What is the appropriate treatment for a 40‑year‑old woman with active systemic lupus erythematosus (SLE) presenting with severe anemia, thrombocytopenia, leukocytosis, hyperbilirubinemia, nephrotic‑range proteinuria, and an acute upper gastrointestinal (GI) bleed from a peptic ulcer?

Treatment Approach for Active SLE with Severe Cytopenias and GI Bleeding

This patient requires immediate high-dose intravenous methylprednisolone (250-1000 mg daily for 1-3 days) as first-line therapy for her life-threatening hematologic manifestations, combined with aggressive management of her upper GI bleed, followed by transition to oral prednisone with addition of a steroid-sparing immunosuppressant. 1

Immediate Priorities

Address the Active GI Bleeding First

• Stop all NSAIDs and iron supplementation immediately (the patient's melena began after starting iberet, suggesting peptic ulcer disease exacerbated by oral iron). 1
• Initiate proton pump inhibitor therapy at high doses (e.g., pantoprazole 80 mg IV bolus followed by continuous infusion) to control peptic ulcer bleeding.
• Arrange urgent upper endoscopy for definitive diagnosis and potential therapeutic intervention (cauterization, clipping) of the bleeding ulcer.
• Continue blood product support as needed to maintain hemoglobin >7-8 g/dL and platelets >10,000-20,000/mm³ (higher if active bleeding persists).

Treat the Severe Hematologic Manifestations

For Severe Thrombocytopenia (Platelet Count 29-31 × 10⁹/L):

• Initiate intravenous methylprednisolone pulse therapy (500-1000 mg daily for 3 days) given the life-threatening context of concurrent GI bleeding and severe thrombocytopenia. 2, 3
• Add IVIG (1 g/kg for 1-2 days) immediately because this patient has active bleeding, which constitutes a life-threatening situation requiring rapid platelet elevation beyond what glucocorticoids alone can provide. 2, 3
• The combination of high-dose glucocorticoids plus IVIG is strongly recommended for patients refractory to glucocorticoids alone, those with life-threatening bleeding, or those requiring surgery. 2

For Severe Anemia (Hemoglobin 38-40 g/L):

• The negative Coombs test argues against autoimmune hemolytic anemia as the primary mechanism, making this more likely anemia of chronic disease compounded by acute blood loss. 1, 4
• However, the elevated indirect bilirubin (B2 9.19), elevated LDH (1.81), and markedly elevated reticulocyte count (11.89%) suggest some component of hemolysis despite the negative Coombs test. 1
• High-dose glucocorticoids (as initiated above) will address any autoimmune hemolytic component. 2, 1
• Continue transfusion support cautiously, balancing the need to maintain adequate oxygen delivery against the risk of volume overload in the setting of nephrotic-range proteinuria.

Evaluate for Infection Before Escalating Immunosuppression

Critical: Rule Out Active Infection

• The leukocytosis (WBC 20 × 10⁹/L) with marked neutrophilia (94%) is highly concerning for infection, which is the predominant cause of elevated WBC in SLE patients and a leading cause of mortality. 5
• The patient's recent dengue infection, UTI treatment, and current epigastric pain with positive FOBT raise concern for ongoing or new infection.
• Obtain blood cultures, repeat urine culture, and consider CMV testing given the plan for high-dose glucocorticoids. 5
• The elevated lipase (480.01) and amylase (139.51) suggest possible pancreatitis, which could be infectious, drug-induced, or lupus-related.
• Do not add additional immunosuppression beyond initial pulse steroids until infection is excluded, as SLE patients have a 5-fold increased mortality risk from infections. 1

Transition and Maintenance Therapy

After Initial Pulse Therapy (Days 4-7)

• Transition to oral prednisone 0.5-1 mg/kg/day (approximately 40-60 mg daily for this patient). 1
• Continue hydroxychloroquine (if not already on it, or verify current dose is ≤5 mg/kg actual body weight) as foundational therapy for all SLE patients, providing steroid-sparing effects. 1, 6

Add Steroid-Sparing Immunosuppressant (Week 2-4)

Once infection is excluded and the patient is stabilizing:

Preferred options based on this patient's profile:

• Mycophenolate mofetil (MMF) is the preferred choice given her nephrotic-range proteinuria (UPCR 765.64 mg/g), which suggests lupus nephritis requiring aggressive treatment. 3, 6
  • Start MMF 1000 mg twice daily, titrating to 1500 mg twice daily as tolerated.
  • MMF is potent for both hematologic manifestations and renal disease. 3
  • Ensure reliable contraception as MMF is teratogenic. 3

Alternative if pregnancy is desired soon:

• Azathioprine (1-2.5 mg/kg/day) is pregnancy-compatible and effective for hematologic manifestations. 3
• However, it is less potent for lupus nephritis than MMF. 3

For refractory thrombocytopenia or hemolytic anemia:

• Rituximab should be considered if the patient fails to respond to high-dose glucocorticoids plus immunosuppressants within 2-4 weeks, or if life-threatening manifestations persist. 2, 3
• Rituximab carries moderate infection risk but provides moderate beneficial effects on platelet count and hemolysis. 2

Glucocorticoid Tapering Strategy

• Begin tapering prednisone after 4-6 weeks of stability, reducing by 5-10 mg every 1-2 weeks initially. 1
• Target prednisone ≤7.5 mg/day within 3-6 months to prevent organ damage from chronic glucocorticoid exposure. 1
• The addition of a steroid-sparing agent (MMF or azathioprine) facilitates this taper. 1, 3

Additional Supportive Measures

Gastroprotection:

• Continue high-dose PPI therapy throughout glucocorticoid treatment.
• Avoid NSAIDs indefinitely given peptic ulcer disease and thrombocytopenia.

Bone Protection:

• Initiate calcium (1200-1500 mg daily) and vitamin D (800-1000 IU daily) supplementation for all patients on long-term glucocorticoids. 1
• Consider bisphosphonate therapy if prolonged high-dose glucocorticoid use is anticipated.

Renal Protection:

• The nephrotic-range proteinuria requires ACE inhibitor or ARB therapy once blood pressure and renal function are stable.
• Formal renal biopsy should be considered to confirm lupus nephritis and guide long-term immunosuppressive therapy.

Infection Prophylaxis:

• Consider Pneumocystis jirovecii prophylaxis (trimethoprim-sulfamethoxazole or alternative) given the combination of high-dose glucocorticoids, severe lymphopenia (lymphocytes 0.02-0.1 × 10⁹/L), and planned additional immunosuppression. 5
• Severe lymphopenia (<0.5 × 10⁹/L) is associated with increased infection susceptibility. 5

Monitoring Parameters

Daily (during acute phase):

• Hemoglobin, platelet count, reticulocyte count
• Signs of bleeding (stool guaiac, vital signs)
• LDH and bilirubin to assess hemolysis 1

Weekly (first month):

• Complete blood count with differential
• Comprehensive metabolic panel
• Urinalysis and UPCR

Ongoing:

• Monitor for infection aggressively, as infections are among the leading contributors to morbidity and mortality in SLE. 5
• CRP levels >50 mg/L suggest superimposed infection rather than SLE disease activity alone. 5

Common Pitfalls to Avoid

• Do not delay IVIG in the setting of active bleeding with severe thrombocytopenia—glucocorticoids alone may not raise platelets quickly enough. 2
• Do not continue oral iron supplementation in a patient with active peptic ulcer disease and thrombocytopenia, as it exacerbates mucosal injury. 1
• Do not overlook infection as the cause of leukocytosis—in SLE, infection is the predominant cause of elevated WBC and must be excluded before escalating immunosuppression. 5
• Do not add cyclophosphamide or rituximab without first excluding active infection, given the patient's leukocytosis and recent infectious history. 1, 5
• Do not neglect the renal manifestations—nephrotic-range proteinuria requires aggressive immunosuppression and likely renal biopsy to guide therapy. 3, 6