Why Steroids Are Given in Dapsone-Induced Pancytopenia
Steroids (prednisone 1-2 mg/kg/day) must be initiated immediately upon detection of dapsone-induced pancytopenia because they suppress the immune-mediated bone marrow destruction and accelerate hematologic recovery, reducing mortality from this life-threatening idiosyncratic reaction. 1
Mechanism and Rationale
Dapsone-induced pancytopenia is an idiosyncratic immune-mediated reaction, not a simple dose-dependent toxicity 2, 3. The pathophysiology involves:
- Immune destruction of bone marrow precursors through metabolites of dapsone that act as haptens, triggering antibody formation against hematopoietic cells 2
- Bone marrow suppression manifesting as acellular or hypocellular marrow on biopsy 4
- Corticosteroids counteract this immune-mediated destruction by suppressing the inflammatory cascade and autoantibody production 1
Critical Management Algorithm
Immediate Actions (Within Hours)
- Stop dapsone permanently - this drug is absolutely contraindicated after pancytopenia develops 1
- Initiate prednisone 1-2 mg/kg/day (or IV equivalent if patient cannot take oral medications) 1
- Admit to hospital for Grade 3-4 pancytopenia 1
- Obtain urgent hematology consultation for Grade 2 or higher pancytopenia 1
Diagnostic Workup
Essential laboratory evaluation includes 1:
- Complete blood count with differential and peripheral smear
- Reticulocyte count, LDH, haptoglobin, bilirubin (direct/indirect), and free hemoglobin to assess concurrent hemolysis
- G6PD level if not previously checked (especially important given dapsone's hemolytic potential) 1
Steroid Continuation Strategy
- Continue prednisone until blood counts recover to safe levels 1
- Taper gradually after recovery - abrupt discontinuation risks relapse 1
- Monitor closely for infections during immunosuppression 1
Why This Differs from Simple Hemolysis
While dapsone commonly causes dose-dependent hemolysis (even in G6PD-normal patients) 5, pancytopenia represents a distinct and far more dangerous reaction:
- Hemolysis is predictable and dose-related; pancytopenia is idiosyncratic 3
- Hemolysis typically occurs early; agranulocytosis peaks at 8-10 weeks after starting therapy 4, 3
- Pancytopenia carries up to 50% mortality if untreated 4
- The risk is dramatically elevated (25-33 fold) in certain inflammatory conditions like dermatitis herpetiformis 3
Supportive Care Beyond Steroids
Additional management includes 1:
- RBC transfusion to maintain hemoglobin 7-8 g/dL in stable patients
- Broad-spectrum antibiotics if fever or infection present
- G-CSF may be considered in severe cases 2
- Close monitoring for respiratory, cardiovascular, and infectious complications 1
Critical Pitfall to Avoid
Never rechallenge with dapsone after pancytopenia - this is a permanent contraindication 1. Additionally, avoid other sulfonamide-containing medications due to cross-reactivity risk 1. For the underlying condition requiring treatment, alternative agents must be selected (rituximab, thrombopoietin receptor agonists, azathioprine, cyclosporine, or mycophenolate mofetil depending on the indication) 1.