Acanthosis nigricans (AN) is a dermatological condition visually characterized by dark, velvety, and thickened patches of skin. This distinctive skin change, known as papillomatous overgrowth of the epidermis, primarily occurs in skin folds and flexures of the body. Common areas affected include the armpits (axillae), groin, beneath the breasts (inframammary regions), and the nape of the neck. The skin in these areas may not only darken (hyperpigmentation) but also develop a thickened texture (hyperkeratosis).
While acanthosis nigricans itself is not a disease, it often serves as a visible marker for an underlying health issue. In the majority of cases, particularly when benign, it is associated with conditions like obesity and diabetes. Though less frequent, acanthosis nigricans can also be a sign of internal malignancy, making proper diagnosis and understanding crucial.
Alt text: Close-up image showing the characteristic dark, velvety texture of acanthosis nigricans on a patient’s neck, highlighting skin folds and hyperpigmentation.
Who is at Risk of Acanthosis Nigricans?
Acanthosis nigricans does not discriminate, affecting individuals across all demographics; however, prevalence rates do vary among different populations. Studies indicate a higher occurrence in certain ethnic groups, with African Americans showing a prevalence of approximately 13.3%, Latinos around 5.5%, and Native Americans notably higher at 34.2%.
This condition can manifest in both males and females and across all age groups, from children to the elderly. A significant cross-sectional study in the United States involving 1730 participants revealed acanthosis nigricans in 18.2% of children and 19.5% of adults. Notably, individuals diagnosed with acanthosis nigricans in this study were twice as likely to also have type 2 diabetes compared to those without the skin condition (35.4% vs. 17.6%).
In rare instances, acanthosis nigricans can be an indicator of internal malignancy. Malignant acanthosis nigricans tends to present in middle-aged individuals who are not obese, and the skin lesions often develop rapidly and abruptly.
Alt text: Detailed view of axillary acanthosis nigricans, illustrating the velvety, hyperpigmented plaques in the armpit area, typical in obesity-related cases.
Unpacking the Causes of Acanthosis Nigricans
The precise etiology of acanthosis nigricans remains not fully understood, yet it is strongly associated with states of insulin resistance. Conditions such as obesity, diabetes mellitus, and metabolic disorders, including metabolic syndrome, polycystic ovary syndrome (PCOS), and generalized lipodystrophy, are frequently observed alongside acanthosis nigricans.
The underlying mechanism often involves insulin’s role at the dermal-epidermal junction. Elevated insulin levels can stimulate growth by binding to type 1 insulin-like growth factor receptors (IGFRs) on keratinocytes, the primary cells of the epidermis. This interaction promotes keratinocyte proliferation, leading to the development of the characteristic skin changes of acanthosis nigricans.
Beyond insulin resistance, rarer benign forms of acanthosis nigricans include:
- Drug-induced acanthosis nigricans: Certain medications can trigger this condition.
- Hereditary benign acanthosis nigricans: This is a rare genetic condition, inherited in an autosomal dominant pattern, that typically progresses until puberty and may then stabilize or improve. It is often present from birth or early childhood and is linked to mutations in the fibroblast growth factor receptor 3 gene.
- Autoimmune acanthosis nigricans: Associated with autoimmune disorders.
- Acral acanthotic anomaly: Predominantly seen in individuals with darker skin tones and is confined to the elbows, knees, and the dorsal aspects of the hands and feet.
- Unilateral acanthosis nigricans: Affecting only one side of the body.
Malignant acanthosis nigricans, while rare, is often associated with internal cancers:
- It is thought to be caused by growth factors released by tumor cells.
- Gastrointestinal malignancies, particularly gastric adenocarcinoma (around 60% of cases), are the most common associations.
- Other related cancers include hepatobiliary cancers, squamous cell carcinoma, malignant melanoma, and Wilms tumor.
- The oral cavity can be affected in 25–50% of malignant cases.
- Tripe palms, a variant of acanthosis nigricans affecting the palms, has a strong (90%) correlation with internal malignancy.
Clinical Presentation of Acanthosis Nigricans
The hallmark of acanthosis nigricans is the appearance of symmetric, thickened, brown to black, velvety patches and plaques on the skin. These lesions typically manifest in:
- Intertriginous areas: most commonly the axillae, groin, and back of the neck.
- In women, lesions can also appear on the nipples, areolae, vulva, and perineum.
- Mucous membranes, such as the oral cavity, nasal and laryngeal mucosa, and esophagus, can be involved. Mucosal lesions tend to be more extensive and severe in malignant acanthosis nigricans.
- Skin tags are frequently observed on both cutaneous and mucosal surfaces in affected areas.
- The lesions can sometimes become macerated or emit an unpleasant odor.
- Itching (pruritus) may be present, and is particularly common and intense in cases of malignant acanthosis nigricans.
Facial acanthosis nigricans, a more recently recognized presentation, is usually seen in individuals with darker skin. It involves velvet-like hyperkeratotic and hyperpigmented areas on the forehead, cheeks, and malar regions, and may also affect the fingers. This variant has a strong association with obesity and metabolic syndrome.
Alt text: Overview of acanthosis nigricans on a patient’s back, demonstrating the extensive, hyperpigmented, and velvety texture changes across a larger skin surface.
Variations in Clinical Features Across Skin Types
The appearance of acanthosis nigricans can vary based on skin phenotype. In individuals with darker skin, the affected areas may appear even darker and have a more leathery texture.
Research indicates that individuals with skin phototype IV have a higher incidence of acanthosis nigricans on the neck compared to those with skin phototypes II and III.
Interestingly, the significance of acanthosis nigricans as a predictor of insulin resistance differs by skin color. In individuals with light skin and acanthosis nigricans, there is a very high likelihood of underlying insulin resistance. However, in people with skin of color, acanthosis nigricans can occur even without concurrent insulin resistance. Facial acanthosis nigricans, as mentioned, is almost exclusively observed in those with darker skin types.
Potential Complications Associated with Acanthosis Nigricans
While acanthosis nigricans itself is not life-threatening, it can lead to several complications:
- Cosmetic disfigurement: The visible skin changes can be a source of cosmetic concern.
- Psychological distress: The appearance of acanthosis nigricans can lead to emotional and psychological distress for some individuals.
- Increased risk of diabetes: Acanthosis nigricans is recognized as an independent risk factor for the presence of diabetes.
- Complications from underlying diseases: The most significant complications arise from the underlying conditions associated with acanthosis nigricans, such as obesity-related health issues or malignancy in rare cases.
Diagnosing Acanthosis Nigricans
Diagnosis of acanthosis nigricans is typically clinical, based on the characteristic appearance of the skin lesions. A thorough medical history is essential, including current and past medical conditions, family history, and medication use.
In cases where the diagnosis is uncertain, a skin biopsy can be performed for histopathological analysis to confirm the diagnosis.
A sudden onset of acanthosis nigricans in a non-obese individual should raise suspicion for an underlying malignancy, prompting a more detailed history, physical examination, and further investigations to rule out cancer.
Acanthosis Nigricans Differential Diagnosis
When considering a diagnosis of acanthosis nigricans, it is important to differentiate it from other skin conditions that may present with similar symptoms. The differential diagnosis for acanthosis nigricans includes:
- Confluent and reticulated papillomatosis (CRP): This condition presents with scaly papules that coalesce into plaques, often on the chest and back. Unlike AN, CRP lesions are typically less velvety and more scaly.
- Terra firma-forme dermatosis: This condition appears as “dirty-appearing” patches that can be easily removed with rubbing alcohol, distinguishing it from the more persistent lesions of acanthosis nigricans.
- Pityriasis versicolor: A fungal infection causing hypopigmented or hyperpigmented patches, which are typically scaly and respond to antifungal treatments. Acanthosis nigricans is not typically scaly and does not respond to antifungals.
- Flexural eczema: While eczema can occur in skin folds, it is usually itchy, inflamed, and may have vesicles or weeping, unlike the velvety, thickened plaques of AN.
- Post-inflammatory hyperpigmentation: This can occur after skin inflammation but usually lacks the velvety texture and thickening seen in acanthosis nigricans. The history of prior inflammation is also a key differentiating factor.
- Darier disease: A genetic disorder characterized by persistent, keratotic papules, often in seborrheic areas and flexures. Darier disease lesions are typically more follicular and rougher than acanthosis nigricans.
- Familial benign chronic pemphigus (Hailey-Hailey disease): This condition presents with vesicles and erosions in skin folds, which are different from the typical lesions of acanthosis nigricans.
- Acanthosis palmaris: Thickening of the skin of the palms, which can be confused with acanthosis nigricans if it occurs in the palmar flexures. However, acanthosis palmaris lacks the velvety texture and is typically more uniformly thickened.
A careful clinical examination, considering the distribution, texture, and associated symptoms, alongside patient history, helps in accurately differentiating acanthosis nigricans from these and other dermatological conditions.
Treatment Strategies for Acanthosis Nigricans
The primary approach to treating acanthosis nigricans is to address the underlying cause. Patient education plays a vital role in management.
General Management
- Lifestyle modifications: Non-pharmacological interventions are crucial. These include adopting a healthy diet and increasing physical activity to improve insulin sensitivity and reduce hyperinsulinemia.
- Medications: Metformin and rosiglitazone have been used to lower insulin levels and may lead to some improvement in acanthosis nigricans lesions.
- Malignancy management: Malignant acanthosis nigricans requires a thorough workup and treatment of the underlying malignancy. Cyproheptadine, an antihistamine, may be used to help regress acanthosis nigricans associated with malignancy by inhibiting the release of tumor-produced substances.
- Drug-induced acanthosis nigricans management: Discontinuation of the causative drug can lead to resolution of the skin condition.
- Syndromic acanthosis nigricans management: Treatment focuses on managing the underlying syndrome. For example, oral contraceptives may be used for acanthosis nigricans associated with polycystic ovary syndrome.
Specific Treatments for Skin Lesions
Treatment of acanthosis nigricans lesions can be considered for cosmetic reasons. Pharmacological and procedural treatment options exist, although they primarily aim to improve appearance rather than cure the underlying condition. Specific treatments were not detailed in the original article and could be expanded upon with further research if needed, but for now maintaining the scope of the original article is prioritized.
Prognosis and Expected Outcomes
The prognosis for acanthosis nigricans is largely dependent on the underlying cause. If the underlying etiology can be effectively managed, such as through weight loss, the acanthosis nigricans may resolve. Conditions like obesity, metabolic syndrome, and diabetes have broader implications for overall health and can increase morbidity and mortality. Hereditary acanthosis nigricans may stabilize or even regress spontaneously in some cases. Malignant acanthosis nigricans carries a more serious prognosis, with an average survival time of approximately 2 years, often due to advanced cancer at the time of diagnosis.
