IgA Vasculitis - Henoch Schönlein Purpura

IgA vasculitis (formerly Henoch Schönlein purpura [HSP]) is classified as a small-vessel vasculitis that can be associated with arthritis and predominantly affects the skin and gastrointestinal tract (Jennette, Chapel Hill, 2012). IgA vasculitis is the most common vasculitis of childhood.

Quick Answers for Clinicians

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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

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
  • Relapses
    • More common in adults, rare in children
    • May recur after renal transplantation

ARUP Laboratory Tests

Aid in evaluation for infectious process

Screen for various metabolic and kidney disorders

Preferred test to detect acute phase inflammation (eg, autoimmune diseases, connective tissue disease, rheumatoid arthritis, infection, or sepsis)

Screening test to evaluate kidney function

Screening test to evaluate kidney function

Assay interference (negative) may be observed when high concentrations of N-acetylcysteine (NAC) are present

Negative interference has also been reported with NAPQI (an acetaminophen metabolite), but only when concentrations are at or above those expected during acetaminophen overdose

Preferred reflex panel for the workup of suspected vasculitis

For patients with a history of vasculitis, refer to the ANCA reflex panel that includes a titer, and MPO and PR3 antibodies

Panel includes antineutrophil cytoplasmic antibodies (ANCA), IgG; myeloperox antibodies, IgG; and serine proteinase 3, IgG

Reflex pattern: if the ANCA screen detects antibodies at a 1:20 dilution or greater, then a titer to end point will be added

Related Tests

Nonspecific test used to detect inflammation associated with infections, cancers, and autoimmune diseases

Determine whether to use IgA or IgG tTG and DGP assays

Medical Experts

Contributor

Genzen

Jonathan R. Genzen, MD, PhD
Associate Professor of Clinical Pathology, University of Utah
Chief Operations Officer, Medical Director of Automated Core Laboratory, ARUP Laboratories
Contributor

Lehman

Christopher M. Lehman, MD
Associate Professor of Clinical Pathology, University of Utah
Medical Director, University of Utah Health Hospital Clinical Laboratory, ARUP Laboratories
Contributor

References

Additional Resources