Incidence of cephalosporin-induced anaphylaxis and clinical efficacy of screening intradermal tests with cephalosporins: A large multicenter retrospective cohort study.

BACKGROUND: Few studies have investigated the incidence of anaphylaxis induced by individual or structurally similar cephalosporins. The aims of the study were to assess the incidence of cephalosporin-induced anaphylaxis and evaluate the clinical efficacy of screening skin tests. METHODS: In this retrospective cohort study, we obtained information on total cephalosporin use and cephalosporin-induced anaphylaxis in intravenous cephalosporin recipients in 12 general hospitals between 2013 and 2015. Cephalosporins were divided into 4 groups according to similar side-chain structures. The incidence of cephalosporin-induced anaphylaxis was assessed for each cephalosporin, cephalosporin generation, and side-chain group. To verify the efficacy of screening intradermal tests (IDT) with cephalosporin, the 12 hospitals were assigned to the intervention or control group depending on whether they performed screening IDT before the administration of cephalosporins. RESULTS: We identified 76 cases of cephalosporin-induced anaphylaxis with 1 123 345 exposures to intravenous cephalosporins (6.8 per 100 000 exposures), and the incidence of fatal anaphylaxis by cephalosporin was 0.1 cases per 100 000 exposures. The highest incidences of anaphylaxis occurred in the ceftizoxime (13.0 cases per 100 000 exposures) and side-chain group 1 (cefepime, cefotaxime, ceftizoxime, ceftriaxone, and cefuroxime; 9.3 per 100 000). There was no case of anaphylaxis induced by cefoxitin, cefmetazole, cefminox, and cefotiam. The clinical effectiveness of routine screening IDT was not significant (P = .06). CONCLUSIONS: The incidence of cephalosporin-induced anaphylaxis differed according to individual drugs and side-chain structure. Screening IDT showed no clinical efficacy at a population level.

Drug reaction with eosinophilia and systemic symptoms syndrome is not uncommon and shows better clinical outcome than generally recognised.

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare disease which can cause severe morbidity and mortality. The aim of this study is to evaluate the clinical manifestation and course of DRESS syndrome. METHODS: We conducted a retrospective analysis of prospectively collected data in 45 patients with DRESS syndrome diagnosed between September 2009 and August 2011. RESULTS: The most common causative drug group was antibiotics (n=13, 28.9%), followed by anticonvulsants (n=12, 26.7%), antituberculosis drugs (n=6, 13.3%), non-steroidal anti-inflammatory drugs (n=4, 8.9%), undetermined agents (n=4, 8.9%), allopurinol (n=3, 6.7%), and others (n=3, 6.7%). The latency period ranged from 2 to 120 days, with a mean of 20.2 ± 24.3 days. The longest latency period was noted for the antituberculosis drug group, at 46.5 ± 29.9 days. Eosinophilia in peripheral blood examination was noted in 35 subjects (77.8%). Atypical lymphocytosis was noted in 16 patients (35.6%), and thrombocytopenia in seven patients (15.6%). Hepatic involvement was noted in 39 (86.7%) study patients, kidney in eight (17.8%), lung in four (8.9%), and central nervous system in one (2.3%). Systemic corticosteroids were administered to 10 patients (22.2%). Forty-three patients (95.6%) showed complete recovery, while two patients had poor outcomes. CONCLUSIONS: DRESS syndrome was not more uncommon than generally recognised. Antibiotics were the most frequently implicated drug group, followed by anticonvulsants. Most patients with this disease showed a better clinical outcome than that which had been generally expected.

Uncertain areas in the diagnosis of allergic bronchopulmonary aspergillosis in patients with asthma.

BACKGROUND AND OBJECTIVE: The prevalence of allergic bronchopulmonary aspergillosis (ABPA) in patients with bronchial asthma remains unknown. We evaluated the roles of various laboratory tests in the diagnosis of ABPA, including, skin prick test (SPT) for Aspergillus fumigatus (Af), and serum Af specific IgE and IgG antibody measurement. METHODS: A total of 50 asthma patients with more than 1000cell/µL of peripheral blood eosinophils were prospectively collected between January 2007 and September 2011. Evaluations using SPT for Af, serum total IgE and specific IgE antibody to Af by CAP system, IgG antibody to Af by enzyme immunoassay (EIA) or CAP system were performed according to the essential minimal criteria for the diagnosis of ABPA - asthma, immediate cutaneous reactivity to Af, elevated total IgE, and raised Af specific IgE and IgG. RESULTS: Among 50 patients, three patients (6.0%) were diagnosed as ABPA, of whom each confirmed five items of the essential minimal diagnostic criteria for the diagnosis of ABPA. Six patients (12.0%) showed negative responses to Af in SPT, but positive responses in specific IgE by CAP system. Eight patients (16.0%) showed negative responses to IgG to Af by CAP system, but positive responses by enzyme immunoassay (EIA). CONCLUSIONS: SPT and serum IgE to Af measurement by CAP system should be performed simultaneously. It is reasonable to set up cut-off values in Af specific IgE/IgG by CAP system for the differentiation of ABPA from Af sensitised asthma patients.

Preliminary study of the cellular characteristics of primary bronchial fibroblasts in patients with asthma: expression of alpha-smooth muscle actin, fibronectin containing extra type III domain A, and smoothelin.

BACKGROUND: The relationship between fibroblasts, myofibroblasts, and smooth muscle cells within the airway wall remains poorly understood. OBJECTIVE: The cellular characteristics of primary bronchial fibroblasts from patients with asthma were investigated by evaluating the expression of 3 proteins: alpha-smooth muscle actin (SMA), fibronectin containing extra type III domain A (EDAcFN), and smoothelin. METHODS: Expression of SMA, EDAcFN, and smoothelin was evaluated in primary fibroblasts from 3 patients with asthma of varying symptom severity, embryonic fibroblasts, and a healthy control. In addition, primary bronchial fibroblasts from patients with asthma were assessed for SMA at various incubation times (4 hours to 76 hours) and with different extracellular matrices (ECMs). Immunofluorescence was assessed by manually counting cells that stained positively as fine filamentous structures under a fluorescence microscope. RESULTS: Expression of filamentous SMA tended to increase with the length of incubation. The positive to total cell ratio for filamentous cells did not differ significantly between the various kinds of ECMs onto which cells were plated (P > .05). Primary bronchial fibroblasts from asthma patients produced more prominent expression of EDAcFN than control fibroblasts. Smoothelin was not expressed in any fibroblasts. CONCLUSIONS: More than 50% of primary bronchial fibroblasts were defined as myofibroblasts. Primary bronchial fibroblasts in patients with asthma had more potential for tissue fibrosis than control fibroblasts. No mature smooth muscle cells were observed in primary bronchial fibroblasts in patients with asthma.

The novel -G646A polymorphism of the TNFalpha promoter is associated with the HLA-B51 allele in Korean patients with Behçet's disease.

OBJECTIVE: This study was performed to examine the influence of tumour necrosis factor-alpha (TNFalpha) promoter polymorphisms on disease susceptibility and clinical features of Behçet's disease (BD) and the association between TNFalpha polymorphisms and human leucocyte antigen (HLA)-B51. METHODS: We examined 115 patients with BD and 114 healthy subjects. Six single nucleotide polymorphisms (SNPs) of the TNFalpha promoter at positions -1031, -863, -857, -308, -238, and -646 were analysed using automated sequencing. We compared the frequencies of alleles and genotypes in patients with BD and controls using the chi(2)-test or Fisher's exact test. Haplotype frequency was also assessed using the chi(2)-test. RESULTS: We found no significant differences in the frequencies of polymorphic genotypes and alleles of the TNFalpha promoter region between BD patients and controls. The resulting haplotype frequencies of the BD patients were also not significantly different from those of controls. None of the TNFalpha promoter polymorphisms analysed here were associated with clinical features. Patients with the novel -646A allele of the TNFalpha promoter region were significantly associated with the expression of the HLA-B51 allele (p(corr) = 0.006), although this novel polymorphic allele was not associated with BD susceptibility. CONCLUSION: The novel -646A TNFalpha allele was associated with the expression of HLA-B51 in Korean BD, although we found no genetic role of TNFalpha promoter polymorphisms in the susceptibility to BD. Further studies to examine the contributions of this gene polymorphism and HLA-B51 to the susceptibility to BD in large populations are required.

Interleukin-18 gene polymorphisms in Korean patients with Behçet's disease.

OBJECTIVE: There is strong evidence that Th1-type cytokines play an important role in the pathogenesis of Behçet's disease (BD). Interleukin (IL)-18 is a proinflammatory cytokine that mediates Th1-polarized immune responses, and elevated levels of IL-18 have been observed in the sera and bronchoalveolar lavage fluid of patients with active BD. Therefore, the aim of this study was to investigate the potential associations of two single nucleotide polymorphisms (SNPs) at positions -137 (G/C) and -607 (C/A) in the promoter region of the IL-18 gene with a susceptibility to BD in the Korean population. METHODS: Ninety-eight patients with BD and 105 healthy controls were studied. All of the subjects were genotyped using sequence specific PCR. The genotypes and alleles between patients with BD and controls were compared using the chi2 test, together with Yate's correction where appropriate. Haplotype analysis was assessed using the EH program. RESULTS: The genotype and allele distributions of the two SNPs did not differ significantly between patients with BD and controls. The haplotype frequencies of the IL-18 promoter polymorphisms were also similar between patients with BD and controls. However, the frequency of the GG genotype at position -137 was significantly higher in BD patients with ocular lesions than in those without ocular lesions (p = 0.026, pc = 0.048, OR = 4.1). CONCLUSION: Although the IL-18 gene polymorphisms were not associated with a susceptibility to BD in the Korean population, the patients carrying the GG genotype at position -137 had a higher risk of developing the ocular lesions. Further studies in other populations are required to confirm these results.

Analysis of genes responding to ultraviolet B irradiation of HaCaT keratinocytes using a cDNA microarray.

BACKGROUND: Ultraviolet (UV) B irradiation causes many important biological changes in skin, which lead to pathophysiological alterations of the homeostatic environment. OBJECTIVES: To gain more insight into the molecular events provoked by UVB irradiation, we performed cDNA microarray analysis. METHODS: Immortalized HaCaT keratinocytes were irradiated with a high cytotoxic dose of UVB (50 mJ cm(-2)), and total RNA was isolated. Fluorescently labelled probes were prepared by reverse transcription and were hybridized with cDNA microarray slides made using 840 cDNA clones. RESULTS: Time-course cDNA microarray analysis revealed the global gene expression profile after UVB exposure. Of 840 genes tested, 192 genes showed changes in their expression levels at one or more of four time points. The genes were clustered into four groups according to their expression patterns in a self-organizing maps analysis. Classification of these genes into nine functional categories revealed that UVB irradiation affected several biological processes. The genes that were first upregulated and then returned to normal levels included several genes related to the inhibition of cell growth and the proteasome pathway. Conversely, the expressions of many genes involved in the cytoskeleton, signal transduction, metabolism and transcription were first downregulated or unchanged and then upregulated later, reflecting the recovery of UVB-damaged cellular activities. CONCLUSIONS: These results demonstrate the complexity of the transcriptional profile of the UVB response, and provide a basis for the global characterization of UV-regulated gene expression.