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.

Estudio CRONO: prevalencia del dolor irruptivo en pacientes con dolor crónico no oncológico en Andalucía, España / CRONO study: prevalence of breakthrough pain in patients with non-cancer chronic pain in Andalusia, Spain

Objetivo: El objetivo de este estudio es evaluar la prevalencia de dolor irruptivo (DI) en pacientes ambulatorios con dolor crónico de origen no oncológico y caracterizar la fisiopatología, localización, intensidad y frecuencia de los episodios de DI. Material y métodos: Estudio observacional, prospectivo y no intervencionista realizado en 16 unidades de dolor ambulatorias de hospitales de Andalucía y Ceuta. Se preguntó a los pacientes consecutivos elegibles si experimentan DI definido como "una exacerbación transitoria del dolor que ocurre espontáneamente, o en relación con un desencadenante predecible o impredecible específico, a pesar del dolor de base estable y controlado". En cada día de la encuesta, los dos primeros pacientes que confirmaron DI fueron preguntados sobre las características clínicas de su PTP (etiología, inicio, intensidad, frecuencia y tratamiento). Resultados: Se realizó un cribaje a un total de 3209 pacientes con dolor crónico no oncológico para identificar a 1118 pacientes con DI, lo que representó una prevalencia del 36 %. Se obtuvieron las características del DI de 350 pacientes: la intensidad media fue de 8,3 (± 1,4) en una Escala Analógica Visual (EVA), con una media de 2 episodios/24 horas (rango 1-5/24 h). El mecanismo del dolor fue mixto en 149 (42,6 %), neuropático en 91 (26 %) y nociceptivo en 72 (20,6 %) de los pacientes. Se encontró correlación positiva entre una mayor intensidad de DI con el nivel de dolor basal (r = 0,243, p < 0,001), y el número de crisis diarias de DI (r = 0,123, p = 0,003), ambas estadísticamente significativas. El 78 % de los pacientes estaba en tratamiento con opioides. Los más frecuentes fueron el citrato de fentanilo (52,6 %) y el tramadol (17,4 %). Conclusiones: La tasa de prevalencia del DI en pacientes con dolor crónico no oncológico es superior a un tercio de los pacientes atendidos en las unidades ambulatorias de dolor hospitalario en España. El DI provoca niveles reducidos de funcionalidad, trastornos psicológicos y un aumento del gasto asistencial. La clave del tratamiento es la individualización

Objective: The aim of this study was to evaluate the prevalence of breakthrough pain (BTP) in ambulatory patients with non-cancer chronic pain in Spain and to characterize physiopathology, location, intensity and frequency of BTP episodes. Methods: Prospective, non-interventional, observational study conducted in 16 pain units of hospitals of Andalusia and Ceuta. Eligible consecutive patients were are asked if they experience BTP defined as "a transient exacerbation of pain that occurs either spontaneously, or in relation to a specific predictable or unpredictable trigger, despite stable and controlled background pain". At each survey day, the first two patients reporting BTP were further interrogated on the clinical characteristics of their BTP (etiology, onset, intensity, frequency and treatment). Results: A total of 3,209 patients with non-cancer chronic pain were screened to identify 1,118 patients with BTP, which represented a prevalence of 36 %. BTP characteristics were retrieved from 350 patients: mean BTP intensity was 8.3 (± 1.4) on a Visual Analogue Scale (VAS), with a mean of 2 episodes/24 hour (range 1-5/24 h). Pain mechanism was mixed in 149 (42.6 %), neuropathic in 91 (26 %) and nociceptive in 72 in (20.6 %) of patients. Significant correlation was found between BTP intensity and both higher background pain (r = 0.243, p < 0.001), and daily BTP episodes frequency (r = 0.123, p = 0.003). 78 % of the patients were on opioid treatment. The most frequent were fentanyl citrate (52.6 %) and tramadol (17.4 %). Conclusions: The prevalence rate of BTP in patients with chronic non-oncologic pain is higher than one-third of the patients seen in outpatient hospital pain units in Spain. BTP causes reduced levels of functionality, psychological disorders, and an increase in health care expenditure. Individualization is the key to treatment

Interstitial lung disease in systemic sclerosis: data from the spanish scleroderma study group.

OBJECTIVES: To evaluate the clinical characteristics of patients with interstitial lung disease (ILD) in the setting of a large cohort of systemic sclerosis (SSc) patients, and to analyse the differences according to the SSc subtype (following the modification of classification criteria of the American College of Rheumatology for SSc proposed by LeRoy and Medsger), factors are associated with moderate-to-severe impairment of lung function, as well as mortality and causes of death. METHODS: A descriptive study was performed, using the available data from the Spanish Scleroderma Study Group. RESULTS: Twenty-one referral centers participated in the registry. By April 2014, 1374 patients with SSc had been enrolled, and 595 of whom (43%) had ILD: 316 (53%) with limited cutaneous SSc (lcSSc), 240 (40%) with diffuse cutaneous SSc (dcSSc), and 39 (7%) with SSc sine scleroderma (ssSSc). ILD in the lcSSc and the ssSSc subsets tended to develop later, and showed a less impaired forced vital capacity (FVC) and a ground glass pattern on high-resolution computed tomography (HRCT) less frequently, compared with the dcSSc subset. Factors related to an FVC < 70% of predicted in the multivariate analysis were: dcSSc, positivity to anti-topoisomerase I antibodies, a ground glass pattern on HCRT, an active nailfold capillaroscopy pattern, lower DLco, older age at symptoms onset, and longer time between symptoms onset and ILD diagnosis. Finally, SSc-associated mortality and ILD-related mortality were highest in dcSSc patients, whereas that related to pulmonary arterial hypertension was highest in those with lcSSc-associated ILD. CONCLUSIONS: Our study indicates that ILD constitutes a remarkable complication of SSc with significant morbidity and mortality, which should be borne in mind in all three subgroups (lcSSc, dcSSc, and ssSSc).

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.

Study of association of CTLA4 gene variants to non-anterior uveitis.

This study was undertaken to investigate the possible genetic association of functional CTLA4 polymorphisms with susceptibility to non-anterior uveitis. Four hundred and seventeen patients with endogenous non-anterior uveitis and 1517 healthy controls of Spanish Caucasian origin were genotyped for the CTLA4 polymorphisms rs733618, rs5742909 and rs231775, using predesigned TaqMan(©) allele discrimination assays. PLINK software was used for the statistical analyses. No significant associations between the CTLA4 polymorphisms and susceptibility to global non-anterior uveitis were found. It was also the case when the potential association of these genetic variants with the anatomical localization of the disease, such as intermediate, posterior or panuveitis, was assessed. Our results do not support a relevant role of these CTLA4 polymorphisms in the non-anterior uveitis genetic predisposition.

Evaluation of the TREX1 gene in a large multi-ancestral lupus cohort.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disorder with a complex pathogenesis in which genetic, hormonal and environmental factors have a role. Rare mutations in the TREX1 gene, the major mammalian 3'-5' exonuclease, have been reported in sporadic SLE cases. Some of these mutations have also been identified in a rare pediatric neurological condition featuring an inflammatory encephalopathy known as Aicardi-Goutières syndrome (AGS). We sought to investigate the frequency of these mutations in a large multi-ancestral cohort of SLE cases and controls. A total of 40 single-nucleotide polymorphisms (SNPs), including both common and rare variants, across the TREX1 gene, were evaluated in ∼8370 patients with SLE and ∼7490 control subjects. Stringent quality control procedures were applied, and principal components and admixture proportions were calculated to identify outliers for removal from analysis. Population-based case-control association analyses were performed. P-values, false-discovery rate q values, and odds ratios (OR) with 95% confidence intervals (CI) were calculated. The estimated frequency of TREX1 mutations in our lupus cohort was 0.5%. Five heterozygous mutations were detected at the Y305C polymorphism in European lupus cases but none were observed in European controls. Five African cases incurred heterozygous mutations at the E266G polymorphism and, again, none were observed in the African controls. A rare homozygous R114H mutation was identified in one Asian SLE patient, whereas all genotypes at this mutation in previous reports for SLE were heterozygous. Analysis of common TREX1 SNPs (minor allele frequency (MAF)>10%) revealed a relatively common risk haplotype in European SLE patients with neurological manifestations, especially seizures, with a frequency of 58% in lupus cases compared with 45% in normal controls (P=0.0008, OR=1.73, 95% CI=1.25-2.39). Finally, the presence or absence of specific autoantibodies in certain populations produced significant genetic associations. For example, a strong association with anti-nRNP was observed in the European cohort at a coding synonymous variant rs56203834 (P=2.99E-13, OR=5.2, 95% CI=3.18-8.56). Our data confirm and expand previous reports and provide additional support for the involvement of TREX1 in lupus pathogenesis.

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.

Linfangioma mediastínico / Lymphangioma of the mediastinum

Resumen. Contamos el caso de un paciente con una imagen quística mediastínica y un nódulo pulmonar, que fue diagnosticado en primera instancia de quiste broncogénico y la intervención se aprovechó para realizar el diagnóstico histológico del nódulo, que descartó malignidad. El quiste resultó ser un linfangioma mediastínico. Hacemos un repaso a esta rara entidad (AU)

Abstract. We speak about the case of a patient with a cystic mediastinic imagen and a pulmonary nodule, which was diagnosed in the first instance of bronchogenic cyst and the surgical intervention took advantage to realize the histological diagnosis of the nodule, which rejected malignance. The cyst turned out to be a lymphangioma of the mediastinum. We do a revision to this rare entity (AU)

Hipernatremia grave por ingesta de cloruro sódico / No disponible

No disponible

Analysis of interleukin-23 receptor (IL23R) gene polymorphisms in systemic lupus erythematosus.

The aim of this study was to evaluate the association between systemic lupus erythematosus (SLE) and polymorphisms in the interleukin-23 receptor (IL23R) gene, which have been previously found to be associated with two autoimmune diseases: inflammatory bowel disease and psoriasis. Our study includes 224 SLE patients and 342 healthy controls. The genotyping of IL23R variants was carried out using a polymerase chain reaction system with predeveloped TaqMan allelic discrimination assays. No statistically significant differences were observed between SLE patients and healthy controls with any of the IL23R genetic variants. In addition, we did not find any significant differences when we stratified SLE patients according to their clinical and demographic features. These results suggest that IL23R polymorphisms do not appear to play an important role in the susceptibility or severity of SLE in the Spanish population.

Study of a functional polymorphism in the p53 gene in systemic lupus erythematosus: lack of replication in a Spanish population.

The aim of this study was to assess the possible association between the p53 suppressor gene codon 72 polymorphism and systemic lupus erythematosus (SLE). Our study population consisted of 513 SLE patients and 567 healthy controls. All the individuals were of Spanish Caucasian origin. Genotyping of the p53 codon 72 polymorphism was performed by allele-specific PCR. No statistically significant differences were observed between SLE patients and healthy controls when p53 codon 72 genotype and allele frequencies were compared. In addition, no evidence for association with clinical subfeatures of SLE was found. In conclusion, the p53 codon 72 polymorphism associated with SLE in a Korean population does not appear to play a major role in the susceptibility or severity of SLE in the Spanish population.

Interleukin 12 (IL12B), interleukin 12 receptor (IL12RB1) and interleukin 23 (IL23A) gene polymorphism in systemic lupus erythematosus.

OBJECTIVE: The aim of this study was to assess the possible association between the interleukin-12B (IL12B) and interleukin-12 receptor beta 1 (IL12RB1) gene polymorphisms with systemic lupus erythematosus (SLE). In addition, we have undertaken a systematic search for genetic variants of interleukin 23 (IL23A). METHODS: The study was conducted on 559 SLE patients and 603 ethnically matched healthy controls. Genotyping of the IL12B [IL12Bpro and IL12B 3' untranslated region (UTR)] and IL12RB1 (641A-->G, 1094T-->C and 1132G-->C) polymorphisms was performed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and PCR-fluorescent methods, whereas IL23A genetic variants were realized with direct sequencing. RESULTS: No statistically significant differences in the distribution of the IL12B and the IL12RB1 genotypes and alleles were observed when comparing SLE patients and control subjects. Additionally, no differences in the genotype and allele distribution were found when SLE patients were stratified according to the presence or absence of lupus nephritis. Despite an extensive analysis in 30 individuals, variations located in the exons and in the 5' and 3' UTR regions of IL23A gene were not found in any case. CONCLUSIONS: These results suggest that polymorphisms located in IL12B, IL12RB1 and IL23A genes may not play a relevant role in the susceptibility or severity of SLE in the Spanish population.

Tratamiento endovascular de un pseudoaneurisma de arteria ilíaca primitiva postrasplante renal / Endovascular resolution of iliac artery pseudoaneurysm in a transplanted patient

Presentamos el caso de un paciente varón de 58 años que al año después de un trasplante renal presenta una tumoración pulsátil en fosa ilíaca derecha acompañado de dolor, motivo por el que ingresa en la unidad de nefrología. Tras el estudio mediante Eco-doppler y angiografía es diagnosticado de un pseudoaneurisma de arteria ilíaca común. Se le practica tratamiento endovascular mediante la colocación de un "stent" cubierto previa embolización de arteria hipogástrica como prevención para evitar una fuga o "endoleak". Resultado clínico y radiológico bueno, desaparición de la masa pulsátil a la exploración y en la imagen radiológica (AU)

Epidemiology of chronic venous insufficiency of the lower limbs in the primary care setting.

AIM: The objective of the study was to describe the general characteristics, risk factors and clinical symptoms of patients seeking medical care at the primary care setting because of chronic venous insufficiency. METHODS: A total of 606 general practitioners throughout Spain participated in this epidemiological, cross-sectional, multicenter study in which 6 695 patients were included. During a 3-month period, each participating physician filled out a questionnaire for all consecutive patients with venous leg complaints attended at his/her consultation. The following data were recorded: demographic features and anthropometric characteristics, level of physical activity, tobacco and/or alcohol consumption, number of pregnancies, other risk factors for chronic venous insufficiency, clinical manifestations, and signs on physical examination. RESULTS: Women accounted for 81.3% of the sample. Risk factors included tobacco smoking in 33.8% of cases, alcohol consumption in 25%, low physical activity in 55.7%, and family history in 47.2%. Patients recognized prolonged standing as the most frequent factor probably related to the origin of the symptoms (30.7%). Heaviness in the legs (84.8%) and itching (53.9%) were the most common symptoms, whereas ankle edema (43.6%) was the most frequent sign followed by telangiectases (37.6%). The presence of family history, a higher body mass index an age older than 45 years seems to be related with an increased frequency of clinical manifestations. CONCLUSION: Among patients seeking medical care because of chronic venous insufficiency, women seemed to ask for attention more frequently than men and the beginning of symptoms was mainly related to a prolonged orthostatic posture, being overweight the second cause stated. Heavy legs was the most frequent symptom followed by itching, and ankle edema was the most frequent sign.

[Endovascular resolution of iliac artery pseudoaneurysm in a transplanted patient]. / Tratamiento endovascular de un pseudoaneurisma de arteria ilíaca primitiva postrasplante renal.

A 58-year-old patient with end-stage idiopatic renal disease underwent kidney transplantation from a cadaveric donor. Approximately one year after the transplant he complained of abdominal pain and presented a pulsating mass in his right pelvic region. Dupplex study and arteriography were performed and showed a large pseudoaneurysm arising from the right common iliac artery. We report the case in which a covered stent placement and an embolization of the right internal iliac artery solved the problem with successful clinical and radiological results.

Rotura de aneurisma de arteria poplíteaseis años después de la intervención / Rupture of popliteal artery aneurysm six years after surgery

Introducción. Los aneurismas de arteria poplítea son los aneurismas periféricos más frecuentes. Su principal complicación es la isquemia aguda por trombosis del mismo; su rotura es rara. El caso que presentamos resulta excepcional porque la rotura tuvo lugar más de seis años después de la intervención. Caso clínico. Paciente de 90 años, intervenido en 1996 de un aneurisma poplíteo bilateral; se le practicó ligadura y by-pass, con prótesis de politetrafluroetileno expandido (PTFE) en la pierna derecha y con vena safena invertida en la izquierda. Sigue controles anuales en nuestras consultas, durante los cuales no se han detectado arteriomegalias y se han mantenido permeables las reconstrucciones. En junio de 2002 ingresó de urgencia por presentar gran tumoración en la cara interna del muslo izquierdo, según el paciente, de 2-3 semanas de evolución. No se apreciaba latido ni signos externos de hemorragia. Se practicó angiorresonancia magnética (angio-RM), que informó de `imagen compatible con pseudoaneurisma, posiblemente originado en la zona de la anastomosis proximal del injerto'. Se intervino al paciente y se encontró un falso aneurisma por rotura de la pared del aneurisma en el hueco poplíteo, con indemnidad de las anastomosis. Se practicó una nueva ligadura de la arteria poplítea distal al final del aneurisma, se resecó parcialmente el falso aneurisma, que estaba trombosado, y se envió una muestra a anatomía patológica. Cuatro meses después de la intervención, coincidiendo con tratamiento anticoagulante por sospecha de trombosis venosa poplítea, la tumoración volvió a crecer y en esta ocasión se practicó embolización de ramas distales de la femoral profunda y de la femoral superficial. Un año después, el paciente permanece estable, sin cambios en una nueva angio-RM (AU)