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.
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
- Rash – palpable purpura
- 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 Laboratory Tests
Preferred test to detect acute phase inflammation (eg, autoimmune diseases, connective tissue disease, rheumatoid arthritis, infection, or sepsis)
Quantitative Immunoturbidimetry
Screening test to evaluate kidney function
Quantitative Spectrophotometry
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
Quantitative Enzymatic Assay
Preferred first-line reflex panel for the evaluation of ANCA-associated vasculitis
Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Multiplex Bead Assay
Determine whether to use IgA or IgG tTG and DGP assays
Quantitative Immunoturbidimetry
References
25688001
Audemard-Verger A, Pillebout E, Guillevin L, et al. IgA vasculitis (Henoch-Shönlein purpura) in adults: Diagnostic and therapeutic aspects. Autoimmun Rev. 2015;14(7):579-585.
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Chen KR, Carlson A. Clinical approach to cutaneous vasculitis. Am J Clin Dermatol. 2008;9(2):71-92.
Choosing Wisely
Choosing Wisely. An initiative of the ABIM Foundation. [Accessed: Dec 2020]
2202310
Mills JA, Michel BA, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classification of Henoch-Schönlein purpura. Arthritis Rheum. 1990;33(8):1114-1121.
20413568
Ozen S, Pistorio A, Iusan SM, et al. 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.
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Reamy BV, Williams PM, Lindsay TJ. Henoch-Schönlein purpura. Am Fam Physician. 2009;80(7):697-704.
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Roberts PF, Waller TA, Brinker TM, et al. Henoch-Schönlein purpura: a review article. South Med J. 2007;100(8):821-824.
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Ruperto N, Ozen S, Pistorio A, et al. 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):790-797.
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Tizard EJ, Hamilton-Ayres MJJ. Henoch Schonlein purpura. Arch Dis Child Educ Pract Ed. 2008;93(1):1-8.
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Yang YH, Yu HH, Chiang BL. The diagnosis and classification of Henoch-Schönlein purpura: an updated review. Autoimmun Rev. 2014;13(5-Apr):355-358.
Medical Experts
Pearson

Peterson

Components: ANCA, IgG; MPO, IgG; PR3, IgG