Pseudo-allergic reactions (PARs) widely occur upon application of drugs or functional foods. Anti-pseudo-allergic ingredients from natural products have attracted much attention. This study aimed to investigate anti-pseudo-allergic compounds in licorice. The anti-pseudo-allergic effect of licorice extract was evaluated in rat basophilic leukemia 2H3 (RBL-2H3) cells. Anti-pseudo-allergic compounds were screened by using RBL-2H3 cell extraction and the effects of target components were verified further in RBL-2H3 cells, mouse peritoneal mast cells (MPMCs) and mice. Molecular docking and human MRGPRX2-expressing HEK293T cells (MRGPRX2-HEK293T cells) extraction were performed to determine the potential ligands of MAS-related G protein-coupled receptor-X2 (MRGPRX2), a pivotal target for PARs. Glycyrrhizic acid (GA) and licorice chalcone A (LA) were screened and shown to inhibit Compound48/80-induced degranulation and calcium influx in RBL-2H3 cells. GA and LA also inhibited degranulation in MPMCs and increase of histamine and TNF-α in mice. LA could bind to MRGPRX2, as determined by molecular docking and MRGPRX2-HEK293T cell extraction. Our study provides a strong rationale for using GA and LA as novel treatment options for PARs. LA is a potential ligand of MRGPRX2.
Animals ; Anti-Allergic Agents/therapeutic use* ; Calcium/metabolism* ; Cell Degranulation ; Glycyrrhiza ; HEK293 Cells ; Humans ; Hypersensitivity/drug therapy* ; Mast Cells/metabolism* ; Mice ; Mice, Inbred C57BL ; Molecular Docking Simulation ; Nerve Tissue Proteins/metabolism* ; Rats ; Receptors, G-Protein-Coupled/metabolism* ; Receptors, Neuropeptide/therapeutic use*

INTRODUCTION: Norwegian or crusted scabies is a rare and highly contagious form of skin parasitosis caused by Sarcoptes scabiei var. hominis. Individuals maffffinly affected are considered to be immunocompromised such as those on prolonged glucocorticosteroid therapy, with AIDS or organ transplant patients. This disease presents as a hyperkeratotic dermatosis with an acral distribution. CASE REPORT: This is a case of a 2-month-old healthy Filipino male, who was previously managed as a case of miliaria rubra and treated with clobetasol 0.05% – ketoconazole 2% cream for 1 week. The papules and plaques became widespread. Consult with a pediatrician revealed widespread scabies and for which patient was prescribed topical permethrin with no improvement. On examination, patient presented with multiple erythematous papules and plaques with crusts on the face, trunk, extremities, palms and soles. Thickened yellowish plaques were observed on the palms and soles. Both parents also presented with widespread papules most prominent on the flexural areas accompanied by nocturnal pruritus. On dermoscopy, numerous mites and burrows were seen in a “jet with contrail pattern.” Prominent yellowish scales were also noted. Patient was admitted due to fever and superimposed bacterial infection and was given IV oxacillin, paracetamol, 8% precipitated sulfur in a hypoallergenic lotion applied twice daily and sodium fusidate ointment. On the 4th hospital day, the patient was afebrile and the lesions were noted to decrease in both erythema and crusting. Follow-up dermoscopy revealed absence scales, burrows and mites. CONCLUSION: Prolonged, unsupervised use of topical corticosteroids in our case most likely induced an immunocompromised state thus predisposing the patient to develop Norwegian scabies. In countries were cases of Norwegian scabies have been unresponsive to permethrin and when ivermectin is not available, the use of precipitated sulfur may still be the best therapeutic and safest option for infants.
Infant ; Scabies ; Mometasone Furoate ; Anti-Allergic Agents ; Adrenal Cortex Hormones

PURPOSE: We report a case of toxic keratoconjunctivitis resulting from the self-application of human breast milk as a traditional folk remedy for allergic conjunctivitis. CASE SUMMARY: An 82-year-old woman presented with pain and conjunctival hyperemia in the right eye that had been worsening for three days. Two months previously, she was treated with antiallergic eye drops for allergic conjunctivitis at another eye clinic. However, the symptoms did not improve. She applied her daughter-in-law's breast milk into her right eye as a folk remedy for three days. The pain and conjunctival hyperemia worsened. At the initial visit, her corrected visual acuity was 0.3 in the right eye. Slit lamp examination demonstrated conjunctival hyperemia, punctate epithelial erosion at the central cornea, corneal keratic precipitates and white-colored deposits in the peripheral cornea combined with irregularly shaped small nodules. There was no anterior chamber inflammation. There was no medical history of rheumatoid arthritis or tuberculosis. Blood tests for serum and other infectious and inflammatory levels for infection and inflammatory markers were performed followed by application of topical steroids and antibiotics with artificial tears. After 3 weeks of treatment, conjunctival hyperemia and corneal deposits had almost resolved and best-corrected visual acuity improved to 1.0. CONCLUSIONS: The self-application of human breast milk may cause toxic keratoconjunctivitis. Therefore, efforts should be made, actively, to inform and educate the elderly in rural areas not to use human breast milk as a folk remedy.
Aged ; Aged, 80 and over ; Anterior Chamber ; Anti-Bacterial Agents ; Arthritis, Rheumatoid ; Breast ; Conjunctivitis, Allergic ; Cornea ; Female ; Hematologic Tests ; Humans ; Hyperemia ; Inflammation ; Keratoconjunctivitis ; Lubricant Eye Drops ; Medicine, Traditional ; Milk, Human ; Ophthalmic Solutions ; Slit Lamp ; Steroids ; Tuberculosis ; Visual Acuity

BACKGROUND: Recent studies have reported that glucosamine (GlcN) showed therapeutic effects in allergic diseases such as asthma and rhinitis, and its mechanisms include the suppression of T helper type 2 immune responses and the nuclear factor-κB pathway. OBJECTIVE: We aimed to investigate the effect of GlcN on atopic dermatitis (AD) in an animal model. METHODS: Twenty-five BALB/c mice were divided into five groups (groups A~E). Group A was the phosphate-buffered saline (PBS)-treated group without AD induction. Group B was the PBS control group with AD induction. Groups C to E were the AD induction groups, which were treated with three different doses of GlcN (10 mg, 20 mg, and 40 mg, respectively). Histopathological examination was performed after GlcN administration. Interleukin (IL)-4, IL-13, and IL-17 cytokine levels were measured by enzyme-linked immunosorbent assay using skin biopsy specimens. Serum total immunoglobulin E (IgE) concentrations were measured before and after administration with GlcN or PBS. RESULTS: Clinical dermatitis scores decreased with increasing GlcN dose (p<0.001). Concentrations of tissue IL-13 and IL-17 decreased after GlcN administration (each group: p=0.002 and p<0.001, respectively), but the concentrations of tissue IL-4 did not show differences across groups. Serum IgE levels tended to be lower after GlcN administration (p=0.004). Histopathological scores were not significantly different among groups B~E (p=0.394). CONCLUSION: GlcN improved AD symptoms and decreased tissue IL-13, IL-17, and serum total IgE levels in an animal model.
Allergy and Immunology ; Animals ; Anti-Allergic Agents ; Asthma ; Biopsy ; Dermatitis ; Dermatitis, Atopic ; Enzyme-Linked Immunosorbent Assay ; Glucosamine ; Immunoglobulin E ; Immunoglobulins ; Interleukin-13 ; Interleukin-17 ; Interleukin-4 ; Interleukins ; Mice ; Models, Animal ; Rhinitis ; Skin ; Therapeutic Uses

PURPOSE: Vitamin D is a potent immunomodulator. However, its role in the pathogenesis of allergic rhinitis is unclear. METHODS: The aim of this study was to evaluate the antiallergic effect of intranasally applied vitamin D in an allergic rhinitis mouse model. BALB/c mice were intraperitoneally sensitized with ovalbumin (OVA) and alum before they were intranasally challenged with OVA. Then, they were intranasally administered 1, 25-dihydroxyvitamin D3 (0.02 μg) or solvent. Allergic symptom scores, eosinophil infiltration, cytokine mRNA levels (interleukin [IL]-4, IL-5, IL-10, IL-13 and interferon-γ) in the nasal tissue, and serum total immunoglobulin E (IgE) and OVA-specific IgE, IgG1, and IgG2a were analyzed and compared with negative and positive control groups. Cervical lymph nodes (LNs) were harvested for flow cytometry analysis and cell proliferation assay. RESULTS: In the treatment group, allergic symptom scores, eosinophil infiltration, and mRNA levels of IL-4 and IL-13 were significantly lower in the nasal tissue than in the positive control group. The IL-5 mRNA level, serum total IgE, and OVA-specific IgE and IgG1 levels decreased in the treatment group; however, the difference was not significant. In the cervical LNs, CD86 expression had been down-regulated in CD11c+major histocompatibility complex II-high (MHCIIhigh) in the treatment group. Additionally, IL-4 secretion in the lymphocyte culture from cervical LNs significantly decreased. CONCLUSIONS: The results confirm the antiallergic effect of intranasal 1,25-dihydroxyvitamin D3. It decreases CD 86 expression among CD11c+MHCIIhigh cells and T-helper type 2-mediated inflammation in the cervical LNs. Therefore, topically applied 1,25-dihydroxyvitamin D3 can be a future therapeutic agent for allergic rhinitis.
Administration, Intranasal ; Animals ; Anti-Allergic Agents ; Calcitriol ; Cell Proliferation ; Dendritic Cells ; Eosinophils ; Flow Cytometry ; Immunoglobulin E ; Immunoglobulin G ; Immunoglobulins ; Inflammation ; Interleukin-10 ; Interleukin-13 ; Interleukin-4 ; Interleukin-5 ; Lymph Nodes ; Lymphocytes ; Major Histocompatibility Complex ; Mice ; Models, Animal ; Ovalbumin ; Ovum ; Rhinitis, Allergic ; RNA, Messenger ; Vitamin D

PURPOSE: Our aim was to explore whether antibiotic exposure in children and adolescents is associated with the later development of allergic diseases, using nationwide population-based claims data. METHODS: We collected information from the National Health Insurance Service (2006–2015) database. A total of 5,626,328 children and adolescents were eligible for the study. We explored whether exposure to antibiotics over the prior 7 years affects the later development of allergic diseases. We ran 3 analytical models after adjusting for confounding factors including age, sex, the number of visits to healthcare providers, income, and the place of residence (urban/rural). RESULTS: Allergic diseases were most common in male children and those aged < 10 years (atopic dermatitis, asthma and allergic rhinitis; all P < 0.01). Also, urban residents with higher incomes were more likely to develop allergic diseases (all P < 0.01). The annual number of days on which antibiotics were prescribed differed significantly between subjects with each allergic disease studied and a comparison group (all P < 0.01). Multiple logistic regression showed that as the duration of antibiotic exposure increased, the incidences of atopic dermatitis, asthma, and allergic rhinitis trended upward, even after adjusting for confounding factors (P for trend < 0.01). CONCLUSIONS: Antibiotic use early in life is associated with an increased risk of allergic disease, especially in young children; the risk increases as the duration of antibiotic therapy rises. Moreover, urban residence was more strongly associated with a longer duration of antibiotic use than was rural residence.
Adolescent* ; Anti-Bacterial Agents* ; Asthma* ; Child* ; Dermatitis ; Dermatitis, Atopic ; Health Personnel ; Humans ; Incidence ; Logistic Models ; Male ; National Health Programs ; Rhinitis, Allergic

Corticosteroids are potent anti-inflammatory and anti-allergic agents used in the treatment of various inflammatory diseases, including allergic disease. They are frequently considered the therapy-of-choice for many skin diseases. However, allergic reactions caused by corticosteroids have been reported. Among these, delayed reactions to topical steroids are more common, whereas immediate reactions to systemic steroids are rare. Herein, we report the case of a 32-year-old woman with triamcinolone-induced immediate hypersensitivity reaction, in which the patient had a positive prick test result with triamcinolone. She has had atopic dermatitis (AD) for three years. She had used systemic steroid, cyclosporine, and antihistamine with topical steroids for AD. In clinic, approximately 10 minutes after intralesional injection of triamcinolone, she complained of erythematous patches with slight elevation and itching on the face, trunk, and both hands. After intravenous injection of dexamethasone, her symptoms got worse. After treatment with epinephrine, all symptoms resolved within two hours. We performed an open test and skin prick test. She had a positive result only from the prick test with triamcinolone; all other steroids showed negative results from the open tests. Dermatologists should be aware of the possibility of anaphylaxis or other allergic hypersensitivity in response to corticosteroids.
Adrenal Cortex Hormones ; Adult ; Anaphylaxis ; Anti-Allergic Agents ; Cyclosporine ; Dermatitis, Atopic* ; Dexamethasone ; Epinephrine ; Female ; Hand ; Humans ; Hypersensitivity ; Hypersensitivity, Immediate* ; Injections, Intralesional ; Injections, Intravenous ; Pruritus ; Skin ; Skin Diseases ; Steroids ; Triamcinolone*

PURPOSE: It remains unknown whether local inhibition of Nuclear factor-kappa B (NF-κB) could have therapeutic value in the treatment of allergic rhinitis (AR). This study aimed to evaluate the effect of selective NF-κB inhibition using NF-κB decoy oligodeoxynucleotides (ODNs) for the local treatment of AR in ovalbumin (OVA)-sensitized wild-type mice. METHODS: BALB/c mice were sensitized with OVA and alum, and then challenged intranasally with OVA. NF-κB decoy ODNs were given intranasally to the treatment group, and NF-κB scrambled ODNs were given to the sham treatment group. Allergic symptom scores, eosinophil infiltration, cytokine levels in the nasal mucosa, nasal lavage fluid, and spleen cell culture, serum total and OVA-specific immunoglobulins, as well as intercellular adhesion molecure-1 (ICAM-1) in the nasal mucosa, were analyzed. RESULTS: NF-κB decoy ODNs significantly reduced allergic symptoms and eosinophil infiltration in the nasal mucosa. They also suppressed serum levels of total IgE, OVA-specific IgE, and IgG1. IL-5 and TNF-α levels and the expression of ICAM-1 were decreased in the nasal mucosa of the treatment group compared to the positive control and sham treatment groups. In addition, IL-6 levels were significantly decreased in the nasal lavage fluid of the treatment group. Furthermore, NF-κB decoy ODNs significantly reduced expression of the systemic Th2 cytokines, IL-4 and IL-5 in spleen cell culture. CONCLUSIONS: This study demonstrates for the first time that local NF-κB inhibition using NF-κB decoy ODNs suppressed the allergic response in a murine AR model. This shows the therapeutic potential of local NF-κB inhibition in the control of AR.
Animals ; Anti-Allergic Agents ; Cell Culture Techniques ; Cytokines ; Eosinophils ; Immunoglobulin E ; Immunoglobulin G ; Immunoglobulins ; Intercellular Adhesion Molecule-1 ; Interleukin-4 ; Interleukin-5 ; Interleukin-6 ; Mice ; Nasal Lavage Fluid ; Nasal Mucosa ; NF-kappa B ; Oligodeoxyribonucleotides* ; Ovalbumin ; Ovum ; Placebos ; Rhinitis, Allergic* ; Spleen

Recent studies reported increased risks for the development of allergic diseases in children after prenatal exposure to drugs. The mechanisms by which drug exposure may actually cause allergic diseases are not known. It has been suggested that these drugs promote transplacental allergen transfer to the fetus, resulting in the preservation of allergens. If transferred to the fetus, these allergens could induce a Th2-dominant immune response and allergic sensitization of the fetus. The development of the fetal immune system is influenced by the allergic state of the mother. Maternal IgE can cross fetal membranes, and a Th2-dominant phenotype in the mother can promote an allergy-prone phenotype in the fetus. The fetal immune system starts early in development but mainly matures in later trimesters. Maternal use of antibiotics during pregnancy may prove to be a risk factor for persistent wheezing and allergy development in early infancy. Paracetamol exposure during pregnancy was associated with allergic rhinitis, its use until 6 months of age was associated with allergic sensitization and a history of asthma in girls. Exposure to proton pump inhibitors (PPIs) and Histamine 2-antagonists (H2As) has been associated with an increased risk for the development of atopic dermatitis, asthma, allergic rhinitis, and especially with the development of multiple allergic diseases. Our reviews showed it is necessary to prescribe such drugs under the consultation of an expert physician and to try and reduce exposure as much as possible to prevent offspring allergies in the case of mothers with a history of allergic diseases.
Acetaminophen ; Allergens ; Anti-Bacterial Agents ; Asthma ; Child ; Dermatitis, Atopic ; Extraembryonic Membranes ; Female ; Fetus ; Histamine ; Humans ; Hypersensitivity ; Immune System ; Immunoglobulin E ; Mothers ; Phenotype ; Pregnancy ; Proton Pump Inhibitors ; Respiratory Sounds ; Rhinitis, Allergic ; Risk Factors

PURPOSE: The nature of allergic rhinitis (AR) in preschool aged children remains incompletely characterized. This study aimed to investigate the prevalence of AR and its associated risk factors in preschool-aged children and to assess the clinical utility of fractional exhaled nitric oxide (FeNO). METHODS: This general population-based, cross-sectional survey included 933 preschool-aged (3- to 7-year-old) children from Korea. Current AR was defined as having nasal symptoms within the last 12 months and physician-diagnosed AR. RESULTS: The prevalence of current AR in preschool children was 17.0% (156/919). Mold exposure (adjusted odds ratio [aOR], 1.67; 95% confidence interval [CI], 1.15-2.43) and the use of antibiotics (aOR, 1.97; 95% CI, 1.33-2.90) during infancy were associated with an increased risk of current AR, whereas having an older sibling (aOR, 0.52; 95% CI, 0.35-0.75) reduced the risk. Children with current atopic AR had significantly higher geometric mean levels of FeNO compared to those with non-atopic rhinitis (12.43; range of 1standard deviation [SD], 7.31-21.14 vs 8.25; range of 1SD, 5.62-12.10, P=0.001) or non-atopic healthy children (8.58; range of 1SD, 5.51-13.38, P<0.001). The FeNO levels were higher in children with current atopic AR compared with atopic healthy children (9.78; range of 1SD, 5.97-16.02, P=0.083). CONCLUSIONS: Mold exposure and use of antibiotics during infancy increases the risk of current AR, whereas having an older sibling reduces it. Children with current atopic AR exhibit higher levels of FeNO compared with non-atopic rhinitis cases, suggesting that FeNO levels may be a useful discriminatory marker for subtypes of AR in preschool children.
Anti-Bacterial Agents ; Child ; Child, Preschool* ; Cross-Sectional Studies ; Fungi ; Humans ; Korea ; Nitric Oxide ; Odds Ratio ; Prevalence ; Rhinitis ; Rhinitis, Allergic* ; Risk Factors ; Siblings