mycophenolic-acid and Encephalitis--Viral

Human herpesvirus 6 (HHV-6) encephalitis is a known life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, few studies have focused on the occurrence of HHV-6 encephalitis in patients receiving mycophenolate mofetil (MMF) combined with a calcineurin inhibitor as prophylaxis for graft-versus-host disease (GVHD). This study aimed to investigate the impact of MMF administered for GVHD prophylaxis in the occurrence of HHV-6 encephalitis after allo-HSCT and the characteristics of this condition.. We retrospectively analyzed 73 patients who underwent allo-HSCT (83 transplants) at our hospital between April 2010 and December 2015. MMF (2-3 g/d) was administered along with a calcineurin inhibitor. Seven patients (8.0%) developed encephalitis due to HHV-6. The median period from allo-HSCT to the onset of HHV-6 encephalitis was 23 days (range, 17-98 days). The cumulative incidence of HHV-6 encephalitis on day 100 after treatment was 12% and 6% in patients who underwent cord blood transplantation (CBT) and non-CBT (ie, bone marrow transplantation and peripheral blood stem cell transplantation), respectively (P = 0.344). Neurological symptoms of encephalitis were more severe in non-CBT cases than those in CBT cases. All patients diagnosed with HHV-6 encephalitis were treated with ganciclovir or foscarnet. None of the enrolled patients died from HHV-6 encephalitis.. Mycophenolate mofetil may have the potential to increase the frequency of severe HHV-6 encephalitis in patients undergoing CBT and non-CBT. Thus, MMF should be administered with caution, and patients should be monitored closely for HHV-6 encephalitis even those who did not undergo CBT.

Topics: Adult; Aged; Antiviral Agents; Calcineurin Inhibitors; Cord Blood Stem Cell Transplantation; Encephalitis, Viral; Female; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Herpesvirus 6, Human; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Incidence; Male; Middle Aged; Mycophenolic Acid; Retrospective Studies; Roseolovirus Infections; Severity of Illness Index; Transplantation, Homologous; Young Adult

Human herpesvirus 6 (HHV-6) encephalitis/myelitis is now a well-known complication after allogeneic stem cell transplantation (allo-HSCT), particularly after cord blood transplantation (CBT). In this study, we evaluated the risk factors of HHV-6 encephalitis/myelitis.. We evaluated 253 patients who received allo-HSCT from 2007 to 2015 at our institute. HHV-6 encephalitis/myelitis was defined as HHV-6 DNA detection in the cerebrospinal fluid or peripheral blood by polymerase chain reaction in the presence of typical manifestations without other concurrent condition that led to the manifestations.. HHV-6 encephalitis/myelitis occurred in 11 patients (4.5%) (9 encephalitis, 3.7%; 2 myelitis, 0.8%). Multivariate analysis showed that CBT, mycophenolate mofetil (MMF) for graft-versus-host disease prophylaxis, history of allogeneic hematopoietic stem cell transplantation (allo-HSCT), and engraftment syndrome (ES) were significantly associated with incidence of HHV-6 encephalitis/myelitis (P=.025, P=.017, P=.017, and P=.014, respectively).. Although it has been shown that CBT, ES, and history of allo-HSCT are risk factors for HHV-6 encephalitis/myelitis, our study demonstrated MMF is also a risk factor for the disease.

Topics: Adolescent; Adult; Aged; Cord Blood Stem Cell Transplantation; DNA, Viral; Encephalitis, Viral; Female; Graft vs Host Disease; Hematologic Diseases; Hematopoietic Stem Cell Transplantation; Herpesvirus 6, Human; Humans; Immunosuppressive Agents; Incidence; Male; Middle Aged; Mycophenolic Acid; Myelitis; Polymerase Chain Reaction; Risk Factors; Roseolovirus Infections; Transplantation Conditioning; Transplantation, Homologous; Young Adult

Mycophenolate mofetil (MMF) is used for immunosuppression in myasthenia gravis (MG). Although there are numerous data on associated infection and prophylaxis in transplant patients who are on MMF, data in MG remains lacking. We report two elderly seropositive MG patients who developed cytomegalovirus (CMV) enteritis and Epstein-Barr virus (EBV) encephalitis while on MMF for 5months and 1year, respectively. Chronic MMF therapy in MG patients may trigger life-threatening infections including CMV and EBV diseases, especially in the elderly. Similar to the practice in transplant patients, viral serology testing and appropriate prophylactic regimen with antiviral agents should be considered, particularly in older MG patients.

Topics: Aged, 80 and over; Antiviral Agents; Cytomegalovirus Infections; Encephalitis, Viral; Enteritis; Epstein-Barr Virus Infections; Humans; Immunocompromised Host; Immunosuppressive Agents; Myasthenia Gravis; Mycophenolic Acid; Opportunistic Infections

The patient was a 55 year-old-woman with chronic renal failure due to idiopathic mesngial deposition of Ig A. She received a second allograft of a kidney from a cadaver. Results of a preoperative serologic Ig G tests for EBV and CMV were positive. She was given triple-drug immunosuppressive therapy, consisting of cyclosporine,azathioprine, and steroids. Seven years later, azathioprine was changed to mycophenolate mofetil. One year later, she was admitted to the hospital with a three to four week history of vertigo (which did not improve after sulpiride was administrated) and an influenza-like syndrome. A CT scan of the brain appeared normal, so paroxysmal positional vertigo was the diagnosis. Two weeks after admission to the hospital, the patient reported visual hallucinations and impairment of consciousness. Results of laboratory tests were leukocyte increase (polymorphonuclear leukocytes), anemia, hyponatremia and renal failure. Chest radiography, brain CT, and electroencephalography revealed no pathologic signs. The CSF examination revealed 300 cells/ml (79% PMNL), glucose 63 mg/dl, protein 45 mg/dl. Six hours later the treatment was initiated with ampicillin, ceftriaxone and ganciclovir iv, she experienced seizures that affected the left side of her body, but without interictal recovery. The patient required intubation and mechanical ventilation in the intensive care unit. An MRI of the brain images, revealed high signal-intensity regions indicating lesions on the bulb, protuberance, mesencephalon, left thalamus and parenchyma adjacent to the corpus callosum (fig. 1). Six days later, the patient partially recovered consciousness, and she had not neurologic sequelae. Intubation was terminated. As soon as PCR revealed EBV DNA in CSF samples, the treatment with ceftriaxone and ampicillin was discontinued. Treatment with ganciclovir was maintained for 8 weeks (4 weeks with iv and another 4 weeks with oral treatment). On day 35, the examination of a specimen of CSF revealed: glucose 46, protein 78, 15 cells/ml (100% lymphocytes). The patient went home on day 55 after admission to our hospital. She regained her normal neurologic function. Three weeks later MRI, showed reduction of the size of the lesions and the lesions on the brain stem had disappeared.

Topics: Adrenal Cortex Hormones; Antiviral Agents; Cyclosporine; DNA, Viral; Encephalitis, Viral; Epstein-Barr Virus Infections; Female; Ganciclovir; Hallucinations; Herpesvirus 4, Human; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Transplantation; Middle Aged; Mycophenolic Acid; Postoperative Complications; Status Epilepticus; Vertigo