On this page
PFAPA syndrome
PFAPA syndrome typically affects young children, causing predictable and recurring episodes of fever and inflammation. It is generally considered a benign condition that often resolves spontaneously as children grow older.
Overview
PFAPA (Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis) syndrome is a common autoinflammatory condition primarily affecting young children. It is characterised by recurrent episodes of high fever, usually lasting three to seven days, accompanied by other specific symptoms. Between these episodes, children typically appear completely healthy and grow normally [PMID:32353139]. The condition was first described in 1987 and is now recognised as the most common cause of periodic fever in childhood.
While the exact cause of PFAPA syndrome is not fully understood, it is thought to involve an abnormal activation of the immune system. This leads to the body's inflammatory response being triggered without an apparent infection or other identifiable cause. PFAPA syndrome is generally considered a benign condition, meaning it does not usually lead to long-term health problems or organ damage.
Symptoms & clinical features
The main symptoms of PFAPA syndrome occur in distinct episodes, often appearing at regular intervals, such as every three to six weeks. The hallmark symptom is a sudden onset of high fever, which can reach 39-40°C and typically lasts for several days. This fever is often accompanied by other characteristic symptoms.
These additional symptoms include aphthous stomatitis (small, painful ulcers inside the mouth), pharyngitis (sore throat, often with redness), and cervical adenitis (swollen, tender lymph nodes in the neck). Other symptoms that may occur during an episode include headache, abdominal pain, joint pain, nausea, vomiting, or diarrhoea. Children are typically well between episodes, with no residual symptoms.
Video: Genetics 101
Affected organs
PFAPA syndrome primarily affects components of the immune system, leading to widespread inflammation during episodes. The throat (pharynx), lymph nodes (especially in the neck), and the mucous membranes of the mouth are consistently involved, giving rise to pharyngitis, adenitis, and aphthous stomatitis, respectively. The systemic nature of the inflammatory response during an episode can also lead to more general symptoms such as fever, headache, and body aches, indicating a broader impact on the body's inflammatory pathways.
Risks & severity
PFAPA syndrome is generally considered a benign condition with no known long-term complications or increased risk of other diseases. The severity of individual episodes can vary, with some children experiencing more intense fevers or discomfort than others. The condition typically begins in early childhood, often between the ages of two and five years. The frequency of episodes can vary from every few weeks to several months apart.
Most children with PFAPA syndrome experience spontaneous resolution of their symptoms as they get older, often by late childhood or early adolescence [PMID:32353139]. There is no evidence that PFAPA syndrome leads to developmental delays or affects a child's growth. While the episodes can be distressing for both the child and their family, the overall prognosis is excellent.
Genetic causes
Unlike many other conditions in the Jeen Health library, PFAPA syndrome does not have a single identified causative gene. Current research suggests a complex, polygenic basis, meaning that multiple genes likely interact with environmental factors to influence an individual's susceptibility to the condition. This complex inheritance pattern makes it challenging to pinpoint specific genetic markers.
While no single gene has been definitively linked to PFAPA, studies have explored various genes involved in immune regulation and inflammatory pathways. These investigations aim to understand the underlying genetic predispositions that contribute to the dysregulation of the immune system seen in PFAPA syndrome. However, specific causative gene associations are not yet established, and further research is ongoing in this area [PMID:34288009].
Inheritance pattern
PFAPA syndrome is considered to have a polygenic or complex inheritance pattern. This means it is not passed down through families in a simple Mendelian fashion (like dominant or recessive traits). Instead, it is likely influenced by a combination of several genes, each contributing a small effect, along with environmental factors. This explains why the condition may occasionally appear in more than one family member, but without a clear pattern of inheritance.
Because of its complex inheritance, predicting the likelihood of another child in the family developing PFAPA syndrome can be difficult. It is not considered a condition that is directly inherited from a parent in the same way as conditions caused by changes in a single gene. Genetic counselling can provide more personalised information regarding familial risks based on individual circumstances.
Diagnosis & testing
The diagnosis of PFAPA syndrome is primarily clinical, meaning it is made based on a child's symptoms and the pattern of their fevers, rather than specific laboratory tests. There are established diagnostic criteria, which include recurrent fevers with a regular pattern, pharyngitis, aphthous stomatitis, and cervical adenitis, along with the exclusion of other causes of periodic fever.
Blood tests during a fever episode typically show signs of inflammation, such as elevated C-reactive protein (CRP) and white blood cell count, but these are not specific to PFAPA. Genetic testing is generally not used to diagnose PFAPA syndrome, as there are no specific causative genes identified. A paediatrician or a specialist in paediatric rheumatology or immunology would typically make the diagnosis after carefully evaluating the child's medical history and ruling out other conditions. The NHS Genomic Medicine Service does not currently have specific R-codes for diagnosing PFAPA syndrome through genetic testing due to its non-monogenic nature.
Management & lifestyle
The management of PFAPA syndrome primarily focuses on managing symptoms during fever episodes. A common and often effective treatment involves a single dose of oral corticosteroids (such as prednisolone) at the onset of a fever episode. This can often shorten the duration and severity of the episode. However, while effective, repeated use of steroids can sometimes shorten the interval between episodes.
Other treatments, such as over-the-counter fever reducers (like paracetamol or ibuprofen), can help manage fever and discomfort. In some cases, for children with very frequent or severe episodes that significantly impact their quality of life, a tonsillectomy (surgical removal of the tonsils) may be considered, which can resolve the condition in a significant number of patients. Long-term follow-up with a paediatrician or specialist is recommended to monitor symptoms and adjust management strategies as needed.
UK care pathway
In the UK, if PFAPA syndrome is suspected, a child would typically be referred by their GP to a paediatrician. If the diagnosis remains unclear or the symptoms are particularly severe, referral to a specialist such as a paediatric rheumatologist or immunologist may be considered. These specialists can confirm the diagnosis, rule out other conditions, and guide management. While PFAPA is not a genetic condition identifiable by a single gene, clinical genetics services can provide support for families seeking to understand complex conditions and discuss recurrence risks.
The NHS Genomic Medicine Service (GMS) pathways are primarily for conditions with identified genetic causes. Since PFAPA syndrome does not have a clear monogenic cause, it does not typically fall under specific GMS R-codes for diagnosis. However, specialist clinicians within the NHS provide comprehensive care and support for children with autoinflammatory conditions, including access to genetic counsellors who can help families understand inheritance patterns and implications.
Frequently asked questions
Is PFAPA syndrome contagious?
No, PFAPA syndrome is not contagious. It is an autoinflammatory condition, meaning it involves a dysfunction of the body's own immune system, rather than an infection caused by bacteria or viruses that can be spread to others.
Will my child grow out of PFAPA syndrome?
Yes, most children with PFAPA syndrome experience spontaneous resolution of their symptoms as they get older. This often occurs by late childhood or early adolescence, though the exact age can vary.
Are there any long-term health problems associated with PFAPA syndrome?
PFAPA syndrome is generally considered a benign condition. It is not associated with long-term health problems, organ damage, or developmental delays. Children typically grow and develop normally.
What triggers PFAPA episodes?
The exact triggers for PFAPA episodes are not well understood. Episodes often appear to occur without any specific trigger, though some parents report viral infections or stress may sometimes precede an episode. The regularity of the episodes suggests an internal clock-like mechanism rather than external triggers.
Is PFAPA syndrome a genetic condition?
PFAPA syndrome is thought to have a complex genetic basis, meaning several genes likely interact with other factors to cause the condition. However, it is not caused by a single gene change that is inherited in a simple pattern, making it different from many other genetic conditions.