Management of hypersensitivity reactions to contrast media

As imaging technologies have become essential for diagnosing various diseases, the use of contrast agents is rapidly expanding. As a result, hypersensitivity reactions (HSRs) to contrast agents have also increased. However, protocols for managing, diagnosing, and preventing these reactions are not fully established yet. Since the guidelines for contrast agent hypersensitivity suggested by domestic and international academic societies are not standardized and sometimes difficult to follow in medical facilities, there is a need for practical recommendations in a real-world setting. This review introduces the strategy to manage, diagnose, and prevent HSRs to contrast agents, which have been successfully implemented at Seoul National University Hospital for a decade. First, every single HSRs should be documented in the medical records because a previous history of hypersensitivity to contrast agents is the most significant risk factor for developing HSR to iodinated contrast media. Secondly, avoidance of culprit agents is the main strategy for preventing recurrences of HSRs to contrast agents. Thirdly, it is important to identify nonsensitized contrast agents using skin tests for future exposure to contrast media. In addition to skin testing, side chains of iodinated contrast media may provide a clue to reactive contrast agents. Fourthly, provocation tests can be performed in selected cases with a nonreactive agent based on the skin testing and side chain commonness. Prior to performing imaging studies, premedication can be applied stratified to the severity of the index HSR. All of these procedures are safe and prove to be executable in the medical facilities.

Desensitization for the prevention of drug hypersensitivity

Drug desensitization is a treatment strategy for patients with hypersensitivity to essential drugs without alternatives. The gradual increase in the drug dosage from low doses to therapeutic levels induces a transient immune tolerance to the culprit drug. Although desensitization has traditionally been recommended for IgE-mediated immediate hypersensitivity, this indication has recently been expanded to include non-IgE-mediated immediate responses, nonimmunological responses, and T-cell-mediated delayed hypersensitivity reactions. Although the exact mechanism behind desensitization remains unclear, the process is thought to attenuate various intracellular signals in target cells through Fcɛ receptor 1 internalization, alteration in signaling pathways in mast cells and basophils, reduction in Ca 2+ influx, and production of anti-drug IgG4 blocking antibody. Desensitization can be used for the safe administration of anti-neoplastic agents, antibiotics, aspirin, and nonsteroidal anti-inflammatory drugs. Various desensitization protocols have been proposed for each drug. The optimization of drug concentration, target dosage, administration interval, and route of administration is key to successful desensitization. In addition, the desensitization protocol should be individualized for each patient with consideration of the severity of the initial hypersensitivity response, the characteristics of the culprit drug, and the nature of the breakthrough reactions.

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.

Management of hereditary angioedema in pediatric, pregnant, and breast-feeding patients: An expert opinion

Hereditary angioedema (HAE) is a rare inherited condition marked by recurrent skin and submucosal edema. HAE is caused by a C1 inhibitor deficiency or decreased C1 inhibitor function. The initial attack may occur during childhood or pregnancy, with symptoms ranging from classic angioedema to nonspecific stomach cramps. In this review, we discuss strategies for children and pregnant women to manage HAE attacks effectively and safely in light of the recent increase in HAE diagnosis. To begin, aggressive work-up is necessary to confirm HAE–1/2 and to determine the most effective countermeasures. Secondly, in the event of an acute attack, plasma-derived C1-inhibitor is the first line of defense for children and pregnant women. Icatibant is also appropriate for use, except in pregnant women. Fresh frozen plasma (FFP) may be suggested as an alternative. Thirdly, proactive measures to prevent HAE attacks should be considered whenever a procedure is performed that may result in an exacerbation. Finally, FFP, attenuated androgen and antifibrinolytic agents are recommended for long-term prophylaxis in South Korea where the C1-inhibitor is scarce. However, when making a decision, it is necessary to consider both the efficacy and the risk of adverse effects. For proper management, written action plans and first-aid kits are required. The action plans should be customized to the patients‘ unique circumstances.

Cigarette smoke extract contributes to the inception and aggravation of asthmatic inflammation by stimulating innate immunity

Purpose@#Smoking is a risk factor for the development of asthma and worsens the long-term prognosis of asthma. This study investigated the effect of cigarette smoke extract (CSE) on innate immune cells such as innate lymphoid cells (ILCs) and macrophages in a murine model of induced asthma. @*Methods@#Six-week-old female BALB/C mice were exposed to ovalbumin (OVA) via an intranasal route with or without CSE for 8 weeks to establish a chronic murine asthma model. Airway hyperresponsiveness (AHR), airway inflammatory cells from bronchoalveolar lavage fluid, and the population of CD4 + T cells, ILCs, and macrophages in the lungs were studied to evaluate the effect of chronic CSE exposure on asthma. @*Results@#Mice intranasally exposed to CSE along with OVA treatment (CSE/OVA) had significantly enhanced AHR, eosinophilic inflammation, increased IL-13 and IL-17 producing CD4 + T cells compared to mice intranasally exposed to OVA only. On the contrary, the frequency of Foxp3 + in CD4 + T cells was reduced in the CSE/OVA group. CSE enhanced the dendritic cell (DC) population, especially MHCII + DC with antigen-presenting capacity. Among ILCs, the CSE/OVA group showed a significant increase of IL-13-producing type 2 ILCs, but not interferon-γ+ ILC1s and IL-17 + ILC3s. . Among macrophages, alveolar macrophage and Ym-1 and FIZZ1 positive M2 macrophage populations were significantly induced by CSE exposure alone and when combined with OVA treatment. @*Conclusion@#In this study, we showed that long-term exposure to cigarette smoke contributes to the inception and aggravation of asthmatic inflammation by enhancing DCs, ILC2, and M2 alveolar macrophage populations in the mouse model.

A successful shortening of desensitization protocol in a patient with cetuximab anaphylaxis

Desensitization therapy can help overcome severe hypersensitivity reactions and allow continuing administration of the culprit agents. However, this is time- and labor-intensive due to a prolonged infusion time and the serial adjustment of infusion rate between steps. Therefore, simplified protocols using fewer steps have been tested, although currently there is no established standard strategy. Cetuximab plays an important role in the treatment of metastatic colorectal cancer. Although cetuximab is well tolerated, severe infusion reactions occur in 1.1% of patients, and most occur within 1 hour of receiving the first dose. Here, we report a recent attempt to shorten the steps of gradual cetuximab desensitization. A 57-year-old male patient diagnosed with obstructive sigmoid colon cancer received cetuximab chemotherapy and experienced immediate anaphylaxis at the first cycle. A one-bag, 17-step desensitization protocol was applied to cetuximab administration. After the first successful desensitization cycle, the process of desensitization was shortened 1–2 step(s) per cycle, down to 2 steps, without a breakthrough reaction. The patient ultimately received regular infusions. Shortening of the rapid desensitization protocol can be considered if the previous cycle is well-tolerated, even in a patient who suffered previous anaphylaxis to cetuximab.

Diagnosis and treatment of hereditary angioedema: An expert opinion

Hereditary angioedema (HAE) is a rare disease, but it severely interrupts daily life activities and can sometimes be life-threatening. Therefore, early diagnosis and prompt treatment of HAE attacks are critical. Physicians should be aware of how to diagnose and manage HAE to prepare not to miss a diagnosis when treating HAE patients. Physicians must also carry out tests to confirm the diagnosis of HAEs caused by C1 inhibitor deficiency (type 1) or C1 inhibitor dysfunction (type 2) in patients with recurrent angioedema. In addition, recent studies revealed another type of HAE which is not related to C1 inhibitor (normal C1 inhibitor HAE). Once HAE is confirmed, patients and their caregivers should be given with short-term and long-term treatment plans to relieve or prevent HAE attacks. HAE requires life-long measures, including psychological support for patients and self-management education.

Interactions between NCR + ILC3s and the Microbiome in the Airways Shape Asthma Severity

Asthma is a heterogeneous disease whose development is shaped by a variety of environmental and genetic factors. While several recent studies suggest that microbial dysbiosis in the gut may promote asthma, little is known about the relationship between the recently discovered lung microbiome and asthma. Innate lymphoid cells (ILCs) have also been shown recently to participate in asthma. To investigate the relationship between the lung microbiome, ILCs, and asthma, we recruited 23 healthy controls (HC), 42 patients with non-severe asthma, and 32 patients with severe asthma. Flow cytometry analysis showed severe asthma associated with fewer natural cytotoxicity receptor (NCR) + ILC3s in the lung.Similar changes in other ILC subsets, macrophages, and monocytes were not observed. The asthma patients did not differ from the HC in terms of the alpha and beta-diversity of the lung and gut microbiomes. However, lung function correlated positively with both NCR + ILC3 frequencies and microbial diversity in the lung. Sputum NCR + ILC3 frequencies correlated positively with lung microbiome diversity in the HC, but this relationship was inversed in severe asthma. Together, these data suggest that airway NCR + ILC3s may contribute to a healthy commensal diversity and normal lung function.

Pathophysiology, diagnosis, and management of chronic pruritus

“Itch” is an unpleasant sensation that elicits a desire to scratch. It is a common complaint among many patients and is associated with a markedly reduced quality of life. The pathogenesis of itch begins with various pruritogens stimulating free nerve endings in the skin, which causes an itch signal to travel through the spinothalamic tract to the brain where the sensation is processed. Scratching an itch initially activates the reward systems in the midbrain and striatum, and this positive reinforcement leads to the repetitive scratching behavior that damages the skin barrier. Mediators such as histamine, serotonin and cytokines are released from the damaged skin, which further aggravates the itch and initiates a vicious “itch-scratch cycle.” Such processes may eventually lead to neural sensitization, where weaker stimuli can cause a more severe pruritic sensation. Chronic itch is one that lasts beyond 6 weeks. Pathologic pruritus can be classified into four different categories based on its cause: dermatologic, systemic, neuropathic, and psychogenic itch. Regardless of the cause, antihistamines are often prescribed as a first-line treatment of chronic itch, but more often than not they prove to be ineffective in bringing symptom relief. Both topical and systemic therapies are used to treat itch, and adequate treatment selection is considered according to symptom severity and chronicity. As the pathogenesis of itch becomes elucidated, more exciting new therapeutic options targeting pruritogenic mediators are becoming increasingly available. This review provides an overview of the pathophysiology, causes and the treatment of chronic itch.

Therapeutic effect of atorvastatin on interleukin-13-induced lung pathology

Purpose@#Asthma is a common chronic lung disease, in which interleukin (IL)-13 is implicated as a central regulator of IgE synthesis, mucus hypersecretion, airway hyperresponsiveness (AHR), and fibrosis. This study was designed to determine the anti-inflammatory effect of atorvastatin, a widely used lipid-lowering agent, on the IL-13-induced lung pathology through the modulation of macrophages. @*Methods@#Atorvastatin (40 mg/kg) was given to transgenic mice overexpressing IL-13 (IL-13 TG mice) and their wild type littermates by oral gavage for 2 weeks. AHR, numbers of inflammatory cells in the airway, and cytokine levels in IL-13 TG mice were measured.Using the alveolar macrophage cell line CRL-2456, the direct effect of atorvastatin on macrophages activated by recombinant IL-13 was assessed. @*Results@#Significant reduction in total leukocytes and alleviation of AHR were observed with administration of atorvastatin in IL-13 TG mice compared to those without atorvastatin treatment (P< 0.05). Atorvastatin administration resulted in upregulation of IL-10 in the lungs of IL-13 TG mice (P< 0.05). In addition, mRNA expression of connective tissue growth factor, fibronectin, and type III collagen as well as chord length enhanced by IL-13 overexpression were reduced by atorvastatin administration (P< 0.05). M2 macrophage markers, such as Ym-1 and CD206, were decreased, while M1 macrophage marker, inducible nitric oxide synthase, was increased upon atorvastatin treatment (P< 0.05). Administration of atorvastatin resulted in improved removal of apoptotic cells (P< 0.05). @*Conclusion@#The results of this study reveal a potential of atorvastatin as an effective antiasthmatic agent by reducing IL-13-induced lung inflammation via the modulation of macrophage polarization.

A 10-Year Single-Center Experience of Adverse Drug Reaction Monitoring / 대한내과학회지

Background/Aims@#Despite proper use of pharmaceuticals, adverse drug reactions (ADRs) can lead to problems related to patient safety. We analyzed the characteristics of ADRs, particularly serious adverse events (SAEs), in a single tertiary medical institution. @*Methods@#Spontaneous ADR report data collected from 2010 to 2019 in Seoul National University Hospital were assessed. Causality was evaluated according to the World Health Organization-Uppsala Monitoring Centre criteria. Age, sex, onset, severity, seriousness, and system organ class (SOC) of ADRs and SAEs were analyzed. @*Results@#During the study period, a total of 49,955 individual case safety reports were assessed as possible, probable, or certain. Although the number of gastrointestinal ADR reports was high (25.9%), severe cases were uncommon (2.6%). By contrast, the number of hematologic disorders was low (6.6%) but 39.2% of them were severe. Among ADRs, 10.2% were assessed as SAEs, the proportion of which was high at extreme ages and in males. Body as a whole-general disorders were the most frequently reported SOC for SAEs, followed by skin and appendage disorders. Antineoplastic agents and antibiotics were the most common causative agents of SAEs and ADRs. Anaphylactic reaction was the most frequent SAE (6.5%). @*Conclusions@#The proportion of SAE differs according to SOC and drug. Attention should be paid to SAEs in children and older adults because the rate of SAEs is significantly higher at extreme ages.

A 10-Year Single-Center Experience of Adverse Drug Reaction Monitoring / 대한내과학회지

Background/Aims@#Despite proper use of pharmaceuticals, adverse drug reactions (ADRs) can lead to problems related to patient safety. We analyzed the characteristics of ADRs, particularly serious adverse events (SAEs), in a single tertiary medical institution. @*Methods@#Spontaneous ADR report data collected from 2010 to 2019 in Seoul National University Hospital were assessed. Causality was evaluated according to the World Health Organization-Uppsala Monitoring Centre criteria. Age, sex, onset, severity, seriousness, and system organ class (SOC) of ADRs and SAEs were analyzed. @*Results@#During the study period, a total of 49,955 individual case safety reports were assessed as possible, probable, or certain. Although the number of gastrointestinal ADR reports was high (25.9%), severe cases were uncommon (2.6%). By contrast, the number of hematologic disorders was low (6.6%) but 39.2% of them were severe. Among ADRs, 10.2% were assessed as SAEs, the proportion of which was high at extreme ages and in males. Body as a whole-general disorders were the most frequently reported SOC for SAEs, followed by skin and appendage disorders. Antineoplastic agents and antibiotics were the most common causative agents of SAEs and ADRs. Anaphylactic reaction was the most frequent SAE (6.5%). @*Conclusions@#The proportion of SAE differs according to SOC and drug. Attention should be paid to SAEs in children and older adults because the rate of SAEs is significantly higher at extreme ages.

Antiasthmatic effect of atorvastatin via modulation of macrophage activation

Purpose@#Asthma is a chronic airway inflammatory disorder and is associated with macrophages. Statin, a well-known lipid-lowering agent, has recently been noted for its anti-inflammatory effect on macrophage. This study was designed to evaluate the antiasthmatic effect of atorvastatin via modulation of macrophage activation by using an animal model of allergic asthma. @*Methods@#Atorvastatin 40 mg/kg was given by gavage once a day for 3 days before challenge of ovalbumin (OVA); airway hyperresponsiveness (AHR), airway inflammatory cells, and cytokines were evaluated in the murine asthma model. The direct effect of atorvastatin on the activation of macrophages In vitro was determined using the alveolar macrophage cell line CRL-2456. @*Results@#Administration of atorvastatin reduced the numbers of total inflammatory cells, macrophages, and eosinophils as well as lung histology enhanced in the murine asthma model. AHR measured by enhanced pause was significantly reduced after atorvastatin administration in the murine asthma model (P< 0.05). Atorvastatin administration resulted in the reduction in serum OVA-specific IgE levels and the increase in serum OVA-specific IgG2a levels (P< 0.05). The mRNA levels of Ccr3, Il-17, and Muc5ac enhanced by OVA challenge were decreased by treatment with atorvastatin (P< 0.05). Along with these improvement in allergic inflammatory changes, the population of CD11c-CD206+ macrophages as well as the expression of Ym-1 and Relm-α in the lungs were reduced with atorvastatin (P< 0.05). In vitro test with CRL-2456 showed that atorvastatin reduced the expression of Cd206, Arg-1, and Fgf-2 induced by IL-4 stimulation (P< 0.05). @*Conclusion@#This study highlighted the antiasthmatic effect of atorvastatin on the suppression of M2 macrophage activation in allergic asthma.

Adverse Drug Reactions to First-line Anti-tubercular Drugs Based on Individual Case Safety Report in a Single Tertiary Hospital / 대한내과학회지

Background/Aims@#Tuberculosis has incidence and mortality rates that are among the highest for all communicable diseases. Adverse drug reactions (ADRs) to anti-tubercular drugs are common, and have a major impact on treatment maintenance and prognosis. It is important to understand the characteristics of ADRs and establish a suitable management plan. @*Methods@#We retrospectively reviewed patients with ADRs during treatment with first-line antitubercular drugs such as isoniazid, rifampicin, ethambutol, and pyrazinamide from 2009 to 2018. Age, sex, and total treatment period, and the onset, severity, seriousness, and system organ class of ADRs, were analyzed to understand the characteristics of first-line anti-tubercular drug-related ADRs. @*Results@#A total of 1,606 of 5,482 patients (29.3%) experienced ADRs after administration of first-line anti-tubercular drugs. The incidence of ADRs related to isoniazid, rifampicin, ethambutol, and pyrazinamide was 22.2%, 21.3%, 24.5%, and 29.6%, respectively. A total of 2,098 ADR reports were made (mean of 1.3 ± 0.6 per patient). The rates of mild, moderate, and severe ADRs were 32.4%, 61.1%, and 6.5%, respectively. There were 127 reports (6.1%) of serious ADRs. Skin and appendage disorders were most frequently reported (27.5%), followed by gastrointestinal disorders (17.5%), and liver and biliary system disorders (13.1%). The total treatment period was longer in patients who experienced ADRs (224.0 ± 3.1 days vs. 247.0 ± 4.7 days, p = 0.009). @*Conclusions@#The incidence of ADRs to first-line anti-tuberculosis drugs was 29.3%, and 6.5% were severe ADRS. ADRs prolonged the overall treatment duration, indicating the importance of their detection and management.

Recent updates of iodinated contrast media hypersensitivity

Previously, immediate reactions to ionic high-osmolar iodinated contrast media (ICM) were regarded as nonimmunological. However, despite the use of lower-osmolar ICM, ICM hypersensitivity still occurs in some patients and recent studies suggest that there would be a true allergic response, especially in more severe form. Currently, it is important to identify the sensitized ICM and avoid the agent; however, the usefulness of skin tests and challenge tests has not yet been established, since there are few large-scale studies on them. Although, skin test-negative ICM can be safely used in clinical practice, conflicting results have been reported through various studies, depending on the challenge protocols used. Therefore, standard protocols need to provided. Even if a culprit agent is not proven by skin tests, its use should be avoided. Reuse of contrast media increases the risk of occurrence of hypersensitivity reactions. For patients with previous hypersensitivity reactions to contrast media, premedication can help prevent recurrence, but breakthrough in hypersensitivity is not fully achieved by premedication, especially when the previous reaction was a severe form such as anaphylaxis. Therefore, it is necessary to establish an optimal strategy to choose alternative ICM and premedication protocols to prevent recurrence of hypersensitivity reactions to nonionic contrast media.

Comparison of one-bag and multibag desensitization protocols for the prevention of rituximab hypersensitivity

Purpose@#Rituximab is prone to infusion-related reactions, which commonly requires desensitization to maintain its administration. Conventional desensitization protocols are using multistep infusion by diluting solutions. However, the process of diluting drugs and stepwise delivery needs additional time and effort. The objective of this study was to investigate the safety and efficacy of a nondiluting, one-bag protocol of rituximab desensitization. @*Methods@#A retrospective study was performed by reviewing the medical records of patients who underwent rituximab desensitization between 2009 and 2018. The completion rate, occurrence and severity of breakthrough reactions (BTR), and time required to complete the therapy were compared between one-bag protocol and multibag protocol. Results were analyzed by generalized estimation equation method, and odds ratios (ORs) of completion rate and BTR incidence were estimated. @*Results@#Total 190 cases of desensitization therapy were performed in 49 patients; the incidence of BTR was 16.84% and the overall completion rate was 96.32%. No significant difference in completion rate was found (OR, 3.58; 95% confidence interval [CI], 0.79– 16.38) and there was no significant difference in BTR incidence (OR, 0.81; 95% CI, 0.23–2.82) in one-bag protocol. BTR in the one-bag protocol tended to occur even through entire steps, whereas most of the BTR in the multibag protocol occurred at later steps of the process. The average time spent in the desensitization was 60 minutes shorter in the one-bag than the multibag protocol (258.15 minutes vs. 329.81 minutes, P< 0.001). @*Conclusion@#One-bag desensitization protocol showed no significant difference in safety and efficiency compared to the conventional multibag protocol, with shortening the time required for completion.

Prevalence of Toxocariasis and Its Risk Factors in Patients with Eosinophilia in Korea

Eosinophilia occurs commonly in many diseases including allergic diseases and helminthic infections. Toxocariasis has been suggested as one cause of eosinophilia. The present study was undertaken to examine the prevalence of toxocariasis in patients with eosinophilia and to identify the risk factors for toxocariasis. This prospective cohort study recruited a total of 81 patients with eosinophilia (34 males and 47 females) who visited the outpatient clinic at Seoul National University Hospital from January 2017 to February 2018 and agreed to participate in this study. The prevalence of toxocariasis was examined by T. canis-specific ELISA, and the various risk factors for toxocariasis were evaluated by a questionnaire survey. Among 81 patients with eosinophilia, 18 were positive for anti-T. canis antibodies (22.2%); 88.9% were male (16/18) and 11.1% were female (2/18). Multivariate statistical analysis revealed that males (OR 21.876, 95% CI: 1.667-287.144) with a history of consuming the raw meat or livers of animals (OR 5.899, 95% CI: 1.004-34.669) and a heavy alcohol-drinking habit (OR 8.767, 95% CI: 1.018-75.497) were at higher risk of toxocariasis in patients with eosinophilia. Toxocariasis should be considered a potential cause of eosinophilia when the patient has a history of eating the raw meat or livers of animals in Korea. A single course of albendazole is recommended to reduce the migration of Toxocara larvae in serologically positive cases with eosinophilia.

A Prospective Observation of Psychological Distress in Patients With Anaphylaxis

PURPOSE: Anaphylaxis is an immediate allergic reaction characterized by potentially life-threatening, severe, systemic manifestations. While studies have evaluated links between serious illness and posttraumatic stress disorder (PTSD), few have investigated PTSD after anaphylaxis in adults. We sought to investigate the psychosocial burden of recent anaphylaxis in Korean adults.METHODS: A total of 203 (mean age of 44 years, 120 females) patients with anaphylaxis were recruited from 15 university hospitals in Korea. Questionnaires, including the Impact of Event Scale-Revised-Korean version (IES-R-K), the Korean version of the Beck Anxiety Inventory (K-BAI), and the Korean version of the Beck Depression Inventory (K-BDI), were administered. Demographic characteristics, causes and clinical features of anaphylaxis, and serum inflammatory markers, including tryptase, platelet-activating factor, interleukin-6, tumor necrosis factor-α, and C-reactive protein, were evaluated.RESULTS: PTSD (IES-R-K ≥ 25) was noted in 84 (41.4%) patients with anaphylaxis. Of them, 56.0% had severe PTSD (IES-R-K ≥ 40). Additionally, 23.2% and 28.1% of the patients had anxiety (K-BAI ≥ 22) and depression (K-BDI ≥ 17), respectively. IES-R-K was significantly correlated with both K-BAI (r = 0.609, P < 0.0001) and K-BDI (r = 0.550, P < 0.0001). Among the inflammatory mediators, tryptase levels were lower in patients exhibiting PTSD; meanwhile, platelet-activating factor levels were lower in patients exhibiting anxiety and depression while recovering from anaphylaxis. In multivariate analysis, K-BAI and K-BDI were identified as major predictive variables of PTSD in patients with anaphylaxis.CONCLUSIONS: In patients with anaphylaxis, we found a remarkably high prevalence of PTSD and associated psychological distresses, including anxiety and depression. Physicians ought to be aware of the potential for psychological distress in anaphylactic patients and to consider psychological evaluation.

Altered T cell and monocyte subsets in prolonged immune reconstitution inflammatory syndrome related with DRESS (drug reaction with eosinophilia and systemic symptoms)

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe cutaneous adverse reaction involving various internal organs. Flare-ups after recovery from the initial presentation of DRESS are caused by relapse of drug-induced T-cell-mediated reactions. However, the specific underlying mechanism is unclear. Here, we report a case of a 60-year-old man with allopurinol-induced DRESS who suffered recurrent episodes of generalized rash with eosinophilia, which mimicked immune reconstitution inflammatory syndrome. Analysis of immunological profiles revealed that the percentages of T lymphocytes and regulatory T cells in the patient with DRESS were higher than those in healthy controls. In addition, there was a notable change in the subtype of monocytes in the patient with DRESS; the percentage of nonclassical monocytes increased, whereas that of classical monocytes decreased. Upon viral infection, nonclassical monocytes exhibited strong pro-inflammatory properties that skewed the immune response toward a Th2 profile, which was associated with persistent flare-ups of DRESS. Taken together, the results increase our understanding of the pathogenesis of DRESS as they suggest that expansion of nonclassical monocytes and Th2 cells drives disease pathogenesis.

Drug hypersensitivity reactions in Asia: regional issues and challenges

There are geographical, regional, and ethnic differences in the phenotypes and endotypes of patients with drug hypersensitivity reactions (DHRs) in different parts of the world. In Asia, aspects of drug hypersensitivity of regional importance include IgE-mediated allergies and T-cell-mediated reactions, including severe cutaneous adverse reactions (SCARs), to beta-lactam antibiotics, antituberculous drugs, nonsteroidal anti-inflammatory drugs (NSAIDs) and radiocontrast agents. Delabeling of low-risk penicillin allergy using direct oral provocation tests without skin tests have been found to be useful where the drug plausibility of the index reaction is low. Genetic risk associations of relevance to Asia include human leucocyte antigen (HLA)-B*1502 with carbamazepine SCAR, and HLA-B*5801 with allopurinol SCAR in some Asian ethnic groups. There remains a lack of safe and accurate diagnostic tests for antituberculous drug allergy, other than relatively high-risk desensitization regimes to first-line antituberculous therapy. NSAID hypersensitivity is common among both adults and children in Asia, with regional differences in phenotype especially among adults. Low dose aspirin desensitization is an important therapeutic modality in individuals with cross-reactive NSAID hypersensitivity and coronary artery disease following percutaneous coronary intervention. Skin testing allows patients with radiocontrast media hypersensitivity to confirm the suspected agent and test for alternatives, especially when contrasted scans are needed for future monitoring of disease relapse or progression, especially cancers.