acanthosis nigricans

Acanthosis nigricans appears as dark brown-black, poorly defined, velvety patches of skin, typically affecting the face, neck, underarms, genitals, groin, elbows, knees, anus, umbilicus and nasal crease.

It typically occurs in individuals younger than age 40, is associated with insulin resistance, type 2 diabetes, obesity or endocrinopathies, such as hypothyroidism, acromegaly, polycystic ovary syndrome or Cushing's disease, and may be genetically inherited.{{Cite web |title=Acanthosis nigricans - Symptoms and causes |url=https://www.mayoclinic.org/diseases-conditions/acanthosis-nigricans/symptoms-causes/syc-20368983 |access-date=2021-08-13 |website=Mayo Clinic |language=en}}{{Cite web |title=What Is Acanthosis Nigricans? |url=https://www.webmd.com/skin-problems-and-treatments/acanthosis-nigricans-overview |access-date=2021-08-13 |website=WebMD |language=en}}

Familial acanthosis{{Cite book |last=Thomas B. Fitzpatrick |title=Fitzpatrick's color atlas and synopsis of clinical dermatology |publisher=McGraw-Hill Medical Pub. Division |year=2005 |isbn=978-0-07-144019-6 |edition=5th |location=New York |display-authors=etal}}{{rp|86}} may arise as a result of an autosomal dominant trait, presenting at birth or developing during childhood.{{rp|506}}{{Cite book |last=Rapini, Ronald P. |title=Dermatology: 2-Volume Set |last2=Bolognia, Jean L. |last3=Jorizzo, Joseph L. |publisher=Mosby |year=2007 |isbn=978-1-4160-2999-1 |location=St. Louis}}{{rp|676}}

File:Familial acanthosis nigricans.jpg

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Endocrine syndromes associated with acanthosis nigricans{{rp|506–7}} can develop in many conditions, particularly:{{rp|978}} {{rp|86}}

• starts with insulin resistance, such as diabetes mellitus and metabolic syndrome
• excess circulating androgens, particularly Cushing's disease, acromegaly, polycystic ovary syndrome
• Addison's disease and hypothyroidism
• Rare diseases, including pinealoma, leprechaunism, lipoatrophic diabetes, pineal hyperplasia syndrome, pituitary basophilism, ovarian hyperthecosis, stromal luteoma, ovarian dermoid cysts, Prader-Willi syndrome, and Alström syndrome.

Acanthosis nigricans associated with endocrine dysfunction is more insidious in its onset, is less widespread, and the patients are often concurrently obese.{{rp|676}}

File:Fibrome.jpg|A. nigricans, right armpit; notice the skin tags,{{Cite journal |vauthors=Tamega A, Aranha AM, Guiotoku MM, Miot LD, Miot HA |date=1 January 2010 |title=[Association between skin tags and insulin resistance] |journal=Anais Brasileiros de Dermatologia |volume=85 |issue=1 |pages=25–31 |doi=10.1590/S0365-05962010000100003 |pmid=20464083 |doi-access=free}} an indicator for elevated blood sugar and hyperinsulinaemia

File:Acanthosis nigricans, axillär, ©WIKIDERM.jpg|A. nigricans, axillary

In young persons, acanthosis nigricans 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 cure it, but acanthosis nigricans may lighten up and possibly disappear by treating the root cause, insulin resistance, but it can take months or years to do so.{{Cite web |date=2018-04-12 |title=Nueces County Medical Society {{!}} Health Education - Insulin Resistance and Acanthosis Nigricans in Kids |url=http://www.nuecesmedsociety.org/Template.aspx?id=873 |url-status=dead |archive-url=https://web.archive.org/web/20180412212317/http://www.nuecesmedsociety.org/Template.aspx?id=873 |archive-date=2018-04-12 |access-date=2020-03-01 |website=www.nuecesmedsociety.org}} Insulin resistance syndromes may be divided into type A (HAIR-AN) and type B syndromes.{{rp|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.{{rp|968}} This can also be referred to as pseudoacanthosis nigricans.{{rp|86}} In some cases, AN attributable to obesity and insulin resistance will occur on ones face. Most typically it will be present as a horizontal band on the forehead, but may also appear as perioral hyperpigmentation, periorbital hyperpigmentation, or generalized facial skin darkening.{{Cite journal |last=Verma |first=Shyam |last2=Vasani |first2=Resham |last3=Joshi |first3=Rajiv |last4=Phiske |first4=Meghana |last5=Punjabi |first5=Pritesh |last6=Toprani |first6=Tushar |date=2016 |title=A descriptive study of facial acanthosis nigricans and its association with body mass index, waist circumference and insulin resistance using HOMA2 IR |journal=Indian Dermatology Online Journal |volume=7 |issue=6 |pages=498–503 |doi=10.4103/2229-5178.193898 |issn=2229-5178 |pmc=5134163 |pmid=27990384 |doi-access=free}}

Acanthosis nigricans has been linked to the use of nicotinic acid, glucocorticoid use, combined oral contraceptive pills, and growth hormone therapy.{{rp|86}}

Malignant acanthosis nigricans{{rp|86}} 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.{{rp|86}}{{Cite journal |last=Rigel DS |last2=Jacobs MI |year=1980 |title=Malignant acanthosis nigricans:a review |journal=The Journal of Dermatologic Surgery and Oncology |volume=6 |issue=11 |pages=923–7 |doi=10.1111/j.1524-4725.1980.tb01003.x |pmid=6257767}}

This form of acanthosis nigricans is more likely to involve mucous membranes (25–50% of cases){{Cite journal |last=Schnopp C |last2=Baumstark J |year=2007 |title=Oral acanthosis nigricans |journal=N Engl J Med |volume=357 |issue=9 |pages=e10 |doi=10.1056/NEJMicm062917 |pmid=17761587}} Malignant acanthosis nigricans that may either precede (18%), accompany (60%), or follow (22%) the onset of an internal cancer.{{rp|506}} Malignancy-associated acanthosis nigricans is usually rapid in onset and may be accompanied by skin tags, multiple seborrheic keratoses, or tripe palms.{{rp|676}}

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.{{Cite journal |last=Schwartz RA |date=February 2007 |title=Acral acanthosis nigricans (acral acanthotic anomaly) |journal=J. Am. Acad. Dermatol. |volume=56 |issue=2 |pages=349–50 |doi=10.1016/j.jaad.2006.09.027 |pmid=17224380 |doi-access=free}}{{Cite journal |last=Schwartz RA |date=September 1981 |title=Acral acanthotic anomaly (AAA) |journal=J. Am. Acad. Dermatol. |volume=5 |issue=3 |pages=345–6 |doi=10.1016/S0190-9622(81)80155-7 |pmid=7263979 |doi-access=free}}{{Cite journal |last=Schwartz RA |date=July 1994 |title=Acanthosis nigricans |journal=J. Am. Acad. Dermatol. |volume=31 |issue=1 |pages=1–19; quiz 20–2 |doi=10.1016/S0190-9622(94)70128-8 |pmid=8021347}}{{Cite book |last=Tilgen W |title=Braun-Falco's Dermatology |publisher=Springer |year=2009 |isbn=978-3-540-29312-5 |editor-last=WHC Burgdorf |edition=3rd |location=Heidelberg |pages=1340–7 |chapter=Benign epidermal tumors |editor-last2=G Plewig |editor-last3=HH Wolff |editor-last4=M Landthaler |editor-last5=O Braun-Falco}} While the etiology remains unknown, its presence does not suggest a likelihood of malignancy.

Acanthosis nigricans is caused by increased activation of growth factor receptor proteins, usually due to endocrine dysfunction. This is most commonly insulin-mediated activation of IGF receptors on keratinocytes, as a result of hyperinsulinaemia or insulin resistance, as seen in diabetes mellitus.{{Cite journal |last=Higgins |first=SP |last2=Freemark, M |last3=Prose, NS |date=Sep 15, 2008 |title=Acanthosis nigricans: a practical approach to evaluation and management. |journal=Dermatology Online Journal |volume=14 |issue=9 |pages=2 |doi=10.5070/D37MF6G290 |pmid=19061584}}

Factors involved in the development of acanthosis nigricans include:

• Increased circulating insulin. This activates keratinocyte IGF receptors, particularly IGF-1. At high concentrations, insulin may also displace IGF-1 from insulin-like growth factor-binding protein (IGFBP). Increased circulating IGF may lead to keratinocyte and dermal fibroblast proliferation.
• In hereditary forms of acanthosis nigricans, fibroblast growth factor receptor (FGFR) defects
• Increased transforming growth factor (TGF), which appears to be the mechanism for malignancy-associated acanthosis nigricans. TGF acts on epidermal tissue via the epidermal growth factor receptor (EGFR).{{rp|86}}

In conjunction with increased end levels of IGF, it is likely that perspiration and friction may be necessary predeterminants for lesions, since the level of insulin is usually not enough to activate IGF receptors across the body.

Acanthosis nigricans is typically diagnosed clinically. 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.{{rp|87}}

On biopsy, hyperkeratosis, epidermal folding, leukocyte infiltration, and melanocyte proliferation may be seen.{{rp|979}}{{rp|87}}

Acanthosis nigricans is conventionally divided into benign and malignant forms,{{Cite book |last=Habif |first=Thomas P. |title=Clinical dermatology |publisher=Mosby |year=2009 |isbn=978-0-7234-3541-9 |edition=5th |location=Edinburgh}}{{Cite web |last=Ngan |first=Vanessa |title=Acanthosis nigricans |url=http://dermnetnz.org/systemic/acanthosis-nigricans.html |access-date=23 August 2013}} although may be divided into syndromes according to cause:James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. {{ISBN|0-7216-2921-0}}.{{rp|506}}

• Benign: This may include obesity-related, hereditary, and endocrine forms of acanthosis nigricans.
• Malignant: This may include forms that are associated with tumour products and insulin-like activity, or tumour necrosis factor.

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.{{Cite journal |last=Garofalo |first=L. |last2=A.M. Biscozzi |last3=V. Mastrandrea |last4=E. Bonifazi |year=2003 |title=Acanthosis nigricans vulgaris. A marker of hyperinsulinemia. |url=http://www.dermatologiapediatrica.com/volume13/acanthosis.pdf |url-status=dead |journal=Eur. J. Pediat. Dermatol. |volume=13 |pages=85–8 |archive-url=https://web.archive.org/web/20110709013808/http://www.dermatologiapediatrica.com/volume13/acanthosis.pdf |archive-date=2011-07-09 |access-date=2010-07-29}}{{Cite journal |last=Schwartz |first=Robert A. |year=1994 |title=Acanthosis nigricans |journal=Journal of the American Academy of Dermatology |volume=31 |issue=1 |pages=1–19 |doi=10.1016/S0190-9622(94)70128-8 |pmid=8021347}}

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. Selenium sulfide topical 2 percent applied in thin layer to dry skin ten minutes prior to bathing may clear symptoms. Selenium sulfide applied to dry scalp or skin is an inexpensive well tolerated treatment to balance skin's biome and works by drying fungus like tinea versicolor that can coexist with acanthosis and exacerbate discoloration. Acanthosis nigricans maligna may resolve if the causative tumor is successfully removed.{{Cite journal |last=Brown J |last2=Winkelmann RK |year=1968 |title=Acanthosis nigricans: study of 90 cases |journal=Medicine |volume=47 |issue=1 |pages=33–51 |doi=10.1097/00005792-196801000-00002 |pmid=4868603 |s2cid=2241453 |doi-access=free}}

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. {{rp|87}}

Acanthosis Nigricans was first reported by Unna in 1889.{{Cite book |last=Levine |first=Norman |title=The Pigmentary System: Physiology and Pathophysiology |last2=Burk |first2=Cynthia |date=2008 |publisher=Blackwell Publishing |isbn=978-1-4051-2034-0 |editor-last=Nordlund |editor-first=James J. |edition=2nd |location=Massachusetts |page=907 |language=en |chapter=50. Acquired epidermal hypermelanoses |editor-last2=Boissy |editor-first2=Raymond E. |editor-last3=Hearing |editor-first3=Vincent J. |editor-last4=King |editor-first4=Richard A. |editor-last5=Oetting |editor-first5=William S. |editor-last6=Ortonne |editor-first6=Jean-Paul |chapter-url=https://books.google.com/books?id=4sn46U1uexoC&pg=PA907}}

{{Reflist}}

{{Commons category}}

{{Medical resources

| DiseasesDB = 58

| ICD10 = {{ICD10|L|83||l|80}}

| ICD9 = {{ICD9|701.2}}

| ICDO =

| OMIM = 100600

| MedlinePlus = 000852

| eMedicineSubj = derm

| eMedicineTopic = 1

| MeshID = D000052

| SNOMED CT = 402599005

}}

{{Pigmentation disorders}}

{{Cutaneous ketatosis, ulcer, atrophy, and necrobiosis}}

{{Paraneoplastic syndromes}}

Category:Endocrine-related cutaneous conditions

Category:Medical signs

Category:Medical conditions related to obesity