Clinical and Epidemiological Aspects of Periodic Fever with Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA)

Abstract

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) is an autoinflammatory syndrome characterised by regularly recurring febrile episodes with oropharyngeal symptoms, primarily affecting young children. This thesis aims to synthesise current knowledge and to investigate the clinical spectrum, epidemiology, treatment outcomes and aspects of life with PFAPA. Paper I is a retrospective study including patients diagnosed with PFAPA at three hospitals in western Sweden between 2006 and 2017. A cohort of 336 patients was established and their clinical features described. Almost 90% had symptom onset before five years of age. The estimated annual incidence of PFAPA was 2.6/10,000 in children < 5 years of age and 0.86/10,000 in children < 18 years. Paper II is a prospective observational study using validated questionnaires to assess health-related quality of life and family impact of PFAPA before and after tonsillectomy. PFAPA was associated with a substantial family impact, which decreased after symptom resolution following surgery. Paper III is a register-based study examining antibiotic prescriptions, demonstrating frequent exposure prior to diagnosis which decreased significantly after the diagnosis was established. Paper IV investigates the initial and long-term symptom course of PFAPA after tonsillectomy using retrospective and cross-sectional data collected through structured telephone interviews, showing heterogeneous outcomes with residual symptoms in a substantial minority of patients. These findings highlight that awareness and timely recognition of PFAPA are important to improve health-related quality of life, alleviate family impact and reduce antibiotic use. The variable disease course after tonsillectomy, with symptoms remaining in the long-term in a substantial proportion of patients, should be considered when evaluating tonsillectomy as a treatment option.