Urticarial Reaction Caused by Ethanol

Background: We report a case of an urticarial reaction after drinking alcohol beverages. The patient was a 47-year-old man suffering urticarial and anaphylactoid reaction to alcohol for two years. These reactions were observed at every alcohol beverages intake. Case Summary: We performed a prick test with diluted ethanol, alcohol beverages and their metabolites (acetaldehyde, acetic acid). Only acetic acid showed a positive result. Oral challenge test with diluted-ethanol caused pruritus and swelling of his lips. An oral challenge test with 8% diluted Shochu (Japanese distilled alcohol from rice or wheat) caused wheals on his upper back. Discussion: Only acetic acid, a metabolite of alcohol, induced a positive prick test in the patient with alcohol-induced urticaria. This result was not observed in normal volunteers. An oral challenge test with diluted-alcohol or Shochu showed a positive wheal reaction in a dose dependent-manner which suggests that urticaria seen in this patient might be induced by alcohol-intolerance. However possible allergic reaction to acetaldehyde could not be excluded

ΔNp63 Controls a TLR3-Mediated Mechanism That Abundantly Provides Thymic Stromal Lymphopoietin in Atopic Dermatitis

<div><p>In the skin lesions of atopic dermatitis (AD), keratinocytes release large quantities of thymic stromal lymphopoietin (TSLP), causing unfavorable inflammation along with skin damage. Nevertheless, how TSLP influences keratinocytes themselves is still unknown. In this study, we showed that ΔNp63, a p53-homologue, predominantly expressed in keratinocytes regulated the receptor complex of TSLP, which determines susceptibility to self-derived TSLP. Expression of TSLP receptors in skin tissues and keratinocytes was assessed by immunohistochemistry and quantitative RT-PCR, and <i>in vitro</i> studies were also performed to examine the functional relevance of ΔNp63 in the expression of TSLP receptors and the constituting autocrine and/or paracrine pathway of TSLP under the condition of stimuli to innate receptors sensing cell damage. The results showed that normal keratinocytes in the upper epidermis preferentially expressed TSLP receptors and conversely lacked ΔNp63, which has an inhibitory effect on the expression of TSLP receptors. Interestingly, the epidermis of AD lesions was found to abundantly contain keratinocytes with low or undetectable levels of ΔNp63 (ΔNp63^lo/-). Moreover, in the absence of ΔNp63, keratinocytes readily presented TSLP and other cytokines by stimuli through Toll-like receptor 3 (TLR3). Together with the evidence that extrinsic TSLP itself augments TSLP production by keratinocytes without ΔNp63, the results indicate that ΔNp63^lo/- keratinocytes generate TSLP through a putative autocrine and/or paracrine pathway upon TLR3 stimulation within AD lesions, since moieties of damaged cells and pathogens stimulate TLR3.</p></div

TSLP induces signal transduction in ΔNp63-deficient HaCaT keratinocytes.

<p>Immunoblot analysis demonstrating phosphorylation of the p65 subunit of NF-κB at 24 hr after treatment with 10 µg/ml poly I:C and exogenous TSLP (10 ng/ml). The histogram shows the relative phospho- NF-κB expression normalized to NF-κB as determined by densitometric analysis. β-actin was used as a loading control. Data are representative of three independent experiments.</p

TSLP enhances inflammatory responses in ΔNp63-deficient keratinocytes.

<p>(<b>a, b</b>) Quantitative RT-PCR (<b>a</b>) and ELISA (<b>b</b>) demonstrate the level of endogenous TSLP at 24 hr (<b>a</b>) or 72 hr (<b>b</b>) after treatment with exogenous TSLP (1 or 10 ng/ml) under the condition of TLR3 stimulation (5 µg/ml poly I:C) in primary keratinocytes. (<b>c, d</b>) Quantitative RT-PCR (<b>c</b>) and ELISA (<b>d</b>) show the level of endogenous TSLP at 24 hr (<b>c</b>) or 72 hr (<b>d</b>) after stimulation with 10 µg/ml poly I:C and 10 ng/ml TSLP in siControl and sip63 HaCaT keratinocytes. (<b>e</b>) Quantitative RT-PCR confirming whether neutralization of TSLP inhibits the generation of TSLP under the condition of TLR3 stimulation (5 µg/ml poly I:C) in primary keratinocytes. One-way ANOVA followed by Tukey's multiple-comparison test. *<i>P</i><0.05, ***<i>P</i><0.005 and N.S., not significant. Data are representative of at least three independent experiments.</p

Schematic diagram of findings in this study.

<p>AD lesions possess many ΔNp63^lo/- keratinocytes, which might be considered as a major source of TSLP. A potential TLR3 ligand such as damaged-cell-derived dsRNA suppresses the expression of ΔNp63, which eventually further upregulates TSLPR and IL-7Rα and augments the susceptibility to TSLP in ΔNp63^lo/- keratinocytes. Since TSLP itself can help ΔNp63^lo/- keratinocytes to produce endogenous TSLP under the condition of TLR3 stimulation, an autocrine and/or paracrine loop of TSLP are generated in ΔNp63^lo/- keratinocytes, leading to undesired inflammation of AD lesions.</p