Vyzhga Y, Wittkowski H, Hentgen V, Georgin-Lavialle S, Theodoropoulou A , et al.
Pediatric rheumatology online journal •
Systemic autoinflammatory disorders (SAIDs) represent a growing spectrum of diseases characterized by dysregulation of the innate immune system. The most common pediatric autoinflammatory fever syndrome, Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA), has well defined clinical diagnostic criteria, but there is a subset of patients who do not meet these criteria and are classified as undefined autoinflammatory diseases (uAID). This project, endorsed by PRES, supported by the EMERGE fellowship program, aimed to analyze the evolution of symptoms in recurrent fevers without molecular diagnosis in the context of undifferentiated AIDs, focusing on PFAPA and syndrome of undifferentiated recurrent fever (SURF), using data from European AID registries. Data of patients with PFAPA, SURF and uSAID were collected from 3 registries including detailed epidemiological, demographic and clinical data, results of the genetic testing and additional laboratory investigations with retrospective application of the modified Marshall and PRINTO/Eurofever classification criteria on the cohort of PFAPA patients and preliminary SURF criteria on uSAID/SURF patients. Clinical presentation of PFAPA is variable and some patients did not fit the conventional PFAPA criteria and exhibit different symptoms. Some patients did not meet the criteria for either PFAPA or SURF, highlighting the heterogeneity within these groups. The study also explored potential overlaps between PFAPA and SURF/uAID, revealing that some patients exhibited symptoms characteristic of both conditions, emphasizing the need for more precise classification criteria. Patients with recurrent fevers without molecular diagnoses represent a clinically heterogeneous group. Improved classification criteria are needed for both PFAPA and SURF/uAID to accurately identify and manage these patients, ultimately improving clinical outcomes.
MARSHALL SYNDROME. Marshall syndrome also known as PFAPA syndrome belongs to the group of autoinflammatory diseases. The acronym reflects the main clinical features of the disease: periodic fever, aphthous stomatitis, pharyngitis, and adenitis. It is the most common autoinflammatory disease, beginning between 1 and 5 years of age. There is little or no impact on growth, but the recurrence of febrile seizures can compromise the quality of life of patients. Clinical diagnosis meets positive and exclusion criteria. Putting it correctly allows a reassuring framework of care and avoids many unnecessary antibiotic treatments. Corticosteroid therapy is the reference treatment for the crisis. Tonsillectomy associated with adenoidectomy can be discussed but is not systematically recommended in this pathology, which is generally benign and most often heals spontaneously with age.
Dingulu G, Georgin-Lavialle S, Koné-Paut I, Pillet P, Pagnier A , et al.
Rheumatology (Oxford, England) •
The new classification criteria for the hereditary recurrent fever (HRF) syndrome [cryopyrin-associated periodic syndrome (CAPS), TNF-α receptor-associated periodic syndrome (TRAPS), FMF and mevalonate kinase deficiency] have been published recently. These criteria define two core sets of criteria for each HRF: mixed criteria, including genetic and clinical variables, and clinical criteria, relying on clinical variables only. Our aim was to validate the criteria for HRF in an independent cohort, the JIR Cohort database, an international repository of systemic inflammatory diseases. We enrolled patients with HRF, periodic fever, adenitis, pharyngitis and aphthous stomatitis syndrome (PFAPA) and syndrome of undefined recurrent fever (SURF). A score ranging from zero to two was attributed to their respective genotypes: zero (no mutation), one (non-confirmatory genotype) or two (confirmatory genotype). The criteria were applied to all patients based on genotype scoring. The treating physician's diagnosis served as the gold standard for the determination of specificity. We included 455 patients. The classification criteria showed excellent specificity for CAPS and TRAPS (98% specificity each), fair specificity for FMF (88%), but poor specificity for mevalonate kinase deficiency (58%). Sub-analysis showed excellent accuracy of the mixed criteria for all four HRFs. Misclassification was mainly attributable to clinical criteria sets, with false-positive patients in all four HRF clinical criteria sets. This study represents the final validation step of the HRF classification criteria as recommended by the ACR. Genetic data appear to be necessary to classify patients with HRF correctly.
Pillet P, Ansoborlo S, Carrère A, Perel Y, Guillard JM
Archives de pediatrie : organe officiel de la Societe francaise de pediatrie •
The (P)FAPA syndrome (periodic fever, adenitidis, pharyngitis, aphthous stomatitis) was described in 1987. The etiology of this periodic syndrome remains unknown. We report three new cases. Three girls, aged from 23 months to eight years, developed (P)FAPA. The other causes of periodic fevers were eliminated and the various treatments (antibiotics, antipyretics, nonsteroidal anti-inflammatory agents) proved ineffective. The repetition of the periodic bouts resulted in depressive disorders, absenteeism from school and a drop in weight in the youngest patient. Two of them suffered a sinusal involvement (chronic sinusitis, polyp) and had an increase in the level of immunoglobulin A. In all three cases, cimetidine at a dose of 20 mg/kg/d was well tolerated and resulted in a disappearance of the periodic fevers. Cimetidine, as an immunomodulating agent, appears to be beneficial in the in-depth treatment of (P)FAPA syndrome.