Gharra A, Amarilyo G, Harel L, Levinsky Y, Tal R , et al.
Orphanet journal of rare diseases •
To characterize the clinical presentation of PFAPA and the response to treatment in an ethnic subgroup- Druze and analyze the differences compared to other ethnic groups. Retrospective data were collected from medical records of patients with PFAPA attending 2 pediatric tertiary medical centers in Israel between March 2014-December 2022. Patients with concomitant familial Mediterranean fever were excluded. Ethnicity was categorized as Mediterranean, non-Mediterranean, multiethnic and Druze. Of 386 patients with PFAPA, 52 (13.5%) were with a corresponding FMF diagnosis (PFAPA/FMF) information was lacking regarding FMF status in 9 (2.3%) patients and 8 (2.1%) patients were excluded because of poor follow-up. The study included 317 PFAPA patients, 178 (56.2%) of which were of Mediterranean descent (Sephardic Jews or Israeli Arabs), 87 (27.4%) were multiethnic, 19 (6%) were of non-Mediterranean descent (all Ashkenazi Jews), and 33 (10.4%) were of Druze ethnicity. No noteworthy differences in age of onset or age of diagnosis were found among ethnic groups. Clinical presentation analysis revealed statistical significance ( = 0.025) of the prevalence of abdominal pain across ethnic groups. No significance association was found regarding other symptoms including pharyngitis, adenitis, aphthous, myalgia, arthralgia, rash, and headache. Additionally, no significant association was observed between the response to treatment and ethnic group. Genetic testing was performed in 127 (40%) patients, no significant association was shown between number of mutations and ethnic origin. The clinical presentation of PFAPA in patients of Druze ethnicity is not significantly different from other ethnic groups in Israel. This finding fails to support the hypothesis that PFAPA is on the Behҫet spectrum. The online version contains supplementary material available at 10.1186/s13023-026-04278-6.
Kasem AliSliman R, Regev S, Ghanim B, Hamad Saied M
Seminars in arthritis and rheumatism •
PFAPA (periodic fever, aphthous stomatitis, pharyngitis, adenitis) syndrome is the most common periodic fever disorder in children, causing recurrent debilitating episodes that impose a substantial burden on children and their families. Current therapeutic approaches primarily rely on corticosteroid administration, which provides rapid symptom resolution but fails to address the underlying inflammatory cascade, prevent future attacks, and carries the risk of side effects. To determine the therapeutic efficacy of colchicine prophylaxis in reducing attack frequency and extending disease-free intervals in PFAPA patients, compared to standard of care management alone. This retrospective cohort study included 55 pediatric PFAPA patients, 15 receiving colchicine prophylaxis, and 40 controls managed with standard care alone. The primary outcome was the change in inter-attack interval duration from baseline study completion. Secondary analyses examined treatment response by FMF genetic status and survival analysis for time to next attack. Both groups showed comparable baseline characteristics, except higher FMF mutation prevalence in the colchicine group (73.3% vs. 27.5%, P = 0.002). Patients receiving colchicine experienced a dramatic improvement in inter-attack intervals (median change: 60 days, IQR: 51) compared with controls (median change: 0 days, IQR: 0; P < 0.001). Colchicine's therapeutic benefit was consistent regardless of FMF genetic status. Colchicine prophylaxis significantly reduces PFAPA attack frequency, with therapeutic benefits that are independent of FMF genetic status. These findings support colchicine as an effective first-line prophylactic treatment for PFAPA patients with frequent episodes or families concerned about frequent steroid use, representing a paradigm shift from reactive to preventive management.
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery •
To compare surgical versus medical treatment approaches for periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome. PubMed, Embase, Web of Science, and Cochrane. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses-Network Meta-analyses checklist. Two authors independently reviewed the studies. Inclusion criteria comprised randomized controlled trials and cohort studies. Non-English studies, along with case series and review articles, were excluded. The primary outcome was the incidence of persistent symptoms following surgery, compared to medical treatment. Secondary outcomes included complications. The search identified 693 publications. After applying the inclusion and exclusion criteria, nine studies were included (three randomized controlled trials and six cohort studies), comprising a total of 691 patients (256 [37%] females, mean age: 2.97 years, and interquartile range: 2.3-3.3). Patients were treated with either tonsillectomy (n = 201), intracapsular tonsillectomy (IT, n = 24), or medical treatment (n = 466). Surgery was associated with a higher likelihood of symptom resolution compared to medical treatment (odds ratio [OR]: 11.7, 95% CI: 2.14-63.94). However, heterogeneity was observed across studies (I = 80.8%, P < .01). A sensitivity analysis was performed, including randomized controlled trials. Both tonsillectomy (OR: 34.15, 95% CI: 3.77-308.95) and IT (OR: 21, 95% CI: 1.5-293.25) were associated with a greater likelihood of symptom resolution. The pooled complication rate was 6.6%, with a higher incidence in patients who underwent tonsillectomy versus IT (46/201 vs 0/24, P = .008). The pooled rate of symptom recurrence was 13.6% in patients following tonsillectomy and 37.5% in IT. Surgical management of PFAPA with tonsillectomy was superior to medical treatment. Tonsillectomy resulted in a lower recurrence rate of symptoms compared to IT, with a comparable incidence of complications to existing literature. However, given the limited number of patients in the IT group, these findings should be interpreted with caution, and further randomized studies are warranted.
Amarilyo G, Harel L, Abu Ahmad S, Abu Rumi M, Brik R , et al.
The Journal of pediatrics •
To evaluate the ethnic distribution of Israeli patients with the syndrome of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA). The medical records of patients with PFAPA attending 2 pediatric tertiary medical centers in Israel from March 2014 to March 2019 were retrospectively reviewed. Patients with concomitant familial Mediterranean fever were excluded. Ethnicity was categorized as Mediterranean, non-Mediterranean, and multiethnic. Findings were compared with patients with asthma under treatment at the same medical centers during the same period. The cohort included 303 patients with PFAPA and 475 with asthma. Among the patients with PFAPA, 178 (58.7%) were of Mediterranean descent (Sephardic Jews or Israeli Arabs), 96 (33.0%) were multiethnic, and 17 (5.8%) were of non-Mediterranean descent (all Ashkenazi Jews). Patients with PFAPA had a significantly higher likelihood of being of Mediterranean descent than the patients with asthma (58.7% vs 35.8%; P < .0001). The Mediterranean PFAPA subgroup had a significantly earlier disease onset than the non-Mediterranean subgroup (2.75 ± 1.7 vs 3.78 ± 1.9 years, P < .04) and were younger at disease diagnosis (4.77 ± 2.3 vs 6.27 ± 2.9 years, P < .04). PFAPA was significantly more common in patients of Mediterranean than non-Mediterranean descent. Further studies are needed to determine the genetic background of these findings.
Butbul Aviel Y, Harel L, Abu Rumi M, Brik R, Hezkelo N , et al.
The Journal of pediatrics •
To describe a cohort of pediatric patients diagnosed with periodic fever aphthous stomatitis, pharyngitis and adenitis (PFAPA) and familial Mediterranean fever (FMF) and compare them with children diagnosed solely with PFAPA (sPFAPA). Clinical, laboratory, and genetic data of all pediatric patients diagnosed with sPFAPA or PFAPA/FMF were retrospectively collected from 2 primary Israeli medical referral centers and compared. Of 270 patients with PFAPA, more than one-half were of Mediterranean ancestry. Among patients with PFAPA, 51 (18.9%) also were diagnosed with FMF (PFAPA/FMF). Genetic data on the 9 most common MEFV variants were available for 45 children (88%) in the PFAPA/FMF group. Two variants were found in 15 children (33.3 %), 1 variant was found 27 patients (60%), and 3 patients (6.6%) had no variants. Abdominal pain, myalgia, and arthralgia each were more commonly reported in the PFAPA/FMF group compared with the sPFAPA group (90% vs 49% [P < .0001]; 46% vs 23% [P = .02]; and 30% vs 17% [P = .049], respectively). Colchicine was more commonly prescribed for the PFAPA/FMF group compared with the sPFAPA group (82% vs 29%; P < .0001), but alleviation of PFAPA symptoms with colchicine was similar between groups (75% vs 63%; P = .23). We show a strong association between 2 common autoinflammatory syndromes, PFAPA and FMF, in patients from Mediterranean ancestry. Clinicians should be aware that presentation of 1 disease may clinically evolve into another. The association between PFAPA and FMF poses the question similar pathogenesis and genetic influence of the MEFV gene on PFAPA.
Butbul Aviel Y, Tatour S, Gershoni Baruch R, Brik R
Seminars in arthritis and rheumatism •
To evaluate the efficacy of colchicine in reducing the frequency of attacks in patients with PFAPA. We conducted a 6-month open label, randomized, controlled study among patients with PFAPA who attend the Pediatric Rheumatology Clinic at the Rambam Medical Center in Israel. A total of 18 patients aged4 -11 years (males:females ratio = 11:7) were randomized into a control group (I, 10 children) and a study group (II, 8 children). Group I was followed for 6 months without any intervention, and group II was initially followed for 3 months and was thereafter treated with colchicine for 3 additional months, according to standard regimen. During the 6-month period of the study the patients and their physician recorded all the episodes of PFAPA in a constructed log. DNA analyses for the 5 common FMF mutations in Israel were performed in 17 out of the 18 patients. The number of episodes during the first 3 months was similar in both groups (group I 3.2 ± 1.5, group II 4.9 ± 2.3; p ≤ 0.12). Group II had significantly less PFAPA attacks in the second period while on colchicine therapy (4.9 ± 2.3 vs. 1.6 ± 1.2; p ≤ 0.01), in opposition to group I, where no difference in the number of attacks was noted between the first and second period of follow-up (3.2 ± 1.5 vs. 2.7 ± 1.5; p = 0.33). Of the 17 patients tested, 8 were carriers for FMF mutations (2 in group I and 6 in group II). Colchicine prophylaxis seems to be effective in reducing the number of attacks in PFAPA.
The symptoms fever, aphthous stomatitis, pharyngitis and cervical lymph node enlargement are among the most frequent complaints that particularly make children and adolescents consult an ENT specialist. In cases where these symptoms occur periodically, a PFAPA syndrome may be present. We report on an atypical process in a 22 year old woman in whom the PFAPA syndrome first occurred during early infancy with recurrences since adolescence. Since the age of eight months the patient suffered from periodically occurring fever and pharyngitis with cervical lymph node enlargement. Therefore, by age four a tonsillectomy was performed and the symptoms disappeared. At age 15 similar symptoms occurred again with fever thrusts over approximately four to five days with temperatures up to 39.8 degrees C associated with pharyngitis, weakness and cervical lymphadenitis. Those symptoms relapsed periodically every four weeks. Treatment regimens with different antibiotics, Dimepranol and Inosin did not show any effect. Hyper-IgD syndrome and cyclic neutropenia were excluded. There were no signs for a humoral or cellular immune defect or a juvenile idiopathic arthritis. It is often very difficult to make the right diagnosis in a child or a young adolescent presenting with periodically occurring fever. So far the PFAPA syndrome is relatively unknown. Nevertheless, we think that it should be considered in the differential diagnosis by the ENT specialist patients with periodic fever, aphthous stomatitis, pharyngitis and cervical lymphadenopathy.