Autoinflammatory diseases (AID) and autoimmune disorders both result from the immune system attacking the body’s own tissues. Both of these disorders also cause inflammation. However, in autoinflammatory diseases the innate or primitive immune system causes inflammation for unknown reasons, whereas in autoimmune diseases the immune system mistakenly reacts with the body’s own cellular components as if they were foreign antigens. Autoinflammatory diseases also have a hereditary component usually associated with a gene mutation.
What are Autoinflammatory Diseases?
Also known as periodic fever syndrome, the autoinflammatory diseases are characterized by recurrent unprovoked inflammation in the absence of high titers of autoantibodies, infection, or antigen-specific T lymphocytes. Disorders in this class primarily include familial Mediterranean fever; tumour necrosis factor a (TNF-alpha) receptor-associated periodic fever syndrome; hyperimmunoglobulinemia D and periodic fever syndrome (HIDS; cryopyrin-associated periodic syndrome (CAPS), familial cold autoinflammatory syndrome; Muckle-Wells syndrome; and neonatal onset multi-system inflammatory disease (NOMID)/chronic infantile neurological cutaneous and articular (CINCA) syndrome. Recent evidence suggests that Behcet’s disease also falls into this class.
Acute-phase reactants such as C-reactive protein (CRP) are elevated in autoinflammatory diseases. Autoinflammatory disorders can also lead to the development of type AA amyloidosis, a potentially fatal condition characterized by accumulations of amyloid protein in vital organs. Amyloidosis is the most common and serious complication of AID. Renal amyloidosis is the most common form of amyloidosis and studies show that it may occur in 11.4 percent of people with familial Mediterranean fever.
Familial Mediterranean Fever
An article in Rheumatology (Yao and Furst 2008) describes a 35-year old Jewish male who presented with recurrent episodes of joint inflammation of the ankles since childhood along with shoulder, knee, and foot pain that developed over the previous 10 years. Other symptoms included episodes of testicular pain and swelling, fever, diarrhea, and abdominal pain. The most common of the autoinflammatory disorders, FMF primarily affects individuals younger than 20 years although it can affect people of any age. Arthritis primarily occurs in the knees, ankles and hips. This disorder primarily occurs in Jews, Armenians, Turks and Arabs in the Mediterranean Basin, central Asia and Japan. Men are affected nearly twice as often as women.
Neonatal Onset Multisystem Inflammatory Disease (NOMID)
Neonatal onset multisystem inflammatory disease, which is also known as chronic infantile neurologic cutaneous articular (CINCA) syndrome, can affect numerous organs and bodily systems, primarily the skin, joints, eyes, and central nervous system. At the onset, which is typically by six weeks, a rash occurs and may be followed by fever, meningitis, joint disorders, vision and hearing loss, and mental retardation. Up to 20 percent of children with NOMID do not reach adulthood. NOMID is associated with mutations in the LNRP3 gene in approximately 60 percent of cases (NIAMS 2010).
Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS)
TRAPS, previous called Hibermian fever, causes long, recurrent episodes of high fever, severe abdominal pain, chest and joint pain, rash, and eye inflammation. This disorder, which is associated with a gene mutation in the TNF receptor, can occur in early childhood to adulthood, with males and females affected equally. The earliest cases occurred in people of Irish-Scottish descent and since have been found in nearly all ethnic groups. Attacks of TRAPS can be prevented with colchicines, whereas glucocorticoid steroids are used to reduce symptoms.
Deficiency of the Interleukin-1 Receptor Antagonist (DIRA)
DIRA is a recently discovered disorder seen in children that causes a cluster of different potentially fatal symptoms. Symptoms include swelling of bone tissue, bone pain and deformity, inflammation of the connective tissue surrounding bone (periosteum) and a pustular rash. Mutations to the interleukin-1 receptor, which may be more common in individuals of Dutch descent, are responsible.
Hyperimmunoglobulinemia D and periodic fever syndrome (HIDS)
Another case report in Rheumatology (Yao and Furst 2008) describes a German Caucasian man who presented with nephrotic syndrome at the age of 22. Kidney biopsy showed the presence of amyloidosis. Within three years, dialysis was needed. The patient reported having periodic episodes of fever since early childhood. In addition, the patient’s fever was sometimes accompanied by headache, swollen lymph glands, vomiting, and diarrhea. As a child, he was also found to have a deficiency of immunoglobulin G2/4 and at diagnosis he was found to have elevated levels of immunoglobulin D. In HIDS, recurrent high fever occurs approximately every four to six weeks and persists for three to seven days. Other symptoms seen in HIDS include rash, tendonitis, an elevated white blood cell count, and oral and genital ulcers.
Other Autoinflammatory Disorders
Cryopyrin-associated periodic syndrome (CAPS) includes conditions of familial cold autoinflammatory syndrome (FCAS). Similar to Muckle-Wells syndrome (MWS) these disorders also cause high fever, arthritis symptoms, hearing loss and cold-induced inflammation. Other symptoms include conjunctivitis and rashes with itching (urticaria). Behcet’s disease is characterized by canker sores or ulcers in the mouth and on the genitals as well as eye inflammation. The disease can also have systemic manifestations, causing arthritis, skin problems and inflammation of the digestive tract, brain and spinal cord. Behcet’s also causes inflammation of the blood vessels.
Sources:
Yao, Q. and D. Furst. 2008. Autoinflammatory diseases: an update of clinical and genetic aspects. Rheumatology 47(7): 946-951.
Autoinflammatory Diseases. March 2010. National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of Health (NIH) Division of the Department of Health and Human Services, accessed May 10, 2010.
Elaine Moore - I'm a retired medical technologist and medical writer with more than 30 years experience working in hospital laboratories. Currently, I ...
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