What is the diagnosis and management for an elderly patient with leukopenia, thrombocytopenia, anemia, elevated blood urea, impaired renal function, and symptoms of hand and joint pain that resolve throughout the day?

Diagnosis and Management of Elderly Patient with Cytopenias and Joint Pain

Most Likely Diagnosis

This clinical presentation is most consistent with systemic lupus erythematosus (SLE) with hematologic manifestations, given the combination of bicytopenia (leukopenia and thrombocytopenia), mild anemia, elevated blood urea, renal impairment, and inflammatory arthritis that improves throughout the day. 1

Diagnostic Approach

Immediate Laboratory Evaluation

First, exclude pseudothrombocytopenia by collecting blood in heparin or sodium citrate tube and repeating the platelet count, as EDTA-dependent platelet agglutination causes false low counts in up to 0.1% of samples. 2, 3, 4

• Peripheral blood smear examination by a qualified hematologist or pathologist is mandatory before proceeding with any further workup to identify morphologic abnormalities, schistocytes, dysplasia, and confirm true cytopenias 2, 3, 5
• Complete blood count with differential and reticulocyte count to determine if this represents isolated bicytopenia or evolving pancytopenia 2, 3

Targeted Autoimmune and Infectious Workup

Given the high suspicion for SLE-related hematologic disease:

• Antinuclear antibodies (ANA), anti-dsDNA, complement levels (C3, C4), and antiphospholipid antibodies are essential to establish SLE diagnosis 1
• HIV, hepatitis C, and hepatitis B testing in all adult patients with suspected immune-mediated cytopenias 2, 3
• Helicobacter pylori testing where eradication may have clinical impact 2, 3
• Urinalysis with microscopy to assess for proteinuria, hematuria, and cellular casts indicating lupus nephritis 1

Additional Investigations Based on Clinical Context

• Vitamin B12 and folate levels should be checked, as megaloblastic anemia can present with bicytopenia and elevated blood urea, and can coexist with autoimmune conditions 6, 7
• Thyroid function tests given association with autoimmune diseases 2
• Direct antiglobulin test (Coombs) if autoimmune hemolytic anemia is suspected 1

Bone Marrow Examination Indications

Bone marrow evaluation is indicated in this patient given age >60 years and presence of bicytopenia with renal dysfunction to exclude myelodysplastic syndrome, bone marrow infiltration, or other primary marrow disorders 2, 3. This was diagnostic in 69.6% of cases in recent studies 3.

Management Strategy

Treatment of SLE-Related Hematologic Manifestations

For significant lupus-related thrombocytopenia (platelet count <110,000/mm³), initiate moderate to high-dose corticosteroids as first-line therapy: 1

• Intravenous methylprednisolone pulses (1-3 days) followed by oral prednisone 0.5-2 mg/kg/day OR
• Dexamethasone 40 mg/day for 4 days 2, 3

Combine corticosteroids with an immunosuppressive agent (azathioprine, mycophenolate mofetil, or cyclosporine) to facilitate corticosteroid-sparing and prevent relapses. Cyclosporine has the least myelotoxic potential, which is particularly relevant given existing leukopenia 1.

Management of Lupus Nephritis

Given elevated blood urea (475.07 mg/dL, assuming this is BUN) and creatinine (83.4 μmol/L):

• Kidney biopsy should be performed to determine class of lupus nephritis and guide specific treatment 1
• For proliferative lupus nephritis, induction therapy with mycophenolate mofetil or low-dose cyclophosphamide (Euro-Lupus regimen) combined with corticosteroids is recommended 1
• Target early reduction in proteinuria (≤1 g/day at 6 months or ≤0.8 g/day at 12 months) as predictor of favorable renal outcome 1

Adjunctive Therapies

• Intravenous immunoglobulin (IVIG) may be considered in the acute phase for severe thrombocytopenia or to avoid corticosteroid-related infectious complications 1
• Rituximab should be considered for refractory or relapsing thrombocytopenia that fails to respond to corticosteroids and initial immunosuppression 1

Management of Joint Pain

The pattern of joint pain resolving throughout the day is consistent with inflammatory arthritis:

• Corticosteroid therapy initiated for hematologic manifestations will simultaneously address arthritis 1
• NSAIDs should be used cautiously given renal impairment and thrombocytopenia 1

Critical Pitfalls to Avoid

• Do not initiate treatment for thrombocytopenia without first excluding pseudothrombocytopenia by repeating count in non-EDTA tube and examining peripheral smear 2, 4
• Avoid unnecessary bone marrow examination in young patients with typical ITP features, but this patient's age >60 years and bicytopenia mandate evaluation 2
• Do not overlook vitamin B12 deficiency, which can coexist with autoimmune conditions and cause similar cytopenias with elevated blood urea 6, 7
• Monitor for macrophage activation syndrome, a rare but serious complication of SLE that can present with cytopenias 1
• Treatment of lupus thrombocytopenia is typically lengthy with frequent relapses during corticosteroid tapering, requiring close monitoring 1