Pyogenic Arthritis, Pyoderma Gangrenosum and Acne (PAPA) and PAPA-Like Syndromes: Systematic Review of the Literature

Pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome is a rare autosomal dominant autoinflammatory disorder caused by mutations in the PSTPIP1/CD2BP1 gene. We systematically reviewed 93 patients with PAPA and PAPA-like syndrome. Most patients were male (65.9%) mainly born to non-consanguineous parents. The median (IQR) age at the onset of symptoms and diagnosis was 6.0 (2.0- 8.0) and 25.0 (7.0-32.0) years, respectively. 62.5% of patients were presented with arthropathies and septic arthritis was the most common (54.2%) initial diagnosis. Joint disorders were the most common findings (n=71, 78.9%) starting at the median (IQR) age of 4.0 (2.0-8.0) years, mainly in the knee (56.5%), ankle (36.9%), and elbow (47.8%). Skin involvement (62 (66.7%)) initially presented at a median (IQR) age of 12.0 (20.-10.0) years and included pyoderma gangrenosum (n=41, 44.1%), acne (n=43, 46.2%), and nodulocystic acne (n=19, 20.4%). There was a stronger association between skin manifestations and the development of the classic triad (P<0.001) compared to joint disorders (P=0.05) and patients with lower age of onset were more prone to the progression of the complete triad (P=0.18). Corticosteroids (n=45, 50.0%) with or without anakinra (33.3%) were the treatments applied in the majority of patients. PAPA/PAPA-like syndromes involve mainly non-axial joints in early childhood and later skin in the second decade of life. Only 26.4% of the patients manifested the classical triad of PAPA syndrome. There is no clear genotype-phenotype association in these disorders. More studies are required to investigate the therapeutic options in PAPA/PAPA-like syndromes.