Colchicine versus cimetidine: the better choice for Periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) syndrome prophylaxis, and the role of MEFV gene mutations

Abstract

Background During childhood, the most common periodic fever is periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome. The effective treatment and prevention of febrile attacks improve these patients' and their families’ quality of life. However, there is no single strategy or evidence-based guideline to manage this syndrome, and most of them are based on consensus treatment plans. Methods This randomized controlled trial was carried out on 67 PFAPA patients referred to three tertiary centers of pediatric rheumatology. The patients were divided into two groups, including group 1 (n = 36) receiving prednisolone plus colchicine and group 2 (n = 31) receiving prednisolone plus cimetidine. Demographic characteristics and the number of febrile episodes were compared between the two groups before and after the intervention. Results In both groups, the number of febrile episodes after the treatment decreased (P ≤ 0.001). Statistical Analysis showed no significant difference between the two groups (P = 0.88). Moreover, 44 patients from both groups were checked for the MEFV gene. There were no statistical differences between MEFV positive and negative subgroups in response to colchicine (P = 1). Conclusion This study showed that both drug regimens are significantly effective in preventing febrile attacks in PFAPA syndrome, and the presence of a MEFV gene mutation might not be the only significant risk factor for a response to colchicine. Trial registration IRCT, IRCT20191222045847N1. Registered 23 October 2019, https://fa.irct.ir/search/result?query=IRCT20191222045847N1

What is PFAPA syndrome? Genetic clues about the pathogenesis

“…Due to its efficacy in patients with FMF, it has been studied in PFAPA as well [31][32][33]. Additional studies over the past two years showed that colchicine reduces the frequency of flares in children with PFAPA [25,26,34,35]. In one of these, 67 Iranian children were randomly assigned to either prophylaxis with colchicine or cimetidine; both of these prophylactic agents were found to have similar efficacy [35].…”

PFAPA syndrome in children

“…Several studies with small patient cohorts have found that cimetidine, a histamine- 2 (H 2 ) receptor antagonist, shows some preventive effect in 27% to 44% of patients, though that means that more than half of patients are not responsive 5,12. Evidence supporting use of cimetidine is insufficient, but studies are ongoing 24,25…”

“…5,12 Evidence supporting use of cimetidine is insufficient, but studies are ongoing. 24,25 Colchicine, an anti-inflammatory medication most commonly used to treat gout, is showing some promise as a preventive agent for PFAPA. 5 Because it is used as the treatment of choice in FMF, colchicine was trialed for PFAPA, given the two disordersÕ somewhat similar inflammatory pathways.…”

Preliminary data revealing efficacy of Streptococcus salivarius K12 (SSK12) in Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis (PFAPA) syndrome: A multicenter study from the AIDA Network PFAPA syndrome registry

“…Treatment of the syndrome is usually symptomatic with a single low-dose betamethasone (0.1 mg/kg) or prednisone (1 mg/kg), being the most effective option to abort acute disease flares ( 8 ). Colchicine has also been proven to be effective in preventing PFAPA flares ( 9 ). Different reports have also revealed that tonsillectomy may provide symptom resolution in PFAPA syndrome, though the disease might reoccur later, at least in a minority of patients ( 10 ).…”