Idiopathic Pulmonary Hemosiderosis (IPH)

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

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

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

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

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

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

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

References

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