Garavello 2009.

Methods	Non‐blinded, parallel‐group, randomised controlled trial with 18 months duration of follow‐up
Participants	Setting: ENT department of University Hospital of Milano‐Bicocca (Italy) between 2003 and 2006 Sample size: Number randomised: 39 Number completed: 39 Participant (baseline) characteristics: Age: 2 to 13 years Gender: number male 9 (47%) tonsillectomy group; 7 (35%) control group Baseline characteristics balanced. *Signs of criterion 2 (below) were present in the following proportions of participants: aphthous stomatitis ‐ 61% of surgery group, 58% of controls; pharyngitis ‐ 98% surgery, 97% controls; cervical adenitis ‐ 89% surgery, 82% controls. Inclusion criteria: Met the following diagnostic criteria for PFAPA syndrome: Onset of disease in early childhood (before 5 years of age) Regularly recurring, abrupt episodes of fever lasting approximately 5 days associated with constitutional symptoms and at least 1 of the following: aphthous stomatitis, pharyngitis and cervical adenitis, in the absence of other signs of respiratory tract infection* Prompt remission of symptoms after corticosteroid administration and completely asymptomatic interval Normal growth and development Exclusion criteria: Cyclic neutropenia, as assessed by serial neutrophil counts before, during and after a symptomatic episode (twice a week from one episode to the other) Other auto‐inflammatory syndromes such as familial Mediterranean fever, hyperimmunoglobulinaemia D syndrome, Behcet disease, as assessed by family history and by the absence of typical clinical features and laboratory findings (IgD, gene analysis) Clinical and laboratory evidence of immunodeficiency, autoimmune disease or chronic infection
Interventions	Intervention group: Adenotonsillectomy (method not described); N = 19 (N = 19 included in analysis at 6 months) Comparator group: Watchful waiting (medical treatment); N = 20 (N = 20 included in analysis at 6 months) Use of additional medication/treatment (common to both groups): Use of corticosteroids was allowed
Outcomes	Primary outcome: Proportion of patients experiencing immediate and persistent resolution of symptoms during the 18‐month study period Secondary outcome: Number of PFAPA episodes during follow‐up, resolution of symptoms over time
Funding sources	Not stated
Declarations of interest	"The authors declare no conflicts of interest"
Notes	Proportion of children in treatment group that did not receive surgery: not described Proportion of children in control group electing for surgical treatment: 0/20 (0%)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated random number list
Allocation concealment (selection bias)	Low risk	Sealed, opaque envelopes were prepared by an independent researcher not engaged in the study
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	No blinding: unclear if this could have affected treatment for the control arm
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No blinding, but measurement for the main outcomes of PFAPA resolution unlikely to be affected by blinding
Incomplete outcome data (attrition bias) All outcomes	Low risk	No loss to follow‐up or missing outcome data All patients were analysed according to the group randomised (ITT)
Selective reporting (reporting bias)	Unclear risk	No information about original protocol ‐ insufficient information to make judgement of risk
Other bias	Unclear risk	Baseline characteristics ‐ balanced