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.     

Defective phagocyte adherence in acute poststreptococcal glomerulonephritis: clinical and laboratory observations

The adherence of circulating phagocytes to glass was studied in 15 children with acute poststreptococcal glomerulonephritis and in 27 healthy adults, 21 healthy children, and 14 children with normocomplementemic renal disease. The phagocytic adherence to glass in the patients with hypocomplementemic PSGN differed significantly from that of the control groups (p=less than 0.001). There was a positive correlation of phagocyte adherence with plasma C3 but not with plasma C4, C3, properdin factor B, severity of illness, or drugs administered. In addition, the adherence defect was present in two normocomplementemic PSGN patients. The defect gradually resolved in all patients with clinical improvement: it was useful as an index of recovery. The in vitro addition of functional C3 to whole blood produced the adherence defect in normal subjects and failed to correct the defect in patients with PSGN. It was postulated that a fragment of activated complement may have blocked a membrane receptor on these phagocytes and interfered with their adherence to glass.     

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.     

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.     

Morphology of poststreptococcal glomerulonephritis in adults

The authors followed the evolution of morphologic changes in adult patients with poststreptococcal glomerulonephritis (PSGN). In all the patients the kidney biopsies repeated in the period of 2 to 5 years after the acute phase, showed certain histopathologic changes as follows: increased number of mesangial cells, increase of mesangial matrix with scattered axiation and lobulation, segmental thickening of Bowman's capsule, interstitial fibrosis along with preservation of capillary lumen and absence of changes in major blood vessels. According to severity of histopathologic changes, the patients were classified into 4 groups: moderate severe changes--2 patients, mild--15 patients, small--12 and minimal changes were seen in 5 patients. It was proved that after acute stage of PSGN, in which morphologic appearance was more or less typical but not pathognomonic as well, increased number of secretory active mesangial cells was kept, which lead to gradual increasing of mesangial matrix and in slowly evolutive process by the model of glomerulosclerosis lead to irreversible damage of glomerules and interstitial fibrosis.     

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.     

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.     

Serum and glomerular IgG in poststreptococcal glomerulonephritis are correlated

Sinus histiocytosis is as a rule a benign disease of lymph nodes, infiltrated by large histiocytes. These cells show typical cytophagocytosis, particularly lymphophagocytosis. Other organs may be also involved by this disease, often including the skin. Exclusive cutaneous sinus histiocytosis without infiltration of lymph nodes seems to be very rare. To exclude other non-X histiocytoses or histiocytosis-X, it is advisable to use immunohistochemistry. We report on a patient with sinus histiocytosis and discuss the problems of differential diagnosis.     

Acute poststreptococcal glomerulonephritis mimicking Henoch-Sch?nlein purpura

Two children with acute glomerulonephritis, cutaneous vasculitis, and abdominal pain are reported. One child also had transient arthralgia and gastrointestinal hemorrhage. Although the clinical presentation mimicked many of the features of Henoch-Sch?nlein purpura, both patients had unusual variants of poststreptococcal glomerulonephritis.     

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.     

Raised serum immunoglobulin E in Wegener's granulomatosis

Five patients with Wegner's granulomatosis were found to have significantly raised serum immunoglobulin E (IgE) levels. The rise in IgE was not related to the extent of clinical involvement, was not part of a generalized serum immunoglobulin rise, and was not associated with eosinophilia. Raised serum IgE may be a clue to the pathogenesis of this disease.