Acanthosis nigricans

Acanthosis nigricansis a medical sign characterised by brown-to-black, poorly defined, velvetyhyperpigmentationof theskin.It is usually found in body folds,such as the posterior and lateral folds of theneck,thearmpits,groin,navel,foreheadand other areas.

Acanthosis nigricans
Acanthosis nigricans onaxilla
Specialty	Dermatology

It is associated withendocrine dysfunction,especiallyinsulin resistanceandhyperinsulinaemia,as seen indiabetes mellitus.This activates theinsulin-like growth factor receptors,which leads to proliferation ofkeratinocytes,fibroblastsand other cells in the skin. Activation of othergrowth factor receptorssuch asfibroblast growth factor receptorsorepidermal growth factor receptorcan also be responsible.

Signs and symptoms

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

Causes

It typically occurs in individuals younger than age 40, is associated withinsulin resistance,Type 2 diabetes,obesity or endocrinopathies, such ashypothyroidism,acromegaly,polycystic ovary syndromeorCushing's disease,and may be genetically inherited.

Type I – familial

Familial acanthosismay arise as a result of anautosomal dominanttrait, presenting at birth or developing during childhood.

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Type II – endocrine

Endocrine syndromes associated with acanthosis nigricanscan develop in many conditions, particularly:

• starts withinsulin resistance,such asdiabetes mellitusandmetabolic syndrome
• excess circulatingandrogens,particularlyCushing's disease,acromegaly,polycystic ovary syndrome
• Addison's diseaseandhypothyroidism
• Rare diseases, includingpinealoma,leprechaunism,lipoatrophic diabetes,pineal hyperplasia syndrome, pituitary basophilism, ovarian hyperthecosis, stromal luteoma, ovarian dermoid cysts,Prader-Willi syndrome,andAlström syndrome.

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

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  A. nigricans, right armpit; notice theskin tags,an indicator for elevated blood sugar andhyperinsulinaemia
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  A. nigricans, axillary

Type III – obesity and pseudoacanthosis nigricans

In young persons, acanthosis nigricans is a visible marker which strongly suggestsinsulin 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.Insulin resistance syndromes may be divided into type A (HAIR-AN) and type B syndromes.

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.This can also be referred to as pseudoacanthosis nigricans.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.

Type IV – drug-related

Acanthosis nigricans has been linked to the use ofnicotinic acid,glucocorticoiduse,combined oral contraceptive pills,andgrowth hormonetherapy.

Type V – malignancy

Malignant acanthosis nigricansrefers to acanthosis nigricans occurring as aparaneoplastic syndromeassociated with a cancer. Malignant acanthosis nigricans is most commonly associated with gastrointestinal adenocarcinomas, as well asgenitourinarycancers 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.

This form of acanthosis nigricans is more likely to involve mucous membranes (25–50% of cases)Malignant acanthosis nigricans that may either precede (18%), accompany (60%), or follow (22%) the onset of an internal cancer.Malignancy-associated acanthosis nigricans is usually rapid in onset and may be accompanied byskin tags,multipleseborrheic keratoses,ortripe palms.

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.While the etiology remains unknown,its presence does not suggest a likelihood of malignancy.

Pathophysiology

Acanthosis nigricans is caused by increased activation ofgrowth factor receptorproteins, usually due toendocrine dysfunction.This is most commonlyinsulin-mediated activation ofIGF receptorsonkeratinocytes,as a result ofhyperinsulinaemiaorinsulin resistance,as seen indiabetes mellitus.

Factors involved in the development of acanthosis nigricans include:

• Increased circulating insulin. This activates keratinocyte IGF receptors, particularlyIGF-1.At high concentrations, insulin may also displace IGF-1 frominsulin-like growth factor-binding protein(IGFBP). Increased circulating IGF may lead to keratinocyte and dermalfibroblastproliferation.
• In hereditary forms of acanthosis nigricans,fibroblast growth factor receptor(FGFR) defects
• Increasedtransforming growth factor(TGF), which appears to be the mechanism for malignancy-associated acanthosis nigricans. TGF acts on epidermal tissue via theepidermal growth factor receptor(EGFR).

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.

Diagnosis

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, anendoscopy,orX-raysmay be required to eliminate the possibility ofdiabetesorcanceras the cause.

On biopsy, hyperkeratosis, epidermal folding, leukocyte infiltration, and melanocyte proliferation may be seen.

Classification

Acanthosis nigricans is conventionally divided into benign and malignant forms,although may be divided into syndromes according to cause:

• 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, ortumour 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.

Treatment

People with acanthosis nigricans should be screened for diabetes and, although rare, cancer. Controllingblood glucoselevels 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 sulfidetopical 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.

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.

History

AN was first reported byUnnain 1889.