Reactive Arthritis
“Inflammatory arthritis that appears from several days to weeks after a gastrointestinal or genitourinary infection.”
Causes:
Reactive arthritis is stimulated by a bacterial infection of the genitourinary tract (Chlamydia trachomatis, Neisseria gonorrhea, Mycoplasma hominis, and Ureaplasma urealyticum) and gastrointestinal tract (Salmonella enteritidis, Shigella flexneri, Shigella dysenteriae, Yersinia enterocolitica, Campylobacter jejuni, and Clostridium difficile.
The occurrence of the disease is about 2-4% after urogenital infection (mostly with Chlamydia trachomatis) and 0-5% after gastrointestinal infection which may change by different factors like environmental, epidemiological factors, bacterial pathogenicity, and changes in study design.
These days, it is known as an autoimmune response to gastrointestinal and genitourinary infections.
Symptoms:
The symptoms of reactive arthritis include a sausage-shaped finger, toe, or heel pain, conjunctivitis, acute diarrhea within 4 weeks of infection, asymmetric oligo-arthritis, and urethritis or genital ulcers. Patients having acute oligo-arthritis mainly involve the sacroiliac joint and lumber spine. Not more than 6 large joints affect at the same time. The knee and ankle are the most affected joints. Extra-articular symptoms are manifested in the skeletal system (enthesitis, dactylitis), eye (30% conjunctivitis, anterior uveitis, episcleritis, and keratitis can lead to vision loss), urogenital tract (urethritis, cervicitis, prostatitis, salpingo-oophoritis, cystitis or circulation balanitis), mucosal and skin involvement (mucosal ulcers, keratoderma blennorrhagica and erythema nodosum), cardiac (carditis, aortic, diverticular and valvular abnormalities) and nail changes (onycholysis, subungual keratosis or nail pits).
These symptoms appear from several days to weeks after infection initiation. The infection may be self-limiting, recurrent, or continuous, and about 20-25% of patients may progress to chronic infection. This disease is very common in HIV-infected patients with severe psoriasiform dermatitis on the scalp, soles, palms, and flexures.
Epidemiology:
Reactive arthritis is a very rare disorder. The occurrence is reported to be 0.6-27 per 100,000 in population-based studies. It is more common in adult males in their second and third decades of life.
About 1-3% of patients with nonspecific urethritis will develop continuous symptoms leading to the chronicity of arthritis. Overall, higher disease activity is mostly shown in lower-educated populations.
Pathophysiology:
In reactive arthritis, T lymphocytes are induced by bacterial fragments of lipopolysaccharide and nucleic acids during the attack by invasive bacteria in the blood. These activated cytotoxic-T cells attack the synovium and other self-antigens through molecular mimicry to induce autoimmunity. This is supported by the availability of Chlamydia trachomatis and Chlamydia pneumonia ribosomal RNA transcripts, enteric bacterial DNA, and bacterial degradation products in the synovial tissue and fluid.
Genetic Reasons:
Reactive arthritis is linked with the HLA-B27(human leukocyte antigen B27 gene or protein) gene on chromosome 6 and its greater protein level develops autoimmune disorders. The prevalence of HLA-B27 in reactive arthritis is 30-50% and varies generally. In hospital-based studies, the frequency of disease of 60-80% is reported. The HLA-B27 presence increases reactive arthritis by introducing bacterial antigens to T cells, altering the self-tolerance of the host immune system, enhancing TNF-alpha (tumor necrosis factor) production, engaging the microbial attack in the gut, and delaying clearance of causative organisms.
Histopathology:
The dermal histopathological characteristics of reactive arthritis are similar to psoriasis (skin chronic disorder of itchy rashes mostly on the knees). Synovial fluid analysis reveals large macrophages, reiter cells with phagocytosed neutrophils, lymphocytes, and plasma cells. Extensive pannus (extra layer) formation is very rare.
Evaluation:
Reactive arthritis is a subclass of seronegative spondyloarthropathies that affect the axial skeleton. The diagnostic guidelines for reactive arthritis are
• A combination of genitourinary symptoms, metatarsophalangeal joint involvement, elevated C reactive protein, and positive HLA- B27 provide a 69% sensitivity and 93.5% specificity for disease treatment.
• Nucleic acid amplification, polymerase chain reaction (PCR), serological tests, and stool culture may be helpful to detect enteric pathogens.
• HLA B 27 can be measured as it relates to the chronicity of reactive arthritis but is not diagnostic. Sacroiliitis occurs mostly in HLA-B27-positive patients.
Treatment:
First, antimicrobial therapy is prescribed for 3-6 months to reduce chronicity but is not best for patients with the least infection. The purpose of therapy is to provide relief in reactive arthritis and prevent its chronicity. Non-steroidal anti-inflammatory drugs are given in the initial treatment. Intra-articular or local glucocorticoids in case of mono or oligo-arthritis, mechanical devices like orthotics and insole, disease-modifying antirheumatic drugs (DMARDs) mainly sulphasalazine, methotrexate, azathioprine, tumor necrosis factor (TNF) blocking agents like infliximab and etanercept are useful in acute arthritis.
There is no proper treatment for reactive arthritis but proper care is supportive to decrease chronicity. It can be managed by a team of healthcare professionals that includes a rheumatologist, ophthalmologist, gastroenterologist, physical therapist, nurse, and pharmacist. Patient education about the disease and its treatment to follow regular treatment patterns can improve patient health. All patients must be physically active. Strengthening exercises play a key role in long-term therapy to prevent muscle wasting.
Complications:
Complications of reactive arthritis may be recurrent arthritis (15-50%), chronic arthritis or sacroiliitis, ankylosing spondylitis (30-50% in case of HLA-B27 is positive), urethral stricture, aortic root necrosis, cataracts, and cystoid macular edema.
Outcomes:
The progression of reactive arthritis varies until symptoms resolve by 6-8 months. The death rate is very rare and usually due to treatments. Sexually transmitted infection is worse than gastrointestinal infection. 25-50% chances of recurrences mainly in patients having HLA-B27 positive that may cause new infection or stress. 20% of patients develop enthesitis and destructive arthritis due to long-term infection. Elevation of erythrocyte sedimentation rate (ESR), lack of response to NSAIDs, and hip joint involvement usually indicate poor outcomes.
