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Biomedical subjects

F Lhote

Publications and source records attributed to F Lhote.

At least 37 records · Page 2Linked to original sources
PubMed1998

Polyarteritis nodosa, microscopic polyangiitis and Churg-Strauss syndrome.

Polyarteritis nodosa (PAN), first described by Küssmaul and Maier, is a well-known form of necrotizing angiitis whose manifestations are weight loss, fever, asthenia, peripheral neuropathy, renal involvement, musculoskeletal and cutaneous manifestations, hypertension, gastrointestinal tract involvement, and cardiac failure. Recently individualized from PAN, microscopic polyangiitis (MPA) is a systemic vasculitis of small-size vessels whose clinical manifestations are very similar to those of PAN, but it is characterized by the presence of rapidly progressive glomerulonephritis (RPGN), which is nearly constant, and pulmonary involvement usually absent in PAN. Churg Strauss syndrome (CSS) is a disorder characterized by hypereosinophilia and systemic vasculitis similar to that of PAN and occurring in individuals with asthma and allergic rhinitis. Considering the etiologies of PAN, primary and secondary vasculitides can also be distinguished because PAN can be the consequence of hepatitis B virus (HBV) infection and sometimes of other etiologic agents. The prognosis of systemic vasculitides has been transformed by corticosteroids that are, except in HBV-related PAN, the basic treatment. Immunosuppressive drugs, especially cyclophophamide, have also contributed to improving the prognosis, but their precise role in the management of these vasculitides is still being elucidated.

Churg-Strauss Syndrome↗
PubMed1997

[Prevention of opportunistic infections in HIV seropositive patients. Prevention of parasitic infections].

PNEUMOCYSTIS CARINII PNEUMONIA: Below a threshold 200 CD4 cont, the risk of P. carinii infection is sufficiently high to propose systematic prophylaxis. Trimethoprim-sulfamethoxazole is the treatment of choice for primary and secondary prevention. Pentamidine-isothionate can also be used, possibly with dapsone. TOXOPLASMOSIS: There is a consensus on primary prevention in patients with positive toxoplasmosis serology whose CD4 count is under 100. Trimethoprime-sulfamethoxazole is the first intention drug, but poor tolerance may require conversion to dapsone-pyrimethamine. For secondary prophylaxis, the consensus is for life-long treatment with low-doses after initiating treatment with sulfadiazine and pyrimethamine. LEISHMANIASIS: Secondary prevention is reasonable using monthly infusions of pentamidine.

AIDS-Related Opportunistic Infections↗
PubMed1997

[Prevention of opportunistic infections in HIV seropositive patients. Prevention of bacterial infections].

TUBERCULOSIS: Primary prophylaxis is indicated in subjects at risks, i.e. those with a positive tuberculine test or a negative test and major immunodepression. BCG vaccine is definitely contraindicated in case of AIDS. Prescription of isoniazid in combination with vitamin B6 has been found to be effective. MYCOBACTERIUM AVIUM INTRACELLULARE: Prophylaxis concerns highly immunodepressed patients and is based on rifabutine. Prophylaxis is contraindicated in case of active tuberculosis. OTHER GERMS: Preventive care in food intake for potential digestive tract infections is required as well as antipneumococcal vaccine. Secondary prophylaxis is based on continuous antibiotics. The positive effect of intravenous immunoglobulins, especially in children, remains a question of debate.

AIDS-Related Opportunistic Infections↗
PubMed1997

[Prevention of opportunistic infections in HIV seropositive patients. Prevention of viral infections and mycoses].

CYTOMEGALOVIRUS INFECTION: Primary prophylaxis is logical in high-risk subjects (CD4 < 50) who are asymptomatic; per os ganciclovir is under evaluation. Systematic secondary prophylaxis relies on intravenous ganciclovir or foscarnet. HERPES SIMPLEX AND ZOSTER: Secondary prevention with acyclovir is not recommended due to the risk of resistance. Herpes zoster retinitis is an absolute indication for continuous oral treatment with acyclovir. CRYPTOCOCCUS: Oral fluconazol is required for secondary prophylaxis. CANDIDIASIS: Due to the risk of resistant strains, neither primary nor secondary prophylasis is recommended. HISTIOPLASMOSIS: Risk of recurrence justifies secondary prophylaxis with itraconazole or fluconazole. COCCIDIODOMYCOSIS: Secondary prophylaxis with amphotericin B or fluconazole is mandatory. ASPERGILLOSIS: Itraconazole is the best agent when prophylaxis is needed.

AIDS-Related Opportunistic Infections↗
PubMed1997

A prospective, multicenter, randomized trial comparing steroids and pulse cyclophosphamide versus steroids and oral cyclophosphamide in the treatment of generalized Wegener's granulomatosis.

OBJECTIVE: To investigate the effectiveness and side effects of oral versus pulse cyclophosphamide (CYC) in combination with corticosteroids (CS) in the treatment of systemic Wegener's granulomatosis (WG). METHODS: Patients with newly diagnosed systemic WG were enrolled in a prospective, randomized trial. At the time of diagnosis, prior to randomization, every patient received a daily injection of methylprednisolone for 3 days, followed by daily oral prednisone (1 mg/kg/day) and a 0.7-gm/m2 pulse of CYC. Patients were then randomly assigned to receive either prednisone plus intravenous pulse CYC (group A) or prednisone plus oral CYC (group B) as first-line treatment. CYC was given for at least 1 year and was then progressively tapered and discontinued. RESULTS: Fifty patients were included in the study: 27 in group A and 23 in group B. At 6 months, 24 group A patients (88.9%) were in remission, versus 18 group B patients (78.3%). At the end of the trial, 18 group A patients (66.7%) and 13 group B patients (56.5%) were in remission. In group A, 66.7% of the patients experienced side effects, versus 69.6% in group B. Infectious side effects were significantly more frequent in group B (69.6%) than in group A (40.7%) (P < 0.05). The incidence of Pneumocystis carinii pneumonia was higher in oral CYC-treated patients (30.4%) than in pulse CYC-treated patients (11.1%). Nine group A patients (33.3%) and 10 group B patients (43.5%) died. Actuarial curves showed that relapses were significantly more frequent in group A (59.2%) than in group B (13%) (P = 0.02). CONCLUSION: Our results indicate that pulse CYC is as effective as oral CYC in achieving initial remission of WG and is associated with fewer side effects and lower mortality. However, in the long term, treatment with pulse CYC does not maintain remission or prevent relapses as well as oral CYC.

Administration, Oral↗
PubMed1997

Treatment of good-prognosis polyarteritis nodosa and Churg-Strauss syndrome: comparison of steroids and oral or pulse cyclophosphamide in 25 patients. French Cooperative Study Group for Vasculitides.

Twenty-five patients with good-prognosis polyarteritis nodosa or Churg-Strauss syndrome entered a prospective, randomized, multicentre study comparing two treatments: either oral corticosteroids and oral cyclophosphamide (CY; 2 mg/kg/day) for 1 yr (group A), or oral corticosteroids and monthly i.v. CY pulses (0.6 g/m2) (group B) for 1 yr. The objective was to determine the optimal CY regimen. Judgement criteria were the efficacy of the treatment in controlling the disease and the development of side-effects. Among the 25 patients who could be analysed, complete recovery was achieved with the experimental treatment in 9/12 patients in group A and 10/13 patients in group B. Two patients in each group relapsed after the end of therapy and were well controlled by corticosteroids or other drugs. One failure occurred in each group. The mean follow-up was 60.8 +/- 14.5 months after the beginning of the treatment. Side-effects associated with the administration of CY and steroids were noted 27 times in group A vs 14 times in group B (not significant). The oldest patient in these series (group B) died of pneumonia. No superiority in terms of efficacy could be established between the two regimens; however, the number of patients included was too small to conclude definitively. Toxic side-effects were significantly more frequent in women (P < 0.02). The high number of adverse effects leads us to recommend pulse over oral CY and an overall lowering of the doses of immunosuppression.

Adult↗
PubMed1997

The spectrum and treatment of virus-associated vasculitides.

It is admitted that viral infections can be responsible for systemic vasculitides. Viruses can be responsible for various types of vasculitis that affect vessels of different sizes. Clinical manifestations are the same as those observed in previously described vasculitides such as polyarteritis nodosa or cryoglobulinemia. When viral infection is diagnosed and considered to be responsible for vasculitis, a specific therapeutic approach must be prescribed. Treatment is based on the combination of antiviral agents and symptomatic or immunomodulating therapies. Antiviral therapy facilitates virus clearance and seroconversion to specific antibodies. In systemic vasculitides, plasma exchanges are a powerful treatment that clears circulating immune complexes. In the case of digital ischemia, vasodilators are also useful. Conversely, steroids and cytotoxic agents stimulate virus replication and favor disease chronicity and deleterious effects due to the presence of the virus. Hepatitis B virus-related polyarteritis nodosa can be cured with the combination of antiviral agents (mainly interferon alpha) and plasma exchanges. Hepatitis C virus-related cryoglobulinemia responds to interferon alpha and sometimes to plasma exchanges, but responses are usually partial and relapses occur in the majority of cases. In HIV-related vasculitides, currently available antiretroviral agents are not able to definitively eradicate the virus but their combination with plasma exchanges can cure the vasculitis. Due to common epidemiologic factors, several viruses can be present in the same patient, and determining their responsibility in the vasculitic process requires careful clinical and virologic analysis and then the selection of a specifically adapted therapeutic regimen. The therapeutic strategy applied in virus-associated vasculitides is therefore based on the etiologic investigations and the choice of a treatment is adapted to the pathogenetic mechanisms.

Humans↗
PubMed1997

Classification and management of necrotising vasculitides.

Systemic vasculitides are a heterogeneous group of diseases. Having only a partial understanding of the aetiologies and pathogenetic mechanisms of these disorders explains the difficulties encountered in classifying and treating patients. Nevertheless, some important points have been established. Classification is mainly based on the size of vessels affected and, from the polyarteritis nodosa group, microscopic polyangiitis (MPA) has been separated from classic polyarteritis nodosa (c-PAN). The latter is a rare disease which is, in a small number of cases, the consequence of hepatitis B or C virus (HBV/HCV) infection. In the other cases of c-PAN and in MPA, the aetiology is unknown as for Churg-Strauss syndrome (CSS) and Wegener's granulomatosis (WG). MPA, CSS and WG are mainly antineutrophil cytoplasmic antibodies (ANCA)-related vasculitides. ANCA play a part in the pathogenesis of diseases and are sometimes useful markers for diagnosis and follow-up. Vasculitis treatments should be chosen according to classification, aetiology, pathogenetic mechanisms, severity and predictable outcome. In virus-associated vasculitides, treatment is based on the combination of antiviral agents and symptomatic or immunomodulating therapies. HBV-related PAN and HCV-related cryoglobulinaemia respond to interferon-alpha and to plasma exchange. Responses are excellent in HBV-PAN but usually partial in HCV-cryoglobulinaemia, and relapses occur in the majority of cases. MPA, c-PAN, WG and other vasculitides respond to corticosteroids and cytotoxic agents, mainly cyclophosphamide. Treatment duration and ways of administration can vary from one disease to another. Plasma exchange is not recommended as the first-line treatment. Immunoglobulins and other immunomodulating treatments are indicated in limited cases and their indications necessitate further prospective studies.

Blood Vessels↗
PubMed1997

Treatment of glomerulonephritis in microscopic polyangiitis and Churg-Strauss syndrome. Indications of plasma exchanges, Meta-analysis of 2 randomized studies on 140 patients, 32 with glomerulonephritis.

UNLABELLED: Although plasma exchanges (PE) have no added benefit in the treatment of vasculitides of the polyarteritis nodosa (PAN) group with steroids (CS) +/- cyclophosphamide (CY), this has not been demonstrated in patients presenting with glomerulonephritis (GN). We therefore reanalyzed the records of microscopic polyangiitis (MPA) or Churg-Strauss syndrome (CSS) patients presenting with GN. PATIENTS AND METHODS: Patients were included consecutively in 2 randomized trials: a) comparing CS vs CS + PE (n = 78) and b) comparing CS + pulse CY +/- PE in PAN and CSS with factors of poor prognosis (n = 62); 9-12 PE/patient were performed. RESULTS: 32 patients, 18 men and 14 women, presented with GN, 28 MPA and 4 CSS, mean age 53.2 +/- 17 years. Clinical/biological manifestations before treatment were comparable in both groups: weight loss 84.4%, fever 62.5%, mononeuritis multiplex 62.5%, purpura 28.1%, GI tract involvement 43.8%, arthritis 37.5%, asthma 12.5%, CNS manifestations 9.4%; cardiac involvement 9.4%; mean creatininemia was 303 +/- 286 mumol/l, proteinuria > 0.5 g/l or 1g/d was found in every case, microscopic hematuria in 20/32 patients, leukocyturia in 12/32. Eight out of/16 were ANCA-positive, ELISA detected anti-MPO antibodies in 5 and anti-PR3 in 3. HBV infection was never observed. After 1 year of treatment, creatininemia decreased from 374.4 +/- 352 to 290 +/- 352 mumol/l in the PE group and from 287 +/- 292 to 170 +/- 67 in the non PE group (NS). Six patients of the PE group and 2 of the non-PE group were dialyzed at onset of treatment. Four of the 6 PE patients and 1 of the 2 not treated with PE were off dialysis 1 year later. In addition 1 patient from the PE group developed a flare with renal failure and required chronic dialysis. The 5-year survival was higher in the PE group (4 deaths/19) than in the non PE group (7/13). The survival curve was 74% in the PE group vs 54% in the non-PE group (NS). CONCLUSION: This study confirms that PE have no added benefit in the treatment of GN in MPA and CSS.

Adolescent↗
PubMed1996

Antineutrophil cytoplasmic antibodies, abnormal angiograms and pathological findings in polyarteritis nodosa and Churg-Strauss syndrome: indications for the classification of vasculitides of the polyarteritis Nodosa Group.

The present study attempted to define the clinical, radiological, immunological and pathological characteristics of microscopic polyangiitis (MPA), and to separate them from classic PAN (c-PAN) and Churg-Strauss syndrome (CSS). In most cases, patients presenting microaneurysms and/or multiple vessel stenoses, which reflect medium-sized vessel involvement, did not have antineutrophil cytoplasmic antibodies (ANCA) (6.6%). Conversely, patients with glomerulonephritis almost never had abnormal angiograms. Furthermore, the clinical characteristics of ANCA-positive patients also indicate small-sized vessel involvement. Skin involvement (73.1 vs 26.7%, P < or = 0.05), glomerulonephritis (38.5 vs 0%, P < or = 0.001) and the presence of ANCA (34.6 vs 6.7%, P < or = 0.05) were significantly more frequent in patients with normal than abnormal angiograms, respectively. Conversely, hypertension (66.7 vs 23.1%, P < or = 0.02), renal vasculitis (46.7 vs 0%, P < or = 0.001) and hepatitis B antigenaemia (60 vs 11.5%, P < or = 0.01) were significantly more common in patients with abnormal angiograms. Stratification of patients according to vessel size showed that, except for skin involvement (P < or = 0.05) and glomerulonephritis (P < or = 0.01), which are direct manifestations of small-sized vessel diseases, clinical symptoms of PAN or CSS, angiographic findings and ANCA were not correlated to arteriole size. Although at present it is not possible to separate definitively MPA from c-PAN, our results show that ANCA should be considered diagnostic for MPA and, in most cases, should be an exclusion criterion for c-PAN. Conversely, small-sized vessel involvement can be observed in patients presenting characteristics of c-PAN, MPA or CSS and, therefore, is not a sufficient criterion for assigning diagnosis.

Adult↗
PubMed1996

Prognostic factors in polyarteritis nodosa and Churg-Strauss syndrome. A prospective study in 342 patients.

We undertook this study to determine the clinical, biologic, immunologic, and therapeutic factors associated with the prognoses of polyarteritis nodosa (PAN) and Churg-Strauss syndrome (CSS). Three hundred forty-two patients (260 with PAN, 82 with CSS) followed from 1980 to 1993 were included in a prospective study on prognostic factors. Two hundred eighty-eight of these patients were included in the prospective studies on PAN and CSS. Items to be considered for analysis were collected at the time of diagnosis, during the acute phase of the disease. A survival curve was plotted for each clinical and biologic symptom observed in PAN or CSS. Each treatment arm of the prospective therapeutic trials was also tested: 1) prednisone (CS) + oral cyclophosphamide (CYC) + plasma exchanges (PE) versus CS E, 2) CS + PE versus CS, 3) CS + oral CY versus CS + pulse CY, 4) CS + pulse CY + PE versus CS + pulse CY in severe PAN and CSS, and 5) PE + antiviral agents after short-term CS in hepatitis B virus-related PAN. Of the parameters thus evaluated, the following had significant prognostic value and were responsible for higher mortality: proteinuria > 1 g/d (p < 0.0001; relative risk [RR] 3.6), renal insufficiency with serum creatinine > 1.58 mg/DL (p < 0.02; RR 1.86), GI tract involvement (p < 0.008. RR 2.83 for surgery). Cardiomyopathy and CNS involvement were associated with a RR of mortality of 2.18 and 1.76, respectively; these were not statistically significant. Similar survival rates were obtained with the prospectively tested therapies. The five-factors score (FFS) we established considered the prognostic factors creatinemia, proteinuria, cardiomyopathy, GI tract involvement, and CNS signs. Multivariate analysis showed that proteinuria (due to vascular or glomerular disease) and GI tract involvement were independent prognostic factors. When FFS = 0 (none of the 5 prognostic factors present), mortality at 5 years was 11.9%; when FFS = 1 (1 of the 5 factors present), mortality was 25.9% (p < 0.005); when FFS > 2 (3 or more of the 5 factors present), mortality was 45.95% (p < 0.0001 between 0 and 2, p < 0.05 between 1 and 2). We conclude that an initial assessment of PAN or CSS severity enables outcome and mortality to be predicted. The FFS is a good predictor of death and can be used to help the clinician choose the most adequate treatment. Renal and GI signs are the most serious prognostic factors.

Adolescent↗
PubMed1996

Microscopic polyangiitis: clinical aspects and treatment.

Recently individualized from polyarteritis nodosa (PAN), microscopic polyangiitis (MPA) is defined as a systemic necrotizing vasculitis that clinically and histologically affects small-sized vessels (ie, capillaries, venules or arterioles) without granulomata and is associated with focal segmental necrotizing glomerulonephritis. Males are more frequently affected than females and the average age of onset is about 50 years old. Most patients experience some systemic symptoms before diagnosis of vasculitis. Clinically, renal involvement is the major feature of MPA and is characterized by rapidly progressive glomerulonephritis (RPGN). Most of the patient have renal impairment at admission and renal function deteriorates rapidly without treatment. Lung involvement is also common. Lung hemorrhage is observed in 12 to 29% of the patients with MPA and is an important contributory factor to morbidity and mortality. Some patients with small-vessel lung vasculitis may present clinical, radiologic and functional findings consistent with an interstitial process mimicking idiopathic pulmonary fibrosis. Others clinical features are similar to those observed in PAN. Musculoskeletal involvement (myalgias, arthralgias and arthritis) are present in 65 to 72% of the patients. Cutaneous lesions (purpura, splinter hemorrhages) are found in 44 to 58% of the patients. Gastrointestinal symptoms are characterized by abdominal pain (32 to 58%) and digestive tract bleeding (29%). Peripheral neuropathy is found in only 14 to 36% of the cases, thus occurring less frequently than in PAN. Ocular manifestations and ear, nose and throat lesions are commonly seen, more frequently than in PAN. Non-specific laboratory tests reflect the systemic inflammatory nature. Almost all patients are negative for hepatitis B virus (HBV) surface antigen. Renal insufficiency with creatininemia > 120 microns/l is present in the majority of patients. Antineutrophil cytoplasm antibodies (ANCA) are found in 75% of MPA patients and the majority of these ANCA detected are perinuclear-staining anti-myeloperoxidase ANCA, although anti-proteinase 3 has also be detected. Microaneurysms, commonly present in PAN, are rarely seen on at visceral angiograms. MPA is part of a spectrum of systemic vasculitides. Differentiation between PAN and MPA should be based on clinical manifestations (especially lung and kidney involvement), biologic signs (ANCA, HBV or HCV infection) and angiographic data. The therapeutic strategies for treatment of PAN and MPA do not differ extensively. Prognosis of systemic vasculitides have been transformed by corticosteroids that are the basis of the treatment. Immunosuppressive drugs, especially cyclophosphamide, also contribute to a better prognosis. Considering the high frequency of renal involvement in MPA, most of the patients should considered as having factors or poor prognosis and the high number of relapses that can occur in patients with MPA could justify prolonged steroid administration or immunosuppressive treatment.

Humans↗
PubMed1995

Corticosteroids plus pulse cyclophosphamide and plasma exchanges versus corticosteroids plus pulse cyclophosphamide alone in the treatment of polyarteritis nodosa and Churg-Strauss syndrome patients with factors predicting poor prognosis. A prospective, randomized trial in sixty-two patients.

OBJECTIVE: To define the most effective treatment for severe polyarteritis nodosa (PAN) and Churg-Strauss syndrome (CSS) and to investigate the indication for plasma exchange treatment. METHODS: We conducted a prospective, randomized, multicenter trial in which 62 patients were randomly assigned to receive either prednisone plus cyclophosphamide (intravenous bolus) (group A; n = 28) or prednisone plus cyclophosphamide (intravenous bolus) plus plasma exchanges (group B; n = 34) as first-line treatment for severe PAN or CSS. Factors predicting poor prognosis were renal symptoms, gastrointestinal tract involvement, cardiomyopathy, central nervous system involvement, weight loss > 10% of body weight, and age > 50 years old. Patients with hepatitis B virus-related PAN were not included in this study. The end point of the study was control of the disease (recovery or remission) or death. RESULTS: Clinical symptoms and laboratory findings did not differ significantly in the 2 groups. Initial control of the disease was similar in both groups. Relapse after initial control of the disease was observed in 7 patients (4 in group A and 3 in group B). The mean +/- SD followup period was 31.1 +/- 20 months for group A and 35.9 +/- 16.8 months for group B. At 5 years of followup, 38 patients (61.3%) were cured (16 in group A and 22 in group B), and 5 (8.1%) were in remission without treatment but had not yet completed the cure-defining period of 18 months (3 in group A and 2 in group B). Eight (12.9%) (2 in group A and 2 in group B) were considered to be in clinical remission and required a maintenance regimen of low-dose corticosteroids. Eleven patients died during the study period (7 in group A [25%], 4 in group B [11.8%]). Uncontrolled vasculitis was responsible for 4 deaths (2 in each group), and treatment side effects caused the death of 1 patient in group A. There was no significant difference between the 5-year cumulative survival rates of the 2 groups (75% and 88%, respectively). CONCLUSION: Based on our data, combined treatment with prednisone, cyclophosphamide, and plasma exchanges is not superior to treatment with prednisone and cyclophosphamide alone, and plasma exchanges should not be systematically proposed for initial treatment of severe PAN or CSS.

Adolescent↗
PubMed1995

Polyarteritis nodosa related to hepatitis B virus. A prospective study with long-term observation of 41 patients.

Hepatitis B virus (HBV)-related polyarteritis nodosa (PAN) is a rare disease whose frequency has been decreasing over the past 10 years. We evaluated 41 patients with HBV-related PAN to determine the circumstances leading to infection, the clinical features of vasculitis, the prognostic factors, and the response to therapy. Most patients were first treated briefly with corticosteroids, and all were included in 2 nonrandomized prospective therapeutic trials of an antiviral agent (35 patients with vidarabine, 6 patients with interferon-alpha 2b) and plasma exchanges. The mean duration of follow-up was 69.6 +/- 44.8 months. At the end of the study, 21 (51.2%) patients had seroconverted to anti-HBeAb and 10 (24.4%) also had seroconverted to anti-HBsAb. In all, 23 (56%) patients no longer expressed serologic evidence of HBV replication. All 33 (80.5%) patients still alive at the end of follow-up recovered from PAN. Nineteen also recovered from HBV infection and were considered to be cured; 13 patients had persistent HBV infection and were considered to be in clinical recovery; and 1 patient was in remission, maintained with steroid therapy. Eight patients died during the study period; 3 deaths were directly attributable to PAN. HBV-related PAN is an acute disease, occurring shortly after infection and sharing the characteristics of classic PAN. It is not an antineutrophil cytoplasm antibodies (ANCA)-mediated vasculitis. The outcome was good for patients treated with short-term steroid therapy, antiviral agents, and plasma exchanges. We propose this protocol as the first treatment for HBV-related PAN, because it surpasses the conventional treatment with corticosteroids and cyclophosphamide, which facilitates viral replication and the development of chronic HBV infection.

Adolescent↗