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P Vanhille

Publications and source records attributed to P Vanhille.

At least 19 recordsLinked to original sources
PubMed2000

Adult Fanconi syndrome secondary to light chain gammopathy. Clinicopathologic heterogeneity and unusual features in 11 patients.

Fifty-seven cases of Ig light chain-associated Fanconi syndrome (FS) have been reported so far, mostly as isolated reports. The pioneering work by Maldonado and associates (35), who reviewed the first 17 cases in 1975, led to the unifying concept that patients with FS and Bence Jones proteinuria have a special form of plasma cell dyscrasia characterized by slow progression of the tumor and by prominent crystal formation in proximal tubule cells, in the absence of myeloma casts in the distal tubule. We carefully reappraised these characteristics in a series of 11 patients. Ten renal biopsy specimens were available for electron microscopy, adding to the 15 previously reported cases with ultrastructural studies. Moreover, 10 of the kappa light chains could be entirely or partially sequenced and tested for their resistance to cathepsin B, a lysosomal protease present in proximal tubule cells. Our series showed an unexpected clinicopathologic heterogeneity. Seven patients presented with the typical clinical and pathologic features of FS and low-mass myeloma or monoclonal gammopathy of undetermined significance (MGUS), in keeping with Maldonado et al's description. Crystals in bone marrow cells were detected in patients of this group, only. Three patients who presented with full-blown FS exhibited, however, the characteristic features of myeloma cast nephropathy in the setting of high-mass myeloma. One patient of this group also had numerous crystals in proximal tubule cells. The eleventh patient had complete FS with MGUS, but no crystals in proximal tubule cells even after electron microscopy. Contrasting with the clinicopathologic heterogeneity, genetic and biochemical analyses of the light chains showed a striking homogeneity. First, they all were of the kappa type. Second, 8 of 9 belonged to the V kappa I variability subgroup, which indicates that FS light chains are related by the sequence of their variable regions. Third, the 8 V kappa I light chain sequences most likely originated from only 2 germline genes, LCO2/012 and LCO8/018. Fourth, all 5 LCO2/012-derived sequences presented an unusual hydrophobic or nonpolar residue at position 30. These sequence peculiarities may account for unusual physicochemical properties of the light chains including the resistance of their variable domain V kappa to proteolysis by cathepsin B, observed in 7 of 9 patients in our series, while light chains isolated from patients with myeloma cast nephropathy are completely digested. Resistance of V kappa to proteolysis in FS patients can explain the accumulation of the light chain in the endocytotic compartment of the proximal tubule cells, leading to impairment of proximal tubule functions.

Adult↗
PubMed1999

[Extracapillary glomerulonephritis with anti-myeloperoxidase antibodies in 2 patients with systemic scleroderma treated with penicillamine D].

BACKGROUND: Side-effects, including autoimmune disorders, are frequent with D-penicillamine therapy. Proteinuria is observed in 10% of the patients, often secondary to extramembranous glomerulopathy. Necrotizing extracapillary glomerulonephritis is however exceptional. CASE REPORTS: Two patients with systemic sclerodermia were treated with D-penicillamine for 7 and 14 years. Both developed necrotizing extracapillary glomerulonephritis with anti-myeloperoxidase antibodies (anti-MPO), associated with hemorrhagic alveolitis in one case. Partial regression of the renal failure was obtained after withdrawal of D-penicillamine and combination treatment with prednisone and cyclophosphamide. DISCUSSION: Extracapillary glomerulonephritis or a lung-kidney syndrome are frequently associated with anti-MPO antineutrophil cytoplasm antibodies (ANCA). In systemic sclerodermia, the presence of anti-MPO appears to define a group of patients at risk of pauci-immune extracapillary glomerulonephritis or a lung-kidney syndrome. In addition, the presence of ANCA in patients with renal failure would suggest extracapillary glomerulonephritis rather than sclerodermic microangiopathy. Development of extracapillary glomerulonephritis with anti-MPO in patients who are taking D-penicillamine suggests that inductor mechanisms other than D-penicillamine are involved in the pathogenesis of these glomerulopathies.

Aged↗
PubMed1999

Serial measurements of antineutrophil cytoplasmic autoantibodies in patients with systemic vasculitis.

PURPOSE: To assess the value of serial determinations of antineutrophil cytoplasmic autoantibodies (ANCA) for monitoring disease activity in patients with systemic vasculitis. PATIENTS AND METHODS: Forty-three patients with histologically proven vasculitis (21 with Wegener's granulomatosis, 17 with microscopic polyangiitis, and 5 with renal-limited vasculitis) were studied for a median follow-up of 22 months. Disease activity was prospectively assessed and quantified by the Birmingham Vasculitis Activity Score. A total of 347 sera were analyzed for ANCA determination. RESULTS: Relapses occurred in 23 (54%) of 43 patients. Diagnostic category (Wegener's granulomatosis vs micropolyangiitis and renal-limited vasculitis), severity of initial symptoms (mean vasculitis activity score, mean number of organs involved), and ANCA pattern [cytoplasmic-ANCA (c-ANCA) vs perinuclear-ANCA (p-ANCA)] did not significantly differ between relapsers and nonrelapsers. Lung involvement was more frequent at onset among relapsers [16 of 23 (70%) vs 6 of 20 (30%); P = 0.02]. Relapses were slightly, but not significantly, more frequent in patients with Wegener's granulomatosis or a c-ANCA pattern. The percentage of relapsers was greater in patients with persistently positive ANCA than in patients with negative or decreasing ANCA titers (86% vs 20%, P = 0.0001). However, the predictive value of an increase in ANCA titers for the occurrence of a subsequent relapse was only 28% (4 of 14) for c-ANCA, 12% (2 of 17) for anti-proteinase 3-ANCA, and 43% (6 of 14) for anti-myeloperoxidase-ANCA. An increase in ANCA occurred before or during relapse in 33% (10 of 30) of cases for c-ANCA/anti-proteinase 3 antibodies, and 73% (11 of 15) of cases for anti-myeloperoxidase antibodies. CONCLUSION: The persistence of ANCA positivity is strongly associated with relapses. However, an increase in ANCA titers has a poor value for the early prediction of a subsequent relapse and should not be used as a sole parameter for therapeutic intervention. In addition, our results suggest that serial anti-myeloperoxidase determination may be useful as a prognostic marker in patients who are p-ANCA positive.

Aged↗
PubMed1998

Acalculous ischemic gallbladder necrosis in the catastrophic antiphospholipid syndrome.

A 29-year-old woman was referred for abdominal pain. Results of tests for lupus anticoagulant and antibodies to phosphatidylserine and to beta2-glycoprotein I were positive, but the patient had no features of systemic lupus erythematosus (SLE). Abdominal ultrasonography showed a thickening of the gallbladder wall without cholelithiasis. A surgical procedure revealed necrotic areas of the gallbladder wall, and a cholecystectomy was performed. Histologic examination of the gallbladder showed multiple thrombi and no vasculitis. Despite full-dose heparin, the patient developed a catastrophic antiphospholipid syndrome (APS) and subsequently died. Among connective tissue disorders, acute acalculous cholecystitis has been reported in patients with polyarteritis nodosa and/or SLE. APS should be considered as a possible cause of acalculous cholecystitis.

Adult↗
PubMed1998

Long-term outcome according to renal histological lesions in 118 patients with monoclonal gammopathies.

BACKGROUND: The prognosis of monoclonal gammopathies with multiple myeloma and renal involvement is poor, and the indication for renal replacement therapy is controversial. Few studies address the value of renal histology for determining prognosis according to initial pathology findings. METHODS: We studied the course of 118 patients with multiple myeloma according to renal biopsy lesions. The monoclonal component was identified and quantified in serum and urine. Tumor cell mass was classified as stage 1, 2 or 3, according to Durie and Salmon. End-points were death, or survival on dialysis, or serum creatinine level at last examination. RESULTS: Renal biopsy showed myeloma kidney in 48 cases (41%), AL-amyloidosis in 35 (30%), light chain deposit disease in 22 (19%), chronic tubulointerstitial nephritis in 12 (10%) and cryoglobulinaemic kidney with multiple myeloma in 1. Maintenance haemodialysis was required in 46 patients (39%), earlier (P<0.0001) in myeloma kidney (mean: 3 months after diagnosis) than in AL-amyloidosis (mean: 15 months) and light chain deposit disease (mean: 18 months). Median survival was 12 months in myeloma kidney, 24 months in AL-amyloidosis and 48 months in light chain deposit disease. Dialysis increased survival in light chain deposit disease, in contrast with myeloma kidney and AL-amyloidosis patients whose survival was shorter when dialysed. The main cause of death during first year of dialysis was cardiac involvement in AL-amyloidosis, and sepsis or cardiac insufficiency in myeloma kidney. There was a trend to increased survival with multidrug chemotherapy which seemed to slow progression to end-stage renal failure. At last follow-up (median: 12 months, range 1-297), 65 (55%) patients had died. By multivariate analysis, independent predictors of survival were: age < 70, serum creatinine < or = 300 micromol/l, and serum calcium < or = 2.5 mmol/l. CONCLUSIONS: Initial renal biopsy helps predict prognosis in patients with multiple myeloma and renal involvement. Maintenance haemodialysis is a reasonable indication in light chain deposit disease and AL-amyloidosis, especially in patients aged < 70. Multidrug therapy tends to prolong survival and slow progression to end-stage renal disease.

Aged↗
PubMed1998

Renal thrombotic microangiopathy in systemic lupus erythematosus: clinical correlations and long-term renal survival.

BACKGROUND: Renal thrombotic microangiopathy (TMA) is an uncommon vascular complication of systemic lupus erythematosus (SLE). Its clinical symptoms and impact on renal survival remain unclear. METHODS: Eight patients aged 25 +/- 6 years with biopsy-proven renal TMA and at least four ARA criteria for the diagnosis of SLE were retrospectively studied over a 7-year period. RESULTS: All patients presented with renal failure (creatinine 3.3 +/- 2.1 mg/dl), six had proteinuria (2.5 +/- 1.3 g/day) with microscopic haematuria in four cases. Six patients had hypertension, which was severe in five cases. Renal histology disclosed arterial and/or arteriolar thrombosis with parietal thickening without angeitis (8 patients), glomerular microthrombi (3 patients), and vascular fibrin deposits (5/6 patients). In two cases, vascular lesions were associated with a mesangial or a proliferative glomerulonephritis. Thrombocytopenia was present in four patients with haemolytic microangiopathic anaemia in one case. Lupus anticoagulant (LA) was detected in five of eight patients, who also had anticardiolipin antibodies (3/7 patients) and/or were positive for VDRL (3/6 patients). Four patients with LA experienced arterial thrombosis and/or repeated spontaneous abortions. Treatment consisted of corticosteroids (8 patients), cytotoxic drugs (4 patients), plasma exchanges and/or intravenous immunoglobulins (4 patients) and antiplatelet and/or anticoagulant therapy (3 patients). Two patients recovered normal renal function and five had persistent renal insufficiency. One patient started haemodialysis on admission and died of sepsis 2 months later. CONCLUSIONS: TMA may be the sole renal complication in SLE and is not usually associated with haemolytic microangiopathic anaemia. In our series renal survival was influenced by the extent and severity of vascular lesions. Despite a frequent association with antiphospholipid antibodies, pathophysiological mechanisms of renal TMA in SLE remain unknown. Renal histology is mandatory for the diagnosis and the prognostic evaluation of renal vasculopathy in SLE.

Adult↗
PubMed1998

Respiratory involvement in relapsing polychondritis. Clinical, functional, endoscopic, and radiographic evaluations.

Although respiratory involvement occurs in 50% of patients with relapsing polychondritis (RP) and augurs a poor prognosis, few previous studies have provided complete descriptions of respiratory tract involvement. For this reason, we investigated the respective role of clinical, functional, endoscopic, and radiographic (computed tomography [CT]) examinations in 9 consecutive patients with RP and lower respiratory tract localization. All exhibited cough, dyspnea, and wheezing. Eight had a nonreversible obstructive pattern with a marked decrease of the maximal flow ratio at 75% and 25% of vital capacity. Rotman functional criteria were evaluated to differentiate upper from lower respiratory tract involvement; they were consistent with the results of other examinations in 4/9 cases. Endoscopic examination showed moderate to severe inflammation in 8/9 patients; tracheal stenosis was present in 6/9 patients, bronchial stenosis in 4/9 patients, and tracheal collapse in 7 cases. CT showed tracheal stenosis in 8/9 patients (diffuse, 7; localized, 1) and bronchial stenosis in 6/9 patients. Tracheobronchial wall thickening and/or calcifications were observed in 7 cases. Clinical symptoms are of poor specificity for defining respiratory involvement precisely, although degree of dyspnea is correlated to the decrease in forced expiratory volume in 1 second (FEV1). Functional criteria were helpful in evaluating the obstructive ventilatory defect but did not differentiate, in most cases, the respective part of lower and upper respiratory involvement when using Rotman criteria. Compared to CT findings, endoscopic examination failed to identify tracheal and bronchial stenosis and tracheal wall alterations at an early stage of the disease. In our series CT appears to be a reliable method to identify tracheal and bronchial involvement and can be repeated safely during the course of the disease.

Adult↗
PubMed1998

Genetic analysis of the cytochrome P450 CYP2D6 polymorphism in patients with systemic lupus erythematosus.

Previous reports of an association between the polymorphic cytochrome P450 CYP2D6 and systemic lupus erythematosus are conflicting. Following the elucidation of the molecular basis of the CYP2D6 genetic polymorphism, we re-examined the hypothesis of an association of this gene with a susceptibility to system lupus erythematosus by analysing the complete CYP2D6 coding sequence. For this purpose, we studies the occurrence of 16 mutations in genomic DNA from 69 systemic lupus erythematosus patients and a large control group using a previously described polymerase chain reaction-single strand confirmation polymorphism analysis. In addition, we studied the occurrence of 11 alleles and 21 genotypes in the same individuals by the combined use of restriction fragment length polymorphism and allele-specific polymerase chain reaction followed by polymerase chain reaction-single strand confirmation polymorphism analysis. No significant differences in the distribution of overall genotypes and predicted phenotypes were observed between system lupus erythematosus patients and controls. The only new finding of our study is the higher frequency of one non functional allele, namely the CYP2D6*4A, in systemic lupus erythematosus versus control individuals (P = 0.007). This increased frequency was not statistically significant in multiple comparison analysis and was not related to any specific clinical features of systemic lupus erythematosus. These results suggest that CYP2D6 genotype as well as CYP2D6 phenotype are not determinant of susceptibility to systemic lupus erythematosus but the presence of the inactive CYP2D6*4A allele may be a contributory factor.

Adult↗
PubMed1997

Structural analysis of human antibodies to proteinase 3 from patients with Wegener granulomatosis.

We determined the structure of five IgM autoAbs to proteinase-3 (PR3). These Abs are highly specific for Wegener's granulomatosis (WG) and may be involved in the pathogenesis of vasculitis in WG. Five clonal lymphoblastoid cell lines secreting Abs to PR3 were derived from four patients' B cells. From 3 to 5% of supernatants from wells contained detectable anti-PR3 Abs, indicating that anti-neutrophil cytoplasmic Ab specificity represents a sizable part of the IgM B cell repertoire in patients with WG. Mu heavy chains of WG1, WG4-1, and WG4-2 clones belonged to the VH3 subgroup. WG4-1 and WG4-2 heavy chains were identical, indicating an oligoclonal expansion of autoreactive B cells in this patient. WG4-1 (and WG4-2) used the VH3-23 V(H) gene, the product of which was shown to directly bind PR3. Heavy chains of WG2 and WG3 derived from VH4-59 and VH1-2 genes, respectively. Comparison with germline sequences showed that three of the five V(H) genes from clonal lines were somatically mutated with a R:S ratio in complementarity-determining regions of 3:0, 5:1, and 5:1, respectively. Three kappa light chains derived from the Vkappa4 gene, and one derived from a Vkappa1 gene. In these four Vkappa genes, there were overall R:S ratios of mutation of 8:1 and 0:7 in complementarity-determining regions and framework regions, respectively. These data suggest that the production of these autoantibodies, which are increasingly important in the diagnosis and management of WG, are influenced by an Ag-driven process.

Amino Acid Sequence↗
PubMed1997

[Granulomatous interstitial nephritis with acute renal insufficiency, a potential complication of intravesicular bcg therapy].

Intravesical Bacillus Calmette-Guerin has proved to be the most effective treatment of superficial bladder carcinoma. This therapy may induce a renal failure of variable severity, sometimes associated with multiple organ failure. Renal prognosis of this complication is not well defined. We report on a 68 year-old male patient who developed granulomatous hepatitis and acute tubulo-interstitial nephritis with mononuclear infiltrates containing numerous epithelioid cells, following the third course of intravesical BCG. Eleven cases of renal impairment due to intravesical BCG have been previously described, as part of a systemic disease in seven patients. The potential pathophysiological mechanisms of this rare complication are precised.

Acute Kidney Injury↗
PubMed1996

Prospective and serial study of primary amyloidosis with serum amyloid P component scintigraphy: from diagnosis to prognosis.

OBJECTIVE: The purpose of this study was to assess the value of the serum amyloid P (SAP) component scintigraphy in patients with primary amyloidosis (AL). MATERIAL AND METHODS: Pure human SAP labeled with iodine-123 (123I-SAP) was given intravenously to 24 patients with biopsy-proven systemic amyloidosis (15 without multiple myeloma = group 1, and 9 with multiple myeloma = group 2) and to 6 patients with multiple myeloma without any clinical or biological signs of amyloidosis (group 3). Whole-body images as well as regional views and tissue retention levels were obtained after 24 hours. Our study was approved by the institutional review committee and all individuals gave informed consent and were prospectively studied (median 13 months, range 1 to 47 from the date of the scintigraphy to May 1995). RESULTS: Organ localization of 123I-SAP, indicating the presence of substantial visceral amyloid deposits, was observed in all patients in group 1 and 2. The organ uptake of 123I-SAP included the spleen (1 patient was splenectomized) in 20 of 23 cases (87%), the liver in 15 of 24 (60%), and the kidneys in 6 of 24 (25%). Myocardial 123I-SAP was never seen although 13 out of the 24 patients had clinical or echographic data for amyloidosis. Twenty-four hour tissue retention was significantly elevated in all patients (group 1 and group 2): 55.66% +/- 19.16% in group 1 and 34.37% +/- 24.92% in group 2, as compared with normal levels < 24%. The sensitivity of the technique was 79% when only organ uptake was considered but reached 100% when tissue retention was also considered. The 24-hour tissue retention might be correlated with the severity of the amyloidosis: mean survival in patients with tissue retention greater than 50% was 11.3 months versus 24.5 months in patients with levels less or equal to 50%. Five of the 6 patients with multiple myeloma without evidence of amyloidosis had abnormal 123I-SAP imaging and 24-hour tissue retention levels. In 2 of them, amyloidosis was secondly detected. In the 9 patients who had two scintigraphies, variations in 24-hour tissue retention values were in accordance with the clinical evaluation. CONCLUSIONS: Spleen and liver distribution of amyloidosis is mostly revealed by 123I-SAP scintigraphy in patients with AL amyloidosis. The uptake of 123I-SAP appeared in proportion to the quantity of amyloidosis present in different tissues, and the relative quantity of amyloid deposits in the myocardium, carpal tunnel, digestive tract, and kidneys was often small and seldom visualized by 123I-SAP scintigraphy. In contrast 24-hour tissue retention levels were abnormal in all cases of known AL amyloidosis. This may be a positive argument for the diagnosis of amyloidosis when histopathological tests are normal. Tissue retention levels appear important as they may be correlated with survival.

Aged↗
PubMed1994

[Acute interstitial nephritis and streptococcal infection].

Two patients with acute renal failure and streptococcal erysipela are reported. In both cases, renal biopsy showed acute interstitial nephritis with a predominantly mononuclear infiltrate. Beta lactam antibiotic without steroid therapy was followed by complete recovery of renal function. It seems likely that some cases of AIN related to infection are erroneously attributed to antibiotic hypersensitivity.

Acute Kidney Injury↗
PubMed1993

Labial salivary gland biopsy is a reliable test for the diagnosis of primary and secondary amyloidosis. A prospective clinical and immunohistologic study in 59 patients.

OBJECTIVE: Reports of the detection of amyloidosis by labial salivary gland (LSG) biopsy have been mostly anecdotal. The aim of this study was to assess the value of this method in the diagnosis of amyloidosis. METHODS: LSG biopsy tissues were studied with a combination method using Congo red stain and immunohistologic characterization using an antibody directed against the serum amyloid P (SAP) component. Electron microscopy was performed in all cases. In a prospective study, we evaluated 30 patients with biopsy-proven AA or AL amyloidosis. We compared these patients with a control group of 29 age-matched patients without clinical or biologic evidence of amyloid disease (14 had rheumatoid arthritis and 15 had plasma cell dyscrasia). RESULTS: In 26 of the 30 patients with known systemic amyloidosis, amyloid deposits were identified on LSG biopsy (sensitivity of 86%). In 1 of the remaining patients, amyloid deposits were identified on LSG biopsy and systemic amyloidosis was confirmed by abdominal fat biopsy and 123I-labeled SAP scintigraphy. CONCLUSION: This study emphasizes the high sensitivity of LSG biopsy in the diagnosis of amyloidosis, even in the absence of oral symptoms.

Adult↗
PubMed1993

Necrotizing crescentic glomerulonephritis without significant immune deposits: a clinical and serological study.

To determine the spectrum of systemic diseases associated with pauci-immune necrotizing crescentic glomerulonephritis, we have analysed extra-renal manifestations, occurrence of extra-glomerular vasculitis and incidence and specificity of antinuclear cytoplasmic antibodies (ANCA) in 40 patients selected only on renal histological criteria. Extra-renal symptoms were unexpectedly observed in all patients but one, and were suggestive of vasculitis in 24. Extra-glomerular vasculitis was seen in 18 kidney biopsies and four biopsies from other organs. Among the 33 patients with suspected or established vasculitis, 13 had presumed or biopsy-proven Wegener's granulomatosis, three had a macroscopic form of polyarteritis nodosa and 17 could not be adequately classified. An additional patient had clinical signs of Wegener's granulomatosis without clinical and histological evidence of vasculitis. ANCAs were detected in 28 of 33 and 25 of 34 sera tested by immunofluorescence and enzyme-linked immunoassay, respectively: 19 contained anti-myeloperoxidase antibodies and six had anti-proteinase 3 activity. Anti-myeloperoxidase and anti-proteinase 3 antibodies were present in all clinical subgroups but with various frequencies: anti-myeloperoxidase antibodies were more common (six of 12) than anti-proteinase 3 (four of 12) in patients with suspected or histologically proven Wegener's granulomatosis. Anti-proteinase 3 antibodies were 3- to 4-fold more common in patients with Wegener's granulomatosis than in those with systemic vasculitis of other causes (one of 12) or necrotizing crescentic glomerulonephritis without evidence of extra-renal vasculitis (one of 10). These results strongly suggest that pauci-immune necrotizing crescentic glomerulonephritis belongs to the broad spectrum of necrotizing vasculitides affecting glomerular capillaries. This study shows substantial improvement in renal prognosis and life expectancy with aggressive immunosuppressive therapy despite the older age of the patients, dissemination of the vasculitic process and often delayed diagnosis.

Adult↗