IgA Vasculitis - Henoch Schönlein Purpura

Diagnosis

Indications for Testing

Palpable purpura in patient ≤20 years with other systemic symptoms.

Criteria for Diagnosis

• Diagnosis is primarily clinical
  • Criteria have not been widely validated in adults
• European League Against Rheumatism (EULAR) criteria (Ozen, 2010)
  • Palpable purpura, not thrombocytopenic/petechiae (mandatory)
  • And ≥1 of the following
    • Diffuse abdominal pain
    • Histopathology – typically leukocytoclastic vasculitis (LCV) with predominant IgA deposits or proliferative glomerulonephritis with predominant IgA deposits
    • Arthritis or arthralgias
    • Renal involvement

    • Indicators for Renal Involvement

      Proteinuria	0.3 g/24 hrs OR >30 mmol/mg of urine albumin to creatinine ratio on a spot morning sample
      AND/OR
      Hematuria or red blood cell casts	>5 red cells per high power field OR ≥2+ on dipstick OR Red blood cell casts in urinary sediment

Laboratory Testing

• Nonspecific testing – helpful in excluding other diagnoses or identifying organ dysfunction
  • In children, usually a clinical diagnosis – typically no need for antineutrophil cytoplasmic antibody (ANCA) testing or biopsy
  • CBC – normal platelet count rules out idiopathic thrombocytopenic purpura and thrombotic microangiopathies
  • Urinalysis – hematuria common
  • Urine protein – 24-hour collection or spot albumin/creatinine on morning sample
  • C-reactive protein (CRP)
    • Preferred test to detect inflammatory processes (Choosing Wisely, 2016; American Society for Clinical Pathology)
    • May be elevated
    • If CRP not available, order erythrocyte sedimentation rate (ESR)
  • Blood urea nitrogen (BUN)/creatinine – may be elevated from renal involvement or dehydration
  • Serum IgA – elevated in many patients

Histology

• Granulocytes in small vessel (arterioles and venule walls) with IgA and C3 immune deposition
• Glomerulonephritis of IgA vasculitis may be indistinguishable from IgA nephropathy or other glomerulonephritis

Differential Diagnosis

• Hematuria/glomerulonephritis
  • IgA nephropathy
  • Poststreptococcal glomerulonephritis
  • Systemic lupus erythematosus (SLE)
  • Idiopathic thrombocytopenic purpura (ITP)
  • Hemolytic uremic syndrome
  • Disseminated intravascular coagulation
  • Granulomatosis with polyangiitis (GPA)
  • Thrombotic microangiopathy (eg, thrombotic thrombocytopenic purpura [TTP])
• Abdominal pain
  • Intussusception
  • Sepsis
  • Pancreatitis
  • Liver disease
  • Mediterranean fever
  • Acute surgical abdomen
  • Inflammatory bowel disease (IBD)
• Arthralgias
  • Endocarditis
  • Sepsis
  • Juvenile rheumatoid arthritis
  • Ankylosing spondylitis
  • Connective tissue diseases
    • SLE
    • Sjögren syndrome
    • Mixed connective tissue disease
    • Juvenile dermatomyositis
• Purpuric rash
  • Meningitis
  • Other vasculitis
    • Hypersensitivity vasculitis
    • Urticarial vasculitis
    • Mixed cryoglobulinemia
    • Cutaneous polyarteritis
    • ANCA-associated vasculitis
  • Thrombocytopenic purpura
    • ITP
    • Thrombotic microangiopathies
  • Acute lymphoblastic leukemia (ALL)
  • Acute myeloid leukemia (AML)

Background

Epidemiology

• Incidence (Audemard-Verger, 2015)
  • Children – 3-26/100,000
  • Adults – 0.1-1.8/100,000
• Age – typically diagnosed in children 3-10 years
  • Majority are diagnosed in children >5 years
• Sex – M>F, 1.5:1

Pathophysiology

Systemic necrotizing small-vessel vasculitis characterized by tissue deposition of IgA-containing immune complexes, most commonly in skin and kidney

Clinical Presentation

• Typically a benign, self-limited disorder
  • Suspected triggers include viral, bacterial, and parasitic pathogens
  • A few cases cause chronic symptoms
  • Very small number of cases progress to end-stage renal failure
• Classic clinical tetrad of symptoms
  • Rash – palpable purpura
    • Often concentrated on extensor surfaces of lower extremities
  • Polyarthralgia – most common in knees and ankles
    • Edema often present
  • Abdominal pain – associated with nausea, emesis, diarrhea
    • Colicky quality to pain
  • Renal disease – mild glomerulonephritis with microscopic hematuria, red cell casts, proteinuria
• Other organ involvement (uncommon)
  • Neurologic – headache, encephalopathy, seizures, focal neurologic deficits
  • Pulmonary – diffuse alveolar hemorrhage
  • Cardiac – myocarditis
  • Ophthalmic  – episcleritis
  • Genitourinary – orchitis
  • May present as single organ vasculitis
• Disease onset mostly occurs in winter months, suggesting infectious trigger
  • Frequently preceded by upper respiratory tract infection – ~50% of cases
  • Also associated with gastrointestinal infection
• May be associated with other diseases or these diseases may be causal
  • Liver disease
  • Inflammatory bowel disease (IBD)
  • Ankylosing spondylitis
• Relapses
  • More common in adults, rare in children
  • May recur after renal transplantation