Periodic fever syndromes are a set of disorders characterized by recurrent episodes of
systemic and organ-specific
inflammation
Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...
. Unlike
autoimmune disorder
An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly ...
s such as systemic lupus erythematosus, in which the disease is caused by abnormalities of the
adaptive immune system
The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system ...
, people with autoinflammatory diseases do not produce
autoantibodies or antigen-specific T or B cells. Instead, the autoinflammatory diseases are characterized by errors in the
innate immune system.
The syndromes are diverse, but tend to cause episodes of fever,
joint pains, skin rashes,
abdominal pain
Abdominal pain, also known as a stomach ache, is a symptom associated with both non-serious and serious medical issues.
Common causes of pain in the abdomen include gastroenteritis and irritable bowel syndrome. About 15% of people have a m ...
s and may lead to chronic complications such as
amyloidosis.
Most autoinflammatory diseases are genetic and present during childhood. The most common genetic autoinflammatory syndrome is
familial Mediterranean fever
Familial Mediterranean fever (FMF) is a hereditary inflammatory disorder. FMF is an autoinflammatory disease caused by mutations in Mediterranean fever gene, which encodes a 781–amino acid protein called pyrin. While all ethnic groups are sus ...
, which causes short episodes of fever, abdominal pain,
serositis
Serositis refers to inflammation of the serous tissues of the body, the tissues lining the lungs (pleura), heart (pericardium), and the inner lining of the abdomen (peritoneum) and organs within. It is commonly found with fat wrapping or creeping ...
, lasting less than 72 hours. It is caused by mutations in the
MEFV
''MEFV'' (Mediterranean fever) is a human gene that provides instructions for making a protein called pyrin (also known as marenostrin). Pyrin is produced in certain white blood cells (neutrophils, eosinophils and monocytes) that play a role in in ...
gene, which codes for the protein
pyrin.
Pyrin is a protein normally present in the
inflammasome
Inflammasomes are cytosolic multiprotein oligomers of the innate immune system responsible for the activation of inflammatory responses. Activation and assembly of the inflammasome promotes proteolytic cleavage, maturation and secretion of pro-in ...
. The mutated pyrin protein is thought to cause inappropriate activation of the inflammasome, leading to release of the pro-inflammatory cytokine
IL-1β
Interleukin-1 beta (IL-1β) also known as leukocytic pyrogen, leukocytic endogenous mediator, mononuclear cell factor, lymphocyte activating factor and other names, is a cytokine protein that in humans is encoded by the ''IL1B'' gene."Catabolin" ...
. Most other autoinflammatory diseases also cause disease by inappropriate release of IL-1β. Thus, IL-1β has become a common therapeutic target, and medications such as
anakinra
Anakinra, sold under the brand name Kineret, is a biopharmaceutical medication used to treat rheumatoid arthritis, cryopyrin-associated periodic syndromes, familial Mediterranean fever, and Still's disease. It is a recombinant and slightly modif ...
,
rilonacept
Rilonacept, sold under the brand name Arcalyst, is a medication used to treat cryopyrin-associated periodic syndromes, including familial cold autoinflammatory syndrome, and Muckle–Wells syndrome; deficiency of interleukin-1 receptor antagonist ...
, and
canakinumab have revolutionized the treatment of autoinflammatory diseases.
However, there are some autoinflammatory diseases that are not known to have a clear genetic cause. This includes
PFAPA, which is the most common autoinflammatory disease seen in children, characterized by episodes of fever,
aphthous stomatitis
Aphthous stomatitis, or recurrent aphthous stomatitis (RAS), is a common condition characterized by the repeated formation of benign and non-contagious mouth ulcers (aphthae) in otherwise healthy individuals. The informal term ''canker sore'' i ...
,
pharyngitis
Pharyngitis is inflammation of the back of the throat, known as the pharynx. It typically results in a sore throat and fever. Other symptoms may include a Rhinorrhea, runny nose, cough, headache, difficulty swallowing, swollen lymph nodes, and a ...
, and cervical
adenitis
Adenitis is a general term for an inflammation of a gland. Often it is used to refer to lymphadenitis which is the inflammation of a lymph node.
Classification
Lymph node adenitis
''Lymph adenitis'' or ''lymph node adenitis'' is caused by infec ...
. Other autoinflammatory diseases that do not have clear genetic causes include
adult-onset Still's disease
Adult-onset Still's disease (AOSD) is a form of Still's disease, a rare systemic autoinflammatory disease characterized by the classic triad of fevers, joint pain, and a distinctive salmon-colored bumpy rash. The disease is considered a diagno ...
,
systemic-onset juvenile idiopathic arthritis,
Schnitzler syndrome There have been several people named Schnitzler ( he, שניצלר):
* Arthur Schnitzler (born 1862), an Austrian playwright and author, son of Johann
* Barbara Schnitzler (born 1953, Berlin), a German actress (de)
* Claude Schnitzler (born 1949 ...
, and
chronic recurrent multifocal osteomyelitis. It is likely that these diseases are multifactorial, with genes that make people susceptible to these diseases, but they require an additional environmental factor to trigger the disease.
Individual periodic fever syndromes
See also
*
Kawasaki disease
Kawasaki disease is a syndrome of unknown cause that results in a fever and mainly affects children under 5 years of age. It is a form of vasculitis, where blood vessels become inflamed throughout the body. The fever typically lasts for more th ...
- possible autoinflammatory mechanism
*
Multisystem inflammatory syndrome in children
*
List of cutaneous conditions
Further reading
*
Hobart A. Reimann, ''Periodic Disease: a probable syndrome including periodic fever, benign paroxysmal peritonitis, cyclic neutropenia and intermittent arthralgia.'' JAMA, 1948.
* Hobart A Reimann, ''Periodic Disease: periodic fever, periodic abdominalgia, cyclic neutropenia, intermittent arthralgia, angioneurotic edema, anaphylactoid purpura and periodic paralysis.'' JAMA, 1949.
* Hobart A Reimann, Moadié, J; Semerdjian, S; Sahyoun, PF, ''Periodic Peritonitis—Heredity & Pathology: report of seventy-two cases.'' JAMA, 1954.
* Hobart A Reimann, ''Periodic fever, an entity: A collection of 52 cases.'' AmJMedSci, 1962.
References
External links
{{Medical resources
, DiseasesDB = 9836
, ICD10 = {{ICD10, E, 85, 0, e, 85
, ICD9 = {{ICD9, 277.31
, ICDO =
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, eMedicineSubj = article
, eMedicineTopic = 952254
, MeshID = D056660
Understanding Autoinflammatory Diseasesnbsp;- US National Institute of Arthritis and Musculoskeletal and Skin Diseases
Inflammations
Autoinflammatory syndromes