How to manage a patient with Systemic Lupus Erythematosus (SLE) and familial leukocytosis?

Management of SLE with Familial Leukocytosis

In patients with SLE and familial leukocytosis, manage the SLE according to standard treatment protocols while recognizing that the elevated white blood cell count is a benign hereditary condition that does not require treatment and should not be confused with infection or disease activity. 1

Distinguishing Familial Leukocytosis from SLE-Related Changes

• Familial leukocytosis is a benign hereditary condition characterized by persistently elevated white blood cell counts without underlying pathology, and should not trigger changes in SLE management 2
• In SLE patients, monitor for disease-related cytopenias (leukopenia, lymphopenia, thrombocytopenia) which are common hematological manifestations, but familial leukocytosis will mask typical SLE-associated leukopenia 1, 3
• Establish the patient's baseline white blood cell count early in the disease course to distinguish familial leukocytosis from glucocorticoid-induced leukocytosis or infection 2

Foundation Therapy for All SLE Patients

• Initiate hydroxychloroquine at ≤5 mg/kg real body weight for all patients unless contraindicated, as this reduces disease activity, prevents flares, and improves survival 1, 4
• Perform ophthalmological screening at baseline, after 5 years, then yearly thereafter using visual fields examination and/or spectral domain-optical coherence tomography to monitor for retinal toxicity 1
• Add glucocorticoids tailored to disease severity, with IV methylprednisolone pulse therapy (250-1000 mg daily for 1-3 days) for acute flares 1, 5
• Minimize chronic glucocorticoid exposure to <7.5 mg/day prednisone equivalent and withdraw when possible to prevent organ damage 1, 5

Critical Monitoring Parameters

• Assess disease activity at each visit using validated indices such as SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) 2, 6
• Monitor anti-dsDNA, C3, C4, complete blood count, creatinine, proteinuria, and urine sediment at each visit to track disease activity 2, 6
• In patients with familial leukocytosis, focus on other inflammatory markers (ESR, CRP, complement levels, anti-dsDNA) rather than white blood cell count to assess disease activity 2

Immunosuppressive Therapy Selection

• Add methotrexate for skin and joint manifestations when hydroxychloroquine and low-dose glucocorticoids are insufficient 1
• Use azathioprine for maintenance therapy, particularly suitable for women contemplating pregnancy 1, 7
• Initiate mycophenolate mofetil for renal and non-renal manifestations (except neuropsychiatric disease) 1, 7
• Reserve cyclophosphamide for severe organ-threatening disease, especially renal, cardiopulmonary, or neuropsychiatric manifestations 1, 7

Special Considerations for Infection Risk

• The presence of familial leukocytosis does not increase infection risk, but SLE patients have a 5-fold increased mortality risk from infections due to disease and immunosuppression 1, 2
• Exclude infection aggressively before attributing fever or symptoms to lupus activity alone, even in the presence of elevated white blood cell counts 2
• Screen systematically for common and opportunistic infections, including HIV (based on risk factors), HCV, HBV, tuberculosis, and CMV in immunosuppressed patients 2

Critical Pitfalls to Avoid

• Do not misinterpret familial leukocytosis as infection or active disease, which could lead to inappropriate escalation of immunosuppression 2
• Do not withhold necessary immunosuppression due to concerns about elevated white blood cell counts from familial leukocytosis 1
• Do not use white blood cell count as a marker of disease activity in these patients; rely instead on complement levels, anti-dsDNA, and clinical manifestations 2, 6
• Do not discontinue hydroxychloroquine unless there is a specific contraindication, as it is the cornerstone of SLE therapy 1, 4, 7