High-dose Intravenous Acyclovir Research Articles

Varicella-zoster virus (VZV) acute retinal necrosis and recombinant zoster vaccine

Varicella zoster virus (VZV) is responsible for chickenpox. Like all herpes viruses, after primary infection it enters into latency and can be reactivated afterwards. Many forms of symptomatic reactivation of VZV exist including acute retinal necrosis (ARN), an ophthalmic emergency which can lead to blindness. ARN is treated starting with high-dose intravenous acyclovir then with oral valaciclovir for a total duration of up to 3 months. Symptomatic reactivations of VZV are public health issues. The new Swiss 2022 vaccination plan includes the recombinant vaccine Shingrix. It effectively prevents VZV symptomatic reactivations even in elderly and immuno suppressed patients.

High-Dose Intravenous Acyclovir Is Safe and Effective in the Treatment of EBV Reactivation Post Allogeneic Hematopoietic Stem Cell Transplantation

Backgroud:Reactivation of nasopharyngeal carcinoma virus (EBV) post allogeneic hematopoietic stem cell transplantation(allo-HSCT) is very common, but sustained EBV activation maybe induce EBV-associated lymphoproliferative disease (PTLD), transplant-associated hemophagocytic syndrome and thrombocytopenia after transplantation, which is extremely harmful for long-term survival. Currently, the first-line therapeutic strategy for sustained EBV activation is rituximab, but rituximab leads to increased rates of infections and delayed immune reconstitution. Therefore, for the patients with EBV-DNA copies under 1000000/mL, the pros and cons of rituximab are worth weighing.Objective:To evaluate the efficacy and safety of high-dose intravenous acyclovir in the treatment of EBV reactivation post allo-HSCT.Method:Retrospective analysis of clinical data of patients with EBV reactivation post transplantation treated with high-dose intravenous acyclovir (0.5g Q8H) in Sichuan Provincial People's Hospital from January 2019 to May 2021. A total of 49 patients post allo-HSCT from from January 2019 to May 2021 were enrolled in this study. In this population, 38 patients accepted haplo-SCT and 11 patients accepted sibling-SCT. These patients all don't suffer from PTLD and transplant-associated hemophagocytic syndrome, but are resistant to oral antiviral drugs (Acyclovir, valacyclovir, and famciclovir). Simultaneously with intravenous acyclovir, all patients received human immunoglobulin with one dose of 0.4g/kg. The clinical efficacy was evaluated as follows: Overall response(ORR) was defined as the decrease of EBV copies; Complete remission(CR) was defined as the negative turn of EBV copies; Partial response(PR), Stable disease(SD) and Progression of disease(PD) were respectively defined as the decrease, no significant change and increase of EBV copies.Results:The median transplantation time was +86 (+38 to +1587) days. The median number of EBV-DNA copies/ml was 177000 (6620-8200000). After treatment with high-dose intravenous acyclovir, 29 (59.2%) of 49 patients achieved CR, 10 (20.4%) of 49 patients achieved PR, and 10 (20.4%) of 49 patients had no response, including 2 patients with SD and 8 patients with PD. All 49 patients had responded to this regimen with 79.6% ORR. The median time of response and negative turn was 4 days (2 to 11 days) and 9 days (2 to 23 days) respectively. After 100 days for follow-up, 14 of 39 responding patients suffered from EBV activation again, and the EBV copies were higher than that when high-dose acyclovir was initiated. All 24 patients who did not turn negative were recommended with the treatment of rituximab, and 19 of 20 patients who completed treatment turned negative during the three months post acyclovir treatment. The main adverse events (AEs) of this regimen were neutropenia (CTCAE grade 2-3, 8 in 49 patients), thrombocytopenia (CTCAE grade 2-3, 10 in 49 patients), increased serum creatinine (CTCAE grade 1-2, 4 in 49 patients), phlebitis (6 in 49 patients). These AEs were all reversible, which recovered after withdrawal. There was no significant change in the counts of CD4 + T cells and CD8 + T cells before and after intravenous high-dose acyclovir.Conclusion:High-dose intravenous acyclovir is safe and effective in the treatment of EBV reactivation post allo-HSCT, although nearly half of patients still need rituximab treatment. It is a reasonable strategy for patients with oral antiviral resistance. Most patients can avoid the prescription of rituximab in the first six months post allo-HSCT, without interference of immune reconstitution. DisclosuresNo relevant conflicts of interest to declare.

Neonatal Herpes Simplex Virus: The Long Road to Improved Outcomes.

Herpes simplex virus (HSV) acquired during delivery places the neonate at risk for mortality or long-term neurodevelopmental disability. Exposure generally occurs from recurrent genital herpes infection, although primary infections result in the highest risk of neonatal disease. Neonates generally present in the second or third week of life with lesions. Encephalitis with seizures indicates the presence of central nervous system involvement, and other end organs may also be impacted. Clinical suspicion for neonatal HSV infection warrants immediate initiation of appropriate antiviral therapy. In the last 50 years, antiviral therapy has progressed from agents with prohibitive toxicity or cumbersome administration to herpes virus-specific agents that dramatically improve clinical outcomes with manageable toxicity. Multicenter clinical trials have demonstrated the superiority of high-dose intravenous acyclovir for acute therapy, followed by long-term oral suppressive therapy. This work has dramatically reduced morbidity and mortality from neonatal HSV, representing the benchmark for future clinical trials in neonatal pharmacotherapy.

Challenges in the care of young infants with suspected neonatal herpes simplex virus.

As pediatric hospitalists, we often care for neonates and young infants <2 months of age that are admitted to the hospital because of concern for serious infection. Although there are certain clinical signs and symptoms that raise our concern for neonatal herpes simplex virus (HSV; eg, seizures, vesicular rash, critical illness), there is considerable variability in the management of this population when these provocative symptoms are absent. Should we test for HSV in all well-appearing newborns with fever? Or should there be an age cutoff below which all newborns are tested? If we perform testing, should we always start acyclovir? Should we obtain viral studies of mucosal surfaces routinely or only when we have a high level of suspicion? What role should HSV PCR from suspected HSV lesions of the skin, eye or mouth play, as opposed to viral culture? Under what circumstances is it safe to discontinue acyclovir after the CSF HSV PCR is negative? Neonatal HSV is rare, with only ∼1500 cases in the United States each year,1 yet the consequences of delayed treatment are significant.2 There is little controversy concerning the initiation of HSV testing for infants with clinical signs and symptoms suggestive of HSV. Empiric treatment with high-dose intravenous acyclovir is also not controversial because high-dose acyclovir has been the standard treatment for more than a decade and has a low side-effect profile relative to the risk of untreated HSV infection.3,4 However, for infants without clinical signs of HSV, the decision to include empiric testing and treatment is less clear. Although a maternal history of fever and primary HSV infection are associated with neonatal HSV,5 the absence of maternal history of known HSV is not helpful in predicting which infants should be evaluated for HSV infection.6 Given that many …

A Case of Herpes Simplex Virus Type 2 Encephalitis of a Newborn Delivered by a Mother without Prenatal Screening

Neonatal herpes simplex virus (HSV) encephalitis is a rare disease nowadays because of prenatal screening test and management. It shows progressive central nervous system manifestations affecting predominantly temporal and frontal lobes. Early diagnosis of HSV encephalitis is important since even with the early initiation of highdose intravenous acyclovir therapy, it results in serious morbidity among survivors. A 14-day-old neonate with fever and poor oral intake was admitted via emergency department. The next day she had seizures and the brain was damaged with permanent sequelae despite of early administration of intravenous acyclovir on day 2 of admission. We report a serious case of HSV encephalitis diagnosed as type 2 HSV by polymerase chain reaction and culture of a newborn without proper prenatal screening test.

Gastric Ulcers Due to Varicella-Zoster Reactivation

We report on an 18-year-old man with common variable immunodeficiency presenting with abdominal pain and vomiting due to gastric ulcers caused by reactivation of varicella-zoster virus (VZV). Endoscopy revealed multiple ulcers in the gastric antrum. Fever and rash developed the next day. Skin biopsy showed multinucleated cells with intranuclear inclusions highly suggestive of VZV infection, and high-dose intravenous acyclovir was started. VZV was detected on direct immunofluorescence from skin biopsy and polymerase chain reaction from endoscopic biopsy. His course was complicated by encephalopathy, pancreatitis, hepatitis, renal impairment, and hyponatremia. After 3 weeks of antiviral therapy, he gradually improved. Skin lesions cleared within a week. He remained well on follow-up 1 year later. Disseminated zoster presenting as gastric ulcers in the absence of the classic rash is unusual but has been reported in immunosuppressed patients with a history of bone marrow and stem cell transplant. We report this rare presentation in a patient with common variable immunodeficiency and highlight the importance of considering zoster as a cause for severe abdominal pain and of seeking endoscopic diagnosis to facilitate early therapy and reduced mortality risk.

Antiviral selection in the management of acute retinal necrosis

There is no consensus on the optimal antiviral regimen in the management of acute retinal necrosis, a disease caused by herpetic viruses with devastating consequences for the eye. The current gold standard is based on retrospective case series. Because the incidence of disease is low, few well-designed, randomized trials have evaluated treatment dosage and duration. Newer oral antiviral agents are emerging as alternatives to high-dose intravenous acyclovir, avoiding the need for inpatient intravenous treatment. Drug resistance is uncommon but may also be difficult to identify. Antiviral drugs have few side effects, but special attention needs to be paid to patients who have underlying renal disease, are pregnant or are immunocompromised.

Herpetic leg paralysis and abdominal ileus in a patient with idiopathic myelofibrosis

A 78-year-old man was referred to our department because of the sudden onset of motor paralysis of the legs (Fig. 1). The patient reported a sudden fall to the ground the day before admission 4 years prior, he had been diagnosed with idiopathic myelofibrosis (PMF) in the hypercellular phase. He was currently under hydroxiurea based cytoreductive therapy. The past medical history included atrial fibrillation still in therapy with oral anticoagulants and digitalis. Over the previous month, the patient reported the onset of lower right limb pain with weakness. The physical examination was positive for fever and a scattered vesicular eruption of the lower half of the right limb involving the knee and the thigh. Blood tests revealed severe anemia and leucopenia, immediately treated with a prophylactic wide-spectrum antibiotic, granulocyte colony-stimulating factor (G-CSF) and erythrocyte transfusions. Blood cultures were negative. X-ray studies of the chest and of the right femur and pelvis were normal. Magnetic resonance was not performed because the patient was wearing a pacemaker. Brain computed tomography (CT scan) was normal, without any evidence of active encephalytic lesions. Since the vesicular eruption was suggestive for herpes zoster infection, a lumbar puncture was performed showing the presence of lympho-monocytosis, hyperproteinorrachia and hypoglycorrachia. Spinal fluid analysis for the detection of Varicella zoster virus (VZV) by real time polymerase chain reaction was highly positive (49,309 copies/ml). Therapy with high-dose intravenous acyclovir (10 mg/kg 9 3/day) was immediately started. During treatment he developed a major genital oedema and abdominal distention. The abdominal X-ray (Fig. 2) and CT scan showed multiple fluid levels suggestive of ileus. After 1 day, the patient presented urinary retention with bladder distention, dyspnea with a persistent irritative cough prompting a repeat chest X-ray study, which showed ground glass features (Fig. 3). Blood gas analysis revealed: pH: 7.35; PaCO2: 40 mmHg; PaO2: 54 mmHg; HCO3 : 21 mmol/L. This clinical picture can be associated with a widespread VZV infection involving the central nervous system (CNS). Indeed, it is documented that VZV infection at the CNS level can produce transient ischemic attack (TIA) or a stroke in adults [1], suggesting that VZV encephalitic vasculopathy could represent the cause for the right limb paralysis. The bowel and bladder paralysis are probably related to persistent VZV infection in the autonomic ganglia. It is reported that the intestinal pseudo-obstruction can be directly caused by VZV infection in the immunodeficient host (Ogilvie’s syndrome) [2]. After 1 week of treatment with acyclovir, a slow and gradual resolution of all the symptoms was observed. This clinical response to the treatment and the presence of a demonstrated VZV infection correlate with observed complications of a systemic herpes zoster infection. Nonetheless, after two further weeks, a progressive worsening of the clinical conditions, complicated by pulmonary bacterial infection, resulted in the patient’ death. Herpes zoster is a common vesicular eruption due to the reactivation of latent VZV in the dorsal sensory ganglia. Herpes zoster occurs at some point in the lifetime in 10–20% of the population [3]. The most common clinical presentation is represented by a painful cutaneous rash, Paolo Nicoli and Marco Bosa contributed equally to this paper.

Chronic Hand Ulcer in a Woman With HIV Infection

CASE PRESENTATION A 23-year-old female resident of an AIDS hospice in Ho Chi Minh City had a chronic ulcer on her left hand (Fig. 1). The lesion started on the tip of the third finger and over the course of 1 year slowly progressed to include the ventral palm. On examination, the ulcer was well circumscribed with mild surrounding edema and tenderness. There was no bleeding or purulence. Sensation in the unaffected areas was normal. Motor function of the hand was normal. She had similar lesions on her buttocks, which had also appeared around the same time as the finger ulcer. She had been diagnosed as HIV positive 3 years earlier. CD4 testing was not available, and she had never taken antiretroviral medications. The patient had no history of fever, weight loss, cough, or other systemic symptoms except for intermittent diarrhea. She was single and had previously sold seafood in a local market, which involved regularly handling live fish.FIGURE 1: Chronic left-hand ulcer.What is your diagnosis? Differential diagnosis: Cutaneous tuberculosis or atypical mycobacterium, cutaneous fungal infection, herpes simplex virus (HSV), varicella-zoster virus, malignancy, bacterial infection. Diagnosis: Herpes simplex virus infection DISCUSSION Complete blood count and liver function tests were within normal limits. VDRL was negative. The pathology reading on a biopsy performed at local hospital was reported as "nonspecific inflammation" with negative acid-fast bacillus and fungal stains. The patient had taken multiple courses of antibiotic and antifungal medications without improvement. The patient was treated empirically with acyclovir 200 mg 5 times a day, and within 2 weeks, the ulcers had almost completely healed (Fig. 2). After 4 weeks of treatment, the dose of acyclovir was reduced to 200 mg 3 times a day. Three months later, the patient left the hospice and was lost to follow-up.FIGURE 2: Left hand after 2 weeks' treatment with acyclovir.The diagnosis of HSV infection can usually be made by viral culture or direct fluorescent antibody testing. A Tzanck preparation from direct smear of the lesion can help to narrow the differential to herpesviruses. Polymerase chain reaction for HSV DNA is sensitive, but the test has not been FDA cleared for use on genital lesions.1 Serological testing for HSV antibodies is available, but only the newer glycoprotein G-based type-specific assays can differentiate between HSV-1 and HSV-2. Testing for HSV was not available in Vietnam at the time this patient was treated. A presumptive diagnosis of a herpesvirus infection was made based on the rapid response of the ulcer to treatment with acyclovir. More than 80% of adults in Asia have evidence of previous HSV-1 infection by antibody testing.2 The prevalence of HSV-2 infection is lower in Asian countries than in African and western nations.3 There are little data on HSV infection rates in Vietnam, but 1 study of female sex workers in 3 Mekong Delta provinces showed HSV-2 antibody prevalence rates of 30% to 33%.4 Atypical presentations of herpes are not uncommon in immunocompromised patients.4 Ulcers can appear in single or multiple locations and are more likely to become chronic and extensive. Herpes simplex virus lesions in the HIV-infected patient can usually be treated with acyclovir, although acyclovir-resistant HSV has been reported.5,6 Severe or disseminated HSV infections may require treatment with high-dose intravenous acyclovir. In the immunocompromised patient, chronic ulcers may be due to infectious causes (bacterial, mycobacterial, fungal, or viral) or noninfectious causes such as malignancy. Opportunistic infections of the hand due to Cryptococcus and Candida have been reported.6 Ulcers can also become secondarily infected with bacteria, making the underlying primary etiology more difficult to diagnose. Varicella-zoster virus is another herpesvirus that can cause skin disease in immunocompromised hosts. The lesions usually appear as clusters of vesicles localized to one or more dermatomes, but can coalesce into large ulcers or become disseminated. Varicella-zoster virus may also respond to treatment with acyclovir, but generally requires higher doses than are used for treatment of HSV disease. This patient had a history of regular live fish exposure, occasionally associated with bacterial infections such as Erysipelothrix rhusiopathiae or Mycobacterium marinum. In this case, the acid-fast bacillus stain on the biopsy was negative, and the diagnosis of HSV infection was made by the rapid and complete response to an empiric trial of acyclovir. Initial management of ulcerative diseases in HIV patients should include microbiological evaluation of the lesion. Biopsy may be indicated when microbiological evaluation is nondiagnostic. In resource-limited settings where laboratory capabilities are limited, however, empiric treatment of chronic ulcers with antiviral medication active against HSV may be both diagnostic and curative.

Prophylaxis of Cytomegalovirus (CMV) Infection and Disease after Unrelated-Donor Umbilical Cord-Blood Transplantation (UCBT) with Intravenous Ganciclovir or Oral Valganciclovir.

Prophylactic antiviral treatment for prevention of CMV infection and disease could be valuable after UCBT, where the incidence of CMV infection is very high. The purpose of this study was to evaluate the efficacy and safety of a strategy of prophylaxis of CMV infection and disease in patients undergoing UCBT. From May 1997 to May 2005, 52 CMV-seropositive adults with hematologic malignancies (15 in advanced phases) underwent UCBT at our institution. CMV prophylaxis consisted of high-dose intravenous acyclovir from day −5 until engraftment followed until day +100 by intravenous ganciclovir (GAN, 5 mg/kg per day 3 to 7 days per week) in the first 38 patients and by oral valganciclovir (VALGAN, 900 mg per day as a single daily dose) in the last 14 patients. All patients received thiotepa, busulfan, cyclophosphamide and antithymocyte globulin as conditioning, cyclosporine and prednisone as GVHD prophylaxis, and filgrastim from day +7 until engraftment. All 52 patients were considered as evaluable for efficacy and those actually receiving the scheduled CMV prophylaxis with GAN or VALGAN were considered evaluable for toxicity. Median age was 33 yr (range, 18–47), HLA match was 6/6 in 2 (4%), 5/6 in 19 (37%), and 4/6 in 31 cases (60%), and median number of nucleated and CD34+ cells infused was 2.1 x 10E7/kg (range, 0.9–5) and 0.9 x 10E5/kg (range, 0.1–5.7) respectively. The cumulative incidence of CMV infection was 46% at day 100 and 54% at days 180 and 365, and the cumulative incidence of CMV disease was 2% at day 100, 8% at day 180 and 15% at day 365. No clear differences between patients taking GAN or VALGAN were observed in the cumulative incidence of CMV infection (45% and 50% at day 100 and 53% and 57% at days 180 and 365, respectively; P=0.89) and CMV disease (3% and 0% at day 100, 10% and 0% at day 180 and 16% and 14% at day 365, respectively; P=0.75). Twenty-two patients assigned to receive GAN and 8 patients assigned to receive VALGAN experienced 31 and 11 episodes of other severe infections respectively. GAN was withdrawn in 2 patients due to renal toxicity and VALGAN in 2 patients due to neutropenia. Ten patients (7 receiving GAN and 3 receiving VALGAN) experienced at least one episode of recurrent CMV infection. Two of the 8 patients who developed CMV disease, both with GAN, died from CMV. Higher doses of nucleated (P=0.008) and CD3+ (P=0.04) cells infused, presence of acute GVHD below grade II (P=0.01), and use of Thymoglobulin (P=0.008) were associated with a lower risk of CMV infection. The CD3+ cell dose was inversely associated with the risk of CMV disease (P=0.01). These results suggest that CMV prophylaxis with intravenous GAN or oral VALGAN is both safe and effective to reduce and/or delay the occurrence of CMV infection and disease after UCBT. Further, these data show, for the first time, the importance of the CD3+ cell dose infused and of other characteristics in the development of CMV infection and disease after UCBT.

Herpes Simplex Virus Encephalitis During Suppressive Therapy With Acyclovir in a Premature Infant

Cutaneous herpes simplex virus type 2 (HSV-2) infection was recognized at 19 days of age in a 1415-g female infant born at 31 weeks of gestation. Cerebrospinal fluid (CSF) HSV polymerase chain reaction (PCR) was negative, and MRI of the brain was normal. After a 14-day course of high-dose intravenous acyclovir, the infant developed a cutaneous recurrence at 38 days of age. CSF HSV PCR again was negative. She was subsequently begun on oral acyclovir to prevent cutaneous reactivation of HSV. At 3 months of age, the infant developed HSV encephalitis as manifested by fever, seizures, abnormal CSF indices, abnormal brain MRI, and positive CSF HSV PCR. No cutaneous disease was present. It is not known whether the HSV encephalitis in our patient represented reactivation of previously unrecognized central nervous system infection or new onset of central nervous system disease as a result of spread from other tissue or site to the brain. The failure of oral acyclovir to prevent such an occurrence, however, highlights gaps in our understanding of the pathogenesis of neonatal HSV disease and questions the use of acyclovir suppression to prevent neurologic sequelae.

Recurrent herpes simplex virus hepatitis after liver retransplantation despite acyclovir therapy

Herpes virus hepatitis (HSV) represents a form of acute necrotizing hepatitis, which most frequently develops in immunocompromised patients. Therapeutic options include high-dose intravenous acyclovir and liver transplantation. We report the first case of recurrent HSV hepatitis after liver retransplantation, which occurred despite continuous administration of high-dose intravenous antiviral therapy. Because explant histology pointed to initial therapy response, we thought that the reason for recurrence might be due to acyclovir resistance. Most acyclovir resistance is caused by inactivating mutations in the herpes virus thymidine kinase gene. HSV infection was detected by histology and proofed by immunohistochemistry. PCR amplification of the herpes virus thymidine kinase gene was performed on histology specimens to demonstrate the course of viral infection in liver tissue. Genotypic resistance testing of the herpes virus was performed by sequencing the thymidine kinase amplicon. In serial biopsy, HSV-DNA sequences were only detectable when histology revealed herpes hepatitis. Whereas the primary explant exhibited the wild-type thymidine kinase gene, a biopsy of the second graft one month after retransplantation, which showed recurrent herpes virus hepatitis, had a single base insertion within a homopolymeric cytosine stretch. This mutation causes a frame shift leading to a premature stop codon and results in a known acyclovir-resistant herpes strain. In conclusion, we believe that testing for acyclovir-resistant herpes strains should be considered in high-risk patients in whom viral clearance is not achieved serologically to prevent fatal recurrence of disease by using antiviral drugs such as inhibitors of HSV-DNA polymerase or viral helicase primase inhibitors.

Exacerbation of atopic dermatitis in the emergency department

A 38-year-old man was admitted to the Emergency Department suffering from an exacerbation of atopic dermatitis, fever and a burning sensation in the eyes. He was first treated with systemic corticosteroids. A subsequent dermatological and ophthalmological examination established the diagnosis of Kaposi-Juliusberg disease or eczema herpeticum with bilateral herpetic keratitis. Eczema herpeticum is an uncommon herpes simplex virus infection that occurs in patients with atopic dermatitis. Because it is a possible life-threatening condition, this disease must be recognized by all emergency physicians. The association with herpetic keratitis is not frequent but is a major ophthalmological problem. Treatment consists of the administration of high-dose intravenous acyclovir and acyclovir ophthalmic ointment.

Management of neonatal herpes simplex virus infections.

As many as 2,500 infants develop neonatal herpes each year, most of whom are born to women with no history or physical findings suggestive of genital herpes. Infection usually takes one of three forms: 1) disease localized to skin, eyes, and mucous membranes, 2) localized central nervous system infection, or 3) disseminated infection. Exposure to the virus occurs during passage through an infected birth canal, but 5% of infants acquire the infection in utero. The mortality rate is 31% for disseminated infection and 6% for localized central nervous system disease; long-term neurologic sequelae are seen in 17% and 70% of survivors, respectively. Diagnosis is made by isolating of the virus from skin lesions or other involved sites. The polymerase chain reaction for the detection of viral DNA in cerebrospinal fluid or serum is now the diagnostic test of choice for central nervous system or disseminated neonatal herpes because it has higher sensitivity than traditional culture methods. Treatment is with high-dose intravenous acyclovir (60 mg/kg per day in three divided doses), with adjustments made for infants with renal or hepatic insufficiency. Supportive measures and neuroimaging studies are often required. Acyclovir is administered for three weeks, but infants with disease localized to the skin, eyes, and mucous membranes can be treated for two weeks if the cerebrospinal fluid polymerase chain reaction assay is negative for herpes simplex virus DNA. Prevention of infection in infants can be accomplished by cesarean delivery when women have active lesions at the onset of labor. Neonates delivered through an infected birth canal should be screened between 24 and 48 hours of age with viral cultures of eyes, nasopharynx, mouth, and rectum. If positive, they should be treated with acyclovir even if asymptomatic. Suppressive acyclovir therapy beginning at 36 weeks gestation is often prescribed for women with frequent recurrences of genital herpes.

Clinical characteristics of acute HSV-2 retinal necrosis

Purpose To report the clinical features and evaluate the visual outcome of eleven cases of herpes simplex virus-2 (HSV-2) related acute retinal necrosis syndrome (ARN). Design Retrospective interventional case series. Methods Twelve eyes of eleven patients from two European centers, diagnosed with HSV-2 related acute retinal necrosis syndrome were retrospectively reviewed. Herpes simplex virus-2 DNA was detected by polymerase chain reaction in intraocular fluids (aqueous and/or vitreous). Findings at initial examination, clinical evolution with antiviral therapy, complications and final visual acuity were evaluated. Results Herpes simplex virus-2 DNA was detected in all cases. No sample was positive for more than one virus. The mean age of disease in the first eye was 36 years (ranged from 10 to 57 years). Five patients were women and six were men. All patients were immunocompetent. Previous medical history included neonatal herpes (n = 1), previous ARN (n = 3), trauma (n = 1) and systemic corticosteroid administration before occurrence of ARN (n = 3). Preexisting pigmented chorioretinal scars were found in three cases. Patients were treated with high dose intravenous acyclovir or foscarnet ± intravitreal ganciclovir ± interferon. The mean follow-up was 14.5 months (from 5 to 22 months). At the end of the follow-up period, five eyes (41.7%) showed improvement of visual acuity of two or more lines. Final visual acuity was 20/60 or better in four eyes (33.3%), 20/400 or better in four eyes (33.3%) and less than 20/400 in four eyes. Conclusion History of neonatal herpes, triggering events such as neurosurgery, periocular trauma, high-dose corticosteroids, and chorioretinal scars suggest that HSV-2 retinitis reflects reactivation of HSV-2 infection.

Impact of long-term acyclovir on cytomegalovirus infection and survival after allogeneic bone marrow transplantation

Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality after allogeneic bone marrow transplantation (BMT). Our aim was to study the prophylactic effect of high-dose intravenous acyclovir given around the time of BMT followed by oral acyclovir on CMV infection and survival. 310 BMT recipients at risk of developing CMV infection were randomised to one of three regimens in a double-blind and double-dummy design: intravenous acyclovir (500 mg/m2, three times a day) for 1 month followed by oral acyclovir (800 mg four times a day for a further 6 months) (intravenous/oral group); intravenous acyclovir followed by oral placebo (intermediate group); or low-dose oral acyclovir (200 or 400 mg, four times a day) followed by placebo ("controls"). Analysis was by intention-to-treat. Intravenous acyclovir significantly reduced the probability of and delayed the onset of CMV infection. There was no further reduction in infection risk with the addition of long-term oral acyclovir. Time to CMV viraemia was delayed in the intravenous/oral acyclovir group compared with controls. Extending the prophylaxis with oral acyclovir significantly improved survival: 79 of 105 recipients were still alive at 7 months compared with 60 of 102 controls (p=0·012). Although the intravenous/oral acyclovir group did significantly better than controls in terms of survival, the difference between the intravenous/oral acyclovir group and the intermediate group was of borderline statistical significance (p=0·054). Adverse events that were possibly treatment related were similar in all three groups. The most commonly reported events were nausea, vomiting, elevated creatinine, and renal failure. High-dose intravenous followed by oral acyclovir improved survival and was of benefit in prophylaxis against the effects of CMV after BMT. Interpretation of CMV infection was made difficult because an intermediate treatment (intravenous acyclovir followed by oral placebo) was as effective as high-dose intravenous/oral acyclovir.

Disseminated Multifocal Herpes Zoster Leukoencephalitis and Subcortical Hemorrhage in an Immunosuppressed Child

We describe a rare case of multifocal varicella-zoster leukoencephalitis in an immunosuppressed adolescent boy who developed a herpetiform rash on his groin and subsequently presented with a subacute encephalopathy, aphasia, and hemiparesis. Magnetic resonance imaging scan of the brain revealed multifocal bi-hemispheric target-like lesions predominantly in the white matter. A magnetic resonance imaging scan 2 weeks later showed a subcortical hemorrhage in the left insular region. He received long-term high-dose intravenous acyclovir and had significant improvement in his neurologic status.

Association of Herpes Zoster Ophthalmicus With Acquired Immunodeficiency Syndrome and Acute Retinal Necrosis

We conducted a review to investigate the prevalence of human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS), in patients with herpes zoster ophthalmicus, as well as the incidence of acute retinal necrosis after herpes zoster ophthalmicus. All charts of patients seen at our institution between 1987 and 1992 with a primary diagnosis of herpes zoster ophthalmicus were reviewed. Of 112 patients with herpes zoster ophthalmicus, 29 (26%) had HIV or AIDS. All these patients were younger than 50 years at the time of diagnosis. Five of 29 (17%) immunocompromised patients had acute retinal necrosis after herpes zoster ophthalmicus. No acute retinal necrosis was identified in the nonimmunocompromised patients after herpes zoster ophthalmicus. We recommend that all patients younger than 50 years who have herpes zoster ophthalmicus at initial examination be tested for HIV. Additionally, HIV-infected patients should be monitored closely after herpes zoster ophthalmicus for development of acute retinal necrosis. Long-term oral prophylactic as well as initial high-dose intravenous acyclovir may be appropriate in HIV-infected individuals with herpes zoster.

Shingles

SELECTED CASES Case 1 A 56-year-old woman with advanced lymphoma presented with numerous coalescing lesions confined to the distributions of the left maxillary and ophthalmic divisions of the fifth cranial nerve. Ulcerations were also apparent on the left hemipalate. She had completed radiotherapy months before, but she continued to receive aggressive, multidrug chemotherapy, with the last course within days of the onset of the rash. Lesions were culture positive for varicella-zoster virus (VZV). Treatment was begun with high-dose intravenous acyclovir and continued for 7 days until new vesicles stopped forming. Nonetheless, existing lesions evolved into a confluent eschar (Fig 1, left). She then experienced an episode of mental confusion and right-sided paresis presumed to be secondary to virus-associated granulomatous angiitis of the left middle cerebral artery. Then all the teeth in her left maxillary arch loosened and were lost. Left maxillary sinusitis developed, necessitating antibiotics and surgical creation of a

Visual outcome in acute retinal necrosis.

Acute retinal necrosis (ARN) is generally a progressive retinitis, often complicated by retinal detachment and a poor visual outcome. A series of 12 consecutive patients (13 eyes) with ARN is reported. All patients were examined early, with a limited extent of disease (in 77% of the eyes, less than 25% of retina involved). Patients were treated with high-dose intravenous acyclovir (10 mg/kg every 8 hours) and laser photocoagulation. During a follow-up period of 3 to 21 months, only 1 patient developed a rhegmatogenous retinal detachment resulting in visual loss. No patients developed bilateral disease once intravenous antiviral therapy was begun. Final visual acuity was 20/40 or better in 6 eyes (46%), and 20/400 or better in 12 eyes (92%). Two patients were examined within 6 weeks of extracapsular cataract extraction with intraocular lens implantation. In the majority of the cases, clinical findings were limited to several quadrants of the peripheral retina. Eyes with limited disease, if aggressively treated, have a relatively good visual prognosis.