Reiter's : Pathogenesis and Symptoms
Quoted from: http://www.chronicprostatitis.com/reiters.html
Etiology And Pathogenesis
The first bacterial infection to be causally related to reactive arthritis was Shigella flexneri. An outbreak of shigellosis among Finnish troops in 1944 resulted in numerous cases of reactive arthritis. Of the four species of Shigella, sonnei, boydii, flexneri, and dysenteriae, S. flexneri has most often been implicated in cases of reactive arthritis, both sporadic and epidemic. S. sonnei, although responsible for the majority of cases of shigellosis in the United States, has only rarely been implicated in cases of reactive arthritis.
Other bacteria that have been definitively identified as triggers of reactive arthritis include several Salmonella species, Yersinia enterocolitica, and Campylobacter jejuni. There is suggestive evidence implicating several other microorganisms. including Brucella, Yersinia pseudotuberculosis. Clostridium difficile; the genitourinary pathogens Chlamydia trachomatis, Neisseria gonorrhoeae, and Urea-plasma urealyticum; and Streptococcus pyogenes. There are also numerous isolated reports of acute arthritis preceded by other bacterial. viral, or parasitic infections, but whether the microorganisms involved are actual triggers of reactive arthritis remains to be determined.
It has not been determined whether reactive arthritis occurs by the same pathogenetic mechanism following infection with each of these microorganisms, nor has the mechanism been fully elucidated in the case of any one of the known bacterial triggers. The immune response is presumed to play a principal role, but there is not yet general agreement on the relative importance of humoral versus cellular mechanisms. Most, if not all, of the triggering organisms share a capacity to invade host cells and survive intracellularly.
The largest body of data regarding the immune response in reactive arthritis has been generated by studies of Y. enterocolitica, particularly serotypes 0:3 and 0:9 in Finland, where these organisms frequently cause enteric infection in a population in which the prevalence of HLA-B27 is 14 percent. In comparison with individuals who fail to develop reactive arthritis following enteric infection with Yersinia, patients with Yersinia-triggered reactive arthritis show far fewer gastrointestinal symptoms attributable to the infection, a smaller initial 1gM response, stronger and more persistent IgA and lgG responses, higher levels of IgA anti-Yersinia antibodies with a secretory component. and reduced T-cell proliferative responses to Yersinia antigens. These findings suggest an unusual persistence of the immune response to the infecting organism in those individuals in whom reactive arthritis develops. Circulating immune complexes containing Yersinia antigens have been found in a higher proportion of arthritic than nonarthritic individuals, and occasionally in the inflamed joints, but the significance of these findings is not clear.
It is not known to what extent reactive arthritis represents an autoimmune response against host tissues, as opposed to an immune response against antigens of the triggering organism that have disseminated to the target tissues. Both mechanisms appear to operate in animal models. Chlamydial antigens have been demonstrated in the synovium of a few patients with venereally acquired reactive arthritis, but it is not known whether they are the inciting antigenic stimulus. Similarly, Yersinia enterocolitica antigen has been detected in synovial fluid cells in patients with Y. enterocolitica-induced reactive arthritis, but the significance of this is unclear.
The role of HLA-B27 in reactive arthritis has yet to be fully elucidated. At present. the evidence favors some form of molecular mimicry. or the sharing of antigenic determinants between the HLAB27 molecule and molecules encoded by the inciting microbial agent. Several reports have documented antigenic cross-reactivity between the B27 molecule and envelope glycoproteins of arthritogenic bacteria, including Shigella fiexneri and Yersinio pseudotuberculosis. but the pathogenetic significance of this is not known. Many but not all B27-negative individuals with reactive arthritis possess HLA-B alleles that are antigenically cross-reactive with HLA-B27, notably HLA-B7.
(....)
Clinical Features
The clinical manifestations of reactive arthritis constitute a spectrum that ranges from an isolated, transient monarthritis to a more severe multisystem disease. In the majority of cases, a careful history will elicit some evidence of an antecedent infection 1 to 4 weeks before the onset of symptoms of the reactive disease. However, in a sizeable minority, particularly in cases of relapse, no clinical or laboratory evidence of an antecedent infection can be found. In many cases of presumed venereally acquired reactive disease, there is a history of a recent new sexual partner, even in the absence of laboratory evidence of infection.
Constitutional symptoms are common, including fatigue, malaise, fever, and weight loss. The musculoskeletal symptoms are usually acute in onset. Arthritis is usually asymmetric and additive, with involvement of new joints occurring over a period of a few days to 1 or 2 weeks. The joints of the lower extremities, especially the knee, ankle, and subtalar, metatarsophalangeal, and toe interphalangeal joints, are the most common sites of involvement, but the wrist and fingers can be involved as well. The arthritis is usually quite painful, and tense joint effusions are not uncommon, especially in the knee. Dactylitis, or "sausage digit," a diffuse swelling of a solitary finger or toe, is a distinctive feature of both reactive arthritis and psoriatic arthritis. Tendinitis and fasciitis are particularly characteristic lesions, producing pain at multiple insertion sites, especially the Achilles insertion, the plantar fascia, and sites along the axial skeleton. Spinal and low back pain are quite common, and may be caused by insertional inflammation, muscle spasm, acute sacroiliitis, or presumably, arthritis in intervertebral articulations.
Urogenital lesions may occur throughout the course of the disease. In males, urethritis may be marked or relatively asymptomatic, and may be either an accompaniment of the triggering infection or a result of the reactive phase of the disease. Prostatitis is also common. Similarly, in females cervicitis or salpingitis may be caused either by the infectious trigger or the sterile reactive process.
Ocular disease is common, ranging from transient, asymptomatic conjunctivitis to an aggressive anterior uveitis that occasionally proves refractory to treatment and results in blindness.
Mucocutaneous lesions are frequent. Oral ulcers tend to be superficial, transient, and often asymptomatic. The characteristic skin lesion, keratoderma blennorrhagica, consists of vesicles that become hyperkeratotic, ultimately forming a crust before disappearing. It is most common on the palms and soles, but may occur elsewhere as well. In patients with HIV infection, these lesions are often extremely severe and extensive, dominating the clinical picture. Lesions on the glans penis (circinate balanitis) are common; these consist of vesicles that quickly rupture to form painless superficial erosions, which in circumcised individuals can form crusts similar to those of keratoderma blennorrhagica. Nail changes are common and consist of onycholysis, distal yellowish discoloration, and/or heaped up hyperkeratosis.
Less frequent or rare manifestations of reactive arthritis include cardiac conduction defects, aortic insufficiency, central or peripheral nervous system lesions, and pleuropulmonary infiltrates.
Long-term follow-up studies suggest that some joint symptoms persist in many, if not most, patients with reactive arthritis. Recurrences of the acute syndrome are common, and as many as 25 percent of patients either become unable to work or are forced to change occupations because of persistent joint symptoms. Chronic heel pain is often a particularly distressing symptom. Ankylosing spondylitis is also a common sequela. In most studies, HLA-B27-positive patients have a worse outcome than B27-negative patients. The extent to which the long-term prognosis varies with different inciting agents is not known. However, patients with Yersinia-induced arthritis appear to have less chronic disease than those whose initial episode follows epidemic shigellosis.
The first bacterial infection to be causally related to reactive arthritis was Shigella flexneri. An outbreak of shigellosis among Finnish troops in 1944 resulted in numerous cases of reactive arthritis. Of the four species of Shigella, sonnei, boydii, flexneri, and dysenteriae, S. flexneri has most often been implicated in cases of reactive arthritis, both sporadic and epidemic. S. sonnei, although responsible for the majority of cases of shigellosis in the United States, has only rarely been implicated in cases of reactive arthritis.
Other bacteria that have been definitively identified as triggers of reactive arthritis include several Salmonella species, Yersinia enterocolitica, and Campylobacter jejuni. There is suggestive evidence implicating several other microorganisms. including Brucella, Yersinia pseudotuberculosis. Clostridium difficile; the genitourinary pathogens Chlamydia trachomatis, Neisseria gonorrhoeae, and Urea-plasma urealyticum; and Streptococcus pyogenes. There are also numerous isolated reports of acute arthritis preceded by other bacterial. viral, or parasitic infections, but whether the microorganisms involved are actual triggers of reactive arthritis remains to be determined.
It has not been determined whether reactive arthritis occurs by the same pathogenetic mechanism following infection with each of these microorganisms, nor has the mechanism been fully elucidated in the case of any one of the known bacterial triggers. The immune response is presumed to play a principal role, but there is not yet general agreement on the relative importance of humoral versus cellular mechanisms. Most, if not all, of the triggering organisms share a capacity to invade host cells and survive intracellularly.
The largest body of data regarding the immune response in reactive arthritis has been generated by studies of Y. enterocolitica, particularly serotypes 0:3 and 0:9 in Finland, where these organisms frequently cause enteric infection in a population in which the prevalence of HLA-B27 is 14 percent. In comparison with individuals who fail to develop reactive arthritis following enteric infection with Yersinia, patients with Yersinia-triggered reactive arthritis show far fewer gastrointestinal symptoms attributable to the infection, a smaller initial 1gM response, stronger and more persistent IgA and lgG responses, higher levels of IgA anti-Yersinia antibodies with a secretory component. and reduced T-cell proliferative responses to Yersinia antigens. These findings suggest an unusual persistence of the immune response to the infecting organism in those individuals in whom reactive arthritis develops. Circulating immune complexes containing Yersinia antigens have been found in a higher proportion of arthritic than nonarthritic individuals, and occasionally in the inflamed joints, but the significance of these findings is not clear.
It is not known to what extent reactive arthritis represents an autoimmune response against host tissues, as opposed to an immune response against antigens of the triggering organism that have disseminated to the target tissues. Both mechanisms appear to operate in animal models. Chlamydial antigens have been demonstrated in the synovium of a few patients with venereally acquired reactive arthritis, but it is not known whether they are the inciting antigenic stimulus. Similarly, Yersinia enterocolitica antigen has been detected in synovial fluid cells in patients with Y. enterocolitica-induced reactive arthritis, but the significance of this is unclear.
The role of HLA-B27 in reactive arthritis has yet to be fully elucidated. At present. the evidence favors some form of molecular mimicry. or the sharing of antigenic determinants between the HLAB27 molecule and molecules encoded by the inciting microbial agent. Several reports have documented antigenic cross-reactivity between the B27 molecule and envelope glycoproteins of arthritogenic bacteria, including Shigella fiexneri and Yersinio pseudotuberculosis. but the pathogenetic significance of this is not known. Many but not all B27-negative individuals with reactive arthritis possess HLA-B alleles that are antigenically cross-reactive with HLA-B27, notably HLA-B7.
(....)
Clinical Features
The clinical manifestations of reactive arthritis constitute a spectrum that ranges from an isolated, transient monarthritis to a more severe multisystem disease. In the majority of cases, a careful history will elicit some evidence of an antecedent infection 1 to 4 weeks before the onset of symptoms of the reactive disease. However, in a sizeable minority, particularly in cases of relapse, no clinical or laboratory evidence of an antecedent infection can be found. In many cases of presumed venereally acquired reactive disease, there is a history of a recent new sexual partner, even in the absence of laboratory evidence of infection.
Constitutional symptoms are common, including fatigue, malaise, fever, and weight loss. The musculoskeletal symptoms are usually acute in onset. Arthritis is usually asymmetric and additive, with involvement of new joints occurring over a period of a few days to 1 or 2 weeks. The joints of the lower extremities, especially the knee, ankle, and subtalar, metatarsophalangeal, and toe interphalangeal joints, are the most common sites of involvement, but the wrist and fingers can be involved as well. The arthritis is usually quite painful, and tense joint effusions are not uncommon, especially in the knee. Dactylitis, or "sausage digit," a diffuse swelling of a solitary finger or toe, is a distinctive feature of both reactive arthritis and psoriatic arthritis. Tendinitis and fasciitis are particularly characteristic lesions, producing pain at multiple insertion sites, especially the Achilles insertion, the plantar fascia, and sites along the axial skeleton. Spinal and low back pain are quite common, and may be caused by insertional inflammation, muscle spasm, acute sacroiliitis, or presumably, arthritis in intervertebral articulations.
Urogenital lesions may occur throughout the course of the disease. In males, urethritis may be marked or relatively asymptomatic, and may be either an accompaniment of the triggering infection or a result of the reactive phase of the disease. Prostatitis is also common. Similarly, in females cervicitis or salpingitis may be caused either by the infectious trigger or the sterile reactive process.
Ocular disease is common, ranging from transient, asymptomatic conjunctivitis to an aggressive anterior uveitis that occasionally proves refractory to treatment and results in blindness.
Mucocutaneous lesions are frequent. Oral ulcers tend to be superficial, transient, and often asymptomatic. The characteristic skin lesion, keratoderma blennorrhagica, consists of vesicles that become hyperkeratotic, ultimately forming a crust before disappearing. It is most common on the palms and soles, but may occur elsewhere as well. In patients with HIV infection, these lesions are often extremely severe and extensive, dominating the clinical picture. Lesions on the glans penis (circinate balanitis) are common; these consist of vesicles that quickly rupture to form painless superficial erosions, which in circumcised individuals can form crusts similar to those of keratoderma blennorrhagica. Nail changes are common and consist of onycholysis, distal yellowish discoloration, and/or heaped up hyperkeratosis.
Less frequent or rare manifestations of reactive arthritis include cardiac conduction defects, aortic insufficiency, central or peripheral nervous system lesions, and pleuropulmonary infiltrates.
Long-term follow-up studies suggest that some joint symptoms persist in many, if not most, patients with reactive arthritis. Recurrences of the acute syndrome are common, and as many as 25 percent of patients either become unable to work or are forced to change occupations because of persistent joint symptoms. Chronic heel pain is often a particularly distressing symptom. Ankylosing spondylitis is also a common sequela. In most studies, HLA-B27-positive patients have a worse outcome than B27-negative patients. The extent to which the long-term prognosis varies with different inciting agents is not known. However, patients with Yersinia-induced arthritis appear to have less chronic disease than those whose initial episode follows epidemic shigellosis.
