Non-Cochrane · intervention · PM42443943
Surgical versus medical management of PFAPA (Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis): a systematic review and network meta-analysis.
Alsabri Mohammed, Rath Shree, Elkarargy Mohamed Amr, et al. · Pediatric rheumatology online journal · 2026 · PubMed · doi:10.1186/s12969-026-01242-3
Findings
Population Children with PFAPA syndrome
11 findings
| Medical therapy (glucocorticoids and cimetidine combined as one node) | Surgery (tonsillectomy, adenotonsillectomy, partial tonsillectomy or tonsillotomy) | Clinical remission or symptom resolution Not specified · Bayesian random-effects meta-regression: mean study age as covariate (effect modification) | OR 0.72 [0.17, 3.20] GRADE not reported 9 studies |
| Medical therapy (glucocorticoids and cimetidine combined as one node) | Surgery (tonsillectomy, adenotonsillectomy, partial tonsillectomy or tonsillotomy) | Clinical remission or symptom resolution Not specified · Sensitivity analysis: Bayesian random-effects model 4 (Normal(0,2) intercept; Exponential(2) sd) | OR 1.05 [0.22, 4.75] GRADE not reported Studies not reported |
| Medical therapy (glucocorticoids and cimetidine combined as one node) | Surgery (tonsillectomy, adenotonsillectomy, partial tonsillectomy or tonsillotomy) | Clinical remission or symptom resolution Not specified · Sensitivity analysis: Bayesian random-effects model 5 (Normal(0,2) intercept; Half-Normal(0,1) sd) | OR 1.08 [0.16, 6.36] GRADE not reported Studies not reported |
| Medical therapy (glucocorticoids and cimetidine combined as one node) | Surgery (tonsillectomy, adenotonsillectomy, partial tonsillectomy or tonsillotomy) | Clinical remission or symptom resolution Not specified · Bayesian random-effects meta-regression: episode duration as covariate (effect modification) | OR 1.13 [0.19, 6.21] GRADE not reported 9 studies |
| Medical therapy (glucocorticoids and cimetidine combined as one node) | Surgery (tonsillectomy, adenotonsillectomy, partial tonsillectomy or tonsillotomy) | Clinical remission or symptom resolution Not specified · Sensitivity analysis: Bayesian random-effects model 1 (Normal(0,1) intercept; Exponential(1) sd) | OR 1.03 [0.23, 4.22] GRADE not reported Studies not reported |
| Medical therapy (glucocorticoids and cimetidine combined as one node) | Surgery (tonsillectomy, adenotonsillectomy, partial tonsillectomy or tonsillotomy) | Clinical remission or symptom resolution Not specified · Sensitivity analysis: Bayesian random-effects model 3 (Normal(0,2) intercept; Exponential(1) sd) | OR 1.04 [0.30, 3.79] GRADE not reported Studies not reported |
| Medical therapy (glucocorticoids and cimetidine combined as one node) | Surgery (tonsillectomy, adenotonsillectomy, partial tonsillectomy or tonsillotomy) | Clinical remission or symptom resolution Not specified · Sensitivity analysis: Bayesian random-effects model 2 (Normal(0,1) intercept; Exponential(2) sd) | OR 1.04 [0.15, 7.85] GRADE not reported Studies not reported |
| Medical therapy (glucocorticoids and cimetidine combined as one node) | Surgery (tonsillectomy, adenotonsillectomy, partial tonsillectomy or tonsillotomy) | Clinical remission or symptom resolution Not specified | OR 1.10 [0.21, 5.69] Very low Downgraded: imprecision, inconsistency 10 studies · 2048 participants |
| Glucocorticoids | Surgery (tonsillectomy, adenotonsillectomy, partial tonsillectomy or tonsillotomy) | Clinical remission or symptom resolution Not specified | OR 0.36 [0.09, 1.49] Very low Downgraded: imprecision, inconsistency 9 studies · 1498 participants |
| Cimetidine | Surgery (tonsillectomy, adenotonsillectomy, partial tonsillectomy or tonsillotomy) | Clinical remission or symptom resolution Not specified | OR 0.23 [0.03, 1.57] Very low Downgraded: imprecision, inconsistency 5 studies · 674 participants |
| Colchicine | Surgery (tonsillectomy, adenotonsillectomy, partial tonsillectomy or tonsillotomy) | Clinical remission or symptom resolution Not specified | Colchicine could not be incorporated into the network; most available studies were non-comparative and did not meet eligibility criteria for comparative meta-analysis. No studies found 0 studies · 0 participants |
Included primary studies 16
Open in Studies| Study | Year | Also included by | Outcomes it informs here | Trial data |
|---|---|---|---|---|
| Abunejma 2025 Understanding PFAPA Syndrome in Palestine: A Retrospective Cohort Analysis of Epidemiological and Clinical Data. PMID:41122191 | 2025 | this review only | not stated | not extracted yet |
| Chong 2025 Efficacy of partial tonsillectomy in periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome: a STROBE retrospective… PMID:39322492 | 2025 | this review only | not stated | not extracted yet |
| Erdogan 2016 Surgery vs medical treatment in the management of PFAPA syndrome: a comparative trial. PMID:26256936 | 2016 | this review only | not stated | not extracted yet |
| Espahbodi 2024 Assessment of recurrent fever among children undergoing tonsillectomy. PMID:39725936 | 2024 | this review only | not stated | not extracted yet |
| Feder 2009 A clinical review of 105 patients with PFAPA (a periodic fever syndrome). PMID:19889105 | 2010 | this review only | not stated | not extracted yet |
| Garavello 2009 Effectiveness of adenotonsillectomy in PFAPA syndrome: a randomized study. PMID:19464029 | 2009 | this review only | not stated | not extracted yet |
| Kalayci 2023 Assessment of Attack Frequency in PFAPA Patients Based on Therapeutic Modalities. PMID:39690914 | 2025 | this review only | not stated | not extracted yet |
| Koru 2025 Colchicine treatment in PFAPA: how long should we wait for the clinical response? PMID:40316831 | 2025 | this review only | not stated | not extracted yet |
| Lantto 2024 Tonsillotomy for Periodic Fever Syndrome: A Randomized and Controlled Trial. PMID:37477273 | 2024 | this review only | not stated | not extracted yet |
| Madgar 2024 Risk of immediate postoperative fever in PFAPA patients undergoing tonsillectomy. PMID:39111023 | 2024 | this review only | not stated | not extracted yet |
| Manthiram 2025 Features Associated with Response to Tonsillectomy in Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome in… PMID:40122279 | 2025 | this review only | not stated | not extracted yet |
| Moberg 2025 Long-Term Symptoms in Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome after Tonsillectomy. PMID:39613141 | 2025 | this review only | not stated | not extracted yet |
| Pignataro 2009 Outcome of tonsillectomy in selected patients with PFAPA syndrome. PMID:19528401 | 2009 | this review only | not stated | not extracted yet |
| Renko 2007 A randomized, controlled trial of tonsillectomy in periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome. PMID:17719940 | 2007 | this review only | not stated | not extracted yet |
| Vigo 2014 Tonsillectomy efficacy in children with PFAPA syndrome is comparable to the standard medical treatment: a long-term observational study. PMID:24387830 | 2014 | this review only | not stated | not extracted yet |
| Wurster 2011 Long-term follow-up of children with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome. PMID:21798555 | 2011 | this review only | not stated | not extracted yet |
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Children or adults diagnosed with PFAPA by clinical or consensus criteria | Children with PFAPA (n=2,048; 16 studies) |
| Intervention | Surgery (tonsillectomy, adenoidectomy, adenotonsillectomy, tonsillotomy); medical therapies (corticosteroids, colchicine, cimetidine, montelukast, vitamin D, biologics, probiotics) | Surgery (tonsillectomy, adenotonsillectomy, partial tonsillectomy); glucocorticoids; cimetidine (colchicine could not be included in the network) |
| Comparison | Any eligible intervention, placebo, or observation/no treatment | Surgery as network reference; pooled medical therapy (glucocorticoids and cimetidine); observation |
| Outcomes | Remission or symptom resolution, time to remission, attack frequency, interval, severity, attack duration, rescue treatment, adverse events, quality of life, steroid dependence | Clinical remission or symptom resolution (n=2,048, k=10); effect modification by age and episode duration (k=9) |
| Study designs | RCTs, quasi-experimental studies, cohort and case-control studies with a comparator group | RCTs (Renko 2007, Garavello 2009, Lantto 2024) and non-randomized comparative or cohort studies |
| Timing | Not specified | Follow-up from about 2-3 months to more than 12 years |
AMSTAR 2 items
Two independent extractors rated each item. Their ratings are shown side by side because they have not been reconciled yet. The overall rating follows Shea et al. 2017: one critical flaw gives Low, more than one gives Critically Low.
| Item | Extractor A | Extractor B | Agree |
|---|---|---|---|
| 1Research question includes PICO components | Yes | Yes | yes |
| 2Protocol established before the reviewcritical | Partial Yes | Partial Yes | yes |
| 3Choice of study designs explained | No | Yes | no |
| 4Comprehensive literature searchcritical | Partial Yes | Partial Yes | yes |
| 5Study selection in duplicate | Yes | Yes | yes |
| 6Data extraction in duplicate | Yes | Yes | yes |
| 7List of excluded studies with reasonscritical | No | No | yes |
| 8Included studies described in detail | Partial Yes | Partial Yes | yes |
| 9Risk of bias assessed satisfactorilycritical | RCT: Yes · NRSI: Yes | NRSI: Yes · RCT: Yes | no |
| 10Funding of included studies reported | No | No | yes |
| 11Appropriate meta-analysis methodscritical | RCT: No · NRSI: No | NRSI: No · RCT: No | no |
| 12Impact of risk of bias on the pooled results | No | No | yes |
| 13Risk of bias accounted for in interpretationcritical | Yes | Yes | yes |
| 14Heterogeneity explained | Yes | Yes | yes |
| 15Publication bias investigatedcritical | Yes | Yes | yes |
| 16Conflicts of interest reported | Yes | Yes | yes |
| Overall | Critically Low | Critically Low | yes |