UNDERSTANDING PFAPA SYNDROME: CAUSES, SYMPTOMS, AND TREATMENT OPTIONS
Medically Reviewed by Dr. Sony Sherpa (MBBS)
PFAPA Syndrome, an acronym for Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis Syndrome, is a rare and complex condition. It features recurrent episodes of high fever, mouth lesions, a sore throat, and swollen lymph nodes.
The syndrome typically begins in early childhood and can significantly impact a child's quality of life. However, it is not exclusive to children. Adults can also be diagnosed with PFAPA Syndrome, although it's less common.
This article seeks to provide a comprehensive understanding of PFAPA Syndrome, addressing its symptoms, causes, diagnosis, and treatment options.
What is PFAPA Syndrome?
PFAPA Syndrome is a rare, non-hereditary disease that primarily affects children. The average age of onset occurs in children between 2 and 5 years.
The syndrome is named after its four main features: Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis.
- Periodic Fever: This refers to recurrent high fever episodes that can last several days. These fevers often occur regularly, typically every three to eight weeks.
- Aphthous Stomatitis: This term describes painful mouth sores that can make eating and drinking difficult.
- Pharyngitis: This disorder is characterized by inflammation of the throat, which makes swallowing difficult and causes sore throats.
- Adenitis: This refers to the swelling of the lymph nodes, particularly those in the neck, which can cause discomfort and pain.
Despite its challenging symptoms, PFAPA Syndrome is not fatal and does not cause long-term damage to the body. However, it can substantially impact the quality of life of those affected and their families.
Symptoms of PFAPA Syndrome
The symptoms of PFAPA Syndrome can vary from person to person, but some common signs are typically present.
The most noticeable symptom is the periodic fever. These fevers often come on suddenly and can reach high temperatures of up to 104°F (40°C). They usually last for three to six days and then disappear as suddenly as they appeared.[1]
During these fever episodes, other symptoms may also occur. These include:
- Aphthous Stomatitis: Painful mouth sores that can interfere with eating and drinking.
- Pharyngitis: Inflammation of the throat, causing a sore throat and difficulty swallowing.
- Cervical Adenitis: Swelling of the lymph nodes in the neck, causing discomfort and pain.
It is also common for children with PFAPA Syndrome to experience symptoms such as headaches, abdominal pain, and joint pain during fever episodes. Some children may also show signs of general malaise, such as fatigue and lack of appetite.
It is important to note that children with PFAPA Syndrome are usually healthy and symptom-free between fever episodes.
PFAPA Syndrome in Adults
While PFAPA Syndrome is more commonly diagnosed in children, it can also occur in adults. The symptoms and fever patterns may be similar, but the diagnosis can be more challenging due to the rarity of adult-onset PFAPA. Symptoms generally resolve in children at age ten or younger and persist into adulthood in up to 15% of patients.
Adults with PFAPA may experience disruptions in their work and personal lives due to the unpredictable fever episodes. They usually become less frequent during adulthood and often disappear in the individual's twenties[2]. They need to have a comprehensive treatment plan and a supportive network to manage the condition effectively.
Research on adult-onset PFAPA is still ongoing. Increased awareness and understanding among healthcare providers can help improve diagnosis and treatment for adults with this condition.
Causes and Risk Factors of PFAPA Syndrome
The exact cause of PFAPA Syndrome is still unknown. However, it is believed to be related to an abnormal immune system response. This response leads to inflammation and the periodic fevers that characterize the syndrome.
There is ongoing debate about whether PFAPA syndrome is an autoimmune disease. Autoimmune disorders emerge when the body's immune system continues to mistakenly attacks its own cells. Research shows that while PFAPA has autoimmune elements, those affected do not display autoantibodies or autoreactive T lymphocytes (a specialized white blood cell), which indicate autoimmune disease. More research is required to clarify the underlying cause of PFAPA Syndrome.[3]
Genetic factors may also play a role in PFAPA Syndrome[4]. Some studies have found that the condition can run in families, implying a genetic link. However, the specific genes involved remain to be identified.
Environmental factors, such as exposure to certain infections or toxins, may also contribute to the development of PFAPA. However, more research is needed to understand these potential risk factors.
Diagnosis of PFAPA Syndrome
Diagnosing PFAPA Syndrome can be challenging due to its overlapping symptoms with other conditions. The diagnosis is predominantly clinical, based on a pattern of symptoms that a doctor identifies after excluding other potential causes.
In order to diagnose PFAPA, a complete medical history and physical examination are essential. The doctor will look for signs of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis. They will also consider the frequency and duration of febrile episodes.
Laboratory tests can also aid in the diagnosis. An elevated erythrocyte sedimentation rate (ESR) during fever episodes can indicate PFAPA. ESR is a marker for inflammation during the acute phase response, which occurs during injury or fever.
Other blood tests may help to check for a mildly elevated white blood count and low platelet count (thrombocytosis). Indicators such as Hemoglobin, urinalysis, liver function tests, and serum immunoglobulins remain unchanged in those with PFAPA Syndrome[5]. However, these tests are not definitive and are mainly used to rule out other conditions.
The diagnostic criteria for PFAPA Syndrome include:
- Onset of symptoms before the age of 5
- Regularly recurring fevers with a predictable pattern
- Absence of symptoms between fever episodes
- Exclusion of other causes of recurrent fever
It is essential to note that while these criteria are commonly used, they may not apply to all cases. A healthcare professional should always make a diagnosis based on a comprehensive evaluation.
The differential diagnosis for PFAPA Syndrome includes:
- Infectious Diseases: Tuberculosis, CMV, brucellosis, rat-bite fever, relapsing fever, and HIV/AIDS
- Autoimmune Diseases: Systemic lupus erythematosus, relapsing polychondritis, ANCA-mediated vasculitis (Wegener's granulomatosis, microscopic polyangiitis), Takayasu's arteritis, and other systemic autoinflammatory diseases
- Hematologic Disorders: Cyclic neutropenia, malignancies (leukemia, lymphoma), and autoimmune lymphoproliferative syndrome (ALPS)
- Metabolic Disorders: Acute intermittent porphyria
- Gastrointestinal Emergencies: Surgical emergencies (appendicitis, intussusception) and relapsing pancreatitis
- Other: Fever of unknown origin, HLA B27-associated juvenile spondyloarthropathies, and Sarcoidosis
Treatment Options for PFAPA
The treatment of PFAPA Syndrome primarily aims to control the symptoms and improve life quality.
Medication is often the first line of treatment.[6]
Corticosteroids are commonly used to treat fever episodes in PFAPA. They can quickly alleviate symptoms, yet they do not prevent future episodes. Corticosteroid side effects can include weight gain, mood changes, and a weakened immune system.
Other medications often prescribed include:
- Colchicine: This anti-inflammatory medication might help reduce the frequency of PFAPA episodes in some children.
- Cimetidine: While sometimes mentioned, limited evidence supports cimetidine's effectiveness in PFAPA treatment.
Another treatment option is a tonsillectomy, which involves the surgical removal of the tonsils. This procedure is effective in some cases, with many patients experiencing a significant reduction or even cessation of symptoms post-surgery.[7] However, the success rate varies, and the procedure carries risks like surgery.
The treatment plan for PFAPA is often individualized, based on the patient's symptoms, age, overall health, and response to medication. Some patients may need an assortment of treatments to manage their symptoms effectively.
Patients and caregivers must evaluate all possible treatment options with their healthcare provider. Regular follow-up and monitoring are also crucial to keep track of the effectiveness of the treatment and make any necessary adjustments.
Living with PFAPA Syndrome
Living with PFAPA Syndrome can be challenging, both for the patient and their families. The unpredictable nature of the fever episodes can disrupt daily activities and cause significant distress.
The condition can impact children with PFAPA's school attendance and academic performance. Parents and educators need to provide the necessary support and accommodations to help them cope.
Adults with PFAPA may also face challenges in managing their work and personal life during fever episodes. Having a supportive network and open communication with employers about the condition is crucial.
Mental health support is also essential for patients and families dealing with PFAPA. Chronic illness can have psychological effects, and many patients and their families benefit from professional therapy. Support groups and resources also offer valuable assistance and a sense of community.
Latest Advancements in PFAPA Research
The field of PFAPA research is continually evolving, with scientists striving to understand the syndrome's causes better and develop more effective treatments.
Recent studies have focused on the genetic and immunological aspects of PFAPA, aiming to uncover the underlying mechanisms that trigger periodic fevers.
Researchers have discovered several genes that may be linked to PFAPA syndrome[8], such as IL12A. This gene encodes for an inflammation-related protein that sounds the alarm for the immune system, prompting an inflammatory reaction by alerting various white blood cells. Other genes implicated in the immune response of children with the syndrome include STAT4, IL10, and CCR1-CCR3.
One promising area of research are biologics that temper the immune response. These could potentially offer a new treatment option for patients resistant to conventional therapies, with fewer side effects.[9]
- Examples include potential treatment options for monogenic autoinflammatory diseases, including anakinra, anti-TNF agents, canakinumab, tocilizumab, and dapsone.
However, more clinical trials are needed to confirm their efficacy and safety.
Another significant advancement is the development of potential diagnostic biomarkers. These could help doctors diagnose PFAPA more accurately and quickly, reducing the risk of misdiagnosis and enabling earlier intervention. One such advancement is the discovery of galectin 3 as a potential marker differentiating PFAPA Syndrome from Mediterranean fever.[10]
Despite these advancements, there is still much to learn about PFAPA Syndrome. Continued research is crucial to improving the lives of those affected by this condition.
Frequently Asked Questions
Regarding PFAPA Syndrome, several questions often arise. Here, we address some of the most common queries.
- Can periodic fever syndrome be cured? Currently, there is no known cure for PFAPA Syndrome. Treatments are available for symptom control and improved quality of life.
- Do kids grow out of PFAPA? Many children with PFAPA Syndrome see a decrease in symptoms as they grow older. However, the syndrome can persist into adulthood in some cases.
- Is PFAPA a rare disease? Yes, PFAPA is considered a rare disease. It is the most common periodic fever syndrome in children but still relatively rare in the general population.
- Is PFAPA an autoimmune disorder? The exact cause of PFAPA is unknown, and it is a topic of ongoing research. Some experts believe it may be an autoimmune disorder, but this has not been definitively proven.
- Are PFAPA fevers contagious? No, fevers associated with PFAPA are not contagious. PFAPA is an auto-inflammatory condition, which means that it is not caused by an infection. Therefore, it cannot be spread from person to person.
Conclusion
PFAPA Syndrome, with its periodic fevers and characteristic symptoms, remains a challenging condition for both children and adults. While treatment options aim to alleviate symptoms and improve quality of life, ongoing research into genetic and immunological factors holds promise for better understanding and management of this rare disorder. Continued advancements and support are crucial in enhancing the lives of individuals affected by PFAPA Syndrome.
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