Severe Cytomegalovirus Infection Research Articles

Comparative Study of Mizoribine and Mycophenolate Mofetil Combined with a Calcineurin Inhibitor-Based Immunosuppressive Regimen in Patients with Alternative Donor Hematopoietic Cell Transplantation.

Cytomegalovirus (CMV) infection and graft-versus-host disease (GVHD) remain the major causes of nonrelapse mortality (NRM) in patients following alternative donor hematopoietic stem cell transplantation (HCT). Mizoribine (MZR) showed an anti-CMV effect in addition to its immunosuppressive effect in patients with renal transplantation. In this study, we aimed to evaluate the efficacy and safety of MZR combined with a calcineurin inhibitor (CNI) as a method of prophylactic immunosuppression in recipients following alternative donor HCT. Eighty patients were enrolled in the study and randomized to the MZR (n=40) or MMF (n=40) cohort before transplantation conditioning. Analyses involved a comparison of the outcomes between the 2 cohorts, as well as risk analyses of early nonrelapse mortality (NRM) and severe CMV infection. In contrast to MMF, MZR was associated with a lower but statistically nonsignificant median CMV DNA peak load (P=.075), significantly fewer episodes of persistent/refractory infection (odds ratio [OR], .12), and a lower failure rate of CMV treatment (OR, .82), but a significantly higher rate of hyperuricemia (OR, 2.75). Transplantation efficacy was comparable in the 2 cohorts regarding engraftment, the development of secondary poor graft function and GVHD, and the estimated OS and PFS. The 1-year NRM of the MZR cohort did not differ from that of the MMF cohort, whereas the rate of 1-year NRM caused by viral infections was reduced in the MZR cohort and was of borderline statistical significance (P=.05). In the multivariate analysis, lower doses of CD34+ cells in grafts (hazard ratio [HR], 3.65) and persistent/refractory CMV infections (versus no CMV infection: HR, 7.31; versus CMV infection that was not persistent/refractory: HR, 4.46) were predictors of increased 1-year NRM. The use of MMF (versus MZR cohort: OR, 11.54) and grade II-IV acute GVHD (OR, 15.32) were independent risk factors for developing persistent/refractory CMV infection. When combined with CNIs, MZR functioned well in terms of both immunosuppression and reduced severity of CMV infection; however, further studies are warranted to verify its use as a potential immunosuppressant for alternative donor HCT.

Isolated thrombotic microangiopathy of the small intestine in a patient with atypical hemolytic uremic syndrome \u2013 a case report

BackgroundAtypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by systemic thrombotic microangiopathy (TMA) reflected by hemolysis, anemia, thrombocytopenia and systemic organ injury. The optimal management of aHUS-patients when undergoing kidney transplantation to prevent recurrence in the allograft is eculizumab, an approved recombinant antibody targeting human complement component C5.Case presentationA 39 year-old woman presented with severe abdominal pain, diarrhea and emesis for 3 days. In her past medical history she had experienced an episode of aHUS leading to end stage renal disease (ESRD) in 2007 and a genetic workup revealed a heterozygous mutation in the membrane cofactor protein gene. In 2014 she underwent cadaveric kidney transplantation. Four years later she had to go back on hemodialysis due to allograft failure following a severe systemic cytomegalovirus infection resulting in transplant failure. At presentation she still received calcineurin-inhibitor therapy and reported subfebrile temperatures and pain projecting over the transplant prior to the current symptoms. A contrast enhanced CT-scan of the abdomen revealed inflammatory wall thickening of the small intestine. Diagnostic endoscopy discovered fresh blood in the small intestine without a clear source of bleeding. Histopathology of the small intestine biopsies showed severe thrombotic microangiopathy. Of note, the patient persistently had no signs of systemic hemolysis. Since the TMA of the small intestine was most likely due to aHUS, eculizumab treatment was initiated which abolished the symptoms.ConclusionHere we report a patient with thrombotic microangiopathy with predominant manifestation in a single organ, the small intestine, due to aHUS with absence of systemic signs and symptoms. aHUS patients usually require a secondary trigger for the disease to manifest. In this case, the trigger may be attributed to the dysfunctional renal transplant, which was subsequently explanted. Histology of the explanted kidney showed severe inflammation due to purulent nephritis and signs of cellular rejection. After nephrectomy, we continued eculizumab therapy until the patient completely recovered. No signs of TMA recurred after discontinuation of eculizumab, further supporting the concept of the renal transplant as the main trigger of TMA of the small intestine in our patient.

A case of neonatal cytomegalovirus infection with severe thrombocytopenia that was successfully managed with empiric antiviral therapy.

Antiviral therapy against cytomegalovirus (CMV) infection is indicated for symptomatic infection in the fetus and premature neonates. In mature neonates, the benefit of antiviral therapy for severe CMV infection remains controversial. Additionally, when diagnosing symptomatic CMV disease occurring during the early neonatal period, it is difficult to differentiate between congenital and acquired infections. We herein report a neonatal case of CMV infection complicated with severe thrombocytopenia that was successfully managed with antiviral treatment. A 21-day-old male infant presented with low-grade fever and erythema on his extremities. During outpatient follow-up, he developed petechiae and thrombocytopenia (platelet count 17,000/μL). Subsequent serological examination and molecular detection of CMV confirmed the diagnosis of CMV infection. In consideration of the severe thrombocytopenia, antiviral therapy with valganciclovir 32 mg/kg/day was initiated. The platelet counts increased with decreasing CMV loads. After excluding congenital CMV infection, we discontinued antiviral therapy without relapse of the disease. The present case suggests that neonatal cases of severe symptomatic CMV infection may require antiviral therapy while excluding the possibility of congenital infection.

AN ATYPICAL PRESENTATION OF CYTOMEGALOVIRUS PNEUMONIA

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Cytomegalovirus (CMV) is a viral pathogen that is seen in 40-100% of adults by the fourth decade (1). Infection in an immunocompetent individual is usually subclinical, with severe life-threatening infection seen in immunocomprised individuals. Steroid use has a weak association for infection reactivation in an immunocompetent host. We present the case of a chronic kidney disease (CKD) patient on steroids who was diagnosed and treated for CMV interstitial pneumonia. CASE PRESENTATION: 78-year-old female with a past medical history of interstitial lung disease, idiopathic thrombocytopenia purpura on steroids, CKD stage III who presented from a nursing facility where she was recuperating from a recent hospitalization due to pneumonia. During her prior admission, she was treated with steroids, vancomycin and cefepime for a presumed bacterial pneumonia. Patient presented with shortness of breath. Vital signs were notable for a temperature of 98.4 F, heart rate 102 bmp, RR 24/min, and SaO2 90% on 7L NC. Physical exam revealed bibasilar rales. Labs showed a white blood cell count of 10.1 Thou/uL, creatinine of 1.5 mg/dL, lactic acid 2.8 mmol/L, procalcitonin of 0.12 ng/mL, lactate dehydrogenase (LDH) of 544 U/L. Computed tomography (CT) of the chest showed increasing ground glass changes compared to previous admission imaging. Patient was started on steriods, vancomycin and cefepime. Given worsening radiographical findings, history of ILD, and elevated LDH in the setting of chronic steroids, there was a suspicion for pneumocystis pneumonia. She underwent a video-assisted thoracoscopic surgery lung biopsy, bronchoalveolar lavage and wedge resection of the right lung. Pathology showed microscopic honey combing and extensive subpleural fibrosis, consistent with interstitial pneumonia. CMV cytopathic effect was confirmed with immunoperoxidase staining. PCR testing and tissue culture also returned positive for CMV; viral load was 81,581 IU/mL. Patient was started on a six-week course of valganciclovir with a plan to taper steroids as an outpatient. Patient was unfortunately lost to follow up thereafter. DISCUSSION: Severe life threatening CMV infection is seen in immunocomprised risk groups particularly transplant recipients, patients affected with AIDS, malignancy and neonates. Steroid use has a weak association with CMV reactivation; CKD also has been postulated as a risk factor for reactivation due to malfunctioning white cells. CONCLUSIONS: Although CMV pneumonia targets a subtype of immunosuppressed patients, it should be considered a differential in patient’s on chronic steroid treatment and CKD. This case emphasizes the importance of having a high degree of suspicion of CMV pneumonia in a patient on chronic high dose steroids, in clinical setting, such as this one. Without the correct diagnosis, obtained by PCR of a BAL sample, treatment opportunities will be missed, leading to poor outcomes. Reference #1: Grilli, Elisabetta, et al. “Cytomegalovirus Pneumonia in Immunocompetent Host: Case Report and Literature Review.” Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology, U.S. National Library of Medicine, Dec. 2012. Reference #2: Al-Omari, A., Aljamaan, F., Alhazzani, W., Salih, S., & Arabi, Y. (2016). Cytomegalovirus infection in immunocompetent critically ill adults: literature review. Annals of intensive care, 6(1), 110 Reference #3: Carpani, G., Foresti, S., Dell'Oro, R., Grassi, G., & Bombelli, M. (2019). Severe systemic cytomegalovirus infection in an immunocompetent patient outside the intensive care unit: a case report. BMC infectious diseases, 19(1), 34. https://doi.org/10.1186/s12879-018-3621-8 DISCLOSURES: No relevant relationships by Antonie Auguste, source=Web Response No relevant relationships by Amreet Aujla, source=Web Response No relevant relationships by Sarah Banks, source=Web Response No relevant relationships by Manmeet Grewal, source=Web Response No relevant relationships by Ann Palmer, source=Web Response

Severe systemic cytomegalovirus infection in an immunocompetent patient outside the intensive care unit: a case report

BackgroundCytomegalovirus is responsible for an opportunistic infection that can be life threatening in immunocompromised patients, while it is usually mild or completely asymptomatic in immunocompetent subjects. In the recent years, however, some cases of severe cytomegalovirus infection in immunocompetent patients have been reported, showing this to be a less rare occurrence than previously reported.Case presentationWe report the case of an 83-year-old man, admitted to our hospital for gastroenteritis, complicated by dehydration and severe prothrombin time prolongation due to oral anticoagulant therapy accumulation, who developed hospital-acquired pneumonia; neither of these illnesses responded to several lines of antibiotic therapy. All microbiologic tests were negative, except cytomegalovirus DNA test in blood, which showed high viral load. Antiviral therapy with ganciclovir was then started and a quick favourable response followed. A state of immunodeficiency was excluded, based on normal CD4 count and patient’s clinical history.ConclusionDifferent risk factors for severe cytomegalovirus disease in immunocompetent patients may exist, besides the ones already known, which could be responsible for severe cytomegalovirus disease in immunocompetent patients; thus, these patients should be tested for cytomegalovirus infection, if the clinical picture is compatible, to avoid delay in diagnosis and allow prompt start of specific therapy.

Congenital Cytomegalovirus Infection: A rare cause of neonatal morbidity in Nigeria

Background: Cytomegalovirus (CMV), a member of the herpes virus family is a known cause of intrauterine infections with attendant sequelae on the newborn. Symptomatic CMV is grossly underdiagnosed and rarely reported in Nigeria and elsewhere. A.O was a 6-week old male with features suggestive of severe CMV infection that was misdiagnosed and managed for bacterial sepsis in another hospital without improvement necessitating referral to our facility. He had generalised “blueberry muffin” skin rashes from birth, respiratory distress, pyrexia,recurrent anemia, severe jaundice with massive hepatosplenomegaly; in addition to symptoms of central nervous system involvement. Serological tests and polymerase chain reaction were positive for Cytomegalovirus. He received intravenous and oral ganciclovir, blood transfusions and intravenous antibiotics for anaemia and bacteria sepsis with satisfactory outcome. This case highlights the need for high index of suspicion, and prompt appropriate intervention in order to minimize morbidity and improve outcome in cases of congenital CMV infection.

Colitis por citomegalovirus en paciente inmunocompetente

Severe cytomegalovirus infection in immunocompetent patients is unusual with colitis being its main manifestation. It occurs predominantly in elderly patients with high burden of comorbidities. A case of a woman with acute heart failure and coronary heart disease who had lower gastrointestinal bleeding due to cytomegalovirus colitis in the absence of apparent immunosuppression is presented.

Cytomegalovirus acute infection with pulmonary involvement in an immunocompetent patient.

IntroductionCytomegalovirus (CMV) infection in healthy adults is usually asymptomatic or causes a mild mononucleosis syndrome, while severe infections are rare in immunocompetent patients and poorly documented. When described, gastrointestinal tract and the central nervous systems are the most frequent sites of severe CMV infection. Lung disease can occur, but it’s rare.Clinical caseA 29 years old man presenting with a 2-weeks history of fever, headache, malaise, dry non-productive cough and thoracic pleuritic pain, without improvement after one-week therapy with levofloxacin. Blood exams showed lymphocytosis of almost 50%, nine percent of atypical lymphocytes and elevated transaminases. Thoracic CT-scan showed bilateral infiltrate with internal air bronchogram. Blood serology showed positivity for CMV IgG and IgM, with low CMV IgG avidity. Serum and bronchoalveolar detection of CMV by polymerase chain reaction (PCR) technique was also positive. Cultures were all negative. The patient became increasingly hypoxemic and the liver transaminases worsening, the reason for which ganciclovir was started. He made a full recovery and was discharged seven days later with oral valganciclovir, completing a 3 weeks antiviral course at home.DiscussionCMV pneumonia is a rare condition, however it’s one of the three most common cause of severe viral community acquired pneumonia (CAP), along with influenza and adenovirus. CMV pneumonia should be considered in patients with atypical lymphocytes and mildly elevated serum transaminases.ConclusionIn immunocompetent hosts, even with severe CMV-CAP, the prognosis is good. However, antiviral treatment should be considered in the rare occasion of severe CMV infection. Nevertheless, more studies are needed to clarify the clinical benefit of antiviral treatment.

Pre-Transplant Cytomegalovirus Immunoglobulin G Antibody Levels Could Prevent Severe Cytomegalovirus Infections Post-Transplant in Liver Transplant Recipients: Experience from a Tertiary Care Liver Centre

Background: Humoral immune responses in cytomegalovirus (CMV) are not studied well. Pre-transplant CMV immunoglobulin G (IgG) antibody levels (Pre-Tx IgG) could influence the occurrence of post-transplant CMV infections. Objective: Correlation between pre-Tx IgG and post-Tx risk of acquiring CMV infection was investigated. Materials and Methods: A total of 146 liver Tx recipients, not on CMV prophylaxis, were included. Pre-Tx IgG in donor (D) and recipient (R) were estimated and all the recipients were followed up for 1 year for CMV infections. Results: D+ R+ serostatus was seen in 142 (97.3%) and D− R+ in 4 (2.7%). A total of 113 (77.4%) recipients had pre-Tx IgG of ≥250 AU/ml. Overall, post-Tx CMV infections were seen in 54 (36.9%) recipients. In 32 (59.2%) patients, CMV infection was seen during the 1st month after TX. Incidences of post-Tx CMV infection in recipients with pre-Tx IgG <250 AU/mL and ≥250 AU/mL were 42.4% and 34.5%, respectively (P = 0.99). Median viral load was significantly higher in patients with pre-Tx IgG <250 AU/ml: 4log10 (R: 2.8–6.6 log 10) copies/ml than those with ≥250 AU/ml: 2.2 log10 (R: 1.6–3.8 log10) copies/ml, P = 0.04. There was no difference in the time of occurrence of CMV infection in both the groups. Concurrent occurrence of rejection and CMV infection was seen in significantly more patients 18/54 (32.7%) than in patients without CMV infection (12/99, 12%, P = 0.002). Conclusions: Higher pre-Tx CMV IgG levels might prevent severe CMV infections post-Tx. Recipients with low pre-Tx CMV titre might be benefitted by CMV prophylaxis or aggressive pre-emptive treatment.

Potential role of plasmapheresis in severe cytomegalovirus infection with ongoing immunemediated hemolysis and low complement level

Symptomatic cytomegalovirus (CMV) infections are rare in patients with no previous history of immunosuppressive therapy or condition. A 33-year-old woman with type-2 diabetes, endstage renal disease (ESRD) and unexplained lower extremity weakness was admitted with failure to thrive, ongoing hemolysis, low haptoglobin and C3 levels and suppressed IgM and IgG globulin fractions. Multiple cultures and serologic workup for autoimmune disorders remained negative. CMV viral titer by serum polymerase chain reaction (PCR) revealed massive elevation at 9.2 million copies/mL. Initial CMV IgG titer was positive, IgM titer remained consistently negative and CMV was recovered from cerebrospinal fluid, as well. She received treatment with I.V. ganciclovir, CMV immune globulin (CytoGam) and three sessions of plasmapheresis (PLEX). The extreme viremia without neutropenia, lack of IgM antibody reconversion and CMV-mediated hemolysis with a low complement level were all very unusual features. Timely initiation of PLEX may have contributed to recovery

Impressive tissue regeneration of severe oral mucositis post stem cell transplantation using cord blood platelet gel

Platelet gel from cord blood (CBPG) is a recently developed blood component for topical use. We report a case of life-threatening mucositis after high-dose chemotherapy with fotemustine and cytarabine that was successfully treated with CBPG. A patient with non-Hodgkin lymphoma who was undergoing autologous hematopoietic stem cell transplantation developed severe oral and esophageal mucositis with severe bacterial sepsis and cytomegalovirus infection, causing prolonged neutropenia. CBPG was topically administered daily to the oral cavity. The CBPG was partially reabsorbed and partially swallowed. After 8 consecutive days of administration, the patient's oral mucosa markedly improved, showing restitutio ad integrum, and the patient's clinical status progressively improved. No side effects were seen after CBPG application. This case supports the need to conduct controlled studies comparing the efficacy of autologous and allogeneic platelet gel from adult and umbilical cord blood for the topical treatment of severe oral mucositis occurring after high-dose chemotherapy.

Severe Symptomatic Primary Human Cytomegalovirus Infection despite Effective Innate and Adaptive Immune Responses.

Primary human cytomegalovirus (HCMV) infection usually goes unnoticed, causing mild or no symptoms in immunocompetent individuals. However, some rare severe clinical cases have been reported without investigation of host immune responses or viral virulence. In the present study, we investigate for the first time phenotypic and functional features, together with gene expression profiles in immunocompetent adults experiencing a severe primary HCMV infection. Twenty primary HCMV-infected patients (PHIP) were enrolled, as well as 26 HCMV-seronegative and 39 HCMV-seropositive healthy controls. PHIP had extensive lymphocytosis marked by massive expansion of natural killer (NK) and T cell compartments. Interestingly, PHIP mounted efficient innate and adaptive immune responses with a deep HCMV imprint, revealed mainly by the expansion of NKG2C+ NK cells, CD16+ Vδ2(-) γδ T cells, and conventional HCMV-specific CD8+ T cells. The main effector lymphocytes were activated and displayed an early immune phenotype that developed toward a more mature differentiated status. We suggest that both massive lymphocytosis and excessive lymphocyte activation could contribute to massive cytokine production, known to mediate tissue damage observed in PHIP. Taken together, these findings bring new insights into the comprehensive understanding of immune mechanisms involved during primary HCMV infection in immunocompetent individuals.IMPORTANCE HCMV-specific immune responses have been extensively documented in immunocompromised patients and during in utero acquisition. While it usually goes unnoticed, some rare severe clinical cases of primary HCMV infection have been reported in immunocompetent patients. However, host immune responses or HCMV virulence in these patients has not so far been investigated. In the present study, we show massive expansion of NK and T cell compartments during the symptomatic stage of acute HCMV infection. The patients mounted efficient innate and adaptive immune responses with a deep HCMV imprint. The massive lymphocytosis could be the result of nonadapted or uncontrolled immune responses limiting the effectiveness of the specific responses mounted. Both massive lymphocytosis and excessive lymphocyte activation could contribute to massive cytokine production, known to mediate tissue damage. Furthermore, we cannot exclude a delayed immune response caused by immune escape established by HCMV strains.

Coombs-Negative Severe Hemolytic Anemia and Possible Autoimmune Disease in an Adult Following Cytomegalovirus Infection

Hemolysis is a quite uncommon complication of Cytomegalovirus (CMV) infection, which could rarely present with severe manifestations. Diagnosis is usually based on exclusion of other causes of hemolytic anemia, history of CMV infection, accompanied by positive serological tests and positive direct Coombs (DAT) Test, evidence indicative of post-infection autoimmune response. Although most cases present no symptoms, there have been reports of severe post CMV infection hemolysis requiring treatment with steroids, immunoglobulin or even splenectomy. It is herby described the case of a 19-year-old immune competent woman, who presented with severe hemolytic anemia following primary CMV infection. The patient’s Hemoglobin (Hb) level was 5.8 g/dl on the day of admission. Extensive laboratory testing for causes of anemia, active infections, systemic diseases and autoimmunity showed positive Antinuclear Antibodies and positive CMV IgM and IgG Antibodies. Although direct Coombs Test were persistently negative, post infection autoimmunity was suspected and after steroid treatment was initiated, the patient achieved full recovery. In immune competent individuals suffering from post CMV infection hemolysis a stay and watch policy could be employed. However, as far as an autoimmune mechanism is suspected the patient is eligible for steroid treatment.

Hematopoietic stem cell transplantation corrects WIP deficiency

Hematopoietic stem cell transplantation corrects WIP deficiency

Severe Acute Cytomegalovirus Infection Complicated by Disseminated Intravascular Coagulation and Pneumonitis in a Healthy Female

Cytomegalovirus (CMV) is an endemic infection worldwide. Among healthy individuals, infections are usually asymptomatic. An infectious mononucleosis-type syndrome is classically described. More serious manifestations, such as pneumonitis, hepatitis, and meningoencephalitis have been described in otherwise healthy populations. Disseminated intravascular coagulation is a life-threatening complication that is extremely rare in competent hosts. We describe a case of pneumonitis and DIC associated with acute CMV infection that resolved with antiviral therapy.

Severe Cytomegalovirus Infection in a Late-Preterm Infant at 2 Months of Age

여러 기관을 침범하는 중증 주산기 거대세포바이러스 감염은 극저출생체중아 또는 면역저하 환자 이외의 경우에는 매우 드물다. 저자들은 재태연령 34주 6일, 2,460 g으로 출생한 후기 미숙아에서 다기관(중추신경계, 간, 폐, 위장관)을 침범한 거대세포바이러스에 의한 주산기 감염을 의심하고 ganciclovir투약 후 회복된 증례를 경험하여 문헌 보고하는 바이다.

Clinical observation over the dynamic of the intrauteral mixed infection in the child of early age

Difficulty in diagnosis of the intrauterine infections (IUI) is associated with the low specificity of clinical manifestations and the multiple organ injury, prolonged persistence of the pathogen in the body, a significant prevalence of mixed infections and their frequent combination with the somatic disorders in newborns. The clinical case of mixed intrauterine infection in the child of early age is presented. The full-term boy was under the observation, he was born with severe anemic syndrome, indirect hyperbilirubinemia and hepatosplenomegaly. According to clinical observation and ultrasound of the abdomen the size of his liver and spleen increased progressively for six days after birth, it was accompanied by dynamic increase of total bilirubin due to its direct fraction, decrease of platelets count. ELISA-diagnostics of the child’s serum revealed the presence of the anti-toxoplasma and anti-cytomegalovirus antibodies. Taking into account obtained clinical and paraclinical data, the newborn child was diagnosed with intrauterine mixed infection with primary hematopoietic and liver damage (cholestatic-cytolytic variant). Anti-toxoplasma immunoglobulin was administered to child, but because of severe liver injury specific causal treatment of toxoplasmosis was postponed due to its hepatotoxicity. Later on anemic syndrome with indirect hyperbilirubinemia recurrently repeated in a child, it was dependent on transfusions but refractory to treatment. The presence of DNA of CMV and herpes virus type 6 was confirmed by PCR in the dynamic study of the five-month old child’s blood. Taking into account the obtained results of the examination, the child was diagnosed with severe congenital cytomegalovirus infection in the replication phase and comorbid congenital nonspherocytic hemolytic anemia of unknown origin with continuous crisis. The patient received anti-cytomegalovirus ganciclovir intravenously, antiherpetic valaciclovir orally. As a result of the treatment positive clinical dynamics was observed, which was accompanied by a decrease of the hepatolienal syndrome and gaining weight, but multiple red blood cell transfusions were not accompanied by significant or prolonged rise in hemoglobin levels. After the treatment twice done PCR child’s blood tests for CMV DNA were negative. Taking into account the crisis duration of the disease, splenectomy was discussed. The clinical case refers to the rare clinical diagnostic situations in medical practice when it is difficult to make a final conclusion about the etiology of the IUI. Verification of the intrauterine mixed infection was problematic in the neonatal period and during follow-up. The complexity of the diagnostic process was caused by the absence of the typical neurological symptoms. The diagnosis of mixed IUI was complicated by coexistence of the congenital nonspherocytic hemolytic anemia, the genesis of which could not be set, despite the study of enzyme activity in red blood cells, assessment of their osmotic resistance and Coombs tests. Damage of the erythroid stem hematopoiesis probably was caused by the infectious factors during the intrauteral period as well as by the hereditary pathology of the erythron.

Cytomegalovirus hepatitis and severe cytomegalovirus infection in immunocompetent patients

Cytomegalovirus hepatitis and severe cytomegalovirus infection in immunocompetent patients

Risk of Rotavirus Vaccination for Children with SCID

To the Editors: Quinn et al.1 demonstrated reduced morbidity and mortality from acute gastroenteritis by rotavirus vaccination in young children in Australia. We agree with the consensus statement highlighting these benefits in both developed and developing settings, which clearly outweigh the small increased risk of intussusception.2 Nevertheless, we think that the additional risk rotavirus vaccination poses for children with severe combined immunodeficiency (SCID) needs comment. Recently, we saw a 21-month-old boy from a country in the Middle-East who was in reduced general condition for further diagnosis and management at our center. Although his older brother died at 20 months of age suffering from postvaccinational BCGitis and severe cytomegalovirus infection, our patient had received rotavirus vaccine (Rotarix, GlaxoSmithKline Biologicals, Rixensart, Belgium) twice at 3 and 4 months of age. Ever since, he suffered from chronic gastroenteritis, which resulted in severe stunting and wasting. The patient had a x-linked hemizygous mutation in Exon 2 of the IL2RG gene (c.252C>A, p.Asn84Lys; MIM# 300400) and curative therapy with stem cell transplantation was initiated at our specialized medical center.3 We identified rotavirus vaccine strain in stool samples by sequencing of 8 different gene segments (VP1, VP2, VP4, VP6, VP7, NSP2, NSP4 and NSP5). In all segments vaccine-associated sequences harboring few new mutations were found, leading to the conclusion that the child’s chronic gastroenteritis was caused by persisting infection with the vaccine rotavirus strain (see Table, Supplemental Digital Content 1, https://links.lww.com/INF/B978). No other pathogen could be identified in multiple stool samples, including uncommon parasites, coccidia and helminths. Notably, all stool, blood and respiratory specimens were also tested by Luminex xTAG respiratory and xTAG gastrointestinal pathogen panel (Abbott Molecular, Wiesbaden, Germany). In samples from the respiratory tract, we detected high copy numbers of human bocavirus (HBoV) and rhinovirus, which most likely subsequently caused respiratory failure in our patient. Despite all intensive supportive care and treatment, the boy’s condition deteriorated and he died on day 1 after stem cell transplantation. In addition to the association with intussusception, shedding of rotavirus for a period of time after oral vaccination and vaccine-induced severe gastroenteritis including infection of healthy siblings have been reported.4 The observation of acute and chronic infections by vaccine strain rotavirus in immunocompromised children led to the addition of SCID as contraindication for administration of rotavirus vaccine.5–7 Our SCID patient presented already with advanced disease and severely reduced general condition. We believe that viral shedding of rotavirus for such a prolonged period of time has not been previously reported and might be explained by the lack of timely adequate medical management. We cannot completely exclude that other gastrointestinal infections and other comorbidities might have been involved, but we propose that vaccine-acquired rotavirus-infection had probably contributed significantly to the fatal outcome. The clinical manifestation and diagnosis of SCID patients might be delayed well into the life period after the recommended vaccination schedule. Therefore, we emphasize the negative effect that rotavirus vaccination might have in these endangered patients and we strongly support efforts of mandatory newborn screening for SCID.8TABLE 1: Comparison of Rotavirus Sequences From Patient Sample and Vaccine StrainDennis Klinkenberg, MD Martin Blohm, MD Department of Paediatrics University Medical Center Hamburg-Eppendorf Hamburg, Germany Marina Hoehne, PhD Andreas Mas Marques, PhD Robert-Koch-Institute Berlin, Germany Monika Malecki, PhD Kliniken der Stadt Köln gGmbH Institut für Hygiene Köln-Merheim, Germany Verena Schildgen, PhD Klinken der Stadt Köln gGmbH Institut für Pathologie Furth, Germany Reinhard Schneppenheim, MD, PhD Ingo Müller, MD, MSc Department for Paediatric Haematolog and Oncology University Medical Center Hamburg-Eppendorf Bone Marrow Transplantation Unit Hamburg, Germany Oliver Schildgen, PhD Klinken der Stadt Köln gGmbH Institut für Pathologie Furth, Germany Robin Kobbe, MD Department of Paediatrics University Medical Center Hamburg-Eppendorf Hamburg, Germany

Tocilizumab in giant cell arteritis: Multicenter open-label study of 22 patients

ObjectiveTo assess the efficacy of tocilizumab (TCZ) in giant cell arteritis (GCA) patients with refractory disease and/or with unacceptable side effects due to corticosteroids. MethodsA retrospective multicenter open-label study on 22 GCA patients treated with TCZ at standard dose of 8mg/kg/month. The main outcomes were achievement of disease remission and reduction of corticosteroid dose. ResultsThe mean age ± standard deviation of patients was 69 ± 8 years. The main clinical features at TCZ onset were polymyalgia rheumatica (n = 16), asthenia (n = 7), headache (n =5), constitutional symptoms (n = 4), jaw claudication (n = 2), and visual loss (n = 2). Besides corticosteroids and before TCZ onset, 19 of 22 patients had also received several conventional immunosuppressive and/or biologic drugs. Of 22 patients, 19 achieved rapid and maintained clinical improvement following TCZ therapy. Also, after a median follow-up of 9 (interquartile range: 6–19) months, the C-reactive protein level had fallen from 1.9 (1.2–5.4) to 0.2 (0.1–0.9)mg/dL (p < 0.0001) and the erythrocyte sedimentation rate decreased from 44 (20–81) to 12 (2–20)mm/1st hour (p = 0.001). The median dose of prednisone was also tapered from 18.75 (10–45) to 5 (2.5–10)mg/day (p < 0.0001). However, TCZ had to be discontinued in 3 patients due to severe neutropenia, recurrent pneumonia, and cytomegalovirus infection. Moreover, 1 patient died after the second infusion of TCZ due to a stroke in the setting of an infectious endocarditis. ConclusionTCZ therapy leads to rapid and maintained improvement in patients with refractory GCA and/or with unacceptable side effects related to corticosteroids. However, the risk of infection should be kept in mind when using this drug in patients with GCA.