- Acanthosis nigricans (AN) is a benign dermatosis characterized by velvety, hyperpigmented, hyperkeratotic plaques, which
- Are usually symmetric
- Most often occur on the posterior neck, flexural and intertriginous surfaces (axilla, elbow, inframammary areas, groin and anogenital regions), and sometimes in mucocutaneous areas
- Are most often asymptomatic but may cause pruritus
- Typically a sign of hyperinsulinemia and insulin resistance but can be a marker of malignancy
- Individuals with AN are at risk of developing metabolic syndrome.
- Etiologies include obesity, insulin resistance, genetic syndromes, familial AN, malignant AN, and drug reactions (1).
- AN is more common between the ages of 11 and 40 years and in those with body mass index (BMI) ≥30.
- It is more common in individuals with diabetes or risk factors for diabetes.
- It may be a useful indicator of risk of diabetes mellitus (2) and subclinical atherosclerosis (3).
- Prevalence of AN in unselected populations varies from 7% to 74% according to age, race, frequency of type, degree of obesity, and concomitant endocrinopathies (2).
- It is more prevalent in Hispanic, African American, and Native American individuals compared to white or Asian individuals (1).
- In a study of 89 African Americans with AN, there was a 21.3% frequency of DM2 (2).
Etiology and Pathophysiology
- Obesity-induced (pseudo AN) and insulin resistance (2)
- Are the most common etiologies of AN
- More prevalent in individuals with BMI >30. It is weight dependent and may regress with weight loss.
- Higher prevalence of AN in individuals with more risk factors for diabetes and those with type 2 diabetes
- Other endocrinopathies associated with AN include polycystic ovarian syndrome (PCOS), acromegaly, Cushing syndrome, thyroid diseases, hirsutism, and Addison disease.
- Syndromic AN (1)
- Genetic disorders characterized by insulin resistance can also present with AN. Examples include Down syndrome, leprechaunism, congenital generalized lipodystrophy, and familial partial lipodystrophy.
- Familial AN (1)
- Autosomal dominant mutation of the fibroblast growth factor receptor 3 gene
- Lesions are usually seen in early childhood.
- Malignant AN (1)
- A rare cause of AN characterized by
- Sudden onset, rapid progression, and more extensive lesions
- Presents in atypical locations such as in the mucosa, palms, and soles
- It usually presents in older adults who are often not obese.
- 90–95% are associated with abdominal cavity adenocarcinomas.
- A rare cause of AN characterized by
- May also present with other cutaneous disorders representing internal malignancy such as Leser-Trélat sign (sudden onset of multiple seborrheic keratosis) or tripe palms (ridged velvety lesions of the palms)
- Drug-induced AN (1)
- A rare cause that can be seen with drugs that promote hyperinsulinemia such as systemic glucocorticoids, insulin, oral contraceptives (OCPs), niacin, testosterone, and protease inhibitors.
- Lesions usually regress after discontinuation of these drugs.
High levels of insulin stimulate epidermal keratocytes and dermal fibroblasts via insulin-like growth factor receptors (IGF-1). The keratocyte proliferation leads to skin changes like papillomatosis and hyperkeratosis (4).
Encourage diet and exercise to all age groups to reduce likelihood of insulin resistance syndrome.
- Age of onset
- Most common between the ages of 11 and 40 years
- Occurrence in infancy suggests familial or syndromic AN.
- Malignant AN is more common in older adults.
- Past medical history
- Obesity, diabetes, PCOS, acromegaly, Cushing syndrome, malignancy
- Medication history
- OCPs, corticosteroids, subcutaneous insulin, testosterone, HIV protease inhibitors
- Family history of AN
- Height, weight, and BMI
- Growth rate in children
- Blood pressure measurement to screen for hypertension
- Physical exam significant for an endocrinopathy such as diabetes, PCOS, or Cushing syndrome (5)
- Skin exam: Early or mild lesions may appear as a macular discoloration. It may also have a dirty appearance on the affected skin with a rough texture.
- Often appears as a symmetric hyperpigmented, hyperkeratotic, velvety to verrucous brown plaques
- Most commonly found on the sides of the neck and flexural surfaces
- Postinflammatory hyperpigmentation
- Superficial spreading melanoma
- Skin staining
- Melanocytic nevus
- Linear epidermal nevus
- Poor hygiene
- Tinea versicolor
- Granular parakeratosis
- Confluent and reticulated papillomatosis
- Mycosis fungoides
Diagnostic Tests & InterpretationInitial Tests (lab, imaging)
- Glycohemoglobin or fasting blood glucose, fasting lipid panel, thyroid function studies, electrolytes to rule out diabetes or other endocrinopathies
- Rule out PCOS in obese women with features of PCOS.
- Biopsy is not indicated unless malignant skin conditions are likely.
- Consider screening for malignancies in individuals with atypical presentations.
- Low testosterone levels may be a predictor of AN in male obese patients (6).
Medications are not generally indicated; however, metformin has the most promising data to support its use in reducing AN lesions. Also added benefits include improvement in insulin levels and weight loss with minimal adverse reactions (7)[A].
Issues For Referral
Refer to dermatologist if diagnosis of AN is not definite.
- Close monitoring of BMI, glycohemoglobin, and blood pressure in obese individuals and those with insulin resistance
- Close follow-up and appropriate interventions in individuals with history of malignant AN
Maintain a well-balanced, low-calorie diet to achieve weight loss, if applicable.
Related to underlying cause of AN
- L83 Acanthosis nigricans
- Q82.8 Other specified congenital malformations of skin
- 701.2 Acquired acanthosis nigricans
- 757.39 Other specified anomalies of skin
- 238634000 Benign acanthosis nigricans (disorder)
- 238635004 Drug-induced acanthosis nigricans (disorder)
- 72129000 acquired acanthosis nigricans (disorder)
- AN is a benign dermatosis that is commonly associated with hyperinsulinemia and may be a useful indicator of diabetes mellitus.
- It may also be a marker of malignancy.
- AN due to obesity, drugs, and malignancy improves with treatment of these inciting causes.
- Metformin can provide modest improvement of skin texture in individuals affected by insulin resistance.
Ronald L. Cook, DO, MBA
Jessica Gray, MD
- Puri N. A study of pathogenesis of acanthosis nigricans and its clinical implications. Indian J Dermatol. 2011;56(6):678–683. [PMID:22345770]
- Barbato MT, Criado PR, Silva AK, et al. Association of acanthosis nigricans and skin tags with insulin resistance. An Bras Dermatol. 2012;87(1):97–104. [PMID:22481657]
- Guevara-Gutiérrez E, Tlacuilo-Parra A, Gutiérrez-Fajardo P, et al. A study of the association of acanthosis nigricans with subclinical atherosclerosis. Indian J Dermatol Venereol Leprol. 2017;83(2):190–194. [PMID:18035980]
- Abraham C, Rozmus CL. Is acanthosis nigricans a reliable indicator for risk of type 2 diabetes in obese children and adolescents? A systematic review. J Sch Nurs. 2012;28(3):195–205. [PMID:22179051]
- Higgins SP, Freemark M, Prose NS. Acanthosis nigricans: a practical approach to evaluation and management. Dermatol Online J. 2008;14(9):2. [PMID:19061584]
- Huang Y, Chen J, Wang X, et al. The clinical characteristics of obese patients with acanthosis nigricans and its independent risk factors. Exp Clin Endocrinol Diabetes. 2017;125(3):191–195. [PMID:18492785]
- Romo A, Benavides S. Treatment options in insulin resistance obesity-related acanthosis nigricans. Ann Pharmacother. 2008;42(7):1090–1094. [PMID:18492785]
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