Batu ED, Sener S, Rodrigues M, Vinit C, Hofer F , et al.
Rheumatology (Oxford, England) •
CS are used to abort disease flares in periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome. We aimed to obtain a global overview of physicians' CS usage strategies and analyse the data in the literature regarding CS use in PFAPA syndrome. The Juvenile Inflammatory Rheumatism Clinical Practice Strategies (JIR-CliPS) PFAPA questionnaire included nine questions on CS use in addition to the demographic data questions. The survey was distributed via e-mail to potential respondents. The MEDLINE/PubMed and Scopus databases were searched systematically to extract the data regarding CS use in PFAPA syndrome. From 47 countries, 144 physicians (female/male = 2.6; 67.4% paediatric rheumatologists) answered the survey. Most respondents (n = 133; 92.4%) prescribe CS in PFAPA flares. The most frequently prescribed CS was prednisolone (63.2%). The definition of response to CS was indicated as 'response within 12 h' by the highest number of respondents (n = 61; 42.4%). When CS cause an increase in attack frequency, most (57.9%) consider another treatment if this causes a decrease in quality of life. Forty-four (30.6%) respondents were 'routinely' prescribing CS to PFAPA patients, and this practice was more frequent among more experienced physicians (P < 0.001). We identified 46 articles in the literature describing 4564 PFAPA patients treated with CS. Prednisone was the most frequently preferred CS (48.2%). Response to CS was around 95%, although an increase in attack frequency was noted in almost 35% of the patients. Physicians frequently use CS for PFAPA in their routine clinical practice. Regarding treatment modification, the quality of life was a prominent consideration for physicians.
Karamanakos A, Vougiouka O, Sapountzi E, Venetsanopoulou AI, Tektonidou MG , et al.
Frontiers in immunology •
To assess the impact conferred by variants on the clinical spectrum of patients with systemic autoinflammatory diseases (SAIDs) in Greece. Consecutive patients (n=167) with confirmed SAIDs who underwent screening by next generation sequencing (NGS) targeting 26 SAID-associated genes, and carried at least one gene variant, were retrospectively studied. The demographic, clinical and laboratory parameters were recorded. In total, 24 rare variants in 23/167 patients (14%) were detected. Notably, 18 patients had at least one co-existing variant in 13 genes other than . Nine patients had juvenile- and 14 adult-onset disease. All patients presented with symptoms potentially induced by the variants. In particular, the candidate clinical diagnosis was Yao syndrome (YAOS) in 12 patients (7% of the whole SAID cohort). The clinical spectrum of patients with YAOS (mean episode duration 8 days) was fever (n=12/12), articular symptoms (n=8), gastrointestinal symptoms (n=7; abdominal pain/bloating in 7; diarrhea in 4; oral ulcers in 3), serositis (n=7), and rash (n=5), while the inflammatory markers were elevated in all but one patient. Most of these patients showed a poor response to nonsteroidal anti-inflammatory drugs (n=7/9), colchicine (n=6/8) and/or anti-TNF treatment (n=3/4), while a complete response was observed in 6/10 patients receiving steroids and 3/5 on anti-IL1 treatment. Another 8 patients were diagnosed with either FMF (n=6) or PFAPA syndrome (n=2) presenting with prominent diarrhea (n=7), oral ulcers (n=2), periorbital swelling and sicca-like symptoms (n=1), or maculopapular rash (n=1). One patient had a clinically undefined SAID, albeit characterized by oral ulcers and diarrhea. Finally, one patient presented with chronic relapsing urticaria with periorbital edema and inflammatory markers, and another one had a Crohn-like syndrome with good response to anti-IL-1 but refractory to anti-TNF treatment. variants were detected in 1 out of 7 SAID patients and seem to have an impact on disease phenotype and treatment response. Further studies should validate combined molecular and clinical data to better understand these distinct nosological entities.
La Torre F, Sota J, Insalaco A, Conti G, Del Giudice E , et al.
Frontiers in medicine •
To evaluate the potential role of K12 (SSK12) in controlling febrile flares in patients with Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis (PFAPA) syndrome. Further aims were to assess the impact of SSK12 on (i) flare duration, (ii) variation in the degree of the highest body temperature during flares, (iii) steroid-sparing effect, and (iv) change of PFAPA accompanying symptoms before and after SSK12 introduction. The medical charts from 85 pediatric patients with PFAPA syndrome (49 males and 36 females) enrolled in the AIDA registry and treated with SSK12 for a median period of 6.00 ± 7.00 months in the period between September 2017 and May 2022 were examined. Children recruited had a median time of disease duration of 19.00 ± 28.00 months. The number of febrile flares significantly decreased comparing the 12 months before [median (IQR), 13.00 (6.00)] and after SSK12 initiation [median (IQR), 5.50 (8.00), < 0.001]. The duration of fever was significantly reduced from 4.00 (2.00) days to 2.00 (2.00) days [ < 0.001]. Similarly, the highest temperature in°C was found significantly lower in the last follow-up assessment [median (IQR), 39.00 (1.00)] compared to the period prior to SSK12 start [median (IQR), 40.00 (1.00), < 0.001]. Steroid load (mg/year) of betamethasone (or any equivalent steroid) significantly decreased between 12 months before treatment with SSK12 [median (IQR), 5.00 (8.00) mg/year] and the last follow-up visit [median (IQR), 2.00 (4.00) mg/year, < 0.001]. The number of patients experiencing symptoms including pharyngitis/tonsillitis ( < 0.001), oral aphthae ( < 0.001) and cervical lymphadenopathy ( < 0.001) significantly decreased following SSK12. SSK12 prophylaxis given for at least 6.00 months was found to reduce febrile flares of PFAPA syndrome: in particular, it halved the total number per year of fever flares, shortened the duration of the single febrile episode, lowered body temperature by 1°C in the febrile flare, provided a steroid-sparing effect, and significantly reduced the accompanying symptoms related to the syndrome.
Karamanakos A, Tektonidou M, Vougiouka O, Gerodimos C, Katsiari C , et al.
Seminars in arthritis and rheumatism •
To assess the possible impact conferred by co-existing variants in MEditerranean FeVer (MEFV) and other genes on systemic autoinflammatory disease (SAID) phenotype. Consecutive patients (n = 42) who underwent screening for SAIDs by next generation sequencing (NGS) targeting 26 genes, and carried at least one MEFV gene variant, were retrospectively studied. A total of 63 MEFV gene variants mainly located in exon 10 (n = 29) and exon 2 (n = 19) were identified in 21 patients with juvenile- and 21 with adult-onset disease. The candidate clinical diagnosis was Familial Mediterranean Fever (FMF) in 11, polygenic SAIDs (PFAPA, Still's disease, atypical SAPHO and inflammatory bowel disease) in 9, whereas the disease could not be clinically defined in 22 patients. Notably, 33 out of the 42 patients (79%) had at least one co-existing variants in 19 genes other than MEFV. NGS confirmed all clinical diagnoses and helped defining diagnosis in 59% of the remaining cases. Patients with undefined SAIDs (n = 9) or atypical FMF phenotype (n = 12) carried significantly more disease-causing variants in genes other than MEFV compared to patients with typical FMF (n = 9). More than one variants in these genes were significantly associated with adult-onset disease, while disease-causing variants in the same genes were also associated with an overall more severe SAID phenotype. Co-existing variants in SAID-related genes may explain the phenotypic variability of these diseases. Further studies should validate combined molecular and clinical data in order to better understand the cumulative gene dosage effect and improve the classification of these patients.
Maritsi DN, Syrmou A, Vartzelis G, Diamantopoulos S, Tsolia MN
Pediatrics international : official journal of the Japan Pediatric Society •
The aim of this study was to compare the immunogenicity and side-effects of hepatitis A virus (HAV) vaccination between periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) patients and healthy controls who have not been previously exposed to HAV. A prospective observational study was carried out of 28 PFAPA patients and 76 controls who received two doses of the vaccine. Immunogenicity was expressed as seroconversion and seroprotection rates; mean HAV-immunoglobulin G concentration was measured at 0, 1, 7 and 18Â months. Side-effects were defined as incidence of adverse events and the effect of vaccination on PFAPA symptoms. All participants were seronegative and seroconverted at 1Â month. One month after primary vaccination, 92.9% of PFAPA patients and 77.6% of the controls attained seroprotection, while the rates increased to 100% and 96.1%, respectively, 1Â month after the second dose. Seroprotection rates remained adequate 1Â year after completion of vaccination. In conclusion, two doses of the inactivated HAV vaccine are well-tolerated and effective in children with PFAPA.
