PSTPIP1 (proline-serine-threonine phosphatase-interactive protein 1)-associated myeloid-related proteinemia inflammatory (PAMI) syndrome, previously known as Hyperzincemia/Hypercalprotectinemia (Hz/Hc) syndrome, is a recently described, rare auto-inflammatory disorder caused by specific deleterious variants in the PSTPIP1 gene (p.E250K and p.E257K). The disease is characterized by chronic systemic inflammation, cutaneous and osteoarticular manifestations, hepatosplenomegaly, anemia, and neutropenia. Increased blood levels of MRP 8/14 and zinc distinguish this condition from other PSTPIP1-associated inflammatory diseases (PAID). The aim of this systematic review is to provide a comprehensive overview of the disease phenotype, course, treatment, and outcome based on reported cases. This systematic review adheres to the PRISMA guidelines (2020) for reporting. A literature search was performed in Embase, Medline, and Web of Science on 13 October 2022. The quality of the case reports and case series was assessed using the JBI checklists. Out of the 43 included patients with PAMI syndrome, there were 24 females and 19 males. The median age at onset was 3.9 years. The main clinical manifestations included anemia (100%), neutropenia (98%), cutaneous manifestations (74%), osteoarticular manifestations (72%), splenomegaly (70%), growth failure (57%), fever (51%), hepatomegaly (56%), and lymphadenopathy (39%). Systemic inflammation was described in all patients. Marked elevation of zinc and MRP 8/14 blood levels were observed in all tested patients. Response to treatment varied and no consistently effective therapy was identified. The most common therapeutic options were corticosteroids (N = 30), anakinra (N = 13), cyclosporine A (N = 11), canakinumab (N = 6), and anti-TNF (N = 14). Hematopoietic stem cell transplantation has been recently reported to be successful in five patients. Our review highlights the key characteristics of PAMI syndrome and the importance of considering this disease in the differential diagnosis of patients presenting with early-onset systemic inflammation and cytopenia.

Background PAMI syndrome is a recently described condition, previously known as Hyperzincemia/Hypercalprotectinemia (Hz/Hc) syndrome. It is a very rare auto-inflammatory disorder characterized by a chronic systemic inflammation, cutaneous and osteo-articular manifestations, hepatosplenomegaly, anemia and neutropenia. Increased blood levels of MRP 8/14 (S100A8/A9 or calprotectin) and zinc distinguish this condition. Specific pathogenic mutations in PSTPIP1 gene (p.E250K and p.E257K) were identified as the genetic cause of this condition. Objectives Case presentation and review of literature Case Presentation: We report a case of 13 months age female referred to our unity for recurrent episodes of osteoarthritis. Physical examination showed hepatosplenomegaly. Blood work revealed a systemic inflammation, a microcytic anemia and neutropenia. A complete workup for metabolic disorders, oncologic processes and uncommon infections was negative. Because of history of recurrent osteoarthritis, a whole-body MRI was performed and confirmed a multifocal osteomyelitis. Whole exome sequencing identified the missense p.E250K in the PSTPIP1 gene. Methods A literature search on PAMI syndrome was performed until the15 October 2018. Pubmed was screened using a combination of the following terms: Hyperzincemia, Hypercalprotectinemia, E250K mutation, PSTPIP1 mutation, PAPA with E250K mutation. Results We identified 20 cases of PAMI syndrome in the literature. PAMI syndrome is an early onset inflammatory disease with a median age of 2.4 years. Clinical manifestations include Osteo-articular manifestations (80%), skin lesions (71%), splenomegaly (89%), hepatomegaly (68%), lymphadenopathy (42%), growth failure (58%) and hemorragic diasthesis with recurrent epistaxis and/or haematoma tendency in 5 patients. All cases had relevant abnormalities in hematologic parameters: mild to severe neutropenia and anemia (100%). Thrombocytopenia (42%). Systemic inflammation was confirmed in 94% using the monitoring of CRP, ESR or SAA. Zinc and MRP 8/14 blood concentrations were markedly elevated in all tested patients. Genetic analyses of PSTPIP1 gene revealed the two specific identified mutations (p.E250K and p.E257K) in all patients. Response to the treatment was variable with no consistently effective therapy. Most common therapeutic options were AINS, Corticosteroids (n=9), Anakinra (n=9), Anti-TNF (n=6) and Cyclosporine A (n=4). Conclusion PAMI syndrome is a rare auto inflammatory condition which should be considered in patients with undefined systemic inflammation and neutropenia, even without skin or osteo-articular manifestations. Zinc and serum MRP 14/8 measurement may be helpful tools for the diagnostic orientation in these cases. References [1] HOLZINGER D, FASSL SK, de JAGER D, et al.: Single amino acid charge switch defines clinically distinct proline-serine-threonine phosphatase- interacting protein 1 (PSTPIP1)- associated inflammatory diseases. [2] E. BELELLI, C.PASSARELLI, M.PARDEO, et al: Haematological involvement associated with a mild autoinflammatory phenotype, in two patients carrying the E250K mutation of PSTPIP1 [3] SAMAN K. HASHIMI, KATIE BERGSTROM, ALISON A BERTUCH, et al: PSTPIP1-associatedmyeloid-related proteinemia inflammatory syndrome: A rare cause of childhood neutropenia associated with systemic inflammation and hyperzincemia [4] SAMPSON B, FAGERHOL MK, SUNDERKOTTER C, et al.: Hyperzincemia and hypercalprotectinemia: a new disorder of zinc metabolism. [5] FESSATOU S, FAGERHOL MK, ROTH J, et al.: Severe anemia and neutropenia associated with hyperzincemia and hypercalprotectinemia. Disclosure of Interests Manel Mejbri: None declared, Katerina Theodoropoulou: None declared, michael hofer Grant/research support from: novartis, SOBI, Consultant for: Novartis, SOBI

PFAPA syndrome (Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis) is the most common periodic fever condition in children. Vaccination in this population can be challenging due to concerns about immune hyperreactivity, the potential to trigger febrile episodes, and uncertainty regarding vaccine efficacy. Data on immunization coverage and vaccine response in PFAPA remain limited. This study aimed to describe the clinical characteristics of children with PFAPA, with a particular focus on vaccination coverage and serological responses. We conducted a prospective study of children with PFAPA followed at Geneva University Hospitals between February 2022 and April 2025. Clinical, laboratory, and genetic data were collected, along with vaccination status according to the Swiss national immunization schedule and serological results for major vaccine antigens. Forty-one patients were included. All exhibited elevated inflammatory markers during febrile episodes, and none had a monogenic cause identified. Vaccination coverage was high, with 90–95% of patients receiving the primary DTaP-IPV-Hib-HBV series on time. Minor delays were observed for the third pneumococcal and second MMR doses. Meningococcal (MenC/MenACWY) vaccination was administered on time in 58% of patients. Serological testing confirmed protective antibody levels for most antigens, including diphtheria, tetanus, and measles, but only 40% achieved protective pneumococcal titers. Only 65% showed varicella immunity because of past infection, as none had received the vaccine, which was only introduced in Switzerland in 2023. Children with PFAPA demonstrate high adherence to vaccination schedules and adequate immune responses, supporting the safety and effectiveness of routine immunization in this group. The reduced pneumococcal seroprotection suggests that monitoring antibody levels and considering booster doses may be warranted. Larger controlled studies are needed to assess vaccine immunogenicity and reactogenicity, particularly for highly reactogenic vaccines such as meningococcal B.

Background: Children with rheumatologic diseases often require immunosuppressive therapies, which can compromise their immune response and increase susceptibility to infections. Despite the heightened risk, vaccination coverage in this population is frequently suboptimal, largely due to concerns over vaccine safety, especially live attenuated vaccines, and the absence of clear, universally adopted guidelines. Objective: This retrospective study aims to evaluate the vaccination status and serological immunity of pediatric patients with rheumatologic diseases at the time of diagnosis, prior to initiation of immunosuppressive therapy. Methods: We conducted a retrospective review of medical records from children under 16 years of age diagnosed with a rheumatologic disease at Geneva University Hospitals (HUG) between 2005 and 2023. Demographic data, clinical diagnosis, vaccination history, and available vaccine-specific serologies were collected and analysed. Results: Seventy-four patients were included, with a median age at diagnosis of 6 years. At the time of diagnosis, vaccination coverage was highest for Haemophilus influenzae type b (Hib; 93%), followed by diphtheria and tetanus (91%), measles-mumps-rubella (MMR; 80%), pertussis and poliomyelitis (77–78%), pneumococcus (77%), varicella-zoster virus (VZV; 72%), and hepatitis B virus (HBV; 64%). Baseline serological testing was available in only half of the patients (38/74, 51%). Among those tested, seroprotection was highest for Hib (100%), followed by tetanus (91%), measles (89%), diphtheria (88%), hepatitis B (58%), varicella (47%), and pneumococcus (42%). Longitudinal follow-up revealed limited and inconsistent serological monitoring, with only a minority of patients undergoing repeat testing, and very few receiving booster vaccinations, despite the generally stable protection levels observed over time. Conclusions: Vaccination coverage in children with rheumatologic diseases remains suboptimal, particularly for varicella, hepatitis B, and pneumococcus. These findings underscore the critical importance of optimizing vaccination coverage at diagnosis and establishing systematic serologic surveillance protocols in this high-risk population, rather than relying solely on vaccine history.