View source for Acanthosis nigricans

{{Infobox medical condition
| name          = Acanthosis nigricans
| image         = Acanthosis-nigricans4.jpg
| caption       = Acanthosis nigricans on the [[axilla|armpit]]
| field         = [[Dermatology]]
}}

'''Acanthosis nigricans''' is a cutaneous finding characterized by brown-to-black, velvety [[hyperpigmentation]] of the [[skin]], most often affecting body folds such as the posterior neck, axillae, groin and umbilicus.<ref name="Andrews2020" /> It is strongly associated with [[insulin resistance]] and [[hyperinsulinaemia]], including in [[type 2 diabetes]] and [[metabolic syndrome]]. Excess insulin activates insulin and insulin-like growth factor signalling pathways, stimulating proliferation of [[keratinocytes]] and [[fibroblasts]] and producing the characteristic plaques.<ref name="Higgins2008" />

Acanthosis nigricans may also occur in hereditary syndromes, as a reaction to medications or as a [[paraneoplastic syndrome]] associated with internal malignancy. In children, it is an important clinical marker of metabolic and cardiometabolic risk.<ref name="Pollock2022" />

== Signs and symptoms ==
Acanthosis nigricans presents as hyperpigmented, velvety plaques with poorly defined borders. Common sites include:
* posterior and lateral neck folds
* axillae
* groin and genitals
* umbilicus
* elbows and knees
* forehead, periorbital and perioral areas

Lesions are usually asymptomatic, though mild pruritus may occur.<ref name="Andrews2020" />

== Causes ==
Acanthosis nigricans arises from several distinct mechanisms. It most commonly reflects insulin resistance and is frequently associated with type 2 diabetes, obesity and endocrine disorders such as hypothyroidism, acromegaly, polycystic ovary syndrome and Cushing's disease.<ref name="Mayo" /><ref name="WebMD" /> It may also be inherited, medication-related or associated with internal malignancy. Review articles describe acanthosis nigricans primarily as a marker of systemic metabolic dysfunction rather than a primary skin disease.<ref name="Parmar2025" /><ref name="Karadag2018" /><ref name="Popa2019" />

=== Acral acanthotic anomaly ===
Acral acanthotic anomaly is a localized variant affecting the elbows, knees, knuckles and dorsal feet. It occurs in otherwise healthy individuals, and its etiology is unknown.<ref name="Schwartz2007" /><ref name="Schwartz1981" /> It is not associated with internal disease.<ref name="Tilgen2009" />

=== Familial (Type I) ===
Familial acanthosis nigricans is an [[autosomal dominant]] condition presenting at birth or during childhood.<ref name="Fitzpatrick2005" /><ref name="Andrews2006" />

<gallery>
File:Familial acanthosis nigricans3.jpg|Familial acanthosis nigricans
</gallery>

=== Endocrine (Type II) ===
Endocrine-associated acanthosis nigricans occurs in metabolic or hormonal disorders that alter glucose or androgen levels.<ref name="Habif2009" />{{rp|978}}

Common associated conditions include:
* marked insulin resistance (diabetes mellitus, metabolic syndrome)
* androgen excess (acromegaly, Cushing's disease, polycystic ovary syndrome)
* Addison's disease and hypothyroidism
* rare syndromes including Alström syndrome, Prader–Willi syndrome, leprechaunism, pinealoma, lipoatrophic diabetes, pituitary basophilism, pineal hyperplasia, ovarian hyperthecosis, stromal luteoma and ovarian dermoid cysts

This form usually has a gradual onset and often occurs in people who are also obese.<ref name="Bolognia2007" />{{rp|676}}

<gallery>
File:Fibrome.jpg|Skin tags (acrochordons), which may accompany endocrine-associated AN
</gallery>

=== Malignancy (Type V) ===
Malignant acanthosis nigricans is a paraneoplastic syndrome most often associated with gastrointestinal adenocarcinomas, particularly gastric cancer.<ref name="Popa2019" /><ref name="Rigel1980" /> Less commonly, it occurs with malignancies of the breast, ovary, prostate, thyroid, lung or lymphoid tissues.

It may precede, accompany or follow a cancer diagnosis.<ref name="Andrews2006" />{{rp|506}} Mucosal involvement is more common than in benign forms.<ref name="Schnopp2007" /> Additional findings may include multiple [[seborrhoeic keratoses]], [[skin tags]] and [[tripe palms]].<ref name="Bolognia2007" />{{rp|676}}

=== Obesity and pseudoacanthosis nigricans (Type III) <span id="Pseudoacanthosis_nigricans"></span> ===
In young people, acanthosis nigricans is a visible marker of insulin resistance. Elevated insulin stimulates epidermal proliferation.<ref name="Nueces2018" /> Insulin resistance syndromes may be classified as type A (HAIR-AN) or type B.<ref name="Habif2009" />{{rp|978}}

Most cases are obesity-associated and otherwise idiopathic. This pattern is more common in darker-skinned individuals and is sometimes termed ''pseudoacanthosis nigricans''.<ref name="Fitzpatrick2005" />{{rp|86}}

Facial involvement may appear as a horizontal forehead band or as periorbital or perioral hyperpigmentation.<ref name="Verma2016" />

=== Pediatric associations ===
In children and adolescents, acanthosis nigricans commonly co-occurs with overweight and obesity and functions as a clinical marker of insulin resistance and increased cardiometabolic risk.<ref name="Pollock2022" /> Longitudinal studies show higher rates of subsequent metabolic syndrome.<ref name="Taren2023" /> Cross-sectional studies link acanthosis nigricans with low serum 25-hydroxyvitamin D levels.<ref name="Isart2022" />

=== Drug-related (Type IV) ===
Medications associated with acanthosis nigricans include nicotinic acid, glucocorticoids, combined oral contraceptives and growth hormone therapy.<ref name="Fitzpatrick2005" />{{rp|86}} A systematic review has reported additional agents, including insulin, hormonal therapies, antineoplastic medications and certain biologics.<ref name="Mourad2021" />

== Pathophysiology ==
Acanthosis nigricans results from activation of [[growth factor receptor]] pathways, most commonly insulin-mediated stimulation of [[insulin-like growth factor receptor]] on keratinocytes and fibroblasts.<ref name="Higgins2008" /> Hyperinsulinaemia may also displace IGF-1 from its binding proteins, amplifying epidermal proliferation.

Contributing mechanisms include:
* insulin and IGF-1 driven proliferation of keratinocytes and fibroblasts<ref name="Higgins2008" />
* fibroblast growth factor receptor abnormalities in hereditary forms<ref name="Higgins2008" />
* transforming growth factor-α overexpression in malignancy-associated cases, activating the [[epidermal growth factor receptor]]<ref name="Fitzpatrick2005" />{{rp|86}}

Sweat, friction and occlusion may accentuate lesion development in predisposed areas.<ref name="Higgins2008" />

== Diagnosis ==
Acanthosis nigricans is typically diagnosed clinically based on its characteristic velvety hyperpigmentation and distribution.<ref name="Habif2009" /> A skin biopsy is rarely needed but, when performed, shows hyperkeratosis, papillomatosis and mild basal hyperpigmentation.<ref name="Fitzpatrick2005" />{{rp|87}}

Evaluation aims to identify associated conditions. Investigations may include:
* fasting glucose or HbA1c
* thyroid function tests
* androgen measurements, when indicated
* endoscopy or imaging when malignancy is suspected<ref name="Fitzpatrick2005" />{{rp|87}}

== Classification ==
A conventional clinical distinction separates:
* '''Benign acanthosis nigricans''': obesity-related, endocrine-associated, hereditary and drug-induced forms<ref name="Habif2009" />
* '''Malignant acanthosis nigricans''': associated with internal malignancy, particularly gastrointestinal adenocarcinoma<ref name="Rigel1980" />

A broader classification proposed in 1994 groups acanthosis nigricans into benign, malignant, obesity-associated, drug-induced, acral, unilateral and mixed or syndromic variants.<ref name="Schwartz1994" />

==Treatment==
Management of acanthosis nigricans (AN) generally involves evaluating for and addressing any associated underlying condition rather than treating the skin changes alone. When AN occurs in the setting of obesity, insulin resistance or type 2 diabetes mellitus, improvement in metabolic status may be followed by gradual softening or lightening of the lesions, although the degree of change varies.<ref name="Rogers2017">{{cite journal
 |last=Rogers
 |first=R S
 |title=Current treatment options for acanthosis nigricans
 |journal=Clinical, Cosmetic and Investigational Dermatology
 |date=2017
 |volume=10
 |pages=423–429
 |doi=10.2147/IJN.S139215
 |doi-access=free
 |pmid=28860760
 |pmc=5577798
}}</ref>

Drug-induced AN may improve after reduction or discontinuation of the causative medication when clinically appropriate. Reported associations include systemic corticosteroids, high-dose nicotinic acid and certain hormonal therapies.<ref name="Rogers2017"/>

In malignancy-associated AN, particularly that linked to gastrointestinal adenocarcinomas, regression of the cutaneous changes has been observed following treatment of the underlying tumour, though this is not universal.<ref name="Curth1963">{{cite journal
 |last=Curth
 |first=H O
 |title=Significance of acanthosis nigricans
 |journal=Archives of Dermatology
 |date=1963
 |volume=88
 |issue=1
 |pages=67–76
 |doi=10.1001/archderm.1963.01590250069011
 |doi-broken-date=16 November 2025
 |pmid=13968919
}}</ref> Sudden onset, rapid progression or mucosal involvement have been described in malignant forms and may prompt further evaluation.<ref name="Rogers2017"/>

===Topical and procedural therapies===
Topical therapies are used mainly for cosmetic reasons. Small clinical studies have reported improvement with topical retinoids, urea preparations and other keratolytic agents, although evidence remains limited and results vary among individuals.<ref name="Rogers2017"/> Topical treatment does not modify the underlying cause of AN.

Procedural interventions, including fractional carbon dioxide (CO<sub>2</sub>) laser and various chemical peels, have been explored in pilot studies and small comparative trials. A randomized controlled trial involving 38 participants reported that fractional CO<sub>2</sub> laser resulted in greater reduction of lesion severity compared with retinoic-acid peel; however, the study was short-term and limited in size.<ref name="Gnanasuriyan2025">{{cite journal
 |last1=Gnanasuriyan
 |first1=R
 |last2=Shanmugam
 |first2=S
 |title=Comparison of the Effectiveness of Fractional Carbon Dioxide Laser and Retinoic Acid Peel in the Treatment of Acanthosis Nigricans: A Randomized Controlled Trial
 |journal=Cureus
 |date=June 2025
 |volume=17
 |issue=6
 |article-number=e86047
 |doi=10.7759/cureus.86047
 |doi-access=free
 |pmid=40666598
|pmc=12261829
 }}</ref> Procedural therapies generally require specialised equipment, and availability and cost may limit use.

===Systemic therapies===
Because many cases of AN are associated with metabolic dysfunction, improvement in weight or insulin sensitivity may coincide with changes in the skin. Metformin, which is widely used for insulin resistance and type 2 diabetes, has been reported in case series and observational studies to coincide with improvement in AN; however, high-quality randomized trials with AN as a primary outcome are not available.<ref name="Hamdani2020">{{cite journal
 |last1=Hamdani
 |first1=G
 |last2=Birch
 |first2=M P
 |last3=Mason
 |first3=A R
 |title=Oral metformin for treating dermatological diseases: A systematic review
 |journal=Journal of Drugs in Dermatology
 |date=August 2020
 |volume=19
 |issue=8
 |pages=780–787
 |pmid=32845585
}}</ref>

Glucagon-like peptide-1 (GLP-1) receptor agonists, used for obesity and diabetes, have also been associated with improvement in some individuals with AN in observational reports, likely secondary to changes in metabolic status. These medications are not used specifically to treat AN, and evidence remains indirect.<ref name="Elmasry2025">{{cite journal
 |last1=Elmasry
 |first1=M F
 |last2=Ali
 |first2=Z
 |title=Metformin: Old drug, new therapeutic potential in the skin? A brief narrative review
 |journal=Advances in Therapy
 |date=2025
 |volume=42
 |issue=8
 |pages=3606–3620
 |doi=10.1007/s12325-025-03256-x
 |pmid=40291350
 |publisher=Springer
|pmc=12020976
 }}</ref>

== Prognosis ==
The prognosis depends on the underlying cause. Obesity- and insulin resistance–related forms often improve with weight loss and metabolic control. Drug-induced cases typically resolve with withdrawal of the causative agent. Hereditary variants may persist. Malignancy-associated acanthosis nigricans may regress following tumour treatment.<ref name="Fitzpatrick2005" />{{rp|87}}

== History ==
Acanthosis nigricans was first described by [[Paul Gerson Unna]] in 1889.<ref name="Nordlund2008" />

== Epidemiology ==
Acanthosis nigricans is reported worldwide, with prevalence varying by age, ethnicity and underlying metabolic risk. In clinic- and community-based samples of people with obesity and insulin resistance, reported prevalence ranges from about 7% to over 70%, depending on the population and diagnostic criteria used.<ref name="Karadag2018" /><ref name="Popa2019" />

Higher rates are consistently observed among individuals of African, Hispanic/Latino, Native American and some Asian ancestries, reflecting both genetic susceptibility and a higher burden of obesity and metabolic syndrome in many of these populations.<ref name="Karadag2018" /><ref name="Pollock2022" /> In children and adolescents, the prevalence of acanthosis nigricans has risen alongside increasing rates of overweight and obesity and is common in pediatric cohorts with insulin resistance or metabolic syndrome.<ref name="Pollock2022" /><ref name="Taren2023" />

Across studies, acanthosis nigricans is more frequent among people with higher body mass index, increased waist circumference and biochemical markers of insulin resistance.<ref name="Karadag2018" /><ref name="Pollock2022" /><ref name="Isart2022" />

== References ==
{{Reflist|refs=
<!-- BOOKS -->
<ref name="Andrews2006">{{Cite book |last=James |first=William D. |title=Andrews' Diseases of the Skin: Clinical Dermatology |edition=10th |publisher=Saunders Elsevier |year=2006 |isbn=978-0-7216-2921-6 |page=506}}</ref>

<ref name="Andrews2020">{{Cite book |last1=James |first1=William D. |last2=Elston |first2=Dirk |last3=Treat |first3=James R. |last4=Rosenbach |first4=Misha A. |last5=Neuhaus |first5=Isaac |title=Andrews' Diseases of the Skin: Clinical Dermatology |edition=13th |year=2020 |publisher=Elsevier |pages=502–504 |isbn=978-0-323-54753-6}}</ref>

<ref name="Bolognia2007">{{Cite book |last=Bolognia |first=Jean L. |title=Dermatology |edition=2nd |publisher=Mosby |year=2007 |isbn=978-1-4160-2999-1 |page=676}}</ref>

<ref name="Fitzpatrick2005">{{Cite book |last=Fitzpatrick |first=Thomas B. |title=Fitzpatrick's Color Atlas and Synopsis of Clinical Dermatology |edition=5th |publisher=McGraw-Hill Medical |year=2005 |isbn=978-0-07-144019-6 |pages=86–87}}</ref>

<ref name="Habif2009">{{Cite book |last=Habif |first=Thomas P. |title=Clinical Dermatology |edition=5th |publisher=Mosby Elsevier |year=2009 |isbn=978-0-323-04852-1 |pages=968–979}}</ref>

<ref name="Nordlund2008">{{Cite book |last=Levine |first=Norman |editor-last=Nordlund |editor-first=James J. |title=The Pigmentary System: Physiology and Pathophysiology |edition=2nd |publisher=Blackwell Publishing |year=2008 |isbn=978-1-4051-2034-0 |page=907}}</ref>

<ref name="Tilgen2009">{{Cite book |last=Tilgen |first=W. |editor-last=Burgdorf |editor-first=WHC |title=Braun-Falco's Dermatology |edition=3rd |publisher=Springer |year=2009 |isbn=978-3-540-29312-5 |pages=1340–1347}}</ref>

<!-- JOURNAL ARTICLES -->
<ref name="Higgins2008">{{Cite journal |last1=Higgins |first1=S. P. |last2=Freemark |first2=M. |last3=Prose |first3=NS |year=2008 |title=Acanthosis nigricans: a practical approach to evaluation and management |journal=Dermatology Online Journal |volume=14 |issue=9 |page=2 |doi=10.5070/D37MF6G290 |pmid=19061584}}</ref>

<ref name="Isart2022">{{Cite journal |last=Isart |first=F. A. |year=2022 |title=Acanthosis nigricans is a strong predictor of low blood calcidiol levels in children and adolescents |journal=Metabolic Syndrome and Related Disorders |volume=20 |issue=9 |pages=509–516 |doi=10.1089/met.2022.0005 |pmid=35834574}}</ref>

<ref name="Karadag2018">{{Cite journal |last=Karadağ |first=A. S. |year=2018 |title=Acanthosis nigricans and the metabolic syndrome |journal=Clinical Dermatology |volume=36 |issue=1 |pages=48–53 |doi=10.1016/j.clindermatol.2017.09.008 |pmid=29241752}}</ref>

<ref name="Mourad2021">{{Cite journal |last1=Mourad |first1=A. I. |last2=Haber |first2=R. M. |year=2021 |title=Drug-induced acanthosis nigricans: a systematic review and new classification |journal=Dermatologic Therapy |volume=34 |issue=2 |article-number=e14794 |doi=10.1111/dth.14794 |pmid=33480113}}</ref>

<ref name="Parmar2025">{{Cite journal |last=Parmar |first=S. |year=2025 |title=A comprehensive review of acanthosis nigricans: pathogenesis, clinical manifestation and management |journal=Recent Advances in Inflammation & Allergy Drug Discovery |volume=19 |issue=2 |pages=135–145 |doi=10.2174/0127722708314530240919054410 |pmid=40667590}}</ref>

<ref name="Pollock2022">{{Cite journal |last=Pollock |first=Samara |display-authors=etal |year=2022 |title=Acanthosis nigricans in the pediatric population: a narrative review |journal=Pediatric Medicine |volume=5 |page=42 |doi=10.21037/pm-21-70 |doi-access=free |pmid=36420374 |pmc=9678372 }}</ref>

<ref name="Popa2019">{{Cite journal |last=Popa |first=M. L. |display-authors=etal |year=2019 |title=Acanthosis nigricans: to be or not to be afraid |journal=Oncology Letters |volume=17 |issue=5 |pages=4133–4138 |doi=10.3892/ol.2018.9736 |pmid=30944606 |pmc=6444334 }}</ref>

<ref name="Rigel1980">{{Cite journal |last1=Rigel |first1=DS |last2=Jacobs |first2=MI |year=1980 |title=Malignant acanthosis nigricans: a review |journal=Journal of Dermatologic Surgery and Oncology |volume=6 |issue=11 |pages=923–927 |doi=10.1111/j.1524-4725.1980.tb01003.x |pmid=6257767}}</ref>

<ref name="Schnopp2007">{{Cite journal |last1=Schnopp |first1=C. |last2=Baumstark |first2=J. |year=2007 |title=Oral acanthosis nigricans |journal=New England Journal of Medicine |volume=357 |issue=9 |pages=e10 |doi=10.1056/NEJMicm062917 |pmid=17761587}}</ref>

<ref name="Schwartz1981">{{Cite journal |last=Schwartz |first=Robert A. |year=1981 |title=Acral acanthotic anomaly (AAA) |journal=Journal of the American Academy of Dermatology |volume=5 |issue=3 |pages=345–346 |doi=10.1016/S0190-9622(81)80155-7 |pmid=7263979}}</ref>

<ref name="Schwartz1994">{{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}}</ref>

<ref name="Schwartz2007">{{Cite journal |last=Schwartz |first=Robert A. |year=2007 |title=Acral acanthosis nigricans (acral acanthotic anomaly) |journal=Journal of the American Academy of Dermatology |volume=56 |issue=2 |pages=349–350 |doi=10.1016/j.jaad.2006.09.027 |pmid=17224380}}</ref>

<ref name="Taren2023">{{Cite journal |last=Taren |first=D. |display-authors=etal |year=2023 |title=Diet and acanthosis nigricans over two years in children |journal=Nutrients |volume=15 |issue=12 |page=2718 |doi=10.3390/nu15122718 |doi-access=free |pmid=37375623 |pmc=10302045 }}</ref>

<ref name="Verma2016">{{Cite journal |last=Verma |first=Shyam |display-authors=etal |year=2016 |title=Facial acanthosis nigricans and its association with BMI, waist circumference and insulin resistance |journal=Indian Dermatology Online Journal |volume=7 |issue=6 |pages=498–503 |doi=10.4103/2229-5178.193898 |doi-access=free |pmid=27990384 |pmc=5134163}}</ref>

<!-- WEB SOURCES -->
<ref name="Mayo">{{Cite web |title=Acanthosis nigricans – Symptoms and causes |url=https://www.mayoclinic.org/diseases-conditions/acanthosis-nigricans/symptoms-causes/syc-20368983 |website=Mayo Clinic |access-date=2021-08-13}}</ref>

<ref name="WebMD">{{Cite web |title=What is Acanthosis Nigricans? |url=https://www.webmd.com/skin-problems-and-treatments/acanthosis-nigricans-overview |website=WebMD |access-date=2021-08-13}}</ref>

<ref name="Nueces2018">{{Cite web |title=Insulin Resistance and Acanthosis Nigricans in Kids |url=http://www.nuecesmedsociety.org/Template.aspx?id=873 |archive-url=https://web.archive.org/web/20180412212317/http://www.nuecesmedsociety.org/Template.aspx?id=873 |archive-date=2018-04-12 |website=Nueces County Medical Society |access-date=2020-03-01}}</ref>
}}

== External links ==
{{Commons category|Acanthosis nigricans}}

{{Medical resources
| DiseasesDB    = 58
| ICD10         = {{ICD10|L|83||l|80}}
| ICD9          = {{ICD9|701.2}}
| MedlinePlus   = 000852
| eMedicineSubj = derm
| eMedicineTopic= 1
| MeshID        = D000052
| SNOMED CT     = 402599005
}}

{{Cutaneous keratosis, ulcer, atrophy, and necrobiosis}}
{{Paraneoplastic syndromes}}
{{Pigmentation disorders}}

[[Category:Endocrine-related cutaneous conditions]]
[[Category:Medical conditions related to obesity]]
[[Category:Medical signs]]