Bullous pemphigoid and its immune-mediated comorbidities / 中华皮肤科杂志

Bullous pemphigoid (BP) can be comorbid with a variety of immune diseases, such as immune skin diseases (psoriasis, vitiligo, alopecia areata and various other immune bullous diseases) , immune digestive diseases (inflammatory bowel disease, primary biliary cirrhosis) , autoimmune thyroid diseases, autoimmune rheumatic diseases (rheumatoid arthritis, dermatomyositis, scleroderma and systemic lupus erythematosus) , immune renal diseases (immune nephropathy, renal allograft rejection) and acquired hemophilia A. The above comorbidities markedly affect the quality of life of and treatment options for patients. This review elaborates on currently reported immune diseases associated with BP and their concomitant mechanisms.

Identification of a thaumatin-like protein as a new allergen in persimmon (Diospyros kaki) with cross-reactivity with banana (Musa acuminata) / Identificação de uma proteína semelhante à taumatina como um novo alérgeno no caqui (Diospyros kaki) com reatividade cruzada com a banana (Musa acuminata)

Allergy to persimmon (Diospyros kaki ) has been only rarely reported. The antigenic composition of the fruit is not entirely known. Thaumatin-like proteins (TLPs) have been described as allergens in pollens and various fruits, such as kiwi and banana, but not in persimmon. We report the case of a 22-year-old man, with persistent moderate-to-severe allergic rhinitis, sensitized to house dust mites. The patient describes an episode of oral mucosa and ear canal pruritus, followed by diffuse urticaria, which rapidly evolved to dysphonia, dyspnea, and dizziness, after eating raw persimmon. A few months later he developed similar cutaneous symptoms accompanied by nausea, vomiting, abdominal colic, and hypotension immediately after the intake of banana. The prick-prick test with raw persimmon and banana were positive, as well as the serum specific IgE to the extract of these fruits. The ImmunoCAP ISAC_112i test demonstrated a positive specific IgE against Act d 2 (kiwi thaumatin), which is homologous to banana TLP (Mus a 4). Serum IgE inhibition test with "sponge" of Diospyros kaki ImmunoCAP (f301) showed partial inhibition (40%) of IgE to Act d 2. This raises the suspicion that a TLP is at least partially responsible for the referred sensitization. This patient is sensitized to Diospyros kaki and Musa acuminata. An anaphylactic reaction to consumed persimmon, presumably as a result from cross-allergy with banana thaumatin was diagnosed in our patient. Thaumatin has not been previously described as an allergen of persimmon with cross-reactivity with banana, and in vitro with Act d 2 (kiwi TLP).

A alergia ao caqui (Diospyros kaki ) tem sido raramente documentada, não sendo a composição antigênica da fruta totalmente conhecida. Proteínas semelhantes à taumatina (TLPs) foram descritas como alergênicos em pólens e várias frutas, como no kiwi e banana, mas não no caqui. Apresenta-se o caso de um doente de 22 anos, com rinite alérgica persistente moderadagrave, sensibilizado a ácaros do pó doméstico. O doente refere episódio de prurido na mucosa oral e canal auditivo, seguido de urticária generalizada, que rapidamente evoluiu para disfonia, dispneia e tontura, após ingestão de caqui. Poucos meses depois, desenvolveu sintomas cutâneos semelhantes, acompanhados de náuseas, vómitos, cólica abdominal e hipotensão imediatamente após ingestão de uma banana. O teste cutâneo por picada com caqui e banana em natureza foram positivos, bem como o doseamento de IgE específica. O teste ImmunoCAP ISAC_112i identificou a presença de IgE específica para Act d 2 (taumatina do kiwi), homóloga da TLP da banana (Mus a 4). O estudo de inibição ImmunoCAP ISAC com "esponja" de Diospyros kaki (f301) produziu uma inibição parcial (40%) da ligação de IgE a Act d 2, permitindo presumir que uma proteína semelhante à taumatina é, pelo menos, parcialmente responsável pela referida sensibilização. Este doente encontra-se sensibilizado a Diospyros kaki e Musa acuminata. Uma anafilaxia ao caqui ingerido, presumivelmente resultante de reatividade cruzada com a taumatina da banana foi diagnosticada. Não estão descritas na literatura TLPs como alergênicos do caqui com reatividade cruzada com a banana e com Act d 2 in vitro (TLP do kiwi).

Estandarización y validación de una prueba molecular RT-LAMP in house para el diagnóstico de SARS-CoV-2 / Standardization and validation of an in house RT-LAMP molecular test for the diagnosis of SARS-CoV-2

RESUMEN Objetivos: Estandarizar una prueba RT-LAMP in house para la detección de SARS-CoV-2 y validarla con muestras de laboratorio y de campo en pacientes con sospecha clínica de COVID-19. Materiales y métodos: Se estandarizó una prueba molecular RT-LAMP in house para la detección de SARS-CoV-2 estableciéndose el límite de detección con células Vero de cepas peruanas aisladas de SARS-CoV-2. Se validó la prueba en laboratorio con 384 muestras de hisopado nasal y faríngeo (HNF) obtenidas entre marzo y julio de 2020. Para la validación de campo se obtuvieron muestras de HNF de 383 casos sintomáticos sospechosos de COVID-19. Todas las muestras fueron evaluadas por RT-LAMP y RT-qPCR. Para la validación de laboratorio y de campo se consideró como estándar de referencia al RT-qPCR, se calcularon medidas de concordancia y rendimiento diagnóstico. Resultados: El límite de detección fue consistente en los casos con umbral de ciclo (Ct) Ct < 30 en ambas pruebas, mostrando eficiencia para detectar hasta 1000 copias/µL del gen diana. Se evidenció robustez con la mitad de las concentraciones de cebadores y 20 µL de volumen final. Se identificó ausencia de amplificación para otros coronavirus humanos. La concordancia en laboratorio obtuvo un Kappa de 0,88 (IC 95%: 0,83-0,93) y en campo fue de 0,89 (IC 95%: 0,84−0,94); la sensibilidad en laboratorio fue de 87,4% (IC 95%: 80,8−92,4) y en campo fue de 88,1% (IC 95%: 81,6−92,9), la especificidad en ambos escenarios fue de 98,8% (IC 95%: 96,4−99,7). Conclusiones: La prueba RT-LAMP in house fue validada por presentar una adecuada robustez, sin reacciones cruzadas, buena concordancia y rendimiento diagnóstico comparado con el RT-qPCR.

ABSTRACT Objectives: To standardize and validate an in-house RT-LAMP test for the detection of SARS-CoV-2, based on laboratory and field assays using samples from COVID-19 suspected patients. Materials and methods: An in-house SARS-CoV-2 RT-LAMP molecular test was standardized, establishing the detection limit with Vero cells of isolated Peruvian strains of SARS-CoV-2, and the robustness to various concentrations of primers. The laboratory validation was performed with 384 nasal and pharyngeal swab samples (UFH) obtained between March and July 2020. The field validation was performed with 383 UFH obtained from COVID-19 suspected symptomatic cases. All samples were tested by RT-LAMP and RT-qPCR. The RT-qPCR was considered as the reference standard test. The concordance measures and diagnostic performance were calculated. Results: The detection limit was consistent in cases with Ct <30 in both tests, showing efficiency to detect up to 1000 copies/μL of the target gene. Robustness was evidenced with half of the primer concentrations and 20 μL of final volume. Absence of amplification was identified for other HCoVs. Concordance showed a kappa index of 0.88 (95% CI: 0.83-0.93) and 0.89 (95% CI: 0.84 - 0.94) in laboratory and field settings, respectively. The sensitivity value in the laboratory was 87.4% (95% CI: 80.8 - 92.4) and 88.1% in the field (95% CI: 81.6 - 92.9). The specificity value in both settings was 98.8% (95% CI: 96.4-99.7). Conclusions: The in-house SARS-CoV-2 RT-LAMP test was successfully validated based on its adequate robustness, no cross-reactions, good concordance, and diagnostic performance compared to RT-qPCR.

Estandarización y validación de una prueba molecular RT-LAMP in house para el diagnóstico de SARS-CoV-2 / Standardization and validation of an in house RT-LAMP molecular test for the diagnosis of SARS-CoV-2

RESUMEN Objetivos: Estandarizar una prueba RT-LAMP in house para la detección de SARS-CoV-2 y validarla con muestras de laboratorio y de campo en pacientes con sospecha clínica de COVID-19. Materiales y métodos: Se estandarizó una prueba molecular RT-LAMP in house para la detección de SARS-CoV-2 estableciéndose el límite de detección con células Vero de cepas peruanas aisladas de SARS-CoV-2. Se validó la prueba en laboratorio con 384 muestras de hisopado nasal y faríngeo (HNF) obtenidas entre marzo y julio de 2020. Para la validación de campo se obtuvieron muestras de HNF de 383 casos sintomáticos sospechosos de COVID-19. Todas las muestras fueron evaluadas por RT-LAMP y RT-qPCR. Para la validación de laboratorio y de campo se consideró como estándar de referencia al RT-qPCR, se calcularon medidas de concordancia y rendimiento diagnóstico. Resultados: El límite de detección fue consistente en los casos con umbral de ciclo (Ct) Ct < 30 en ambas pruebas, mostrando eficiencia para detectar hasta 1000 copias/µL del gen diana. Se evidenció robustez con la mitad de las concentraciones de cebadores y 20 µL de volumen final. Se identificó ausencia de amplificación para otros coronavirus humanos. La concordancia en laboratorio obtuvo un Kappa de 0,88 (IC 95%: 0,83-0,93) y en campo fue de 0,89 (IC 95%: 0,84−0,94); la sensibilidad en laboratorio fue de 87,4% (IC 95%: 80,8−92,4) y en campo fue de 88,1% (IC 95%: 81,6−92,9), la especificidad en ambos escenarios fue de 98,8% (IC 95%: 96,4−99,7). Conclusiones: La prueba RT-LAMP in house fue validada por presentar una adecuada robustez, sin reacciones cruzadas, buena concordancia y rendimiento diagnóstico comparado con el RT-qPCR.

ABSTRACT Objectives: To standardize and validate an in-house RT-LAMP test for the detection of SARS-CoV-2, based on laboratory and field assays using samples from COVID-19 suspected patients. Materials and methods: An in-house SARS-CoV-2 RT-LAMP molecular test was standardized, establishing the detection limit with Vero cells of isolated Peruvian strains of SARS-CoV-2, and the robustness to various concentrations of primers. The laboratory validation was performed with 384 nasal and pharyngeal swab samples (UFH) obtained between March and July 2020. The field validation was performed with 383 UFH obtained from COVID-19 suspected symptomatic cases. All samples were tested by RT-LAMP and RT-qPCR. The RT-qPCR was considered as the reference standard test. The concordance measures and diagnostic performance were calculated. Results: The detection limit was consistent in cases with Ct <30 in both tests, showing efficiency to detect up to 1000 copies/μL of the target gene. Robustness was evidenced with half of the primer concentrations and 20 μL of final volume. Absence of amplification was identified for other HCoVs. Concordance showed a kappa index of 0.88 (95% CI: 0.83-0.93) and 0.89 (95% CI: 0.84 - 0.94) in laboratory and field settings, respectively. The sensitivity value in the laboratory was 87.4% (95% CI: 80.8 - 92.4) and 88.1% in the field (95% CI: 81.6 - 92.9). The specificity value in both settings was 98.8% (95% CI: 96.4-99.7). Conclusions: The in-house SARS-CoV-2 RT-LAMP test was successfully validated based on its adequate robustness, no cross-reactions, good concordance, and diagnostic performance compared to RT-qPCR.

Cross-reactivity of pink peppercorn in cashew and pistachio allergic individuals

BACKGROUND: The Pink peppercorn belongs to the same Anacardiaceae family as cashew and pistachio. However, the cross-reactivity of pink peppercorn with cashew and pistachio has yet to be studied. To date, there has been a single case report of anaphylaxis to pink peppercorn in a cashew and pistachio allergic individual. OBJECTIVE: We aim to demonstrate cross-sensitization to pink peppercorn in cashew and/or pistachio allergic children. METHODS: A small descriptive cohort study looking at cross-sensitization of pink peppercorn in cashew and/or pistachio allergic children was conducted. Children with a history of reaction to pistachio and/or cashew nut underwent skin prick tests to the pink peppercorn species Schinus terebinthifolius to determine cross-sensitization. RESULTS: Out of the 21 cashew and/or pistachio allergic subjects, 16 (76.2%) demonstrated cross-sensitization to pink peppercorn. None of the subjects had any knowledge of previous exposure or allergic reactions to pink peppercorn. DISCUSSION: This study demonstrates potential cross-reactivity between pink peppercorn and cashew and pistachio. While an oral food challenge to pink peppercorn would have been important in demonstrating clinical cross-reactivity, this was not performed due to ethical constraints. We hope to increase the awareness of pink peppercorn as a potential and hidden source of allergen and encourage further studies to demonstrate the clinical cross-reactivity and to better delineate the major allergen involved.

Multiple food allergy – unexpected culprits

Food allergy has an estimated prevalence of 6%–8% in children. Meat allergy and multiple food allergy due to sensitization to cross-reactive components in infancy is, however, less frequent. A 5-year-old girl was referred to our department with a multiple food allergy history. She had severe immediate worsening of her atopic dermatitis with hen's egg (6 months) and cow's milk introduction (7 months). At the age of 9 months, she presented with recurrent and reproducible atopic dermatitis' worsening and lip edema with the introduction of different meats (chicken, turkey, cow, pork, and rabbit), having the same complaints with fish at 12 months (salmon and hake). At her first appointment she was avoiding hen's egg, cow's milk, meat, and fish (except fresh tuna, codfish, and pollock). We performed skin prick tests (commercial extract and prick-to-prick with whole food) and specific IgE, which revealed sensitization to hen's egg, raw meat (cow, pork, chicken, turkey, duck, lamb, goat, and rabbit; negative for cooked meat), codfish and cow's milk (mild). ISAC was performed, revealing sensitization to 3 cross-reactive components (serum albumins Bosd6, Canf3, and Feld2) and specific food components of chicken's egg/meat (Gald1, 2, 3, and 5), cod (Gadc1), hazelnut (Cora9), and kiwi (Actd1). We present a rare case of multiple food allergy in infancy, where sensitization to cross-reactive components was responsible for most of the children complaints. The detection of serum albumins' involvement was especially important, because it can possibly mean tolerance to these foods in well-cooked forms, substantially improving patient and family's quality of life.

Evaluation of the allergenic relationship between Humulus japonicus and Humulus lupulus pollen allergens

PURPOSE: Humulus japonicus pollen (Hop J) is a major cause of inhalant allergy in autumn of the Far East countries, and its allergenic potency has been increasing with climate changes. Allergen immunotherapy has been considered in Hop J-sensitized allergic patients; however, Hop J allergen extracts for immunotherapy are not commercially available. We speculate that Humulus lupulus pollen (Hop L) belonged to the same genus may share cross-reacting allergens with Hop J and evaluated allergenic relationships between these 2 pollens. METHODS: Thirteen patients with allergic rhinitis and/or asthma sensitive to Hop J pollens were enrolled in Ajou University Hospital, Suwon, Korea. Hop J pollens were collected locally and lyophilized extracts were prepared, while lyophilized Hop L extracts were provided by Lofarma S.p.A. IgE-ELISA/enzyme-linked immunosorbent assay (ELISA) inhibition tests, sodium dodecyl sulphate-polyacrylamide gel electrophoresis and IgE-immunoblot/immunoblot inhibition analysis using sera from the enrolled subjects were performed. RESULTS: All patients had high serum specific IgE to both Hop J and Hop L extracts by ELISA, but no significant correlation was found between these 2 extracts. ELISA inhibition tests showed significant dose-dependent inhibitions on IgE-bindings to Hop L with serial additions of Hop J extracts in a dose-dependent manner, while minimal inhibitions of IgE binding to Hop J were noted with additions of Hop L. IgE-immunoblot analysis demonstrated that the major allergenic component of Hop J at 12 kDa was inhibited by Hop J, while no inhibitions were noted by Hop L extracts on IgE-immunoblot inhibition analysis. CONCLUSION: These findings suggest that there may not be a significant cross-allergenicity between Hop J and Hop L.

Bepotastine-induced urticaria, cross-reactive with other antihistamines

Second-generation antihistamines are widely prescribed for the control of symptoms of allergic inflammation such as itchy hives, coryza, and itchy eyes. In rare circumstances, these drugs might provoke allergic inflammation. Hypersensitivity to bepotastine besilate, a second-generation antihistamine has never been reported. A 17-year-old schoolgirl, whose paroxysmal itchy hives had been controlled with bepotastine, experienced aggravation of the hives. An oral provocation test confirmed her hypersensitivity to bepotastine and cross-reactivity to levocetirizine. She showed no reaction to chlorpheniramine, ketotifen, or olopatadine among the 13 antihistamines tested. While searching for an antihistamine to control her itchy hives, we found that she also exhibited cross-reactivity to various antihistamines with different chemical structures from that of bepotastine, which is not predicted according to the chemical classification of antihistamines. We report a case of hypersensitivity to bepotastine besilate in a patient with chronic spontaneous urticaria.

Carbohydrates as food allergens

The literature supports the notion that carbohydrate epitopes, on their own, do not contribute significantly to the induction of allergic reactions. They bind weakly to IgE antibodies and have been termed as cross reactive carbohydrate determinants. These epitopes cause confusion in in vitro IgE testing through nonspecific cross-reactivity. Coincident with the rising trends in food allergy prevalence, there has recently been reports of anaphylaxis induced by carbohydrate epitopes. There are two distinct groups, each with unique characteristics and geographical distribution. Anaphylaxis and acute allergic reactions related to the carbohydrate galactose-α-1,3-galactose (α-Gal) epitope that are present in the monoclonal antibody, cetuximab and red meat have been described in the United States and Europe populations where tick bites have been found to be the primary sensitizer. Another carbohydrate inducing anaphylaxis is galacto-oligosaccharides in commercial milk formula which has been described in the several Asian populations including Singapore. The latter is unique in that the allergen is a pure carbohydrate. We summarize the current literature on carbohydrate-induced food allergy, and evaluate the two new groups of carbohydrate allergy that have defied previous findings on carbohydrates and their role.

Oral antiplatelet agent hypersensitivity and cross-reactivity managed by successful desensitisation

Oral platelet aggregation inhibitors are widely used for the treatment and prevention of cardiovascular diseases, including coronary stent thrombosis. Premature discontinuation following percutaneous coronary intervention would pose a grave risk of in-stent thrombosis, acute myocardial infarction and eventual death. Although they share the same mechanism of adenosine diphosphate P2Y12 platelet receptor inhibition, they belong to either the chemical class of thienopyridines (clopidogrel, prasugrel, and ticlopidine) or cyclopentyl-triazolo-pyrimidines (ticagrelor and cangrelor). This case describes the first documented cross-reactive hypersensitivity of clopidogrel towards both its fellow thienopyridine, prasugrel, as well as the structurally dissimilar ticagrelor, and its subsequent successful desensitisation.

Cross-reactivity of tree shrew sera with various secondary antibodies:extensive application to tree shrew models of diseases / 中国组织工程研究

BACKGROUND:Tree shrew is a representative between insectivore and primates, has a high degree of evolution, is more inexpensive primates, has high use of medical biology, and has been attached by scholars. OBJECTIVE:To detect whether the commonly used secondary antibodies have immune response with tree shrew serum. METHODS:Western blot assay and enzyme linked immunosorbent assay were utilized to detect whether the tree shrew serum had cross-reacts with anti-rabbit, anti-goat, anti-human, anti-mouse, anti-rat, and anti-monkey secondary antibodies. RESULTS AND CONCLUSION:Western blot assay results indicated that tree shrew serums did not react with anti-rabbit, anti-goat, anti-human, anti-mouse, and anti-rat secondary antibodies and had cross reaction with anti-monkey secondary antibody. Enzyme linked immunosorbent assay results also indicated that tree shrew serums were cross-reactive with anti-monkey secondary antibody, but did not have cross-reactivity with the other secondary antibodies. Above data confirmed that the usual y soled secondary antibody cannot be used to immunoassay with tree shrews IgG. Only anti-monkey secondary antibody has cross-react with tree shrew serum. It is necessary to prepare anti-tree shrew IgG monoclonal and polyclonal antibodies. When no antibody is readily available at present, anti-monkey secondary antibody can be used to substitute detection, and can be widely applied in the study of tree shrew models of disease.

Discrepancy between Vitamin D Total Immunoassays due to Various Cross-reactivities

BACKGROUND: The purpose of this study was to find out the cause of discrepancy between various automated immunoassays for 25-hydroxy-vitamin D (25-[OH]D). METHODS: National Institute of Standards & Technology Standard Reference Material (SRM) 972a is SRM for 25-(OH)D and consists of 4 vials of frozen serum with different concentrations of 25-(OH)D. Each concentration was measured 6 times in 3 different immunoassays: ADVIA Vitamin D Total assay (Siemens Healthcare, Erlangen, Germany), ARCHITECT 25-(OH)D (Abbott Laboratories, Abbott Park, IL, USA), and COBAS Vitamin D Total assay (Roche Diagnostics, Basel, Switzerland). RESULTS: When using the certified reference values of SRM 972a as it is, discarding the cross-reactivity of each immunoassay, for ADVIA, the coefficient of determination (R2) as a score of regression analysis was 0.8995 and maximal difference between measured value and certified reference value was 3.6 ng/mL in level 3. The R2 and maximal differences of ARCHITECT were 0.5377 and 6.9 ng/mL, respectively, in level 4. Those of COBAS were 0.3674 and 22.3 ng/mL, respectively, in level 4. When considering cross-reactivities of each immunoassays to various 25-(OH)D metabolites, the ADVIA had R2 and maximal difference of 0.9254 and 3.3 ng/mL, respectively, in level 3. For ARCHITECT, the R2 and maximal differences were 0.7602 and 5.1 ng/mL, respectively, in level 1. Those of COBAS were 0.9284 and 4.9 ng/mL, respectively, in level 1. CONCLUSIONS: The cause of discrepancies between vitamin D immunoassays was mainly on the difference in cross-reactivities to various vitamin D metabolites. The discrepancies can be considerably decreased by considering cross-reactivities of each immunoassay.

Utilização de três métodos imuno-histoquímicos na detecção de aspergilose e zigomicose em animais / Usage of three immunohistochemical methods in the detection of aspergillosis and zygomycosis in animals

Visando a otimização do uso da técnica de imuno-histoquímica (IHQ) na detecção de Aspergillus spp. e zigomicetos (membros da família Mucoraceae), utilizaram-se dois anticorpos monoclonais fungo-específicos em fragmentos de tecidos de animais (fixados em formol e embebidos em parafina) com diagnóstico histomorfológico prévio de aspergilose e zigomicose, os quais foram submetidos a três sistemas de detecção diferentes (dois biotinilados e um não biotinilado). Os dois anticorpos apresentaram alta especificidade e sensibilidade nos tecidos examinados. Não ocorreram reações cruzadas entre os anticorpos utilizados e os agentes etiológicos avaliados (incluindo casos de aspergilose, zigomicose, candidíase e pitiose). No entanto, reações inespecíficas foram observadas nas hifas em alguns casos, as quais puderam ser eliminadas através de um dos métodos de detecção utilizados. Para a aspergilose, o método da estreptavidina-biotina-fosfatase alcalina não apresentou reações inespecíficas nas hifas. Enquanto que nos casos de zigomicoses, as reações inespecíficas não ocorreram no método por polímero (não biotinilado). A técnica de IHQ mostrou-se uma ferramenta muito útil na detecção e confirmação dos casos de aspergilose e zigomicose neste estudo retrospectivo.

Aiming to optimize the usage of the immunohistochemical technique (IHC) in the detection of Aspergillus spp. and zygomycetes (members of the Mucoraceae family), two fungal-specific monoclonal antibodies were used in tissue fragments (formalin-fixed paraffin-embedded), previously diagnosed by histomorphology as aspergillosis and zygomycosis. Tissues were submitted to three different detection systems (two biotinilated and one non biotinilated). Both antibodies showed high specificity and sensitivity in the examined tissues. No cross-reactions were observed between the antibodies used and the agents evaluated (including cases of aspergillosis, zygomycosis, candidiasis and pythiosis). However, nonspecific reactions in hyphae were observed in some cases, but were eliminated by mean of one of the detection systems used. In the aspergillosis cases, with the streptavidin-biotin-alkaline phosphatase method, nonspecific reactions were not observed. In the zygomycosis cases, nonspecific reactions did not occur using a polymer (nonbiotinilated). The IHC technique showed to be a useful tool detecting and confirming aspergillosis and zygomycosis in this retrospective study.

Drug hypersensitivity to various antihistamines with cross-reactions

Antihistamines (histamine receptor antagonists) are widely prescribed medicines in the treatment of allergic disorders, especially the symptoms of hypersensitivity reactions, mainly blocking the activity of vasoactive amines to their receptors. Drug adverse reactions such as sleepiness and dry mouth are frequently encountered. However, drug hypersensitivity provoking itchy hives by antihistamines were rarely reported. A 41-year-old female patient visited allergy clinic for generalized itchy hives from time to time, which had been aggravated 3 months before. Whenever she was exposed to antihistamines for treatment, she felt her hives got immediately full-blown. As a screening, she was tested with various antihistamines on her skin, then skin test-negative antihistamines were orally administered. Finally we failed to choose a safe antihistamine for the treatment of her symptoms. We report a case of drug hypersensitivity to various antihistamines with cross-reactions in a patient with chronic urticaria.

Cross-reactivity to Acetaminophen and Celecoxib According to the Type of Nonsteroidal Anti-inflammatory Drug Hypersensitivity

PURPOSE: Identification of tolerable alternative analgesics is crucial for management in nonsteroidal anti-inflammatory drug (NSAID)-sensitive patients. We investigated cross-reactivity of acetaminophen and celecoxib according to the type of aspirin/NSAID hypersensitivity and aimed to determine the risk factors for cross-intolerance. METHODS: We retrospectively reviewed the medical records of patients intolerant to aspirin and NSAIDs who had undergone an acetaminophen and/or celecoxib oral provocation test. Aspirin/NSAID hypersensitivity was classified into 4 types according to a recently proposed classification: aspirin-exacerbated respiratory disease (AERD), aspirin-exacerbated chronic urticaria (AECU), aspirin-induced acute urticaria/angioedema (AIAU), and NSAID-induced blended reaction (NIRD). RESULTS: A total of 180 patients with hypersensitivity to aspirin and NSAIDs were enrolled; 149 acetaminophen provocation test results and 145 celecoxib provocation test results were analyzed. The overall cross-reaction rates to acetaminophen and celecoxib were 24.8% and 10.3%, respectively. There was a significant difference in the cross-reactivity to acetaminophen according to the type of NSAID hypersensitivity. Cross-reactivity to acetaminophen was highest in the AECU group (43.9%), followed by the AERD (33.3%), NIBR (16.7%), and AIAU (12.5%) groups. Underlying chronic urticaria was more prevalent in patients with cross-intolerance to both acetaminophen (P=0.001) and celecoxib (P=0.033). Intolerance to acetaminophen was associated with intolerance to celecoxib (P<0.001). CONCLUSIONS: Acetaminophen and celecoxib may induce adverse reactions in a non-negligible portion of aspirin/NSAID-sensitive patients. Physicians should be aware of the possible cross-reactions of these alternative drugs and consider an oral challenge test to confirm their tolerability.

Identification of IgE binding components of two major weed pollens, ragweed and mugwort

PURPOSE: Ragweed and mugwort pollens are the major weed allergens that cause pollinosis in Korea. The IgE-binding components to these 2 pollens and their cross-reactivity have not been reported in Korea, while several reports had been made in Western countries. We investigated IgE-binding components to ragweed and mugwort pollens and their allergenic relationship in patients sensitive to the 2 pollens. METHODS: We enrolled 33 allergic rhinitis patients with typical seasonal pollinosis symptoms in autumn and elevated serum specific IgE levels to ragweed and/or mugwort pollens (>10 kU/L by ImmunoCAP). The protein bands of the 2 pollen extracts were determined using sodium dodecyl sulphate-polyacrylamide gel electrophoresis, and IgE immunoblot analysis was performed to determine the IgE-binding components of each pollen extract. Enzyme-linked immunosorbent assay (ELISA) inhibition and immunoblot inhibition tests were performed to evaluate the cross-reactivity between ragweed and mugwort pollen extracts. RESULTS: Eight IgE-binding components (9, 10, 11, 12, 27, 30, 38, and 80 kDa) were found in ragweed pollen extracts, of which 4 (38, 11, 27, and 80 kDa) were major IgE-binding components. Eight IgE-binding components (10, 14, 16, 20-24, 26-30, 42, 60-66, and 80-90 kDa) were found in mugwort pollen extracts, of which 2 components (26-30 and 20-24 kDa) were major IgE-binding components. No significant inhibitions were noted between ragweed and mugwort pollen extracts by the ELISA inhibition test. No significant changes were noted in IgE immunoblot inhibition analysis. CONCLUSION: We identified 4 major IgE-binding components (38, 11, 35, 27, and 80 kDa) in ragweed pollens and 2 major IgE-binding components (26-30 and 20-24 kDa) in mugwort pollens. No cross-reactivity was found between ragweed and mugwort pollens.

Anaphylaxis to lansoprazole with tolerance to other proton pump inhibitors

Anaphylaxis to proton pump inhibitors (PPIs) has rarely been reported. Different patterns of cross-reactivity between PPIs have also been demonstrated using skin tests. Here, we report a case of anaphylaxis to lansoprazole with tolerance to other commercially available PPIs, which was proved by skin tests and oral provocation tests (OPTs). A 47-year-old female patient visited our Emergency Department with a sudden onset of whole body urticaria, facial swelling, dyspnea, and loss of consciousness that developed 1 hour after ingestion of 30 mg of lansoprazole for her episodic epigastric soreness. The skin prick test (SPT) and the intradermal test (IDT) with lansoprazole, esomeprazole, rabeprazole, and pantoprazole were performed. Lansoprazole showed positive reactions in both the SPT (3 mg/mL) and the IDT (0.003 mg/mL). Rabeprazole (3 mg/mL) showed a positive reaction only in IDT. The SPT and the IDT with esomeprazole and pantoprazole were all negative. The OPT with 30 mg of lansoprazole was positive (showing generalized rash and facial swelling 30 minuites after ingestion), while OPTs with esomeprazole, pantoprazole, and rabeprazole were all negative. Other PPIs could be safe alternatives in cases of anaphylaxis to 1 PPI. Skin tests seem to be helpful to define cross-reactivity between PPIs.

Diagnosis and Management of Immediate Hypersensitivity Reactions to Cephalosporins

Cephalosporins can cause a range of hypersensitivity reactions, including IgE-mediated, immediate reactions. Cephalosporin allergy has been reported with use of a specific cephalosporin, as a cross-reaction between different cephalosporins or as a cross-reaction to other beta-lactam antibiotics. Unlike penicillins, the exact allergenic determinants of cephalosporins are less well understood and thus, standardized diagnostic skin testing is not available. Nevertheless, skin testing with diluted solutions of cephalosporins can be valuable in confirming IgE-mediated hypersensitivity reactions. In vitro tests are in development using recent technological advances and can be used as complementary tests. However, they are not commonly used because of their reduced sensitivity and limited availability. In selected cases of inconclusive results in both skin tests and IgE assays, a graded challenge or induction of drug tolerance with the implicated cephalosporin should be performed.

Identification of immunoglobulin E binding components of two major tree pollens, birch and alder

PURPOSE: Pollinosis is one of the major allergic diseases caused by airborne pollens. Alder and birch pollens are the major sensitizing tree pollens in this country. The immunoglobulin E (IgE) reactivity to each pollen allergen is known to be variable according to the region. We determined the major IgE binding components of these tree pollens in sera of adult patients with allergic rhinitis. METHODS: Allergic rhinitis patients, of whom specific IgE level to birch and/or alder pollens (>10 kU/L by ImmunoCAP) were included. The protein bands of two pollen extracts were determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, and their IgE-binding components were identified by IgE immunoblot analysis. The binding specificity and cross-reactivity between two pollens were evaluated by IgE enzyme linked immunosorbent assay (ELISA) inhibition test. RESULTS: Six IgE binding components were found in birch pollens in which two (14 kDa and 17 kDa) were major components. Two IgE binding components were found in alder pollens in which the 17 kDa was a major component. The IgE binding component to the major allergen component of 17 kDa was observed in 90.3% of the study subjects sensitive to alder pollens and 72.7% of them sensitive to birch pollens. The ELISA inhibition tests showed significant inhibitions with additions of birch/alder pollen extracts. CONCLUSION: We identified two major IgE binding components (17 kDa and 14 kDa) from birch pollens and one component (17 kDa) from alder pollens. Significant cross reactivity was noted between these two pollens.

Food allergy / 소아과

Food allergy is an important public health problem affecting 5% of infants and children in Korea. Food allergy is defined as an immune response triggered by food proteins. Food allergy is highly associated with atopic dermatitis and is one of the most common triggers of potentially fatal anaphylaxis in the community. Sensitization to food allergens can occur in the gastrointestinal tract (class 1 food allergy) or as a consequence of cross reactivity to structurally homologous inhalant allergens (class 2 food allergy). Allergenicity of food is largely determined by structural aspects, including cross-reactivity and reduced or enhanced allergenicity with cooking that convey allergenic characteristics to food. Management of food allergy currently focuses on dietary avoidance of the offending foods, prompt recognition and treatment of allergic reactions, and nutritional support. This review includes definitions and examines the prevalence and management of food allergies and the characteristics of food allergens.