Rapid therapeutic response of palmoplantar pustulosis under biologic treatment with guselkumab

Abstract

Dear Editor, Palmoplantar pustulosis (PPP) is a chronic inflammatory disorder of the palmoplantar skin of unknown origin. It presents with isolated and/or coalescing sterile pustules relapsing repeatedly over a long time. Erythema, scaling, and pruritus as well as painful erosions and fissures may complicate its course and result in reduced functionality regarding daily activities. Experts are still uncertain whether PPP is a subtype of psoriasis or a distinct clinical entity. Epidemiologic data are limited but PPP occurs usually in middle-aged patients with predominance of the female gender and is aggravated by multiple factors particularly smoking. Data from preclinical and clinical studies suggest the interleukin 17/23 (IL-17/IL-23) pathway playing a key role in pathogenesis of the disease. Furthermore, recent studies showed that the IL-36 pathway correlates with generalized psoriasis pustulosa (GPP) as well as PPP. Ongoing clinical studies evaluate the role of its inhibition in both diseases. Guselkumab (TREMFYA) is a pure human monoclonal immunglobuline G1-lambda antibody against IL-23 (p19-subunit) and inhibits selectively the interleukin-23 pathway. The clinical efficacy of guselkumab concerning plaque psoriasis is well proven and superior to the tumor necrosis factor antagonist adalimumab (VOYAGE 1 and 2). However, there is little evidence in countries outside from Asia supporting its use for PPP treatment. A 59-year-old female patient developed a PPP for the first time in 2006. In her medical history and clinical examination were no signs of plaque psoriasis, psoriatic arthritis nor psoriatic onychopachydermo-periostitis. Over years many therapeutic regimens such as local and long-term systemic steroids (10 mg/day) and PUVAphotochemotherapy combined with acitretin (approved treatment option in Germany) were used without sufficient effect. Systemic therapies such as cyclosporine and apremilast showed no effectiveness while fumaric acid esters and methotrexate were interrupted because of intolerability. At the point of presentation (September 2019) the clinical examination showed multiple pustules on palms and soles. In addition, there were clinical aspects of acrodermatitis continua suppurativa with pustules on the fingertips and dystrophic nails (IGA 4, PPPASI 3; Figure 1). Her medical history included acetylsalicylic acid and oxcarbazepine intake as well as smoking (three pack years). Because of the chronic recurring course with resisting pustules, plaques, pruritus, and reduced quality of life treatment with guselkumab was initiated. An almost total clearance of the palmoplantar skin as well as a significant improvement of the onychodystrophy was noted within 3 months after initiation of guselkumab treatment (IGA 1, PPPASI 1; Figure 2). This excellent response persisted through the point of last presentation 8 months later. The treatment of PPP can be challenging especially in cases with moderate to severe activity and chronic relapsing course. But only a few treatments (acitretin for systemic therapy) are licensed for this indication. PPP is most commonly treated with conventional therapies used for plaque psoriasis such as topical corticosteroids, PUVA-photochemotherapy (psoralen and UVA) and acitretin. For recalcitrant forms systemic therapy with methotrexate or cyclosporine can be used. Apart from Japan where PPP is one of the common skin