In the latest Case Record of the Massachusetts General Hospital, a 34-year-old woman with a history of Raynaud’s phenomenon and symmetric joint pain was admitted to the hospital because of increasing dyspnea. An echocardiogram showed severe pulmonary hypertension. Diagnostic test results were received.
A diagnosis of pulmonary hypertension can be confirmed in a straightforward manner by echocardiography followed by right heart catheterization. Since there are many causes of pulmonary hypertension, defining the underlying cause is critical for choosing the most effective disease-specific therapy.
• What are the causes of pulmonary hypertension?
The causes of pulmonary hypertension are typically classified into five groups that are based on the underlying disorder. Group 1 is the pulmonary arterial hypertension group, which contains many broad categories of disease, such as idiopathic pulmonary arterial hypertension, inherited pulmonary arterial hypertension, and pulmonary arterial hypertension that is associated with any of a variety of entities (e.g., drugs and toxins, HIV infection, and connective-tissue diseases). Group 2 comprises disorders associated with pulmonary hypertension that are due to left-sided heart disease. Group 3 includes pulmonary hypertension attributed to underlying lung diseases and hypoxemia). Group 4 includes pulmonary hypertension due to chronic thromboembolic disease, and group 5 disorders include pulmonary hypertension due to hematologic, systemic, metabolic, or other disorders.
• What are clinical and serologic features associated with systemic lupus erythematosus (SLE)?
SLE is a chronic inflammatory disease that can affect multiple organ systems. The cause is unknown, although autoantibodies (especially ANA and anti-double-stranded DNA [dsDNA], anti-Smith [Sm], and antiphospholipid antibodies) are associated with this disease. Approximately 80% of patients with lupus have a positive test for anti-dsDNA antibodies. Women are affected more often than men, and the incidence is greatest in the third and fourth decades of life. Pulmonary hypertension is an uncommon complication of lupus, typically occurring in patients with Raynaud’s phenomenon and serous effusions. SLE often manifests with fever, fatigue or weight loss, and patients may present with a photosensitive rash, arthralgia or arthritis, alopecia, serositis, and nephritis or nephrotic syndrome.
Morning Report Questions
Q: What are the characteristics of scleroderma and what are the associated autoantibodies?
A: Scleroderma involves collagen deposition in the skin of patients in their fourth through sixth decades of life, more often women than men. When internal organs are also involved, the disease is termed systemic sclerosis, which is further divided into limited cutaneous and diffuse cutaneous systemic sclerosis. The skin changes may progress from early pruritus to edema to sclerodactyly. Other common associations include Raynaud’s phenomenon, pulmonary hypertension, esophageal involvement, and interstitial lung disease. Scleroderma renal crisis, which may be precipitated by the use of glucocorticoids, develops in a small percentage of patients and, if present, might explain this patient’s apparently new systemic hypertension. Pulmonary hypertension is much more common in scleroderma than in lupus, with or without interstitial lung disease. Several autoantibodies are associated with scleroderma, especially ANA and antitopoisomerase I (anti-Scl-70), anticentromere, anti-RNA polymerase III, and anti-(beta)2-glycoprotein I antibodies.
Q: What is mixed connective tissue disease, and what are the clinical features and serologic markers?
A: Mixed connective-tissue disease is an overlap syndrome, with features of lupus, scleroderma, and polymyositis. It is much more common in women than in men, is typically diagnosed in the second or third decade of life, and is associated with substantial morbidity and mortality. Arthralgias, arthritis (with swollen hands), Raynaud’s phenomenon, and pulmonary hypertension are particularly prominent features of mixed connective-tissue disease. Pulmonary hypertension may be relatively rapid in onset and is often the cause of death. Some other possible manifestations of mixed connective-tissue disease are pericarditis and interstitial lung disease. There are several schemes for diagnostic criteria for mixed connective-tissue disease, and patients with the disease may ultimately meet criteria for lupus or scleroderma. Testing for the anti-U1-ribonucleoprotein (RNP) antibody (an extractable nuclear antigen antibody) is positive in patients with mixed connective-tissue disease, and is a prerequisite for the diagnosis.