[Wegener granulomatosis and aneurysmal subarachnoid hemorrhage: an insignificant association?]. / Hémorragie sous-arachnoïdienne anévrismale et maladie de Wegener: une association peu commune.

BACKGROUND: Wegener granulomatosis (WG) is an uncommon systemic necrotizing vasculitis that demonstrates renal and respiratory tropism. While the pathogenesis of WG remains controversial, autoimmune and inflammatory mechanisms are likely to be involved. The nervous system could be affected in up to 54% of cases. Although central nervous system involvement has been reported in 7-11% of cases, aneurysmal subarachnoid hemorrhage (SAH) occurrence is exceptional. METHODS: We describe the third reported case of WG-related aneurysmal SAH and then discuss the diagnosis and pathogenesis of WG along with the physiopathology of intracranial aneurysm in light of recent data reported in the literature. RESULTS: A 63-year-old woman with WG was referred to our neurosurgical department for aneurysmal SAH. The vasculitis diagnosis had been established 4 years earlier when she presented with chronic sinusitis, recurrent cystitis, and renal failure. The cerebral angiography revealed an anterior communicating artery dysplastic aneurysm. The neurosurgical management of the aneurysm was scheduled but delayed because the patient was experiencing a vasculitis flare-up. Immunosuppressive therapy and intravenous corticotherapy were given, with the patient's improvement, allowing neurosurgical clipping of the aneurysm. CONCLUSIONS: Wegener granulomatosis-related aneurysmal SAH is an exceptional condition in neurovascular pathology. As inflammatory mechanisms are involved in the pathogenesis of aneurysm, the vasculitis flare-up could account for this SAH. The management of WG could benefit from anti-inflammatory therapy, as could the vasculitis-related SAH. SAH occurrence in patients with systemic vasculitis could indicate a vasculitis flare-up.

[Granulomatous arteritis through sarcoidosis]. / Antrite granulomateuse par sarcoïdose.

INTRODUCTION: Digestive localisation of sarcoidosis is rare. OBSERVATION: A 35 year-old man presented with sarcoidosis revealed by a mediastinal hilum lymphadenopathy 13 years earlier. Epigastric pain led to oeso-gastroduodenal fibroscopy and biopsies, showing inflammatory mucosa and numerous giant-cell epithelioid granulomas, without concomitant necrosis or fibrosis. COMMENTS: The clinical manifestations and endoscopic profile of gastric localisations of sarcoidosis are not specific. Diagnosis relies on several elements: presence of epithelioid granulomas without necrosis, history of sarcoidosis or the simultaneous existence of other localisations, evocative biological signs and the absence of elements evoking any other diagnosis. Treatment relies on corticosteroid therapy and sometimes requires endoscopic or surgical management.

Induction versus noninduction in renal transplant recipients with tacrolimus-based immunosuppression.

BACKGROUND: The aim of this study was to compare the efficacy and safety of induction treatment with antithymocyte globulins (ATG) followed by tacrolimus therapy with immediate tacrolimus therapy in renal transplant recipients. METHODS: This 12-month, open, prospective study was conducted in 15 centers in France and 1 center in Belgium; 309 patients were randomized to receive either induction therapy with ATG (n=151) followed by initiation of tacrolimus on day 9 or immediate tacrolimus-based triple therapy (n=158). In both study arms, the initial daily tacrolimus dose was 0.2 mg/kg. Steroid boluses were given in the first 2 days and tapered thereafter from 20 mg/day to 5 mg/day. Azathioprine was administered at 1-2 mg/kg per day. RESULTS: At month 12, biopsy-confirmed acute rejections were reported for 15.2% (induction) and 30.4% (noninduction) of patients (P=0.001). The incidence of steroid-sensitive acute rejections was 7.9% (induction) and 22.2% (noninduction)(P=0.001). Steroid-resistant acute rejections were reported for 8.6% (induction) and 8.9% (noninduction) of patients. A total of nine patients died. Patient survival and graft survival at month 12 was similar in both treatment groups (97.4% vs. 96.8% and 92.1% vs. 91.1%, respectively). Statistically significant differences in the incidence of adverse events were found for cytomegalovirus (CMV) infection (induction, 32.5% vs. noninduction, 19.0%, P=0.009), leukopenia (37.3% vs. 9.5%, P<0.001), fever (25.2% vs. 10.1%, P=0.001), herpes simplex (17.9% vs. 5.7%, P=0.001), and thrombocytopenia (11.3% vs. 3.2%, P=0.007). In the induction group, serum sickness was observed in 10.6% of patients. The incidence of new onset diabetes mellitus was 3.4% (induction) and 4.5% (noninduction). CONCLUSION: Low incidences of acute rejection were found in both treatment arms. Induction treatment with ATG has the advantage of a lower incidence of acute rejection, but it significantly increases adverse events, particularly CMV infection.

Hodgkin's disease after transplantation.

Hodgkin's disease (HD) has seldom been reported after transplantation. Epstein-Barr virus (EBV) is present in about 50% of Reed-Sternberg cells in HD developing in immunocompetent individuals, but is more frequently found in HD of acquired immune deficiency syndrome patients. We report 7 cases of HD that occurred in transplant recipients. Clinical and pathological data and studies of EBV reveal specific features of HD after transplantation. Six patients received kidney transplants and 1 patient received combined kidney and pancreas transplantation. Immunosuppressive therapy consisted of cyclosporine, steroids, azathioprine, and antilymphocyte globulins. One patient received, in addition, anti-CD3 mAb therapy and an EBV+ B cell lymphoma developed. Retrospective EBV serological data from patients were collected. Tumors were classified according to pathology. EBV studies were conducted by immunohistochemical methods with monoclonal antibodies to EBV-latent membrane protein (LMP) or EBV-nuclear antigen 2 (EBNA2), and by in situ hybridization for latent nuclear EBV-early RNAs (EBERs). The mean lapse of time between transplantation and HD was 49 months. Six patients presented with enlarged lymph nodes and 1 patient presented with liver involvement. HD was classified as IA in 2 patients, IIA in 3 patients, IIIB in 1 patient, and IVB in 1 patient. Four patients had primary EBV infection after graft, before HD, and the others reactivated latent EBV infection. Histological subtypes were mixed cellularity in 6 cases and lymphocytic depletion in 1 case. Latent EBV infection was detected with EBERs in all tumors. Reed-Sternberg cells expressed LMP, and were negative for EBNA2 expression. Six patients were treated: 2 patients at stage I received radiotherapy, and relapsed within 1 year with a more advanced stage of HD; chemotherapy was indicated as primary therapy in 5 patients, and as salvage therapy in 2 patients; it was associated with radiotherapy in 4 patients. Immunosuppressive therapy was reduced in all patients. Four patients were alive and in complete remission 18, 25, 31, and 67 months after chemotherapy, with a functioning graft in 3 patients. Two patients died of infection. Mixed cellularity is the most frequent histological subtype observed in HD occurring in transplant patients. EBV is present in all Reed-Sternberg cells. Posttransplant HD shows similarities with human immunodeficiency virus-associated HD. These facts argue for a role of EBV infection and immunosuppression in the progression of HD after transplantation.

Crescentic glomerulonephritis and crystals within glomerular capillaries in an AIDS patient treated with foscarnet.

We report on a 28-year-old AIDS patient who developed a rapidly progressive glomerulonephritis while being treated with foscarnet for cytomegalovirus retinitis. Renal biopsy showed crescentic proliferation related to crystals within the glomerular capillaries. The role of foscarnet in this unusual renal syndrome is discussed.

[Volumetric analysis of urinary erythrocytes in the etiological diagnosis of hematuria]. / Analyse volumétrique des hématies urinaires dans le diagnostic étiologique des hématuries.

Intravenous pyelography and cystography may fail to localize the origin of haematuria. Microhaematuria is known to be present in 2 to 10 percent of the general population, usually without pathological consequences. Study of red cell morphology by phase contrast microscopy is effective in distinguishing between "glomerular" (from renal tissue) and "non-glomerular" (from urinary tract) erythrocytes, but this technique is not currently available in all laboratories. Urinary blood cell volume analysis has been presented as a simple and automatic alternative method. We compared these two techniques in 100 cases of haematuria of various origins. The cut-off point between glomerular and non-glomerular erythrocytes was set at 71 fl. Phase contrast microscopy always confirmed the clinical and/or histological diagnosis, but volume analysis did not: mean erythrocyte volume of glomerular origin was 66.6 +/- 10.4 fl, while non-glomerular volume was 94.5 +/- 17 fl (P < 0.001); cell volume analysis was confirmative in only 72 percent of all diagnoses (65 percent of microhaematurias, 83 percent of macrohaematurias); sensitivity was 65 percent and specificity 85 percent for glomerular erythrocytes. Due to poor performance, urinary red volume analysis is not an acceptable alternative method to phase contrast microscopy when searching for the site of bleeding.

Aetiology of membranous glomerulonephritis: a prospective study of 82 adult patients.

Eighty-two consecutive Caucasian adults (52 males, 30 females, aged 17-86 years) with membranous glomerulonephritis were prospectively evaluated for possible aetiological factors 1-4 weeks after renal biopsy. Presumed causes were identified in 17 patients (21%) as follows: drugs in five (D-penicillamine 3, captopril 1, fenoprofen 1); malignancy in four; chronic thyroiditis in three; systemic lupus erythematosus (SLE) in two; secondary syphilis in one; hepatitis B virus (HBV) infection in one and non-insulin-dependent diabetes mellitus in one patient. Except for age (patients with secondary membranous glomerulonephritis were older), clinical presentation and histological stage distribution did not differ between the secondary and the primary groups. Ten out of the 17 patients with secondary membranous glomerulonephritis (59%) achieved complete clinical remission within 12 months. The incidence of associated conditions in adults with membranous glomerulonephritis in this study corresponds with that reported in the few previous series. Although membranous glomerulonephritis is deemed to be idiopathic in most cases, it seems warranted to search for medication, malignancy, SLE, HBV infection, syphilis and thyroiditis as possible aetiological factors. Further evaluation should be orientated by the clinical context. An improved outcome of membranous glomerulonephritis may be expected insofar as the underlying condition is controlled.

[Glomerular nephropathy in the Bardet-Biedl syndrome]. / La néphropathie glomérulaire du syndrome de Bardet-Biedl.

A case of Bardet-Biedl syndrome (BBS) with kidney involvement and renal failure is reported. Light microscopy demonstrates fibrosis of 40% of glomeruli, altered tubules and interstitial fibrosis; no cystic formation is present and immunofluorescence studies are negative. In electron microscopy, the glomerular basement membrane (GBM) looks twisted and uniformly thickened with segmental effacement of the trilaminar architecture; fibrillary material is accumulated close to the inner layer of the GBM. Intermittent peritoneal dialysis is initiated 2 years later; death occurs, after one year of dialysis, due to a bleeding duodenal ulcer. Chronic renal failure seems to be the most frequent cause of death in BBS and several mechanisms are involved. Tubulo-interstitial lesions and renal cysts have been well documented. Glomerular damage with early ultrastructural changes of the GBM may be implicated in the occurrence of renal failure. Further studies are needed to define the incidence and the specificity of the GBM abnormalities in BBS.

[Preventive medical treatment of recurrent urinary calcium calculi]. / Traitement médical prophylactique des lithiases urinaires calciques récidivantes.

In 59 out of 80 patients with recurrent renal calcium stones studied between 1977 and 1982 and followed up for 4,5 to 7 years, an index has been used to determine the activity of the disease, before and after treatment with diet, high water intake, thiazide and/or allopurinol. As estimated by variations of the "activity index", the treatment was effective in all groups studied: patients with idiopathic hypercalciuria were prescribed a low purine and oxalate diet and a large water intake associated or not with thiazide; hyperuricosuric patients were treated by the same diet and allopurinol; patients with no metabolic abnormality were submitted to diet and/or thiazide and/or allopurinol. The association of thiazide and allopurinol seems to be a more effective therapy in recurrent stone formers with primary hyperoxaluria than high diuresis and succinimide.

[Localized pulmonary pseudo-tumoral form of Wegener's disease and fulminating evolution. Apropos of a case]. / Maladie de Wegener à forme pulmonaire pseudo-tumorale localisée et d'évolution fulminante. A propos d'une observation.

A case of Wegener's granulomatosis starting as a localized pseudo-tumoral lung lesion and following a fulminating course is reported. The histological diagnosis required thoracotomy. New pulmonary lesions developed post-operatively, together with severe renal failure which was responsible for the patient's death 5 weeks after the thoracotomy. The authors describe the lesions characteristic of the disease and their pathogenesis and discuss the relationship between Wegener's syndrome and other granulomatous angiitis.

[The kidney in systemic scleroderma. A report of 38 consecutive cases ]. / Le rein de la sclérodermia. A propos de 38 cas consécutifs.

The renal status of 38 patients with progressive systemic sclerosis (scleroderma) has been investigated by the usual clinical tests, urine electrophoresis, glomerular filtration rate (GFR) and renal plasma flow (RPF) determinations and in 4 cases by renal biopsy. Fourteen patients presented with proteinuria and/or a high serum creatinine and/or hypertension with low clearance values in all cases. In 14 other patients, an abnormality was apparent from clearance results (12 cases), renal biopsy (1), urine electrophoresis (1). The earliest sign of renal involvement that could be demonstrated was a reduced RPF and an elevated filtration fraction. Subsequently, a glomerular proteinuria with a electrophoretic pattern was observed as either the only sign (9 cases) or in association with abnormal clearance values (8 cases). The incidence of clinical renal involvement (proteinuria, renal failure, hypertension) ranged from 16 to 60%; 2/3 of patients who presented with proteinuria and hypertension died within 3 years. A mucoid thickening of intima and a fibrosis of adventitia in the proximal part of interlobar and arciform arteries, a fibrinoid necrosis in the distal part of lobular and preglomerular arteries are distinctive although inconstant features. The vascular lesions (seen in 70% of cases) and superimposed but reversible vasoconstriction, account for the decreased RPF. An effective control of blood pressure is mandatory; the therapeutic value of angiotensin converting enzyme inhibition remains to be corroborated.