Article by Dr Manasa S
Introduction to Acanthosis Nigricans
Acanthosis nigricans is a dermatological condition characterized by the presence of velvety, hyperpigmented skin, predominantly occurring in intertriginous areas where skin folds are common. This hyperpigmentation often manifests with poorly defined borders and is typically observed in regions such as the back of the neck, axilla, and groin. Additionally, the affected skin may exhibit notable thickening.
The condition is most frequently associated with diabetes and insulin resistance, serving as a cutaneous marker of these metabolic disorders. However, in rare cases, acanthosis nigricans can be indicative of an underlying internal malignancy, necessitating a thorough evaluation to rule out serious pathology. Furthermore, acanthosis nigricans can also be linked to various hormonal disorders and may emerge as a side effect of certain medications, including systemic glucocorticoids and oral contraceptives.
Given its associations with significant systemic conditions, the presence of acanthosis nigricans warrants a comprehensive clinical assessment to identify and address any underlying health issues.
Causes for acanthosis nigricans
Acanthosis nigricans are characterized by the appearance of dark, thickened patches of skin. This condition occurs when epidermal skin cells proliferate abnormally. The most common trigger for this atypical skin cell growth is elevated insulin levels in the bloodstream.
In rare instances, acanthosis nigricans can also be induced by medications, cancer, or other underlying medical conditions.
Excess Insulin
The primary cause of acanthosis nigricans is an excess of insulin in the blood.
When you consume carbohydrates, your body converts them into sugar molecules like glucose. Some of this glucose is used immediately for energy, while the rest is stored. Insulin is the hormone that facilitates glucose entry into cells for energy use.
Individuals with overweight or obesity often develop insulin resistance over time. Although the pancreas produces insulin, the body becomes inefficient at utilizing it. This inefficiency leads to an accumulation of glucose in the bloodstream, resulting in high levels of both blood glucose and insulin.
Excess insulin stimulates the rapid reproduction of skin cells. In people with darker skin tones, these new cells contain more melanin, leading to the formation of darker skin patches compared to the surrounding skin.
The presence of acanthosis nigricans is a significant predictor of future diabetes.
Medications
– Systemic corticosteroids
– Birth control pills
– Injected supplementary insulin
– Human growth hormones
– Nicotinic acid
– Thyroid medications
– Protease inhibitors
– Oestrogen
All the above said medications can cause changes in insulin levels. Once the above medications are stopped then the condition clears up in the skin.
Few other important causes
– Adrenal gland disorders, such as Addison’s disease
– Disorders of the pituitary gland
– Low levels of thyroid hormones
– Some types of stomach cancer, or gastric adenocarcinoma
– High doses of niacin
– Genetics
– Some autoimmune disorders like Sjogren’s disease or Hashimoto’s thyroiditis
Symptoms
– Dark, thick, velvety skin in body folds and creases
– It develops gradually
– The affected skin might be itchy, have and odour
– The affected skin might develop skin tags
The usual places it appears are sides / back of neck, arms, groin, and anal or genital regions. Sometimes it may be seen in skinfolds, like behind the knees, under the breasts, or the crooks of the elbows.
Acanthosis nigricans aren’t contagious.
Acanthosis is not a harmful condition, but it may be a sign of an underlying condition that requires treatment.
Pathophysiology of Acanthosis Nigricans
The development of acanthosis nigricans is associated with increased growth factor levels and insulin-mediated activation of insulin-like growth factor (IGF) on skin cells (keratinocytes). This condition involves the proliferation of fibroblasts and enhanced stimulation of epidermal keratinocytes.
In benign acanthosis nigricans, insulin or an insulin-like growth factor promotes the growth of epidermal cells. Other key mediators include fibroblast growth factor and tyrosine kinase receptors. High insulin levels bind to IGF-1 receptors, causing increased cell growth and differentiation. Elevated free IGF-1 levels are also found in individuals with metabolic syndrome, contributing to rapid cell proliferation.
Syndromic and familial forms of acanthosis nigricans have been identified, often associated with conditions like hyperinsulinemia, craniosynostosis, and obesity. These are categorized into insulin-resistant syndromes and fibroblast growth factor defects. Examples of insulin-resistant syndromes include Rabson Mendenhall syndrome, leprechaunism, Berardinelli-Seip syndrome, Dunningan syndrome, and Alstrom syndrome. Friction or sweating may also play a role.
In malignant acanthosis nigricans, cancer cells likely secrete growth factors such as transforming growth factor and epidermal growth factor, which are elevated in gastric adenocarcinoma patients. Surgical removal of tumours can lead to normalization of growth factor levels and regression of skin lesions.
Certain medications like insulin can activate IGF receptors, contributing to the condition. Rare cases of acanthosis nigricans have been reported following skin grafts from affected areas.
Risk Factors for Acanthosis Nigricans
Acanthosis nigricans can develop in both males and females. It is most prevalent among the following groups:
– Overweight individuals
– People with ancestral roots in Africa, the Caribbean, and South or Central America, as noted by the American Academy of Dermatology
– Native Americans
– Individuals with diabetes or prediabetic conditions
– Those with a family history of acanthosis nigricans
– Children who develop acanthosis nigricans, as they are at a higher risk of developing type 2 diabetes later in life
Diagnosis
Physical examination
– Blood tests to confirm the underlying conditions such as diabetes
– Skin biopsy on rare occasions when diagnosis is not clear
Preventive measures
– If obesity is the cause of acanthosis, then weight management forms the important preventive measure
– A diet that helps in keeping the blood sugar levels at bay
– Managing medical conditions like thyroid and diabetes
– Avoiding medications such as birth control pills that cause or worsen acanthosis
Treatment and management
– The main aim of treatment of acanthosis nigricans should focus on the underlying disease process.
– Cosmetic resolution also plays an important role in improving the quality of life.
– Weight reduction in obesity related acanthosis nigricans helps in resolving hyperkeratotic lesions
– Correction of hyperinsulinemia might reduce the burden of acanthosis
– Stopping of medication that induced acanthosis
– Surgical removal of tumours are the main step in acanthosis induced by malignancy
– Topical retinoids are considered as the first line of treatment
– Topical vitamin D analogs like Calcipotriene helps to inhibit keratinocyte proliferation
– Chemical peels
– Laser therapy or dermabrasion to reduce thickness
– Antibiotics to get rid of odour or discomfort
– Oral retinoids like isotretinoin and acitretin are also considered as effective options for treating acanthosis
– Metformin and rosiglitazone form the first line of treatment for acanthosis associated with insulin resistance.
Prognosis for Individuals with Acanthosis Nigricans
Acanthosis nigricans (AN) itself is not inherently dangerous or harmful, and individuals with this condition can lead normal, healthy lives.
However, managing the underlying conditions that may contribute to AN, such as diabetes, obesity, or hormonal disorders, is crucial. Effective management of these conditions can help mitigate the skin changes associated with AN and improve overall health outcomes.
Importantly, if the dark patches of skin associated with AN appear suddenly, it is imperative to consult a healthcare provider promptly. Sudden onset of AN can be a sign of an underlying malignancy, and early evaluation and diagnosis are essential for timely intervention and treatment.
Study – In ‘A study of pathogenesis of Acanthosis Nigricans and its clinical implications’ study, these observations were found. The commonest histopathological feature of patients with Acanthosis Nigricans was hyperkeratosis – seen in 100% patients, papillomatosis – in 90% patients, dermal infiltrate of lymphocytes and plasma cells – in 60% patients, horn pseudocysts were seen in 30% patients and irregular acanthosis in 26.6% patients.
Study – Yet another study tells that Acanthosis nigricans is a dermatological marker of metabolic disease.
Study – Another study explains that adolescent obesity and Acanthosis nigricans are closely related. AN was once considered as a rare paraneoplastic dermatosis but is now frequently observed in obese adolescents.
Acanthosis Nigricans: Ayurveda Understanding
No particular disease explained in Ayurveda texts can be exactly correlated with Acanthosis Nigricans.
Hyperpigmentation or darkness of the skin (hyperkeratosis) can be said to be caused by aggravated Vata since Karshnya – darkness or blackish discoloration has been mentioned among the symptoms of pathological vata increase. Likewise, thickening of the skin which is also a main feature of this disease Acanthosis Nigricans, vata and kapha can be said to be jointly causing this condition. Bhrajaka Pitta and Udana Vata may play a key role in this condition.
Looking from ‘disease perspective’ explanation as given in Ayurveda treatises, the picture of Acanthosis Nigricans, though not exactly and completely, will fit into the description of Kapala Kushta, Eka Kushta, Charma / Charmakhya Kushta and Vata predominant Kushta. Some clues of understanding Acanthosis Nigricans can be obtained from the description of Purvarupa – premonitory symptoms of Kushta.
Understanding Medoroga, Sthoulya, Medovaha Sroto dushti and Prameha in a loop will help in getting other clues of manifestation of this condition and ways of dealing with it.
As far as treatment is considered, avoidance of causative factors and treating the primary dosha or disease-causing Acanthosis Nigricans will be the key strategy.
Related Reading – ‘Acanthosis Nigricans – Ayurveda Understanding’
