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Reactive arthritis, previously known as Reiter's syndrome, is a form of inflammatory arthritis that develops in response to an
infection An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...
in another part of the body (cross-reactivity). Coming into contact with
bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...
and developing an infection can trigger the disease. By the time a person presents with symptoms, the "trigger" infection has often been cured or is in remission in chronic cases, thus making determination of the initial cause difficult. The manifestations of reactive arthritis include the following triad of symptoms: inflammatory arthritis of large joints, inflammation of the eyes in the form of
conjunctivitis Conjunctivitis, also known as pink eye or Madras eye, is inflammation of the conjunctiva, the thin, clear layer that covers the white surface of the eye and the inner eyelid. It makes the eye appear pink or reddish. Pain, burning, scratchiness ...
or
uveitis 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 ...
, and urethritis in men or cervicitis in women. Arthritis occurring alone following sexual exposure or enteric infection is also known as reactive arthritis. Affected people may present with mucocutaneous lesions, as well as
psoriasis Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by patches of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small localized patches to complete b ...
-like skin lesions such as circinate balanitis, and keratoderma blennorrhagicum. Enthesitis 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 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'', '' ...
of fewer than five joints which often includes the knee or
sacroiliac joint The sacroiliac joint or SI joint (SIJ) is the joint between the sacrum and the ilium bones of the pelvis, which are connected by strong ligaments. In humans, the sacrum supports the spine and is supported in turn by an ilium on each side. The ...
. 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). As a seronegative spondyloarthropathy, laboratory analysis of blood will show that the patient is rheumatoid factor negative and often HLA-B27 positive. The most common triggers are intestinal infections (with ''
Salmonella ''Salmonella'' is a genus of bacillus (shape), rod-shaped, (bacillus) Gram-negative bacteria of the family Enterobacteriaceae. The two known species of ''Salmonella'' are ''Salmonella enterica'' and ''Salmonella bongori''. ''S. enterica'' ...
'', ''
Shigella ''Shigella'' is a genus of bacteria that is Gram negative, facultatively anaerobic, non–spore-forming, nonmotile, rod shaped, and is genetically nested within ''Escherichia''. The genus is named after Kiyoshi Shiga, who discovered it in 1 ...
'' or '' Campylobacter'') and sexually transmitted infections (with ''
Chlamydia trachomatis ''Chlamydia trachomatis'' () is a Gram-negative, Anaerobic organism, anaerobic bacterium responsible for Chlamydia infection, chlamydia and trachoma. ''C. trachomatis'' exists in two forms, an extracellular infectious elementary body (EB) and an ...
''); however, it also can happen after
group A streptococcal infection Group A streptococcal infections are a number of infections with ''Streptococcus pyogenes'', a group A streptococcus (GAS). ''S. pyogenes'' is a species of beta-hemolytic Gram-positive bacteria that is responsible for a wide range of infectio ...
s. It most commonly strikes individuals aged 20–40 years of age, is more common in men than in women, and is 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 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 A mnemonic device ( ), memory trick or memory device is any learning technique that aids information retention or retrieval in the human memory, often by associating the information with something that is easier to remember. It makes use of e ...
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 Frequency is the number of occurrences of a repeating event per unit of time. Frequency is an important parameter used in science and engineering to specify the rate of oscillatory and vibratory phenomena, such as mechanical vibrations, audio ...
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 Stimulus (physiology), stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sense, sensory and emotional experience associated with, or res ...
and swelling. An asymmetrical inflammatory arthritis 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 Plantar fasciitis or plantar heel pain is a disorder of the plantar fascia, which is the connective tissue that supports the Arches of the foot, arch of the foot. It results in pain in the heel and Sole (foot), bottom of the foot that is usuall ...
, 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 called keratoderma blennorrhagicum 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 Conjunctivitis, also known as pink eye or Madras eye, is inflammation of the conjunctiva, the thin, clear layer that covers the white surface of the eye and the inner eyelid. It makes the eye appear pink or reddish. Pain, burning, scratchiness ...
and
uveitis 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 ...
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 Gout ( ) is a form of inflammatory arthritis characterized by recurrent attacks of pain in a red, tender, hot, and Joint effusion, swollen joint, caused by the deposition of needle-like crystals of uric acid known as monosodium urate crysta ...
and
sarcoidosis Sarcoidosis (; also known as Besnier–Boeck–Schaumann disease) is a disease involving abnormal collections of White blood cell, inflammatory cells that form lumps known as granulomata. The disease usually begins in the lungs, skin, or lymph n ...
. * 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 A mouth also referred to as the oral is the body orifice through which many animals ingest food and vocalize. The body cavity immediately behind the mouth opening, known as the oral cavity (or in Latin), is also the first part of the alime ...
, 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, fever, abdominal distension, and weight loss. Complications outside of the ...
. * 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 conse ...
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 whe ...
. Reactive arthritis has been described as a precursor of other joint conditions, including ankylosing spondylitis.


Causes

Reactive arthritis is associated with the HLA-B27 gene on chromosome 6 and by the presence of enthesitis as the basic pathologic lesion and is triggered by a preceding
infection An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...
. The most common triggering infection in the US is a genital infection with ''
Chlamydia trachomatis ''Chlamydia trachomatis'' () is a Gram-negative, Anaerobic organism, anaerobic bacterium responsible for Chlamydia infection, chlamydia and trachoma. ''C. trachomatis'' exists in two forms, an extracellular infectious elementary body (EB) and an ...
''. Other bacteria known to cause reactive arthritis which are more common worldwide are '' Ureaplasma urealyticum'', ''
Salmonella ''Salmonella'' is a genus of bacillus (shape), rod-shaped, (bacillus) Gram-negative bacteria of the family Enterobacteriaceae. The two known species of ''Salmonella'' are ''Salmonella enterica'' and ''Salmonella bongori''. ''S. enterica'' ...
'' spp., ''
Shigella ''Shigella'' is a genus of bacteria that is Gram negative, facultatively anaerobic, non–spore-forming, nonmotile, rod shaped, and is genetically nested within ''Escherichia''. The genus is named after Kiyoshi Shiga, who discovered it in 1 ...
'' spp., '' Yersinia'' spp., and '' Campylobacter'' spp. A bout of
food poisoning Foodborne illness (also known as foodborne disease and food poisoning) is any illness resulting from the contamination of food by pathogenic bacteria, viruses, or parasites, as well as prions (the agents of mad cow disease), and toxins such ...
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 tract is the largest of the body's systems, after the cardiovascular system. ...
infection may also precede the disease (the last four
genera Genus (; : genera ) is a taxonomic rank above species and below family as used in the biological classification of living and fossil organisms as well as viruses. In binomial nomenclature, the genus name forms the first part of the binomial s ...
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 (: urethras or urethrae) is the tube that connects the urinary bladder to the urinary meatus, through which Placentalia, placental mammals Urination, urinate and Ejaculation, ejaculate. The external urethral sphincter is a striated ...
,
cervix The cervix (: cervices) or cervix uteri is a dynamic fibromuscular sexual organ of the female reproductive system that connects the vagina with the uterine cavity. The human female cervix has been documented anatomically since at least the time ...
, 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 Human pharynx, pharynx and larynx. An important section of it is the epiglottis, separating the esophagus from the t ...
may be swabbed in an attempt to
culture Culture ( ) is a concept that encompasses the social behavior, institutions, and Social norm, norms found in human societies, as well as the knowledge, beliefs, arts, laws, Social norm, customs, capabilities, Attitude (psychology), attitudes ...
the causative organisms. Cultures may also be carried out on
urine Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...
and stool samples or fluid obtained by arthrocentesis. Tests for C-reactive protein and erythrocyte sedimentation rate 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 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 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. Analgesics, particularly NSAIDs, are used.
Steroid A steroid is an organic compound with four fused compound, fused rings (designated A, B, C, and D) arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes t ...
s, sulfasalazine and immunosuppressants 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 invo ...
s are useful in the case of iritis.


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,
heart disease Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina pectoris, angina, myocardial infarction, heart attack), heart failure, ...
,
amyloid Amyloids are aggregates of proteins characterised by a fibrillar morphology of typically 7–13 nm in diameter, a β-sheet secondary structure (known as cross-β) and ability to be stained by particular dyes, such as Congo red. In the human ...
deposits, ankylosing spondylitis, immunoglobulin A nephropathy, cardiac conduction abnormalities, or aortitis 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 conse ...
. 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 countries, Nordic country located on the Scandinavian Peninsula in Northern Europe. The remote Arctic island of Jan Mayen and the archipelago of Svalbard also form part of the Kingdom of ...
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, officially the Republic of Finland, is a Nordic country in Northern Europe. It borders Sweden to the northwest, Norway to the north, and Russia to the east, with the Gulf of Bothnia to the west and the Gulf of Finland to the south, ...
, 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 noun after which or for which someone or something is, or is believed to be, named. Adjectives derived from the word ''eponym'' include ''eponymous'' and ''eponymic''. Eponyms are commonly used for time periods, places, innovati ...
"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 or the First World War (28 July 1914 – 11 November 1918), also known as the Great War, was a World war, global conflict between two coalitions: the Allies of World War I, Allies (or Entente) and the Central Powers. Fighting to ...
. Many physicians have suggested that the eponym is undeserved. Reiter's
Nazi Party The Nazi Party, officially the National Socialist German Workers' Party ( or NSDAP), was a far-right politics, far-right political party in Germany active between 1920 and 1945 that created and supported the ideology of Nazism. Its precursor ...
affiliation, and in particular his involvement in forced human experimentation in the
Buchenwald concentration camp Buchenwald (; 'beech forest') was a German Nazi concentration camp established on Ettersberg hill near Weimar, Nazi Germany, Germany, in July 1937. It was one of the first and the largest of the concentration camps within the Altreich (pre-1938 ...
(which, after his capture at the end of
World War II World War II or the Second World War (1 September 1939 – 2 September 1945) was a World war, global conflict between two coalitions: the Allies of World War II, Allies and the Axis powers. World War II by country, Nearly all of the wo ...
, resulted in his prosecution in Nuremberg as a
war criminal A war crime is a violation of the laws of war that gives rise to individual criminal responsibility for actions by combatants in action, such as intentionally killing civilians or intentionally killing prisoners of war, torture, taking hostage ...
), 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 (; between 25 August and 31 October 1451 – 20 May 1506) was an Italians, Italian explorer and navigator from the Republic of Genoa who completed Voyages of Christopher Columbus, four Spanish-based voyages across the At ...
had reactive arthritis, dying from a heart attack caused by the condition. * Pat Buchanan, American conservative political commentator, author, syndicated columnist, politician and broadcaster * P. J. Gallagher * Ian Murray, Scottish
football Football is a family of team sports that involve, to varying degrees, kick (football), kicking a football (ball), ball to score a goal (sports), goal. Unqualified, football (word), the word ''football'' generally means the form of football t ...
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 (band), Kiss from April to November 1984. His work can be heard on the ...
, one-time guitarist for
Kiss A kiss is the touching or pressing of one's lips against another person, animal or object. Cultural connotations of kissing vary widely; depending on the culture and context, a kiss can express sentiments of love, passion, romance, sex ...
* Kirk Brandon, 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 Lead vocalist, frontman, guitarist, and main songwriter of the Rock music, rock band Silverchair. Johns is also one half of The Dissociat ...
, Australian musician, lead singer for Silverchair * Steve Walters, football player and survivor of sexual abuse by football trainer Barry Bennell


See also

* List of medical eponyms with Nazi associations


References


External links


eMedicine

Overview of 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