University of Milan

An Italian multidisciplinary Delphi Consensus on new insights about the clinical relevance of Pidotimod.

Pidotimod is a synthetic dipeptide that modulates both innate and acquired immunity, with the highest number of scientific publications (as documented in PubMed) which have demonstrated its efficacy and safety in different clinical settings. A board of experts promoted a multidisciplinary Delphi Consensus to increase clinicians' knowledge of the possible areas of pidotimod use and also offer useful tools for informed use based on consolidated data. A series of statements concerning the use of pidotimod in different clinical settings and conditions was anonymously voted on by a panel of qualified Italian specialists, including pediatricians, otorhinolaryngologists, allergologists, and pulmonologists, using a web platform. All the statements obtained full agreement from the panel about the scientific value of evidence on pidotimod efficacy and safety in managing children and adults with recurrent respiratory infections, both in prevention and add-on therapy. In addition, there was agreement about the use of pidotimod in specific situations, including combined therapy (antibiotics plus pidotimod) for pneumonia, Down syndrome, COVID-19, PFAPA, wheezing, and urinary infections. In conclusion, pidotimod is a safe and effective drug helpful in preventing recurrent respiratory infections in susceptible patients and as an adjuvant in managing patients with infections.

Development and implementation of the AIDA International Registry for patients with Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis syndrome.

Aim of this paper is to illustrate the methodology, design, and development of the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to patients with the Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis (PFAPA) syndrome. This is a physician-driven, non-population- and electronic-based registry proposed to gather real-world demographics, clinical, laboratory, instrumental and socioeconomic data from PFAPA patients. Data recruitment is realized through the on-line Research Electronic Data Capture (REDCap) tool. This registry is thought to collect standardized information for clinical research leading to solid real-life evidence. The international scope and the flexibility of the registry will facilitate the realization of cutting-edge study projects through the constant updating of variables and the possible merging and transfer of data between current and future PFAPA registries. A total of 112 centers have already been involved from 23 countries and 4 continents starting from August 24th, 2021, to April 6th, 2022. In total 56/112 have already obtained the formal approval from their local Ethics Committees. The platform counts 321 users (113 principal investigators, 203 site investigators, two lead investigators, and three data managers). The registry collects retrospective and prospective data using 3,856 fields organized into 25 instruments, including PFAPA patient's demographics, medical histories, symptoms, triggers/risk factors, therapies, and impact on the healthcare systems. The development of the AIDA International Registry for PFAPA patients will enable the on-line collection of standardized data prompting real-life studies through the connection of worldwide groups of physicians and researchers. This project can be found on https://clinicaltrials.gov NCT05200715.

The enigma of periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome.

Tonsillectomy in children with periodic fever with aphthous stomatitis, pharyngitis, and adenitis syndrome.

To seek evidence supporting a role for tonsillectomy or adenotonsillectomy in the management of affected children with periodic fever with aphthous stomatitis, pharnygitis, and adenitis (PFAPA) syndrome. A comprehensive literature search was conducted to identify all published English-language observational and randomized studies evaluating the efficacy of tonsillectomy or adenotonsillectomy on PFAPA syndrome. A combination of keywords was used to identify relevant articles. A total of 15 studies including 149 treated children were found, including 13 observational noncomparative studies and 2 randomized controlled trials. The pooled rate of complete resolution emerging from the combined analysis of all treated children was 83% (95% CI, 77%-89%). A meta-analysis of the two randomized controlled trials showed homogeneity of the results (P=.37, Breslow-Day test) and a common odds ratio for complete resolution of 13 (95% CI, 4-43; P<.001). Surgery appears to be a possible option for management of PFAPA syndrome. Available evidence is limited, however, and the precise role of surgery remains to be clarified. We suggest considering this option when symptoms markedly interfere with the child's quality of life and medical treatment has failed.

Outcome of tonsillectomy in selected patients with PFAPA syndrome.

To assess the practicability of integrated medical and surgical management and the effectiveness of tonsillectomy in children with PFAPA syndrome (periodic fever, aphthous stomatitis, pharyngitis, and cervical lymphadenopathy). A prospective study. Secondary pediatric and otolaryngological university center. Of 30 patients evaluated for periodic fever, 18 children with PFAPA syndrome were included in the study. Patients underwent long-term pediatric and otolaryngological assessments, and their parents were asked to keep monthly diaries with reports of any subsequent episodes, symptom, and related sign. Patients received traditional medical therapies, and 9 patients underwent tonsillectomy for the lack of lasting recovery. The association between postoperative outcomes and age at tonsillectomy and the differences in the patients' condition before and after tonsillectomy were statistically tested. In addition, the removed tonsillar tissue was analyzed molecularly to evaluate concomitant infections. All of the surgical patients reported a symptomatic improvement, with complete clinical recovery in 5 cases (56%) and significant reduction in number (P = .005) and duration (P = .03) of recurrences in the remaining 4 (44%). Results of molecular analysis of tonsillar specimens were negative for bacteria in all but 1 patient. Otolaryngologists should be trained to recognize PFAPA syndrome, for which management consists of a regular and prolonged second-level pediatric and otolaryngological follow-up, with surgery only after the failure of traditional medical therapy.