4.3 Article

Nonulcerated Necrobiosis Lipoidica Successfully Treated with Tapinarof: A Case Report

Journal

CLINICAL COSMETIC AND INVESTIGATIONAL DERMATOLOGY
Volume 16, Issue -, Pages 1373-1376

Publisher

DOVE MEDICAL PRESS LTD
DOI: 10.2147/CCID.S408070

Keywords

aryl hydrocarbon receptor; AHR; granulomatous disease; JAK-STAT pathway; macrophage activation disorder; necrobiosis lipoidica diabeticorum; therapeutic aryl hydrocarbon receptor-modulating agent; TAMA; tumor necrosis factor-alpha antagonists; TNF-alpha antagonists

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Necrobiosis lipoidica (NL) is a chronic granulomatous disorder of the skin that commonly causes red papules and plaques on the lower extremities. NL is associated with diabetes mellitus, but the exact cause is unknown. NL is difficult to treat, and options often rely on limited case reports. We present a successful case of treating NL using tapinarof cream, a novel anti-inflammatory agent targeting multiple pathways without serious adverse reactions.
Necrobiosis lipoidica (NL) is a chronic granulomatous disorder of the skin which usually presents with red papules and plaques on the lower extremities. Diabetes mellitus has been found to be associated with NL, but the pathophysiology of the disease is unknown. Based on a Doppler flowmetry study showing increased blood flow at NL lesions and the macrophage upregulation of granulomatous disorders, it is reasonable to conclude that there is an inflammatory component to it. NL is extremely challenging to manage. The initial treatment of choice is usually topical or intralesional corticosteroids, and if this fails to work, many dermatologists depend on the small number of case reports for more treatment options. We present a pre-diabetic patient with nonulcerative NL who was successfully treated with the first-in-class therapeutic aryl hydrocarbon receptor (AHR)-modulating agent tapinarof cream (VTAMA, Dermavant). Following the case presentation is a discussion of this topical novel agent and its unique anti-inflammatory mechanism of action. Tapinarof specifically binds to and activates AHR leading to downregulation of TNF-a/IL-23/IL-17 and inhibition of IL-4/IL-13 mediated STAT6 activation. Anti-TNF-a agents and JAK-inhibitors have also been found to be beneficial in treating NL; tapinarof seems to target both these pathways without the risk of their serious adverse reactions.

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