Reactive arthritis overview

# Overview
Reactive arthritis (ReA) is the result of previous gastrointestinal or genitourinary infections, which results in an autoimmune condition. The most commonly associated organisms include Chlamydia, Yersinia, Salmonella, Shigella, and Campylobacter infection. In fourth century B.C, Hippocrates was the first to associate the presence of arthritis and infection in the genitourinary tract. In 1818, Sir Benjamin Brodie, an English physician was the first to describe the triad of urethritis, arthritis, and conjunctivitis. It is estimated around 75% patients of reactive arthritis are positive for HLA-B27. The exact mechanism by which infecting organism cause reactive arthritis is not fully understood. It is thought that microbial antigens are similar to certain body proteins (self proteins). When an immune response is mounted against the microbial proteins, the antibodies produced against microbial proteins also reacts with the self proteins of the body causing reactive arthritis.
Reactive arthritis (ReA) can be classified on the basis of previous gastrointestinal (GI) or genitourinary (GU) infection in to venereal or dysenteric ReA. Reactive arthritis should be distinguished from other HLA-B27 diseases causing arthritis of the peripheral skeleton, which present as arthralgia. The differentials include psoriatic arthritis, rheumatoid arthritis and ankylosing spondylitis. The incidence of reactive arthritis following a gastrointestinal or genitourinary infection is approximately 3-27 cases per 100,000 individuals worldwide. The prevalence of reactive arthritis is approximately 30-40 cases per 100,000 individuals worldwide. If left untreated, patients with reactive arthritis may progress to develop myalgias and joint pain especially in the lower extremities.
Reactive arthritis is diagnosed based on the clinical presentation with supporting laboratory evidence. The gold standard for diagnosis of reactive arthritis include spondyloarthritis and clear evidence of preceding infection by culture or polymerase chain reaction. The majority of cases (two-thirds) of reactive arthritis are self-limited and require only supportive care. Arthritis is the most common symptom and initially treated with NSAIDs. As the disease progresses or in case of no response, further management includes intra-articular and systemic steroids, DMARDs and finally TNF inhibitors. The role of antibiotics in reactive arthritis is not clear and their efficacy in reactive arthritis is not completely established. Surgical intervention is not recommended for the management of reactive arthritis. However, young adults who develop a chronic course may benefit from arthroscopic synovectomy. Patients with severe reactive arthritis with involvement of heart and vitreous chamber may require valve replacement surgery and vitrectomy respectively.

# Historical Perspective
In fourth century B.C, Hippocrates was the first to associate the presence of arthritis and infection in the genitourinary tract. In 1818, Sir Benjamin Brodie, an English physician was the first to describe the triad of urethritis, arthritis, and conjunctivitis. In 1916, several reports from France & Germany showed association between diarrhea and post-infection arthritis.

# Classification
Reactive arthritis (ReA) can be classified on the basis of previous gastrointestinal (GI) or genitourinary (GU) infection in to venereal or dysenteric ReA.

# Pathophysiology
It is thought that reactive arthritis is the result of previous gastrointestinal or genitourinary infections, which results in an autoimmune condition. The most commonly associated organisms include Chlamydia, Yersinia, Salmonella, Shigella, and Campylobacter infection. It is estimated around 75% patients of reactive arthritis are positive for HLA-B27. The exact mechanism by which infecting organism cause reactive arthritis is not fully understood. It is thought that microbial antigens are similar to certain body proteins (self proteins). When an immune response is mounted against the microbial proteins, the antibodies produced against microbial proteins also reacts with the self proteins of the body causing reactive arthritis.

# Causes
Common causes of reactive arthritis include infection with Chlamydia trachomatis, Neisseria gonorrhoeae, Salmonella enteritidis, Shigella flexneri, Campylobacter jejuni, Mycoplasma pneumoniae, Lymphogranuloma venereum, Mycobacterium tuberculosis, Clostridium difficile, and Streptococci viridans.

# Differentiating Reactive arthritis overview from Other Diseases
Reactive arthritis should be distinguished from other HLA-B27 diseases causing arthritis of the peripheral skeleton, which present as arthralgia. The differentials include psoriatic arthritis, rheumatoid arthritis and ankylosing spondylitis.

# Epidemiology and Demographics
The incidence of reactive arthritis following a gastrointestinal or genitourinary infection is approximately 3-27 cases per 100,000 individuals worldwide. The prevalence of reactive arthritis is approximately 30-40 cases per 100,000 individuals worldwide. Reactive arthritis commonly affects young adults in the age group of 18-35 years of age. Men are more commonly affected with reactive arthritis than females with male to female ratio of approximately 4:1. There is no racial predilection to reactive arthritis.

# Risk Factors
Common risk factors in the development of reactive arthritis include abnormal joint structure (most important risk factor), male sex (four times more likely) rheumatoid arthritis, diabetes mellitus, malignancy, old age, use of systemic steroids, HIV infection, hemodialysis, previous joint surgery and injection drug abuse.

# Screening
There is insufficient evidence to recommend routine screening for reactive arthritis.

# Natural History, Complications, and Prognosis
If left untreated, patients with reactive arthritis may progress to develop myalgias and joint pain especially in the lower extremities. Over the course of time, patient develops urethritis and conjunctivitis. Complications of reactive arthritis are seen with chronic course and may include chronic arthritis with remitting relapsing course, urethral stricture, vitreous floaters, macular edema, cataracts or glaucoma, ankylosing spondylitis, and aortitis. Prognosis is generally good for patients with reactive arthritis. Patients who receive and respond to treatment generally have rapid reversal of symptoms. It is estimated that around 25% of patients may develop long term complication of arthropathy.

# Diagnosis

## Diagnostic Criteria
Reactive arthritis is diagnosed based on the clinical presentation with supporting laboratory evidence. The gold standard for diagnosis of reactive arthritis include spondyloarthritis and clear evidence of preceding infection by culture or polymerase chain reaction.

## History and Symptoms
Obtaining history is an important aspect in making a diagnosis of reactive arthritis. The areas of focus should be on onset, duration, and progression of symptoms with special focus on past medical history and current medications. Previous history of gastrointestinal or genitourinary infections may predispose an individual to develop reactive arthritis. Symptoms start to appear after days to weeks of initial gastrointestinal or genitourinary infection. Common symptoms of reactive arthritis include urinary changes (increased frequency, dysuria/burning micturation and urgency), irritation and redness of eyes, and joint pain (arthralgia-commonly of lower limbs). Less common symptoms include inflammation of soft tissue, swollen toes, and skin rash. If symptoms are present for more than six months, it is termed as chronic reactive arthritis.

## Physical Examination
Physical examination of patients with reactive arthritis is usually remarkable for arthritis (lower extremity; weight bearing), conjunctivitis, and urethritis. As the duration and severity of reactive arthritis increases other signs include dactylitis (sausage-shaped fingers), enthesopathy, sacroiliitis, keratoderma blennorrhagicum, circinate balanitis, myocarditis, and pericarditis.

## Laboratory Findings
Laboratory findings consistent with the diagnosis of reactive arthritis include elevated erythrocyte sedimentation rate (ESR), elevated C-reactive protein (CRP), and elevated total leukocyte count (TLC) showing increased polymorphonuclear cells (PMNs). Synovial fluid or synovial membrane biopsy for detection of bacterial DNA by polymerase chain reaction (PCR) or immunofluorescence microscopy.

## Imaging Findings

### X ray
An x-ray may be helpful in the diagnosis of reactive arthritis. Reactive arthritis primarily involves the lower extremities and an x-ray of hip with sacroiliac joint, knees, ankles and feet may show juxta-articular osteoporosis, soft tissue swelling, bilateral asymmetric distribution uniform joint space loss, and bone proliferation.

### MRI
MRI of the affected joints may be helpful in the diagnosis of reactive arthritis. Findings on MRI suggestive of reactive arthritis include bone edema, bone erosion and bony proliferation.

### Ultrasound
Ultrasound may be helpful in the diagnosis of reactive arthritis. Findings on an ultrasound suggestive of reactive arthritis include thickening of synovial sheath, synovial tendon and increased volume of synovial fluid.

## Other Diagnostic Studies
There are no other diagnostic studies associated with reactive arthritis.

# Treatment

## Medical Therapy
The majority of cases (two-thirds) of reactive arthritis are self-limited and require only supportive care. Arthritis is the most common symptom and initially treated with NSAIDs. As the disease progresses or in case of no response, further management includes intra-articular and systemic steroids, DMARDs and finally TNF inhibitors. The role of antibiotics in reactive arthritis is not clear and their efficacy in reactive arthritis is not completely established.

## Surgery
Surgical intervention is not recommended for the management of reactive arthritis. However, young adults who develop a chronic course may benefit from arthroscopic synovectomy. Patients with severe reactive arthritis with involvement of heart and vitreous chamber may require valve replacement surgery and vitrectomy respectively.

## Prevention
Effective measures for the primary prevention of reactive arthritis include early treatment of GI or GU infections, educating patients about association of GI and GU infection with reactive arthritis and use of barrier methods such as condoms can prevent spread of sexually transmitted disease.