Fatal disseminated cytomegalovirus infection with necrotizing oophoritis in a patient with acquired immunodeficiency syndrome

Disseminated human cytomegalovirus (CMV) disease occurs mainly as a congenital infection and among immunocompromised hosts. Patients with acquired immunodeficiency syndrome (AIDS) are at increased risk for CMV infection, and the most prevalent clinical manifestation is retinitis, followed by colitis, esophagitis, pneumonitis, and encephalitis. CMV oophoritis is poorly described in the literature with some cases reported in patients with hematological or solid malignancies, bone marrow or solid organ transplantation, immunosuppressive therapy, and advanced AIDS cases. We report the case of a 61-year-old woman with a recent diagnosis of AIDS, which was associated with a wasting syndrome. The patient presented with abdominal pain, headache, cutaneous vesicular lesions on the abdomen, anemia, lymphopenia, and hyponatremia; she died suddenly on the fourth day of hospitalization. The autopsy was performed and demonstrated disseminated CMV infection with hemorrhagic encephalitis as the immediate cause of death. Additionally, pneumonitis, extensive adrenalitis, ulcerated enteritis, focal hepatitis, and necrotizing oophoritis were found.

Evolución clínica, funcional y radiológica de pacientes trasplantados pulmonares con síndrome de bronquiolitis obliterante y disfunción de injerto pulmonar restrictivo / Clinical, functional and radiological evolution of pulmonary transplant patients with bronchiolitis obliterans syndrome and restrictive graft dysfunction

Resumen La principal complicación a largo plazo en trasplantados de pulmón es la disfunción crónica de injerto identificado como bronquiolitis obliterante, existiendo un nuevo patrón denominado Disfunción de Injerto Restrictivo. Objetivo: Evaluar seguimiento espirométrico, radiológico y clínico entre pacientes con síndrome de bronquiolitis obliterante (SBO) y Disfunción de Injerto Restrictivo (DIR) post trasplante pulmonar. Metodología: Se revisaron registros clínicos de trasplantados pulmonares desde 1999 hasta 2017. Se efectuó seguimiento espirométrico e imágenes por tomografía de tórax y factores asociados: infección por Citomegalovirus(CMV), reflujo gastro-esofágico (RGE) y episodios de rechazo agudo. Se analizó sobrevida por Kaplan Meier. Resultados: De 88 pacientes trasplantados de pulmón, 40 desarrollaron disfunción crónica de injerto: 31 (80%) presentaron SBO y 9 (20%) tuvieron DIR. Edad promedio: 47 años en SBO y 46 años en DIR. Siendo fibrosis pulmonar la patología basal predominante en ambos. En SBO se consignaron 14 episodios de rechazo agudo (50%), infección por CMV en 18% y RGE activo en 26%. En la serie DIR hubo 5 episodios de rechazo agudo (62%), 13% de infección por CMV y 67% de RGE activo 6 (p = 0,02). En el seguimiento a 1-2-4-5 años el promedio del VEF1 en SBO fue: 67,3,65, 60 y 48% del valor predicho y en DIR fue 61, 65, 62 y 45% respectivamente. Las imágenes tomográficas en SBO mostraron: hiperinflación y en DIR: fibrosis pleuropulmonar superior. La sobrevida fue de 96,9 meses en SBO y 65,6 meses en DIR (p = 0,06). Conclusions: La disfunción restrictiva presentó menor sobrevida que SBO. RGE se asoció a rechazo restrictivo. La tomografía de tórax difiere en ambos tipos de rechazo crónico.

The main long-term complication in lung transplant patients is chronic graft dysfunction identified as bronchiolitis obliterans, and there is a new pattern called Restrictive Graft Dysfunction. Objective: To evaluate spirometric, radiological and clinical follow-up among patients with bronchiolitis obliterans syndrome (BOS) and Restrictive Allograft Syndrome (RAS) after lung transplantation. Methodology: Lung transplant recipients ' clinical records were reviewed from 1999 to 2017. We carried out a follow up of spirometry, chest tomography imaging and associated factors: cytomegalovirus (CMV) infection, gastroesophageal reflux (GER) and episodes of acute rejection. Survival was analyzed by Kaplan Meier. Results: Out of 88 lung transplant patients, 40 developed chronic graft dysfunction: 31 (80%) presented BOS and 9 (20%) had RAS. Mean age: 47 yr.o. in BOS and 46 yr. o. in RAS. Lung fibrosis was the primary pathology predominant in both conditions. In BOS were reported 14 episodes of acute rejection (50%), CMV infection in 18% and active GER in 26%. In RAS there were 5 episodes of acute rejection (62%), CMV infection in 13% and active GER in 67% (p = 0.02). VEF1 follow-up at 1-2-4-5 years averaged 67, 65, 60 and 8% of reference value in BOS and 61, 65, 62 and 45% in RAS respectively. CT scans showed hyperinflation in BOS and upper pleuropulmonary fibrosis in RAS. BOS survival time was 96.9 months versus 65.6 months in RAS (p = 0.06). Conclusiones: Restrictive dysfunction presented a lower survival rate than BOS. GER was associated with restrictive rejection. Chest tomography differs in both types of chronic rejection.

Gastrointestinal cytomegalovirus disease in a patient with pemphigus vulgaris treated with corticosteroid and mycophenolate mofetil

Pemphigus vulgaris is an autoimmune disease characterized by the formation of suprabasal intra-epidermal blisters on the skin and mucosal surfaces. Infectious diseases are the main cause of death in patients with pemphigus due to the disrupture of the physiological skin barrier, immune dysregulation, and the use of immunosuppressive medications leaving the patient prone to acquire opportunistic infections. We report the case of a 67-year-old woman diagnosed with pemphigus vulgaris, who was irregularly taking prednisone and mycophenolate mofetil. She was hospitalized because of a 1-month history of watery diarrhea and oral ulcers. Unfortunately, the patient died suddenly on the ward. The autopsy revealed a bilateral saddle pulmonary embolism, Gram-positive cocci bronchopneumonia, and gastrointestinal cytomegalovirus infection, causing extensive gastrointestinal mucosal ulcers.

Cutaneous involvement by cytomegalovirus in a renal transplant recipient as an indicator of severe systemic infection

Abstract Cytomegalovirus is an opportunistic virus that commonly affects immunosuppressed patients. Cutaneous involvement by this virus is rare and occurs in significantly immunocompromised hosts, with a poor prognosis. Skin ulcers may represent the first sign of systemic infection by cytomegalovirus in these patients. Herein, a case of a systemic infection by Cytomegalovirus presenting as genital and oral ulcers in a kidney-transplant recipient is reported.

Cytomegalovirus (CMV)-related cutaneous necrotizing vasculitis: case report and literature review

Cytomegalovirus (CMV) infection is usually asymptomatic in immunocompetent patients. A mononucleosis-like syndrome may develop in some patients. Various organ involvements (eg: encephalitis, meningitis, retinitis, myocarditis, pneumonia, hepatitis, enterocolitis, neuritis), which rarely occur in immunocompetent patients, have also been reported. Cutaneous necrotizing vasculitis caused by CMV infection has been reported very rarely in the literature. Here, a case with a very rare clinical form of CMV infection, presenting with persistent fever and livedo reticularis on the extremities and cutaneous necrotizing vasculitis of the toes, is described, and the relevant literature is reviewed. This case report aims to highlight the possibility of CMV infection to be a cause of cutaneous necrotizing vasculitis.

Comparative analysis of presence of Cytomegalovirus (CMV) and Epsteinbarr virus -1 (EBV-1) in cases of chronic periodontitis and aggressive periodontitis with controls.

Aim : The aim of the present study was to evaluate the presence of Cytomegalovirus (CMV) and Epsteinbarr virus -1 (EBV-1)viruses in sub gingival plaque of chronic periodontitis (groupA), aggressive periodontitis patients (group B), periodontally healthy controls (group C) and to compare the clinical parameters between virus negative and positive sites in each of these groups. Materials and Methods : Sixty subjects were included in the study and equally divided into the 3 groups (group A - 20, group B - 20, group C - 20). Sub gingival plaque samples were obtained from the 3 deepest periodontal pocket sites in case of subjects suffering from periodontitis, and from one random bleeding site per quadrant in healthy groups. Clinical parameters like plaque index (PI), gingival index (GI), pocket depth (PD) and clinical loss of attachment (CAL) were recorded. Viral Deoxyribonucleic acid (DNA) was extracted using Proteinase-K DNA Extraction method, and the presence of CMV and EBV-1 was detected by polymerase chain reaction and 2% agarose gel. Results: Results of our study showed a 45% prevalence of CMV and EBV-1 in Aggressive periodontitis cases. Prevalence of CMV in chronic periodontitis and healthy subjects was 20% and 10%, respectively; while for EBV-1 it was 25% and 0%, respectively. In terms of comparison of the clinical parameters with virus presence, both CMV and EBV-1 positive sites showed a significantly higher mean pocket depth compared to virus negative sites. Conclusion: Our studyshowed that the prevalence of EBV1 was higher in chronic and aggressive periodontitis subjects compared to controls and the prevalence of CMV was higher in aggressive periodontitis patients. The virus positive sites showed higher pocket depth compared to virus negative sites.

Prevalencia de la infección por citomegalovirus en mujeres fértiles de comunidades indígenas Yukpa, estado Zulia, Venezuela / Prevalence of cytomegalovirus infection among fertile women from Yukpa amerindians communities, State of Zulia, Venezuela

La infección por Citomegalovirus (CMV) es considerada un problema de salud en mujeres fértiles cuando la infección es adquirida durante el embarazo. Con el fin de conocer la prevalencia de CMV en mujeres fértiles de algunas comunidades Yukpa, durante el año 2007 se seleccionaron 112 mujeres de un total de 151, procedentes de las comunidades del Tokuko (n=41), Kasmera (n=35), Yasa (n=20) y Neremú (n=16), en edades entre 16 - 45 años. La determinación de anticuerpos de tipo IgG e IgM anti-CMV se realizó por la técnica de inmunoensayo enzimático (ELISA). La presencia de anticuerpos IgG-anti-CMV fue detectada en el 72,3 por ciento (81/112) de la población estudiada. El 8,6 por ciento (7/81) de las muestras reactivas para IgG fueron positivas para IgM anti-CMV. El análisis por comunidad indica una diferencia significativa (p<0,001) en la prevalencia de CMV en la comunidad del Tokuko con respecto a la comunidad de Yasa. Factores como edad, hacinamiento, número de pareja, número de hijos y abortos, no presentaron asociación con la presencia de anticuerpos para CMV. La prevalencia encontrada en esta población está por debajo a la indicada en mujeres fértiles en otros países y homogéneamente distribuida en las comunidades evaluadas. El porcentaje de mujeres susceptibles debe ser considerado a través de controles pre y durante el embarazo

Infection by Cytomegalovirus (CMV) is considered a health problem in fertile women when the infection is acquired during pregnancy. In order to find the prevalence of CMV among fertile women in Yukpa communities,112 women out of 151, ages 16 - 45, were selected during 2007, coming from Tokuko (n=41), Kasmera (n=35), Yasa (n=20) and Neremu (n=16). IgG and IgM antibodies for CMV were determined by enzymatic immunoassay technique (EIA). The presence of CMV antibodies was detected in 72, 3 percent (81/112) of the population studied. The 8, 6 percent (7/81) of those reactive for IgG were positive for anti-CMV IgM. A significant difference (p<0,001) in CMV prevalence was detected in the Tokuko community compared to the Yasa community. Factors such as age, overcrowding, number of partner, number of children and abortions, were not association with the presence of CMV antibodies. CMV prevalence in this population is below that indicated for fertile women in other countries and is distributed homogeneously among the communities studied. The percentage of susceptible women must be taken into account through controls before and during pregnancy

Infección congénita por citomegalovirus: nuevos aspectos terapéuticos / Congenital cytomegalovirus infection: new therapeutic aspects

La infección por citomegalovirus es la infección congénita más frecuente, presentando morbimortalidad perinatal y secuela neurológica tanto en primoinfección como en reactivación durante el embarazo. Se presenta el caso de una embarazada con lupus eritematoso sistémico, en tratamiento inmunosupresor, que presentó reactivación de infección por citomegalovirus. Se discuten los mecanismos de transmisión y de diagnóstico prenatal, así como nuevas alternativas terapéuticas in útero.

Cytomegalovirus infection is the most common congenital infection, causing perinatal morbidity and neurological sequel in both primary infection and reactivation during pregnancy. A case of a pregnant woman with lupus, in immunosuppressive therapy that suffered reactivation of the cytomegalovirus infection is presented. We discuss the mechanisms of transmission and prenatal diagnosis, as well as new therapeutic alternatives wail in uterus.

Cytomegaloviral colitis in HIV positive patients: endoscopic findings / Colite por citomegalovírus em pacientes HIV positivo: aspectos endoscópicos

BACKGROUND: Diarrhea in seropositive human immunodeficiency virus patients is one of the most important and disabling symptoms, and often decreases their quality of life. Cytomegalovirus colitis is among the principal causes of this symptom and colonoscopy is the gold standard examination to diagnose it. AIM: To define the main endoscopic findings in seropositive human immunodeficiency virus patients with cytomegalovirus colitis. METHODS: Two hundred and forty-three colonoscopies were performed in 200 seropositive human immunodeficiency virus patients with diarrhea associated or not to abdominal pain or gastrointestinal bleeding, over 10-year period, whom 51 patients were diagnosed with cytomegalovirus colitis. Full length colonoscopy with ileum intubation was always tried and multiple biopsies of all segments examined, including endoscopically normal segments, were attempted. All diagnoses were confirmed by histologic and immunohistochemical studies. RESULTS: Total colonoscopy was possible in 98.03 percent and ileum intubation in 88.23 percent of these cytomegalovirus colitis patients. At colonoscopy, a heterogeneous ulcerative pattern was presented in 72.54 percent, an inflammatory process of the mucosa in 21.56 percent and 5.88 percent of the patients mucosa was endoscopically normal. CONCLUSION: Full length colonoscopy with ileum intubation and multiples biopsies of all segments, even when they are endoscopically normal, have always to be attempted in cases of seropositive human immunodeficiency virus patient with diarrhea.

RACIONAL: Diarréia em pacientes soropositivos para o vírus da imunodeficiência adquirida é um dos sintomas mais importantes e debilitantes e freqüentemente reduz sua qualidade de vida. Colite por citomegalovírus está entre as principais causas desse sintoma e a colonoscopia é o exame padrão-ouro para seu diagnóstico. OBJETIVO: Definir os principais achados endoscópicos em pacientes HIV+ com colite por citomegalovírus. MÉTODO: Duzentas e quarenta e três colonoscopias foram realizadas em 200 pacientes HIV+ com diarréia associada ou não à dor abdominal ou sangramento gastrointestinal, em período de 10 anos, dos quais 51 pacientes foram diagnosticados com colite por citomegalovírus. Colonoscopia total com entubação ileal foi sempre tentada e múltiplas biopsias de todos os segmentos, incluindo segmentos endoscopicamente normais, foram realizadas. Todos os resultados foram confirmados por estudos histológicos e imunoistoquímicos. RESULTADOS: A colonoscopia total foi possível em 98,03 por cento e entubação ileal em 88,23 por cento dos pacientes com colite por citomegalovírus. Nestes pacientes, identificou-se padrão ulcerativo heterogêneo em 72,54 por cento, processo inflamatório da mucosa em 21,56 por cento e mucosa de aspecto normal em 5,93 por cento das colonoscopias. CONCLUSÃO: Podemos concluir que colonoscopia total com entubação ileal com múltiplas biopsias de todos os segmentos, mesmo quando são endoscopicamente normais, têm que ser sempre realizadas em casos de pacientes HIV+ com diarréia.

Despistaje de infección por citomegalovirus en niños VIH positivos mediante PCR: relación con serología y evolución clínica / PCR screening for cytomegalovirus infection in HIV-positive children: relationship between serology and clinical evolution

En pacientes VIH positivos es fundamental diagnósticar infección por CMV. La relación entre serología, detección viral y evolución clínica no está plenamente establecida. Detectar la presencia de CMV por PCR en sangre periférica en pacientes pediátricos, sin síntomas de infección, VIH positivos; relacionar estos resultados con la serología y la evolución clínica durante un año de seguimiento. Criterios de inclusión: Niños menores de 12 años, ambos sexos, infección diagnosticada por VIH, recibiendo terapia antirretroviral altamente efectiva (TARAE), consentimiento informado por escrito, firmado. La serología anti CMV se realizó mediante el método ELISA, la semicuantificación de CMV en sangre periférica, mediante PCR, y el inmunofenotipaje por citometría de flujo. Aquellos niños con carga viral inicial detectable para CMV fueron evaluados un año después (valoración cualitativa y oftalmológica). Correlación de Pearson, t Student. Se estudiaron 23 niños, 17 menores de 6 años; 21 de ellos (82.6 por ciento): lgG CMV +. Dos pacientes (8.7 por ciento): lgM CMV+ y promedio de carga viral: 11920 VID, dos IgM-IgG+, promedio de carga de 23129 VID; el resto negativos; todos con linfocitos CD4+ por encima del 25 por ciento. 50 por ciento de los niños con carga viral negativa para CMV, con contajes de CD4+ inferiores al 25 por ciento. El análisis de correlación de Pearson no mostró correlación entre la carga viral del VIH y los valores de VID para CMV (R²=0.13). Linfocitos CD8+: 32,3 ± 6,8 por ciento en los pacientes con carga para CMV, estadísticamente inferior al promedio del grupo sin cargas virales CMV: 49,1 ± 8,8. (t Student= 3,508; g.l: 17. P<0,003). Ningún niño presentó evidencia de enfermedad órgano específica (EOE), incluyendo retinitis. Independientemente de la presencia o no de IgM positiva para CMV, 4 pacientes tuvieron carga viral detectable. No hay correlación entre las cargas virales de ambos virus. Ningún niño con carga viral detectable para CMV...

In HIV-positive patients the diagnosis of CMV infection is essential. The relationship between serology, viral detection and clinical evolution has not been fully established. To detect the presence of CMV in peripheral blood by PCR testing in HIV positive pediatric patients with no infection symptoms, and to relate the results with serology and clinical evolution during a year follow up. Inclusion criteria: Children under twelve years of age, both genders, with a diagnosis of HIV infection, and receiving HAART therapy, written consent signed by parents. Anti CMV serology was performed by ELISA, semi-quantification of CMV in peripheral blood by PCR and immunophenotyping by flow-cytometry. Children with detectable initial viral load for CMV were submitted to aqualitative and ophtalmologic assessment one year later. Statistics: Pearson’s Correlation, Student’s t. 23 children, both genders, 17 under 6 years of age; 21 (82.6%): IgG CMV+. Two patients (8.7%): IgM CMV+ and viral load. 11920 IDV, two with IgM- IgG+, viral load average: 23129 IDV. The rest of the children were negative, all with lymphocytes CD4+ above 25%. 50% of the children had a negative viral load for CMV with CD4+ counts under 25%. There was no correlation between the HIV viral load and IDV values for CMV (r2=0.13). Lymphocytes CD8+32.3+ 6.8% in patients with viral load for CMV.This is statistically lower than the average for the group without viral loads CMV: 49.1 + 8.8 (Student’s t= 3.508; g.l: 17. p<0.003). No child showed evidence of specific organ disease (SOD), including retinitis. Regardless of serology for IgM, 4 patients had detectable viral loads. There was no correlation between the viral loads of the two viruses. No child with detectable viral load for CMV developed a specific organ disease, probably due to a highly efficient antiretroviral treatment. Viral load quantification for CMV in HIV + patients is recommended, regardless of specific IgM result.

Schistosomiasis mansoni and severe gastrointestinal cytomegalovirus disease in a patient with acquired immunodeficiency syndrome

The behavior of the Schistosoma mansoni infection in patients with AIDS has not been explored. The case of a young woman with schistosomiasis mansoni, AIDS, and cytomegalovirus disease is reported. The authors suggest that the helminth was not a bystander in this case, or rather, by interfering with the host's immune response, it set the stage for the development and/or aggravation of the viral infection.

O comportamento da infecção pelo Schistosoma mansoni não foi explorado em pacientes com AIDS. Relatamos aqui o caso de uma paciente com esquistossomose mansoni, AIDS, e doença pelo citomegalovírus. Os autores sugerem que o helminto não foi apenas um espectador neste caso, mas, que, ao interferir na resposta imune do hospedeiro, promoveu o surgimento e/ou agravamento da infecção causada pelo citomegalovírus.

Multiple lymphoid nodules in bone marrow biopsy in immunocompetent patient with cytomegalovirus infection: an immunohistochemical analysis

In Brazil, a high prevalence of cytomegalovirus (CMV) infection has been documented. In immunocompetent adults CMV infection is usually asymptomatic and therefore morphologic and immunophenotypic bone marrow changes have rarely been described. The authors report the case of a previously healthy patient who developed fever of undetermined origin. The diagnosis of acute CMV infection was based on serological testing. A computed tomographic scan showed mediastinal lymphadenopathy. A bone marrow biopsy revealed a hypercellular haematopoiesis with eosinophilia and large mixed T- and B-cell lymphoid aggregates. In spite of bcl-2 positivity, their reactive nature was demonstrated. Polymerase chain reaction (PCR) and immunohistochemistry were unable to detect CMV-DNA in paraffin-embedded bone marrow sections. Much like in other systemic disorders, the lymphoid nodules in this case seemed to be caused by immunological mechanisms, possibly due to cytokines released in response to the systemic infectious process.

Uma elevada prevalência de infecção pelo citomegalovírus (CMV) está documentada no Brasil. Em adultos imunocompetentes a infecção pelo CMV é, em geral, assintomática e, portanto, as alterações morfológicas e imunohistoquímicas na medula óssea têm sido raramente descritas. Relatamos o caso de um paciente previamente assintomático que desenvolveu febre de origem obscura. O diagnóstico de infecção aguda pelo CMV foi baseado em estudo sorológico. A tomografia computadorizada do tórax mostrou linfadenopatia mediastinal. A biópsia óssea revelou medula hipercelular com eosinofilia e grandes agregados linfóides mistos de células B e T. Apesar da positividade para bcl-2, a sua natureza reacional foi demostrada. A reação em cadeia da polimerase (PCR) e a imunohistoquímica não detectaram DNA viral nos cortes de medula óssea em parafina. Assim como em outros distúrbios sistêmicos, os nódulos linfóides no nosso caso parecem ser causados por mecanismos imunológicos, possivelmente relacionados a citoquinas liberadas em resposta ao processo infeccioso sistêmico.

Congenital cytomegalovirus infection: three autopsy case reports

We report three autopsy cases of congenital cytomegalovirus (CMV) infection in fetuses with a review of literature. The clinical manifestations in these cases of congenital CMV infection include intrauterine fetal death, hydrops fetalis, and CMV pneumonia associated with cardiovascular defect. The pathological characteristics were as follows: 1) the kidney was the most frequently involved organ, followed by lung and liver, 2) CMV inclusions were found predominantly in epithelial cells and to a lesser degree in endothelial cells, 3) intrahepatic bile duct epithelial cells were frequently involved, and 4) inflammatory reaction around CMV inclusions was not prominent in the early stage of pregnancy. Diagnostic confirmation was obtained by in situ hybridization (ISH) using a biotinylated CMV-DNA probe, which demonstrated intranuclear inclusions and sometimes recognized cells that did not show intranuclear inclusion.

Congenital cytomegalovirus infection: three autopsy case reports

We report three autopsy cases of congenital cytomegalovirus (CMV) infection in fetuses with a review of literature. The clinical manifestations in these cases of congenital CMV infection include intrauterine fetal death, hydrops fetalis, and CMV pneumonia associated with cardiovascular defect. The pathological characteristics were as follows: 1) the kidney was the most frequently involved organ, followed by lung and liver, 2) CMV inclusions were found predominantly in epithelial cells and to a lesser degree in endothelial cells, 3) intrahepatic bile duct epithelial cells were frequently involved, and 4) inflammatory reaction around CMV inclusions was not prominent in the early stage of pregnancy. Diagnostic confirmation was obtained by in situ hybridization (ISH) using a biotinylated CMV-DNA probe, which demonstrated intranuclear inclusions and sometimes recognized cells that did not show intranuclear inclusion.