Overview
Definition:
Henoch-Schönlein Purpura (HSP) nephritis, also known as IgA vasculitis with renal involvement, is a systemic vasculitis characterized by deposition of IgA-containing immune complexes in small vessels, most commonly affecting the skin, joints, gastrointestinal tract, and kidneys
Renal involvement, or HSP nephritis, occurs in approximately 30-50% of children with HSP, and is a major determinant of long-term prognosis.
Epidemiology:
HSP is the most common childhood systemic vasculitis, typically affecting children aged 3-10 years, with a bimodal peak in early childhood and adolescence
Incidence varies geographically but is estimated to be around 10-20 cases per 100,000 children per year
Renal involvement is more common in older children and adults, and in males.
Clinical Significance:
HSP nephritis is a significant cause of secondary glomerulonephritis in children
Early recognition and appropriate management, including the judicious use of ACE inhibitors for proteinuria, are crucial to prevent progression to chronic kidney disease and end-stage renal disease, impacting long-term patient outcomes and healthcare resource utilization.
Clinical Presentation
Symptoms:
Macroscopic or microscopic hematuria
Proteinuria, ranging from mild to nephrotic-range
Edema, particularly periorbital and lower limb edema
Hypertension, especially with more severe renal involvement
Abdominal pain, arthralgia, and rash (palpable purpura) are often preceding or concurrent symptoms of HSP.
Signs:
Renal biopsy findings may include mesangial IgA deposition, mesangial proliferation, endocapillary hypercellularity, and crescent formation, all indicative of glomerular inflammation and injury
Hypertension may be detected on physical examination.
Diagnostic Criteria:
Diagnosis of HSP is typically clinical based on the presence of palpable purpura plus at least one of the following: arthritis/arthralgia, abdominal pain, or renal involvement
Renal involvement is diagnosed by urinalysis showing hematuria and/or proteinuria, or by renal biopsy showing characteristic IgA deposition.
Diagnostic Approach
History Taking:
Detailed history of preceding infections (especially upper respiratory tract)
Presence and timeline of characteristic rash (often on lower extremities and buttocks), joint pain, and gastrointestinal symptoms
History of allergies or drug intake
Family history of renal disease or autoimmune disorders.
Physical Examination:
Thorough examination for palpable purpura, joint swelling, abdominal tenderness, and signs of fluid overload (edema, hypertension)
Evaluation of renal tenderness or masses
Assessment of neurological status and skin lesions.
Investigations:
Urinalysis: For hematuria (red blood cell casts) and proteinuria (albuminuria)
Urine protein-to-creatinine ratio (UPCR) is used to quantify proteinuria
Serum creatinine and estimated glomerular filtration rate (eGFR): To assess renal function
Complete blood count: To rule out anemia and thrombocytosis
Serology: Antistreptolysin O (ASO) titer or throat swab for recent streptococcal infection
IgA levels may be elevated
Renal biopsy: Gold standard for grading severity of glomerular injury and guiding prognosis, showing IgA deposition.
Differential Diagnosis:
Other causes of palpable purpura: Immune thrombocytopenic purpura (ITP), platelet dysfunction disorders, meningococcemia
Other causes of glomerulonephritis: Post-infectious glomerulonephritis, IgA nephropathy (primary), lupus nephritis, membranoproliferative glomerulonephritis (MPGN).
Management
Initial Management:
Supportive care: Hydration, pain management for arthritis, and management of gastrointestinal symptoms
Close monitoring of blood pressure and renal function
Education of parents/guardians about the disease course and potential complications.
Medical Management:
Corticosteroids: Oral prednisone (1 mg/kg/day, max 60 mg/day, tapered over 4-8 weeks) are often used for initial management of severe HSP manifestations, including severe renal involvement, although evidence for benefit in renal outcomes is mixed
Immunosuppressants: Azathioprine, mycophenolate mofetil, or cyclophosphamide may be considered in severe cases with progressive renal disease or in those unresponsive to corticosteroids, based on renal biopsy findings
ACE Inhibitors: For proteinuria
Initially, ACE inhibitors (e.g., enalapril, lisinopril) are recommended for patients with significant proteinuria (>0.5 g/day or UPCR >0.5) or hypertension, aiming to reduce proteinuria and slow disease progression
Doses are titrated to achieve proteinuria reduction and maintain normal blood pressure
Typical starting doses in children may include enalapril 0.07-0.1 mg/kg/day, titrated upwards.
Surgical Management:
Not applicable for HSP nephritis itself
Plasma exchange and tonsillectomy have been explored but are not standard practice and have limited evidence of benefit for renal outcomes.
Supportive Care:
Nutritional support: Adequate fluid and electrolyte balance
Monitoring for signs of infection and managing co-existing conditions
Psychological support for patients and families due to the chronic nature of the illness.
Complications
Early Complications:
Acute kidney injury (AKI) due to severe glomerular inflammation or interstitial nephritis
Nephrotic syndrome
Severe hypertension
Gastrointestinal bleeding or perforation
Testicular torsion or infarct.
Late Complications:
Chronic kidney disease (CKD)
End-stage renal disease (ESRD)
Recurrent HSP flares
Increased risk of cardiovascular disease due to long-standing hypertension and renal impairment.
Prevention Strategies:
Prompt diagnosis and initiation of appropriate therapy for significant renal involvement
Adherence to prescribed medications, particularly ACE inhibitors and immunosuppressants, as indicated
Regular follow-up to monitor renal function and proteinuria
Management of hypertension aggressively.
Prognosis
Factors Affecting Prognosis:
Severity of renal involvement at diagnosis (presence of crescents on biopsy, nephrotic-range proteinuria, significant hematuria, and hypertension are poor prognostic markers)
Promptness of treatment
Response to therapy
Age at presentation (younger children tend to have better renal outcomes).
Outcomes:
Most children with mild HSP nephritis (microscopic hematuria, mild proteinuria) recover normal renal function
However, approximately 25-50% may develop chronic kidney disease, and 10-20% may progress to end-stage renal disease
ACE inhibitors play a key role in improving long-term renal outcomes by reducing proteinuria and slowing GFR decline.
Follow Up:
Long-term follow-up is essential for all children with HSP nephritis
Regular monitoring of urinalysis, blood pressure, and renal function is required for at least 5-10 years, or even indefinitely, especially in those with significant proteinuria or renal impairment
Periodic reassessment of proteinuria and renal function helps detect relapses or progression of disease.
Key Points
Exam Focus:
HSP nephritis is a mesangioproliferative glomerulonephritis with IgA deposition
ACE inhibitors are the cornerstone of proteinuria management and renal protection in HSP nephritis
Renal biopsy findings, especially crescents, are critical prognostic indicators.
Clinical Pearls:
Always consider HSP in a child with purpura, arthritis, and abdominal pain
Urinalysis is paramount in assessing renal involvement
Proteinuria > 0.5 g/day or UPCR > 0.5 in HSP mandates consideration of ACE inhibitors and potential immunosuppression if severe.
Common Mistakes:
Delaying diagnosis of renal involvement
Underestimating the significance of proteinuria
Inadequate titration of ACE inhibitors or failure to use them when indicated
Over-reliance on corticosteroids without considering immunosuppressants for severe disease
Neglecting long-term follow-up.