What is the best management approach for a 23-year-old female with a 2-year history of multiple joint pains, subsequent development of a skin rash, hair loss, severe anemia, acute kidney injury, and possible Systemic Lupus Erythematosus (SLE), currently presenting with respiratory symptoms and impaired renal function?

Management of Suspected Systemic Lupus Erythematosus with Multi-Organ Involvement

This patient requires immediate initiation of hydroxychloroquine, aggressive treatment of severe community-acquired pneumonia with consideration for tuberculosis, urgent nephrology consultation for probable lupus nephritis, and blood transfusion for life-threatening anemia. 1, 2, 3

Immediate Life-Threatening Priorities

Severe Anemia Management

• Transfuse packed red blood cells immediately for hemoglobin of 4.8 g/dL (hematocrit 13.9%), as this represents life-threatening anemia requiring urgent correction before any other interventions 2, 4
• Target hemoglobin >7-8 g/dL initially, then reassess based on clinical stability 2
• Investigate etiology: obtain reticulocyte count, iron studies, vitamin B12, folate, direct Coombs test (to evaluate for autoimmune hemolytic anemia common in SLE), and peripheral smear 4, 5

Respiratory Management

• Continue oxygen at 5L/min to maintain SpO2 >92% 1
• Adjust antibiotic regimen to renal dosing immediately given creatinine 2.13 mg/dL 1, 2
• Send sputum for acid-fast bacilli (AFB) smear and culture, GeneXpert MTB/RIF for tuberculosis given 2-month history of productive cough, night sweats, and pleural effusion in endemic area 1
• Analyze pleural fluid for cell count, differential, protein, LDH, glucose, AFB smear/culture, and cytology 1

Acute Kidney Injury Assessment

• Obtain 24-hour urine protein, urine microscopy for cellular casts, and repeat renal function tests to distinguish acute kidney injury from chronic kidney disease and assess for lupus nephritis 1, 4
• The combination of hematuria (3+), proteinuria (1+), elevated creatinine (2.13 mg/dL), and RBC casts on microscopy strongly suggests lupus nephritis 1, 2
• Urgent nephrology consultation is mandatory for consideration of kidney biopsy to confirm lupus nephritis and guide immunosuppressive therapy 1

Diagnostic Workup for SLE

Essential Serological Testing

• Repeat ANA testing (reported negative, but this is unusual given clinical presentation; consider testing at different laboratory or with different methodology) 2, 3
• Obtain anti-double-stranded DNA (anti-dsDNA), anti-Smith (anti-Sm), anti-U1-RNP antibodies 1, 2, 3
• Measure complement levels (C3, C4) - low levels support active SLE and correlate with disease activity 1, 4
• Check antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-beta-2-glycoprotein I) 2, 3
• Obtain ESR and CRP - CRP >50 mg/L strongly suggests superimposed infection rather than lupus flare alone 4

Additional Laboratory Monitoring

• Complete blood count with differential to assess for cytopenias (leucopenia, lymphopenia, thrombocytopenia) associated with SLE 2, 4
• Comprehensive metabolic panel including serum albumin 4
• Urinalysis with microscopy for RBC casts, WBC casts, and cellular elements 1, 4

Pharmacological Management

Hydroxychloroquine - Foundation of SLE Treatment

• Initiate hydroxychloroquine 400 mg daily (or 5 mg/kg/day) immediately unless contraindicated 1, 2, 3
• Hydroxychloroquine reduces flares, increases remission rates, reduces organ damage including in lupus nephritis, and significantly reduces mortality 1, 2, 3
• This is standard of care for all SLE patients and should be continued indefinitely 1, 3, 6
• Baseline ophthalmologic examination should be arranged within first year of treatment 2

Glucocorticoid Management

• Discontinue current prednisolone 30 mg BID (60 mg/day total) immediately - this excessive dose likely contributed to severe immunosuppression, infection risk, and potential steroid-induced complications 2, 5
• Once infection is controlled and immunosuppressive agent initiated, restart prednisone at 0.5 mg/kg/day (approximately 30 mg daily for this patient) 2, 5
• Target maintenance dose <7.5 mg/day prednisone equivalent as chronic doses above this cause significant organ damage including osteoporosis, avascular necrosis, and steroid myopathy 2, 5
• Taper by 2.5-5 mg every 2-4 weeks as tolerated once disease control achieved 5

Immunosuppressive Therapy Selection

After kidney biopsy confirms lupus nephritis class:

• For Class III or IV lupus nephritis: initiate mycophenolate mofetil 1-3 g/day in divided doses (adjust for renal function) or low-dose intravenous cyclophosphamide combined with glucocorticoids 1, 2, 3
• For maintenance therapy: azathioprine 1-2.5 mg/kg/day is preferred, particularly suitable for women of childbearing age as it is safe during pregnancy 5, 3
• Alternative: methotrexate 15-25 mg weekly for predominant articular and cutaneous manifestations (contraindicated if planning pregnancy) 2, 5

Infection Treatment

• Initiate antifungal therapy with fluconazole 100-200 mg daily (adjust for renal function) for probable oral candidiasis given chronic high-dose steroid use 5
• Continue renal-dosed antibiotics for pneumonia until culture results available 1
• If tuberculosis confirmed, initiate standard four-drug anti-TB therapy with rifampin, isoniazid, pyrazinamide, and ethambutol (doses adjusted for renal function) 1

Monitoring Strategy

Acute Phase (Weekly for First Month)

• Complete blood count, creatinine, urinalysis with microscopy, urine protein-to-creatinine ratio 4, 5
• Anti-dsDNA and complement levels (C3, C4) to monitor disease activity 4, 5
• Strict input/output monitoring as documented in plan 1

Stabilization Phase (Every 3 Months for First 2-3 Years)

• Disease activity assessment using SLEDAI or BILAG indices 2, 5
• Complete blood count, comprehensive metabolic panel, urinalysis, urine protein-to-creatinine ratio 4, 5
• Anti-dsDNA, C3, C4, ESR 4, 5
• Blood pressure monitoring at each visit 4

Long-Term Monitoring (Every 6-12 Months After Stabilization)

• Continue above parameters less frequently if disease remains quiescent 4
• Annual ophthalmologic examination for hydroxychloroquine retinopathy screening 2

Comorbidity Prevention

Bone Health

• Initiate calcium 1000-1500 mg daily and vitamin D 800-1000 IU daily immediately for osteoporosis prevention given chronic glucocorticoid exposure 5
• Consider DEXA scan for baseline bone density assessment 5

Cardiovascular Risk Management

• Screen for hypertension (already present: BP 140/86), dyslipidemia, diabetes - SLE patients have 5-fold increased cardiovascular mortality risk 5
• Consider low-dose aspirin for primary prevention once platelet count normalized and if antiphospholipid antibodies positive 2, 5

Infection Prevention

• High index of suspicion for infections is mandatory given immunosuppression and lymphopenia 4, 5
• Pneumocystis jirovecii pneumonia (PCP) prophylaxis with trimethoprim-sulfamethoxazole should be considered if lymphocyte count <500/μL or if receiving high-dose glucocorticoids plus additional immunosuppression 5
• Update vaccinations per guidelines once acute infection controlled (avoid live vaccines during immunosuppression) 5

Photoprotection

• Advise strict photoprotection to prevent lupus flares: avoid direct sun exposure during high UV index days, use physical barriers (hats, long sleeves, sunglasses), apply broad-spectrum sunscreen 1, 2
• UV radiation is a well-established trigger for cutaneous and systemic lupus flares 1

Critical Pitfalls to Avoid

• Do not delay blood transfusion - hemoglobin 4.8 g/dL requires immediate correction before pursuing other diagnostic or therapeutic interventions 2, 4
• Do not restart high-dose glucocorticoids (60 mg/day) without concurrent immunosuppressive therapy - this increases infection risk, organ damage, and does not provide adequate long-term disease control 2, 5
• Do not rely solely on complement levels to predict future flares - they correlate with current activity but lack predictive value for future disease course 4
• Do not assume lupus flare if CRP >50 mg/L - this strongly suggests superimposed infection and requires aggressive infectious workup 4
• Do not initiate aggressive immunosuppression until active tuberculosis is excluded - this could be fatal in endemic areas 1
• Do not proceed with immunosuppressive therapy without kidney biopsy if lupus nephritis suspected - biopsy classification guides treatment intensity and predicts prognosis 1

Expected Treatment Goals

• Achieve at least partial remission of lupus nephritis within 6-12 months (defined as ≥50% reduction in proteinuria, stable renal function) 2
• Achieve overall disease remission or low disease activity (minimal symptoms, low autoimmune inflammatory markers, prednisone ≤7.5 mg/day) 2, 3, 6
• Prevent disease exacerbations, hospitalizations, and organ damage 3, 6
• Maintain quality of life while minimizing treatment-related toxicity 3, 6