Arthritis typically presents in childhood and is often how the disorder initially manifests. Joint involvement is monoarticular, aseptic, and characterized by a prominent neutrophilic infiltrate. The arthritis is recurrent and often induced by a traumatic event, but episodes can occur spontaneously. As the disease progresses, joint erosion can ensue, eventually leading to articular destruction.
Cutaneous involvement varies. Nodulocystic acne and PG typically develop in puberty and persist into adulthood. However, pathergy is frequently observed, so minimal trauma may induce ulcers earlier in life. In PAPA syndrome, PG is typically similar to its classical presentation and the inflammatory components of acne typically predominate.
Various mutations in the PSTPIP1 gene on chromosome 15q have been identified in PAPA syndrome. These mutations impair the interaction between PSTPIP1 and PTP-PEST phosphatases, causing the hyperphosphorylation of PSTPIP1. It is suggested that this leads to the activation of the inflammasome, overproduction of IL-1ß, and thus neutrophil-mediated inflammation.
M04.8 – Other autoinflammatory syndromes
724015007 – Pyogenic arthritis, pyoderma gangrenosum, acne syndrome
Differential Diagnosis & Pitfalls
- PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome
- Pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PAPASH) syndrome
- Pyoderma gangrenosum, acne, and hidradenitis suppurativa (PASH) syndrome
- Pyoderma gangrenosum, acne, and ulcerative colitis (PAC) syndrome
- SAPHO syndrome
- Familial Mediterranean fever
- Blau syndrome
- Early-onset granulomatosis
- CANDLE syndrome
- Deficiency of IL-1 receptor antagonist (DIRA) syndrome
- Deficiency of IL-36 receptor antagonist (DITRA) syndrome
- Cryopyrin-associated periodic syndromes (CAPS)
- TNF receptor-associated periodic syndrome (TRAPS)
- Mevalonate kinase deficiency (see Hyper-IgD syndrome)
- Hyper-IgD syndrome
- Macrophage activation syndrome