Henoch-Schönlein Purpura Nephritis

Ref: nelsons

1. Definition:
○ HSP is an idiopathic systemic immune complex–mediated vasculitis
associated with IgA deposition in small-vessel walls.
○ Now termed IgA vasculitis.
2. Epidemiology:
○ Most common small-vessel vasculitis in children.
○ Peak incidence: 4–6 years of age.
○ 90% of cases occur in children; 50% are preceded by an upper respiratory
infection.
3. Clinical Features (Tetrad):
○ Palpable purpura.
○ Arthritis/arthralgia.
○ Abdominal pain.
○ Renal disease (manifestations vary from mild hematuria to severe
glomerulonephritis).
4. Renal Involvement:
○ Occurs in ~50% of cases, usually after the rash onset.
○ More common and severe in older children (>8 years).
○ Can progress from mild microscopic hematuria to acute nephritic and
nephrotic syndrome.

Pathogenesis

1. IgA Deposition:
○ Polymeric IgA1 immune complexes deposit in the glomerular mesangium,
leading to inflammation.
○ Triggered by mucosal infections or food antigens.
2. Defective Glycosylation:
○ IgA1 glycosylation defects expose the hinge region, forming immune
complexes recognized by autoantibodies.
3. Histology:
○ Leukocytoclastic vasculitis on skin biopsy (IgA, C3, fibrin deposition).
○ Immunofluorescence: IgA as dominant immunoglobulin in glomeruli.
 ○ Glomerular lesions: Range from mild mesangial proliferation to necrotic
and crescentic changes.

Clinical and Laboratory Manifestations

1. Timeline of Symptoms:
○ Rash typically precedes nephritis by weeks/months.
○ Rarely, nephritis occurs before the rash.
2. Urinary Findings:
○ Initially: Microscopic hematuria without significant proteinuria in 80% of
cases.
○ Severe cases: Nephritic-nephrotic syndrome (hematuria, proteinuria,
hypertension, renal insufficiency).
3. Risk Factors for Severe Nephritis:
○ Age > 8 years.
○ Nephrotic syndrome, elevated serum creatinine, or significant proteinuria
(>1 g/day).
○ Histologic findings: Crescentic changes (>50% crescents indicate poor
prognosis).
4. Monitoring:
○ Weekly urinalysis during active disease.
○ Monthly urinalysis for up to 6 months post-onset.
5. Indications for Kidney Biopsy:
○ Significant proteinuria: Urine protein >1 g/day or protein/creatinine ratio
>1.0.
○ Hypertension or elevated serum creatinine.

Prognosis

1. General Prognosis:
○ Excellent in mild cases (spontaneous resolution common).
○ Risk of chronic kidney disease (CKD) in severe cases:
■ Overall: 2–5%.
■ Severe nephritis: Up to 50%.
2. Progression:
○ Early mild cases may progress despite resolution of non-renal symptoms.
Treatment

1. Mild Nephritis:
○ No specific treatment required; resolves spontaneously.
2. Moderate/Severe Nephritis:
○ Immunosuppression: Corticosteroids combined with azathioprine or
mycophenolate mofetil.
○ Severe cases: Intravenous methylprednisolone pulses + extended oral
corticosteroids.
3. High-Risk Severe Nephritis (>50% crescents):
○ Consider plasmapheresis or rituximab.
○ Steroid regimen + azathioprine/mycophenolate mofetil.
4. End-Stage Renal Disease (ESRD):
○ Renal transplantation is the treatment of choice. IgA deposition in the graft
is common but often subclinical.
5. Ineffective Treatments:
○ Short-term corticosteroids do not prevent nephritis.
○ Tonsillectomy does not impact renal outcomes.

Important Exam Pointers

● Age-related risk: Older children (>8 years) have higher nephritis risk and severity.
● Key biopsy findings: Crescents >50% indicate poor prognosis.
● Monitoring requirement: Weekly to monthly urinalysis.
● Renal prognosis: Severe nephritis increases the risk of CKD significantly.
● Treatment: Tailored based on severity; no randomized studies guide therapy.

Hemolytic-Uremic Syndrome (HUS)

HUS is a leading cause of community-acquired acute kidney injury in children, presenting
as a type of thrombotic microangiopathy (TMA) with:

1. Microangiopathic hemolytic anemia

2. Thrombocytopenia
3. Renal insufficiency
● There are two major categories:

1. Diarrhea-associated HUS (STEC-HUS): Commonly triggered by Shiga

toxin-producing Escherichia coli (STEC).
2. Atypical HUS (aHUS): Often genetic, involving complement pathway
dysregulation.

Etiology

1. Infection-Induced HUS:

○ STEC-HUS: Often follows ingestion of undercooked meat, unpasteurized

milk, or contaminated water.
○ Shigella dysenteriae (in Asia/Africa) and Streptococcus pneumoniae
(neuraminidase-associated HUS) are other causative agents.
○ Rare triggers: HIV, influenza.
2. Genetic (Atypical) HUS:

○ Related to deficiencies in complement regulators (e.g., factor H, I) or

ADAMTS13.
○ May manifest during infections or spontaneously.
3. Other Causes:

○ Systemic diseases (e.g., lupus, malignant hypertension).

○ Drug-induced (e.g., calcineurin inhibitors).
○ Post-transplant complications.

Pathogenesis
 ● Endothelial injury leads to platelet activation and microthrombi formation in small
vessels.
● Shiga toxin binds to endothelial cells, causing damage, platelet aggregation, and
red blood cell destruction.
● Genetic forms involve defective regulation of the complement system, resulting in
unchecked endothelial damage.

Clinical Features

● Typical STEC-HUS:

○ Begins with gastroenteritis (5-7 days post-exposure): diarrhea (often

bloody), abdominal pain.
○ Followed by sudden pallor, fatigue, and oliguria/anuria.
● Complications:

○ Acute kidney injury (50% may require dialysis).

○ Neurological involvement (irritability, seizures, encephalopathy).
○ Cardiovascular (hypertension, heart failure).
○ Gastrointestinal (colitis, bowel perforation).

Diagnosis

● Key Findings:

○ Microangiopathic hemolytic anemia (schistocytes, Coombs-negative).

○ Thrombocytopenia.
○ Acute kidney injury (elevated BUN/creatinine, hematuria).
○ Exclude other TMAs (e.g., lupus, malignancy-associated HUS).
● Microbial Detection: Stool culture (may not always yield STEC).

Management
 ● Supportive Care is the cornerstone:

○ Fluid/electrolyte management, dialysis for severe renal failure.

○ Red cell transfusions (washed in pneumococcal HUS).
○ Avoid platelet transfusions (except in active bleeding).
● Contraindicated Therapies:

○ Antibiotics for STEC-HUS (may exacerbate toxin release).

○ Anticoagulants and fibrinolytics.
● Specific Therapies:

○ Eculizumab: Effective in atypical HUS (requires meningococcal vaccination).

○ Plasma exchange/infusion: Beneficial in ADAMTS13 or complement
deficiencies.

Prognosis

● STEC-HUS:
○ Mortality <5% with care.
○ Long-term renal sequelae in 30%.
● Atypical/Genetic HUS:
○ Worse prognosis; high risk of recurrence and chronic kidney disease.
○ May require lifelong monitoring and tailored therapies.

Key Points for Long-Term Follow-Up

● Monitor for hypertension, proteinuria, or chronic kidney disease.

● Genetic counseling in familial cases.

This summary emphasizes the critical aspects of HUS, aiding in understanding its
multifaceted presentation, management, and outcomes. Let me know if you'd like detailed
guidance on a specific area.