Systemic lupus erythematosus in Europe at the change of the millennium: lessons from the "Euro-Lupus Project".

The "Euro-Lupus Cohort" is composed by 1000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium--the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors.

Systemic lupus erythematosus: clinical and immunologic patterns of disease expression in a cohort of 1,000 patients. The European Working Party on Systemic Lupus Erythematosus.

In the present study we have analyzed the prevalence and characteristics of the most relevant clinical and immunologic features in 1,000 patients with SLE. Several differences in the expression of the disease have been observed in relation to the patients' age at onset, sex, and autoantibody serology. The childhood-onset patients more often had malar rashes (55% vs 39%) and nephropathy (28% vs 15%) as presenting manifestations. During the evolution of the disease, these patients had an increased prevalence only of malar rash (79% vs 56%) and a lower prevalence of rheumatoid factor (6% vs 19%). The older-onset patients (age 50 or older) less often showed malar rash (21% vs 42%), arthritis (52% vs 71%), and nephropathy (3% vs 17%) as the first symptom. During the evolution of their disease, these patients had a decreased prevalence of malar rash (33% vs 60%), photosensitivity (29% vs 47%), arthritis (73% vs 85%), nephropathy (22% vs 41%), thrombosis (4% vs 15%), and anti-La antibodies (6% vs 20%), but an increased prevalence of sicca syndrome (33% vs 15%). Males more often had serositis (28% vs 16%) as a first symptom, but they presented with a lower prevalence of arthritis (74% vs 85%) during the evolution of the disease. The presence of ANA, a high titer of anti-dsDNA, rheumatoid factor, anti-ENA, and antiphospholipid antibodies also distinguished additional homogeneous SLE subsets of clinical significance.

Morbidity and mortality in systemic lupus erythematosus during a 5-year period. A multicenter prospective study of 1,000 patients. European Working Party on Systemic Lupus Erythematosus.

In the present study we assessed the frequency and characteristics of the main causes of morbidity and mortality in SLE during a 5-year period and analyzed the prognostic significance for morbidity and mortality of the main immunologic parameters used in clinical practice. We started in 1990 a multicenter study of 1,000 patients from 7 European countries. All had medical histories documented and underwent medical interview and routine general physical examination when entered in the study, and all were followed prospectively by the same physicians during the ensuing 5 years (1990-1995). Four hundred thirteen patients (41.3%) presented 1 or more episodes of arthritis, 264 (26.4%) had malar rash, 222 (22.2%) active nephropathy, 139 (13.9%) fever, 136 (13.6%) neurologic involvement, 132 (13.2%) Raynaud phenomenon, 129 (12.9%) serositis (pleuritis and/or pericarditis), 95 (9.5%) thrombocytopenia, and 72 (7.2%) thrombosis. Two hundred seventy patients (27%) presented infections, 113 (11.3%) hypertension, 75 (7.5%) osteoporosis, and 59 (5.9%) cytopenia due to immunosuppressive agents. Sixteen patients (1.6%) developed malignancies, with the most frequent primary localizations the uterus and the breast. Several immunologic parameters (anti-dsDNA or antiphospholipid antibodies) were found to have a predictive value for the development of SLE manifestations during the period of the study. Forty-five patients (4.5%) died; the most frequent causes of death were divided similarly among active SLE (28.9%), infections (28.9%), and thromboses (26.7%). A survival probability of 95% at 5 years was found. A lower survival probability (92%) was detected in those patients who presented at the beginning of the study with nephropathy.

Hydrochlorothiazide versus spironolactone: long-term metabolic modifications in patients with essential hypertension.

The metabolic side effects of thiazide diuretics are believed to be responsible for the failure of thiazide diuretics to reduce cardiovascular morbidity in patients with hypertension. However, the decrease in the incidence of osteoporotic fractures that are associated with thiazide administration may be relevant in elderly patients with arterial hypertension. Spironolactone (SP) appears not to influence the metabolic risk profile of the patient with hypertension, and no studies have examined its effect on calcium metabolism. Therefore, in 22 patients with mild to moderate essential hypertension, the authors performed a parallel, randomized, double-blind, placebo-controlled study that compared the effects on serum urate and lipid, potassium, magnesium, and calcium metabolism of hydrochlorothiazide (HC) (mean [+/- SD] dose, 72 +/- 26 mg/d) and SP (144 +/- 53 mg/d) during a 52-week period. As compared with placebo, HC significantly increased serum urate and total cholesterol concentrations, and decreased serum potassium levels. SP did not affect serum urate or cholesterol levels but increased serum potassium concentrations. Neither diuretic significantly modified magnesium metabolism. Little changes were seen in serum calcium levels during HC or SP treatment, whereas urinary calcium excretion was significantly decreased by HC (mean decrease, 45%; P less than .01) or SP (40%; P less than .01). The authors conclude that SP, in addition to its potassium-sparing properties, has a calcium-sparing effect that may be beneficial for patients in whom reduction of urinary calcium excretion has a therapeutic value.

[Neoplasms associated with human immunodeficiency virus infection. Study of the clinical course of 70 patients]. / Neoplasias asociadas a la infección por el virus de la inmunodeficiencia humana. Estudio clínico y evolutivo de 70 pacientes.

BACKGROUND: A different epidemiologic pattern of the neoplasms associated to the human immunodeficiency virus (HIV) has been described in the Mediterranean area. The aim of the present study was to analyze the epidemiologic, clinical and evolutive characteristics of these patients. METHODS: A retrospective study of 74 neoplasms in 70 patients (15% of AIDS cases) was carried out. The following variables were analyzed: risk group, state of the infection (HIV), stage and type of tumor, immunohematologic data, opportunistic infections (OI), response to treatment, evolution and prognostic factors. RESULTS: Thirty-four Kaposi's sarcomas (SK) were diagnosed, 32 non Hodgkin's lymphomas (NHL), 4 Hodgkin's disease (HD), 2 seminomas, 1 cutaneous carcinoma and one undifferentiated tumor. Sixty-eight patients were males with a mean age of 32 years. The risk group was: homosexual (52%), drug abuse (24%), hemophilia (14%), and heterosexual contact (10%). The neoplasm was the first manifestation of HIV infection in 60% of the patients. Sixteen patients with SK were treated with chemotherapy (CMT), radiotherapy (RT) or interferon and stabilization of the disease was achieved in 50% of the cases. Twenty-six patients with NHL received treatment: 26 with CMT, 9 with RT and 4 with surgery. Complete remission was achieved in 27% and partial in 61% of the cases. Overall mortality was 56% and median survival 13 months. Most of the patients died due to progression of the tumor or infection. The prognostic factors associated to shortened survival were: advanced stage of AIDS, OI at the time of diagnosis of the tumor and a decrease in hemoglobin, total lymphocytes and CD4. CONCLUSIONS: The lower incidence of neoplasms among patients with acquired immunodeficiency disease and the differences in the distribution of the histologic types may be related with the demographic features of the risk groups in Spain. Survival is determined more by opportunistic infections than by the tumor itself.

[Treatment of esophageal candidiasis with fluconazole in acquired immunodeficiency syndrome. Comparative study of 2 therapeutic schemes]. / Tratamiento de la candidiasis esofágica con fluconazol en el síndrome de la inmunodeficiencia adquirida. Estudio comparativo de dos pautas terapéuticas.

BACKGROUND: To evaluate the efficacy and pharmacological safety of 2 therapeutic trials with fluconazole in candida esophagitis in AIDS patients. METHODS: A total of 75 episodes of candida esophagitis in 70 AIDS patients were included in an open prospective study. In group I 36 patients were included who received 200 mg of fluconazole orally the first day followed by 100 mg daily for 4 weeks. In group II (34 patients) the length of treatment was reduced to 10 days with the same daily doses. Therapeutic response was evaluated by esophagoscopy, biopsy and fungal culture. RESULTS: The protocol was completed at 68 episodes with a cure being obtained in all but 2 patients in group II. No significant differences in clinical response were found between the 2 groups. The incidence of oropharyngeal colonization at the end of treatment was greater in patients from group I than from group II (43% vs 11%). Fluconazole was well tolerated in all the patients. A slight alteration of the hepatic enzymes was observed in 29 cases (40%) with a lower incidence in the shorter time group (p less than 0.001), however, treatment was discontinued only in 1 patient because of severe asymptomatic hepatic dysfunction to which a relation with the drug is unclear. CONCLUSIONS: Fluconazole in an efficient and safe agent in the treatment of candida esophagitis in AIDS patients. A 10 day treatment is a useful as longer treatment and has a lower risk of adverse effects.

[Drug surveillance for adverse reactions in patients with human immunodeficiency virus infection]. / Farmacovigilancia de reacciones adversas en pacientes con infección por el virus de la inmunodeficiencia humana.

Human immunodeficiency virus (HIV) carrier patients experience several secondary effects with drugs, being mainly skin reactions and myelosuppression. Owing to this, close observation of patients is necessary with regard to therapeutic and prophylactic schedules. In this paper, we describe the secondary effects of zidovudine in 60 patients of groups III and IV from CDC. The main toxicity was found in bone marrow; with anemia in 50% and leukopenia in 53% of patients. Finally, the more frequent secondary effects of therapy for opportunist infections are analysed. A guide for identifying the drugs' secondary effects is also included, based on our experience and on a wide range of literature reviews.

[Azidothymidine in the treatment of patients with human immunodeficiency virus infection and persistent generalized adenopathies]. / La azidotimidina en el tratamiento de los pacientes con infección por el virus de la inmunodeficiencia humana y adenopatías generalizadas persistentes.

The effectiveness and security of azidothymidine (AZT) in the treatment of patients with infection by the human immunodeficiency virus (HIV) and persistent generalized adenopathies (PGA), were assessed. Thirty six patients with HIV infection and PGA participate in the study. Eighteen were treated with AZT and the other 18 were included in the control group, since they did not accept the treatment. Both groups were homogeneous with respect to their clinical, immunological and virological characteristics. A common study protocol was used and the clinical, immunological and virological effectiveness was assessed. Lymphocyte subpopulations were quantified by flow cytometry, viral antigens were determined by sandwich-type ELISA and antibodies against viral proteins (anti-gp120, anti-gp160, anti-gp41, anti-gp24 and anti-p18) were detected by Western blot. Naranjo and Busto's algorithm was used for the causality of adverse effects. We did not observe any significant differences regarding the presence of infection and the evolution of AIDS in both groups. A positive response to thrombocytopenia was observed, more evident in patients under low doses of AZT. The small initial transitory improvement of the immunological parameters was not statistically significant. The viral antigen was not modified by the treatment. With respect to the behaviour of the several antibodies studied, no differences were observed. The initial doses of AZT had to be modified in 44% of patients due to their hematological toxicity, more frequent in the first stages of the treatment. In two patients, the treatment had to be finally discontinued due to severe neutropenia. 25% of patients showed mild to moderate gastrointestinal manifestations.(ABSTRACT TRUNCATED AT 250 WORDS)

[Infection by Mucorales fungi]. / Infección por hongos mucorales.

Mucormycosis is a rare opportunistic fungal infection of immunosuppressed patients. We describe here 5 cases of mucormycosis: three with facial and eye involvement, one with lung involvement and one affecting skin and joints. All five patients had underlying diseases: diabetes, leukemia, lymphoma, neoplasia and AIDS. Four patients were treated with amphotericin B and also with surgical debridement. Infection could be controlled only in two patients. Both survived but with major sequelae. In two additional patients, death was directly related to the infection and the remaining patient was lost to follow-up.

X-linked agammaglobulinemia and gastric adenocarcinoma.

BACKGROUND: The incidence and mortality rate for cancer in patients with primary immunodeficiency diseases have increased greatly. Lymphomas constitute more than 50% of tumors identified in the Immunodeficiency Cancer Registry, but solid tumors are frequent in these patients, especially gastric carcinomas. In addition to immunologic impairment, other local conditions such as chronic atrophic gastritis with intestinal metaplasia and pernicious anemia, usually observed in these patients, may play an important role in the genesis of gastrointestinal tumors. METHODS AND RESULTS: This report describes a 23-year-old patient with X-linked agammaglobulinemia who had previously documented chronic atrophic gastritis with intestinal metaplasia, pernicious anemia, and parasitization with Giardia lamblia in whom an adenocarcinoma of the stomach developed. CONCLUSION: The authors believe that it may be useful to perform a periodic gastrointestinal evaluation for all patients with primary immunodeficiencies to establish early detection and treatment of these tumors.

Do antibodies to beta2-glycoprotein 1 contribute to the better characterization of the antiphospholipid syndrome?

The aim of this study was to determine if the measurement of anti-beta2-glycoprotein I antibodies (abeta2-GPI) in serum levels contributes to the better characterization of the clinical situation of patients with antiphospholipid syndrome (APS). For this purpose abeta2-GPI of both isotypes was measured in 42 patients with APS and 32 SLE patients without APS. Clinical records of all patients were thoroughly reviewed. The presence of abeta2-GPI was correlated with the clinical manifestations of APS and compared with the presence of anticardiolipin antibodies (aCL) and lupus anticoagulant (LA) activity. There was a positive correlation between levels of aCL and abeta2-GPI for both IgG and IgM isotypes (rho of Spearman=0.82 and 0. 64 respectively, P=0.0001). Both antibodies presented significantly higher titres in LA positive patients (P<0.05). The specificity for APS was 91% for IgG abeta2-GPI vs 75% for IgG aCL and 87% for IgM abeta2-GPI vs 81% for IgM aCL. 68% of patients with thrombosis of 100% of patients with thrombocytopenia showed positive tests for all three markers (aCL, LA, abeta2-GPI). Simultaneous presence of circulating LA and high titres of both aCL and abeta2-GPI identify a subset of patients with primary APS (PAPS) who have a more severe clinical course of the disease. Although the specificity of abeta2-GPI IgG is higher than that of aCL IgG, when all three tests are performed abeta2-GPI testing provides only additional information to that of aCL and LA. Therefore, we concluded that the abeta2-GPI test should not be considered as a substitute for conventional LA or aCL assays. However, performance of abeta2-GPI seems to be important in PAPS with high aCL titres, to alert the physician about the risk for the worst course of the illness.

[Angiothrombotic pulmonary granulomatosis in intravenous drug addicts]. / Granulomatosis pulmonar angiotrombótica en adictos a drogas por vía parenteral.

Two cases of angio-thrombotic lung granulomatosis in intravenous drug addicts are described. This entity has been previously described in drug addicts who inject oral drugs intravenously. Talc, which is used in the preparation of several drugs, cotton and other substances provoke at lung vessels level, thrombotic phenomena with strange body granuloma formations. Depending on the predominating localization of these lesions, interstitial pneumonia or pulmonary hypertension can later occur, such is the case in one of our patients who had a fatal evolution in a short period of time.

[Rhino-cerebral mucormycosis and hematological neoplasia]. / Mucormicosis rinocerebral y neoplasia hematológica.

Mucormycosis is a rare infection that occurs in immunocompromised patients. The rhinocerebral form presents in diabetics as a severe necrotizing sinusitis and is not frequent in patients with haematologic malignancies. Diagnosis requires direct examination and culture of biopsy specimens. Two patients with rhinocerebral mucormycosis and haematologic neoplasms (Non-Hodgkin's lymphoma and acute myeloblastic leukaemia) are described. Both patients had severe drug-induced neutropenia when the infection appeared. One patient died in spite of aggressive treatment with surgery and amphotericin.