Eye Complications During Dupilumab Treatment for Severe Atopic Dermatitis.

Dupilumab, the first biologic approved for treatment of atopic dermatitis, has demonstrated significant clinical effect and quality of life-enhancing capacity in clinical trials. In these, dupilumab-associated conjunctivitis where reported in a minority of patients. The present case series describe 10 patients treated with dupilumab where eye complications were very common. We have described patient characteristics, including FLG mutations, atopic history and clinical effect of dupilumab. Nine of 10 developed eye-complications, most commonly conjunctivitis (in 7/10). Other adverse events were herpes simplex virus uveitis and varicella-zoster virus meningitis. Although our case series is small, we conclude that dupilumab is an effective treatment option in severe atopic dermatitis, but that the risk of adverse events from the eyes and recurrence of herpes virus infections should be kept in mind. Close collaboration with an ophthalmologist is recommended, especially among patients with severe, long-lasting atopic dermatitis and/or previous eye disease.

Correlates of adjuvanticity: A review on adjuvants in licensed vaccines.

After decades of slow progress, the last years have seen a rapid acceleration of the development of adjuvanted vaccines which have lately been approved for human use. These adjuvants consist of different components, e.g. aluminium salts, emulsions such as MF59 and AS03, Toll-like receptor (TLR) agonists (CpG ormonophosphoryl lipid A (MPL) adsorbed on aluminium salts as in AS04) or combination of immunopotentiators (QS-21 and MPL in AS01). Despite their distinctive features, most of these adjuvants share some key characteristics. For example, they induce early activation (although at different levels) of innate immunity which then translates into higher antibody and cellular responses to the vaccine antigens. In addition, most of these adjuvants (e.g. MF59, AS03, AS04) clearly induce a wider breadth of adaptive responses able to confer protection against, for example, heterovariants of the influenza viruses (MF59, AS03) or against human papillomavirus strains not contained in the vaccine (AS04). Finally, the use of some of these adjuvants has contributed to significantly enhance the immune response and the efficacy and effectiveness of vaccines in the elderly who experience a waning of the immune responsiveness to infection and vaccination, as shown for MF59- or AS03-adjuvanted influenza vaccines and AS01-adjuvanted herpes zoster vaccine. These results, together with the track record of acceptable safety profiles of the adjuvanted vaccines, pave the way for the development of novel vaccines at the extremes of age and against infections with a high toll of morbidity and mortality. Here, we review the mechanisms associated with the performance of those adjuvanted vaccines in animal models and in humans through recent advances in systems vaccinology and biomarker discovery. We also provide some perspectives on remaining knowledge gaps but also on opportunities that could accelerate the development of new vaccines.

A critical appraisal of 'Shingrix', a novel herpes zoster subunit vaccine (HZ/Su or GSK1437173A) for varicella zoster virus.

HZ/Su, branded as 'Shingrix', is one of the newest vaccines to be submitted for multi-national regulatory approval. It is targeted to prevent shingles, a global concern with aging populations. A live attenuated vaccine for shingles has been available for over a decade, however it is contraindicated in specific subgroups of people, and there are added concerns regarding long-term immunogenicity. HZ/Su is the first subunit vaccine developed to protect against shingles. This paper provides a critical appraisal of current evidence regarding HZ/Su.

Non-clinical safety assessment of single and repeated administration of gE/AS01 zoster vaccine in rabbits.

HZ/su is an investigational recombinant subunit vaccine for the prevention of shingles, a disease resulting from the reactivation of varicella zoster virus. The vaccine is composed of recombinant varicella zoster virus glycoprotein E (gE), and liposome-based Adjuvant System AS01. To evaluate the potential local and systemic effects of this vaccine, three studies were performed in rabbits. In the first two studies, rabbits received a single intramuscular (IM; study 1) or subcutaneous (SC; study 2) dose of gE/AS01, AS01 alone (in study 2 only) or saline, and the local tolerance was evaluated up to 3 days after administration. Under these conditions, only local inflammatory reactions at the injection sites were detected by microscopic evaluation. In the third study, gE/AS01, AS01 alone or saline, were injected SC or IM on four occasions at 2 week intervals. General health status, local tolerance, ophthalmology, haematology and blood chemistry parameters were monitored. Macroscopic and microscopic evaluations were performed after termination of the study. The only treatment-related changes included a transient increase in neutrophils, C-reactive protein and fibrinogen levels and microscopic signs of inflammation at the injection sites, which are expected observations related to the elicited inflammatory reaction. The SC and IM routes of administration produced similar systemic effects. However, microscopic findings at the injection sites differed. One month after the last injection, recovery was complete in all groups. In conclusion, the single and repeated SC and IM administration of the gE/AS01 vaccine were locally and systemically well-tolerated in rabbits and support the clinical development of the vaccine. Copyright © 2016 John Wiley & Sons, Ltd.

Preventative Care in the Patient with Inflammatory Bowel Disease: What Is New?

Patients with inflammatory bowel disease (IBD) do not receive routine preventative care at the same rate as general medical patients. This patient population is at increased risk of vaccine preventable illness such as influenza and pneumococcal pneumonia. This review will discuss health maintenance needs and preventative care issues in patients with IBD.

[Effects of bloodletting pricking, cupping and surrounding acupuncture on inflammation-related indices in peripheral and local blood in patients with acute herpes zoster].

OBJECTIVE: To observe the effects of bloodletting pricking, cupping and surrounding acupuncture on blood inflammation-related indices in patients with acute herpes zoster (HZ), and to explore the mechanism of pain control and treatment. METHODS: A total of 60 patients were randomly divided into an observation group and a control group, 30 cases in each one. In the observation group, the patients were treated with bloodletting pricking at herpes, followed by cupping treatment; also the surrounding acupuncture was performed at injured skin. The treatment was given once a day and once every other day after the first 3 days; totally one-week treatment was given. In the control group, the patients were treated with intravenous drip of acyclovir and oral administration of vitamin B1 and B12, once a day for total one week. The visual analogue scale (VAS) and percentages of neutrophil, lymphocyte in peripheral and local blood were observed before and after treatment in the two groups. RESULTS: After treatment, the score of VAS was significantly reduced in both groups (both P < 0.05); compared with the control group, the score of VAS and the time of pain relieve were significantly improved in the observation group (P < 0.01, P < 0.05). Compared before treatment, the percentages of lymphocyte in peripheral and local blood were reduced after treatment (both P < 0.05) and the percentages of neutrophil in local blood were increased (both P < 0.05). The lymphocyte in local blood was also reduced after treatment in the control group (P < 0.05); compared with peripheral blood in the observation group and local blood in the control group, the percentages of lymphocyte in local blood were reduced (both P < 0.05). CONCLUSION: The efficacy of bloodletting pricking, cupping and surrounding acupuncture on acute herpes zoster is positive, and it can significantly lower the number of lymphocytes in the local blood and increase the number of neutrophil, which is likely to be one of the anti-virus mechanisms.

Herpes simplex virus and varicella zoster virus: recent advances in therapy.

PURPOSE OF REVIEW: The mainstay of antiviral therapy for the alpha-herpesviruses [herpes simplex virus (HSV)-1, HSV-2, and varicella zoster virus (VZV)] over the past 40 years has been the nucleoside analogues such as aciclovir. Although conventional antiviral therapy has reduced mortality in severe disease, novel agents are needed to address the emergence of resistance and toxicity associated with current second-line therapy. Treatment and prophylaxis of VZV and HSV reactivations remains a challenge. RECENT FINDINGS: A number of compounds have recently been evaluated in human clinical trials, amongst them brincidofovir, an intracellularly acting derivative of cidofovir currently undergoing phase III trials. The helicase-primase inhibitors are a new class of antiviral agent and may circumvent resistance to existing agents. Amenamevir and pritelivir are two examples of these agents that have been evaluated clinically along with novel nucleoside analogues such as valomaciclovir and FV-100. Tenofovir, an agent used in HIV and hepatitis B therapy, may also have a role in the prevention of HSV-2 acquisition and reduce viral shedding. SUMMARY: Although several novel antiviral agents have undergone clinical trials in recent years, all are yet to gain licensure. Brincidofovir appears to be the candidate with most promise for adoption into routine practice in the near future.

[Viral vaccines in the national vaccination program--views of the near future]. / Virusrokotteet kansallisessa rokotus- ohjelmassa--lähitulevaisuuden näkymät.

Both conventional virus vaccines and those being introduced in the near future are either live attenuated viruses or nonliving inactivated viruses, mere virus-like particles (VLP) or purified proteins. Live vaccines yield a "more natural" immunity, but in many cases also a nonliving vaccine is sufficient to protect from viral infections. Influenza vaccines are of both types. The commencing HPV vaccination program will be conducted with a VLP vaccine comprising two serotypes. A live chickenpox vaccine will be introduced in the national vaccination program in the next few years. In addition, a shingles vaccine is needed. The live oral rotavirus vaccine works well.

Nutritional factors in herpes zoster, postherpetic neuralgia, and zoster vaccination.

Herpes zoster (HZ) results from a reactivation of latent varicella-zoster virus (VZV). HZ and its most common complication, termed postherpetic neuralgia (PHN), often cause long-term psychological distress and physical disabilities leading to profoundly negative impacts on the quality of patients' lives. The incidence and severity of HZ and PHN increase with advanced age as a consequence of declining cell-mediated immunity. Aging has been linked to progressive senescence of the immune system and also is associated with a greater susceptibility to nutritional deficiencies. Suppressing VZV reactivation depends on intact cell-mediated immunity, which requires adequate nutrients to maintain its efficient function. Contrarily, nutritional deficiencies may lead to dysfunction of the host immune responses. Recently, micronutrient deficiencies have been shown to increase the risk of HZ and PHN and to affect the immune response to vaccinations, whereas nutritional supplements effectively reduce herpetic pain and pain in patients with PHN. As the elderly population grows, the incidence and severity of HZ and PHN are expected to increase and cause a substantial financial burden on the health care system. Thus, enhancing knowledge of the risk factors of HZ and PHN and developing better interventions to treat and prevent HZ and PHN are important to public health. This article provides an overview of the present understanding of the association among nutritional deficiencies, diminished cell-mediated immunity, and the risk of HZ and PHN, and then illustrates the potential of nutritional intervention in the prevention, vaccination, and management of HZ and PHN.

Management of chickenpox with frozen mother's milk.

OBJECTIVES: If a mother has contracted chickenpox, the antibodies in her milk confer immunity against chickenpox to her breastfed babies. This passive immunization may avoid or spare the breastfed babies' symptoms of chickenpox. It is hypothesized that frozen breast milk may shorten chickenpox duration because specific antibodies against varicella zoster have been detected in human milk and they are resistant to digestion and are stable in frozen milk. DESIGN: The clinical outcomes of chickenpox in a 9-year-old boy and his father on frozen breast milk are reported. SETTINGS: The study comprised a varicella-vaccine-refusing family attending a private office of pediatrics. INTERVENTIONS AND RESULTS: The boy presented with a crusted varicella rash. The medical history revealed premature cessation of the typical varicella rash on day 3. It was coincidental with a supply of frozen human milk by his mother. Next, the father (41 years old) of this patient contracted chickenpox: he was on frozen breast milk from day 2, and no new pox emerged thereafter. CONCLUSIONS: The rash spread and numbered 50 to 150 lesions on day 2. Instead, the typical rash was expected to appear in three successive crops of lesions throughout the first week. The disease usually numbers approximately 250-500 lesions in unvaccinated healthy persons. Frozen breast milk may shorten chickenpox duration.

Augmenting immune responses to varicella zoster virus in older adults: a randomized, controlled trial of Tai Chi.

OBJECTIVES: To evaluate the effects of a behavioral intervention, Tai Chi, on resting and vaccine-stimulated levels of cell-mediated immunity (CMI) to varicella zoster virus (VZV) and on health functioning in older adults. DESIGN: A prospective, randomized, controlled trial with allocation to two arms (Tai Chi and health education) for 25 weeks. After 16 weeks of intervention, subjects were vaccinated with VARIVAX, the live attenuated Oka/Merck VZV vaccine licensed to prevent varicella. SETTING: Two urban U.S. communities between 2001 and 2005. PARTICIPANTS: A total of 112 healthy older adults aged 59 to 86. MEASUREMENTS: The primary endpoint was a quantitative measure of VZV-CMI. Secondary outcomes were scores on the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36). RESULTS: The Tai Chi group showed higher levels of VZV-CMI than the health education group (P<.05), with a significant rate of increase (P<.001) that was nearly twice that found in the health education group. Tai Chi alone induced an increase in VZV-CMI that was comparable in magnitude with that induced by varicella vaccine, and the two were additive; Tai Chi, together with vaccine, produced a substantially higher level of VZV-CMI than vaccine alone. The Tai Chi group also showed significant improvements in SF-36 scores for physical functioning, bodily pain, vitality, and mental health (P<.05). CONCLUSION: Tai Chi augments resting levels of VZV-specific CMI and boosts VZV-CMI of the varicella vaccine.

Effects of a behavioral intervention, Tai Chi Chih, on varicella-zoster virus specific immunity and health functioning in older adults.

OBJECTIVE: Both the incidence and severity of herpes zoster (shingles) increase markedly with increasing age in association with a decline in varicella-zoster virus (VZV) specific cell-mediated immunity (CMI). This study examined whether a behavioral intervention, Tai Chi Chih (TCC), affects VZV specific immunity and health functioning in older adults who, on average, show impairments of health status and are at risk for shingles. METHODS: Thirty-six men and women (age > or =60 years) were assigned randomly to a 15-week program of TCC instruction (three 45 minute classes per week; N = 18) or a wait list control condition (N = 18). VZV-specific CMI was measured at baseline and at 1-week postintervention. Health functioning (Medical Outcome scale: SF-36) was assessed at baseline, and at 5, 10, and 15 weeks during the intervention, and at 1-week postintervention. RESULTS: In the intent-to-treat sample, VZV-specific CMI increased 50% from baseline to 1-week postintervention in the TCC group (p < 0.05) but was unchanged in the wait list control group. In those who completed the study, 1-week postintervention SF-36 scale scores for role-physical (p < 0.05) and physical functioning (p < 0.05) were higher in the TCC group (N = 14) as compared with controls (N = 17). Older adults who had impairments of physical status at baseline showed the greatest increases of SF-36 role-physical (p < 0.01) and physical functioning (p < 0.001) during the TCC intervention. CONCLUSIONS: Administration of TCC for 15 weeks led to an increase in VZV-specific CMI. Gains in health functioning were found in participants who received TCC and were most marked in those older adults who had the greatest impairments of health status.

Effect of hypnotic suggestion on the delayed-type hypersensitivity response.

OBJECTIVE: To determine whether individuals selected for good general health, high hypnotizability, and the ability to alter skin temperature under hypnotic suggestion can influence the delayed-type hypersensitivity (DTH) response to varicella-zoster (VZ) antigen under hypnotic suggestion. DESIGN: A blinded clinical trial using a repeated measures design with subjects serving as their own controls. Subjects were randomly assigned to undergo a predetermined sequence of four different experimental conditions, occurring at weekly intervals, with each condition including VZ skin testing: (1) hypnosis with suggestions to enhance the DTH response to VZ antigen; (2) hypnosis with suggestions to suppress the DTH response; (3) hypnosis with suggestions for relaxation only; and (4) skin testing without hypnosis. SETTING: A National Institutes of Health-supported clinical research center in a teaching hospital. SUBJECTS: A stratified sample of 24 ambulatory, healthy, highly hypnotizable, volunteer college students selected for their above-average ability to alter skin temperature after hypnotic suggestions and their positive baseline responses to VZ antigen. There were 11 males and 13 females with a mean +/- SD age of 22 +/- 6 years. The mean +/- SD hypnotizability score (Harvard Group Scale of Hypnotic Susceptibility) was 11 +/- 1. INTERVENTIONS: Intradermal skin testing with VZ antigen (Mantoux method) and hypnotic suggestion. MAIN OUTCOME MEASURES: Areas of induration of the DTH response measured at 24 and 48 hours after injection of antigen. RESULTS: The area of the DTH response was not affected by the experimental interventions. The area of erythema was likewise unaffected. CONCLUSIONS: Our subjects were unable to alter their DTH responses using hypnotic suggestion.