Connective tissue disease-associated pulmonary arterial hypertension in the modern treatment era.
ABSTRACT Pulmonary arterial hypertension in association with connective tissue disease (CTD-PAH) has historically had a poor prognosis, with a 1-year survival rate among patients with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) of 45%. However, more therapies have become available.
To investigate the survival and characteristics of all patients diagnosed with CTD-PAH in the U.K. pulmonary hypertension service.
National registry of all incident cases of CTD-PAH diagnosed consecutively between January 2001 and June 2006.
Patients with CTD-PAH (429; 73% SSc-PAH) were diagnosed by a catheter-based approach. One- and 3-year survival rates were 78 and 47% for patients with isolated SSc-PAH. Survival was worse for those with respiratory disease-associated SSc-PAH (3-yr survival, 28%; P = 0.005) whereas survival among patients with exercise-induced SSc-PAH was superior (3-yr survival, 86%; P = < 0.001). Age, sex, mixed venous oxygen saturation, and World Health Organization functional class were independent predictors of survival in isolated SSc-PAH. Nineteen percent of patients with exercise-induced SSc-PAH and 39% of patients with isolated SSc-PAH who were in functional classes I and II had evidence of disease progression. The prevalence of diagnosed SSc-PAH is 2.93 per 1 million. The 3-year survival rate of 75% for those with pulmonary arterial hypertension associated with systemic lupus erythematosus (SLE-PAH) was significantly better than that for patients with SSc-PAH (P = 0.01).
Survival of patients with SSc-PAH in the modern treatment era is better than in historical series. A significant proportion of patients with mild functional impairment or exercise-induced SSc-PAH have evidence of disease progression. Survival of patients with respiratory disease-associated pulmonary hypertension is inferior. SLE-PAH has a better prognosis than SSc-PAH.
Article: Sklerodermie[Show abstract] [Hide abstract]
ABSTRACT: Die Sklerodermie (Synonyme: systemische Sklerose, systemische Sklerodermie) ist eine Systemerkrankung, die neben der Haut auch innere Organe wie die Lunge, den Gastrointestinaltrakt, die Niere und das Herz befällt. Pathogenetisch ist zwischen einer unkontrollierten Bindegewebsvermehrung (Fibrose) und einer Vaskulopathie zu unterscheiden. Dies führt klinisch neben den Organfibrosen auch zu Gefäßmanifestationen. Hierzu zählen Fingerkuppenulzera, die pulmonalarterielle Hypertonie und die akute Nierenkrise. Von der systemischen Sklerose sind lokalisierte Sklerodermieformen wie die Morphea abzugrenzen, die ohne Organkomplikationen verlaufen. Aufgrund ihrer klinischen Heterogenität, ihrer hohen Morbidität und Mortalität stellt die systemischen Sklerose für den klinischen Alltag eine große diagnostische und therapeutische Herausforderung dar. Dieser Übersichtsartikel fasst den aktuellen Stand zur Klassifikation und Epidemiologie, Pathogenese, den wichtigsten klinischen Manifestationen wie interstitielle Fibrose, pulmonalarterielle Hypertonie, akute Nierenkrise und periphere Vaskulopathie zusammen und gibt einen Überblick aktueller und zukünftiger Therapiemöglichkeiten. Scleroderma (synonyms: systemic sclerosis, systemic scleroderma) is a systemic disease which affects the skin as well as internal organs such as the lungs, gastrointestinal tract, kidneys, and the heart. Pathogenetically a distinction should be made between uncontrolled formation of extracellular matrix proteins (fibrosis) and vasculopathy. In addition to organ fibrosis, this leads to a clinical picture of vascular manifestations. These include fingertip ulcers, pulmonary arterial hypertension, and acute renal crisis. Localized forms of scleroderma, such as morphea, which do not involve organ complications, should be differentiated from systemic sclerosis. Due to its clinical heterogeneity and high rate of morbidity and mortality, systemic sclerosis poses an enormous diagnostic and therapeutic challenge in everyday clinical practice. This review article summarizes the current status of classification and epidemiology, pathogenesis, and the most important clinical manifestations such as interstitial fibrosis, pulmonary arterial hypertension, acute renal crisis, and peripheral vasculopathy and provides an overview of current and future treatment options. SchlüsselwörterSklerodermie-Systemische Sklerose-Fibrosierende Erkrankungen-Lungenfibrose-Pulmonalarterielle Hypertonie KeywordsScleroderma-Systemic sclerosis-Fibrotic diseases-Pulmonary fibrosis-Pulmonary arterial hypertensionDer Internist 01/2010; 51(1):30-38. · 0.33 Impact Factor
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ABSTRACT: Few studies have focused on pulmonary arterial hypertension (PAH) associated with connective tissue diseases (CTDs). The optimal treatment for CTD-PAH has yet to be established. Meta-analysis of the data from evaluations of treatment for PAH generally (19 studies) and CTD-PAH specifically (nine studies) to compare the effects of pulmonary vasodilative PAH agents. MEDLINE, EMBASE and BIOSIS were searched. English-language full-text articles published between January 1990 and August 2012 were eligible. International. Patients with PAH generally (n=3073) and CTD-PAH specifically (n=678). Exercise capacity (6 min walk distance, 6 MWD). Patients with PAH (all forms) had mean age 32-55 years (women, 61-87%); CTD-PAH patients had mean age 45-55 years (women, 74-95%). Overall estimate of mean change in 6 MWD from baseline (95% CI) for the active treatment group versus the control group in all patients with PAH was 34.6 m (27.4-41.9 m). Pooled mean differences from the results for patients receiving placebo by subgroup of patients receiving phosphodiesterase (PDE)-5 inhibitors, endothelin receptor antagonists (ERAs) and prostacyclin (PGI2) analogues were 22.4-45.5, 39.5-44.2 and 12.4-64.9 m, respectively. Overall estimate of mean difference between changes in 6 MWD in patients with CTD-PAH was 34.2 m (23.3-45.0 m). Pooled mean differences by subgroup of patients receiving PDE-5 inhibitors, ERAs and PGI2 analogues in patients with CTD-PAH were 37.0-47.1, 14.1-21.7 and 21.0-108.0 m, respectively. ERAs were less effective in patients with CTD-PAH than all-form patients with PAH: 14.1 m (-4.4-32.6 m) vs 39.5 m (19.5-59.6 m) for bosentan and 21.7 m (2.2-41.3 m) vs 44.2 m (30.2-58.2 m) for ambrisentan. All three types of PAH agent are effective. However, ERAs may be a less effective choice against CTD-PAH; further studies are needed. Limitations include the limited number of studies for some agents and for patients with CTD-PAH.BMJ Open 01/2013; 3(8). · 1.58 Impact Factor
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ABSTRACT: The focus of this review is to increase awareness of pulmonary arterial hypertension (PAH) in patients with rheumatic diseases. Epidemiology and pathogenesis of PAH in rheumatic diseases is reviewed, with recommendations for early screening and diagnosis and suggestion of possible role of immunosuppressive therapy in treatment for PAH in rheumatic diseases. A MEDLINE search for articles published between January 1970 and June 2012 was conducted using the following keywords: pulmonary hypertension, scleroderma, systemic sclerosis, pulmonary arterial hypertension, connective tissues disease, systemic lupus erythematosus, mixed connective tissue disease, rheumatoid arthritis, Sjogren's syndrome, vasculitis, sarcoidosis, inflammatory myopathies, dermatomyositis, ankylosing spondylitis, spondyloarthropathies, diagnosis and treatment. Pathogenesis and disease burden of PAH in rheumatic diseases was highlighted, with emphasis on early consideration and workup of PAH. Screening recommendations and treatment were touched upon. PAH is most commonly seen in systemic sclerosis and may be seen in isolation or in association with interstitial lung disease. Several pathophysiologic processes have been identified including an obliterative vasculopathy, veno-occlusive disease, formation of microthrombi and pulmonary fibrosis. PAH in systemic lupus erythematosus is associated with higher prevalence of antiphospholipid and anticardiolipin antibodies and the presence of Raynaud's phenomenon. Endothelial proliferation with vascular remodeling, abnormal coagulation with thrombus formation and immune-mediated vasculopathy are the postulated mechanisms. Improvement with immunosuppressive medications has been reported. Pulmonary fibrosis, extrinsic compression of pulmonary arteries and granulomatous vasculitis have been reported in patients with sarcoidosis. Intimal and medial hyperplasia with luminal narrowing has been observed in Sjogren's syndrome, mixed connective tissue disease and inflammatory myopathies. Pulmonary arterial hypertension (PAH) associated with rheumatic diseases carries a particularly grim prognosis with faster progression of disease and poor response to therapy. Though largely associated with systemic sclerosis, it is being increasingly recognized in other rheumatic diseases. An underlying inflammatory component may explain the poor response to therapy in patients with rheumatic diseases and is a rationale for consideration of immunosuppressive therapy in conjunction with vasodilator therapy in treatment for PAH. Further studies identifying pathogenetic pathways and possible targets of therapy, especially the role of immunomodulatory medications, are warranted.Rheumatology International 01/2013; · 2.21 Impact Factor