Varicella Zoster Infection Research Articles

Reduction of Serum Prostate-Specific Antigen Levels following Varicella-Zoster Infection and Valaciclovir Treatment in Prostate Cancer

We present two prostate cancer patients, including one with a castration-resistant cancer whose rising serum prostate-specific antigen (PSA) levels showed a remarkable drop after a reactivated varicella-zoster virus infection treated with valaciclovir. In one patient, we found a temporary decrease in serum PSA lasting for at least 4 mo. In the patient with castration-resistant prostate cancer, serum PSA decreased to <0.01μg/l and has remained undetectable since.

Acute cerebellar ataxia in the Netherlands: A study on the association with vaccinations and varicella zoster infection

Aim Acute cerebellar ataxia (ACA, sudden onset of truncal ataxia and gait disturbances) usually follows a benign illness (25% varicella). It is also described after vaccination, like MMR and varicella zoster virus (VZV). We will establish incidence rates of (varicella related) ACA and assess the attributable risk of vaccination to ACA in the Netherlands. Method Data on ACA in children, following infections, like varicella, and vaccinations, obtained from prospective, active pediatric surveillance and passive surveillance on adverse events following immunizations (AEFI) were compared with hospitalization data for ataxia. Capture–recapture (CRC) method was used to estimate the burden of ACA in the Netherlands. Results 45 children with ACA were included (44 and 1 reported by pediatric and AEFI surveillance respectively, 30 were hospitalized). Chickenpox preceded ACA in 15 cases, one case followed MMR. Of the hospitalization reports, 13 fulfilled the criteria for ACA. Using CRC the estimated number of hospitalized ACA cases was 42. For varicella related ACA, this estimate was 10, resulting in an incidence rate of 0.7:100,000 (95%CI 0.52–0.94, all cases) and 0.17:100,000 (95%CI 0.09–0.31, varicella related cases) for children under 15 years of age. Conclusion The incidence rates were comparable with other studies. We found no association with MMR, but chickenpox was clearly related to ACA. According to age-specific seroprevalence data the incidence rate of ACA was 5:100,000 VZV infections for children up to 5 years, compared to an ACA-reporting rate of 0.15:100,000 doses VZV-vaccine. Therefore, uptake of VZV-vaccine in the immunization programme will diminish the incidence rate of ACA.

Severe autoimmune hepatitis triggered by varicella zoster infection

Autoimmune hepatitis (AIH) is a chronic disease of unknown etiology that is characterized by the presence of circulatory autoantibodies and inflammatory histological changes in the liver. Although the pathogenesis of AIH is not known, it is thought that, in a genetically predisposed individual, environmental factors such as viruses can trigger the autoimmune process. Herpes simplex virus, Epstein-Barr virus, measles virus, and hepatitis viruses are thought to play a role in the etiology of AIH. Proteins belonging to these viruses may be similar to the amino acid chains of different autoantigens in the liver, this causes immune cross reactions and liver tissue damage. We report a case of severe AIH following varicella zoster infection in a 23-year-old man, and speculate that, based on the molecular mimicry hypothesis, the liver damage was caused by an immune cross reaction to the viral proteins. Varicella-zoster-induced AIH has not been reported previously.

Results of a Phase II Open-Label Trial of Bortezomib in Patients with Multiple Myeloma Who Have Undergone High-Dose Melphalan Therapy Followed by Autologous Peripheral Blood Stem Cell Transplantation and Failed to Achieve a Complete Response

Multiple myeloma (MM) is the second most common hematologic malignancy. Presently, the majority of suitable MM patients who undergo high-dose melphalan therapy followed by autologous peripheral blood stem cell transplantation (PBSCT) fail to achieve a complete response (CR). This suggests that treatment options following autologous transplantation are needed. Moreover, there is a need to determine the optimal role of maintenance therapy following PBSCT in MM. Over time, Bortezomib (B) has been shown to be an active agent in the treatment of newly diagnosed, and relapsed or refractory MM. Therefore, the primary objective of this study was to determine the efficacy of B treatment after high-dose melphalan therapy followed by PBSCT in MM. Fifty patients (pts) were enrolled between March 2004 and November 2007, and 47 were evaluable (2 pts ineligible and 1 pt data pending). Pts received B 1.3 mg/m2 IV on Days 1, 4, 8, and 11 of each 21-day cycle. Pts were treated for 4 cycles or until evidence of disease progression or intolerable toxicity. If an improvement in response was noted after Cycle 4, pts could receive up to 4 additional cycles. To reduce the incidence of varicella zoster infection, antiviral prophylaxis (acyclovir 400 mg PO BID) was taken for the duration of the study. The median patient age was 56 years (range, 39–74), 82% were white, and 68% were male. The majority of pts (64%) had ECOG PS 0, 44% were Durie-Salmon Stage IIIA prior to induction therapy. Forty percent had symptomatic IgG-kappa multiple myeloma. Of all pts, 74% had a single transplant, while 24% had tandem transplants (2% [n=1 pt] data pending). Sixty-eight percent of pts had a PR and 18% had a MR following their transplant(s). While on study, pts received a median of 4 cycles (range, 2–8) of therapy with B. Efficacy results for the evaluable population are: CR 4%, unconfirmed (u) CR 4%, PR 21%, uPR 17%, MR 11%, and No Change 36%. Median time-to-treatment failure was 5.8 months (mos) (range, 0.2–19.4). There were 2 on-study deaths (sepsis and PD). Grade 3–4 treatment-related toxicities reported in >1 pt were thrombocytopenia (15%), asthenia (10%), neutropenia or neuropathy (8% each), peripheral neuritis (6%), and nausea (4%). Twenty patients discontinued study treatment due to toxicity (22%), pt request (6%), disease progression, ineligibility, and intercurrent illness/protocol deviation (4% each). 26 pts (52%) completed the study; 4 pts are still on study (8%). Sixteen pts started new treatment; median time from start of study treatment to the start of new treatment was 5.2 mos (range, 1.5–17.6 mos). The study was closed earlier than the planned due to the widespread availability of B, and the inability to find B-naïve patients. Bortezomib given after high-dose melphalan therapy and autologous PBSCT was well-tolerated with manageable adverse events. Updated cytogenetic analysis will be available for presentation.

Alemtuzumab-CHOP for Aggressive T Cell Lymphoma. A Phase II HOVON 69 Trial.

The prognosis of patients with aggressive mature T cell lymphoma is very poor. We wondered whether the addition of the anti-CD52 monoclonal antibody alemtuzumab to 2-weekly CHOP chemotherapy as 1st line treatment would result in acceptable toxicity, improved response, and outcome. In a multicenter phase II design, 20 patients were to receive 8 cycles of CHOP14 (d 1: cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2, 2 mg max, and day 1–5 prednisone 100 mg; repeat at day 15). Alemtuzumab 30 mg subcutaneously was added at day 1, 5 and 10 of each cycle (total of 24 administrations). Valaciclovir, cotrimoxazol and fluconazol were given as prophylaxis for herpes viral, PCP and fungal infections, respectively; G-CSF was given to enhance neutrophil recovery. Blood products were irradiated. Monitoring for CMV (re)activation by PCR or pp65 antigenemia was mandatory. Between Nov 2005 and Oct 2007, 20 patients with newly diagnosed T-NHL were included by 10 different centers (55% male; median age 50, range 20 to 65 years; 19 stage III/IV; 11 IPI high/high-intermediate). T-NHL histologies were: peripheral T cell lymphoma NOS (n=10), angioimmunoblastic lymphoma (n=6), subcutaneous panniculitis-like lymphoma (n=3), enteropathy-associated T cell lymphoma (n=1). Patients received a median of 8 CHOP cycles, 85% received 6 or more. Response to treatment was: 12 CR, 6 PR (ORR 85%) and 2 NR. At a median follow-up of 18 months, 11 patients are still alive, 9 patients have relapsed; the median FFS is 20 months (range 2–25) and median OS is 23 months (5–29). Toxicity was considerable, with CMV reactivation in 7/20 patients; one patient developed CMV disease; hospital admissions because of (mostly neutropenic) fever occurred in 8 patients. However, none of these patients died from these adverse events. One patient died in CR, 5 months after treatment due to sepsis complicating an extensive varicella zoster infection. Three patients (two with peripheral T cell lymphoma, one with angioimmunoblastic lymphoma without initial EBV activity) developed an EBV-related lymphoproliferative disorder. These patients ultimately died of relapse T-NHL.In conclusion, an intensive alemtuzumab-CHOP14 regimen is feasible and effective in aggressive T-NHL as far as response and early outcome are concerned. Toxicity, especially the high percentage of herpes viral reactivation including EBV-related lymphoproliferation requires careful monitoring.

ACYCLOVIR-RESISTANT CHRONIC VERRUCOUS VACCINE STRAIN VARICELLA IN A PATIENT WITH NEUROBLASTOMA

A 21-month-old girl with neuroblastoma developed chronic verrucous Oka strain varicella-zoster infection during chemotherapy. Virus isolated from the patient demonstrated high-level acyclovir resistance, and its thymidine kinase had no in vitro enzymatic activity. After foscarnet therapy, she underwent stem cell transplantation without varicella reactivation. This is only the second reported case of resistant varicella zoster virus caused by Oka strain virus.

Pseudozoster clinical presentation ofDemodexinfestation after prolonged topical steroid use

A 60-year-old man presented with a plaque lesion on the upper right half of the face, which had developed after ophthalmic varicella zoster infection about 2 years previously. The lesion, which was burning and itchy, included a few tiny erythematous pustules, and was slightly squamous and infiltrated. The lesion covered the upper two-thirds of the right trigeminal nerve dermatome, involving half of the face with the forehead, the periorbital area, upper part of the cheek and the nose. The lesion became more marked after continuous topical anaesthetic and corticosteroid use. A standardized skin-surface biopsy was taken, and revealed a large number of Demodex folliculorum (38/cm(2)) in the lesion area. The lesions completely abated after topical 5% permethrin treatment, and no recurrence was observed during follow-up. Demodicosis may have atypical clinical presentations, other than the well-known classic forms. To our knowledge, this is the first unilateral trigeminal, pseudozoster presentation in the literature.

Tularemia with Vesicular Skin Lesions May Be Mistaken for Infection with Herpes Viruses

The original reports of human infection with Francisella tularensis noted vesicular skin rash as a manifestation. We present 2 cases of tularemia initially diagnosed as herpes simplex or varicella zoster infection. Clinicians must recognize the cutaneous manifestations of tularemia and be able to distinguish these from lesions seen with herpes viruses.

Does Shingles Run in the Family

The possibility of genetic susceptibility to reactivated varicella zoster infection has been suggested by studies of the gene for interleukin-10; they

Allogeneic bone marrow transplantation for severe aplastic anaemia--the London experience.

Using the Seattle protocol with minor modifications, 23 patients with severe aplastic anaemia received allogeneic bone marrow transplants from HLA/mixed leucocyte culture matched sibs in three London centres between 1973 and 1977. Ten patients (43.5%) are alive 6 months to 5 years after transplantation, and are well with full haemopoietic reconstitution, two with autologous bone marrow recovery following the graft procedure. A failure of the marrow graft to take, or take followed by rejection occurred in 12 patients (52%). Failure of marrow recovery was associated with a high early mortality from bacterial or fungal infection. The only survivors amongst those who rejected the first graft were four patients in whom a subsequent graft from the same donor was successful, and two in whom autologous recovery occurred. Graft versus host disease (GVHD) occurred in seven patients, and was fatal in one case. The most frequent complication after successful engraftment was varicella-zoster infection which occurred in five patients and was fatal in one patient. The overall results compare favourably with those from other transplant centres, but the high rate of graft rejection and low incidence of GVHD differ from other series. The results should encourage further referral of patients with severe AA for bone marrow transplantation.

Recurrent pancreatitis after renal transplantation in a child

A five-yr-old girl, who was a renal transplant recipient, presented with nausea, vomiting, epigastric discomfort, papules, and vesicles on her body. She was diagnosed with acute pancreatitis and varicella zoster infection because her serum amylase and lipase levels were positive. Fourteen months later, she was readmitted with nausea, vomiting, and epigastric pain similar to the previous symptoms and was diagnosed with acute pancreatitis. This case report indicates that acute pancreatitis can be one of a number of complications following pediatric renal transplantation and can recur because of various causes.

Clarification

Articles| April 01 2008 Clarification Pediatr Rev (2008) 29 (4): 120. https://doi.org/10.1542/pir.29-4-120 Connected Content This is a correction to: Varicella-Zoster Virus Infections Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Clarification. Pediatr Rev April 2008; 29 (4): 120. https://doi.org/10.1542/pir.29-4-120 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search nav search search input Search input auto suggest search filter All PublicationsAll JournalsPediatrics In ReviewPediatricsHospital PediatricsNeoReviewsAAP Grand RoundsAAP NewsAll AAP Sites Search Advanced Search Topics: acyclovir, chickenpox, herpes zoster disease, tablet dosage form In the article on varicella-zoster infections in the January issue (Pediatr Rev. 2008;29:5–11), the oral dose of acyclovir for children is given as 20 mg/kg qid. To clarify, the dose is 20 mg/kg per dose qid. The dose recommended in the article for adolescents is 4,000 mg/day and is based on the treatment for adults who have zoster. The American Academy of Pediatrics Red Book (27th ed. 2006:785) cites a dose of 800 mg qid (3,200 mg/day) for adolescents, and the author of the article in the January issue recommends using that dose, although there should be no significant clinical difference between the two regimens. Acyclovir is available in 800-mg tablets. Patients at serious risk for or who have severe or potentially severe infections should be treated with intravenous acyclovir. View Original Article You do not currently have access to this content.

Atteinte bronchique au cours d’une pneumonie varicelleuse chez un adulte immunocompétent

Pneumonitis caused by varicella infection is a serious and potentially life-threatening complication of the disease when it occurs in adults. The incidence of this complication has increased in the last 10 years. We report the case of a non-immunocompromised patient admitted to hospital because of varicella pneumonia not requiring intensive care. Bronchoscopy revealed vesicular lesions on the bronchial mucosa. The patient made a full recovery with anti-viral therapy. Vesicular lesions can be observed on the bronchial mucosa of adult patients with varicella zoster infection.

Allergic Drug Eruption Secondary to Intravenous Acyclovir

A 62-year-old woman presented at our department 10 days after returning from a trip to Alaska. Over the previous 7 days she had developed headache, elevated temperature and disseminated erythematous vesicles. The only medication she was taking at this time was L-thyroxine 75 mg once daily for treatment of hypothyroidism. Her skin showed widespread vesicles on an erythematous base without palmar and plantar affection. There was no mucous membrane involvement. The patient was otherwise healthy. A diagnosis of disseminated herpes zoster infection was made subsequently, indicating the need for systemic antiviral treatment. A polymerase chain reaction (PCR) was performed and confirmed varicella zoster infection. According to the patient, she had formerly developed eczema to external acyclovir and external betamethasone. Otherwise, her personal and family history was negative for skin diseases. Due to this medical history of a potential acyclovir sensitization a prick-test was performed, whose results were negative. Given the negative prick results, a test dose of 70 mg acyclovir (1 mg/kg bodyweight), equivalent to 10% of the regular dose, was given intravenously. After 8 h, the patient developed a plain macular erythema with slight infiltration of the popliteal fossae and the trunk (Fig. 1). There was no other medication given at that point. The rash was topically treated with corticosteroids (betamethasone), leading to a complete remission of the exanthema within 2 days. The zoster infection also regressed with out any further treatment or any complications. There was no evidence for neurological involvement at any point. For further diagnostic work-up, we presented the patient to our allergy department, where prick-testing and epicutaneous testing for acyclovir (tablets), valacyclovir (tablets) and a topical preparation (acyclovir, propylene glycol, natrium lauryl) were performed. Patch tests showed a pronounced eczematous reaction (++) at 48, 72 and 96 h for each of the 3 substances. Prick-testing remained negative, as did epicutaneous and prick-testing of corticosteroid series (Fig. 2).

Vaginal discharge due to primary varicella

Cervicitis is an important cause of abnormal vaginal discharge. We describe a case of vaginal discharge due to cervicitis caused by primary varicella zoster infection in a patient with chronic immunosuppression. Though a few reports of genital infection due to chicken pox are available, to the best of our knowledge, there are no reports of abnormal vaginal discharge due to cervicitis caused by chicken pox.

Vaccination of Children following Allogeneic Stem Cell Transplantation

Vaccination of Children following Allogeneic Stem Cell Transplantation

Cellulitis with Compartment Syndrome as a Complication of Varicella Zoster Infection

Varicella zoster infection (chickenpox) is a common and usually benign self limiting disease of childhood in non-vaccinated populations. Although varicella usually goes along with mild to moderate illness in immunocompetent patients, serious complications can arise. Varicella is highly infectious, with attack rates in susceptible individuals ranging from 61% to 100%. This case describes a rare but life threatening complication of varicella zoster infection in a child. High morbidity in non-vaccinated populations that led to rare cases of severe complications became a significant health burden all over the world. This aspect must be considered in the discussion about the importance and benefit of a population wide varicella vaccination programme as it was added to the childhood immunization schedule in Germany in 2004. The case described here might have been avoided by vaccination.

High variability in viral load in cerebrospinal fluid from patients with herpes simplex and varicella-zoster infections of the central nervous system

Infections of the central nervous system (CNS) caused by herpes viruses can result in severe diseases, often with a fatal outcome. In this study, the viral load in the cerebrospinal fluid (CSF) of patients with herpes simplex or varicella-zoster infections of the CNS was measured using a quantitative real-time PCR. The results suggest a high variability in viral load, with relatively mild disease associated with a high viral load in CSF and vice versa. Determination of the viral load in CSF does not therefore seem to be useful in assessing the prognosis of disease caused by these viruses.

Bortezomib, Dexamethasone and Concomitant or Sequential Thalidomide (VTD): An Effective Combination for Relapsed/Refractory Multiple Myeloma Failing Thalidomide and Dexamethasone.

Twenty one relapsed/refractory myeloma patients who failed thalidomide and dexamethasone received VTD combination treatment at our institution. Median age was 57 years (range, 43–80) and median number of previous lines of therapy was 3. Ten had prior autologous SCT and one had reduced intensity allogeneic SCT. All patients had active and measurable disease. Treatment plan was as follows: bortezomib iv on 1st, 4th, 8th and 11th days of a 21-day cycle (up to 8 cycles), dexamethasone 40 mg iv before each bortezomib dose and thalidomide 100 mg each evening. Elderly (≥65 year-old, n=6, 4 of whom also had grade 1 peripheral neuropathy (PN)) and two younger patients with grade 1 PN received bortezomib 1.5 mg iv (low dose) and thalidomide 100 mg each evening only during 10 day rest periods after bortezomib treatments (sequential, n=8). All other patients received bortezomib 1.75 mg iv (higher dose) and thalidomide 100 mg each evening (concomitant, n=13). The patients received a median of 6 cycles of the treatment (range, 2–8 cycles). DVT prophylaxis was aspirin 100 mg po qd. All patients who had at least 2 cycles of the treatment were evaluable for response according to EBMT criteria and 16 (76%) were the responders: 4 CR, 9 PR (5 VGPR by IMWG criteria), 3 MR. Five were the progressive ones. Among these, 8 went on to receive autologous and 2 had reduced intensity allogeneic SCT immediately after planned VTD treatment. Median number of cycles to the best response was 6 cycles. Among responders who did not go on to transplant, duration of response lasted from 2 to 15 months. Three patients had pneumonia (14%), three had varicella zoster infection (14%). No case of DVT was recorded. No treatment related deaths occurred. Four patients had grade 3 toxicity (PN, n=2; fatigue, n=2; and pancytopenia, n=1). Thalidomide was discontiuned in two patients after 2 cycles and in one patient after 3 cycles owing to grade 3 toxicities of fatigue and/or PN that were down-graded and reversible after cessation of thalidomide. Bortezomib was temporarily discontinued in one patient owing to grade 3 pancytopenia and re-started at the dose of 1.5 mg iv. The most frequently observed adverse effects were as follows: PN, n=14 (67%); fatigue, n=13 (62%); anemia, n=13 (62%); thrombocytopenia, n=10 (48%); leucopenia, n=9 (43%); constipation, n=6 (28%); peripheral edema, n=5 (24%); insomnia, n=3 (14%). Elderly and the patients with low-grade PN who received low dose bortezomib and sequential thalidomide experienced less PN (no new cases except two patients with grade 1 PN were upgraded to grade 2 and 3) compared to the patients who received higher dose bortezomib and concomitant thalidomide treatment (newly developed PN in 8: grade 1, n=6; grade 2, n=1; grade 3, n=1). Response rates were comparable between two groups (concomitant, 77% versus sequential, 75%). We conclude that VTD combination may induce high quality responses with acceptable toxicity in a significant proportion of relapsed/refractory myeloma patients with progression after thalidomide, dexamethasone and transplantation. This may be explained by synergism and/or additive effect. Low dose bortezomib and sequential thalidomide are well tolerated with less PN by elderly and the patients with low-grade PN. Increased incidences of infections may justify antibacterial and antiviral prophylaxis.

Varicella-zoster virus infection induces the secretion of interleukin-8

Interleukin-8 (IL-8) is an important mediator in neutrophil-mediated acute inflammation but has also a wide range of actions on various cells types. We demonstrated that infection of melanoma cells and fibroblasts with cell-associated varicella-zoster virus (VZV) and infection of a T cell line with cell-free VZV resulted in an induction of IL-8 secretion in vitro. The inhibition of the VZV replication with a drug interfering with its DNA replication had no effect on the IL-8 release. Since the IL-8 promoter contains binding sites for NF-kappaB and AP-1, melanoma cells and the T cell line were treated with inhibitors of NF-kappaB, JNK/SAPK or p38/MAPK prior to infection. In melanoma cells, the JNK/SAPK pathway was shown to be important for the IL-8 secretion during the VZV replication, whereas in the T cell line, not only the JNK/SAPK but also the p38/MAPK pathways were required for IL-8 secretion. The neutralisation of the IL-8 bioactivity had no significant consequence on the VZV replication, suggesting that IL-8 acts neither as a proviral nor as an antiviral cytokine during the VZV replication in vitro.