Determining positive food challenges are not easy as there is an absence of simple and objective tests. Histamine, an essential mediator for allergic reactions, is involved in the pathogenesis of atopic dermatitis (AD) and food challenges can change histamine levels. The significances of a prick test with histamine (histamine prick test, HPT) relating to the interpretation of food challenges in AD were evaluated. A total of 467 AD patients participated in this study. Skin prick tests, identification of specific IgE and open food challenge were conducted for the identification of food allergy. Elimination diet was performed with HPT. HPTs were conducted before and after food challenges. The wheal sizes by HPT were significantly decreased after an elimination diet. The relative changes of wheal sizes significantly correlated with those of clinical severity scores in AD patients (p<0.001). The wheal sizes in HPT were increased with a positive provocation in open food challenges. In conclusion, HPT may be a simple and objective test to interprete the results of food challenges in patients with AD. The exact mechanisms of the changes in skin reactivity by HPT need further investigation.
Child ; Dermatitis, Atopic/immunology/*metabolism ; Food ; Histamine/*metabolism ; Human ; Skin Tests

Atopic dermatitis (AD) is among the most common skin disorders in humans. Although a variety of regimens are available for the treatment of AD, preventive approaches are limited. Recent studies have demonstrated that certain naturally-occurring herbal medicines are effective in preventing the development of AD via divergent mechanisms, such as inhibiting cytokine and chemokine expression, IgE production, inflammatory cell infiltration, histamine release, and/or enhancement of epidermal permeability barrier function. Yet, they exhibit few adverse effects. Since herbal medicines are widely available, inexpensive and generally safe, they could represent an ideal approach for preventing the development of AD, in both highly developed and developing countries.
Animals ; Chemokines ; metabolism ; Dermatitis, Atopic ; prevention & control ; Disease Models, Animal ; Herbal Medicine ; Humans ; Immunoglobulin E ; metabolism ; Inflammation ; pathology

PURPOSE: It is controversial whether folate status is a risk factor for the development of asthma or other allergic diseases. This study was conducted to investigate whether indirect or direct exposure to folate and impaired folate metabolism, reflected as methylene-tetrahydrofolate reductase (MTHFR) C677T polymorphism, would contribute to the development of asthma and other allergic diseases. METHODS: Electronic databases were searched to identify all studies assessing the association between folate status and asthma or other allergic diseases. Two reviewers independently assessed the eligibility of studies and extracted data. The relative risk (RR) or odds ratio (OR) with 95% confidence intervals (CI) was calculated and pooled. RESULTS: Twenty-six studies (16 cohort, 7 case-control, and 3 cross-sectional studies) were identified. Maternal folic acid supplementation was not associated with the development of asthma, atopic dermatitis (AD), eczema, and sensitization in the offspring, whereas exposure during early pregnancy was related to wheeze occurrence in the offspring (RR=1.06, 95% CI=[1.02-1.09]). The TT genotype of MTHFR C677T polymorphism was at high risk of asthma (OR=1.41, 95% CI=[1.07-1.86]). CONCLUSIONS: It is indicated that maternal folic acid supplementation during early pregnancy may increase the risk of wheeze in early childhood and that the TT genotype of MTHFR C677T polymorphism impairing folic acid metabolism would be at high risk of asthma development. These results might provide additional information for recommendations regarding forced folate consumption or folic acid supplements during pregnancy based on its well-established benefits for the prevention of congenital malformations. However, currently available evidence is of low quality which is needed to further elucidate.
Asthma* ; Case-Control Studies ; Cohort Studies ; Dermatitis, Atopic ; Eczema ; Folic Acid* ; Genotype ; Metabolism ; Odds Ratio ; Oxidoreductases ; Pregnancy ; Risk Factors*

Ceramide metabolism is known to be an essential etiology for various diseases, such as atopic dermatitis and Gaucher disease. Glucosylceramide synthase (GCS) is a key enzyme for the synthesis of glucosylceramide (GlcCer), which is a main ceramide metabolism pathway in mammalian cells. In this article, we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to determine GCS activity using synthetic non-natural sphingolipid C8-ceramide as a substrate. The reaction products, C8-GlcCer for GCS, could be separated on a C18 column by reverse-phase high-performance liquid chromatography (HPLC). Quantification was conducted using the multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z 588.6 → 264.4 for C8-GlcCer at positive ionization mode. The calibration curve was established over the range of 0.625–160 ng/mL, and the correlation coefficient was larger than 0.999. This method was successfully applied to detect GCS in the human hepatocellular carcinoma cell line (HepG2 cells) and mouse peripheral blood mononuclear cells. We also evaluated the inhibition degree of a known GCS inhibitor 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) on GCS enzymatic activity and proved that this method could be successfully applied to GCS inhibitor screening of preventive and therapeutic drugs for ceramide metabolism diseases, such as atopic dermatitis and Gaucher disease.
Animals ; Calibration ; Carcinoma, Hepatocellular ; Cell Line ; Chromatography, Liquid ; Dermatitis, Atopic ; Gaucher Disease ; Humans ; Mass Screening ; Mass Spectrometry ; Metabolism ; Methods ; Mice

OBJECTIVES: Ozone is widely applied to treat allergic skin diseases such as eczema, atopic dermatitis, and contact dermatitis. However, the specific mechanism remains unclear. This study aims to investigate the effects of ozonated oil on treating 2,4-dinitrochlorobenzene (DNCB)-induced allergic contact dermatitis (ACD) and the underling mechanisms. METHODS: Besides the blank control (Ctrl) group, all other mice were treated with DNCB to establish an ACD-like mouse model and were randomized into following groups: a model group, a basal oil group, an ozonated oil group, a FcεRI-overexpressed plasmid (FcεRI-OE) group, and a FcεRI empty plasmid (FcεRI-NC) group. The basal oil group and the ozonated oil group were treated with basal oil and ozonated oil, respectively. The FcεRI-OE group and the FcεRI-NC group were intradermally injected 25 µg FcεRI overexpression plasmid and 25 µg FcεRI empty plasmid when treating with ozonated oil, respectively. We recorded skin lesions daily and used reflectance confocal microscope (RCM) to evaluate thickness and inflammatory changes of skin lesions. Hematoxylin-eosin (HE) staining, real-time PCR, RNA-sequencing (RNA-seq), and immunohistochemistry were performed to detct and analyze the skin lesions. RESULTS: Ozonated oil significantly alleviated DNCB-induced ACD-like dermatitis and reduced the expressions of IFN-γ, IL-17A, IL-1β, TNF-α, and other related inflammatory factors (all P<0.05). RNA-seq analysis revealed that ozonated oil significantly inhibited the activation of the DNCB-induced FcεRI/Syk signaling pathway, confirmed by real-time PCR and immunohistochemistry (all P<0.05). Compared with the ozonated oil group and the FcεRI-NC group, the mRNA expression levels of IFN-γ, IL-17A, IL-1β, IL-6, TNF-α, and other inflammatory genes in the FcεRI-OE group were significantly increased (all P<0.05), and the mRNA and protein expression levels of FcεRI and Syk were significantly elevated in the FcεRI-OE group as well (all P<0.05). CONCLUSIONS Ozonated oil significantly improves ACD-like dermatitis and alleviated DNCB-induced ACD-like dermatitis via inhibiting the FcεRI/Syk signaling pathway.
Animals ; Mice ; Dinitrochlorobenzene/metabolism* ; Skin/metabolism* ; Cytokines/metabolism* ; Interleukin-17/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Dermatitis, Allergic Contact/pathology* ; Dermatitis, Atopic/chemically induced* ; Signal Transduction ; RNA, Messenger/metabolism* ; Mice, Inbred BALB C

PURPOSE: In addition to regulating calcium and phosphorus homeostasis and bone metabolism, vitamin D is known as an immune modulator. Recently, there has been increased worldwide interest in the association between low levels of vitamin D and allergic diseases. The purpose of this study was to assess the relationship between serum vitamin D levels and allergic/vasomotor rhinitis (AR/VR) in children. METHODS: This study included 164 patients. The sample included 59 patients with AR, 42 patients with VR, and 63 controls. Their ages ranged from 0 to 16 years. We examined the levels of 25-hydroxyvitamin D, Immunoglobulin E, specific IgE, and eosinophil cationic protein; peripheral blood eosinophil count; and the results of a skin prick test. RESULTS: Serum 25-hydroxyvitamin D levels were 19.0+/-8.5 ng/mL in the AR group, 25.5+/-10.9 ng/mL in the VR group, and 26.9+/-10.7 ng/mL in the control group. After adjustment for body mass index and season at the time of blood sampling, vitamin D levels in the AR group were lower than those of the VR group (P=0.003) and control group (P<0.001). Vitamin D levels were inversely correlated with Immunoglobulin E levels (r=-0.317, P<0.001). AR patients with food allergy or atopic dermatitis did not have lower levels of 25-hydroxyvitamin D than AR patients without these diseases. CONCLUSION: This study demonstrates a possible relationship between vitamin D levels and allergic rhinitis in Korean children.
Body Mass Index ; Calcium ; Child* ; Dermatitis, Atopic ; Eosinophil Cationic Protein ; Eosinophils ; Food Hypersensitivity ; Homeostasis ; Humans ; Immunoglobulin E ; Immunoglobulins ; Metabolism ; Phosphorus ; Rhinitis ; Rhinitis, Vasomotor* ; Seasons ; Skin ; Vitamin D* ; Vitamins*

PURPOSE: The purpose of this study was to evaluate the efficacy and metabolism of inhaled steroids to prevent recurrent wheezing after bronchiolitis. METHODS: Sixty two patients were randomly divided into study (n=31) and control (n=31) groups. All of them received budesonide 500 microgram and salbutamol 1.25 mg 4 times a day via nebulizer during admission period (5.5+/-2.5 days). After discharge, the study group patients received fluticasone 50 microgram twice a day with metered dose inhaler with mask spacer for 12 weeks, and the control group received none of inhaled steroids. Serum cortisol and dehydroepiandrosterone sulfate (DHEA-S) concentrations were measured at admission and at the end of the inhaled corticosteroid (ICS) therapy. Weight and height of all patients were checked during the follow-up period. RESULTS: Atopic dermatitis of the patient and allergy family history proved statistically significant. Among high risk group patients, the attack rate of recurrent wheezing in the study group was significantly reduced as compared with the control group. Cortisol levels checked at the end of the ICS therapy were not significantly different from the level checked at admission. In the study group, there was no statistically significant difference between dehydroepiandrosterone sulfate (DHEA-S) level at admission and at the end of the ICS therapy. There was no statistically significant difference of height and weight SDS (standard deviation score) between baseline and 12 weeks later. CONCLUSION: This study suggest that inhaled corticosteroid can be used prophylactically for reducing recurrent wheezing after bronchiolitis in high risk group for asthma.
Albuterol ; Asthma ; Bronchiolitis* ; Budesonide ; Dehydroepiandrosterone Sulfate ; Dermatitis, Atopic ; Follow-Up Studies ; Humans ; Hydrocortisone ; Hypersensitivity ; Masks ; Metabolism ; Metered Dose Inhalers ; Nebulizers and Vaporizers ; Respiratory Sounds* ; Steroids ; Fluticasone

OBJECTIVETo investigate the role of chemokine receptor CXCR3 in patients with atopic dermatitis.

METHODSThe expression of CXCR3 mRNA was measured by fluorescent quantitative polymerase chain reaction, and the relationship between CXCR3 mRNA expression and the disease severity (graded according to SCORAD index system) was assessed by correlation analysis.

RESULTSCXCR3 mRNA expression was significantly higher in patients with atopic dermatitis than in healthy control subjects (P7lt;0.01), and showed obvious positive correlation with SCORAD index system.

CONCLUSIONThese data suggest an important role of CXCR3 in the development and progression of atopic dermatitis.

Adolescent ; Case-Control Studies ; Child ; Dermatitis, Atopic ; genetics ; Female ; Gene Expression Regulation ; Humans ; Male ; RNA, Messenger ; genetics ; metabolism ; Receptors, CXCR3 ; genetics

Proteases in the skin are essential to epidermal permeability barrier homeostasis. In addition to their direct proteolytic effects, certain proteases signal to cells by activating protease-activated receptors (PARs), the G-protein-coupled receptors. The expression of functional PAR-2 on human skin and its role in inflammation, pruritus, and skin barrier homeostasis have been demonstrated. Atopic dermatitis (AD) is a multifactorial inflammatory skin disease characterized by genetic barrier defects and allergic inflammation, which is sustained by gene-environmental interactions. Recent studies have revealed aberrant expression and activation of serine proteases and PAR-2 in the lesional skin of AD patients. The imbalance between proteases and protease inhibitors associated with genetic defects in the protease/protease inhibitor encoding genes, increase in skin surface pH, and exposure to proteolytically active allergens contribute to this aberrant protease/PAR-2 signaling in AD. The increased protease activity in AD leads to abnormal desquamation, degradation of lipid-processing enzymes and antimicrobial peptides, and activation of primary cytokines, thereby leading to permeability barrier dysfunction, inflammation, and defects in the antimicrobial barrier. Moreover, up-regulated proteases stimulate PAR-2 in lesional skin of AD and lead to the production of cytokines and chemokines involved in inflammation and immune responses, itching sensation, and sustained epidermal barrier perturbation with easier allergen penetration. In addition, PAR-2 is an important sensor for exogenous danger molecules, such as exogenous proteases from various allergens, and plays an important role in AD pathogenesis. Together, these findings suggest that protease activity or PAR-2 may be a future target for therapeutic intervention for the treatment of AD.
Anti-Infective Agents/pharmacology ; Dermatitis, Atopic/*enzymology ; Endopeptidases/metabolism ; Homeostasis ; Humans ; Hydrogen-Ion Concentration ; Inflammation ; Models, Biological ; Models, Genetic ; Peptide Hydrolases/*metabolism ; Receptor, PAR-2/*metabolism ; Serine Proteases/metabolism ; Signal Transduction ; Skin/enzymology/pathology ; Treatment Outcome

Atopic dermatitis (AD) is an inflammatory skin disorder that is both uncomfortable and distressing to patients, and its prevalence has been steadily increasing. It is obvious that the identification of efficient markers of AD in plasma would offer the possibility of effective diagnosis, prevention, and treatment strategies. In this study, a proteomic approach was used to analyze plasma glycoproteins from both children with AD and healthy child donors. Several protein spots showing significant quantitative changes in the AD patients were identified. Through sequential studies, it was confirmed that CD5L and ApoE were significantly up-regulated or down-regulated, respectively, in the plasma from AD patients compared with that from healthy donors. In addition, we suggest that the up-regulated CD5L in AD patients causes eosinophilia by inhibiting apoptosis or promoting the proliferation of eosinophils either in combination with or without IL-5. The glycoproteomic data in this study provides clues to understanding the mechanism of atopic alterations in plasma and suggests AD-related proteins can be used as candidate markers for AD.
Apolipoproteins E/*blood ; Biological Markers/blood ; Cell Line ; Cell Proliferation ; Child ; Dermatitis, Atopic/*metabolism ; Eosinophilia/metabolism ; Eosinophils/physiology ; Female ; Glycoproteins/*blood ; Humans ; Interleukin-5/metabolism ; Male ; Proteomics ; Scavenger Receptors, Class B/*blood