Does having MEFV gene sequence variants affect the clinical course and colchicine response in children with PFAPA syndrome?

The primary aim of this study was to document the treatment modalities used in periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome and look for the efficacy and safety of colchicine in the treatment of PFAPA patients. The secondary aim was to search for whether having MEFV (Mediterranean fever) gene sequence variants affect the clinical course and response to colchicine. The study was conducted in 2 pediatric rheumatology centers. The patients that have been diagnosed with PFAPA syndrome between December 2017 and December 2021 were evaluated retrospectively. The study included 157 patients with PFAPA syndrome (54.8% boys and 45.2% girls). The median follow-up duration was 18 (IQR: 12-30) months. One hundred and fifty-five patients (98.7%) had exudative pharyngitis, 120 patients (76.4%) had aphthous stomatitis, and 82 patients (52.2%) had cervical lymphadenitis during the attacks. Clinical features during attacks were not affected by the presence or absence of the MEFV gene sequence variants. Corticosteroid treatment during attacks was given to 152 patients (96.8%). The frequency of fever attacks did not change in 57 patients (37.5%), increased in 57 patients (37.5%), and decreased in 38 patients (25%) after corticosteroid use. Colchicine was given to 122 patients (77.7%) in the cohort. After colchicine treatment, complete/near-complete resolution of the attacks was observed in 57 patients (46.7%). Colchicine led to partial resolution of the attacks in 59 patients (48.4%). In only 6 patients (4.9%), no change was observed in the nature of the attacks with colchicine treatment. The median duration of the attacks was 4 (IQR: 4-5) days before colchicine treatment, and it was 2 (IQR: 1-2.5) days after colchicine treatment. Also, a significant decrease in the frequency of the attacks was observed before and after colchicine treatment [every 4 (IQR: 3-4) weeks versus every 10 (IQR: 8-24) weeks, respectively, (p < 0.001)]. The overall response to colchicine was not affected by MEFV sequence variants. It was seen that the frequency of fever attacks decreased dramatically in both groups, and children with MEFV variants had significantly less attacks than children without MEFV variants after colchicine treatment (every 11 weeks vs every 9.5 weeks, respectively, p: 0.02).

Conclusion: Colchicine seems to be an effective and safe treatment modality in PFAPA treatment. It led to a change in the nature of the attacks either in the frequency, duration, or severity of the attacks in 95.1% of the patients. This study has shown that having MEFV gene sequence variants did not affect the clinical course or response to colchicine. We recommend that colchicine should be considered in all PFAPA patients to see the response of the patient, irrespective of the MEFV gene mutations.

What is known: • Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome is the most common periodic fever syndrome in the world. Familial Mediterranean fever (FMF) is the most common cause of periodic fever syndrome in Turkey. • Colchicine has become a new treatment option in PFAPA.

What is new: • Some PFAPA patients have Mediterranean fever (MEFV) gene variants, and it is speculated that PFAPA patients with MEFV gene mutations respond better to colchicine. • The aim of this study was to look for this hypothesis. We have seen that the clinical phenotype and colchicine response of PFAPA patients were not affected by MEFV gene sequence variants.