Tehran University of Medical Sciences Immunology and Genetics Journal 2645-4831 5 1 2022 03 22 20 29 Amirhossein Hajialigol Alborz Office of Universal Scientific Education and Research Network (USERN), Alborz University of Medical Sciences, Karaj, Iran Mahnaz Jamee Pediatric Infections Research Center, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran Sharareh Kamfar Pediatric Congenital Hematologic Disorders Research Center, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Niusha Sharafinejad Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran. Soheil Ashouri Alborz University of Medical Sciences, Karaj,Alborz province ,Iran Seyed Yasin Tabatabaeimehr Alborz University of Medical Sciences, Karaj,Alborz province ,Iran Afsane Soltani School of Medicine, Iran University Of Medical Sciences, Tehran, Iran Seyed Alireza Mahdaviani Pediatric Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. Ali Akbar Velayati Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. 2022 12 01 2023 02 27 Abstract Background: PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) 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 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. Conclusion: 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.     https://igj.tums.ac.ir/index.php/igj/article/view/107 https://igj.tums.ac.ir/index.php/igj/article/download/107/91