Pulmonary Vasculitis

The vasculitides represent a diverse range of disease entities that are linked by the presence of blood vessel inflammation resulting in tissue injury. Pulmonary vasculitis is a prominent feature of many vasculitic diseases and can result in significant morbidity and mortality. Respiratory tract involvement is additionally significant because patients with a systemic vasculitis may first seek medical attention for symptoms related to the upper and lower airways. In this issue of Seminars in Respiratory and Critical Care Medicine, the vasculitic diseases are reviewed with an emphasis toward examining the pathophysiology, clinical features, and treatment of differing forms of pulmonary vasculitis.

Epidemiological studies have provided important information toward the understanding of the vasculitic diseases. Different vasculitides possess unique rates of incidence and prevalence as well as individual patterns for age of onset, and distribution based on gender and ethnicity. These factors have played a role in the classification of the vasculitic diseases and have also offered clues as to possible pathogenic mechanisms. Dr. Richard Watts and Dr. David Scott contribute a detailed review of the epidemiology of the vasculitides and how these studies continue to enhance our knowledge of these diseases.

Recent advances have allowed us to examine in much greater detail the pathogenetic mechanisms of vascular inflammation. The discovery of antineutrophil cytoplasmic antibodies (ANCA) and their association with vasculitis affecting the small vessels raised important questions as to their role in these diseases. The investigation of ANCA has led to a greater understanding of these antibodies as well as the initiation of a diverse range of pathophysiologic studies examining cellular and humoral pathways that may be involved in disease. The pathogenesis of pulmonary vasculitis, with an emphasis on the possible role of ANCA, is discussed in this issue by Dr. Peter Heeringa, Dr. Adrian Schreiber, Dr. Ronald Falk, and Dr. J. Charles Jennette.

Tissue histopathology provides the foundation of diagnosis for most of the vasculitic diseases. The histopathologist is therefore a critically important part of the patient care team in differentiating a primary vasculitis from another process that may have clinical and histological similarities. The challenges of interpreting tissue histology in the vasculitic diseases are compounded by the fact that histological changes may be patchy, and diverse pathological features can be seen within individual diseases. Dr. William Travis provides an in-depth description of the pathology of pulmonary vasculitis and the differential diagnosis for the vasculitic diseases associated with such findings.

Imaging modalities form an integral component in the diagnosis and ongoing assessment of patients with pulmonary vasculitis. Although this began with the use of chest radiography to detect pulmonary parenchymal disease, diagnostic imaging has diversified to include a wide range of studies, including computed tomography, magnetic resonance imaging, and positron emission tomography. The ability of these and other techniques to assess disease activity and better define remission and relapse remains an area of intense interest. Dr. Melanie Peachell and Dr. Nestor Müller summarize the radiological manifestations of different forms of vasculitis that have prominent pulmonary manifestations.

Within the vasculitic diseases, Wegener's granulomatosis presents amongst the widest spectrum of respiratory tract manifestations. These include involvement of the upper airways that can lead to a destructive sinusitis, collapse of the nasal cartilage, and tracheal stenosis. Wegener's granulomatosis can also be associated with a diverse range of lower airways manifestations affecting the pulmonary parenchyma, endobronchial airways, and pleura. Dr. Joseph Lynch, Dr. Eric White, Dr. Henry Tazelaar, and Dr. Carol Langford review the clinical features, diagnosis, and therapeutic approaches in Wegener's granulomatosis.

Microscopic polyangiitis (MPA) is an important cause of potentially life-threatening pulmonary vasculitis. The designation of MPA as a unique entity was proposed by a collective group of clinicians and histopathologists during the Chapel Hill Consensus Conference. In this nomenclature system, MPA is defined as a necrotizing vasculitis with few or no immune complexes affecting the small vessels in which necrotizing glomerulonephritis is common and pulmonary capillaritis often occurs. With the increased recognition of MPA, investigation of the pathophysiology and treatment of this disease has grown. Dr. Lucy Smyth, Dr. Gillian Gaskin, and Dr. Charles Pusey examine the history of MPA and current data regarding its clinical features and management.

Churg-Strauss syndrome can be associated with a variety of respiratory complications. Patients with Churg-Strauss syndrome frequently present with new onset asthma and allergic rhinitis, followed by peripheral and tissue eosinophilia and features of systemic vasculitis. The radiographic presentations of pulmonary parenchymal disease in Churg-Strauss syndrome are diverse and represent inflammation that histologically may be eosinophilic, granulomatous, or vasculitic. Dr. Loïc Guillevin, Dr. Christian Pagnoux, and Dr. Luc Mouthon review Churg-Strauss syndrome and recent advances made in understanding its pathogenesis and treatment.

Pulmonary capillaritis is not one specific disease entity but rather the histopathologic finding of alveolar wall infiltration with inflammation involving the capillary walls and small veins. Clinically, pulmonary capillaritis presents as diffuse alveolar hemorrhage. Within the primary vasculitic diseases, pulmonary capillaritis can occur most prominently in Wegener' granulomatosis and MPA. Pulmonary capillaritis can have an unpredictable and potentially fulminant course that can include hemoptysis, hypoxia, and respiratory failure. Rapid diagnosis and prompt treatment are essential and can be life saving. Dr. Augustine Lee and Dr. Ulrich Specks outline a systematic approach to the evaluation and management of patients who present with diffuse alveolar hemorrhage and discuss the differential diagnosis of pulmonary capillaritis.

Behçet's disease is a distinctive systemic disorder characterized by oral and genital ulcers, ocular inflammation, and skin lesions. Although pulmonary vascular manifestations are uncommon in Behçet's disease, they represent an important cause of patient mortality and have historically been associated with a poor prognosis. The care of patients with Behçet's disease presents many diagnostic and therapeutic challenges. Behçet's disease and its pulmonary manifestations are discussed by Dr. Manae Kurokawa, Dr. Hideshi Yoshikawa, and Dr. Noboru Suzuki.

The large vessel vasculitides are amongst the most common of the primary systemic vasculitic diseases. Although these are infrequently associated with pulmonary parenchymal disease they can present with respiratory tract symptoms. For these reasons, knowledge of the large vessel vasculitides and their range of clinical manifestations is important. Disease processes in which vascular inflammation of the large arteries may be seen include not only giant cell arteritis and Takayasu's arteritis but also sarcoidosis. Dr. Kathleen Maksimowicz-McKinnon and Dr. Gary Hoffman review the clinical features, diagnosis, and treatment of the vasculitic diseases that predominantly affect the large vessels.

Immunosuppressive therapies have formed the foundation of treatment for most primary systemic vasculitic diseases. Particularly in the case of the small vessel vasculitides, the introduction of combined treatment with cyclophosphamide and glucocorticoids brought the potential for long-term survival to these once fatal diseases. Despite this success, immunosuppressive agents are associated with both short- and long-term side effects. Monitoring and prevention of medication toxicities therefore play a critical part in patient management. Dr. Wendy Marder and Dr. W. Joseph McCune review the immunosuppressive agents that are used in the treatment of pulmonary vasculitis and provide an analysis of their mechanism of action and toxicity.

Advances in monoclonal antibody and recombinant DNA technology have allowed the development of immunomodulatory agents that are capable of targeting selected components of the immune response. Therapeutic application of these novel therapies has brought about significant advances in several immunologically mediated diseases and published reports of their use for treatment of the vasculitides continue to increase. Dr. Carol Langford examines the rationale for investigating novel immunomodulatory agents in the vasculitides, the need for clinical trials to examine safety and efficacy, and the available published experience in individual diseases.