What are the other Names for this Condition? (Also known as/Synonyms)

• Marshall Syndrome
• Marshall’s Syndrome with Periodic Fever
• PFAPA Syndrome

What is Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome? (Definition/Background Information)

• Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome (PFAPA Syndrome) is an autoinflammatory disorder that primarily affects young children and is characterized by recurrent episodes of fever, sore throat (pharyngitis), mouth sores (aphthous stomatitis), and swollen lymph nodes in the neck (cervical adenitis)
• The exact cause of Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis is unknown, but it is thought to be related to an abnormal response of the immune system. Some research suggests that the disorder may be caused by a genetic mutation. However, a family history of the disorder is not reported
• The signs and symptoms may also include abdominal pain, headache, joint pain, and fatigue. The diagnosis of Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome is made based on a combination of clinical examination, laboratory tests, and exclusion of other possible causes
• Currently, there is no known way to prevent the disorder as the cause is poorly understood. However, it may be treated using oral or intravenous steroids to reduce inflammation and suppress the immune system. Sometimes, additional medications may be prescribed to manage the symptoms
• The prognosis for Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome is generally good with proper treatment. In many cases, the condition resolves of its own accord as a child reaches the second decade of his/her life. In rare cases, the disorder can lead to serious complications such as kidney inflammation or blood clots

Who gets Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome? (Age and Sex Distribution)

• Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome (PFAPA Syndrome) primarily affects children, with onset typically occurring between the ages of 2 and 6 years. However, children up to 13 years of age are known to be affected
• In sporadic cases, the condition can occur in adults as well
• Both males and females may be affected; although the condition is slightly more prevalent among boys in comparison to young girls by a ratio of 3:2
• Worldwide, no racial/ethnic group preference is observed
• PFAPA Syndrome is a very rare inflammatory disorder. It has been reported so far in only over 500 individuals in the medical literature

What are the Risk Factors for Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome? (Predisposing Factors)

The risk factors for Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome include 

• Being a male child
• Viral fever
• Autoimmune disorders

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others. 

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome? (Etiology)

The exact cause of Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome is not well-understood.

• It is thought to be related to an abnormal response of the immune system
• Overexpression of genes involved in the inflammatory response has been reported during fever episodes in individuals with this disorder
• These genes include IL-2 and TNF-alpha, IL-1-related genes (IL-1B, IL-1RN, CASP1, IL18RAP), and IFN-induced genes (AIM2, IP-10/CXCL10)
• It has been suggested that a viral fever or an autoimmune disorder may trigger the immune response observed in this disorder

Some research suggests that a genetic mutation may cause the disorder. Presently, the disorder occurs in a sporadic manner and is believed to be non-hereditary (a family history of the disorder is not observed).

What are the Signs and Symptoms of Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome?

The common signs and symptoms of Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome (PFAPA Syndrome) include:

• Recurrent episodes of high fever lasting 3-6 days; these may recur on a monthly basis (typically between 21-28 days)
• Sore throat (pharyngitis) that may be recurrent
• Mouth sores (aphthous stomatitis)
• Swollen lymph nodes in the neck (cervical adenitis)
• Generally, the symptoms resolve completely between flares; if symptoms persist between flares, other autoinflammatory disorders (AID) should be considered by the healthcare professional

Other signs and symptoms may include:

• Abdominal pain
• Headache
• Nausea and vomiting
• Joint pain and arthritis
• Fatigue

The signs and symptoms of PFAPA Syndrome can vary from one individual to another and may be mild or severe.

How is Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome Diagnosed?

Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome (PFAPA Syndrome) is typically diagnosed based on a combination of the following:

• Clinical examination and medical history evaluation
• Assessment of presenting signs and symptoms
• Laboratory tests, including throat swabs testing for bacterial pharyngitis
• Imaging studies, as needed
• Tissue biopsy, if required
• Exclusion of other possible causes: Differential diagnosis to rule out conditions that may present with signs and symptoms similar to PFAPA Syndrome

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome?

Complications of Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome may include:

• Eating and drinking difficulties
• Malabsorption and weight loss
• Chronic fatigue
• Kidney inflammation (rarely observed)
• Blood clots (rarely observed)
• Swollen liver and spleen (hepatomegaly and splenomegaly)
• Behavioral abnormality
• Failure to respond to treatment
• Increased frequency of episodes of fever with steroid treatment
• Reduced quality of life

How is Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome Treated?

• Treatment for Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome typically includes oral or intravenous steroids to reduce inflammation and suppress the immune system
• In some cases, additional medications, such as antihistamines, may be prescribed to manage the symptoms
• For cervical adenitis, tonsillectomy with adenoidectomy surgical procedure may be considered

How can Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis be Prevented?

• Presently, there are no known preventive measures for Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome, as the cause is not well understood
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders
• Regular medical screening at periodic intervals with tests and physical examinations is recommended

What is the Prognosis of Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome? (Outcomes/Resolutions)

• The prognosis for Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome (PFAPA Syndrome) is generally good with appropriate treatment
• Most children with PFAPA Syndrome will outgrow the disorder by age 10
• Surgical removal of tonsils and/or adenoids may also lead to complete recovery from the condition in most cases

Additional and Relevant Useful Information for Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome:

The following link is a useful resource for further information on rare diseases and disorders:

https://www.dovemed.com/diseases-conditions/rare-disorders/