A 27-year-old sexually active male who does not use condoms presents with dysuria, especially at the beginning of urine flow, and a purulent discharge from his penis. A diagnosis of gonorrhea is made and later confirmed by the laboratory, so he is treated with a single dose of Ciprofloxacin (500 mg, PO), followed by doxycycline (100 mg, PO, bid) for 7 days. The treatment is successful and the man's symptoms disappear within 3 days.

Several weeks after the above incident, the man begins to experience painful, asymmetric polyarthritis in his right knee, ankle, and foot. He also notices the appearance of mucocutaneous lesions in his mouth. The arthritis persists over the next several days and is joined by some lower back pain. At this point, he develops a very noticeable conjunctivitis, begins to worry, and finally seeks medical help. His vital signs are normal. On physical examination, there are no remarkable findings in addition to those already described. Specimens of synovial fluid are obtained and sent to the laboratory for culturing, but the results are negative. X-rays of the affected joints are not overly instructive.

Question 3.1: What is your diagnosis?

The combination of polyarthritis, conjunctivitis, and oral mucocutaneous lesions is suggestive of Reiter's syndrome, a reactive polyarthritis that may sometimes develop after certain types of microbial infections. In addition to polyarthritis (which is often asymmetric), the classic syndrome includes urethritis, conjunctivitis, uveitis, oral ulcers, and rash. However, only a minority of patients experience the additional symptoms, so they may present with only the polyarthritis, or any combination of the additional symptoms and polyarthritis.

Question 3.2: What is the differential?

The differential could conceivably include ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis, gonococcal arthritis tenosynovitis, and rheumatic fever.

Question 3.3: What is the most likely causative agent?

The history of STD is suggestive here. When the patient was treated for gonorrhea, he may have been co-infected with Chlamydia trachomatis (which causes nongonococcal urethritis). Reiter's syndrome is known to develop after about 1% of NGU cases. C. trachomatis has never been cultured from synovial fluid samples during Reiter's syndrome, so the negative culture result in this case does not preclude C. trachomatis as the causative agent.

Question 3.4: How does this condition come about?

The pathogenesis of Reiter's syndrome is still poorly understood. It is most common in young men and has been linked to the HLA-B27 locus as a potential genetic predisposing factor. Most likely, chlamydial infection initiates an aberrant and hyperactive immune response that produces inflammation at the involved target organs in genetically predisposed individuals. This hypothesis is supported by good evidence for exaggerated cell-mediated and humoral immune responses to chlamydial antigens during Reiter's syndrome. Chlamydial elementary bodies and DNA have been detected in synovial fluid (even though the organism has not been cultured), so it is possible that chlamydiae actually spread from the genital region to joint tissues, perhaps in macrophages.

Question 3.5: Can anything else lead to this syndrome?

Yes, Reiter's syndrome has been known to develop following other types of mucosal infections, especially enteric infections caused by Yersinia enterocolitica, Shigella flexneri, Campylobacter jejuni, and Salmonella spp. More than 80% of the victims in these cases also have the HLA-B27 phenotype that predisposes individuals to post-NGU Reiter's syndrome.

Question 3.6: How can you treat this problem?

Unfortunately, there isn't much you can do, other than to provide physical therapy to maintain range of motion of the back and other joints. Anti-inflammatory drugs help to relieve symptoms. The use of long-term antibiotic therapy to treat Reiter's syndrome is controversial. Most patients recover within 6 months, but prolonged recurrent disease is more common in cases following NGU than those following other types of infections.