The true prevalence of PFAPA syndrome, first described in 1987 and known in foreign literature as Marshall syndrome (fever, aphthous stomatitis, pharyngitis and cervical lymphadenitis), has not been established, but it is much more common compared to other autoimmune diseases accompanied by a periodic fever syndrome: familial Mediterranean fever, periodic syndrome associated with the tumor necrosis factor receptor (TNF), known by the abbreviation TRAPS, hyper-IG syndrome- D, etc.

Marshall syndrome is characterized by a wave course. The attack begins with a high fever, accompanied by symptoms of pharyngitis (sore throat, congestion of the tonsils), aphthous stomatitis (mouth ulcers) and enlarged cervical lymph nodes. Children may also experience joint pain, abdominal pain, headaches, and symptoms of general intoxication. The attack lasts several days, relapses occur every 1-2 months. The age of the patients is on average 5 years and at 10 years, children generally recover.

The high efficacy of glucocorticoids, consisting of rapid relief of fever under the influence of prednisone, confirms the diagnosis. In the interictal period, children are in perfect health without the presence of residual symptoms. Antibiotics in this category of patients are not effective. In some cases, NSAID drugs were moderately effective; cimetidine and other H2 antagonists which inhibit the proliferation of T suppressors have also been shown to be effective in some cases. One treatment for PFAPA syndrome is surgery.

The objective of the meta-analysis performed by Italian scientists was to provide evidence of the effectiveness of tonsillectomy and adenotonzyllectomy in the treatment of children with PFAPA syndrome.

To select the studies that could be included in the meta-analysis, the MEDLINE, PubMed and Clinicaltrial.gov databases were used. An in-depth and detailed search of literary sources in English was carried out with the publication of the results of observational and randomized trials evaluating the efficacy of tonsillectomy or adenotonzyllectomy in PFAPA syndrome.

A total of 15 studies that could be included in the meta-analysis were found - 13 observational studies and two large randomized controlled studies. One of the studies is dated 1989, the other 14 were carried out from 1999 to 2010.

In 8 studies, tonsillectomy was considered a treatment method, in 3 - adenotonsillectomy, and in 4 the combined method was analyzed. On average, the follow-up period varied from 3 to 60 months.

A total of 124 out of 149 children (83%) showed complete recovery after surgery (95% confidence interval, 77-89%).

In a randomized trial that studied tonsillectomy as a treatment method, no treatment was performed in the control group. Among the patients who underwent a tonsillectomy, a significant improvement was noted in the 14 versus 6 patients out of 12 in the control group. In another randomized trial comparing adenotonsillectomy and glucocorticoid therapy, 12 out of 19 patients after surgery showed complete recovery, compared to 1 in 20 in the glucocorticoid group.

Based on the above information, a meta-analysis of two randomized controlled trials demonstrated consistency of results (p = 0.37). In the remaining 13 studies, a similar odds ratio was observed for complete resolution of disease symptoms (95% confidence interval, 4-43; p less than 0.001).

At the same time, the researchers point out the shortcomings of the meta-analysis, which include a small sample size (a limited number of studies and participants) and differences in the length of the observation periods. According to the authors, it is imperative to conduct a study with clearly defined criteria for PFAPA syndrome and a follow-up period after surgery of at least 18 months. Nevertheless, the high percentage of complete recovery and the uniformity of results obtained in two randomized trials testify to the effectiveness of surgical treatment of PFAPA syndrome, and since the two surgical approaches were accompanied by similar results, performing an adenectomy did not not play an essential role in determining the outcome of the disease.

Thus, surgery must be considered as an effective means of managing patients with PFAPA syndrome. However, the limited amount of evidence available requires further clarification of the role of surgery. According to the authors, surgical treatment should be used if there is a significant deterioration in the quality of life and ineffective drug treatment.