Pulmonary hypertension in rheumatic diseases

Pulmonary hypertension (PH) is a progressive disease of the pulmonary vasculature characterized by increased vascular resistance and pressure overload of the right ventricle. Histologically, PH lungs demonstrate medial hypertrophy of small pulmonary arteries and proliferation of endothelial cells resulting in plexiform lesions. Recent studies have identified mutations of the bone morphogenetic protein receptor 2 (BMPR2) gene and the activin-receptor-like kinase 1 (ALK1) gene, that affect the transforming growth factor beta (TGF-beta) receptor superfamily, a group of transmembrane signaling molecules with serine-threonine kinase activity that are involved in the regulation of cell growth. Several lines of evidence indicate that the development of PH is a multi-hit process, where one of the events is having a gene mutation and another might be a circumstantial condition or other disease-modifying genes. It is unknown which mechanism that is critical in rheumatic diseases causes pulmonary vascular disease. PH is most frequently associated with systemic sclerosis (SS), systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD), however, it is still a rare manifestation of these disorders. For example, approximately 10% of SS cases manifest pulmonary vascular disease. In recent years symptomatic vasodilator therapies have been employed and have been able to improve exercise capacity and survival in these patients.     

Ultrastructural pathology of skeletal muscle in various rheumatic diseases

Seventy-three muscle biopsies from patients with various rheumatic diseases were analyzed using immunofluorescence, light, and ultrastructural microscopy. Pathologic data were correlated with clinical variables of local muscle and systemic disease. Light and immunofluorescence findings were generally normal. Ultrastructure differed from normals, showing a spectrum of nonspecific changes. There were no disease specific pathologic features. Myofibrillar damage was the most common pathologic change, with atrophy or degeneration occurring in a majority of biopsies. Semiquantitative analysis showed a general correlation between the extent of pathologic change and muscle weakness.     

Pulmonary hypertension in rheumatic diseases: epidemiology and pathogenesis

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.     

Pulmonary alveolar hemorrhage in patients with rheumatic diseases in Korea

Pulmonary alveolar hemorrhage (PAH) is a rare and often fatal presenting feature of rheumatic diseases, with high mortality rate ranging from 40% to 90%. This study was undertaken to review the clinical manifestations, disease course, prognosis, and treatment of PAH in rheumatic diseases in Korea. A retrospective analysis was performed from October 1995 to March 1999 at the Samsung Medical Center. Ten cases were diagnosed as having pulmonary hemorrhage with rheumatic diseases that comprised the following: 6 systemic lupus erythematosus (SLE), 3 microscopic polyangiitis (MPA), and 1 mixed connective tissue disease (MCTD). In 80% of the patients in the present series, PAH was the first clinical manifestation of rheumatic diseases. The most consistent systemic manifestation occurring in conjunction with PAH was renal involvement (80%). The overall patient mortality rate was 50% (5/10) in the current series. Our study suggests that PAH often occurs as the first clinical manifestation of rheumatic diseases and needs urgent medical treatment including plasmapheresis in addition to cyclophosphamide and methylprednisolone.     

Commented glossary for rheumatic spinal diseases, based on pathology.

OBJECTIVES--To redefine and comment on terms on a pathological basis, in order to avoid the confusion due to the use of terms with different meanings, to standardise usage among clinicians, radiologists and pathologists, and to facilitate literature searches. METHODS--Within the Committee of Pathology of the European League against Rheumatism, a study group was set up to analyse the medical literature and common practice concerning the nomenclature of rheumatic spinal diseases. The group tried to amalgamate the main trends in the field, to reconcile etymology, historical background, morphology, and common practice. RESULTS--The group warns against use of the terms 'acquired hyperostosis syndrome', '(von) Bechterew's disease', 'Kümmel's disease', 'pseudospondylolisthesis', 'rheumatoid spondylitis', 'spondylarthropathy' in the sense of spondarthritis, and 'spondylosis'. It recommends intercorporal or interapophyseal rather than intervertebral (osteo) chondrosis, zygapophyseal diverticulum rather than cyst, disc hernia rather than prolapse, spondyloarthritis rather than spondyloarthropathy, marginal rather than anterior spondylitis, and discarthrosis. It proposes 'zygarthrosis' to designate zygapophyseal osteoarthrosis. CONCLUSIONS--Knowledge of the pathological basis of diseases and an understanding of the original definitions given by those who coined new terms make it possible to avoid most of the confusion arising from improper use of spinal terms.     

Pain in the rheumatic diseases

The importance of pain in the health status and health behavior of patients with chronic rheumatic disease was evaluated. The Arthritis Impact Measurement Scales were used to estimate physical disability, psychological status, and pain in a large set of rheumatic disease patients. Explanatory regression models were built to explore the contribution of pain in physician and patient assessments of overall health, medication usage, and changes in health status over time. Results confirm that pain makes a highly significant contribution to explaining both physician and patient overall health assessments (P < 0.001). Pain is also the most important of the 3 health status components in explaining medication usage (P < 0.001). Finally, using prospective data, it is shown that current pain, rather than current physical or psychological disability, is the best predictor of subsequent pain (P < 0.001). Current pain also is most associated with subsequent physical disability (P < 0.05). These findings confirm the importance of pain in determining the health status and health behavior of individuals with chronic rheumatic disease, and suggest that doctors and other health professionals should continue to solicit and address the patient's complaints of pain.     

Mortality in the rheumatic diseases

Objective. To review mortality data in published studies of various rheumatic diseases. Methods. A MEDLINE search of the literature on the rheumatic diseases, including osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, scleroderma, polymyositis, and vasculitis. Results. Mortality rates higher than expected have been reported in most rheumatic conditions, considerably higher for inflammatory rheumatic diseases. The mortality rates in patients with systemic lupus erythematosus, scleroderma, polymyositis, and vasculitis are often comparable to mortality rates seen in patients with neoplastic or cardiovascular diseases, although the causes of death often are not identified as the rheumatic disease. Conclusion. Mortality has been found to be predicted in most instances by more severe clinical status, and therefore death should not be considered as “unrelated” to the rheumatic disease. These observations may have important implications for clinical care and health policies regarding patients with rheumatic diseases.