Epidemiology

• Age: occurs mainly in children, but 20% of cases occur in adults (mainly in >30 y/o group)
• Age Range for Onset: 4 months-62 y/o
• Sex: M:F ratio is 2:1 (in adults)
• Familial Clustering: has been reported
• Associated with:
  • Celiac Disease
  • HLA-B8

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Physiology

• Probable immune disorder
  • Some cases may be secondary to environmental exposure to Stachybotrys atra fungus: this fungus has been putatively linked to idiopathic diffuse alveolar hemorrhage

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Pathology

• Absence of Pulmonary Capillaritis: bland alveolar hemorrhage
• Hemosiderin accumulation within macrophages and in interstitium (interstitial hemosiderin probably promotes interstitial fibrosis)
• Type II pneumocyte hyperplasia with capillary dilatation and tortuosity
• Absence of pulmonary immune complexes (rules out Goodpasture’s)
• EM (diffuse alveolar injury): degeneration of type I alveolar epitelial cells with exposure of their basement membranes
  • Breaks in (with fibrillar material in split areas) and thickening of alveolar-capillary basement membrane
  • Focal rupture of basement membrane with collagen deposition

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Diagnosis

• PFT’s: restrictive pattern
  • DLCO: increased during DAH (decreases with development of interstitial lung disease)
• FOB: BAL reveals hemosiderin-laden macrophages
• OLB: required in adult cases to exclude isolated pulmonary capillaritis
  • Tissue Ab staining: negative
• CXR/Chest CT Patterns
  • Diffuse or patchy focal alveolar infiltrates (resolve slowly over days-weeks)
  • Interstitial infiltrates may appear with chronic or recurrent disease
    • HRCT: diffuse ground-glass infiltrates, ill-defined centrilobular nodules
  • Hilar/mediastinal adenopathy has been seen in some pediatric cases
• Serology
  • ANA: negative
  • Anti-DNA: negative
  • RF: negative
  • C3/C4/ CH50: normal
  • ANCA: negative
  • Anti-GBM: negative
• Serum IgA: increased in 50% of cases
• CBC: leukocytosis, anemia (iron deficiency may occur if bleeding is severe and recurrent)
• ESR: elevated
• Urinalysis: usually normal

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Clinical Presentation

(usually a diagnosis of exclusion)

Pulmonary Manifestations

• Recurrent Diffuse Alveolar Hemorrhage (see [[Diffuse Alveolar Hemorrhage]])
  • Cough
  • Dyspnea
  • Hemoptysis: may be absent on initial presentation in some cases, even after significant bleed
    • May be streaky or life-threatening
  • Chest Pain
  • Crackles
• Interstitial Lung Disease (see [[ILD-Etiology]])

Other Manifestations

• Fever
• Fatigue
• Clubbing: may occur over time as interstitial lung disease develops
• Lympadenopathy and Splenomegaly (present in 20% of pediatric cases)
• Absence of Renal, Rheum, and Derm involvement

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Treatment

• Corticosteroids: may help acute bleed but unclear long-term benefit
• Azathioprine: successful in a few cases
• Plasmapheresis: used in one refractory case Prognosis: in 75% of cases, mean survival is 3-5 years
• Lung Transplantation: controversial, as disease recurs after bilateral lung transplant

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Prognosis

• Adults have better prognosis than children
  • 25% of adults remit after first episode
  • 25% have persistent dyspnea with anemia (without active disease)
  • 25% have active disease and progress to fibrosis
  • 25% progress to hemorrhage and respiratory failure -> average survival: 3-5 years

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References

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