Acanthosis Nigricans

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) and subclinical atherosclerosis (3).

Prevalence
  • 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.
  • 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.

Genetics
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).

Risk Factors

  • Obesity (3)
  • Insulin resistance (3)
  • Race and ethnicity (3)
  • Family history of DM2 (3)

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.
  • Low testosterone levels may be a predictor of AN in male obese patients (6).

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 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.

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]

Codes

ICD-10

  • L83 Acanthosis nigricans
  • Q82.8 Other specified congenital malformations of skin

ICD-9

  • 701.2 Acquired acanthosis nigricans
  • 757.39 Other specified anomalies of skin

SNOMED

  • 238634000 Benign acanthosis nigricans (disorder)
  • 238635004 Drug-induced acanthosis nigricans (disorder)
  • 72129000 acquired 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 can provide modest improvement of skin texture in individuals affected by insulin resistance.

Authors


Ronald L. Cook, DO, MBA
Jessica Gray, MD

Bibliography

  1. Puri N. A study of pathogenesis of acanthosis nigricans and its clinical implications. Indian J Dermatol. 2011;56(6):678–683.  [PMID:22345770]
  2. 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]
  3. 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]
  4. 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]
  5. Higgins SP, Freemark M, Prose NS. Acanthosis nigricans: a practical approach to evaluation and management. Dermatol Online J. 2008;14(9):2. [PMID:19061584]
  6. 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]
  7. 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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TY - ELEC T1 - Acanthosis Nigricans ID - 816911 Y1 - 2019 PB - 5-Minute Clinical Consult, Updating UR - https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816911/all/Acanthosis_Nigricans ER -