Acanthosis nigricans (AN) is a skin condition characterized by areas of dark, thick, velvety skin in body folds and creases. It typically affects the armpits, groin, and neck, but can appear anywhere on the body. The hyperpigmentation has poorly defined borders and may include thickening of the skin. While AN itself isn't harmful or contagious, it can be a sign of an underlying condition that requires treatment.
Introduction to Acanthosis Nigricans
Acanthosis nigricans is a cutaneous manifestation of an underlying condition. It presents as velvety hyperpigmented patches with poorly defined borders, usually in skin fold areas, such as the back of the neck, axilla, and groin, and may include thickening of the skin. This skin disorder results in light-brown-to-black spots. It often happens to otherwise healthy people, but in some cases, it may be a sign of an underlying condition. The markings look like a spot or stain that you might think you can scrub off, but washing will not remove acanthosis nigricans (AN).
Etiology and Associated Conditions
Multiple factors are involved in the development of acanthosis nigricans. AN is most commonly associated with diabetes and insulin resistance, but rarely it can be a sign of internal malignancy. It can also occur with hormone disorders and with the use of certain medications like systemic glucocorticoids and oral contraceptives.
Insulin Resistance and Hyperinsulinemia
Increased circulating insulin activates keratinocyte insulin-like growth factor (ILGF) receptors, particularly IGF-1. At high concentrations, insulin may displace IGF-1 from IGF binding protein. Increased circulating IGF may lead to keratinocyte and dermal fibroblast proliferation. Insulin in high concentrations has been shown to cross the dermal-epidermal junction, and in high concentrations to have growth-stimulating effects through its binding to type 1 insulin-like growth factor receptor (IGFR) on keratinocytes. There is a very high prevalence of insulin resistance in those with light skin who have acanthosis nigricans. However, in darker skinned individuals, acanthosis nigricans may present without concurrent insulin resistance.
Obesity
Obesity is one of the most common conditions associated with Acanthosis nigricans. Lesions are usually common in adulthood but can occur at any age. It was once labeled as “pseudoacanthosis nigricans." It may be associated with insulin resistance. Being very overweight is a big risk factor for getting acanthosis nigricans. Carrying extra weight puts more strain on the body's processes, including how it regulates insulin. Fat cells release hormones that can mess up how insulin works, causing insulin resistance and higher insulin levels. That's why obese people are more prone to getting acanthosis nigricans because of these changes in their metabolism.
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Medications
Multiple medications have been linked to Acanthosis nigricans. These include the use of nicotinic acid, systemic glucocorticoids, diethylstilbestrol, combined oral contraceptive pill, growth hormone therapy, estrogen, protease inhibitors, niacin, and injected insulin.
Endocrine Dysfunction
Acanthosis nigricans associated with endocrine dysfunction is more insidious in onset, less widespread, and patients are often obese. Insulin-resistance syndromes may be divided into type A (HAIR-AN) and type B syndromes. Type A syndromes present with hyperandrogenemia, insulin resistance, and Acanthosis nigricans. Type B syndrome usually occurs in females who have uncontrolled diabetes, ovarian hyperandrogenism, or autoimmune diseases like SLE, Sjogren syndrome, or scleroderma. Polycystic ovarian syndrome (PCOS) is associated with acanthosis nigricans. Hormone imbalances linked to conditions such as polycystic ovary syndrome (PCOS) or thyroid disorders can also raise the risk of getting acanthosis nigricans.
Malignancy
Increased transforming growth factor (TGF) appears to be the mechanism for malignancy-associated acanthosis nigricans. Malignant acanthosis nigricans syndrome is associated with gastrointestinal adenocarcinomas and genitourinary cancers such as prostate, breast, and ovary. Lung cancer and lymphoma rarely are associated with acanthosis nigricans. Malignant acanthosis nigricans may precede, accompany, or follow the onset of internal cancer. Malignant AN is a rare paraneoplastic syndrome likely due to the release of stimulatory growth factors by tumour cells and is typically associated with gastrointestinal malignancies, especially gastric adenocarcinoma (60%); other associated cancers include hepatobiliary carcinoma, squamous cell carcinoma, malignant melanoma, and Wilms tumour.
Genetic Factors
Familial acanthosis nigricans may arise as a result of an autosomal dominant trait, presenting at birth or during childhood. Hereditary variants are associated with fibroblast growth factor defects. Genes also play a part in determining how likely someone is to get this condition.
Rare Associations
Acanthosis nigricans is also associated with rare diseases such as pinealoma, Cushing disease, ovarian hyperthecosis, stromal luteoma, ovarian dermoid cysts, Prader-Willi syndrome, leprechaunism, lipoatrophic diabetes, pineal hyperplasia syndrome, and Alstrom syndrome.
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Epidemiology of Acanthosis Nigricans
Acanthosis nigricans typically occurs in individuals younger than the age of 40 years and is associated with obesity, hypothyroidism, acromegaly, polycystic ovary disease, insulin-resistant diabetes, and Cushing and Addison diseases. In the United States population, acanthosis nigricans is more common in Native Americans, African Americans, and Hispanics when compared to Whites or Asian origin individuals. Acanthosis nigricans affects < 1% of Caucasians. Acanthosis nigricans was found in 18.2% of children and 19.5% of adults in a cross-sectional study (n=1730) in the United States. Those diagnosed with AN were twice as likely to have type 2 diabetes compared to those without (35.4% vs.
Pathophysiology Explained
The pathogenesis of acanthosis nigricans is likely related to growth factor levels and insulin-mediated activation of insulin-like growth factor (IGF) on keratinocytes and increased growth factor levels. The pathophysiological process behind acanthosis nigricans appears to be related to the proliferation of fibroblasts and the enhanced stimulation of epidermal keratinocytes.
In patients with benign acanthosis nigricans, evidence suggests that insulin or an insulin-like growth factor is enhancing the propagation of epidermal cells. Other mediators that have been identified include fibroblast growth factor and tyrosine kinase receptors (epidermal growth factor receptor). High concentrations of insulin are thought to cause proliferative effects by binding to IGF-1 receptors. It is important to note that free IGF-1 levels also are high in people with metabolic syndrome, leading to faster cell differentiation and cell growth.
In patients with malignant acanthosis nigricans, the most probable stimulating factor is secreted by the cancer cells. Two possibilities are transforming growth factor and epidermal growth factor because both have high levels in people with gastric adenocarcinoma. Other reports indicate normalization of urine transforming growth factor after surgical removal of a tumor, followed by regression of the skin lesions.
Histopathology of Acanthosis Nigricans
The histological exam will reveal papillomatosis, hyperkeratosis with minimal hyperpigmentation. The dermal papillae usually have an upward projection with thinning of the epidermis. There is usually no dermal inflammatory infiltrate.
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History, Physical Examination, and Symptoms
Patients usually present with an asymptomatic area of darkening and thickening of the skin, pruritus, and lesions that are velvety, hyperpigmented macules and patches and progress to palpable plaques. In approximately one-third of cases, malignant acanthosis nigricans presents with skin changes before any signs of cancer. In another one-third of cases, lesions arise simultaneously with the neoplasm. In the remaining one-third of cases, the skin findings manifest sometime after the diagnosis of cancer. Malignant acanthosis nigricans can appear suddenly and often is associated with intense pruritus.
The lesions of acanthosis nigricans typically occur in areas of skin folds like the groin, axilla, or posterior neck. In children, the most common site of acanthosis nigricans is the posterior neck. Rarely, acanthosis nigricans may occur on the mucous membranes of the nose, oral cavity, esophagus, or larynx. Women also may develop lesions on the nipple. Rare cases of acanthosis nigricans have been reported in the conjunctiva. In some patients, there also may be associated with skin tags in the same area. Nail changes like hyperkeratosis and leukonychia may be present. Clinically, it is not possible to differentiate the lesions of benign versus malignant acanthosis nigricans. The velvety markings that are characteristic of acanthosis nigricans (a-can-THO-sis NIH-grih-cans) can appear anywhere on the body. They most often show up on the skin folds of the neck, armpits and groin and under the breasts.
Evaluation and Diagnosis
Acanthosis nigricans is diagnosed clinically and confirmed with a skin biopsy. Blood tests, endoscopy, or X-rays may be required to eliminate diabetes or cancer. On biopsy, hyperkeratosis, leukocyte infiltration, epidermal folding, and melanocyte proliferation may be seen. The workup focuses on ruling out malignancy. Since the vast majority of cases are associated with insulin resistance and/or obesity, screening for diabetes and measuring glycosylated hemoglobin is recommended. Doctors can diagnose acanthosis nigricans by looking at the affected skin. Acanthosis nigricans itself isn't harmful or contagious. But it can be a sign that a person is at risk for diabetes. So the doctor may order blood tests to look for diabetes or other conditions associated with it. At Mid-County Dermatology in St. Louis, Missouri we diagnose this condition often. It is usually diagnosed visually and rarely requires a skin biopsy.
Differential Diagnosis
- Seborrhea
- Tinea
- Erythrasma
- Candidiasis
- Pellagra
- Ichthyosis
- Linear epidermal nevus
- Granular parakeratosis
- Cutaneous hyperpigmentation related to Addison disease
- Confluent and reticulated papillomatosis, which occurs more commonly in females with a mean age of 18-21 years. Reticulation is heterogeneous (as opposed to homogeneous in acanthosis nigricans).
- Erythrasma, which is characterised by well-demarcated red patches often with maceration and possible scaling and is found mainly in intertriginous regions.
- Intertrigo, which is characterised by erythematous patches or plaques, is often macerated or fissured, may show satellite pustules if complicated with candidiasis, and/or may have accompanying pruritus or tenderness.
- Tinea versicolor, especially when hyperpigmented and presenting on the neck, may also be confused with acanthosis nigricans.
Treatment and Management Strategies
Acanthosis nigricans is not directly treatable, but it may fade over time by treating the underlying cause, such as insulin resistance. The goal of treatment is to treat the underlying disease. In the majority of patients, the treatment is done only for aesthetic reasons.
Addressing Underlying Conditions
Treating the underlying cause of acanthosis nigricans can make the dark patches of skin fade or even disappear. This can mean stopping any medicine that’s causing the problem or treating diabetes and other health conditions. Malignant acanthosis nigricans should be addressed with careful workup and management of any underlying malignancy.
Lifestyle Modifications
In some patients, weight loss and correction of insulin resistance lower the burden of hyperkeratotic lesions. Losing weight will help acanthosis nigricans fade. If you’re concerned about your weight, talk to your doctor before going on a diet. One of the main treatment approaches is focusing on weight loss and exercise. Losing extra weight can reduce insulin resistance and improve overall health. Regular physical activity not only helps with weight loss but also increases insulin sensitivity, which can lessen the severity of acanthosis nigricans.
Topical Treatments
Acanthosis nigricans associated with insulin resistance can be treated with drugs such as metformin and rosiglitazone, which are insulin-sensitizing agents. Topical fade creams can lighten skin in less severe cases. Dermatologists sometimes prescribe keratolytics, such as topical retinoids (e.g. topical tretinoin 0.1% or a combination of tretinoin 0.05% and 12% ammonium lactate) and podophyllin. Topical vitamin D analogs (e.g. calcipotriol (calcipotriene) 0.005%) act by decreasing keratinocyte proliferation and cause an improvement of the acanthosis nigricans lesions. Doctors may prescribe creams or lotions that can help lighten the skin. Dermatologists may prescribe creams containing retinoids (Vitamin A) or keratolytic creams (like Amlactin or urea or salicylic acid or glycolic acid) to be applied directly to the skin. These medications work by promoting cell turnover and reducing darkening, gradually improving the appearance of acanthosis nigricans.
Other Therapies
The success of these treatments is variable. Other agents that have been tried include metformin and etretinate. In one report, octreotide also showed marked improvement in a patient with insulin resistance. Melatonin can also improve cutaneous symptoms in obese patients with Acanthosis nigricans by improving the inflammatory status and insulin sensitivity. Cosmetic treatments that have been tried include using alexandrite laser, dermabrasion, and chemical peels. Laser therapy may also help reduce the thickness of the affected skin. If creams don't give satisfactory results, other options like laser therapy or chemical peels may be recommended. Laser therapy targets the pigmented areas, breaking down excess pigmentation and stimulating collagen production for a more even skin tone. Chemical peels involve applying a chemical solution that removes the top layer of skin, revealing healthier skin underneath. In severe or treatment-resistant cases, additional interventions may be considered: Oral retinoids: These medications, derived from vitamin A, can be prescribed for more widespread or stubborn cases of acanthosis nigricans. Surgical options: In rare instances, surgical procedures like dermabrasion or cryosurgery may be used to remove the affected skin.
Discontinuation of Inciting Agents
All inciting agents and medications should be discontinued.
Dietary Considerations
One should make attempts to lower the lipid profile. Reports suggest that dietary fish and niacin may help. Eating a healthy diet and getting regular physical activity can help lower insulin levels and improve skin appearance. Eat whole grains and plenty of fruits and vegetables. Drink water or low-fat milk instead of soda, juice, or other sugary drinks. Limit highly processed foods, fatty foods, and sugary treats. Be physically active every day.
Prognosis and Potential Complications
Patients with the benign form of acanthosis nigricans have few or no skin complications, good prognosis, and potential for resolution with treatment. Complications can stem from underlying diseases like diabetes and insulin resistance. Prognosis in patients with the malignant form of acanthosis nigricans is poor as the malignancy is advanced usually at the time of diagnosis in these patients.
Complications depend on the cause of acanthosis nigricans. Most cases of acanthosis nigricans are due to insulin resistance, but however serious complications like malignancy can also be associated with this condition. Outcomes depend on the cause. Outcomes naturally depend on the underlying cause of the AN. If the underlying etiology can be addressed, such as through weight loss interventions, then the acanthosis nigricans is expected to improve or fully resolve. Obesity, metabolic syndrome, and diabetes have deleterious effects on overall morbidity and mortality. Hereditary acanthosis nigricans may stabilise or even regress spontaneously in some cases.
Consultations and Interprofessional Approach
A dermatology referral may be warranted if the diagnosis is uncertain. Referral to an endocrinologist may be needed in patients with diabetes and other metabolic disorders. Finding and treating acanthosis nigricans early is really important. If doctors identify it early, they can act quickly and use the right methods to manage it. This not only helps with the symptoms but also lowers the chances of complications. Having a primary care doctor (like a general practitioner or GP) on the healthcare team is really important too. They help keep an eye on any other health issues related to acanthosis nigricans and make sure people get regular check-ups. Doctors who specialize in the skin (dermatologists), hormone-related issues (endocrinologists), and other healthcare professionals all work together to give the best care to people with acanthosis nigricans. This team approach makes sure that all parts of the condition are addressed, including how it affects overall health.
Deterrence and Patient Education
Patients need to be educated that hyperpigmentation of the skin may not solely be a skin condition and should be evaluated further, especially if it occurs in middle-aged to elderly patients. Patients need to follow up with their primary care physicians regarding any abnormal pigmentation in their skin. Hyperpigmentation of the skin due to acanthosis nigricans can be treated and sometimes resolves with adequate treatment of the skin condition or treatment of the underlying condition. Patients need to be educated on identifying the risk factors and signs and symptoms of a malignant condition associated with acanthosis nigricans. Depression and low self-esteem can occur in patients with acanthosis nigricans and diagnosis and psychological treatment should be started early in these patients. Skin areas with acanthosis nigricans can look dirty, but they’re not. Scrubbing the skin does not help and can irritate it. Gently clean the skin and don’t use bleaches, skin scrubs, or over-the-counter exfoliating treatments.
Enhancing Healthcare Team Outcomes
Acanthosis nigricans is a common skin disorder, but when it presents, the diagnosis can often be difficult. The condition can be benign or malignant, and hence an interprofessional approach is necessary to make a prompt diagnosis. Healthcare workers in primary care, including nurse practitioners, should always refer the patient to a dermatologist if unsure about the rash. The overall prognosis for patients with the malignant form of acanthosis nigricans is poor, with an average survival of fewer than 24 months. Those with the benign form have an excellent prognosis, provided the condition causing it is treated. The majority of practitioners are likely to see acanthosis nigricans in the younger population with insulin resistance; hence a referral to an endocrinologist is recommended. Finally, patients should be educated that acanthosis nigricans is not a primary skin disorder but is usually due to an underlying condition.
Acanthosis Nigricans and Weight Loss: A Closer Look
Acanthosis nigricans is often linked to insulin resistance, which is commonly seen in individuals who are overweight or obese. When the body becomes resistant to insulin, it compensates by producing more insulin. This excess insulin can stimulate the growth of skin cells, leading to the development of acanthosis nigricans. Therefore, weight loss can play a significant role in improving the condition.
The Impact of Weight Loss
Losing weight can reduce insulin resistance and lower insulin levels, which in turn can help to fade the dark patches associated with acanthosis nigricans. Regular physical activity not only aids in weight loss but also enhances insulin sensitivity, further contributing to the improvement of the skin condition.
Lifestyle Changes for Weight Management
Adopting a healthy lifestyle that includes a balanced diet and regular exercise is crucial for managing weight and improving acanthosis nigricans. A diet rich in whole grains, fruits, and vegetables, along with limiting processed foods, fatty foods, and sugary treats, can help regulate insulin levels and promote weight loss.
Conclusion: Managing Acanthosis Nigricans for Better Health
Understanding acanthosis nigricans is essential for effective identification and management of this skin condition. While AN itself is not harmful, it can be a sign of underlying health issues like insulin resistance, diabetes, or hormonal imbalances. Seeking medical attention for accurate diagnosis and addressing the underlying cause are crucial steps. Lifestyle modifications, including weight management, a healthy diet, and regular exercise, play a significant role in improving the condition. Consulting with a healthcare team, including dermatologists, endocrinologists, and nutritionists, can provide personalized care plans for optimal results. By taking proactive measures, individuals can manage acanthosis nigricans, improve their overall well-being, and potentially prevent further complications.
FAQs About Acanthosis Nigricans
Q: Can acanthosis nigricans be cured completely?
A: While there is no definitive cure for acanthosis nigricans at present, it can be managed effectively through lifestyle modifications and targeted treatments.
Q: Is acanthosis nigricans a sign of diabetes?
A: Acanthosis nigricans can be associated with insulin resistance, which is commonly seen in individuals with type 2 diabetes. However, not all cases of acanthosis nigricans are indicative of diabetes.
Q: Can weight loss help improve acanthosis nigricans?
A: Yes, losing weight through healthy lifestyle changes such as regular exercise and a balanced diet can often lead to an improvement in the appearance of acanthosis nigricans.
Q: Are there any medications that can worsen acanthosis nigricans?
A: Certain medications, such as oral contraceptives and high-dose niacin, have been linked to the development or exacerbation of acanthosis nigricans in some individuals.
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