Effects of plant protease inhibitors (Pep-3-EcTI, Pep-BbKI, and Pep-BrTI) versus corticosteroids on inflammation, remodeling, and oxidative stress in an asthma-COPD (ACO) model.

The peptide derived from E. contortisiliquum trypsin inhibitor (Pep-3-EcTI), peptide derived from kallikrein inhibitor isolated from B. bauhinioides (Pep-BbKI), and B. rufa peptide modified from B. bauhinioides (Pep-BrTI) peptides exhibit anti-inflammatory and antioxidant activities, suggesting their potential for treating asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO). We compared the effects of these peptides with dexamethasone (DX) treatment in an ACO model. In this study, 11 groups of male BALB/c mice were pre-treated under different conditions, including sensitization with intraperitoneal injection and inhalation of ovalbumin (OVA), intratracheal instillation of porcine pancreatic elastase (ELA), sensitization with intraperitoneal injection, and various combinations of peptide treatments with Pep-3-EcTI, Pep-BbKI, Pep-BrTI, dexamethasone, and non-treated controls (SAL-saline). Respiratory system resistance, airway resistance, lung tissue resistance, exhaled nitric oxide, linear mean intercept, immune cell counts in the bronchoalveolar lavage fluid, cytokine expression, extracellular matrix remodeling, and oxidative stress in the airways and alveolar septa were evaluated on day 28. Results showed increased respiratory parameters, inflammatory markers, and tissue remodeling in the ACO group compared to controls. Treatment with the peptides or DX attenuated or reversed these responses, with the peptides showing effectiveness in controlling hyperresponsiveness, inflammation, remodeling, and oxidative stress markers. These peptides demonstrated an efficacy comparable to that of corticosteroids in the ACO model. However, this study highlights the need for further research to assess their safety, mechanisms of action, and potential translation to clinical studies before considering these peptides for human use.

Overlap Syndrome of Diffuse Systemic Sclerosis, Sjögren Syndrome, and ANCA-Associated Renal-Limited Vasculitis: Three Entities in One Patient - Case Report.

Introduction: The presence of three different entities in a single patient is usually of clinical interest and mostly anecdotal. The overlap of systemic sclerosis (SSc), Sjögren syndrome (SS), and ANCA-associated renal-limited vasculitis has been reported only once previously. Case Presentation: A 61-year-old female was evaluated at consultation with 2 years of symptomatology, presenting cardboard-like skin, sclerodactyly, limited oral opening, and dry skin and eyes. She was admitted for progressive renal failure (serum creatinine, 5.5 mg/dL). Her serology work-up showed positive anti-SCL-70, anti-Ro, anti-La, anti-MPO, and antinuclear antibodies. Renal biopsy was performed and confirmed histological findings for SSc, SS, and ANCA-associated vasculitis with active extracapillary glomerulonephritis with fibrous predominance (EUVAS-Berden sclerotic class), active tubulointerstitial nephritis, focal tubular injury, and moderate chronic arteriolopathy. Treatment with 6 monthly doses of methylprednisolone and cyclophosphamide was established. At the last follow-up, the patient maintained a stable serum creatinine level of 2.6 mg/dL and had decreased proteinuria, no erythrocyturia, and no requirement for renal replacement therapy. Conclusion: Systemic sclerosis is a rare autoimmune disease; nevertheless, overlap with Sjögren syndrome is relatively common, although its association with ANCA vasculitis is anecdotal. Diagnostic integration presents a challenge for nephrologists to define the prognosis and a specific treatment.

Prevalence and impact of Sjögren's syndrome in primary biliary cholangitis: a systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: We performed a systematic review and meta-analysis to evaluate the prevalence of concomitant Sjögren's syndrome (SS) with primary biliary cholangitis (PBC) in adults and quantify the impact of SS on PBC. METHODS: PubMed, Web of Science and Cochrane library were searched using subject terms and predefined inclusion and exclusion criteria. RESULTS: Seventeen articles were included. The prevalence of SS in PBC patients ranged from 3.5 to 73% (35% pooled) (95% CI: 28-41%; p < 0.01). Seven studies included various biochemical indicators, including alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyltransferase (γ-GT), total bilirubin (TBiL), albumin (ALB) and platelet (PLT), and immunological indexes including IgG, IgM, antinuclear antibody (ANA), anti-mitochondrial antibody (AMA), AMA-M2 and anti-Ro/Sjögren's syndrome antigen A (SSA) antibodies. Meta-analysis showed that there were no significant differences in ALT, AST, ALP, γ-GT, TBiL and IgM levels between PBS and PBC with SS. Pooled analysis showed that ALB (MD=0.82; 95% CI: 0.08-1.56) and PLT (MD=30.41; 95% CI: 10.16-50.66) levels were lower, IgG levels (MD=-1.55; 95% CI: -2.39 to -0.72) were higher, and the positive ratios of ANA (RR=0.92; 95% CI: 0.87-0.98), AMA (RR=0.94; 95% CI: 0.89-0.98), AMA-M2 (RR=0.77; 95% CI: 0.70-0.85) and anti-Ro/SSA antibodies (RR=0.29; 95% CI: 0.08-1.01) were significantly higher in PBC patients with SS than in PBC patients. CONCLUSIONS: Our study confirms that SS is common in PBC. Comorbid SS appears to influence the clinical phenotype of PBC and may therefore influence the management of PBC.

Evaluation of sports ability to improve patients with pulmonary disease / Avaliação da habilidade no esporte para a melhoria de pacientes com doença pulmonar / Evaluación de la habilidad en el deporte para la mejoría de pacientes con enfermedad pulmonar

ABSTRACT Introduction: Chronic obstructive pulmonary disease (COPD) is one of the most common diseases in the lungs. Objective: To evaluate the clinical effect of respiratory rehabilitation training combined with Traditional Chinese and western medicine on the clinical treatment of motor function in patients with COPD. Methods: 156 patients with chronic obstructive pulmonary disease admitted to a hospital from December 2013 to June 2015 were selected as study subjects and randomly divided into groups for treatment. Results: comparing blood gas exchange rates of patients in the four groups, the experimental group, trained using integrated Chinese and Western medicine, was significantly better than the control groups A, B and C, in aspects such as PaCO2, PaO2, SaO2, pH, etc., the difference was statistically significant (p < 0.05). The improvement of lung function in the experimental group was significantly better than in the other three groups, with statistical significance (p < 0.05). Conclusions: Applying Chinese and Western Medicine combined with comprehensive respiratory rehabilitation training has a significant clinical effect. It effectively improved patients' related clinical indicators and should be widely promoted. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução: A doença pulmonar obstrutiva crônica (DPOC) é uma das doenças pulmonares mais comuns. Objetivo: Avaliar os efeitos clínicos de treino para reabilitação respiratória somado ao uso de medicina ocidental e medicina tradicional chinesa combinadas, no tratamento da função motora de pacientes com DPOC. Métodos: 156 pacientes com DPOC, hospitalizados entre dezembro de 2013 e junho de 2015, foram selecionados como objetos de estudo e aleatoriamente divididos em grupos de tratamento. Resultados: Quanto aos níveis de troca gasosa dos pacientes nos quatro grupos, o grupo experimental, treinado por meio de práticas de medicina ocidental e de medicina tradicional chinesa combinadas teve uma performance significativamente melhor que a dos grupos A, B, e C, em aspectos tais como PaCO2, PaO2, SaO2, pH, etc., com significância estatística (p<0,05). A melhoria da função pulmonar no grupo experimental também foi significativamente maior que nos outros grupos, mais uma vez com significância estatística (p<0,05). Conclusões: A aplicação da medicina chinesa e da medicina ocidental combinadas, somadas a um treino de reabilitação respiratória abrangente, teve um efeito clínico significativo, efetivamente melhorando indicadores clínicos relevantes. Tal aplicação deveria ser largamente promovida. Nível de evidência II; Estudos terapêuticos - investigação de resultados de tratamento.

RESUMEN Introducción: La enfermedad pulmonar obstructiva crónica (EPOC) es una de las enfermedades pulmonares más comunes. Objetivo: Evaluar los efectos clínicos de entrenamiento para rehabilitación respiratoria sumado al uso de medicina occidental y medicina tradicional china combinadas en el tratamiento de la función motora de pacientes con EPOC. Métodos: 156 pacientes con EPOC, hospitalizados entre diciembre de 2013 y junio de 2015, fueron seleccionados como objetos de estudio y aleatoriamente divididos en grupos de tratamiento. Resultados: En cuanto a los niveles de intercambio gaseoso de los pacientes de los cuatro grupos, el grupo experimental, entrenado mediante prácticas combinadas de medicina occidental y medicina tradicional china, obtuvo un rendimiento significativamente mejor que los grupos A, B y C, en aspectos como PaCO2, PaO2, SaO2, pH, etc., con significancia estadística (p<0,05). La mejora de la función pulmonar en el grupo experimental también fue significativamente mayor que en los otros grupos, una vez más con significancia estadística (p<0,05). Conclusiones: La aplicación de la medicina china y de la medicina occidental combinadas, sumadas a un entrenamiento de rehabilitación respiratorio abarcativo, tuvo un efecto clínico significativo, efectivamente mejorando indicadores clínicos relevantes. Tal aplicación debería ser largamente promovida. Nivel de evidencia II; Estudios terapéuticos - investigación de resultados de tratamiento.

Classic and overlapping Miller-Fisher syndrome: clinical and electrophysiological features in Mexican adults.

Classic and overlapping Miller-Fisher syndrome (MFS) have divergent clinical courses. Few studies have addressed the electrophysiological evaluation of MFS patients, most of them carried out in Asia. This work describes and compares their clinical and neurophysiological characteristics. From a Guillain-Barré syndrome (GBS) patient cohort, we made a selection of twenty MFS cases. We defined classic and overlapping MFS, as stated by Wakerley et al. (Nat Rev Neurol 10(9):537-544, 2014). We describe and compare clinical, biochemical, and electrodiagnostic parameters between groups. Seventy-five percent were men, mean age was 42.2 ± 13.6 years, and 45% had a Hughes score ≥ 3. MFS/GBS was the most frequent clinical subtype with 50%. Almost one-third had unaltered electrophysiological studies. Comparative analysis between groups showed statistically significant differences in length of stay, dysautonomia presence, and treatment type. Kaplan-Meier survival analysis showed that 100% of the patients had an independent walk at 3 months. This study reports Mexican MFS patient's characteristics and represents the most extensive case series in Latin America. We observed a high proportion of overlapping syndromes, a good recovery profile, and no significant severe complications.

Clinical Spectrum of SCN5A Channelopathy in Children with Primary Electrical Disease and Structurally Normal Hearts.

Sodium voltage-gated channel α subunit 5 (SCN5A)-mutations may cause an array of arrhythmogenic syndromes most frequently as an autosomal dominant trait, with incomplete penetrance, variable expressivity and male predominance. In the present study, we retrospectively describe a group of Mexican patients with SCN5A-disease causing variants in whom the onset of symptoms occurred in the pediatric age range. The study included 17 patients with clinical diagnosis of primary electrical disease, at least one SCN5A pathogenic or likely pathogenic mutation and age of onset <18 years, and all available first- and second-degree relatives. Fifteen patients (88.2%) were male, and sixteen independent variants were found (twelve missense, three truncating and one complex inframe deletion/insertion). The frequency of compound heterozygosity was remarkably high (3/17, 17.6%), with early childhood onset and severe disease. Overall, 70.6% of pediatric patients presented with overlap syndrome, 11.8% with isolated sick sinus syndrome, 11.8% with isolated Brugada syndrome (BrS) and 5.9% with isolated type 3 long QT syndrome (LQTS). A total of 24/45 SCN5A mutation carriers were affected (overall penetrance 53.3%), and penetrance was higher in males (63.3%, 19 affected/30 mutation carriers) than in females (33.3%, 5 affected/15 carriers). In conclusion, pediatric patients with SCNA-disease causing variants presented mainly as overlap syndrome, with predominant loss-of-function phenotypes of sick sinus syndrome (SSS), progressive cardiac conduction disease (PCCD) and ventricular arrhythmias.

Hepatopatías autoinmunes. Hallazgos clínicos y de laboratorio en pacientes de un hospital de referencia nacional / Autoimmune liver diseases. Clinical and laboratory findings in patients in a national reference hospital

Introducción. Las enfermedades autoinmunes del hígado son un grupo de patologías caracterizadas por una respuesta autoinmune contra los hepatocitos y/o el epitelio biliar. Sus manifestaciones clínicas son variadas, con alteraciones en las pruebas de función hepática y presencia de autoanticuerpos. Metodología. Estudio observacional descriptivo con 101 pacientes atendidos en el Hospital Universitario de La Samaritana de Bogotá D.C., entre enero a diciembre de 2019, con los diagnósticos de hepatitis autoinmune, colangitis biliar primaria, colangitis esclerosante primaria y síndrome de sobreposición. Se evaluaron los parámetros clínicos y de laboratorio, con el fin de caracterizar su frecuencia en estas patologías, debido a la importancia de un diagnóstico precoz. Resultados. Se encontraron 54 casos de hepatitis autoinmune, 19 casos de colangitis biliar primaria, 4 casos de colangitis esclerosante primaria y 24 casos de síndrome de sobreposición. El 81% fueron mujeres y la edad promedio fue de 55 años. El 39% de los pacientes tenían cirrosis. En general, los resultados se ajustaron a lo descrito internacionalmente, como es el predominio en mujeres y la comorbilidad autoinmune. Conclusión. Los hallazgos indican que cualquier alteración del perfil bioquímico hepático debe ser considerado, y se debe descartar la presencia de hepatopatías autoinmunes para diagnosticarlas de manera precoz, evitando que lleguen a cirrosis y sus complicaciones, con la necesidad de un trasplante hepático como única alternativa terapéutica.

Introduction. Autoimmune liver diseases are a group of pathologies characterized by an autoimmune response against hepatocytes and/or the biliary epithelium. Their clinical manifestations are varied, with alterations in liver function tests and the presence of autoantibodies. Methodology. Descriptive study with 101 patients who attended at the Hospital Universitario de La Samaritana in Bogota D.C., between January and December 2019, with the diagnoses of autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis and overlap syndrome. Clinical and laboratory parameters were evaluated in order to characterize their frequency in these pathologies, due to the importance of an early diagnosis. Results. There were 54 cases of autoimmune hepatitis, 19 cases of primary biliary cholangitis, 4 cases of primary sclerosing cholangitis, and 24 cases of overlap syndrome. Of all patients, 81% were women, the average age was 55 years, and 39% had cirrhosis. In general, the findings were consistent with what has been described worldwide, such as a higher prevalence in women and autoimmune comorbidity. Conclusion. The findings indicate that any alteration in the liver biochemical profile should be considered to rule out an autoimmune liver disease for an early diagnosis, avoiding the possibility of cirrhosis and its complications, with the need for a liver transplant as the only therapeutic alternative.

Síndrome de Superposición de Esclerosis Sistémica y Lupus

Resumen Las patologías autoinmunes son condiciones causadas por una respuesta anormal del sistema inmune. La esclerosis sistémica es un trastorno autoinmune que afecta la microvasculatura del tracto gastrointestinal, pulmones, riñones, corazón, piel y articulaciones, con la consiguiente fibrosis de los órganos afectados, mientras que el lupus eritematoso sistémico se caracteriza por una actividad aberrante del sistema inmunológico considerada como un prototipo de enfermedad mediada por formación de inmunocomplejos, que conduce a síntomas clínicos variables; es poco usual la superposición de dos patologías del sistema inmune, sin hacer mención de la enfermedad mixta del tejido conectivo, y es de gran importancia identificar una patología combinada ya que tiene un gran impacto en las características clínicas, el diagnóstico, tratamiento y pronóstico del paciente.

Abstract Autoimmune pathologies are conditions caused by an abnormal response of the immune system. Systemic sclerosis is an autoimmune disorder that affects the microvasculature of the gastrointestinal tract, lungs, kidneys, heart, skin and joints, with consequent fibrosis of the affected organs, while systemic lupus erythematosus is characterized by an aberrant activity of the immune system considered as a prototype of immune complex-mediated disease, leading to variable clinical symptoms; the overlap of two pathologies of the immune system is unusual, without mentioning the mixed connective tissue disease, and it is of great importance to identify a combined pathology since it has a great impact on the clinical characteristics, diagnosis, treatment and prognosis of the patient.

Clinical, laboratory, and functional characteristics of asthma-COPD overlap in patients with a primary diagnosis of COPD / Características clínicas, laboratoriais e funcionais da sobreposição asma-DPOC em pacientes previamente diagnosticados com DPOC

ABSTRACT Objective: To evaluate the frequency of asthma-COPD overlap (ACO) in patients with COPD and to compare, from a clinical, laboratory, and functional point of view, patients with and without ACO, according to different diagnostic criteria. Methods: The participants underwent evaluation by a pulmonologist, together with spirometry and blood tests. All of the patients were instructed to record their PEF twice a day. The diagnosis of ACO was based on the Proyecto Latinoamericano de Investigación en Obstrucción Pulmonar (PLATINO, Latin American Project for the Investigation of Obstructive Lung Disease) criteria, the American Thoracic Society (ATS) Roundtable criteria, and the Spanish criteria. We investigated patient histories of exacerbations and hospitalizations, after which we applied the COPD Assessment Test and the modified Medical Research Council scale, to classify risk and symptoms in accordance with the GOLD criteria. Results: Of the 51 COPD patients, 14 (27.5%), 8 (12.2%), and 18 (40.0) were diagnosed with ACO on the basis of the PLATINO, ATS Roundtable, and Spanish criteria, respectively. The values for pre-bronchodilator FVC, post-bronchodilator FVC, and pre-bronchodilator FEV1 were significantly lower among the patients with ACO than among those with COPD only (1.9 ± 0.4 L vs. 2.4 ± 0.7 L, 2.1 ± 0.5 L vs. 2.5 ± 0.8 L, and 1.0 ± 0.3 L vs. 1.3 ± 0.5 L, respectively). When the Spanish criteria were applied, IgE levels were significantly higher among the patients with ACO than among those with COPD only (363.7 ± 525.9 kU/L vs. 58.2 ± 81.6 kU/L). A history of asthma was more common among the patients with ACO (p < 0.001 for all criteria). Conclusions: In our sample, patients with ACO were more likely to report previous episodes of asthma and had worse lung function than did those with COPD only. The ATS Roundtable criteria appear to be the most judicious, although concordance was greatest between the PLATINO and the Spanish criteria.

RESUMO Objetivo: Avaliar a frequência de asthma-COPD overlap (ACO, sobreposição asma-DPOC) em pacientes com DPOC e comparar, do ponto de vista clínico, laboratorial e funcional, os pacientes com e sem essa sobreposição conforme diferentes critérios diagnósticos. Métodos: Os participantes foram submetidos à avaliação com pneumologista, espirometria e exame sanguíneo, sendo orientados a manter o registro do PFE duas vezes ao dia. O diagnóstico de ACO deu-se através dos critérios Projeto Latino-Americano de Investigação em Obstrução Pulmonar (PLATINO), American Thoracic Society (ATS) Roundtable e Espanhol. Foram investigados os históricos de exacerbações e hospitalizações e aplicados os instrumentos COPD Assessment Test e escala Medical Research Council modificada, utilizados para a classificação de risco e sintomas da GOLD. Resultados: Entre os 51 pacientes com DPOC, 14 (27,5%), 8 (12,2%) e 18 (40,0) foram diagnosticados com ACO segundo os critérios PLATINO, ATS Roundtable e Espanhol, respectivamente. Pacientes com sobreposição significativamente apresentaram pior CVF pré-broncodilatador (1,9 ± 0,4 L vs. 2,4 ± 0,7 L), CVF pós-broncodilatador (2,1 ± 0,5 L vs. 2,5 ± 0,8 L) e VEF1 pré-broncodilatador (1,0 ± 0,3 L vs. 1,3 ± 0,5 L) quando comparados a pacientes com DPOC. Os níveis de IgE foram significativamente mais elevados em pacientes com sobreposição diagnosticados pelo critério Espanhol (363,7 ± 525,9 kU/L vs. 58,2 ± 81,6 kU/L). O histórico de asma foi mais frequente em pacientes com a sobreposição (p < 0,001 para todos os critérios). Conclusões: Nesta amostra, pacientes com ACO relataram asma prévia com maior frequência e possuíam pior função pulmonar quando comparados a pacientes com DPOC. O critério ATS Roundtable aparenta ser o mais criterioso em sua definição, enquanto os critérios PLATINO e Espanhol apresentaram maior concordância entre si.

Overlap syndrome: the coexistence of OSA further impairs cardiorespiratory fitness in COPD.

BACKGROUND: Cardiorespiratory fitness (CRF) is an important prognostic marker in chronic obstructive pulmonary disease (COPD). Obstructive sleep apnea (OSA) also negatively affects exercise tolerance. However, the impact of their association on CRF has not been evaluated. We hypothesized that patients with overlap syndrome would demonstrate a greater impairment in CRF, particularly those with severe COPD. METHODS: Individuals with COPD were recruited. First, subjects underwent clinical and spirometry evaluation. Next, home-based sleep evaluation was performed. Subjects with an apnea-hypopnea index (AHI) < 15 episodes/h were allocated to the COPD group and those with an AHI ≥ 15 episodes/h to the overlap group. On the second visit, subjects underwent a cardiopulmonary exercise test. Subsequently, they were divided into four groups according to the severity of COPD and coexistence of OSA: COPDI/II; overlap I/II; COPDIII/IV; and overlap III/IV. RESULTS: Of the 268 subjects screened, 31 were included. The overlap group exhibited higher values for peak carbon dioxide (COPD: 830 [678-1157]; overlap: 1127 [938-1305] mm Hg; p < 0.05), minute ventilation (COPD: 31 [27-45]; overlap: 48 [37-55] L; p < 0.05), and peak systolic blood pressure (COPD: 180 [169-191]; overlap: 220 [203-227] mm Hg; p <; 0.001) and peak diastolic blood pressure COPD: 100 [93-103]; overlap: 110 [96-106] mm Hg; p < 0.001). COPD severity associated with OSA produced a negative impact on exercise time (COPDIII/IV: 487 ± 102; overlap III/IV: 421 ± 94 s), peak oxygen uptake (COPDIII/IV: 12 ± 2; overlap III/IV: 9 ± 1 ml.Kg.min-1 ; p < 0.05) and circulatory power (COPDIII/IV: 2306 ± 439; overlap III/IV: 2162 ± 340 ml/kg/min.mmHg; p < 0.05). CONCLUSION: Overlap syndrome causes greater hemodynamic and ventilatory demand at the peak of dynamic exercise. In addition, OSA overlap in individuals with more severe COPD impairs CRF.

Acoustic Radiation Force Impulse (ARFI) Elastography in Autoimmune and Cholestatic Liver Diseases.

INTRODUCTION: Acoustic Radiation Force Impulse (ARFI) elastography evaluates hepatic fibrosis non-invasively and has been mainly validated in viral hepatitis. Data on rare liver diseases such as autoimmune hepatitis (AIH), overlap syndrome, primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC) are sparse. MATERIAL AND METHODS: 85 patients (including 31 AIH, 26 PBC, 16 PSC and 3 PSC-and 9 PBC-AIH-overlap syndromes) were retrospectively analysed pointing at ARFI elastography of the liver and the correlation with histologic Ishak fibrosis score (F0-6). Results of shear wave velocities (m/s) were expressed as mean ± standard deviation. RESULTS: The mean shear wave velocity of all 85 patients showed 1.80 ± 0.84 m/s (0.74-3.98). The ARFI elastography values correlated with the degree of fibrosis in all patients overall and in patients with AIH, overlap syndrome and PSC, respectively. The subgroup of 26 patients with PBC (only with Ishak F > 3) revealed no correlation between ARFI and these early fibrosis stages (r = 0.019, p = 0.927). ARFI elastography correlated with bilirubin, AST, but not with patient age, body mass index or measurement depth. The cut-off of 2.04 m/s for detecting cirrhosis (Ishak F > 5) leads to a sensitivity of 90.0% and specificity of 74.7% (AUROC 87.2%). CONCLUSION: ARFI elastography can evaluate fibrosis in AIH, PSC and PSC-/PBC-AIH-overlap syndrome with good accuracy for the detection of hepatic cirrhosis. Shear wave velocities in PBC should be interpreted with caution in early stages of fibrosis.

Treatment response in primary biliary cholangitis: The role of autoimmune hepatitis features.

INTRODUCTION AND AIM: Primary biliary cholangitis is a rare disease with scarce epidemiological data in Southern Europe. The authors aimed to evaluate treatment response in a cohort of patients. MATERIALS AND METHODS: This retrospective observational single-centre study included patients with diagnostic criteria of primary biliary cholangitis. Data on disease presentation, laboratory results, treatment and clinical endpoints were collected and analyzed. RESULTS: Fifty-three patients were included, 89% women, with mean age of 62±15 years at diagnosis. The majority was asymptomatic (49%), tested positive for antimitochondrial antibodies (96%) and had increased alkaline phosphatase (median=214U/L). 75% of the patients had liver histology and the majority were in Ludwig's stage I (42%). Autoimmune hepatitis (AIH) features were found in seven patients (13%). All were treated with ursodeoxycholic acid (UDCA) and 56% achieved biochemical response at one year; patients with AIH features exhibited steeper decreases in alkaline phosphatase (p=0.007) and reached the endpoint of 40% decrease in alkaline phosphatase more frequently (p=0.017). CONCLUSION: In conclusion a significant proportion of patients failed to achieve an adequate response to UDCA treatment. The response rate of patients with AIH features was better, which could be related to a different phenotype or to the potential impact of immunosuppressive agents.

Síndrome de sobreposição asma e DPOC / Asthma-COPD overlap syndrome

Asma e doença pulmonar obstrutiva crônica (DPOC) são doenças crônicas altamente prevalentes na população geral. Ambas são caracterizadas por inflamação crônica heterogênea e obstrução das vias aéreas. Em ambas as condições, a inflamação crônica afeta todo o trato respiratório das grandes e pequenas vias aéreas, com recrutamento de diferentes células e com diferentes mediadores produzidos. A obstrução das vias aéreas é tipicamente intermitente e reversível na asma, mas é progressiva e frequentemente irreversível na DPOC. Quando asma e DPOC ocorrem juntas, o termo síndrome de sobreposição asma e DPOC tem sido usado. Realizou-se revisão de artigos originais, revisões e publicações indexadas nos bancos de dados PubMed, MEDLINE, LILACS e SciELO nos últimos 20 anos. Uma forma prática de diagnóstico da Síndrome de sobreposição asma e DPOC é incluir pacientes com diagnóstico de DPOC pelo critério do GOLD (Global Initiative for Chronic Obstructive Lung Disease) e da Asma pelo critério do GINA (Global Initiative for Asthma). Assim, a síndrome inclui pacientes que preenchem os critérios de DPOC (obstrução fixa das vias aéreas) e que também têm típicos achados de asma (sibilância, atopia, eosinofilia e resposta positiva a broncodilatador). A presença de diferentes fenótipos ou componentes das doenças aéreas obstrutivas crônicas necessita ser analisada para individualizar e otimizar o tratamento para se alcançar os melhores resultados. Embora intervenções específicas variem conforme a doença, o objetivo do tratamento para as doenças obstrutivas respiratórias é semelhante e dirigido primariamente para a necessidade de controlar os sintomas, otimizar a saúde geral, e prevenir exacerbações.

Asthma and chronic obstructive pulmonary disease (COPD) are highly prevalent chronic diseases in the general population. Both conditions are characterized by heterogeneous chronic airway inflammation and airway obstruction. In both cases, chronic inflammation affects the whole respiratory tract, from central to peripheral airways, with different inflammatory cells recruited and different mediators produced. Airway obstruction is typically intermittent and reversible in asthma, but it is progressive and largely irreversible in COPD. When asthma and COPD co-occur, the term asthma-COPD overlap syndrome has been applied. This paper presents a review of original articles, reviews and other materials indexed in the PubMed, MEDLINE, LILACS, and SciELO databases and published over the last 20 years. A practical approach to diagnosis of the asthma-COPD overlap syndrome has been to include patients with a diagnosis of COPD according to GOLD criteria (Global Initiative for Chronic Obstructive Lung Disease) and of asthma according to GINA criteria (Global Initiative for Asthma). Therefore, the combined syndrome includes patients who meet criteria for COPD (fixed airflow obstruction) and also have typical features of asthma (wheezing, atopy, eosinophilia, and positive bronchodilator response). The presence of different phenotypes or components of obstructive airway diseases needs to be analyzed so that treatment can be individualized and optimized to achieve the best results for each patient. Even though specific interventions vary by disease, treatment goals for patients with obstructive airway diseases are similar and driven primarily by the need to control symptoms, optimize health status, and prevent exacerbations.

Lupus Eritematoso Cutáneo Discoide en una paciente con Esclerodermia Sistémica limitada / Cutaneous Discoid Erythematosus Lupus in a patient with limited Systemic Scleroderma

La esclerodermia sistémica (ES) puede asociarse con otros trastornos del tejido conectivo, como dermatomiositis o poliomiositis, síndrome de Sjôgren, artritis reumatoide y lupus eritematoso sistémico. Con menos frecuencia se ha descrito asociación con lupus eritematoso cutáneo discoide(LECD). Cuando un mismo paciente cumple simultáneamente los criterios para dos o más enfermedades del tejido conectivo, se realiza el diagnóstico de síndrome de superposición (SS). Presentamos el caso de una mujer de 32 años, que consultó por presentar placas deprimidas hipopigmentadas en zonas fotoexpuestas de 2 años de evolución, y fenómeno de Raynaud (FR) de 1 año de evolución. Además, telangiectasias en tronco, labios y cara. En manos se observan úlceras digitales dolorosas en pulpejos de los dedos, edema, esclerodactilia y esclerosis del dorso. En laboratorio destacó ANA (1/80 con patrón moteado), perfil ENA (133 con anticuerpo anti-Ro/SS-A en 47) y biopsia de piel compatible con lupus discoide. Se diagnostica SS cutáneosistémico, con LECD y ES limitada. Se realiza una breve revisión bibliográfica de los casos publicados con esta asociación, con un total de 20 casos reportados al año 2010. Las enfermedades reumatológicas pueden manifestarse inicialmente de manera inespecífica, presentando clínica común entre ellas, como es el caso del FR. Es por esta razón que es relevante determinar un diagnóstico en forma temprana, para definir el manejo y búsqueda de complicaciones asociadas a este. Pese a esto el diagnóstico puede ir modificándose en el tiempo principalmente por la aparición de nueva sintomatología.

Systemic Scleroderma (SS) can be associated to other connective tissue disordes such as Dermatomyositis, Polymiositis, Sjogren Syndrome, Rheumatoid Arthritis and Systemic Erythematosus Lupus. With less frecuency the association to Cutaneus Discoid Erithematosus Lupus (CDEL) has been described. When the same patient presents two or more criteria for a connective tissue disorder Overlap Syndrome (OS) is diagnosed. We present the case of a 32 year-old woman that consulted by presenting hypopigmented depressed plates in sun-exposed áreas for two years and Raynaud phenomenon (RPh) for one year. Also she had chest , lips and facial telangiectasia. She presented painful digital ulcers in her finger pads and edema, sclerodactyly and dorsal sclerosis. Laboratory findings showed ANA (1/80 motted pattern ) , ENA profile ( 133 with anti-Ro/SS-A in 47 ) and a cutaneous biopsy compatible with Discoid Lupus. The diagnosis was Cutaneo-Systemic OS with DCEL and limited SS. In this context we made a bibliographyc review of this published association finding a total of 20 cases in year 2010. Rheumatologic diseases can initially manifest in inespecific ways showing common clinical findings such as RPh. This is why it is relevant to make an early diagnosis in order to define treatment and search for associated complications. Despite this the diagnosis can be modified in time mostly because of the appearance of new symtoms.

Sleep Apnea Clinical Score, Berlin Questionnaire, or Epworth Sleepiness Scale: which is the best obstructive sleep apnea predictor in patients with COPD?

INTRODUCTION: The Sleep Apnea Clinical Score (SACS) and the Berlin Questionnaire (BQ) are used to predict the likelihood of obstructive sleep apnea (OSA). The Epworth Sleepiness Scale (ESS) is used to assess daytime sleepiness, a common OSA symptom. These clinical tools help prioritize individuals with the most severe illness regarding on whom polysomnography (PSG) should be performed. It is necessary to check the applicability of these tools in patients with chronic obstructive pulmonary disease (COPD). The aim of this study is to compare SACS, BQ, and ESS performance in patients with COPD. METHODS: The SACS, BQ, and ESS were applied to 91 patients with COPD. From this group, 24 underwent PSG. In this transversal study, these three tests were compared regarding their likelihood to predict OSA in patients with COPD using receiver-operating characteristic curve statistics. RESULTS: In this sample, 58 (63.7%) patients were men, and their mean age was 69.4±9.6 years. Fourteen patients (15.4%) had a high probability of OSA by SACS, 32 (32.5%) had a high probability by BQ, and 37 (40.7%) had excessive diurnal somnolence according to the ESS. From the 24 patients who underwent PSG, OSA diagnosis was confirmed in five (20.8%), according to the American Academy of Sleep Medicine criteria. BQ and ESS did not accurately predict OSA in this group of patients with COPD, with a receiver-operating characteristic curve area under the curves of 0.54 (95% CI: 0.329-0.745, P=0.75) and 0.69 (95% CI: 0.47-0.860, P=0.10), respectively. SACS performance was significantly better, with an area under the curve of 0.82 (95% CI: 0.606-0.943, P=0.02). CONCLUSION: SACS was better than BQ and ESS in predicting OSA in this group of patients with COPD.

[Childhood-onset systemic polyarteritis nodosa and systemic lupus erythematosus: an overlap syndrome?] / Poliartrite nodosa sistêmica e lúpus eritematoso sistêmico de início na infância: uma síndrome de sobreposição?

We described herein a patient who presented an overlap syndrome of childhood-onset systemic polyarteritis nodosa (c-PAN) and childhood-onset systemic lupus erythematosus (c-SLE). A 9-year-old girl presented tender subcutaneous nodules on feet, arterial hypertension, right hemiplegia and dysarthric speech. She was hospitalized due to stroke and left foot drop. Brain computer tomography showed ischemic stroke. Magnetic resonance angiography revealed stenosis in the middle cerebral and internal carotid arteries. Electroneuromyography identified a mononeuropathy of left posterior tibial nerve and she fulfilled the c-PAN validated criteria. She was treated with intravenous methylprednisolone pulse therapy followed by prednisone, that was progressively tapered, six months of intravenous cyclophosphamide and after that she received azathioprine for 19 months. At the age of 14 years and 9 months, she presented malar rash, photosensitivity, edema in lower limbs and arterial hypertension. The proteinuria was 1.7g/day. Antinuclear antibodies (ANA) were 1/1280 (homogeneous nuclear pattern) and anti-dsDNA antibodies were positive. Renal biopsy showed focal proliferative and membranous glomerulonephritis. Therefore, she fulfilled the American College of Rheumatology classification criteria for SLE and she was treated with prednisone, hydroxychloroquine and mycophenolate mofetil. In conclusion, we described herein a possible overlap syndrome of two autoimmune diseases, where c-PAN occurred five years before the c-SLE diagnosis.

Síndrome pulmón-riñón en lupus severo asociado aANCA: ¿un síndrome de sobreposición? / Lung - kidney syndrome in severe lupus ANCA associated: overlap syndrome?

Presentamos el caso de una mujer de 30 años, mexicana, que luego de permanecer sin datos de actividad lúpica renal por 13 años, desde su diagnóstico, sin inmunosupresión crónica, experimenta un deterioro general por un estado autoinmune severo desencadenado tras un embarazo a término sin complicaciones, presentando, incluso, hemorragia alveolar difusa en 2 ocasiones,durante 12 meses, en el contexto de anticuerpos anti citoplasma de neutrófilos ANCA (+), volviendo su manejo difícil desde el punto de vista terapéutico con esquemas de inmuno-supresión triple y cuádruple. Durante su evolución ha desarrollado microangiopatía cerebral y laringitis, por lo que se plantea la posibilidad de un síndrome de sobreposición lupus eritematoso sistémico – vasculitispauciinmune, una entidad no bien descrita en la literatura, cuyo diagnóstico está plagado de dificultades al no existir criterios definidos, ni la verdadera implicación de los ANCA en un paciente con lupus.

We report the case of a woman of 30 years, Mexican, who after spending without renal lupus activity data for 13 years after diagnosis, without chronic immunosuppression, experienced a general decline for severe autoimmune condition triggered after an uncomplicated term preg-nancy presenting even diffuse alveolar hemorrhage in 2 occasions within 12 months, in the context of Anti neutrophil cytoplasmic ANCA (+), becoming its handling difficult from the point of view of therapeutic immunosuppression regimens triple and quadruple. During its evolution has developed cerebral microangiopathy and laryngitis which raises the possibility of an overlap syndrome lupuserythematosus – ANCA associated vasculitis, an entity not well described in the literature, whose diagnosis is fraught with difficulties in the absence of defined criteria or true ANCA involvement in a patient with lupus.

Reporte de dos casos de síndrome de sobreposición entre hepatitis autoinmune y cirrosis biliar primaria / Report of two overlap syndrome cases with autoimmune hepatitis and primary biliary cirrhosis

Se presentan los casos de dos pacientes mujeres con características clínicas, serológicas, inmunológicas, e histológicas mixtas entre hepatitis autoinmune y cirrosis biliar primaria; y para quienes el trasplante ortotópico de hígado se presentó como la mejor alternativa terapéutica dado el avanzado deterioro de su enfermedad.

We present the cases of two female patients with clinical, serological, immunological, and histological characteristics which mixed symptoms of autoimmune hepatitis and primary biliary cirrhosis. Orthotopic liver transplantation was chosen as the best therapeutic alternative for both patients given the advanced deterioration of their disease.