Overview
Definition:
PFAPA (Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis) syndrome is the most common autoinflammatory disorder in children, characterized by recurrent episodes of fever and systemic inflammation
While typically self-limiting, recurrent severe episodes can impact growth and quality of life, prompting management discussions around tonsillectomy and corticosteroid therapy.
Epidemiology:
PFAPA syndrome typically presents in early childhood, with onset usually between 6 months and 5 years of age
It affects both sexes equally and is more prevalent in Caucasians
The incidence is estimated at 1.4-4.2 per 10,000 children
Recurrent episodes can lead to decreased caloric intake and altered metabolism, potentially contributing to failure to thrive in some children.
Clinical Significance:
Recognizing and managing PFAPA syndrome is crucial for preventing unnecessary antibiotic use and addressing the impact of recurrent inflammation on a child's growth and development
Understanding the comparative efficacy and indications for tonsillectomy versus systemic steroids is key for pediatricians to optimize patient outcomes and prepare for DNB/NEET SS examinations.
Clinical Presentation
Symptoms:
Recurrent episodes of fever, often high-grade (39-40°C) and lasting 3-7 days
Presence of aphthous ulcers in the mouth
Severe pharyngitis, often exudative, mimicking streptococcal pharyngitis
Cervical lymphadenopathy, typically anterior
Symptoms are usually regular, occurring at predictable intervals (e.g., every 3-6 weeks)
Patients are generally well between episodes
In some severe or prolonged cases, poor oral intake and systemic inflammation can lead to a temporary failure to thrive.
Signs:
Fever
Pharyngeal erythema and exudates
Enlarged, tender cervical lymph nodes
Aphthous stomatitis
Occasionally, mild adenopathy in other lymph node chains
Absence of significant respiratory symptoms, cough, or otitis media during most episodes
Normal growth trajectory between episodes, but potential plateau or decline during frequent exacerbations.
Diagnostic Criteria:
Woodruff criteria (most widely accepted): 1
Recurrent episodes of fever lasting 3-7 days
2
Absence of specific pathogens on culture
3
Aphthous stomatitis
4
Cervical lymphadenitis
5
At least one of the following: abdominal pain, vomiting, diarrhea, headache, malaise, arthralgia/myalgia
6
Normal growth and development between episodes (though chronic or severe cases may show temporary impact on growth)
7
Symptoms typically starting before age 5
8
Episodes occurring at regular intervals (e.g., 2-6 weeks).
Diagnostic Approach
History Taking:
Detailed menstrual history of fever, including onset, duration, temperature, associated symptoms (mouth sores, sore throat, swollen glands), frequency of episodes, and interval well-being
Inquiry about nutritional intake and weight gain patterns to assess for failure to thrive
Family history of similar episodes or autoinflammatory diseases
Review of previous investigations and treatments, including antibiotic use and response.
Physical Examination:
Thorough examination of the oropharynx for aphthous ulcers and erythema
Palpation of cervical lymph nodes for size, tenderness, and mobility
Assessment of hydration status
Auscultation of chest and abdomen
Measurement of height and weight to assess growth trajectory, noting any deviations from standard growth curves.
Investigations:
Routine blood work during an episode: Elevated ESR and CRP
Mild leukocytosis with neutrophilia
Normal procalcitonin
Absence of significant anemia or thrombocytopenia
Throat swab for culture to rule out bacterial pharyngitis
Viral serology is usually not indicated
Genetic testing for autoinflammatory disorders is generally not required for typical PFAPA, but may be considered in atypical presentations or strong family history.
Differential Diagnosis:
Recurrent streptococcal pharyngitis (though PFAPA typically lacks response to antibiotics and has more systemic features)
Other periodic fever syndromes (e.g., Familial Mediterranean Fever, TRAPS, Hyper-IgD syndrome - usually have more severe systemic involvement and different characteristic markers)
Viral pharyngitis
Infectious mononucleosis
Behçet's disease (more prevalent in adults, different systemic involvement).
Management
Initial Management:
For mild, infrequent episodes, symptomatic treatment with antipyretics (paracetamol, ibuprofen) is often sufficient
Education of parents regarding the benign nature and self-limiting course of PFAPA is crucial
Monitoring growth parameters is essential to identify any impact on weight and height gain.
Medical Management:
Prophylactic treatment is generally not recommended for mild PFAPA
Acute treatment for moderate to severe episodes: A single oral dose of corticosteroids (e.g., Prednisolone 1-2 mg/kg, max 40 mg) at the onset of an episode can abort the fever within hours
However, this can lead to shorter intervals between episodes and potentially increased frequency in the long run
Daily low-dose corticosteroids are generally avoided due to the risk of growth suppression and side effects.
Surgical Management:
Tonsillectomy is considered the definitive treatment for PFAPA syndrome, particularly in children with frequent, severe episodes impacting quality of life, growth, or with a significant burden of symptoms
It is highly effective in most patients, leading to resolution of symptoms in 80-90% of cases
The decision for tonsillectomy should be made after careful consideration of the frequency and severity of episodes, impact on growth, and parental preference, in consultation with an ENT surgeon.
Supportive Care:
Ensuring adequate hydration and nutrition during febrile episodes is important
Close monitoring of weight and height to detect any failure to thrive
Providing emotional support to the child and family dealing with recurrent illness
Nutritional counseling may be beneficial if significant impact on caloric intake is observed.
Complications
Early Complications:
Short-term impact on caloric intake leading to temporary weight plateau or loss
Increased parental anxiety due to recurrent unexplained fevers
Side effects from oral steroid treatment (if used acutely) include insomnia, mood changes, and gastrointestinal upset.
Late Complications:
Chronic or severe episodes can lead to a sustained failure to thrive, impacting overall growth parameters
While rare, repeated inflammatory insults could theoretically have long-term effects on immune system maturation
Post-tonsillectomy complications are those typical of the procedure, such as bleeding, infection, or anesthetic risks.
Prevention Strategies:
For children with very frequent or severe episodes, tonsillectomy is the most effective strategy to prevent ongoing complications of the syndrome
For those managed conservatively, prompt intervention with corticosteroids at the first sign of an episode can sometimes mitigate symptom severity, though this requires careful monitoring for increased frequency
Regular nutritional assessment helps in early identification and management of growth faltering.
Prognosis
Factors Affecting Prognosis:
The presence of failure to thrive prior to treatment is a significant factor
Frequency and severity of episodes before intervention
Response to different treatment modalities (steroids vs
tonsillectomy)
The inherent self-limiting nature of PFAPA means that most children eventually outgrow the condition, typically by late childhood or adolescence, regardless of treatment.
Outcomes:
With tonsillectomy, the vast majority of children experience complete resolution of symptoms, leading to improved growth and quality of life
Those managed with symptomatic care or occasional steroids have a more variable outcome, with episodes eventually decreasing in frequency and severity over time
Failure to thrive usually resolves with effective management of the underlying inflammatory process.
Follow Up:
Regular growth monitoring is essential, especially for children with a history of failure to thrive
For those who undergo tonsillectomy, follow-up is similar to any post-tonsillectomy patient
For those managed conservatively, periodic review to assess episode frequency, symptom burden, and growth is recommended, with re-evaluation for tonsillectomy if symptoms persist or worsen.
Key Points
Exam Focus:
PFAPA is a diagnosis of exclusion characterized by recurrent fever, aphthous stomatitis, pharyngitis, and cervical adenitis
Woodruff criteria are key for diagnosis
Tonsillectomy is the definitive treatment for symptomatic relief and improved growth in selected patients
Corticosteroids can abort acute episodes but may increase frequency.
Clinical Pearls:
Always consider PFAPA in a child with recurrent fevers and sore throat, especially if pharyngeal exudates are present but cultures are negative
Differentiate from recurrent bacterial pharyngitis by lack of response to antibiotics and consistent periodicity
Assess growth trajectory carefully
significant failure to thrive is an important indication for considering tonsillectomy
Educate parents that PFAPA is typically benign and self-limiting, reducing anxiety.
Common Mistakes:
Over-reliance on antibiotic therapy for recurrent pharyngitis in PFAPA
Misdiagnosing PFAPA as other periodic fever syndromes without appropriate workup if atypical features are present
Delaying consideration of tonsillectomy in children with significant growth impact or severe quality of life issues due to frequent, debilitating episodes.