Management of Leukopenia in Sjögren's Syndrome

Initial Assessment and Workup

The American Thoracic Society recommends checking if the patient is on immunosuppressive medications, such as azathioprine, mycophenolate mofetil, rituximab, or methotrexate, as these commonly cause bone marrow suppression in Sjögren's patients 1, 2

The American College of Rheumatology suggests testing for thiopurine methyltransferase (TPMT) activity or genotype immediately if azathioprine is the culprit, as complete lack of TPMT activity causes severe, life-threatening leukopenia 1, 3, 4, 2
The European League Against Rheumatism recommends discontinuing azathioprine if severe leukopenia develops or if TPMT deficiency is confirmed 1
The American College of Rheumatology advises switching to alternative immunosuppression, such as mycophenolate mofetil, if steroid-sparing therapy is still needed 2, 5
The American Thoracic Society notes that bone marrow suppression and cytopenias are known side effects of mycophenolate mofetil and rituximab 1, 2
The American College of Rheumatology suggests considering dose reduction or temporary discontinuation of mycophenolate mofetil or rituximab depending on the severity of leukopenia 1

The American College of Rheumatology recommends considering short-term moderate-dose glucocorticoids (0.5-1.0 mg/kg) for moderate leukopenia with lymphopenia accompanied by severe systemic manifestations requiring treatment 6, 5
The American Thoracic Society advises assessing infection risk and considering prophylactic antibiotics if ANC <500/μL in severe neutropenia 1

The American College of Rheumatology strongly recommends testing TPMT before starting azathioprine to prevent life-threatening leukopenia, with a HIGH strength, STRONG recommendation 1, 3, 4, 2
The American Thoracic Society notes that medication-induced bone marrow suppression from azathioprine, mycophenolate, or rituximab should not be missed 1, 2

The American College of Rheumatology recommends establishing a surveillance protocol, including baseline CBC with differential before starting any immunosuppressive therapy 1, 2
The American Thoracic Society suggests weekly CBC monitoring for the first month after starting azathioprine or mycophenolate 1, 2
The American College of Rheumatology advises monthly CBC monitoring once stable on immunosuppression 5