13-Week Repeated Oral Toxicity and Toxicokinetic Studies of Rabeprazole Sodium and Sodium Bicarbonate Combination in Dogs.

The subchronic toxicity and toxicokinetics of a combination of rabeprazole sodium and sodium bicarbonate were investigated in dogs by daily oral administration for 13 consecutive weeks with a 4-week recovery period. The dose groups consisted of control (vehicles), (5 + 200), (10 + 400), and (20 + 800) mg/kg of rabeprazole sodium + sodium bicarbonate, 20 mg/kg of rabeprazole sodium only, and 800 mg/kg of sodium bicarbonate only. Esophageal ulceration accompanied by inflammation was observed in only one animal in the male (20 + 800) mg/kg rabeprazole sodium + sodium bicarbonate group. However, the severity of the ulceration was moderate, and the site of occurrence was focally extensive; thus, it was assumed to be a treatment-related effect of rabeprazole sodium + sodium bicarbonate. In the toxicokinetics component of this study, systemic exposure to rabeprazole sodium (AUClast and Cmax at Day 91) was greater in males than females, suggesting sex differences. AUClast and Cmax at Day 91 were increased compared to those on Day 1 in a dose-dependent manner. A delayed Tmax and no drug accumulation were observed after repeated dosage. In conclusion, we suggest under the conditions of this study that the no-observed-adverse-effect level (NOAEL) of the combination of rabeprazole sodium + sodium bicarbonate in male and female dogs is (10 + 400) and (20 + 800) mg/kg, respectively.

Immunologic evaluation of patients with cefotetan-induced anaphylaxis.

Cefotetan is a commonly prescribed second-generation cephalosporin that acts against a wide range of bacteria. However, cefotetan-induced hypersensitivity has rarely been reported. We report 2 cases of cefotetan-induced anaphylaxis with immunologic evaluation. The first case was a 70-year-old asthmatic woman who had dyspnea and hypotension during administration of cefotetan, in which high serum-specific IgE to cefotetan-human serum albumin (HSA) conjugate was detected by enzyme-linked immunosorbent assay. The second case was a 63-year-old asthmatic woman who complained of chest tightness and dyspnea during cefotetan infusion, in which high serum-specific IgG1 and IgG4 with no serum specific IgE to cefotetan-HSA conjugate was detected. The basophil activation test using basophils from the patient showed a significant up-regulation of CD63 with the addition of anti-IgG4 antibody compared with that in non-atopic healthy controls. In conclusion, cefotetan can induce anaphylaxis, which may involve both IgE- and IgG4-mediated responses in the pathogenic mechanism.

Comparison of specific IgE antibodies to wheat component allergens in two phenotypes of wheat allergy.

Specific IgE to gliadin was proposed as a marker for wheat dependent exercise induced anaphylaxis, while Tri a 14 was found to induce IgE response in baker's asthma. We evaluated whether these components could be used for discriminating phenotypes of wheat allergy. Twenty-nine patients who were wheat-induced anaphylaxis and/or urticaria (n=21, group I) and baker's asthma (n=8, group II) were enrolled. The prevalence of serum specific IgE to Tri a 14 was higher in group II (25%) than in group I (4.8%), while the serum specific IgE to gliadin was significantly higher in group I (70%) than in group II (12.5%). The cutoff value for predicting the baker's asthma using the ratio of serum specific IgE to Tri a 14 to gliadin was 742.8 optical density×1,000/(kU/L) with high sensitivity and specificity. These findings suggest that Tri a 14/gliadin may be a potential marker for predicting baker's asthma.

IL-5 Promoter Polymorphism Enhances IgE Responses to Staphylococcal Superantigens in Adult Asthmatics.

Interleukin 5 (IL-5) is a key cytokine involved in the induction of T-helper type 2 (Th2) responses in the asthmatic airway. We investigated IL-5 genetic polymorphisms associated with asthma phenotypes, including IgE responses to staphylococcal enterotoxins A and B (SEA and SEB, respectively), in asthmatics. Adult asthmatics (n=310) and normal controls (n=160) were enrolled in the present study. Serum total and specific IgE to SEA and SEB were measured. Two IL-5 polymorphisms, -746A>G and +4499T>G, were genotyped using the primer-extension method. There were no significant differences in genotype or haplotype frequencies of these polymorphisms between the two groups. Asthmatics carrying the AG/GG genotype at -746A>G had a significantly higher prevalence of serum specific IgE to SEA (P=0.008), higher total IgE levels (P=0.014), and lower PC20 methacholine levels (P=0.002) compared to those with the AA genotype. These findings suggest that the IL-5 promoter polymorphism at -746A>G enhances serum total and specific IgE responses to SEA, which may augment airway hyperresponsiveness in adult asthmatics.

Clinical features of immediate hypersensitivity to isopropylantipyrine.

Hypersensitivities induced by isopropylantipyrine (IPA), a pyrazolone derivative within the wider family of non-steroidal anti-inflammatory drugs (NSAIDs), are rarely reported. We characterized the clinical features of 12 patients with IPA-induced hypersensitivity. Twelve patients with immediate hypersensitivity to IPA were enrolled and classified into two groups: group I, consisting of eight patients (66.7%) with selective hypersensitivity; and group II, consisting of four patients (33.3%) showing cross-intolerance to other NSAIDs. Skin prick and intradermal and oral provocation tests with IPA were performed. To confirm selective hypersensitivity, an aspirin oral provocation test was also conducted. The most common manifestations were cutaneous reactions (91.7%), followed by anaphylaxis (66.7%), respiratory (41.7%), ocular (16.7%), and gastrointestinal reactions (16.7%). The median age and the median age at onset were 34.5 (range, 23-55) years and 28.0 (range, 7-47) years, respectively. In both groups I and II, all patients showed negative responses to skin prick testing, whereas only two patients in group I were positive in response to intradermal IPA tests. The response time after drug exposure was shorter in group I than in group II. Here, we report on two types of IPA hypersensitivity: selective and cross-intolerant NSAID hypersensitivity. An immediate IgE-mediated reaction may be involved in patients with selective hypersensitivity, whereas a cyclooxygenase-1-related inhibition mechanism may be a responsible mechanism for the patients with cross-intolerance to multiple NSAIDs.

Co-existence of chronic urticaria and metabolic syndrome: clinical implications.

A systemic pro-inflammatory and pro-coagulating state occurs in subjects who have both chronic urticaria and metabolic syndrome. To investigate the prevalence and clinical impact of metabolic syndrome in Korean patients with chronic urticaria, a hospital-based cross-sectional study of 131 patients was performed. Metabolic syndrome was assessed by the criteria of the National Cholesterol Education Program's Adult Treatment Panel III. Urticaria disease activity was assessed by total urticaria activity score (range 0-15). Thirty-nine patients (29.8%) had metabolic syndrome compared to 17.8% in a matched control group (p=0.001). Patients with chronic urticaria and metabolic syndrome were older, had a higher mean urticaria activity score and serum levels of eosinophil cationic protein, tumour necrosis factor-α, and complements, and showed a higher rate of negative autologous serum skin tests compared with those with-out metabolic syndrome. Logistic regression analysis indicated that an urticaria activity score of ≥ 13 (p=0.025) and the presence of metabolic syndrome (p=0.036) were independent predictors of uncontrolled chronic urticaria. We conclude that patients with severe and uncontrolled chronic urticaria should be evaluated for metabolic syndrome in order to reduce cardiovascular risk and improve chronic urticaria outcomes.

Identifying genetic susceptibility to sensitization to cephalosporins in health care workers.

Exposure to cephalosporins could cause occupational allergic diseases in health care workers (HCWs). We evaluated the prevalence of serum specific IgE and IgG antibodies to cephalosporin-human serum albumin (HSA) conjugate and to identify potential genetic risk factors associated with sensitization to cephalosporins in exposed HCWs. The study population consisted of 153 HCWs who had been exposed to antibiotics in a single university hospital and 86 unexposed healthy controls. A questionnaire survey of work-related symptoms (WRS) was administered. A skin-prick test (SPT) was performed, and serum-specific IgE and IgG antibodies to 3 commonly prescribed cephalosporins were measured by ELISA. Four single-nucleotide polymorphisms of the candidate genes related to IgE sensitization were genotyped. The prevalence of WRS to cephalosporins was 2.6%. The prevalence rates of serum-specific IgE and IgG antibodies to cephalosporins were 20.3% and 14.7%, respectively. The FcεR1ß-109T > C polymorphism was significantly associated with IgE sensitization to cephalosporins in HCWs (P = 0.036, OR = 3.553; CI, 1.324-9.532). The in vitro functional assay demonstrated that the T allele of FcεR1ß-109T had greater promoter activity than did the C allele (P < 0.001). The FcεR1ß-109T > C polymorphism may be a potential genetic risk factor for increased IgE sensitization to cephalosporins.

Effects of omalizumab treatment in patients with refractory chronic urticaria.

PURPOSE: Chronic urticaria (CU) is a common and debilitating disease, and the need for effective treatment has increased. Omalizumab may be an alternative regimen in patients with CU who do not respond to conventional treatments. The aim of this study is to investigate the efficacy and to observe the clinical results of omlizumab in patients with refractory CU. METHODS: We conducted a retrospective analysis of 26 patients with refractory CU who were treated with omalizumab. Omalizumab was administered every 2 or 4 weeks, depending on body weight and the total serum IgE level, for 24 weeks. RESULTS: Fourteen patients (53.8%) achieved remission after the treatment; they had a significantly higher prevalence of personal (P=0.033) and family history of allergic diseases (P=0.002) than those who did not achieve remission. During omalizumab treatment, the urticaria activity score declined significantly (12.11±1.97 to 2.7±4.23; P=0.001) and the CU-quality of life score improved significantly (34.65±13.58 to 60.88±11.11; P=0.004). There were significant decreases in the use of systemic steroids (42.3%-11.5%; P=0.027) and immunomodulators (65.4%-19.2%; P=0.002). The dose of antihistamines required to control CU also decreased significantly (215.66±70.06 to 60.85±70.53 mg/week of loratadine equivalents; P<0.001). No serious adverse event was noted. CONCLUSIONS: These findings suggest that omalizumab can be an effective and safe treatment in patients with refractory CU.

Immunologic evaluation of ofloxacin hypersensitivity.

Quinolone hypersensitivity, most of which is immediate type, is rare but has increased in recent years. The pathogenic mechanisms underlying immediate reactions are not defined clearly. This study was aimed to observe the clinical characteristics of immediate hypersensitivity to ofloxacin and to investigate the pathogenic mechanism with detection of serum specific IgE to ofloxacin using an enzyme-linked immunoasorbent assay (ELISA). We recruited 5 patients with immediate hypersensitivity reactions to ofloxacin (group I), and as control groups, 5 subjects with ciprofloxacin hypersensitivity (group II) and 20 healthy subjects with no history of drug allergy. Serum specific-IgE to ofloxacin-human serum albumin (HSA) conjugate was detectable in four group I subjects (80%) and three group II subjects (60%). The ELISA inhibition test showed significant inhibition with both ofloxacin-HSA conjugate and free ofloxacin in a dose-dependent manner. As to ciprofloxacin, significant inhibition was noted upon addition of free ciprofloxacin in one subject, while minimal inhibition was noted in the other. We confirmed that an IgE-mediated response is a major pathogenic mechanism of ofloxacin hypersensitivity. Cross reactivity between ofloxacin and ciprofloxacin was noted with individual difference.

Successful treatment of chronic eosinophilic pneumonia with anti-IgE therapy.

Anti-IgE therapy, using recombinant humanized anti-IgE antibodies, is clinically effective in patients with eosinophil-related disorders such as allergic asthma, allergic rhinitis, and chronic urticaria. Chronic eosinophilic pneumonia tends to respond promptly to systemic corticosteroid therapy, however; relapses are common following corticosteroid tapering. We treated two patients (17- and 19-yr-old males) of chronic eosinophilic pneumonia whose symptoms were cough and dyspnea on exertion. The symptoms were recurrent while tapering off corticosteroid. They were treated with anti-IgE antibody without recurrence for 2 yr and 15 months. Here, we first describe clinical experience of the 2 cases of chronic eosinophilic pneumonia.

The predictors of poorly controlled asthma in elderly.

PURPOSE: To evaluate asthma control in elderly individuals and identify the factors that predict poor control. METHODS: A retrospective, observational study evaluating 108 elderly individuals with asthma (59 females: ≥60 years, mean age: 70.5 years) was conducted at Ajou University Hospital from October 2010 to March 2011. Subjects were classified into two groups according to scores on the asthma control test (ACT). Group I consisted of 38 patients with ACT scores ≤19 (poor controllers) and group II included 70 patients with ACT scores >19 (controllers). Clinical data was analyzed. Spirometry was performed, and the ACT and asthma quality-of-life survey were completed. Medication possession ratios were calculated to evaluate compliance. RESULTS: Of the 108 enrolled subjects, 54.6% were female, 7.5% were obese, and 49.0% were atopic. The mean age of the patients was 70.5, and the average of time patients had suffered from asthma was 15.5 years. Comorbid conditions were found in more than 80% of the patients. Allergic rhinitis was most common comorbid condition; this was followed by cardiovascular disease and degenerative arthritis (76.9%, 65.7%, and 51.9%, respectively). Many patients (35.2%) were in poorly controlled states characterized by significantly lower asthma quality of life scores (P<0.001) and higher admission rates (P=0.034). Multivariate logistic regression analysis showed that a history of pulmonary tuberculosis was a predictor of poorly controlled asthma in elderly individuals even after adjusting for age, sex, smoking, lung function and other comorbidities (OR=4.70, CI=1.06-20.81, P=0.042). CONCLUSIONS: The asthma of more than one-third of elderly individuals with this condition was poorly controlled, and a history of pulmonary tuberculosis may have contributed to this outcome. Proper evaluation and management of comorbid conditions in elderly patients with asthma is essential for the achievement of better control of the disease and a higher quality of life for those who suffer from it.

Clinical Features and the Diagnostic Value of Component Allergen-Specific IgE in Hymenoptera Venom Allergy.

PURPOSE: Although patient history is vital for the diagnosis of hymenoptera venom allergy, specific IgE detection is also important to identify the culprit insect and monitor the effect of immunotherapy. We evaluated the diagnostic value of serum-specific IgE detection of hymenoptera venom component allergens and documented changes in allergen-specific IgE after immunotherapy. METHODS: Fifty-six hymenoptera venom allergy patients receiving venom immunotherapy were recruited from Ajou University Hospital, Korea. The clinical manifestations of the patients were noted, and serum-specific IgE detection was performed, using conventional venom extracts as well as component allergens. Data were analyzed retrospectively. RESULTS: A total of 35 (62.5%) patients were male, and 33 (73.3%) patients were atopic. The mean patient age was 44.9±13.8 years. Localized reactions occurred in 23.2% of patients, and systemic reactions occurred in 76.8%. The most common clinical manifestations included skin involvement, such as urticaria and angioedema, and respiratory involvement. Yellow jackets were the most frequent culprit insect, followed by yellow hornets, white-faced hornets, honeybees, and paper wasps, as determined at the time of diagnosis. Double sensitization to both Apidae and Vespidae species was detected in 70.9% of patients. The positive predictive values (PPV) of rVes v 5-specific and rPol d 5-specific IgE detection were 85.7% and 87.5%, respectively, which correlated well with conventional venom extract-specific IgE detection (r=0.762 and r=0.757, respectively). In contrast, the PPV of rApi m 1-specific IgE detection at the time of diagnosis was 34.8%. Three years of venom immunotherapy resulted in decreased venom-specific IgE, particularly IgE specific for Vespidae venom components. CONCLUSIONS: Stings by yellow jackets and male sex may be risk factors for hymenoptera venom allergy in Korea. Vespidae component-specific IgE, but not Apidae component-specific IgE, had diagnostic and monitoring value in hymenoptera venom allergy comparable to that of conventional hymenoptera venom extract-specific IgE.

Clinical features of allergic bronchopulmonary aspergillosis in Korea.

Allergic bronchopulmonary aspergillosis (ABPA) is a complex disease, triggered by a hypersensitivity reaction to the allergen Aspergillus fumigatus. This disease occurs frequently in patients with cystic fibrosis and severe asthma in Western countries, with a prevalence of 2%-15%. However, there have been only a few case reports in Korea. We investigated the clinical and immunological features of patients with ABPA. Ten adult patients diagnosed with ABPA, according to Greenberger's criteria, were analyzed during the period January 2001 to December 2010 in a tertiary hospital. Skin-prick tests, pulmonary function tests, and high-resolution computed tomography (HRCT) were performed, and total serum IgE and A. fumigatus-specific IgE were measured. The patient cohort consisted of men who were middle-aged (median, 62.5; range, 19.0-79.0 years) at the diagnosis of ABPA with a long duration of asthma (median, 15.0; range, 1-48 years). Approximately 40% of the patients had a history of pulmonary tuberculosis more than 10 years prior to the study (median 23.5; range, 10.0-31.0 years) accompanied by severe obstructive lung function and radiological post-tuberculous destructive lung lesions. These patients also tended to have increased levels of immunologic parameters, such as total eosinophil count, total IgE, and A. fumigates-specific IgE, compared to those without tuberculosis sequels. Two patients with steroid-dependent asthma were treated with anti-IgE therapy and showed good responses. We report the clinical features of 10 ABPA patients, including 4 with histories of post-tuberculosis destructive lesions. Furthermore, anti-IgE antibody therapy may be an alternative strategy in cases of steroid-dependent ABPA.

Oral muscle relaxant may induce immediate allergic reactions.

Eperisone and afloqualone act by relaxing both skeletal and vascular smooth muscles to improve circulation and suppress pain reflex. These drugs are typically prescribed with non-steroidal anti-inflammatory drugs (NSAIDs) as painkillers. However, there have been no reports on serious adverse reactions to oral muscle relaxants; and this is the first report to describe three allergic reactions caused by eperisone and afloqualone. All three patients had histories of allergic reactions after oral intake of multiple painkillers, including oral muscle relaxants and NSAIDs, for chronic muscle pain. An open-label oral challenge test was performed with each drug to confirm which drugs caused the systemic reactions. All patients experienced the same reactions within one hour after oral intake of eperisone or afloqualone. The severity of these reactions ranged from laryngeal edema to hypotension. To confirm that the systemic reaction was caused by eperisone or afloqualone, skin prick testing and intradermal skin tests were performed with eperisone or afloqualone extract in vivo, and basophil activity tests were performed after stimulation with these drugs in vitro. In one patient with laryngeal edema, the intradermal test with afloqualone extract had a positive result, and CD63 expression levels on basophils increased in a dose-dependent manner by stimulation with afloqualone. We report three allergic reactions caused by oral muscle relaxants that might be mediated by non-immunoglobulin E-mediated responses. Since oral muscle relaxants such as eperisone and afloqualone are commonly prescribed for chronic muscle pain and can induce severe allergic reactions, we should prescribe them carefully.

Genetic variability of prostaglandin E2 receptor subtype EP4 gene in aspirin-intolerant chronic urticaria.

Prostaglandin E2 receptor subtype EP4 (PTGER4) is one of the four subtypes of receptors for prostaglandin E2 (PGE2). Overproduction of cysteinyl leukotriene in mast cells may be related with suppression of PGE2 in patients with aspirin hypersensitivity. Considering the association of PTGER4 in mast cells, urticaria- and aspirin-related disease, we hypothesized the genetic variability of PTGER4 may be associated with aspirin-intolerant chronic urticaria (AICU). The case-control study was performed in 141 with AICU, 153 with aspirin-tolerant chronic urticaria (ATCU) and 174 with normal controls (NCs). PTGER4 promoter single-nucleotide polymorphism was genotyped using a primer extension method with the SNAPshot ddNTP primer extension kit. The functional variability of PTGER4 promoter polymorphism was carried out by dual-luciferase system and electrophoretic mobility shift assay (EMSA) in human mast cells (HMC-1). Furthermore, the effect of aspirin was performed for PTGER4 mRNA expression using real-time PCR, and PGE2 production was checked in HMC-1 cells using ELISA. AICU patients carrying GG genotype at -1254 G>A showed significantly higher frequency compared with NC (P=0.032). Similarly, the minor allele frequency, G allele was significantly higher in AICU compared with NC (P=0.031). In vitro functional study demonstrated that the -1254 G allele had lower luciferase activity (P<0.001) in HMC-1 cells. EMSA finding showed that PTGER4 -1254 G produced a specific band. Significantly decreased PTGER4 expression (P=0.008) and PGE2 production by aspirin exposure was confirmed in in vitro HMC cell line model (P=0.001). The PTGER4 -1254 G allele demonstrated a higher frequency in AICU patients and lower promoter activity with decreased expression of PTGER4 and contributes to the development of AICU.

IgE Sensitization to Cephalosporins in Health Care Workers.

PURPOSE: Cephalosporins can induce occupational allergies, such as asthma, urticaria, and anaphylaxis. We investigated the prevalence and risk factors of sensitization to cephalosporin. METHODS: A total of 161 health care workers (HCW), including 138 nurses and 23 pharmacists, and 86 unexposed non-atopic healthy controls were recruited from a single tertiary hospital and the general population. A questionnaire regarding work-related symptoms was administered along with skin prick tests (SPT) to the three most commonly used cephalosporins (cefotiam, ceftriaxone, and ceftizoxime). Serum specific IgE antibodies to conjugates of the three cephalosporins and human serum albumin (HSA) were measured by enzyme-linked immunosorbent assay (ELISA). Binding specificities were confirmed by ELISA inhibition tests. RESULTS: The prevalence of work-related symptoms in association with cephalosporins was 17.4%. The sensitization rate to any cephalosporin was 3.1% by SPT. Sensitization rates determined by measurement of serum specific IgE antibodies were 17.4% for any cephalosporin, 10.4% for cefotiam, 6.8% for ceftriaxone, and 3.7% for ceftizoxime. A personal history of any antibiotic allergy was a risk factor for work-related symptoms (OR, 24.93; 95% CI, 2.61-238), but not for the presence of serum specific IgE antibodies to cephalosporins (OR, 0.9; 95% CI, 0.18-4.53). A personal history of atopic dermatitis was a risk factor for the presence of serum specific IgE antibodies to cefotiam-HSA conjugate (OR, 6.30; 95% CI, 1.23-32.3). CONCLUSIONS: A high cephalosporin sensitization rate (17.4%) was detected by ELISA in HCW exposed to cephalosporins. Monitoring of serum specific IgEs to cephalosporin-HSA conjugates will be useful for detecting sensitized subjects.

Occupational rhinitis induced by capsaicin.

Capsaicin is the spice component of red pepper. It can be easily inhaled, inducing a reproducible cough and provokes a secretory response from the human nasal mucosa. To date, there has been no report of occupational rhinitis (OR) caused by capsaicin. We report the case of a 44-year-old female mill worker who developed occupational rhinitis after 4 years of exposure to capsaicin. She developed nasal congestion, rhinorrhea, and itchy nose, which were all aggravated upon exposure at the workplace. The patient had negative responses to all common inhalant allergens, including capsaicin, by skin prick tests. The nasal provocation test with capsaicin showed that the nasal symptom score and eosinophil count increased 10 minutes after the provocation and decreased after 1 to 3 hours; no significant response was noted to house dust mite allergen. The patient's work-related rhinitis improved 1 month after she relocated and started pharmacological treatment. To our knowledge, this is the first case of OR caused by capsaicin exposure in the workplace. We provide evidence suggesting that OR may be mediated by a non-immunological mechanism.

Genetic mechanisms in aspirin-exacerbated respiratory disease.

Aspirin-exacerbated respiratory disease (AERD) refers to the development of bronchoconstriction in asthmatics following the exposure to aspirin or other nonsteroidal anti-inflammatory drugs. The key pathogenic mechanisms associated with AERD are the overproduction of cysteinyl leukotrienes (CysLTs) and increased CysLTR1 expression in the airway mucosa and decreased lipoxin and PGE2 synthesis. Genetic studies have suggested a role for variability of genes in disease susceptibility and the response to medication. Potential genetic biomarkers contributing to the AERD phenotype include HLA-DPB1, LTC4S, ALOX5, CYSLT, PGE2, TBXA2R, TBX21, MS4A2, IL10, ACE, IL13, KIF3A, SLC22A2, CEP68, PTGER, and CRTH2 and a four-locus SNP set composed of B2ADR, CCR3, CysLTR1, and FCER1B. Future areas of investigation need to focus on comprehensive approaches to identifying biomarkers for early diagnosis.

Vancomycin-associated spontaneous cutaneous adverse drug reactions.

PURPOSE: With the increase in vancomycin use, adverse drug reactions (ADRs) associated with vancomycin have been reported increasingly more often. However, the characteristics of cutaneous ADRs with and without systemic reactions (SRs) have not been described. This study investigated the characteristics of spontaneously reported and assessed ADRs associated with vancomycin by a pharmacovigilance center. METHODS: ADRs (n=121) associated with vancomycin in 96 patients were collected from 2008 to 2009. Records from physician- and nurse-reported suspected cases of vancomycin ADRs, ADR type, latent period, and laboratory results were compared between cutaneous ADRs with and without SRs. RESULTS: The main vancomycin-related ADRs were skin rashes (47.9%), hematologic abnormalities (17.36%), fever (12.4%), and elevated serum creatinine (12.4%). Significant differences were observed in latent period (days) and the mean change in eosinophils (%) between cutaneous (9.21±9.71 and 1.4±3.4, respectively) and other ADRs (14.03±11.71 and -0.5±3.5, respectively). Twelve cases of cutaneous ADRs with SRs had been initially reported as cutaneous ADRs only. Mean changes in the eosinophil count were significantly higher for cutaneous ADRs with SRs compared to those without SRs. CONCLUSIONS: Skin rashes accompanied by peripheral eosinophilia, representing suspected immune-mediated delayed hypersensitivity reactions, are a common vancomycin ADR. For the early and exact detection of ADRs associated with vancomycin administration, close monitoring of laboratory tests, including complete blood counts with differential analysis, is recommended.