Mesalamine-Induced Leukocytosis Management
Discontinue mesalamine immediately if leukocytosis is confirmed, as this represents a rare but serious idiosyncratic hematologic reaction that requires prompt drug withdrawal. 1
Initial Assessment and Confirmation
- Verify true leukocytosis by obtaining a complete blood count with differential to distinguish from reactive leukocytosis due to underlying IBD activity 1
- Rule out active disease flare by checking inflammatory markers (CRP, ESR) and fecal calprotectin, as elevated white blood cell counts may reflect intestinal inflammation rather than drug toxicity 2
- Assess for other causes including infection, particularly Clostridium difficile, which can present with leukocytosis in IBD patients 2
Immediate Management
- Stop mesalamine immediately upon confirmation that leukocytosis is drug-related rather than disease-related 1
- Monitor blood counts closely (every 24-48 hours initially) until normalization occurs 1
- Consider G-CSF therapy if severe neutropenia develops paradoxically after drug withdrawal, though this is exceedingly rare 1
Important Clinical Distinction
The provided evidence primarily describes mesalamine-induced neutropenia rather than leukocytosis 1. True mesalamine-induced leukocytosis is not well-documented in the literature. More commonly, mesalamine causes:
- Neutropenia or pure white cell aplasia (rare idiosyncratic reaction) 1
- Hemolytic anemia in G6PD deficiency (though recent evidence suggests safety up to 4500 mg/day) 3
- Interstitial nephritis (insidious onset requiring routine renal monitoring) 4
Alternative Therapy Selection
Once mesalamine is discontinued, treatment options depend on disease extent and severity:
For Distal Disease (Proctitis/Proctosigmoiditis):
- Topical corticosteroids (rectal foam or enemas) as second-line therapy for patients intolerant of mesalamine 2, 5
- Oral prednisolone 40 mg daily if topical therapy fails, tapered over 8 weeks 2
For Extensive or Left-Sided Disease:
- Oral corticosteroids (prednisolone 40 mg daily) for active disease 2
- Consider immunosuppressive therapy (azathioprine, 6-mercaptopurine) for steroid-dependent disease 5
- Biologic agents may be appropriate for moderate-to-severe disease refractory to conventional therapy
Critical Monitoring Recommendations
- Baseline and periodic blood counts should be performed in all patients on mesalamine, particularly during the first year of treatment 1, 4
- Renal function monitoring is essential, as interstitial nephritis can develop insidiously over months 4
- Annual monitoring thereafter for both hematologic and renal parameters 4
Common Pitfalls to Avoid
- Do not attribute leukocytosis solely to IBD activity without first excluding drug-induced causes, as this delays appropriate management 1
- Do not rechallenge with mesalamine after confirmed hematologic toxicity, as this represents an idiosyncratic hypersensitivity reaction 1
- Do not delay switching to alternative therapy, as continued mesalamine exposure risks progression to severe cytopenia 1