Du Le Thi Huong

RENAL INVOLVEMENT IN SYSTEMIC LUPUS ERYTHEMATOSUS : A STUDY OF 180 PATIENTS FROM A SINGLE CENTER

Charts of 180 patients (147 women, 33 men) with systemic lupus erythematosus (SLE) complicated by renal involvement were retrospectively analyzed from a series of 436 patients. Mean age at renal disease onset was 27 years. Thirty-six percent of the patients had renal involvement after diagnosis of lupus, for 30.7% of that group it was more than 5 years later. Renal involvement occurred more frequently in young male patients of non-French non-white origin. Patients with renal involvement suffered more commonly from malar rash, psychosis, myocarditis, pericarditis, lymphadenopathy, and hypertension. Anemia, low serum complement, and raised anti-dsDNA antibodies were more frequent. According to the 1982 World Health Organization classification, histologic examination of initial renal biopsy specimen in 158 patients showed normal kidney in 1.5% of cases, mesangial in 22%, focal proliferative in 22%, diffuse proliferative in 27%, membranous in 20%, chronic sclerosing glomerulonephritis in 1%, and other forms of nephritis in 6.5%. Distribution of initial glomerulonephritis patterns was similar whether renal involvement occurred before or after the diagnosis of lupus. Transformation from 1 histologic pattern to another was observed in more than half of the analyzable patients (those who underwent at least 2 renal biopsies). Nephritis evolved toward end-stage renal disease in 14 patients despite the combined use of steroids and cyclophosphamide in 12. Initial elevated serum creatinine levels, initial hypertension, non-French non-white origin, and proliferative lesions on the initial renal biopsy were indicators of poor renal outcome. Twenty-four patients died after a mean follow-up of 109 months from SLE diagnosis. Among our 436 patients, the 10-year survival rate was not significantly affected by the presence or absence of renal involvement at diagnosis (89% and 92%, respectively).

Cardiac Sarcoidosis: A Retrospective Study of 41 Cases

Abstract: This retrospective study concerned 18 female and 23 male patients with cardiac sarcoidosis (CS). The average age at CS diagnosis was 38 years. CS was observed in white (73% of cases) and in black or Caribbean patients (27% of cases). All patients had extracardiac histologic proof of sarcoid tissue. In 63% of cases, the CS arose during the follow-up of systemic sarcoidosis. Systemic sarcoidosis was not specific except for a high frequency of neurosarcoidosis. Revealing cardiac signs were clinical in 63% of cases and electrical in 22%. In most patients these signs were associated with an abnormal echocardiography (77%) and/or a defect on thallium-201 or sestamibi imaging (75%). Thirty-nine patients received steroid therapy (initial dose mostly equal to 1 mg/kg per day), associated in 13 cases with another immunosuppressive treatment. In 26% of cases the immunosuppressive treatment was associated with a specific cardiac treatment. In the long-term follow-up (average follow-up, 58 mo), 87% of the cases showed an improvement, and 54% were cured from a clinical and laboratory point of view (electrocardiogram, 24-hour monitoring, echocardiography, radionuclide imaging). There was no sudden death. Two patients worsened, which can be explained in 1 case by very late treatment and in the other case by lack of treatment, except for a pacemaker. Our experience leads us to treat CS with corticosteroids as soon as possible and to use another immunosuppressive treatment where there is an insufficient therapeutic response or where there are contraindications to corticosteroids. Abbreviations: CS = cardiac sarcoidosis, ECG = electrocardiogram, NYHA = New York Heart Association.

Late-onset systemic lupus erythematosus : a personal series of 47 patients and pooled analysis of 714 cases in the literature

Abstract: Systemic lupus erythematosus (SLE) is uncommon after the age of 50 years, and studies of elderly patients with SLE are scarce. We conducted the current study to analyze characteristics and outcome of patients with late-onset SLE in a French tertiary referral center, and to compare them with those of younger patients with SLE. From 1980 to 2000, 47 patients were identified as having late-onset SLE, defined as SLE diagnosed at or over the age of 50 years. These patients were compared with a group of 114 randomly selected patients aged younger than 50 years at SLE diagnosis. We compared clinical characteristics, laboratory data, therapy, and course. The female to male ratio was smaller in the late-onset SLE group (p = 0.0012). Some manifestations occurred less frequently in late-onset SLE: arthritis (p = 0.009), malar rash (p = 0.013), and nephropathy (p = 0.009). High-dose corticosteroids (p = 0.0016) and immunosuppressive drugs (p = 0.006) were less commonly used in the elderly. Deaths occurred more frequently in late-onset SLE (p = 0.019), with a 10-year survival rate of 71% versus 95% in early-onset SLE (p < 0.01). In patients with late-onset SLE, causes of death were usually unrelated to SLE. Analysis of pooled data from the literature, based on 714 old and 4700 young SLE patients, confirmed that late-onset SLE was characterized by a smaller female to male ratio (4.4:1 vs. 10.6:1; p = 3.10−14); a higher occurrence of serositis (36.7% vs. 28.6%; p = 7.10−4) and pulmonary involvement (21.2% vs. 11.3%; p = 6.10−8); and a lower occurrence of malar rash (31.1% vs. 62.4%; p = 10−44), photosensitivity (26.2% vs. 38.2%; p = 6.10−6), purpura/cutaneous vasculitis (13.4% vs. 25.9%; p = 9.10−4), alopecia/hair loss (24% vs. 44.9%; p = 3.10−11), Raynaud phenomenon (24.8% vs. 37.2%; p = 3.10−7), neuropsychiatric manifestations (15.3% vs. 20.2%; p = 0.025), lymphadenopathy (9.1% vs. 19.6%; p = 2.10−4), nephrotic syndrome (8.1% vs. 24.3%; p = 0.015), and nephritis (28.6% vs. 42.7%; p = 2.10−10). Regarding laboratory features, rheumatoid factor positivity was more frequent (32.7% vs. 20.1%; p = 3.10−5), whereas anti-RNP positivity (10.4% vs. 20.9%; p = 9.10−5), anti-Sm positivity (9.1% vs. 17.1%; p = 0.001), and a low CH50 complement fraction (45% vs. 64.9%; p = 0.002) were less frequent in old compared with young SLE patients. In conclusion, the clinical pattern of late-onset SLE is characterized by a lower disease severity. The reduced survival observed in this group seems to result mainly from the consequences of aging.

Efficacy of interferon alpha in the treatment of refractory and sight threatening uveitis: a retrospective monocentric study of 45 patients

Aim: Severe uveitis is potentially associated with visual impairment or blindness in young patients. Therapeutic strategies remain controversial. The efficacy of interferon alpha-2a (IFN-α2a) in severe uveitis, refractory to steroids and conventional immunosuppressive agents, was evaluated. Patients and methods: Patients were included after a major relapse of uveitis following corticosteroids and immunosuppressants. IFN-α2a (3 million units three times a week) was administered subcutaneously. Efficacy was assessed by improvement in visual acuity, decrease in vitreous haze, resolution of retinal vasculitis and macular oedema, assessed by fundus examination and fluorescein angiography, and decrease in oral prednisone threshold. Results: 45 patients were included. Median age was 32.3 years (range 8–58) and sex ratio (F/M) was 0.66. Uveitis was associated with Behçet’s disease in 23 cases (51.1%) and with other entities in 22 cases (48.9%). Median duration of uveitis before interferon therapy was 34.9 months (range 3.4–168.7) and an average of 3.26 relapses following corticosteroids and immunosuppressants was noted. Uveitis was controlled in 82.6% of patients with Behçet’s disease and 59% of patients with other types of uveitis (p = 0.07). During a mean follow-up of 29.6 months (range 14–55), median oral prednisone threshold decreased significantly from 23.6 mg/day (range 16–45) to 10 mg/d (range 4–14) (p<0.001). Interferon was discontinued in 10 patients (22.2%) with Behçet’s disease and in four patients without Behçet’s disease. Relapses occurred in four and one cases, respectively. Conclusions: Interferon therapy appears to be an efficient strategy in severe and relapsing forms of Behçet’s disease but also in other uveitic entities. However, it seems to act more to suspend rather than cure the disease. Therefore, IFN-α2a may be proposed as a secondline strategy after failure of conventional immunosuppressants.

Pregnancy in past or present lupus nephritis: a study of 32 pregnancies from a single centre

OBJECTIVE To study maternal and fetal outcome in women with past or present histologically proven systemic lupus erythematosus (SLE) nephritis. METHOD Retrospective study of 32 pregnancies in 22 women with past or present histologically proven SLE nephritis in a single French centre. RESULTS Pregnancy (25 planned and 7 not planned) occurred in a mean (SD) of 8 (5) years after SLE diagnosis and 6 (4) years after renal disease onset. Seven occurred in women with antiphospholipid syndrome. At pregnancy onset, all but one woman had creatininaemia below 100 μmol/l, five had proteinuria >0.5 g/day, none had hypertension. Twelve pregnancies occurred in women previously treated with immunosuppressant drugs. Treatment comprised prednisone (n=31), hydroxychloroquine (n=11), aspirin (n=22), heparin (n=12), and azathioprine in one patient with steroid resistant nephrotic syndrome disclosing SLE. No therapeutic abortion was done. During pregnancy or the postpartum period, or both, proteinuria >0.5 g/day occurred in 10 women (five related to pre-eclampsia, four to renal flare, one to stable nephrotic syndrome). One flare consisted of mild arthralgias. Pregnancy outcome comprised one feto-maternal death in SLE disclosed by pregnancy, five embryonic losses, two fetal deaths, and 18 premature (one neonatal death) and six full term births. No criterion appeared to influence fetal survival significantly. At long term, one patient died during an SLE flare, three women had renal relapses. At the last visit, all had creatininaemia below 100 μmol/l except one woman with creatinine level 115 μmol/l, nine had proteinuria >0.5 g/day, and one was treated for hypertension. CONCLUSION Pregnancy need not be discouraged in women with a history of SLE nephritis with normal or mildly impaired renal function. Deterioration of renal function rarely occurs. However, these pregnancies are at high risk of pre-eclampsia and prematurity.

Spectrum of cardiac lesions in Behçet disease: a series of 52 patients and review of the literature.

AbstractCardiac abnormalities in patients with Behçet disease (BD) include pericarditis, myocarditis, endocarditis with valvular regurgitation, intracardiac thrombosis, endomyocardial fibrosis, coronary arteritis with or without myocardial infarction, and aneurysms of the coronary arteries or sinus of Valsalva. Data regarding the clinical spectrum, prevalence, and outcome of cardiac lesions in BD are lacking. In this study, we report the main characteristics, treatment, and long-term outcomes of 52 patients with cardiac lesions from a cohort of 807 (6%) BD patients. Forty-five (86.5%) patients were male, with a mean (±SD) age at BD diagnosis of 29.3 ± 10.3 years.Cardiac involvement was the first feature of BD in 17 (32.7%) patients. Cardiac lesions included pericarditis (n = 20; 38.5%), endocarditis (mostly aortic insufficiency) (n = 14; 26.9%), intracardiac thrombosis (n = 10; 19.2%), myocardial infarction (n = 9; 17.3%), endomyocardial fibrosis (n = 4; 7.7%) and myocardial aneurysm (n = 1; 1.9%). Patients with cardiac involvement were more frequently male (86.5% vs. 64.9%; p < 0.01) and had more arterial (42.3% vs. 11.1%; p < 0.01) and venous lesions (59.6% vs. 35.8%; p < 0.01) compared to those without cardiac manifestations. Factors associated with complete remission of cardiac involvement were treatment regimens with oral anticoagulants, immunosuppressants, and colchicine. The 5-year survival rate was 83.6% and 95.8% (p = 0.03) in BD patients with and without cardiac involvement, respectively. After a median (Q1–Q3) follow-up of 3.0 (1.75–4.2) years, 8 patients had died, in 3 cases directly related to cardiac involvement.In conclusion, cardiac lesions affected 6% of our large cohort of BD patients. The prognosis of cardiac involvement in BD is poor and improves with oral anticoagulation, immunosuppressive therapy, and colchicine.

Endomyocardial fibrosis in Behçet’s disease

OBJECTIVE To report on four patients with Behçet’s disease associated with endomyocardial fibrosis involving the right or the left ventricle. METHODS Charts of more than 350 patients with Behçet’s disease were reviewed. Endomyocardial fibrosis was confirmed because of cardiac failure in three patients and incidentally discovered by histological examination of an operative specimen in one patient. Echocardiography displayed bright echogen endocardium. Angiocardiography showed a reduced ventricular size. Electron beam computed tomography demonstrated a lowdense area involving the endocardium. Magnetic resonance imaging showed a mass of intermediate intensity on T1 weighted images. Diagnosis of endomyocardial fibrosis was based on histological study of a biopsy specimen in one patient and of an operative specimen in three. RESULTS Six other similar cases of endomyocardial fibrosis complicating Behçet’s disease were previously reported in the medical literature. Endomyocardial fibrosis predominantly involved the right ventricle. It can be considered a feature of Behçet’s disease because: (a) no other cause was discovered; (b) arteritis, valvulopathy, and intraventricular thrombus were closely linked, and (c) all patients with endomyocardial fibrosis had vasculo-Behçet pattern. CONCLUSION Endomyocardial fibrosis may be the sequelae of vasculitis involving endocardium or myocardium, or both and complicated with intraventricular thrombosis. Behçet’s disease should be added to the list of causes of endomyocardial fibrosis.

Tumor Antigen Markers for the Detection of Solid Cancers in Inflammatory Myopathies

Dermatomyositis and polymyositis patients have an increased risk of developing cancers. We have assessed the diagnostic values of serum tumor markers for the detection of solid cancer in dermatomyositis/polymyositis patients. Serum carcinoembryonic antigen, CA15-3, CA19-9, and CA125 were assayed by immunoradiometric methods in 102 dermatomyositis/polymyositis patients. All the patients had complete physical examination, chest X-ray, echocardiogram, gastrointestinal tract endoscopic explorations, thoracoabdomino-pelvic computed tomography scan, and all women had gynecologic examination and mammogram. Exclusion criteria for study were childhood dermatomyositis, inclusion body myositis, myositis associated with a connective tissue disease, prior history of cancer, and the presence of benign conditions known to elevate serum tumor markers. After a median follow-up of 59 months, 10 (9.8%) patients had a solid cancer. Initial elevation of CA125 was associated with an increased risk of developing solid cancer [P = 0.0001 by Fishers exact test; odds ratio (OR), 29.7; 95% confidence interval (95% CI), 8.2-106.6]. For CA19-9, there was a trend towards a significant association (P = 00.7; OR, 4.5; 95% CI, 1-18.7, respectively). Diagnostic values of elevated CA125 and CA19-9 at screening increased when the study analysis was restricted to patients who developed a cancer within 1 year (P < 0.0001 and P = 0.018, respectively) or to patients without interstitial lung disease (P = 0.00001; OR, 133; 95% CI, 6.5-2733 and P = 0.027; OR, 9; 95% CI, 1.5-53, respectively). Individual comparisons of the baseline and the second CA125 value showed that three of the eight patients with cancers versus 3 of the 76 patients without, displayed an increase of their CA125 level (P = 0.01 by Fishers exact test). We conclude that CA125 and CA19-9 assessment could be useful markers of the risk of developing tumors for patients with dermatomyositis and polymyositis and should therefore be included in the search for cancer in dermatomyositis/polymyositis patients, especially for patients without interstitial lung disease.

Pregnancy in patients with Wegener's granulomatosis: report of five cases in three women

Five cases of pregnancy occurring in three women with previously diagnosed Wegeners granulomatosis are described. The disease was diffuse in one case and localised in the other. Initial treatment consisted of a combination of corticosteroids and intravenous cyclophosphamide in two women, and methotrexate in one. Four pregnancies ended in live births despite pre-eclampsia in two cases. One therapeutic abortion was induced because of encephalocele. Comparable reported cases were reviewed to examine the implications of immunosuppressive treatment on the fetus. A relapse occurred during pregnancy in 40% of the cases, but in 25% if only pregnancies beginning during inactive disease were taken into account. No other indicator for maternal and fetal outcome was obvious. Pregnancy should be planned after complete disappearance of disease activity. In the case of a relapse a combination of immunosuppressive drugs and corticosteroids should be chosen rather than corticosteroids alone because the outcome of pregnancy is poor in cases of undertreatment. Prematurity remains common.

Urogenital manifestations of Wegener granulomatosis.

We report 8 patients with Wegener granulomatosis (WG) who suffered from symptomatic urogenital involvement including acute urinary retention related to prostatitis, orchitis, ureteral stenosis, bladder pseudotumor, and penile ulceration. Urogenital manifestations occurred as an isolated manifestation of WG in 4 patients, at the onset of the disease in 1 patient, and as the only symptom of relapse in 3. Data used to distinguish specific WG involvement from infection or cyclophosphamide urothelial toxicity are discussed. Four patients needed a surgical procedure consisting of suprapubic cystostomy for acute urinary retention, bilateral ureteral double J stents for bilateral ureteral stenosis, and prostate transurethral resection. Urogenital symptoms promptly resolved with medical therapy. High-dose corticosteroids and immunosuppressive drugs should be used as first-line therapy to avoid unnecessary surgery.