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Hereditary angioedema (HAE) is a rare genetic disease with significant morbidity and mortality for which early diagnosis and effective therapy are critical. Many Asia Pacific (AP) countries still lack access to diagnostic tests and evidence-based therapies. Epidemiologic data from the AP is needed to formulate regional guidelines to improve standards of care for HAE.

The development of hypersensitivity reactions (HSRs) to carboplatin can interrupt anticancer treatment and may shorten patient survival. Several studies have evaluated the risk factors for carboplatin HSRs, but the results have been inconclusive.

The development of molecular imaging probes to identify key cellular changes within lung metastases may lead to noninvasive detection of metastatic lesions in the lung. In this study, we constructed a macrophage-targeted clickable albumin nanoplatform (CAN) decorated with mannose as the targeting ligand using a click reaction to maintain the intrinsic properties of albumin in vivo. We also modified the number of mannose molecules on the CAN and found that mannosylated serum albumin (MSA) harboring six molecules of mannose displayed favorable pharmacokinetics that allowed high-contrast imaging of the lung, rendering it suitable for in vivovisualization of lung metastases. Due to the optimized control of functionalization and surface modification, MSA enhanced blood circulation time and active/passive targeting abilities and was specifically incorporated by mannose receptor (CD206)-expressing macrophages in the metastatic lung. Moreover, extensive in vivoimaging studies using single-photon emission computed tomography (SPECT)/CT and positron emission tomography (PET) revealed that blood circulation of time-optimized MSA can be used to discern metastatic lesions, with a strong correlation between its signal and metastatic burden in the lung.

In addition to the absence of premedication and repeated use of the culprit gadolinium-based contrast agents (GBCAs), a history of hypersensitivity reactions to iodinated contrast media and GBCAs may increase the risk of hypersensitivity reactions to GBCAs.

This Practice Advisory presents a comprehensive and evidence-based set of position statements and recommendations for the use of contrast media in interventional pain procedures. The advisory was established by an international panel of experts under the auspices of 11 multinational and multispecialty organizations based on a comprehensive review of the literature up to December 31, 2019. The advisory discusses the risks of using gadolinium-based contrast agents. These include nephrogenic systemic fibrosis, gadolinium brain deposition/retention, and encephalopathy and death after an unintentional intrathecal gadolinium injection. The advisory provides recommendations on the selection of a specific gadolinium-based contrast agent in patients with renal insufficiency, those who had multiple gadolinium-enhanced magnetic resonance imaging examinations, and in cases of paraspinal injections. Additionally, recommendations are made for patients who have a history of mild, moderate, or severe hypersensitivity reactions to contrast medium.

ABSTRACTBackgroundThe human leukocyte antigen (HLA)-B*13:01 was reported as an important risk factor for dapsone hypersensitivity syndrome (DHS) in Chinese and Thai populations.Research design and methodsFrom the Korean nationwide registry, seven subjects with previous DHS were included. Their HLA allele/phenotype frequencies were compared with 8 dapsone-tolerant subjects recruited from a single institution, and general population (n = 485) in Korea. The authors also performed a meta-analysis with these data using previous Chinese and Thai studies.ResultsAmong the seven DHS subjects, 85.7% presented with the HLA-B*13:01 allele. The HLA-C*03:04, HLA-DRB1*12:02 (both in linkage disequilibrium with HLA-B*13:01), and HLA-A*02:01 alleles were also presented in 85.7%, 71.4%, and 71.4%, respectively. Subjects with HLA-B*13:01 were susceptible to developing DHS compared to dapsone-tolerant controls (odds ratio [OR]: 73.667) and the Korean general population (OR: 139.500). HLA-C*03:04 (OR: 40.935), HLA-DRB*12:02 (OR: 36.613), and HLA-A*02:01 (OR: 5.862) showed similar results. In meta-analysis, HLA-B*13:01 was associated with dapsone-induced hypersensitivity (overall OR: 42.692), and subgroup analyses according to the control types demonstrated similar results (OR:43.694 and 41.866, respectively).ConclusionsSimilar to previous Asian population studies, HLA-B*13:01 is significantly associated with the risk of DHS in Korea. These associations may be useful for preventing DHS and improving drug safety.

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Desensitization is used to safely continue treatment with a culprit drug in patients with drug hypersensitivity. Currently, a multi-bag protocol is widely used for rapid desensitization, but performing the desensitization procedure is labor intensive as pharmacists and nurses need to prepare and administer diluted solutions. However, it has not been investigated whether dilution is essential for successful desensitization.

Family history and previous individual history of hypersensitivity reaction to iodinated contrast media were risk factors for new hypersensitivity occurrence. Premedication and change of iodinated contrast media type were useful measures to prevent recurrent hypersensitivity reaction.

Supplemental digital content is available in the text.

Although HLA-B*58:01 is a well-known risk factor for the development of allopurinol-induced severe cutaneous adverse reactions (SCARs), most of the HLA-B*58:01 carriers do not suffer from SCARs despite a long-term use of allopurinol. This suggests that there are other risk factors that determine the fate of HLA-B*58:01 carriers.

The rate of mild hypersensitivity reaction at reexposure to low-osmolar iodinated contrast media was significantly reduced when the culprit contrast agent was changed. However, recurrence rates vary according to the specific combinations of iodinated contrast media used in the index reaction and at reexposure.

Substitution with a low-osmolar iodinated contrast agent that does not share a common carbamoyl side chain may be a practical strategy to reduce the recurrence of immediate hypersensitivity reactions.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening, severe mucocutaneous adverse reactions. Severity prediction at early onset is urgently required for treatment. However, previous prediction scores have been based on data of blood tests.

Epidemiology and risk factors of drug-induced anaphylaxis are difficult to estimate due to lack of confirmative diagnosis and under reporting. Here we report the current state of drug-induced anaphylaxis in Korea based on an in-hospital pharmacovigilance database in a tertiary hospital.

Some western countries recently have shown a slowdown in the incidence of allergic diseases after worldwide increasing trends, but there are few data from Asian populations concerning changing trend of allergic diseases. We evaluated the recent trends in the prevalence of asthma and other allergic diseases in Korea.

Neuromuscular blocking agents (NMBAs) are one of the most common causes of perioperative anaphylaxis. Although skin test positivity may help identify reactive NMBAs, it is unclear whether skin test negativity can guarantee the safety of systemically administered NMBAs.

Purpose:This study was conducted to evaluate the usefulness of human leukocyte antigen (HLA) typing in preventing allopurinol-induced severe cutaneous adverse reactions (SCARs) through the application of an allopurinol tolerance induction protocol or prescription of other alternative medications in high-risk patients.Methods:HLA typing was performed in patients with chronic renal insufficiency who needed allopurinol. HLA-B*58:01-negative patients were prescribed the usual dose of allopurinol. For HLA-B*58:01-positive patients, administration of either allopurinol based on a 28-day tolerance induction protocol or alternative medications was initiated. Hypersensitivity reactions were surveyed for 90 days and compared with the result of a previous retrospective cohort study.Results:Among a total of 401 study subjects, no SCARs were noted in HLA-B*58:01-positive patients with application of the tolerance induction protocol (n = 30) or alternative medications (n = 16), nor were any SCARs observed in HLA-B*58:01-negative patients who started allopurinol at the usual dose (n = 355). Compared with the previous retrospective cohort study, a significant reduction in SCARs was observed in HLA-B*58:01-positive patients (0 vs. 18%; P = 0.002).Conclusion:This study shows the usefulness of HLA-B*58:01 screening in identifying patients at high risk for the development of allopurinol-induced SCARs and suggests that application of a tolerance induction protocol or alternative medications could be an effective strategy to prevent allopurinol-induced SCARs in HLA-B*58:01-positive patients.Genet Med 17 10, 807–814.

An optimal strategy for choosing safe alternative low osmolar contrast media (LOCM) has not yet been established in patients with a history of LOCM-induced anaphylaxis.

High doses of vancomycin increase the risk of nephrotoxicity, but the quantitative relationship between vancomycin exposure and nephrotoxicity is still controversial. This study evaluated the relationship between vancomycin trough concentration and nephrotoxicity, and risk factors for nephrotoxicity in patients undergoing therapeutic drug monitoring.

Recent studies suggest an association between allergic diseases, including asthma, and lower vitamin D level, a well-known risk factor of osteoporosis. However, it is not yet clearly known whether patients with asthma are prone to bone loss.

Recently, it has been suggested that airway hyper-responsiveness, asthma, and atopic dermatitis are associated with a low vitamin D level.

Recent investigations suggest genetic susceptibility of allopurinol-induced severe cutaneous adverse reactions (SCARs). However, the strength of association was variable according to phenotypes and ethnic backgrounds. To explore genetic markers for allopurinol-induced SCARs in Koreans, we genotyped human leukocyte antigen (HLA) class I alleles of 25 cases of allopurinol-induced SCARs (20 cases of drug-induced hypersensitivity syndrome and five cases of Stevens–Johnson syndrometoxic epidermal necrolysis) and 57 patients tolerant to allopurinol. Frequencies of B5801 92.0 vs. 10.5, Pc=2.45×10−11, odds ratio (OR)=97.8, Cw0302 (92.0 vs. 12.3, Pc=9.39×10−11, OR=82.1), and A3303 (88.0 vs. 26.3, Pc=3.31×10−6, OR=20.5) were significantly higher in SCARs compared with tolerant controls. In contrast, A0201 was not found in SCARs patients despite relatively high frequency in tolerant controls (29.8). We found strong positive association of HLA-B5801 and negative association of HLA-A0201 with the development of allopurinol-induced SCARs in the Korean population.

Early detection of drug-resistant Mycobacterium tuberculosisis important for the control and prevention of disease transmission. However, conventional drug susceptibility tests for drug-resistant M tuberculosistake at least 3 to 8 weeks. Here, we report the clinical efficacy of direct DNA sequencing analysis for detecting drug-resistant TB on sputum specimens in a clinical setting.

TGF-1 is a multifunctional molecule that is expressed in an exaggerated fashion during injury, inflammation and repair. Its expression is dysregulated in lung tissues from patients with pulmonary fibrosis and chronic obstructive pulmonary disease. In animal models, introduction of TGF-1 expression in the lung causes prominent tissue fibrosis and alveolar destruction. On the other hand, the exaggerated production of TGF-1, an inability to activate TGF-1 or a block in TGF-1 signaling have all been associated with the development of emphysematous pulmonary lesions. A number of studies have demonstrated that TGF-1 is a major player in the pathogenesis of pulmonary fibrosis and emphysema. In this review, we discuss how TGF-1 expression is regulated and mechanistically related to the development of tissue fibrosis and emphysema in experimental animal models and humans. We further highlight potential therapeutic options that control TGF-1-associated genes or signals to restore extracellular matrix homeostasis in which TGF-1 plays a central role.

Because severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) rarely occur, clinical data based on large-scale studies are still lacking.

Patients who suffered drug reaction with eosinophilia and systemic symptom (DRESS) during the treatment of tuberculosis (TB) commonly experience multi-drug hypersensitivity reactions resulting in limited anti-TB drug choices. Therefore, reintroduction based on desensitization protocol may be an option to resume anti-TB medication.

Ethnic differences exist in relation to culprit drugs for Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We wanted to determine culprit drugs for SJS and TEN in Korean population.

Allopurinol is the most common cause of severe cutaneous adverse reactions (SCARs) in Korea due to the relatively high prevalence of the HLA-B*58:01 genotype (8%-13%).

Although the severity of hypersensitivity reactions to iodinated contrast media varies, it is well correlated with the severity of recurrent reactions; however, prophylaxis protocols are not severity-stratified.

Trimebutine maleate [2-dimethylamino-2-phenylbutyl 3,4,5-trimethoxybenzoic acid] has been demonstrated to be active for relieving abdominal pain and it is widely used for patients with irritable bowel syndrome. Adverse drug reactions are mostly mild and well-tolerated. To our knowledge, only two cases of trimebutine induced hypersensitivity have been reported, and both were delayed type reactions. Here, we report the first case of trimebutine maleate-induced anaphylaxis.