Consenso Delphi sobre Estrategias Terapéuticas y de Prevención Sanitaria de la hipovitaminosis D / Delphi Consensus on Therapeutic and Preventive Health Strategies for Hypovitaminosis D

Antecedentes: La elevada prevalencia de hipovitaminosis D en España es considerada una verdadera epidemia con importantes implicaciones para la salud por las múltiples funciones que ejerce la vitamina D tanto a nivel esquelético como extraesquelético. Para que las personas con insuficiencia o deficiencia en vitamina D alcancen los niveles séricos más adecuados, deben recibir suplementos de vitamina D. Este estudio se realizó con la finalidad de evaluar si en la práctica clínica habitual, el manejo de la hipovitaminosis D era llevada a cabo según las recomendaciones internacionales establecidas por las sociedades científicas.Métodos: Se realizaron dos rondas de circulación de un cuestionario Delphi entre un panel formado por médicos prescriptores habituales de vitamina D.Resultados: En general, los médicos del panel reconocieron la alta prevalencia de la hipovitaminosis D en España, la necesidad del cribado en los distintos grupos de riesgo y los beneficios de la suplementación en los pacientes con insuficiencia o déficit de vitamina D. Sin embargo, no se alcanzó el consenso en algunas de las aseveraciones relacionadas con los métodos de cuantificación de la vitamina D o con las recomendaciones para el manejo de la hipovitaminosis D.Conclusiones: La ausencia de acuerdo para algunos de los ítems reveló la necesidad de realizar acciones formativas destinadas a proporcionar un conocimiento adecuado y actualizado sobre las evidencias científicas y las recomendaciones para la práctica clínica de la suplementación de vitamina D. (AU)

The Pathogenesis of Extraintestinal Manifestations: Implications for IBD Research, Diagnosis, and Therapy.

This article reports on the sixth scientific workshop of the European Crohn's and Colitis Organisation [ECCO] on the pathogenesis of extraintestinal manifestations [EIMs] in inflammatory bowel disease [IBD]. This paper has been drafted by 15 ECCO members and 6 external experts [in rheumatology, dermatology, ophthalmology, and immunology] from 10 European countries and the USA. Within the workshop, contributors formed subgroups to address specific areas. Following a comprehensive literature search, the supporting text was finalized under the leadership of the heads of the working groups before being integrated by the group consensus leaders.

Evolution After Anti-TNF Discontinuation in Patients With Inflammatory Bowel Disease: A Multicenter Long-Term Follow-Up Study.

OBJECTIVES: The aims of this study were to assess the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) drugs in patients with inflammatory bowel disease (IBD), to identify the factors associated with relapse, and to evaluate the overcome after retreatment with the same anti-TNF in those who relapsed. METHODS: This was a retrospective, observational, multicenter study. IBD patients who had been treated with anti-TNFs and in whom these drugs were discontinued after clinical remission was achieved were included. RESULTS: A total of 1,055 patients were included. The incidence rate of relapse was 19% and 17% per patient-year in Crohn's disease and ulcerative colitis patients, respectively. In both Crohn's disease and ulcerative colitis patients in deep remission, the incidence rate of relapse was 19% per patient-year. The treatment with adalimumab vs. infliximab (hazard ratio (HR)=1.29; 95% confidence interval (CI)=1.01-1.66), elective discontinuation of anti-TNFs (HR=1.90; 95% CI=1.07-3.37) or discontinuation because of adverse events (HR=2.33; 95% CI=1.27-2.02) vs. a top-down strategy, colonic localization (HR=1.51; 95% CI=1.13-2.02) vs. ileal, and stricturing behavior (HR=1.5; 95% CI=1.09-2.05) vs. inflammatory were associated with a higher risk of relapse in Crohn's disease patients, whereas treatment with immunomodulators after discontinuation (HR=0.67; 95% CI=0.51-0.87) and age (HR=0.98; 95% CI=0.97-0.99) were protective factors. None of the factors were predictive in ulcerative colitis patients. Retreatment of relapse with the same anti-TNF was effective (80% responded) and safe. CONCLUSIONS: The incidence rate of inflammatory bowel disease relapse after anti-TNF discontinuation is relevant. Some predictive factors of relapse after anti-TNF withdrawal have been identified. Retreatment with the same anti-TNF drug was effective and safe.

Therapeutic approach to Crohn disease: possible parallels with hidradenitis suppurativa. / Abordaje terapéutico de la enfermedad de Crohn: posibles paralelismos con la hidradenitis supurativa.

The current controversy in the setting of dermatology surrounding the treatment of inflammatory diseases, and specifically hidradenitis suppurativa, bears strong similarities with the debate concerning inflammatory bowel disease (IBD) that took place several years ago. That debate led to new perspectives on this disease and, in particular, its treatment after the development of biological agents.

Clinical features of hidradenitis suppurativa and Crohn disease: what do these two entities have in common? / Aspectos clínicos de la hidradenitis supurativa y de la enfermedad de Crohn: ¿qué hay en común?

Hidradenitis suppurativa (HS) and Crohn disease (CD) are chronic, recurrent inflammatory diseases. They share certain clinical characteristics and flares are common in both. Both entities are usually diagnosed between the second and third decades of life and share risk factors such as smoking and overweight. In CD, as in HS, acute untreated episodes of inflammation can lead to sequels such as abscesses, fistulas and stenosis. Consequently, early management is of the utmost importance. Some patients have both diseases. The estimated prevalence of SH in CD patients is 12.4%-17.9%, while the prevalence of CD in HS patients is around 3%. The presence of HS in patients with inflammatory bowel disease (IBD) is associated with an earlier onset of IBD and with more frequent need for anti-TNF-alpha therapy and surgical resection.

Hidradenitis suppurativa and perianal Crohn disease: differential diagnosis. / Hidradenitis supurativa y enfermedad de Crohn perianal: diagnóstico diferencial.

The first description of perianal fistulas and complications in Crohn disease was made 75 years ago by Penner and Crohn. Published studies have subsequently confirmed that perianal fistulas are the most common manifestations of fistulising Crohn disease. Hidradenitis suppurativa was described in 1854 by a French surgeon, Aristide Verneuil. It is a chronic, inflammatory, recurrent and debilitating disease of the pilosebaceous follicle, that usually manifests after puberty with deep, painful and inflamed lesions in the areas of the body with apocrine glands, usually the axillary, inguinal and anogenital regions. The differential diagnosis between hidradenitis suppurativa and Crohn disease can be challenging, especially when the disease is primarily perianal. When they occur simultaneously, hidradenitis suppurativa and Crohn disease show severe phenotypes and patients can respond to anti-tumour necrosis factor therapy, although adalimumab is currently the only treatment with demonstrated efficacy in hidradenitis suppurativa and Crohn disease. In addition, there is sometimes a need for different complementary surgical procedures.

Management of patients with hidradenitis suppurativa. / Manejo del paciente con hidradenitis supurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease with a high prevalence in the population. Treatment options are both medical and surgical. Medical treatment is based on the use of antibiotics, retinoids, and anti-inflammatory drugs, in which anti-TNFα agents (infliximab y adalimumab) play a central role in the treatment of moderate-to-severe HS and enjoy the highest level of scientific support. Currently, adalimumab is the only drug approved in the summary of product characteristics for the treatment of this disease. Due to the scarcity of clinical trials in HS, there is still no therapeutic guideline backed by solid evidence and the evidence for most drugs is low. However, early treatment in patients with HS would probably reduce the complications of this disease. This review analyses the distinct treatments used in this dermatological disease and provides a therapeutic algorithm with different treatment options.

Thiopurine methyl-transferase activity and azathioprine metabolite concentrations do not predict clinical outcome in thiopurine-treated inflammatory bowel disease patients.

BACKGROUND: Low thiopurine-methyl-transferase (TPMT) activity and high 6-thioguanine-nucleotide (6TGN) concentrations have been linked to therapeutic success in inflammatory bowel disease patients treated with thiopurines; however, this has not been implemented in clinical practice. AIM: To identify a therapeutic threshold value for TPMT or 6TGN concentrations, and their capability to predict treatment safety and efficacy. METHODS: Prospective multicentre study including steroid-resistant/dependent patients starting thiopurines. The TPMT activity was determined at inclusion (>5 U/mL required). Azathioprine metabolites [6TGN, 6-methyl-mercaptopurine ribonucleotides (6MMP), and 6TGN/6MMP and 6TGN/TPMT ratios] were periodically monitored during steroid tapering and after withdrawal for 6 months or until a new flare occurred. RESULTS: A total of 113 patients were analysed (62% clinical response). Areas under the receiver operating characteristic (ROC) curve (AUC) relating clinical response and metabolite levels at 2, 4 and 6 months after steroid withdrawal were less than 0.7. The AUCs relating final response and initial TPMT activity or metabolite concentrations at 2, 4, 8 and 16 weeks after starting thiopurines were less than 0.7. No cut-off point with worthwhile sensitivity/specificity was found. Eight (7%) patients developed thiopurine-related toxicity that could not be linked to TPMT activity or 6TGN levels. CONCLUSIONS: Our results do not support determination of TPMT activity or 6TGN concentrations to predict treatment outcome, and no useful serum metabolites threshold value to adjust the drug's dose was identified.

Systematic review: Infliximab therapy in ulcerative colitis.

AIM: To perform a systematic review and meta-analysis on the efficacy and tolerance of infliximab in ulcerative colitis. SELECTION OF STUDIES: evaluating efficacy of infliximab in ulcerative colitis. For the meta-analysis, randomized clinical trials comparing infliximab vs. placebo/steroids. SEARCH STRATEGY: electronic and manual. Study quality: independently assessed by two reviewers. DATA SYNTHESIS: meta-analysis combining the odds ratios (OR). RESULTS: Thirty-four studies (896 patients) evaluated infliximab therapy in UC, with heterogeneous results. Mean short-term (2.3 weeks) response and remission with infliximab was 68% (95% CI 65-71%) and 40% (36-44%). Mean long-term (8.9 months) response and remission was 53% (49-56%) and 39% (35-42%). Five randomized double-blind studies compared infliximab with placebo, the meta-analysis showing an advantage (P < 0.001) of infliximab in all endpoints (short-/long-term response/remission): ORs from 2.7 to 4.6, and number-needed-to-treat (NNT) from 3 to 5. Similar infliximab response was calculated independently of the indication (steroid-refractory/non-steroid-refractory) or the dose (5/10 mg/kg). Adverse effects were reported in 83% and 75% of the infliximab and placebo-treated patients (OR = 1.52; 95% CI 1.03-2.24; number-needed-to-harm (NNH) was 14). CONCLUSION: Infliximab is more effective than placebo, with an NNT from 3 to 5, for the treatment of moderate-to-severe UC, achieving clinical remission in 40% of the patients at approximately 9 months of follow-up. Further studies are necessary to confirm the long-term efficacy of infliximab in ulcerative colitis.

[Breath tests in the diagnosis of gastrointestinal diseases]. / Pruebas de aliento en el diagnóstico de enfermedades digestivas.

Determination of carbon or hydrogen markers in breath has allowed closer investigation of the pathogenic mechanisms of several gastrointestinal diseases. Thus, the 13C-urea breath test is a nonaggressive, simple and safe test with excellent accuracy both in the initial diagnosis of Helicobacter pylori infection and in confirmation of its eradication following treatment. Moreover, because of the simplicity, reproducibility and safety of these types of procedure, they have tended to substitute more uncomfortable and expensive techniques that were traditionally used in gastroenterology. Several breath tests have been developed that allow reliable evaluation of liver or exocrine pancreatic function, gastrointestinal motility, as related to gastric emptying or orocecal transit time, and a diagnostic approach to clinical problems that could be due to bacterial overgrowth or malabsorption of various sugars.

Pruebas de aliento en el diagnóstico de enfermedades digestivas / Breath tests in the diagnosis of gastrointestinal diseases

La determinación de carbono o hidrógeno marcados en el aliento ha permitido un acercamiento a los mecanismos patogénicos más íntimos de diversas enfermedades digestivas. Así, la prueba del aliento con urea marcada con 13C es un método diagnóstico no agresivo, sencillo y seguro, que posee una excelente exactitud tanto para el diagnóstico inicial de la infección por Helicobacter pylori como para la confirmación de su erradicación tras la administración de tratamiento. Además, la sencillez, la reproducibilidad y la inocuidad de este tipo de exploraciones las ha hecho atractivas para sustituir a otras más molestas, caras e incómodas que se han utilizado de forma tradicional para explorar diferentes ámbitos de la gastroenterología. En este sentido, se han desarrollado diversos tests del aliento que permiten una estimación fiable de la función hepática o pancreática exocrina, de la motilidad gastrointestinal, en lo que se refiere al vaciamiento gástrico o al tiempo de tránsito orocecal, y un acercamiento diagnóstico a los problemas clínicos que se pueden derivar del sobrecrecimiento bacteriano o de la malabsorción de diferentes azúcares

Determination of carbon or hydrogen markers in breath has allowed closer investigation of the pathogenic mechanisms of several gastrointestinal diseases. Thus, the 13C-urea breath test is a nonaggressive, simple and safe test with excellent accuracy both in the initial diagnosis of Helicobacter pylori infection and in confirmation of its eradication following treatment. Moreover, because of the simplicity, reproducibility and safety of these types of procedure, they have tended to substitute more uncomfortable and expensive techniques that were traditionally used in gastroenterology. Several breath tests have been developed that allow reliable evaluation of liver or exocrine pancreatic function, gastrointestinal motility, as related to gastric emptying or orocecal transit time, and a diagnostic approach to clinical problems that could be due to bacterial overgrowth or malabsorption of various sugars

[Gastric metastasis from renal cell carcinoma. Pathogenical hypothesis and literature revision]. / Metástasis gástrica de un adenocarcinoma renal. Hipótesis patogénica y revisión de la literatura.

Secondary gastric tumours are very uncommon clinical entities and even more so when the site for the primary tumour is the kidney. Only 11 cases of life diagnosis have been described up to now. Contribution of one case report: a female patient presenting with upper GI tract haemorrhage secondary to gastric metastasis from renal cell carcinoma four years after radical nephrectomy. A literature review is made on the cases described up to date in living patients and a pathogenic hypothesis established based on the theoretical dissemination routes for the cases of gastric location of the metastasis.

Metástasis gástrica de un adenocarcinoma renal. Hipótesis patogénica y revisión de la literatura / Gastric metastasis from renal cell carcinoma. Pathogenical hypothesis and literature revision

Los tumores gástricos secundarios constituyen una entidad clínica poco habitual, más aún si la localización del tumor primitivo es el riñón. Hasta la actualidad tan solo se han descrito 11 casos diagnosticados en vida. Se presenta un caso clínico de una mujer que presentó una hemorragia digestiva alta secundaria a la presencia de una metástasis gástrica de carcinoma de células renales cuatro años después de la nefrectomía radical. Se realiza una revisión bibliográfica de los casos descritos hasta la fecha en pacientes vivos y se establece una hipótesis patogénica de acuerdo a las teóricas rutas de diseminación para los casos de localización metastática gástrica

Secondary gastric tumours are very uncommon clinical entities and even more so when the site for the primary tumour is the kidney. Only 11 cases of life diagnosis have been described up to now. Contribution of one case report: a female patient presenting with upper GI tract haemorrhage secondary to gastric metastasis from renal cell carcinoma four years after radical nephrectomy. A literature review is made on the cases described up to date in living patients and a pathogenichy pothesis established based on the theoretical dissemination routes for the cases of gastric location of the metastasis

[Chronic liver disease associated with cystic fibrosis: energy expenditure at rest, risk factors, and impact on the course of the disease]. / Hepatopatía crónica asociada a fibrosis quística: gasto energético en reposo, factores de riesgo y repercusión en la evolución de la enfermedad.

INTRODUCTION AND GOALS: Cystic fibrosis is the most frequent recessive disease. There are various hepato-biliary alterations, of which the most important is the development of biliary obstruction and periportal fibrosis. The goal is to assess the influence of liver disease on the nutritional status, the progress of the disease and the associated risk factors. SCOPE: Nutrition Unit of the Gastroenterology Department at La Paz Children's Hospital. MATERIAL AND METHODS: Prospective longitudinal study with 53 patients assessed on three occasions over 3 years: at inclusion, after 1 year and after 3 years. Only 37 of them were followed-up for 3 years. A total of 111 measurements were taken, including analysis of body composition, energy expenditure, intake and energy losses as well as nitrogen balance. Simultaneously, respiratory function tests were performed and the presence of repeated acute respiratory problems was evaluated. RESULTS: 37 patients, 19 females and 18 males (mean age 13.04 years +/- 3.28). Twelve (32.43%) were diagnosed as having liver disease (mean age 12.16% +/- 3.86 SD, 11 males, 1 female), of whom 1 presented meconial ileum, 5 were homozygotic, 5 heterozygotic and the other two presented other mutations. Those with liver disease presented anthropometric parameters that were better than or similar to the patients without liver involvement (p NS). Mean Waterlow index in liver disease sufferers: 93.62% +/- 7.87 SD; without liver disease: 93.06% +/- 10.97 SD (p NS). Mean of LVEF in liver disease sufferers: 88.81 +/- 27.32 SD; without liver disease: 75.21 +/- 27.92 SD (p < 0.05). Mean FVC in liver disease sufferers: 95.38 +/- 22.92 SD; without liver disease: 83 +/- 23.7 SD (p < 0.05). Mean energy expenditure at rest/lean body mass in liver disease sufferers: 38.81 kcal +/- 7.26 SD; without liver disease: 42.36 kcal +/- f 6.91 SD (p < 0.05). CONCLUSIONS: The prevalence of chronic liver disease in patients with cystic fibrosis increases with age and is more frequent in males. Liver disease sufferers present a better evolution in pulmonary function and present less energy expenditure.

Hepatopatía crónica asociada a fibrosis quística: gasto energético en reposo, factores de riesgo y repercusión en la evolución de la enfermedad / Chronic liver disease associated with cystic fibrosis: energy expended at rest, risk factors and impact on the disease's progress

Introducción y objetivos: La fibrosis quística es la enfermedad recesiva más frecuente. Existen diferentes alteraciones hepatobiliares; la más importante es el desarrollo de obstrucción biliar y fibrosis periportal. El objetivo es valorar la influencia de la hepatopatía en el estado nutricional, la evolución de la enfermedad y los factores de riesgo asociados. Ámbito: Unidad de Nutrición del Servicio de Gastroenterología del Hospital Infantil La Paz. Material y métodos: Estudio longitudinal prospectivo con 53 pacientes valorados en tres momentos durante 3 años; al inicio, al año y a los 3 años. Solo 37 se siguieron los 3 años. Se realizan 111 mediciones que incluyen: análisis de la composición corporal, del gasto energético, de la ingesta y de las pérdidas energéticas así como balance nitrogenado. Simultáneamente se realizan pruebas de función respiratoria y se valora la presencia de reagudización respiratoria. Resultados: 37 pacientes, 19 mujeres y 18 varones (edad media 13,04 años ñ 3,28). Doce (32,43 por ciento) fueron diagnosticados de hepatopatía (edad media 12,16 años ñ 3,86 DS, 11 varones, 1 mujer) de los cuales 1 presentó íleo meconial, 5 eran homocigotos, 5 heterocigotos y los 2 restantes presentaban otras mutaciones. Los hepatópatas presentan parámetros antropométricos mejores o similares que los pacientes sin hepatopatía (p NS). Media del índice de Waterlow en hepatópatas: 93,62 por ciento ñ 7,87 DS; no hepatópatas: 93,06 por ciento ñ 10,97 DS (p NS). Media de FEV1 en hepatópatas: 88,81 ñ 27,32 DS; no hepatópatas: 75,21 ñ 27,92 DS (p < 0,05). Media de FVC en hepatópatas: 95,38 ñ 22,92 DS; no hepatópatas: 83 ñ, menos satisfactorios han sido los logros obtenidos en cuanto a su caracterización clínica. La prevalencia de la enfermedad hepática crónica en los pacientes con FQ varía según los criterios diagnósticos empleados. Se considera que los datos actuales sobre la prevalencia subestiman el riesgo real debido a la ausencia de marcadores diagnósticos de alta sensibilidad de enfermedad hepática en la FQ y a la cuestionable precisión de la histología8 la 23,7 DS (p < 0,05). Media del gasto energético en reposo/masa corporal magra en hepatópatas: 38,81 kcal ñ 7,26 DS; no hepatópatas: 42,36 kcal ñ 6,91 DS (p < 0,05).Conclusiones: La prevalencia de hepatopatía crónica en pacientes con fibrosis quística aumenta con la edad y es más frecuente en varones. Los pacientes hepatópatas tienen mejor evolución de la función pulmonar y presentan menor gasto energético (AU)

Introduction and goals: Cystic fibrosis is the most frequent recessive disease. There are various hepato-biliary alterations, of which the most important is the development of biliary obstruction and periportal fibrosis. The goal is to assess the influence of liver disease on the nutritional status, the progress of the disease and the associated risk factors. Scope: Nutrition Unit of the Gastroenterology Department at La Paz Children’s Hospital. Material and methods: Prospective longitudinal study with 53 patients assessed on three occasions over 3 years: at inclusion, after 1 year and after 3 years. Only 37 of them were followed-up for 3 years. A total of 111 measurements were taken, including analysis of body composition, energy expenditure, intake and energy losses as well as nitrogen balance. Simultaneously, respiratory function tests were performed and the presence of repeated acute respiratory problems was evaluated. Results: 37 patients, 19 females and 18 males (mean age 13.04 years ± 3.28). Twelve (32.43%) were diagnosed as having liver disease (mean age 12.16% ± 3.86 SD, 11 males, 1 female), of whom 1 presented meconial ileum, 5 were homozygotic, 5 heterozygotic and the other two presented other mutations. Those with liver disease presented anthropometric parameters that were better than or similar to the patients without liver involvement (p NS). Mean Waterlow index in liver disease sufferers: 93.62% ± 7.87 SD; without liver disease: 93.06% ± 10.97 SD (p NS). Mean of LVEF in liver disease sufferers: 88.81 ± 27.32 SD; without liver disease: 75.21 ± 27.92 SD (p < 0.05). Mean FVC in liver disease sufferers: 95.38 ± 22.92 SD; without liver disease: 83 ± 23.7 SD (p < 0.05). Mean energy expenditure at rest/lean body mass in liver disease sufferers: 38.81 kcal ± 7.26 SD; without liver disease: 42.36 kcal ±f 6.91 SD (p < 0.05). Conclusions: The prevalence of chronic liver disease in patients with cystic fibrosis increases with age and is more frequent in males. Liver disease sufferers present a better evolution in pulmonary function and present less energy expenditure (AU)