The connective tissue diseases (CTDs) are a heterogeneous group of disorders characterized by inflammatory and fibrotic tissue injury. The lung is commonly affected by CTD. Because of the abundant connective tissue in the lung (and perhaps because of its large blood supply), any of its compartments (airways, parenchyma, vasculature, or pleura)—and not uncommonly multiple compartments simultaneously—are affected in cases of CTD, The interstitial lung diseases (ILDs) or diffuse parenchymal lung diseases are a group of heterogeneous disorders with both unknown and known causes. Known causes include inhalational exposures and drugs; in addition, ILD occasionally occurs as a manifestation of an underlying systemic illness, The association between CTD and ILD has been known for many years, and it is estimated that among patients who present with ILD, approximately 15% have or will acquire a defined CTD. However, therapy for CTD-related ILD (CTD-ILD) has been based largely on biological rationale, uncontrolled series, case reports, and anecdotal experience. review
Although it is recommended that therapy be considered on a case-by-case basis, a common approach to treating a patient with any CTD-ILD extends from the increasingly accepted scheme for treating patients with ILD related to the scleroderma spectrum of disease. In that framework, patients with evidence of a more inflammatory pulmonary phenotype (eg, ground-glass opacities on chest high-resolution CT [HRCT] scans, BAL cellular differential showing neutrophils or eosinophils, or cellular interstitial infiltrates in surgical lung biopsy specimens) are treated more aggressively—and respond more favorably—than patients with a fibrotic pulmonary phenotype. A large, retrospective study showed that cyclophosphamide (CYC) improves lung function and survival in patients with scleroderma-related alveolitis. Further, the results from a recently completed, multicentered, placebo-controlled trial (The Scleroderma Lung Study), which were presented at the 2005 international meeting of the American Thoracic Society, revealed that CYC preserved lung function and improved quality of life.
In an effort to limit a patient’s exposure to the adverse effects of glucocorticoids, certain immunomodulatory agents (eg, CYC or azathioprine [AZA]) have been incorporated into CTD-ILD treatment regimens as steroid-sparing agents. However, like glucocorticoids, these agents carry their own potential toxicities and side effects. Recently, mycophenolate mofetil (MMF), an inhibitor of proliferating lymphocytes via its effects on the purine synthesis pathway, has been used to treat patients with several connective tissue and other diseases, including lupus nephritis, Wegener granulomatosis, polymyositis, and dermatomyositis.