Centre Hospitalier de Versailles

Symptom course of PFAPA syndrome.

Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is the most common cause of autoinflammatory periodic fever in children. It is generally considered to be a self-limiting condition that resolves spontaneously over time. To evaluate age and delay to recovery of patients with PFAPA syndrome. We retrospectively reviewed the medical records of patients diagnosed with PFAPA syndrome at the Versailles Hospital (Paris, France) and included in the Juvenile Inflammatory Rheumatism (JIR) cohort between 2016 and February 2023. Recovery was defined as the absence of any febrile PFAPA episode in the past year. Patients with either no reported febrile episode or insufficient information on fever status over the last 12 months were contacted by telephone. 209 patients with PFAPA syndrome were included. Overall, 56 (27%) patients experienced resolution of periodic fever, 119 (57%) were still active and 34 (16%) patients were lost to follow-up. Among recovered patients, the median duration of symptoms was 5.43 years (Q1-Q3: 2.97–8.65) and the median age at last febrile episode was 8.34 years (Q1-Q3: 5.44–10.24). Of the 119 patients with persistent fever, 10 patients were initially declared cured but relapsed. In patients whose fever resolved, most experienced their last febrile episode before adolescence. The identification of relapses after at least 12 months without a febrile episode raises questions about the definition of recovery.

Do we need the PFAPA syndrome in adults with non-monogenic periodic fevers?

Suboptimal vaccination coverage of recommended vaccines among French children with recurrent autoinflammatory fever syndromes: a study from the Juvenile Inflammatory Rheumatism cohort.

To determine vaccination coverage among a French cohort of children with recurrent autoinflammatory fever syndromes (RFS). All RFS children aged 2 to 19 years from the Juvenile Inflammatory Rheumatism cohort and followed at the French Reference Center for Autoinflammatory Diseases, Versailles Hospital, were included in our observational study. Immunisation status at ages 2, 7 and 15 years and at the last outpatient visit was evaluated according to the standard French vaccine schedule and recommended supplementary vaccines for patients with immunosuppressive therapy. Of 200 patients, 90 (45%) had periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome; 52 (26%) had familial Mediterranean fever and 50 (25%) had undefined recurrent fever. Complete immunisation as per the standard schedule was obtained by 32% of patients at 2 years, 28% at 7 years, 6% at 15 years and 44% at the last outpatient visit. Similar or higher coverage was obtained by the last outpatient visit for most vaccines, compared to immunisation coverage at 2 years: pneumococcus (91% vs 88%), diphtheria tetanus poliomyelitis (82% vs 86%), hepatitis B (79% vs 69%) and measles, mumps, rubella (91% vs 50%). No patients with immunosuppressive therapy (n = 14) were up to date for all supplementary immunisations recommended for them. Vaccination coverage for RFS children is suboptimal, especially for infants who present with recurrent febrile episodes. The initial vaccination delay is partially corrected through specialist follow-up in later years. Coverage according to the supplementary vaccine recommendations for immunosuppressed patients is poor. Key Points • Vaccination coverage for RFS children is suboptimal, especially at 2 years of age which is likely due to the prevalence of early recurrent febrile symptoms. • The initial vaccination delay is partially recovered during later follow-up at an expert rheumatology center. • Specific recommendations are particularly difficult to apply to patients on immunosuppressive therapy.

Health-related quality of life in children with PFAPA syndrome.

Conventionally, PFAPA syndrome is considered as a benign disease compared to other recurrent fevers because it completely passes before adulthood. However, in our clinical practice, fever episodes have a huge impact on daily activities. Observational cohort study using the Pediatric Quality of Life Inventory (PedsQL™ 4.0) Generic Core and Fatigue Scales. PedsQL™ uses a modular approach to measure the HRQOL in children with acute and chronic health conditions. We used pediatric FMF patients as the control group. We included 33 children with PFAPA and compared them to 27 FMF patients matched for age: preschool-age children (2 to 7 years) and school-age children and youths (8 to18 years). PedsQL™ self-reported scores of children with PFAPA were systematically lower than those of FMF peers for general quality of life and physical and psychosocial functioning (significant only in the preschool-age group). PedsQL™ self-reported fatigue scores of children with PFAPA were significantly lower than those of FMF peers for both preschoolers and school-age children and youths. Parent proxy-reports were not significantly different, even though scores were systematically lower for the parents of PFAPA children. Our study demonstrates, for the first time, that the wellbeing of PFAPA children is poor, with a major impact on psychosocial functioning and increased fatigue. The quality of life of PFAPA children appears to be even lower than that of FMF patients, for whom a lower than normal HRQOL has already been demonstrated.

An international delphi survey for the definition of the variables for the development of new classification criteria for periodic fever aphtous stomatitis pharingitis cervical adenitis (PFAPA).

Diagnosis of Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) is currently based on a set of criteria proposed in 1999 modified from Marshall's criteria. Nevertheless no validated evidence based set of classification criteria for PFAPA has been established so far. The aim of this study was to identify candidate classification criteria PFAPA syndrome using international consensus formation through a Delphi questionnaire survey. A first open-ended questionnaire was sent to adult and pediatric clinicians/researchers, asking to identify the variables thought most likely to be helpful and relevant for the diagnosis of PFAPA. In a second survey, respondents were asked to select, from the list of variables coming from the first survey, the 10 features that they felt were most important, and to rank them in descending order from most important to least important. The response rate to the first and second Delphi was respectively 109/124 (88%) and 141/162 (87%). The number of participants that completed the first and second Delphi was 69/124 (56%) and 110/162 (68%). From the first Delphi we obtained a list of 92 variables, of which 62 were selected in the second Delphi. Variables reaching the top five position of the rank were regular periodicity, aphthous stomatitis, response to corticosteroids, cervical adenitis, and well-being between flares. Our process led to identification of features that were felt to be the most important as candidate classification criteria for PFAPA by a large sample of international rheumatologists. The performance of these items will be tested further in the next phase of the study, through analysis of real patient data.

Is colchicine an effective treatment in periodic fever, aphtous stomatitis, pharyngitis, cervical adenitis (PFAPA) syndrome?

PFAPA syndrome is the most frequent periodic fever syndrome in non-Mediterranean patients. The pathogenesis is unclear and the treatment is purely symptomatic and not standardized. The aim of this study was to assess colchicine's efficacy as prophylactic treatment in PFAPA syndrome and to identify factors able to predict response to treatment. We performed a retrospective, multicentric, cohort study of PFAPA patients under colchicine prophylaxis. PFAPA diagnosis was established according to Feder's criteria. Medical records were reviewed and analyzed for demographic, clinical and laboratory data. We distinguished one responder's group, defined as patients who had no more or twice fewer crises under colchicine and another one of non-responders. Subgroup analyses were performed using non-parametric Mann-Whitney test for quantitative data and calculating odds ratio and confidence interval for qualitative data. Difference between the two groups was considered significant for P-value<0.05 or a confidence interval different from 1. Twenty children, 65% of whom were boys, were analyzed. Their mean age at disease onset was 2.3±1.5 years. Among the nine responder patients, five were MEFV (71%) heterozygotes: M694V mutation in four and V726A once. Heterozygous MEFV gene mutation tended to be more frequent in the responders group (71% versus 43%; OR=0.3 [0.03-2.7]). Non-responder patients had more chronic fatigue (82% versus 33%; OR=9 [1,14-71]) and had more oral aphtosis (82% versus 11%; OR=36 [1,7-141]) than the responders ones. Although not significant, colchicine treatment appeared more effective in patients with less complete PFAPA phenotype and MEFV heterozygosity.