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.