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Disease Profile

Periodic fever, aphthous stomatitis, pharyngitis and adenitis

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Childhood

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ICD-10

E85.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

PFAPA; Marshall Syndrome

Categories

Congenital and Genetic Diseases; Immune System Diseases; Musculoskeletal Diseases

Summary

Periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) is a periodic disease, which is a heterogeneous group of disorders characterized by short episodes of illness that regularly recur for several years alternated with healthy periods.[1] PFAPA is characterized by high fevers lasting three to six days and recurring every 21 to 28 days, accompanied by some or all of the signs noted in its name, namely mouth sores (aphthous stomatitis), sore throat (pharyngitis), and enlarged lymph nodes (cervical adenitis). The syndrome usually occurs in children younger than five years; although it has been reported in children up to 13 years.[2] The syndrome is sporadic and non-hereditary.[3] The course of PFAPA can be persistent for years before spontaneous, full resolution.[4]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal oral cavity morphology
Abnormality of the oral cavity
0000163
Abnormality of temperature regulation
Poor temperature regulation
0004370
Arthralgia
Joint pain
0002829
Behavioral abnormality
Behavioral changes
Behavioral disorders
Behavioral disturbances
Behavioral problems
Behavioral/psychiatric abnormalities
Behavioural/Psychiatric abnormality
Psychiatric disorders
Psychiatric disturbances

[ more ]

0000708
Encephalitis
Brain inflammation
0002383
Lymphadenopathy
Swollen lymph nodes
0002716
Migraine
Intermittent migraine headaches
Migraine headache
Migraine headaches

[ more ]

0002076
Recurrent pharyngitis
Recurrent sore throat
0100776
Weight loss
0001824
30%-79% of people have these symptoms
Fatigue
Tired
Tiredness

[ more ]

0012378
5%-29% of people have these symptoms
Abdominal pain
Pain in stomach
Stomach pain

[ more ]

0002027
Arthritis
Joint inflammation
0001369
Hepatomegaly
Enlarged liver
0002240
Malabsorption
Intestinal malabsorption
0002024
Nausea and vomiting
0002017
Splenomegaly
Increased spleen size
0001744

Cause

The underlying cause of PFAPA is not yet known. While it appears to involve inflammatory processes, it is not clear why episodes develop. No gene or infection has been found to be responsible for causing PFAPA and it is not contagious.[5]

Diagnosis

There are no laboratory tests or imaging procedures specific to the diagnosis of PFAPA.[6] This condition is clinically diagnosed in individuals who have a history of 3 or more episodes of fevers that last up to 5 days and recur at regular intervals without other evidence of acute illness. Pharyngitis (sore throat) plus adenopathy (swollen lymph nodes) or aphthous ulcers (canker sores) are also noted.[7][8] Blood tests like white blood cell count, C-reactive protein, and erythrocyte sedimentation rate (ESR) are often elevated during an acute attack (but normal between attacks).[6][7][8] It is important to rule out other conditions that may present with similar symptoms (for example, strep throat). The dramatic response to treatment can help to confirm the diagnosis.[6]

Treatment

Treatment options that have been successful in improving symptoms of this condition include: oral steroids (prednisone or prednisolone), tonsillectomy with adenoidectomy and cimetidine.[9]

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Learn more

    These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

    Where to Start

    • The Cleveland Clinic provides an overview of the different types of periodic fever syndromes.
    • The Merck Maual provides information on periodic fever syndromes in general. The Merck Manuals are a series of healthcare books for medical professionals and consumers.

      In-Depth Information

      • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
      • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
      • PubMed is a searchable database of medical literature and lists journal articles that discuss Periodic fever, aphthous stomatitis, pharyngitis and adenitis. Click on the link to view a sample search on this topic.

        Selected Full-Text Journal Articles

          References

          1. Berlucchi M, Nicolai P. Marshall’s syndrome or PFAPA (periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis) syndrome. Orphanet encyclopedia. 2004; https://www.orpha.net/data/patho/GB/uk-PFAPA.pdf. Accessed 10/7/2013.
          2. Ovetchkine P, Bry ML, Reinert P. [Marshall syndrome: results of a retrospective national survey].. Arch Pediatr. 2000; https://www.ncbi.nlm.nih.gov/pubmed/10941483. Accessed 10/7/2013.
          3. Kurtaran H, Karadað A, Catal F, Aktaþ D. PFAPA syndrome: a rare cause of periodic fever. Turk J Pediatr. 2004; https://www.ncbi.nlm.nih.gov/pubmed/15641271. Accessed 10/7/2013.
          4. Long S.. Tonsillectomy as treatment of PFAPA syndrome. Journal of Pediatrics. 2007;
          5. Hashkes P. Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis Syndrome (Juvenile). American College of Rheumatology. March, 2017; https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Periodic-Fever-Aphthous-Stomatitis-Pharyngitis-Adenitis-Syndrome-Juvenile.
          6. Periodic Fever Syndrome. Cleveland Clinic Web site. 2015; https://my.clevelandclinic.org/services/orthopaedics-rheumatology/diseases-conditions/periodic-fever-syndrome. Accessed 7/9/2015.
          7. PFAPA. Autoinflammatory Alliance. 2014; https://www.nomidalliance.org/pfapa.php. Accessed 7/9/2015.
          8. Stephen E. Goldfinger. PFAPA Syndrome. Merck Manual Professional Version. February 2013; https://www.merckmanuals.com/professional/pediatrics/hereditary-periodic-fever-syndromes/pfapa-syndrome. Accessed 7/9/2015.
          9. Lee WI., Yang MH, et al. PFAPA syndrome (Periodic Fever, Aphthous stomatitis, Pharyngitis, Adenitis).. Clin Rheumatology. 1999; https://www.ncbi.nlm.nih.gov/pubmed/11206345. Accessed 8/16/2013.

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