IgA Vasculitis - Henoch Schönlein Purpura

  • Diagnosis
  • Algorithms
  • Background
  • Lab Tests
  • References
  • Related Topics

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
  • American College of Rheumatology Criteria (1990)
    • 2 of 4 must be present (sensitivity 87.1%, specificity 82.7%)
      • Palpable purpura
      • Age – ≤20 years
      • Bowel angina – defined as abdominal pain
      • Vascular wall granulocytes on biopsy seen in the arterioles and venules
  • EULAR criteria (2010)
    • Palpable purpura, not thrombocytopenic/petechiae (mandatory) and ≥one of the following
      • Diffuse abdominal pain
      • Histopathology – typical LCV with predominant IgA deposits or proliferative glomerulonephritis with predominant IgA deposits
      • Arthritis or arthralgias
      • Renal involvement

      • Proteinuria

        0.3 g/24 h

        OR

        >30 mmol/mg of urine albumin to creatinine ratio on a spot morning sample

        AND/OR

        Hematuria – red blood cell casts

        >5 red cells per high power field

        OR

        ≥2+ on dipstick

        OR

        Red blood cell casts in the urinary sediment

Laboratory Testing

  • Nonspecific testing – helpful in excluding other diagnoses or identifying organ dysfunction
    • In children usually a clinical diagnosis – usually no need for ANCA testing, biopsy
    • CBC – normal platelet count rules out idiopathic thrombocytopenic purpura, thrombotic microangiopathies
    • Urinalysis – hematuria common
    • C-reactive protein (CRP)
    • 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

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

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 commonly 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 the winter months, suggesting an 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
    • IBD
    • Ankylosing spondylitis
  • Relapses
    • More common in adults, rare in children
    • May recur after renal transplantation
Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Recommended Use 

Aid in evaluation for infectious process

C-Reactive Protein 0050180
Method: Quantitative Immunoturbidimetry

Recommended Use 

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

Urinalysis, Complete 0020350
Method: Reflectance Spectrophotometry/Microscopy

Recommended Use 

Screen for various metabolic and kidney disorders

Urea Nitrogen, Serum or Plasma 0020023
Method: Quantitative Spectrophotometry

Recommended Use 

Screening test to evaluate kidney function

Creatinine, Serum or Plasma 0020025
Method: Quantitative Enzymatic

Recommended Use 

Screening test to evaluate kidney function

Limitations 

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

ANCA-Associated Vasculitis Profile (ANCA/MPO/PR-3) with Reflex to ANCA Titer 2006480
Method: Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Multiplex Bead Assay

Recommended Use 

Preferred reflex panel for the workup of suspected vasculitis; panel detects ANCA, MPO, and PR-3 antibodies

For patients with a history of vasculitis, refer to the ANCA reflex panel that includes a titer, and MPO and PR-3 antibodies

Individual antibody tests are available; refer to serine protease 3 antibody or MPO antibody tests

Initial test in conjunction with autoimmune liver disease panel for evaluation of ALD

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

Clinical sensitivity – ~85-90% for AMA

Limitations 

All interpretation of antibody patterns must be done in conjunction with clinical presentation

There may be overlap between diseases and antibodies detected

No single test shows absolute specificity

Guidelines

American Society for Clinical Pathology. Choosing Wisely - Five Things Physicians and Patients Should Question. An initiative of the ABIM Foundation. [Last revision Feb 2015; Accessed: Jan 2016]

Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, Flores-Suarez LF, Gross WL, Guillevin L, Hagen EC, Hoffman GS, Jayne DR, Kallenberg CG, Lamprecht P, Langford CA, Luqmani RA, Mahr AD, Matteson EL, Merkel PA, Ozen S, Pusey CD, Rasmussen N, Rees AJ, Scott DG, Specks U, Stone JH, Takahashi K, Watts RA. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013; 65(1): 1-11. PubMed

Mills JA, Michel BA, Bloch DA, Calabrese LH, Hunder GG, Arend WP, Edworthy SM, Fauci AS, Leavitt RY, Lie JT. The American College of Rheumatology 1990 criteria for the classification of Henoch-Schönlein purpura Arthritis Rheum. 1990; 33(8): 1114-21. PubMed

Ruperto N, Ozen S, Pistorio A, Dolezalova P, Brogan P, Cabral DA, Cuttica R, Khubchandani R, Lovell DJ, O'Neil KM, Quartier P, Ravelli A, Iusan SM, Filocamo G, Magalhães CS, Unsal E, Oliveira S, Bracaglia C, Bagga A, Stanevicha V, Manzoni SM, Pratsidou P, Lepore L, Espada G, Kone-Paut I, Paut IK, Zulian F, Barone P, Bircan Z, Maldonado Md, Russo R, Vilca I, Tullus K, Cimaz R, Horneff G, Anton J, Garay S, Nielsen S, Barbano G, Martini A, Paediatric Rheumatology International Trials Organisation (PRINTO). EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part I: Overall methodology and clinical characterisation. Ann Rheum Dis. 2010; 69(5): 790-7. PubMed

General References

Audemard-Verger A, Pillebout E, Guillevin L, Thervet E, Terrier B. IgA vasculitis (Henoch-Shönlein purpura) in adults: Diagnostic and therapeutic aspects Autoimmun Rev. 2015; 14(7): 579-85. PubMed

Chen K, Carlson A. Clinical approach to cutaneous vasculitis. Am J Clin Dermatol. 2008; 9(2): 71-92. PubMed

Reamy BV, Williams PM, Lindsay TJ. Henoch-Schönlein purpura. Am Fam Physician. 2009; 80(7): 697-704. PubMed

Roberts PF, Waller TA, Brinker TM, Riffe IZ, Sayre JW, Bratton RL. Henoch-Schönlein purpura: a review article. South Med J. 2007; 100(8): 821-4. PubMed

Tizard EJ, Hamilton-Ayres MJ. Henoch Schonlein purpura. Arch Dis Child Educ Pract Ed. 2008; 93(1): 1-8. PubMed

Yang Y, Yu H, Chiang B. The diagnosis and classification of Henoch-Schönlein purpura: an updated review. Autoimmun Rev. 2014; 13(4-5): 355-8. PubMed

Medical Reviewers

Genzen, Jonathan R., MD, PhD, Co-Medical Director, Automated Core Laboratory at ARUP Laboratories; Assistant Professor of Clinical Pathology, University of Utah

Tebo, Anne E., PhD, D(ABMLI), Medical Director, Immunology at ARUP Laboratories; Associate Professor of Clinical Pathology, University of Utah

Last Update: August 2016

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