Interactive Guide: PFAPA Syndrome in Children

Introduction to PFAPA Syndrome

Periodic Fever with Thrush, Pharyngitis and Cervical Adenitis Syndrome (PFAPA) is the most common cause of recurrent fever in children. It was first described in 1987 by Marshall, and although its exact etiology is unknown, it is believed to be a non-genetic autoinflammatory disease.

It is characterized by recurrent episodes of high fever, accompanied by oral thrush, pharyngitis and/or cervical adenitis, which recur with a fairly regular periodicity (generally every 3-6 weeks) and last 3-7 days. Between episodes, the child is completely asymptomatic and has normal growth and development.

Diagnosis

The diagnosis of PFAPA syndrome is mainly clinical, that is, it is based on the observation of characteristic symptoms and the exclusion of other causes of fever. Marshall's criteria are widely used:

  • Recurrent fever with regular periodicity.
  • Onset before 5 years of age.
  • One or more of the following symptoms: oral thrush, pharyngitis, or cervical adenitis.
  • Exclusion of cyclic neutropenia.
  • Normal growth and development between episodes.

It is essential to rule out bacterial, viral infections or other autoinflammatory diseases or immunodeficiencies before establishing the diagnosis of PFAPA.

Clinical Findings

The cardinal symptoms of PFAPA are grouped in its acronym:

  • Periodic Fever: High fever (generally >39°C), with sudden onset and duration of 3-7 days. The episodes repeat with striking regularity, often every 2-8 weeks.
  • Aphthous Stomatitis (Oral Thrush): Small painful ulcers in the mouth or throat.
  • Pharyngitis (Pharingitis): Inflammation of the throat, with redness and pain, often without purulent exudate.
  • ACervical denitis (Cervical Adenitis): Enlarged and painful lymph nodes in the neck.

Other symptoms that may accompany fever include: abdominal pain, headache, chills, malaise, joint pain and rash. Importantly, the children are completely healthy and asymptomatic between febrile episodes.

Laboratory Tests

During a febrile episode, laboratory tests often show signs of acute inflammation, such as:

  • Elevated C-Reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR): Inflammation indicators.
  • Leukocytosis: Increased number of white blood cells, often with neutrophilia.

It is crucial to note that between episodes, all of these markers usually return to normal. Normality of testing between attacks is an important finding that helps differentiate PFAPA from other chronic inflammatory diseases. Throat and blood culture tests are usually negative, helping to rule out bacterial infections.

Treatment

Treatment of PFAPA syndrome focuses on managing symptoms during attacks and, in some cases, preventing episodes.

Treatment of acute crises:

  • Corticosteroids: A single dose of prednisone or prednisolone (approximately 1 mg/kg) at the onset of febrile symptoms is usually very effective in aborting the episode. However, it can shorten the interval between seizures.
  • Non-steroidal anti-inflammatory drugs (NSAIDs) or paracetamol: They can be used for symptomatic control of fever and malaise, although they do not usually abort the episode as effectively as corticosteroids.

Preventive treatment:

  • Cimetidine: Some studies suggest that cimetidine may be effective in preventing seizures in some children, although the evidence is limited.
  • Colchicine: It is used in some cases as prophylaxis, especially if the attacks are very frequent or severe and the response to corticosteroids is not optimal.
  • Tonsillectomy: In selected cases with very frequent episodes that are refractory to medical treatment, tonsillectomy (removal of the tonsils) can be curative in a high percentage of children. It is an option considered when the child's quality of life is significantly affected.
Final Evaluation

1. What does the acronym PFAPA mean?

2. What is the main diagnostic method for PFAPA syndrome?

3. During an episode of PFAPA, how are inflammatory markers such as CRP and ESR typically?

4. Which of the following treatments is commonly used to abort an acute episode of PFAPA?

5. What surgical intervention can be considered in severe and frequent cases of PFAPA?

Bibliographic References

The information in this guide is based on recognized medical sources and clinical consensus. Below are some key references on PFAPA Syndrome:

  • Marshall, G.S., et al. (1987). "Prolonged and recurrent fevers in children: a new syndrome?" Pediatric Infectious Disease Journal, 6(11), 1011-1012.
  • Thomas, K.T., et al. (1999). "The PFAPA syndrome: a practical approach to diagnosis and treatment." Pediatrics, 103(1), 1-6.
  • Rigante, D., et al. (2019). "PFAPA syndrome: a comprehensive review of diagnosis and treatment." Clinical and Experimental Rheumatology, 37 Suppl 118(1), S120-S127.
  • Feder, H. M. Jr. (2018). "Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA syndrome)." UpToDate. (Accessed June 2025).
  • Spanish Association of Pediatrics. "PFAPA syndrome." Clinical guides. (Consulted in June 2025).