Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis – PFAPA syndrome. Literature review

Norvilė Jotautaitė1, Akvilė Papievytė1, Artūras Kriukas1

1Lithuanian University of Health Sciences, Academy of Medicine, Faculty of Medicine


The syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis was first described in 1987 by Marshall et al. It was called Marshall syndrome until the acronym PFAPA (Periodic Fever, Aphthous stomatitis, Pharyngitis, cervical Adenitis) was proposed in 1989.

The syndrome belongs to the spectrum of auto-inflammatory diseases, which are characterized by unprovoked, accidental inflammatory episodes without the production of autoantibodies or autoreactive T lymphocytes. The disease most commonly occurs in children under 5 years of age and is characterized by spontaneous episodes of periodic fever that recur every 3-8 weeks and last from 3 to 6 days. One or more other symptoms of PFAPA syndrome also occur: pharyngitis, cervical adenitis, aphthous stomatitis. Sometimes headache or abdominal pain, arthralgia, myalgia, nausea, vomiting, and diarrhea may also occur. The diagnosis is based on the Marshall criteria modified by Thomas and other co-authors in 1999 and excluding diseases that can cause recurrent febrile episodes: familial Mediterranean fever (FMF), tumor necrosis factor receptor-associated periodic fever syndrome (TRAPS), mevalonate kinase deficiency (MVKD) and cryopirin-associated periodic syndrome (CAPS).

Treatment for PFAPA syndrome consists of several treatment strategies. Nonsteroidal anti-inflammatory drugs or paracetamol may be used to relieve the symptoms of a fever. Glucocorticoids are also effective in terminating an acute episode but do not prevent their recurrence. Colchicine, cimetidine, or tonsillectomy are suitable for the prevention of exacerbations. A larger sample of prospective studies is needed to elucidate the efficacy of these methods in the treatment of PFAPA syndrome.

Aim of the study. Review the prevalence of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome, etiopathogenic factors, clinic, diagnostic and treatment peculiarities based on the available scientific literature.

Material and methods. A search of scientific articles was performed in PubMed, ClinicalKey databases. The literature review includes 22 scientific publications describing the syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA).

Keywords: periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis, PFAPA syndrome, children, glucocorticoids, tonsillectomy.