Periodic fever syndromes are a set of disorders characterized by recurrent episodes of systemic and organ-specific

inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...

. Unlike

autoimmune disorder An autoimmune disease is a condition that results from an anomalous response of the adaptive immune system, wherein it mistakenly targets and attacks healthy, functioning parts of the body as if they were foreign organisms. It is estimated tha ...

s such as systemic lupus erythematosus, in which the disease is caused by abnormalities of the

adaptive immune system The adaptive immune system (AIS), also known as the acquired immune system, or specific immune system is a subsystem of the immune system that is composed of specialized cells, organs, and processes that eliminate pathogens specifically. The ac ...

, people with autoinflammatory diseases do not produce

autoantibodies An autoantibody is an antibody (a type of protein) produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases (notably lupus erythematosus) are associated with such antibodies. Pr ...

or antigen-specific T or B cells. Instead, the autoinflammatory diseases are characterized by errors in the

innate immune system The innate immune system or nonspecific immune system is one of the two main immunity strategies in vertebrates (the other being the adaptive immune system). The innate immune system is an alternate defense strategy and is the dominant immune s ...

. 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. Since the abdomen contains most of the body's vital organs, it can be an indicator of a wide variety of diseases. Given th ...

s and may lead to chronic complications such as

amyloidosis Amyloidosis is a group of diseases in which abnormal proteins, known as amyloid fibrils, build up in tissue. There are several non-specific and vague signs and symptoms associated with amyloidosis. These include fatigue, peripheral edema, weigh ...

. 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 the Mediterranean fever (MEFV) gene, which encodes a 781–amino acid protein called pyrin. While all ethnic ...

, 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 creepin ...

, lasting less than 72 hours. It is caused by mutations in the MEFV gene, which codes for the protein pyrin. Pyrin is a protein normally present in the

inflammasome Inflammasomes are cytosolic multiprotein complexes of the innate immune system responsible for the activation of inflammatory responses and cell death. They are formed as a result of specific cytosolic pattern recognition receptors (PRRs) sens ...

. 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 slightly modified recombin ...

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 antago ...

, 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 Periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome is a medical condition, typically occurring in young children, in which high fever occurs periodically at intervals of about 3–5 weeks, frequently accompanied by aphthous-lik ...

, which is the most common autoinflammatory disease seen in children, characterized by episodes of fever,

aphthous stomatitis Aphthous stomatitis, or recurrent aphthous stomatitis (RAS), commonly referred to as a canker sore or salt blister, is a common condition characterized by the repeated formation of benignity, benign and non-contagious disease, contagious mouth ...

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 runny nose, cough, headache, difficulty swallowing, swollen lymph nodes, and a hoarse vo ...

, 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 diagn ...

systemic-onset juvenile idiopathic arthritis Systemic-onset juvenile idiopathic arthritis (sJIA), also known as Still disease, Still's disease, and systemic juvenile idiopathic arthritis, is a subtype of juvenile idiopathic arthritis (JIA) that is distinguished by arthritis, a characteristic ...

Schnitzler syndrome Schnitzler syndrome or Schnitzler's syndrome is a rare disease characterised by onset around middle age of chronic hives (urticaria) and periodic fever, bone and joint pain (sometimes with joint inflammation), weight loss, malaise, fatigue, swol ...

, and

chronic recurrent multifocal osteomyelitis Chronic recurrent multifocal osteomyelitis (CRMO) is a rare condition (1:1,000,000), in which the bones have lesions, inflammation, and pain. It is called ''multifocal'' because it can appear in different parts of the body, primarily bones, and ...

. 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

References

External links

{{Medical resources , DiseasesDB = 9836 , ICD10 = {{ICD10, E, 85, 0, e, 85 , ICD9 = {{ICD9, 277.31 , ICDO = , OMIM = , MedlinePlus = , eMedicineSubj = article , eMedicineTopic = 952254 , MeshID = D056660
Understanding Autoinflammatory Diseases
nbsp;- US National Institute of Arthritis and Musculoskeletal and Skin Diseases Inflammations Autoinflammatory syndromes

Individual periodic fever syndromes

See also

References

Further reading

External links