What is the most likely cause of a patient's current presentation with abdominal pain, bilateral ankle swelling, hematuria, and proteinuria, who has a history of Henoch-Schonlein Purpura (HSP) and a family history of Systemic Lupus Erythematosus (SLE)?

Most Likely Diagnosis: Lupus Nephritis

The most likely cause of this patient's current presentation is lupus nephritis (LN), not a flare of HSP nephritis, given the combination of new-onset nephritic features (hematuria, proteinuria), systemic symptoms, and strong family history of SLE. 1, 2

Key Diagnostic Reasoning

Why Lupus Nephritis is Most Likely

• Family history of SLE is a critical red flag that substantially increases pre-test probability for lupus over HSP recurrence, as SLE has well-established familial clustering and genetic predisposition 2, 3

• The clinical presentation with hematuria, proteinuria, and bilateral ankle swelling (suggesting edema from nephrotic-range proteinuria) is classic for active proliferative lupus nephritis 1, 2

• HSP and SLE can present with overlapping clinical features, and cases have been documented where patients initially diagnosed with HSP were later found to have SLE 4

• The combination of abdominal pain, renal involvement, and joint swelling can occur in both conditions, but the family history tips the balance strongly toward lupus 1, 3

Why HSP Recurrence is Less Likely

• HSP nephritis typically presents early in the disease course (within weeks to months of initial HSP diagnosis), not as a late complication 5, 6

• While HSP and IgA nephropathy share pathogenic mechanisms and can occur sequentially, the family history of SLE makes lupus far more probable 7, 6

• HSP recurrences are relatively uncommon, and when they occur, they typically involve the classic tetrad of purpura, arthritis, abdominal pain, and renal involvement 8

Immediate Diagnostic Workup Required

Serologic Testing (Urgent)

• Check ANA, anti-dsDNA antibodies, complement levels (C3, C4), and complete metabolic panel immediately to confirm or exclude active lupus 1, 2, 3

• Low C3 and C4 with elevated anti-dsDNA antibodies are significantly associated with active lupus nephritis and have established predictive value for kidney involvement 2, 3

• Quantify proteinuria with spot urine protein-to-creatinine ratio or 24-hour collection to determine if nephrotic-range (>3.5 g/day) 1, 3

Urine Studies

• Perform urine sediment microscopy looking specifically for red blood cell casts, white blood cell casts, or acanthocytes (≥5%), which indicate active glomerulonephritis 1, 3

• The presence of cellular casts strongly suggests active proliferative glomerulonephritis requiring urgent intervention 2, 3

Kidney Biopsy Indication

• Kidney biopsy is indispensable and should be performed urgently given the constellation of findings suggesting active renal disease 1, 3

• Biopsy is indicated when proteinuria ≥500 mg/24 hours and/or unexplained decrease in GFR, as clinical findings do not correlate reliably with histologic severity 3

• The biopsy will differentiate between lupus nephritis (typically showing "full house" immunofluorescence with IgG, IgA, IgM, C3, C4, C1q) versus HSP nephritis (predominantly IgA deposits) 5

Treatment Implications if Lupus Nephritis Confirmed

Urgent Immunosuppressive Therapy

• Initiate combination therapy with mycophenolate mofetil 3 g/day or cyclophosphamide 500-750 mg/m² monthly for 6 months as first-line induction therapy 1

• Administer three consecutive pulses of intravenous methylprednisolone 500-750 mg, followed by oral prednisone 0.5 mg/kg/day for 4 weeks, then taper to ≤10 mg/day by 4-6 months 1

Essential Adjunctive Therapy

• Start hydroxychloroquine 200-400 mg/day immediately unless contraindicated, as it reduces renal flares and improves overall outcomes 1, 3

• Initiate ACE inhibitor or ARB for proteinuria reduction and blood pressure control, targeting BP <130/80 mmHg 1

Critical Clinical Pitfalls to Avoid

• Do not assume this is simply HSP recurrence without excluding lupus, especially given the family history—this could lead to inadequate treatment and progression to end-stage renal disease 2, 4

• Do not delay kidney biopsy waiting for serologic results if clinical suspicion is high, as early aggressive treatment significantly improves long-term kidney survival 1, 2

• Do not use fixed monitoring schedules—individualize frequency based on disease activity, with twice weekly to weekly monitoring when renal impairment is first suspected 3

• Recognize that lupus nephritis can remain asymptomatic for prolonged periods, emphasizing the importance of regular screening in all SLE patients 3