Acyclovir-Induced Nephrotoxicity in Adults with Viral Encephalitis.

OBJECTIVE: To determine the frequency of parenteral Acyclovir-induced Acute Kidney Injury (AKI) in patients with viral encephalitis. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Neurology, Liaquat National Hospital, Karachi, from January to December 2021. METHODOLOGY: A total of 89 suspected and proven cases of encephalitis receiving IV Acyclovir were collated. All had extensive medical histories and underwent CSF studies with +/- brain imaging. CSF routine and viral PCR were done. Acyclovir-induced AKI was defined as a rise in serum creatinine of >0.3 mg/dl in 48 h or by ≥1.5 times the baseline value, and its severity was staged into 1 (risk), 2 (injury), and 3 (failure) according to the KDIGO guidelines (Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group, 2012). Patients' variables, including age, gender, presenting features, comorbid conditions, and CSF findings, were divided into two groups, i.e. with and without AKI. RESULTS: This research included 89 patients with a mean age of 48 years. AKI occurred in 34 patients (38.2%). The frequency of AKI with Stage 1 was 24%, Stage 2 was 44%, and Stage 3 was 32%; approximately two-thirds of cases were in Stage 2 and 3 (p >0.05). Five patients (5.6%) from Stage 3, required dialysis. CONCLUSION: AKI is an important adverse effect of parenteral acyclovir, which necessitates its early identification and timely management. Renal function monitoring is essential for patients on Acyclovir treatment as they are at risk for AKI. KEY WORDS: Acyclovir, Acute kidney injury, Viral encephalitis, Creatinine, Kidney Disease Improving Global Outcomes.

Human herpesvirus 6 encephalitis in a patient treated with everolimus for renal cell carcinoma.

INTRODUCTION: Everolimus is a mammalian target of rapamycin inhibitor and is approved as second-line treatment or beyond for renal cell carcinoma. We report a case of a 75-year-old male treated with everolimus for metastatic renal cell carcinoma, after sunitinib treatment, who was diagnosed with human herpesvirus 6 encephalitis. CASE REPORT: After 39 months of everolimus, 10 mg per day, our patient was admitted with fever, consciousness disorders and a partial epileptic crisis. Laboratory tests revealed lymphopenia (170 lymphocytes/mm3), and polymerase chain reaction in cerebrospinal fluid was positive for human herpesvirus 6. Brain magnetic resonance imaging study demonstrated hippocampal abnormality and a pontine lesion. MANAGEMENT AND OUTCOME: The patient stopped everolimus treatment indefinitely. He received ganciclovir initially intravenously, with a rapid clinical improvement, as well as polyvalent immunoglobulins were given to correct hypogammaglobulinemia. Two months later, antiviral therapy was switched to oral ganciclovir, which was never stopped. A new lumbar puncture was performed one month after the initiation of antiviral treatment, which did not reveal human herpesvirus 6 DNA anymore. DISCUSSION: Human herpesvirus 6 encephalitis is more common in hematopoietic stem cell transplant recipients and HIV patients. This is the first case probably associated to everolimus treatment. In contrast to most patients diagnosed with this infection, who either die or develop neurologic sequelae, our patient almost fully recovered two months later.

Viral encephalitis associated with rituximab maintenance therapy: two cases and a review of literature.

Rituximab is increasingly used in the treatment of CD20-positive B-cell-mediated disease. Prolonged use may cause B-cell dysfunction, dose-dependent T-cell dysfunction, and hypogammaglobulinaemia and result in severe non-neutropenic infections. We present two cases of viral encephalitis in patients treated with rituximab maintenance therapy: one patient presented with deafness; the other patient with paroxysmal light flashes, apraxia, and weakness.

Enteroviral Encephalitis in a Child With CNS Relapse of Burkitt Leukemia Treated With Rituximab.

A boy with central nervous system relapse of Burkitt leukemia developed fever and neurologic symptoms and cognitive impairment. He had received multi-drug chemotherapy including rituximab. Enterovirus (EV) was detected in cerebrospinal fluid by polymerase chain reaction, and magnetic resonance imaging findings were consistent with viral infection. The patient was treated with intravenous immunoglobulin and within 1 month cleared his EV. Rituximab can cause a profound B-cell deficiency predisposing patients to infections including EV encephalitis. This is the first report of enteroviral encephalitis in a child undergoing treatment for lymphoma with rituximab and suggests the need to watch for this complication of therapy.

Opportunistic infections in myasthenia gravis treated with mycophenolate mofetil.

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.

Enteroviral encephalitis in a patient with a marginal zone lymphomatreated with rituximab.

A 64-year-old woman with a progressive marginal zone lymphoma for which she had received induction therapy with six courses of rituximab and fludarabine presented with fever while receiving maintenance therapy with rituximab. In addition to the fever she complained of nausea, vomiting, weight loss and fatigue. After an extensive diagnostic procedure no cause was found for the fever. Finally, additional testing showed a positive polymerase chain reaction (PCR) for enterovirus in the cerebrospinal fluid and faeces. Because the immunoglobulin G level of our patient was 4.06 g/l (normal values 5.2 to 16 g/l), she was treated with intravenous immunoglobulins (IVI g) weekly with the goal to maintain an IgG level above 10 g/l. This resulted in a significant rise in anti-enteroviral antibodies from 10 IE /ml to 106 IE /ml. One month after treatment with IVI g, while withholding the rituximab, the PCR for enterovirus on faeces was negative and antibodies to the enterovirus in the serum had returned to normal levels. Rituximab can cause a prolonged B-cell deficiency resulting in hypogammaglobulinaemia. We believe that treatment with ritxumab may have played a significant role in the development of this rare central nervous system infection.

Risks of serious complications and death from smallpox vaccination: a systematic review of the United States experience, 1963-1968.

BACKGROUND: The United States (US) has re-instituted smallpox vaccinations to prepare for an intentional release of the smallpox virus into the civilian population. In an outbreak, people of all ages will be vaccinated. To prepare for the impact of large-scale ring and mass vaccinations, we conducted a systematic review of the complication and mortality risks of smallpox vaccination. We summarized these risks for post-vaccinial encephalitis, vaccinia necrosum (progressive vaccinia), eczema vaccinatum, generalized vaccinia, and accidental infection (inadvertant autoinoculation). METHODS: Using a MEDLINE search strategy, we identified 348 articles, of which seven studies met our inclusion criteria (the number of primary vaccinations and re-vaccinations were reported, sufficient data were provided to calculate complication or case-fatality risks, and comparable case definitions were used). For each complication, we estimated of the complication, death, and case-fatality risks. RESULTS: The life-threatening complications of post-vaccinial encephalitis and vaccinia necrosum were at least 3 and 1 per million primary vaccinations, respectively. Twenty-nine percent of vaccinees with post-vaccinial encephalitis died and 15% with vaccinia necrosum died. There were no deaths among vaccinees that developed eczema vaccinatum; however, 2.3% of non-vaccinated contacts with eczema vaccinatum died. Among re-vaccinees, the risk of post-vaccinial encephalitis was reduced 26-fold, the risk of generalized vaccinia was reduced 29-fold, and the risk of eczema vaccinatum was reduced 12-fold. However, the risk reductions of accidental infection and vaccinia necrosum were modest (3.8 and 1.5 fold respectively).

Encephalitis and myocarditis in a child with acute lymphoblastic leukemia: role of coxsackievirus B5?

Enteroviruses are common causes of viral encephalitis in childhood and the most common cause of myocarditis. The prognosis is good with exception of the immunocompromised children who are at higher risk with increased mortality. A case of a 7-year-old boy with acute lymphoblastic leukemia and coxsackievirus B5-associated encephalitis and myocarditis is described. The boy was in complete remission and coxsackievirus B5 infection occurred 22 months after the beginning of chemotherapy. The clinical manifestations were fever, seizures, and altered consciousness. He underwent only supportive treatment. He had an excellent outcome; 2 years later he is still in complete remission with normal electroencephalogram and normal cardiac function.