Pulmonary Complications of Connective Tissue Disease

Philip Clements, M.D., Daniel E. Furst, M.D., Athol U. Wells, M.D.

Pulmonary complications are responsible for a substantial number of deaths and morbidity among patients with connective tissue diseases (CTDs). The advent of computed tomographic (CT) scans has allowed earlier recognition of pulmonary, pleural, and bronchiolar complications associated with CTDs. Historically, approach to pulmonary complications (PCs) of CTD has been nihilistic, since no therapy had proven efficacy. Within the past few years, improvement in clinical outcomes with immunosuppressive and cytotoxic agents has led to increasing optimism and more aggressive treatment regimens for these diverse PCs. For the practicing clinician, numerous questions remain unanswered. What is the frequency of clinically significant PC among specific CTDs? What is the role of lung biopsy to establish a specific histological diagnosis? What tests are appropriate to diagnose PCs? When PCs are identified, what is the appropriate therapy? In this issue, a group of international experts contribute their insights to these difficult problems.

In the opening article, Drs. Leslie, Trahan, and Gruden describe the salient pathologic and histopathologic features of the myriad pulmonary and bronchiolar complications of CTDs. These authors note that each of the CTDs typically are associated with a characteristic set of pleuropulmonary manifestations. They discuss the cardinal pathological features of several PCs including: Usual interstitial pneumonia (UIP) pattern; organizing pneumonia (OP); nonspecific interstitial pneumonia (NSIP); lymphoid interstitial pneumonia (LIP); acute interstitial pneumonia (AIP) (associated with diffuse alveolar damage [DAD] pattern); obliterative (constrictive) bronchiolitis (OB); follicular bronchiolitis; lymphoid follicles; vasculitis; acute lupus pneumonitis; pulmonary hemorrhage; and pulmonary hypertensive changes.

In the next article, Dr. Athol Wells reviews the role of pulmonary physiological tests (including pulmonary function tests [PFTs] and cardiopulmonary exercise tests [CPETs]) to diagnose PCs and assess prognosis and responsiveness to therapy.

Drs. Devaraj, Wells, and Hansell describe the salient CT features observed in the diverse CTDs, and the role of CT to detect and monitor the evolution of PCs.

Drs. Marder and McCune delineate the mechanisms of action, administration, toxicities, efficacy, and clinical role of diverse immunosuppressive and cytotoxic agents used to treat the diverse CTDs.

In articles 5-9, PCs for each of the 5 most common CTDs are covered in detail.

Drs. Highland, Garin, and Brown describe the wide spectrum of PCs associated with progressive systemic sclerosis (PSS). Pulmonary arterial hypertension (PAH) is a leading cause of mortality in PSS and the diagnosis and management of PAH in patients with PSS is discussed in detail. The authors then review the interstitial lung disorders (ILDs) that may complicate PSS (particularly NSIP and UIP). Additional topics covered include pleural disease, lung cancer, and aspiration (due to esophageal involvement).

Drs. Gauhar, Gaffo, and Alarcón discuss the diverse pleuropulmonary complications of rheumatoid arthritis, and outline therapeutic strategies including newer immunosuppressive agents and monoclonal antibodies.

Drs. Memet and Ginzler describe the myriad PCs of systemic lupus erythematosus (including pleural complications, acute lupus pneumonitis, diffuse alveolar hemorrhage, pulmonary arterial hypertension, antiphospholipid syndrome, ILDs, and others).

Drs. Fathi, Lundberg, and Tornling elegantly discuss polymyositis and dermatomyositis, including pathogenesis, serological markers (particularly anti-Jo1 antibodies), myopathic, non-pulmonary and pulmonary manifestations.

Finally, Drs. Papiris, Tsonis, and Moutsopoulos delineate the myriad PCs of Sjogren's syndrome including lymphoid interstitial pneumonia (LIP) and lymphomas.

We are pleased that this issue provides a comprehensive, state-of-the-art review of a difficult and evolving subject.