Pulmonary Artery Hypertension (PAH) with severe diffusion capacity (DLCO) reduction complicating Systemic Onset Juvenile Rheumatoid (SOJRA) is extremely rare, only one case being reported. (1) In children with JRA, Pulmonary Function Tests (PFT) rarely show DLCO impairment and if present is usually only to a mild to moderate. (2) We describe a case of SOJRA complicated by a severely reduced DLCO with mild PAH.
A 13 year old female with SOJRA and partial Macrophage Activation Syndrome (MAS) developed dyspnea and tachycardia during the 5th month of active disease. During the 9th month, she experienced a life threatening MAS episode. PFT showed hypoxia and severe hemoglobin (hgb) corrected DLCO at 24% without obstruction or restriction. High Resolution Chest CT with angiography and Ventilation Perfusion scan showed no interstitial pulmonary fibrosis or macrovascular thromboembolism. Despite aggressive immunosuppressive therapy with pulsed methylprednisolone, cyclosporine A and methotrexate, the patient’s dyspnea and hypoxia worsened. Heart catheterization at month 13 demonstrated mild PAH with mean pulmonary artery pressure (mPAP) of 37 mm Hg without intrapulmonary or significant intracardiac shunting. Bosentan was started in month 14. The patient experienced a second life threatening MAS episode in month 15. Etoposide was instituted to suppress the activated macrophages, which was followed by rapid clinical improvement in the MAS. Open lung biopsy at month 16 showed changes on light microscopy (LM) of preplexogenic pulmonary hypertension with intimal thickening and on electron microscopy (EM), multilamellated thickening of the alveolar capillary basement membrane (BM). There was no evidence of pulmonary fibrosis or thrombosis. The patient’s hgb DLCO reached it’s nadir of 21% by month 16 and has improved to 52 % by month 21. Repeat heart cath at month 18 showed normalization of the mPAP at 25 mm Hg.
The severe hypoxia and diffusion capacity limitation described were markedly out of proportion to degree of PAH found.The etiology of the hypoxia is the ultramicroscopic structural changes at the level of the alveolar capillary endothelium. Similar pathologic microvascular endotheliopathy lesions have been described on electron microscopy of the pulmonary alveolar capillary basement membrane in patients with plexogenic primary pulmonary hypertension. (3) The likely pathologic cascade that led to these BM changes was likely excess release of endothelin-1 and cytokines from the activated macrophages, which triggered further endothelin-1 synthesis and release from the vascular endothelium. (4, 5, 6).
PAH and pulmonary microvascular endotheliopathy should be suspected when hypoxia and DLCO reduction are present in systemic rheumatologic disease. Early lung biopsy with LM and EM should be pursued to allow expeditious implementation of potentially life saving medications before irreversible pathology develops in the lungs.
Paul Nolan, None.