Could Targeting IL-23–TH17-Pathway Help Treat Pityriasis Rubra Pilaris?
Pityriasis rubra pilaris (PRP) is a chronic inflammatory skin disease that is characterized by reddish orange scaly plaques that tend to cluster, leaving distinct areas of uninvolved skin, known as the islands of sparing. Due to PRP’s association with other autoimmumne diseases such as myasthenia gravis, arthritis, and myositis, the pathogenesis has been hypothesized to be driven by an aberrant immune response, but this has not been confirmed. Because of a close resemblance to psoriasis, treatment options are often mimicked, with treatment using topical corticosteroids, vitamin D analogues, phototherapy, systemic retinoids, methotrexate, cyclosporine, and more recently anti–tumor necrosis factor (TNF) agents. However, these treatments are not based on pathophysiological rationale.
A recent case report found that the cytokine expression in PRP shows a helper T cell 17 (TH17) and TH1 profile indicating that there may be a role for TH17 cytokines in PRP. This discovery could provide the basis for a targeted treatment in blocking the IL-23–TH17 axis. Using skin samples from three patients with PRP, researchers analyzed the messenger RNA (mRNA) expression of innate and adaptive cytokines that are typically involved in psoriasis pathogenesis. The authors found a particular increase of TH17 cytokines IL-17A, IL-17F, and IL-22 in PRP and cytokines of the IL-23–TH17 axis showed comparable mRNA expression levels in all 3 patients with PRP and in those with psoriasis.
One PRP patient was then treated with ustekinumab (Stelara®), a human anti–IL-12/IL-23 antibody approved for severe psoriasis. The results showed that lesions resolved within one month of treatment and remained resolved at 6 month follow up. Of particular interest was the finding that TH17 expression was increased in skin lesions of 3 patients with PRP and the expression levels of TH17 cytokines (and not others) paralleled the clinical improvement during anti–IL-12/IL-23 treatment.
The authors conclude that while this is a case study that requires further exploration, this study identifies a role of the IL-23–TH17-axis in PRP, and suggests a shared pathogenic inflammatory pathway with psoriasis. They state that the findings provide a rationale for targeting the IL-23–TH17 axis as a treatment option which could replace previous serendipitous therapeutic approaches.
Byline: Martha L. Sikes, MS, RPh, PA-C
Posted: June 6, 2017
Source: JAMA Network
Adapted from the original article.
[Image: DermNet New Zealand]