Recomendaciones del Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) sobre el cribado y tratamiento de la infección tuberculosa en pacientes con enfermedad inflamatoria intestinal

There is evidence that following the recommendations on screening and treatment of tuberculosis infection does not completely prevent the onset of tuberculosis in patients with inflammatory bowel disease. This fact, and the increasing use of new biologics and immunomodulators, has led the Spanish Group Working on Crohn's Disease and Ulcerative Colitis to update their recommendations for the prevention of tuberculosis in patients with inflammatory bowel disease. Diagnostic methods for latent tuberculosis infection, different scenarios in which screening is to be performed, strategies to reduce the risk of tuberculosis once biological treatment is initiated and chemoprophylaxis guidelines for latent tuberculosis infection are reviewed, as well as the management of active tuberculosis during biological treatment. Finally, there is a summary of the current recommendations within the paper and in an algorithm.     

Hepatitis B and C infection in patients undergoing biologic and targeted therapies for rheumatic diseases

Hepatitis B and C are common viral infections that affect more than 430 million population worldwide. In patients with rheumatic diseases, the prevalence of inactive/chronic hepatitis B infection ranges from 0.4% to 38% and that of past/resolved infection is much higher (7.3%–69%). The prevalence of hepatitis C infection in rheumatic disorders is less clear but probably lower than that of hepatitis B (1.7%–4%). With the increasing use of biologic and targeted disease-modifying antirheumatic drug therapies, reactivation of past and chronic hepatitis B and C infection is increasingly recognized, with presentation ranging from asymptomatic viremia to serious clinical hepatitis with liver failure. The concomitant use of effective antiviral therapies helps reduce the risk of hepatitis B reactivation and control of active hepatitis C infection. This article summarizes the prevalence and risk factors of hepatitis B and C reactivation in patients with rheumatic diseases undergoing biologic and targeted therapies, as well as the recommendations for screening, monitoring, and treatment of these infections.     

Infections and inflammatory bowel disease: Challenges in Asia

The diagnosis and management of inflammatory bowel disease (IBD) in Asia can be challenging as certain infections can mimic IBD and lead to a misdiagnosis. Colitis can be caused by bacterial infections, ileitis can result from Yersinia and Salmonella infections and ileocolonic ulcers can be seen in intestinal tuberculosis and amebiasis. In addition, cytomegalovirus and Clostridium difficile infection may mimic a flare of IBD and their presence is associated with an increased risk of colectomy and mortality. Because of the increasing use of corticosteroids, immunosuppressive drugs and biological agents the risk of opportunistic infection and the reactivation of latent infection including tuberculosis and hepatitis B, are also higher in IBD patients. Screening and prevention of infection, timely vaccination and the education of the patient is paramount before initiating immunosuppressive drugs. The role of the physician lies not only in the diagnosis and management of IBD but also in the ability to prevent, recognize and treat infections.     

Infectious mononucleosis in patients with inflammatory bowel disease under treatment with azathioprine

The use of immunomodulators for the treatment of inflammatory bowel disease is increasing. One of the most common adverse effects associated with this kind of drugs are infectious complications. In recent years, special attention has been paid to certain latent infections which, in patients under immunomodulatory therapy, can be reactivated and prove lethal. Consequently, preventive actions have been adopted, such as screening for hepatitis B virus and tuberculosis infection before starting these treatments. Primary infection with the Epstein-Barr herpesvirus is usually asymptomatic. However, this virus can have an aggressive course and even lead to the development of lymphoma. We report two cases of atypical infectious mononucleosis in patients with inflammatory bowel disease under azathioprine therapy and review the available evidence on the most appropriate therapeutic approach in this subset of patients.     

Mycobacteria and biological response modifiers: two sides of the relationship

With increasing use of biological response modifiers (BRMs) for various systemic inflammatory diseases there is a need to be vigilant about complications with the use of these therapies. It is important to have appropriate screening for the infections in patients requiring BRMs. However, many studies have reported benefits of certain BRMs in the treatment of infections such as tuberculosis as adjuncts. Continued research and technical advances in immunogenetics helps understand complex mechanisms in the usage of the BRMs. This article summarizes the different aspects of the relationship between mycobacterial infections and the use of various BRMs for inflammatory conditions.     

Preventing infective complications in inflammatory bowel disease

Over the past decade there has been a dramatic change in the treatment of patients with Crohn’s disease and ulcerative colitis,which comprise the inflammatory bowel diseases(IBD).This is due to the increasing use of immunosuppressives and in particular the biological agents,which are being used earlier in the course of disease,and for longer durations,as these therapies result in better clinical outcomes for patients.This,however,has the potential to increase the risk of opportunistic and serious infections in these patients,most of which are preventable.Much like the risk for potential malignancy resulting from the use of these therapies long-term,a balance needs to be struck between medication use to control the disease with minimization of the risk of an opportunistic infection.This outcome is achieved by the physician’s tailored use of justified therapies,and the patients’education and actions to minimize infection risk.The purpose of this review is to explore the evidence and guidelines available to all physicians managing patients with IBD using immunomodulating agents and to aid in the prevention of opportunistic infections.     

Serious infection during etanercept,infliximab and adalimumab therapy for rheumatoid arthritis: A literature review

The purpose of this review is to establish whether there is a significantly increased incidence of serious infections during treatment for rheumatoid arthritis (RA) with etanercept, infliximab or adalimumab, to determine the background risk of serious infection in RA patients without treatment with any biological therapy and to ascertain which organisms are involved in serious infections in RA patients while being treated with etanercept, infliximab or adalimumab. Randomised controlled trials (RCTs), meta‐analyses of RCTs, Cochrane reviews, national registry articles and case reports were identified using PubMed/MEDLINE, The Cochrane Library and Google Scholar. The medical subject heading “rheumatoid arthritis” was combined with “serious infection” or “infection” or “adverse drug events” with each of the three reference biological therapies separately: etanercept, infliximab and adalimumab. These electronic searches were limited to human studies, adult studies, those published in the last 10 years (2004–14) and in the English language. Studies which involved the tumor necrosis factor‐α inhibitors certolizumab pegol or golimumab were excluded. The background risk of serious infection appears to be approximately two‐fold more than non‐RA patients before any treatment with biological therapy. The national registries, which may represent the typical RA patient more accurately than clinical trials, suggest a small but significantly increased incidence of serious infection ranging 1.2–2.78 times that of control (treatment with methotrexate). Mycobacteria spp., Staphyloccus aureus, Listeria monocytogenes, Varicella zoster virus and Leishmania species (spp.) repeatedly appear in the case report literature and should be in the mind of the clinician faced with a serious infection in a RA patient with an unknown pathogen who is being treated with either etanercept, infliximab or adalimumab.     

Risks of immunosuppressive therapies including biologic agents in patients with rheumatic diseases and co-existing chronic viral infections

PURPOSE OF REVIEW: A number of chronic viral infections could be reactivated by immunosuppressive agents used in rheumatic diseases. In this review, we will focus on the complex effect of immunosuppressive agents, including biologic agents, on the natural course of chronic viral infections as well as an approach to the prevention and management of therapy-induced viral reactivation. RECENT FINDINGS: Chronic viral infections that are affected by immunosuppression in the setting of an underlying rheumatic disease include those due to hepatitis B virus, hepatitis C virus, or human immunodeficiency virus, and latent infections from Epstein-Barr virus, JC virus, or varicella zoster virus. The most recent data of the effects of immunosuppressive agents are reviewed, with special emphasis on the effects of biologic therapies (anti-tumor necrosis factor, anti-B cell), on these viral agents. SUMMARY: Clinicians should be aware of the risk for viral reactivation of an underlying chronic viral infection during immunosuppressive therapy. Despite the existence of such risk, the presence of chronic viral infection is not a contraindication to immunosuppressive therapy, given that appropriate pretherapy screening and close monitoring is applied.     

Infektionskomplikationen unter Biologika-Therapie bei Patienten mit rheumatoider Arthritis

The introduction of biological disease-modifying drugs (DMARDs) has substantially improved the treatment options for patients with rheumatoid arthritis. However, infectious complications represent the most common side effects of these drugs, including severe infections as well as rare opportunistic infections. Treating patients on biological DMARDs is therefore one of the biggest challenges in rheumatology care. The present review describes the current state of knowledge regarding frequency and type of infectious complications associated with biological DMARDs. The article focuses mainly on risk management, in particular on diagnosis and recurrence prevention of tuberculosis and reactivation of hepatitis B virus infection. Furthermore, we discuss the importance of vaccinations in primary disease prevention in patients with rheumatoid arthritis.     

What is the best way to manage screening for infections and vaccination of inflammatory bowel disease patients?

The use of biological agents and immunomodulators for inflammatory bowel disease(IBD) is associated with an increased risk of opportunistic infections, in particular of viral or bacterial etiology. Despite the existence of international guidelines, many gastroenterologists have not adopted routine screening and vaccination in those patients with IBD, which are candidate for biologic therapy. Available strategies to screen, diagnose and prevent bacterial and viral infections in patients with IBD prior to start biological therapy are discussed in this review.     

制定我国潜伏性结核感染全人群防控策略

加强潜伏性结核感染(latent tuberculosis infection,LTBI)人群的有效管理,是实现结核病防控目标的重要路径之一。目前,我国LTBI管理存在高危人群对结核病发病率贡献率偏低、发病风险特征尚未明确、现有筛查手段普遍存在局限性、预防性服药推广困难等问题。为改善上述现状,笔者提出LTBI全人群防控策略,通过加强全社会健康教育,尤其是国家政策引导及采用适宜在全人群中普及的公共卫生手段,降低疾病对全社会的危害。作为患者管理策略及高危人群策略的重要补充,科学可行的LTBI全人群管理策略,包括充分借助现阶段创新技术手段开展主动筛查、人群监测等措施,对于制定新时代我国结核感染控制规划和政策,逐步实现“终止结核病”战略目标将具有重要意义。     

Management of chronic hepatitis B in children: An unresolved issue

Although a rather benign course of chronic hepatitis B virus (HBV) infection during childhood has been described, 3–5% and 0.01–0.03% of chronic carriers develop cirrhosis or hepatocellular carcinoma before adulthood. Considering the whole lifetime, the risk of hepatocellular carcinoma rises to 9–24% and the incidence of cirrhosis to 2–3% per year. The aim of this article is to review the current knowledge regarding the natural history and treatment of chronic hepatitis B in children and to focus on critical aspects and unresolved questions in the management of childhood HBV infection. A literature search was carried out on MEDLINE, EMBASE, and Web of Science for articles published in English in peer‐reviewed journals from January 1980 to February 2013. The search terms used included “Hepatitis B virus infection,” “children,” “HBV,” “interferon,” “lamivudine,” “adefovir,” “entecavir,” and “tenofovir.” Articles resulting from these searches and relevant references cited in the articles retrieved were reviewed. The current goals of therapy are to suppress viral replication, reduce liver inflammation, and reverse liver fibrosis. Therapeutic options for children are currently limited, and the risk for viral resistance to current and future therapies is a particular concern. Based on the data available at this time, it is the consensus of the panel that it is not appropriate to treat children in the immune‐tolerant phase or in the inactive carrier state. For children in the immune‐active or reactivation phases, liver histology can help guide treatment decisions. Outside of clinical trials, interferon is the agent of choice in most cases; currently, available nucleoside analogs are secondary therapies.     

Prescreening versus empirical immunization for hepatitis A in patients with chronic liver disease: a prospective cost analysis

OBJECTIVES: There are few prospective studies estimating the prevalence of hepatitis A in chronic liver disease patients. Furthermore, there are minimal cost-comparative data as to whether or not screening for hepatitis A exposure before immunization is an effective fiscal strategy. The objectives of this study were to determine the prevalence of prior hepatitis A infection and to perform a prospective cost analysis for hepatitis A immunization in patients with chronic liver disease. METHODS: This is a prospective cohort study of 100 patients with chronic liver diseases. Patients were screened for potential risk factors for hepatitis A including history of jaundice, socioeconomic status, birth origin, and ethnic background. Each patient underwent testing for evidence of prior infection using an ELISA. Seronegative patients then went on to receive an immunization series. Cost analysis of vaccination without prescreening (universal strategy) was compared to cost analysis of prescreening and selective immunization of those without prior infection (selective strategy). RESULTS: Fifty-three patients (53%) had serological evidence of prior hepatitis A infection (95% CI = 43-63%). Of the risk factors assessed, foreign birth was associated with prior hepatitis A exposure (p = 0.0002). Cost analysis revealed that prescreening for hepatitis A before vaccination was cost saving given the current prevalence. CONCLUSIONS: The seroprevalence of hepatitis A in those with chronic liver diseases was 53%. Cost analysis revealed that screening for hepatitis A before immunization is cost saving, and this strategy should be applied to follow current vaccination guidelines.     

Diabetes mellitus and immunization

Principles of prevention of infectious diseases have been known for several thousands of years. One of the most significant tools of infection prophylaxis is immunization. Vaccines containing thymus-dependent antigens produce massive and complex immune response and feature immunologic memory. That is why they can successfully protect patients with diabetes. Lately, it has been thought by general public and even experts that application of vaccines within national immunization programmes is one of the etiopathogenetic factors in the development of type 1 diabetes mellitus (DM). However, analysis of extensive studies performed by the experts of the Institute for Vaccine Safety proved that there is no positive or negative impact of immunization on the development of type 1 diabetes mellitus. The basic vaccinations recommended for diabetics include immunizations against influenza, pneumococcal infections, tetanus and viral hepatitis B. Other vaccines are administered only after individual assessment of benefits and risks for the diabetic patient. Most often, these are vaccinations against viral hepatitis A, tick-borne encephalitis, meningococcal infections and other infections that put in risk diabetic patients travelling abroad.     

风湿性疾病患者结核分枝杆菌潜伏感染激活机制的研究进展

风湿性疾病是一组自身免疫与炎症性疾病,其主要特征是免疫系统的紊乱。同时,随着各种免疫抑制剂、生物制剂在风湿性疾病中的应用,机体的免疫状态大大改变,从而使结核分枝杆菌潜伏感染激活的风险增加。为更好地了解风湿性疾病患者结核分枝杆菌潜伏感染激活的机制,以期进一步降低结核病的发生率和患者病亡率,笔者从结核感染的免疫反应机制、风湿性疾病患者结核分枝杆菌潜伏感染激活的机制、增加结核分枝杆菌潜伏感染激活风险的治疗药物等方面进行综述,以供参考。     

Prevalence of comorbidities and evaluation of screening in Chinese patients with spondyloarthritis

The aim of the study was to determine whether the presence of spondyloarthritis (SpA) is associated with particular comorbidities and evaluate the prevalence of comorbidities, risk factors, and monitoring status in China. Three hundred forty-six patients fulfilling ASAS criteria for SpA were recruited from the Third Affiliated Hospital of Sun Yat-sen University. The prevalence of comorbidities and percentage of patients optimally monitored for comorbidities were calculated. The most frequent comorbidities were osteoporosis (31.0%) and hepatitis B virus infection (18.5%). Only 1 patient was found to have active tuberculosis. Several cancer screenings were performed in very few patients. Among 45 patients ever exposed to a biological DMARDs, 35 (77%) and 36 (80%) underwent a screening test for viral hepatitis and tuberculosis. Among patients without a history of hypertension, elevated blood pressure was detected in 5.8% of the patients. Hyperglycemia and hyperlipidemia were also found in patients during the study. One hundred twenty-two (35.3%) of the 346 patients never had either calcium or vitamin D for prevention of osteoporosis. Patients with SpA have high risks of comorbidities but have not monitored properly. More attention should be paid for systematic screening and an early detection of comorbidities in patients with SpA.     

Insufficient Knowledge of Korean Gastroenterologists Regarding the Vaccination of Patients with Inflammatory Bowel Disease

Background/Aims

There is an increased risk for inflammatory bowel disease (IBD) patients to develop infections due to the use of immunomodulators and biologics. Several infections are preventable by immunizations. This study investigated the knowledge and awareness of Korean gastroenterologists regarding the vaccination of patients with IBD.

Methods

A self-reported questionnaire was sent by e-mail to the faculty members of tertiary hospitals. Gastroenterologists were asked ten questions regarding the immunization of patients with IBD. A total of 56 gastroenterologists completed the questionnaire.

Results

A majority of gastroenterologists (>60%) had rarely or never recorded an immunization history from their patients with IBD. Moreover, 50% to 70% of the gastroenterologists did not know that live vaccines should be avoided in immunosuppressed patients. The most commonly mentioned resistance to vaccinations was "the lack of concern and knowledge regarding vaccination." Gastroenterologists more frequently asked about the immunization history of influenza, pneumococcal, hepatitis A, and hepatitis B vaccines and recommended these vaccines more often than others.

Conclusions

Korean gastroenterologists'' awareness and knowledge regarding the vaccination of patients with IBD were very poor. Intensive educational programs on immunization guidelines directed toward gastroenterologists who care for patients with IBD are required to ensure that these patients receive the necessary vaccinations.     

Nosocomial infections in immunocompromised children

Within the last decade several advances in medicine have resulted in extended longevity of children with cancer, cystic fibrosis, certain congenital immunodeficiency disorders, chronic renal diseases and aplastic anemia. Forthwith, the population of such immunocompromised children has increased and accounts for a greater portion of the hospital census than heretofore. To avoid emotional, infectious and financial burdens of hospitalization, efforts have been successful in developing ambulatory outpatient programs within specialized centers. Although infection control policies have been reasonably well-established for the hospitalized inpatient, policies for the hospital outpatient are lacking. Investigations into the problems of “nosocomial outpatient infections” are needed.Accomplishments in recent years in the control of nosocomial infections include the development of preparations for passive immunization for varicella-zoster virus and hepatitis B virus exposures and the application of certain antibiotic regimens for prophylaxis. Currently a vaccine is under study for active immunization to varicella with possible efficacy for exposed susceptible persons.It is obvious that the proportion of children at increased risk for infection in the hospital environment will continue to increase.