Acanthosis nigricans is a skin condition where patches of dark, thickened, velvety skin appears on the neck, thighs, or the vulva. The disease itself isn't harmful or contagious, although you may not like how it looks. It can be the symptom of underlying medical conditions and so it is necessary to bring this up with your doctor.
What is acanthosis nigricans?
Treatment options for acanthosis nigricans
Acanthosis nigricans (AN) is a common skin condition that can be an indication of systemic disease that is linked with insulin resistance, diabetes mellitus, obesity, internal malignancy, endocrine dysfunctions, and drug reactions. It is identified by thick velvety hyperpigmented plaques of the intertriginous skin. When AN is linked with internal sickness, skin changes occur quickly and are often accompanied by mucus, liver spots, skin tags, and tripe palms. Endocrinopathy-linked AN develops more gradually and covers a smaller part of the body.
Patients are usually overweight and may have a family history of diabetes or polycystic ovarian syndrome. Treatment of AN should focus on addressing the underlying diseases. Weight loss in obesity-related AN can resolve hyperkeratotic lesions while curing hyperinsulinemia can reduce the number of injuries. Stopping the use of the specific medicine in drug-induced AN often fixes the condition, and surgical removal of tumors is the foundation of treatment in malignancy-associated acanthosis nigricans. While therapy aims to treat the leading cause, cosmetic resolution of the lesions can improve the quality of life of the patients.
Causes of AN
Acanthosis nigricans can appear in otherwise healthy people, so its occurrence is not always related to a medical condition. However, it relates commonly associated with these conditions:
1. Obesity is the most common connection, and losing excess weight can reverse it.
2. Type 2 diabetes: 75% of kids with type 2 diabetes get acanthosis nigricans. Adults with diabetes may manifest it as well.
3. Pre-diabetes or having insulin resistance: Insulin resistance means that you are not responding as well to insulin as you could. Insulin allows for glucose absorption into the body which is used for energy. A person with insulin resistance will need more insulin to be secreted before glucose being absorption by body tissues, and eventually improve how the body deals with sugar like making extra pigment.
4. Genetic disorders like Down syndrome.
5. AD also hardly manifests when one has cancer of the digestive tract, liver, kidney, bladder, or lymphoma
6. In patients with polycystic ovary syndrome (PCOS) or ovarian cysts
7. Oral contraceptives, human growth hormone, high-doses of niacin, prednisone, and some other medicines.
Signs and Symptoms of AD
Dark, thick, velvety skin slowly grows in areas of your body where there are skin folds like in the armpits, groin, and folds of the neck. Some call the line that appears on the neck the sugar line or sugar necklace. This pigmentation may also appear on the joints in your fingers and toes. The skin remains soft, unlike with some other conditions where the skin toughens. This pigmentation will appear less often on the lips, palms or soles, and more frequently associated with cancer patients.
Diagnosis: Report symptoms of acanthosis nigricans to your physician. The doctor will examine the skin and usually diagnose based on the appearance. The physician will most likely ask for blood tests for insulin level or blood sugar level. At times you can also undergo endoscopy or X-rays to check for cancer and other causes.
Treatment options for AN
Primary treatment of acanthosis nigricans aims to correct the underlying cause. Weight loss and reversing insulin resistance are the most effective ways to eliminate any skin changes. It is reversible and will disappear as treatment commences.
Topical treatments
Topical Retinoids
Topical retinoids are considered one of the most common treatment options for AN. In a trial of thirty patients, clinical improvement of treatment-resistant AN was conspicuous in all patients after fourteen days of 0.05% tretinoin application. Six of the thirty patients, 24, i.e., 80% showed total clearance at sixteen weeks. However, intermittent tretinoin was needed to keep the improvement as relapse noted within four weeks after discontinuation of treatment. Histopathologically, the typical changes of hyper-keratosis and keratotic material between papillae were taken care on biopsy after eight weeks of tretinoin application.Use of topical tretinoin of 0.1% also improved AN per the two case reports. An 18-year-old lady with AN got clearance of her neck AN in ten days and axillae within two weeks.7
Another patient experienced a clearing of left axilla AN after tretinoin 0.1% gel was applied twice daily for two weeks, while the right axilla was used as a control and did not show any improvement.Combination therapy may also be used to treat AN successfully. In one trial report, the mixing of 0.05% tretinoin cream and 12 percent ammonium lactate cream led to resolution of obesity-related AN.11 In another trial report of idiopathic AN, a triple-combination depigmenting cream composed of 0.05% tretinoin, 4% hydroquinone, and 0.01% fluocinolone acetonide is put on at night along with daily sunscreen, which showed successful results after one month of use.
Topical vitamin D analogs
Calcipotriene, a vitamin D analog, is another local treatment used for AN. It is said to inhibit keratinocyte proliferation and promote differentiation by increasing keratinocyte intracellular calcium and cyclic GMP levels. When you reduce the number of keratinocytes, it may minimize the cutaneous effects of insulin. One study report in the literature demonstrated improvement of a mixed-type AN in the flexural areas of an obese man after three months of 0.005% calcipotriol cream application twice daily. In a different report, it showed that a woman who was overweight with AN showed improvement in her lesions with use of calcipotriol ointment twice a day, reported calcipotriol to be a safe, effective, and well-tolerated treatment for AN, mainly when etiological treatment is not an option.
Chemical peels
Although considered cosmetic naturally, superficial chemical peels are relatively safe and a practical option for AN as treatment. TCA (Trichloroacetic acid) is a chemical exfoliating agent that destroys the epidermis with subsequent repair and rejuvenation. TCA causes coagulation and precipitation proteins of the skin because it acts as a caustic substance, leading to epidermal necrosis. The destruction is associated with inflammation and wound repair activation, causing re-epithelialization to smooth skin. The improvement was reported by Zayed et al. in AN, in 6 female patients who used TCA peels in a pilot study. An increase was notable with regards to hyperpigmentation, thickening, and overall appearance. TCA has many advantages: it is safe, easily accessible, inexpensive, and can be made quickly. Furthermore, TCA is a stable compound with known precipitation, absorption, and peel depth, which makes judging its endpoint exfoliation simple.
Oral treatment
Oral Retinoids ( acitretin and isotretinoin )
Oral retinoids such as;- acitretin and isotretinoin can be said to be among the effective treatment options for AN. However, improvement requires large dosage and extended courses, with relapses after stopping treatment. One advanced form of action for these drugs is to normalize the growth and differentiation of the epithelial. Extensive AN which is associated with obesity has been treated successfully with isotretinoin (3 mg/kg/day) but is said to relapse when treatment is interrupted.
Another patient noted an improvement of palmar AN by 90% and recovery of axillary AN by 50% within two months using isotretinoin 80 mg/day. After continuously tapering this dosage over a year receiving a total of 30 g and above, there was a recurrence of the patient's skin lesions that got improved by taking 180 mg. A 17-year-old female with dorsum of the hands and Costello syndrome showed improvement in AN of the neck by use of oral isotretinoin treatment started for nodulocystic acne.
There are fewer reports of AN treatment with acitretin present in the literature; however, those that exist are a success in cases of benign AN and syndromic. One trial showed an 18-year-old male with generalized idiopathic AN recovered completely after 45 days of acitretin 0.8 mg/kg divided into daily doses of two. After going for maintenance therapy of 25 mg acitretin for two months daily, lesions recurred that it was resolved subsequently by topical application of 0.1% retinoic acid. Because of acitretin’s longer terminal elimination 1/2-life and fewer lipophilic properties, its use is limited, causing the threat of early recurrence. One case was on the treatment done successfully with retinoid in a patient with generalized lipodystrophy.
Metformin and Rosiglitazone
For the treatment of AN which is related to insulin resistance, conventional insulin-sensitizing agents such as metformin can supplement. Metformin increases peripheral insulin responsiveness, resulting in lowering the production of glucose, hyperinsulinemia, fat mass, body weight, as well as improved insulin sensitivity in patients with AN and insulin resistance.
One clinical trial done in India treated 40 patients with insulin resistance (detected by the Homeostatic Model Assessment for Insulin Resistance) and AN with 500 mg metformin taken thrice daily for three months. Compared to 20 control patients who were treated using a placebo, patients treated using metformin showed statistical and clinically significant improvement in the axilla and AN of the neck, but not in AN of the elbows, fingers or knuckles. In one published case series, three adolescent patients with obesity started on dietary modification and metformin. All the patients had before failed topical therapy for AN, either with calcipotriol / with corticosteroids. Improvement occurred in the patients with no relapse reported after a year. A case report of a 14-year-old boy treated with 850 mg metformin dosage administered twice in a day said no resolution of AN after six months of treatment.A prospective, random, open-label trial compared metformin and rosiglitazone in 27 insulin-resistant patients for 12 weeks.
While a more significant reduction in fasting insulin levels with rosiglitazone, only minimal improvement in AN lesions and skin texture appeared with either agent. Treatment duration can also play a role in observing changes to the skin clinically; metformin improves both AN and insulin resistance if used for 6 or more months. In a smaller prospective six-month trial of metformin in patients with AN and insulin resistance, improvement in AN resulted in 3 out of 5 patients, two adolescents and an adult.
Other Oral Agents
Metformin combined with thiazolidinones, medications that increase insulin sensitivity in peripheral muscles, has also been said to give good results in patients with AN. Insulin resistance, Hyperandrogenemia, and AN syndrome (HAIR-AN syndrome) patients can also use a combination of metformin and oral contraceptives. The spontaneous regression of AN was made known after addition of TZD pioglitazone and sitagliptin, a dipeptidyl peptidase four inhibitors which increase insulin secretion, in an insulin-resistant patient. The long-term use of octreotide, a synthetic analog of somatostatin, sustained the improvement of AN and body weight reduction in a severely obese boy with insulin resistance six months after treatment cessation.
Other therapies
Other therapies have improved AN according to published trial reports including fish oil, podophyllin, and combination therapy with urea, and triple-combination depigmenting cream. Fish oil containing omega-3 fatty acids improves hyperpigmentation and skin texture in one woman with AN and a lipodystrophic form of diabetes after six months of treatment in spite of continued therapy with niacin.20% of Podophyllin in alcohol has been reported to resolve AN lesions of the hands temporarily; however, a resolution preceded by a local reaction after applying the mixture.
Other treatment options that are said to have varying results include salicylic acid and topical urea application.The use of alexandrite laser is another cosmetic treatment option that has been proved to improve AN lesions effectively. More than 95% clearance in the left axilla appeared after seven treatments with long-pulsed (5 msec) alexandrite laser at 4–8 weeks interval. This laser was designed targeting melanin in the hair and was hypothesized to improve skin darkening in affected parts. Although it is expensive compared to oral and other topical treatment options, the use of alexandrite laser as treatment of AN is promising for the future.Current treatment paradigms for AN are changing to include taking care of cutaneous pathology as well as the underlying condition/drug. Solid options include weight loss and exercise to increase insulin sensitivity in insulin-resistant AN. Treatment of AN is multifactorial because the underlying condition often accompanies the skin findings. Initial considerations for the AN workup include evaluating patients for insulin resistance syndrome characterized by obesity, dyslipidemia, hypertension, and diabetes mellitus type II. Providers should obtain a fasting lipid panel, glucose, and insulin, as well as a complete blood count and liver function testing.
If malignancy-associated AN looked into, imaging studies such as plain radiography and computerized tomography/magnetic resonance imaging might provide valuable information. Oral metformin and combinations of other insulin-mediating medications are useful, as they are therapies aimed at resolving the underlying causes contributing to AN.For cosmetic treatment, topical retinoids are considered the first-line therapy for insulin-resistant AN by modifying keratinization rate. However, topical tretinoin requires the application for long durations and improves hyperkeratosis, but not hyperpigmentation. Topical salicylic acid, podophyllin, urea, and calcipotriol also need a frequent use, while TCA peels may provide a faster and less time-intense burden.
Other options include dermabrasion or alexandrite laser; however, you must look at the cost of these treatments as well as the potential for post-inflammatory hyperpigmentation.An important consideration when evaluating a patient with AN is the potential for psychological distress. In one study, obese female adolescents with AN showed significantly lower self-esteem status than healthy control. Testosterone levels significantly correlated with poor self-esteem scores among the obese females with AN. While correction of underlying causes remains the mainstay of treatment, it is crucial to consider cosmetic options to improve patient quality of life that may be affected by the presence of AN lesions.
