Atopic Dermatitis Is Associated With Cervical High Risk Human Papillomavirus Infection.

OBJECTIVE: High-risk human papillomavirus (hrHPV) infection is more likely to persist and cause cervical cancer in immunosuppressed women. Atopic dermatitis, which is known to affect cell-mediated immunity and skin barrier function, is associated with recalcitrant warts; therefore, we hypothesized that women with atopic dermatitis may be more likely to be positive for hrHPV infection and progress to high-grade cervical dysplasia. MATERIALS AND METHODS: A retrospective case-control study of 1,160 women who were either positive or negative for hrHPV in their index cervical cytology. Patient age, race, history of atopic dermatitis, allergic rhinitis, smoking, body mass index, socioeconomic status, marital status, hormone contraceptive use, and 2-year clinical outcomes (follow-up hrHPV testing and cervical biopsy results) were recorded. All cases with atopic dermatitis (n = 74) were confirmed by a dermatologist. Analyses were restricted to females with documented clinical follow-up, which yielded 577 hrHPV-positive and 583 hrHPV-negative cases for comparison. Associations were examined by t test, χ test, and multivariate logistic regression. RESULTS: Atopic dermatitis was more common in the hrHPV-positive cases (48/577, 8.3%) compared with HPV-negative controls (26/583, 4.5%, p = .007). Multivariate logistic regression analysis revealed an adjusted odds ratio of 3.75 (95% CI = 1.3-10.9, p = .02) after controlling for significant covariates, such as age and marital status. Smoking was not associated with hrHPV infection, persistence, or high-grade cervical dysplasia in these cases. CONCLUSIONS: Atopic dermatitis is associated with cervical hrHPV infection in adult women.

Transcutaneous yellow fever vaccination of subjects with or without atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease with a global prevalence ranging from 3% to 20%. Patients with AD have an increased risk for complications after viral infection (eg, herpes simplex virus), and vaccination of patients with AD with live vaccinia virus is contraindicated because of a heightened risk of eczema vaccinatum, a rare but potentially lethal complication associated with smallpox vaccination. OBJECTIVE: We sought to develop a better understanding of immunity to cutaneous viral infection in patients with AD. METHODS: In a double-blind randomized study we investigated the safety and immunogenicity of live attenuated yellow fever virus (YFV) vaccination of nonatopic subjects and patients with AD after standard subcutaneous inoculation or transcutaneous vaccination administered with a bifurcated needle. Viremia, neutralizing antibody, and antiviral T-cell responses were analyzed for up to 30 days after vaccination. RESULTS: YFV vaccination administered through either route was well tolerated. Subcutaneous vaccination resulted in higher seroconversion rates than transcutaneous vaccination but elicited similar antiviral antibody levels and T-cell responses in both the nonatopic and AD groups. After transcutaneous vaccination, both groups mounted similar neutralizing antibody responses, but patients with AD demonstrated lower antiviral T-cell responses by 30 days after vaccination. Among transcutaneously vaccinated subjects, a significant inverse correlation between baseline IgE levels and the magnitude of antiviral antibody and CD4(+) T-cell responses was observed. CONCLUSIONS: YFV vaccination of patients with AD through the transcutaneous route revealed that high baseline IgE levels provide a potential biomarker for predicting reduced virus-specific immune memory after transcutaneous infection with a live virus.

Do early skin care practices alter the risk of atopic dermatitis? A case-control study.

The rise in atopic dermatitis prevalence observed in industrialized countries is unexplained. We hypothesized that certain skin care practices early in life may increase the risk for developing atopic dermatitis. Our case-control study could not identify any one practice that increased the odds of developing atopic dermatitis, but it revealed that regular lotion use was very common in infants who later develop atopic dermatitis.

Effects of a novel formulation of fluocinonide 0.1% cream on skin barrier function in atopic dermatitis.

OBJECTIVE: To determine the effect a novel formulation of fluocinonide cream on skin barrier function in subjects with atopic dermatitis. DESIGN: The authors performed an open-label, investigator-blinded, side-by-side, controlled trial examining skin barrier function before and after a two-week course of a class I, super-potent topical steroid. SETTING: Outpatient university-based dermatology clinic in Portland, OR. SUBJECTS: Twenty-five subjects aged 12 or older with a diagnosis of moderate, severe, or very severe AD were recruited for this study. INTERVENTION: Fluocinonide 0.1% cream, a novel formulation of a class I super-potent topical steroid was applied to all affected areas, except a control site, once daily for two weeks or until clear. The control target site was treated with the vehicle once daily. MAIN OUTCOME MEASURE(S): The study's primary outcome was change in skin barrier function as measured by basal transepidermal water loss (TEWL) in acute lesional skin from baseline as measured at two weeks. RESULTS: TEWL readings significantly decreased (reflecting improved barrier function) in both the active and control target sites. The active target site decreased 14.35+/-16 mg/cm2 per hour; 95 percent confidence interval, P<0.001. The control target site decreased 8.75+/-11.80 mg/cm2 per hour in 25 subjects; 95 percent confidence interval, P<0.001. Skin electrical capacitance also improved significantly, reflecting improved stratum corneum hydration with therapy. Pruritus, clinical severity, and quality of life scores all showed significant improvement by the end of the study. CONCLUSION: The authors have shown that short-term treatment with a novel formulation of 0.1% fluocinonide led to significantly improved barrier function as measured by basal TEWL in subjects with active moderate to severe AD. These data suggest short-term treatment with AD with a super-potent corticosteroid improves skin barrier function.

Are biologics safe in the treatment of atopic dermatitis? A review with a focus on immediate hypersensitivity reactions.

Traditional systemic agents used for the treatment of atopic dermatitis (AD) are associated with significant potential toxicities and often do not provide adequate therapeutic responses. Biologic agents hold promise for a more targeted and less toxic approach to AD systemic therapy. Patients with AD, however, may theoretically be at higher risk of developing IgE-mediated reactions to protein-based therapies. We performed a review of publications reporting the use of biologics in the treatment of AD. Of the 261 patients with AD identified who were exposed to a biologic therapy, no type-I immediate hypersensitivity reactions were reported. One infusion reaction occurred with infliximab and two patients had "mild respiratory difficulty" with interferon-gamma. Thrombocytopenia may occur at a higher rate than expected in patients treated with efalizumab. Combined, these data support the safety of biologics in the treatment of AD and the further development of new biologics for this population should be encouraged.

Unexpectedly robust assembly of the Axin destruction complex regulates Wnt/Wg signaling in Drosophila as revealed by analysis in vivo.

Secreted proteins in the Wnt family regulate gene expression in target cells by causing the accumulation of the transcriptional activator beta-catenin. In the absence of Wnt, a protein complex assembled around the scaffold protein Axin targets beta-catenin for destruction, thereby preventing it from transducing inappropriate signals. Loss of Axin or its binding partners APC and GSK3 results in aberrant activation of the Wnt signaling response. We have analyzed the effects of mutant forms of Drosophila Axin with large internal deletions when expressed at physiological levels in vivo, either in the presence or absence of wild type Axin. Surprisingly, even deletions that completely remove the binding sites for fly APC, GSK3 or beta-catenin, though they fail to rescue to viability, these mutant forms of Axin cause only mild developmental defects, indicating largely retained Axin function. Furthermore, two lethal Axin deletion constructs, AxinDeltaRGS and AxinDeltabeta cat(DeltaArm), can complement each other and restore viability. Our findings support a model in which the Axin complex is assembled through cooperative tripartite interactions among the binding partners, making the assembly of functional complexes surprisingly robust.

Wingless/Wnt signal transduction requires distinct initiation and amplification steps that both depend on Arrow/LRP.

Members of the Wg/Wnt family provide key intercellular signals during embryonic development and in the maintenance of homeostatic processes, but critical aspects of their signal transduction pathways remain controversial. We have found that canonical Wg signaling in Drosophila involves distinct initiation and amplification steps, both of which require Arrow/LRP. Expressing a chimeric Frizzled2-Arrow protein in flies that lack endogenous Wg or Arrow showed that this construct functions as an activated Wg receptor but is deficient in signal amplification. In contrast, a chimeric Arrow protein containing the dimerization domain of Torso acted as a potent amplifier of Wg signaling but could not initiate Wg signaling on its own. The two chimeric proteins synergized, so that their co-expression largely reconstituted the signaling levels achieved by expressing Wg itself. The amplification function of Arrow/LRP appears to be particularly important for long-range signaling, and may reflect a general mechanism for potentiating signals in the shallow part of a morphogen gradient.