterized by symmetrical, darkly pigmented, velvety plaques. They are most common in the skin folds of the axilla, neck and groin.5 Skin tags are also frequently visible in surrounding areas affected by acanthosis nigricans.5 

There are several other causes of acanthosis nigricans in addition to insulin resistance and diabetes mellitus. Schwartz described nine types of acanthosis nigricans: obesity-associated, syndromic, acral, unilateral, generalized, familial, drug-induced, malignant and mixed type.6 Obesity-associated acanthosis nigricans is the most common type of acanthosis nigricans and insulin resistance is most often present in these patients.

With the majority of cases of acanthosis nigricans resulting from obesity and insulin resistance, the initial workup should include a glycosylated hemoglobin level or glucose tolerance test. Screening for insulin resistance with an evaluation of plasma insulin level can detect insulin resistance in younger patients who do not yet have an abnormal glycosylated hemoglobin level.7 Addison’s disease, hypothyroidism and disorders of androgen excess (Cushing’s disease, polycystic ovarian disease) are also common causes of acanthosis nigricans and the clinician's workup should consider these potential etiologies.7 Given the potential association with malignancy in cases of acanthosis nigricans without another identifiable cause that present in middle-age and older patients with extensive skin findings, a workup for internal malignancy is indicated.8

Treatment of acanthosis nigricans involves identifying and correcting the underlying disease process. Correction of hyperinsulinemia can decrease the severity and extent of acanthosis nigricans skin lesions.9,10 Similarly, weight reduction can result in improvement or resolution of acanthosis nigricans in obese patients.9,10

Acanthosis nigricans is a benign skin condition but it can be an important indicator of systemic disease. Podiatric physicians should be aware of the clue that acanthosis nigricans skin lesions in obese patients frequently indicate underlying insulin resistance or diabetes mellitus.

References

1. Schilling WHK, Crook MA. Cutaneous stigmata associated with insulin resistance and increased cardiovascular risk. Int J Dermatol. 2014;53:1062-9.

2. Kahn CR, Flier JS, Bar RS, Archer JA, Gorden P, Martin MM, Roth J. The syndromes of insulin resistance and acanthosis nigricans. Insulin-receptor disorders in man. N Engl J Med. 1976; 205(14):739-745.

3. Sinha S, Schwartz RA. Juvenile acanthosis nigricans. J Am Acad Dermatol. 2007;57(3):502-8.

4. Higgins SP, Freemark M, Prose NS. Acanthosis nigricans: a practical approach to evaluation and management. Dermatol Online J.  2008;14(9):2.

5. James WD, Berger TG, Elston DM. Andrew's Diseases of the Skin: Clinical Dermatology, 11th Edition, Saunders Elsevier Publications, Canada, 2011; pp. 494–5.

6. Schwartz RA. Acanthosis nigricans. J Am Acad Dermatol. 1994;31:1–19.

7. Matsuoka LY, Wortsman J, Gavin JR, Goldman J. Spectrum of endocrine abnormalities associated with acanthosis nigricans. Am J Med.  1987;83(4):719-25.

8. Phiske MM. An approach to acanthosis nigricans. Indian Dermatol Online J. 2014;5(3):239-49.

9. Bellot-Rojas P, Posadas-Sanchez R, Caracas-Portilla N, Zamora-Gonzalez J, Cardoso-Saldaña G, Jurado-Santacruz F, et al. Comparison of metformin versus rosiglitazone in patients with acanthosis nigricans: A pilot study. J Drugs Dermatol. 2006;5(9):884–9.

10. Puri N. A study of pathogenesis of acanthosis nigricans and its clinical implications. Indian J Dermatol. 2011;56(6):678–83.

Comments

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I'm almost certain I have seen this before, but I am looking forward to work tomorrow at the hospital to see if I can spot acanthosis nigricans among the large diabetic type 2 population. Thank you for your informative posting.
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