Wegener's granulomatosis: current and upcoming therapies

Wegener's granulomatosis is a complex multisystem disease that can be associated with morbidity and mortality. The introduction of cyclophosphamide and glucocorticoids brought about the potential for long-term survival and provided the opportunity and impetus to explore treatment options that can reduce the toxicity of therapy and lessen the likelihood of relapse. With the growth of knowledge regarding disease pathophysiology and the increasing ability to selectively target the immune system, the potential options for therapeutic investigation have continued to expand. Careful study of new agents through rigorously designed trials is essential to answering questions of safety and efficacy in Wegener's granulomatosis.     

Multiple paracoccidioidomas simulating Wegener's granulomatosis

Five cases of paracoccidioidomas are reviewed. One case with multiple coin-lesions simulating Wegener's granulomatosis is described.From the Pavilhão Pereira Filho, Santa Casa de Misericórdia, Porto Alegre, RS, Brazil.     

Staphylococcus aureus and Wegener's granulomatosis

Wegener's granulomatosis (WG) is a form of systemic vasculitis. It is characterized by granulomatous inflammation in the upper and lower airways, vasculitis and necrotizing glomerulonephritis, and is strongly associated with antineutrophil cytoplasmic antibodies against proteinase 3. Since the etiology of the disease is not clear, treatment, consisting of corticosteroids and immunosuppressives, is nonspecific and associated with severe side effects. Pinpointing the trigger(s) of the disease would highly improve treatment. Clinical evidence shows that an infectious agent, the bacterium Staphylococcus aureus, is a risk factor for disease relapse, suggesting its involvement in the pathogenesis of WG. Here we review both clinical and experimental data that either indicate or support a role for S. aureus in WG.     

Staphylococcus aureus and Wegener's granulomatosis

Wegener's granulomatosis (WG) is a form of systemic vasculitis. It is characterized by granulomatous inflammation in the upper and lower airways, vasculitis and necrotizing glomerulonephritis, and is strongly associated with antineutrophil cytoplasmic antibodies against proteinase 3. Since the etiology of the disease is not clear, treatment, consisting of corticosteroids and immunosuppressives, is nonspecific and associated with severe side effects. Pinpointing the trigger(s) of the disease would highly improve treatment. Clinical evidence shows that an infectious agent, the bacterium Staphylococcus aureus, is a risk factor for disease relapse, suggesting its involvement in the pathogenesis of WG. Here we review both clinical and experimental data that either indicate or support a role for S. aureus in WG.     

Haemodialysis and transplantation in Wegener's granulomatosis.

Two men with Wegener''s disease began immunosuppressive treatment during severe renal insufficiency. Despite an initial temporary remission new lesions appeared and renal failure progressed. Haemodialysis was started, cytotoxic drugs were stopped, and steroid dosage was reduced. All extrarenal manifestations of the disease remitted, however, suggesting a favourable effect of either the immunosuppression induced by terminal renal failure or the haemodialysis itself. Renal transplantation was then undertaken in both patients. Thirteen and 55 months after the operations respectively renal function was satisfactory and no signs of reactivation of Wegener''s disease had appeared. These results show that whatever the activity of Wegener''s disease and its initial response to immunosuppressive agents, dialysis and transplantation are fully warranted once irreversible renal failure is established.     

Relapses in Wegener's granulomatosis: the role of infection.

Out of 20 relapses that occurred in patients with Wegener''s granulomatosis, nine were provoked by bacterial or viral infection. Seven of these occurred during maintenance treatment in response to infection with common pathogens, and treatment of the infection alone was insufficient to produce remission. Circulating immune complexes were seen only in relapses due to infection and rarely in infections that occurred without relapse. A possible mechanism for infection-provoked relapses is that infection-derived complexes reactivate disease; alternatively, the acute-phase or cellular response to infection may enhance quiescent disease. Infection may exacerbate Wegener''s granulomatosis and other autoallergic diseases, but whether it does so by a common mechanism is not known and further study is required.     

Pulmonary haemorrhage complicating Wegener's granulomatosis and microscopic polyarteritis.

The incidence and characteristics of pulmonary haemorrhage in a series of 89 patients with systemic vasculitis were analysed. Pulmonary haemorrhage occurred in 32 of these patients and was associated with haemoptysis in all 32, alveolar shadowing in the chest radiograph in 28, and a significantly raised transfer coefficient in 30. Pulmonary haemorrhage usually resolved with treatment by immunosuppressive drugs but was the cause of death in 11 patients. In contrast with patients with antibasement membrane antibodies there was no correlation between pulmonary haemorrhage and cigarette smoking. Pulmonary haemorrhage is a cause of serious morbidity in patients with systemic vasculitis.