What is the management of dapsone-induced pancytopenia?

Management of Dapsone-Induced Pancytopenia

Immediately discontinue dapsone and initiate supportive care with corticosteroids (prednisone 1-2 mg/kg/day), hematology consultation, and close monitoring for infection; consider granulocyte colony-stimulating factor (G-CSF) for severe neutropenia. 1, 2

Immediate Actions

Discontinue Dapsone

• Stop dapsone immediately upon detection of pancytopenia 1, 3
• Dapsone-induced bone marrow suppression can be severe and potentially fatal, with agranulocytosis carrying up to 50% mortality if not promptly recognized 3
• This adverse reaction is not necessarily dose-dependent and can occur even at therapeutic doses 3

Assess Severity and Admit if Necessary

• Grade 3-4 pancytopenia requires hospital admission 1
• Obtain immediate hematology consultation for all cases of Grade 2 or higher 1
• Grade 2: Hold drug and strongly consider permanent discontinuation 1
• Grade 3-4: Permanently discontinue dapsone and admit patient 1

Diagnostic Workup

Essential Laboratory Evaluation

• Complete blood count with differential, peripheral smear for morphology 1
• Reticulocyte count, LDH, haptoglobin, bilirubin (direct and indirect), free hemoglobin to assess for concurrent hemolysis 1
• Bone marrow biopsy if diagnosis unclear or to assess severity—expect acellular or hypocellular marrow in dapsone-induced cases 3
• DIC panel (PT/INR, PTT, fibrinogen) 1
• Methemoglobin level (dapsone commonly causes methemoglobinemia) 1, 2
• G6PD level if not previously checked 1

Exclude Alternative Causes

• Autoimmune serology, PNH screening 1
• Viral and bacterial infectious workup (including mycoplasma, parvovirus) 1
• B12, folate, copper, iron studies, thyroid function 1
• Review all concurrent medications that could contribute (cotrimoxazole increases dapsone toxicity risk) 1

Pharmacologic Management

Corticosteroid Therapy

• Prednisone 1-2 mg/kg/day orally or IV equivalent depending on severity 1
• For Grade 2: 0.5-1 mg/kg/day prednisone equivalents 1
• Continue until blood counts recover, then taper gradually 1
• Monitor hemoglobin levels weekly until steroid tapering is complete 1

Growth Factor Support

• Consider G-CSF for severe neutropenia (Grade 3-4) with infection risk or active infection 2
• G-CSF led to prompt improvement in documented case of dapsone-induced agranulocytosis 2

Additional Immunosuppression (if refractory)

• If no improvement on corticosteroids or severe symptoms at presentation, consider additional agents: rituximab, IVIG, cyclosporine, mycophenolate mofetil, or anti-thymocyte globulin 1
• These are typically reserved for cases not responding to initial management 1

Supportive Care

Transfusion Support

• RBC transfusion per existing guidelines: transfuse minimum units necessary to relieve symptoms or achieve safe hemoglobin (7-8 g/dL in stable, non-cardiac inpatients) 1
• Discuss with blood bank team before transfusions that patient has drug-induced cytopenia 1
• Platelet transfusion may be necessary if severe thrombocytopenia with bleeding 1

Infection Prevention and Management

• Broad-spectrum antibiotics if febrile neutropenia develops 2
• Signs or symptoms of infection require immediate investigation given high mortality risk with agranulocytosis 3
• Monitor closely for respiratory, cardiovascular, and other infections 1

Nutritional Support

• Offer folic acid supplementation 1 mg daily 1
• This supports hematopoiesis during recovery 1

Monitoring During Recovery

Frequency of Laboratory Testing

• Monitor CBC weekly until counts normalize and throughout steroid taper 1
• After steroid taper complete, less frequent testing acceptable 1
• Leukocyte counts typically return to baseline after dapsone cessation, though recovery time varies 3, 2

Clinical Monitoring

• Check for signs of infection daily while neutropenic 3
• Monitor blood pressure and cardiovascular status (corticosteroid effect) 1
• Assess for steroid-related complications including hyperglycemia 1

Critical Pitfalls to Avoid

Delayed Recognition

• Neutropenia often develops 8-10 weeks after initiating dapsone therapy—this is the highest-risk period requiring vigilant monitoring 3
• Routine CBC monitoring should occur at least every 2-4 weeks during first 3 months of dapsone therapy to catch this early 3

Drug Interactions

• Cotrimoxazole significantly increases risk of dapsone toxicity and methemoglobinemia 1
• Avoid reintroducing dapsone or structurally similar sulfonamides 1

Pharmacogenetic Considerations

• NAT2 slow acetylator genotype (NAT2 *5/*6) predisposes to dapsone toxicity including agranulocytosis 2
• Consider pharmacogenetic testing in severe cases to inform future drug selection 2

Long-Term Considerations

Permanent Contraindication

• Dapsone is permanently contraindicated after pancytopenia develops 1
• Document allergy clearly in medical record 1
• Avoid other sulfonamide-containing medications due to cross-reactivity risk 1

Alternative Therapies

• For underlying condition (e.g., chronic ITP), consider alternative second-line agents: rituximab, thrombopoietin receptor agonists (romiplostim, eltrombopag), azathioprine, cyclosporine, or mycophenolate mofetil 1, 4
• These alternatives avoid sulfonamide class entirely 1