High Incidence Of Herpes Zoster Research Articles

CD4/CD8 Ratio: An Independent Predictor of Herpes Zoster in Patients With Autoimmune Inflammatory Rheumatic Diseases.

A higher incidence of herpes zoster (HZ) was found in people with decreased cell-mediated immunity. However, the relationship between cellular immunity and HZ infection in patients with autoimmune inflammatory rheumatic diseases (AIRD) remains elusive. To investigate the role of CD4/CD8 ratio in patients with AIRD and HZ. This case-control study compared AIRD patients with and without HZ. We chose 70 AIRD patients with HZ as the experimental group and 140 AIRD patients without HZ as the control group. The clinical and laboratory findings were assessed in each trial participant. The CD4/CD8 ratio (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.10-0.49) was independently associated with the occurrence of HZ after adjusting for various confounders. Nonlinear analysis has unveiled a more profound nonlinear relationship between the CD4/CD8 ratio and the occurrence of HZ in patients with AIRD. The OR of HZ increased with a decreasing CD4/CD8 ratio before the turning point of 2. The adjusted regression coefficient was 0.14 (95% CI, 0.05-0.37, p<0.0001) for CD4/CD8 ratio less than 2. The CD4/CD8 ratio was expected to be a very promising quantitative biomarker for predicting the risk of developing HZ in patients with AIRD.

JAK inhibition in the treatment of inflammatory rheumatic diseases.

The most common immune-mediated inflammatory rheumatic diseases, rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis and have reached significant advances in recent years with the introduction of biological therapies against cytokines and immune cells, but also against intracellular enzymes, specifically Janus kinases (JAKs). Intracellular JAK signalling is activated by binding of various cytokines or growth factors to the respective cellular receptors, allowing the activation of STAT (Signal Transducers and Activators of Transcription) transcription factors and ultimately the transcription of genes with important roles during the innate and adaptive immune response. Four Janus kinases have been described: JAK1, JAK2, JAK3 and tyrosine kinase-2 (TYK2). Four JAK inhibitors (tofacitinib, baricitinib, upadacitinib and filgotinib) are currently approved for the treatment of rheumatoid arthritis, and some for the treatment of psoriatic arthritis and axial spondyloarthritis. JAK inhibitors have varying selectivity against individual kinases. Some JAK inhibitors are being tested in other rarer systemic connective tissue diseases. The general advantages of JAK inhibitors are oral administration, rapid onset of action, and efficacy in monotherapy. The safety profile of JAK inhibitors compared with biologic therapy appears to be comparable, with a higher incidence of herpes zoster, and an increased incidence of major cardiovascular disease, thromboembolic complications, and cancer in at-risk patients is discussed. The aim of this paper will be to summarize the latest findings on JAK inhibitors in approved indications for the most common rheumatic diseases.

High Incidence of Herpes Zoster in Patients Using Ruxolitinib for Myeloproliferative Neoplasms: Need for Prophylaxis.

High Incidence of Herpes Zoster in Patients Using Ruxolitinib for Myeloproliferative Neoplasms: Need for Prophylaxis.

Cost-Effectiveness Analysis of Vaccination With Recombinant Zoster Vaccine Among Hematopoietic Cell Transplant Recipients and Persons With Other Immunocompromising Conditions Aged 19 to 49 Years

This study aimed to estimate the cost-effectiveness of the use of recombinant zoster vaccine (RZV) (Shingrix), which protects against herpes zoster (HZ), among immunocompromised adults aged 19 to 49 years, as a contribution to deliberations of the Advisory Committee on Immunization Practices. Hematopoietic cell transplant (HCT) recipients experience a high incidence of HZ, and the efficacy of RZV in preventing HZ has been studied in clinical trials. The cost-effectiveness model calculated incremental cost-effectiveness ratios that compared vaccination with RZV with a no vaccination strategy among adults aged 19 to 49 years. Costs and outcomes were calculated until age 50 years using the healthcare sector perspective and summarized as cost per quality-adjusted life-year (QALY) gained. The base case represents HCT recipients, with scenario analyses representing persons with other immunocompromising conditions, including hematologic malignancies, human immunodeficiency virus, and autoimmune and inflammatory conditions. Uncertainty was investigated using univariate, multivariate, and probabilistic sensitivity analyses. Base-case results indicated vaccination with RZV would avert approximately 35% of HZ episodes and complications, while saving approximately 11% of net costs. Compared with no vaccination, vaccination of HCT recipients with RZV generated cost-savings (ie, lower costs and improved health) in the base case and in 81% of simulations in the probabilistic analysis. In scenario analyses, vaccination cost US dollar ($) 9500/QALY among patients with hematologic malignancies, $79 000/QALY among persons living with human immunodeficiency virus, and $208 000/QALY among persons with selected autoimmune and inflammatory conditions. Generally favorable economic estimates supported recommendations for vaccination of immunocompromised adults with RZV to prevent episodes of HZ and related complications.

Association between vitamin D and incident herpes zoster: a UK Biobank study.

BackgroundVitamin D has immunomodulatory effects, but any association with herpes zoster (HZ) is unclear.AimTo explore the association between vitamin D status and risk of incident HZ in adults in the UK.Design and settingA cohort study involving participants of UK Biobank (a database containing the health information from half a million individuals) across England, Wales, and Scotland, who had at least one vitamin D testing result with linked primary care electronic health records.MethodThe primary exposure was vitamin D status, categorised as deficient (<25 nmol/L), insufficient (25–49 nmol/L), or sufficient (≥50 nmol/L). The secondary exposures were self-reported vitamin D supplementation at baseline assessment and vitamin D prescription records. The outcome was diagnosed incident HZ, identified from linked primary care or hospital inpatient records. Weibull regression was used, adjusting for potential confounders, including demographic factors, comorbidities, and immunosuppression.ResultsIn total, 177 572 eligible participants were included in the analysis, with a mean follow-up time of 10.1 years (standard deviation 1.9 years). No evidence showed that low vitamin D was associated with a higher incidence of HZ, compared with people with sufficient vitamin D (deficient: adjusted hazard ratio [HR] 0.99, 95% confidence interval [CI] = 0.90 to 1.10; insufficient: HR 1.03, 95% CI = 0.96 to 1.10). No evidence was found that supplementing vitamin D or receiving vitamin D prescription was associated with HZ incidence (supplementation: HR 0.88, 95% CI = 0.67 to 1.16; prescription: HR 1.11, 95% CI = 0.91 to 1.34).ConclusionNo association of vitamin D status, supplementation, or prescription with incident HZ was observed. No evidence supported vitamin D supplementation as a strategy to prevent HZ.

Herpes Zoster in rheumatoid arthritis patients receiving tofacitinib, a single center experience from Taiwan.

In clinical trials of tofacitinib for rheumatoid arthritis (RA), Japanese and Korean patients had higher incidence of herpes zoster (HZ) than subjects from elsewhere; however, post-market data from Asia are lacking. Hence, we investigated the incidence of HZ and its risk factors in Taiwanese RA patients receiving tofacitinib. At a medical center in Taichung, Taiwan, we enrolled patients with active RA treated with tofacitinib between January 4, 2015 and December 9, 2017, following unsuccessful methotrexate therapy and no tofacitinib exposure RA patients as a control group. Demographic characteristics, interferon-gamma levels, and lymphocyte counts were compared. Among 125 tofacitinib-treated RA patients, 7 developed HZ, an incidence rate of 3.6/100 person-years. Patients with HZ had shorter disease duration than those without, but higher frequency of prior HZ. Baseline interferon-gamma levels and HLA-DR+ activated T cell counts were positively correlated and significantly lower in patients with HZ than without. Strikingly, 5/7 HZ cases occurred within 4 months of starting tofacitinib therapy. Incidence of HZ in tofacitinib-treated Taiwanese RA patients is lower than rates in Japan or Korea, and commensurate with the global average. HZ may occur soon after commencing tofacitinib therapy. The role of interferon-gamma and activated T cells in tofacitinib-related HZ deserves further investigation.

High Incidence of Herpes Zoster After Cord Blood Hematopoietic Cell Transplant Despite Longer Duration of Antiviral Prophylaxis.

Cord blood transplant (CBT) recipients have a high incidence of herpes zoster (HZ) in the context of short-term peritransplant antiviral prophylaxis. In 2009, international guidelines recommended HZ prophylaxis for at least 1 year after hematopoietic cell transplant. The impact of longer-term antiviral prophylaxis on HZ incidence after CBT is unknown. We retrospectively analyzed varicella zoster virus (VZV)-seropositive CBT recipients who were transplanted between 2006 and 2016. We abstracted HZ events and other variables for up to 5 years post-CBT. We calculated the cumulative incidence of HZ and used Cox proportional hazards regression to identify variables associated with HZ. The study cohort consisted of 227 patients. Among 1-year survivors, 91% were still receiving prophylaxis, for a median duration of 20.6 months. HZ occurred in 44 patients (19%) at a median of 23.6 months. The cumulative incidence of HZ by 1 year after CBT was 1.8% (95% confidence interval [CI], .1%-4%), but increased to 26% (95% CI, 19%-33%) by 5 years. In a multivariable analysis, acute graft-vs-host disease was associated with increased risk, whereas antiviral prophylaxis was associated with reduced risk for HZ (adjusted hazard ratio, 0.19 [95% CI, .09-.4]). There was no association between CD4+ T-cell counts at 1 year post-CBT and subsequent risk for HZ. We found a high incidence of HZ after CBT despite antiviral prophylaxis for > 1 year. Based on these findings, we suggest longer duration of prophylaxis for HZ after CBT. Compliance with antiviral prophylaxis, VZV-specific immune monitoring, and vaccination to mitigate HZ after CBT also require further study.

Risk of herpes zoster in the Japanese population with immunocompromising and chronic disease conditions: Results from a claims database cohort study, from 2005 to 2014.

Older adults, women and patients with immunocompromised (IC) or chronic medical conditions have a higher incidence of herpes zoster (HZ) and are at higher risk of developing HZ-associated complications such as postherpetic neuralgia. The incidence rates of HZ in various IC and chronic conditions have been previously reported in a retrospective cohort study using claims data from Japanese adults. Here, we report further analyses from this cohort using univariate and multivariable Cox regression to estimate crude and adjusted hazard ratios (HRs) associated with different IC and chronic conditions. After adjusting for multiple covariates (age, sex and other coexisting medical conditions), the risk of HZ was higher in women (HR, 1.14 [95% CI, 1.11-1.17]), irrespective of age and increased with increasing age, being substantially higher in patients aged 65years or older (HR, 3.28 [95% CI, 3.07-3.49]) when compared with those aged 18-29years. The highest HRs were observed for the following specific IC conditions; hematopoietic stem cell transplant recipients (HR, 9.85 [95% CI, 6.80-14.28]), hematological malignancy (HR, 3.22 [95% CI, 2.54-4.09]), systemic lupus erythematosus (HR, 2.46 [95% CI, 1.45-4.15]) and inflammatory bowel disease (HR, 1.59 [95% CI, 1.14-2.21]). For most other IC and chronic medical conditions, a higher risk was also apparent though of a smaller magnitude (HRs ranging from 1.2 to <1.5). These results corroborate our previous findings and demonstrate an increased risk of HZ associated with different IC and chronic conditions.

High Incidence of Herpes Zoster after Cord Blood Hematopoietic Cell Transplant Despite Longer Duration of Antiviral Prophylaxis

Introduction Herpes zoster (HZ) after hematopoietic cell transplant (HCT) is a well-known complication with a peak incidence during the first year post-HCT. Cord blood transplant (CBT) recipients are at increased risk for viral infections and historically have a cumulative incidence of HZ approaching 80% by 2.5 years in the context of short-term peri-HCT antiviral prophylaxis. In 2009, international guidelines for prevention of infections after HCT recommended maintaining HZ prophylaxis for at least 1 year after HCT. We retrospectively studied the impact of longer-term antiviral prophylaxis on the incidence of HZ after CBT. Methods Between 2006 and 2016, we performed 360 CBT at our Institution. Patients who were seronegative for varicella zoster virus (VZV) or received the live varicella vaccine (i.e. Varivax®) pre-CBT without a history of chickenpox or HZ were excluded. From 2006-2008, CBT recipients received acyclovir (ACV) 800 mg BID or valacyclovir (VACV) 500 mg BID for HSV and VZV prophylaxis. From 2008-2016, patients who were CMV seropositive received higher-dose prophylaxis with VACV 2g TID through day +100. Before 2009, institutional guidelines recommended to continue prophylaxis until the end of immunosuppression; after 2009, prophylaxis was recommended for at least 1 year and until 8 months after immunosuppression ends. For patients discharged from our center, data were collected through standardized questionnaires and medical records. We abstracted HZ events and other variables for up to 5 years post-CBT. We calculated the cumulative incidence of HZ after CBT, treating death and second HCT as competing risk events. Variables were evaluated for an association with development of HZ using Cox proportional hazards regression; those of biological interest and with a P value ≤ 0.3 in univariable analyses were considerate for multivariable model. Results The study cohort consisted of 227 CBT recipients with a median follow up of 25.4 months (interquartile range [IQR], 6.8 - 49). Follow up time was truncated at the time of death (n=113), second HCT (n=13) or last available records (n=32). Cohort characteristics are shown in Table 1. Among 1-year survivors, 91% were still receiving prophylaxis for a median duration of 20.6 months post-CBT (IQR, 14.1 - 29.4). HZ occurred in 44 patients (19%) at a median of 23.6 months (IQR, 16.1 - 30.3). Most patients (n=31/44, 70%) were not taking antiviral prophylaxis when HZ developed. The cumulative incidence of HZ by 1-year post-CBT was low (1.8%; 95% CI, 0.1%-4%) but increased starting from the second year and reached 26% (95% CI, 19%-33%) by 5 years (Figure 1). Disseminated HZ occurred in 5 cases (11%), and post-herpetic neuralgia occurred in 14 cases (31.8%). Of the 13 HZ episodes that occurred in patients reportedly taking antiviral prophylaxis, 6/13 had clear documentation of ongoing antiviral prophylaxis and 5/13 were still receiving immunosuppressive treatment for graft-versus-host disease (GvHD). All patients responded to antiviral treatment, which consisted of ACV (n=18), VACV (n=16), and famciclovir (n=1). In a multivariable analysis, patients who received myeloablative conditioning or had acute GvHD grades 2-4 had a higher risk of HZ, whereas the use of antiviral prophylaxis was associated with a lower risk of HZ (Table 2). Among 35 patients who discontinued prophylaxis before completing immunosuppressive therapy, 28.5% developed HZ. We found no association between CD4+ T cell counts at 1-year after-CBT and HZ risk. Conclusions In this cohort of 227 CBT recipients with up to 5 years of follow up, the cumulative incidence of HZ was 26% at 5 years, despite antiviral prophylaxis for &amp;gt;1 year in the majority of patients. Furthermore, these patients had high rates of post-herpetic neuralgia and disseminated VZV. Antiviral prophylaxis protected against HZ but there were breakthrough cases. Given that a high number of patients interrupted prophylaxis while still receiving immunosuppressants, adherence to antiviral prophylaxis should be emphasized by health care providers. Based on our findings, the lack of alternative prophylactic strategies at this time, and the safety of ACV/VACV, longer duration of prophylaxis should be considered, especially in patients with ongoing immunosuppression. Recent data demonstrating the safety and efficacy of the HZ subunit vaccine after autologous HCT support future study of HZ vaccination after allogeneic HCT. Disclosures Delaney: Nohla Therapeutics: Employment, Equity Ownership; Biolife Solutions: Membership on an entity's Board of Directors or advisory committees. Boeckh:Chimerix: Research Funding; GSK: Other: Personal fees; GSK: Research Funding; Merck: Research Funding; Merck: Other: Personal fees; Clinigen: Other: Personal fees. Milano:ExCellThera: Research Funding; Amgen: Research Funding. Hill:Takeda: Other: research support; Karius: Other: research support; Amplyx: Consultancy; Nohla Therapeutics: Consultancy, Other: research support.

Safety of cladribine tablets in the treatment of patients with multiple sclerosis: An integrated analysis

Treating patients with relapsing multiple sclerosis (MS) with cladribine tablets (two times 4 or 5 days of treatment each year for 2 years) results in long-lasting efficacy, with continued stability in many patients for 4 or more years. Safety and tolerability outcomes from individual clinical studies with cladribine tablets have been reported previously. Report safety data from an integrated analysis of clinical trials and follow-up in patients with MS to further characterize the safety profile of cladribine tablets. Data for patients treated with cladribine tablets 10 mg (MAVENCLAD®; 3.5 mg/kg cumulative dose over 2 years, referred to as cladribine tablets 3.5 mg/kg) as monotherapy (n = 923) or placebo (n = 641) in Phase III clinical trials (CLARITY, CLARITY Extension and ORACLE-MS) and followed up in the PREMIERE registry were aggregated (Monotherapy Oral cohort). To better characterize rare events, additional data from earlier studies which involved the use of parenteral cladribine in patients with MS, and the ONWARD study, in which patients were given cladribine tablets in addition to interferon (IFN)-β or placebo plus IFN-β were included in an All Exposed cohort (cladribine, n = 1926; placebo, n = 802). Adjusted adverse events incidences per 100 patient-years (Adj-AE per 100 PY) were calculated for the integrated analyses. The incidence rate of treatment-emergent adverse events (TEAEs) in the Monotherapy Oral cohort was 103.29 vs. 94.26 Adj-AEs per 100 PY for placebo. TEAEs that occurred more frequently with cladribine tablets were mainly driven by the TEAEs of lymphopenia (Adj-AE per 100 PY 7.94 vs. 1.06 for placebo) and lymphocyte count decreased (Adj-AE per 100 PY 0.78 vs. 0.10 for placebo) as anticipated due to the mode of action of cladribine. An increase in TEAE incidence rate was also observed in the cladribine tablets 3.5 mg/kg group vs. placebo for herpes zoster (Adj-AE per 100 PY 0.83 vs. 0.20, respectively). There were no cases of systemic, serious disseminated herpes zoster attributed to treatment with cladribine tablets. In general there was no increase in the risk of infections including opportunistic infections with cladribine tablets versus placebo, except for herpes zoster. Periods of severe lymphopenia (< 0.5 × 109 cells/L) were associated with an increased frequency of infections, but the nature of these was not different to that observed in the overall patient group treated with cladribine tablets 3.5 mg/kg. Within the constraints of a limited sample size, malignancy rates in the overall clinical program for cladribine in MS did not show evidence of an increase compared to placebo-treated patients and there was no increase in the incidence of malignancies over time in cladribine-treated patients. The AE profile for cladribine tablets 3.5 mg/kg as a monotherapy has been well-characterized in a pooled population of patients from early to more advanced relapsing MS. There was no increased risk for infections in general except for a higher incidence of herpes zoster. Lymphopenia was amongst the most frequently observed TEAEs that occurred at a higher incidence with cladribine relative to placebo. There was also no increase in malignancy rates for cladribine relative to placebo.

Varicella-zoster virus-specific cell-mediated immunity and herpes zoster development in multiple myeloma patients receiving bortezomib- or thalidomide-based chemotherapy

The incidence of herpes zoster is substantial during bortezomib treatment in patients with multiple myeloma (MM). This study aimed to elucidate the effect of chemotherapy with or without bortezomib in MM patients on their herpes zoster incidence and varicella zoster virus (VZV)-specific cell-mediated immunity (CMI). Peripheral blood mononuclear cells were collected at baseline and after 1 month of bortezomib-based or thalidomide-based chemotherapy and then analyzed using VZV-specific interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assay. The clinical data from these patients were analyzed in relation to the ELISPOT results. Of 58 patients analyzed, 39 patients received bortezomib and the other 19 patients, thalidomide. Among them, 5 patients developed herpes zoster during chemotherapy; all 5 were being treated with the bortezomib-based regimen and were not receiving prophylactic anti-viral agents. The median onset of herpes zoster was 32 days (range, 15-95 days) from the initiation of chemotherapy. Among patients who received bortezomib therapy, acyclovir prophylaxis significantly reduced the risk for herpes zoster (100-day cumulative incidence, 0% vs. 49.5%; p<0.001). Spot-forming cell (SFC) counts in the IFN-γ ELISPOT assay decreased from baseline after bortezomib (p=0.011) or thalidomide (p=0.096) treatment. Patients with baseline SFCs greater than 20/10(6) mononuclear cells exhibited significantly higher incidence of herpes zoster (100-day cumulative incidence, 34.8% vs. 0%; p=0.040). Bortezomib treatment significantly reduced VZV-specific CMI, and high baseline SFC counts in patients receiving this treatment without acyclovir prophylaxis were associated with a significantly increased risk for herpes zoster.

Risk Factor and Prevention of Postherpetic Neuralgia.

Herpes zoster (HZ) and postherpetic neuralgia (PHN) are common diseases in a pain clinic. In Korea, the rate of clinical visits due to the incidence of herpes zoster was 7.93-12.54/1000 annually [1]. PHN is a painful neuropathy and the most common complication of HZ. A complete recovery from PHN is difficult for doctors despite of proper HZ treatment. In spite of the treatment, some patients suffered from severe PHN for several years. Therefore, the most important aspects are the risk factor of PHN and the method of prevention of PHN. In this issue of the Korean Journal of Pain (KJP), Jung et al. [2] reported the incidence of HZ in Cheonan, Korea. The results show that patients 50 years and older have a higher incidence of HZ, and the most common site of HZ was the thoracic nerve (47.9%), followed by the trigeminal nerve (21.4%). The incidence rate was similar to the affected site of PHN (thoracic area: 52.9%, trigeminal area: 15.6%) in Korea [3]. In patients who suffer from HZ, the risk factors of PHN are old age, presence of a painful prodrome, severe pain of HZ, severe rash, and immuno-compromised status [4,5,6]. In patients with HZ over 60 years, up to 25% progressed to PHN [7]. The proportion of PHN increases steadily from young ages up to 80-84 years [8]. Therefore, patients who are elderly and possess the risk factor with HZ must undergo more intensive treatment. The main treatment of HZ is medication and interventional therapy. Taking antiviral medication beginning within 72 hrs of rash onset is usually recommended [7,9,10]. Two meta-analyses suggest that the antiviral medication can reduce the overall duration of pain and incidence of PHN [11,12]. Epidural injection with a steroid within 2 months of HZ development is also recommended for the prevention of PHN [13]. In the previous survey of Korea, epidural injection was the most commonly performed interventional treatment in PHN patients [3]. Other interventions such as paravertebral block, peripheral block and sympathetic block are clinically effective for the treatment of HZ and PHN. For evidence-based medicine of interventional treatment of HZ and PHN, the investigations of randomized controlled trials regarding the interventions will be necessary. In this issue, Jeon et al. [10] described the prevention and treatment of HZ and PHN. They mention that vaccination against varicella zoster virus (VZV) can be the first line for the prevention of HZ and PHN. A previous review article reported that vaccination of VZV reduced morbidity from HZ and PHN [14]. Vaccination of VZV reduced the occurrence of herpes zoster by approximately 70% in individuals aged 50-59 years old [15]. In persons 60 years or older, the vaccination reduced the burden of illness from HZ by 61.1% and the risk of PHN by 66.5% [16]. Therefore, the vaccination of patients over 50 years old can be effective for the prevention of HZ and PHN. Although PHN is difficult to treat, early and intensive treatment of patients with HZ can reduce the occurrence of PHN. In healthy elderly people, a vaccination of VZV can also decrease the incidence of HZ and PHN.

(319) - Boosting the Adaptive Immune Response Prevents the High Incidence of Herpes Zoster After Lung or Heart Transplantation

(319) - Boosting the Adaptive Immune Response Prevents the High Incidence of Herpes Zoster After Lung or Heart Transplantation

Should we establish standards of care for management of elderly patients with inflammatory bowel disease?

lderly patients with inflammatory bowel disease (IBD) have poorer outcomes than their younger counterparts with increased inpatient mortality rates, infection rates, lymphoma rates (1), and intolerance to immunosuppressive agents or tumour necrosis factor inhibitors (TNFi) (2). These may lead to hesitancy in prescribing effective immunosup- pressive drugs and TNFi to elderly patients, especially in individuals with comorbid conditions. Overuse of corticosteroids, however, has significant deleterious effects in elderly patients including osteopor- osis, hypertension, diabetes, ocular complications, infections and postsurgical complications. Some elderly patients with IBD may also have very indolent disease and it is important not to overtreat them. Several studies, including the report by Stepaniuk et al (3) in the current issue of the Journal (pages 273-277), have clearly shown that elderly patients receive less TNFi and less immunosuppressive drugs than their younger counterparts with IBD (4). While whether such undertreatment contributes to poorer outcome and complications in elderly patients still requires robust evidence, it is also of concern that elderly patients may be treated and monitored less rigorously and objective end points, such as mucosal healing, may never be reached. Introduction of newer therapies, such as the integrin inhibitor vedol- izumab, may offer potentially certain safety advantages. TNFi may also be considered in this population as monotherapy rather than combination therapy in the presence of comorbid conditions such as chronic obstructive airways disease. Rapid control of more severe disease is essential to prevent increased morbidity and complications in elderly individuals. Several areas of management of IBD in elderly patients require specific attention (Box 1). These include establishment of diagnosis by robust exclusion of several conditions such as colon cancer, infections, especially Clostridium difficile, ischemic colitis, diverticular colitis and angiodysplasia. Monitoring by regular use of C-reactive protein, fecal calprotectin, complete blood count and liver function tests is necessary to avoid the necessity of frequent invasive investigations and avoid hematological or other complications. Transabdominal ultrasonography for distal ileal Crohn disease may be a very useful noninvasive monitor- ing modality because it is well tolerated. Endoscopic surveillance to detect dysplasia may be especially challenging in elderly patients due to the high prevalence of diverticular disease and polypoid lesions leading to difficulty in deciding on local endoscopic resection strategies (5) versus panproctocolectomy with potentially increased morbidity. It is also important to vaccinate elderly patients against common infective preventable diseases and be aware of the high incidence of herpes zoster. The use of steroid-sparing agents, such as azathioprine, methotrexate and TNFi, is important in elderly patients to avoid excessive use of steroids in moderate to severe IBD and ensure mucosal healing. Finally, inpatients need careful prophylaxis against thromboembolism, vigilance against nosocomial infections and surgery if required in a timely manner before advanced disease, poor nutrition and infections lead to postopera- tive complications and poor outcome including mortality. Elderly patients are often troubled by fecal incontinence after pouch surgery and a permanent ileostomy is often a preferred approach. However, elderly patients with adequate sphincter function may do well after pouch sur- gery. Multidisciplinary management of these elderly patients is espe- cially important given the comorbid conditions that are often present. While there are many guidelines and an increasing number of standards of care to optimize management of IBD, there are no specific guidelines for comprehensive management of elderly patients with IBD. This appears to be an omission that requires attention by national and international organizations. Many of the issues in the elderly population also require further generation of evidence because these patients form only a small fraction of patients in clinical trials. eDItorIal

High incidence of herpes zoster after lung transplantation

According to Law 91/1999, art. 18, in Italy, health care professionals and administrative staff involved in the process of organ collection and transplantation are required to ensure anonymity of both the donor and the recipient. Against this backdrop, in 2018, the Italian Committee for Bioethics (ICB) released an official opinion titled “Opinion on the preservation of the anonymity of donor and receiver in the transplantation of organs” that offers a new perspective on the topic, effectively opening the possibility of anonymity ending at certain conditions. The relevance of anonymity within the transplant network is a globally recognized principle with a strong ethical value. In this article, based on the experience of one author directly involved in the ICB opinion drafting, we examine the document and discuss how such a proposal could be implemented at the legislative level.

High Incidence of Herpes Zoster After Lung Transplantation.

Primary varicella zoster virus (VZV) infection causes varicella and subsequently lifelong latent infection in ganglia from which it may reactivate leading to herpes zoster (HZ). Recently, we reported that VZV-reactive memory T-cells are significantly lower in transplant recipients than controls. In addition, the VZV-specific IgG titres after transplantation were significantly lower than before transplantation. Data on the incidence and timing of VZV reactivation after lung transplantation is limited. Therefore, we investigated the incidence of HZ after lung transplantation. Additionally, we questioned whether the VZV-specific T-cell and B-cell memory responses are recovered after VZV reactivation. The records of 101 patients (median age: 54 years) who underwent lung transplantation between April 2002 and April 2013 were analysed for VZV-PCR DNA till October 2013. VZV infection was clinically diagnosed and confirmed by PCR in 15 patients. One patient who was VZV IgG negative before transplantation, developed primary VZV infection 1.2 years after transplantation. Fifteen patients developed HZ: one patient had systemic dissemination, one patient developed disseminated vesicular rash in C2-C5 and died 6 days later, and 13 patients had uncomplicated cutaneous HZ involving 1-3 dermatomes. The median time to HZ was 1.4 years after transplantation. The overall incidence rate of HZ after transplantation (38 cases/1000 PY) was significantly higher than the age-matched healthy population (7-8 cases/1000 PY). The VZV-specific B and T-cell memory responses of 5 patients before and after HZ were compared with 5 patients without HZ. In 4 out of 5 patients the number of VZV-specific IgG producing B-cells increased after HZ to higher frequencies than those without HZ (p=0.06). The percentage of VZV-reactive CD4 and CD8 central and effector memory T-cells increased in all patients after HZ to significantly higher frequencies compared to those without HZ (p=0.03).In conclusion, HZ is a frequent complication after lung transplantation and increases VZV-specific T- and B-cell memory responses. Boosting the VZV adaptive immune response by prophylactic VZV vaccination before transplantation may limit the incidence of HZ after transplantation.

High Incidence of Herpes Zoster in Renal Transplant Patients.

High Incidence of Herpes Zoster in Renal Transplant Patients.

Complications of herpes zoster in cancer patients

Cancer patients tend to have a higher incidence of herpes zoster (HZ), but little is known about their risk of HZ complications. We conducted a retrospective study of 424 newly diagnosed hematologic (HM, n = 140) and solid tumor malignancy (STM, n = 284) patients who developed HZ between January 2001 and December 2006 to measure the frequency and identify risk factors of HZ complications. Patients were adult members of Kaiser Permanente Northern California. HZ diagnosis and complications were confirmed by medical chart review. HM patients with HZ tended to have more HZ complications than STM patients (34% vs 23%, p = 0.02), largely due to more frequent non-pain complications. On multivariate analysis, older age and being male were associated with a higher risk of HZ complications in HM patients; more advanced cancer stage was associated with HZ complications in STM patients. HZ complications are frequent and can present extra disease burden in cancer patients who develop HZ.

High Incidence of Herpes Zoster in Nonmyeloablative Hematopoietic Stem Cell Transplantation

Although the use of nonmyeloablative (NMA) hematopoietic stem cell transplantation (HSCT) regimens has expanded in the past decade, little data exist to support antiviral prophylaxis to prevent herpes zoster (HZ) in recipients who are seropositive for varicella-zoster virus in this population. The present study examined the clinical features, incidence, and risk factors for HZ in a homogeneous cohort of NMA allogeneic HSCT recipients. We conducted a retrospective cohort study assessing all patients who underwent sibling NMA HSCT at Maisonneuve-Rosemont Hospital (Montreal) between July 2000 and December 2008. All patients received the same conditioning regimen, immunoprophylaxis, and graft-versus-host disease therapy. The diagnosis of HZ was defined clinically. Factors associated with HZ were identified using a Cox proportional hazards model. A total of 179 patients were followed for a median of 33 months (interquartile range, 21-59). HZ developed in 66 patients (37%) at a median of 8.3 months post-HSCT; the incidence rate was 175 cases/1000 person-years. The estimated cumulative HZ incidence was 27% at 1 year, 36% at 2 years, and 44% at 3 years. Thoracic dermatomes were most frequently involved (30%); dissemination occurred in 5 patients. No deaths resulted from HZ, but 23% of patients developed postherpetic neuralgia. In multivariate analysis, reactivation of cytomegalovirus and herpes simplex virus was associated with a reduced likelihood of HZ (hazard ratio, 0.54 and 0.33, respectively). Antiviral prophylaxis or treatment for cytomegalovirus and herpes simplex virus reactivations were protective against HZ. The incidence of HZ in our cohort of NMA HSCT recipients is similar to the incidence reported in HSCT recipients who received a myeloablative conditioning regimen. Given the observed high risk, we conclude that recommendations for antiviral prophylaxis should apply, at least for the first year, to the NMA HSCT population as well.

The Incidence and Clinical Characteristics of Herpes Zoster Among Children and Adolescents After Implementation of Varicella Vaccination

The varicella-zoster virus (VZV) vaccine strain may reactivate to cause herpes zoster. Limited data suggest that the risk of herpes zoster in vaccinated children could be lower than in children with naturally acquired varicella. We examine incidence trends, risk and epidemiologic and clinical features of herpes zoster disease among children and adolescents by vaccination status. Population-based active surveillance was conducted among <20 years old residents in Antelope Valley, California, from 2000 through 2006. Structured telephone interviews collected demographic, varicella vaccination and disease histories, and clinical information. From 2000 to 2006, the incidence of herpes zoster among children<10 years of age declined by 55%, from 42 cases reported in 2000 (74.8/100,000 persons; 95% confidence interval [95% CI]: 55.3-101.2) to 18 reported in 2006 (33.3/100,000; 95% CI: 20.9-52.8; P<0.001). During the same period, the incidence of herpes zoster among 10- to 19-year-olds increased by 63%, from 35 cases reported in 2000 (59.5/100,000 persons; 95% CI: 42.7-82.9) to 64 reported in 2006 (96.7/100,000; 95% CI: 75.7-123.6; P<0.02). Among children aged<10 years, those with a history of varicella vaccination had a 4 to 12 times lower risk for developing herpes zoster compared with children with history of varicella disease. Varicella vaccine substantially decreases the risk of herpes zoster among vaccinated children and its widespread use will likely reduce overall herpes zoster burden in the United States. The increase in herpes zoster incidence among 10- to 19-year-olds could not be confidently explained and needs to be confirmed from other data sources.