Post infection arthritis reactive
Inflammation of joints, entheses (where tendons insert onto bones), axial skeleton (spine), skin, mucous membranes, gastrointestinal tract, and eyes may occur. The genetic marker, HLA-B27 is positive in 65-96% of patients (75% on average). Patients who are HLA-B27 positive have about a 50-fold increased chance of developing ReA, but this syndrome can occur in patients who are HLA-B27 negative. A tendency exists for more severe and long-term disease in patients with HLA-B27, along with a strong family clustering of the disease. The frequency of ReA after bowel infection averages 1-4% but varies greatly, even among outbreaks of the same organism. The mechanism of the interaction of the inciting organism with the host (often HLA-B27 positive) leading to the development of ReA is not known. The role of HLA-B27 in this scenario remains to be defined. Molecular mimicry, presentation of pathogenic peptides, or an altered host response to the bacteria are all possible. ReA typically follows a self-limited course, with resolution of symptoms by 3-12 months, even in patients who are acutely incapacitated. However, the condition has a high tendency to recur, particularly with ocular and genitourinary tract inflammation. Individuals who are HLA-B27 positive have a higher frequency of recurrence. A new infection or other stress factor could cause a reactivation of the disease. About 15% of patients develop a long-term, sometimes destructive, arthritis or enthesitis or spondylitis. The presence of hip joint involvement, an erythrocyte sedimentation rate (ESR) higher than 30, and unresponsiveness to nonsteroidal anti-inflammatory drugs (NSAIDs) probably are predictive of a severe outcome or chronic disease in ReA. Prevalence of HLA-B27 and ReA is higher in white people than in black people, as in other spondyloarthropathies. ReA following food-borne enteric infections affects males and females with the same frequency. Disease associated with venereally acquired infections occurs in a male-to-female ratio of 9:1. Most patients are aged 20-40 years.
Nongonococcal urethritis, if present, can be one of the presenting symptoms for both postvenereal and postenteric forms. Mild dysuria, mucopurulent discharge, prostatitis and epididymitis in men, and vaginal discharge and/or cervicitis in women can be observed. The onset is most often acute, with malaise, fatigue, and fever. An asymmetrical predominately lower extremity oligoarthritis is the major presenting symptom. Low back pain occurs in 50% of patients. Heel pain is common because of enthesopathies at the Achilles or plantar aponeurosis insertion on the calcaneus.
Peripheral joint involvement is typically asymmetric and most frequently affects the weight-bearing joints (ie, knees, ankles, hips), but the shoulders, wrists, and elbows are also affected. Keratoderma blennorrhagica observed in the palms and soles is indistinguishable from pustular psoriasis and is very suggestive of chronic ReA. Conjunctivitis is part of the classic triad of Reiter syndrome, and it can occur before or at the onset of arthritis. Enteric infections can be the triggering event for ReA. Pathogens include Salmonella, Shigella, Yersinia, and Campylobacter species. The frequency of ReA after these enteric infections is about 1-4%. Some patients continue with intermittent bouts of diarrhea and abdominal pain. Lesions resembling ulcerative colitis or Crohn disease have been described when ileocolonoscopy is performed in patients with established ReA.
Other manifestations of the disease include mild renal pathology with proteinuria and microhematuria. In severe chronic cases, amyloid deposits and immunoglobulin A (IgA) nephropathy have been reported. Cardiac conduction abnormalities can be observed, and aortitis with aortic regurgitation occurs in 1-2% of patients. ReA is usually triggered by a genitourinary or gastrointestinal infection.
Acute phase reactants, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), are usually elevated markedly but later return to the reference range with subsidence of the inflammation. Other laboratory findings include a normocytic normochromic anemia along with mild leukocytosis and thrombocytosis during the acute phase. IgA antibodies to specific bacterial antigens have been reported. Urinalysis can show aseptic pyuria. Synovial fluid analysis reveals a high white blood cell count, most often with elevated polymorphonuclear leukocytes acutely. Gram stain and culture results are negative and are necessary to exclude septic arthritis. Throat, stool, or urogenital tract cultures can be performed in an attempt to isolate the causative organism. Test results for rheumatoid factor and antinuclear antibodies are negative. Early in the disease, no abnormalities are found on radiograph. In more advanced or long-term disease, periosteal reaction and proliferation at sites of tendon insertion can be observed. Exuberant plantar spurs are a common sign in long-term cases. In the hands and feet, marginal erosions with adjacent bone proliferation occur. Spinal radiographic findings include sacroiliitis and syndesmophytes. Sacroiliitis occurs in less than 10% of acute cases but may be observed in 50% of those patients with chronic severe disease. Syndesmophytes are usually asymmetrical and are found most commonly in the thoracolumbar region. Severe ankylosing spondylitis occurs in less than 5% of cases. An ECG should be performed in patients having a prolonged course of the disease to evaluate for conduction disturbances. HLA-B27 testing returns positive results in 65-96% of cases. HLA-B27 testing is not necessary in classic RS but may be helpful to support the diagnosis of ReA in patients with joint-restricted symptoms. Needle aspiration of a joint may be necessary to rule out septic or crystalline arthritis. The treatment of ReA is modified according to the severity of symptoms.
NSAIDs are the foundation of therapy. These agents should be used on a regular basis to achieve a good anti-inflammatory effect. These agents can be used as either intra-articular injection or systemic therapy. Joint injections can produce long-lasting improvement and help avoid the use of other systemic therapy. Sacroiliac joints can be injected, usually under fluoroscopic guidance. Systemic corticosteroids can be used, particularly in patients with poor response to NSAIDs or in those who develop adverse effects related to their use. The starting dose is guided by a patient's symptoms and objective evidence of inflammation. Prednisone 0.5-1 mg/kg/d can be used initially and tapered according to response.
The current concepts on the pathogenesis of ReA indicate that an infectious agent is the trigger of the disease, but antibiotic treatment does not change the course of the disease, even when a microorganism is isolated. In these cases, antibiotics are used to treat the underlying infection, but specific treatment for ReA is lacking. However, in chlamydial-induced ReA, studies have suggested that appropriate treatment of the acute urogenital infection can prevent ReA and that treatment of acute ReA with a 3-month course of tetracycline reduces the duration of illness. No evidence indicates that antibiotic therapy benefits enteric-related ReA or chronic ReA of any cause. Quinolones have been studied because of their broad coverage, but no beneficial effect has been noted.
In patients with chronic symptoms or in patients with persistent inflammation despite the use of the agents mentioned above, other second-line drugs may be used. Clinical experience with these so-called disease-modifying antirheumatic drugs (DMARDs) has been mostly in RA and in psoriatic arthritis. DMARDs have also been used in ReA, although their disease-modifying effects in the ReA setting are uncertain. Sulfasalazine can be beneficial in some patients. The use of this drug in ReA is of interest because of the finding of clinical or subclinical inflammation of the bowel in many patients. Sulfasalazine is more widely used in ankylosing spondylitis. In a recent 36-week trial of sulfasalazine versus a placebo in the spondyloarthropathies, patients with ReA who were taking sulfasalazine had a 62.3% response rate compared to 47.7% for the placebo group in peripheral arthritis (P = 0.09). In patients who present with rheumatoidlike disease, methotrexate can be used. Several reports have shown good response, but controlled studies are lacking. Reports also describe the use of azathioprine and bromocriptine in ReA, but, again, large studies have not been published. Patients with ReA and HIV/AIDS should not be placed on methotrexate or other immunosuppressive agents.
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