化膿性無菌性関節炎・壊疽性膿皮症・アクネ症候群

Pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome is a rare autosomal dominant hereditary autoinflammatory disease caused by PSTPIP1 gene variants and belongs to the PSTPIP1-associated inflammatory diseases (PAIDs). Its core clinical manifestations include recurrent pyogenic arthritis, pyoderma gangrenosum, and severe acne with onset in childhood or adolescence. Some patients may also present with multisystem involvement, such as inflammatory bowel disease and scleritis. Inflammation markers, such as CRP and ESR, are often significantly elevated. Treatment mainly involves targeted inhibition of inflammatory pathways, such as IL-1 inhibitors and TNF-α inhibitors. In this article, we report a Chinese patient with PAPA syndrome with disease onset at 13 years of age, whose main manifestations were pyoderma gangrenosum and acne. Genetic testing revealed a de novo PSTPIP1 gene variant (c.748G>A, p.Glu250Lys). We also reviewed recent literature on PAPA syndrome, summarizing its clinical manifestations, diagnosis, and treatment to enhance physicians' understanding of the condition.

Mutations in the gene PSTPIP1 may cause several different autoinflammatory syndromes, but the mechanisms by which distinct PSTPIP1 mutations lead to these differing phenotypes are not fully understood. The two best characterized autoinflammatory conditions resulting from PSTPIP1 mutation are pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome and PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome. Here, we report a novel gain-of-function PSTPIP1 mutation (p.N236K) causing PAMI syndrome in a patient with systemic autoinflammation and severe neutropenia. This mutant form of PSTPIP1 shows increased binding to pyrin and leads to heightened inflammasome formation, relative to WT PSTPIP1. We also identify a transcriptional signature in blood from PAMI patients suggestive of enhanced T cell activation and altered neutrophil survival and/or function. Further research on PSTPIP1-related autoinflammatory conditions is needed to more deeply understand the genetic and immunological drivers of disease and contribute to improving patient outcomes.

Limb salvage using free tissue transfer in patients with rare autoinflammatory syndromes is poorly described, and the safety of microvascular reconstruction in this population remains uncertain. Hereditary pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome is characterized by dysregulated inflammation, pathergy, and impaired wound healing, raising concern for flap compromise and postoperative complications. We report a rare case of lower extremity free tissue transfer in a patient with PAPA syndrome. A 66-year-old woman with rheumatoid arthritis and PAPA syndrome presented with rapid wound breakdown, violaceous ulceration, exposed hardware, and periprosthetic joint infection following left total knee arthroplasty (TKA). Examination revealed an approximately 9 × 7 cm anterior knee defect with subtotal patellar tendon necrosis. After multidisciplinary optimization, she underwent single-stage irrigation and debridement, hardware removal, revision TKA with patellar tendon reconstruction using gracilis autograft, and immediate coverage with a 22 × 14 cm free latissimus dorsi (LD) muscle flap. The flap was anastomosed end-to-side to the anterior tibial artery with venous outflow via the venae comitantes and loosely inset to preserve future surgical access. The donor site was closed primarily. A 21 × 13 cm staged split-thickness skin graft was performed 1 week later, with adjunctive postoperative hyperbaric oxygen therapy (HBOT). Initial healing was uncomplicated, with complete graft take and donor-site healing. Four months postoperatively, the patient developed chronic sinus tracts and recurrent periprosthetic infection requiring flap re-elevation, debridement, and hardware exchange; the flap pedicle was preserved, and coverage maintained. At one-year follow-up, all wounds had healed; flap coverage was durable with acceptable cosmesis, and the patient was ambulatory for short distances without assistance. She was last seen infection-free and full-weightbearing 4 months later. This case demonstrates that microvascular limb salvage is feasible in PAPA syndrome when guided by multidisciplinary planning and strategic flap design.

PsAPASH syndrome is a rare autoinflammatory disorder comprising psoriatic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa, characterized by severe cutaneous and musculoskeletal manifestations that are often refractory to systemic therapies. Sacroiliitis is a recognized feature of PsAPASH, contributing significantly to functional disability. While cooled radiofrequency ablation has emerged as an effective treatment for chronic sacroiliac joint pain, performing interventional procedures in patients with extensive active hidradenitis suppurativa poses unique challenges due to infection risk from cutaneous lesions near needle insertion sites. We report the first case of ultrasound-guided cooled radiofrequency ablation for sacroiliac joint pain in a patient with PsAPASH syndrome and extensive active hidradenitis suppurativa. A 22-year-old female with PsAPASH syndrome presented with bilateral sacroiliitis confirmed by MRI and positive provocative maneuvers, refractory to systemic biologic therapy, NSAIDs, and physiotherapy. Diagnostic intra-articular corticosteroid injections provided greater than 50% pain relief, establishing indication for definitive treatment. Due to extensive active hidradenitis suppurativa lesions near planned needle insertion sites, a multidisciplinary approach was employed involving Physical and Rehabilitation Medicine, Dermatology, and Interventional Pain specialists. Ultrasound-guided cooled radiofrequency ablation targeting the L5 dorsal ramus and S1-S2-S3 lateral branches was successfully performed with real-time mapping to avoid affected skin areas, supplemented by prophylactic antibiotic coverage. The procedure was uneventful, with no infectious or other complications. At 9-month follow-up, the patient maintained excellent pain control (mean NPRS 0, peak NPRS 2) with restoration of functional capacity. This case demonstrates that ultrasound-guided cooled radiofrequency ablation can be safely and effectively performed for sacroiliac joint pain in patients with PsAPASH syndrome, even in the presence of extensive active cutaneous disease, when appropriate multidisciplinary coordination and infection prevention strategies are employed.

INTRODUCTION: EXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a rare disease caused by somatic mutations in the UBA1 gene, first identified in 2020. Prevalence is unclear, and there are no established treatment guidelines, highlighting the need for disease recognition. CASE PRESENTATION: We report the case of a 34-year-old African American man with a prior diagnosis of rheumatoid arthritis who developed migratory arthritis, pustular acne, and hidradenitis suppurativa. Despite suggestive clinical features, delayed access to biologic therapy contributed to disease progression and resulted in hospitalization. After extensive genetic and clinical evaluation, he was diagnosed with PAPASH syndrome. DISCUSSION: VEXAS syndrome results from dysregulation in the ubiquitylation pathway, causing autoinflammatory and hematologic symptoms. Diagnosis is challenging due to variable presentation. Bone marrow biopsy and genomic testing for UBA1 mutation are crucial for diagnosis. Treatment focuses on controlling inflammation with steroids and IL-6 receptor antagonists such as tocilizumab. CONCLUSIONS: We present this case to raise awareness of this recently established condition. Further understanding will aid in optimizing management and improving clinical outcomes.