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.

Tabs Content

Clinical Overview

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

ARUP Lab Tests

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

Urinalysis, Complete 0020350
Method: Reflectance Spectrophotometry/Microscopy

Recommended Use

Screen for various metabolic and kidney disorders

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)

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

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

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

Medical Experts

Genzen, Jonathan R., MD, PhD, Laboratory Section Chief, Clinical Chemistry, and Medical Director, Automated Core Laboratory, at ARUP Laboratories; Associate Professor of Clinical Pathology, University of Utah

Lehman, Christopher M., MD, Co-Medical Director, University Hospitals and Clinics Clinical Laboratory; 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

References

Guidelines

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
Choosing Wisely. An initiative of the ABIM Foundation. [Accessed: Oct 2018]
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
Ozen S, Pistorio A, Iusan SM, Bakkaloglu A, Herlin T, Brik R, Buoncompagni A, Lazar C, Bilge I, Uziel Y, Rigante D, Cantarini L, Hilario MO, Silva CA, Alegria M, Norambuena X, Belot A, Berkun Y, Estrella AI, Olivieri AN, Alpigiani MG, Rumba I, Sztajnbok F, Tambic-Bukovac L, Breda L, Al-Mayouf S, Mihaylova D, Chasnyk V, Sengler C, Klein-Gitelman M, Djeddi D, Nuno L, Pruunsild C, Brunner J, Kondi A, Pagava K, Pederzoli S, Martini A, Ruperto N, 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 II: Final classification criteria. Ann Rheum Dis. 2010; 69(5): 798-806. 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

Testing Algorithms

Vasculitis in Adults Testing Algorithm

Read more about Vasculitis in Adults Testing Algorithm

Vasculitis in Children Testing Algorithm

Read more about Vasculitis in Children Testing Algorithm

Last Update: December 2018

IgA Vasculitis - Henoch Schönlein Purpura

Diagnosis

Indications for Testing

Criteria for Diagnosis

Laboratory Testing

Histology

Differential Diagnosis

Background

Epidemiology

Pathophysiology

Clinical Presentation

ARUP Lab Tests

Medical Experts

References

Guidelines

General References

Vasculitis in Adults Testing Algorithm

Vasculitis in Children Testing Algorithm

ARUP Laboratories

ARUP Websites

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	IgA Vasculitis - Henoch Schönlein Purpura. ARUP Consult^©. Retrieved December 11, 2018, from: https://arupconsult.com/content/iga-vasculitis