[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.

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

Introducción El objetivo de este estudio es conocer las características de la COVID-19 en pacientes con uveítis asociada a enfermedades autoinmunes sistémicas (EAS) mediante una encuesta telemática. Material y métodos La Sociedad Española de Medicina Interna por medio del Grupo de Trabajo de Enfermedades Autoinmunes realizó una encuesta telemática a pacientes con EAS para conocer las características de la COVID-19 en esta población. Resultados Un total de 2.789 pacientes contestaron la encuesta, de los que 28 tenían un diagnóstico de uveítis asociada a una EAS. La mayoría (82%) eran mujeres y caucásicas (82%), con una media de 48 años. Las EAS más frecuentes fueron la enfermedad de Behçet seguida de la sarcoidosis y del lupus eritematoso sistémico. El 46% de los pacientes estaban recibiendo tratamiento con corticoides a una dosis media de prednisona de 11mg/día. Respecto a la infección, 14 (50%) pacientes referían síntomas compatibles con infección por SARS-CoV-2. Se realizó RT-PCR en el frotis nasofaríngeo en dos pacientes y en uno de ellos (4%) fue positivo. Conclusiones Los pacientes con UNI asociada a EAS tanto los asintomáticos como los sintomáticos de COVID-19 habían recibido de forma similar tratamiento inmunosupresor (AU)

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. Result 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 11mg/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 (AU)

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.

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.

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.

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.

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.

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.

Infections in systemic lupus erythematosus: a prospective and controlled study of 110 patients.

We decided to analyse the incidence and characteristics of infection in systemic lupus erythematosus (SLE) and determine the related risks factors. One-hundred and ten SLE patients and 220 controls were prospectively followed up over three years and all the infectious episodes were recorded. A case-control design was established to identify risk factors of infection. Thirty-nine SLE patients suffered at least one infection (36%) versus 53 controls (22%), RR = 1.63 (P < 0.05). The incidence of urinary infections, pneumonia and bacteraemia without known focus was significantly greater in SLE. E. coli was the chief isolated microorganism (21.3%). In the univariate analysis, nephritis, SLE activity, leucopenia, anti-dsDNA levels above 20 IU/mL, CH50 levels under 300 IU/mL, ever use of steroids, daily dose of prednisone higher than 10 mg and ever use of cyclophosphamide were significantly associated with infection. In the multivariate analysis, total serum complement levels below 300 UU/mL and a daily dose of prednisone above 20 mg during at least one month plus ever use of cyclophosphamide were found to be significant (P < 0.0001). We conclude that patients with SLE have an increased overall risk for infection and they are especially prone to develop urinary infection, pneumonia and bacteraemia without focus. Hypocomplementaemia represents an independent predictive factor for infection. It seems mandatory to closely follow up SLE patients with low complement levels and instruct them to report any suspicious sign of infection, especially in those receiving more than 20 mg/day of prednisone who have also been administered cyclophosphamide.

Allelic diversity and affinity variants of MICA are imbalanced in Spanish patients with Behçet's disease.

The aetiology of Behçet's disease (BD) is still unknown, but genetic and environmental factors are involved. HLA-B*51 is considered a susceptibility marker and some MICA alleles have also been associated. Cytotoxic T lymphocytes have been suggested as responsible for BD lesions by engaging MICA through NKG2D surface molecules. In the present study, HLA-B and MICA alleles were typed by polymerase chain reaction using sequence-specific primers, in 165 healthy Spanish controls and 42 BD patients. In the healthy group, MICA*008 (28.48%), MICA*004 (17.58%), MICA*002 (14.24%) and MICA*009 (9.39%) were the predominant alleles and the most common haplotype was MICA*004-B*44 (12.12%). MICA*001 (5.15%), MICA*004, MICA*011 (4.54%) and MICA*018 (5.15%) were more frequent, and MICA*010 (1.81%) and MICA*008 were less prevalent than in other Caucasoid populations. Similar results have been reported in North African individuals and this could support the hypothesis of a common ancestral origin of both populations. The frequencies of MICA*009 and MICA*019 were significantly increased in our BD patients in comparison with controls: 22.62% versus 9.39% and 10.71% versus 1.81% respectively. The increase of MICA*019 had not been described in other BD cohorts, and it corroborates the genetic heterogeneity at MICA locus in BD patients. High-affinity MICA alleles for NKG2D were more frequent in controls than in patients. Moreover, high-affinity alleles were not found in homozygous BD patients. These results argue against the hypothesis of an autoaggressive response in BD patients through MICA-NKG2D interactions.

Primary Sjögren's syndrome in men: clinical and immunological characteristics.

OBJECTIVE: To determine the clinical and immunological characteristics of primary Sjögren's syndrome (SS) in men from a large series of unselected patients with this condition. METHODS: We studied 223 consecutive patients (204 women and 19 men; mean age at onset 53 y, range 15-87 y, mean disease duration 77 months) with primary SS visited in our units. All these patients fulfilled 4 or more of the diagnostic criteria for SS proposed by the European Community Study Group in 1993. RESULTS: Nineteen (9%) patients were men and they represent the male group described in this paper. Extraglandular manifestations during the course of their disease were present in 10 (53%) of our male patients with primary SS: articular involvement in 4 (21%) patients, interstitial pneumopathy in 3 (16%) and peripheral neuropathy in 2 (11%). ANA were positive in 13 (68%) patients, RF in 5 (31%), anti-Ro/SS-A in 3 (16%) and cryoglobulins in 1/14 (7%). When compared with women, men with primary SS presented a lower prevalence of articular involvement (21 percent; vs 46%, P=0.03, OR 0.32, CI 0.07-0.97). CONCLUSION: Although primary SS is typically a disease of middle-aged women, clinicians should note that it may be diagnosed in male patients. Except for a lower prevalence of articular involvement, we could no find any notable differences in clinical and immunological characteristics between male and female patients with primary SS.

[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.

Primary Sjögren's syndrome in the elderly: clinical and immunological characteristics.

The objective of the study was to determine the clinical and immunological characteristics of primary Sjogren's syndrome (SS) in patients with an older onset of the disease. We included 223 consecutive patients (204 female and 19 male; mean age at onset 53 years; range 15-87 years) visited in our Units. All patients were white and fulfilled four or more of the diagnostic criteria for SS proposed by the European Community Study Group in 1993. Disease onset was determined on the basis of the appearance of symptoms strongly suggestive of SS. In 31 patients the onset of disease occurred after the age of 70 years, and they represent the elderly-onset group described in this report. The remaining 192 patients presented disease onset before the age of 70 years, and they represent the younger-onset group. Of the 31 (14%) patients with elderly onset of primary SS, 26 were female and 5 male, and the disease onset occurred between 70 and 87 years (mean 74 years). The most common extraglandular manifestations were articular involvement (29%), hepatic involvement (20%), peripheral neuropathy (16%) and interstitial pneumopathy (13%). When compared with patients with a younger onset, the prevalences of glandular and extraglandular manifestations and immunological features (cryoglobulinemia, hypocomplementemia and positivity for RF, anti-Ro/SS-A or anti-La/SS-B) were similar in both groups. In conclusion, although primary SS is typically a disease of middle-aged adults, clinicians should note that it may be diagnosed frequently among elderly patients. However, we could not find any notable differences in clinical and immunological characteristics of patients with elderly onset of primary SS.