Is diarrhoea a manifestation of rheumatoid arthritis in a 39‑year‑old woman taking tofacitinib 5 mg twice daily, methotrexate 15 mg weekly, and hydroxychloroquine 400 mg daily?

Is Diarrhea a Manifestation of Rheumatoid Arthritis in This Patient?

Diarrhea is not a manifestation of rheumatoid arthritis itself, but is a well-documented adverse effect of tofacitinib, one of the medications this patient is taking.

Diarrhea and Rheumatoid Arthritis

• Rheumatoid arthritis does not cause diarrhea as a disease manifestation 1
• The primary manifestations of RA are joint inflammation (arthritis), morning stiffness, and systemic symptoms such as fatigue, but gastrointestinal symptoms are not part of the disease presentation 1

Medication-Related Diarrhea in This Patient

Tofacitinib as the Likely Culprit

• Tofacitinib is associated with gastrointestinal side effects, including diarrhea, which is one of the most common adverse events reported with this JAK inhibitor 1
• In clinical trials, gastrointestinal adverse events including diarrhea were documented in patients receiving tofacitinib for rheumatoid arthritis 2, 3, 4
• The safety profile of tofacitinib includes gastrointestinal disturbances as a recognized adverse effect 5

Methotrexate Contribution

• Methotrexate commonly causes gastrointestinal side effects, with nausea being the most frequent (occurring in up to 25% of patients), but diarrhea can also occur 1
• Gastrointestinal problems were reported in 30% of patients receiving methotrexate in one study 5
• These gastrointestinal effects are dose-dependent and typically occur within 12-24 hours of medication administration 1

Hydroxychloroquine Consideration

• Hydroxychloroquine is generally well-tolerated and is less commonly associated with significant gastrointestinal side effects compared to tofacitinib or methotrexate 1, 6
• It is considered compatible with breastfeeding and has a favorable safety profile 1

Clinical Approach to This Patient

Immediate Assessment

• Evaluate the timing of diarrhea onset relative to medication initiation or dose changes, particularly focusing on when tofacitinib was started 1
• Assess severity, frequency, and associated symptoms (fever, blood, weight loss) to rule out infectious causes or other serious complications 1
• Consider that tofacitinib increases the risk of infections, including gastrointestinal infections, which could present with diarrhea 2, 4

Management Strategy

• If diarrhea is mild and medication-related, supportive care and monitoring may be sufficient 1
• For persistent or severe diarrhea attributed to tofacitinib, consider dose reduction or switching to an alternative therapy such as a TNF inhibitor or IL-17 inhibitor 1
• If methotrexate is contributing, ensure adequate folic acid supplementation (at least 5 mg weekly) which can reduce gastrointestinal toxicity 1, 7
• Rule out opportunistic infections, particularly cytomegalovirus colitis in immunosuppressed patients, though this is more relevant in inflammatory bowel disease 1

Key Clinical Pitfall to Avoid

• Do not attribute diarrhea to the underlying rheumatoid arthritis disease process, as RA does not cause gastrointestinal manifestations 1
• Always consider medication adverse effects first in a patient on multiple immunosuppressive agents 1
• Do not overlook infectious causes, as this patient is on triple immunosuppression (tofacitinib, methotrexate, and hydroxychloroquine), which increases infection risk 2, 5, 4