Acanthosis nigricans

Acanthosis nigricans

Acanthosis nigricans on axilla
Classification and external resources
Specialty Dermatology
ICD-10 L83
ICD-9-CM 701.2
OMIM 100600
DiseasesDB 58
MedlinePlus 000852
eMedicine derm/1
MeSH D000052

Acanthosis nigricans is a brown to black, poorly defined, velvety hyperpigmentation of the skin. It is usually found in body folds,[1] such as the posterior and lateral folds of the neck, the armpits, groin, navel, forehead, and other areas.

Classification

Acanthosis nigricans is conventionally divided into benign and malignant forms,[2][3] although may be divided into syndromes according to cause:[4]:506

An alternate classification system still used to describe acanthosis nigricans was proposed in 1994. It delineates acanthosis nigricans syndromes according to their associated syndromes, including benign and malignant forms, forms associated with obesity and drugs, acral acanthosis nigricans, unilateral acanthosis nigricans, and mixed and syndromic forms.[5][6]

Signs and symptoms

Acanthosis nigricans may present with thickened, velvety, relatively darker areas of skin on the neck, armpit and in skin folds.[2]

Causes

It typically occurs in individuals younger than age 40, may be genetically inherited, and is associated with obesity or endocrinopathies, such as hypothyroidism, acromegaly, polycystic ovary disease, insulin-resistant diabetes, or Cushing's disease.

Type I - familial[7]:86

Familial acanthosis may arise as a result of an autosomal dominant trait, presenting at birth or developing during childhood.[4]:506[8]:676

Type II - endocrine[4]:506–7

Endocrine syndromes associated with acanthosis nigricans can develop in many conditions, particularly:[2]:978 [7]:86

Acanthosis nigricans associated with endocrine dysfunction is more insidious in its onset, is less widespread, and the patients are often concurrently obese.[8]:676

Type III - obesity and pseudoacanthosis nigricans[7]:86

In young persons, AN is a visible marker which strongly suggests insulin resistance. Higher than normal insulin levels in the blood stream cause the growth of darkened skin over certain areas of the body. No skin treatment will get rid of AN. Acanthosis nigricans may lighten up and possibly go away by treating the root cause, insulin resistance, but it can take months or years to do so.[9] Insulin resistance syndromes may be divided into type A (HAIR-AN) and type B syndromes.[2]:978 The majority of cases of acanthosis nigricans are associated with obesity and otherwise idiopathic. This is likely because of insulin resistance, and more likely to occur in darker-skinned persons.[2]:968 This can also be referred to as pseudoacanthosis nigricans.

Type IV - drug-related[7]:86

Acanthosis nigricans has been linked to the use of nicotinic acid,[2] glucocorticoid use, combined oral contraceptive pills, and growth hormone therapy.[7]

Type V - malignancy[7]:86

Malignant acanthosis nigricans refers to acanthosis nigricans occurring as a paraneoplastic syndrome associated with a cancer. Malignant acanthosis nigricans is most commonly associated with gastrointestinal adenocarcinomas, as well as genitourinary cancers such as those of the prostate, breast, and ovary. Other cancers, such as those of the lung, stomach, and lymphoma, are occasionally associated with acanthosis nigricans.[7]:86[10]

This form of acanthosis nigricans is more likely to involve mucous membranes (25-50% of cases)[3][11] Malignant acanthosis nigricans that may either precede (18%), accompany (60%), or follow (22%) the onset of an internal cancer.[4]:506 Malignancy-associated acanthosis nigricans is usually rapid in onset and may be accompanied by skin tags, multiple seborrheic keratoses, or tripe palms.[8]:676

Acral acanthotic anomaly

Acral acanthotic anomaly refers to a variant of acanthosis nigricans limited to the elbows, knees, knuckles, and dorsal surfaces of the feet, in the absence of any other findings, in otherwise healthy individuals.[12][13][14][15] While the etiology remains unknown,[15] its presence does not suggest a likelihood of malignancy.[15]

Pathophysiology

The pathogenesis of acanthosis nigricans is poorly understood, and likely to relate to an interplay of factors,[16] including insulin-mediated activation of ILGF receptors on keratinocytes, and increased growth factor levels.[16]

Factors involved in the development of acanthosis nigricans include:

In conjunction with increased end levels of ILGF, it is likely that perspiration and friction may be necessary predeterminants for lesions.[16]

Diagnosis

Acanthosis nigricans is typically diagnosed clinically.[2] A skin biopsy may be needed in unusual cases. If no clear cause is obvious, it may be necessary to search for one. Blood tests, an endoscopy, or X-rays may be required to eliminate the possibility of diabetes or cancer as the cause.[7]:87

On biopsy, hyperkeratosis, epidermal folding, leukocyte infltration, and melanocyte proliferation may be seen.[2]:979[7]:87

Differential diagnosis

Acanthosis nigricans should be distinguished from the casal collar appearing in pellagra.

Prognosis

Acanthosis nigricans is likely to improve in circumstances where a known cause is removed. For example, obesity-related acanthosis nigricans will improve with weight loss, and drug-induced acanthosis nigricans is likely to resolve when the drug is ceased. Hereditary variants may or may not fade with age, and malignancy-associated variants may, after a malignancy is removed, fade.[7] :87

Treatment

People with acanthosis nigricans should be screened for diabetes and, although rare, cancer. Controlling blood glucose levels through exercise and diet often improves symptoms. Topical fade creams (normally used for eliminating age spots) can lighten skin cosmetically in less severe cases. Acanthosis nigricans maligna may resolve if the causative tumor is successfully removed.[17]

References

  1. "acanthosis nigricans" at Dorland's Medical Dictionary
  2. 1 2 3 4 5 6 7 8 9 10 Habif, Thomas P. (2009). Clinical dermatology (5th ed.). Edinburgh: Mosby. ISBN 978-0-7234-3541-9.
  3. 1 2 Ngan, Vanessa. "Acanthosis nigricans". Retrieved 23 August 2013.
  4. 1 2 3 4 James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
  5. Garofalo, L.; A.M. Biscozzi; V. Mastrandrea; E. Bonifazi (2003). "Acanthosis nigricans vulgaris. A marker of hyperinsulinemia." (PDF). Eur. J. Pediat. Dermatol. 13: 85–8. Retrieved 2010-07-29.
  6. Schwartz, Robert A. (1994). "Acanthosis nigricans". Journal of the American Academy of dermatology. 31 (1): 1–19. doi:10.1016/S0190-9622(94)70128-8. PMID 8021347.
  7. 1 2 3 4 5 6 7 8 9 10 11 Thomas B. Fitzpatrick; et al. (2005). Fitzpatrick's color atlas and synopsis of clinical dermatology (5th ed.). New York: McGraw-Hill Medical Pub. Division. ISBN 0-07-144019-4.
  8. 1 2 3 Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 1-4160-2999-0.
  9. What causes AN ? - http://www.nuecesmedsociety.org
  10. Rigel DS; Jacobs MI (1980). "Malignant acanthosis nigricans:a review". J Dermatol Surg Oncol. 6 (11): 923–7. PMID 6257767.
  11. Schnopp C; Baumstark J (2007). "Oral acanthosis nigricans". N Engl J Med. 357 (9): e10. doi:10.1056/NEJMicm062917. PMID 17761587.
  12. Schwartz RA (February 2007). "Acral acanthosis nigricans (acral acanthotic anomaly)". J. Am. Acad. Dermatol. 56 (2): 349–50. doi:10.1016/j.jaad.2006.09.027. PMID 17224380.
  13. Schwartz RA (September 1981). "Acral acanthotic anomaly (AAA)". J. Am. Acad. Dermatol. 5 (3): 345–6. doi:10.1016/S0190-9622(81)80155-7. PMID 7263979.
  14. Schwartz RA (July 1994). "Acanthosis nigricans". J. Am. Acad. Dermatol. 31 (1): 1–19; quiz 20–2. doi:10.1016/S0190-9622(94)70128-8. PMID 8021347.
  15. 1 2 3 Tilgen W (2009). "Benign epidermal tumors". In WHC Burgdorf; G Plewig; HH Wolff; M Landthaler; O Braun-Falco. Braun-Falco's Dermatology (3rd ed.). Heidelberg: Springer. pp. 1340–7. ISBN 3-540-29312-4.
  16. 1 2 3 4 5 Higgins, SP; Freemark, M; Prose, NS (Sep 15, 2008). "Acanthosis nigricans: a practical approach to evaluation and management.". Dermatology online journal. 14 (9): 2. PMID 19061584.
  17. Brown J; Winkelmann RK (1968). "Acanthosis nigricans: study of 90 cases". Medicine. 47 (1): 33–51. doi:10.1097/00005792-196801000-00002. PMID 4868603.

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