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Dupilumab could be treatment option for chronic keloids



A new study has found that keloid formation may be driven by Th2 pathogenesis and, as such, Th2-targeting dupilumab may be useful in treating chronic keloids.

“This preliminary report demonstrates a novel use of dupilumab for chronic keloids, showing major reductions in skin fibrosis and keloidal scarring,” wrote Aisleen Diaz, from the department of dermatology and laboratory of inflammatory skin diseases at the Icahn School of Medicine at Mount Sinai, New York, and coauthors. The study was published as a letter to the editor in the Journal of the European Academy of Dermatology and Venereology.

The authors described a 53-year-old black male patient with severe atopic dermatitis and two keloids who, after 7 months of treatment with dupilumab for AD, had significant improvements in AD – as well as shrinkage of the larger keloid and “complete disappearance” of the smaller keloid.

As a follow-up, the researchers used real-time polymerase chain reaction testing to monitor Th2 gene expression in lesional and nonlesional keloid skin from three black patients (mean age, 47.3 years) with severe keloids and no AD. Five healthy black controls (mean age, 39.8 years) were also included for comparison. In addition, 6-mm whole-skin biopsy specimens were obtained from all patients.

Interleukin-4 receptors, directly targeted by dupilumab, were highly up-regulated in keloid lesions, compared with controls (P less than .1). The Th2 cytokine IL-13 was significantly increased in lesional and nonlesional keloids, compared with controls (P less than .05), and the TH2 cytokine CCL18 was also highly increased in keloids, chiefly in nonlesional skin (P less than .05).

With regard to genes involved in cartilage and bone development that have been recognized as highly expressed in keloids – such as cadherin 11 and fibrillin 2 – all were increased in keloid lesions, compared with both controls and to nonlesional skin (P less than .05), the researchers reported.

“Dupilumab and other Th2-targeting agents may provide treatment options for patients with severe keloids, warranting further studies,” they commented, adding that the patient they described was the first report of a keloid improving with dupilumab, which “blocks type 2 driven inflammation via IL-4/IL-13 signaling.”

Four authors, including Ms. Diaz, had no disclosures. Two authors reported numerous disclosures, including receiving grants, research funds, and personal and consulting fees, from various pharmaceutical companies, including dupilumab manufacturers Regeneron and/or Sanofi.

SOURCE: Diaz A et al. J Eur Acad Dermatol Venereol. 2019 Nov 20. doi: 10.1111/jdv.16097.

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