Jose Gabriel Erdozain

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.

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.

Transiently positive anticardiolipin antibodies and risk of thrombosis in patients with systemic lupus erythematosus.

Fluctuations in the titers of anticardiolipin antibodies (aCL) have been reported in systemic lupus erythematosus (SLE) patients, but their relation with thrombosis is not completely understood. Prospective inception cohort of 237 patients with SLE (American College of Rheumatology criteria). Positivity for antiphospholipid antibodies (aPL) was defined according to Sapporo criteria. aCL was defined as persistently positive when more than two-thirds of the determinations were positive during follow-up. Patients were classified into four groups: A [positive lupus anticoagulant (LA)], B (negative LA and persistently positive aCL), C (negative LA and transiently positive aCL) and D (negative LA and aCL). Of these 237 patients, 211 (89%) patients were women. Median age at diagnosis and follow-up were 32 (2—78) and 10 (1—31) years, respectively; 33 (13.9%), 23 (9.7%), 42 (17.7%) and 139 (58.6%) patients were classified in groups A, B, C and D, respectively. Thirty (12.6%) and 23 (9.7%) patients suffered arterial and venous thrombotic events, respectively. Adjusted risk for arterial thrombosis was increased in groups A [odds ratio (OR) 15.69, 95% confidential interval (CI) 4.79—51.42, P < 0.001] and B (OR 7.63, 95% CI 2.00—29.08, P = 0.003), but not in group C when compared with group D. Adjusted risk of venous thrombosis was increased in group A (OR 4.24, 95% CI 1.36—13.20, P = 0.013), but not in groups B or C when compared with group D. Risk of thrombosis is not increased in SLE patients with negative LA and transiently positive aCL, even fulfilling Sapporo laboratory criteria, when compared with aPL-negative SLE patients. Lupus (2007) 16, 810—816.

Peripheral Arterial Disease in Systemic Lupus Erythematosus: Prevalence and Risk Factors

Objective. To analyze the prevalence of peripheral arterial disease (PAD) and cardiovascular (CV) risk factors in a cohort of patients with systemic lupus erythematosus (SLE) and to identify variables potentially related to PAD. Methods. The study included 216 patients with SLE from the Lupus-Cruces prospective observational cohort. The ankle brachial index (ABI) was determined in each patient, with values < 0.9 considered diagnostic of PAD. Demographic and clinical variables, presence of traditional risk factors and CV events, cardiovascular risk calculated by Systematic Coronary Risk Evaluation (SCORE), and treatments received by each patient were analyzed. Results. Ninety-two percent of patients were women. The mean age (SD) was 49 years (15), with a mean followup (SD) of 12 years (9). The prevalence of low ABI was 21%. CV risk factors were frequent: smoking, 30% of patients; high blood pressure, 32.7%; diabetes mellitus, 3.2%; hypercholesterolemia, 34.1%; and metabolic syndrome, 9.7%. The following variables were associated with low ABI in the univariate analysis: age (p < 0.001), hypertension (p = 0.002), diabetes (p = 0.018), hypercholesterolemia (p = 0.018), CV events (p < 0.001), SCORE (p = 0.004), cumulative dose of cyclophosphamide (p = 0.03), and fibrinogen levels (p = 0.002). In the multivariate analysis, the only independent variable in the final model was age (OR 1.04, 95% CI 1.02–1.07, p < 0.001), with a tendency for the presence of any vascular risk factor (diabetes, hypertension, hypercholesterolemia, or current smoking; OR 2.3, 95% CI 0.99–5.1, p = 0.053). Conclusion. The prevalence of low ABI in patients with SLE is higher than expected. While the association with CV risk factors and vascular disease in other territories was strong, we could not identify SLE-specific variables independently associated with PAD.

Cardiac valve replacement in patients with antiphospholipid syndrome

To analyze the results of cardiac valve replacement in a multicenter cohort of patients with antiphospholipid syndrome (APS) and to identify prognostic factors of poor outcome.

Systemic lupus erythematosus presenting as acute symptomatic hypercalcemia

Hypercalcemia is a common electrolyte abnormality with a wide differential diagnosis. Primary hyperparathyroidismand 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.

Enfermedad de Kikuchi-Fujimoto: estudio de cuatro casos

Kikuchi Fujimoto disease is an uncommon form of lymphadenitis, firstly described in Japan. Etiology is unknown. It affects mainly young women. It commonly manifests as a painful cervical lymphadenitis usually associated with fever and leukopenia. Clinical course users to be benign, leading spontaneously to a complet recovery. Histological findings include necrotizing changes with cariorrhesis, partial loss of ganglionar architecture and foci of histiocytic infiltrates in the cortical and/or paracortical zones of the lymph nodes. A common findings is the absence of neutrophil granulocytes in the inflammatory infiltrates, in contrast to other necrotizing lymphadenitis. We report four cases of Kikuchi Fujimoto disease, recently identified in our hospital.

A restrictive use of oral glucocorticoids in systemic lupus erythematosus prevents damage without worsening long-term disease control: An observational study

To analyze the influence of 2 different treatment strategies on general and specific damage accrual in patients with systemic lupus erythematosus (SLE).

Predictors of peripheral arterial disease in SLE change with patient’s age

Objective To analyse the differential influence of risk factors of peripheral artery disease (PAD) according to age in patients with SLE. Methods 216 patients from the Lupus-Cruces cohort were divided in three age groups: ≤34 years, 35–49 years and ≥50 years. A low ankle–brachial index defined PAD. Significant variables were identified by univariant and multivariant analysis in each age group. Results Different factors were identified in different age groups: antiphospholipid antibodies/antiphospholipid syndrome and glucocorticoids in patients ≤34 years; in patients 35–49 years old, hypertension was the only statistically significant predictor, although a trend was observed for fibrinogen levels; a trend was observed for hypercholesterolaemia in those ≥50 years. Conclusions Age may modulate the influence of risk factors for PAD in patients with SLE.

Síndrome metabólico en pacientes con lupus eritematoso sistémico: causas y consecuencias

Está bien establecido que los pacientes con lupus eritematoso sistémico (LES) presentan un mayor riesgo de sufrir episodios vasculares tales como enfermedad coronaria, ictus y enfermedad arterial periférica, con su consiguiente significado pronóstico. El desarrollo de aterosclerosis subclı́nica es mayor y más precoz en pacientes con LES en comparación con la población general. Si bien los factores de riesgo tradicionales, como la hipertensión arterial (HTA), la diabetes mellitus (DM), la dislipidemia y el tabaquismo, son más prevalentes en estos pacientes, ello no explica completamente esta mayor prevalencia de vasculopatı́a aterosclerótica. El sı́ndrome metabólico (SM) agrupa varios factores de riesgo vascular que se traducen en obesidad central y resistencia a la insulina, lo que condiciona un mayor riesgo de desarrollo de DM tipo 2 y enfermedad cardiovascular. No obstante, existen diferentes definiciones de SM, cada una con distintos criterios: la de la Organización Mundial de la Salud, la de la Federación Internacional de Diabetes o la del Panel de Expertos en Detección, Evaluación y Tratamiento de niveles elevados de colesterol en sangre en adultos, del Adult Treatment Panel III (ATP III). Dentro de los criterios incluidos, algunos son factores muy extendidos en la práctica clı́nica habitual y, por lo tanto, fáciles de evaluar. En cambio, en alguna de las definiciones se incluye la medición de la resistencia a la insulina (HOMA), lo que dificulta su aplicabilidad. La presencia de obesidad abdominal es obligatoria en algunas definiciones de SM, mientras que en otras es solo un criterio de igual peso que otros factores de riesgo vascular, lo que añade dificultades a la hora de identificar a estos pacientes. A pesar de todo ello, la existencia de SM (independientemente de la definición que se elija) se ha asociado con un mayor riesgo de enfermedad cardiovascular, aunque esta asociación no es tan clara como con los factores de riesgo clásicos. Se sabe que el SM es una herramienta clı́nica útil en la población para identificar a los pacientes que precisan una mayor intervención cara a prevenir la aparición de episodios vasculares. Parece claro que es un predictor