Rheumatoid Arthritis: Simonneau G

Launay D, Hachulla E, Hatron PY, Jais X, Simonneau G, Humbert M. · Centre National de Référence de l'Hypertension Artérielle Pulmonaire, UPRES EA2705, Service de Pneumologie et Réanimation Respiratoire, Hôpital Antoine-Béclère, Assistance Publique Hôpitaux de Paris, Université Paris-Sud 11, Clamart, France. · Medicine (Baltimore). · Pubmed #17873760 No free full text.

Abstract: Primary Sjögren syndrome (pSS) is a fairly common autoimmune disease with glandular and extraglandular manifestations. Pulmonary involvement mainly corresponds to small airways and interstitial lung disease. Pulmonary arterial hypertension (PAH) is rare: to our knowledge, only 32 cases have been reported in pSS patients to date. PAH is a disease of the small pulmonary arteries characterized by vascular proliferation and remodeling, resulting in a progressive increase in pulmonary vascular resistance, and, ultimately, right ventricular failure and death. We report 9 new cases of pSS-associated PAH with a complete assessment including clinical characteristics (of both PAH and pSS), hemodynamic parameters, medical management, and outcome. We also review the 19 fully documented PAH patients with pSS reported in the English-language literature, therefore analyzing a total of 28 cases (27 women; mean age at PAH diagnosis, 50 +/- 11 yr; range, 23-68 yr). Functional impairment at diagnosis was severe, with a New York Heart Association (NYHA) functional class of III or IV in most cases. Seven of 15 (47%) patients for whom data were available had history or evidence of right heart failure at PAH diagnosis. Hemodynamic parameters were moderate to severe with a mean pulmonary artery pressure of 44 +/- 11 mm Hg (range, 24-60 mm Hg) and a cardiac index of 2.91 +/- 0.72 Lmin(-1)m(-2) (range, 1.36-3.88 Lmin(-1)m(-2)). Standard PAH therapy (endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, or prostanoids) was initially effective in some patients but had short-term and long-term failures. Some patients were treated with first-line immunosuppressants alone leading to improvement in some, but second-line standard PAH therapy was added in all cases thereafter. The best treatment strategy remains to be defined. Estimated survival rates were low (73% and 66% at 1 and 3 years, respectively). Compared with pSS patients without PAH, patients with pSS-associated PAH had Raynaud phenomenon, cutaneous vasculitis, and interstitial lung disease significantly more frequently. They also more frequently had antinuclear, anti-Ro/SSA, and anti-RNP autoantibodies, as well as positive rheumatoid factor and hypergammaglobulinemia. These data suggest that systemic vasculopathy, B-cell activation, and autoimmunity could play a role in the pathophysiology of pSS-associated PAH. In conclusion, this report underlines the rarity and severity of PAH in pSS patients. The best therapeutic regimen remains to be defined but should include standard PAH therapy and/or immunosuppressants.

Dorfmüller P, Humbert M, Perros F, Sanchez O, Simonneau G, Müller KM, Capron F. · Service d'Anatomie et de Cytologie Pathologiques, Centre Hospitalier Universitaire Pitié-Salpêtrière, 47-83, Boulevard de l'Hôpital, F-75651 Paris Cedex 13, France. · Hum Pathol. · Pubmed #17376507 No free full text.

Abstract: Pulmonary arterial hypertension is a severe complication of connective tissue diseases. It is currently well established that pulmonary arterial hypertension associated with connective tissue diseases such as systemic sclerosis is frequently less responsive or even refractory to pulmonary vasodilator therapies. In that setting, pulmonary venoocclusive disease is believed to contribute to treatment failures. We therefore hypothesized that pulmonary arterial hypertension associated with connective tissue diseases may be associated with obstructive lesions of pulmonary veins. Lung samples from 8 patients with pulmonary arterial hypertension associated with connective tissue disease (4 limited systemic sclerosis, 2 systemic lupus erythematosus, 1 mixed connective tissue diseases, and 1 rheumatoid arthritis) were studied by light microscopy and analyzed by immunohistochemistry (5 postmortem samples, 3 explants after lung transplantation). Findings were compared with 29 pulmonary arterial hypertension cases from patients displaying neither connective tissue diseases nor associated conditions. We found that (a) 6 (75%) of 8 patients with pulmonary arterial hypertension associated with connective tissue diseases showed significant obstructive pulmonary vascular lesions predominating in veins/preseptal venules, as compared with 5 (17.2%) of 29 non-connective tissue diseases control pulmonary arterial hypertension; (b) lesions of small muscular arteries were consistently present in pulmonary arterial hypertension associated with connective tissue diseases, showing mostly intimal fibrosis and thrombotic lesions; and (c) 6 of 8 lung samples from patients with pulmonary arterial hypertension associated with connective tissue diseases revealed perivascular inflammatory infiltration. In conclusion, our study highlights the fact that pulmonary arterial hypertension complicating the course of connective tissue diseases may be characterized by a more frequent involvement of pulmonary veins and may thus explain why these patients are less prone to respond to specific pulmonary arterial hypertension treatment as compared with idiopathic pulmonary arterial hypertension.