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BACKGROUND: The skin-prick and intradermal tests are the main diagnostic methods used to identify the causative agent in patients with suspected perioperative anaphylaxis. Although the intradermal test is more sensitive than the skin-prick test, multiple intradermal injections can be painful for children. Here, we present the case of a child with autism and suspected perioperative anaphylaxis. The causative agent was successfully identified using the intradermal test under general anesthesia. CASE PRESENTATION: An 8-year-old boy with autism developed anaphylaxis during general anesthesia for the fourth cleft lip and palate surgery. An allergic workout was performed, but both the skin-prick and basophil activation tests for suspected causative agents yielded negative results. The patient was afraid of multiple injections, and an intradermal test was performed under general anesthesia by anesthesiologists and allergists. Piperacillin was confirmed as the causative agent, and subsequent surgery using the same anesthetic agents without piperacillin was uneventful. CONCLUSIONS: Concerted efforts should be made to identify the causative agent for diagnosing perioperative anaphylaxis.
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Henna is a plant-based dye obtained from the powdered leaf of the pigmented plant Lawsonia inermis, and has often been used for grey hair dyeing, treatment, and body painting. As a henna product, the leaves of Indigofera tinctoria and Cassia auriculata can be blended to produce different colour variations. Although allergy from henna products attributed to p-phenylenediamine, which is added to enhance the dye, is reported occasionally, raw material plants of henna products could also contribute to the allergy. In this study, we reported that raw material plants of commercial henna products distributed in Japan can be estimated by LC-high resolution MS (LC-HRMS) and multivariate analysis. Principal Component Analysis (PCA) score plot clearly separated 17 samples into three groups [I; henna, II; blended henna primarily comprising Indigofera tinctoria, III; Cassia auriculata]. This grouping was consistent with the ingredient lists of products except that one sample listed as henna was classified as Group III, indicating that its ingredient label may differ from the actual formulation. The ingredients characteristic to Groups I, II, and III by PCA were lawsone (1), indirubin (2), and rutin (3), respectively, which were reported to be contained in each plant as ingredients. Therefore, henna products can be considered to have been manufactured from these plants. This study is the first to estimate raw material plants used in commercial plant-based dye by LC-HRMS and multivariate analysis.
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Espectrometria de Massas , Análise Multivariada , Folhas de Planta/química , Lawsonia (Planta)/química , Indigofera/química , Corantes/química , Corantes/análise , Cassia/química , Cromatografia Líquida , Cromatografia Líquida de Alta Pressão , Análise de Componente Principal , Naftoquinonas/química , Naftoquinonas/análise , Estrutura MolecularRESUMO
This case report presents a case of improvement of vernal keratoconjunctivitis associated with initiation of an oral Janus kinase inhibitor upadacitinib.
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Conjuntivite Alérgica , Compostos Heterocíclicos com 3 Anéis , Humanos , Conjuntivite Alérgica/tratamento farmacológico , Conjuntivite Alérgica/diagnóstico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Masculino , Feminino , CriançaRESUMO
BACKGROUND: Chronic spontaneous urticaria (CSU) is a chronic inflammatory disease characterized by recurrent pruritic wheals (hives) and/or angioedema. Patients with CSU could remain symptomatic despite standard-of-care H1 antihistamines (H1-AH) or anti-IgE (omalizumab) treatment. Dupilumab blocks IL-4/IL-13 signaling and is approved for multiple type 2/atopic indications. OBJECTIVE: We conducted two phase 3, randomized, placebo-controlled, double-blind trials comparing dupilumab with placebo in patients with symptomatic CSU despite H1-AH. METHODS: In LIBERTY-CSU CUPID Study A, patients were omalizumab-naive (n = 138, aged ≥6 years). In Study B, patients were omalizumab-intolerant/incomplete responders (n = 108, aged ≥12 years). The primary end point was either change from baseline over 7 days in the Urticaria Activity Score (UAS7) or Itch Severity Score (ISS7) at week 24, with the other as a key secondary end point, depending on regional regulatory requirements. Studies were pooled for safety assessment. RESULTS: In Study A, UAS7 and ISS7 improved with dupilumab versus placebo (difference -8.5 [95% CI, -13.2 to -3.9; P = .0003] and -4.2 [95% CI, -6.6 to -1.8; P = .0005]). In Study B, tested at α = 0.043 after interim analysis, UAS7 improved (difference -5.8 [95% CI, -11.4 to -0.3; P = .0390]), with a numerical trend in ISS7 (difference -2.9 [95% CI, -5.7 to -0.07; nominal P = .0449, not significant]). Pooled safety data were consistent between dupilumab and placebo and with the known dupilumab safety profile. CONCLUSIONS: Dupilumab reduced urticaria activity by reducing itch and hives severity in omalizumab-naive patients with CSU uncontrolled with H1-AH. Although the primary end point for Study B was not met, dupilumab effects were small in patients who were omalizumab-intolerant/incomplete responders.
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Anticorpos Monoclonais Humanizados , Urticária Crônica , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Adulto , Feminino , Pessoa de Meia-Idade , Urticária Crônica/tratamento farmacológico , Masculino , Método Duplo-Cego , Adolescente , Omalizumab/uso terapêutico , Omalizumab/efeitos adversos , Adulto Jovem , Resultado do Tratamento , Idoso , Criança , Prurido/tratamento farmacológico , Antialérgicos/uso terapêuticoRESUMO
OBJECTIVE: To investigate mechanisms of anaphylaxis in patients with osteoarthritis (OA) of knee and hip after diclofenac etalhyaluronate (product name: JOYCLU® [JCL]) intra-articular injection, and to determine the utility of tests to investigate the mechanism involved. METHODS: In this observational study in Japan, patients aged ≥20 years with knee or hip OA who received JCL intra-articular injection, experienced anaphylactic symptoms considered related to JCL ("experienced patients") or did not experience allergic symptoms considered related to JCL ("non-experienced patients"). Basophil activation tests (BAT), specific immunoglobulin E (IgE) antibody testing by enzyme-linked immunosorbent assays (ELISA) or immunochromatographic kit, and genome-wide association studies (GWAS) were conducted using patient blood and saliva. RESULTS: Thirteen experienced patients and 14 non-experienced patients were tested. Seven experienced patients tested positive by BAT using diclofenac etalhyaluronate (DEH)-containing test substances. Diclofenac (DF)-specific IgE antibodies were detected in 4 of 7 BAT-positive patients, but not in the non-experienced patients. Specific IgE antibody testing by immunochromatographic kit and GWAS showed no clear results. CONCLUSIONS: These findings suggest that anaphylaxis occurs after JCL administration via an IgE-mediated mechanism and that DEH may be involved in this mechanism. BAT and DF-specific IgE ELISA may be useful tests for investigating the mechanisms of anaphylactic reactions after JCL administration.
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Dermatite Alérgica de Contato , Exposição Ocupacional , Humanos , Borracha , Nitrilas , Luvas ProtetorasRESUMO
INTRODUCTION: Screening for ω-5 gliadin specific IgE antibody (sIgE) has high diagnostic utility in cases of suspected wheat-dependent exercise-induced anaphylaxis (WDEIA); however, negative cases may require confirmatory tests, such as the oral challenge test. Thus, newly identified allergens that can be used for the serological diagnosis of WDEIA are needed. This study aimed to identify additional sIgE biomarkers of WDEIA. METHODS: Forty-two patients with WDEIA (5 negative/37 positive for ω-5 gliadin sIgE) were enrolled. For comparison, 8 patients with immediate-type wheat allergy without WDEIA and 20 healthy controls without wheat allergy were also enrolled. Extracted wheat proteins were separated by 2D-PAGE. Proteins that reacted with serum IgE antibody in 2D Western blotting (2D-WB) were identified using mass spectrometry. Recombinant proteins were synthesized in Escherichia coli, and the antigenicity was tested using ELISA and the basophil activation test. RESULTS: In 2D-WB, nine proteins reacted with the serum IgE antibody from at least 60% of patients with WDEIA (n ≥ 25/42). ELISA revealed that alpha/beta gliadin MM1 exhibited the highest positive immunoreactivity in 23 of 26 patients who were positive for ω-5 gliadin sIgE (88%) and in 5 of 5 patients who were negative for ω-5 gliadin sIgE (100%). Alpha/beta gliadin MM1 exhibited significantly higher basophil activation in 14 patients with WDEIA when compared to 5 individuals without a wheat allergy. CONCLUSIONS: Alpha/beta gliadin MM1 sIgE exhibited the highest seropositivity, even among patients who were negative for ω-5 gliadin sIgE. The inclusion of alpha/beta gliadin MM1 in allergen-sIgE tests may improve the sensitivity for diagnosing WDEIA.
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Anafilaxia , Alergias Induzidas por Exercício , Hipersensibilidade a Trigo , Humanos , Gliadina , Hipersensibilidade a Trigo/diagnóstico , Anafilaxia/diagnóstico , Imunoglobulina E , AlérgenosRESUMO
Animal testing of cosmetic ingredients and products has been banned in the European Union since 2013. However, in Japan, the application of new quasi-drugs requires the generation of data on acute oral toxicity through animal testing. A weight of evidence approach for assessing oral toxicity was challenged. This approach used a combination of safety data, including a neutral red uptake cytotoxicity assay using BALB/c3T3 cells (3T3-NRU cytotoxicity assay), which can assess the acute oral toxicity of quasi-drugs or cosmetic ingredients. We conclude that the step-by-step approach can be used to assess test substances that cause low acute oral toxicity, such as the median lethal dose (LD 50) > 2000 mg/kg, thereby avoiding animal testing.
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BACKGROUND: Immediate allergy caused by natto, a popular Japanese food prepared by fermenting soybeans with Bacillus subtilis var. natto, has been reported. Polygamma glutamic acid (PGA) in the sticky substance around natto beans has been reported to be a causative allergen of natto allergy. However, some of our patients with natto allergy were negative for PGA in the skin prick test (SPT). The sticky substance of natto beans contains a subtilisin family serine protease, nattokinase, along with PGA. In this study, we aimed to examine the antigenicity of nattokinase in natto allergy. METHODS: Eight patients, who developed symptoms after ingesting natto and positively reacted to natto (seven to the sticky substance in natto and one to the whole natto product) in their SPT, were enrolled in this study. To analyze IgE reactivity, we performed immunoblotting, ELISA, and SPT for natto (bean and sticky substance), and/or PGA, and/or nattokinase and/or cultured B. subtilis var. natto extract. RESULTS: In the SPT, four cases each were PGA-positive and PGA-negative. Immunoblotting of the sera from PGA-negative patients showed a protein band at 30 kDa, which was identified as nattokinase. Three PGA-negative cases, but not three PGA-positive cases, showed a positive reaction to nattokinase in the SPT and had a history of atopic dermatitis. The ELISA for nattokinase revealed a positive reaction of PGA-negative cases and negative reaction of PGA-positive cases in the SPT. CONCLUSIONS: We identified a subtilisin family serine protease, nattokinase, as a novel allergen in natto allergy patients unsensitized to PGA.
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Dermatite Atópica , Alimentos de Soja , Humanos , Alérgenos/metabolismo , Bacillus subtilis , Serina Endopeptidases , Subtilisina/metabolismoRESUMO
Background: Acne vulgaris (acne) and cutaneous resident microorganisms are considered to be closely related. However, the bacterial and fungal microbiota in the comedonal contents of inflammatory acne lesions have not yet been investigated in detail. Purpose: To clarify the relationship between cutaneous microorganisms and acne, we examined the microbiome in the comedonal contents of inflammatory acne and on the facial skin of patients with acne using 16s rRNA and ITS gene sequencing with a next-generation sequencer (NGS). Patients and Methods: Twenty-two untreated Japanese acne outpatients were examined. The comedonal contents of inflammatory acne lesions on the face were collected using a comedo extractor. Skin surface samples from facial skin were collected using the swab method. Results: The results obtained revealed that the predominant bacteria in the comedonal contents of inflammatory acne were Cutibacterium spp. (more prominent in areas with large amounts of sebum), while those on the skin surface were Staphylococcus spp. Malassezia spp., particularly Malassezia restricta, were the predominant fungi in both the comedonal contents of inflammatory acne and on the skin surface. The bacterial microbiome in comedonal contents exhibited stronger metabolic activity, including the production of enzymes related to acne, than that on the skin surface. Conclusion: These results indicate that acne is an inflammatory disease involving the overgrowth of Cutibacterium acnes and other cutaneous resident microorganisms, including Malassezia spp.
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BACKGROUND: Nickel allergy is the most common contact allergy, and a nickel salt is, therefore, included in most baseline patch test series. In the baseline series of the International Contact Dermatitis Research Group and the American Contact Dermatitis Society, nickel sulfate hexahydrate (NSH) in petrolatum at 2.5% is included, whereas NSH at 5.0% is included in many other baseline series, such as the European and Swedish ones. OBJECTIVE: The aim of the study is to investigate whether NSH at 5.0% detects significantly more contact allergy than NSH 2.5% when both preparations are tested simultaneously in consecutive dermatitis patients. PATIENTS AND METHODS: Two thousand two hundred eighty-seven consecutive dermatitis patients were patch tested simultaneously with NSH in petrolatum at 2.5% and 5.0%. The allergy rates were compared for all clinics individually and combined using McNemar test, 2-sided. RESULTS: Contact allergy to NSH 5.0% and 2.5% was found in 20.3% and 16.8%, respectively ( P < 0.0001). In 6 of 11 clinics, significantly more patients tested positive to the higher NSH concentration. For the 2 clinics in North America combined, significantly more patients tested positive to NSH 5.0%. CONCLUSIONS: The NSH preparation in the International Contact Dermatitis Research Group baseline patch test series should be considered to be changed from NSH 2.5% (1 mg NSH/cm 2 ) to 5.0% (2 mg NSH/cm 2 ).
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Dermatite Alérgica de Contato , Níquel , Humanos , Testes do Emplastro , Níquel/efeitos adversos , Estudos Prospectivos , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/epidemiologia , Dermatite Alérgica de Contato/etiologia , Vaselina , Alérgenos/efeitos adversosRESUMO
BACKGROUND: The Japanese baseline series (JBS), established in 1994, was updated in 2008 and 2015. The JBS 2015 is a modification of the thin-layer rapid-use epicutaneous (TRUE) test (SmartPractice Denmark, Hillerød, Denmark). No nationwide studies concerning the TRUE test have previously been reported. OBJECTIVES: To determine the prevalence of sensitizations to JBS 2015 allergens from 2015 to 2018. METHODS: We investigated JBS 2015 patch test results using the web-registered Skin Safety Care Information Network (SSCI-Net) from April 2015 to March 2019. RESULTS: Patch test results of 5865 patients were registered from 63 facilities. The five allergens with the highest positivity rates were gold sodium thiosulfate (GST; 25.7%), nickel sulfate (24.5%), urushiol (9.1%), p-phenylenediamine (PPD; 8.9%), and cobalt chloride (8.4%). The five allergens with the lowest positivity rates were mercaptobenzothiazole (0.8%), formaldehyde (0.9%), paraben mix (1.1%), mercapto mix (1.1%), and PPD black rubber mix (1.4%). CONCLUSIONS: Nickel sulfate and GST had the highest positivity rates. The JBS 2015, including a modified TRUE test, is suitable for baseline series patch testing.
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Alérgenos/efeitos adversos , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/epidemiologia , Testes do Emplastro/tendências , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Conservantes Farmacêuticos/efeitos adversos , Prevalência , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Adulto JovemAssuntos
Anacardium/efeitos adversos , Anafilaxia/etiologia , Banhos/efeitos adversos , Citrus/efeitos adversos , Hipersensibilidade a Noz/etiologia , Nozes/efeitos adversos , Pectinas/efeitos adversos , Anacardium/imunologia , Anafilaxia/diagnóstico , Anafilaxia/imunologia , Criança , Citrus/imunologia , Humanos , Testes Intradérmicos , Masculino , Hipersensibilidade a Noz/diagnóstico , Hipersensibilidade a Noz/imunologia , Nozes/imunologia , Pectinas/imunologiaRESUMO
Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a life-threatening food allergy triggered by wheat in combination with the second factor such as exercise. The identification of potential genetic risk factors for this allergy might help high-risk individuals before consuming wheat-containing food. We aimed to identify genetic variants associated with WDEIA. A genome-wide association study was conducted in a discovery set of 77 individuals with WDEIA and 924 control subjects via three genetic models. The associations were confirmed in a replication set of 91 affected individuals and 435 control individuals. Summary statistics from the combined set were analyzed by meta-analysis with a random-effect model. In the discovery set, a locus on chromosome 6, rs9277630, was associated with WDEIA in the dominant model (OR = 3.95 [95% CI, 2.31-6.73], p = 7.87 × 10-8). The HLA-DPB1∗02:01:02 allele displayed the most significant association with WDEIA (OR = 4.51 [95% CI, 2.66-7.63], p = 2.28 × 10-9), as determined via HLA imputation following targeted sequencing. The association of the allele with WDEIA was confirmed in replication samples (OR = 3.82 [95% CI, 2.33-6.26], p = 3.03 × 10-8). A meta-analysis performed in the combined set revealed that the HLA-DPB1∗02:01:02 allele was significantly associated with an increased risk of WDEIA (OR = 4.13 [95% CI, 2.89-5.93], p = 1.06 × 10-14). Individuals carrying the HLA-DPB1∗02:01:02 allele have a significantly increased risk of WDEIA. Further validation of these findings in independent multiethnic cohorts is needed.
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Anafilaxia/patologia , Exercício Físico , Estudo de Associação Genômica Ampla , Cadeias beta de HLA-DP/genética , Polimorfismo Genético , Hipersensibilidade a Trigo/patologia , Adulto , Alelos , Anafilaxia/etiologia , Anafilaxia/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hipersensibilidade a Trigo/etiologia , Hipersensibilidade a Trigo/metabolismoRESUMO
A small proportion of individuals utilizing cosmetics containing rhododendrol developed leukoderma with various pathological conditions, in some cases indistinguishable from vitiligo. In this review, we investigate and evaluate the major considerations for developing rhododendrol-induced leukoderma based on data from original or review articles published in the literature to provide a wide range of information regarding the pathophysiology, mechanisms, risk evaluation, and possible mechanism-based treatments. We compile and discuss the latest information, including data related to the cytotoxicity of rhododendrol, cytoprotective functions, and involvement of the immune system, and consider the possibility of novel treatments based on the differences between individual patients and on the mechanism underlying the onset of the condition. Understanding the pathophysiology of rhododendrol-induced leukoderma helps not only elucidate the mechanisms of non-segmental vitiligo onset and progression, but also suggests prevention and treatment.