Polyethylene glycol hypersensitivity, patient outcomes in a 7-year retrospective study.

BACKGROUND: Immediate IgE-mediated hypersensitivity reactions to polyethylene glycol (PEG) are rare. Our understanding of PEG hypersensitivity is limited. OBJECTIVE: To evaluate the clinical characteristics and investigation outcomes of the largest cohort of patients with PEG allergy reported. METHODS: A total of 44 patients investigated for suspected PEG allergy across 4 United Kingdom tertiary allergy centers between October 2013 and December 2020 were studied. Clinical characteristics, index reaction, and approaches to and outcomes of allergy investigations were analyzed. RESULTS: PEG hypersensitivity was confirmed in 42 of 44 cases. Macrogol laxatives were the most common index drugs reported (23%), followed by depo-medroxyprogesterone (19%), oral penicillin V (10%), and depo-methylprednisolone (10%). In general, 61% experienced grade III anaphylaxis. Intradermal testing (IDT) increased the diagnostic sensitivity from 51% to 85%. Five patients experienced systemic reactions during IDT. Of the 5 patients, 2 were skin prick test positive to a high molecular weight PEG. Three patients with negative skin test results had positive drug provocation test results. Seven patients with PEG allergy reported tolerance to H1-antihistamines containing PEG. Administration of messenger RNA COVID-19 or Oxford/AstraZeneca COVID-19 vaccines was tolerated in all 16 patients to whom they were administered. CONCLUSION: PEG hypersensitivity is an uncommon cause of drug-induced anaphylaxis. Four index drugs accounted for two-thirds of the cases, and reactions to these drugs should prompt PEG hypersensitivity investigations. PEG IDT increases diagnostic yield. The role of skin prick test with higher molecular weight PEGs requires further attention. Further studies are required to understand PEG thresholds and PEG equivalent doses of various administration routes. COVID-19 vaccines were tolerated by all exposed.

A randomised, double-blinded trial to assess the effect of oclacitinib and prednisolone on intradermal allergen and prick tests in dogs with atopic dermatitis.

BACKGROUND: Intradermal (IDT) and prick (PT) tests are used to select allergens for allergen-specific immunotherapy in dogs with atopic dermatitis (cAD). However, the use of antipruritic drugs before performing these tests may influence the results. OBJECTIVE: To evaluate the influence of the drugs oclacitinib and prednisolone on the immediate-phase reactions of IDT and PT. ANIMALS: Thirty client-owned dogs with cAD with positive reactions to at least one allergen extract on IDT or PT. MATERIALS AND METHODS: Dogs were randomly assigned to receive oclacitinib 0.4-0.58 mg/kg per os, every 12 h (n = 14), or prednisolone 0.37-0.65 mg/kg p.o., every 12 h (n = 16) for 14 days. IDT and PT were performed on Day (D)0 before treatment and on D14. RESULTS: At D14 there was no significant reduction in the means of the orthogonal diameters of the positive immediate-phase reactions of the IDT (p = 0.064) in the oclacitinib group; however, in the PT, the diameter of the positive reactions reduced significantly (p = 0.048). In both tests, there was no significant reduction in the total number of positive reactions (IDT, p > 0.999; PT, p = 0.735). In the prednisolone group, the means of the orthogonal diameters of positive immediate-phase reactions were significantly reduced in both tests (IDT, p = 0.001; PT, p ≤ 0.001) and there also was a reduction in the total number of positive reactions (IDT, p = 0.022; PT, p = 0.001). CONCLUSIONS AND CLINICAL RELEVANCE: The use of oclacitinib 0.4-0.58 mg/kg twice daily for 14 days does not interfere with IDT results in dogs with cAD. However, oclacitinib may reduce PT reactivity. The use of prednisolone 0.37-0.65 mg/kg twice daily results in a reduction in both IDT and PT results.

Influence of a single oral dose of trazodone on intradermal histamine reactivity in clinically healthy dogs.

BACKGROUND: Drug interactions are significant considerations for intradermal testing (IDT). Trazodone (TRZ) is an anxiolytic and selective histaminergic (H1 ) antagonist with no interaction in human prick tests; however, interaction in canine IDT is unknown. HYPOTHESIS/OBJECTIVES: Trazodone will not adversely affect intradermal histamine reactions in dogs. ANIMALS: Fourteen nonanxious, nonatopic, healthy client-owned dogs were enrolled in this randomised, blinded, cross-over study. MATERIALS AND METHODS: Dogs were randomised to receive low-dose TRZ (4 mg/kg) (Teva Pharmaceuticals), high-dose TRZ (8 mg/kg) or no TRZ per os two hours before intravenous sedation with dexmedetomidine (5 mcg/kg) (Dexdomitor; Zoetis). Intradermal testing was performed with five quadrupling dilutions of histamine (1:100,000 to 1:25,600,000 w/v; Greer) and 0.9% saline (Hospira), observing a minimum two weeks washout period between treatments. Two observers, who were blinded to treatment and the identity of the injections, evaluated each test using previously established subjective and objective methods. RESULTS: The mean wheal diameter of histamine 1:1,600,000 w/v was significantly smaller with low-dose TRZ (4 mg/kg) compared to the control group (p = 0.048; repeated measures ANOVA with post hoc Tukey's test). For all other histamine dilutions and saline, mean wheal diameter was not significantly different among groups. There were no significant differences in the subjective scores of all histamine dilutions and saline (p > 0.05; Friedman test). CONCLUSION AND CLINICAL RELEVANCE: A single oral dose of TRZ does not adversely affect intradermal histamine reactions in dogs.

Comparison of intradermal and serum testing for environmental allergen-specific immunoglobulin E determination in a laboratory colony of cats with naturally acquired atopic syndrome.

BACKGROUND: Allergen testing is used to select antigens included in the desensitisation vaccine. Intradermal skin test (IDT) is the gold standard in cats, yet allergen-specific immunoglobulin (Ig)E serological testing (ASIS) is often used. Feline data are lacking regarding the agreement between IDT and ASIS results. HYPOTHESIS/OBJECTIVES: The first objective of the study was to establish a colony of cats with naturally acquired feline atopic syndrome (FAS). Further objectives were to define their hypersensitivity disorder to detail the allergen tests results, and to assess similarity between the allergen tests. ANIMALS: Thirty-five cats with FAS and 10 control cats. MATERIALS AND METHODS: Enrolled cats went through a five phase-screening and quarantine process before joining the colony. An elimination diet trial was performed on all FAS cats. ASIS and IDT were consecutively performed on all cats under sedation. RESULTS: Reactions to 34 allergens were compiled for the 45 cats. Global sensitivity and specificity of ASIS were 34.7% and 78.9%, respectively. Only flea (ICC = 0.26, p = 0.040) and Dermatophagoides pteronyssinus (ICC = 0.48, p < 0.001) allergens had a significant intraclass correlation (weak agreement). Two FAS cats had negative tests including one cat with a concomitant food allergy. CONCLUSIONS AND CLINICAL RELEVANCE: This study depicts the first reported colony of cats with naturally acquired FAS. This is the first feline study to compare and show the poor agreement between allergen tests with a panel of 34 allergens. This colony also harbours two cats with FAS with negative allergen tests. These may represent the first described cats with an intrinsic form of atopic syndrome.

Cutaneous anaphylactoid reaction to polyoxyethylene hydrogenated castor oil in dogs.

BACKGROUND: Polyoxyethylene hydrogenated castor oil (HCO ethoxylates) is a nonionic surfactant used as an excipient for ointments and injections in human and veterinary drugs. Several polyethylene glycol (PEG) derivatives can be obtained depending on the number of moles of ethylene oxide (EO). HCO ethoxylates have the potential to cause anaphylactoid reactions. There is little published information about these types of reactions in dogs. OBJECTIVE: To determine the potential for HCO-ethoxylate-containing drugs to cause anaphylactoid reactions in dogs, employing intradermal testing (IDT) with various concentrations of HCO ethoxylates (HCO-25, -40, -60 and -80). ANIMALS: Four healthy male laboratory dogs. MATERIALS AND METHODS: We performed IDT with drugs containing HCO ethoxylates and HCO ethoxylates alone to determine threshold concentrations. The IDT scores and threshold concentrations were compared. Analysis of skin biopsies from IDT sites was used to measure the percentage of degranulated mast cells. The effect of histamine at IDT sites was investigated by pre-treatment with an antihistamine. RESULTS: All HCO-ethoxylate-containing drugs caused a wheal-and-flare reaction. The threshold concentrations (0.001% and 0.00001%) of each HCO-ethoxylate depended on the number of moles of EO (p < 0.05). Mast cell degranulation was enhanced by all HCO ethoxylates. The HCO-60-induced reaction was suppressed by an oral antihistamine. CONCLUSIONS AND CLINICAL RELEVANCE: The threshold concentration can serve as a consideration for developing safe new drug formulations and for clinical decision-making around using drugs containing PEG derivatives. IDT is useful to predict the risk of adverse effects. Antihistamines could demonstrate a prophylactic effect.

Atopy, allergen sensitization and development of hypersensitivity reactions to paclitaxel.

BACKGROUND: Paclitaxel is a chemotherapeutic agent used in the treatment of multiple types of malignant tumors which was discovered from the Taxus brevofilia tree. In some patients, anaphylaxis develops during the first exposure to paclitaxel, suggesting that primary sensitization may have occurred through hidden or unidentified allergens that produce cross-reactivity. Skin testing may be useful in identifying sensitization to these allergens. Atopy has also been reported in patients with hypersensitivity reactions (HSR) to paclitaxel.The aim of this study is to evaluate the association between atopy and sensitization to allergens with the development of immediate HSR to paclitaxel. METHODS: Skin prick tests (SPT) for environmental and food allergens were applied to 76 patients recently diagnosed with cancer. A SPT to paclitaxel was applied and if negative, an intradermal test was performed. After paclitaxel's infusion, the development of immediate HSR was observed. RESULTS: Of 76 skin tests, 43% of patients had allergen sensitization and 57% did not. HSR occurred in 12.1% and 11.6% of each group, respectively. Five percent of patients tested positive to paclitaxel and only one had an immediate HSR. Eighty-nine percent of patients who developed an HSR had a family or personal history of atopy. CONCLUSIONS: Sensitization to environmental or food allergens does not appear to be a risk factor for the development of immediate HSR to paclitaxel, suggesting that there are other non-IgE-mediated immunologic mechanisms responsible for their development, however, a personal and family history of atopy increases 8x the risk of developing anaphylaxis.

Characteristics and management of hypersensitivity reactions with rabbit anti-thymocyte globulin in pediatric patients.

Background: Anti-thymocyte globulin (ATG) has been successfully used for decades to prevent graft versus host disease before hematopoietic stem cell transplantation (HSCT) as a part of conditioning regimen. However, sometimes hypersensitivity reactions may limit its use. Objective: To evaluate hypersensitivity reactions experienced during rabbit-ATG infusion among children and present successful desensitization protocol. Methods: The medical records of pediatric patients who were given rabbit-ATG treatment at our tertiary center hospital HSCT unit between 2019 and 2022 were reviewed retrospectively. Diagnosis of the patients, age at the time of HSCT, gender, presence of hypersensitivity reaction to rabbit-ATG, and management were evaluated. Characteristics of the reaction and presence of hypersensitivity reaction to other drugs were also noted. If performed, desensitization protocols were evaluated retrospectively. Results: We evaluated 81 patients; 66.6% of them (n = 54) were boys. The mean age of the patients was 8.78 ± 5.48 years. Hypersensitivity to rabbit-ATG was seen in six patients (7.4%). Four of them (4.9%) had anaphylaxis; two (2.4%) had urticaria. Intradermal test performed to every patient before the first dose of ATG infusion was detected a positive result in 1 patient (1.2%) . None of these seven patients had allergic reactions to other drugs before. Successful ATG desensitization was performed in five patients by using a 12-16 step protocol due to patients' reaction severity. Conclusion: This study aimed to evaluate hypersensitivity reactions with rabbit-ATG in children. A successful desensitization protocol with rabbit-ATG is presented. Desensitization must be performed with an experienced team very carefully in the absence of alternative drug.

Pilot study to determine the concordance between skin prick and intradermal test (IDT) reactivity to environmental allergens in atopic dogs using IDT as the gold standard.

BACKGROUND: Prick testing is widely used as the first-line in vivo test for environmental allergens in people owing to its noninvasive nature and speed of performance. OBJECTIVES: To determine concordance between skin prick testing (SPT) and intradermal testing (IDT) reactivity to environmental allergen mixes in dogs with atopic dermatitis (cAD). ANIMALS: Forty client-owned dogs with cAD. MATERIALS AND METHODS: Skin prick testing (GREER Pick System; Stallergenes Greer) and IDT were performed on 40 dogs using seven glycerinated and aqueous environmental allergen mixes, respectively (tree, grass and weed pollens, house dust mites and three mould mixes). Reactions for IDT and SPT were evaluated both subjectively and objectively (mean wheal diameter; MWD) and compared to saline and histamine controls. RESULTS: Using IDT as the gold standard, with subjective scoring, SPT was 47.0% sensitive [95% confidence interval (CI) 36.0%-58.7%], 92.1% specific (95% CI 87.6%-95.3%) and agreement was moderate (79%, Cohen's kappa = 0.424). The positive predictive value of SPT was 36% and negative predictive value was 95%. Objective and subjective scores had only fair agreement. CONCLUSIONS AND CLINICAL RELEVANCE: Skin prick testing with allergen mixes was specific yet poorly sensitive as compared to IDT. For both IDT and SPT, 95% (38 of 40) dogs failed to react to an allergen mix, despite showing a positive reaction to at least one component. Future studies comparing SPT and IDT should test individual allergens rather than mixes to prevent the dilution of individual components, which may have resulted in false negatives.

Investigation of the diagnostic performance of prick test with two environmental allergens in dogs with atopic dermatitis: A study using intradermal test as the gold standard.

BACKGROUND: There are no studies investigating the correlation between prick test (PT) and intradermal test (IDT) with environmental allergens in dogs with atopic dermatitis (AD). OBJECTIVES: To investigate the correlation between PT and IDT for two environmental allergens, and to calculate the sensitivity, specificity and Youden index of PT, using IDT as the gold standard. MATERIALS AND METHODS: Twenty-two dogs with AD were selected. PT was performed with glycerinated allergen extracts, along with negative and positive controls, using the Greer Prick System. Reactions were interpreted (positive/negative) subjectively and by using seven objective criteria, by an examiner blinded to the IDT results. IDT reactions to the same allergens were interpreted, subjectively and objectively, by another masked investigator. The agreement between PT and IDT, the sensitivity, specificity and Youden index of PT, using IDT as gold standard, were calculated. RESULTS: On subjective evaluation, the correlation between PT and IDT was poor and sensitivity of PT was 0%. Of the seven criteria for the objective evaluation of PT, the best diagnostic performance was attained when allergen-induced wheals were considered positive if their longest diameter was ≥8.5 mm. However, even then, the correlation with IDT was moderate, and the sensitivity of PT, albeit based on few positive IDT reactions, was low. CONCLUSION AND CLINICAL RELEVANCE: At least as performed herein, PT has a poor-to-moderate correlation with IDT, mainly as a consequence of the lack of positive PT reactions. Further studies are needed to improve PT technique, yet, meanwhile, it cannot be recommended as a substitute for IDT.

Effect of glycerin on immediate cutaneous reactions of histamine (positive) and phosphate-buffered saline (negative) controls in intradermal skin testing of healthy dogs: A randomised, blinded study.

BACKGROUND: Glycerinated allergen extracts contain 50% glycerin, an excellent preservative. While glycerin is a recognised irritant in humans, the utility of glycerinated extracts for intradermal testing has not been validated in dogs. HYPOTHESIS/OBJECTIVE: To determine and compare the effects of glycerin on immediate cutaneous reactions to intradermal injections of histamine and saline in healthy dogs. ANIMALS: Eight healthy laboratory beagles. MATERIALS AND METHODS: The study was designed as a randomised, blinded study. Intradermal injections of histamine (positive control) and saline (negative control) in aqueous and glycerinated (50%) forms were performed on the right thorax. Global wheal scores (GWS) at 20 min were evaluated by two independent investigators blinded to the interventions. RESULTS: There were no wheal and flare reactions observed after the intradermal injections of phenolated saline. By contrast, 50% glycerosaline injections induced erythema and induration in all dogs. Global wheal scores were significantly higher in aqueous histamine (Friedman test, p < 0.0001) and 50% glycerinated histamine (Friedman test, p = 0.0084) compared to phenolated saline controls. Interestingly, only aqueous histamine (Friedman test, p = 0.01) had significantly higher GWS than 50% glycerosaline injections, while no significant difference in GWS between 50% glycerinated histamine and 50% glycerosaline groups was observed (Friedman test, p = 0.59). CONCLUSION AND CLINICAL RELEVANCE: This study demonstrates that intradermal injection of 50% glycerosaline induces erythema and induration skin reactions in healthy dogs that can mimic positive reactions to allergenic extracts. Further dilutions of glycerinated positive and negative control solutions need to be optimised for intradermal testing in dogs.

Insulin allergy: a diagnostic and therapeutic strategy based on a retrospective cohort and a case-control study.

AIMS/HYPOTHESIS: Insulin allergy is a rare but significant clinical challenge. We aimed to develop a management workflow by (1) validating clinical criteria to guide diagnosis, based on a retrospective cohort, and (2) assessing the diagnostic performance of confirmatory tests, based on a case-control study. METHODS: In the retrospective cohort, patients with suspected insulin allergy were classified into three likelihood categories according to the presence of all (likely insulin allergy; 26/52, 50%), some (possible insulin allergy; 9/52, 17%) or none (unlikely insulin allergy; 17/52, 33%) of four clinical criteria: (1) recurrent local or systemic immediate or delayed hypersensitivity reactions; (2) reactions elicited by each injection; (3) reactions centred on the injection sites; and (4) reactions observed by the investigator (i.e. in response to an insulin challenge test). All underwent intradermal reaction (IDR) tests. A subsequent case-control study assessed the diagnostic performance of IDR, skin prick and serum anti-insulin IgE tests in ten clinically diagnosed insulin allergy patients, 24 insulin-treated non-allergic patients and 21 insulin-naive patients. RESULTS: In the retrospective cohort, an IDR test validated the clinical diagnosis in 24/26 (92%), 3/9 (33%) and 0/14 (0%) likely, possible and unlikely insulin allergy patients, respectively. In the case-control study, an IDR test was 80% sensitive and 100% specific and identified the index insulin(s). The skin prick and IgE tests had a marginal diagnostic value. Patients with IDR-confirmed insulin allergy were treated using a stepwise strategy. CONCLUSIONS/INTERPRETATION: Subject to validation, clinical likelihood criteria can effectively guide diabetologists towards an insulin allergy diagnosis before undertaking allergology tests. An IDR test shows the best diagnostic performance. A progressive management strategy can subsequently be implemented. Continuous subcutaneous insulin infusion is ultimately required in most patients. CLINICALTRIALS: gov: NCT01407640.

Repeatability and reproducibility of the interpretation of intradermal test results in dogs with atopic dermatitis.

Background - There is lack of studies evaluating the repeatability and reproducibility of the interpretation of intradermal testing in dogs with atopic dermatitis (AD). Objectives - To evaluate the repeatability and reproducibility of the interpretation of intradermal test results in dogs with AD. For comparison, the repeatability of allergen-specific immunoglobulin (Ig)E serology also was examined. Materials and methods - Twenty dogs with AD were used. Intradermal test included injections of known negative and positive controls, and of 25 masked injections of 10 allergens/controls, that were selected randomly and injected at random positions. Reactions to the 25 masked allergens/controls were scored (positive/negative) subjectively by three independent examiners followed by an objective assessment. Allergen-specific IgE serology was performed in blinded duplicate samples collected from all dogs for nine of 10 of the same allergens. Results - Kappa values of intraobserver repeatability (≥2 injections of the same allergen to different positions of the same dog) varied between -0.53 and 0.8 (subjective evaluations), and between 0.03 and 1 (objective evaluation). When the repeatability of the serological test was examined k = 0.91. Kappa values for the interobserver reproducibility (objective and three subjective evaluations of the same allergen injected at the same position of the same dog) varied between 0.6 and 0.74 (overall 0.67). Conclusions and clinical relevance - Intraobserver repeatability of the subjective and objective evaluation of IDT results varied from good to poor and depended on the number of times the same allergen was injected, whereas interobserver reproducibility varied from substantial to moderate. Further studies are needed to optimise the repeatability and reproducibility of IDT in dogs.

Contexte - Il existe un manque d'études évaluant la répétabilité et la reproductibilité de l'interprétation des tests intradermiques chez les chiens atteints de dermatite atopique (DA). Objectifs - Évaluer la répétabilité et la reproductibilité de l'interprétation des résultats des tests intradermiques chez les chiens atteints de MA. À des fins de comparaison, la répétabilité de la sérologie de l'immunoglobuline (Ig)E spécifique de l'allergène a également été examinée. Matériels et méthodes - Vingt chiens atteints de MA ont été utilisés. Le test intradermique comprenait des injections de contrôles négatifs et positifs connus, et de 25 injections masquées de 10 allergènes/contrôles, qui ont été sélectionnés au hasard et injectés à des positions aléatoires. Les réactions aux 25 allergènes/contrôles masqués ont été notées (positives/négatives) subjectivement par trois examinateurs indépendants, suivies d'une évaluation objective. La sérologie IgE spécifique de l'allergène a été réalisée dans des échantillons en double en aveugle prélevés sur tous les chiens pour neuf des 10 allergènes identiques. Résultats - Les valeurs kappa de répétabilité intra-observateur (≥2 injections du même allergène à différentes positions du même chien) variaient entre -0,53 et 0,8 (évaluations subjectives), et entre 0,03 et 1 (évaluation objective). Lorsque la répétabilité du test sérologique a été examinée, k = 0,91. Les valeurs de Kappa pour la reproductibilité interobservateur (évaluations objective et trois évaluations subjectives du même allergène injecté au même endroit du même chien) variaient entre 0,6 et 0,74 (globalement 0,67). Conclusions et pertinence clinique - La répétabilité intra-observateur de l'évaluation subjective et objective des résultats IDT variait de bonne à mauvaise et dépendait du nombre d'injections d'un même allergène, alors que la reproductibilité inter-observateur variait de substantielle à modérée. D'autres études sont nécessaires pour optimiser la répétabilité et la reproductibilité de l'IDT chez le chien.

Introducción- faltan estudios que evalúen la repetibilidad y la reproducibilidad de la interpretación de las pruebas intradérmicas en perros con dermatitis atópica (AD). Objetivos- evaluar la repetibilidad y reproducibilidad de la interpretación de los resultados de las pruebas intradérmicas en perros con AD. A modo de comparación, también se examinó la repetibilidad de la serología de inmunoglobulina (Ig)E específica de alérgeno. Materiales y métodos - Se utilizaron 20 perros con AD. La prueba intradérmica incluyó inyecciones de controles positivos y negativos conocidos, y de 25 inyecciones enmascaradas de 10 alérgenos/controles, que se seleccionaron al azar y se inyectaron en posiciones aleatorias. Las reacciones a los 25 alérgenos/controles enmascarados fueron calificadas (positivas/negativas) subjetivamente por tres examinadores independientes seguido de una evaluación objetiva. La serología de IgE específica para alérgenos se realizó en muestras duplicadas ciegas recolectadas de todos los perros para nueve de 10 de los mismos alérgenos. Resultados - Los valores Kappa de repetibilidad intraobservador (≥2 inyecciones del mismo alérgeno en diferentes posiciones del mismo perro) variaron entre -0,53 y 0,8 (evaluaciones subjetivas) y entre 0,03 y 1 (evaluación objetiva). Cuando se examinó la repetibilidad de la prueba serológica k = 0,91. Los valores de Kappa para la reproducibilidad interobservador (objetivo y tres evaluaciones subjetivas del mismo alérgeno inyectado en la misma posición del mismo perro) variaron entre 0,6 y 0,74 (en general, 0,67). Conclusiones y relevancia clínica- la repetibilidad intraobservador de la evaluación subjetiva y objetiva de los resultados de la IDT varió de buena a mala y dependió del número de veces que se inyectó el mismo alérgeno, mientras que la reproducibilidad interobservador varió de sustancial a moderada. Se necesitan más estudios para optimizar la repetibilidad y reproducibilidad de IDT en perros.

Contexto - Há poucos estudos avaliando a repetibilidade e reprodutibilidade da interpretação do teste intradérmico em cães com dermatite atópica (DA). Objetivos - Avaliar a repetibilidade e reprodutibilidade da interpretação dos resultados de testes intradérmicos em cães com DA. Para comparação, a repetibilidade da sorologia com imunoglobulinas (Ig)E alérgeno-específicas foi também avaliada. Materiais e métodos - Foram utilizados 20 cães com DA. O teste intradérmico incluiu injeções de controles negativos e positivos conhecidos e de 25 injeções mascaradas de 10 alérgenos/controles, que foram selecionados aleatoriamente e injetadas em posições aleatórias. As reações aos 25 alérgenos/controles mascarados foram pontuadas (positiva/negativa) subjetivamente por três examinadores independentes, seguidas de uma avaliação objetiva. A sorologia de IgE específica para alérgenos foi realizada em amostras duplicadas cegas coletadas de todos os cães para nove de 10 dos mesmos alérgenos. Resultados - Os valores Kappa de repetibilidade intraobservador (≥2 injeções do mesmo alérgeno em diferentes posições do mesmo cão) variaram entre -0,53 e 0,8 (avaliação subjetiva) e entre 0,03 e 1 (avaliação objetiva). Quando examinada a repetibilidade do teste sorológico k=0,91. Os valores de Kappa para a reprodutibilidade interobservador (objetiva e três avaliações subjetivas do mesmo alérgeno injetado na mesma posição do mesmo cão) variaram entre 0,6 e 0,74 (total 0,67). Conclusões e relevância clínica - A repetibilidade intraobservador da avaliação subjetiva e objetiva dos resultados do IDT variou de boa a ruim e dependeu do número de vezes que o mesmo alérgeno foi injetado, enquanto a reprodutibilidade interobservador variou de substancial a moderada. Mais estudos são necessários para otimizar a repetibilidade e reprodutibilidade do IDT em cães.

THE USE OF INTRADERMAL SKIN TESTING AND HYPOSENSITIZATION INJECTIONS TO CONTROL SEASONAL DERMATITIS IN GREATER ONE-HORNED RHINOCEROSES (RHINOCEROS UNICORNIS).

Allergic dermatitis was diagnosed in a 25-yr-old female greater one-horned rhinoceros (Rhinoceros unicornis) and her 6-yr-old female offspring by skin biopsy, intradermal skin testing (IDST), and allergen-specific serum IgE testing. Dam and offspring presented with seasonal, erosive, and ulcerative dermatitis affecting the face, legs, and trunk starting at 6 and 2 yr of age, respectively. IDST was performed at the caudal pinnal base using 61 regionally specific allergens. Specific serum allergen responses were detected using Heska's Equine ALLERCEPT® Allergen Panel. Histopathology of the lesions was consistent with an allergic etiology. Injectable allergen-specific immunotherapy was initiated in both animals and within 6 to 18 mon after commencing hyposensitization clinical improvement was noted. This report documents a repeatable methodology for IDST and serological allergen testing for use in rhinoceroses. The hyposensitization protocol detailed here can help guide future treatment protocols.

Delayed hypersensitivity to antiepileptic drugs in children.

BACKGROUND: Antiepileptic drugs (AEDs) are widely used for the treatment of epilepsy, but they can be associated with the development of mainly delayed/non-immediate hypersensitivity reactions (HRs). Although these reactions are usually cutaneous, self-limited, and spontaneously resolve within days after drug discontinuation, sometime HR reactions to AEDs can be severe and life-threatening. AIM: This paper seeks to show examples on practical management of AED HRs in children starting from a review of what it is already known in literature. RESULTS: Risk factors include age, history of previous AEDs reactions, viral infections, concomitant medications, and genetic factors. The diagnostic workup consists of in vivo (intradermal testing and patch testing) and in vitro tests [serological investigation to exclude the role of viral infection, lymphocyte transformation test (LTT), cytokine detection in ELISpot assays, and granulysin (Grl) in flow cytometry. Treatment is based on a prompt drug discontinuation and mainly on the use of glucocorticoids. CONCLUSION: Dealing with AED HRs is challenging. The primary goal in the diagnosis and management of HRs to AEDs should be trying to accurately identify the causal trigger and simultaneously identify a safe and effective alternative anticonvulsant. There is therefore an ongoing need to improve our knowledge of HS reactions due to AED medications and in particular to improve our diagnostic capabilities.

Pilot study of dogs with suppurative and non-suppurative Malassezia otitis: A case series.

BACKGROUND: Rarely, Malassezia otitis presents as a painful, erosive otitis with an otic discharge containing Malassezia and neutrophils on cytology. There are no published reports of this type of suppurative Malassezia otitis (SMO). The role of Malassezia hypersensitivity in otitis is still unknown, and no association has been demonstrated with SMO. We compared Malassezia IgE levels, intradermal test and histology changes in SMO dogs with the more conventional Malassezia otitis (MO) presentation. RESULTS: Three dogs (case 1, case 2 and case 3) were diagnosed with SMO, one dog (case 4) was diagnosed with unilateral MO and unilateral SMO, and one dog (case 5) was diagnosed with MO. Only one case (case 4) with SMO/MO had a positive Intradermal Allergy Test (IDAT) and elevated IgE levels for Malassezia. Histopathology findings from SMO revealed: interface dermatitis (case 1 and 3), lymphocytic dermatitis (case 2) and chronic hyperplastic eosinophilic and lymphoplasmacytic dermatitis (case 4). Histopathology findings from MO showed perivascular dermatitis (case 4 and 5). All the cases were treated successfully. CONCLUSIONS: SMO presents with a distinct clinical phenotype in comparison with conventional MO. No consistent aetiology could be isolated. In these clinical cases it is possible that previous treatments could have influenced the results. More research is needed to understand the possible aetiologies and the pathogenesis of SMO.

Intradermal testing for autoimmune progesterone dermatitis: should we be basing the diagnosis on it?

Autoimmune progesterone dermatitis (APD) is a rare skin disorder with varying presentations, resulting from hypersensitivity to endogenous progesterone during the luteal phase of the menstrual cycle. The diagnosis has been traditionally confirmed with intradermal progesterone testing (IPT) or intramuscular challenge with progesterone or its derivatives. We present a case of a 31-year-old woman with suspected APD who underwent IPT to progesterone. The patient's cyclical symptoms, positive skin reaction and symptoms following IPT were sufficient to make a diagnosis of APD. However, we also tested 10 healthy female controls without symptoms of APD, and found that 9 of these also developed positive skin reactions to intradermal progesterone at 15 min, 24 and 48 h, albeit to a lesser extent. Therefore, these results raise doubts about the validity of using IPT to make a diagnosis of APD. Further research on appropriate testing is needed.

Immunological response and clinical profile in patients with recurrent dermatophytosis.

BACKGROUND: An alarming increase in the number of patients with chronic and recurrent dermatophytosis has invoked the need to study the immunological parameters of the host. OBJECTIVES: To evaluate delayed type of hypersensitivity (DTH) response and immediate hypersensitivity (IH) response by flow cytometry evaluation of immune cells from peripheral blood and intradermal trichophyton skin test in patients with recurrent dermatophytosis. METHODS: A hundred patients with recurrent dermatophytosis and 50 controls (healthy controls and acute dermatophytosis controls) were included. Relevant risk factors for recurrence were analysed, and serum IgE levels were estimated. Flow cytometry evaluation of immune cells in peripheral blood and intradermal trichophyton skin test was done. Dermatophyte pathogens were isolated, and antifungal susceptibility was performed. RESULTS: Trichophyton mentagrophytes complex (95.84%) and T. rubrum (4.16%) were isolated in culture. Serum IgE was elevated in 83.15% cases (p = .01). IFN-γ+ cells (p = .0501, p = .0001, p = .0014), Th1 cells (p = .1197, p = .0024, p = .0169), IL-17+ cells (p = .0127, p = .0006, p = .0007) and Th17 cells (p = .0634, p = .0001, p = .0054) were reduced, and IL-4+ cells (p = .0108, p = .0175, p = .0018) were increased in cases. Intradermal test demonstrated negative DTH response in all cases (p < .001, p < .001, p < .001), strongly positive IH response in 6%, and borderline positive IH response in 85% cases (p = .018, p < .001, p < .001). Topical corticosteroids application, undergarment types (tight fit), poor frequency of washing clothes, family history of tinea, sharing of towels were significant risk factors for recurrent dermatophytosis. CONCLUSIONS: Reduced IFN-γ+ , Th1, IL-17+ and Th17 cells population along with impaired DTH response by the intradermal test was observed in patients with recurrent dermatophytosis.

Rapid desensitization to brentuximab vedotin after severe anaphylaxis in the treatment of refractory Hodgkin's lymphoma.

INTRODUCTION: Brentuximab vedotin is a monoclonal antibody drug conjugate used for the treatment of patients with Hodgkin lymphoma. Hypersensitivity reactions to brentuximab vedotin may include cutaneous, cardiovascular, respiratory, gastrointestinal and neurological signs and symptoms. CASE REPORT: We present the case of a 23-year-old Mexican female with stage IV progressive classical nodular sclerosing Hodgkin lymphoma who received multiple previous chemotherapy regimens. Brentuximab vedotin at 1.8 mg/kg (180 mg total dose), for 21-day cycles was indicated. Within 5 min of infusion of the 5th cycle of brentuximab, she developed severe anaphylaxis (hives, angioedema, diaphoresis, tachycardia, dyspnea, hypoxemia and loss of consciousness), which was successfully controlled with epinephrine, steroids and antihistamines.Management and outcome: Intradermal skin test at a concentration of 0.1 mg/ml was positive. Due to the severity of the symptoms and the lack of access to alternative treatments, we performed a desensitization protocol. A total of 180 mg of brentuximab was given in three bag solutions in 12 steps, with an initial concentration dose of 1/100 of the total dose in a course of 5.56 h with no hypersensitivity reactions. DISCUSSION: Severe anaphylaxis has been reported in 1.2% of patients receiving brentuximab vedotin. Patients who are treated by rapid drug desensitization with their first option therapy present a favorable survival rate with better cost-effectiveness in comparison to second-line treatment.

Safety and efficacy of direct two-step penicillin challenges with an inpatient pharmacist-driven allergy evaluation.

Background: Penicillin allergy is commonly reported and has clinical and financial consequences for patients and hospitals. A penicillin evaluation program can safely delabel patients and optimize antibiotic therapy. Pharmacists who perform this task have focused on a detailed interview or penicillin skin testing (PST). Antibiotic graded challenge after PST requires more resources and is more costly than going directly to a two-step challenge. Objective: To determine whether a pharmacist-driven penicillin allergy evaluation and a testing protocol that primarily uses direct oral challenges can safely delabel patients. Methods: Adult patients (ages >18 years) with a penicillin allergy in their electronic medical record (EMR) who were admitted between September 2019 and June 2020 were eligible. Although all patients with penicillin allergy were eligible, priority was given to patients who required antibiotics. Patients were interviewed, and, if indicated, based on an institutional protocol, were tested by using PST and/or two-step oral challenge. If the patient passed the challenge, then the penicillin allergy label was removed in the EMR and the patient counseled. Demographic information, allergy questionnaire results, testing results, and changes in antimicrobial therapy were collected. Results: Fifty patients were evaluated from September 2019 to June 2020. Ninety-six percent of the patients were delabeled, and antibiotic therapy changed for 54%. Twenty patients were delabeled with an interview alone, and 30 patients underwent oral two-step challenge. Only one patient required PST. Conclusion: A pharmacist-driven penicillin allergy evaluation program focused on direct oral graded challenges and bypassing PST can effectively delabel admitted patients. However, more safety data are needed before implementation of similar programs to optimize antibiotic treatment.

Immediate local anesthetic reactions and diagnostic test results in pediatric patients.

BACKGROUND/OBJECTIVES: Adverse reactions to local anesthetics are relatively common, but proven IgE-mediated allergy is extremely rare. We aimed to determine the frequency of local anesthetic allergy in pediatric patients. PATIENTS AND METHODS: The medical records of 73 patients who presented to our clinic with a history of suspected allergic reaction to local anesthetics and underwent diagnostic testing between 2012 and 2020 were retrospectively analyzed. Diagnoses were based on case histories, skin tests, and subcutaneous challenge tests. RESULTS: A total of 75 test series were carried out on the 73 patients (43 boys; median [IQR] age 9.25 [7.26-14.25] years, range 3-17.8 years). The most commonly tested drugs were lidocaine (n = 38; 50.6%) and prilocaine (n = 15; 20%). Local anesthetic allergy was confirmed in one (1.3%) of the 73 patients by positive subcutaneous challenge test with mepivacaine. CONCLUSION: There are limited data in the current literature regarding local anesthetic allergies and diagnosis test results in pediatric patients. Proven local anesthetic allergy is less common than expected by society and physicians, and therefore diagnostic tests are needed for patients with no contra-indications such as severe or life-threatening reactions.