Chlorpheniramine-induced anaphylaxis diagnosed by basophil activation test

Chlorpheniramine is a widely prescribed H1-antihistamine for relieving urticaria or histamine-mediated allergic reactions. However, although rare, it may cause immediate hypersensitivity reactions. The diagnosis is usually made by provocation test, but its application is often limited due to comorbidities or potential risk of severe reactions. In those cases, skin tests and basophil activation tests can be considered as additional diagnostic tests for the drug allergy. Here, we report a 33-year-old female with underlying chronic urticaria, who recurrently developed anaphylaxis after chlorpheniramine administration. Intradermal test showed positive responses in the patient at 0.02 mg/mL of chlorpheniramine, but not in healthy controls. Basophil activation test showed significant up-regulation of CD63 and CD203c by chlorpheniramine. The present case reminds the rare but potential allergic risk of chlorpheniramine, and also suggests the potential utility of basophil activation test in making the diagnosis.

Predictors of the Severity and Serious Outcomes of Anaphylaxis in Korean Adults: A Multicenter Retrospective Case Study

PURPOSE: Differences in definitions of the condition, relevant triggers, and the geographical locations of study centers, cause estimates of the prevalence of anaphylaxis to vary. Recent epidemiological data indicate that the incidence of anaphylaxis is rising. METHODS: To investigate the causes and clinical features of anaphylaxis in Korean adults, factors associated with the severity of the condition, and serious outcomes, a retrospective medical record review was performed on adult patients diagnosed with anaphylaxis between 2007 and 2011 in 15 University Hospitals of South Korea. RESULTS: A total of 1,806 cases (52% male, age 16-86 years) were reported. Cutaneous symptoms (84.0%), combined with respiratory (53.9%) and/or cardiovascular (55.4%) symptoms, were the most frequent presentations. Using a recognized grading system, 1,776 cases could be classified as either mild, 340; moderate, 690; or severe, 746. Although eliciting factors varied significantly by age, gender, and regional and seasonal factors, drugs (46.5%; including nonsteroidal anti-inflammatory drugs, antibiotics, and radiocontrast media) were the most common cause of anaphylaxis, followed by foods (24.2%), insect stings (16.4%), exercise (5.9%), and unknown etiology (7.0%). All of age, multi-organ involvement, a history of allergic disease, and drug-induced anaphylaxis, were significant predictors of serious outcomes requiring hospital admission or prolongation of hospital stay. Epinephrine auto-injectors were prescribed for 7.4% of reported cases. CONCLUSIONS: The principal causes of anaphylaxis in Korean adults were drugs, food, and insect stings. Drug-associated anaphylaxis, a history of allergic disease, multi-organ involvement, and older age, were identified as predictors of serious outcomes.

Seasonal and regional variations in the causes of anaphylaxis in Korean adults

PURPOSE: To investigate whether causes of anaphylaxis vary according to regions and seasons in Korean adults. METHODS: Based on previous retrospective studies of anaphylaxis between 2007 and 2011 at the 15 university hospitals. Regions were classified into 4 groups: region I, Seoul; region II, Gyeonggi; region III, Chungcheong; and region IV, Chonnam and Busan. The cases induced by 5 major allergens including drugs, food, bee sting, radiocontrast media, and exercise, were analyzed in the present study. RESULTS: Among a total of 1,661 cases reported (53% male, 45.9+/-16.0 years), 367 (22.2%), 706 (42.5%), 319 (19.2%), and 269 cases (16.2%) were enrolled in regions I, II, III, and IV, respectively. Of the 5 major allergens, drugs (37.3%) were the most frequently reported, followed by food (25.7%), bee sting (17.9%), radiocontrast media (12.9%), and exercise (6.2%). There was no significant difference in the total occurrence of anaphylaxis in 4 seasons (374 in spring, 460 in summer, 460 in autumn, and 367 in winter). Multiple logistic regression analysis revealed that drug-induced anaphylaxis was significantly associated with the winter season (odds ratio [OR] 1.0 vs. OR 0.597, P<0.05 for spring; OR 1.0 vs. OR 0.481, P<0.01 for summer; OR 1.0 vs. OR 0.653, P<0.05 for autumn). Food-associated anaphylaxis was mainly reported in region I, whereas the frequency of insect sting was relatively higher in regions II, III, and IV than in region I. Older age and female gender were significantly associated with drug-induced anaphylaxis. CONCLUSION: Specific causative allergens of anaphylaxis in adults may vary according to age, gender, region, and season in Korea.

Erratum: Reference Correction. Updates on desensitization for hypersensitivity reactions related to chemotherapy

There was reference error in references section (p.302, reference #45).

Hymenoptera venom anaphylaxis in adult Korean: a multicenter retrospective case study

PURPOSE: We investigated the causes, clinical features, and risk factors of bee venom anaphylaxis in Korea. METHODS: The medical records of the diagnosis of anaphylaxis during a 5-year period from the 14 hospitals in Korea have been retrospectively reviewed. Cases of bee venom anaphylaxis were identified among anaphylaxis patients, and subgroup analyses were done. RESULTS: A total of 291 patients were included. The common cause of bee species was vespid (24.6%) in bee venom anaphylaxis, followed by honeybee and vespid (8.8%), apitherapy (7.7%), and honeybee (2.0%), although the causative bee species were commonly unknown (56.9%). The severity of anaphylaxis was mostly mild-moderate (72.9%), and common clinical manifestations included cutaneous (80.6%), cardiovascular (39.2%), respiratory (38.1%), and gastrointestinal (13.1%) symptoms. Portable epinephrine auto-injectors were prescribed to 12.1% of the patients. Subject positive to both vespid and honeybee showed more severe symptoms and higher epinephrine use (P<0.05). The severity was significantly associated with older age, but not with gender, underlying allergic disease, or family history. Apitherapy-induced anaphylaxis showed a higher rate of hospitalization and epinephrine use than bee sting anaphylaxis (P<0.05). CONCLUSION: Vespid is the most common cause of bee venom anaphylaxis in Korea. It is suggested that positivity to honeybee and vespid may be associated with more severe symptoms.

CYP1A2 polymorphism and theophylline clearance in Korean non-smoking asthmatics

BACKGROUND: Theophylline is mainly metabolized by cytochrome P450 (CYP) 1A2 and CYP2E1 which show inter-individual variations. However, the underlying mechanism remains unknown in humans. We investigated the relationship between differences in theophylline clearance and genetic polymorphisms in the CYP1A2 and CYP2E1 gene in 89 Korean asthmatic patients. METHODS: Polymerase chain reaction (PCR) was performed on the 5'-flanking region of those genes. PCR products were directly sequenced and confirmed using the SNaP shot method. We determined whether the detected SNPs affected gene transcription using electrophoretic mobility shift assay (EMSA). Theophylline clearance (mL/kg/h) was assessed by using a Bayesian approach.

Updates on desensitization for hypersensitivity reactions related to chemotherapy

As the use of chemotherapeutic agents increased rapidly in recent years, more patients are under the potential risk of chemotherapy related adverse reactions. Multiple regular exposures to the same drug by chemotherapy protocol may increase the risk of sensitization to a chemotherapeutic agent, which can result in hypersensitivity reactions. Once severe hypersensitivity reactions occur, causative drugs should be avoided. However, a substitute with equal efficacy is not always available. When there is no effective alternative, desensitization is a safe tool for maintenance of chemotherapeutic agents causing hypersensitivity reaction. In this review, we introduce the latest knowledge about desensitization protocol for chemotherapeutic agents which are frequently used recently.

Food-dependent exercise-induced anaphylaxis in Korea: a multicenter retrospective case study

PURPOSE: To investigate the causes, clinical features and characteristics of food-dependent exercise-induced anaphylaxis (FDEIA) in Korea. METHODS: A retrospective medical chart review was performed on the patients diagnosed with anaphylaxis between 2007 and 2011 in 14 hospitals in Korea. Cases with FDEIA were subsequently identified among anaphylaxis patients, and subgroup analyses were done to assess clinical characteristics of FDEIA. RESULTS: A total of 62 subjects with FDEIA (male, 72.6%; aged 16 to 70 years) were enrolled in 10 hospitals. Wheat (69.3%) was the most common cause of FDEIA, followed by meat (8.1%), seafood (6.5%), and vegetables (6.5%). The clinical manifestations were cutaneous (100%), respiratory (64.5%), cardiovascular (61.3%), and gastrointestinal (9.7%), respectively. In severity assessment, approximately 40% of FDEIA were classified as severe anaphylaxis. Portable epinephrine auto-injector was prescribed to 17.2% of patients, and about one fifth of the patients experienced redevelopment of anaphylactic symptoms during follow-up period. There was no significant difference of age, gender, latent period, total immunoglobulin E, and past history of allergic disease between patients with severe anaphylaxis group and patients with mild-to-moderate group. CONCLUSION: Wheat is the most common cause of FDEIA in Korea. Because significant number of patients with FDEIA experienced anaphylactic symptoms after diagnosis of FDEIA, more comprehensive therapeutic and educational approaches will be required to prevent recurrent development of anaphylaxis.

A Case of Allopurinol-Induced Fixed Drug Eruption Confirmed With a Lymphocyte Transformation Test

Allopurinol is one of the causative drugs that induce fixed drug eruption (FDE). The lymphocyte transformation test (LTT) is a safe and reliable diagnostic procedure for drug allergy, but is reported to be rarely positive in patients with FDE. In the current case, we performed an LTT and successfully confirmed allopurinol as the offending drug. This case report suggests that an LTT should be an optional diagnostic tool for FDE or delayed reaction due to allopurinol.

Korean Ginseng-Induced Occupational Asthma and Determination of IgE Binding Components

A number of case reports on occupational asthma caused by herbal medicines have been issued, for example, on Sanyak, Chunkung, Banha, and Brazilian ginseng. Recently, cases of occupational asthma induced by Sanyak and Korean ginseng have been reported, but the pathogenic mechanisms involved are unknown. This study was carried out to evaluate the immunologic mechanism underlying Korean ginseng-induced occupational asthma. A patient engaged in Korean ginseng wholesale was referred for recurrent dyspnea, wheezing, and nasal symptoms, which were aggravated at work. Allergen bronchial provocation testing to Korean ginseng extract showed a typical immediate response, and skin prick testing to Korean ginseng extract also showed a strong positive response. Moreover, serum-specific IgE levels to Korean ginseng extract were significantly higher than in controls. Enzymelinked immunosorbent assay (ELISA) inhibition tests showed a dose-dependent inhibition by Korean ginseng, but not by Dermatophagoides farinae, wheat flour, or Chinese balloon flower. Sodium dodecylsulfate-poly-acrylamide gel electrophoresis (SDS-PAGE) and immunoblotting revealed four specific Immunoglobulin E (IgE) binding components at 26, 30, 47, and 60 kDa, which were not bound by control sera. These results strongly suggest that occupation asthma induced by Korean ginseng is induced via an IgE-mediated mechanism.

Correlation between the Korean Version of Asthma Control Test and Health-Related Quality of Life in Adult Asthmatics

The Asthma Control Test (ACT) is a patient-completed questionnaire developed to assess asthma control. Health-related quality of life (HRQL) in asthmatics has shown relatively low correlations with parameters of asthma control and the relationship between the ACT and HRQL in asthmatics is yet unclear. Because revalidations of translated versions of questionnaires are critical for its utilization, we first sought to validate the Korean version of ACT and then to evaluate the relationship between the ACT and HRQL. Patients (n=117) completed the ACT and asthma-related quality of life questionnaire (AQLQ) at 3 physician visits. Pulmonary function was measured and an asthma specialist rated asthma control. The Korean version of ACT was found to be reliable, valid, and responsive to changes in asthma control over time up to three consecutive visits. ACT scores correlated significantly (p=0.001) with symptoms domain (r=0.72), activity domain (r=0.65), emotional domain (r=0.69), and environmental domain (r=0.67) of AQLQ. In conclusion, the Korean version of the ACT was found to be a reliable and valid tool for measuring asthma control, and to correlate well with AQLQ scores. Moreover, the ACT was responsive to changes in AQLQ scores over time.

Atopy May Be an Important Determinant of Subepithelial Fibrosis in Subjects with Asymptomatic Airway Hyperresponsiveness

The bronchial pathology of asymptomatic airway hyperreponsiveness (AHR) subjects is not well understood, and the role of atopy in the development of airway remodeling is unclear. The aim of this study was to evaluate whether atopy is associated with airway remodeling in asymptomatic AHR subjects. Five groups, i.e., atopic or non-atopic subjects with asymptomatic AHR, atopic or non-atopic healthy controls, and subjects with mild atopic asthma, were evaluated by bronchoscopic biopsy. By electron microscopy, mean reticular basement membrane (RBM) thicknesses were 4.3+/-1.7 micrometer, 3.4+/-1.8 micrometer, 2.5+/-1.5 micrometer, 2.6+/-1.1 micrometer, and 2.3+/-1.2 micrometer in the mild atopic asthma, atopic and non-atopic asymptomatic AHR, atopic and nonatopic control groups, respectively (p=0.002). RBM thicknesses were significantly higher in the mild atopic asthma group and in the atopic asymptomatic AHR group than in the other three groups (p=0.048). No significant difference in RBM thickness was observed between the atopic asymptomatic AHR group and the mild atopic asthma group (p>0.05), nor between non-atopic asymptomatic AHR group and the two control groups (p>0.05). By light microscopy, subepithelial layer thicknesses between the groups showed the same results. These findings suggest that RBM thickening occurs in subjects with atopic asymptomatic AHR, and that atopy plays an important role in airway remodeling.

Prevalence of aspirin sensitivity among asthmatic patients with mild to moderate severity and its clinical characteristics / 천식및알레르기

BACKGROUND: While aspirin sensitivity has been known to be common among patients with severe asthma, its frequency among asthmatics with mild to moderate severity remains to be learned. OBJECTIVES: To elucidate the frequency of aspirin sensitivity and its clinical characteristics among asthma patients with mild to moderate severity. MATERIAL AND METHODS: A total of 96 asthmatics with mild to moderate severity were enrolled. They underwent lysine-aspirin and methacholine bronchial provocation tests, and gave their induced sputum after the lysine-aspirin challenge. RESULTS: FEV1 declined greater than 20% compared with baseline FEV1 in 11 of 96 patients on the lysine-aspirin challenge. The frequency of aspirin sensitivity was higher among patients with enhanced bronchial hyperresponsiveness to methacholine (PC20 < 1 mg/ml) than among those without it (27.3% vs. 6.8%). The frequency was also higher in those with induced sputum eosinophil count higher than 3% than among those without it (38.9% vs. 0%). However, it was not associated with other risk factors such as age, sex, atopy, nasal polyps, and rhinosinusitis. CONCLUSION: More than 10% of mild to moderate asthmatics have aspirin sensitivity even though they have experienced no history of aspirin sensitivity which may be related with bronchial hyperresponsiveness to methacholine and eosinophil activation.

Two cases of alcohol-induced asthma / 천식및알레르기

Alcohol-induced asthma is defined as exacerbation of asthmatic symptoms after drinking alcoholic beverages. This phenomenon is rare in Caucasians and is more specific to Asians. It has been observed among 50% of Japanese asthmatic patients and genetic predisposition in acetal-dehyde metabolism is thought to be a main factor in alcohol-induced asthma. Although the genetic predisposition of acetaldehyde metabolism in Koreans may be similar to the Japanese, alcohol-induced asthma has not been reported in Korea. We experienced two cases of alcohol-induced asthma which were confirmed by oral ethanol provocation test. In the first case, a 60-year-old male asthma patient presenting a recurrent episode of wheezing and dyspnea after alcohol consumption visited our clinic. After an oral challenge with 300ml of 10% ethanol solution dissolved in 5% glucose solution, dyspnea and wheezing episode were reproduced and 23% decrease in FEV1 compared to basal level was also shown at 20 minutes after ingestion. In the second case, a 32-year-old female asthma patient was presented with the same symptoms. After oral challenge, dyspnea and wheezing episode were reproduced and 30% decrease in FEV1 compared to basal level was shown at 60 minutes after ingestion. Short acting bronchodilator was applied and 21% increase in FEV1 resulted. They were instructed to avoid alcohol consumption with good results.