Periodic fever, aphthous stomatitis, pharyngitis and adenitis

Title

Other Names:

PFAPA; Marshall Syndrome

Categories:

Congenital and Genetic Diseases; Immune System Diseases; Musculoskeletal Diseases

Summary Summary

Periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) is characterized by short episodes of illness that occur at regular time periods.^[1] The syndrome usually occurs in children younger than five years; but it has also been reported in adults.^[2] Symptoms of PFAPA include high fevers lasting three to six days occurring every 21 to 28 days, along with body aches, fatigue, mouth sores (aphthous stomatitis), sore throat (pharyngitis), and enlarged lymph nodes (cervical adenitis). In children, the symptoms of PFAPA typically go away after a few years, but in adults the symptoms may continue for years.^[3] The cause of PFAPA is unknown, but genetic causes may be involved. PFAPA usually occurs by chance and is not inherited in families.^[4] Diagnosis is based on the symptoms and a clinical examination. Treatment is focused on managing the symptoms. Options include tonsillectomy and medication. Guidelines for the treatment of PFAPA in children have been published.^[5]^[2]

Last updated: 5/6/2021

Symptoms 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.

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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

Showing of 16 |

Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 2/1/2021

Do you have updated information on this disease? We want to hear from you.

Cause 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 infection has been found to be responsible for causing PFAPA and it is not contagious.^[6] Genetic factors may be involved but PFAPA is not inherited in families.

Last updated: 2/6/2018

Diagnosis Diagnosis

There are no laboratory tests or imaging procedures specific to the diagnosis of PFAPA.^[7] 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.^[8]^[9] 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).^[7]^[8]^[9] 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.^[7]

Last updated: 7/9/2015

Treatment Treatment

Treatment of periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) is focused on managing the symptoms and improving the quality of life for someone with this condition. Options that have been successful in improving symptoms of this condition include: oral steroids (prednisone or prednisolone), tonsillectomy with adenoidectomy and cimetidine.^[10] Guidelines have been published for the treatment of PFAPA.^[5]

Specialists involved in the care of someone with this condition include:

Pediatrician or other primary care doctor
Otolaryngologist (ear, nose, and throat doctor)
Rheumatologist (autoimmune disease specialist)

Last updated: 5/6/2021

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnosis includes other diseases characterized by periodic fever such as recurrent tonsillitis, streptococcal infection, juvenile idiopathic arthritis, Behçet's disease, cyclic neutropenia, familial Mediterranean fever, TRAPS syndrome, and mevalonate kinase deficiency (see these terms). Visit the Orphanet disease page for more information.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

The U.S. National Institutes of Health, through the National Library of Medicine, developed ClinicalTrials.gov to provide patients, family members, and members of the public with current information on clinical research studies. There is a study titled ClinicalTrials.gov which may be of interest to you.

Organizations 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

FMF & AID Global Association
Schüracherstrasse 25a
8306 Brüttisellen
Switzerland
Telephone: +41 76 415 4010
E-mail: info@fmfandaid.org
Website: https://www.fmfandaid.org/

Do you know of an organization? We want to hear from you.

Learn More 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

Licameli G, Jeffrey J, Luz J, Jones D, Kenna M. Effect of adenotonsillectomy in PFAPA syndrome. Arch Otolaryngol Head Neck Surg. 2008 Feb;134(2):136-40.
Padeh S, Stoffman N, Berkun Y. Periodic fever accompanied by aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPA syndrome) in adults. Isr Med Assoc J. 2008 May;10(5):358-60.
Wong KK, Finlay JC, Moxham JP. Role of Tonsillectomy in PFAPA Syndrome. Otolaryngol Head Neck Surg. 2008 Jan;134(1):16-9.

News & Events News & Events

News

NIH Researchers Uncover Genes Linked To PFAPA Syndrome
September 1, 2020

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References References

Berlucchi M, Nicolai P. Marshall’s syndrome or PFAPA (periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis) syndrome. Orphanet encyclopedia. 2004; http://www.orpha.net/data/patho/GB/uk-PFAPA.pdf. Accessed 10/7/2013.
Sicignano LL, Rigante D, Moccaldi B Massaro MG, Delli Noci S, Patisso I, at al. Children and Adults with PFAPA Syndrome: Similarities and Divergences in a Real-Life Clinical Setting.. Adv Ther. Feb 2021; 38(2):1078-1093. https://pubmed.ncbi.nlm.nih.gov/33315168/.
Long S.. Tonsillectomy as treatment of PFAPA syndrome. Journal of Pediatrics. 2007;
Kurtaran H, Karadað A, Catal F, Aktaþ D. PFAPA syndrome: a rare cause of periodic fever. Turk J Pediatr. 2004; http://www.ncbi.nlm.nih.gov/pubmed/15641271. Accessed 10/7/2013.
Amarilyo G, Rothman D, Manthira K, Edwards KM, Li SC, Marshall GS, at al. Consensus Treatment Plan Workgroup. Consensus treatment plans for periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome (PFAPA): a framework to evaluate treatment responses from the childhood arthritis and rheumatology research alliance (CARRA) PFAPA work group. Pediatr Rheumatol Online J. Apr 15, 2020; 18(1):31. https://pubmed.ncbi.nlm.nih.gov/32293478/.
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.
Periodic Fever Syndrome. Cleveland Clinic Web site. 2015; http://my.clevelandclinic.org/services/orthopaedics-rheumatology/diseases-conditions/periodic-fever-syndrome. Accessed 7/9/2015.
PFAPA. Autoinflammatory Alliance. 2014; http://www.nomidalliance.org/pfapa.php. Accessed 7/9/2015.
Stephen E. Goldfinger. PFAPA Syndrome. Merck Manual Professional Version. February 2013; http://www.merckmanuals.com/professional/pediatrics/hereditary-periodic-fever-syndromes/pfapa-syndrome. Accessed 7/9/2015.
Lee WI., Yang MH, et al. PFAPA syndrome (Periodic Fever, Aphthous stomatitis, Pharyngitis, Adenitis).. Clin Rheumatology. 1999; http://www.ncbi.nlm.nih.gov/pubmed/11206345. Accessed 8/16/2013.