The Pediatric Infectious Disease Journal • Volume 34, Number 1, January 2015
Treatment of Periodic Fever, Aphthous Stomatitis, Pharyngitis and Adenitis Syndrome To the Editors: he article “The enigma of periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome” summarizes current controversies with regard to diagnosis and treatment of periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome (PFAPA).1 The authors hint that the best treatment may be tonsillectomy. We think there is robust evidence to support tonsillectomy for patients in whom symptoms are significant. A Cochrane systematic review on tonsillectomy for PFAPA, recently updated,2 includes 2 randomized controlled trials (RCTs) involving 67 children with PFAPA with follow up to 183 and 64 months. They show that PFAPA patients treated with surgery have less fever and fewer episodes, which are less severe, compared to those not treated with surgery. The Cochrane review calculated the risk ratio for immediate resolution of symptoms after surgery that persisted until the end of follow up (6- 18 months) to be 4.38 (95% confidence interval 0.64 to 30.11), and the number needed to treat to benefit was 2. For those treated with surgery,
T
The authors have no conflicts of interest or funding to disclose. Copyright © 2014 by Lippincott Williams & Wilkins ISSN: 0891-3668/15/3401-0117 DOI: 10.1097/INF.0000000000000500
© 2014 Lippincott Williams & Wilkins
episodes were reduced from 1 every 2 months on average to slightly less than 1 every 2 years. There were no complications of surgery, however the numbers were small. Of course the benefits of surgery should be explained to the family in context of the risks of general anesthesia, post-operative bleeding and recovery time. And as there is evidence that the condition is potentially self-limiting, surgery should be reserved for those with symptoms causing a significant impact on daily life. Tonsillectomy (±adenoidectomy) for recurrent tonsillitis was more widely undertaken in the past with good success, and it may be that for a proportion of these patients, undiagnosed PFAPA was being treated. Although PFAPA is being increasingly recognized, tonsillectomy is less often performed in children in Europe. The fact that surgery can positively affect the clinical course of PFAPA suggests that nasal-associated lymphoid tissue is critical for the pathophysiologic mechanism of this condition. Further evaluation of the immunologic behavior of tonsillar tissue, as reported by Valenzuela et al.,5 may help elucidate the pathogenesis of this condition.
Emily Chesshyre, BM, MRCPCH Jolanta Bernatoniene, MRCPCH, PhD
Letters
Royal National Hospital for Rheumatic Diseases Bath, United Kingdom
Michael Saunders, MD, FRCS Department of ENT University Hospitals Bristol NHS Foundation Trust Bristol, United Kingdom
Adam Finn, PhD, FRCPCH School of Clinical Sciences School of Cellular and Molecular Medicine University of Bristol Bristol, United Kingdom REFERENCES 1. Esposito S, Bianchini S, Fattizzo M, et al. The enigma of periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome. Pediatr Infect Dis J. 2014;33:650–662. 2. Burton MJ, Pollard AJ, Ramsden JD. Tonsillectomy for periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPA). Cochrane Database Syst Rev. 2010;9:CD008669. 3. Garavello W, Romagnoli M, Gaini RM. Effectiveness of adenotonsillectomy in PFAPA syndrome: a randomized study. J Pediatr. 2009;155:250–253.
Department of Paediatric Infectious Diseases Bristol Royal Hospital for Children Bristol, United Kingdom
4. Renko M, Salo E, Putto-Laurila A, et al. A randomized, controlled trial of tonsillectomy in periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome. J Pediatr. 2007;151:289–292.
Athimalaipet V. Ramanan, FRCPCH, FRCP
5. Valenzuela PM, Araya A, Perez CI, et al. Profile of inflammatory mediators in tonsils of patients with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome. Clin Rheumatol. 2013;32:1743–1749.
Department of Paediatric Rheumatology Bristol Royal Hospital for Children Bristol, United Kingdom
www.pidj.com | 117
Treatment of Periodic Fever, Aphthous Stomatitis, Pharyngitis and Adenitis Syndrome To the Editors: he article “The enigma of periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome” summarizes current controversies with regard to diagnosis and treatment of periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome (PFAPA).1 The authors hint that the best treatment may be tonsillectomy. We think there is robust evidence to support tonsillectomy for patients in whom symptoms are significant. A Cochrane systematic review on tonsillectomy for PFAPA, recently updated,2 includes 2 randomized controlled trials (RCTs) involving 67 children with PFAPA with follow up to 183 and 64 months. They show that PFAPA patients treated with surgery have less fever and fewer episodes, which are less severe, compared to those not treated with surgery. The Cochrane review calculated the risk ratio for immediate resolution of symptoms after surgery that persisted until the end of follow up (6- 18 months) to be 4.38 (95% confidence interval 0.64 to 30.11), and the number needed to treat to benefit was 2. For those treated with surgery,
T
The authors have no conflicts of interest or funding to disclose. Copyright © 2014 by Lippincott Williams & Wilkins ISSN: 0891-3668/15/3401-0117 DOI: 10.1097/INF.0000000000000500
© 2014 Lippincott Williams & Wilkins
episodes were reduced from 1 every 2 months on average to slightly less than 1 every 2 years. There were no complications of surgery, however the numbers were small. Of course the benefits of surgery should be explained to the family in context of the risks of general anesthesia, post-operative bleeding and recovery time. And as there is evidence that the condition is potentially self-limiting, surgery should be reserved for those with symptoms causing a significant impact on daily life. Tonsillectomy (±adenoidectomy) for recurrent tonsillitis was more widely undertaken in the past with good success, and it may be that for a proportion of these patients, undiagnosed PFAPA was being treated. Although PFAPA is being increasingly recognized, tonsillectomy is less often performed in children in Europe. The fact that surgery can positively affect the clinical course of PFAPA suggests that nasal-associated lymphoid tissue is critical for the pathophysiologic mechanism of this condition. Further evaluation of the immunologic behavior of tonsillar tissue, as reported by Valenzuela et al.,5 may help elucidate the pathogenesis of this condition.
Emily Chesshyre, BM, MRCPCH Jolanta Bernatoniene, MRCPCH, PhD
Letters
Royal National Hospital for Rheumatic Diseases Bath, United Kingdom
Michael Saunders, MD, FRCS Department of ENT University Hospitals Bristol NHS Foundation Trust Bristol, United Kingdom
Adam Finn, PhD, FRCPCH School of Clinical Sciences School of Cellular and Molecular Medicine University of Bristol Bristol, United Kingdom REFERENCES 1. Esposito S, Bianchini S, Fattizzo M, et al. The enigma of periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome. Pediatr Infect Dis J. 2014;33:650–662. 2. Burton MJ, Pollard AJ, Ramsden JD. Tonsillectomy for periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPA). Cochrane Database Syst Rev. 2010;9:CD008669. 3. Garavello W, Romagnoli M, Gaini RM. Effectiveness of adenotonsillectomy in PFAPA syndrome: a randomized study. J Pediatr. 2009;155:250–253.
Department of Paediatric Infectious Diseases Bristol Royal Hospital for Children Bristol, United Kingdom
4. Renko M, Salo E, Putto-Laurila A, et al. A randomized, controlled trial of tonsillectomy in periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome. J Pediatr. 2007;151:289–292.
Athimalaipet V. Ramanan, FRCPCH, FRCP
5. Valenzuela PM, Araya A, Perez CI, et al. Profile of inflammatory mediators in tonsils of patients with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome. Clin Rheumatol. 2013;32:1743–1749.
Department of Paediatric Rheumatology Bristol Royal Hospital for Children Bristol, United Kingdom
www.pidj.com | 117
