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Biomedical subjects

G Ruiz-Irastorza

Publications and source records attributed to G Ruiz-Irastorza.

At least 19 recordsLinked to original sources
PubMed2007

Antimalarials may influence the risk of malignancy in systemic lupus erythematosus.

BACKGROUND: Recent studies suggest that antimalarials have antineoplastic properties. OBJECTIVE: To investigate whether antimalarials decrease the risk of cancer in systemic lupus erythematosus (SLE). METHODS: An observational prospective cohort study was carried out. 235 patients were included in the study at the time of diagnosis (American College of Rheumatology criteria). The end point was the diagnosis of cancer. Kaplan-Meier cancer-free survival curves for patients treated and not treated with antimalarials were compared. A Cox proportional hazards model was fitted, with cancer as the dependent variable. Age at diagnosis, gender, treatment with azathioprine, cyclophosphamide and methotrexate, smoking, Systemic Lupus International Collaborating Clinics (SLICC) Damage Index 6 months after diagnosis, year of diagnosis and treatment with antimalarials were entered as independent variables. RESULTS: 209 (89%) patients were women. 233 (99%) patients were white. Mean (SD) age at diagnosis was 37 (16) years. Median (range) follow-up was 10 (1-31) years. 156 (66%) patients had ever received antimalarials. 2/156 (1.3%) ever-treated patients compared with 11/79 (13%) never-treated patients had cancer (p<0.001). Cumulative cancer-free survival in treated and not treated patients was 0.98 and 0.73, respectively (p<0.001). Adjusted hazard ratio for cancer among malaria drug users compared with non-users was 0.15 (95% CI 0.02 to 0.99). CONCLUSIONS: This study launches the hypothesis of a protective action of antimalarials against cancer in patients with SLE. This effect should be confirmed in larger multicentre studies.

Adolescent↗
PubMed2006

[Systematic lupus erythematosus and antiphospholipid syndrome during pregnancy].

Women with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) are subject to several complications during pregnancy, including reactivation of SLE, thrombosis, miscarriage, neonatal lupus, pregnancy-induced hypertension, pulmonary hypertension and drug toxicity. Correct management of these patients requires combined medical-obstetric care, close surveillance of baby's growth and well-being, control of SLE activity and correct thromboprophylaxis. With good care, most pregnancies in women with SLE and APS end successfully.

Anticoagulants↗
PubMed2006

Effect of antimalarials on thrombosis and survival in patients with systemic lupus erythematosus.

Antimalarials have shown beneficial effects on systemic lupus erythematosus (SLE) activity. Our aim was to investigate whether antimalarials protect against thrombosis and influence survival in SLE patients. A prospective cohort including 232 patients with SLE were included in the study at the time of lupus diagnosis. End points were documented thrombosis and death due to any cause. A Cox regression-multiple-failure time survival analysis model was fitted to establish the effect of antimalarials on the development of thrombosis. Kaplan-Meier survival curves and propensity score adjusted-Cox regression analysis were performed to investigate the effect of antimalarials use on survival. Of our subjects, 204 patients (88%) were women. 230 patients (99%) were white. 150 patients (64%) had ever received antimalarials. Median time on antimalarials was 52 months (range three to 228 months). The Cox multiple-failure time survival analysis showed that taking antimalarials was protective against thrombosis (HR 0.28, 95% CI 0.08-0.90), while aPL-positivity (HR 3.16, 95% CI 1.45-6.88) and previous thrombosis (HR 3.85, 95% CI 1.50-9.91) increased the risk of thrombotic events. Twenty-three patients died, 19 of whom (83%) had never received antimalarials. No patient treated with antimalarials died of cardiovascular complications. Cumulative 15-year survival rates were 0.68 for never versus 0.95 for ever treated patients (P < 0.001). Age at diagnosis and propensity score-adjusted HR for antimalarials ever versus never users was 0.14 (95% CI 0.04-0.48). Our study shows a protective effect of antimalarials against thrombosis and an increased survival of SLE patients taking these drugs. These data support the routine use of antimalarials in all patients with SLE.

Adult↗
PubMed2006

High risk of tuberculosis in systemic lupus erythematosus?

The incidence and severity of tuberculosis (TB) in patients with systemic lupus erythematosus (SLE) varies greatly among different series. In addition, prospective data are scarce. The aim of this study is to analyse the frequency and severity of TB in our cohort of lupus patients. We analysed data from a prospective database of a single center cohort of 232 patients with SLE (ACR criteria). Prophylaxis with isoniazid was not regularly administered. We identified all cases of TB diagnosed during 10 years (January 1994 to December 2003). The following variables were analysed: annual incidence of TB, location of infection and response to therapy. Data from published series reporting on the incidence of TB among SLE patients were extracted. Three patients (1.3%) suffered clinically manifest TB in 1603 patient-years of follow-up, resulting in an incidence of 187 cases/100,000 patient-years (95% CI 39-547). The pooled annual incidence of TB infection in our area during this period was 30/100,000 individuals. We recorded two cases of pulmonary TB and one case of tuberculous pleurisy. All patients had good response to therapy. The annual incidence of TB among SLE patients in other series, most of them from developing countries, varied between 150/100,000 patients in Turkey and 2450/100,000 patients in India. Of note, high prevalence of extrapulmonary forms as well as elevated TB-associated mortality was reported in most series. TB was more frequent in SLE patients than expected in the general population. We did not see any cases of disseminated infection and all patients had good response to treatment. Our data compare favourably in terms of incidence, severity and outcome with those from highly endemic areas.

Cohort Studies↗
PubMed2005

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.

Age of Onset↗
PubMed2005

Stroke and antiphospholipid syndrome: the treatment debate.

Antiphospholipid syndrome (APS) is one of the most frequent acquired thrombophilias. Thromboses can be at both the venous and arterial level, are usually recurrent and frequently affect cerebral circulation. Although it is difficult to predict which patients with antiphospholipid antibodies (aPL) will develop thrombosis, once a thrombotic event has taken place, secondary prevention is mandatory. Recommendations for treatment of APS have long been based on studies with a retrospective design. Recently, three prospective studies (two controlled and one uncontrolled small series) have addressed the role of antiaggregant and anticoagulant therapy in patients with stroke and aPL. However, results from prospective and retrospective studies are not in full agreement. In addition to the obvious differences in design, other factors such as the important variability in the study groups account for the discrepancy. While future investigation must better define homogeneous subsets of patients with APS, current secondary prophylaxis of thrombosis in these patients must be tailored according to individual estimated risk of recurrences, risk of haemorrhage and severity of potential recurrent events. Due to the often devastating consequences of stroke, we believe there is a place for prolonged, high-intensity anticoagulation in patients with APS and cerebral arterial thrombosis.

Anticoagulants↗
PubMed2004

Measuring systemic lupus erythematosus activity during pregnancy: validation of the lupus activity index in pregnancy scale.

OBJECTIVE: To validate the Lupus Activity Index in Pregnancy (LAI-P) scale as a diagnostic tool for lupus flares during pregnancy and the puerperium. METHODS: The LAI-P is a modified activity scale specific for pregnancy. Thirty-eight pregnant women with systemic lupus erythematosus (SLE) were prospectively followed in 3 clinics specific for lupus in pregnancy. On each visit, LAI-P was calculated. A modified physician global assessment (m-PGA) scale was used as gold standard (0 = no activity, 1 = mild-moderate activity, 2 = severe activity). A change > or = 0.25 in LAI-P was predefined as a flare according to previous studies in nonpregnant patients. For the purposes of the study, each visit was considered as an independent case. RESULTS: During the study period, 158 visits took place for a total 621 patient-weeks. Sensitivity to change was high (standardized response mean for LAI-P = 1.6). We found a significant association between LAI-P and m-PGA (P < 0.002 in all regression models performed). Sensitivity, specificity, and positive and negative predictive values were 0.93, 0.98, 0.88, and 0.99. Positive and negative likelihood ratios were 49 and 0.07, respectively. CONCLUSIONS: LAI-P has a high sensitivity to changes in lupus activity, a significant correlation with m-PGA, and high sensitivity, specificity, predictive values, and likelihood ratios for diagnosing SLE flares during pregnancy and the puerperium.

Adult↗
PubMed2004

Evaluation of systemic lupus erythematosus activity during pregnancy.

Due to our increasing knowledge on the pathophysiological basis of autoimmunity and the development of combined medical-obstetric clinics, pregnancy is becoming common among women with systemic lupus erythematosus (SLE). However, whether lupus worsens during pregnancy continues to be a controversial issue. SLE assessment during pregnancy is sometimes difficult due to physiological changes during this period, and common tools for measuring lupus activity during pregnancy were not available until recently. Several lupus activity scales in common use have been adapted for pregnancy [systemic lupus erythematosus in pregnancy activity index (SLEPDAI), modified lupus activity measurement (m-SLAM) and lupus activity index in pregnancy (LAI-P)]. All of them take into account the influence of pregnancy on clinical manifestation and common biochemical tests. LAI-P also accounts for specific manifestations of antiphospholipid syndrome in order not to score them as due to SLE activity. LAI-P has recently been validated for use in SLE pregnancy and could be used in future studies. However, daily assessment and management of individual pregnant women with lupus still relies on the clinical skills of attending physicians.

Female↗
PubMed2004

Antiphospholipid antibodies predict early damage in patients with systemic lupus erythematosus.

The aim of this study was to determine whether the different autoantibodies predict early damage in patients with systemic lupus erythematosus (SLE). The patients comprised a prospective inception cohort of 205 patients with SLE, 154 on follow-up for at least five years after diagnosis. Eight patients who died before the fifth year of disease course were included in analyses comprising survival. Organ damage was measured using the Systemic Lupus International Collaborating Clinics--American College of Rheumatology damage index (SDI). Endpoints were the development of some (SDI > or = 1) or severe (SDI > 2) damage at five years after diagnosis or the combined outcome 'SDI > or = 1 or death at five years'. Autoantibodies [anti-DNA, anti-Ro, anti-La, anti-Sm, anti-U1RNP, any anti-ENA and antiphospholipid (aPL)] were included in univariate and multivariate analysis. 'Age at diagnosis' was also included as an independent variable in multivariant analyses. Sapporo criteria were used to define aPL positivity. Eighty-four patients (54.5%) had accrued damage at five years, 17 patients (11.0%) having severe damage. Patients with aPL had damage in a higher proportion (63.2% any damage, 17.6% severe damage). Only aPL were related to damage in univariate analysis (P = 0.03). In logistic regression models, aPL were the only independent predictors of damage at five years (OR 1.94, 95% CI 1.01-3.73), severe damage at five years (OR 3.34, 95% CI 1.11-10.03) and increasing damage since diagnosis (OR 2.46, 95% CI 1.24-4.87). No autoantibody was a predictor of the outcome 'SDI > or = 1 or death at five years'. The conclusion was that aPL predict early damage in patients with SLE.

Adult↗
PubMed2004

Homocysteine, antiphospholipid antibodies and risk of thrombosis in patients with systemic lupus erythematosus.

Cardiovascular disease is a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Antiphospholipid syndrome (APS) is one of the most important causes of thrombosis in SLE. In addition, an association between hyperhomocysteinemia and increased cardiovascular risk has also been reported. Our aim is to analyse the association of thrombosis with plasma total homocysteine (ptHcy), antiphospholipid antibodies (aPL) and other vascular risk factors in SLE patients. Fasting plasma levels of ptHcy, vitamin B12, folate, total cholesterol and creatinine were measured in 117 SLE patients. Clinical and immunological data were obtained from our prospective computerized database. aPL-positivity was defined according to Sapporo criteria. There was no association between aPL and ptHcy. ptHcy was higher in patients with arterial (median 13.02 versus 10.16 micromol/L, P = 0.010) but not venous thrombosis. In the subgroup analysis, this association was only seen in aPL-negative patients. In logistic regression, aPL (OR 6.60, 95% CI 1.86-23.34) and ptHcy (OR 1.10, 95% CI 1.01-1.19) were independently associated with arterial thrombosis. However, when hypertension, smoking and plasma total cholesterol were added to the model, only aPL (OR 7.38, 95% CI 2.02-26.91) and hypertension (OR 7.70, 95% CI 2.33-25.39), but not ptHcy, remained independently related to arterial events. aPL was the only variable independently related to venous thrombosis (OR 7.68, 95% CI 1.60-36.86). ptHcy concentrations are higher in SLE patients with arterial thrombosis. No interaction between homocysteine and aPL was found. Raised ptHcy may be a marker of increased vascular risk in aPL-negative SLE patients. The role of homocysteine as a marker of vascular risk may depend on the presence of traditional risk factors, although a modest intrinsic effect cannot be entirely excluded.

Adult↗
PubMed2004

Systemic lupus erythematosus presenting as acute symptomatic hypercalcemia.

Hypercalcemia is a common electrolyte abnormality with a wide differential diagnosis. Primary hyperparathyroidism and malignancy are the most frequent causes, accounting for more than 90% of cases. We report the case of a woman presenting with symptomatic severe hypercalcemia, who was subsequently diagnosed with systemic lupus erythematosus (SLE) due to the presence of arthritis, lymphopenia, antinuclear antibodies (ANA), anti-DNA and anti-Ro antibodies and low C3 levels. After acute treatment with intravenous fluids, steroids, diuretics and pamidronate, calcium levels corrected and have remained normal on low-dose prednisone. Five similar cases have been reported in the literature. Thus, SLE is an uncommon cause of hypercalcemia, which can also be the presenting feature of lupus.

Adult↗
PubMed2004

Sustained response to rituximab of autoimmune hemolytic anemia associated with antiphospholipid syndrome.

Standard treatment for autoimmune hemolytic anemia (AIHA) due to warm antibodies includes combinations of glucocorticoids, immunosuppressive drugs (mainly azathioprine) and splenectomy. Patients who are refractory or intolerant to these therapies constitute an important therapeutic challenge. Rituximab, an anti-CD20 chimeric monoclonal antibody, can effectively deplete B-cells and is commonly used in B-cell non-Hodgkin lymphoma. In addition, it is being increasingly used in autoimmune disorders, such as idiopathic thrombocytopenic purpura, AIHA, systemic lupus erythematosus or vasculitis. We report a case of warm AIHA associated to primary antiphospholipid syndrome (APS). The patient was refractory to high-dose corticosteroids. Splenectomy was discarded in view of the high risk of thrombotic and/or hemorrhagic perioperative complications, due to the presence of APS. After treatment with four weekly doses of rituximab the patients had a rapid and sustained response which allowed progressive tapering of prednisone dose to 5 mg/d. In addition, IgM anticardiolipin titres decreased from > 600 MPL to < 100 MPL. Thirteen further cases of warm AIHA in adults treated with rituximab have been reviewed, showing excellent tolerance and high response rates. Rituximab may be considered prior to splenectomy in patients with refractory AIHA and high risk of complications following splenectomy.

Anemia, Hemolytic, Autoimmune↗
PubMed2003

Stroke and the antiphospholipid syndrome: consensus meeting Taormina 2002.

Ischaemic stroke is the only neurological manifestation accepted as a clinical diagnostic criterion for the antiphospholipid syndrome (APS). This association is reasonably well established in patients first diagnosed with APS but is less clear in randomly selected stroke patients who test positive on one occasion for antiphospholipid antibodies and who have no other evidence of systemic autoimmune disease. We propose a grading system that posits stroke to be definitely, likely or possibly associated with antiphospholipid antibodies (aPL). Further, there are limited prospective data to determine appropriate treatment. There is controversy as to whether the presence of aPL even increases risk of a recurrent stroke or other thromboembolic event, although data point to persistent medium-high titre aCL and/or LA as risk factors for recurrence. In the absence of data to guide clinicians on the best treatment, we cannot make strong recommnendations as to optimal therapy, nor can we propose clear consensus treatment guidelines.

Administration, Oral↗
PubMed2002

Heparin and osteoporosis during pregnancy: 2002 update.

Although significant bone mass loss is rare during pregnancy, some situations may increase the risk of symptomatic osteoporosis. Heparin may be necessary for a number of pregnant women with systemic lupus erythematosus and antiphospholipid syndrome. The osteopenic effect of heparin is low even during pregnancy, and recent data point to a more favourable profile of low-molecular-weight heparins as compared with unfractionated heparin. Lactation results in a significant increase of calcium demands and may be a higher risk period for women at risk for osteoporosis.

Antiphospholipid Syndrome↗
PubMed2001

Systemic lupus erythematosus.

This review covers major advances in clinical issues related to systemic lupus erythematosus (SLE) published between 1995 and 2000. The classification criteria for both SLE and antiphospholipid syndrome (APS) have been updated, and up to 19 different subsets of neuropsychiatric lupus have been defined. New epidemiological data show that the incidence of new cases and the survival of patients with SLE are both increasing. Several randomised controlled trials have defined the role of cyclophosphamide, methotrexate, antimalarials, and hormonal treatment in the management of SLE. New data are available for drugs such as ciclosporin and thalidomide. Finally, several new treatments for severe refractory cases, such as mycophenolate mofetil and stem-cell transplantation, are being increasingly used. New data also refer to management of thrombosis in APS and high-risk pregnancies in women with SLE or APS.

Antiphospholipid Syndrome↗
PubMed2001

Treatment of systemic lupus erythematosus.

The treatment of systemic lupus erythematosus (SLE) is mainly based on a number of "traditional" drugs such as corticosteroids, antimalarials, azathioprine and cyclophosphamide. However, this scenario is rapidly changing due to the introduction of new compounds. Some of these new agents have been successfully used in other diseases, while others are being specifically designed to interfere with the immune abnormalities seen in SLE. As our knowledge on the mechanisms of immune response increases, new drugs that can interfere with T and B cell interaction and activation, production of anti-dsDNA autoantibodies, immune-complexes deposition and cytokine activation have been developed and some of these are now under investigation in SLE. Although initial data regarding their safety and efficacy are encouraging, caution must be taken before these drugs are considered as the treatment of choice for specific SLE manifestations. Specifically, controlled clinical trials with sufficient number of patients are necessary. If the promising results already available are confirmed, the use of these drugs might represent the keystone in the future management of SLE and other autoimmune diseases.

Adjuvants, Immunologic↗
PubMed2001

Antiaggregant and anticoagulant therapy in systemic lupus erythematosus and Hughes' syndrome.

Antiaggregant and anticoagulant drugs are essential in the management of the manifestations due to antiphospholipid syndrome (APS) in patients with primary Hughes' syndrome or systemic lupus erythematosus. Coumadin derivatives (warfarin and acenocumarol), heparin and aspirin are used for secondary thromboprophylaxis and treatment of recurrent miscarriage. The available evidence for each indication is reviewed in this paper. There is still debate regarding the optimal intensity of oral anticoagulation, the best drug combination for pregnancy failure in APS and the management of asymptomatic patients with antiphospholipid antibodies.

Anticoagulants↗