Pyoderma gangrenosum associated with Wegener's granulomatosis: partial response to mycophenolate mofetil.
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Adult↗
Biomedical subjects
L Guillevin
Publications and source records attributed to L Guillevin.
Characteristics and outcome of 49 patients with symptomatic cryoglobulinaemia.
OBJECTIVE: To describe a population of patients with symptomatic cryoglobulinaemia, comparing manifestations and outcome as a function of hepatitis C virus (HCV) status. PATIENTS AND METHODS: A retrospective study on 179 patients who tested positive for cryoglobulins, seen between 1978 and 1998 in an internal medicine department. RESULTS: Among 179 cryoglobulin-positive patients, only 49 (18 men, 31 women; mean age 59.96+/-12 yr) had clinical manifestations attributable to cryoglobulinaemia. Thirty-three had HCV infection, 20 had systemic autoimmune diseases, two had haematological diseases, one had human immunodeficiency virus and HCV co-infection, one had HCV and HBV co-infection and six had essential mixed cryoglobulinaemia. The clinical manifestations and cryoglobulin levels in HCV(+) and HCV(-) patients did not differ significantly. Only arthralgias and elevated transaminases were significantly more frequent in HCV(+) patients (P<0.02 and <0.05, respectively). Five-year survival rates were comparable for HCV(+) and HCV(-) patients. Eight patients died (six HCV(+), two HCV(-)), with a median time between diagnosis and death of 38.7 months. CONCLUSION: Clinical manifestations of cryoglobulinaemia, except arthralgias, were comparable for HCV(+) and HCV(-) patients. When systemic manifestations are present, the prognosis is poor despite intensive or prolonged therapy.
Cryoglobulinemia↗
Churg-Strauss syndrome in two patients receiving montelukast.
OBJECTIVE: Churg-Strauss syndrome (CSS) has been described in association with the treatment of asthmatic patients with leukotriene receptor antagonist. The main mechanism proposed to explain this condition is the unmasking of CSS after the leukotriene receptor antagonist has allowed corticosteroid tapering. Other hypotheses might be proposed. METHODS: We describe two patients who developed CSS after starting treatment with montelukast, a new antileukotriene drug. RESULTS: Both patients presented with CSS after 4-5 months of treatment with montelukast. Neither patient received long-term systemic steroids for asthma, but both were on inhaled steroids. One patient had a myocardial involvement and experienced a stroke. Our two patients were treated with systemic steroids and cyclophosphamide. CONCLUSIONS: CSS does not appear to relate to steroid tapering in our patients. The other hypotheses are a coincidence or a direct adverse effect of the antileukotriene. Long-term data on these drugs are lacking and leukotriene's role in vasculitis remains to be elucidated.
Acetates↗
Magnetic resonance imaging of skeletal muscle involvement in limb restricted vasculitis.
BACKGROUND: Limb restricted polyarteritis nodosa (PAN) and PAN-type diseases such as isolated vasculitis of skeletal muscle are localised vasculitides affecting the skin, muscles, or peripheral nerves, usually of the lower limbs. These diseases often present with non-specific clinical symptoms and normal laboratory values and electromyograms. The usefulness of magnetic resonance imaging (MRI) of skeletal muscle has been poorly investigated to date. OBJECTIVE: To describe the MRI findings in the legs of three patients with limb restricted vasculitides (two PAN, one isolated vasculitis of the skeletal muscle) with histologically established muscle involvement. METHODS: MRI was carried out on calf muscles and T(2) weighted images, unenhanced T(1) weighted images, and STIR sequences were obtained. RESULTS: Muscle damage resulted in oedema-like changes on MRI characterised by hyperintense signals in T(2) weighted and slow tau inversion recovery (STIR) sequences and normal unenhanced T(1) weighted sequences of one or several leg muscles. CONCLUSIONS: MRI should be considered a useful complementary examination that might facilitate the recognition of limb restricted vasculitides, and possibly indicate the site for muscle biopsy. It could also be useful in monitoring the course of the disease. Future studies should also evaluate MRI for systemic PAN or other systemic vasculitides with muscle involvement.
Adult↗
[Central nervous system and systemic vasculitides].
Central nervous system (CNS) involvement can occur in large, medium, or small-sized vessel vasculitides. It is present in less than 10p. cent of systemic vasculitides. Clinical symptoms are heterogeneous and reflect the various mechanisms involved: vasculitis, blood hypertension, thrombosis and embolism. The symptoms can be present initially, at the time of relapse or occur as a treatment side effect. A primary angiitis of the CNS can also be observed. This granulomatous vasculitis is rare and isolated. Its diagnosis is difficult. The prognosis has improved but the disease remains severe. Diagnosis can be made by histology but is suggested by the association of clinical symptoms and brain imaging. Cognitive modifications, sometimes severe can also be observed but can improve with treatment. Prognosis of CNS manifestations is severe. It counts for one point in the Five Factor Score (FFS) which has been validated in some systemic vasculitides. The death rate is 12p. cent when the score is 0 and 50 percent for 2 points. Patients should be treated with a combination of steroids and cyclophosphamide which improves CNS vasculitis outcome.
Animals↗
Severe perturbations of the blood T cell repertoire in polymyositis, but not dermatomyositis patients.
Polymyositis and dermatomyositis are diseases characterized by muscle weakness and muscle inflammatory infiltrates. Their pathogenesis remains unclear. A central role for endomysial autoaggressive CD8(+) T cells is suspected in polymyositis and for perivascular B cells in dermatomyositis. We compared the T cell repertoire of 10 polymyositis and 10 dermatomyositis patients by immunoscope, a method providing a global assessment of the T cell repertoire and a sensitive detection of clonal T cell expansions. Samples were analyzed qualitatively and quantitatively in the blood (unsorted cells and CD4(+) and CD8(+) cells) and in muscle infiltrates. Dramatic perturbations of the T cell repertoire were observed in the blood of polymyositis but not dermatomyositis patients (p < 0.0005), the latter being undistinguishable from controls. These perturbations were due to oligoclonal expansions of CD8(+) T cells and most blood clonal expansions were also found in muscle. These results indicate that the pathogenesis of polymyositis and dermatomyositis is different and reinforce the view that polymyositis but not dermatomyositis is an autoimmune CD8(+) T cell-mediated disease. Moreover, this method may be helpful for the differential diagnosis of polymyositis and dermatomyositis and for noninvasive follow-up of polymyositis patients.
Adult↗
Treatment of parvovirus B19-associated polyarteritis nodosa with intravenous immune globulin.
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Adult↗
Long-term followup of polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome: analysis of four prospective trials including 278 patients.
OBJECTIVE: To determine the long-term outcome of patients with polyarteritis nodosa (PAN), microscopic polyangiitis (MPA), and Churg-Strauss syndrome (CSS), to compare the long-term outcome with the overall French population, to evaluate the impact on outcome of the type of vasculitis, prognostic factors, and treatments administered at diagnosis, and to analyze treatment side effects and sequelae. METHODS: Data from PAN, MPA, and CSS patients (n = 278) who were enrolled between 1980 and 1993 were collected in 1996 and 1997 and analyzed. Two prognostic scoring systems, the Five-Factors Score (FFS) and the Birmingham Vasculitis Activity Score (BVAS), were used to evaluate all patients at the time of diagnosis. RESULTS: The mean (+/- SD) followup of the entire population was 88.3 +/- 51.9 months (range 3 days to 192 months). Of the 85 deaths recorded, at least 41 were due to progressive vasculitis or its consequences. Death rates reflected disease severity, as assessed by the FFS (P = 0.004) and the BVAS (P < 0.0002), and the 2 scores were correlated (r = 0.69). Relapses, rarer in hepatitis B virus (HBV)-related PAN (7.9%) than in MPA (34.5%) (P = 0.004), occurred in 56 patients (20.1%) and did not reflect disease severity. Survival curves were similar for the subpopulation of 215 patients with CSS, MPA, and non-HBV-related PAN who were given first-line corticosteroids (CS) with or without cyclophosphamide (CYC). However, CS with CYC therapy significantly prolonged survival for patients with FFS scores > or =2 (P = 0.041). Relapse rates were similar regardless of the treatment regimen; only patients treated with CS alone had uncontrolled disease. CYC was associated with a greater frequency of side effects (P < 0.00001). CONCLUSION: Rates of mortality due to PAN (related or unrelated to HBV), MPA, and CSS reflected disease severity and were higher than the mortality rate in the general population (P < 0.0004). Rates of relapse, more common in MPA than HBV-related PAN patients, did not reflect disease severity. Survival rates were better among the more severely ill patients who had received first-line CYC. Based on these findings, we recommend that the intensity of the initial treatment be consistent with the severity of the disease. The use of the FFS and BVAS scores improved the ability to evaluate the therapeutic response.
Adult↗
Polyarteritis nodosa and extrahepatic manifestations of HBV infection: the case against autoimmune intervention in pathogenesis.
Numerous extrahepatic manifestations have been reported in patients with both acute and chronic hepatitis B (arthralgias or arthritis, skin rashes, glomerulonephritis and neuritis), all of which are present in polyarteritis nodosa (PAN) which is the most unique and spectacular extrahepatic manifestation. In the 1970s, the frequency of PAN due to the hepatitis B (HBV) reached 30%. Immunization programs explain the decrease and it is now down to 7%. PAN usually occurs within 6 months of infection. Clinical manifestations reflect this most classic form of PAN, Hepatic manifestations including, ALT/AST elevations are mild and usually overlooked. Besides HBV, other viruses may be responsible for cases of vasculitides including PAN, HIV, Parvovirus B19, and EBV. Different pathogenic mechanisms have been identified but immune complexes are mainly thought to be responsible. In glomerulonephritis, detailed immunostaining and ultrastructural findings indicate that HBe antigen (Ag) is more likely to be the responsible antigen. In PAN, fewer reports are available and early studies with poorly defined antibodies need to be revisited. Interestingly almost all cases of HBV/PAN are associated with wild-type HBV infection, characterised by HBe antigenemia and high HBV replication, supporting the concept that lesions could result from the deposit of viral Ag/Ab complexes soluble in Ag excess, possibly involving HBe Ag. The recent observation of PAN cases associated with precore mutation which abrogates the formation of HBe Ag challenges this view. It may suggest that other, still undefined, circulating HBV-related Ag(s) distinct from HBe Ag could be involved. Remarkably, none of the HBV/PAN cases or glomerulonephritis exhibit antineutrophil cycoplasmic antibodies (ANCA) reactivity. Viral PAN can now be completely separated from other form of vasculitis mostly autoimmune in nature. Based on the efficacy of antiviral agents in chronic hepatitis B and of plasma exchanges in PAN we combined both therapies to treat HBV PAN. This was associated with swift recovery, even in the most severe forms. The perfect time correlation between inhibition of virus replication and resolution of all bioclinical signs suggest a direct pathogenic role of the virus possibly via immune complexes. Traditional immunosuppressive and steroid therapy should no longer be used for HBV PAN cases.
Autoimmunity↗
[Value of methylprednisolone perfusions in the corticodependent forms of Horton's disease].
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Adult↗
Treatments for systemic vasculitides.
The therapeutic strategy in systemic necrotizing vasculitides comprises steroids and, in severe forms, immunosuppressants like cyclophosphamide. A combination of steroids and immunosuppressants should be proposed for severe forms only. When factors of poor prognosis are absent, steroids alone can be prescribed. When vasculitides are related to viral infection, a specific approach is needed that comprises a combination of antiviral treatments and plasma exchanges. In Wegener's granulomatosis, the combination of steroids and cyclophosphamide, either oral or pulse, should be prescribed. A maintenance treatment with azathioprine or methotrexate is recommended. Alternative treatments using other immunosuppressants or immunomodulating agents can be prescribed in the case of relapse or in patients who do not respond to conventional treatments. The different therapeutic modalities should also be adapted to the patient's age and general condition.
Journal Article↗
Breast adenocarcinoma complicating Kallmann's syndrome.
Carcinoma of the breast is relatively rare among men, accounting for less than 1% of all malignancies. An increased risk has been associated with benign breast diseases, such as gynecomastia, Klinefelter's syndrome, testicular disorders, exogenous estrogen use, radiation, or a family history of male or female breast cancer. To date, hypogonadotrophic hypogonadism has never been associated with male breast cancer. We report here the first case of breast cancer coexisting with Kallmann's syndrome in a 66-year-old man.
Journal Article↗
Lack of evidence of a specific role for C4A gene deficiency in determining disease susceptibility among C4-deficient patients with systemic lupus erythematosus (SLE).
The aim of the present study was to investigate the prevalence of C4 and C2 deficiencies and to characterize genomic alterations in C4 genes in a large cohort of 125 unselected patients with SLE. We determined the protein concentration and functional activity of C2 and C4, as well as the C4 phenotype. C4 genotyping included Taq 1 restricted fragment lengh polymorphism (RFLP) analysis and polymerase chain reaction using sequence-specific primers (SSP-PCR). Type I C2 deficiency was diagnosed by PCR. Overall, 79.2% of the patients exhibited abnormalities of the C4 genes including deletion, non-expression, gene conversion and duplication. Among C4-deficient patients (n = 66, 52.8% prevalence), 41.0% of the patients exhibited a C4A deficiency and 59.0% a C4B deficiency. Half of the C4 deficiencies were due to a gene deletion. There was a strong association between C4A and C4B gene deletion and the presence of the DRB1*03 allele. Among the silent C4A genes, only two cases were related to a 2-bp insertion in exon 29 of the C4A gene. A gene conversion was demonstrated in eight patients (6.4%). One patient had a homozygous C4A deficiency. Three (2.4%) patients presented with a heterozygous type I C2 deficiency and none with homozygous deficiency. Our results argue against a specific role for C4A gene deficiency in determining disease susceptibility among patients with SLE that are C4-deficient.
Adolescent↗
Are antineutrophil cytoplasmic antibodies a marker predictive of relapse in Wegener's granulomatosis? A prospective study.
OBJECTIVES: To investigate the predictive value of testing for antineutrophil cytoplasmic antibodies (ANCA) in 55 patients with systemic Wegener's granulomatosis (WG) included in a randomized, prospective trial comparing corticosteroids and oral or pulse cyclophosphamide. METHODS: All 55 patients received corticosteroids. A cyclophosphamide pulse of 0.7 g/m2 was given at the time of diagnosis. After the first pulse, the patients were assigned at random to receive either pulse or oral cyclophosphamide (2 mg/kg/day), independently of ANCA results. ANCA were sought using an immunofluorescence assay and an attempt was made to correlate them with relapse of WG. ANCA were monitored throughout the study. RESULTS: At the time of diagnosis, ANCA were detected in 48 (87%) patients, with a cytoplasmic labelling pattern in 44 and a perinuclear pattern in four. ANCA follow-up was available for 50 patients. ANCA disappeared in 34 patients and persisted in nine. For 79% of the patients, the clinical course improved with the disappearance of ANCA and deteriorated with their persistence or increased titre. Among the patients who were initially ANCA-positive, 23 relapses occurred. Relapses were more frequent when ANCA remained positive or reappeared [13/19 ANCA-positive patients vs 3/29 ANCA-negative patients (P<0.01)]. Nine relapses (39%) occurred in patients with persistent ANCA, and ANCA reappearance preceded relapse in eight (35%). The mean time between inclusion and relapse did not differ between the patients who became ANCA-negative and those who were persistently ANCA-positive (14.6+/-13.2 vs 14.4+/-8.2 months). The mean time to ANCA disappearance was similar for the patients who relapsed and those who did not. Corticosteroids and pulse or oral cyclophosphamide did not significantly modify the time to ANCA disappearance. Throughout the study, seven patients were ANCA-negative. CONCLUSION: Although ANCA positivity was associated with relapse, discordance between cytoplasmic ANCA and disease activity was not unusual. In the absence of clinical manifestations, ANCA titres alone can serve as a warning signal but not indicate whether to adjust or initiate treatment.
Antibodies, Antineutrophil Cytoplasmic↗
Analysis of factors predictive of survival based on 49 patients with systemic Wegener's granulomatosis and prospective follow-up.
OBJECTIVES: This prospective study attempted to determine factors predictive of survival in systemic Wegener's granulomatosis (WG) based on 49 patients. Patients and methods. All patients had previously untreated systemic WG. Treatment was with oral or pulse cyclophosphamide plus corticosteroids. Univariate and multivariate analyses of survival were performed using 13 parameters evaluated at diagnosis. RESULTS: The mortality rate was 37% during a mean follow-up period of 1.9 yr. Among the 13 parameters evaluated, univariate analysis selected the following factors as predictors of a poor outcome: serum creatinine > or =18.1 mg/dl, age > or =57 yr, and erythrocyte sedimentation rate (ESR) > or =90 mm/1st h. The absence of ear, nose and throat (ENT) involvement also tended to predict a greater risk of mortality. Glomerulonephritis, when present and regardless of creatininaemia, and pulmonary involvement had no significant effect. Multivariate analysis retained serum creatinine > or =18.1 mg/dl and age > or =57 yr as significant predictors of poor prognosis. CONCLUSIONS: Our results suggest that impaired renal function and older age are independent factors predicting poor outcome in WG. ESR proved to be a good marker of disease severity. Conversely, univariate analysis indicated that patients with ENT involvement tended to have a better outcome, suggesting a more benign evolution of granulomatous disease compared with more aggressive vasculitis.
Administration, Oral↗
Polyarteritis nodosa and mixed cryoglobulinaemia related to hepatitis B and C virus coinfection.
OBJECTIVE: To determine the responsibility of hepatitis B virus (HBV) and hepatitis C virus (HCV) and therapeutic implications in a patient who developed systemic vasculitis. CASE REPORT: The case of a 38 year old woman who had a past history of addiction to intravenous drugs and developed systemic vasculitis after infection by HBV and HCV is described. The clinical and laboratory findings substantiated not only the diagnosis of polyarteritis nodosa (PAN) but also that of mixed cryoglobulinaemia with a monoclonal IgMkappa component. CONCLUSION: Because cryoglobulins are rarely found in HBV related PAN but often associated with HCV infection, and in light of the histological findings, cryoglobulinaemia was interpreted as being secondary to HCV infection. This example of a highly complex situation emphasises the need to gather all relevant clinical, biological, histological, and complementary data so that the best treatment for overlapping of distinct vasculitides can be selected.
Adult↗
Risk factors and prognostic influence of infection in a single cohort of 87 adults with systemic lupus erythematosus.
OBJECTIVES: To describe infectious complications and analyse their risk factors and prognostic role in adults with systemic lupus erythematosus (SLE). METHODS: A monocentric cohort of 87 adults with SLE (1960-1997) was studied to determine the risk factors for infection (disease activity evaluated by SLAM and SLEDAI scores, type of organ(s) involved or any biological abnormality, specific treatments) by comparing patients who had suffered at least one infectious episode (n=35; 40%) with non-infected patients (n=52; 60%). Prognostic indicators were assessed by comparing survivors at 10 years with non-survivors. RESULTS: Of the 57 infectious episodes, 47 (82%) were of bacterial origin, 16 (28%) were pneumonia, and 46 (81%) were community acquired. According to univariate analysis, significant risk factors for infection were: severe flares, lupus glomerulonephritis, oral or intravenous corticosteroids, pulse cyclophosphamide, and/or plasmapheresis. No predictors were identified at the time of SLE diagnosis. Multivariate analyses retained intravenous corticosteroids (p<0.001) and/or immunosuppressants (p<0.01) as independent risk factors for infection, which was the only factor for death after 10 years of evolution (p<0.001). CONCLUSION: In adults with SLE, infections are common and most often caused by community acquired bacteria. Intravenous corticosteroids and immunosuppressants are independent risk factors for infection, which is the only independent risk factor for death after 10 years of SLE evolution.
Adolescent↗
Cryptogenetic multifocal ulcerous stenosing enteritis: an atypical type of vasculitis or a disease mimicking vasculitis.
BACKGROUND/AIMS: Cryptogenetic multifocal ulcerous stenosing enteritis (CMUSE) is a rare disease whose origin is unknown. The aim of this study was to describe the clinical spectrum of CMUSE, to determine the origin and pathophysiology of the disease, and to propose a treatment strategy. METHODS: A total of 220 French gastroenterology departments were contacted to review patients with unexplained small bowel strictures. Of 17 responses, 12 corresponded to a diagnosis of CMUSE. These patients were hospitalised between 1965 and 1993 and their medical records were reviewed. RESULTS: All patients (mean age 42.1 (4.4) years) had intestinal and five had extraintestinal symptoms (peripheral neuropathy, buccal aphthae, sicca syndrome, polyarthralgia, Raynaud's phenomenon, arterial hypertension). One patient had heterozygous type I C2 deficiency (28 base pair gene deletion). Two to 25 (mean 8.3 (1.9)) small intestine strictures were found. Stenoses of the large jejunoileal arteries were observed on two and aneurysms on three of five mesenteric angiograms. Despite surgery, symptoms recurred in seven of 10 patients and strictures in four. Steroid therapy was effective but caused dependence. One untreated patient died. Small bowel pathology showed superficial ulceration of the mucosae and submucosae, and an inflammatory infiltrate made of neutrophils and eosinophils. CONCLUSIONS: CMUSE is an independent entity characterised by steroid sensitive inflammation of the small bowel which often recurs after surgery. CMUSE may be related to a particular form of polyarteritis nodosa with mainly intestinal expression or with an as yet unclassified vasculitis.
Adolescent↗