[3] 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.

[5][6] As a seronegative spondyloarthropathy, laboratory analysis of blood will show that the patient is rheumatoid factor negative and often HLA-B27 positive.

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.

[13] Reactive arthritis is associated with the HLA-B27 gene on chromosome 6 and by the presence of enthesitis as the basic pathologic lesion[16] and is triggered by a preceding infection.

Other bacteria known to cause reactive arthritis which are more common worldwide are Ureaplasma urealyticum, Salmonella spp., Shigella spp., Yersinia spp., and Campylobacter spp.

Although there are no definitive criteria to diagnose the existence of reactive arthritis, the American College of Rheumatology has published sensitivity and specificity guidelines.

Steroids, sulfasalazine and immunosuppressants may be needed for patients with severe reactive symptoms that do not respond to any other treatment.

Repeated attacks over many years are common, and patients sometimes end up with chronic and disabling arthritis, heart disease, amyloid deposits, ankylosing spondylitis, immunoglobulin A nephropathy, cardiac conduction abnormalities, or aortitis with aortic regurgitation.

[20] 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.

[22] When reactive arthritis appears in a triad that also includes ophthalmic and urogenital manifestations, the eponym "Reiter's syndrome" is often applied;[citation needed] German physician Hans Conrad Julius Reiter described the condition in a soldier he treated during World War I.

Reiter's Nazi Party affiliation, and in particular his involvement in forced human experimentation in the Buchenwald concentration camp (which, after his capture at the end of World War II, resulted in his prosecution in Nuremberg as a war criminal), have come to overshadow his medical accomplishments.