Infections in newly diagnosed Spanish patients with systemic lupus erythematosus: data from the RELES cohort.

OBJECTIVES: Using data of patients from the inception cohort Registro Español de Lupus Eritematoso Sistémico (RELES), we aimed to analyse the incidence of severe infection in the first two years of follow-up and how predictors of infection change during the course of systemic lupus erythematosus (SLE). MATERIAL AND METHODS: The study included 282 patients. Markers of lupus activity, prednisone doses and immunosuppressive therapy were compared between patients with and without infections in the first and second year of the disease. Drug therapy administered during the first month of follow-up has been considered as a potential predictor of infections during the first year and medications administered during the first year have been considered potential predictors of infections during the second. RESULTS: Nineteen patients (6.4%) had a documented episode of major infection during the first year of follow-up and 16 patients (5.67%) during the second. The following variables were associated with infections during the first year: hypocomplementaemia at diagnosis ( p < 0.01), nephritis at diagnosis ( p = 0.03), SLEDAI score ( p < 0.01), prednisone >30 mg/day ( p = 0.01), methylprednisolone pulses ( p = 0.05) and mycophenolate use ( p = 0.02). The independent variables in the final model were hypocomplementaemia (odds ratio (OR) 4.41, 95% confidence interval (CI) 0.96-20.20, p = 0.05) and a dose of prednisone >30 mg/day (OR 6.60, 95% CI 1.34-32.42, p = 0.02). The following variables were associated with infections during the second year: dose of prednisone > 7.5 mg/day ( p = 0.05), methylprednisolone pulses ( p = 0.07), duration of therapy with antimalarials ( p = 0.09), therapy with mycophenolate ( p = 0.01), therapy with cyclophosphamide ( p = 0.05). The independent variables in the final model were a dose of prednisone >7.5 mg/day (OR 4.52, 95% CI 0.99-21, p = 0.054) and duration of therapy with antimalarials as a protective factor (OR 0.99, 95% CI 0.99-1.00, p = 0.053). CONCLUSIONS: The low incidence of early infections in the RELES cohort is partially explained by the extended use of antimalarials and by the general avoidance of prolonged high doses of prednisone. Patients with high baseline activity are at a higher risk of infection during the first months but therapy with medium-high doses of prednisone is the main predictor of infectious events. Thus, every effort should be made to limit oral glucocorticoid use from the very beginning of the SLE course.

[Impact of novel coronavirus infection in patients with uveitis associated with an autoimmune disease: result of the COVID-19-GEAS patient survey]. / Impacto de la infección por el nuevo coronavirus en los pacientes con uveítis asociada a una enfermedad autoinmune: resultado de la encuesta COVID-19-GEAS pacientes.

INTRODUCTION: The objetive of these study is to know the characteristics of COVID-19 in patients with uveitis associated with Systemic Autoimmune Disease (SAD) through telematic survey. MATERIAL AND METHODS: Internal Medicine Society and Group of Systemic Autoimmune disease conducted a telematic survey of patients with SAD to learn about the characteristics of COVID-19 in this population. RESULTS: A total of 2,789 patients answered the survey, of which 28 had a diagnosis of uveitis associated with SAE. The majority (82%) were female and caucasian (82%), with a mean age of 48 years. The most frequent SAEs were Behçet's disease followed by sarcoidosis and systemic lupus erythematosus. 46% of the patients were receiving corticosteroid treatment at a mean prednisone dose of 11 mg/day. Regarding infection, 14 (50%) patients reported symptoms compatible with SARS-CoV-2 infection. RT-PCR was performed on the nasopharyngeal smear in two patients and in one of them (4%) it was positive. CONCLUSIONS: Both asymptomatic and symptomatic COVID-19 patients with ASD-associated UNI had received similar immunosuppressive treatment.

Impact of novel coronavirus infection in patients with uveitis associated with an autoimmune disease: Result of the COVID-19-GEAS patient survey.

INTRODUCTION: The objective of these study is to know the characteristics of COVID-19 in patients with uveitis associated with Systemic Autoimmune Disease (SAD) through telematic survey. MATERIAL AND METHODS: Internal Medicine Society and Group of Systemic Autoimmune disease conducted a telematic survey of patients with SAD to learn about the characteristics of COVID-19 in this population. RESULTS: A total of 2,789 patients answered the survey, of which 28 had a diagnosis of uveitis associated with SAE. The majority (82%) were female and caucasian (82%), with a mean age of 48 years. The most frequent SAEs were Behçet's disease followed by sarcoidosis and systemic lupus erythematosus. 46% of the patients were receiving corticosteroid treatment at a mean prednisone dose of 11 mg/day. Regarding infection, 14 (50%) patients reported symptoms compatible with SARS-CoV-2 infection. RT-PCR was performed on the nasopharyngeal smear in two patients and in one of them (4%) it was positive. CONCLUSIONS: Both asymptomatic and symptomatic COVID-19 patients with ASD-associated UNI had received similar immunosuppressive treatment.

Off-label use of rituximab in 196 patients with severe, refractory systemic autoimmune diseases.

OBJECTIVES: To analyse the safety and efficacy of the off-label use of rituximab in patients with severe, refractory systemic autoimmune diseases. METHODS: In 2006, the Study Group on Autoimmune Diseases of the Spanish Society of Internal Medicine created the BIOGEAS project, a multicenter study devoted to collecting data on the use of biological agents in adult patients with systemic autoimmune diseases refractory to standard therapies (failure of at least two immunosuppressive agents). RESULTS: One hundred and ninety-six patients with systemic autoimmune diseases treated with rituximab have been included in the Registry (158 women and 38 men, mean age 43 years). Systemic autoimmune diseases included systemic lupus erythematosus (107 cases), inflammatory myopathies (20 cases), ANCA-related vasculitides (19 cases), Sjögren's syndrome (15 cases) and other diseases (35 cases). A therapeutic response was evaluable in 194 cases: 99 (51%) achieved a complete response, 51 (26%) a partial response and 44 (23%) were classified as non-responders. After a mean follow-up of 27.56+/-1.32 months, 44 (29%) out of the 150 responders patients relapsed. There were 40 adverse events reported in 33 (16%) of the 196 patients. The most frequent adverse events were infections, with 24 episodes being described in 19 patients. Thirteen (7%) patients died, mainly due to disease progression (7 cases) and infection (3 cases). CONCLUSIONS: Although not yet licensed for this use, rituximab is currently used to treat severe, refractory systemic autoimmune diseases, with the most favourable results being observed in Sjögren's syndrome, inflammatory myopathies, systemic lupus erythematosus and cryoglobulinemia.

Predictive factors for the detection of CIN II-III in the follow-up of women with CIN I.

PURPOSE OF INVESTIGATION: To determine which factors may increase the risk that women diagnosed with CIN I may later develop CIN II-III. METHODS: A prospective study of 174 women with a grade 1 intraepithelial lesion (CIN I) confirmed by biopsy, with a follow-up time of at least one year. The following factors were studied: age, HPV infection, HPV infection by a high-risk genotype, the HPV genotypes involved, coinfection by several HPV genotypes and duration of follow-up. These factors were correlated with later detection of CIN II-III by biopsy during follow-up. Statistical analysis was performed using SPSS. RESULTS: CIN II-III was detected at the follow-up in 24 of 174 women included in the study (13.7%), in four cases by colposcopically directed biopsy and in 20 by LLETZ. Correlation of the factors studied with the incidence of CIN II-III in this group showed that the only statistically significant factors were overall HPV infection and HPV infection by genotypes 31 and 70 (Chi-square and Fisher's test, p < 0.05, respectively), while the duration of follow-up came close to statistical significance (Student's test, p = 0.052). CONCLUSION: HPV infection and duration of follow-up are predictive factors for the detection of CIN II-III in follow-up care for women with CIN I.

Hepatic angiomyolipoma resected by eft hepatectomy: Case report.

El angiomiolipoma hepático es un tumor mesenquimatoso infrecuente perteneciente al grupo de los PEComas (Perivascular Epithelioid Cells), que cuenta con un potencial maligno indeterminado. Los síntomas clínicos son inespecíficos, siendo las características radiológicas principales la alta vascularización de la lesión y la presencia de tejido adiposo macroscópico. Presentamos un caso clínico de un angiomiolipoma hepático izquierdo diagnosticado por tomografía computada de manera incidental y asintomático en una paciente sin antecedentes de importancia que se sometió a hepatectomía lateral izquierda con resección completa del tumor, el cual fue negativo para malignidad y sin complicaciones.Hepatic angiomyolipoma is a mesenchymal tumor known as PEComas (Perivascular Epithelioid Cells) with unknown malignancy pattern. We present a case report of left hepatic angiomyolipoma diagnoses by computed tomography in an asymptomatic patient with no previous medical diseases. The tumor was complete resected during a left lateral hepatectomy with no complications and final histologic report was negative to cancer.

Systemic phenotype of sarcoidosis associated with radiological stages. Analysis of 1230 patients.

BACKGROUND: To analyze the association between Scadding radiological stages of sarcoidosis at diagnosis and the disease phenotype (epidemiology, clinical presentation and extrathoracic involvement) in one of the largest cohorts of patients with sarcoidosis reported from southern Europe. METHODS: The SARCOGEAS-Study Group includes a multicenter database of consecutive patients diagnosed with sarcoidosis according to the WASOG 1999 criteria. Extrathoracic disease at diagnosis was defined according to the 2014 instrument and the clusters proposed by Schupp et al. RESULTS: We analyzed 1230 patients (712 female, mean age 47 yrs.) who showed the following Scadding radiologic stages at diagnosis: stage 0 (n = 98), stage I (n = 395), stage II (n = 500), stage III (n = 195) and stage IV (n = 42). Women were overrepresented in patients presenting with extrathoracic/extrapulmonary disease, while the diagnosis was made at younger ages in patients presenting with BHL, and at older ages in those presenting with pulmonary fibrosis (q values <0.05). Multivariable adjusted analysis showed that patients presenting with pulmonary involvement (especially those with stages II and III) had a lower frequency of concomitant systemic involvement in some specific extrathoracic clusters (cutaneous-adenopathic/musculoskeletal, ENT and neuro-ocular/OCCC) but a higher frequency for others (hepatosplenic), in comparison with patients with extrapulmonary involvement (stages 0 and I). The presence of either BHL or fibrotic lesions did not influence the systemic phenotype of patients with pulmonary involvement. CONCLUSIONS: The key determinant associated with a differentiated systemic phenotype of sarcoidosis at diagnosis was interstitial pulmonary involvement rather than the individual Scadding radiological stage.

First month prednisone dose predicts prednisone burden during the following 11†months: an observational study from the RELES cohort.

AIM: To study the influence of prednisone dose during the first month after systemic lupus erythematosus (SLE) diagnosis (prednisone-1) on glucocorticoid burden during the subsequent 11 months (prednisone-2-12). METHODS: 223 patients from the Registro Español de Lupus Eritematoso Sistémico inception cohort were studied. The cumulative dose of prednisone-1 and prednisone-2-12 were calculated and recoded into a four-level categorical variable: no prednisone, low dose (up to 7.5 mg/day), medium dose (up to 30 mg/day) and high dose (over 30 mg/day). The association between the cumulative prednisone-1 and prednisone-2-12 doses was tested. We analysed whether the four-level prednisone-1 categorical variable was an independent predictor of an average dose >7.5 mg/day of prednisone-2-12. Adjusting variables included age, immunosuppressives, antimalarials, methyl-prednisolone pulses, lupus nephritis and baseline SLE Disease Activity Index (SLEDAI). RESULTS: Within the first month, 113 patients (51%) did not receive any prednisone, 24 patients (11%) received average low doses, 46 patients (21%) received medium doses and 40 patients (18%) received high doses. There was a strong association between prednisone-1 and prednisone-2-12 dose categories (p<0.001). The cumulative prednisone-1 dose was directly associated with the cumulative prednisone-2-12 dose (p<0.001). Compared with patients on no prednisone, patients taking medium (adjusted OR 5.27, 95% CI 2.18 to 12.73) or high-dose prednisone-1 (adjusted OR 10.5, 95% CI 3.8 to 29.17) were more likely to receive prednisone-2-12 doses of >7.5 mg/day, while patients receiving low-dose prednisone-1 were not (adjusted OR 1.4, 95% CI 0. 0.38 to 5.2). If the analysis was restricted to the 158 patients with a baseline SLEDAI of ≥6, the model did not change. CONCLUSION: The dose of prednisone during the first month after the diagnosis of SLE is an independent predictor of prednisone burden during the following 11 months.

Chorea in the antiphospholipid syndrome. Clinical, radiologic, and immunologic characteristics of 50 patients from our clinics and the recent literature.

We analyzed the clinical, radiologic, and immunologic characteristics of 50 patients with chorea and the antiphospholipid syndrome (APS) (6 from our clinics and 44 from a MEDLINE computer-assisted review of the literature from 1985 through 1995). Forty-eight (96%) patients were female and 2 (4%) were male. Twenty-nine (58%) patients had defined systemic lupus erythematosus (SLE), 6 (12%) had "lupus-like" syndrome, and 15 (30%) patients had "primary" APS. Mean age of patients in this series was 23 +/- 12 years (range, 6-77 yr); mean age at presentation of chorea was 21 +/- 12 years (range, 6-77 yr). In 11 (22%) patients, the onset of chorea was in childhood (6-14 yr), and in 2 (4%) patients it presented at 60 years or more. Six (12%) patients developed chorea soon after they started taking estrogen-containing oral contraceptives, 3 (6%) developed chorea gravidarum, and 1 (2%) patient developed chorea shortly after delivery. Most patients (66%) presented only 1 episode of chorea. Chorea was bilateral in 55% of patients. Computed tomography and magnetic resonance imaging scans reported cerebral infarcts in 35% of patients. The following antibodies were detected: lupus anticoagulant (92%), anticardiolipin antibodies (91%), antinuclear antibodies (82%), anti-DNA (59%), anti-Ro (10%), anti-RNP (8%), anti-La (2%), and anti-Sm (2%). The chorea in these patients responded to a variety of medications, for example, steroids, haloperidol, antiaggregants, anticoagulants, or a combination of therapy, usually prescribed in the presence of other manifestations of APS or SLE. However, many patients responded well to haloperidol and to the discontinuation of oral contraceptives if this was the precipitating factor.

The 'primary' antiphospholipid syndrome: antiphospholipid antibody pattern and clinical features of a series of 23 patients.

Twenty-three patients with the 'primary' antiphospholipid syndrome were studied over 2-6 years. Twenty-two (96%) had antiphospholipid antibodies detected by ELISA (87% had antibodies to thromboplastin and 70% to cardiolipin), and 18 out of the 21 tested patients (86%) had lupus anticoagulant activity by coagulative assays. Mean age of the cohort was 29.9 years and the sex ratio (female:male) 4.75:1. Eleven patients presented 18 venous and/or arterial thrombosis and 13 had 25 foetal losses (84% occurred during the second and third trimester). Other clinical features were migraine, livedo reticularis, and epilepsy. Three patients had relatives with systemic lupus erythematosus. Thrombocytopaenia was seen in 33%, antinuclear antibodies in low or moderate titre in 30%, and haemolytic anaemia in 13%. During the follow-up, two patients presented recurrent thrombosis despite anticoagulant therapy, one of them dying because of recurrent pulmonary thromboembolism. Four patients achieved successful term pregnancies after treatment with aspirin and a further patient after treatment with aspirin and low dose prednisolone. No patient developed systemic lupus erythematosus or any other definable connective tissue disease. The 'primary' antiphospholipid syndrome may exist as a distinct clinical entity and all younger patients presenting with thrombotic events, foetal losses and/or thrombocytopaenia, without any evidence of a well defined disease, should be tested for antiphospholipid antibodies in order to rule out this syndrome.

Late thrombotic events in patients with temporal arteritis and anticardiolipin antibodies.

IgG and IgM isotypes of anticardiolipin (aCL) antibodies were measured in a group of 40 patients with biopsy-proven temporal arteritis (TA), 13 of them with ischemic complications related to the disease. High levels of aCL antibodies were found in only 3 (7.5%) patients. Two had high titres of both IgG and IgM isotypes and the third had high titres of the IgM isotype. No relationship between aCL antibody positivity and the development of any of the classical early occlusive complications of TA was found. However, 2 out of the 3 patients with positive aCL antibody titres later developed ischemic phenomena on conventional corticosteroid treatment. This finding suggests that aCL antibodies could perhaps have a role in the development of the late ischemic complications that occasionally occur in adequately treated TA patients.

Anticardiolipin antibodies in patients with autoimmune diseases: isotype distribution and clinical associations.

A prospective study of IgG and IgM isotypes of anticardiolipin antibodies (aCL) was performed in a series of 167 patients with various autoimmune diseases, including rheumatic and nonrheumatic disorders, and in a group of 100 healthy blood donors. The IgG aCL serum was regarded as positive if a binding index (BI) greater than 2.85 (3.77 SD) was detected and a BI greater than 4.07 (3.90 SD) was defined as positive for IgM aCL. Forty patients (24%) were found to be positive for IgG and/or IgM aCL. IgG aCL were detected in 23% of patients with systemic lupus erythematosus (SLE), in 9% with idiopathic thrombocytopenic purpura, in 7% with progressive systemic sclerosis, and in 6% with dermatomyositis-polymyositis. IgM aCL were present in 43% patients with primary biliary cirrhosis, in 33% with rheumatoid arthritis, in 22% with SLE, and in 8% with giant-cell arteritis. IgG aCL were found to have a significant association with thrombosis and thrombocytopenia, and IgM and aCL with haemolytic anaemia and neutropenia, in SLE but not in the other autoimmune diseases. The identification of these differences in the aCL isotype associations, depending on the autoimmune disorder, may improve the clinical usefulness of these tests.

[Systemic lupus erythematosus: a clinical and immunological study of 300 patients]. / Lupus eritematoso sistémico: estudio clínico e inmunológico de 300 pacientes.

BACKGROUND: The aims of the present study were to analyze the clinical and immunologic characteristics of a wide group of patients with systemic lupus erythematosus (SLE) and define homogeneous subgroups with their own characteristics. METHODS: A prospective study of 300 patients diagnosed of SLE were studied. These patients were subdivided according to sex, age at the onset of the disease and immunologic profile. The statistical study was carried out by the chi (2), Fisher, Student's t and Mann-Whitney U tests. RESULTS: The series was made up of 266 (89%) females and 34 (11%) males. The mean age at onset of the disease was 31.8 +/- 14.6 years. In 48 (16%) patients the first manifestations appeared after the age of 50. Males were shown to present a lower prevalence of arthritis (59% vs 82% in woman, p < 0.005) and malar rash (29% vs 50%, p < 0.05), but had more cutaneous discoid lesions (18% vs 3% p < 0.001). In patients in whom the disease appeared after the age of 50 a lower prevalence of arthritis was presented (67% vs 82% in patients of less than 50 years of age, p < 0.005), malar rash (23% vs 53%, p < 0.001) and nephropathy (21% vs 41%, p < 0.05), but had greater myositis (17% vs 6%, p < 0.01). The absence of antinuclear antibodies (ANA) and the presence of anti-ds DNA and anti-ENA antibodies were associated with differences in the prevalence of different clinical manifestations. CONCLUSIONS: Sex, age and immunologic pattern in systemic lupus erythematosus permit the definition of homogeneous subgroups with their own characteristics: a) males present a lower prevalence of arthritis and malar rash, but a greater prevalence of cutaneous discoid lesions; b) patients over the age of 50 develop arthritis, malar rash and nephropathy with a lower prevalence but have a greater prevalence of myositis; c) patients without antinuclear antibodies and those with anti-ds DNA and anti-ENA antibodies present differences in the prevalences of different clinical manifestations.

[Usefulness of photoplethysmography and indexes of digital pressure in Raynaud phenomenon]. / Utilidad de la fotopletismografía y de los índices de presión digital en el fenómeno de Raynaud.

BACKGROUND: To know the usefulness of plethysmography and digital pressure indexes (DPI) to assess the vasospasm and the response to medical treatment in patients with Raynaud's phenomenon. PATIENTS AND METHODS: During a four-month period, we carried out a prospective clinical trial, with a control group (15 subjects) and other of patients with Raynaud's phenomenon (40 patients). We calculated the digital pressures, plethysmography and the DPI, in basal status and after provocation with cold water. The Raynaud's group was divided randomly in two homogeneous subgroups of 20 subjects. One of the groups underwent treatment with calcium antagonists and the other group with placebo. These determinations were repeated at the middle and at the end of the treatment. RESULTS: The basal DPI and after provocation test were lower in the Raynaud's group (0.61 [SD 0.26] and 0.25 [SD 0.26]), than in the control group (0.93 [SD 0.06] and 0.88 [SD 0.07]), with a statistical significance (p < 0.001 and p < 0.0001). After the treatment, in the subgroup treated with calcium antagonists, the DPI were increased in a statistically significative way respect to those in the placebo subgroup (p < 0.0001). Sensitivity and specificity of the DPI associated to the provocation test were of 97 and 93%, respectively. The plethysmographic wave did not suffer significant variations; sensibility and specificity were 48 and 100%. CONCLUSIONS: In the Raynaud's phenomenon the DPI associated to the provocation test have a high sensitivity and specificity, and allows determination of the degree of vasospasm and the response to treatment.

Direct cost of management and treatment of active systemic lupus erythematosus and its flares in Spain: the LUCIE Study.

BACKGROUND AND OBJECTIVE: The cost of control and management of Systemic Lupus Erythematosus (SLE) in Spain is unknown. This study has aimed to describe the healthcare resources associated to control and treatment of LES and its flares and to estimate the associated direct costs. PATIENTS AND METHODS: This was a European, multicentric, retrospective study (2008-2010) carried out with the participation of 5 hospitals in Spain with experience in SLE. Adult SLE patients (ACR criteria), with positive auto-antibodies (ANA and/or anti-ds-DNA) and active disease were included. Patients were stratified into severe and non-severe SLE. Direct healthcare costs were estimated with resources used and their unit costs. RESULTS: Seventy-five out of 79 SLE patients were analyzed. Of these, 52% had severe disease, 91.9% were females and 90.7% were Caucasian. Mean (SD) age was 41.0 (14.5) years. Annual direct cost per patient related to SLE management was €5,968 (7,038) and €3,604 (5,159) for severe and non-severe patients, respectively (P=.002). Costs related to hospitalizations, pharmacological treatment, visits to specialists, and laboratory tests were higher for patients with severe disease. At least one flare during the observation period was present in 90.7% of patients. Severe flares were a significant predictor of increase in cost. CONCLUSIONS: The cost associated with SLE control and treatment is higher for severe SLE patients. Insufficient control of the disease activity results in an increase in flares. Its presence is related to an increase in costs, hospitalization being the major component.