1. J Natl Cancer Inst. 2010 Feb 24. [Epub ahead of print] Immune-Related and Inflammatory Conditions and Risk of Lymphoplasmacytic Lymphoma or Waldenstrom Macroglobulinemia. Kristinsson SY, Koshiol J, Bjorkholm M, Goldin LR, McMaster ML, Turesson I, Landgren O. Affiliations of authors: Department of Medicine, Division of Hematology, Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden (SYK, OL); Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics (JK, LRG, MLM, OL) and Center for Cancer Research (OL), National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Medicine, Section of Hematology, Malmo University Hospital, Malmo, Sweden (IT). Background Chronic immune stimulation appears to be associated with lymphoplasmacytic lymphoma (LPL)-Waldenstrom macroglobulinemia (WM); however, available information is sparse. We conducted, to our knowledge, the most comprehensive study to date to evaluate associations between a personal or family history of many immune-related and/or inflammatory disorders and the subsequent risk of LPL-WM. Methods We used Swedish population-based registries to identify 2470 case patients with LPL-WM, 9698 matched control subjects, and almost 30 000 first-degree relatives of either case patients or control subjects. We evaluated a wide range of autoimmune, infectious, allergic, and inflammatory conditions. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for each condition by use of logistic regression. Results An increased risk of LPL-WM was associated with a personal history of the following autoimmune diseases: systemic sclerosis (OR = 4.7, 95% CI = 1.4 to 15.3), Sjogren syndrome (OR = 12.1, 95% CI = 3.3 to 45.0), autoimmune hemolytic anemia (OR = 24.2, 95% CI = 5.4 to 108.2), polymyalgia rheumatica (OR = 2.9, 95% CI = 1.6 to 5.2), and giant cell arteritis (OR = 8.3, 95% CI = 2.1 to 33.1). An increased risk of LPL-WM was associated with a personal history of the following infectious diseases: pneumonia (OR = 1.4, 95% CI = 1.1 to 1.7), septicemia (OR = 2.4, 95% CI = 1.2 to 4.3), pyelonephritis (OR = 1.7, 95% CI = 1.1 to 2.5), sinusitis (OR = 2.7, 95% CI = 1.4 to 4.9), herpes zoster (OR = 3.4, 95% CI = 2.0 to 5.6), and influenza (OR = 2.9, 95% CI = 1.7 to 5.0). An increased risk of LPL-WM was associated with a family history of the following autoimmune or infectious diseases: Sjogren syndrome (OR = 5.0, 95% CI = 2.1 to 12.0), autoimmune hemolytic anemia (OR = 3.8, 95% CI = 1.1 to 13.2), Guillain-Barre syndrome (OR = 4.1, 95% CI = 1.8 to 9.4), cytomegalovirus (OR = 2.7, 95% CI = 1.4 to 5.3), gingivitis and periodontitis (OR = 1.9, 95% CI = 1.3 to 2.7), and chronic prostatitis (OR = 4.3, 95% CI = 1.7 to 11.1). Conclusions Personal history of certain immune-related and/or infectious conditions was strongly associated with increased risk of LPL-WM. The association of both personal and family history of Sjogren syndrome and autoimmune hemolytic anemia with risk of LPL-WM indicates the potential for shared susceptibility for these conditions. PMID: 20181958 [PubMed - as supplied by publisher] 2. J Clin Virol. 2010 Feb 22. [Epub ahead of print] Disease burden of herpes zoster in Korea. Choi WS, Noh JY, Huh JY, Jo YM, Lee J, Song JY, Kim WJ, Cheong HJ. Division of Infectious Disease, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea. BACKGROUND: The occurrence of herpes zoster can deteriorate the quality of life considerably, resulting in high disease burden. While Korea is assumed to have high disease burden of herpes zoster, there has been no researches analyzing this. OBJECTIVES: We performed this study to investigate the disease burden of herpes zoster in the Korean population as a whole. STUDY DESIGN: We used the database of the Health Insurance Review & Assessment Service of Korea and analyzed the data of patients who had herpes zoster as a principal diagnosis during the period from 2003 to 2007. We investigated the annual prevalence, rate of clinical visits, rate of hospitalization, and the pattern of medical services use. The socioeconomic burden of herpes zoster was calculated by a conversion into cost. RESULTS: Rates of clinic visits and hospitalizations due to herpes zoster during the 5-year period from 2003 to 2007 were 7.93-12.54 per 1000 population and 0.22-0.32 per 1000 population, respectively. Prevalence rates according to age increased sharply after 50 years and reached a peak at 70 years. The total socioeconomic cost of herpes zoster was $75.9-143.8 million per year, increasing every year by 14-20%. CONCLUSIONS: There is a heavy socioeconomic burden due to herpes zoster in Korea and indicate that appropriate policies need to be established to reduce this burden. Additional researches are also necessary to assess the safety, efficacy and cost-effectiveness of a herpes zoster vaccine in the Korean population. Copyright © 2010 Elsevier B.V. All rights reserved. PMID: 20181512 [PubMed - as supplied by publisher] 3. Cases J. 2010 Jan 12;3(1):17. [Epub ahead of print] An unusual cause of visual loss after Herpes zoster ophthalmicus: a case report. Camuglia JE, Beltz JE, Khurana K, Hall AJ. ABSTRACT: INTRODUCTION: The vascular complications of herpes zoster are well recognised, however, there are few reports of central retinal artery occlusion. Central retinal artery occlusion following herpes zoster ophthalmicus is poorly recognised. This is likely due to the difficulties in obtaining tissue for histopathology to establish causality. We report a case of central retinal artery occlusion and complete internal carotid artery occlusion following herpes zoster ophthalmicus. CASE PRESENTATION: A 44 year old Caucasian female presented with sudden painless loss of vision in her right eye on a background of chronic lymphocytic leukaemia and right sided herpes zoster ophthalmicus. She was initially treated with steroids and antivirals for an underlying presumed vasculitic cause, but review at 24 hours demonstrated a right central retinal artery occlusion. Embolic screen identified complete occlusion of the right internal carotid artery. She was treated with oral antiviral medication for three weeks but had no visual recovery. CONCLUSION: This case highlights an uncommon cause of acute visual loss. We propose that the underlying small and large vessel occlusion in this patient was due to herpes zoster related vasculopathy. A review of the literature is presented to trace the historical perspective of herpes zoster related vasculopathy. PMID: 20180950 [PubMed - as supplied by publisher] 4. Clin Infect Dis. 2010 Feb 23. [Epub ahead of print] Increasing Incidence of Herpes Zoster among Veterans. Rimland D, Moanna A. Atlanta Veterans Affairs Medical Center, Decatur, and 2Emory University School of Medicine, Atlanta, Georgia. Background. The incidence of herpes zoster in the United States has been estimated to be 1 million cases annually, with a higher rate in adults older than 60 years. The morbidity of the disease, including postherpetic neuralgia, imposes significant effects on quality of life. We analyzed reports of herpes zoster in the Veterans Affairs (VA) population because these patients are older and could provide a reflection of disease trends in the aging US population. These data will provide a baseline for future analyses of the incidence of herpes zoster after the introduction of the herpes zoster vaccine in late 2007. Methods. To evaluate the trend in the annual incidence of herpes zoster for fiscal year 2000 (beginning October 1999) through fiscal year 2007 (through September 2007), we derived incidence rates using the Veterans Health Administration Decision Support System reports of herpes zoster by International Classification of Diseases, Ninth Revision codes from 2000 through 2007 and the corresponding denominator data for all veterans in care. These rates were validated by review of medical records of patients with diagnoses of herpes zoster at the Atlanta VA Medical Center. Results. The annual incidence of herpes zoster increased from 3.10 episodes per 1000 veterans in 2000 to 5.22 in 2007 ([Formula: see text]; [Formula: see text]). This increasing rate was seen in both men and women but only in groups older than 40 years. Conclusion. The increasing incidence of herpes zoster in our veteran population and its effect on the quality of life of the veterans validate the need for improved rates of vaccination in this population. PMID: 20178416 [PubMed - as supplied by publisher] 5. J Clin Oncol. 2010 Feb 22. [Epub ahead of print] Phase I Study of KW-0761, a Defucosylated Humanized Anti-CCR4 Antibody, in Relapsed Patients With Adult T-Cell Leukemia-Lymphoma and Peripheral T-Cell Lymphoma. Yamamoto K, Utsunomiya A, Tobinai K, Tsukasaki K, Uike N, Uozumi K, Yamaguchi K, Yamada Y, Hanada S, Tamura K, Nakamura S, Inagaki H, Ohshima K, Kiyoi H, Ishida T, Matsushima K, Akinaga S, Ogura M, Tomonaga M, Ueda R. Department of Hematology and Cell Therapy, Aichi Cancer Center; Department of Clinical Pathophysiology and Department of Infectious Diseases, Nagoya University Graduate School of Medicine; Department of Hematology and Oncology, Nagoya Daini Red Cross Hospital, Nagoya; Department of Clinical Pathology and Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Nagaya; Department of Hematology, Imamura Bun-in Hospital; Department of Internal Medicine, National Hospital Organization Kagoshima Medical Center; Department of Hematology and Immunology, Kagoshima University Hospital, Kagoshima; Hematology and Stem Cell Transplantation Division, National Cancer Center Hospital; Department of Safety Research on Blood and Biologics, National Institute of Infectious Diseases; Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo; Kyowa Hakko Kirin Co Ltd, Tokyo; Department of Hematology and Molecular Medicine Unit and Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Science, Nagasaki; Department of Hematology, National Kyushu Cancer Center; The Department of Medicine, Division of Medical Oncology, Infectious Disease, and Endocrinology, School of Medicine, Fukuoka University, Fukuoka; and the Department of Pathophysiology, Kurume University School of Medicine, Kurume, Japan. PURPOSE: KW-0761, a defucosylated humanized anti-CC chemokine receptor 4 (CCR4) antibody, exerts a strong antibody-dependent cellular cytotoxic effect. This phase I study assessed the safety, pharmacokinetics, recommended phase II dose and efficacy of KW-0761 in patients with relapsed CCR4-positive adult T-cell leukemia-lymphoma (ATL) or peripheral T-cell lymphoma (PTCL). PATIENTS AND METHODS: Sixteen patients received KW-0761 once a week for 4 weeks by intravenous infusion. Doses were escalated, starting at 0.01, 0.1, 0.5, and finally 1.0 mg/kg by a 3 + 3 design. RESULTS: Fifteen patients completed the protocol treatment. Only one patient, at the 1.0 mg/kg dose, developed grade 3 dose-limiting toxicities, skin rash, and febrile neutropenia, and grade 4 neutropenia. Other treatment-related grade 3 to 4 toxicities were lymphopenia (n = 10), neutropenia (n = 3), leukopenia (n = 2), herpes zoster (n = 1), and acute infusion reaction/cytokine release syndrome (n = 1). Neither the frequency nor severity of toxicities increased with dose escalation. The maximum tolerated dose was not reached. Therefore, the recommended phase II dose was determined to be 1.0 mg/kg. No patients had detectable levels of anti-KW-0761 antibody. The plasma maximum and trough, and the area under the curve of 0 to 7 days of KW-0761, tended to increase dose and frequency dependently. Five patients (31%; 95% CI, 11% to 59%) achieved objective responses: two complete (0.1; 1.0 mg/kg) and three partial (0.01; 2 at 1.0 mg/kg) responses. CONCLUSION: KW-0761 was tolerated at all the dose levels tested, demonstrating potential efficacy against relapsed CCR4-positive ATL or PTCL. Subsequent phase II studies at the 1.0 mg/kg dose are thus warranted. PMID: 20177026 [PubMed - as supplied by publisher] 6. Aliment Pharmacol Ther. 2010 Feb 18. [Epub ahead of print] Infliximab as rescue medication for patients with severe ulcerative/indeterminate colitis refractory to tacrolimus. Herrlinger KR, Barthel DN, Schmidt KJ, Buning J, Barthel CS, Wehkamp J, Stange EF, Fellermann K. Department of Gastroenterology, Hepatology and Endocrinology, Robert-Bosch-Hospital, Stuttgart, Germany. SUMMARY Background: The calcineurin inhibitor tacrolimus and the anti-TNF-antibody infliximab are established options in steroid refractory ulcerative colitis (UC). The aim of this study was to determine the efficacy of infliximab as rescue medication in patients failing to respond to tacrolimus. Aim: To evaluate the efficacy of infliximab-salvage therapy in patients with refractory ulcerative colitis failing to respond to tacrolimus Methods: Twenty-four patients were enrolled in this evaluation. Reasons for tacrolimus therapy were steroid-refractory disease in 19 patients and steroid dependency in 5 patients. All patients receiving infliximab had tacrolimus refractory active disease (Lichtiger score >10) and were treated with 5mg/kg at weeks 0, 2 and 6 and every 8 weeks thereafter if tolerated. Results: Six of 24 patients (25%) achieved remission following infliximab infusion and 4/24 (17%) had an initial response only but underwent proctocolectomy later due to loss of response (3) or development of a delayed hypersensitivity reaction (1). Fourteen patients (58%) completely failed to respond with 10 undergoing colectomy. Eight patients experienced side effects under infliximab including two infectious complications (herpes zoster and herpes pneumonia). Conclusions: Infliximab offers a therapeutic option as rescue therapy in about a quarter of patients with active UC after failing to respond to tacrolimus. This benefit has to be weighed against the risks of infectious complications. PMID: 20175769 [PubMed - as supplied by publisher] 7. J Pharmacol Sci. 2010 Feb 20. [Epub ahead of print] Blockade of Glycine Transporter (GlyT) 2, but Not GlyT1, Ameliorates Dynamic and Static Mechanical Allodynia in Mice With Herpetic or Postherpetic Pain. Nishikawa Y, Sasaki A, Kuraishi Y. Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan. Glycine is an inhibitory neurotransmitter in the spinal dorsal horn and its extracellular concentration is regulated by glial glycine transporter (GlyT) 1 and neuronal GlyT2. This study was conducted to elucidate the effects of intrathecal injections of GlyT1 and GlyT2 inhibitors on two distinct types of mechanical allodynia, dynamic and static allodynia, in mice with herpetic or postherpetic pain. The GlyT2 inhibitor ALX1393, but not the GlyT1 inhibitor sarcosine, suppressed dynamic and static allodynia at the herpetic and postherpetic stages. Intrathecal ALX1393 suppressed dynamic allodynia induced by intrathecal strychnine and N-methyl-D-aspartate (NMDA). Intrathecal sarcosine suppressed dynamic allodynia induced by intrathecal strychnine, but not NMDA. Expression level of GlyT1, but not GlyT2, mRNA in the lumbar dorsal horn was decreased at the herpetic and postherpetic stages. Glycine receptor alpha1-subunit mRNA was decreased in the lumbar dorsal horn at the herpetic, but not postherpetic stage, without alteration in alpha3-subunit mRNA. The results suggest that GlyT2 is a potential target for treatment of dynamic and static allodynia in patients with herpes zoster and postherpetic neuralgia. The lack of efficacy of GlyT1 inhibitor may be explained by activation of NMDA receptors and the down-regulation of GlyT1 in the lumbar dorsal horn. PMID: 20173309 [PubMed - as supplied by publisher] 8. J Virol Methods. 2010 Feb 17. [Epub ahead of print] The glycoproteins C and G are equivalent target antigens for the determination of herpes simplex virus type 1-specific antibodies. Scheper T, Saschenbrecker S, Steinhagen K, Sauerbrei A, Suer W, Meyer W, Schlumberger W, Wandinger KP. Institute of Experimental Immunology, affiliated to EUROIMMUN AG, Seekamp 31, D-23560 Luebeck, Germany; These authors contributed equally to this work. Seroreactivity to the glycoproteins C and G of herpes simplex virus type 1 (HSV-1) was compared in 310 serum samples using a Western blot assay containing a whole antigen extract of HSV-1 and an ELISA employing gC1 isolated from HSV-1. The prevalence of reactivity to gC1 was 75.8% by Western blot and 73.9% by ELISA, while antibody responses to gG1 were detected in 72.9% of sera by Western blot. An absolute correlation of 96.1% between the reactivity to gC1 and gG1 was demonstrated using the Western blot. The gC1-based ELISA correlated with Western blot detection of anti-gC1 and anti-gG1 antibodies in 95.2% and 97.7% of samples, respectively. 3.2% of all sera were reactive with gC1 in Western blot and/or ELISA, but were negative for anti-gG1. For analysis of cross-reactivity, antibodies against HSV-2, Epstein-Barr virus, varicella-zoster virus and cytomegalovirus were determined. The prevalence of antibodies against each individual virus was identical in the groups of sera reactive with gC1 or gG1. These findings indicate that gC1 and gG1 are equivalent antigenic targets for the type-specific serodiagnosis of HSV-1 infections. Copyright © 2010. Published by Elsevier B.V. PMID: 20171247 [PubMed - as supplied by publisher] 9. Hautarzt. 2010 Feb 19. [Epub ahead of print] [Skin infections after transplantation.] [Article in German] Wolf IH. Universitatsklinik fur Dermatologie und Venerologie, Abteilung fur Allgemeine Dermatologie, Medizinische Universitat Graz, Auenbruggerplatz 8, 8036, Graz, Osterreich, ingrid.wolf@medunigraz.at. Skin infections after transplantation are frequent and of special importance because they may be quite severe. The spectrum of dermatologic infections in transplant recipients includes bacterial, mycotic and viral diseases. Pyoderma, herpes virus 6/7, herpes simplex virus, varicella-zoster virus, cytomegalovirus and candida infections predominate. Rare pathogens must be also considered. Cutaneous infections can be divided into three phases following transplantation. Diagnosis and adequate early therapy together with specific prophylaxis and follow-up of transplant patients should be strived for to avoid life-threatening complications. PMID: 20165826 [PubMed - as supplied by publisher] 10. Arch Phys Med Rehabil. 2010 Feb;91(2):321-5. Herpes zoster-induced trunk muscle paresis presenting with abdominal wall pseudohernia, scoliosis, and gait disturbance and its rehabilitation: a case report. Tashiro S, Akaboshi K, Kobayashi Y, Mori T, Nagata M, Liu M. Department of Rehabilitation Medicine, Ichikawa City Rehabilitation Hospital, Ichikawa City, Japan. s-tashiro@umin.net Herpes zoster (HZ)-induced abdominal wall pseudohernia has been frequently reported, but there has been no report describing HZ-induced trunk muscle paresis leading to functional problems. We describe a 73-year-old man with T12 and L1 segmental paresis caused by HZ presenting with abdominal wall pseudohernia, scoliosis, and standing and gait disturbance who responded well to a systematic rehabilitation approach. He first noticed a right abdominal bulge in the 6th postherpetic week, which was gradually accompanied by right convex thoracolumbar scoliosis, pain, and standing and gait disturbance in the 12th week. Needle electromyography revealed abnormal spontaneous activities at rest in the right T12 myotomal muscles, and motor unit recruitment was markedly decreased. We arranged an outpatient rehabilitation program consisting of using a soft thoracolumbosacral orthosis for pain relief and trunk stability, muscle reeducation of the paretic abdominal muscles, strengthening of the disused trunk and extremity muscles, and gait exercise. Based on electromyographic findings, we instructed him in an effective method of muscle reeducation. After 4 months of rehabilitation, he showed marked improvement and became an outdoor ambulator. We suggest that electromyography is a useful tool to evaluate clinical status and devise an effective rehabilitation program in patients with HZ trunk paresis. Copyright 2010 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved. PMID: 20159140 [PubMed - in process] 11. J Neurol. 2010 Feb 13. [Epub ahead of print] Trigeminal herpes zoster and Ramsay Hunt Syndrome with a lesion in the spinal trigeminal nucleus and tract. Hung CW, Wang SJ, Chen SP, Lirng JF, Fuh JL. Department of Neurology, Yangming Branch, Taipei City Hospital, Taipei, Taiwan, ROC. We report the case of a 77-year-old immuno-competent man who developed herpes zoster in the maxillary and mandibular branches of the trigeminal nerve. Within 3 weeks, he developed ipsilateral peripheral facial palsy, hearing loss, vesicles over the external auditory canal, and pain in the face and ear. A T(2)-weighted MRI of the brain revealed a hyper-intense lesion at the right medulla corresponding to the spinal trigeminal nucleus and tract. Gadolinium enhancement was seen over the right facial nerve. These lesions suggest a possibility of transaxonal spread of the varicella zoster virus between the trigeminal nerve, the facial nerve, and the spinal trigeminal nucleus and tract. PMID: 20155276 [PubMed - as supplied by publisher] 12. Nat Rev Rheumatol. 2010 Feb 9. [Epub ahead of print] Tumor necrosis factor blockade and the risk of viral infection. Kim SY, Solomon DH. Division of Rheumatology, Immunology, and Allergy, and Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. Tumor necrosis factor (TNF) blockers are widely used to treat rheumatoid arthritis and other chronic inflammatory diseases. Many studies have demonstrated an increased risk of opportunistic infections such as tuberculosis and fungal infection in patients treated with TNF blockers, which is thought to be related to the primary role of TNF both in host defense and in the immune response. Little is known, however, about the association between TNF blockade and the development of viral infection. Owing to the critical role of TNF in the control of viral infection, depletion of this cytokine with TNF blockers could facilitate the development or reactivation of viral infection. A number of large observational studies have found an increased risk of herpes zoster in patients receiving TNF blockers for the treatment of rheumatoid arthritis. This Review draws attention to the risk of several viral infections, including HIV, varicella zoster virus, Epstein-Barr virus, cytomegalovirus, and human papillomavirus, in patients receiving TNF-blocking therapy for chronic inflammatory conditions. In addition, implications for clinical practice and possible preventative approaches are discussed. PMID: 20142812 [PubMed - as supplied by publisher] 13. Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2461-6. Epub 2010 Jan 21. Transcriptional coactivator HCF-1 couples the histone chaperone Asf1b to HSV-1 DNA replication components. Peng H, Nogueira ML, Vogel JL, Kristie TM. Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bld 4-131, 4 Center Drive, Bethesda, MD 20892, USA. The cellular transcriptional coactivator HCF-1 interacts with numerous transcription factors as well as other coactivators and is a component of multiple chromatin modulation complexes. The protein is essential for the expression of the immediate early genes of both herpes simplex virus (HSV) and varicella zoster virus and functions, in part, by coupling chromatin modification components including the Set1 or MLL1 histone methyltransferases and the histone demethylase LSD1 to promote the installation of positive chromatin marks and the activation of viral immediately early gene transcription. Although studies have investigated the role of HCF-1 in both cellular and viral transcription, little is known about other processes that the protein may be involved in. Here we demonstrate that HCF-1 localizes to sites of HSV replication late in infection. HCF-1 interacts directly and simultaneously with both HSV DNA replication proteins and the cellular histone chaperone Asf1b, a protein that regulates the progression of cellular DNA replication forks via chromatin reorganization. Asf1b localizes with HCF-1 in viral replication foci and depletion of Asf1b results in significantly reduced viral DNA accumulation. The results support a model in which the transcriptional coactivator HCF-1 is a component of the HSV DNA replication assembly and promotes viral DNA replication by coupling Asf1b to DNA replication components. This coupling provides a novel function for HCF-1 and insights into the mechanisms of modulating chromatin during DNA replication. PMID: 20133788 [PubMed - in process] 14. J Virol. 2010 Feb 3. [Epub ahead of print] Impact of varicella zoster virus on dendritic cell subsets in human skin during natural infection. Huch JH, Cunningham AL, Arvin AM, Nasr N, Santegoets SJ, Slobedman E, Slobedman B, Abendroth A. Department of Infectious Diseases and Immunology, University of Sydney, New South Wales 2006, Australia; Centre For Virus Research, Westmead Millennium Institute and University of Sydney, Westmead, New South Wales 2145, Australia; Departments of Pediatrics and Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pathology, VU University Medical Center, De Boelelaan 1117, Amsterdam 1081HV, The Netherlands; Laverty Pathology, North Ryde, New South Wales, 2113, Australia. Varicella zoster virus (VZV) causes varicella and herpes zoster, diseases characterized by distinct cutaneous rashes. DC are essential for inducing anti-viral immune responses, however the contribution of DC subsets to the immune control during natural cutaneous VZV infection has not been investigated. Immunostaining showed that compared to normal skin, the proportion of cells expressing DC-SIGN (dermal DC marker) or DC-LAMP and CD83 (mature DC markers) were not significantly altered in infected skin. In contrast, the frequency of Langerhans cells was significantly decreased in VZV infected skin, whereas there was an influx of plasmacytoid DC, a potent secretor of type I IFN. Langerhans cells and plasmacytoid DC in infected skin were closely associated with VZV antigen positive cells, and some Langerhans cells and plasmacytoid DC were VZV antigen positive. To extend these in vivo observations, both plasmacytoid DC (PDC) isolated from human blood and Langerhans cells derived from MUTZ-3 cells were shown to be permissive to VZV infection. In VZV infected PDC cultures significant induction of IFN-alpha did not occur, indicating the VZV inhibits the capacity of PDC to induce expression of this host defense cytokine. This study defines changes in the response of DC which occur during cutaneous VZV infection, and implicates infection of DC subtypes in VZV pathogenesis. PMID: 20130046 [PubMed - as supplied by publisher] 15. Sleep Med. 2010 Feb 1. [Epub ahead of print] A case of reversible restless legs syndrome (RLS) and sleep-related eating disorder relapse triggered by acute right leg herpes zoster infection: Literature review of spinal cord and peripheral nervous system contributions to RLS. Mahowald MW, Cramer Bornemann MA, Schenck CH. Minnesota Regional Sleep Disorders Center, Department of Neurology, Hennepin County Medical Center, The University of Minnesota Medical School, Minneapolis, MN, USA. Restless legs syndrome (RLS) is thought to be due to abnormalities of iron metabolism in the central nervous system; however, occasional cases are associated with lesions of the spinal cord, spinal rootlets, and peripheral nervous system. This is a case report of RLS exacerbated by shingles with a review of the literature of extra-cerebral lesions or disorders causing or contributing to RLS. Copyright © 2010 Elsevier B.V. All rights reserved. PMID: 20129821 [PubMed - as supplied by publisher] 16. New Microbiol. 2009 Oct;32(4):333-40. Diagnosis of neurological herpesvirus infections: real time PCR in cerebral spinal fluid analysis. Gaeta A, Verzaro S, Cristina LM, Mancini C, Nazzari C. Clinical Microbiology Department of Science and Public Health, Sapienza University of Rome, Italy. aurelia.gaeta@uniroma1.it Human herpesviruses (HHVs) cause many serious acute and persistent central nervous system (CNS) disorders. Because these infections manifest with various, often non-specific, symptoms and signs, and because specific therapy is often available, accurate diagnosis is essential. Cerebrospinal fluid (CSF) from 146 patients with acute meningitis or meningoencephalitis and 9 with "other neurological disorders" were analyzed by using an automatic system for nucleic acid extraction and quantitative real-time polymerase chain reaction (PCR) for herpes simplex 1 and 2 (HSV-1, HSV-2), Epstein-Barr virus (EBV), human cytomegalovirus (HCMV), herpesvirus-6 (HHV-6), and varicella-zoster virus (VZV). HHVs DNA was detected in 52 of 155 (33.5%) analyzed samples. In 39 CSF samples from patients with meningoencephalitis we found: VZV in 13, HSV-1 in 12, EBV in 6, HHV-6 in 4, and HSV-2 in 4. Co-infections of EBV and HSV-2, HSV-1 and HSV-2, HSV-1 and VZV were also disclosed in four cases. In addition, two patients with Guillain-Barre syndrome had HCMV and one showed HHV6 positivity, two patients with myelitis / polymyeloradiculitis had VZV and HCMV respectively, HHV-6 DNA was found in one patient with lateral amyotrophic sclerosis. Three CSF specimens from HIV-infected patients with CNS complications had HHV-6 or EBV DNA. Moreover quantitative data were also correlated to clinical conditions to obtain more information on the virus aetiopathogenic role. PMID: 20128439 [PubMed - in process] 17. Agri. 2009 Oct;21(4):175-7. [Herpes radiculopathy case presenting first with motor involvement] [Article in Turkish] Cinar SM, Bilge S, Hiz F, Erkutlu L. Department of Neurology, Taksim Training and Research Hospital, Istanbul, Turkey. mercinar@hotmail.com Herpes zoster primarily affects the posterior root ganglions and sensorial nerve fibers, and causes vesicular skin eruptions, radicular pain and loss of sensorial function along the distribution of the affected ganglion. Motor involvement can also be observed. When classical cutaneous lesions are present, the motor paresis consequent to herpes zoster is easily diagnosed. However, diagnosis becomes complicated when the motor weakness is the earlier sign and precedes the cutaneous lesions and sensory symptoms. We present a case in whom the major clinical symptom and sign was the motor weakness in cervical radiculopathy consequent to herpes zoster. PMID: 20127539 [PubMed - in process] 18. J Neurol. 2010 Feb 3. [Epub ahead of print] The clinical course of idiopathic acute transverse myelitis in patients from Rio de Janeiro. Alvarenga MP, Thuler LC, Neto SP, Vasconcelos CC, Camargo SG, Alvarenga MP, Papais-Alvarenga RM. Departamento de Neurologia, Universidade Federal do Estado do Rio de Janeiro, Rua Mariz e Barros 775, Tijuca, Rio de Janeiro, 20270-004, Brazil, alvarenga_marina@hotmail.com. The aim of this study was to describe the demographic, clinical and laboratory features of idiopathic acute transverse myelitis (IATM). Patients with non-compressive ATM receiving care at Hospital da Lagoa, Rio de Janeiro (Brazil) between 2000 and 2008 were selected. Of the 70 cases of acute myelopathies, the idiopathic form was identified in 41 following exclusion of the cases associated with systemic lupus erythematosus (n = 1), Sjogren's syndrome (n = 1), herpes zoster (n = 1), cytomegalovirus in an HIV-positive patient (n = 1), Schistosoma mansoni (n = 1), actinic myelitis (n = 1), infectious myelitis of unknown etiology (n = 2) and those that, following the first attack of myelitis, converted to NMO (n = 19) or to clinically defined MS (n = 2). Of the 41 cases of IATM, the majority of patients were female (68.3%) and white (65.9%). Median age at first myelitis was 37.0 +/- 11.8 years. Over a median observation time of 36 months, 39.0% of patients remained monophasic, while recurrences occurred in 61.0% of cases. The number of ATM/patient ranged from one to seven. Among the recurrent cases the median time between the first and the second ATM was 12 months (range 1-150 months).The first myelitis was characterized mainly by partial myelitis with motor and sensorial dysfunction (63.4%). Complete and severe myelitis occurred more frequently among monophasic patients and partial myelitis with moderate dysfunction at onset in recurrent cases; however, over the long-term, dysfunction and disability were mild in both groups. Serial spine MRI confirmed spinal cord inflammation in 92.0% of cases and extensive spinal cord lesion was identified in 61.0%. Brain MRI was normal or not suggestive of MS in 94.4% of cases. CSF showed pleocytosis in 41.2%, increased IgG index in 24.0% and oligoclonal bands in 38.0% of 34 patients tested. Abnormal visual evoked potentials occurred in 11.5% of 26 patients. Positivity for anti-AQP4 was found in 23.5% of the 17 cases tested, suggesting limited forms of NMO. This study suggests some new aspects of the clinical course of IATM such as the high conversion rate to NMO, the predominance of women and a higher frequency of recurrent forms. PMID: 20127351 [PubMed - as supplied by publisher] 19. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010 Feb;109(2):232-7. Low prevalence of varicella zoster virus and herpes simplex virus type 2 in saliva from human immunodeficiency virus-infected persons in the era of highly active antiretroviral therapy. Wang CC, Yepes LC, Danaher RJ, Berger JR, Mootoor Y, Kryscio RJ, Miller CS. Department of Oral Health Practice, University of Kentucky College of Medicine and College of Dentistry, Lexington, Kentucky 40536-0297, USA. george.sandor@utoronto.ca OBJECTIVES: Human herpesviruses, e.g., herpes simplex virus (HSV) type 1, Epstein-Barr virus, and cytomegalovirus, appear in saliva at greater frequency in persons infected with human immunodeficiency virus (HIV) than in healthy individuals. However, it is not known if varicella zoster virus (VZV) and HSV-2 appear simultaneously during HIV infection at greater frequency in saliva in this era of highly active antiretroviral therapy (HAART). The aim of this study was to investigate the prevalence and amounts of VZV and HSV-2 in the saliva of HIV-infected orally asymptomatic patients. STUDY DESIGN: Quantitative polymerase chain reaction was used to investigate the prevalence, quantity, risk, and correlations of salivary VZV and HSV-2 from 59 HIV-seropositive individuals and 53 healthy control subjects in a case-control cross-sectional study. Seventy-eight percent of the HIV-seropositive patients (46 out of 59) were taking HAART. RESULTS: VZV DNA was detected in the saliva of 5.1% (3 out of 59) of the HIV-positive group and in only 1 healthy control 1.9% (1 out of 53; P = .62). The amount of VZV DNA in the expressors was low, generally <1,100 copies/mL, with no observed difference between the HIV-positive group and the control subjects (P = 1.0). HSV-2 DNA was not detected in either group. In the HIV-infected group, VZV shedding occurred in those on HAART, but was not associated with oral lesions, specific CD4(+) or CD8(+) T-cell levels, or demographic factors. CONCLUSIONS: Varicella zoster virus was detected at low prevalence in the saliva of HIV-infected persons, whereas HSV-2 was not detected in the saliva of this cohort. HAART does not appear to diminish the risk for asymptomatic VZV shedding. Copyright (c) 2010 Mosby, Inc. All rights reserved. PMCID: PMC2818125 [Available on 2011/2/1] PMID: 20123407 [PubMed - in process] 20. Acta Neurol Belg. 2009 Dec;109(4):277-82. Broad screening for human herpesviridae DNA in multiple sclerosis cerebrospinal fluid and serum. Franciotta D, Bestetti A, Sala S, Perucca P, Jarius S, Price RW, Di Stefano AL, Cinque P. Laboratory of Neuroimmunology, IRCCS, Foundation "Neurological Institute C. Mondino", Pavia, Italy. diego.franciotta@mondino.it Members of the human herpesviridae family are candidates for representing the macroenvironmental factors associated with multiple sclerosis (MS) pathogenesis. Real-time PCR was used to search for DNA of herpes simplex virus type-1/-2, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus (EBV), human herpesvirus 6 type A/B in paired cerebrospinal fluid (CSF) and serum samples from 54 patients with MS, 34 of whom with active disease, 10 patients with other non-infectious neurological diseases, and 15 healthy individuals. All the CSF and serum samples were negative for the examined herpesviruses DNA, except one CSF sample from an MS patient, which was positive for EBV DNA. These findings do not support a role for the here-studied herpesviruses replication, whether in systemic or in the intrathecal compartment, as co-pathogenetic factors, nor as inducers of relapses, in MS. PMID: 20120207 [PubMed - in process] 21. Mayo Clin Proc. 2010 Feb;85(2):172-5. Clinical pearls in infectious diseases. Orenstein R, Litin SC. Division of Infectious Diseases, Mayo Clinic, Rochester, MN 55905, USA. orenstein.robert@mayo.edu PMCID: PMC2813826 [Available on 2010/8/1] PMID: 20118393 [PubMed - indexed for MEDLINE] 22. Ann Emerg Med. 2010 Feb;55(2):A15-7. A $9,000 bill to diagnose shingles? Doctor's ED visit highlights cost of care issues. Berger E. PMID: 20116023 [PubMed - indexed for MEDLINE] 23. Expert Opin Biol Ther. 2010 Jan 31. [Epub ahead of print] Shingles vaccine. Willison CB, Morrison LK, Mendoza N, Tyring SK. 451 North Texas Avenue, Webster, Texas 77598, USA +1 281 333 2288 ext 1109 ; +1 281 335 4605 ; bwillison@ccstexas.com. Importance of the field: Herpes zoster or shingles is a condition with the potential to result in severe debilitation. It affects approximately 10 - 30% of the population. Until recently there were only treatments to shorten the duration and lessen the symptoms of herpes zoster, but no practical or approved method of prevention for susceptible immunocompetent adults. The live attenuated zoster vaccine (Zostavax((R)), Merck & Co., Inc.) is effective in preventing shingles in individuals 60 years of age and older and recommended by the Center for Disease Control's (CDC) Advisory Committee for Immunization Practices (ACIP). Areas covered in this review: Literature related to the live attenuated zoster vaccine is reviewed from its beginnings in the early 1970s through to the present. What the reader will gain: Background information on herpes zoster and up to date information on the live attenuated zoster vaccine including pharmacology, efficacy and safety are covered. New areas of research in zoster vaccination are also discussed. Take home message: The live attenuated zoster vaccine is an effective and well-tolerated method of preventing zoster and the potentially debilitating sequelae and is recommended for immunocompetent patients 60 years of age and older. Ongoing clinical trials are investigating new means of effective prevention. PMID: 20113211 [PubMed - as supplied by publisher] 24. Brain Nerve. 2010 Jan;62(1):81-4. [Herpes zoster oticus-associated jugular foramen syndrome] [Article in Japanese] Ono N, Sakabe A, Nakajima M. Department of Neurology, Tokyo Rosai Occupational Disease and Injuries Hospital, Japan. We report a patient with herpes zoster oticus who presented with acute jugular foramen syndrome, and we present the review of 9 similar cases reported previously. Jugular foramen syndrome associated with varicella-zoster virus (VZV) infection is characterized by acute-onset dysphagia and dysphonia, usually accompanied or preceded by cranial, cervical, or pharyngeal pain. Herpetic eruptions on the skin or the mucosal surface may not occur, occur late after onset, or go undetected. Magnetic resonance imaging may reveal contrast enhancement around the jugular foramen, which implying inflammation of the glossopharyngeal or the vagal nerve ganglia, and its extension to the spinal root of the accessory nerve through the cerebrospinal fluid (CSF). The presence of VZV-DNA or VZV antibody in the CSF should be tested for early diagnosis and initiation of anti-viral treatment. PMID: 20112795 [PubMed - in process] 25. Rev Esp Salud Publica. 2009 Sep-Oct;83(5):711-24. [Epidemiology of varicella in spain pre-and post-vaccination periods] [Article in Spanish] Pena-Rey I, Martinez de Aragon MV, Villaverde Hueso A, Terres Arellano M, Alcalde Cabero E, Suarez Rodriguez B. Centro Nacional de Epidemiologia, Instituto de Salud Carlos III, Madrid, Espana. sabela@isciii.es BACKGROUND: Varicella virus can cause two different diseases: chickenpox and herpes zoster. In 2005 varicella vaccine has been introduced in the Spanish national vaccination schedule for 10-14 years old non-immune people, in order to reduce the severity of the disease. In 2007 a new surveillance protocol with aggregate data for chickenpox and herpes zoster was approved in order to detect any change in age distribution, severity and complications of the chickenpox and herpes zoster cases. The aim of this study is to know the burden of diseases (in the last ten years). METHODS: Number of cases, hospitalization and incidence for chickenpox and herpes zoster were study for two periods 1997-2003 and 2005-2007. Analysis for 1996-2007 fatal cases was done too. We decided to remove year 2004 because the extremely high chickenpox incidence registered. Sources of data: RENAVE (Spanish Surveillance Network), Spanish hospital surveillance system (CMBD), and mortality registries. RESULTS: Chickenpox incidence decreased since 2005, but an increasing trend was detected in hospitalisation with an average of 1,311 hospitalizations every year. For the 32%-36% of hospitalized cases, the main diagnosis was not chickenpox. 4-14 deaths per year have been detected; 80% of them were older than 14 years. Annual rate of herpes zoster hospitalization was 2.5 per 100,000 inhabitants, similar in both sexes. Case fatality rate per year was 0.31 per million inhabitants. No significant changes were detected in age and sex in complicated cases between the two periods. 88% of chickenpox cases were younger than 15 years old and 64% of herpes zoster older than 50 years in 2007. CONCLUSIONS: Chickenpox has been decreasing during 2005-2007 in Spain. The impact of vaccination is difficult to asses, because of a peak registered in 2004 but also because the lack of vaccination coverage information for this period and the case-data information is available only for the last year. PMID: 20111819 [PubMed - in process] 26. Lancet. 2010 Jan 16;375(9710):252. An innocent gallbladder? Mumoli N, Cei M, Orlandi F, Luschi R, Niccoli G. Department of Internal Medicine, Ospedale Civile Livorno, Livorno, Italy. nimumoli@tiscali.it PMID: 20109926 [PubMed - indexed for MEDLINE] 27. Postgrad Med. 2010 Jan;122(1):91-107. Treatment of the localized pain of postherpetic neuralgia. Paster Z, Morris CM. University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. zpaster@facstaff.wisc.edu Postherpetic neuralgia (PHN) is a neuropathic pain condition that can arise as a complication following herpes zoster infection, with pain often localized to the affected dermatome. Patients are initially likely to seek treatment for PHN pain from their primary care practitioner; however, adequate pain relief is difficult to achieve in many patients. Combination therapies are often used and have shown promise, but there is still limited clinical evidence in the literature to support them. This article reviews the recent literature and guidelines on PHN treatment, with a focus on combination therapies, and seeks to help primary health care practitioners select treatment strategies that provide immediate relief for patients with localized PHN pain. PMID: 20107293 [PubMed - indexed for MEDLINE] 28. J Virol. 2010 Jan 27. [Epub ahead of print] Comparison of the biological and biochemical activities of several members of the alphaherpesvirus ICP0 family of proteins. Everett RD, Boutell C, McNair C, Grant L, Orr A. MRC Virology Unit, Institute of Virology, Church Street, Glasgow G11 5JR, Scotland, U.K. Immediate-Early protein ICP0 of herpes simplex virus type 1 (HSV-1) is an E3 ubiquitin ligase of the RING finger class that is required for efficient lytic infection and reactivation from latency. Other alphaherpesviruses also express ICP0-related RING finger proteins, but these have limited homology outside of the core RING domain. Existing evidence indicates that ICP0 family members have similar properties, but there has been no systematic comparison of the biochemical activities and biological functions of these proteins. Here we describe an inducible cell line system that allows expression of the ICP0 related proteins of bovine herpes virus type 1 (BHV-1), equine herpesvirus type 1 (EHV-1), pseudorabies virus (PRV) and varicella zoster virus (VZV) and their subsequent functional analysis. We report that the RING domains of all the proteins have E3 ubiquitin ligase activity in vitro. The BHV-1, EHV-1 and PRV proteins complement ICP0-null mutant HSV-1 plaque formation and induce de-repression of quiescent HSV-1 genomes to extents similar to those achieved by ICP0 itself. VICP0 was found to be extremely unstable, which limited its analysis in this system. We compared the abilities of the ICP0 related proteins to disrupt ND10, induce degradation of PML and Sp100, to affect key components of the interferon signalling pathway and to interfere with induction of interferon stimulated genes. We found that the property that correlated most closely with their biological activities was the ability to preclude the recruitment of cellular ND10 proteins to sites closely associated with incoming HSV-1 genomes and early replication compartments. PMID: 20106921 [PubMed - as supplied by publisher] 29. Int J Infect Dis. 2010 Feb;14(2):e141-e146. Epub 2010 Jan 27. Etiology and clinico-epidemiological profile of acute viral encephalitis in children of western Uttar Pradesh, India. Beig FK, Malik A, Rizvi M, Acharya D, Khare S. Department of Paediatrics, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh, India. OBJECTIVES: To study the etiology of viral encephalitis (VE) in the children of western Uttar Pradesh, India and to assess the clinico-epidemiological profile of these children in relation to VE. METHODS: Both cerebrospinal fluid and serum samples were collected from pediatric patients suffering from encephalitis hospitalized at Jawaharlal Nehru Medical College, Aligarh from July 2004 to November 2006. Viral isolation was done on RD cells, HEp-2 cells, and Vero cells from the cerebrospinal fluid samples of children with suspected VE. A microneutralization test was performed for enterovirus 71. An enzyme immunoassay for IgM antibodies was performed for measles virus, mumps virus, varicella zoster virus, herpes simplex virus 1, and Japanese encephalitis virus. RESULTS: Eighty-seven patients were enrolled in the study. The most common etiology of VE was enterovirus 71 (42.1%), followed by measles (21.1%), varicella zoster virus (15.8%), herpes simplex virus (10.5%), and mumps (10.5%). Japanese encephalitis virus was not found in any case. Enterovirus 71 infection caused significant morbidity in children; mortality occurred in 50%. A preponderance of cases occurred in December. In our study generalized convulsions along with altered sensorium were the significant findings in patients with VE. CONCLUSIONS: Enterovirus 71, the major etiology of VE in our study, was associated with significant mortality and morbidity. Such studies should be conducted frequently to assess the role of emerging VE in different regions. Copyright © 2010. Published by Elsevier Ltd. PMID: 20106698 [PubMed - as supplied by publisher] 30. Drugs Aging. 2010;27(2):159-76. doi: 10.2165/10489140-000000000-00000. Zoster vaccine (Zostavax): a review of its use in preventing herpes zoster and postherpetic neuralgia in older adults. Sanford M, Keating GM. Adis, a Wolters Kluwer Business, Auckland, New Zealand. demail@adis.co.nz Individuals who have been infected with varicella zoster virus (VZV) are at risk for developing herpes zoster and this risk appears to be related to a decline in VZV-specific cell-mediated immunity (CMI). Zostavax (zoster vaccine) is a one-dose, high-potency, live, attenuated VZV vaccine that boosts VZV-specific CMI and this is its presumed mechanism of action. Zoster vaccine is registered in the EU for use in adults aged >or=50 years for the prevention of herpes zoster and herpes zoster-related postherpetic neuralgia. In the Shingles Prevention Study, a placebo-controlled trial in adults aged >or=60 years (n = 38 546), zoster vaccine led to a sustained boost of VZV-specific CMI. Over a mean herpes zoster surveillance period of 3.1 years, zoster vaccine reduced the herpes zoster-related burden of illness by 61%, reduced the incidence of herpes zoster by 51% and reduced the incidence of postherpetic neuralgia by 67%. Zoster vaccine recipients who developed herpes zoster had a shorter illness duration and severity than placebo recipients who developed herpes zoster. Zoster vaccine had continuing efficacy in a Shingles Prevention Study subpopulation followed for 7 years post-vaccination. Zoster vaccine was generally well tolerated in older adults. While cost-effectiveness estimates in pharmacoeconomic analyses varied widely according to vaccine and herpes zoster parameter cost/benefit estimates, an analysis from a UK perspective found a zoster vaccine immunization programme in adults aged 65 years to be cost effective. In older adults, the zoster vaccine has the potential to significantly reduce the herpes zoster burden of illness by decreasing the incidence of herpes zoster or reducing its severity. PMID: 20104941 [PubMed - in process] 31. JAMA. 2010 Feb 24;303(8):733-4. Epub 2010 Jan 26. Incomplete financial disclosures in an editorial, clinical crossroads, and reply letter related to herpes zoster. Whitley RJ. Comment on: JAMA. 2009 Jul 1;302(1):73-80. JAMA. 2009 Nov 4;302(17):1862; author reply 1862-3. JAMA. 2009 Feb 18;301(7):774-5. PMID: 20103745 [PubMed - in process] 32. Eur J Dermatol. 2010 Jan 26. [Epub ahead of print] Disseminated cutaneous herpes zoster complicated by acyclovir nephrotoxicity and successfully treated with brivudin. Aksoy B, Altaykan-Hapa A, Cengiz A, Mete Aksoy H, Atakan N. PMID: 20103497 [PubMed - as supplied by publisher] 33. Clin Med. 2009 Dec;9(6):630. Aciclovir neurotoxicity is an important side effect of therapy in patients with renal impairment. Brady M, Main J. Comment on: Clin Med. 2009 Jun;9(3):231-5. PMID: 20095318 [PubMed - indexed for MEDLINE] 34. Rheumatol Int. 2009 Dec 20. [Epub ahead of print] Safety of biologic agents after rituximab therapy in patients with rheumatoid arthritis. Mishra R, Singh V, Pritchard CH. Division of Rheumatology, University of Pennsylvania, 827 Penn Tower Bldg, 3401 Civic Center Blvd, Philadelphia, PA, 19104, USA, richa.mishra@uphs.upenn.edu. The safety of other biologic therapies in rheumatoid arthritis (RA) following B cell-depletion therapy with rituximab has not been established. This retrospective chart review of patients attending an outpatient rheumatology clinic aimed to assess the incidence of adverse events in patients receiving biologic agents to treat RA after an inadequate response or intolerance to rituximab. The charts of 22 patients (18 female; mean age 59 years) were reviewed. Duration of RA was >2 years. Before rituximab, patients had failed one (n = 10), two (n = 4) or three (n = 7) biologic therapies: 1 patient started on rituximab as a first-line biologic. Eighteen patients stopped rituximab due to an inadequate clinical response, while four patients stopped due to adverse events. The mean time to starting a new biologic after rituximab was 4 months, although five patients were started within 1 month of the last rituximab infusion. Abatacept (41%) was the most common biologic used after rituximab. The mean follow-up time from the last rituximab infusion was 14 months. Adverse events occurring after rituximab therapy, but before initiation of a new biologic, included disseminated herpes zoster and aseptic meningitis (both required hospitalization). Adverse events recorded after starting a new biologic post-rituximab included rash, carbuncle, upper respiratory tract infection, urinary tract infection, pneumonia, and eczema, but none was classified as serious. Most of these events occurred in patients receiving abatacept. In conclusion, in this retrospective analysis, no serious adverse events were recorded in patients who received biologic agents following rituximab therapy. PMID: 20091035 [PubMed - as supplied by publisher] 35. N Engl J Med. 2010 Feb 4;362(5):416-26. Epub 2010 Jan 20. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis. Giovannoni G, Comi G, Cook S, Rammohan K, Rieckmann P, Soelberg Sorensen P, Vermersch P, Chang P, Hamlett A, Musch B, Greenberg SJ; CLARITY Study Group. Collaborators: Giovannoni G, Comi G, Cook S, Rammohan K, Rieckmann P, Soelberg Sorensen P, Vermersch P, Sandberg-Wollheim M, Cuzick J, Juliusson G, Reingold S, King J, Pollard J, Sedal L, Aichner F, Eggers C, Dive D, Medaer R, Ferreira M, Manchev I, Milanov I, Haralanov L, Deleva N, Petrova N, Bozhinov P, Zahariev Z, Stamenov B, Shotekov P, Petrov I, Moskov R, Emond F, Freedman M, Grand'Maison F, Jacques F, Vorobeychik G, Demarin V, Kovacicek M, Lusic I, Perhat-Bucevic T, Havrdova E, Talab R, Kanovsky P, Soelberg Sorensen P, Petersen T, Gross-Paju K, Kalbe I, Toomsoo T, Elovaara I, Eralinna JP, Reunanen M, Clavelou P, Damier P, Debouverie M, Edan G, Gout O, Labauge P, Laplaud D, Wiertlewski S, Vermersch P, Heidenreich F, Maurer M, Kieseier B, Limmroth V, Oschmann P, Schimrigk S, Steinbrecher A, Zettl U, Ziemann U, Karageorgiou K, Kyritsis A, Papadimitriou A, Amato MP, Bernardi G, Morra VB, Comi G, Galgani S, Gallo P, Patti F, Marrosu M, Pozzilli C, Trojano M, Mancardi GL, Gebeily S, Koussa S, Wehbe M, Yamout B, Vaitkus A, Metra M, Messouak O, Mossaddaq R, Slassi I, Yahyaoui M, Hupperts RM, Czlonkowska A, Kozubski W, Nyka W, Selmaj K, Szczudlik A, Figueiredo J, Pedrosa R, Alifirova V, Balyazin V, Barbarash O, Belova A, Boyko A, Gusev E, Elchaninov A, Jacoupov E, Julev N, Kotov S, Kudryavtsev A, Laskov V, Lesnyak O, Odinak M, Pasechnik E, Poverennonva I, Skoromets A, Spirin N, Stolyarov I, Vorobieva O, Voskresenskaya O, Zaslavskiy L, Zonova E, Bohlega S, El-Jumah M, Drulovic J, Nadj C, Goebels N, Schluep M, Ayed-Frih M, Hentati F, Mhiri C, Mrabet A, Mrissa R, Idiman E, Karabudak R, Turan OF, Ahmed F, Constantinescu C, Giovannoni G, Hawkins C, Palace J, Sharrack B, Loganovsky K, Moskovko S, Nehrych T, Voloshyna NP, Carlini W, Cook S, English J, Garmany G, Glyman S, Huddlestone J, Hurwitz B, Kresa-Reahl K, Mikol D, Pardo G, Rammohan K, Rao H, Reif M, Thrower B, Royal W, Webb R, Wynn D, Naga C, Allen N, Lin K, Stefoski D, Balabanov R. Queen Mary University London, the Blizard Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, London, United Kingdom. g.giovannoni@qmul.ac.uk Comment in: N Engl J Med. 2010 Feb 4;362(5):456-8. BACKGROUND: Cladribine provides immunomodulation through selective targeting of lymphocyte subtypes. We report the results of a 96-week phase 3 trial of a short-course oral tablet therapy in patients with relapsing-remitting multiple sclerosis. METHODS: We randomly assigned 1326 patients in an approximate 1:1:1 ratio to receive one of two cumulative doses of cladribine tablets (either 3.5 mg or 5.25 mg per kilogram of body weight) or matching placebo, given in two or four short courses for the first 48 weeks, then in two short courses starting at week 48 and week 52 (for a total of 8 to 20 days per year). The primary end point was the rate of relapse at 96 weeks. RESULTS: Among patients who received cladribine tablets (either 3.5 mg or 5.25 mg per kilogram), there was a significantly lower annualized rate of relapse than in the placebo group (0.14 and 0.15, respectively, vs. 0.33; P<0.001 for both comparisons), a higher relapse-free rate (79.7% and 78.9%, respectively, vs. 60.9%; P<0.001 for both comparisons), a lower risk of 3-month sustained progression of disability (hazard ratio for the 3.5-mg group, 0.67; 95% confidence interval [CI], 0.48 to 0.93; P=0.02; and hazard ratio for the 5.25-mg group, 0.69; 95% CI, 0.49 to 0.96; P=0.03), and significant reductions in the brain lesion count on magnetic resonance imaging (MRI) (P<0.001 for all comparisons). Adverse events that were more frequent in the cladribine groups included lymphocytopenia (21.6% in the 3.5-mg group and 31.5% in the 5.25-mg group, vs. 1.8%) and herpes zoster (8 patients and 12 patients, respectively, vs. no patients). CONCLUSIONS: Treatment with cladribine tablets significantly reduced relapse rates, the risk of disability progression, and MRI measures of disease activity at 96 weeks. The benefits need to be weighed against the risks. (ClinicalTrials.gov number, NCT00213135.) 2010 Massachusetts Medical Society PMID: 20089960 [PubMed - indexed for MEDLINE] 36. N Engl J Med. 2010 Feb 4;362(5):402-15. Epub 2010 Jan 20. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. Cohen JA, Barkhof F, Comi G, Hartung HP, Khatri BO, Montalban X, Pelletier J, Capra R, Gallo P, Izquierdo G, Tiel-Wilck K, de Vera A, Jin J, Stites T, Wu S, Aradhye S, Kappos L; TRANSFORMS Study Group. Collaborators: Cohen J, Barkhof F, Comi G, Hartung HP, Kappos L, Khatri B, Montalban X, Pelletier J, Easton JD, Calandra T, DiMarco J, Hudson L, Kesselring J, Laupacis A, Temkin N, Weinshenker B, Zarbin M, Barkhof F, Poppe P, Luetic G, Cristiano E, Caceres F, Garcea O, Correale J, Ballario C, Piedrabuena R, Pollard J, Beran R, Hodgkinson S, Schwartz R, Heard R, King J, Butzkueven H, Maida EM, Vass K, Franta-Elmer C, Berger T, Aichner F, Ladurner G, Bissay V, Sindic C, D'Hooghe M, Mulleners E, Damasceno B, Barreira A, Naylor R, Alvarenga R, Bacellar A, Haussen S, Duquette P, Antel J, Lamontagne A, Grand'maison F, Freedman M, Christie S, O'Connor P, Vorobeychik G, Devonshire V, Ramadan M, Hamdy S, Reda E, Hashem S, Fouad M, Lebrun-Frenay C, Pelletier J, Clanet M, Brochet B, Debouverie M, Heinzlef O, Ziemssen T, Koehler W, Tiel-Wilck K, Bachus R, Altmann N, Faiss J, Baum K, Dressel A, Luckner K, Ebke M, Stangel M, Hartung HP, Diener HC, Bethke F, Limmroth V, Maschke M, Thoemke F, Reifschneider G, Diehm R, Wildemann B, Melms A, Rauer S, Karlbauer G, Berthele A, Lang M, Tumani H, Krauseneck P, Klein M, Papadimitriou A, Karageorgiou K, Liakopoulos D, Tascos N, Plaitakis A, Papathanasopoulos P, Panczel G, Jakab G, Csiba L, Komoly S, Csanyi A, Bartos L, Centonze D, Pozzilli C, Marrosu MG, Bertolotto A, Mancardi G, Scarpini E, Comi G, Protti A, Ghezzi A, Capra R, Bergamaschi R, Gallo P, Stecchi S, Montanari E, Tola MR, Amato MP, Silvestrini M, Lugaresi A, Trojano M, Brescia Morra V, Ruggieri S, Patti F, Kim SM, Lee KH, Kim HJ, Park SP, Ginestal R, Salgado AV, Fontoura P, Cunha L, Sousa L, Sa MJ, Pedrosa R, Montalban X, Arbizu T, Arroyo R, Garcia Merino JA, Fernandez O, Izquierdo G, Casanova B, Antiguedad A, Goebels N, Kappos L, Young C, Lee M, Chaudhuri A, Nicholas R, Chinea Martinez A, Preiningerova J, Greco D, Gross J, Newman S, Mitchell G, Pawar G, Freedman SM, Kaufman M, Absher J, Kantor D, Ayala R, Honeycutt W, Shafer S, Steingo B, Delgado S, Cascione M, Brock C, Keegan A, LaGanke C, Hunter S, Wilson E, Cohen J, Mazhari A, Bauer W, Khatri B, Singer B, Lynch S, Rowe V, Hutton G, Gazda S, Dihenia B, Campagnolo D, Chippendale T, Ash P, Jung L, Olek M. Mellen Center, Cleveland Clinic, Cleveland, OH 44195, USA. cohenj@ccf.org Comment in: N Engl J Med. 2010 Feb 4;362(5):456-8. BACKGROUND: Fingolimod (FTY720), a sphingosine-1-phosphate-receptor modulator that prevents lymphocyte egress from lymph nodes, showed clinical efficacy and improvement on imaging in a phase 2 study involving patients with multiple sclerosis. METHODS: In this 12-month, double-blind, double-dummy study, we randomly assigned 1292 patients with relapsing-remitting multiple sclerosis who had a recent history of at least one relapse to receive either oral fingolimod at a daily dose of either 1.25 or 0.5 mg or intramuscular interferon beta-1a (an established therapy for multiple sclerosis) at a weekly dose of 30 microg. The primary end point was the annualized relapse rate. Key secondary end points were the number of new or enlarged lesions on T(2)-weighted magnetic resonance imaging (MRI) scans at 12 months and progression of disability that was sustained for at least 3 months. RESULTS: A total of 1153 patients (89%) completed the study. The annualized relapse rate was significantly lower in both groups receiving fingolimod--0.20 (95% confidence interval [CI], 0.16 to 0.26) in the 1.25-mg group and 0.16 (95% CI, 0.12 to 0.21) in the 0.5-mg group--than in the interferon group (0.33; 95% CI, 0.26 to 0.42; P<0.001 for both comparisons). MRI findings supported the primary results. No significant differences were seen among the study groups with respect to progression of disability. Two fatal infections occurred in the group that received the 1.25-mg dose of fingolimod: disseminated primary varicella zoster and herpes simplex encephalitis. Other adverse events among patients receiving fingolimod were nonfatal herpesvirus infections, bradycardia and atrioventricular block, hypertension, macular edema, skin cancer, and elevated liver-enzyme levels. CONCLUSIONS: This trial showed the superior efficacy of oral fingolimod with respect to relapse rates and MRI outcomes in patients with multiple sclerosis, as compared with intramuscular interferon beta-1a. Longer studies are needed to assess the safety and efficacy of treatment beyond 1 year. (ClinicalTrials.gov number, NCT00340834.) 2010 Massachusetts Medical Society PMID: 20089954 [PubMed - indexed for MEDLINE] 37. Gan To Kagaku Ryoho. 2010 Jan;37(1):99-102. [Alteration in antibody-mediated immunity in patients with rituximab-combined chemotherapy and incidence of herpes zoster] [Article in Japanese] Ito K, Okamoto M, Maruyama F, Handa K, Yamamoto Y, Watanabe M, Tsuzuki M, Mizuta S, Kumazawa S, Ohta H, Nakano I, Emi N. Department of Pharmacy, Fujita Health University Hospital, Japan. Rituximab, a chimeric monoclonal antibody against the CD20 protein, has an antineoplastic effect resulting from antibody dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). In patients with rituximab-combined chemotherapy, a decline in immunoglobulin can be observed. This is more likely to cause virus reactivation, such as Herpes (H) zoster. However, this fact has not reported in a large-scale study. In order to research immunodeficiency conditions in patients with rituximab-combined therapy, we examined the alteration in immunoglobulin level throughout the treatment among 205 cases with B-cell lymphoma. We also studied the prevalence of H. zoster in those cases. The IgG level throughout the treatment was measured in 89 patients in the research. The median post-chemotherapy IgG level was 41.1% lower than its pre-chemotherapy IgG level. In 58 cases, the IgG level following chemotherapy was below the normal level. In 22 cases, the IgG level dropped to less than half of the pre-chemotherapy level. H. zoster developed in 17 cases (8.3%). There was no significant difference in IgG level between H. zoster-onset cases and non-H. zoster-onset cases. Antibody-mediated immunity can decrease greatly and prolong in cases with rituximab in combination with chemotherapy. Therefore, infection control is considered to be important. PMID: 20087040 [PubMed - indexed for MEDLINE] 38. Cad Saude Publica. 2009;25 Suppl 3:S401-14. Impact of methodology on the results of economic evaluations of varicella vaccination programs: is it important for decision-making? de Soarez PC, Novaes HM, Sartori AM. Departamento de Medicina Preventiva, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brasil. pcsoarez@uol.com.br This study aims to review the literature on economic evaluation of childhood varicella vaccination programs and to discuss how heterogeneity in methodological aspects and estimation of parameters can affect the studies' results. After applying the inclusion criteria, 27 studies published from 1980 to 2008 were analyzed in relation to methodological differences. There was great heterogeneity in the perspective adopted, evaluation of indirect costs, type of model used, modeling of the effect on herpes zoster, and estimation of vaccine price and efficacy parameters. The factor with the greatest impact on results was the inclusion of indirect costs, followed by the perspective adopted and vaccine price. The choice of a particular methodological aspect or parameter affected the studies' results and conclusions. It is essential that authors present these choices transparently so that users of economic evaluations understand the implications of such choices and the direction in which the results of the analysis were conducted. PMID: 20027388 [PubMed - in process] 39. Proc Natl Acad Sci U S A. 2010 Jan 12;107(2):866-71. Epub 2009 Dec 22. Myelin-associated glycoprotein mediates membrane fusion and entry of neurotropic herpesviruses. Suenaga T, Satoh T, Somboonthum P, Kawaguchi Y, Mori Y, Arase H. Department of Immunochemistry, Research Institute for Microbial Diseases and WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan. Varicella-zoster virus (VZV) and herpes simplex virus (HSV) are prevalent neurotropic herpesviruses that cause various nervous system diseases. Similar to other enveloped viruses, membrane fusion is an essential process for viral entry. Therefore, identification of host molecules that mediate membrane fusion is important to understand the mechanism of viral infection. Here, we demonstrate that myelin-associated glycoprotein (MAG), mainly distributed in neural tissues, associates with VZV glycoprotein B (gB) and promotes cell-cell fusion when coexpressed with VZV gB and gH/gL. VZV preferentially infected MAG-transfected oligodendroglial cells. MAG also associated with HSV-1 gB and enhanced HSV-1 infection of promyelocytes. These findings suggested that MAG is involved in VZV and HSV infection of neural tissues. PMCID: PMC2818916 [Available on 2010/7/12] PMID: 20080767 [PubMed - in process] 40. Radiat Oncol. 2010 Jan 16;5(1):3. Tailored total lymphoid irradiation in heart transplant patients: 10-years experience of one center. Ghadjar P, Joos D, Martinelli M, Hullin R, Zwahlen M, Lossl K, Carrel T, Aebersold DM, Mohacsi P. Department of Cardiovascular Surgery, Swiss Cardiovascular Center, University Hospital Bern, Freiburgstrasse, 3010 Bern, Switzerland. Paul.mohacsi@insel.ch. ABSTRACT: BACKGROUND: To assess safety and efficacy of tailored total lymphoid irradiation (tTLI) in cardiac transplant patients. METHODS: A total of seven patients, of which five had recalcitrant cellular cardiac allograft rejection (RCCAR), confirmed by endomyocardial biopsies, and two had side effects of immunosuppressive drug therapy, were all treated with tTLI. tTLI was defined by the adjustment of both the fraction interval and the final irradiation dosage both being dependent on the patients general condition, irradiation-dependent response, and the white blood and platelet counts. A mean dose of 6.4 Gy (range, 1.6 - 8.8 Gy) was given. Median follow-up was 7 years (range, 1.8 - 12.2 years). RESULTS: tTLI was well tolerated. Two patients experienced a severe infection during tTLI (pneumocystis jirovecii pneumonia, urosepsis and generalized herpes zoster) and one patient developed a lymphoproliferative disorder after tTLI. The rate of rejection episodes before tTLI was 0.43 episodes/patient/month and decreased to 0.02 episodes/patient/month after tTLI (P < .001). At the end of the observation time, all patients except one were alive. CONCLUSIONS: tTLI is a useful treatment strategy for the management of RCCAR and in patients with significant side effects of immunosuppressive drug therapy. In this series tTLI demonstrated significantly decreased rejection rates without causing relevant treatment-related toxicity. PMCID: PMC2822786 PMID: 20078889 [PubMed - in process] 41. Zhongguo Ji Hua Mian Yi. 2009 Aug;15(4):327-9. [Epidemiological characteristic of Varicella and Varicella-Zoster virus genotype in Minhang District of Shanghai] [Article in Chinese] Du Y, Jiang LF, Zhang LP. Minhang District Center for Disease Control and Prevention of Shanghai, Shanghai 201101, China. OBJECTIVE: To describe the epidemiological characteristic of varicella, and to find out the genotype of the prevalent Varicella-Zoster Virus (VZV) in Minhang, Shanghai. Analysis was carried out during Nov. 2007 to Apr 2008. METHODS: The data collected from the National Diseases Reporting Management System (NDRS) and Provincial Disease Surveillance Point System (DSP). Samples from herpes of patients were also collected to isolate VZV in Vero and Vero-E6 cell lines, then to detected if cytopathic effect (CPE) by PCR, and finally to identify the genotype by sequence analysis. RESULTS: 29 outbreaks of 271 cases occurred in Minhang during Nov. 2007 to Apr. 2008, and attack rate was 0.42% in average. Among the cases, 37 (13.65%) had vaccinated before getting varicella. Most cases occurred in November and December, and clustered in some areas with population migrant frequently. 2 VZV strains were isolated and identified as genotype J. CONCLUSION: The prevalence of varicella in Minhang was serious. The varicella prevention and control among schools and kindergartens should be strengthened by propaganda and vaccination. PMID: 20077731 [PubMed - indexed for MEDLINE] 42. Zhongguo Ji Hua Mian Yi. 2009 Feb;15(1):78-82. [Varicella] [Article in Chinese] Xu ST. State Key Laboratory for Molecular Virology and Genetic Engineering, Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100050, China. Varicella is an acute, highly contagious respiratory and caused by Varicella-zoster virus (VZV). After the primary infection, VZV induce Varicella, then the virus remains dormant in sensory nerve roots in life. Upon the reactivation, shingles can occur. Most of patients can recovery very soon, but kinds of potentially severe complication can induce death. Nowadays the VZV vaccination isn't included in the expanded immunization program in our country. Varicella outbreaks take place at times in the middle of children of our country. The paper offers concise description about pathogen characteristics, diagnosis methods, clinical character, epidemiology knowledge and strategy of prevention. PMID: 20077683 [PubMed - indexed for MEDLINE] 43. Zhongguo Ji Hua Mian Yi. 2009 Apr;15(2):127-30. [Isolation identification and serological analysis on varicella-zoster virus from an outbreak in Shanghai in 2007] [Article in Chinese] Lu J, Li CS, Hu JY. Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China. OBJECTIVE: To make serological analysis and identify the etiology of an outbreak of chickenpox in Zhabei District of Shanghai in 2007. METHODS: IgM and IgG of the paired serums were detected by ELISA. The collected herpes were inoculated into MRC-5 cells to get VZV isolations and identify them by VZV standard serums. A 268bp fragment was amplified by specific PCR primers. RESULTS: Among the five paired serums, two of the acute phase serums were VZV IgM positive, one was VZV IgG positive, and two were equivocal for anti-VZV IgG. All of the convalescent serums were VZV IgG positive, and four of them were 4 times higher in antibody titer than those of acute phase serums. Viruses were isolated from all of the 5 herpes, and then identified by VZV standard serum. The electrophoresis result of PCR products showed the single specific strap. CONCLUSIONS: This outbreak was caused by VZV virus. 47.4% of the patients were inoculated in postnatal or domestic VZV vaccines in China 3 years after delivery. The effectiveness of VZV vaccine has been certified. It is necessary to consider the immunization strategy of VZV vaccine. PMID: 20077657 [PubMed - indexed for MEDLINE] 44. Am J Public Health. 2010 Jan 14. [Epub ahead of print] Herpes Zoster and Exposure to the Varicella Zoster Virus in an Era of Varicella Vaccination. Donahue JG, Kieke BA, Gargiullo PM, Jumaan AO, Berger NR, McCauley JS, Belongia EA. Marshfield Clinic Research Foundation. Objectives. We performed a case-control study to determine if participants with herpes zoster had fewer contacts with persons with varicella or zoster, and with young children, to explore the hypothesis that exposure to persons with varicella zoster virus (VZV) results in "immune boosting."Methods. Participants were patients of the multispecialty Marshfield Clinic in Wisconsin. We identified patients aged 40 to 79 years with a new diagnosis of zoster from August 2000 to July 2005. We frequency matched control participants to case participants for age. We confirmed diagnoses by chart review and assessed exposures by interview.Results. Interviews were completed by 633 of 902 eligible case participants (70.2%) and 655 of 1149 control participants (57.0%). The number of varicella contacts was not associated with zoster; there was no trend even at the highest exposure level (3 or more contacts). Similarly, there was no association with exposure to persons with zoster or to children, or with workplace exposures.Conclusions. Although exposure to VZV in our study was relatively low, the absence of a relationship with zoster reflects the uncertain influence of varicella circulation on zoster epidemiology. PMID: 20075320 [PubMed - as supplied by publisher] 45. Rinsho Ketsueki. 2009 Dec;50(12):1720-4. [Multiple autologous transplantations with intermediate-dose melphalan for two elderly patients with relapsed or refractory diffuse large B-cell lymphoma] [Article in Japanese] Nishimoto T, Hatanaka K, Matsuoka A, Ueda K, Yonetani N, Tamaki T. Department of Hematology, Rinku General Medical Center Izumisano Municipal Hospital. High-dose chemotherapy supported by autologous peripheral blood stem cell transplantation (PBSCT) is beneficial for patients with relapsed or refractory but chemosensitive diffuse large B-cell lymphoma (DLBCL). However, most elderly patients are not indicated for that therapy and receive supportive treatment only. We describe here two elderly patients with relapsed or refractory DLBCL who achieved prolonged disease-free survival after undergoing intermediate-dose melphalan therapy supported by PBSCT (MEL100) three times. Case 1 was an early relapse (within one year) after the first remission and case 2 was a second relapse. Both cases are currently alive without relapse and have maintained a good performance status for 41 months and 32 months, respectively, after MEL100. Febrile neutropenia and herpes zoster as non-hematological toxicities (grade > or = 3) occurred only in case 1. Considering the benefits vs. toxic effects, this regimen may improve the prognosis of elderly patients with relapsed or refractory DLBCL by MEL100. PMID: 20068281 [PubMed - in process] 46. Rheumatol Int. 2010 Jan 12. [Epub ahead of print] A case of rheumatoid arthritis presenting with postherpetic neuralgia and abdominal-wall pseudohernia. Dobrev HP, Atanassova PA, Sirakov VN, Zisova LG. Department of Dermatology, Medical University, Plovdiv, 4000, Bulgaria. Postherpetic neuralgia is a common complication, while the postherpetic abdominal-wall pseudohernia (AWP) is a quite rare complication of herpes zoster (HZ). We report a patient >45 years of age with a history of rheumatoid arthritis (RA) who presented with two chronic HZ complications. A 75-year-old woman was admitted with neuralgia following cutaneous herpes zoster 6 weeks before. She was on long-term glucocorticoid, antimalarial and non-steroidal anti-inflammatory treatment. Confluent ulcers began to fill with granulation tissue, crusts, scars and skin discoloration in the area of the left T12-L2 dermatomes and reducible, painless swelling of the left flank, 20 x 20 cm, without palpable defect in abdominal-wall. There were typical joint deformity and positive rheumatoid factor. On neurological examination superficial abdominal reflexes were diminished in the left side, with hypesthesia of the overlying skin. Needle electromyography revealed denervational changes limited to the left-side muscles (on affected dermatomes T12-L2). Thoracoabdominal CT did not reveal the presence of existing hernia. There was an abdominal distension, the left abdominal-wall was thinner than the right side. The patient was treated with an oral preparation containing benfotiamine and vitamins B6 and B12, carbamazepine, amitriptyline, gabapentin, and local lidocaine. Skin rash left with scarring and pigmentary changes and the abdominal-wall swelling resolved within 8 months, however, the pain still persisted. To our best knowledge, this is the first observation of RA-associated postherpetic AWP. This rare motor complication appears to be self-limited with a good prognosis for recovery, while postherpetic neuralgia may require a combination of treatments for adequate pain relief. Older age, female sex, greater rash and acute pain severity are considered as risk factors associated with severe postherpetic neuralgia. In addition, patients with RA, mainly those treated with oral corticosteroids, are also at increased risk of HZ complications. PMID: 20066424 [PubMed - as supplied by publisher] 47. Surg Oncol. 2010 Jan 5. [Epub ahead of print] Neuropathic pain and its assessment. Cruccu G, Truini A. Department of Neurological Sciences, University La Sapienza, Rome, Italy; IRCCS San Raffaele Pisana, Rome, Italy. Neuropathic pain, i.e., pain arising as a direct consequence of a lesion or disease affecting the somatosensory system, is a frequent complaint in the elderly. The frequency of herpes zoster and peripheral neuropathy, the commonest diseases that cause neuropathic pain, increases with age. More than half of all persons in whom herpes zoster develops are older than 60 years and about 30% of these patients will ultimately suffer from chronic postherpetic neuralgia. The prevalence of peripheral neuropathy rises from 2.4% in the general population to 8% in subjects older than 55 years. With advancing age, the nociceptive pathway undergoes degenerative changes, mainly consisting of axonal loss. This age-related nociceptive pathway degeneration probably explains why elderly patients tend to under-report pain in many medical conditions including myocardial infarction, fractures, and arthritis. This age-related impairment probably plays a key role in the development of neuropathic pain. In this report we describe the most reliable methods for assessing neuropathic pain such as laser evoked potential (LEP) recordings and skin biopsy, procedures that selectively assess nociceptive pathways in order to obtain a rapid diagnosis and hence determine treatment. Copyright © 2009. Published by Elsevier Ltd. PMID: 20056406 [PubMed - as supplied by publisher] 48. Acta Clin Croat. 2009 Sep;48(3):359-65. Neuropathic pain. Basic-Kes V, Zavoreo I, Bosnar-Puretic M, Ivankovic M, Bitunjac M, Govori V, Demarin V. University Department od Neurology, Reference Center for Neurovascular Disorders, Ministry of Health and Social Welfare of Republic of Croatia, Sestre milosrdnice University Hospital, Zagreb. vanjakes@net.hr Neuropathic pain refers to pain that originates from pathology of the nervous system. Common causes of neuropathic pain are diabetes mellitus, reactivation of herpes zoster, nerve compression or radiculopathy, alcohol, chemotherapy or abuse of some drugs, and trigeminal neuralgia. Specific symptoms of neuropathic pain are mechanical allodynia and cold hyperalgesia. Drugs to treat neuropathic pain can be divided into adjuvant analgesics (antidepressants and anticonvulsants), opioids and topical agents. The use of multiple drug therapies is common in practice. Despite considerable increase in the number of randomized placebo-controlled trials in neuropathic pain in the last few years, the medical treatment of neuropathic pain is still far from being satisfactory, with less than half of patients achieving significant benefit with any pharmacological drug. PMID: 20055264 [PubMed - indexed for MEDLINE] 49. Indian J Dermatol. 2009;54(1):62-4. Childhood herpes zoster: a clustering of ten cases. Prabhu S, Sripathi H, Gupta S, Prabhu M. Department of Skin and STD, Kasturba Medical College, Manipal, India. Herpes zoster occurs due to reactivation of the latent varicella zoster virus and is usually a disease of the elderly. Childhood herpes zoster is believed to be rare, though recent studies suggest increasing incidence in children. Here we report ten cases of childhood herpes zoster, seven of which occurred within a short span of six months, at a tertiary care level hospital in Pokhara, Nepal. Only three of the ten children reported previous history of varicella infection and none was immunized against varicella. Though childhood herpes zoster accounted for less than 1% of the total zoster cases in the past, recent reports show an increase in the number of cases in apparently healthy children. So far, no studies have been done linking childhood herpes zoster with HIV, though there are many studies linking it with other immunocompromised conditions. PMCID: PMC2800875 PMID: 20049274 [PubMed - in process] 50. Wien Klin Wochenschr. 2009;121(23-24):776-9. Ischemic stroke associated with adenoviral infection in a 4-year-old boy. Kutlesa M, Tesovic G, Knezovic I, Mise B, Viskovic K, Barisic N. Department of Pediatric Infectious Diseases, University Hospital for Infectious Diseases Dr. Fran Mihaljevic, Zagreb, Croatia. kutlesam@yahoo.com We present a case of childhood arterial ischemic stroke associated with proven adenoviral upper respiratory tract infection in a previously healthy 4-year-old boy. Adenoviral meningitis and encephalitis have been reported repeatedly, thus confirming the neuroinvasive capability of these viruses. However, an association between adenoviral infection and arterial ischemic stroke has not been described thus far. HIV and varicella zoster virus are the only microorganisms that have been consistently associated with arterial ischemic stroke in the absence of acute central nervous system infection. In HIV-infected individuals ischemic stroke can be caused by vasculitis and hypercoagulability. Granulomatous arteritis of the vessel wall causes post-varicella cerebral infarction and ischemic stroke after herpes zoster ophthalmicus. We suggest that in our patient a post-varicella cerebral infarction-like mechanism of adenoviral spread to the affected artery wall occurred through the ophthalmic branch of the trigeminal nerve. Adenoviruses are neuroinvasive and inflamed conjunctiva might have permitted introduction of the virus into ophthalmic nerve tissue. In consequence, the stenotic lesion of the artery might have been induced by the presence of adenovirus and the subsequent inflammatory reaction. We recommend a prompt quest for adenoviral infection in all previously healthy children with fever and clinical presentation compatible with ischemic stroke, because timely diagnosis and treatment could improve the outcome and hasten neurological recovery. PMID: 20047116 [PubMed - in process] 51. Acta Dermatovenerol Alp Panonica Adriat. 2009 Dec;18(4):179-82. Zosteriform lymphangioma circumscriptum. Patel GA, Siperstein RD, Ragi G, Schwartz RA. Dermatology, New Jersey Medical School, 185 South Orange Avenue, Newark, New Jersey 07103-2714, USA. Lymphangioma circumscriptum (LC) is a form of lymphangioma involving skin and subcutaneous tissue. It is evident as translucent vesicles of varying size, though commonly 2 to 4 mm, and of a pink, red, or black hue. It is localized to the dermis, frequently extending deeply and laterally. LC may resemble other entities, such as metastatic carcinoma of the skin, lymphangiectasis, or herpes zoster. We report an unusual verruciform, zosteriform form of LC. PMID: 20043057 [PubMed - in process] 52. Neurology. 2010 Jan 5;74(1):85-6. Polyneuritis cranialis caused by varicella zoster virus in the absence of rash. Murata KY, Miwa H, Kondo T. Department of Neurology, Wakayama Medical University, 840-1 Kimiidera, Wakayama, Japan 641-8510. kemurata@wakayama-med.ac.jp PMID: 20038777 [PubMed - indexed for MEDLINE] 53. Antimicrob Agents Chemother. 2010 Mar;54(3):1146-51. Epub 2009 Dec 28. Pharmacokinetics of acyclovir and its metabolites in cerebrospinal fluid and systemic circulation after administration of high-dose valacyclovir in subjects with normal and impaired renal function. Smith JP, Weller S, Johnson B, Nicotera J, Luther JM, Haas DW. Division of Infectious Diseases, Vanderbilt University School of Medicine, 345 24th Avenue North, Suite 105, Nashville, TN 37203. david.w.haas@vanderbilt.edu. Valacyclovir, the l-valyl ester prodrug of acyclovir (ACV), is widely prescribed to treat infections caused by varicella-zoster virus or herpes simplex virus. Rarely, treatment is complicated by reversible neuropsychiatric symptoms. By mechanisms not fully understood, this occurs more frequently in the setting of renal impairment. We characterized the steady-state pharmacokinetics of ACV and its metabolites 9-[(carboxymethoxy)methyl]guanine (CMMG) and 8-hydroxy-acyclovir (8-OH-ACV) in cerebrospinal fluid (CSF) and the systemic circulation. We administered multiple doses of high-dose valacyclovir to 6 subjects with normal renal function and 3 subjects with chronic renal impairment (creatinine clearance [CrCl], approximately 15 to 30 ml/min). Dosages were 2,000 mg every 6 h and 1,500 mg every 12 h, respectively. Indwelling intrathecal catheters allowed serial CSF sampling throughout the dosing interval. The average steady-state concentrations of acyclovir, CMMG, and 8-OH-ACV were greater in both the systemic circulation and the CSF among subjects with impaired renal function than among subjects with normal renal function. However, the CSF penetration of each analyte, reflected by the CSF-to-plasma area under the concentration-time curve over the 6- or 12-h dosing interval (AUC(tau)) ratio, did not differ based on renal function. Renal impairment does not alter the propensity for ACV or its metabolites to distribute to the CSF, but the higher concentrations in the systemic circulation, as a result of reduced elimination, are associated with proportionally higher concentrations in CSF. PMCID: PMC2825963 [Available on 2010/9/1] PMID: 20038622 [PubMed - in process] 54. Hawaii Med J. 2009 Dec;68(11):277-8. Varicella zoster virus infection in patients taking the TNF-alpha inhibitor, etanercept: coincidence or causal? Izumi A. Department of Dermatology, John A. Burns School of Medicine, University of Hawai'i, Honolulu, HI 96813, USA. Ninety percent of varicella infections are seen in children under the age of ten and usually follow a benign clinical course with complete resolution of symptoms in one to three weeks. Herpes zoster an acute vesicular eruption due to the varicella-zoster virus (VZV), occurs mostly in adults. Biologic agents include tumor necrosis factor alpha (TNF-alpha) inhibitors that have significantly impacted the treatment of autoimmune and inflammatory conditions. Therapy with TNF-alpha inhibitors poses a potential risk of serious infections secondary to their immunomodulating properties; however multiple studies have demonstrated acceptable safety and tolerability profiles. A case of documented VZV infection (varicella) in an adult receiving the TNF-alpha inhibitor etanercept is described here. PMID: 20034255 [PubMed - indexed for MEDLINE] 55. Antivir Ther. 2009;14(8):1051-64. Herpesviridae and novel inhibitors. Siakallis G, Spandidos DA, Sourvinos G. Department of Virology, Faculty of Medicine, University of Crete, Crete, Greece. Herpesviridae comprises a large family of double-stranded DNA viruses that infect both animals and humans. Eight herpesviruses are known to infect humans: herpes simplex virus type-1 and -2, varicella zoster virus, human cytomegalovirus, Epstein-Barr virus, human herpesvirus 6 type-A and -B, human herpesvirus type-7 and -8 or Kaposi's sarcoma virus. Despite the fact that the past two decades have been evolutionary in the development of antiviral agents, therapeutic choices are restricted by limited efficacy and toxicity. Viral infections remain the cause of significant mortality worldwide, thus indicating the high medical need for the introduction of novel promising compounds in the antiviral chemotherapy era. This review focuses on recent data regarding several novel groups of agents that have proved to be effective as antiherpetic drugs. The agents mentioned are those considered to be the most likely candidates for entering clinical trials and those in the process of being granted approval by the US Food and Drug Administration. The diversity in their molecular mechanism of action highlights the different perspectives currently encountered in the era of antiviral therapy. PMID: 20032535 [PubMed - in process] 56. Ophthalmology. 2009 Dec 21. [Epub ahead of print] Acute Retinal Necrosis The Effects of Intravitreal Foscarnet and Virus Type on Outcome. Wong R, Pavesio CE, Laidlaw DA, Williamson TH, Graham EM, Stanford MR. Guy's and St. Thomas' Hospital NHS Foundation Trust, London, United Kingdom; Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom. PURPOSE: To study the effects of intravitreal foscarnet and the clinical differences between varicella zoster virus (VZV-ARN) and herpes simplex virus (HSV-ARN) induced acute retinal necrosis. DESIGN: Retrospective comparative case series. PARTICIPANTS: Eighty-one eyes of 74 patients. METHODS: A retrospective case note analysis was performed in 2 tertiary referral centers. MAIN OUTCOME MEASURES: Presenting and final visual acuity, and progression to retinal detachment. RESULTS: Thirty-three eyes had HSV-ARN and 48 had VZV-ARN. The average age for HSV-ARN was 34 years and 51 for VZV-ARN (P<0.001). Visual acuity on presentation was similar (P = 0.48), but a larger proportion had better vision (>/=20/60) in the HSV-ARN group (52%) than the VZV-ARN group (35%). A greater proportion of eyes with poor vision ( or = .05). CONCLUSIONS: Patients with dermatologic toxic effects following treatment with EGFRIs have a high prevalence of cutaneous infections. Most notably, bacterial infections developed at sites previously affected by dermatologic toxic effects, with leukopenic patients being at greater risk. PMID: 20007525 [PubMed - indexed for MEDLINE] 65. Transplant Proc. 2009 Dec;41(10):4169-71. Characteristics of long-term immunosuppressive therapy in chinese pediatric renal transplant patients: a single-center experience. Yang S, Wu Z, Wu W, Lin W, Xu T, Cai J, Wang Q, Liao L, Tan J. Transplant Center, Fuzhou General Hospital, Fuzhou, China. We performed this study to investigate the trend and characteristics of various immunosuppressive regimens as well as their efficacy and safety for long-term survival of Chinese pediatric renal allograft recipients. METHODS: Thirty-four patients who underwent kidney transplantation between January 1985 and July 2002 had >/=5 years follow up. We retrospectively reviewed the baseline characteristics, patient and kidney survival rates, renal function, immunosuppressive regimens, drug levels, and adverse effects of immunosuppressive medications. RESULTS: The 1-, 3-, and 5-year recipient versus graft survival rates were 100% and 97.1%; 91.2% and 88.2%; 85.3% and 82.4%, respectively. The proportions of patients treated with cyclosporine- or tacrolimus-based immunosuppressive regimen at these times were 48.5%/51.5%; 60.0%/40.0%; and 53.6/46.4%. There were no significant differences in the dosages and drug levels after 1 year (P > .05). The proportions of azathioprine versus mycophenolate mofetil adjunctive therapy were 21.3/78.8%; 23.3%/70%; and 32.1%/60.7%, respectively. Forty percent of the surviving recipients developed complications, including hypertension, hyperlipidemia, gingival hyperplasia, hirsutism, liver dysfunction, herpes zoster, diabetes mellitus or cataracts. CONCLUSIONS: Cyclosporine or tacrolimus, plus mycophenolate mofetil or azathioprine, and prednisone triple therapies showed promising long-term results with similar efficacy and safety in pediatric renal recipients. Periodic drug level monitoring is required to facilitate individualization of immunosuppressive regimens. Drug doses and levels differed markedly from non-Chinese patients because of the ethnic discrepancy. PMID: 20005361 [PubMed - in process] 66. J Card Surg. 2010 Jan-Feb;25(1):28-9. Epub 2009 Nov 30. Herpes zoster following saphenous venectomy for coronary bypass surgery. Sachdeva S, Prasher P. Department of Dermatology, Prasher Eye and Skin Care Centre, Ludhiana, India. siloniederm@yahoo.com PMID: 20002233 [PubMed - in process] 67. Clin Infect Dis. 2010 Jan 1;50(1):121-2. High serum cholesterol levels are associated with herpes zoster infection after heart transplantation. Del Pozo JL, van de Beek D, Mandrekar JN, Daly RC, McGregor CG, Azanza JR, Patel R. Comment on: Clin Infect Dis. 2009 Mar 15;48(6):745-55. PMCID: PMC2803068 [Available on 2011/1/1] PMID: 20001524 [PubMed - in process] 68. Adv Nurse Pract. 2008 Dec;16(12):47-9. Herpes zoster alert. Prevent shingles with vaccination and awareness. Carcio H. Health and Continence Institute, Deerfield, Massachusetts, USA. PMID: 19999464 [PubMed - indexed for MEDLINE] 69. Acta Derm Venereol. 2009 Nov;89(6):612-6. Epidemiological features and costs of herpes zoster in Taiwan: a national study 2000 to 2006. Jih JS, Chen YJ, Lin MW, Chen YC, Chen TJ, Huang YL, Chen CC, Lee DD, Chang YT, Wang WJ, Liu HN. Department of Dermatology, National Yang Ming University, Department of Dermatology, Taipei Veterans General Hospital, Taipei, Taiwan. To analyse the epidemiological characteristics and related costs of herpes zoster in Taiwan, a nationally representative cohort of 1,000,000 individuals from the National Health Insurance register was followed up from 2000 to 2006 and their claims data analysed. Overall, 34,280 patients were diagnosed with zoster (incidence 4.89/1000 person-years) and 2944 patients (8.6%) developed post-herpetic neuralgia 3 months after the start of the zoster rash (incidence 0.42/1000 person-years). People with older age, diabetes, and immunocompromising conditions were at higher risk of developing zoster and post-herpetic neuralgia. The overall hospitalization rate for zoster was 16.1 cases per 100,000 person-years. The cost for each home care case and per hospitalized case were approximately 53.30 euro and 1224.70 euro, respectively. Further research into the cost-effectiveness of zoster vaccine is needed. PMID: 19997693 [PubMed - in process] 70. Zhongguo Zhen Jiu. 2009 Nov;29(11):887-90. [Observation on therapeutic effect of electroacupuncture at Jiaji (EX-B 2) combined with blood-letting and cupping on herpes zoster] [Article in Chinese] Liu YN, Zhang HX, Huang GF, Zou R, Wei W. Department of Acupuncture and Moxibustion, Wuhan Hospital of Integrated Chinese and Western Medicine, Wuhan 430022, China. shuiyueliang813@163.com OBJECTIVE: To compare the therapeutic effect differences between electroacupuncture at Jiaji (EX-B 2) combined with blood-letting plus cupping and western medicine therapy. METHODS: Fifty-three cases were randomly divided into an observation group (n=31) and a control group (n=22). The observation group was treated by electroacupuncture at Jiaji (EX-B 2) combined with blood-letting with a plum-blossom needle at the affected parts plus cupping, once each day. The control group was treated by oral administration of Valaciclovir Hydrochlordide, Indomethacin, Vitamin B1 and Vitamin B12. RESULTS: The cured and markedly effective rate of 96.8% in the observation group was better than that of 81.8% in the control group (P < 0.05), and improvements of pain, pruritus, burning sensation and sleep in the observation group were superior to those of the control group (all P < 0.01). CONCLUSION: Electroacupuncture at Jiaji (EX-B 2) combined with blood-letting and cupping is a better therapy for herpes zoster and its therapeutic effect is better than that of routine western medicine therapy. PMID: 19994687 [PubMed - indexed for MEDLINE] 71. J Oncol Pharm Pract. 2009 Dec 4. [Epub ahead of print] Prophylactic antivirals may be helpful in prevention of varicella-zoster virus reactivation in myeloma, but are they safe? Dasanu CA, Alexandrescu DT. Department of Hematology-Oncology, Saint Francis Hospital and Medical Center. Purpose. Retrospective analysis of two recent multiple myeloma (MM) clinical trials suggested that the use of bortezomib may be associated with an increased incidence of herpes zoster infections. Therefore, prophylactic use of antivirals has been advocated by some authors. This article explores the potential risks and pitfalls linked to routine acyclovir prophylaxis in bortezomib-treated MM.Summary. Use of antivirals can be associated with important nephro- and neurotoxicity. The nephrotoxicity induced by MM itself and its supportive therapies, superimposed to aging and inherent immunosuppression in myeloma, makes the development of renal impairment even more likely. On the other hand, sensory neuropathy is known to occur both during myeloma progression and in the setting of bortezomib therapy. Furthermore, preexisting nephropathy in MM patients can contribute to the occurrence of serious neurologic toxicity with acyclovir. CONCLUSIONS: /B>. Long-term acyclovir prophylaxis in MM patients treated with bortezomib may cause severe renal and neurological toxicity. Prevention of these complications can be achieved through either withholding of the antivirals or a very close monitoring of both neurologic status and renal function in this patient population. This highlights the importance of both clinician's and pharmacist's involvement in optimization of myeloma patient care. PMID: 19965947 [PubMed - as supplied by publisher] 72. Rev Prat. 2009 Nov 20;59(9):1287-93. [Herpesvirus infections of the immunocompetant child and adult] [Article in French] Vitrat-Hincky V, Brion JP. Clinique de maladies infectieuses, CHU de Grenoble, BP 217, 38043 Grenoble Cedex 9, France. vhinckyvitrat@chu-grenoble.fr PMID: 19961091 [PubMed - indexed for MEDLINE] 73. Can J Neurol Sci. 2009 Nov;36(6):787-8. MRI changes with acute shingles. Khu KJ, Bernstein M. Division of Neurosurgery, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada. PMID: 19960763 [PubMed - indexed for MEDLINE] 74. Pediatr Infect Dis J. 2009 Dec 2. [Epub ahead of print] Risk Factors of Herpes Zoster Among Children Immunized With Varicella Vaccine: Results From a Nested Case-Control Study. Tseng HF, Smith N, Marcy SM, Sy LS, Chao CR, Jacobsen SJ. From the *Department of Research and Evaluation, Southern California Permanente Medical Group, Kaiser Permanente, Pasadena, CA; and daggerHarbor-UCLA Medical Center, UCLA Center for Vaccine Research, Torrance, CA. BACKGROUND:: Previous studies of varicella-zoster virus reactivation in children have provided little information on potential risk factors. The aim of this study was to investigate the effects of race, chronic medical conditions and treatments, and recent vaccination, on the risk of herpes zoster (HZ) in children vaccinated with one dose of varicella vaccine. METHODS:: Case subjects were identified from a cohort of subjects who were members of the Southern California Kaiser Permanente Health Plan and received primary immunization with a single-antigen live varicella vaccine at age