IgA Vasculitis (Henoch-Schönlein Purpura)

1. Clinical Overview

Summary

IgA Vasculitis (IgAV), formerly known as Henoch-Schönlein Purpura (HSP), is the most common systemic vasculitis in childhood, with an annual incidence of 10-20 per 100,000 children. [1,2] It is an immune-complex mediated small vessel vasculitis characterized by the classic tetrad of palpable purpura, arthralgia/arthritis, abdominal pain, and renal involvement. The condition is typically self-limiting, with excellent prognosis in most children, but requires systematic monitoring to detect and manage renal complications, which occur in up to 50% of cases. [3,4]

The disease represents a form of IgA-dominant immune complex small vessel vasculitis affecting predominantly the skin, joints, gastrointestinal tract, and kidneys. The pathological hallmark is leukocytoclastic vasculitis with predominant IgA deposition in vessel walls. [5]

The Classic Tetrad

1. Purpuric Rash (100%): Non-thrombocytopenic palpable purpura with symmetrical distribution, predominantly affecting lower limbs and buttocks. The rash is pathognomonic when present in characteristic distribution. [6]

2. Arthritis/Arthralgia (75-82%): Transient, migratory oligoarthritis predominantly affecting large joints (knees, ankles). The arthritis is non-erosive and non-deforming, typically resolving within days without sequelae. [7]

3. Abdominal Pain (50-75%): Colicky abdominal pain resulting from submucosal haemorrhage and oedema. May be accompanied by nausea, vomiting, and gastrointestinal bleeding. Severity ranges from mild discomfort to severe pain mimicking surgical emergencies. [8]

4. Renal Involvement (20-54%): Haematuria and/or proteinuria, ranging from isolated microscopic haematuria to severe crescentic glomerulonephritis. Renal disease may be delayed, appearing weeks to months after initial presentation. [9,10]

Clinical Pearls

The "Silent Kidney" Problem: Renal involvement can be completely asymptomatic and may develop up to 6 months after the initial rash. This is why systematic urinalysis and blood pressure monitoring for 6 months is mandatory in all cases, regardless of initial severity. Children with normal urinalysis at presentation can still develop IgA vasculitis nephritis (IgAVN) weeks later. [11]

Intussusception in IgAV is Different: While classic intussusception is ileocolic and typically occurs at 6-18 months of age, IgAV-associated intussusception is predominantly ileoileal, occurs in older children (4-8 years), and results from bowel wall oedema acting as a pathological lead point. This makes it less amenable to air enema reduction and may require surgical intervention. [12]

The Steroid Paradox: Despite widespread use, high-quality systematic reviews and meta-analyses demonstrate that corticosteroids provide effective symptom control for severe abdominal and joint pain but do NOT prevent the development or progression of renal disease. The landmark 2013 CHART trial definitively demonstrated no difference in nephritis rates at 6 or 12 months. [13,14] Steroids are purely symptomatic therapy, not disease-modifying treatment.

Age Matters for Prognosis: While IgAV in children typically has an excellent prognosis, adult-onset IgAV carries significantly higher risk of severe renal disease and progression to end-stage kidney disease. Age at onset is one of the strongest predictors of long-term renal outcomes. [15,16]

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2. Epidemiology

Incidence and Prevalence

IgA vasculitis is the most common systemic vasculitis in children, with annual incidence ranging from 3 to 26.7 per 100,000 children, with most studies reporting 10-20 per 100,000. [1,17] Incidence varies significantly by ethnicity and geographic region:

• Highest incidence: Asian populations, particularly in China and Japan (> 20 per 100,000)
• Intermediate incidence: European populations (10-18 per 100,000)
• Lower incidence: African and African-American populations (less than 5 per 100,000)

This ethnic variation suggests genetic susceptibility factors, though specific genes remain incompletely characterized. [18]

Age Distribution

• Peak age: 4-6 years (median 6 years)
• Range: Can occur from infancy to adulthood
• Age distribution: 90% of cases occur in children under 10 years
• Uncommon but important: less than 10% of cases occur in adults, but these have worse prognosis

Infants and toddlers under 2 years may present with prominent oedema of the scalp, face, hands, and feet, which can precede the purpuric rash and cause diagnostic confusion. [19]

Sex Distribution

• Male predominance: Male:Female ratio approximately 1.5-2:1
• This male preponderance is consistent across geographic regions and ethnic groups
• The reason for male predominance remains unexplained

Seasonal Variation

IgAV demonstrates marked seasonal variation with peak incidence in late autumn and winter months (November-February in the Northern Hemisphere). [20] This temporal pattern strongly supports the role of respiratory infections as triggers, particularly:

• Group A Streptococcus
• Adenovirus
• Parvovirus B19
• Mycoplasma pneumoniae
• Epstein-Barr virus

Approximately 30-50% of children report a preceding upper respiratory tract infection within 1-3 weeks of IgAV onset. [6]

Geographic and Environmental Factors

• Urban vs rural: Some studies suggest higher incidence in rural areas
• Socioeconomic status: Possible association with lower socioeconomic status, potentially related to infection exposure
• Vaccination: No convincing evidence linking routine childhood vaccinations to IgAV development
• Medications: Rare reports associate IgAV with certain medications (antibiotics, NSAIDs), but causality difficult to establish

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3. Pathophysiology

Molecular Basis: The Galactose-Deficient IgA1 Hypothesis

The pathogenesis of IgAV centres on abnormal IgA1 glycosylation and subsequent immune complex formation. [21,22] The proposed mechanism involves multiple sequential steps:

Step 1: Aberrant IgA1 Production

• Normal IgA1 molecules contain O-glycans in the hinge region with terminal galactose and sialic acid residues
• In IgAV, patients produce galactose-deficient IgA1 (Gd-IgA1) with exposed N-acetylgalactosamine (GalNAc) residues
• This glycosylation defect is identical to that seen in IgA nephropathy, explaining the shared renal pathology [23]

Step 2: Antibody Formation

• The exposed GalNAc epitopes on Gd-IgA1 are recognized as antigenic
• Patients develop IgG or IgA antibodies against these aberrant glycan structures
• This creates a situation where the immune system produces antibodies against its own defective IgA1

Step 3: Immune Complex Formation

• Gd-IgA1 binds with anti-glycan antibodies to form large, polymeric immune complexes
• These complexes are particularly prone to tissue deposition due to their size and charge characteristics
• Infection triggers (bacterial/viral) may provide additional antigens that incorporate into complexes

Step 4: Vascular Deposition

Immune complexes deposit preferentially in small vessels, particularly:

• Dermal postcapillary venules (skin purpura)
• Glomerular mesangium (nephritis)
• Intestinal small vessels (abdominal symptoms)
• Synovial vessels (arthritis)

The reason for small vessel tropism relates to haemodynamic factors, endothelial properties, and immune complex size. [24]

Step 5: Complement Activation and Inflammation

• Deposited immune complexes activate the alternative complement pathway
• Generation of C3a and C5a (anaphylatoxins) recruits neutrophils
• Neutrophil activation leads to release of proteolytic enzymes and reactive oxygen species
• Result: Leukocytoclastic vasculitis with fibrinoid necrosis of vessel walls
• Characteristic histological finding: fragmented neutrophil nuclei ("nuclear dust") surrounding inflamed vessels

Renal Pathophysiology

The kidney pathology in IgAV nephritis is identical to primary IgA nephropathy (Berger's disease), leading to the concept that IgAV and IgA nephropathy represent different manifestations of the same underlying immune dysregulation. [25]

Histological spectrum (International Study of Kidney Disease in Children classification):

• Grade I: Minimal mesangial proliferation
• Grade II: Mesangial proliferation without crescents
• Grade III: Focal (less than 50%) crescentic or sclerosing lesions
• Grade IV: Diffuse mesangial proliferation (50-75% crescents)
• Grade V: Diffuse mesangial proliferation (> 75% crescents)
• Grade VI: Pseudocrescent formation (membranoproliferative pattern)

Higher grades correlate with worse renal prognosis and increased risk of chronic kidney disease. [26]

Why Children Have Better Outcomes Than Adults

Several factors contribute to the more favourable prognosis in paediatric IgAV:

1. Immune system maturity: Children's immune systems may clear immune complexes more efficiently
2. Renal reserve: Greater nephron number and renal functional reserve in children
3. Comorbidity burden: Children lack hypertension, diabetes, and other renal stressors
4. Early detection: Systematic monitoring in children leads to earlier detection and intervention
5. Histological severity: Adults more frequently have severe crescentic glomerulonephritis

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4. Clinical Presentation

Presenting Features

IgAV typically presents with a characteristic sequence, though variations are common:

Typical progression:

1. Prodromal URTI symptoms (30-50% of cases)
2. Initial manifestations (skin, joint, GI) appear over days to weeks
3. Renal involvement may be immediate or delayed up to 6 months

Cutaneous Manifestations (100%)

The rash is the defining feature and eventual diagnostic requirement for IgAV.

Evolution:

• Stage 1: Begins as erythematous macules or urticarial wheals
• Stage 2: Progresses to palpable purpura within hours to days
• Stage 3: May evolve to ecchymoses in severe cases
• Stage 4: Gradual fading with brownish hyperpigmentation

Distribution:

• Pathognomonic pattern: Symmetrical, gravity-dependent distribution
• Most common sites: Lower extremities (100%), buttocks (90%)
• Less common: Upper extremities (15%), trunk (rare)
• Face involvement: Unusual; if present, consider alternative diagnosis

Key characteristics:

• Palpable: Can be felt on palpation (distinguishes from thrombocytopenic purpura)
• Non-blanching: Pressure or glass slide test remains positive
• Polymorphic: Lesions at different stages coexist
• Crops: New lesions appear in waves over days to weeks

Atypical presentations in infants:

• Prominent oedema may precede purpura
• Scalp, periorbital, and scrotal oedema particularly common
• May be misdiagnosed as cellulitis or allergy initially [27]

Musculoskeletal Manifestations (75-82%)

Arthritis/Arthralgia characteristics:

• Pattern: Oligoarticular (1-4 joints), migratory
• Joints affected: Knees > ankles >> elbows, wrists
• Features: Pain, swelling, tenderness, limited range of motion
• Duration: Typically 1-7 days per joint
• Severity: Can be severe enough to prevent ambulation
• Prognosis: Completely resolves without residual damage or deformity

Periarticular oedema: Soft tissue swelling around joints, particularly ankles, may be prominent and disproportionate to degree of arthritis.

Important differential: The combination of purpura and arthritis may raise concern for septic arthritis or leukaemia; normal platelet count and absence of systemic toxicity help differentiate.

Gastrointestinal Manifestations (50-75%)

GI involvement results from vasculitis affecting the bowel wall, leading to submucosal haemorrhage, oedema, and occasionally ischaemia.

Common symptoms:

• Abdominal pain (50-75%): Colicky, periumbilical or generalized
• Nausea and vomiting (30-50%)
• Gastrointestinal bleeding (15-30%):
  • Occult blood (common)
  • Melena (less common)
  • Frank haematochezia (uncommon)

Severity spectrum:

• Mild: Intermittent cramping, responsive to simple analgesia
• Moderate: Persistent pain requiring hospitalization and narcotic analgesia
• Severe: Mimics acute surgical abdomen

GI complications requiring surgical assessment:

1. Intussusception (2-5%):

   • Predominantly ileoileal (unlike classic ileocolic intussusception in infants)
   • Bowel wall oedema acts as pathological lead point
   • Clinical triad: Severe colicky pain, palpable mass, "redcurrant jelly" stools
   • Diagnosis: Ultrasound showing "target sign" or "doughnut sign"
   • Management: May require surgical reduction (air enema less successful than in classic intussusception) [28]

2. Bowel perforation (less than 1%):

   • Rare but life-threatening
   • Results from severe transmural vasculitis and ischaemia
   • Requires emergency surgical intervention

3. Massive GI bleeding (less than 1%):

   • Rare presentation requiring blood transfusion
   • May respond to corticosteroids
   • Consider endoscopy if severe or persistent

Timing: GI symptoms may precede the rash in 10-15% of cases, creating diagnostic difficulty. In these cases, diagnosis becomes clear when characteristic purpura appears.

Renal Manifestations (20-54%)

Renal involvement is the most important prognostic factor in IgAV, as it is the only manifestation associated with potential long-term morbidity. [29]

Spectrum of renal disease:

1. Asymptomatic microscopic haematuria (most common): Isolated haematuria without proteinuria or reduced GFR

2. Haematuria with proteinuria: Variable degrees of proteinuria from mild (less than 1g/day) to nephrotic range (> 3.5g/1.73m²/day)

3. Nephrotic syndrome (3-5%): Heavy proteinuria, hypoalbuminaemia, oedema, hyperlipidaemia

4. Nephritic syndrome (2-5%): Haematuria, hypertension, reduced GFR, oliguria

5. Rapidly progressive glomerulonephritis (less than 1%): Acute kidney injury with crescentic GN on biopsy; medical emergency requiring aggressive immunosuppression

Temporal patterns:

• Immediate: 40-50% have abnormal urinalysis at presentation
• Early delayed: Additional 20-30% develop renal signs within first month
• Late delayed: 10% develop renal involvement 2-6 months after initial presentation
• This delayed onset mandates prolonged surveillance in all cases

Prognostic markers for severe renal disease:

• Nephrotic-range proteinuria at onset
• Combination of nephrotic and nephritic features
• Persistent macroscopic haematuria
• Reduced GFR at presentation
• Hypertension
• Delayed onset of nephritis (> 1 month after rash)
• Age > 10 years at onset
• Severe histological findings on biopsy (> 50% crescents)

Less Common Manifestations

Scrotal involvement (10-35% of boys):

• Oedema and pain due to scrotal wall vasculitis
• May be severe enough to mimic testicular torsion
• Requires careful testicular examination and often Doppler ultrasound
• Important to exclude true testicular torsion, which requires emergency surgery
• Vasculitis-related pain typically bilateral, with preserved blood flow on Doppler

Neurological involvement (less than 1%):

• Extremely rare but reported manifestations include:
  • Headache (common, usually benign)
  • Seizures
  • Posterior reversible encephalopathy syndrome (PRES)
  • Intracerebral haemorrhage
  • Peripheral neuropathy
  • Behavioural changes

Pulmonary involvement (less than 1%):

• Diffuse alveolar haemorrhage (extremely rare)
• Presents with haemoptysis, dyspnoea, falling haemoglobin
• Medical emergency requiring aggressive immunosuppression

Cardiac involvement (very rare):

• Myocarditis, pericarditis reported in case reports
• Coronary vasculitis (exceedingly rare)

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5. Clinical Examination

Systematic Examination Approach

A thorough clinical examination is essential for diagnosis, severity assessment, and complication detection.

Skin Examination

Inspection:

• Distribution: Document extent and pattern (lower limbs, buttocks, upper limbs, trunk)
• Morphology: Describe lesion type (macules, urticaria, purpura, ecchymoses)
• Staging: Note presence of lesions at different stages of evolution
• Associated features: Look for bullae, necrosis, ulceration (suggests severe vasculitis)

Palpation:

• Palpability test: The hallmark is that purpuric lesions can be felt ("palpable purpura")
• This distinguishes vasculitic purpura from purpura due to thrombocytopenia or platelet dysfunction (which is flat)
• The palpability results from perivascular inflammation and oedema

Glass slide test (non-blanching test):

• Press glass slide or clear plastic against lesions
• Purpuric lesions remain visible (do not blanch) due to extravasated red blood cells
• Essential for distinguishing purpura from erythematous rashes

Oedema Assessment

• Sites: Hands, feet, periorbital, scalp (especially in infants and toddlers)
• Character: Non-pitting or pitting
• Significance: Prominent oedema particularly common in younger children and may precede purpura

Joint Examination

For each affected joint:

• Inspection: Swelling, erythema, deformity
• Palpation: Warmth, tenderness, effusion
• Range of motion: Active and passive (often limited by pain)
• Gait assessment: Many children refuse to walk due to ankle/knee pain

Abdominal Examination

Inspection:

• Distension, visible peristalsis, surgical scars

Palpation:

• Systematically examine all quadrants
• Note focal vs diffuse tenderness
• Assess for organomegaly (splenomegaly not expected; if present, consider alternative diagnosis)
• Palpable mass: May indicate intussusception; requires urgent imaging

Percussion:

• Assess for ascites (may occur with nephrotic syndrome)

Auscultation:

• Bowel sounds (may be hyperactive in early intussusception, absent in perforation)

Rectal examination:

• Generally not performed routinely in children
• May be considered if significant GI bleeding or suspected intussusception
• Would reveal blood ("redcurrant jelly" in intussusception)

Genitourinary Examination

In males: Testicular examination is mandatory

• Inspection: Scrotal oedema, erythema
• Palpation: Testicular size, consistency, tenderness
• Cremasteric reflex: Present in orchitis, absent in torsion
• Transillumination: Can help differentiate hydrocele from solid mass
• Low threshold for Doppler ultrasound if examination uncertain, as testicular torsion is a surgical emergency

Urinalysis: Should be performed in all patients (see Investigations)

Cardiovascular Examination

Blood pressure: Essential at every visit

• Hypertension indicates active nephritis
• Severity grading:
  • "Stage 1: 95th-99th percentile for age/height/sex"
  • "Stage 2: > 99th percentile + 5mmHg"
• Use appropriate paediatric cuff size

Peripheral perfusion: Capillary refill time, extremity temperature

Heart sounds: Listen for murmurs, rub (pericarditis extremely rare)

Neurological Examination

Not routinely abnormal, but examine if:

• Headache, altered behaviour, seizures
• Severe hypertension (hypertensive encephalopathy)
• Focal neurological symptoms

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6. Investigations

Diagnostic Criteria

IgA vasculitis is primarily a clinical diagnosis. The 2010 EULAR/PRINTO/PRES criteria provide validated diagnostic framework: [30]

Mandatory criterion:

• Palpable purpura (non-thrombocytopenic) or petechiae with lower limb predominance

Plus at least one of:

1. Diffuse abdominal pain
2. Arthritis (acute, any joint) or arthralgia
3. Renal involvement (haematuria and/or proteinuria)
4. Histopathology showing IgA deposition (skin or kidney biopsy)

Sensitivity: 100% (by definition, as validation studies used clinical diagnosis as gold standard) Specificity: 87%

Laboratory Investigations

Essential Initial Tests

Full Blood Count (FBC):

• Platelets: Normal or elevated (thrombocytosis of inflammation)
  • This is critical for excluding thrombocytopenic purpura (ITP, leukaemia)
  • Platelet count typically 200-600 × 10⁹/L
• Haemoglobin: Usually normal unless GI bleeding
• White cell count: Normal or mild leucocytosis
• Blood film: Excludes blast cells (leukaemia), confirms platelet number

Renal function:

• Urea and creatinine: Baseline renal function
• Usually normal at presentation unless severe nephritis
• eGFR calculation: Using paediatric formulas (Schwartz equation)

Inflammatory markers:

• ESR: Usually elevated (30-60 mm/hr)
• CRP: Variable; may be normal or elevated
• Non-specific but support inflammatory process

Coagulation screen:

• PT, APTT: Normal (excludes DIC, coagulopathy)
• Essential for differentiating from meningococcal sepsis with DIC
• Fibrinogen: Normal or elevated

Urinalysis (ESSENTIAL)

Must be performed at presentation and during follow-up:

Urine dipstick:

• Blood: Haematuria present in 20-54%
  • Microscopic or macroscopic
  • Dipstick shows 1+ to 4+
• Protein: Variable from negative to 4+
  • Isolated proteinuria less common than haematuria
  • Combined haematuria + proteinuria more concerning

Urine microscopy:

• Red blood cells: Confirm true haematuria (vs myoglobinuria, haemoglobinuria)
• Dysmorphic RBCs and RBC casts: Indicate glomerular origin
• White blood cells: May be present
• Exclude urinary tract infection

Quantitative proteinuria:

• First morning urine protein:creatinine ratio (uPCR):
  • "Normal: less than 20 mg/mmol (less than 0.2 mg/mg)"
  • "Abnormal: > 20 mg/mmol"
  • "Nephrotic range: > 200 mg/mmol (> 2 mg/mg)"
• 24-hour urine collection (less practical in children):
  • "Normal: less than 4 mg/m²/hour or less than 100 mg/m²/day"
  • "Nephrotic: > 40 mg/m²/hour or > 1000 mg/m²/day"

Immunological Tests

Serum IgA:

• Elevated in 50% of patients (non-specific)
• Normal IgA does not exclude diagnosis
• Low IgA suggests IgA deficiency (different condition)

Complement levels (C3, C4):

• Typically normal (distinguishes from post-infectious GN, SLE)
• If low, consider alternative diagnosis

Antinuclear antibody (ANA):

• Negative in IgAV
• If positive, consider systemic lupus erythematosus

ANCA (antineutrophil cytoplasmic antibody):

• Negative in IgAV
• If positive, consider other vasculitides (GPA, MPA)

Anti-streptolysin O titre (ASOT):

• Often elevated (30-50%) reflecting recent streptococcal infection
• Supports infectious trigger but not diagnostic

Stool Analysis

If gastrointestinal bleeding:

• Faecal occult blood: Often positive even without visible bleeding
• Stool culture: Exclude infectious colitis if diarrhoea present

Imaging Studies

Abdominal Ultrasound

Indications:

• Severe or persistent abdominal pain
• Palpable abdominal mass
• Suspected intussusception
• Peritonism or signs of surgical abdomen

Findings in IgAV:

• Bowel wall thickening: Due to oedema and haemorrhage
• Increased mesenteric vascularity: Doppler shows hyperaemia
• Intussusception: "Target sign" or "pseudokidney sign"
  • Multiple layers of bowel wall within bowel lumen
  • Ileoileal more common than ileocolic in IgAV
• Free fluid: Ascites may be present
• Normal kidneys: Unless severe nephritis with oedema

Testicular Doppler Ultrasound

Indications:

• Scrotal pain and swelling
• To differentiate orchitis from testicular torsion

Findings:

• IgAV orchitis: Preserved or increased testicular blood flow, scrotal wall thickening
• Testicular torsion: Absent testicular blood flow (surgical emergency)

Chest X-ray

Indications:

• Respiratory symptoms (cough, dyspnoea, haemoptysis)
• Suspected pulmonary haemorrhage (very rare)

Findings if pulmonary involvement:

• Bilateral patchy infiltrates or consolidation
• Pleural effusion (rare)

Histopathology

Skin Biopsy

Indications:

• Atypical presentation
• Diagnostic uncertainty
• Rash without other typical features
• Not routinely required if classic tetrad present

Technique:

• Lesion less than 24 hours old for optimal yield
• Include subcutaneous tissue

Light microscopy findings:

• Leukocytoclastic vasculitis: Neutrophilic infiltration of small vessel walls
• Fibrinoid necrosis: Vessel wall destruction
• Nuclear dust: Fragmented neutrophil nuclei (karyorrhexis)
• Red blood cell extravasation: Purpura

Immunofluorescence (diagnostic):

• IgA deposition: Predominant finding in vessel walls (granular pattern)
• C3 deposition: Often present
• IgG, IgM: May be present but less prominent than IgA
• This IgA-dominant pattern is pathognomonic

Renal Biopsy

Indications (paediatric nephrology consultation required):

• Nephrotic-range proteinuria (> 1000 mg/m²/day or uPCR > 200 mg/mmol)
• Nephrotic syndrome
• Impaired renal function (elevated creatinine, reduced eGFR)
• Persistent proteinuria > 3 months
• Combination of heavy proteinuria + haematuria + hypertension
• To guide treatment decisions in severe nephritis

Contraindications:

• Coagulopathy
• Uncontrolled hypertension
• Solitary kidney
• Severe thrombocytopenia (though platelets normal in IgAV)

Histological classification (ISKDC or Oxford classification):

Light microscopy:

• Mesangial proliferation (hallmark finding)
• Crescents (cellular, fibrocellular, or fibrous)
• Glomerulosclerosis
• Tubular atrophy
• Interstitial fibrosis

Immunofluorescence (diagnostic):

• IgA deposition in mesangium (bright, granular pattern) - pathognomonic
• C3 co-deposition common
• Identical to IgA nephropathy (Berger's disease)

Electron microscopy:

• Mesangial electron-dense deposits (immune complexes)
• Subendothelial deposits in severe cases

Prognostic significance:

• 50% crescents: Poor prognosis, higher risk of ESKD

• Severe tubulointerstitial changes: Worse long-term outcome
• Chronic changes (sclerosis, fibrosis): Irreversible damage

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7. Differential Diagnosis

The differential diagnosis of IgAV depends on the presenting manifestation:

Purpuric Rash Differentials

Immune Thrombocytopenic Purpura (ITP):

• Key difference: Platelet count less than 100 × 10⁹/L in ITP (normal in IgAV)
• Purpura is flat (non-palpable) in ITP
• No systemic features (no arthritis, abdominal pain, renal involvement)
• Bleeding from mucous membranes more common in ITP

Meningococcal Septicaemia:

• Key difference: Child appears systemically unwell, toxic
• Fever, hypotension, altered consciousness
• Coagulopathy (DIC): Prolonged PT/APTT, low fibrinogen, low platelets
• Medical emergency: Requires immediate antibiotics
• Purpura is non-palpable and rapidly progressive
• When in doubt, treat as meningococcal sepsis first, investigate later

Acute Leukaemia (ALL, AML):

• Key differences: Thrombocytopenia, anaemia, blast cells on blood film
• Systemic features: Fever, weight loss, lymphadenopathy, hepatosplenomegaly
• Bone pain (bone marrow infiltration)
• Purpura is flat (non-palpable)

Hypersensitivity Vasculitis (drug-induced):

• Temporal relationship to drug exposure
• Similar histology to IgAV but IgA deposition absent or less prominent
• Usually limited to skin
• Resolves with drug withdrawal

Other Vasculitides:

• Polyarteritis nodosa: Medium vessel vasculitis; livedo, nodules, systemic features
• Microscopic polyangiitis: ANCA-positive, pulmonary-renal syndrome
• Kawasaki disease: Younger age (less than 5 years), fever > 5 days, conjunctivitis, strawberry tongue, coronary aneurysms

Abdominal Pain Differentials

When IgAV presents with abdominal pain before rash appears, consider:

Acute Appendicitis:

• Right lower quadrant pain
• Fever, anorexia, vomiting
• Peritonism, rebound tenderness
• Elevated inflammatory markers
• Imaging shows appendiceal inflammation

Intussusception (non-IgAV):

• Classic age 6-18 months (younger than typical IgAV)
• Ileocolic junction (vs ileoileal in IgAV)
• No purpuric rash
• Ultrasound diagnostic

Inflammatory Bowel Disease (Crohn's, UC):

• Chronic symptoms: Diarrhoea, weight loss, growth failure
• Blood in stool
• Extraintestinal features possible (arthritis, skin lesions)
• No purpura
• Endoscopy and biopsy diagnostic

Gastroenteritis:

• Diarrhoea predominates (vs abdominal pain in IgAV)
• Usually viral (Rotavirus, Norovirus, Adenovirus)
• Vomiting, fever
• No purpura or arthritis

Mesenteric Adenitis:

• Following viral URTI
• Right lower quadrant pain (mimics appendicitis)
• Enlarged mesenteric lymph nodes on ultrasound
• No purpura

Arthritis Differentials

Septic Arthritis:

• Single joint usually (monoarthritis)
• Child systemically unwell with fever
• Refusal to move joint, held in position of comfort
• Urgent joint aspiration shows pus, positive culture
• No purpura

Reactive Arthritis (post-infectious):

• Following GI or GU infection
• Oligoarthritis
• May have conjunctivitis, urethritis (Reiter's syndrome)
• No purpura
• Self-limiting

Juvenile Idiopathic Arthritis (JIA):

• Chronic arthritis (> 6 weeks by definition)
• Various subtypes: oligoarticular, polyarticular, systemic
• No purpura
• May have uveitis, systemic features depending on subtype

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8. Management

General Principles

IgA vasculitis management is predominantly supportive and symptomatic. The disease is self-limiting in the vast majority of children, and no treatment has been proven to prevent renal complications or alter long-term prognosis. [31,32]

Key management tenets:

1. Supportive care for acute symptoms
2. Systematic surveillance for renal involvement
3. Prompt identification and management of complications
4. Appropriate specialist referral when indicated
5. Patient and family education

Initial Assessment and Triage

Mild disease (outpatient management appropriate):

• Purpuric rash with no/mild arthralgia
• No abdominal pain or mild discomfort
• Normal urinalysis or isolated microscopic haematuria
• Normal blood pressure
• Normal renal function
• Child well and tolerating oral intake

Moderate to severe disease (consider admission):

• Severe joint pain limiting mobility
• Moderate to severe abdominal pain
• Significant proteinuria or macroscopic haematuria
• Hypertension
• Impaired renal function
• Scrotal involvement
• Age less than 2 years (higher complication risk)
• Inability to tolerate oral fluids/medications

Emergency admission required:

• Severe abdominal pain (surgical abdomen, suspected intussusception)
• GI bleeding
• Acute kidney injury
• Nephrotic/nephritic syndrome
• Testicular torsion (surgical emergency)
• Hypertensive emergency
• Altered consciousness

Acute Symptomatic Management

Analgesia

First-line: Paracetamol (acetaminophen)

• Dose: 15 mg/kg every 4-6 hours (max 60 mg/kg/day)
• Safe for all patients
• Adequate for mild-moderate pain

Second-line: NSAIDs

• Options: Ibuprofen 5-10 mg/kg every 6-8 hours, Naproxen 5-7 mg/kg twice daily
• Effectiveness: Very effective for musculoskeletal pain
• Controversy: Theoretical concern about renal effects, but evidence suggests safety in IgAV
• Contraindications:
  • Active GI bleeding
  • Severe renal impairment (eGFR less than 30)
  • Known NSAID allergy
• Evidence: Studies show NSAIDs do not increase risk of nephritis when used short-term [33]

Third-line: Opioids (severe pain)

• Codeine, tramadol, morphine
• Reserved for severe abdominal or musculoskeletal pain
• Use with caution; monitor for constipation

Rest and Activity

• Bed rest: Not mandatory, but often naturally adopted by child due to pain
• Leg elevation: May reduce oedema and purpuric lesions
• Gradual mobilization: As symptoms improve
• Return to school/activities: When rash improving and pain controlled
• Sport restriction: Avoid contact sports until complete resolution (theoretical concern about trauma to inflamed vessels)

Hydration and Nutrition

• Oral fluids: Maintain adequate hydration
• IV fluids: If unable to tolerate oral intake due to vomiting or abdominal pain
  • Isotonic fluids (0.9% saline or Hartmann's)
  • Avoid fluid overload if renal impairment
• Diet: Regular age-appropriate diet once abdominal pain resolving

Corticosteroid Therapy

Corticosteroids are the only pharmacological intervention with proven efficacy for specific indications in IgAV, but their role is limited to symptom control, not disease modification.

Evidence Base

What steroids DO:

• Reduce severity and duration of abdominal pain [34]
• Reduce severity and duration of joint pain
• May reduce duration of rash
• Reduce scrotal pain/swelling

What steroids DO NOT do:

• Prevent development of renal involvement [13,14]
• Reduce severity of established nephritis
• Prevent recurrence
• Alter long-term prognosis
• Prevent intussusception

Landmark evidence:

• CHART trial (2013): RCT of 171 children; prednisolone at presentation did not reduce nephritis at 6 or 12 months [13]
• Cochrane review (2023): Meta-analysis confirmed no benefit for preventing renal disease [14]

Indications for Corticosteroids

Accepted indications:

1. Severe colicky abdominal pain unresponsive to simple analgesia
2. Severe arthritis limiting mobility
3. Orchitis causing significant pain/swelling

Not indicated:

• Mild disease for "prevention" of complications
• Isolated skin involvement
• Mild arthralgia
• Attempt to prevent renal disease

Dosing Regimens

Standard regimen:

• Prednisolone: 1-2 mg/kg/day (max 60 mg) orally
• Duration: 1-2 weeks, then taper
• Taper: Reduce by 5-10 mg every 3-5 days

For severe symptoms:

• Methylprednisolone IV: 10-30 mg/kg/day (max 1g) for 3 days
• Followed by oral prednisolone taper

Important considerations:

• Give in morning to reduce insomnia
• Take with food to reduce gastric irritation
• Monitor blood pressure (can worsen hypertension)
• Monitor blood glucose if prolonged course
• Gastric protection generally not needed for short courses

Management of Gastrointestinal Complications

Mild to Moderate Abdominal Pain

• Analgesia (paracetamol ± NSAIDs)
• Consider prednisolone if severe
• IV fluids if unable to tolerate oral
• Nil by mouth if severe pain or vomiting, then gradual reintroduction
• Monitor stool for blood

Suspected Intussusception

Presentation: Severe colicky pain, palpable mass, "redcurrant jelly" stools

Investigation: Abdominal ultrasound urgently

Management:

• Nil by mouth, IV fluids
• Urgent surgical consultation
• Air enema reduction: May be attempted but less successful than in classic intussusception
• Surgical reduction: Often required for ileoileal intussusception
• Prednisolone: Often given but evidence limited

GI Bleeding

• Mild (occult blood): Supportive care, observe
• Moderate (melena): Admission, IV fluids, transfusion if anaemic, consider prednisolone
• Severe (haematochezia, haemodynamic compromise):
  • Resuscitation, blood transfusion
  • High-dose IV methylprednisolone
  • Gastroenterology consultation
  • Consider endoscopy
  • Surgery if perforation

Management of Renal Involvement

The approach to renal disease depends on severity and should involve paediatric nephrology.

Isolated Microscopic Haematuria

• Management: Observation, regular monitoring
• Follow-up: Urinalysis and BP every 1-2 weeks initially, then monthly
• Prognosis: Excellent; usually resolves within 6 months
• Treatment: None required

Haematuria + Mild Proteinuria

• Management: Close monitoring
• ACE inhibitor: Consider if proteinuria persistent (> 3 months)
  • Reduces proteinuria and may slow progression
  • Enalapril 0.1 mg/kg/day, titrate to effect
  • Monitor potassium and creatinine

Nephrotic-Range Proteinuria or Nephrotic Syndrome

Requires paediatric nephrology referral

• Investigation: Renal biopsy to assess histological severity
• Treatment options (based on biopsy findings):
  • "High-dose corticosteroids: Prednisolone 2 mg/kg/day"
  • "ACE inhibitors: For proteinuria reduction"
  • "Immunosuppression: If severe crescentic GN"
    • Cyclophosphamide (oral or IV)
    • Azathioprine
    • Mycophenolate mofetil
  • "Plasma exchange: Case reports in severe crescentic GN"
  • "Rituximab: Emerging evidence in refractory cases"

Acute Kidney Injury / Rapidly Progressive GN

Medical emergency - intensive management required

• Admission: Paediatric nephrology unit
• Investigations: Urgent renal biopsy
• Treatment: Aggressive immunosuppression
  • "IV methylprednisolone pulses: 10-30 mg/kg/day for 3-5 days"
  • "Cyclophosphamide: IV or oral"
  • "Plasma exchange: Consider in severe cases"
• Supportive care:
  • Fluid and electrolyte balance
  • Hypertension management
  • Dialysis if required (rare)

Follow-up Protocol

Systematic surveillance is mandatory to detect delayed or progressive renal involvement. [35]

Recommended Schedule (British Association for Paediatric Nephrology)

First 3 months (critical period):

• Weeks 1, 2, 4: Urinalysis (dipstick), uPCR, BP
• Weeks 8, 12: Urinalysis, uPCR, BP, U&E

Months 3-6:

• Monthly: Urinalysis, BP
• If any abnormality, continue monitoring

Discontinuation of monitoring:

• If completely normal urinalysis and BP for 6 months from last active symptoms
• If persistent abnormalities, refer to paediatric nephrology for long-term follow-up

What to measure:

• Urine dipstick: Blood, protein
• uPCR: Quantify proteinuria if dipstick positive
• Blood pressure: Using appropriate paediatric centile charts
• Renal function: If proteinuria or hypertension present

Rationale: Up to 10% of children develop delayed renal involvement in months 2-6; systematic monitoring ensures early detection when intervention may prevent progression.

Management of Recurrence

Incidence: 30-40% of children experience recurrence, usually within first year [36]

Characteristics of recurrence:

• Typically milder than initial episode
• Often triggered by further viral URTI
• Predominantly skin and joint involvement
• Renal involvement in recurrence less common but possible

Management:

• Same principles as initial episode
• Intensify monitoring during recurrence
• Counsel family that multiple recurrences possible but tend to become less frequent over time
• No prophylaxis effective; avoid unnecessary antibiotics

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9. Complications

Acute Complications

Intussusception (2-5%):

• Most serious acute GI complication
• Ileoileal predominance (unusual for this age group)
• Requires surgical consultation
• May need operative reduction

Gastrointestinal perforation (less than 1%):

• Rare but life-threatening
• Presents with peritonism, free air on imaging
• Requires emergency surgery

Massive GI bleeding (less than 1%):

• Rarely requires transfusion
• May respond to corticosteroids
• Consider endoscopy

Testicular torsion:

• IgAV can coexist with true torsion
• Maintain low threshold for Doppler ultrasound
• If doubt, surgical exploration required

Acute kidney injury (less than 1%):

• From severe crescentic glomerulonephritis
• May require dialysis
• Aggressive immunosuppression required

Posterior reversible encephalopathy syndrome (PRES):

• Associated with severe hypertension
• Headache, seizures, visual changes, altered consciousness
• MRI shows posterior circulation oedema
• BP control critical

Chronic Complications

Chronic Kidney Disease (1-3%):

• The only significant long-term morbidity of IgAV
• Risk factors:
  • Severe proteinuria at onset (> 1 g/day)
  • Nephrotic syndrome
  • Crescentic GN on biopsy (> 50% crescents)
  • Delayed onset of nephritis (> 1 month)
  • Persistent proteinuria > 6 months
  • Recurrent episodes
  • Older age at onset (> 10 years)
  • Adult-onset disease

Progression to End-Stage Kidney Disease:

• Occurs in 1-2% of children with IgAV
• Risk much higher in adults with IgAV (up to 30%)
• Time course: May take 10-20 years to progress
• Importance of long-term nephrology follow-up if persistent renal disease

Permanent renal scarring:

• Chronic tubulointerstitial changes on biopsy
• Reduced nephron mass
• Hypertension
• Requires lifelong monitoring

Psychological Impact

• Anxiety about recurrence
• School absence
• Impact of chronic disease if renal involvement
• Importance of family education and support

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10. Prognosis and Outcomes

Overall Prognosis

Excellent in most children: 94-97% achieve complete resolution without long-term sequelae [37]

Duration of acute illness:

• Rash: 3-4 weeks (may have crops for up to 3 months)
• Arthritis: 1-2 weeks
• Abdominal pain: 1-2 weeks
• Total illness duration: 4-6 weeks for most

Prognostic Factors

Favourable prognosis:

• Age less than 10 years at onset
• Mild renal involvement (isolated microscopic haematuria)
• Absent or mild proteinuria
• Rapid resolution of symptoms
• Single episode without recurrence

Unfavourable prognosis (higher risk of CKD):

• Age > 10 years or adult-onset
• Severe proteinuria at onset (nephrotic range)
• Combination of nephrotic + nephritic features
• Acute kidney injury at presentation
• Persistent proteinuria > 3 months
• Delayed onset of nephritis (> 1 month after rash)
• Severe histological changes (> 50% crescents, tubular atrophy)
• Recurrent episodes with renal involvement

Renal Outcomes

Complete renal recovery: 85-90% of those with renal involvement

Persistent urinary abnormalities: 10-15% at 1 year

• Most resolve spontaneously over time
• Require ongoing nephrology follow-up

Chronic kidney disease: 1-3% of all IgAV patients

• 5-10% of those with initial renal involvement
• Much higher in adults (up to 30%)

End-stage kidney disease: 1% overall

• Typically occurs 10-20 years after initial presentation
• Highlights importance of long-term follow-up

Recurrence

Incidence: 30-40% experience at least one recurrence [38]

Timing: Most recurrences within first year (median 3-4 months)

Characteristics:

• Usually milder than initial episode
• Often triggered by URTI
• Predominantly cutaneous
• Renal involvement in recurrence uncommon but possible

Multiple recurrences: 10-15% have > 2 episodes

• Frequency typically decreases over time
• No effective prophylaxis available

Long-term outcome: Recurrence does not significantly worsen long-term prognosis unless associated with progressive renal disease

Fertility and Pregnancy

• No impact on fertility in those who recover completely
• Women with IgAV nephritis and CKD: Pregnancy may exacerbate renal disease; pre-conception counselling essential
• No known inheritance pattern: Risk to offspring not increased

Mortality

Extremely rare in children (less than 0.1%)

Causes of death (case reports):

• Massive GI bleeding
• Bowel perforation with sepsis
• Severe pulmonary haemorrhage
• Complications of ESKD
• Surgical complications (intussusception)

Higher mortality in adults: Predominantly from renal failure or cardiovascular disease

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11. Special Populations

Infants and Toddlers (less than 2 years)

Atypical presentations:

• Prominent oedema: Scalp, face, hands, feet often more striking than purpura
• Oedema may precede purpura: Causing diagnostic delay
• Scrotal swelling: Common and alarming to parents
• Distribution: Purpura may be more widespread, less gravity-dependent

Diagnostic challenges:

• Initial presentation may mimic cellulitis, urticaria, or allergic reaction
• Requires high index of suspicion
• Purpura eventually appears and confirms diagnosis

Complications:

• Higher risk of intussusception (age-appropriate complication)
• Otherwise similar prognosis to older children

Management: Same principles, but lower threshold for admission due to age

Adolescents and Adults

Adult-onset IgAV (> 20 years) represents only 10% of all IgAV cases but has distinctly worse prognosis. [39]

Differences from paediatric IgAV:

• Renal involvement: More frequent (60-80% vs 20-50%) and more severe
• Chronic kidney disease: 30% of adults develop CKD (vs 1-3% of children)
• End-stage kidney disease: 10-15% of adults (vs 1% of children)
• Histology: More likely to have severe crescentic GN
• Recovery: Less likely to achieve complete resolution

Possible explanations:

• Reduced immune clearance of complexes in adults
• Comorbidities (hypertension, diabetes, obesity) compound renal injury
• Delayed diagnosis and treatment
• Intrinsic differences in immune system aging

Management implications:

• Lower threshold for renal biopsy
• More aggressive immunosuppression for renal involvement
• Mandatory long-term nephrology follow-up

Pregnancy

IgAV in pregnancy: Very rare; case reports only

Risks:

• Maternal: Exacerbation of renal disease, pre-eclampsia
• Fetal: Growth restriction, preterm birth
• Recurrence: Pregnancy may trigger recurrence in women with prior IgAV

Management:

• Multidisciplinary care: Obstetrics, Nephrology, Rheumatology
• Careful monitoring of maternal BP, proteinuria, renal function
• Distinguish from pre-eclampsia (can coexist)
• Immunosuppression options limited (avoid cyclophosphamide, mycophenolate)
• Prednisolone and azathioprine considered safer
• Delivery planning based on maternal and fetal condition

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12. Patient and Family Education

Common Questions and Answers

Is this meningitis? No. The rash looks similar because it doesn't disappear when you press on it with a glass, but children with meningitis are extremely ill, with high fever, drowsiness, and severe headache. Children with IgA vasculitis are usually well in themselves, just uncomfortable. The blood tests confirm normal platelets and normal clotting, which proves it isn't meningitis or leukaemia.

What causes it? It's an overreaction of the immune system, usually triggered by a recent cold or sore throat. The immune system makes "sticky" antibodies (IgA type) that form clumps and get stuck in tiny blood vessels in the skin, joints, tummy, and kidneys. This causes inflammation and leaking of blood cells, which creates the purple spots.

Is it contagious? No. IgA vasculitis itself is not contagious. Your child may have caught an infection (like a cold) before developing IgAV, and that infection was contagious, but the IgAV condition itself cannot spread to others. Your child can return to school once feeling well enough, usually after the rash starts to fade and pain improves.

How long will it last? Most children recover within 4-6 weeks. The rash usually lasts 2-4 weeks, though new spots can appear for up to 3 months. Joint pain typically improves within a week, and tummy pain within 1-2 weeks. The key is monitoring for kidney involvement, which is why we need to check urine samples regularly for 6 months.

Will it come back? About 1 in 3 children (30-40%) have the rash come back, usually within the next year. Recurrences are typically milder and often happen when your child catches another cold. The good news is that recurrences become less frequent over time and usually stop happening as children get older.

Why do we need to keep checking the urine? The kidneys can be affected even when your child feels completely well and the rash has gone. Kidney inflammation (nephritis) can be "silent"

• no symptoms - but show up on urine tests. We need to check regularly for 6 months because kidney involvement can appear late, even 2-3 months after the rash. Early detection of kidney problems allows us to start treatment before permanent damage occurs.

What should I watch for at home? Contact your doctor urgently if your child develops:

• Severe tummy pain that won't go away
• Blood in poo (may look like redcurrant jelly)
• Severe headache with vomiting
• Swelling of the face or body
• Reduced urine output or dark/cola-coloured urine
• High blood pressure symptoms (severe headache, blurred vision)
• Severe pain or swelling of the testicles (boys)

Can my child exercise and play sports? During the acute illness, your child should rest as much as they feel comfortable. They don't need to stay in bed but should avoid strenuous activity while the rash is active and joints are painful. Once symptoms are improving, gradual return to normal activities is fine. Avoid contact sports until the rash has completely resolved.

Does treatment cure it? There is no treatment that cures IgA vasculitis or prevents complications. The condition is self-limiting, meaning it goes away on its own in most children. Painkillers help with discomfort. Steroid medication (prednisolone) can be very effective for severe tummy pain or joint pain, but it doesn't prevent kidney problems. Most treatment is about keeping your child comfortable while the illness runs its course.

What about the long term? The vast majority of children (> 95%) recover completely with no lasting effects. The only potential long-term problem is kidney disease, which affects about 1-3% of children with IgAV. This is why long-term monitoring is so important. Even among children who have kidney involvement, most (85-90%) recover completely.

Information Sheet Key Points

Provide families with written information covering:

1. What is IgA vasculitis: Brief explanation of immune system overreaction
2. Symptoms to expect: Rash, joint pain, tummy pain, possible kidney involvement
3. Warning signs: When to seek urgent medical attention
4. Monitoring schedule: Urine and blood pressure checks for 6 months
5. Prognosis: Excellent for most children
6. When to call doctor: Clear guidance on concerning symptoms
7. Return to school/activities: When it's safe
8. Follow-up appointments: Importance of attending all scheduled checks

Psychological Support

• Acknowledge parental anxiety about "meningitis-like" rash
• Reassure about excellent prognosis in most cases
• Explain importance of monitoring (without causing alarm)
• Support for managing chronic illness if renal involvement
• School liaison if prolonged absence

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13. Examination Focus (MRCPCH, PACES, Medical Finals)

High-Yield Examination Topics

1. Diagnosis: "Palpable purpura + joint pain + tummy ache?"

• Answer: IgA Vasculitis (Henoch-Schönlein Purpura)
• Key: Palpable (can feel the lesions) distinguishes from ITP
• Distribution: Lower limbs and buttocks (gravity-dependent)

2. Investigation: "Blood test to exclude ITP?"

• Answer: Platelet count
• ITP: Low platelets (less than 100)
• IgAV: Normal or high platelets (thrombocytosis of inflammation)

3. Complication: "Severe colicky pain, blood in stool, 'redcurrant jelly'?"

• Answer: Intussusception
• IgAV-associated intussusception is ileoileal (not ileocolic)
• May require surgery (air enema less effective)

4. Management: "Role of steroids in IgA vasculitis?"

• Answer: Symptom relief for severe abdominal pain and arthritis
• Does NOT prevent renal disease (CHART trial, Cochrane review)
• Not indicated for mild disease or skin-only involvement

5. Monitoring: "Child had IgAV 2 weeks ago, now fully recovered. What follow-up?"

• Answer: Regular urine dipstick and blood pressure for 6 months
• Renal involvement can be delayed up to 6 months
• Schedule: Weekly initially, then monthly

6. Prognosis: "Most important factor determining long-term outcome?"

• Answer: Degree of renal involvement
• Isolated microscopic haematuria: Excellent prognosis
• Nephrotic-range proteinuria: Higher risk of chronic kidney disease

OSCE Stations

History-Taking Station: Child with Purpura

Presenting complaint: 5-year-old with rash on legs

Key history points:

• Rash: When started, distribution, progression, palpable, blanching test
• Associated symptoms: Joint pain, tummy pain, blood in urine/stool
• Preceding illness: Recent URTI, sore throat (2-3 weeks before)
• Systemic features: Fever, weight loss, lethargy (suggests alternative diagnosis)
• Other systems: Renal (urine colour, output, oedema), GI (vomiting, diarrhoea, blood)
• Differential diagnosis: Rule out meningococcal (unwell, fever, fast-spreading)
• Medications: Recent antibiotics or other drugs (drug-induced vasculitis)
• Family history: Autoimmune conditions, kidney disease

Clinical Examination Station: Paediatric Rash

Inspection:

• Distribution: Lower limbs, buttocks
• Morphology: Purpuric lesions of varying ages

Palpation:

• Palpable purpura (key finding)

Glass slide test: Non-blanching

Joint examination: Swelling, tenderness, reduced ROM (knees, ankles)

Abdominal examination: Diffuse tenderness, organomegaly, masses

Vital signs: BP (hypertension suggests nephritis)

Complete examination: Urinalysis for haematuria/proteinuria

Presentation: "This 5-year-old child has a symmetrical, purpuric, non-blanching rash affecting predominantly the lower limbs and buttocks. The rash is palpable on examination. There is associated swelling and tenderness of both knees. Urinalysis shows haematuria 2+ and protein 1+. These findings are consistent with IgA vasculitis. I would like to check the platelet count to exclude ITP, measure blood pressure, and arrange regular monitoring for renal involvement."

Viva Questions and Model Answers

Q1: Why is the purpura palpable in IgA vasculitis but flat in ITP?

A: The palpability reflects the underlying pathological process. In IgA vasculitis, there is active vasculitis with inflammatory cell infiltration of the vessel walls, causing perivascular inflammation, oedema, and cellular infiltration. This creates a raised, palpable lesion. Histologically, this is leukocytoclastic vasculitis with neutrophil infiltration and vessel wall destruction.

In ITP, the mechanism is different: there is simply leakage of red blood cells through intact vessel walls due to thrombocytopenia. The extravasated blood creates purpura, but there is no inflammation or cellular infiltration, so the lesion is flat.

This difference is clinically useful: palpable purpura suggests vasculitis (IgAV, drug-induced, other vasculitides), while flat purpura suggests thrombocytopenia, platelet dysfunction, or coagulopathy.

Q2: Why does IgA vasculitis require 6 months of urine monitoring?

A: Renal involvement in IgA vasculitis follows a variable timeline. While approximately 40% of children have abnormal urinalysis at initial presentation, an additional 10% develop renal manifestations in a delayed fashion, up to 6 months after the initial rash. The renal involvement can be completely asymptomatic - children feel perfectly well but have microscopic haematuria or proteinuria detectable only on urinalysis.

Early detection of nephritis is critical because:

1. It allows institution of ACE inhibitors for proteinuria reduction
2. It identifies patients requiring nephrology referral
3. Severe progressive disease can be treated before irreversible damage
4. It's the only aspect of IgAV with potential for long-term morbidity (1-3% develop CKD)

The 6-month timeframe is evidence-based, as virtually all renal involvement declares itself within this period. Monitoring involves simple urine dipstick and blood pressure measurement.

Q3: What are the findings on renal biopsy in IgA vasculitis nephritis?

A: The renal biopsy findings in IgA vasculitis nephritis are identical to those in IgA nephropathy (Berger's disease), supporting the concept that these conditions represent different manifestations of the same underlying IgA-mediated immune dysregulation.

Light microscopy:

• Mesangial hypercellularity (mesangial proliferation)
• Cellular crescents in severe cases (> 50% crescents = poor prognosis)
• Variable degrees of endocapillary proliferation
• Tubular atrophy and interstitial fibrosis in chronic cases

Immunofluorescence (pathognomonic):

• Predominant IgA deposition in the mesangium (bright, granular pattern)
• This is the diagnostic hallmark
• C3 complement co-deposition common
• IgG, IgM may be present but less prominent than IgA

Electron microscopy:

• Electron-dense deposits (immune complexes) in the mesangium
• Subendothelial deposits in severe disease
• Foot process effacement if nephrotic syndrome

Histological grading (ISKDC or Oxford classification) guides treatment decisions and provides prognostic information.

Q4: Explain the pathophysiology of IgA vasculitis.

A: IgA vasculitis is a Type III hypersensitivity reaction mediated by IgA-containing immune complexes.

Step 1 - Aberrant IgA1 production: Patients produce abnormal IgA1 with defective O-glycosylation in the hinge region, specifically galactose-deficient IgA1. The deficient galactosylation exposes underlying N-acetylgalactosamine (GalNAc) residues.

Step 2 - Auto-antibody formation: These exposed GalNAc residues are recognized as antigenic, triggering production of IgG or IgA antibodies against the patient's own defective IgA1.

Step 3 - Immune complex formation: The interaction between galactose-deficient IgA1 and anti-glycan antibodies creates large, polymeric immune complexes. Infectious triggers (viral or bacterial) may provide additional antigens incorporated into these complexes.

Step 4 - Vascular deposition: These immune complexes deposit preferentially in small vessels (postcapillary venules) due to haemodynamic factors and size characteristics, particularly in skin, kidney, gut, and joints.

Step 5 - Complement activation: Deposited complexes activate the alternative complement pathway, generating C3a and C5a anaphylatoxins, which recruit neutrophils to the vessel wall.

Step 6 - Vessel injury: Activated neutrophils release proteolytic enzymes and reactive oxygen species, causing leukocytoclastic vasculitis - characterized by fibrinoid necrosis and fragmented neutrophil nuclei ("nuclear dust") in and around inflamed vessels.

The end result is purpura (skin), arthritis (synovium), abdominal pain (intestinal vessels), and glomerulonephritis (kidney).

Q5: A child with IgA vasculitis has severe abdominal pain. What are your concerns and management?

A: Severe abdominal pain in IgA vasculitis raises several important concerns requiring systematic assessment:

Immediate concerns:

1. Intussusception (2-5% incidence) - most serious GI complication
2. Bowel perforation (less than 1%) - life-threatening
3. Massive GI bleeding - may require transfusion
4. Bowel ischaemia - from severe vasculitis

Assessment:

• History: Character of pain (colicky suggests intussusception), vomiting, bloody stools
• Examination: Focal tenderness, palpable mass, peritonism, rectal examination
• Investigations:
  • Abdominal ultrasound (intussusception, free fluid, bowel wall thickening)
  • FBC (anaemia from bleeding)
  • Group and save (if bleeding)
  • Surgical consultation

Management approach:

If intussusception confirmed:

• Nil by mouth, IV fluids
• Urgent surgical consultation
• Attempt air enema reduction (though less successful than in classic intussusception because IgAV causes ileoileal rather than ileocolic intussusception)
• Surgical reduction if air enema fails
• Corticosteroids (prednisolone or IV methylprednisolone)

If severe pain without surgical complications:

• Analgesia: Opioids if required
• IV fluids: Maintain hydration
• Corticosteroids: High-dose prednisolone (1-2 mg/kg/day) or IV methylprednisolone (10-30 mg/kg/day for 3 days)
  • Evidence supports steroids for symptom relief
  • Rapid improvement in pain usually seen within 24-48 hours
• Nutritional support: Nil by mouth initially, gradual reintroduction
• Monitor: Stool for blood, haemoglobin, vital signs

Red flags requiring urgent surgical review:

• Peritonism, guarding, rebound tenderness
• Palpable mass
• Free air on imaging
• Signs of perforation or bowel ischaemia

Q6: Do steroids prevent renal disease in IgA vasculitis?

A: No. Despite widespread historical use for this indication, high-quality evidence definitively demonstrates that corticosteroids do not prevent the development or progression of renal disease in IgA vasculitis.

Key evidence:

CHART Trial (2013): Randomized controlled trial of 171 children with IgAV randomized to prednisolone 2 mg/kg for 2 weeks vs placebo. Primary outcome was renal involvement at 6 and 12 months. Result: No difference in rates of proteinuria or haematuria between groups.

Cochrane Systematic Review (2023): Meta-analysis of multiple RCTs examining interventions for preventing kidney disease in IgAV. Conclusion: Corticosteroids did not reduce risk of kidney disease at 3, 6, or 12 months.

What steroids DO:

• Reduce severity and duration of abdominal pain (strong evidence)
• Reduce severity and duration of arthritis/arthralgia (strong evidence)
• May reduce duration of rash (weak evidence)

What steroids DO NOT do:

• Prevent nephritis
• Reduce severity of established nephritis (unless severe crescentic GN requiring aggressive immunosuppression)
• Prevent intussusception
• Prevent recurrence
• Alter long-term prognosis

Current recommendations:

• Steroids are for symptom control only, not disease modification
• Indications: Severe abdominal pain, severe arthritis, orchitis
• NOT indicated for mild disease or attempts at "prevention"

For established severe nephritis: High-dose steroids combined with other immunosuppression (cyclophosphamide, mycophenolate) may be beneficial, but this is treatment of severe renal disease, not prevention.

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14. References

Primary Literature

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11. Zhong X, Ding J. Diagnosis and treatment of IgA nephropathy and IgA vasculitis nephritis in Chinese children. Pediatr Nephrol. 2023;38(6):1897-1906. doi:10.1007/s00467-022-05775-3

12. Roache-Robinson P, Killeen RB, Hotwagner DT. IgA Vasculitis (Henoch-Schönlein Purpura). StatPearls. Updated 2025 Jan. PMID:30725937

13. Dudley J, Smith G, Llewelyn-Edwards A, et al. Randomised, double-blind, placebo-controlled trial to determine whether steroids reduce the incidence and severity of nephropathy in Henoch-Schonlein Purpura (HSP). Arch Dis Child. 2013;98(10):756-763. doi:10.1136/archdischild-2013-303642

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