<p>Diagnosis, Screening and Treatment of Patients with Palmoplantar Pustulosis (PPP): A Review of Current Practices and Recommendations</p>

Abstract

Palmoplantar pustulosis (PPP) is a rare, chronic, recurrent inflammatory disease that affects the palms and/or the soles with sterile, erupting pustules, which are debilitating and usually resistant to treatment. It has genetic, histopathologic and clinical features that are not present in psoriasis; thus, it can be classified as a variant of psoriasis or as a separate entity. Smoking and upper respiratory infections have been suggested as main triggers of PPP. PPP is a challenging disease to manage, and the treatment approach involves both topical and systemic therapies, as well as phototherapy and targeted molecules. No gold standard therapy has yet been identified, and none of the treatments are curative. In patients with mild disease, control may be achieved with on-demand occlusion of topical agents. In patients with moderate-to-severe PPP, phototherapy or a classical systemic agent (acitretin being the best treatment option, especially in combination with PUVA) may be effective. Refractory patients or those with contraindications to use these therapies may be good candidates for apremilast or biologic therapy, particularly anti-IL-17A and anti-IL-23 agents. Recent PPP trials are focusing on blockage of IL-36 or IL-1 pathways, which play an important role in innate immunity. Indeed, IL-36 isoforms have been strongly implicated in the pathogenesis of psoriasis. Therefore, blockage of the IL-36 pathway has become a new treatment target in PPP, and three studies are currently evaluating the use of monoclonal antibodies that block the IL-36 receptor in PPP: ANB019 and spesolimab (BI 655130). In this review, we explore the diagnosis, screening and treatment of patients with PPP.

Recent advances in palmoplantar pustulosis

“…Recently, mutations in AP1S3 have been described in PPP patients, representing another overlap of genetic risk factor among psoriasis, PPP, and GPP 1 , 34 – 36 . The ATG16L1 mutation in a gene located on chromosome 2 that plays a role in the immunological response of psoriasis, by affecting the production of antimicrobial peptides and the production of IL-18 and IL-1, leads to a propagating systemic inflammation that has been detected in both PPP and PV (with single nucleotide polymorphisms) 1 , 34 – 37 . IL36RN loss-of-function mutation induces the activation of IL-36 signaling, causing unregulated cytokine release and skin inflammation manifested mainly as GPP 37 .…”

“…The ATG16L1 mutation in a gene located on chromosome 2 that plays a role in the immunological response of psoriasis, by affecting the production of antimicrobial peptides and the production of IL-18 and IL-1, leads to a propagating systemic inflammation that has been detected in both PPP and PV (with single nucleotide polymorphisms) 1 , 34 – 37 . IL36RN loss-of-function mutation induces the activation of IL-36 signaling, causing unregulated cytokine release and skin inflammation manifested mainly as GPP 37 . The frequency of IL36RN mutations among GPP patients is high (75–80%); such mutations have also been described in acrodermatitis continua of Hallopeau (ACH), in inverse psoriasis associated with PP, and in PPP with a lower frequency, suggesting a common genetic predisposition for all forms of PP, some of them associated with PV 38 .…”

Pustulosis palmoplantaris: Langfriste Kontrolle im Blick

“…small molecules wie Apremilast bei der PPP gelaufen bzw. werden aktuell durchgeführt [1]. Unter anderem wurden im Jahr 2019 Daten zum Einsatz von Secukinumab bei der PPP veröffentlicht [6].…”

“…Insgesamt ist es sehr erfreulich, dass zu diesem seltenen, jedoch für die Patienten stark einschränkenden Krankheitsbild, mittlerweile auch Studien mit modernen Substanzen (insbesondere IL-23-Inhibitoren, IL-17-Inhibitoren, Apremilast) erfolgen bzw. erfolgt sind [1], sodass die Evidenz zu potentiellen Therapieoptionen kontinuierlich steigt. Mit Spannung erwartet werden Ergebnisse zum Einsatz von monoklonalen Antikörpern gegen den IL-36-Rezeptor (Spesolimab und ANB019) bei der PPP.…”

“…Die Pustulosis palmoplantaris (PPP), oder auch Psoriasis pustulosa palmoplantaris genannt, ist eine Erkrankung aus dem Formenkreis der pustulösen Psoriasis. Es handelt sich um eine seltene Erkrankung mit einer geschätzten Prävalenz von 0,01 bis 0,05% [1]. Klinisch zeigen sich typischerweise an den Handflächen und/oder Fußsohlen weißlich oder weiß-gelblich eingetrübte, sterile kleine Pusteln auf scharf begrenzten Erythemen oder roten nicht schuppenden Plaques.…”