SAT0497 CLINICAL PICTURE OF 7 PAPA PATIENTS FOLLOWED IN A SINGLE PEDIATRIC RHEUMATOLOGIC CENTER
Authors: Silvia Federici, Camilla Celani, Virginia Messia, Giulia Marucci, Christoph Kessel, Fabrizio De Benedetti, Antonella Insalaco
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Pyogenic sterile arthritis, pyoderma and acne (PAPA) syndrome is an autosomal dominant inflammatory disorder caused by mutations in the <i>PSTPIP1</i> gene primarily affecting joints and skin. The E250K mutation cause the hyperzincaemia/hypercalprotectinemia syndrome termed <i>PSTPIP1</i>-associated-related proteinemia inflammatory (PAMI) syndrome in which a bone marrow involvement is reported <h3>Objectives:</h3> To describe the clinical presentation of 7 PAPA patients followed at a single pediatric rheumatology center <h3>Methods:</h3> For each patient clinical and laboratory data were collected from medical charts. <i>PSTPIP1</i> was sequenced through Sanger Sequencing or targeted resequencing using a customized panel, and analyzed with the NextSeq® platform (Illumina) <h3>Results:</h3> We describe 7 patients from 4 unrelated families with the E250K mutation in a mother and 2 siblings, the A230T variant in a father and his son and the R405C and D266N respectively in the last 2 unrelated patients. Disease onset occurred within the 7th year of life in all patients. Patients 3 and 4 (table) presented since the 1st year of life recurrent episodes of fever without any cutaneous or articular symptoms. In both patients inflammatory markers were elevated during fever episodes, but persistently negative during wellbeing not requiring any therapy. The variants described in these patients were not previously reported. However their pathogenic role is supported by the detection of markedly high serum calprotectin levels (&gt;10.000 microg/ml). The predominant feature of patients 1 and 2 was articular involvement with recurrent episodes of arthritis associated to acne. Patient 1 was initially treated with prednisone with good clinical response but relapse of arthritis at discontinuation followed by the development of a sterile muscle abscess. An anti-TNF drug was started in both patients with complete clinical response. Patient 5 reported severe acne and psoriasis, and recurrent episodes of sterile arthritis. She presented a persistent elevation of acute phase reactants with severe anemia and leukopenia not resolving after splenectomy. His son (pts 6) presented with recurrent episodes of sterile arthritis, hepato-splenomegaly, anemia and neutropenia. Zinc and calprotectin serum levels resulted respectively 728 micromol/l and 2600 microg/ml. IL-1 inhibition determined a complete normalization of inflammatory parameters with no effects on anemia and neutropenia. In patient 6 zinchemia decreased to almost normal value after 4 months of therapy. Patient 7 presented at the age of 4 years a sterile lymphnode abscess. She also presented with splenomegaly and neutropenia with persistent elevation of acute phase reactants. Anakinra was proposed but not administered for poor compliance <h3>Conclusion:</h3> The clinical picture of patients carrying <i>PSTPIP1</i> mutation may be heterogeneous. In our cohort TNF-inhibitors were successfully used in PAPA patients preventing new arthritis episodes and resolving cutaneous manifestation where present. In 2 patients the clinical picture was mild not requiring continuous treatment. One PAMI patient had a good response to IL-1 inhibition, which however, had no effect on hematological manifestations <h3>Disclosure of Interests: :</h3> Silvia Federici: None declared, Camilla Celani: None declared, Virginia Messia: None declared, Giulia Marucci: None declared, christoph kessel: None declared, Fabrizio De Benedetti Grant/research support from: Abbvie, SOBI, Novimmune, Roche, Novartis, Sanofi, Pfizer, Antonella Insalaco: None declared