INTRODUCTION: Pulmonary arterial hypertension (PAH) is a poorly understood disease associated with increased morbidity and mortality. Multicentric Castleman disease (MCD) is an uncommon idiopathic lymphoproliferative disorder noted to result in an increase of interleukin-6 (IL-6) secretion and is associated with PAH in some patients. Recent data suggests that IL- 6 might promote pulmonary arteriole endothelial and smooth muscle proliferation leading to the development of PAH. We present a rare case of severe PAH due to rheumatoid arthritis (RA) complicated with MCD which responded to a combination of PAH targeted and biologic (Anti CD20) therapy. CASE PRESENTATION: A 50 year old African American female with RA, pernicious anemia and MCD presented with a 3 month history of progressive dyspnea (NYHA functional Class III) and peripheral edema. MCD was diagnosed by lymph node biopsy in 2010. Serology for HIV and HHV 8 was negative. Prior treatment regimen included methotrexate, hydroxychloroquine and 8 cycles of rituximab with good clinical response. Examination revealed a loud P2 and bilateral coarse crepitations. An echocardiogram (ECHO) showed a normal EF of 60%, a D shaped septum with increased right ventricular systolic pressure (RVSP) of 80 mmHg. CT angiography of the chest showed interstitial scarring unchanged from baseline and was negative for pulmonary embolism. Right and left heart catheterization revealed pulmonary artery pressures of 101/36 mmHg, mean pulmonary artery pressure of 64 mmHg, LVEDP of 9 mmHg, cardiac output of 4.15L/min and pulmonary vascular resistance (PVR) of 13 Wood units. Pulmonary vasodilator therapy with sildenafil, dual endothelin receptor blocker (bosentan) and prostanoids was initiated in addition to conventional therapy (i.e. diuretics and home oxygen). Laboratory data revealed a grossly elevated IL-6 level of 257.4 pg/ml (normal range 0.0-12.2pg/ml) for which 4 cycles of rituximab was administered. On follow up, her dyspnea improved from NYHA Class III to II with a decrease of pro- BNP from 116.1 to 32 pg/ml and IL-6 from 257.4 to 20 pg/ml. Follow-up ECHO showed resolution of RV pressure overload with improvement of RVSP from 80mmHg to 44mmHg. DISCUSSION: PAH is a rare complication of RA and MCD with few cases reported in literature. Elevated IL- 6 has been linked to PAH in these cases which improved with targeted biologic therapy1 (tocilizumab and rituximab). IL-6 blockade may hold promise as a therapeutic target in Connective Tissue Diease (CTD) associated PAH. CONCLUSIONS: Further studies of IL-6 blockade in PAH patients with and without CTD are warranted.
Bekele, D., Thomas, A., Kerr, G., O’Neal, P., & Mehari, A. (2016). Interleukin-6 as a Potential Therapeutic Target in PAH. Chest, 150(4), 1219A. https://doi.org/10.1016/j.chest.2016.08.1328