Treating Acanthosis Nigricans

The skin condition acanthosis nigricans manifests as dry patches that appear in areas where the skin forms folds and creases. Acanthosis nigricans (AN) is not a standalone disease, but a symptom of an underlying health condition; and, as such, managing and treating the condition involves careful consideration of the underlying cause.

Obesity-associated AN

Also known as pseudoacanthosis nigricans, this is the most common type of AN and is strongly associated with insulin resistance. Losing weight can be sufficient to improve the appearance of any AN patches in those who are overweight or obese. Making relatively simple lifestyle changes, such as eating a healthy, balanced diet and undertaking more physical activity, can have a profound effect on a person’s overall health and wellbeing. Those who are insulin resistant are at high risk of developing type 2 diabetes mellitus (T2DM). Losing weight can lower this risk.

Medication-induced AN 

Certain prescription medications have been shown to trigger AN in some patients. If AN occurs as a direct result of medication use, stopping that medication should resolve the condition. This would need to be discussed with your doctor first, as it may be necessary to find an alternative way of managing whatever your underlying condition is.

Malignant AN

In some cases AN presents as a physical symptom of cancer. This type of AN is usually accompanied by pronounced weight loss. In the case of cancer-induced AN, typical treatments used for AN, such as retinoids and insulin sensitisers will have no effect. These patches will disappear when the underlying cancer is treated. Their reappearance after treatment can be a sign of cancer recurrence.

Treating AN: Topical options 

Retinoids. The most widely used example is tretinoin. Topical retinoids are generally the first line treatment approach for AN, they are less likely to exhibit adverse effects than oral retinoids. Retinoids are thought to work by regulating the growth and differentiation of the cells that make up the outer layer of the skin. They can be used alone or alongside other treatments. One preliminary study showed that tretinoin, in combination with ammonium lactate, was an effective treatment strategy for AN. Whilst clinical trials do show effectiveness of topical retinoids, the study sizes are small and in some cases single case reports. So further work is required to really establish their efficacy and effectiveness. 

Topical vitamin D analogues. Calcipotriol is an example of a vitamin D analogue. It is thought to work by inhibiting the proliferation of keratinocytes. Keratinocytes are the cells on the outer layer of the skin; they contain receptors, which insulin can bind to. By inhibiting the growth and division of these cells, there will be fewer active target sites for the insulin to bind to and thus, its effects will be reduced. Most of the evidence for the use of topical vitamin D analogues comes from single case reports.

Peels. Trichloroacetic acid (TCA) is used to perform chemical peeling, which is a cosmetic procedure that aims to smoothen the texture of the skin. Peels work by destroying the outer layer of the skin. Used at a 15% concentration, TCA causes necrosis of the skin. Wound repair mechanisms are activated to repair and rejuvenate the damaged cells. This procedure is considered to be safe, cost effective and readily available. It produces faster results than other methods and the limited trials that have been completed, suggest it is comparable in efficacy to retinoids.

Treating AN: Systemic options 

Oral retinoids. Examples include isotretinoin, acitretin and etretinate. It is not fully understood exactly how these medications work, but they probably help to normalise skin cell growth. They usually need to be taken in large doses over a long time period and relapse is common once treatment stops. Most trials investigating their effectiveness have involved single case studies.

Insulin sensitisers. The fact that AN is intrinsically linked to insulin resistance in many cases, suggests a role for insulin sensitisers in the management of the condition. Metformin is one of the most widely used insulin sensitisers. It is used to treat T2DM and, due to the association between PCOS and insulin resistance, it is often prescribed for women with PCOS. As with all of the proposed treatment approaches for AN, experimental data is lacking, but the limited results indicate that metformin and two other insulin sensitisers (alpha-lipoic acid and rosiglitazone), work for some patients, but not all. It has been suggested that to see an improvement, these medications would need to be taken for at least six months.

Melatonin. Evidence for the use of melatonin in the treatment of AN comes from the knowledge that, amongst other things, it improves insulin sensitivity; meaning it has potential for managing insulin resistant-dependent AN. The results of an initial clinical trial, published in 2018, suggested that melatonin improved the appearance of AN patches in obese patients, but unfortunately there is no further clinical evidence in support of its use. 

Treating AN: Laser therapy

Long-pulsed Alexandrite laser. Laser treatment of the affected area has been shown to reduce the appearance of AN patches, although multiple sessions are required. The laser targets melanin, which is the pigment that gives the skin, eyes and hair their colour. Less pigment availability should improve the signs of AN. However, this may not be a suitable option for darker skinned individuals as there is a risk of post-procedure hyperpigmentation. Preliminary studies suggested that, in some patients, laser therapy was more effective at treating AN than topical retinoids. However, at the moment, the requirement for multiple sessions and the cost of treatment may mean this is not a feasible solution for all patients.

Other lasers. The fractional 1550-nm erbium fiber laser and the carbon dioxide laser are both  proposed as potential therapies for AN. However, early work suggests that carbon dioxide lasering is less effective than chemical peels and experimental data on both is very limited.

Conclusion

When it comes to managing AN, many of the treatments described in this article aim to resolve the cosmetic issue, but do not rectify the underlying cause. Certainly, considering the condition from a cosmetic perspective is important because AN can impact a patient’s confidence and self-esteem. However, by failing to uncover and manage the underlying cause, long-term medication usage is common and relapse rates are high. 

Whilst a large number of treatment options exist, the evidence in support of their use is very limited. Much of the data comes from single case studies and there is a need for larger scale, longer-term investigations.

AN is not straightforward to manage, it might involve a multidisciplinary team of specialists to identify the cause and treat the clinical manifestations. This could include dermatologists, endocrinologists, oncologists and dietitians. 

Establishing and treating the underlying cause remains the best way of finding permanent relief.          

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Sources:

• “Acanthosis Nigricans.” NORD (National Organization for Rare Disorders), rarediseases.org/rare-diseases/acanthosis-nigricans/.
• Das, Anupam, et al. “Acanthosis Nigricans: A Review.” Journal of Cosmetic Dermatology, vol. 19, no. 8, Aug. 2020, pp. 1857–1865., doi:10.1111/jocd.13544.
• Higgins, S. P, Freemark, M., & Prose, N. S. (2008). Acanthosis Nigricans: A practical approach to evaluation and management. Dermatology Online Journal, 14(9). Retrieved from https://escholarship.org/uc/item/7mf6g290
• Patel, Nupur Uma, et al. “Current Treatment Options for Acanthosis Nigricans.” Clinical, Cosmetic and Investigational Dermatology, vol. 11, 7 Aug. 2018, pp. 407–413., doi:10.2147/ccid.s137527.
• Sun, Hang, et al. “Melatonin Treatment Improves Insulin Resistance and Pigmentation in Obese Patients with Acanthosis Nigricans.” International Journal of Endocrinology, 12 Mar. 2018, doi:10.1155/2018/2304746.