Nicotinamide activates latent HIV-1 ex vivo in ART suppressed individuals, revealing higher potency than the association of two methyltransferase inhibitors, chaetocin and BIX01294

ABSTRACT Background: Latent HIV-1 is a major hurdle in obtaining HIV-1 sustained virological remission (SVR). Here we explored histone deacetylation inhibition property of nicotinamide (NAM; n = 17) for the first time in comparison to a combination of methyltransferase inhibitors (MTIs; Chaetocin and BIX01294; n = 25) to reactivate latent HIV ex vivo in CD8-depleted PBMCs from antiretroviral treated aviremic individuals. Results: NAM reactivated HIV-1 from 13/17 (76.4%) samples compared to 20/25 (80.0%) using MTIs with mean viral load (VLs) of 4.32 and 3.22 log10 RNA copies/mL, respectively (p = 0.004). Mean purging time after NAM and MTIs stimulation was 5.1 and 6.75 days, respectively (p = 0.73). Viral purging in autologous cultures exhibited blunted HIV recovery with fluctuating VLs followed by a complete viral extinction when expanded in allogenic system. Electron microscopy from five supernatants revealed anomalous viral particles, with lack of complete viral genomes when characterized by ultradeep sequencing through metagenomics approach (n = 4). Conclusion: NAM alone was more potent HIV-1 activator than combination of MTIs, with potential of clinical use.

Challenging management of hepatitis B infection in ankylosing spondylitis patients in an endemic area during immunosuppressive therapy

Abstract Hepatitis B infection is a global health issue. When considering patients with rheumatic diseases, this is no different. By using immunosuppressant drugs, such as DMARDs and biologics, viral reactivation is possible, leading to serious consequences on the patient. We report 3 cases of association between ankylosing spondylitis and hepatitis B with the use of immunosuppressant drugs. Case 1 was a patient with previous HBV infection using DMARD. Cases 2 and 3 were patients chronically infected by HBV during immunosuppressant therapy. The management of HBV infection during immunosuppressant therapy is challenging and needs multidisciplinary support.

Encephalitis associated with Zika virus infection and reactivation of the varicella-zoster virus in a Brazilian child

Abstract We report a case of encephalitis associated with Zika virus infection and reactivation of varicella-zoster virus in the central nervous system of a Brazilian child. This case raises the possibility that reactivation of the latent varicella-zoster virus may be a mechanism of neurological impairment induced by acquired Zika virus infection.

Human polyomaviruses and cancer: an overview

The name of the family Polyomaviridae, derives from the early observation that cells infected with murine polyomavirus induced multiple (poly) tumors (omas) in immunocompromised mice. Subsequent studies showed that many members of this family exhibit the capacity of mediating cell transformation and tumorigenesis in different experimental models. The transformation process mediated by these viruses is driven by viral pleiotropic regulatory proteins called T (tumor) antigens. Similar to other viral oncoproteins T antigens target cellular regulatory factors to favor cell proliferation, immune evasion and downregulation of apoptosis. The first two human polyomaviruses were isolated over 45 years ago. However, recent advances in the DNA sequencing technologies led to the rapid identification of additional twelve new polyomaviruses in different human samples. Many of these viruses establish chronic infections and have been associated with conditions in immunosuppressed individuals, particularly in organ transplant recipients. This has been associated to viral reactivation due to the immunosuppressant therapy applied to these patients. Four polyomaviruses namely, Merkel cell polyomavirus (MCPyV), Trichodysplasia spinulosa polyomavirus (TSPyV), John Cunningham Polyomavirus (JCPyV) and BK polyomavirus (BKPyV) have been associated with the development of specific malignant tumors. However, present evidence only supports the role of MCPyV as a carcinogen to humans. In the present review we present a summarized discussion on the current knowledge concerning the role of MCPyV, TSPyV, JCPyV and BKPyV in human cancers.

Viral Outcome in Patients with Occult HBV Infection or HCV-Ab Positivity Treated for Lymphoma

ABSTRACT HBV and HCV reactivation has been widely reported in patients undergoing immunosuppressive therapy for oncohaematological diseases. We aimed to evaluate the HBV and HCV reactivation events in patients with non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) underwent cytotoxic chemotherapy containing or not rituximab. This is a retrospective observational study, including all patients with NHL and HL attending an Italian tertiary referral hospital, the University of Naples "Federico II". A total of 322 patients were enrolled. We evaluated serum HBV and HCV markers. A total of 47 (38%) patients with occult HBV infection were enrolled. Seven/47 were treated with therapeutic cytotoxic schedule containing rituximab. Of them, 6/7 received prophylaxis with lamivudine. HBV reactivation was observed in two patients treated with rituximab. A reactivation was observed in the only patient (HBcAb+/HBsAb+) not receiving lamivudine prophylaxis, and the other one was observed in 1 patient with isolated HBcAb positivity during lamivudine prophylaxis. Moreover, 8 patients with HCV-Ab positivity were enrolled. No viral reactivation was observed in these patients. In conclusion, patients with occult HBV infection receiving chemotherapy containing rituximab for lymphoma without antiviral prophylaxis are at risk of viral reactivation. On the contrary, there is no risk of reactivation in patients undergoing rituximab-free schedule. Our findings suggest that there is also very low risk of HCV reactivation. This preliminary report underlines the concept that HBV reactivation is strongly related to the type of immunosuppressive therapy administered and that antiviral prophylaxis needs to be tailored.

Sofosbuvir and Daclatasvir in Mono-and HIV-coinfected Patients with Recurrent Hepatitis C After Liver Transplant

Abstract: Background and aims. Pegylated interferon (Peg-INF) and ribavirin (RBV) based therapy is suboptimal and poorly tolerated. We evaluated the safety, tolerability and efficacy of a 24-week course of sofosbuvir plus daclatasvir without ribavirin for the treatment of hepatitis C virus (HCV) recurrence after liver transplantation (LT) in both HCV-monoinfected and human immunodeficiency virus (HIV)-HCV coinfected patients. Material and methods. We retrospectively evaluated 22 consecutive adult LT recipients (16 monoinfected and 6 coinfected with HIV) who received a 24-week course of sofosbuvir plus daclatasvir treatment under an international compassionate access program. Results. Most patients were male (86%), with a median age of 58 years (r:58-81y). Median time from LT to treatment onset was 70 months (r: 20-116 m). HCV genotype 1b was the most frequent (45%), 55% had not responded to previous treatment with Peg-INF and RBV and 14% to regiments including first generation protease inhibitors. Fifty-six percent of the patients had histologically proven cirrhosis and 6 had ascites at baseline. All patients completed the 24-week treatment course without significant side effects except for one episode of severe bradicardya, with only minor adjustments in immunosuppressive treatment in some cases. Viral suppression was very rapid with undetectable HCV-RNA in all patients at 12 weeks. All 22 patients achieved a sustained virological response 12 weeks after treatment completion. Conclusion. The combination of sofosbuvir plus daclatasvir without ribavirin is a safe and effective treatment of HCV recurrence after LT in both monoinfected and HIV-coinfected patients, including those with decompensated cirrhosis.

Alemtuzumab as graft-versus-host disease (GVHD) prophylaxis strategy in a developing country: lower rate of acute GVHD, increased risk of cytomegalovirus reactivation

Acute graft-versus-host disease (aGVHD) and cytomegalovirus reactivation are important complications after allogeneic stem cell transplantation (alloHSCT). Here, we evaluated the impact of treatment with alemtuzumab on the occurrence of aGVHD, cytomegalovirus reactivation and survival after alloHSCT. This was a prospective cohort study conducted at the allo-HSCT unit of Hospital das Clínicas, Universidade Federal de Minas Gerais, Brazil, from January 2009 to December 2011. Fifty-seven patients who underwent alloHSCT were included. Forty-five (79%) patients had a malignant disease. Alemtuzumab was administered before the conditioning regimen at a dose of 1 mg/kg in children and 30 mg/day for 2 days in adults or children weighing more than 40 kg (a total dose of 60 mg) with a non-malignant disease or patients with a malignant disease and high-risk for GVHD mortality. Alemtuzumab was used in 23 (40%) patients, of whom 17 received a reduced-intensity conditioning. Eleven patients presented aGVHD (grade 2–4) and only 1 of them received alemtuzumab. Cumulative incidence of aGVHD (grade 2–4) at day 100 after transplantation (D+100) was 4 for patients receiving alemtuzumab and 29% for patients not receiving alemtuzumab. Cumulative incidence of cytomegalovirus reactivation for patients receiving or not alemtuzumab was 62 and 38%, respectively. Sixteen patients died in the first 100 days after alloHSCT, most of them due to bacterial sepsis. Only 2 patients died of aGVHD until D+100. Overall survival was 50% without any impact of alemtuzumab. Alemtuzumab effectively controlled aGVHD but increased the risk of cytomegalovirus reactivation without improving survival.

Infección por virus herpes humano 6 en un paciente inmunocompetente con síndrome DRESS secundario a carbamazepina / Human herpes virus 6 infection in an inmunocompetent patient with carbamazepine-induced DRESS syndrome

El síndrome DRESS (drug reaction with eosinophilia and systemic symptoms) constituye una reacción adversa a fármacos, potencialmente mortal, caracterizada por una erupción cutánea polimorfa asociada a fiebre, linfadeno-patías y compromiso multiorgánico con eosinofilia. Presentamos el caso clínico de un hombre inmunocompetente con un síndrome DRESS secundario a carbamazepina que cursó concomitantemente con una meningoencefalitis por virus herpes humano 6 (VHH-6). El rol patogénico del VHH-6 en el síndrome DRESS sigue siendo controversial; sin embargo, dada la importancia diagnóstica y eventualmente pronóstica de la infección por VHH-6, su tamizaje sería recomendable dentro del estudio de estos pacientes.

DRESS syndrome (drug reaction with eosinophilia and systemic symptoms) is an adverse life-threatening drug reaction characterized by a polymorphous rash associated with fever, lymphadenopathy and multiorgan involvement with eosinophilia. We present the case of an immunocompetent man with DRESS syndrome secondary to carbamazepine, that developed concomitantly meningoencephalitis caused by human herpes virus 6 (HHV-6), and a review of literature. The pathogenic role of HHV-6 in DRESS syndrome remains controversial. Given the diagnostic and possibly prognostic significance of HHV-6, the screening seems to be a good measure to use in the clinical management of these patients.

Cytomegalovirus infection in renal transplantation: clinical aspects, management and the perspectives / Infecção pelo citomegalovírus no transplante de rim: aspectos clínicos, manejo e perspectivas

Cytomegalovirus infection is one of most frequent infectious complications after renal transplantation, and can be classified as primo-infection, when the transmission occurs through the graft, or reactivation, when the recipient is cytomegalovirus seropositive. After transplantation, cytomegalovirus can appear as an infection, when the patient presents with evidence of viral replication without symptoms or disease, which has two clinical spectra: typical viral syndrome or invasive disease, which is a less common form. Their effects can be classified as direct, while the disease is developed, or indirect, with an increase of acute rejection and chronic allograft dysfunction risks. Diagnosis must be made based on viremia by one of the standardized methods: antigenemia or PCR, which is more sensitive. The risk factors related to infection after transplantation are the serologic matching (positive donor and negative recipient) and anti-lymphocyte antibody drugs. One of the strategies to reduce risk of disease should be chosen for patients at high risk: preemptive treatment or universal prophylaxis. Recent clinical research has described ganciclovir resistance as an emergent problem in management of cytomegalovirus infection. Two types of mutation that cause resistance were described: UL97 (most frequent) and UL54. Today, sophisticated methods of immunologic monitoring to detect specific T-cell clones against cytomegalovirus are used in clinical practice to improve the management of high-risk patients after renal transplantation.

A infecção pelo citomegalovírus é uma das principais complicações após o transplante de rim, podendo ser classificada em primoinfecção, quando a transmissão ocorre por meio do enxerto, ou em reativação, quando o receptor é soropositivo. Do ponto de vista clínico, pode se apresentar como infecção, na ausência de sintomas, ou como doença, com dois diferentes espectros: a síndrome viral típica ou, menos comumente, a doença invasiva. Os efeitos podem ser diretos, que é o desenvolvimento da doença, ou indiretos, como aumento no risco de rejeição aguda e de disfunção crônica do enxerto. O diagnóstico deve ser feito por pesquisa de viremia por meio de um dos dois métodos padronizados: antigenemia ou PCR − sendo essa última a mais sensível. Os fatores de risco relacionados com a infecção após o transplante são o match sorológico (doador positivo e receptor negativo) e o uso de anticorpos antilinfócitos. Uma das estratégias de redução de risco de doença deve ser escolhida após o transplante nos pacientes de alto risco: tratamento preemptivo ou profilaxia. Recentemente, linhas de pesquisa clínica têm apontado a resistência ao ganciclovir como um problema emergente no manejo da infecção pelo citomegalovírus. Duas formas de mutação que causam resistência são descritas: UL97, que é a mais frequente, e a UL54. Atualmente, sofisticados métodos de monitorização imunológica, como a detecção de clones específicos de células T contra o citomegalovírus podem ser utilizados na prática clínica para o melhor manejo após o transplante renal dos pacientes de alto risco.

Optic neuritis complicating herpes zoster ophthalmicus in an immunocompetent patient / Zoster optic neuritis in immunocompentent

A 58-year-old woman presented with rash over the left side of the face and intense acute uveitis. Following careful review of the symptoms and dilated fundus examination unilateral optic neuritis was discovered. The rash was typical of varicella zoster dermatitis. Patients presenting with herpes zoster ophthalmicus should always undergo dilated fundus examination, as there is a potential risk of unexpected posterior segment inflammation. Early diagnosis and prompt treatment can avoid visual sequelae.

Paciente de 58 anos de idade apresentando erupção cutânea no lado esquerdo da face e intensa uveíte unilateral. Após cuidadosa revisão dos sintomas e exame de fundo do olho foi detectada neurite óptica. O rash era típico de dermatite por varicella zoster. Pacientes apresentando quadro de herpes zoster oftálmico devem ser submetidos ao exame de fundo do olho devido ao risco de inesperada inflamação do segmento posterior. Diagnóstico precoce e tratamento imediato podem evitar danos visuais.

Varicella zoster virus reactivation during or immediately following treatment of tegumentary leishmaniasis with antimony compounds

Antimony compounds are the cornerstone treatments for tegumentary leishmaniasis. The reactivation of herpes virus is a side effect described in few reports. We conducted an observational study to describe the incidence of herpes zoster reactivation during treatment with antimony compounds. The global incidence of herpes zoster is approximately 2.5 cases per 1,000 persons per month (or 30 cases per 1,000 persons per year). The estimated incidence of herpes zoster in patients undergoing antimony therapy is higher than previously reported.

The use of ustekinumab in a patient with severe psoriasis and positive HBV serology

Psoriasis is a chronic inflammatory, immune-mediated disease that affects 1% to 2% of the world's population. Immunobiological medications are prescribed for certain patients with severe forms of psoriasis, however, these drugs increase the risk of reactivation of viral diseases such as hepatitis B. We report the case of a patient with severe psoriasis with positive serology for the Hepatitis B virus, who received ustekinumab (a human monoclonal antibody against interleukin 12 and 23). In this patient, the use of ustekinumab did not reactivate the Hepatitis B virus. Given the high prevalence of chronic viral infections in patients who are candidates for biologic therapy, as well as the potential for reactivate chronic viral illness, randomized controlled studies are needed to assess the risks and benefits of such therapy in these populations.

Mapping the sites of latency and reactivation by bovine herpesvirus 5 (BoHV-5) and a thymidine kinase-deleted BoHV-5 in lambs / Mapeamento dos sítios de latência e reativação pelo herpesvírus bovino tipo 5 (BoHV-5) e por mutante deletado no gene da timidina quinase em ovinos

A thymidine kinase (tk)-deleted bovine herpesvirus 5 (BoHV-5tkΔ) was previously shown to establish latent infection and reactivate - even poorly - in a sheep model (Cadore et al. 2013). As TK-negative alphaherpesviruses are unlike to reactivate in neural tissue, this study investigated the sites of latency and reactivation by this recombinant in lambs. For this, groups of lambs were inoculated intranasally with the parental BoHV-5 strain (SV-507/99) or with the recombinant BoHV-5tkΔ. During latent infection (40 days post-inoculation, pi), the distribution of recombinant virus DNA in neural and non-neural tissues was similar to that of the parental virus. Parental and recombinant virus DNA was consistently detected by PCR in trigeminal ganglia (TGs); frequently in palatine and pharyngeal tonsils and, less frequently in the retropharyngeal lymph nodes. In addition, latent DNA of both viruses was detected in several areas of the brain. After dexamethasone (Dx) administration (day 40pi), the recombinant virus was barely detected in nasal secretions contrasting with marked shedding of the parental virus. In tissues of lambs euthanized at day 3 post-Dx treatment (pDx), reverse-transcription-PCR (RT-PCR) for a late viral mRNA (glycoprotein D gene) demonstrated reactivation of parental virus in neural (TGs) and lymphoid tissues (tonsils, lymph node). In contrast, recombinant virus mRNA was detected only in lymphoid tissues. These results demonstrate that BoHV-5 and the recombinant BoHV-5tkΔ do establish latent infection in neural and non-neural sites. Reactivation of the recombinant BoHV-5tkΔ, however, appeared to occur only in non-neural sites. In anyway, the ability of a tk-deleted strain to reactivate latent infection deserves attention in the context of vaccine safety.

Um recombinante do herpesvírus bovino tipo 5 com deleção no gene da timidina quinase (BoHV-5tkΔ) foi capaz de estabelecer latência e reativar - embora ineficientemente - em modelo experimental em ovinos (Cadore et al. 2013). Como a reativação de alfaherpesvírus defectivos na TK em tecido neural é improvável, o presente estudo investigou os sítios de latência e reativação por esse recombinante em ovinos. Para isso, grupos de ovinos foram inoculados com a cepa de BoHV-5 parental (SV-507/99) ou com o recombinante BoHV-5tkΔ. Durante a infecção latente (dia 40 pós-infecção, pi) a distribuição do DNA do vírus recombinante no encéfalo de ovinos infectados experimentalmente foi similar ao do vírus parental (SV-507/99). O DNA de ambos os vírus foi detectado consistentemente por PCR nos gânglios trigêmeos (TGs), frequentemente nas tonsilas faríngeas e palatinas e, com menos frequência, nos linfonodos retrofaríngeos. Após administração de dexametasona (Dx), o vírus recombinante foi raramente detectado nas secreções nasais, contrastando com excreção abundante do vírus parental. RT-PCR para mRNA de um gene tardio (glicoproteína D) realizado em tecidos de animais eutanasiados 3 dias pós-Dx demonstrou reativação do vírus parental em tecido neural (TGs) e não-neural (tonsilas, linfonodo). Em contraste, a reativação do vírus recombinante ficou restrita ao tecido linfoide. Esses resultados demonstram que tanto o BoHV-5 parental quanto o recombinante estabelecem latência em sítios neurais e não-neurais. No entanto, o recombinante BoHV-5tkΔ parece reativar apenas nos tecidos não-neurais (linfoide). De qualquer forma, a capacidade do recombinante reativar a infecção latente deve ser considerada no contexto de segurança vacinal.

Mapping the sites of latency and reactivation by bovine herpesvirus 5 (BoHV-5) and a thymidine kinase-deleted BoHV-5 in lambs / Mapeamento dos sítios de latência e reativação pelo herpesvírus bovino tipo 5 (BoHV-5) e por mutante deletado no gene da timidina quinase em ovinos

A thymidine kinase (tk)-deleted bovine herpesvirus 5 (BoHV-5tkΔ) was previously shown to establish latent infection and reactivate - even poorly - in a sheep model (Cadore et al. 2013). As TK-negative alphaherpesviruses are unlike to reactivate in neural tissue, this study investigated the sites of latency and reactivation by this recombinant in lambs. For this, groups of lambs were inoculated intranasally with the parental BoHV-5 strain (SV-507/99) or with the recombinant BoHV-5tkΔ. During latent infection (40 days post-inoculation, pi), the distribution of recombinant virus DNA in neural and non-neural tissues was similar to that of the parental virus. Parental and recombinant virus DNA was consistently detected by PCR in trigeminal ganglia (TGs); frequently in palatine and pharyngeal tonsils and, less frequently in the retropharyngeal lymph nodes. In addition, latent DNA of both viruses was detected in several areas of the brain. After dexamethasone (Dx) administration (day 40pi), the recombinant virus was barely detected in nasal secretions contrasting with marked shedding of the parental virus. In tissues of lambs euthanized at day 3 post-Dx treatment (pDx), reverse-transcription-PCR (RT-PCR) for a late viral mRNA (glycoprotein D gene) demonstrated reactivation of parental virus in neural (TGs) and lymphoid tissues (tonsils, lymph node). In contrast, recombinant virus mRNA was detected only in lymphoid tissues. These results demonstrate that BoHV-5 and the recombinant BoHV-5tkΔ do establish latent infection in neural and non-neural sites. Reactivation of the recombinant BoHV-5tkΔ, however, appeared to occur only in non-neural sites. In anyway, the ability of a tk-deleted strain to reactivate latent infection deserves attention in the context of vaccine safety.

Um recombinante do herpesvírus bovino tipo 5 com deleção no gene da timidina quinase (BoHV-5tkΔ) foi capaz de estabelecer latência e reativar - embora ineficientemente - em modelo experimental em ovinos (Cadore et al. 2013). Como a reativação de alfaherpesvírus defectivos na TK em tecido neural é improvável, o presente estudo investigou os sítios de latência e reativação por esse recombinante em ovinos. Para isso, grupos de ovinos foram inoculados com a cepa de BoHV-5 parental (SV-507/99) ou com o recombinante BoHV-5tkΔ. Durante a infecção latente (dia 40 pós-infecção, pi) a distribuição do DNA do vírus recombinante no encéfalo de ovinos infectados experimentalmente foi similar ao do vírus parental (SV-507/99). O DNA de ambos os vírus foi detectado consistentemente por PCR nos gânglios trigêmeos (TGs), frequentemente nas tonsilas faríngeas e palatinas e, com menos frequência, nos linfonodos retrofaríngeos. Após administração de dexametasona (Dx), o vírus recombinante foi raramente detectado nas secreções nasais, contrastando com excreção abundante do vírus parental. RT-PCR para mRNA de um gene tardio (glicoproteína D) realizado em tecidos de animais eutanasiados 3 dias pós-Dx demonstrou reativação do vírus parental em tecido neural (TGs) e não-neural (tonsilas, linfonodo). Em contraste, a reativação do vírus recombinante ficou restrita ao tecido linfoide. Esses resultados demonstram que tanto o BoHV-5 parental quanto o recombinante estabelecem latência em sítios neurais e não-neurais. No entanto, o recombinante BoHV-5tkΔ parece reativar apenas nos tecidos não-neurais (linfoide). De qualquer forma, a capacidade do recombinante reativar a infecção latente deve ser considerada no contexto de segurança vacinal.

Caso clínico de una meningitis por reactivación del virus varicela zóster en un paciente inmunocompetente / Case report of an inmunocompetent patient with reactivation of varicela zoster as meningitis

En este reporte presentamos el caso de un niño de 15 años sin antecedentes mórbidos, que consulta por un cuadro de cefalea febril, erupción cutánea de características herpéticas en tórax, en quien finalmente se confirma el diagnóstico de meningitis por varicela zóster. La literatura nos muestra que la reactivación del virus varicela zóster en forma de meningitis es rara y en general afecta a la población inmunocomprometida, sin embargo, existen algunos reportes de casos similares al que se presenta, por lo que se debiese considerar como germen causal de meningitis, en la población inmunocompetente.

This is a case report about a 15-year-old boy with no other previous medical history than chicken pox. His symptoms were headache, fever and a rash with vesicles in the dermatome that corresponds to T8. He was diagnosed with meningitis by the varicella-zoster virus. The information in the literature is scarce and shows that reactivation of the varicella-zoster virus as meningitis is rare and generally affects immunodeficient patients; however, there are some case reports similar to this case in which the varicella-zoster virus is the agent involved, so it should also be considered in immunocompetent patients diagnosed with meningitis.

Reactivación de Citomegalovirus en crisis de enfermedad inflamatoria intestinal: un análisis retrospectivo / Cytomegalovirus reactivation in inflammatory bowel disease: a retrospective analysis

Cytomegalovirus (CMV) is considered an agent involved in reactivation of inflammatory bowel disease (IBD). In our country there are no studies or guidelines to standardize CMV search in that setting. Objective: To describe the prevalence of CMV infection in hospitalized patients with IBD. Methods: Retrospective analysis of patients hospitalized due to IBD crisis from June 2007 to June 2009 at a university health center. Electronic cards, laboratory data, and endoscopic study were reviewed. CMV reactivation was diagnosed by means of antigenemia assay, and/or histopathology. Results: 88 IBD crises were identified (74 patients), in 52 a CMV study was requested (47 with antigenemia assay). Mean age was 38.5 years-old, 54 percent female, ulcerative colitis 67.3 percent, Crohn disease 32.7 percent. IBD crisis were classified as follows; severe 57.7 percent, moderate or mild 42.3 percent. The CMV diagnosis test was positive in 5 cases (9.6 percent), all of them were severe crisis (16.6 percent in severe crisis versus 0 percent in moderate/mild crisis, p = 0.055). In the group of steroid resistant disease the CMV antigenemia was positive in 66.6 percent versus 2.17 percent of non-steroid resistant patients (p = 0.0002). Test to detect CMV performed after the third day of hospitalization were positive in 36.36 percent versus those performed earlier, which were positive in 2.43 percent (p = 0.004). Conclusion: High prevalence of CMV infection in cases of severe IBD crisis was detected, specifically in a subgroup of steroid-resistant patients and three days after hospital admission. These findings suggest the importance to search CMV in this subgroup of patients.

Introducción: El citomegalovirus (CMV) puede participar en la reactivación de la enfermedad inflamatoria intestinal (EII). En nuestro medio no se ha estudiado el rol de CMV en pacientes hospitalizados por crisis de EII. Objetivo: Estimar la prevalencia de la reactivación de CMV en crisis de EII que requirieron hospitalización. Métodos: Análisis retrospectivo de pacientes hospitalizados en un centro de salud universitario por EII entre junio de 2007 y junio de 2009. Se revisaron registros clínicos electrónicos, laboratorio y estudio endoscópico. La reactivación de CMV se diagnosticó mediante antigenemia y/o histología. Resultados: Se identificaron 88 crisis de EII (74 pacientes), en 52 se solicitó estudio de CMV (47 con antigenemia). 67,3 por ciento fueron colitis ulcerosa; 32,7 por ciento enfermedad de Crohn. Edad promedio 38,5 años, 54 por ciento sexo femenino. La exacerbación fue catalogada como grave en 57,7 por ciento de los casos, moderada o leve en 42,3 por ciento. Se detectó reactivación de CMV en 5 pacientes (9,6 por ciento), los que se caracterizaron por presentar crisis grave (16,6 por ciento en crisis grave versus 0 por ciento en crisis leve/moderada, p = 0,055), refractariedad a corticoides (66,6 por ciento en corticorrefractarios versus 2,17 por ciento en sensibles a corticoides, p = 0,0002) y hospitalización mayor de 3 días (36,36 por ciento en hospitalización > 3 días versus 2,43 por ciento en estudio temprano, p = 0,004). Conclusión: En pacientes hospitalizados por crisis de EII es frecuente detectar evidencia de reactivación de CMV, la que se concentra en las crisis graves, corticorrefractarias y con hospitalización mayor de 3 días. Estos datos sugieren que la búsqueda de CMV debiera ser dirigida a este subgrupo de pacientes.

Citomegalovirus en enfermedad inflamatoria intestinal / Cytomegolavirus in inflammatory bowel disease

Cytomegalovirus (CMV) gastrointestinal infection in inflammatory bowel disease (IBD) is a diagnostic challenge with close relationship with clinical course and treatment response. This article summarizes biology, pathology, clinical manifestation and diagnosis of CMV disease and especially in IBD.

La infección gastrointestinal por citomegalovirus (CMV) en paciente con enfermedad inflamatoria intestinal (EII) constituye un desafío diagnóstico importante y se encuentra íntimamente relacionada con la evolución y respuesta a tratamiento de la EII. El presente artículo resume las características biológicas del CMV, sus características patogénicas, sus manifestaciones clínicas y sus métodos diagnósticos. Se expone con mayor detalle la implicancia de esta infección en pacientes portadores con EII y su enfrentamiento clínico.

Reactivación del virus de la hepatitis B secundaria a tratamiento inmunosupresor / Hepatitis B virus reactivation secondary to immunosuppressive treatment

Se presenta el caso de una mujer de 57 años con síntomas dispépticos, con ANAS +, manejada con terapia inmunosupresora y sospecha clínica de LES. Posteriormente presenta ascitis y elevación de las aminotransferasas. Se detecta HBsAg + con carga viral DNA-HBV elevada. Conclusión: Se deben tomar pruebas para hepatitis B antes de iniciar una terapia inmunosupresora. Los corticoesteroides y otros inmunosupresores pueden reactivar el virus de la hepatitis B y producir cuadros clínicos severos que ponen en riesgo la vida del paciente.

Reactivation of hepatitis B virus (HBV) replication in patients undergoing immunosuppressive therapy may precipitate flare ups of chronic HBV infections. We present the case of a 57 year old female who had suffered six weeks of abdominal discomfort, dyspepsia, and joint paint. After three weeks of therapy with prednisolone, methotrexate and chloroquine, the patient developed ascites and increased serum levels of AST and ALT. Chronic hepatitis B infection was confirmed by liver biopsy. Conclusion: Tests for hepatitis B should be conducted before immunosuppressive therapy is begun. Corticosteroids and other immune suppressors can reactivate hepatitis B and produce severe clinical symptoms and can put the patient's life at risk.

Chronic hepatitis virus infection in patients with multiple myeloma: clinical characteristics and outcomes

OBJECTIVES: Cytotoxic agents and steroids are used to treat lymphoid malignancies, but these compounds may exacerbate chronic viral hepatitis. For patients with multiple myeloma, the impact of preexisting hepatitis virus infection is unclear. The aim of this study is to explore the characteristics and outcomes of myeloma patients with chronic hepatitis virus infection. METHODS: From 2003 to 2008, 155 myeloma patients were examined to determine their chronic hepatitis virus infection statuses using serologic tests for the hepatitis B (HBV) and C viruses (HCV). Clinical parameters and outcome variables were retrieved via a medical chart review. RESULTS: The estimated prevalences of chronic HBV and HCV infections were 11.0 percent (n = 17) and 9.0 percent (n = 14), respectively. The characteristics of patients who were hepatitis virus carriers and those who were not were similar. However, carrier patients had a higher prevalence of conventional cytogenetic abnormalities (64.3 percent vs. 25.0 percent). The cumulative incidences of grade 3-4 elevation of the level of alanine transaminase, 30.0 percent vs. 12.0 percent, and hyperbilirubinemia, 20.0 percent vs. 1.6 percent, were higher in carriers as well. In a Kaplan-Meier analysis, carrier patients had worse overall survival (median: 16.0 vs. 42.4 months). The prognostic value of carrier status was not statistically significant in the multivariate analysis, but an age of more than 65 years old, the presence of cytogenetic abnormalities, a beta-2-microglobulin level of more than 3.5 mg/L, and a serum creatinine level of more than 2 mg/ dL were independent factors associated with poor prognosis. CONCLUSION: Myeloma patients with chronic hepatitis virus infections might be a distinct subgroup, and close monitoring of hepatic adverse events should be mandatory.