학술논문
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.
Document Type
Academic Journal
Author
La Torre F; Department of Pediatrics, Pediatric Rheumatology Center, Giovanni XXIII Pediatric Hospital, University of Bari, Bari, Italy.; Sota J; Division of Rheumatology, Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, University of Siena, Siena, Italy.; Insalaco A; Ospedale Pediatrico Bambino Gesù, IRCCS (European Reference Network for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases Center), Rome, Italy.; Conti G; Pediatric Nephrology and Rheumatology Unit, Azienda Ospedaliera Universitaria G. Martino, Messina, Italy.; Del Giudice E; Pediatric and Neonatology Unit, Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, Polo Pontino, Latina, Italy.; Lubrano R; Pediatric and Neonatology Unit, Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, Polo Pontino, Latina, Italy.; Breda L; Pediatric Rheumatology Unit, S.S. Annunziata Hospital, Chieti, Italy.; Maggio MC; Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE) 'G. D'Alessandro', University of Palermo, Palermo, Italy.; Civino A; Pediatric Rheumatology and Immunology Unit, Vito Fazzi Hospital, Lecce, Italy.; Mastrorilli V; Department of Pediatrics, Pediatric Rheumatology Center, Giovanni XXIII Pediatric Hospital, University of Bari, Bari, Italy.; Loconte R; Department of Pediatrics, Pediatric Rheumatology Center, Giovanni XXIII Pediatric Hospital, University of Bari, Bari, Italy.; Natale MF; Ospedale Pediatrico Bambino Gesù, IRCCS (European Reference Network for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases Center), Rome, Italy.; Celani C; Ospedale Pediatrico Bambino Gesù, IRCCS (European Reference Network for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases Center), Rome, Italy.; Romeo M; Pediatric Nephrology and Rheumatology Unit, Azienda Ospedaliera Universitaria G. Martino, Messina, Italy.; Patroniti S; Pediatric Nephrology and Rheumatology Unit, Azienda Ospedaliera Universitaria G. Martino, Messina, Italy.; Gentile C; Pediatric Rheumatology Unit, S.S. Annunziata Hospital, Chieti, Italy.; Vitale A; Division of Rheumatology, Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, University of Siena, Siena, Italy.; Caggiano V; Division of Rheumatology, Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, University of Siena, Siena, Italy.; Gaggiano C; Division of Rheumatology, Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, University of Siena, Siena, Italy.; Diomeda F; Pediatric Rheumatology and Immunology Unit, Vito Fazzi Hospital, Lecce, Italy.; Cattalini M; Pediatric Clinic, University of Brescia and Spedali Civili di Brescia, Brescia, Italy.; Lopalco G; Rheumatology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.; Emmi G; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.; Centre for Inflammatory Diseases, Department of Medicine, Monash Medical Centre, Monash University, Clayton, VIC, Australia.; Parronchi P; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.; Gentileschi S; Division of Rheumatology, Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, University of Siena, Siena, Italy.; Cardinale F; Department of Pediatrics, Pediatric Rheumatology Center, Giovanni XXIII Pediatric Hospital, University of Bari, Bari, Italy.; Aragona E; Division of Gastroenterology, Ospedali Riuniti Villa Sofia-Vincenzo Cervello, Palermo, Italy.; Shahram F; Behcet's Disease Unit, Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.; Marino A; Unit of Pediatric Rheumatology, ASST Gaetano Pini-CTO, Milan, Italy.; Barone P; Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.; Moscheo C; Pediatric Unit, Azienda Ospedaliero-Universitaria Policlinico 'Rodolico-San Marco', Catania, Italy.; Ozkiziltas B; Division of Rheumatology, Department of Internal Medicine, Gazi University Faculty of Medicine, Ankara, Turkey.; Carubbi F; Department of Life, Health & Environmental Sciences and Internal Medicine and Nephrology Unit, Department of Medicine, University of L'Aquila and ASL Avezzano-Sulmona-L'Aquila, San Salvatore Hospital, L'Aquila, Italy.; Alahmed O; Pediatric Rheumatology, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.; Iezzi L; Department of Life Sciences and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.; Ogunjimi B; Department of Pediatrics, Antwerp University Hospital, Antwerp, Belgium.; Center for Health Economics Research and Modelling Infectious Diseases (CHERMID), Vaccine and Infectious Disease Institute, University of Antwerp, Wilrijk, Belgium.; Mauro A; Pediatric Rheumatology Unit, Department of Childhood and Developmental Medicine, Fatebenefratelli-Sacco Hospital, Milan, Italy.; Tarsia M; Clinical Pediatrics, Department of Molecular Medicine and Development, University of Siena, Siena, Italy.; Mahmoud AAA; Rheumatology and Clinical Immunology Unit, Department of Internal Medicine, Faculty of Medicine, Cairo University, Giza, Egypt.; Giardini HAM; Rheumatology Division, Hospital das Clinicas (HCFMUSP), Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.; Sfikakis PP; Joint Academic Rheumatology Program, Medical School, National and Kapodistrian University of Athens, Athens, Greece.; Laskari K; Joint Academic Rheumatology Program, Medical School, National and Kapodistrian University of Athens, Athens, Greece.; Więsik-Szewczyk E; Department of Internal Medicine, Pulmonology, Allergy and Clinical Immunology, Central Clinical Hospital of the Ministry of National Defence, Military Institute of Medicine, Warsaw, Poland.; Hernández-Rodríguez J; Vasculitis Research Unit, Autoinflammatory Diseases Clinical Unit, Department of Autoimmune Diseases, Hospital Clinic of Barcelona, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Barcelona, Spain.; Frediani B; Division of Rheumatology, Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, University of Siena, Siena, Italy.; Gómez-Caverzaschi V; Vasculitis Research Unit, Autoinflammatory Diseases Clinical Unit, Department of Autoimmune Diseases, Hospital Clinic of Barcelona, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Barcelona, Spain.; Tufan A; Division of Rheumatology, Department of Internal Medicine, Gazi University Faculty of Medicine, Ankara, Turkey.; Almaghlouth IA; Rheumatology Unit, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia.; College of Medicine Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia.; Balistreri A; Bioengineering and Biomedical Data Science Lab, Department of Medical Biotechnologies, University of Siena, Siena, Italy.; Ragab G; Rheumatology and Clinical Immunology Unit, Department of Internal Medicine, Faculty of Medicine, Cairo University, Giza, Egypt.; Faculty of Medicine, Newgiza University, 6th of October City, Egypt.; Fabiani C; Ophthalmology Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.; Cantarini L; Division of Rheumatology, Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, University of Siena, Siena, Italy.; Rigante D; Department of Life Sciences and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.; Rare Diseases and Periodic Fevers Research Centre, Università Cattolica del Sacro Cuore, Rome, Italy.
Source
Publisher: Frontiers Media S.A Country of Publication: Switzerland NLM ID: 101648047 Publication Model: eCollection Cited Medium: Print ISSN: 2296-858X (Print) Linking ISSN: 2296858X NLM ISO Abbreviation: Front Med (Lausanne) Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
2296-858X
Abstract
Objective: To evaluate the potential role of Streptococcus salivarius K12 (SSK12) in controlling febrile flares in patients with Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis (PFAPA) syndrome. Further aims were to assess the impact of SSK12 on (i) flare duration, (ii) variation in the degree of the highest body temperature during flares, (iii) steroid-sparing effect, and (iv) change of PFAPA accompanying symptoms before and after SSK12 introduction.
Patients and Methods: The medical charts from 85 pediatric patients with PFAPA syndrome (49 males and 36 females) enrolled in the AIDA registry and treated with SSK12 for a median period of 6.00 ± 7.00 months in the period between September 2017 and May 2022 were examined. Children recruited had a median time of disease duration of 19.00 ± 28.00 months.
Results: The number of febrile flares significantly decreased comparing the 12 months before [median (IQR), 13.00 (6.00)] and after SSK12 initiation [median (IQR), 5.50 (8.00), p < 0.001]. The duration of fever was significantly reduced from 4.00 (2.00) days to 2.00 (2.00) days [ p < 0.001]. Similarly, the highest temperature in°C was found significantly lower in the last follow-up assessment [median (IQR), 39.00 (1.00)] compared to the period prior to SSK12 start [median (IQR), 40.00 (1.00), p < 0.001]. Steroid load (mg/year) of betamethasone (or any equivalent steroid) significantly decreased between 12 months before treatment with SSK12 [median (IQR), 5.00 (8.00) mg/year] and the last follow-up visit [median (IQR), 2.00 (4.00) mg/year, p < 0.001]. The number of patients experiencing symptoms including pharyngitis/tonsillitis ( p < 0.001), oral aphthae ( p < 0.001) and cervical lymphadenopathy ( p < 0.001) significantly decreased following SSK12.
Conclusion: SSK12 prophylaxis given for at least 6.00 months was found to reduce febrile flares of PFAPA syndrome: in particular, it halved the total number per year of fever flares, shortened the duration of the single febrile episode, lowered body temperature by 1°C in the febrile flare, provided a steroid-sparing effect, and significantly reduced the accompanying symptoms related to the syndrome.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 La Torre, Sota, Insalaco, Conti, Del Giudice, Lubrano, Breda, Maggio, Civino, Mastrorilli, Loconte, Natale, Celani, Romeo, Patroniti, Gentile, Vitale, Caggiano, Gaggiano, Diomeda, Cattalini, Lopalco, Emmi, Parronchi, Gentileschi, Cardinale, Aragona, Shahram, Marino, Barone, Moscheo, Ozkiziltas, Carubbi, Alahmed, Iezzi, Ogunjimi, Mauro, Tarsia, Mahmoud, Giardini, Sfikakis, Laskari, Więsik-Szewczyk, Hernández-Rodríguez, Frediani, Gómez-Caverzaschi, Tufan, Almaghlouth, Balistreri, Ragab, Fabiani, Cantarini and Rigante.)
Patients and Methods: The medical charts from 85 pediatric patients with PFAPA syndrome (49 males and 36 females) enrolled in the AIDA registry and treated with SSK12 for a median period of 6.00 ± 7.00 months in the period between September 2017 and May 2022 were examined. Children recruited had a median time of disease duration of 19.00 ± 28.00 months.
Results: The number of febrile flares significantly decreased comparing the 12 months before [median (IQR), 13.00 (6.00)] and after SSK12 initiation [median (IQR), 5.50 (8.00), p < 0.001]. The duration of fever was significantly reduced from 4.00 (2.00) days to 2.00 (2.00) days [ p < 0.001]. Similarly, the highest temperature in°C was found significantly lower in the last follow-up assessment [median (IQR), 39.00 (1.00)] compared to the period prior to SSK12 start [median (IQR), 40.00 (1.00), p < 0.001]. Steroid load (mg/year) of betamethasone (or any equivalent steroid) significantly decreased between 12 months before treatment with SSK12 [median (IQR), 5.00 (8.00) mg/year] and the last follow-up visit [median (IQR), 2.00 (4.00) mg/year, p < 0.001]. The number of patients experiencing symptoms including pharyngitis/tonsillitis ( p < 0.001), oral aphthae ( p < 0.001) and cervical lymphadenopathy ( p < 0.001) significantly decreased following SSK12.
Conclusion: SSK12 prophylaxis given for at least 6.00 months was found to reduce febrile flares of PFAPA syndrome: in particular, it halved the total number per year of fever flares, shortened the duration of the single febrile episode, lowered body temperature by 1°C in the febrile flare, provided a steroid-sparing effect, and significantly reduced the accompanying symptoms related to the syndrome.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 La Torre, Sota, Insalaco, Conti, Del Giudice, Lubrano, Breda, Maggio, Civino, Mastrorilli, Loconte, Natale, Celani, Romeo, Patroniti, Gentile, Vitale, Caggiano, Gaggiano, Diomeda, Cattalini, Lopalco, Emmi, Parronchi, Gentileschi, Cardinale, Aragona, Shahram, Marino, Barone, Moscheo, Ozkiziltas, Carubbi, Alahmed, Iezzi, Ogunjimi, Mauro, Tarsia, Mahmoud, Giardini, Sfikakis, Laskari, Więsik-Szewczyk, Hernández-Rodríguez, Frediani, Gómez-Caverzaschi, Tufan, Almaghlouth, Balistreri, Ragab, Fabiani, Cantarini and Rigante.)