Wegener's granulomatosis

Diagnostic difficulties have been described together with the course of hospital treatment of a 48-year old female patient who suffered from Wegener's granulomatosis. A first, the patient was treated by various specialists because of otolaryngological, ophthalmic, rheumatic and respiratory symptoms. Despite numerous symptoms suggesting Wegener's granulomatosis, ineffective treatment had been instituted for two months. Appropriate diagnosis was made on the basis of clinical symptoms and histological examination od lung biopsy. In the course of hospital diagnostic procedures, symptoms of kidney failure occurred. Treatment with cyclophosphamide and prednisone was instituted which resulted in remission of both radiological and clinical symptoms, however, the prognosis is still poor. The patient will requires long-term therapy with cyclophosphamide and a number of complications related to the therapy can be expected.     

Early experience with intravenous immunoglobulin treatment in Wegener's granulomatosis with ocular involvement

BACKGROUND: Pooled intravenous gammaglobulin (IVIg) was reported to be effective in the treatment of Wegener's granulomatosis (WG). No reports have been made on the effects of this new treatment on ocular manifestations of WG. METHOD: IVIg treatment was given to two patients suffering from WG with ocular involvement after several other treatment regimes had failed. RESULTS: Although the systemic disease was under control, the ocular symptoms of both patients worsened during and after IVIg treatment. In one case an adverse effect consisting of retinal vasculitis was noted on two occasions. CONCLUSION: Although beneficial effects of IVIg treatment on WG have been previously described, the two cases with ocular involvement presented here did not reveal any positive response. Paradoxical and unpredictable reactions cannot be ruled out. Thus, patients treated with IVIg should be closely surveyed by an ophthalmologist.     

Meningeal involvement in Wegener's granulomatosis

We describe a rare neurological manifestation of Wegener's granulomatosis, meningeal involvement, which occurred despite therapy resulting in disease quiescence in other organs. Clinical, radiographic, and neuropathological features are described.     

Pathogenesis of Wegener's granulomatosis

Although a single disease entity, Wegener's granulomatosis (WG) displays a set of clinical manifestations, each with a different immunopathogenesis. Granuloma formation, "pauci-immune" vasculitis and glomerulonephritis (= renal vasculitis) are the histologic hallmarks of WG which can occur together (WG triad) in full-blown disease, or separately in "initial phase" disease or the formes frustes. The different clinical manifestations are characterised by multiple immune abnormalities that culminate in the over-production of autoantibodies directed mainly against proteinase 3 (PR3-ANCA). A number of in vitro observations point to the potential mechanisms by which ANCA could induce neutrophil-mediated vascular injury, i.e. vasculitis. The most commonly postulated scenario for ANCA-mediated vasculitis involves the interaction of polymorphonuclear neutrophils (PMN) and endothelial cells (EC) via cell adhesion molecule interactions. The initiating event is ANCA-induced leukocyte activation, in which PMN-derived mediators (i.e. cytokines, lipid metabolites, etc.) are intimately involved. The result is necrotizing inflammation of blood vessel walls. However, the clinical and pathological hallmark of WG is the coexistence of vasculitis and granuloma. The causative agent(s) leading to granuloma formation, predominantly in the respiratory tract, is still unknown, but the presence of T cells in the granulomatous inflammation indicates T-cell hyperactivity. Immunohistochemical studies have shown that the cellular infiltrations in renal and pulmonary lesions of WG primarily contain CD4+ T-cells and macrophages. Recent investigations have demonstrated that CD4+ T-cells from granulomatous lesions in the nose and from bronchoalveolar lavage (BAL) mainly express the Th1 cytokine profile, which stimulates predominantly cell-mediated immune responses. This result supports the hypothesis that due to the two-phase course of WG there occurs a polarisation of the T-cell sub-population (Th1 versus Th2 type) which may explain the transition from the initial (granulomatous) phase of WG (so-called localized or locoregional restricted WG) to the generalized (vasculitic) phase. In conclusion, although the initiating events in the development of WG are still unknown, remarkable advances have been made in characterizing the infiltrating inflammatory cells and their products, which is of major importance in understanding the pathogenesis of this disease. In this regard, the use of specific mediators (i.e. cytokines, adhesions molecule antagonists, anti-Id ANCA, etc.) to modulate the inflammatory response may prove beneficial in the therapy of WG.     

Wegener's granulomatosis, immunosuppressive therapy

We present a study of 11 patients with Wegener's granulomatosis. Seven of these were treated with Azathioprine (Imurel) combined with prednisone. Of these, 4 patients rapidly improved after the treatment was started. Atelectatic changes in the lungs disappeared. A rapidly progressive renal failure was reversed, and renal function returned to normal. Large lesions of the skin also improved. The treatment has now lasted 2 1/2-4 1/2 years without interruption. We have not had any serious side effects due to Imurel. We believe that the good effect of the treatment is due to immunosuppression by the drugs.     

Disseminated histoplasmosis and Wegener's granulomatosis

Disseminated histoplasmosis is an unusual complication in endemic areas and has been reported in patients with an immunodeficient state, either from human immunodeficiency virus (HIV) infection or transplantation. In the non-HIV population, rare cases of disseminated histoplasmosis have been reported in patients with leukemia and Hodgkin's disease and patients receiving steroid therapy for various diseases. We report a case of disseminated histoplasmosis in a patient with Wegener's granulomatosis.     

Wegener's granulomatosis presenting with a renal mass

Wegener's granulomatosis (WG) is a systemic disease characterized by necrotizing granulomatous vasculitis that involves primarily the upper and lower respiratory tracts and, in most cases, the kidneys. Kidney involvement in WG presenting as a mass is recognized, but is very rare. We describe a case of WG presenting with upper and lower respiratory symptoms and a renal mass due to both WG and renal cell carcinoma.     

High dose methylprednisolone for retroorbital Wegener's granulomatosis

Wegener's granulomatosis (WG) is frequently associated with retroorbital involvement, which typically responds slowly to the standard therapy of oral corticosteroids and cytotoxic agents. We describe the case of a 61-year-old man with WG, who developed marked retroorbital granulomatous inflammatory tissue and experienced a dramatic clinical and radiographic response to the administration of high dose intravenous (iv) methylprednisolone. We believe that high dose iv methylprednisolone may have distinct advantages over standard therapies in the treatment of retroorbital WG.     

Antineutrophil cytoplasmic antibodies in 2 patients with Wegener's granulomatosis

We describe two patients with diffuse alveolar hemorrhage and Wegener s Granulomatosis. In both cases, ANCA were demonstrated. We discuss the profit about ANCA s in the diagnosis and management the systemic vasculitis.     

Wegener's granulomatosis with meningeal involvement: clinic-radiological correlations

INTRODUCTION: Wegener's granulomatosis is a systemic vasculitis which, in its classical form, is characterized by involvement of the superior and inferior respiratory tract and the kidneys. The vasculitis may be multisystemic. Ophthalmic and neurological involvement are common (22% and 54% of those affected respectively). When considering involvement of the nervous system, the commonest finding is peripheral neuropathy, particularly in the form of multiple mononeuritis. Meningeal involvement is exceptional. CLINICAL CASE AND CONCLUSIONS: We present a case of Wegener's granulomatosis with meningeal involvement, studied using CT and MR. The findings using imaging techniques are described, and conditions which should be considered in the differential diagnosis are discussed.     

Pulmonary Wegener's granulomatosis: changes at follow-up CT

The objective of this study was to assess the reversibility of pulmonary lesions in Wegener's granulomatosis using serial CT. We reviewed the follow-up CT scans of ten treated patients with confirmed Wegener's granulomatosis. The delay between the first evaluation before treatment and the second, on patients in clinical and biological remission, ranged from 6 to 54 months (mean 20.5 months). Follow-up CT showed a decrease in the extent of disease in all cases. Lesions disappeared completely, without scarring, in 4 of 4 ground-glass opacities, 25 of 36 nodules, and 4 of 9 pulmonary consolidations; they disappeared with residual scarring in 8 of 8 masses, 3 of 9 pulmonary consolidations, and 2 of 36 nodules. The majority of lesions disappear without scarring. Residual fibrosis may follow the occurence of masses and pulmonary consolidation. Computed tomography permits assessment of cicatricial lesions.