History Of Shingles Research Articles

A Case of Seronegative NMOSD-Related Myelitis Masquerading as VZV-Related Myelitis (P13-5.013)

<h3>Objective:</h3> NA <h3>Background:</h3> Longitudinally extensive transverse myelitis (LETM) is caused by a myriad of etiologies. We present a case of Neuromyelitis Optica Spectrum Disorder (NMOSD)-related myelitis, initially seronegative, masquerading as VZV-related myelitis. <h3>Design/Methods:</h3> A case report. <h3>Results:</h3> A woman in her sixties reported a one-month history of bilateral lower extremity paresthesias and weakness. Days prior, she felt tingling on her back with eruption of a painful rash, and was diagnosed with varicella zoster (VZV). She had transient improvement, before worsening 2 months later with involvement of the arms and signs of myelopathy on exam. MR imaging revealed a long segment T2 hyperintense cord expansion extending from the medulla throughout the thoracic spine with additional hyperintensities in the conus medullaris with patchy enhancement. Work up was significant for lymphocytic-predominant CSF pleocytosis with elevated protein and IgG index. Serum VZV IgG was positive with negative IgM. CSF VZV PCR was negative. Aquaporin-4 antibody was negative. Testing for other causes of myelopathy was unrevealing. She was treated with IV Acyclovir, IV pulse steroids, and subsequently plasma exchange. She improved without further immunomodulation. Three months later, she had another attack and imaging showed new occipital enhancing lesion consistent with demyelination. At this visit, aquaporin-4 antibodies returned positive with a titer of 1:100. She received IV steroids and started rituximab. The patient was diagnosed with LETM from NMOSD. Due to symptom severity, she underwent plasma exchange despite a potential alternative etiology. VZV myelitis and her history of shingles were likely a red herring in the setting of her positive NMO testing. This emphasizes the importance of rechecking antibodies for high clinical suspicion, as the results can drastically influence management and outcome. In the presence of unconfirmed alternative etiologies, neurologists should have low threshold for aggressively treating inflammatory myelitis, using intravenous immunoglobulin or plasma exchange if indicated. <h3>Conclusions:</h3> NA <b>Disclosure:</b> Dr. Alshaer has nothing to disclose. Dr. Cavanagh has nothing to disclose. Dr. Antzoulatos has nothing to disclose.

Stress Is a Risk Factor for Shingles Among Older Adults

Stress is a risk factor for shingles. Empirical evidence of how stress affects getting shingles is lacking for the older population. This paper examines how chronic stress and stressful events are associated with incident shingles in a nationally representative sample of the population over age 50, the Health and Retirement Study. Using data for 2010-2016, we tracked 12,628 persons aged 50 and older with no history of shingles at 2010 until the first shingles occurrence and linked shingles to chronic stress appraisal and stressful events in the prior period. Chronic stress appraisal was measured in eight life domains: health, spousal/children, finance, work, residence, relationship, alcohol/drug, and caregiving. Adverse life events including spousal loss, involuntary job loss, residential move, negative wealth shock, and spousal onset of disability were included in an index of stressful events. 3.3% of sample members developed new shingles cases. Regression results suggest that having a higher burden of stressful events significantly increased the risk for shingles (OR:1.13, 95% CI=1.05, 1.22), whereas ongoing chronic appraisal was not associated with shingles onset (OR:0.99, 95% CI=0.96, 1.03). Our findings highlight the importance of preventive efforts on stress management in reducing risks for zoster.

Survivorship after Autologous Hematopoietic Cell Transplantation for Lymphoma and Multiple Myeloma: Late Effects and Quality of Life.

Although autologous hematopoietic cell transplantation (AHCT) is standard therapy for patients with lymphoma and multiple myeloma (MM), few studies have addressed late effects and quality of life (QoL) in long-term survivors after AHCT. Using long-term follow-up (LTFU) annual questionnaires with self-reported outcomes, we surveyed 665 patients who were at ≥5 years after AHCT for the diagnosis of lymphoma or MM. Three-hundred and eighty-nine patients completed the questionnaire (58% response rate) at a median of 11 years (range, 5-30 years) after AHCT. The median patient age was 63 years (range, 22-88 years) in the 268 patients with lymphoma and 69 years (range, 34-84 years) in the 121 patients with multiple myeloma. The most commonly reported medical conditions (>10% incidence) were sexual dysfunction, history of shingles, cataracts, osteoporosis or osteopenia, joint replacement, and skin cancer. Current medication use was more frequent in the patients with MM for infection prevention/treatment (19% for MM versus 5% lymphoma; P < .001), hypertension (41% versus 26%; P = .004), osteoporosis (23% versus 10%; P < .001), and pain (32% versus 11%, P < .001). Treated hypothyroidism was more common in lymphoma patients. In multivariate analysis combining lymphoma and MM, worse physical functioning was associated with older age, shorter interval since AHCT, comorbidities, relapse, and treatment for depression and/or pain. Worse mental functioning was associated with younger age and treatment for anxiety, depression, or pain. In conclusion, AHCT survivors report generally good QoL but many late effects and symptoms that are potentially amenable to intervention.

Increased polyfunction in CD4 T cells from persons with acute vs. remote shingles

Abstract Little is known about CD4 T cell function in Varicella Zoster Virus (VZV) infection. Here we sampled peripheral blood of individuals (n=31) with acute shingles as a result of reactivation of VZV and persons with a remote history of shingles (n=15). Mitogen and whole VZV were added to peripheral blood mononuclear cells (PBMC) for an in vitro stimulation assay. IFN-γ, IL-2, TNF-α, CD107a, T-bet, EOMES and KLRG1 were examined by flow cytometry. Mitogen- and whole VZV-stimulated total memory CD4 T cells showed significant differences in polyfunction (p&amp;lt;0.0001) while the mitogen-activated groups were equal in acute vs history of shingles. There were significant differences between polyfunctional profiles in VZV-responding total and central memory CD4 T cells in acute vs remote shingles (p&amp;lt;0.002). Acute patients’ VZV-specific total memory cells had higher frequencies of IFN-γ (p&amp;lt;0.001) and IL-2 (p&amp;lt;0.02) producing cells, perhaps due to differences in effector memory subsets. Acute patients' VZV-specific but not mitogen-responding CD4 T cells showed significantly higher levels of T-bet+ than donors with only a history of shingles (p&amp;lt;=0.01). RNASeq analysis of ex vivo total memory CD4 T cells from these individuals showed differential regulation of T cell survival and differentiation pathways, including differential expression of IFN, TNF and mTOR signaling (p&amp;lt;0.05 for genes/pathways). These gene signatures correlated with the frequency of IFN-γ and IL-2 producing cells responding to VZV above with linear regression analysis. In summary, CD4 T cells respond differently in individuals with acute vs. remote shingles, and recognize VZV-specific epitopes upon reactivation via T-bet-mediated pathways. Supported by NIH and VA.

CD4+ T-Cell Lymphopenia in Frequent Platelet Donors Who Have Ceased Platelet Donation for at Least 1 Year

IntroductionWe recently discovered that a number of frequent apheresis platelet donors at our donor center had CD4+ T-lymphocyte counts below 200 cells/µL. The cause appears to be repeated extraction of these cells by the Trima Accel Automated Blood Collection System's leukoreduction system chamber. Plateletpheresis at our donor center has been conducted exclusively with this instrument since 2006. How long CD4+ T-cell lymphopenia persists after stopping plateletpheresis is unknown. Whether there are infectious or other complications that could relate to CD4+ T-cell lymphopenia in former donors is also unknown. We therefore investigated the blood counts (including CD4+ T-lymphocyte counts) and medical histories of former platelet donors who had a history of frequent platelet donation but had stopped donating platelets for at least 12 months.MethodsWe mailed a questionnaire to former frequent apheresis platelet donors who had not donated platelets at our donor center for at least 12 months. Donors who replied to the questionnaire were contacted by phone to schedule a study visit. Frequent platelet donation was defined as 20-24 plateletpheresis sessions in at least one 365-day period starting in 2011. Donors who consented to participate in the study confirmed that they had not donated platelets in the prior 12 months, provided a blood sample for analysis, and completed a health questionnaire that included questions about opportunistic infections and malignancies. Medical records of these donors were also reviewed, where available. Approval for the study was obtained from the Partners HealthCare Institutional Review Board (2017P002880) and all participants provided written informed consent.ResultsOf 52 former frequent platelet donors identified as eligible to receive a questionnaire, one was known to have died of a myocardial infarction and another had requested not to receive communications from the donor center. Therefore, 50 potential study candidates were mailed a questionnaire. Twelve questionnaires were returned as undeliverable. Five potential study candidates returned the questionnaire but either declined to participate in the study or did not respond when contacted to schedule a study visit. Fourteen former frequent platelet donors elected to participate in the study after receiving the first mailing of the questionnaire. Of these 14 study participants, 6 were female and all were Caucasian. The median age was 65. The most common reason for ceasing platelet donation was a positive HLA antibody test (5 participants) followed by “low white blood cells,” “heart trouble,” and “inconvenience” (2 participants each). All former donors had tested negative for HIV while donating platelets. There were 2 participants with CD4+ T-lymphocyte counts below 200 cells/µL (Figure 1); one of these participants had prior CD4+ T-lymphocyte counts available for review. These showed that the CD4+ T-lymphocyte count in this former donor had improved slightly since ceasing donation one year earlier (Figure 2). Three study participants had a CD4+ T-lymphocyte count between 200 and 300 cells/µL. A review of prescription medications and medical problems did not identify an etiology for the low CD4+ T-lymphocyte counts. Responses to the health questionnaire showed that no study participant had ever had a severe infection, an infection with an unusual pathogen (“bug”), or thrush. Two former frequent platelet donors had a history of shingles, both of whom had CD4+ T-lymphocyte counts slightly below the normal range (441-2156 cells/µL) at the time of participation in the study. Five former donors had a history of cancer: Two episodes of squamous cell skin cancer (1 participant), papillary thyroid carcinoma (1 participant), glioblastoma (1 participant), basal cell skin cancer (1 participant), and squamous cell skin cancer as well as melanoma in situ (1 participant).ConclusionIn our small cohort, there is no evidence that CD4+ T-cell lymphopenia predisposes to opportunistic infections or to malignancies classically associated with immune dysregulation. Plateletpheresis-associated CD4+ T-cell lymphopenia has improved slightly in one former frequent platelet donor a year after ceasing plateletpheresis but the count remains below 200 cells/µL. Frequent plateletpheresis involving a leukoreduction system chamber should be considered in the differential diagnosis of idiopathic CD4+ lymphopenia. [Display omitted] DisclosuresGansner:Novimmune SA: Research Funding; UpToDate: Patents & Royalties.

Shingles and pneumonia and risk of cutaneous basal and squamous cell carcinoma

Shingles and pneumonia and risk of cutaneous basal and squamous cell carcinoma

The effectiveness of shingles vaccine among Albertans aged 50 years or older: A retrospective cohort study.

We assessed the effectiveness of shingles vaccine in preventing incident shingles among Alberta residents aged 50 years or older over the period 2009 - 2015, using administrative health data. The cohort comprised of Albertans from the Alberta Health Care Insurance Plan Registry (AHCIP) as of June 30, 2009 and aged 50 years or older. Those who received shingles vaccine were identified from the provincial pharmaceutical information network. The occurrence of incident shingles was identified through both inpatient and outpatients/community care data. Incident shingles was defined as the earliest dated record of ICD 9-CM 053 or ICD-10-CA B02. Starting on November 1, 2009, individuals with no history of shingles or shingles vaccination were followed until Nov 1, 2015 (6 years), or until shingles incidence, death, or AHCIP cancellation (including leaving Alberta). Vaccine effectiveness (VE) was estimated as the inverse of the relative risk of developing incident shingles in each year following vaccination compared to time at risk without vaccination, while adjusting for age, sex, income quintile, and immune compromising conditions (identified from physician claims, inpatient, and cancer registry data). There were 1,094,236 individuals in the cohort, with 85,439 (7.80%) vaccinated individuals. The shingles incidence rate was 9.03 [95% CI: 8.95, 9.11] cases per 1,000 person years (49,243 cases). Adjusted VE in the first year following immunization was 50.02% [95% CI: 44.71%, 54.83%] against incident shingles, decreasing to no effect by the fifth year (VE = 14.00% [95% CI: -20.99%, 38.88%]). Our findings are consistent with observations from other population based studies and provide population level data for policy-makers to review when making decisions related to public funding of shingles vaccine.

Evaluation of human cell mediated immune responses to VZV antigens (VAC7P.993)

Abstract Zostavax© is a safe and effective vaccine against Herpes Zoster. The precise immune correlate of protection and the corresponding VZV antigens responsible for protective immunity are not currently defined. A few key pieces of data suggest that cell mediated immune responses are more important than humoral responses in the immune control over viral re-activation from latent infection. Primarily, the majority of Herpes Zoster outbreaks occur in the aging population in which antibody titers against VZV are maintained but cell mediated immune responses wane. Additionally, individuals who are immunocompromised as a result of disease or drug treatment have difficulty controlling the virus. A group of ten viral proteins of Varicella were chosen for evaluating human cell mediated immune responses. Donor samples were recruited in the following cohorts: i; Herpes Zoster outbreak within the last 5 years, ii; Subjects age 35+ with no history of Shingles or Zostavax© vaccination, and iii subjects pre and post Zostavax© vaccination. Blood samples from these donors were stimulated with the set of VZV antigens and a panel of cytokine responses from the plasma was measured. Here we show a ranking of VZV viral protein immunogenicity from these cohorts, as well as the cytokine profiles for each. These studies will help to define the viral proteins involved in generating protective cell mediated immunity correlated with protection.

Herpes zoster vaccine awareness among people ≥ 50 years of age and its implications on immunization

Herpes zoster (HZ) vaccine was recently approved for adults ≥ 50 years of age and has been shown to reduce the incidence of zoster, postherpetic neuralgia (PHN), and associated healthcare costs. However, currently HZ immunization is sub-optimal. We examined awareness of HZ and of the HZ vaccine. Information was gathered via a one-page survey given to patients ≥ 50 years of age presenting at the dermatology clinic. From the surveyed population of 1000 individuals, the HZ vaccination rate was 11.9 percent. Vaccination coverage was highest for the ≥ 70 age group (18.3%), followed by age groups 60-69 (8.9%) and 50-59 (1.4%). Individuals with female gender, older age (≥ 70 years), higher level of education (college and beyond), retired employment status, memory of chickenpox, knowledge of shingles, and history of shingles and influenza vaccination in the past year all were more likely to have heard of and have received the HZ vaccine (except female gender, education level, and awareness of shingles). Our study suggests lack of awareness to be a significant factor in non-immunization with zoster vaccine. Targeting adults in younger age groups and minorities would be beneficial towards increasing zoster vaccine awareness and thus preventing herpes zoster and its many complications.

Secondary syphilis: a multisystem disease not to be forgotten

A42-year-old homosexual man presented with a 3-month history of painful mouth ulcers and a hyperkeratotic, erythematous scaly rash affecting his palms and soles (Figure 1). He also had a 2-month history of bilateral anterior tibial pain, balanitis and a panuveitis. There was a recent history of a non-specific urethritis and a past history of shingles. In addition to the rash affecting his palms and soles, he had facial seborrhoeic dermatitis, mucosal ulceration with leukoplakia, and a balanitis with phimosis. A tender firm lump was noted over his left anterior shin. He was apyrexial and there was no lymphadenopathy or hepatosplenomegaly. Routine investigations revealed a raised erythrocyte sedimentation rate of 42 mm/h, associated with a polyclonal rise of immunoglobulins with a normal full blood count and C-reactive protein. A plantar skin biopsy showed numerous plasma cells in addition to lymphocytes within the papillary dermis (Figure 2). A Warthin–Starry stain for bacteria was negative. At the same time as the skin biopsy his vision worsened with bilateral mid-peripheral retinitis in addition to panuveitis. The skin biopsy showing numerous plasma cells and the mid-peripheral distribution of the retinitis were highly suggestive of secondary syphilis. The diagnosis of secondary syphilis was confirmed by a positive venereal disease research laboratory (VDRL) titre of 1:256, in association with a positive fluorescent treponemal antibody (FTA) test and treponema pallidum haemagglutination assay. He was also found to be positive for human immunodeficiency virus with a CD4 (t-helper cell) count of 145 × 106/litre (10.5%), and a viral load of 115 305 copies/ml. X-rays of his tibial bones revealed bilateral lytic cortical lesions, in keeping with a syphilitic osteitis. The firm tender lump over his left shin corresponded to a cortical lesion with a marked periosteal reaction (Figure 3). He was given a 10-day course of high-dose intravenous benzylpenicillin, after which his skin and mucosal lesions had almost resolved. The initial ocular inflammatory reaction settled quickly but visual acuity deteriorated 2 days after the commencement of penicillin, thought to result from an intraocular Jarisch–Herxheimer reaction. This complication was treated with a tapering dose of oral prednisolone, starting at a dose of 60 mg/day. His visual acuity subsequently returned to normal leaving a residual typical ‘salt and pepper’ scarring in the fundus (Figure 4).

Prevalence and indicators of HIV and AIDS among adults admitted to medical and surgical wards in Blantyre, Malawi

Despite high seroprevalence there are few recent studies of the effect of human immunodeficiency virus (HIV) on hospitals in sub-Saharan Africa. We examined 1226 consecutive patients admitted to medical and surgical wards in Blantyre, Malawi during two 2-week periods in October 1999 and January 2000: 70% of medical patients were HIV-positive and 45% had acquired immune deficiency syndrome (AIDS); 36% of surgical patients were HIV-positive and 8% had AIDS. Seroprevalence rose to a peak among 30–40 year olds; 91% of medical, 56% of surgical and 80% of all patients in this age group were HIV-positive. Seropositive women were younger than seropositive men (median age 29 vs. 35 years, P < 0.0001). Symptoms strongly indicative of HIV were history of shingles, chronic diarrhoea or fever or cough, history of tuberculosis (TB), weight loss and persistent itchy rash (adjusted odds ratios [AORs] all > 5). Clinical signs strongly indicative of HIV were oral hairy leukoplakia, shingles scar, Kaposi's sarcoma, oral thrush and hair loss (AORs all > 10). Of surgical patients with ‘deep infections’ (breast abscess, pyomyositis, osteomyelitis, septic arthritis and multiple abscesses), 52% were HIV-positive (OR compared with other surgical patients = 2.4). Severe bacterial infections, TB and AIDS caused 68% of deaths. HIV dominates adult medicine, is a major part of adult surgery, is the main cause of death in hospital and affects the economically active age group of the population.

Risk factors for development of systemic lupus erythematosus: Allergies, infections, and family history

We examined risk factors for systemic lupus erythematosus (SLE) in 265 recently diagnosed patients in North Carolina and South Carolina and 355 control subjects identified through driver's license records and frequency matched to patients by age, sex, and state. Analyses were limited to exposures before diagnosis (cases) or reference year (control subjects). SLE patients were more likely than control subjects to report a history of allergy to medications (odds ratio [OR] 3.1, 95% confidence interval [CI], 2.1–4.5), particularly to antibiotics. SLE risk increased with history of shingles (OR 2.5, 95% CI 1.1–5.9) and with frequent (more than once per year) cold sores in the 3 years before diagnosis (OR 2.8, 95% CI 1.4–5.4). There was little association with history of mononucleosis, a marker of late infection with Epstein-Barr virus, implanted medical devices, or hepatitis B vaccination. History of lupus in parents or siblings was associated with an increased risk (OR 3.3, 95% CI 1.2–8.6). Further research is needed to clarify whether medication allergies and specific infectious agents are involved in the etiology of SLE. Published by Elsevier Science Inc.

Human Immunodeficiency Virus: The Initial Physician-Patient Encounter

Human Immunodeficiency Virus: The Initial Physician-Patient Encounter

Shingles, Allergies, Family Medical History, Oral Contraceptives, and Other Potential Risk Factors for Systemic Lupus Erythematosus

The authors undertook a case-control study to explore the many factors that have been postulated to be related to the etiology of systemic lupus erythematosus. A total of 195 cases of systemic lupus diagnosed in the Philadelphia, Pennsylvania, metropolitan area between 1985 and 1987 were compared with 143 controls, friends of the cases matched to them according to age (+/- 5 years) and sex. Through personal interviews and chart reviews, data were collected on demographic factors, personal and familial medical history, reproductive history, medication history, and environmental exposures. Associations were found between systemic lupus erythematosus and having a family history of autoimmune disease (age-, sex-, and race-adjusted odds ratio (OR) = 2.3, 95% confidence interval (CI) 1.2-4.6), a history of shingles (adjusted OR = 6.4, 95% CI 1.4-28.0), a history of hives (adjusted OR = 1.8, 95% CI 1.1-3.0), and a history of medication allergies (adjusted OR = 2.6, 95% CI 1.5-4.5). No association was present between systemic lupus erythematosus and either any use or recent use of oral contraceptives (e.g., OR = 0.6 (95% CI 0.2-1.4) for use in the 3 years prior to diagnosis), family history of multiple other diseases, or a history of numerous other infections or various other types of allergies. Thus, these data indicate that systemic lupus erythematosus is associated with a family history of autoimmune diseases, a history of shingles, and a history of allergies. In contrast, if the development of systemic lupus is affected by use of oral contraceptives, this effect must be extremely modest. These findings may help clarify the possible pathogenesis of systemic lupus erythematosus, and they provide clues as to when the presence of systemic lupus should be suspected.