Pulmonary arterial hypertension: a rare complication of primary Sjögren syndrome: report of 9 new cases and review of the literature.
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.
Launay
David
D
From 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 (DL, XJ, GS, MH) and Service de Médecine Interne, Centre National de Référence de la Sclérodermie, Hôpital Claude-Huriez, CHRU Lille, Université Lille 2, Lille (DL, EH, PYH), France.
Hachulla
Eric
E
Hatron
Pierre-Yves
PY
Jais
Xavier
X
Simonneau
Gérald
G
Humbert
Marc
M
D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000276:immunology; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D065128:Endothelin Receptor Antagonists; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D005602:France; D006333:Heart Failure / Q000209:etiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis* / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D058986:Phosphodiesterase 5 Inhibitors; D011453:Prostaglandins / Q000627:therapeutic use; D011669:Pulmonary Wedge Pressure; D012189:Retrospective Studies; D012859:Sjogren's Syndrome / Q000150:complications* / Q000276:immunology / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome
D000974:Antibodies, Antinuclear; D065128:Endothelin Receptor Antagonists; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D058986:Phosphodiesterase 5 Inhibitors; D011453:Prostaglandins