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Reactive arthritis, also known as Reiter's syndrome, is a form of inflammatory
arthritis Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In som ...
that develops in response to an infection in another part of the body (cross-reactivity). Coming into contact with bacteria and developing an infection can trigger the disease. By the time the patient presents with symptoms, often the "trigger" infection has been cured or is in remission in chronic cases, thus making determination of the initial cause difficult. The arthritis often is coupled with other characteristic symptoms; this has been called Reiter's syndrome, Reiter's disease or Reiter's arthritis. The term "reactive arthritis" is increasingly used as a substitute for this designation because of Hans Reiter's war crimes with the Nazi Party. The manifestations of reactive arthritis include the following triad of symptoms: an inflammatory arthritis of large joints, inflammation of the eyes in the form of conjunctivitis or uveitis, and urethritis in men or cervicitis in women. Arthritis occurring alone following sexual exposure or enteric infection is also known as reactive arthritis. Patients can also present with mucocutaneous lesions, as well as psoriasis-like skin lesions such as
circinate balanitis Balanitis circinata (also known as circinate balanitis) is a skin condition of reactive arthritis comprising a serpiginous ring-shaped dermatitis of the glans penis. Circinate balanitis is one of the most common cutaneous manifestation of reactive ...
, and
keratoderma blennorrhagicum Keratoderma blennorrhagicum etymologically meaning keratinized (kerato-) skin (derma-) mucousy (blenno-) discharge (-rrhagia) (also called keratoderma blennorrhagica) are skin lesions commonly found on the palms and soles but which may spread to ...
.
Enthesitis Enthesitis is inflammation of the entheses, the sites where tendons or ligaments insert into the bone. It is an enthesopathy, a pathologic condition of the entheses. Early clinical manifestations are an aching sensation akin to "working out too ...
can involve the Achilles tendon resulting in heel pain. Not all affected persons have all the manifestations. The clinical pattern of reactive arthritis commonly consists of an inflammation of fewer than five joints which often includes the knee or sacroiliac joint. The arthritis may be "additive" (more joints become inflamed in addition to the primarily affected one) or "migratory" (new joints become inflamed after the initially inflamed site has already improved). Reactive arthritis is an RF-seronegative, HLA-B27-linked arthritis often precipitated by genitourinary or gastrointestinal infections. The most common triggers are intestinal infections (with ''
Salmonella ''Salmonella'' is a genus of rod-shaped (bacillus) Gram-negative bacteria of the family Enterobacteriaceae. The two species of ''Salmonella'' are ''Salmonella enterica'' and ''Salmonella bongori''. ''S. enterica'' is the type species and is fur ...
'', '' Shigella'' or ''
Campylobacter ''Campylobacter'' (meaning "curved bacteria") is a genus of Gram-negative bacteria. ''Campylobacter'' typically appear comma- or s-shaped, and are motile. Some ''Campylobacter'' species can infect humans, sometimes causing campylobacteriosis, a d ...
'') and sexually transmitted infections (with '' Chlamydia trachomatis''); however, it also can happen after group A streptococcal infections. It most commonly strikes individuals aged 20–40 years of age, is more common in men than in women, and more common in white than in black people. This is owing to the high frequency of the HLA-B27 gene in the white population. It can occur in epidemic form. Patients with
HIV The human immunodeficiency viruses (HIV) are two species of '' Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immu ...
have an increased risk of developing reactive arthritis as well. Numerous cases during World Wars I and II focused attention on the triad of arthritis, urethritis, and conjunctivitis (often with additional mucocutaneous lesions), which at that time was also referred to as Fiessenger-Leroy-Reiter syndrome.


Signs and symptoms

* Because common systems involved include the eye, the urinary system, and the hands and feet, one clinical mnemonic in reactive arthritis is "Can't see, can't pee, can't climb a tree." * The classic triad consists of: ** Conjunctivitis ** Nongonococcal urethritis ** Asymmetric oligoarthritis * Symptoms generally appear within 1–3 weeks but can range from 4 to 35 days from the onset of the inciting episode of the disease. * The classical presentation of the syndrome starts with urinary symptoms such as burning pain on urination ( dysuria) or an increased frequency of urination. Other urogenital problems may arise such as prostatitis in men and cervicitis, salpingitis and/or vulvovaginitis in women. * It presents with monoarthritis affecting the large joints such as the
knee In humans and other primates, the knee joins the thigh with the leg and consists of two joints: one between the femur and tibia (tibiofemoral joint), and one between the femur and patella (patellofemoral joint). It is the largest joint in the hu ...
s and sacroiliac spine causing
pain Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...
and swelling. An asymmetrical inflammatory
arthritis Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In som ...
of interphalangeal joints may be present but with relative sparing of small joints such as the wrist and hand. * Patient can have enthesitis presenting as heel pain, Achilles tendinitis or plantar fasciitis, along with balanitis circinata (circinate balanitis), which involves penile lesions present in roughly 20 to 40 percent of the men with the disease. * A small percentage of men and women develop small hard
nodules Nodule may refer to: *Nodule (geology), a small rock or mineral cluster *Manganese nodule, a metallic concretion found on the seafloor *Nodule (medicine), a small aggregation of cells *Root nodule Root nodules are found on the roots of plants, p ...
called
keratoderma blennorrhagicum Keratoderma blennorrhagicum etymologically meaning keratinized (kerato-) skin (derma-) mucousy (blenno-) discharge (-rrhagia) (also called keratoderma blennorrhagica) are skin lesions commonly found on the palms and soles but which may spread to ...
on the soles of the feet and, less commonly, on the palms of the hands or elsewhere. The presence of keratoderma blennorrhagica is diagnostic of reactive arthritis in the absence of the classical triad. Subcutaneous nodules are also a feature of this disease. * Ocular involvement (mild bilateral conjunctivitis) occurs in about 50% of men with urogenital reactive arthritis syndrome and about 75% of men with enteric reactive arthritis syndrome. Conjunctivitis and uveitis can include redness of the eyes, eye pain and irritation, or blurred vision. Eye involvement typically occurs early in the course of reactive arthritis, and symptoms may come and go. * Dactylitis, or "sausage digit", a diffuse swelling of a solitary finger or toe, is a distinctive feature of reactive arthritis and other peripheral spondylarthritides but can also be seen in polyarticular gout and sarcoidosis. * Mucocutaneous lesions can be present. Common findings include oral ulcers that come and go. In some cases, these ulcers are painless and go unnoticed. In the oral cavity, the patients may experience recurrent aphthous stomatitis, geographic tongue and migratory stomatitis in higher prevalence than the general population. * Some patients experience serious gastrointestinal problems similar to those of
Crohn's disease Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever, abdominal distension ...
. * About 10 percent of people with reactive arthritis, especially those with a prolonged course of the disease, will develop cardiac manifestations, including
aortic regurgitation Aortic regurgitation (AR), also known as aortic insufficiency (AI), is the leaking of the aortic valve of the heart that causes blood to flow in the reverse direction during ventricular diastole, from the aorta into the left ventricle. As a conseq ...
and
pericarditis Pericarditis is inflammation of the pericardium, the fibrous sac surrounding the heart. Symptoms typically include sudden onset of sharp chest pain, which may also be felt in the shoulders, neck, or back. The pain is typically less severe when si ...
. Reactive arthritis has been described as a precursor of other joint conditions, including
ankylosing spondylitis Ankylosing spondylitis (AS) is a type of arthritis characterized by long-term inflammation of the joints of the spine typically where the spine joins the pelvis. Occasionally areas affected may include other joints such as the shoulders or hi ...
.


Causes

Reactive arthritis is associated with the HLA-B27 gene on chromosome 6 and by the presence of
enthesitis Enthesitis is inflammation of the entheses, the sites where tendons or ligaments insert into the bone. It is an enthesopathy, a pathologic condition of the entheses. Early clinical manifestations are an aching sensation akin to "working out too ...
as the basic pathologic lesion and is triggered by a preceding infection. The most common triggering infection in the US is a genital infection with '' Chlamydia trachomatis''. Other bacteria known to cause reactive arthritis which are more common worldwide are '' Ureaplasma urealyticum'', ''
Salmonella ''Salmonella'' is a genus of rod-shaped (bacillus) Gram-negative bacteria of the family Enterobacteriaceae. The two species of ''Salmonella'' are ''Salmonella enterica'' and ''Salmonella bongori''. ''S. enterica'' is the type species and is fur ...
'' spp., '' Shigella'' spp., ''
Yersinia ''Yersinia'' is a genus of bacteria in the family Yersiniaceae. ''Yersinia'' species are Gram-negative, coccobacilli bacteria, a few micrometers long and fractions of a micrometer in diameter, and are facultative anaerobes. Some members of ''Ye ...
'' spp., and ''
Campylobacter ''Campylobacter'' (meaning "curved bacteria") is a genus of Gram-negative bacteria. ''Campylobacter'' typically appear comma- or s-shaped, and are motile. Some ''Campylobacter'' species can infect humans, sometimes causing campylobacteriosis, a d ...
'' spp. A bout of
food poisoning Foodborne illness (also foodborne disease and food poisoning) is any illness resulting from the spoilage of contaminated food by pathogenic bacteria, viruses, or parasites that contaminate food, as well as prions (the agents of mad cow disea ...
or a
gastrointestinal The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
infection may also precede the disease (the last four
genera Genus ( plural genera ) is a taxonomic rank used in the biological classification of living and fossil organisms as well as viruses. In the hierarchy of biological classification, genus comes above species and below family. In binomial ...
of bacteria mentioned above are enteric bacteria). ''Shigella'' is the most common organism causing reactive arthritis following diarrhea. ''Chlamydia trachomatis'' is the most common cause of reactive arthritis following urethritis. ''Ureaplasma'' and ''mycoplasma'' are rare causes. There is some circumstantial evidence for other organisms causing the disease, but the details are unclear. Reactive arthritis usually manifests about 1–3 weeks after a known infection. The mechanism of interaction between the infecting organism and the host is unknown. Synovial fluid cultures are negative, suggesting that reactive arthritis is caused either by an autoimmune response involving cross-reactivity of bacterial antigens with joint tissues or by bacterial antigens that have somehow become deposited in the joints.


Diagnosis

There are few clinical symptoms, but the clinical picture is dominated by arthritis in one or more joints, resulting in pain, swelling, redness, and heat sensation in the affected areas. The
urethra The urethra (from Greek οὐρήθρα – ''ourḗthrā'') is a tube that connects the urinary bladder to the urinary meatus for the removal of urine from the body of both females and males. In human females and other primates, the urethra c ...
,
cervix The cervix or cervix uteri (Latin, 'neck of the uterus') is the lower part of the uterus (womb) in the human female reproductive system. The cervix is usually 2 to 3 cm long (~1 inch) and roughly cylindrical in shape, which changes durin ...
and the
throat In vertebrate anatomy, the throat is the front part of the neck, internally positioned in front of the vertebrae. It contains the pharynx and larynx. An important section of it is the epiglottis, separating the esophagus from the trachea (windpi ...
may be swabbed in an attempt to
culture Culture () is an umbrella term which encompasses the social behavior, institutions, and norms found in human societies, as well as the knowledge, beliefs, arts, laws, customs, capabilities, and habits of the individuals in these grou ...
the causative organisms. Cultures may also be carried out on
urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra. Cellular ...
and stool samples or on fluid obtained by
arthrocentesis Arthrocentesis, or joint aspiration, is the clinical procedure performed to diagnose and, in some cases, treat musculoskeletal conditions. The procedure entails using a syringe to collect synovial fluid from or inject medication into the joint caps ...
. Tests for
C-reactive protein C-reactive protein (CRP) is an annular (ring-shaped) pentameric protein found in blood plasma, whose circulating concentrations rise in response to inflammation. It is an acute-phase protein of hepatic origin that increases following interleukin ...
and
erythrocyte sedimentation rate The erythrocyte sedimentation rate (ESR or sed rate) is the rate at which red blood cells in anticoagulated whole blood descend in a standardized tube over a period of one hour. It is a common hematology test, and is a non-specific measure of ...
are non-specific tests that can be done to corroborate the diagnosis of the syndrome. A blood test for the genetic marker HLA-B27 may also be performed. About 75 percent of all the patients with reactive arthritis have this gene.


Diagnostic criteria

Although there are no definitive criteria to diagnose the existence of reactive arthritis, the
American College of Rheumatology The American College of Rheumatology (ACR; until 1985 called American Rheumatism Association) is an organization of and for physicians, health professionals, and scientists that advances rheumatology through programs of education, research, advocacy ...
has published
sensitivity and specificity In medicine and statistics, sensitivity and specificity mathematically describe the accuracy of a test that reports the presence or absence of a medical condition. If individuals who have the condition are considered "positive" and those who do ...
guidelines.


Treatment

The main goal of treatment is to identify and eradicate the underlying infectious source with the appropriate
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy, ...
s if still present. Otherwise, treatment is symptomatic for each problem. Nonspecific urethritis may be treated with a short course of
tetracycline Tetracycline, sold under various brand names, is an oral antibiotic in the tetracyclines family of medications, used to treat a number of infections, including acne, cholera, brucellosis, plague, malaria, and syphilis. Common side effects ...
.
Analgesics An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of Pharmaceutical drug, drugs used to achieve relief from pain (that is, analgesia or p ...
, particularly NSAIDs, are used.
Steroid A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and ...
s,
sulfasalazine Sulfasalazine, sold under the brand name Azulfidine among others, is a medication used to treat rheumatoid arthritis, ulcerative colitis, and Crohn's disease. It is considered by some to be a first-line treatment in rheumatoid arthritis. It is ...
and
immunosuppressant Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system. Classification Immunosuppressive drugs can be classified into ...
s may be needed for patients with severe reactive symptoms that do not respond to any other treatment. Local
corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are in ...
s are useful in the case of
iritis Uveitis () is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and ...
.


Prognosis

Reactive arthritis may be self-limiting, frequently recurring, chronic or progressive. Most patients have severe symptoms lasting a few weeks to six months. 15 to 50 percent of cases involve recurrent bouts of arthritis. Chronic arthritis or sacroiliitis occurs in 15–30 percent of cases. Repeated attacks over many years are common, and patients sometimes end up with chronic and disabling
arthritis Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In som ...
,
heart disease Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, ...
,
amyloid Amyloids are aggregates of proteins characterised by a fibrillar morphology of 7–13 nm in diameter, a beta sheet (β-sheet) secondary structure (known as cross-β) and ability to be stained by particular dyes, such as Congo red. In the hu ...
deposits,
ankylosing spondylitis Ankylosing spondylitis (AS) is a type of arthritis characterized by long-term inflammation of the joints of the spine typically where the spine joins the pelvis. Occasionally areas affected may include other joints such as the shoulders or hi ...
,
immunoglobulin A Immunoglobulin A (Ig A, also referred to as sIgA in its secretory form) is an antibody that plays a role in the immune function of mucous membranes. The amount of IgA produced in association with mucosal membranes is greater than all other t ...
nephropathy Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an inflammatory kidney disease and has several types according to the location of the inflammation. Inflammation can b ...
, cardiac conduction abnormalities, or
aortitis Aortitis is the inflammation of the aortic wall. The disorder is potentially life-threatening and rare. It is reported that there are only 1–3 new cases of aortitis per year per million people in the United States and Europe. Aortitis is most com ...
with
aortic regurgitation Aortic regurgitation (AR), also known as aortic insufficiency (AI), is the leaking of the aortic valve of the heart that causes blood to flow in the reverse direction during ventricular diastole, from the aorta into the left ventricle. As a conseq ...
. However, most people with reactive arthritis can expect to live normal life spans and maintain a near-normal lifestyle with modest adaptations to protect the involved organs.


Epidemiology

Because women may be underdiagnosed, the exact incidence of reactive arthritis is difficult to estimate. A few studies have been completed, though. In
Norway Norway, officially the Kingdom of Norway, is a Nordic country in Northern Europe, the mainland territory of which comprises the western and northernmost portion of the Scandinavian Peninsula. The remote Arctic island of Jan Mayen and t ...
between 1988 and 1990, the incidence was 4.6 cases per 100,000 for chlamydia-induced reactive arthritis and 5 cases per 100,000 for that induced by enteric bacteria. In 1978 in
Finland Finland ( fi, Suomi ; sv, Finland ), officially the Republic of Finland (; ), is a Nordic country in Northern Europe. It shares land borders with Sweden to the northwest, Norway to the north, and Russia to the east, with the Gulf of Bo ...
, the annual incidence was found to be 43.6 per 100,000.


History

When reactive arthritis appears in a triad that also includes ophthalmic and urogenital manifestations, the
eponym An eponym is a person, a place, or a thing after whom or which someone or something is, or is believed to be, named. The adjectives which are derived from the word eponym include ''eponymous'' and ''eponymic''. Usage of the word The term ''epon ...
"Reiter's syndrome" is often applied; German physician Hans Conrad Julius Reiter described the condition in a soldier he treated during
World War I World War I (28 July 1914 11 November 1918), often abbreviated as WWI, was List of wars and anthropogenic disasters by death toll, one of the deadliest global conflicts in history. Belligerents included much of Europe, the Russian Empire, ...
. A number of physicians have suggested that the eponym is undeserved. Reiter's Nazi Party affiliation, and in particular his involvement in forced human experimentation in the
Buchenwald concentration camp Buchenwald (; literally 'beech forest') was a Nazi concentration camp established on hill near Weimar, Germany, in July 1937. It was one of the first and the largest of the concentration camps within Germany's 1937 borders. Many actual or s ...
(which, after his capture at the end of
World War II World War II or the Second World War, often abbreviated as WWII or WW2, was a world war that lasted from 1939 to 1945. It involved the World War II by country, vast majority of the world's countries—including all of the great power ...
, resulted in his prosecution in Nuremberg as a war criminal), have come to overshadow his medical accomplishments. Furthermore, he was not the first physician to make associations between the arthritis and other symptoms—the names arthritis urethritica, venereal arthritis and polyarteritis enterica had previously been applied—and the full triad was described by another physician in the 19th century.


Notable cases

* It has been postulated that Italian-born explorer
Christopher Columbus Christopher Columbus * lij, Cristoffa C(or)ombo * es, link=no, Cristóbal Colón * pt, Cristóvão Colombo * ca, Cristòfor (or ) * la, Christophorus Columbus. (; born between 25 August and 31 October 1451, died 20 May 1506) was a ...
had reactive arthritis, dying from a heart attack caused by the condition. *
Pat Buchanan Patrick Joseph Buchanan (; born November 2, 1938) is an American paleoconservative political commentator, columnist, politician, and broadcaster. Buchanan was an assistant and special consultant to U.S. Presidents Richard Nixon, Gerald Ford, ...
, American conservative political commentator, author, syndicated columnist, politician and broadcaster * P. J. Gallagher * Ian Murray, Scottish football player *
Mark St. John Mark Leslie Norton (February 7, 1956 – April 5, 2007), better known as Mark St. John, was an American guitarist best known for his brief stint with the hard rock band Kiss from April to November 1984. His work can be heard on the band's 1984 ...
, one-time guitarist for
Kiss A kiss is the touch or pressing of one's lips against another person or an object. Cultural connotations of kissing vary widely. Depending on the culture and context, a kiss can express sentiments of love, passion, romance, sexual attraction, ...
*
Kirk Brandon Kirk Brandon (born 3 August 1956) is an English musician best known as the leader of the bands Theatre of Hate and Spear of Destiny and a former lover of Boy George. Musical career Brandon's music career started in 1978, in Clapham, south Lo ...
, lead singer for Spear of Destiny *
Daniel Johns Daniel Paul Johns (born 22 April 1979) is an Australian musician, singer, and songwriter best known as the former frontman, guitarist, and main songwriter of the rock band Silverchair. Johns is also one half of The Dissociatives with Paul Mac ...
, Australian musician, lead singer for
Silverchair Silverchair were an Australian rock band, which formed in 1992 as Innocent Criminals in Newcastle, New South Wales, with Ben Gillies on drums, Daniel Johns on vocals and guitars, and Chris Joannou on bass guitar. The group got their big break ...
* Steve Walters, football player and survivor of sexual abuse by football trainer Barry Bennell


See also

List of medical eponyms with Nazi associations This article lists medical eponyms which have been associated with Nazi human experimentation or Nazi politics. While normally eponyms used in medicine serve to honor the memory of the physician or researcher who first documented a disease or pione ...


References


External links


eMedicine

Questions and Answers about Reactive Arthritis
nbsp;- US National Institute of Arthritis and Musculoskeletal and Skin Diseases {{Hypersensitivity and autoimmune diseases Infectious arthropathies Autoimmune diseases Conditions diagnosed by stool test Pustular dermatitis Steroid-responsive inflammatory conditions Syndromes Medical triads Medical mnemonics