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, characterised by IgA1-dominant immune complex-mediated small vessel vasculitis affecting the skin, joints, gastrointestinal tract, and kidneys. [1,2] The condition results from deposition of galactose-deficient IgA1 (Gd-IgA1) immune complexes in small vessel walls, leading to leucocytoclastic vasculitis. [3]

The classic clinical tetrad comprises: [4]

1. Palpable purpura (100% - mandatory for diagnosis) - non-thrombocytopaenic, predominantly affecting lower extremities and buttocks
2. Arthritis/arthralgia (75%) - typically large joints (knees, ankles)
3. Abdominal pain (50-75%) - colicky, may precede rash
4. Renal involvement (30-50%) - haematuria, proteinuria, nephritis

IgAV predominantly affects children aged 3-15 years (peak incidence 4-6 years), with an annual incidence of 10-20 per 100,000 children. [5] Males are affected more frequently than females (M:F ratio 1.5-2:1). While the disease is typically self-limiting in children (resolving within 4-6 weeks), adult-onset disease tends to be more severe with higher rates of renal involvement and poorer long-term outcomes. [6]

The long-term prognosis is primarily determined by renal involvement, with 1-2% of paediatric cases progressing to end-stage renal disease (ESRD), though this rate is significantly higher (up to 30%) in adults with severe nephritis. [7] Recurrence occurs in approximately 30% of cases, usually within the first 4-6 months and typically following a milder course. [8]

Key Clinical Pearls

"Palpable Purpura on Legs and Buttocks in a Child": Classic presentation in dependent/gravitational areas. The rash is palpable (raised) due to underlying vasculitis, distinguishing it from simple petechiae.

"Normal Platelet Count Excludes ITP": Critical differentiator. HSP has normal platelets, whereas immune thrombocytopaenia (ITP) presents with thrombocytopaenia despite similar purpuric rash.

"The Kidney Determines the Future": While most manifestations resolve, renal involvement dictates long-term prognosis. Persistent nephritis requires prolonged monitoring and may necessitate immunosuppression.

"Ileo-Ileal Intussusception is the Surgical Emergency": Unlike typical ileocolic intussusception in children, HSP causes ileo-ileal intussusception in 1-5% of cases, which may not reduce with air enema and requires surgical intervention. [9]

"Abdominal Pain May Precede Rash": In 15-30% of cases, GI symptoms appear before the characteristic purpura, creating diagnostic challenges and potential for misdiagnosis as acute abdomen. [10]

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2. Epidemiology

Incidence and Prevalence

Demographics

Exam Detail: MRCP/MRCPCH Examination Points:

• Be able to quote the incidence (10-20/100,000 children)
• Know the peak age (4-6 years) and that 90% occur less than 10 years
• Understand the male predominance (1.5-2:1)
• Recognise seasonal clustering (autumn/winter, post-URTI)
• Appreciate that adult disease has poorer prognosis

Precipitating and Associated Factors

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3. Aetiology and Pathophysiology

Molecular Pathogenesis

IgA Vasculitis results from a complex interplay of genetic susceptibility, environmental triggers, and immune dysregulation leading to production and deposition of pathogenic IgA1-containing immune complexes. [3,12]

Step 1: Genetic Predisposition

Step 2: Environmental Trigger

• Upper respiratory tract infections (most common, ~50% of cases) expose the immune system to bacterial/viral antigens
• Molecular mimicry: Microbial antigens may share epitopes with host tissues
• Leads to mucosal immune system activation in the respiratory or GI tract

Step 3: Aberrant IgA1 Production

Central pathogenic mechanism: Production of galactose-deficient IgA1 (Gd-IgA1). [3]

Normal IgA1 Glycosylation:

• IgA1 has a hinge region with O-linked glycans
• Normal glycosylation includes galactose residues attached to N-acetylgalactosamine (GalNAc)

Abnormal Glycosylation in IgAV:

• Deficiency of β1,3-galactosyltransferase enzyme
• Results in undergalactosylated IgA1 (Gd-IgA1)
• Exposes GalNAc residues that are normally hidden
• These exposed GalNAc residues are antigenic

Step 4: Autoantibody Formation

• The exposed GalNAc on Gd-IgA1 triggers production of anti-glycan antibodies (IgG or IgA class)
• These antibodies bind to Gd-IgA1, forming circulating immune complexes (ICs)
• The ICs are of large molecular weight and have altered clearance

Step 5: Immune Complex Deposition

Site-Specific Deposition:

Why Dependent Areas?

• Hydrostatic pressure in lower extremities increases vascular permeability
• Enhanced IC deposition in gravitational-dependent zones (legs, buttocks)
• Explains the characteristic "symmetrical lower limb purpura" pattern

Step 6: Complement Activation and Inflammation

• Deposited IgA1-containing ICs activate the alternative complement pathway (not classical pathway)
• C3 deposition (C4 typically normal)
• Generates anaphylatoxins (C3a, C5a) → neutrophil recruitment
• Leucocytoclastic vasculitis: Neutrophils release proteolytic enzymes → vessel wall necrosis → extravasation of RBCs → purpura

Step 7: Vascular Injury and Clinical Disease

• Endothelial activation with upregulation of adhesion molecules (ICAM-1, VCAM-1)
• Fibrinoid necrosis of vessel walls
• Extravasation of erythrocytes → palpable purpura
• Increased vascular permeability → oedema, haemorrhage

Exam Detail: Viva Question: "What is the fundamental defect in IgA Vasculitis?"

Model Answer: "The fundamental defect is the production of galactose-deficient IgA1 due to reduced activity of β1,3-galactosyltransferase. This abnormal glycosylation exposes N-acetylgalactosamine residues in the hinge region of IgA1, which become antigenic. Anti-glycan antibodies then bind to these Gd-IgA1 molecules, forming large immune complexes. These complexes deposit in small vessel walls—particularly in the skin, kidneys, GI tract, and joints—where they activate the alternative complement pathway, leading to leucocytoclastic vasculitis and the clinical manifestations of the disease."

Key Point for Exams: The pathophysiology is identical to IgA nephropathy in terms of the glomerular lesion (both show mesangial IgA deposition); however, IgAV is a systemic disease with extrarenal manifestations.

Histopathology

Critical Diagnostic Feature:

• IgA dominance or co-dominance on immunofluorescence is the hallmark
• If IgG or IgM are dominant, consider alternative diagnoses (e.g., lupus nephritis, infection-related GN)

Renal Histological Classification: The International Study of Kidney Disease in Children (ISKDC) Classification grades severity: [14]

• Grade I: Minimal alterations (isolated mesangial proliferation)
• Grade II: Mesangial proliferation (less than 50% crescents)
• Grade IIIa: Focal proliferative GN with less than 50% crescents
• Grade IIIb: Diffuse proliferative GN with less than 50% crescents
• Grade IV: Mesangial proliferative GN with 50-75% crescents
• Grade V: Mesangial proliferative GN with > 75% crescents
• Grade VI: Membranoproliferative-like GN

Higher grades (IV-VI) correlate with worse renal prognosis.

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4. Clinical Presentation

Classic Tetrad (Revised for Comprehensive Detail)

1. Cutaneous Manifestations (95-100% - Mandatory for Diagnosis)

Palpable Purpura:

• Appearance: Non-blanching, raised (palpable due to vasculitis), red-to-purple macules/papules
• Evolution: Initially urticarial or erythematous → purpuric → may become ecchymotic or necrotic (rare)
• Distribution:
  • "Symmetrical and dependent areas: Lower extremities (legs, ankles), buttocks"
  • Extensor surfaces > flexor surfaces
  • May involve upper extremities, trunk, face (less common)
• Size: 2-10 mm diameter, may coalesce
• Associated features: Perilesional oedema, pruritus (occasionally)
• Crops: Appear in crops over days to weeks; individual lesions fade in 7-10 days
• Triggering factors: Standing/walking exacerbates; leg elevation improves

Other Cutaneous Features:

• Subcutaneous oedema: Particularly face (periorbital), hands, feet, scrotum
• Bullous lesions: Rare; associated with severe disease
• Ulceration/necrosis: Very rare; suggests severe vasculitis

Exam Detail: OSCE Examination Scenario:

Station: Examine this 6-year-old child who presented with a rash on the legs.

Findings:

• Multiple non-blanching, palpable purpuric lesions on bilateral lower legs and buttocks
• Symmetrical distribution
• Lesions of varying ages (some fresh, some fading)
• No facial/truncal involvement
• No lymphadenopathy or hepatosplenomegaly
• Periarticular swelling of ankles

Examiner Question: "What is your differential diagnosis?"

Model Answer: "The key finding is palpable purpura in a symmetrical distribution on dependent areas. The differential includes:

1. IgA Vasculitis (HSP) - most likely given age, distribution, and palpability
2. Meningococcal septicaemia - excluded by lack of systemic toxicity
3. Immune thrombocytopaenia - would have non-palpable petechiae/purpura
4. Acute leukaemia - would expect other systemic features

I would confirm the diagnosis by checking a normal platelet count, performing urinalysis for renal involvement, and assessing for GI and joint symptoms."

2. Musculoskeletal Manifestations (60-84%)

Arthritis/Arthralgia:

• Pattern: Oligoarticular (1-4 joints)
• Joints affected: Large joints predominantly
  • Knees and ankles (most common, ~75%)
  • Wrists, elbows (less common)
  • Small joints of hands/feet (rare)
• Characteristics:
  • Painful and swollen with periarticular oedema
  • Non-erosive, non-deforming (unlike rheumatoid arthritis)
  • Transient (resolves within days to weeks, no sequelae)
  • Migratory pattern may occur
• Functional impact: May limit mobility, cause limping/refusal to walk in children
• Timing: Often one of the first manifestations; may precede rash in 15% of cases

Myalgia:

• Diffuse muscle pain, particularly lower limbs
• No true myositis on investigation

3. Gastrointestinal Manifestations (50-75%)

Abdominal Pain:

• Incidence: 50-75% of cases
• Character: Colicky, cramping pain
• Location: Typically periumbilical or diffuse; may localize to RLQ (mimicking appendicitis)
• Severity: Ranges from mild discomfort to severe, incapacitating pain
• Timing: May precede rash in 15-30% of cases → diagnostic dilemma

GI Bleeding:

• Occult blood: Positive faecal occult blood test in ~50% with GI involvement
• Overt bleeding:
  • "Haematemesis: Coffee-ground vomitus or frank haematemesis"
  • Melaena or haematochezia: "Redcurrant jelly" stool (suggests intussusception)
• Severity: Usually mild; massive bleeding rare but reported

Other GI Manifestations:

• Nausea and vomiting (common)
• Diarrhoea (may be bloody)
• Protein-losing enteropathy (rare)
• Pancreatitis (rare)
• Cholecystitis (rare)

Intussusception (1-5% of cases):

• Type: Typically ileo-ileal (unlike typical ileocolic intussusception in children) [9]
• Mechanism: Submucosal haemorrhage and oedema act as lead point
• Presentation: Severe colicky abdominal pain, vomiting, "redcurrant jelly" stool, palpable abdominal mass
• Diagnosis: Abdominal ultrasound ("target" or "doughnut" sign)
• Management: Air/contrast enema may not be successful for ileo-ileal intussusception; surgical reduction often required

Bowel Ischaemia/Perforation (Rare but Serious):

• Due to severe vasculitis of mesenteric vessels
• Presents with peritonism, sepsis
• Requires emergency surgical intervention

Clinical Pearl: Red Flag: Severe Abdominal Pain Before Rash

When a child presents with severe abdominal pain before the characteristic rash appears, consider HSP in the differential. The absence of rash makes diagnosis challenging. Investigations may show:

• Normal platelet count
• Mildly elevated inflammatory markers
• Positive faecal occult blood
• Ultrasound: Bowel wall thickening, free fluid

Management Dilemma: Surgical teams may be involved to exclude acute abdomen (appendicitis, intussusception). The appearance of purpuric rash over subsequent 24-72 hours clinches the diagnosis.

4. Renal Manifestations (30-50%)

Incidence and Timing:

• Occurs in 30-50% of paediatric cases
• Usually develops within 4 weeks of rash onset (90% within 3 months)
• Can occur up to 6 months after rash resolution (hence need for prolonged monitoring)

Spectrum of Renal Involvement:

Clinical Features:

• Often asymptomatic (discovered on urinalysis screening)
• Macroscopic haematuria (tea-/cola-coloured urine) in minority
• Hypertension (if significant glomerular involvement)
• Oedema (periorbital, peripheral if nephrotic)
• Oliguria/anuria (in severe AKI)

Prognostic Indicators for Renal Outcomes:

Poor Prognostic Factors: [7,14]

• Nephrotic-range proteinuria at onset
• Nephritic syndrome
• Persistent proteinuria > 1 g/day after 3 months
• Renal impairment at presentation
• Severe histology (ISKDC Grade IV-VI): crescentic GN
• Adult age
• Delayed treatment

Good Prognostic Factors:

• Isolated microscopic haematuria
• Transient proteinuria less than 1 g/day
• Mild histological changes (ISKDC Grade I-II)
• Early treatment of severe nephritis

Exam Detail: Viva Question: "How does IgA Vasculitis nephritis differ from IgA nephropathy?"

Model Answer:

"Both conditions share identical glomerular pathology—mesangial IgA deposition on immunofluorescence and mesangial proliferative glomerulonephritis on light microscopy. The fundamental difference is:

• IgA Vasculitis (HSP nephritis) is a systemic vasculitis with extrarenal manifestations (purpura, arthritis, GI involvement). Renal disease is part of a multi-system disorder.

• IgA Nephropathy is a renal-limited disease without extrarenal features. It is the most common primary glomerulonephritis worldwide.

Some authorities consider them part of a spectrum of IgA-mediated disease, with the possibility that IgAN represents a forme fruste of IgAV confined to the kidneys. However, current classification treats them as distinct entities. Notably, the long-term renal prognosis is similar in both conditions when matched for initial severity."

Other Manifestations

Genitourinary (Beyond Renal)

Orchitis/Scrotal Involvement (2-35% of boys): [15]

• Presentation: Testicular pain, swelling, tenderness; scrotal oedema; may be unilateral or bilateral
• Mechanism: Vasculitis of testicular/epididymal vessels
• Differential Diagnosis: Critical to exclude testicular torsion (requires urgent surgical exploration)
• Diagnosis:
  • "Doppler ultrasound: Increased blood flow (orchitis) vs decreased flow (torsion)"
  • Presence of HSP rash aids diagnosis
• Management: Analgesia; scrotal support; usually self-limiting
• Prognosis: Generally resolves without long-term sequelae; rare cases of testicular atrophy

Central Nervous System (Rare, less than 1%)

• Headache (most common CNS symptom; often benign)
• Seizures (generalized or focal)
• Altered consciousness, encephalopathy
• Stroke (ischaemic or haemorrhagic due to CNS vasculitis)
• Posterior reversible encephalopathy syndrome (PRES) (associated with hypertension)
• Intracerebral haemorrhage (very rare)

Investigation: MRI brain (may show vasculitis, ischaemia, haemorrhage)

Pulmonary (Very Rare, less than 1%)

• Pulmonary haemorrhage (life-threatening)
• Interstitial lung disease
• Requires aggressive immunosuppression

Cardiac (Very Rare)

• Myocarditis, pericarditis
• Coronary arteritis (case reports)

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5. Investigations

Diagnostic Criteria

EULAR/PRINTO/PRES Criteria (2010): [4]

Diagnosis of IgA Vasculitis requires:

• Palpable purpura (mandatory criterion)

PLUS at least ONE of:

1. Abdominal pain (diffuse, colicky)
2. Arthritis (acute, any joint) or Arthralgia
3. Renal involvement (haematuria and/or proteinuria)
4. Histology showing leucocytoclastic vasculitis with predominant IgA deposition OR proliferative glomerulonephritis with predominant IgA deposition

Sensitivity: 100%; Specificity: 87% (for childhood vasculitis)

Exam Detail: MRCP Question Scenario:

A 5-year-old boy presents with a purpuric rash on his legs and buttocks, knee pain, and colicky abdominal pain. His platelet count is 250 × 10⁹/L. Urinalysis shows 2+ blood and 1+ protein.

Which ONE of the following is MANDATORY for diagnosis? A. Renal biopsy showing IgA deposition B. Palpable purpura C. Elevated serum IgA D. Low complement C3 E. Positive ANCA

Answer: B. Palpable purpura

Palpable purpura is the mandatory criterion in the EULAR/PRINTO/PRES criteria. The patient also fulfils additional criteria (arthralgia, abdominal pain, renal involvement), making the diagnosis highly likely. Normal platelets exclude ITP.

Laboratory Investigations

Essential First-Line Tests:

Supportive/Additional Tests:

Tests to Exclude Differentials:

Imaging

Biopsy

Skin Biopsy:

• Indication: Atypical presentation; diagnostic uncertainty
• Technique:
  • Biopsy fresh lesion (less than 24-48 hours old) for histology
  • Separate sample for direct immunofluorescence (DIF) (requires special transport medium)
• Findings:
  • "Light microscopy: Leucocytoclastic vasculitis (neutrophilic infiltration of vessel walls, nuclear debris/karyorrhexis, fibrinoid necrosis, RBC extravasation)"
  • "Immunofluorescence: IgA deposition (predominant or co-dominant) in dermal vessel walls; C3 usually positive; IgG/IgM may be present but not dominant"
• Note: Typically not required if classic clinical presentation

Renal Biopsy:

• Indications: [14]
  • Nephrotic syndrome (proteinuria > 3.5 g/day or > 40 mg/m²/hr in children)
  • Nephritic syndrome (haematuria, proteinuria, hypertension, AKI)
  • Acute kidney injury (rising creatinine, oliguria)
  • Persistent significant proteinuria (> 1 g/day for > 3 months)
  • Declining renal function
• Findings:
  • "Light microscopy: Mesangial proliferative GN; endocapillary proliferation; crescents (in severe cases); interstitial inflammation; tubular atrophy (chronic)"
  • "Immunofluorescence: IgA dominant or co-dominant mesangial deposition; C3 positive; kappa and lambda light chains (polyclonal)"
  • "Electron microscopy: Mesangial electron-dense deposits"
• ISKDC Grading: Guides prognosis and treatment intensity
• Role: Helps stratify severity, guide immunosuppressive therapy, provide prognostic information

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6. Differential Diagnosis

Clinical Pearl: The "Normal Platelet Count" Manoeuvre:

When seeing a child with purpura/petechiae, the first reflex test should be a platelet count. This single test immediately narrows the differential:

• Platelets NORMAL → Vasculitis (IgAV most common in children), infection (meningococcal), NAI
• Platelets LOW → ITP, leukaemia, TTP, HUS, consumptive coagulopathy, aplastic anaemia

In the context of a purpuric rash with systemic features (arthritis, abdominal pain, renal involvement), normal platelets strongly suggest IgA Vasculitis.

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7. Management

Management Algorithm

┌─────────────────────────────────────────────────────────────┐
│         SUSPECTED IgA VASCULITIS (HSP)                      │
│   (Palpable purpura ± arthritis/abdominal pain/haematuria)  │
└────────────────────┬────────────────────────────────────────┘
                     ↓
┌─────────────────────────────────────────────────────────────┐
│             IMMEDIATE ASSESSMENT                            │
│  • Confirm palpable purpura (examine skin, note distribution)│
│  • Exclude life-threatening differentials:                  │
│    - Meningococcal septicaemia (sepsis, meningism)          │
│    - Acute leukaemia (pancytopaenia, hepatosplenomegaly)    │
│  • Assess severity of organ involvement:                    │
│    - GI: severity of pain, bleeding, peritonism             │
│    - Renal: urinalysis, BP, fluid status                    │
│    - Joints: functional impairment                          │
│    - Scrotal: exclude torsion if orchitis                   │
└────────────────────┬────────────────────────────────────────┘
                     ↓
┌─────────────────────────────────────────────────────────────┐
│           DIAGNOSTIC INVESTIGATIONS                         │
│  Essential:                                                 │
│  • FBC (NORMAL PLATELET COUNT differentiates from ITP)      │
│  • Coagulation screen (PT, APTT - normal)                   │
│  • U&Es, creatinine (renal function)                        │
│  • Urinalysis + Urine PCR (ESSENTIAL - renal involvement)   │
│  • Blood pressure                                           │
│  • Stool occult blood (if GI symptoms)                      │
│  • ESR/CRP (non-specific)                                   │
│  Additional (if indicated):                                 │
│  • Serum albumin (if nephrotic/protein-losing enteropathy)  │
│  • Complement C3/C4 (normal - excludes SLE/PSGN)            │
│  • Abdominal US (if severe GI pain - intussusception?)      │
│  • Scrotal Doppler US (if testicular pain - torsion?)       │
└────────────────────┬────────────────────────────────────────┘
                     ↓
┌─────────────────────────────────────────────────────────────┐
│       CONFIRM DIAGNOSIS (EULAR/PRINTO/PRES Criteria)        │
│  Palpable purpura (mandatory)                               │
│  + ≥1 of: Abdominal pain, Arthritis/arthralgia,             │
│           Renal involvement, IgA on biopsy                  │
└────────────────────┬────────────────────────────────────────┘
                     ↓
┌─────────────────────────────────────────────────────────────┐
│            STRATIFY DISEASE SEVERITY                        │
│                                                             │
│  ┌─────────────────────────────────────────────────────┐   │
│  │ MILD (Majority of cases)                            │   │
│  │ • Rash (purpura without ulceration/necrosis)        │   │
│  │ • Mild arthralgia (able to mobilize)                │   │
│  │ • No/minimal GI symptoms (no bleeding)              │   │
│  │ • No renal involvement OR isolated microscopic      │   │
│  │   haematuria without proteinuria                    │   │
│  └─────────────────────────────────────────────────────┘   │
│                                                             │
│  ┌─────────────────────────────────────────────────────┐   │
│  │ MODERATE                                            │   │
│  │ • Moderate-severe arthritis (limiting mobility)     │   │
│  │ • Moderate GI pain (requiring analgesia)            │   │
│  │ • Mild renal involvement (haematuria + proteinuria  │   │
│  │   less than 1 g/day, normal renal function, normotensive)    │   │
│  └─────────────────────────────────────────────────────┘   │
│                                                             │
│  ┌─────────────────────────────────────────────────────┐   │
│  │ SEVERE                                              │   │
│  │ • GI bleeding (haematemesis, melaena)               │   │
│  │ • Intussusception                                   │   │
│  │ • Bowel perforation/ischaemia                       │   │
│  │ • Nephrotic syndrome (proteinuria > 3.5 g/day)       │   │
│  │ • Nephritic syndrome (haematuria, proteinuria,      │   │
│  │   hypertension, oedema, AKI)                        │   │
│  │ • Rapidly progressive GN (RPGN)                     │   │
│  │ • Orchitis with suspected torsion                   │   │
│  │ • CNS involvement (seizures, stroke, encephalopathy)│   │
│  │ • Pulmonary haemorrhage                             │   │
│  └─────────────────────────────────────────────────────┘   │
└────────────────────┬────────────────────────────────────────┘
                     ↓
┌─────────────────────────────────────────────────────────────┐
│                   TREATMENT                                 │
└─────────────────────────────────────────────────────────────┘

┌───────────────────────────────────────────────────────────┐
│  MILD DISEASE (Outpatient Management)                     │
├───────────────────────────────────────────────────────────┤
│  • **Supportive Care** (Mainstay)                         │
│    - Rest, adequate hydration (oral fluids)               │
│    - Analgesia: Paracetamol 15 mg/kg QDS                  │
│    - Avoid NSAIDs (theoretical GI/renal concerns)         │
│    - Leg elevation (reduces dependent oedema/purpura)     │
│  • **Reassurance**                                        │
│    - Self-limiting disease (resolves in 4-6 weeks)        │
│    - Rash will fade; joints will recover fully            │
│  • **Safety-netting**                                     │
│    - Return if: severe abdominal pain, vomiting, bloody   │
│      stools, reduced urine output, scrotal pain           │
│  • **Monitoring** (see below)                             │
└───────────────────────────────────────────────────────────┘

┌───────────────────────────────────────────────────────────┐
│  MODERATE DISEASE (Consider Admission)                    │
├───────────────────────────────────────────────────────────┤
│  • **Moderate-Severe Joint Symptoms**                     │
│    - **Oral Corticosteroids**: [16]                       │
│      Prednisolone 1-2 mg/kg/day (max 60 mg/day)           │
│      Duration: 1-2 weeks, then taper over 1-2 weeks       │
│    - Speeds resolution of arthritis and abdominal pain    │
│    - **Does NOT prevent nephritis or improve renal        │
│      outcomes** (evidence from RCTs) [17]                 │
│  • **Moderate GI Pain** (no bleeding)                     │
│    - Oral prednisolone (as above)                         │
│    - IV fluids if vomiting/unable to tolerate oral        │
│    - Monitor for complications (intussusception)          │
│  • **Mild Renal Involvement** (haematuria + proteinuria   │
│    less than 1 g/day)                                              │
│    - Supportive care                                      │
│    - Monitor urinalysis weekly → monthly (see below)      │
│    - Consider ACE inhibitor/ARB if persistent proteinuria │
│      (reduces proteinuria, renoprotective)                │
└───────────────────────────────────────────────────────────┘

┌───────────────────────────────────────────────────────────┐
│  SEVERE DISEASE (Hospital Admission Required)             │
├───────────────────────────────────────────────────────────┤
│  • **Severe GI Symptoms** (bleeding, severe pain)         │
│    - **IV Corticosteroids**: Methylprednisolone 1-2 mg/kg │
│      IV daily (or IV hydrocortisone)                      │
│    - NBM (nil by mouth) initially                         │
│    - IV fluids, electrolyte replacement                   │
│    - Monitor haemoglobin (GI bleeding)                    │
│    - Surgical consult if:                                 │
│      → Suspected intussusception (US diagnosis; air/barium│
│         enema reduction; surgical reduction if fails)     │
│      → Peritonism (perforation, ischaemia)                │
│                                                           │
│  • **Significant Renal Involvement**                      │
│    **Refer urgently to Paediatric Nephrology/Rheumatology**│
│                                                           │
│    - **Isolated Haematuria/Mild Proteinuria (less than 1 g/day):** │
│      → Supportive care, close monitoring                  │
│                                                           │
│    - **Nephrotic Syndrome** (proteinuria > 3.5 g/day):     │
│      → Renal biopsy (assess severity - ISKDC grading)     │
│      → High-dose corticosteroids:                         │
│         Prednisolone 2 mg/kg/day (max 60 mg) or pulse IV  │
│         methylprednisolone 10-30 mg/kg (max 1 g) for 3 days│
│      → Consider immunosuppression if steroid-resistant:   │
│         • Azathioprine 2-3 mg/kg/day, or                  │
│         • Mycophenolate Mofetil (MMF) 600 mg/m² BD, or    │
│         • Cyclophosphamide (for crescentic GN/RPGN)       │
│           2 mg/kg/day PO or IV pulses 500-750 mg/m²       │
│      → ACE inhibitor/ARB (renoprotective, reduce          │
│         proteinuria): e.g., Enalapril 0.1 mg/kg/day       │
│      → Supportive: Diuretics (if oedema), salt restriction│
│                                                           │
│    - **Nephritic Syndrome / AKI / RPGN (Crescentic GN):** │
│      → Renal biopsy (urgent - high-grade ISKDC)           │
│      → **Aggressive immunosuppression**: [18]             │
│         • High-dose IV methylprednisolone (pulse therapy) │
│         • Cyclophosphamide IV (induction)                 │
│         • Consider plasma exchange (if severe RPGN)       │
│         • Maintenance: Azathioprine or MMF                │
│      → Renal replacement therapy (dialysis) if ESRD       │
│                                                           │
│  • **Orchitis** (Testicular Pain)                         │
│    - Urgent **scrotal Doppler ultrasound** to exclude     │
│      testicular torsion (surgical emergency)              │
│    - If orchitis confirmed (not torsion):                 │
│      → Analgesia, scrotal support, rest                   │
│      → Consider corticosteroids (prednisolone)            │
│                                                           │
│  • **CNS Involvement**                                    │
│    - MRI brain, neurology consult                         │
│    - High-dose corticosteroids ± cyclophosphamide         │
│    - Anticonvulsants if seizures                          │
│    - Manage hypertension (if PRES)                        │
│                                                           │
│  • **Pulmonary Haemorrhage**                              │
│    - ICU admission, ventilatory support                   │
│    - High-dose IV corticosteroids                         │
│    - Cyclophosphamide                                     │
│    - Consider plasma exchange, rituximab                  │
└───────────────────────────────────────────────────────────┘

                     ↓
┌─────────────────────────────────────────────────────────────┐
│                MONITORING (ESSENTIAL)                       │
├─────────────────────────────────────────────────────────────┤
│  **ACUTE PHASE (First 4-6 weeks)**                          │
│  • Weekly urinalysis + Urine PCR                            │
│  • Weekly BP measurement                                    │
│  • Monitor for new/worsening symptoms (GI, renal, joints)   │
│  • If on corticosteroids: monitor weight, BP, glucose       │
│                                                             │
│  **FOLLOW-UP (3-6 months after resolution of rash)**        │
│  • Monthly urinalysis + Urine PCR for 3-6 months            │
│  • Some guidelines recommend up to 6-12 months [8]          │
│  • Rationale: Nephritis can develop AFTER initial illness   │
│    resolves (up to 6 months post-rash)                      │
│  • If persistent haematuria/proteinuria → extend monitoring │
│                                                             │
│  **LONG-TERM (If Renal Involvement)**                       │
│  • Annual BP + urinalysis for 5 years (some say lifelong)   │
│  • Women with history of HSP nephritis: counsel re:         │
│    increased pregnancy complications (pre-eclampsia, IUGR); │
│    close antenatal monitoring                               │
└─────────────────────────────────────────────────────────────┘

                     ↓
┌─────────────────────────────────────────────────────────────┐
│              RECURRENCE (30% of cases) [8]                  │
│  • Usually milder than initial episode                      │
│  • Typically occurs within 4-6 months of first episode      │
│  • Manage as per initial episode (based on severity)        │
│  • Does NOT predict worse long-term renal outcome           │
└─────────────────────────────────────────────────────────────┘

Evidence for Treatment Approaches

Corticosteroids for Joint/GI Symptoms:

• RCTs show: Steroids provide faster resolution of arthritis and abdominal pain [16]
• RCTs show: Steroids do NOT prevent development of nephritis or improve renal outcomes [17]
• Current practice: Use steroids for symptomatic relief in moderate-severe joint/GI disease, NOT as prophylaxis against nephritis

Corticosteroids for Renal Disease:

• Mild nephritis (isolated haematuria, mild proteinuria): No benefit from steroids
• Moderate-severe nephritis (nephrotic/nephritic syndrome): High-dose steroids recommended [18]
• Crescentic GN: Combination of steroids + cyclophosphamide improves outcomes [18]

Immunosuppression:

• Azathioprine, MMF, Cyclophosphamide: Used for steroid-resistant or severe nephritis (particularly crescentic GN) [18]
• Plasma exchange: Case reports/series suggest benefit in severe RPGN; no high-quality RCT data

ACE Inhibitors/ARBs:

• Reduce proteinuria, renoprotective effect
• Recommended for persistent proteinuria > 1 g/day

Evidence Debate: Controversial Area: Early Corticosteroids to Prevent Nephritis?

Historical Practice: Some clinicians gave early corticosteroids (within 72 hours of rash) to all patients in hopes of preventing nephritis.

Current Evidence: Multiple RCTs (including the SHARE initiative) have shown that early corticosteroids do NOT prevent nephritis development or improve long-term renal outcomes. [17]

Current Consensus: Corticosteroids should be reserved for:

1. Symptomatic relief (moderate-severe arthritis, abdominal pain)
2. Treatment of established nephritis (nephrotic/nephritic syndrome)

Not Indicated: Routine prophylactic steroids in all patients with HSP.

Multidisciplinary Team (MDT) Involvement

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8. Complications

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9. Prognosis and Outcomes

Overall Prognosis

Factors Influencing Renal Prognosis

Poor Prognostic Factors: [7,14]

• Age: Adults > children
• Presentation:
  • Nephrotic-range proteinuria (> 3.5 g/day) at onset
  • Nephritic syndrome (haematuria, proteinuria, hypertension, AKI)
  • Acute kidney injury
• Persistence: Proteinuria > 1 g/day beyond 3 months
• Histology (renal biopsy):
  • Crescentic GN (ISKDC Grade IV-VI)

  • 50% glomeruli with crescents

  • Tubulointerstitial fibrosis, glomerulosclerosis (chronicity markers)
• Treatment delay: Delayed initiation of immunosuppression in severe nephritis

Good Prognostic Factors:

• Young age (children 3-10 years)
• Isolated microscopic haematuria (without proteinuria)
• Transient, mild proteinuria (less than 1 g/day) resolving within 3 months
• Mild histology (ISKDC Grade I-II)
• Early treatment (if severe nephritis)

Long-Term Outcomes (Renal)

Paediatric Studies: [7]

• 10-year follow-up: ~85-90% of children with nephritis have normal renal function
• 20-year follow-up: ~80% have normal renal function; 1-2% progress to ESRD
• Risk of ESRD: Overall 1-2% in paediatric cohorts; up to 10-15% in those with severe initial nephritis

Adult Studies: [6]

• 5-year follow-up: ~50% of adults with nephritis have persistent urinary abnormalities
• ESRD: Up to 30% of adults with severe nephritis progress to ESRD over 15-20 years

Women with History of HSP Nephritis:

• Increased risk of pregnancy complications: pre-eclampsia, intrauterine growth restriction (IUGR), preterm delivery [19]
• Antenatal monitoring recommended: serial BP, urinalysis, renal function
• Counsel regarding risks prior to conception

Recurrence

• Incidence: ~30% of cases [8]
• Timing: Typically within 4-6 months of initial episode
• Severity: Usually milder than first episode
• Prognosis: Recurrence does not predict worse long-term renal outcome
• Triggers: May follow URTI, as with initial episode
• Management: Same approach as initial episode (supportive vs steroids based on severity)

Exam Detail: MRCP Viva Question: "What determines the long-term prognosis in IgA Vasculitis?"

Model Answer:

"The long-term prognosis in IgA Vasculitis is primarily determined by the severity of renal involvement. The cutaneous, joint, and GI manifestations typically resolve completely within 4-6 weeks without sequelae. However, nephritis—which occurs in 30-50% of patients—can lead to chronic kidney disease.

Poor prognostic renal factors include:

1. Nephrotic-range proteinuria (> 3.5 g/day) at presentation
2. Nephritic syndrome with AKI
3. Persistent proteinuria > 1 g/day beyond 3 months
4. Severe histology on renal biopsy, particularly crescentic GN (ISKDC Grade IV-VI)
5. Adult age at onset

Overall, 1-2% of children progress to end-stage renal disease, whereas this figure is significantly higher—up to 30%—in adults with severe nephritis. This underscores the importance of long-term urinalysis monitoring (monthly for 3-6 months, then annually for 5 years) to detect late-developing or progressive nephritis.

Recurrence occurs in ~30% of cases but is usually milder and does not worsen long-term renal prognosis."

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10. Prevention and Screening

Primary Prevention

No established primary prevention strategy exists for IgA Vasculitis, as the exact aetiology is unknown. [1]

General Measures:

• Infection control: Good hygiene, handwashing (may reduce URTI triggers)
• Prompt treatment of streptococcal pharyngitis: Antibiotics for confirmed Group A Strep (unclear if this prevents IgAV; treats infection itself)

Avoidance of Triggers:

• In patients with previous IgAV, some clinicians advise caution with medications implicated in triggering disease (certain antibiotics, NSAIDs), though evidence is weak

Screening and Monitoring

During Acute Illness:

• Urinalysis: Weekly during acute phase (first 4-6 weeks)
• BP monitoring: Weekly
• Renal function: If any urinary abnormalities or hypertension

Post-Resolution:

• Urinalysis: Monthly for 3-6 months after rash resolution
• Extended monitoring: Some guidelines recommend 6-12 months, as late-onset nephritis can occur [8]
• Annual checks: If persistent urinary abnormalities, continue annual BP and urinalysis for 5 years (some say lifelong)

Special Populations:

• Women with history of HSP nephritis: Pre-pregnancy counselling; close antenatal monitoring (BP, urinalysis, renal function) due to increased risk of pre-eclampsia and IUGR [19]

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11. Evidence and Guidelines

Key Guidelines

Landmark Studies

Evidence Levels

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12. Patient and Layperson Explanation

What is IgA Vasculitis (Henoch-Schönlein Purpura)?

IgA Vasculitis (formerly called Henoch-Schönlein Purpura or HSP) is a condition where small blood vessels become inflamed (vasculitis). This inflammation causes a characteristic rash and can affect the joints, tummy, and kidneys. It is the most common type of vasculitis in children and usually occurs after a viral infection like a cold.

What causes it?

The exact cause is unknown, but IgA Vasculitis often happens after an infection (such as a sore throat or cold). The body's immune system produces abnormal antibodies (called IgA) that form clumps (immune complexes) and get stuck in small blood vessels, causing inflammation.

What are the symptoms?

The main features are:

1. Rash (Purpura):

   • Small, raised, purple-red spots that don't fade when you press on them
   • Usually appear on the legs, buttocks, and sometimes arms
   • Comes and goes in "crops" over several weeks

2. Joint Pain and Swelling:

   • Mainly affects knees and ankles
   • Can make it difficult to walk
   • Resolves completely without lasting damage

3. Tummy Pain:

   • Cramping, colicky pain (like stomach cramps)
   • May have vomiting or diarrhoea
   • Sometimes blood in the poo

4. Kidney Involvement:

   • Often no symptoms initially
   • Blood or protein found in urine on testing
   • Can lead to high blood pressure or swelling if severe

How is it diagnosed?

Diagnosis is based on recognizing the typical rash and symptoms. Tests include:

• Blood test: Platelet count is normal (this helps distinguish it from other causes of purpura)
• Urine test: To check for kidney involvement (blood or protein in urine)
• Blood pressure: To check if kidneys are affected

How is it treated?

Most children get better on their own within 4-6 weeks. Treatment focuses on managing symptoms:

• Rest and fluids
• Paracetamol for pain (avoiding ibuprofen if there are tummy or kidney problems)
• Steroids (prednisolone tablets or injections) if joint or tummy pain is severe
• Specialist treatment if kidneys are significantly affected (medications to reduce inflammation)

What are the possible complications?

• Tummy complications: Rarely, the bowel can telescope into itself (intussusception), causing severe pain and requiring urgent treatment
• Kidney problems: Most children have no lasting kidney problems, but regular urine checks are needed to detect any issues early

What is the outlook?

Excellent for most children. The rash, joint pain, and tummy symptoms resolve completely. The main concern is the kidneys:

• Most children (> 95%) have no long-term kidney problems
• A small number (1-2%) may develop chronic kidney disease, especially if they had severe kidney involvement at the start
• Regular urine checks are essential for several months after the illness to monitor the kidneys

Can it come back?

About 1 in 3 children (30%) may have a second episode, usually within a few months. If it comes back, it is usually milder than the first time.

What should I watch out for at home?

Return to the doctor urgently if your child has:

• Severe tummy pain or vomiting
• Blood in poo or vomit
• Severe headache or unusual sleepiness
• Reduced urine output or very swollen face/legs
• Testicular pain (in boys)

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13. Examination Focus

Common MRCP/MRCPCH Exam Questions

1. Classic Tetrad

Question: "A 5-year-old boy presents with a purpuric rash on his legs, arthralgia, abdominal pain, and haematuria. What is the most likely diagnosis?"

Answer: IgA Vasculitis (Henoch-Schönlein Purpura). The classic tetrad is:

1. Palpable purpura (mandatory)
2. Arthritis/arthralgia
3. Abdominal pain (GI involvement)
4. Renal involvement (haematuria/proteinuria)

---

2. Platelet Count

Question: "What differentiates IgA Vasculitis from Immune Thrombocytopaenia (ITP) in a child with purpura?"

Answer:

• IgA Vasculitis: Normal platelet count. The purpura is due to vasculitis (inflammation of blood vessel walls), not reduced platelets. The rash is palpable (raised).
• ITP: Low platelet count (less than 100 × 10⁹/L). The purpura/petechiae are due to thrombocytopaenia. The rash is non-palpable (flat).

A normal platelet count in a child with purpura strongly suggests vasculitis (IgAV) rather than a platelet disorder.

---

3. Main Long-Term Concern

Question: "What is the main determinant of long-term prognosis in IgA Vasculitis?"

Answer: Renal involvement (nephritis). While the rash, joint, and GI symptoms resolve completely, kidney involvement can lead to chronic kidney disease. 1-2% of children (and up to 30% of adults with severe nephritis) progress to end-stage renal disease. Therefore, long-term monitoring of urinalysis is essential.

---

4. Histology and Immunofluorescence

Question: "What is the characteristic finding on direct immunofluorescence of a skin biopsy in IgA Vasculitis?"

Answer: IgA deposition in dermal vessel walls. This is the hallmark of IgA Vasculitis. Light microscopy shows leucocytoclastic vasculitis (neutrophilic infiltration, vessel wall necrosis, RBC extravasation).

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5. Complement Levels

Question: "What is the expected complement profile (C3, C4) in IgA Vasculitis?"

Answer: Normal C3 and C4. IgA Vasculitis activates the alternative complement pathway (not the classical pathway), so C3 may be consumed but is usually normal or only mildly reduced; C4 remains normal. This helps differentiate IgAV from:

• SLE (low C3 and C4)
• Post-streptococcal GN (low C3, normal C4)

---

6. Intussusception

Question: "How does intussusception in IgA Vasculitis differ from typical childhood intussusception?"

Answer:

• Typical childhood intussusception: Ileocolic (ileum telescopes into colon); common ages 6 months - 2 years; often idiopathic or post-viral; may respond to air/contrast enema reduction
• IgAV-associated intussusception: Ileo-ileal (small bowel into small bowel); submucosal haemorrhage/oedema acts as lead point; less likely to respond to air enema; often requires surgical reduction [9]

Incidence in IgAV: 1-5%.

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7. Treatment of Nephritis

Question: "A child with IgA Vasculitis develops nephrotic syndrome (proteinuria 5 g/day, albumin 18 g/L). What is your management approach?"

Answer:

1. Urgent referral to Paediatric Nephrology
2. Renal biopsy to assess severity (ISKDC grading)
3. Immunosuppression:
   • High-dose corticosteroids (prednisolone 2 mg/kg/day or IV methylprednisolone pulses)
   • If steroid-resistant or crescentic GN: add cyclophosphamide, azathioprine, or mycophenolate mofetil
4. Renoprotection: ACE inhibitor/ARB (reduce proteinuria)
5. Supportive: Diuretics for oedema, salt restriction, monitor BP

Key Point: Mild nephritis (isolated haematuria) requires monitoring only. Severe nephritis (nephrotic/nephritic syndrome, RPGN) requires aggressive immunosuppression.

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8. Corticosteroid Controversy

Question: "Should all children with IgA Vasculitis receive early corticosteroids to prevent nephritis?"

Answer: No. Multiple RCTs have shown that early corticosteroids do NOT prevent the development of nephritis or improve long-term renal outcomes. [17] Corticosteroids should be used for:

1. Symptomatic relief of moderate-severe arthritis or abdominal pain
2. Treatment of established nephritis (nephrotic/nephritic syndrome)

They are not indicated as routine prophylaxis.

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Viva Scenario

Examiner: "Examine this 6-year-old child."

Findings:

• Palpable purpuric rash on bilateral lower legs and buttocks (symmetrical distribution)
• Periarticular swelling of ankles
• No lymphadenopathy, hepatosplenomegaly, or other rashes

Examiner: "What is your diagnosis?"

Candidate: "This child has a palpable purpuric rash in a symmetrical distribution affecting dependent areas (lower legs and buttocks), along with periarticular swelling suggesting arthritis. The most likely diagnosis is IgA Vasculitis (Henoch-Schönlein Purpura), the most common childhood vasculitis."

Examiner: "How would you confirm the diagnosis?"

Candidate: "IgA Vasculitis is a clinical diagnosis based on the EULAR/PRINTO/PRES criteria:

• Palpable purpura (mandatory, which this child has)
• Plus ≥1 of: arthritis/arthralgia, abdominal pain, renal involvement, or IgA deposition on biopsy

I would:

1. Check platelet count (must be normal; differentiates from ITP)
2. Urinalysis (essential to screen for renal involvement - haematuria/proteinuria)
3. Blood pressure (hypertension suggests nephritis)
4. Take a history for abdominal pain and joint pain
5. Coagulation screen (normal; excludes coagulopathy)

No specific diagnostic test exists; diagnosis is clinical."

Examiner: "The urinalysis shows 3+ blood and 2+ protein. What is your management?"

Candidate: "This indicates renal involvement (nephritis). My management would be:

1. Quantify proteinuria: Urine protein:creatinine ratio or 24-hour urine collection
2. Assess renal function: U&Es, creatinine
3. Monitor blood pressure
4. Refer to Paediatric Nephrology for consideration of renal biopsy (especially if nephrotic-range proteinuria, hypertension, or renal impairment)
5. Monitor urinalysis weekly during acute phase, then monthly for 3-6 months (nephritis can develop late)
6. Supportive care for mild disease; immunosuppression (high-dose steroids ± cyclophosphamide) if severe nephritis (nephrotic syndrome, AKI, crescentic GN)
7. Consider ACE inhibitor/ARB if persistent proteinuria (renoprotective)

Prognosis: Most children with mild nephritis recover fully. The presence and severity of renal involvement is the main determinant of long-term prognosis, with 1-2% progressing to CKD/ESRD."

Examiner: "Excellent."

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Model Viva Answers

Q1: What is the pathophysiology of IgA Vasculitis?

A: "IgA Vasculitis results from deposition of galactose-deficient IgA1 immune complexes in small vessel walls. The process involves:

1. A trigger (often URTI) leads to production of undergalactosylated IgA1 due to reduced β1,3-galactosyltransferase activity
2. The exposed N-acetylgalactosamine residues are antigenic, triggering anti-glycan antibodies
3. These antibodies bind Gd-IgA1, forming large immune complexes
4. ICs deposit in small vessels (skin, kidneys, GI tract, joints), particularly in dependent areas due to hydrostatic pressure
5. Alternative complement pathway activation causes leucocytoclastic vasculitis

The glomerular lesion is identical to IgA nephropathy—both show mesangial IgA deposition—but IgAV is a systemic disease with extrarenal manifestations."

---

Q2: How would you investigate a child with suspected IgA Vasculitis?

A: "Essential first-line investigations:

1. FBC: Normal platelet count is key (differentiates from ITP)
2. Coagulation screen: Normal PT/APTT (excludes coagulopathy)
3. Urinalysis: Mandatory screening for renal involvement (haematuria/proteinuria)
4. Urine PCR: Quantify proteinuria
5. U&Es, creatinine: Assess renal function
6. BP: Hypertension suggests nephritis

Additional tests:

• ESR/CRP (non-specific)
• Complement C3/C4 (normal; excludes SLE/post-strep GN)
• Stool occult blood (if GI symptoms)
• Abdominal US (if severe GI pain - intussusception?)

Biopsy (rarely needed):

• Skin biopsy (if diagnostic uncertainty): IgA deposition on immunofluorescence
• Renal biopsy (if nephrotic syndrome, AKI, or severe nephritis): Guides treatment and prognosis"

---

Q3: What is the prognosis for children with IgA Vasculitis?

A: "Overall prognosis is excellent - most children (> 95%) make a full recovery within 4-6 weeks. The key determinant is renal involvement:

Extrarenal manifestations (rash, arthritis, GI symptoms) resolve completely with no sequelae.

Renal prognosis:

• Isolated haematuria or mild proteinuria: Usually resolves
• 1-2% progress to CKD/ESRD (higher in adults: up to 30% with severe nephritis)
• Poor prognostic factors: Nephrotic-range proteinuria, nephritic syndrome, crescentic GN (ISKDC Grade IV-VI), adult age

Recurrence: ~30%, usually milder, within 4-6 months.

Long-term monitoring: Urinalysis monthly for 3-6 months (nephritis can develop late), then annually for 5 years if persistent abnormalities. Women with history of HSP nephritis require antenatal monitoring due to increased pregnancy complications."

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Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists and follow local guidelines.

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14. References

Primary Sources

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2. Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013;65(1):1-11. doi:10.1002/art.37715. PMID: 23045170.

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6. Pillebout E, Thervet E, Hill G, Alberti C, Vanhille P, Nochy D. Henoch-Schönlein Purpura in adults: outcome and prognostic factors. J Am Soc Nephrol. 2002;13(5):1271-1278. doi:10.1097/01.asn.0000013883.99976.22. PMID: 11961015.

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8. Calviño MC, Llorca J, García-Porrúa C, Fernández-Iglesias JL, Rodriguez-Ledo P, González-Gay MA. Henoch-Schönlein purpura in children from northwestern Spain: a 20-year epidemiologic and clinical study. Medicine (Baltimore). 2001;80(5):279-290. doi:10.1097/00005792-200109000-00001. PMID: 11552081.

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11. Rigante D, Castellazzi L, Bosco A, Esposito S. Is there a crossroad between infections, genetics, and Henoch-Schönlein purpura? Autoimmun Rev. 2013;12(10):1016-1021. doi:10.1016/j.autrev.2013.04.003. PMID: 23684700.

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17. Dudley J, Smith G, Llewelyn-Edwards A, Bayliss K, Pike K, Tizard J. Randomised, double-blind, placebo-controlled trial to determine whether steroids reduce the incidence and severity of nephropathy in Henoch-Schönlein Purpura (HSP). Arch Dis Child. 2013;98(10):756-763. doi:10.1136/archdischild-2013-303642. PMID: 23898157.

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19. Ronkainen J, Autio-Harmainen H, Nuutinen M. Cyclosporin A for the treatment of severe Henoch-Schönlein glomerulonephritis. Pediatr Nephrol. 2003;18(11):1138-1142. doi:10.1007/s00467-003-1253-8. PMID: 14523638.

20. Ozen S, Marks SD, Brogan P, et al. European consensus-based recommendations for diagnosis and treatment of immunoglobulin A vasculitis-the SHARE initiative. Rheumatology (Oxford). 2019;58(9):1607-1616. doi:10.1093/rheumatology/kez041. PMID: 30879081.

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