Pulmonary Capillary Hemangiomatosis

Pulmonary capillary hemangiomatosis (PCH) is a rare pulmonary vascular disease causing severe precapillary pulmonary hypertension. It is characterized histopathologically by proliferation of capillary-sized vessels within alveolar walls, with capillaries arranged in multiple layers (capillary septation), congestion, and microhemorrhages. Despite its name, PCH is not a true neoplasm—the term 'hemangiomatosis' is descriptive of the proliferative pattern. PCH and pulmonary veno-occlusive disease (PVOD) often coexist and are now classified together under WHO Group 1' (1 prime) due to shared pathophysiology, clinical features, and management challenges.

Etiology includes hereditary forms with biallelic EIF2AK4 (eukaryotic translation initiation factor 2 alpha kinase 4) mutations causing autosomal recessive familial PCH/PVOD, sporadic forms (most cases), associations with connective tissue diseases (especially scleroderma), and occupational/environmental exposures (organic solvents, mitomycin C). EIF2AK4 encodes GCN2, a kinase important in cellular response to amino acid deprivation and oxidative stress; loss of function leads to abnormal pulmonary vascular development.

Clinical presentation includes progressive exertional dyspnea, severe and disproportionate hypoxemia (often without significant lung disease), syncope, fatigue, and signs of right heart failure. Imaging is critical for distinguishing PCH/PVOD from pulmonary arterial hypertension (PAH): chest HRCT shows centrilobular ground-glass opacities, septal thickening (interlobular and intralobular), mediastinal lymphadenopathy, and pleural effusions—features that should raise suspicion. Right heart catheterization shows precapillary pulmonary hypertension (mPAP ≥25 mmHg, PCWP ≤15 mmHg), distinguishing from postcapillary causes. Lung biopsy shows characteristic capillary proliferation but is rarely performed due to bleeding risk. Treatment: cautious supportive care with diuretics and oxygen; pulmonary vasodilators (epoprostenol, ambrisentan, sildenafil) often cause paradoxical pulmonary edema worsening due to increased flow into a fixed venous obstruction; lung transplantation is the definitive treatment, though waiting list mortality is high; genetic counseling for hereditary cases. Prognosis is poor with median survival 12-24 months without transplantation.