Acanthosis Nigricans: Symptoms, Types, Causes and Treatment

Acanthosis nigricans (AN) is more than just a skin condition—it's often a visible sign of deeper health issues. Commonly appearing as dark, velvety patches in body folds and creases, AN can be a marker for underlying metabolic, hormonal, or even malignant disorders. Understanding its symptoms, varieties, root causes, and available treatments is essential for early recognition and effective management.

Symptoms of Acanthosis Nigricans

Acanthosis nigricans reveals itself in ways that are both visually striking and texturally distinct. Recognizing these features is crucial for timely intervention, as AN can be the first sign of metabolic or systemic disease. Let’s explore the most common symptoms and their nuances.

Symptom	Description	Common Sites	Source(s)
Hyperpigmentation	Dark, brown-to-black skin discoloration	Neck, axillae, groin, elbows	2 3 4 8
Thickening	Skin becomes noticeably thicker	Flexural areas (folds)	2 3 4 8
Velvety Texture	Skin feels soft and velvety to the touch	Neck, armpits, groin	2 3 4 8
Papillomatosis	Fine, wart-like elevations	Affected plaques	3 8

Table 1: Key Symptoms

Hyperpigmentation and Thickening

The hallmark of AN is a gradual darkening of the affected skin, often accompanied by thickening. The color can range from brownish to nearly black, and the skin may look slightly raised compared to the surrounding areas. This is most often seen on the back and sides of the neck, but can also appear in the armpits, groin, elbows, and behind the knees 2 3 4 8.

Velvety and Papillomatous Texture

AN lesions are not just darker; they feel different. The skin develops a soft, velvety texture, sometimes compared to suede or velvet. When examined closely, the surface may show delicate ridges or tiny, wart-like projections—a feature known as papillomatosis 3 8.

Distribution and Symmetry

Lesions typically appear symmetrically—on both sides of the body—and favor skin folds (intertriginous areas) due to increased friction and moisture. The neck and axillae are the most common sites, but the groin, antecubital (elbow), and popliteal (knee) fossae are also frequently involved 3 4 8.

Other Possible Features

• Itching or mild irritation (occasionally)
• Rare involvement of mucosal surfaces (such as lips or oral cavity), more common in malignant forms 4 7 8
• In severe cases, thickened, rough skin may develop on the palms, soles, nipples, or even the umbilicus 7
• In children and adolescents, the presence of AN is often linked to obesity and insulin resistance 4 8

Types of Acanthosis Nigricans

AN is not a one-size-fits-all diagnosis. Its types vary by underlying cause, age of onset, and clinical course. Recognizing the specific type is essential for identifying the associated health risks and guiding management.

Type	Key Features	Population / Associations	Source(s)
Benign	Gradual, stable plaques, no malignancy	Children, healthy adults	6 7 8
Obesity-associated	Linked to obesity & insulin resistance	Overweight children & adults	3 4 6 8
Syndromic	Part of genetic syndromes	Rare, with other congenital anomalies	3 10 11 12
Malignant	Rapid, extensive, mucosal involvement	Older adults, often with adenocarcinoma	6 7 8
Medication-induced	Linked to specific drugs	All ages, recent medication history	3
Acral	Localized to hands and feet	Children, African descent	3
Unilateral	Only one side of body affected	Very rare	3
Mixed	Features of more than one type	Variable	3

Table 2: Types of Acanthosis Nigricans

Benign Acanthosis Nigricans

This is the most common type, presenting as slowly developing, stable plaques typically without any associated systemic disease. It often occurs in healthy children or adults and may have a hereditary component 6 7 8.

Obesity-Associated (Pseudo-AN)

With the global rise in obesity, this form has become increasingly prevalent, especially in children and adolescents. It's strongly linked with insulin resistance and may be an early sign of developing type 2 diabetes 3 4 8. Lesions are similar to benign AN but more closely associated with metabolic risk factors.

Syndromic AN

Certain rare genetic syndromes, such as those involving mutations in fibroblast growth factor receptors (FGFRs), can present with AN as part of a constellation of congenital abnormalities. Notable examples include SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans), Crouzon syndrome with AN, and other skeletal dysplasias 10 11 12.

Malignant Acanthosis Nigricans

This form is a paraneoplastic syndrome, most commonly associated with aggressive internal malignancies, particularly adenocarcinomas of the stomach and other abdominal organs. It tends to have rapid onset, widespread involvement (including mucous membranes), and can be accompanied by itching and thickening of the palms and soles 6 7 8. Its appearance may precede, accompany, or follow the diagnosis of cancer.

Medication-Induced AN

Certain medications, such as high-dose nicotinic acid, corticosteroids, or even some hormonal therapies, can trigger AN. The lesions typically resolve after discontinuation of the offending drug 3.

Acral, Unilateral, and Mixed Forms

• Acral AN: Localized to extremities (hands, feet), more frequently seen in children of African descent 3.
• Unilateral AN: Rarely, AN affects only one side of the body.
• Mixed AN: Patients may present with a combination of features from different types 3.

Causes of Acanthosis Nigricans

While AN is visible on the skin, its causes are often systemic. Understanding these underlying mechanisms is vital for effective treatment and for identifying potentially serious associated conditions.

Cause	Mechanism / Association	Risk Factors / Example Conditions	Source(s)
Insulin Resistance	High insulin stimulates skin cell growth	Obesity, type 2 diabetes, PCOS	1 3 4 9 11
Genetic Syndromes	Abnormal receptor signaling (e.g., FGFR3)	SADDAN, Crouzon syndrome	10 11 12
Malignancy	Tumor-derived growth factors stimulate skin	Gastric adenocarcinoma, other cancers	6 7 8
Medications	Drug-induced stimulation of epidermal growth	Nicotinic acid, steroids, hormones	3
Endocrine Disorders	Hormonal imbalances promote skin changes	Hypothyroidism, Cushing’s, PCOS	3 4 8
Obesity	Increased insulin production/resistance	Overweight children/adults	3 4 8

Table 3: Causes of Acanthosis Nigricans

Insulin Resistance and Hyperinsulinemia

By far the most common cause, especially in children and young adults, is insulin resistance. Excess insulin in the blood acts as a growth factor—either directly, through insulin receptors, or indirectly, through cross-reactivity with insulin-like growth factor 1 (IGF-1) receptors on keratinocytes and dermal fibroblasts. This leads to increased proliferation of skin cells and the characteristic thickening and pigmentation 1 3 4 9 11.

Key conditions associated with insulin resistance include:

• Obesity
• Type 2 diabetes mellitus
• Polycystic ovary syndrome (PCOS)
• Certain rare syndromes with primary insulin receptor defects (Type A and Type B insulin resistance) 1

Genetic and Syndromic Causes

Rare genetic mutations can result in AN as part of a syndrome. Specific mutations in genes encoding FGFR3 (fibroblast growth factor receptor 3) lead to conditions such as SADDAN and Crouzon syndrome with AN 10 11 12. These syndromes often include skeletal abnormalities and developmental delays.

Malignancy

In older adults, sudden onset of widespread or rapidly progressive AN—especially with mucosal involvement—may signal an underlying malignancy, most often a gastrointestinal adenocarcinoma. Tumor-secreted growth factors may drive the excessive growth and pigmentation of the skin 6 7 8.

Medication-Induced and Endocrine Causes

Certain medications can provoke AN by altering hormone levels or stimulating skin growth. Endocrine disorders, such as hypothyroidism and Cushing's syndrome, may also contribute through hormonal dysregulation 3 4 8.

Treatment of Acanthosis Nigricans

While the appearance of AN can be distressing, effective treatment hinges on addressing the underlying cause. Local therapies may help improve skin appearance, but systemic management is key to long-term resolution.

Treatment	Mechanism / Purpose	Effectiveness / Notes	Source(s)
Treat underlying	Manage obesity, diabetes, malignancy	Most important for resolution	2 3 4 8 13 16
Metformin	Improves insulin sensitivity	Useful for obesity/IR-associated	13
Retinoids (topical/oral)	Promote skin turnover	Topical more effective, well-tolerated	3 14 15 17
Urea cream	Softens thickened skin	Some benefit, less than retinoids	15
Laser/Surgery	Remove resistant plaques	For severe or isolated cases	16
Discontinue drugs	Stop causative medication	Resolves drug-induced cases	3

Table 4: Treatment Options

Addressing the Underlying Condition

The cornerstone of AN management is identifying and treating the root cause:

• Obesity and Insulin Resistance: Weight loss, dietary changes, and increased physical activity can lead to marked improvement or even resolution of AN. Medications like metformin may be helpful, especially in pediatric and adolescent cases linked to obesity and insulin resistance. Some studies show significant improvement in AN lesions and insulin levels after metformin or octreotide therapy, although results can be variable 13.
• Malignancy: For malignant AN, treating the underlying cancer often leads to improvement in skin lesions 6 7 8.
• Medication-Induced: Discontinuation of the offending drug usually results in gradual regression of skin changes 3.

Topical Treatments

• Retinoids (Tretinoin): Topical tretinoin cream, available in concentrations such as 0.025% and 0.05%, has been shown to significantly lighten and smooth AN lesions. Both concentrations appear equally effective and are generally well tolerated, with only mild skin irritation reported 15 17.
• Urea Cream: While 10% urea cream can soften and improve the skin, it is generally less effective than retinoids 15.
• Calcipotriol: Has shown limited success in some cases 16.

Systemic Treatments

• Oral Retinoids: In severe or resistant cases, oral isotretinoin has been used with some success, particularly in extensive AN 14.
• Other Agents: Agents such as rosiglitazone, octreotide, and vitamin D analogs have been explored, mainly for insulin resistance–related AN. Results are mixed, with metformin and octreotide showing the most promise 13.

Procedural Options

• Laser Therapy and Surgical Excision: For persistent, cosmetically bothersome lesions that do not respond to medical therapy, laser ablation or surgical removal may be considered 16.

Additional Measures

• Patient Support and Education: Addressing underlying health risks and providing emotional support is crucial, as AN can be distressing and affect self-esteem.

Conclusion

Acanthosis nigricans is not just a cosmetic concern—it is a vital clinical sign that can indicate underlying metabolic, genetic, endocrine, or neoplastic disease. Early recognition, thorough evaluation, and targeted treatment are essential for optimal outcomes.

Key Takeaways:

• AN appears as dark, velvety, thickened skin—most often in body folds.
• Types include benign, obesity-associated, syndromic, malignant, medication-induced, and more.
• The most common cause is insulin resistance, but it can also signal cancer, genetic syndromes, or medication effects.
• Treatment focuses on the underlying cause, with local therapies (retinoids, urea) providing additional cosmetic improvement.
• Early intervention and a multidisciplinary approach are crucial for addressing both skin changes and associated health risks.

By paying close attention to these distinctive skin changes, healthcare providers and patients alike can catch important health conditions early and improve both dermatologic and overall health outcomes.