Disease activity accounts for long-term efficacy of IL-1 blockers in pyogenic sterile arthritis pyoderma gangrenosum and severe acne syndrome

Abstract

PAPA patients with active lesions display increased NLRP3-mediated IL-1β secretion, and long-term efficacy of IL-1 blockade was demonstrated. Even if other mechanisms related to the complex proline-serine-threonine phosphatase-interacting protein 1 protein networking might play additional roles, this study further supports the potential of IL-1 blockade as an effective therapeutic strategy in PAPA syndrome.

The expanding spectrum of clinical phenotypes associated with PSTPIP1 mutations: from PAPA to PAMI syndrome and beyond

“…In PAMI the response to either anti‐IL‐1 or anti‐tumour necrosis factor‐α blockade is inconsistent . In contrast, PAPA usually shows good response to anti‐IL‐1 blockade . Our trial with a novel IL‐17A antagonist, secukinumab, showed only a partial effect.…”

“…In addition to PAPA syndrome, PSTPIP1 mutations have been associated with PG, acne and hidradenitis suppurativa with or without pyogenic arthritis (PASH and PAPASH, respectively) . Isolated aseptic abdominal abscesses, pyogenic arthritis and osteolytic lesions have also been linked to PSTPIP1 variants (review table available upon request to the corresponding author) …”

Pyogenic arthritis pyoderma gangrenosum and acne syndrome: A rare but important diagnosis for antibiotic‐resistant erysipelas‐like erythema and osteonecrosis

“…weeks, with complete resolution of arthritis and full functional recovery. Subsequently, we contacted the physicians following up the father's relatives with reported recurrent arthritis and found that they are all affected by PAPA syndrome and present the same mutation in the PSTPIP1 gene as our patient 1. Six months later, radiological examination showed marked deformity of navicular bone both on standard X-rays and MRI(Fig.…”

Inflammasomes in the pathophysiology of autoinflammatory syndromes

“…In PAPA syndrome, PSTPIP1 mutations decrease the ability of PSTPIP1 to interact with proline-, glutamic acid-, serine-, and threonine-rich phosphatase, leading to hyperphosphorylated PSTPIP1 variants that have increased avidity for pyrin. 82 Although there is clear evidence of inflammasome deregulation in PAPA syndrome, 83 the syndrome's pathophysiology is complex and probably involves functions of PSTPIP1 other than its regulation of the pyrin inflammasome. 84 These studies demonstrate that pyrin, although known for its association with FMF, can also modulate other autoinflammatory skin disorders.…”