Goodpasture Disease in Children

Introduction to Goodpasture Disease in Children

Goodpasture disease, also known as anti-glomerular basement membrane (anti-GBM) disease, is a rare autoimmune disorder characterized by the production of antibodies against type IV collagen in the basement membranes of the kidneys and lungs. While it primarily affects young adults, it can occur in children, presenting unique challenges in diagnosis and management.

Key points:

Rare in children, but can occur at any age
Characterized by rapidly progressive glomerulonephritis and pulmonary hemorrhage
Early diagnosis and treatment are crucial for improving outcomes
Requires a multidisciplinary approach involving pediatric nephrologists, pulmonologists, and rheumatologists

Epidemiology of Goodpasture Disease in Children

Understanding the epidemiology of Goodpasture disease in children is challenging due to its rarity:

Incidence: Extremely rare in children, estimated at less than 1 case per million per year
Age: Can occur at any age, but most pediatric cases are reported in adolescents
Gender: In adults, it's more common in males, but this gender predilection is less clear in children
Ethnicity: More commonly reported in Caucasians, but can affect all ethnic groups
Geographic distribution: No clear geographic pattern, cases reported worldwide

Risk factors and associations:

Genetic predisposition: Association with HLA-DR15 and DR4
Environmental triggers: Exposure to hydrocarbons, smoking (in older adolescents)
Infections: Upper respiratory tract infections may precede disease onset

Pathophysiology of Goodpasture Disease

The pathophysiology of Goodpasture disease involves an autoimmune response against specific components of basement membranes:

Autoantibody production: Development of antibodies against the NC1 domain of the α3 chain of type IV collagen
Antibody binding: These antibodies bind to basement membranes in the kidneys (glomeruli) and lungs (alveoli)
Complement activation: Binding of antibodies activates the complement system
Inflammation: Recruitment of inflammatory cells, including neutrophils and macrophages
Tissue damage: Inflammation leads to disruption of the basement membrane, causing glomerulonephritis and alveolar hemorrhage
Crescentic formation: In the kidneys, this process can lead to the formation of crescents in the glomeruli

Key points in pathophysiology:

The α3 chain of type IV collagen is predominantly expressed in the glomerular and alveolar basement membranes, explaining the kidney-lung specificity of the disease
Environmental factors or infections may expose these normally sequestered antigens, triggering the autoimmune response
The exact mechanism of loss of tolerance to these self-antigens in children is not fully understood

Clinical Presentation of Goodpasture Disease in Children

The clinical presentation of Goodpasture disease in children can vary, but typically involves both renal and pulmonary symptoms:

Renal manifestations:

Hematuria (microscopic or gross)
Proteinuria (can be in the nephrotic range)
Oliguria or anuria
Hypertension
Edema
Rapidly progressive glomerulonephritis

Pulmonary manifestations:

Cough
Hemoptysis (can range from mild to life-threatening)
Dyspnea
Chest pain
Hypoxemia

General symptoms:

Fatigue
Weight loss
Fever
Pallor (due to anemia from pulmonary hemorrhage or iron deficiency)

Important considerations in children:

The classic triad of glomerulonephritis, pulmonary hemorrhage, and anti-GBM antibodies may not be present initially
Some children may present with predominant renal or pulmonary symptoms
Pulmonary symptoms may be less common in children compared to adults
Non-specific symptoms like fatigue may be the initial presentation, leading to delayed diagnosis

Diagnosis of Goodpasture Disease in Children

Diagnosis of Goodpasture disease in children requires a high index of suspicion and a combination of clinical, laboratory, and histological findings:

1. Laboratory investigations:

Urinalysis: Hematuria, proteinuria, red cell casts
Serum creatinine and BUN: To assess renal function
Complete blood count: Anemia (due to pulmonary hemorrhage)
Anti-GBM antibodies: Detected by ELISA or indirect immunofluorescence
ANCA: Some patients may have concurrent ANCA positivity (double-positive)
Complement levels: Usually normal

2. Imaging studies:

Chest X-ray: May show diffuse alveolar infiltrates
Chest CT: More sensitive for detecting pulmonary hemorrhage
Renal ultrasound: May show enlarged kidneys with increased echogenicity

3. Pulmonary function tests:

Diffusion capacity for carbon monoxide (DLCO): Elevated in pulmonary hemorrhage

4. Renal biopsy:

Essential for definitive diagnosis and prognosis. Findings include:

Light microscopy: Crescentic glomerulonephritis
Immunofluorescence: Linear deposition of IgG along the glomerular basement membrane
Electron microscopy: Rupture of glomerular basement membrane

5. Lung biopsy:

Rarely performed, but may show:

Alveolar hemorrhage
Linear deposition of IgG along the alveolar basement membrane

6. Differential diagnosis:

ANCA-associated vasculitis
Lupus nephritis
Post-streptococcal glomerulonephritis
IgA nephropathy
Other causes of pulmonary-renal syndrome

Early diagnosis is crucial for improved outcomes. In children with unexplained renal dysfunction or pulmonary hemorrhage, Goodpasture disease should be considered and anti-GBM antibody testing performed promptly.

Treatment of Goodpasture Disease in Children

Treatment of Goodpasture disease in children is aimed at rapidly removing pathogenic antibodies and suppressing antibody production. It requires aggressive and prompt intervention:

1. Plasmapheresis:

Removes circulating anti-GBM antibodies
Usually performed daily for 14 days or until antibodies are undetectable
May be extended in severe cases or if antibodies persist

2. Immunosuppression:

Corticosteroids:
- Pulse methylprednisolone: 30 mg/kg/day (max 1g) for 3 days
- Followed by oral prednisone: 1 mg/kg/day, tapered over 6 months
Cyclophosphamide:
- Oral: 2 mg/kg/day for 3 months
- IV: 15 mg/kg every 2-3 weeks for 3 months
Rituximab: May be considered in refractory cases or as an alternative to cyclophosphamide

3. Supportive care:

Renal support: Dialysis if needed
Respiratory support: Oxygen therapy, mechanical ventilation if necessary
Blood pressure control
Anemia management: Blood transfusions if severe
Nutritional support
Infection prophylaxis: Consider PCP prophylaxis during immunosuppression

4. Management of complications:

Treatment of infections
Thrombosis prophylaxis
Gastrointestinal protection (e.g., proton pump inhibitors)

5. Monitoring and follow-up:

Regular monitoring of anti-GBM antibody levels
Frequent assessment of renal function and urinalysis
Pulmonary function tests and chest imaging as needed
Long-term follow-up to monitor for relapse and manage chronic kidney disease

Treatment decisions should be individualized based on disease severity, patient age, and presence of complications. A multidisciplinary approach involving pediatric nephrologists, pulmonologists, and rheumatologists is essential for optimal management.

Prognosis of Goodpasture Disease in Children

The prognosis of Goodpasture disease in children has improved with early diagnosis and aggressive treatment, but it remains a serious condition with potential for significant morbidity:

Factors affecting prognosis:

Timing of diagnosis and treatment initiation
Severity of renal involvement at presentation
Presence and severity of pulmonary hemorrhage
Response to initial treatment
Presence of concurrent ANCA positivity (double-positive cases may have a worse prognosis)

Renal outcomes:

Better outcomes if treatment is started when serum creatinine is <5.7 mg/dL
10-30% of patients may progress to end-stage renal disease despite treatment
Patients with creatinine >6.8 mg/dL at presentation or those requiring dialysis initially have poorer renal outcomes

Pulmonary outcomes:

Generally good if treated promptly
Most patients recover normal lung function
Some may have residual mild impairment in diffusion capacity

Relapse:

Relapse is uncommon but can occur, especially within the first two years
Regular monitoring of anti-GBM antibodies and renal function is important

Long-term follow-up:

Patients should be monitored for chronic kidney disease progression
Regular assessment of growth and development in children
Monitoring for long-term complications of immunosuppression
Transition to adult care services as appropriate

While the immediate prognosis has improved, long-term outcomes in children with Goodpasture disease are not well established due to the rarity of the condition. Ongoing research and long-term follow-up studies are needed to better understand the long-term prognosis in the pediatric population.

Complications of Goodpasture Disease in Children

Goodpasture disease can lead to various complications, both from the disease itself and its treatment:

Disease-related complications:

Acute kidney injury progressing to chronic kidney disease
End-stage renal disease requiring dialysis or transplantation
Severe pulmonary hemorrhage leading to respiratory failure
Anemia due to pulmonary hemorrhage or chronic kidney disease
Hypertension
Growth retardation
Developmental delays due to chronic illness
Cardiovascular complications secondary to chronic kidney disease

Treatment-related complications:

Infections due to immunosuppression
Osteoporosis from long-term steroid use
Cushing's syndrome from corticosteroid therapy
Hemorrhagic cystitis from cyclophosphamide
Infertility concerns with cyclophosphamide use
Increased risk of malignancies with long-term immunosuppression

Psychosocial complications:

Depression and anxiety
Social isolation due to chronic illness
Educational challenges due to frequent hospitalizations
Family stress and financial burden

Management of complications:

Regular monitoring of renal function and pulmonary status
Prompt treatment of infections
Bone health management (calcium and vitamin D supplementation, bone density scans)
Growth hormone therapy if significant growth retardation occurs
Psychosocial support and counseling
Educational accommodations and support
Transition planning for adolescents moving to adult care

Early recognition and management of these complications are crucial for improving long-term outcomes and quality of life for children with Goodpasture disease. A multidisciplinary approach involving pediatric subspecialists, psychologists, social workers, and educators is essential for comprehensive care.

Goodpasture Disease in Children (continued)

Q: What is the typical age of onset for Goodpasture disease in children?
A: Late childhood to adolescence, typically between 10-20 years old
Q: Which genetic factor is associated with an increased risk of Goodpasture disease?
A: HLA-DRB1*15 allele
Q: What is the role of plasmapheresis in the treatment of Goodpasture disease in children?
A: To rapidly remove circulating anti-GBM antibodies and reduce kidney and lung damage
Q: How long should immunosuppressive therapy be continued after achieving remission in Goodpasture disease?
A: Typically 6-9 months, with gradual tapering
Q: What is the prognosis for children with Goodpasture disease who require dialysis at presentation?
A: Generally poor, with less than 5% chance of renal recovery
Q: Can Goodpasture disease recur after successful treatment?
A: Recurrence is rare but possible, occurring in less than 5% of cases
Q: What is the role of genetic testing in the management of Goodpasture disease in children?
A: It may help identify at-risk siblings and guide family counseling
Q: How does smoking affect the course of Goodpasture disease in adolescents?
A: Smoking can exacerbate lung involvement and worsen prognosis
Q: What is the recommended frequency of anti-GBM antibody testing during remission?
A: Every 3-6 months for at least 2 years
Q: Can children with Goodpasture disease receive kidney transplants?
A: Yes, but typically only after circulating anti-GBM antibodies have been undetectable for at least 6-12 months