Expert opinion: The clinical usefulness of skin tests prior to the administration of beta-lactam antibiotics

An allergy skin test is used to diagnose certain allergies by identifying sensitized allergens. In other words, it is a test for patients who are already sensitized to certain allergens. Because of the prevailing perception that beta-lactam allergy can be dangerous and potentially lethal, the intradermal test has long been routinely performed before use to screen beta-lactam allergy in Korea. The prevalence of penicillin allergy is estimated to be 1% to 2%. However, only 14% of the subjects with perceived penicillin allergy is considered to have true penicillin allergy. Moreover, it is difficult to justify performing a skin test on subjects who are very unlikely to be sensitized to beta-lactam, such as those who never used beta-lactam or never experienced allergy after previous use of beta-lactam.Therefore, allergists recommend beta-lactam skin testing in those who have allergy after the use of beta-lactam. Nevertheless, many hospitals in Korea are conducting routine skin tests on patients regardless of a history of beta-lactam allergy, which are not clinically validated but consume considerable human and material resources. False-positive results can consequently result in inappropriate labeling of beta-lactam allergy, leading to the unnecessary restriction of medication prescriptions and the increase in medical expenses. Herein, the drug allergy working group affiliated with the Korean Academy of Asthma, Allergy, and Clinical Immunology announces an expert opinion on the preuse beta-lactam skin test for subjects without a history of beta-lactam allergy based on the objective evidence from the literature and clinical relevance.

Validation of a Multiplex Assay for Measuring Specific IgG4

Purpose@#Specific IgG4 (sIgG4) increases with allergen specific immunotherapy and may reflect a state of immune tolerance in food allergy. While ImmunoCAP® has been widely used to measure sIgG4 to a single allergen, PROTIATM Specific IgG4® has been designed as a multiplex assay for measuring sIgG4. This study sought to validate this assay in comparison to ImmunoCAP®. @*Materials and Methods@#Measurements of sIgG4 were compared between PROTIATM Specific IgG4® and ImmunoCAP® using sera from 519 allergy patients (asthma: 114, allergic rhinitis: 318, food allergy: 146) with 731 paired tests. sIgG4 was measured against nine inhalant allergens (Dermatophagoides pteronyssinus, Dermatophagoides farinae, cat dander, dog dander, birch pollen, oak pollen, ragweed pollen, mugwort pollen, and Alternaria alternata spores) and nine food allergens (egg white, casein, wheat, peanut, walnut, crab, shrimp, apple, and peach). @*Results@#PROTIATM Specific IgG4® showed 95.6% agreement rate with ImmunoCAP® in the positivity comparison. For sIgG4 positivity to each individual allergen, an agreement rate of more than 84.8% was observed. In Cohen’s kappa analysis, these assays displayed substantial correlations [Cohen’s kappa coefficient (κ) ≥0.699], except for shrimp (κ=0.448). Furthermore, both assays displayed strong correlations in quantitative comparisons [correlation coefficients value (ρ) ≥0.8014], except for apple (ρ=0.6571, p=0.175). Serial dilution tests also showed consistency between the assays. @*Conclusion@#PROTIATM Specific IgG4® showed high consistency with ImmunoCAP® in measuring sIgG4. This assay is applicable to various clinical fields, including allergen immunotherapy and food allergy.

Effects of Air Purifiers on Patients with Allergic Rhinitis: a Multicenter, Randomized, Double-Blind, and Placebo-Controlled Study

Purpose@#Exposure to particulate matter (PM) is a well-known risk factor in the triggering and exacerbation of allergic airway disease. Indoor environments, where people spend most of their time, are of utmost importance. To assess the effects of air purifiers [equipped with high-efficiency particulate air (HEPA) filters] on allergic rhinitis (AR) in adult patients, we performed a multicenter, randomized, double-blind, and placebo-controlled study. @*Materials and Methods@#Patients with house dust mite (HDM)-induced AR were randomly assigned to either active or mockup (placebo) air-purification groups. Two air purifiers (placed in living room and bedroom) were operated for 6 weeks in each home environment. The primary study endpoint was to achieve improvement in AR symptoms and medication scores. Secondary endpoints were to achieve improvement in the quality of life (QoL) and visual analog scale (VAS) scores, as well as in the indoor (bedroom and living room) concentrations of PM2.5 and PM10. @*Results@#After 6 weeks of air purifier use, medication scores improved significantly in the active (vs. placebo) group, although subjective measures (symptoms, VAS, and QoL scores) did not differ. Bedroom PM2.5 concentrations initially exceeded living room or outdoor levels, but declined (by up to 51.8%) following active purifier operation. Concentrations of PM2.5 in living room and PM10 in bedroom and living room were also significantly reduced through active purification. @*Conclusion@#The use of air purifiers with HEPA filters significantly reduced medication requirements for patients with HDM-induced AR and significantly lowered indoor PM2.5 concentrations, regardless of room placement. Active intervention to reduce household air pollutants may help improve allergic airway disease (clinicaltrials.gov NCT03313453).

Biologic agents for asthma treatment

Most treatment strategies for asthma currently include inhaled corticosteroids, with the addition of long-acting beta-2-agonists or leukotriene modifiers, if necessary. However, some patients may not respond to conventional treatment. A better understanding of the pathophysiology of asthma has recently led to the development of biological agents, which have shown promising results for symptom control and future risk reduction in severe asthmatics. This article reviews currently available biologic agents, introduces related studies, and describes the subgroup of patients benefitting from each of biologic agents in the view point of precision medicine.

Validation of PROTIA™ Allergy-Q 64 Atopy® as a Specific IgE Measurement Assay for 10 Major Allergen Components

PURPOSE: Component-resolved diagnostics (CRD) is expected to provide additional diagnostic information in allergic patients. PROTIA™ Allergy-Q 64 Atopy®, a recently developed CRD-based multiplex specific immunoglobulin E (sIgE) assay, can quantitatively measure sIgE to major allergen components. METHODS: The sIgE detection by PROTIA™ Allergy-Q 64 Atopy® and ImmunoCAP® assays was compared using the sera of 125 Korean allergic patients. Group 1 and 2 allergens of house dust mites (HDMs; Dermatophagoides farinae (Der f) 1 and Der f 2 in PROTIA™ Allergy-Q 64 Atopy®, Dermatophagoides pteronyssinus (Der p) 1 and Der p 2 in ImmunoCAP®), Bet v 1, Fel d 1, Que a 1, ω-5 gliadin, α-lactalbumin, β-lactoglobulin, casein and α-Gal were measured by both assays. RESULTS: Comparing the results from the 2 assays, the agreement rate for all the 10 allergens was > 88% (group 1 HDM allergen, 100%; group 2 HDM allergen, 94.6%; Bet v 1, 97.4%; Fel d 1, 90.5%; Que a 1, 89.2%; α-lactalbumin, 96%; β-lactoglobulin, 88%; casein, 88%; ω-5 gliadin, 96%; α-Gal, 100%). Correlation analysis indicated that, all the 10 allergen sIgEs showed more than moderate positive correlation (Pearson correlation coefficients > 0.640). Additionally, intra-class comparison showed more than high correlation for all the 10 allergens (Spearman's rank correlation coefficients > 0.743). CONCLUSIONS: PROTIA™ Allergy-Q 64 Atopy® is reliable and comparable to the ImmunoCAP® assay for component-resolved diagnosis.

Eperisone-Induced Anaphylaxis: Pharmacovigilance Data and Results of Allergy Testing

PURPOSE: Eperisone is an oral muscle relaxant used in musculoskeletal disorders causing muscle spasm and pain. For more effective pain control, eperisone is usually prescribed together with nonsteroidal anti-inflammatory drugs (NSAIDs). As such, eperisone may have been overlooked as the cause of anaphylaxis compared with NSAIDs. This study aimed to analyze the adverse drug reaction (ADR) reported in Korea and suggest an appropriate diagnostic approach for eperisone-induced anaphylaxis. METHODS: We reviewed eperisone-related pharmacovigilance data (Korea Institute of Drug Safety-Korea Adverse Event Reporting System [KIDS-KAERS]) reported in Korea from 2010 to 2015. ADRs with causal relationship were selected. Clinical manifestations, severity, outcomes, and re-exposure information were analyzed. For further investigation, 7-year ADR data reported in a single center were also reviewed. Oral provocation test (OPT), skin prick test (SPT) and basophil activation test (BAT) were performed in this center. RESULTS: During the study period, 207 patients had adverse reactions to eperisone. The most common ADRs were cutaneous hypersensitive reactions (30.4%) such as urticaria, itchiness or angioedema. Fifth common reported ADR was anaphylaxis. There were 35 patients with anaphylaxis, comprising 16.9% of the eperisone-related ADRs. In the single center study, there were 11 patients with eperisone-induced anaphylaxis. All the patients underwent OPT and all the provoked patients showed a positive reaction. Four of the 11 patients with anaphylaxis also underwent SPT and BAT, which were all negative. CONCLUSIONS: Incidence of eperisone-induced anaphylaxis calculated from the KIDS-KAERS database was 0.001%. Eperisone can cause hypersensitive reactions, including anaphylaxis, possibly by inducing non-immunoglobulin E-mediated immediate hypersensitivity.

Clinical Features and Culprit Food Allergens of Korean Adult Food Allergy Patients: A Cross-Sectional Single-Institute Study

PURPOSE: To investigate the causative allergens and clinical characteristics of Korean adult patients with food allergy (FA). METHODS: This retrospective, cross-sectional single-institutional study enrolled Korean adult patients (n = 812) suspected of having FA. For diagnosis, causality assessment history taking, ImmunoCAP specific immunoglobulin E measurement and/or skin prick test were performed. RESULTS: Among 812 patients, 415 were diagnosed as having FA. The most common causative allergen was fruit, with a diagnosis of pollen food allergy syndrome (PFAS: 155, 37.3%), followed by crustaceans (111, 26.7%), wheat (63, 15.1%), fruits in patients without PFAS(43, 10.3%), buckwheat (31, 7.4%), peanut (31, 7.4%), walnut (25, 6.0%), red meat due to reaction to galactose-α-1,3-galactose (α-Gal) (8, 1.9%), and silkworm pupa (13, 3.1%). Allergy to egg, milk, fish, or shellfish was rare in Korean adults. One-third of patients with FA exhibited multiple FAs (238/415, 57.3%); the average number of causative allergens was 2.39. About 129 patients (31.0%) were diagnosed as having anaphylaxis; in these patients, wheat was the most frequent causative food. Twenty patients were further diagnosed with food-dependent exercise-induced anaphylaxis (FDEIA); all were due to wheat. In particular, crustaceans, wheat, PFAS, buckwheat, and red meat (α-Gal) were also frequent causes of anaphylaxis. CONCLUSIONS: Wheat, fruits with or without PFAS, and crustaceans are important and frequent causative allergens in Korean adult FA; these allergens differ from those found in childhood FA. It is notable that non-classic allergies, such as PFAS, FDEIA, and α-Gal allergy, are the important causes of anaphylaxis in Korean adult FA.

IgE Sensitization Patterns to Commonly Consumed Foods Determined by Skin Prick Test in Korean Adults

Offending food allergens can vary with regional preferences in food consumption. In this study, we analysed sensitization rates to commonly consumed foods in Korean adults suspected of having food allergy. One hundred and thirty four subjects underwent a skin prick test (SPT) with 55 food allergens, of which 13 were made by our laboratory and the rest were commercially purchased. Of the 134 patients, 73 (54.5%) were sensitized to one or more food allergens. Sensitization to chrysalis was detected most frequently, at a rate of 25.4%. Sensitization rates to other food allergens were as follows: maize grain (13.4%), shrimp (11.9%), almond (11.1%), wheat flour (8.2%), lobster (8.2%), buckwheat (8.2%), mackerel (5.2%), pollack (5.2%), halibut (4.5%), peanut (4.5%), anchovy (4.4%), squid (3.7%), saury (3.0%), common eel (3.0%), yellow corvina (3.0%), hairtail (2.2%), octopus (2.2%), and others. In addition to well-known food allergens, sensitivity to mackerel, chrysalis, pollack, and halibut, which are popular foods in Korea, was observed at high rates in Korean adults. We suggest that the SPT panel for food allergy in Korea should include these allergens.

Critical pathway of acute asthma attack for the Emergency Center: patients' outcomes and effectiveness

PURPOSE: Early recognition and management of asthma attack is critical before it becomes worse. We developed critical pathway (CP) of asthma attack at Emergency Center (EC) for making undelayed decision and management of asthma attack. METHODS: Acute asthma attack assessment and treatment (4AT) CP began on April 1st 2012 and recruited the patients for 18 months. This study enrolled the patients who were older than 15 years and visited EC for dyspnea and wheezing. Initial assessment was done measuring peak expiratory flow rate (PEFR), oxygen saturation (SaO2). Once CP is activated, oxygen, inhalation of short acting beta2 agonist, and injection of corticosteroid were administered to the patients. Every hour after CP activated, we reassess the patients' response and make decisions whether to admit or discharge. RESULTS: Until January 10th 2014, 62 patients enrolled in this study. Seven patients hospitalized for asthma and 40 patients discharged. The other 15 patients were deactivated as they were diagnosed of heart failure, myocardial infarction, aortic dissection, anaphylaxis, chronic obstructive pulmonary disease and pneumonia for the causes of dyspnea. Mean Interval from EC arrival to 4AT activation was 32.6+/-29.1 minutes and the mean interval from 4AT activation to position decision was 254.5+/-302.0 minutes. Among 47 patients who were diagnosed with asthma attack, 13 patients were not aware of asthma before this attack. Forty patients were discharged at EC after management of CP. Among them, 34 patients revisited clinic, but 6 patients did not. We called back to the lost 6 patients but only 3 patients were connected. Even they visited EC due to asthma attack, 2 patients had no insight of importance of regular management and the other one promised to revisit. CONCLUSION: CP was successful for early management of asthma attack. However, 15% of discharged patients never show up again. So, education program about the importance of ongoing management of asthma for prevention of asthma attack is needed.

A Case of Azathioprine Induced Warfarin Resistance in Behcet's Disease

Behcet's disease is characterized by recurrent oral aphthous ulcers, genital ulcers, uveitis, and skin lesions. Thrombosis associated with vascular inflammation in patients with Behcet's disease presents various clinical symptoms. Warfarin is usually administered for treatment of thrombosis. However, warfarin can interact with many medications that cause various problems. A 43-year-old woman with Behcet's disease presented with a swollen right leg. Deep vein thrombosis (DVT) was confirmed, and treated with warfarin. Due to exacerbation of Behcet's disease, she received azathioprine along with warfarin. Subsequently, the international normalized ratio (INR) decreased and DVT was exacerbated. Despite an increase in the warfarin dose, the patient did not reach the target INR. After discontinuation of azathioprine, DVT improved and the warfarin dose was decreased. There were no specific findings associated with a hypercoagulable status. This finding suggests the interaction of azathioprine and warfarin. Therefore, clinicians should be cautious regarding the possibility of drug interactions between azathioprine and warfarin.

Drug-Induced Anaphylaxis in a Single Korean Tertiary Hospital / 대한내과학회지

BACKGROUND/AIMS: Drug-induced anaphylaxis (DIA) is a severe, acute, and potentially life-threatening condition. In Korea, only a few well-documented cases of DIA have been described. Therefore, the aim of this study was to investigate the clinical characteristics, causes, and management of DIA in a single Korean medical institute. METHODS: This was a retrospective medical record review of all DIA patients who visited the in-patient, out-patient, and emergency departments of our hospital from January 1 2006 to October 30 2013. RESULTS: Among 605 cases of anaphylaxis, 167 were drug-induced. The culprit drugs were contrast agents (43 cases, 25.7%), antibiotics (38, 22.8%), non-steroidal anti-inflammatory drugs (35, 21.0%), anti-cancer drugs (22, 13.2%), parenteral vitamins (9, 5.4%), ranitidine (6, 3.6%), and neuromuscular blockers (3, 1.8%). The most common organ-specific symptoms/signs were cardiovascular (74.3%), cutaneous (71.3%), respiratory (55.7%), and gastrointestinal manifestations (19.2%). In most cases, DIA was treated with antihistamines (77.2%) and systemic corticosteroids (76.5%); the use of epinephrine was considerably less frequent (35.3%). CONCLUSIONS: In our institution, contrast agents were the leading cause of DIA. Although epinephrine is the drug of choice in the treatment of acute anaphylaxis, fewer than 50% of the study patients received epinephrine to treat DIA.

Adverse drug reactions after taking the extract of Cudrania tricuspidata

Cudrania tricuspidata is a deciduous tree belonging to the Moraceae plant, which has been widely used as a folk remedy or health supplements in the Asian countries including Korea. As far as we know, side effects from taking the extract of C. tricuspidata has not yet been reported. We reviewed the electronic medical records of 2 patients who had adverse drug reactions to C. tricuspidata. The first case was a 30-year-old woman without a specific medical history. She was admitted with a 2-week history of jaundice and dyspepsia after taking extract of C. tricuspidata for 3 days. Initial laboratory findings were as follows: aspartate aminotransferase, 364 IU/L; alanine aminotransferase, 574 IU/L; total bilirubin, 36.3 mg/dL; and direct bilirubin, 18.3 mg/dL. She was conservatively treated for liver and renal failure while awaiting liver transplantation. However, she was expired due to combined pneumonia and progressed hepatic and renal failure. The second case was a 42-year-old woman who has chronic urticaria without other medical history. She was admitted with a 3-month history of whole body rash with small pustular vesicle after taking extract of C. tricuspidata. She was treated with intravenous steroids and antihistamines. Skin lesions were improved after 1 week. Here, we report 2 cases of adverse drug reaction to C. tricuspidata. It should be considered that C. tricuspidata ingestion could cause severe adverse drug reactions such as liver failure and acute generalized exanthematous pustulosis.