Henoch-Schönlein Purpura Nephritis in Children

Introduction to Henoch-Schönlein Purpura Nephritis

Henoch-Schönlein Purpura (HSP), also known as IgA vasculitis, is a systemic small vessel vasculitis that predominantly affects children. When it involves the kidneys, it is termed Henoch-Schönlein Purpura Nephritis (HSPN). HSPN is a significant complication that can lead to long-term renal sequelae and requires careful management.

Key points:

HSPN occurs in approximately 30-50% of children with HSP
It typically develops within 4-6 weeks of the initial presentation of HSP
HSPN can range from mild, self-limiting disease to severe, progressive renal impairment

Epidemiology of HSPN

Understanding the epidemiology of HSPN is crucial for early recognition and management:

Incidence: HSPN occurs in about 30-50% of children with HSP
Age: Most common in children aged 3-15 years, with a peak incidence at 4-6 years
Gender: Slightly more common in males (M:F ratio approximately 1.5:1)
Seasonal variation: More frequent in autumn and winter
Geographic distribution: Higher incidence reported in Asian populations

Risk factors for developing HSPN include:

Older age at HSP onset
Persistent purpura
Severe abdominal pain
Relapsing course of HSP

Pathophysiology of HSPN

The pathophysiology of HSPN involves immune complex deposition and inflammation:

Trigger: Often follows an upper respiratory tract infection (streptococcal, viral)
Immune response: Production of abnormal IgA1 molecules
Complex formation: IgA1 complexes deposit in small blood vessels
Renal involvement: Complexes deposit in the mesangium and along the glomerular basement membrane
Inflammation: Activation of complement and recruitment of inflammatory cells
Tissue damage: Endothelial injury, mesangial proliferation, and potential sclerosis

Histopathological classification (International Study of Kidney Disease in Children):

Grade I: Minimal glomerular abnormalities
Grade II: Mesangial proliferation
Grade III: Focal or diffuse proliferative glomerulonephritis
Grade IV: Crescentic glomerulonephritis
Grade V: Membranoproliferative-like glomerulonephritis
Grade VI: Pseudomesangiocapillary glomerulonephritis

Clinical Presentation of HSPN

The clinical presentation of HSPN can vary from asymptomatic urinary abnormalities to severe renal impairment:

Renal manifestations:

Microscopic hematuria (most common)
Gross hematuria
Proteinuria (ranging from mild to nephrotic range)
Hypertension
Acute nephritic syndrome
Nephrotic syndrome (in severe cases)
Acute kidney injury (rare)

Extra-renal manifestations (typical of HSP):

Palpable purpura (non-thrombocytopenic)
Arthralgia or arthritis
Abdominal pain (may be severe)
Gastrointestinal bleeding
Subcutaneous edema

It's important to note that renal manifestations may occur before, concurrent with, or after the appearance of extra-renal symptoms. Regular urinalysis is crucial for early detection of HSPN.

Diagnosis of HSPN

Diagnosis of HSPN involves a combination of clinical, laboratory, and histological findings:

1. Clinical criteria:

Presence of HSP symptoms (purpura, arthritis, abdominal pain)
Evidence of renal involvement (hematuria, proteinuria, hypertension)

2. Laboratory investigations:

Urinalysis: Hematuria, proteinuria
24-hour urine collection: Quantification of proteinuria
Serum creatinine and BUN: Assessment of renal function
Serum albumin: If nephrotic syndrome is suspected
Complement levels (C3, C4): Typically normal in HSPN
ANCA, ANA: To exclude other vasculitides
Serum IgA: Often elevated

3. Imaging studies:

Renal ultrasound: To assess kidney size and echogenicity

4. Renal biopsy:

Indications for renal biopsy include:

Nephrotic-range proteinuria
Persistent proteinuria > 1g/day
Impaired renal function
Chronic hypertension

Typical biopsy findings:

Light microscopy: Mesangial proliferation, endocapillary proliferation, crescents
Immunofluorescence: Dominant or co-dominant IgA deposition in the mesangium
Electron microscopy: Electron-dense deposits in the mesangium and subendothelial space

5. Differential diagnosis:

Post-streptococcal glomerulonephritis
IgA nephropathy
ANCA-associated vasculitis
Lupus nephritis

Treatment of HSPN

Treatment of HSPN depends on the severity of renal involvement and may range from supportive care to immunosuppressive therapy:

1. Supportive care (for mild cases):

Adequate hydration
Rest during the acute phase
Analgesics for pain relief (avoid NSAIDs)
Regular monitoring of blood pressure and urinalysis

2. Management of hypertension:

ACE inhibitors or ARBs: First-line agents, also help reduce proteinuria
Calcium channel blockers: If additional agents are needed

3. Immunosuppressive therapy (for moderate to severe cases):

Corticosteroids:
- Oral prednisone: 1-2 mg/kg/day for 4-8 weeks, followed by tapering
- Pulse methylprednisolone: 30 mg/kg/day for 3 days in severe cases
Other immunosuppressants (for steroid-resistant or relapsing cases):
- Cyclophosphamide: 2 mg/kg/day for 8-12 weeks
- Azathioprine: 1-2 mg/kg/day for 6-12 months
- Mycophenolate mofetil: 600 mg/m2 twice daily for 6-12 months

4. Novel therapies (under investigation):

Rituximab
Tacrolimus
Intravenous immunoglobulin (IVIG)

5. Management of complications:

Diuretics for edema
Calcium and vitamin D supplementation if on long-term steroids
Treatment of hypertension and hyperlipidemia

Treatment decisions should be individualized based on the severity of renal involvement, histological findings, and the patient's overall clinical status. Close monitoring and follow-up are essential to assess treatment response and detect any deterioration in renal function.

Prognosis of HSPN

The prognosis of HSPN is generally favorable, but it can vary depending on the severity of renal involvement:

Short-term prognosis:

Majority of children (70-80%) with HSPN have complete recovery
Most improve within 3-6 months of onset
Recurrence of HSP occurs in about 30% of cases, usually within 4 months

Long-term prognosis:

1-3% of children with HSPN progress to end-stage renal disease (ESRD)
Risk of chronic kidney disease (CKD) is higher in those with severe initial presentation
Long-term follow-up (5-10 years) is recommended due to the risk of late deterioration

Prognostic factors:

Factors associated with poor prognosis include:

Nephrotic-range proteinuria at onset
Persistent proteinuria > 1g/day
Hypertension
Renal impairment at presentation
Severe histological findings (crescents in >50% of glomeruli)
Older age at onset (>10 years)

Monitoring and follow-up:

Regular urinalysis and blood pressure monitoring for at least 6 months after resolution
Annual check-ups for several years, including urinalysis, blood pressure, and serum creatinine
Transition to adult nephrology care for patients with persistent renal abnormalities

Complications of HSPN

While many children with HSPN recover completely, some may develop complications:

Renal complications:

Chronic kidney disease (CKD)
End-stage renal disease (ESRD)
Hypertension
Proteinuria
Recurrent hematuria

Extra-renal complications:

Growth retardation (due to CKD or prolonged steroid use)
Osteoporosis (associated with long-term steroid therapy)
Cardiovascular disease (secondary to hypertension and CKD)
Psychological impact (due to chronic illness)

Treatment-related complications:

Steroid-related side effects: weight gain, growth suppression, osteoporosis, diabetes
Immunosuppressant-related side effects: increased risk of infections, bone marrow suppression

Prevention and management of complications:

Regular monitoring of renal function and proteinuria
Strict blood pressure control
Minimizing steroid exposure when possible
Calcium and vitamin D supplementation for patients on long-term steroids
Vaccination against encapsulated organisms for patients on immunosuppressants
Psychosocial support for patients and families
Timely referral to pediatric nephrology for specialized care

Early recognition and management of these complications can significantly improve long-term outcomes for children with HSPN.