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 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]

Last updated: 10/7/2013

Symptoms Symptoms

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Abnormality of temperature regulation	90%
Abnormality of the oral cavity	90%
Arthralgia	90%
Behavioral abnormality	90%
Encephalitis	90%
Lymphadenopathy	90%
Migraine	90%
Recurrent pharyngitis	90%
Weight loss	90%
Abdominal pain	7.5%
Arthritis	7.5%
Hepatomegaly	7.5%
Malabsorption	7.5%
Nausea and vomiting	7.5%
Splenomegaly	7.5%

Last updated: 9/1/2016

Cause Cause

The cause of PFAPA is unknown, although viral or autoimmune causes have been suggested.^[1]

Last updated: 8/16/2011

Diagnosis Diagnosis

There are no laboratory tests or imaging procedures specific to the diagnosis of PFAPA.^[5] 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.^[6]^[7] 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).^[5]^[6]^[7] 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.^[5]

Last updated: 7/9/2015

Treatment Treatment

Treatment options that have been successful in improving symptoms of this condition include: oral steroids (prednisone or prednisolone), tonsillectomy with adenoidectomy and cimetidine.^[8]

Last updated: 8/16/2013

Organizations Organizations

Nonprofit support and advocacy groups bring together patients, families, medical professionals, and researchers. These groups often raise awareness, provide support, and develop patient-centered information. Many are the driving force behind research for better treatments and possible cures. They can direct people to research, resources, and services. Many groups also have experts who serve as medical advisors. Visit their website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD. Suggest an organization to add.

Organizations Supporting this Disease

Autoinflammatory Alliance
P.O. Box 590354
San Francisco, CA 94118
Telephone: 415-831-8782
E-mail: karen@autoinflammatory.org
Website: http://www.autoinflammatory.org/
Stop CAID Now
PO Box 992
Chadds Ford, PA 19317
Toll-free: 877-CAID-644
Fax: 877-CAID-640
E-mail: stopcaidnow@aol.com
Website: http://www.stopcaidnow.org/

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.
TheDoctorsDoctor.com web site provides additional information on PFAPA syndrome. Click on the link above to view this information page.

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

Young Investigator Initiative Career Development and Grant Mentoring Program
June 21, 2016

NCATS Co-Sponsored Conferences

Autoinflammation 2013: The Seventh International Congress of FMF and Autoinflammatory Diseases Wednesday, May 22, 2013 - Sunday, May 26, 2013
Location: Lausanne, Switzerland
Description: The goals of this meeting include the exchange of clinical and scientific information regarding the autoinflammatory diseases. This is likely to result in improvements in the diagnosis and treatment of these diseases. Past Congresses have resulted in new scientific collaborations, development of registries for patients with specific autoinflammatory disorders, and the initiation of multicenter clinical trials.

Contact: Daniel Kastner, M.D., Ph.D., 301-496-8364kastnerd@nih.gov

Co-funding Institute(s): National Human Genome Research Institute, Office of Rare Diseases Research
Autoinflammation 2010, the Sixth International Conference on FMF and other Autoinflammatory Diseases Thursday, September 2, 2010 - Monday, September 6, 2010
Location: Royal Tropical Institute, Amsterdam, The Netherlands
Description: Autoinflammation 2010 was the sixth conference in a series that started more than 10 years ago in Jerusalem. The first conference focused primarily on familial Mediterranean fever (FMF), but soon other hereditary periodic fever syndromes were included. These syndromes were the first to be recognized as autoinflammatory disorders. Recent years have seen an exciting development of scientific knowledge on inflammation and its regulation, and these rare disorders have played a major role in this development. Experts in the field of autoinflammatory disorders, both clinicians and basic scientists, from all over the world met in Amsterdam to exchange research results and opinions on clinical practice. The scientific program included plenary talks, meet-the-expert sessions, interactive workshops, and laptop presentations. Topics ranged from FMF and the other hereditary autoinflammatory diseases to acquired autoinflammatory disorders, such as gout, and from pathogenesis and genetics to clinical phenotype and therapy. Also included was a 1-day program for patients.

Contact: Daniel Kastner, M.D., Ph.D., 301-496-8364kastnerd@nih.gov

Co-funding Institute(s): Office of Rare Diseases Research, National Institute of Arthritis and Musculoskeletal and Skin Diseases
- Agenda ( - 82KB)

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

How is PFAPA diagnosed? See answer
Are there any treatment options for PFAPA (periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis) syndrome? See answer
What is PFAPA (periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis) syndrome? What causes it? Are there any support groups? Are there any research studies? See answer

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.
Ovetchkine P, Bry ML, Reinert P. [Marshall syndrome: results of a retrospective national survey].. Arch Pediatr. 2000; http://www.ncbi.nlm.nih.gov/pubmed/10941483. Accessed 10/7/2013.
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.
Long S.. Tonsillectomy as treatment of PFAPA syndrome. Journal of Pediatrics. 2007;
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.