Basics
Description
- 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).
Epidemiology
- 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 (2,3)[A].
Prevalence
- A multiethnic cohort study conducted in the United States in 2007 found that 19% of its 1,730 participants had AN (2).
- It is more prevalent in Hispanic, African American, and Native American individuals compared to White or Asian individuals (1).
Etiology and Pathophysiology
- Obesity-induced (pseudo AN) and insulin resistance (4)
- 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 metabolic disorders associated with AN include polycystic ovarian syndrome (PCOS), acromegaly, and Cushing syndrome.
- 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.
- May also present with other cutaneous disorders representing internal malignancy such as Leser-Tr ©lat 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.
Genetics
- Hyperinsulinemia stimulates insulin-like growth factor 1 (IGF-I), which in turn induces the proliferation of dermal fibroblasts and keratinocytes, resulting in the hyperkeratosis and papillomatosis of AN (4).
- Another mechanism not associated with insulin resistance is a mutation in fibroblast growth receptor factor (FGFR) (4).
Risk Factors
- Obesity
- Insulin resistance
General Prevention
Encourage diet and exercise to all age groups to reduce likelihood of insulin resistance syndrome
Diagnosis
History
- 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
Physical Exam
- 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
Differential Diagnosis
- 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 & Interpretation
Initial Tests (lab, imaging)
Although AN is a clinical diagnosis, one may consider the following tests if risk factors are present (5)[C]:
- 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.
Treatment
General Measures
- Improvement of AN in obese individuals who succeed at weight loss
- Discontinue offending drugs in drug-induced AN (1)[B].
- Improvement of malignant AN with treatment of underlying malignancy
Medication
First Line
Medications are not generally recommended; however, metformin and rosiglitazone can modestly improve skin texture in individuals with insulin resistance (6)[A].
Issues for Referral
Refer to dermatologist if diagnosis of AN is not definite.
Additional Therapies
Only case reports exist regarding the use of topical and other oral agents aiming to improve AN (5),(6)[A].
Ongoing Care
Follow-up Recommendations
- 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
Diet
Maintain a well-balanced, low-calorie diet to achieve weight loss, if applicable.
Prognosis
Related to underlying cause of AN
Complications
- Metastasis in malignant AN
- End-organ damage in untreated hyperinsulinemia associated AN (1)[B]
References
1.Puri N. A study of pathogenesis of acanthosis nigricans and its clinical implications. Indian J Dermatol. 2011;56(6):678-683.
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2.Kong AS, Williams RL, Rhyne R, et al. Acanthosis Nigricans: high prevalence and association with diabetes in a practice-based research network consortium-a PRImary care Multi-Ethnic network (PRIME Net) study. J Am Board Fam Med. 2010;23(4):476-485.
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3.Brickman WJ, Binns HJ, Jovanovic BD, et al. Acanthosis nigricans: a common finding in overweight youth. Pediatr Dermatol. 2007;24(6):601-606.
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4.Litonjua P, Pi ±ero-Pilo ±a A, Aviles-Santa L, et al. Prevalence of acanthosis nigricans in newly-diagnosed type 2 diabetes. Endocr Pract. 2004;10(2):101-106.
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5.Higgins SP, Freemark M, Prose NS. Acanthosis nigricans: a practical approach to evaluation and management. Dermatol Online J. 2008;14(9):2.
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6.Badr D, Kurban M, Abbas O. Metformin in dermatology: an overview. J Eur Acad Dermatol Venereol. 2013;27(11):1329-1335.
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Codes
ICD09
- 701.2 Acquired acanthosis nigricans
- 757.39 Other specified anomalies of skin
ICD10
- L83 Acanthosis nigricans
- Q82.8 Other specified congenital malformations of skin
SNOMED
- 72129000 acquired acanthosis nigricans (disorder)
- 238634000 Benign acanthosis nigricans (disorder)
- 238635004 Drug-induced acanthosis nigricans (disorder)
Clinical Pearls
- 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 and rosiglitazone can provide modest improvement of skin texture in individuals affected by insulin resistance.