Reactive Arthritis
This patient most likely has reactive arthritis (ReA) triggered by Clostridium difficile infection, making option C the correct answer.
Clinical Reasoning and Diagnostic Algorithm
The presentation strongly supports reactive arthritis based on the following key features:
- Classic temporal relationship: Arthritis developed 2 weeks after gastrointestinal infection with documented C. difficile toxin positivity, which is the typical interval for ReA to manifest after enteric infection 1, 2, 3
- Characteristic joint pattern: Asymmetric oligoarthritis affecting large lower extremity joints (left knee) with additional involvement of the right wrist and left Achilles tendon insertion (enthesitis), which is pathognomonic for ReA 4, 2
- Sterile synovial fluid: Negative blood, stool, and synovial cultures effectively exclude septic arthritis (option A) and gonococcal arthritis (option B) 1, 4
Why Not Septic Arthritis?
Septic arthritis is definitively ruled out by the following:
- Negative synovial fluid culture with adequate sampling 5
- While the patient has fever and elevated inflammatory markers (ESR 75, WBC 18, CRP 20), these findings are consistent with reactive arthritis and do not require positive cultures for diagnosis 1, 3
- Synovial fluid cultures are positive in approximately 80% of non-gonococcal septic arthritis cases, making the negative culture highly significant 5
Why Not Gonococcal Arthritis?
- No history of genitourinary symptoms or sexual exposure mentioned 6
- Negative cultures from multiple sites (blood, stool, synovial fluid) 5
- The clinical pattern with enthesitis is more consistent with ReA than disseminated gonococcal infection 4
Why Not IBD-Associated Peripheral Arthritis?
Peripheral arthritis associated with inflammatory bowel disease (option D) is excluded because:
- The patient had acute, self-limited watery diarrhea lasting 5 days, not chronic inflammatory bowel disease 1, 3
- C. difficile infection causes pseudomembranous colitis, not IBD 2
- The temporal relationship (arthritis developing after resolution of acute infection) is classic for ReA, not IBD-associated arthritis 3
Clostridium difficile as a Cause of Reactive Arthritis
While less commonly recognized than other enteric pathogens (Salmonella, Shigella, Campylobacter, Yersinia), C. difficile is an established trigger for ReA:
- Approximately 40-49 cases have been reported in the literature as of 2016 4, 3
- ReA-CDI typically occurs a median of 10 days (range 0-55 days) after the gastrointestinal infection 3
- The pathogenesis involves an immunological response in joints against bacterial antigens that gain systemic access through increased intestinal permeability 2
- Patients are typically younger (mean age 38 years) and 68% have HLA-B27 genotype 3
Supporting Laboratory Findings
- Elevated inflammatory markers (ESR 75, CRP 20, WBC 18) are expected in ReA and do not indicate septic arthritis in the context of negative cultures 1, 3
- Normal rheumatoid factor (35, reference <58 kIU/L) helps exclude rheumatoid arthritis 7
- Normal uric acid (260 μmol/L, within normal range) makes gout unlikely 8
Critical Diagnostic Pitfall
The most important pitfall to avoid is assuming that elevated inflammatory markers with fever automatically indicate septic arthritis. In this case, the negative synovial fluid culture, characteristic joint distribution with enthesitis, and temporal relationship to documented C. difficile infection all point definitively toward reactive arthritis 1, 4, 2.
Expected Clinical Course
- Outcome is favorable in 90% of ReA-CDI patients 3
- Non-steroidal anti-inflammatory drugs are required in 55% of cases 3
- Despite possible persistent articular involvement after gastrointestinal symptoms resolve, long-term prognosis is excellent 2
- Treatment with anticlostridial agents combined with anti-inflammatory therapy is effective 2