Acanthosis Nigricans (AN) is a skin condition characterized by dark, velvety, thickened patches or plaques, typically appearing in body folds and creases. Common sites include the axillae (armpits), posterior and lateral neck folds, antecubital fossae (inner elbows), popliteal fossae (behind the knees), inframammary areas, and the groin. These skin changes usually develop gradually and may be accompanied by a roughened or papillomatous texture, occasional odor, or the formation of skin tags (acrochordons).¹ Dr. Paul Gerson Unna introduced the term AN, and the first case report was published by Dr. Sigmund Pollitzer.²

It is not harmful itself, but it is frequently associated with underlying health issues, particularly insulin resistance and obesity. It can serve as an essential marker for conditions like type 2 diabetes and metabolic syndrome. In rare cases, malignant acanthosis nigricans may occur and is most often associated with intra-abdominal malignancies, particularly gastric adenocarcinoma. Certain medications (e.g., nicotinic acid, corticosteroids, oral contraceptives) and endocrine disorders (e.g., polycystic ovary syndrome, Cushing’s disease, hypothyroidism) may also trigger AN.³

Causes of Acanthosis Nigricans

Acanthosis nigricans (AN) arises from a variety of underlying causes, and its pathogenesis typically involves stimulation of epidermal keratinocytes and dermal fibroblast proliferation. The most common etiologies include:

Hereditary Variants: They may be associated with fibroblast growth factor defects.
Insulin Resistance (Most Common Cause):
Elevated circulating insulin levels, as seen in obesity, type 2 diabetes, and polycystic ovary syndrome, stimulate keratinocyte proliferation. This occurs when excess insulin binds to insulin-like growth factor-1 (IGF-1) receptors on keratinocytes. At high concentrations, insulin can displace IGF-1 from its binding proteins, increasing free IGF-1 levels, which promotes epidermal and dermal proliferation.
Malignancy-Associated AN (Paraneoplastic):
This rare but important variant is most commonly linked to gastric adenocarcinoma and other intra-abdominal malignancies. The proposed mechanism involves tumor-secreted growth factors such as transforming growth factor-alpha (TGF-α), which activate epidermal growth factor receptors (EGFRs) in the skin, causing rapid and extensive skin changes.

Types of Acanthosis Nigricans

The types of AN were based on their underlying etiology. Types of AN include:

Obesity-Associated Acanthosis Nigricans:

This is one of the most common forms of AN and was historically referred to as “pseudoacanthosis nigricans.” Obesity, which is frequently linked with insulin resistance, plays a central role in its development. Management primarily involves lifestyle changes, dietary interventions, medications, and weight reduction strategies.⁴

Familial Acanthosis Nigricans:

This rare form appears in childhood or at birth and follows an autosomal dominant inheritance pattern. Mutations in the fibroblast growth factor receptor 3 (FGFR3) gene are usually responsible.⁵

Medication-Associated Acanthosis Nigricans:

The medications linked with AN include:

Systemic glucocorticoids
Nicotinic acid
Diethylstilbestrol
Growth hormone therapy
Combined oral contraceptive pill
Estrogen
Injected insulin
Niacin
Protease inhibitors

AN usually resolves when you stop using the offending medications.

Endocrine Dysfunction Associated with AN:

This form is associated with underlying endocrine disorders, such as insulin resistance, polycystic ovary syndrome (PCOS), diabetes mellitus, and hypoandrogenism. It tends to have a slower onset and milder skin involvement, often in obese individuals.

Unilateral Acanthosis Nigricans:

The other name for unilateral AN is nevoid AN. This rare variant is inherited in an autosomal dominant pattern and typically affects only one side of the body. It can manifest at any age.

Autoimmune Acanthosis Nigricans:

This type is linked with autoimmune disorders, including systemic lupus erythematosus (SLE), scleroderma, Hashimoto’s thyroiditis, and Sjögren’s syndrome.⁶

Malignant AN Syndrome:

This aggressive form of AN is often associated with internal malignancies, particularly gastrointestinal adenocarcinomas and genitourinary cancers. It presents with a sudden onset and may be accompanied by additional features such as skin tags, “tripe palms,” and multiple seborrheic keratoses.

Acral Acanthotic Anomaly:

This variant presents with hyperpigmentation limited to areas like the knuckles, elbows, knees, and the dorsal surfaces of the feet. It is more common in individuals with darker skin tones.⁷

Symptoms of Acanthosis Nigricans

The clinical features of AN include:

Dark, Thickened & Velvety Skin:

The gradual development of dark, thickened, and velvety patches or plaques of the skin is the hallmark of AN.

Symmetrical Distribution:

These body changes are symmetric and commonly affect these areas:

The neck (especially the nape and sides)
Armpits
Elbows
Knees
Knuckles
Belly button
Under the breast
Groin

Other Possible Locations

In more severe or atypical cases, lesions can also affect the:

Face, lips, and eyelids
Palms and soles
Mucosal surfaces (particularly in malignancy-associated AN)
Areola and nipples in women
Perineum and vulva

Image shows Acanthosis Nigricans on different body parts — (A) A 19-year-old female diagnosed with obesity and PCOS showing acanthosis nigricans on the neck, (B) Pigmented plaques located between and beneath the breasts, (C) Hyperpigmented lesions of AN visible in the antecubital fossa. Image Courtesy: Radu, A., Carsote, M., Dumitrascu, M. C., & Sandru, F. (2022). Acanthosis Nigricans: Pointer of Endocrine Entities. available via MDPI under license CC BY 4.0

Associated Symptoms:

Odor: Thickened plaques may emit an unpleasant smell due to moisture and bacterial colonization.
Itching: More commonly seen in malignant cases.
Maceration: Moisture buildup in body folds may lead to softening and increased susceptibility to secondary infections.
Skin Tags: These benign outgrowths may appear near the affected regions.
Rapid Onset: A sudden appearance, particularly in adults, can signal an underlying malignancy and requires urgent evaluation.
Rare Associations: Nail changes and conjunctival involvement have occasionally been reported.⁸

Diagnosis of Acanthosis Nigricans

Evaluation and diagnosis of this condition include:

Clinical Assessment

The diagnosis of Acanthosis Nigricans is primarily clinical. A dermatologist or healthcare provider typically identifies it based on the presence of hallmark features: dark, velvety, hyperkeratotic plaques commonly located in intertriginous areas. A detailed medical history and physical examination are essential to evaluate associated risk factors such as obesity, insulin resistance, endocrine disorders, and medication use.

Dermoscopic image of Acanthosis Nigricans skin patches — Dermoscopy Image of AN lesions. Image Courtesy: Acanthosis Nigricans: Pointer of Endocrine Entities by Radu et al., 2022, doi.org/10.3390/diagnostics12102519, available via MDPI under license CC BY 4.0

Dermoscopy

Dermoscopy may support diagnosis by revealing characteristic patterns such as exaggerated skin markings and pigmentary network changes.

Skin Biopsy

A skin biopsy may be performed to confirm the diagnosis or rule out other skin conditions if the presentation is atypical.Histological findings typically include:

Basal layer hyperpigmentation
Hyperkeratosis
Papillomatosis
Mild acanthosis

Laboratory Investigations:

Lab tests are essential when AN appears abruptly, is extensive, or is seen in a non-obese individual:

Fasting glucose and insulin levels: to assess insulin resistance or diabetes
Hemoglobin A1c (if not already known)
Thyroid function tests: if hypothyroidism is suspected
Hormonal panel: including androgens in females with PCOS features like hirsutism
Cancer screening (in older patients with sudden onset or extensive disease): e.g., abdominal imaging, endoscopy, or tumor markers based on clinical suspicion

Treatment & Management of Acanthosis Nigricans

AN is not treatable, but it can fade over time by treating the underlying cause.

Treating the Underlying Cause:

Obesity is the most common cause of AN, so significant weight loss can lead to partial or complete resolution of skin changes.
Nutritional counseling and a healthy, balanced diet are recommended.
Improving blood sugar control through diet, exercise, and medications (e.g., metformin, rosiglitazone) can improve or resolve AN.
If AN is linked to hormonal imbalances (e.g., PCOS), treating the underlying endocrine disorder may help.
If due to medications (e.g., corticosteroids, nicotinic acid, estrogen), discontinuation or substitution may lead to regression.
In rare cases of internal malignancies, surgical removal of the tumor or cancer treatment can resolve the skin lesions.

Skin-Directed Treatments:

Some patients seek cosmetic improvement. The options include:

Topical Treatments

Retinoids (tretinoin 0.1% gel)
Vitamin D analogs (calcipotriol 0.005%)⁹
Ammonium lactate creams
Alpha-hydroxy acids (e.g., lactic acid, glycolic acid)
Keratolytics (salicylic acid)
Topical metformin (investigational in some studies)

Systemic treatments (selective cases):

Etretinate (oral retinoid; rarely used now due to side effects)
Oral metformin, especially in insulin-resistant individuals

Procedural Treatments

Cosmetic treatments have been tried to include:

Dermabrasion
Laser therapy
Chemical peels (e.g., trichloroacetic acid)

Cosmetic treatments can only improve the appearance of the condition, but can not cure the underlying causes.

Self-Care & Lifestyle Measures:

lean the affected areas gently with mild soap
Avoid harsh scrubbing or exfoliants
Avoid bleaching creams
Maintain a healthy diet
Engage in regular physical activity
Monitor for sudden or widespread changes in skin¹⁰

Prognosis

Patients with the benign form of AN have no or only a few skin complications and a good prognosis. They have the potential for resolution with treatment. The prognosis in patients with the malignant form of AN is poor, as the malignancy is usually advanced at the time of diagnosis.

Acanthosis Nigricans vs. Hyperpigmentation

AN and hyperpigmentation both involve the darkening of the skin but differ significantly in their causes, appearance, and locations. The key differences are summarized in the table.

Features	AN	Hyperpigmentation
Causes	Insulin resistance Endocrine disorders Malignancy	Excess melanin production due to sun Hormonal changes Inflammation Systemic disorders
Symptoms	Sun-exposed areas such as the face, hands, or anywhere on the skin	Dark patches without thickening
Locations	Generally, the body folds	Sun-exposed areas such as face, hands, or anywhere on the skin
Associated conditions	Diabetes Metabolic conditions Cancer	Sun damage Hormonal changes Skin injury
Treatment	Addressing the underlying cause Skin treatments	Sun protection Lightening agents Treating the underlying inflammation

Conclusion

AN is a common skin disorder. Recognizing AN is clinically significant, as addressing the underlying cause can often lead to improvement of the skin changes and may help identify and manage serious systemic diseases. Any new, unexplained, or rapidly developing skin changes should prompt medical evaluation, especially if accompanied by other systemic symptoms or risk factors for diabetes or malignancy.

Refrences

1
Das, A., et al., Acanthosis nigricans: a review. Journal of Cosmetic Dermatology, 2020. 19(8): p. 1857-1865.
2
Pollitzer, S., Acanthosis nigricans: a symptom of a disorder of the abdominal sympathetic. Journal of the American Medical Association, 1909. 53(17): p. 1369-1373.
3
Shiana, et al., A Comprehensive Review of Acanthosis Nigricans: Pathogenesis, Clinical Manifestation and Management. Recent Advances in Inflammation & Allergy Drug Discovery, 2024.
4
Ng, H.Y., Acanthosis nigricans in obese adolescents: prevalence, impact, and management challenges. Adolescent health, medicine and therapeutics, 2016: p. 1-10.
5
Fukuchi, K., et al., Familial acanthosis nigricans with p. K650T FGFR 3 mutation. The Journal of Dermatology, 2018. 45(2): p. 207-210.
6
Kondo, Y., et al., A case of generalized acanthosis nigricans with positive lupus erythematosus-related autoantibodies and antimicrosomal antibody: autoimmune acanthosis nigricans. Case Reports in Dermatology, 2012. 4(1): p. 85-91.
7
Anand, V., et al., Acral acanthosis nigricans (acral acanthotic anomaly). Indian Dermatology Online Journal, 2014. 5(Suppl 2): p. S140-S141.
8
Rawla, E.K.H.M.F.B.P., Acanthosis Nigricans. 2025.
9
Rawla, E.K.H.M.F.B.P., Acanthosis Nigricans. 2025.
10
Rawla, E.K.H.M.F.B.P., Acanthosis Nigricans. 2025.

Acanthosis Nigricans: What You Need to Know

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