IgA vasculitis (IgAV), previously known as Henoch-Schönlein purpura (HSP), is a small-vessel vasculitis characterized by IgA immune complex deposition affecting the skin, joints, gastrointestinal tract, and kidneys. The presence of red cell casts in the urine is a significant finding in IgAV, indicating glomerular involvement (IgAV nephritis), which is histologically similar to IgA nephropathy (IgAN). Below is a concise explanation of IgAV, the significance of red cell casts, and their clinical implications.

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IgA Vasculitis (HSP): Overview

• Pathophysiology:
  • Abnormal galactose-deficient IgA1 (Gd-IgA1) forms immune complexes that deposit in small vessels, triggering inflammation and complement activation (C3).
  • Renal involvement occurs when IgA complexes deposit in the glomerular mesangium, causing glomerulonephritis.
• Clinical Features (Classic Tetrad):
  • Palpable purpura: Non-blanching rash on lower extremities/buttocks (mandatory for diagnosis).
  • Arthralgia/arthritis: Transient pain in knees/ankles (~60–80%).
  • Gastrointestinal symptoms: Abdominal pain, GI bleeding (~50–75%).
  • Renal involvement: Hematuria, proteinuria, or acute kidney injury (AKI) (~20–50%).
• Epidemiology:
  • Most common in children (4–10 years); less frequent in adults.
  • Often follows infections (e.g., streptococcal pharyngitis).

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Red Cell Casts in IgAV

• Definition:
  • Red cell casts are cylindrical structures formed in renal tubules, containing red blood cells (RBCs) embedded in a protein matrix (Tamm-Horsfall protein).
  • They indicate glomerular bleeding, as RBCs leak into the tubular lumen from damaged glomeruli.
• Significance in IgAV:
  • Red cell casts are a hallmark of glomerulonephritis in IgAV nephritis.
  • They confirm renal involvement, distinguishing glomerular hematuria from non-glomerular causes (e.g., urinary tract infection, stones).
  • Their presence suggests active glomerular inflammation, which may range from mild to severe (e.g., crescentic glomerulonephritis).
• Prevalence:
  • Found in ~30–50% of IgAV patients with renal involvement, particularly those with significant hematuria or proteinuria.
  • More common in patients with macroscopic hematuria or progressive renal disease.
• Associated Findings:
  • Urinalysis: Microscopic or macroscopic hematuria, dysmorphic RBCs (acanthocytes), proteinuria (mild to nephrotic-range).
  • Serum Creatinine: Normal early; elevated in AKI or chronic kidney disease (CKD).
  • Proteinuria: Spot urine protein/creatinine ratio >0.2 mg/mg indicates significant renal involvement.

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Clinical Implications of Red Cell Casts

• Diagnostic Role:
  • Red cell casts strongly suggest IgAV nephritis, which is histologically identical to IgA nephropathy.
  • They differentiate glomerular hematuria from lower urinary tract bleeding (e.g., no casts in cystitis).
• Prognostic Significance:
  • Presence of red cell casts indicates active glomerular inflammation, increasing the risk of progressive renal disease.
  • Associated with worse outcomes if accompanied by:
    • Heavy proteinuria (>1 g/day).
    • Hypertension.
    • Reduced eGFR or AKI.
    • Crescentic changes on biopsy (severe cases).
• Indications for Further Evaluation:
  • Red cell casts warrant close monitoring of renal function (creatinine, eGFR, proteinuria).
  • Kidney biopsy may be considered if:
    • Proteinuria >1 g/day persists despite supportive therapy.
    • AKI or rapidly declining eGFR.
    • Nephrotic syndrome or crescentic glomerulonephritis is suspected.
  • Biopsy findings: Mesangial IgA deposits, proliferation, or crescents (Oxford MEST-C score for prognosis).

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Diagnosis

1. IgAV Diagnosis (EULAR/PRINTO/PReS Criteria):
   • Mandatory: Palpable purpura without thrombocytopenia.
   • Plus one of: Abdominal pain, arthritis/arthralgia, renal involvement (hematuria/proteinuria), or IgA deposits on biopsy.
2. Urinalysis:
   • Microscopy: Red cell casts, dysmorphic RBCs (confirm glomerular origin).
   • Proteinuria: Quantified via spot urine protein/creatinine ratio.
3. Labs:
   • Serum IgA: Elevated in ~50% (non-specific).
   • Complement: Normal C3/C4 (unlike lupus nephritis).
   • Renal Function: Monitor creatinine, eGFR.
4. Biopsy (Rarely Needed):
   • Skin: Leukocytoclastic vasculitis with IgA/C3 deposits.
   • Kidney: Mesangial IgA deposits, similar to IgAN; crescents in severe cases.
5. Differential Diagnosis:
   • IgA Nephropathy: Renal-limited IgA deposition, no systemic vasculitis.
   • Lupus Nephritis: Positive ANA, low C3/C4.
   • Post-Infectious Glomerulonephritis: Low C3, recent streptococcal infection.
   • ANCA Vasculitis: Positive ANCA, no IgA deposits.
   • HUS/TTP: Microangiopathic anemia, thrombocytopenia.