Successful desensitization to atezolizumab-induced near-fatal anaphylaxis in patients with hepatocellular carcinoma: A case report and literature review.

Atezolizumab, a humanized antiprogrammed death ligand 1 monoclonal immunoglobulin G1 antibody, is a targeted therapeutic drug known as an immune checkpoint inhibitor. It is currently used to treat various types of cancer, including unresectable hepatocellular carcinoma (HCC), nonsmall cell lung cancer, urothelial cancer, and breast cancer, and is becoming a therapeutic option in the forefront of oncology treatment. However, it may sometimes lead to undesirable adverse reactions owing to the activation of immune responses in various organs. Cutaneous adverse reactions to atezolizumab are well known; however, cases of anaphylaxis are very rare. In this report, we present the first case of HCC who experienced near-fatal anaphylaxis to atezolizumab in South Korea.

PGAP3 regulates human bronchial epithelial cell mRNAs present in asthma and respiratory virus reference data sets.

PGAP3 is a glycosylphosphatidylinositol (GPI) phospholipase gene localized within chromosome 17q12-21, a region highly linked to asthma. Although much is known about the function of other chromosome 17q12-21 genes expressed at increased levels in bronchial epithelium such as ORMDL3 and GSDMB, little is known about the function of increased PGAP3 expression in bronchial epithelium in the context of asthma. The aim of this study was therefore to determine whether increased PGAP3 expression in human bronchial epithelial cells regulated expression of mRNA pathways important to the pathogenesis of asthma by utilizing RNA-sequencing and bioinformatic analysis. We performed RNA-sequencing on normal human bronchial epithelial cells transfected with PGAP3 for 24 and 48 hours. PGAP3 regulated genes were compared to asthma and respiratory virus (influenza A, rhinovirus, respiratory syncytial virus) reference data sets to identify PGAP3 target genes and pathways. Approximately 9% of the upregulated PGAP3-induced genes were found in an asthma reference data set, 41% in a rhinovirus reference data set, 33% in an influenza A reference data set, and 3% in a respiratory syncytial virus reference data set. PGAP3 significantly upregulated the expression of several genes associated with the innate immune response and viral signatures of respiratory viruses associated with asthma exacerbations. Two of the highest expressed genes induced by PGAP3 are RSAD2, OASL, and IFN-λ, which are anti-viral genes associated with asthma. PGAP3 also upregulated the antiviral gene BST2, which like PGAP3 is a GPI-anchored protein. We conclude that PGAP3 expression in human bronchial epithelial cells regulates expression of genes known to be linked to asthma, and also regulates the bronchial epithelial expression of genes pertinent to the pathogenesis of respiratory viral triggered asthma exacerbations.

KAAACI Allergic Rhinitis Guidelines: Part 2. Update in Non-pharmacological Management.

Allergic rhinitis is the most common chronic disease worldwide. Various upper airway symptoms lower quality of life, and due to the recurrent symptoms, multiple treatments are usually attempted rather than one definitive treatment. There are alternatives to medical (medication-based) and non-medical treatments. A guideline is needed to understand allergic rhinitis and develop an appropriate treatment plan. We have developed guidelines for medical treatment based on previous reports. The current guidelines herein are associated with the "KAAACI Evidence-Based Guidelines for Allergic Rhinitis in Korea, Part 1: Update in pharmacotherapy" in which we aimed to provide evidence-based recommendations for the medical treatment of allergic rhinitis. Part 2 focuses on non-pharmacological management, including allergen-specific immunotherapy, subcutaneous or sublingual immunotherapy, nasal saline irrigation, environmental management strategies, companion animal management, and nasal turbinate surgery. The evidence to support the treatment efficacy, safety, and selection has been systematically reviewed. However, larger controlled studies are needed to elevate the level of evidence to select rational non-medical therapeutic options for patients with allergic rhinitis.

KAAACI Allergic Rhinitis Guidelines: Part 1. Update in Pharmacotherapy.

The prevalence of allergic rhinitis (AR) and the socioeconomic burden associated with the medical cost and quality of life (QOL) of AR have progressively increased. Therefore, practical guidelines for the appropriate management of AR need to be developed based on scientific evidence while considering the real-world environment, values, and preferences of patients and physicians. The Korean Academy of Asthma, Allergy and Clinical Immunology revised clinical guidelines of AR to address key clinical questions of the management of AR. Part 1 of the revised guideline covers the pharmacological management of patients with AR in Korea. Through a meta-analysis and systematic review, we made 4 recommendations for AR pharmacotherapy, including intranasal corticosteroid (INCS)/intranasal antihistamine (INAH) combination therapy, oral antihistamine/INCS combination therapy, leukotriene receptor antagonist treatment in AR patients with asthma, and prophylactic treatment for patients with pollen-induced AR. However, all recommendations are conditional because of the low or very low evidence of certainty. Well-designed and strictly executed randomized controlled trials are needed to measure and report appropriate outcomes.

Idiopathic Hypereosinophilia: A Multicenter Retrospective Analysis.

Purpose: Physicians can sometimes encounter idiopathic hypereosinophilia (HE), but little is known about it. In this multicenter study, we analyzed the clinical characteristics, treatment, and outcomes of patients with idiopathic HE. Patients and Methods: Patients diagnosed with idiopathic HE (idiopathic hypereosinophilic syndrome: iHES or hypereosinophilia with undetermined significance: HEus) at six tertiary hospitals between January 2010 and June 2021 were included in this retrospective observational study. Demographics, clinical and laboratory data, and treatment responses were obtained from the electronic medical records of the study subjects. Results: A total of 73 patients with idiopathic HE (45 with iHES and 28 with HEus) were included in the present study. Overall, 12 (26.7%) and 5 (17.9%) were women, and mean age of patients at diagnosis was 51.84 ± 17.29 years and 60.21 ± 18.01 years in iHES and HEus groups, respectively. Forty-three (95.6%) patients of iHES and 15 (53.6%) patients of HEus received corticosteroids as 1st-line treatment. Treatment response to corticosteroids in patients with iHES was generally good: complete response (n=25, 58.1%), partial response (n=12, 27.9%), no response (n=6, 14.0%). Treatment response to corticosteroids in HEus was complete response (n=7, 46.7%), partial response (n=6, 40.0%), and no response (n=2, 13.3%). There were 13 patients (46.4%) with HEus who were not treated. Conclusion: Corticosteroid treatment is generally effective and well tolerated by patients with iHES. Some patients with HEus are treated with corticosteroids in clinical practice. Extensive research is needed to establish a standardized management guidelines for iHES and determine whether treatment for HEus is required.

Prescription Patterns of Oral Corticosteroids for Asthma Treatment and Related Asthma Phenotypes in University Hospitals in Korea.

PURPOSE: Oral corticosteroids (OCSs) are frequently prescribed for asthma management despite their adverse effects. An understanding of the pattern of OCS treatment is required to optimize asthma treatment and reduce OCS usage. This study evaluated the prescription patterns of OCSs in patients with asthma. METHODS: This is a retrospective multicenter observational study. We enrolled adult (≥18 years) patients with asthma who had been followed up by asthma specialists in 13 university hospitals for ≥3 years. Lung function tests, the number of asthma exacerbations, and prescription data, including the days of supply and OCS dosage, were collected. The clinical characteristics of OCS-dependent and exacerbation-prone asthmatic patients were evaluated. RESULTS: Of the 2,386 enrolled patients with asthma, 27.7% (n = 660) were OCS users (the median daily dose of OCS was 20 mg/day prednisolone equivalent to a median of 14 days/year). OCS users were more likely to be female, to be treated at higher asthma treatment steps, and to show poorer lung function and more frequent exacerbations in the previous year than non-OCS users. A total of 88.0% of OCS users were treated with OCS burst with a mean dose of 21.6 ± 10.2 mg per day prednisolone equivalent to 7.8 ± 3.2 days per event and 2.4 times per year. There were 2.1% (51/2,386) of patients with OCS-dependent asthma and 9.5% (227/2,386) with exacerbation-prone asthma. These asthma phenotypes were consistent over the 3 consecutive years in 47.1% of OCS-dependent asthmatic patients and 34.4% of exacerbation-prone asthmatic patients when assessed annually over the 3-year study period. CONCLUSIONS: We used real-world data from university hospitals in Korea to describe the OCS prescription patterns and relievers in asthma. Novel strategies are required to reduce the burden of OCS use in patients with asthma.

Successful Treatment of Imatinib-Induced DRESS Syndrome Using Reslizumab without Cessation of Imatinib: A Case Report.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous adverse drug reaction; reported cases are sometimes imatinib mesylate induced. The main treatment is the withdrawal of the causative drug, and most cases with imatinib-induced DRESS syndrome required withdrawal of imatinib. However, in such cases involving anticancer drugs, this may compromise cancer treatment. Herein, we report a patient with imatinib-induced DRESS syndrome that was successfully treated with reslizumab while continuing imatinib treatment. A 65-year-old female presented with facial edema and generalized skin rash after being given 400 mg imatinib 2 weeks ago for metastatic gastrointestinal stromal tumor. After stopping imatinib, the clinical symptoms improved. Imatinib desensitization was performed, and it was administered again. However, the clinical symptoms reappeared more severely 2 months after restart of imatinib, and the peripheral absolute eosinophil count increased to 1,690/µL. A diagnosis of imatinib-induced DRESS syndrome was made, based on the Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) criteria. Imatinib desensitization was repeated, but the clinical symptoms reappeared, and the peripheral eosinophilia persisted. We administered reslizumab, an interleukin-5 monoclonal antibody, without cessation of imatinib. The absolute eosinophil count decreased immediately, and the clinical symptoms improved gradually. After 2 weeks, the clinical symptoms reappeared mildly, but after administering reslizumab again, these disappeared completely. Reslizumab can be considered in the management of DRESS syndrome in cases wherein the causative medication needs to be continued.

A case of bortezomib (Velcade)-induced Stevens-Johnson syndrome confirmed by patch test.

Bortezomib, a highly selective reversible inhibitor of the proteasome complex, is used to the current standard of care in the treatment of multiple myeloma. Although its most commonly reported side effects are gastrointestinal symptoms, peripheral neuropathy, neuropathic pain, and thrombocytopenia, cutaneous adverse reactions are also frequently seen. However, severe cutaneous adverse reactions (SCAR) such as Stevens-Johnson syndrome (SJS) occur very rarely. Here we report the first case of bortezomib-induced SJS with confirmed by patch test. In this case, we performed a patch test that proved bortezomib was the offensive drug in this patient, who had been treated with multiple drugs including antibiotics, allopurinol, and anticancer drugs. Although bortezomib-induced SCARs are generally very rare, we suggest that clinicians be aware of potential adverse reactions including SJS.

Fasciola Hepatica Induced Hepatic Abscess Treated with Triclabendazole.

Fascioliasis is a zoonotic disease caused by Fasciola hepatica that infects mainly cattle, sheep, and goats. Humans can be infected by water or aquatic plants contaminated with metacercariae. The authors encountered two cases of F. hepatica infection. One patient reported abdominal discomfort with marked eosinophilia. The other patient had chest discomfort with marked eosinophilia. The abdominal CT images revealed hypodense lesions in the liver. The ultrasonography-guided liver biopsy findings in both patients were indicative of parasitic infections. Serological tests confirmed the definite diagnoses. Both patients were treated with a single dose of triclabendazole, which is the treatment of choice for fascioliasis. These findings suggest that a diagnosis of fascioliasis, particularly in the acute phase, should be considered in patients with abdominal pain, marked eosinophilia, and hypodense hepatic lesions on CT.

The Degree of Stress in Patients With Empty Nose Syndrome, Compared With Chronic Rhinosinusitis and Allergic Rhinitis.

BACKGROUND: Depression is a mental health disease of growing public health concern because depressive mood affects the sufferer's daily life and is also associated with productivity decline. Depression that is caused by other diseases or substances is referred to as secondary depression, which is an important distinction because curing the underlying cause could subsequently regulate depressive mood. Empty nose syndrome (ENS), also known as "paradoxical obstruction of the nose," is a condition in which the major symptom is difficulty breathing, despite having sufficient breathing space in the nose. Empty nose syndrome has been increasing in prevalence in Korea. We found that patients with this ENS have a tendency toward depressive mood, which can escalate so far as to lead to suicide attempts. Thus, herein, we aimed to investigate the psychological burden on patients with ENS. METHODS: We divided patients into 4 groups: ENS (group A), chronic rhinosinusitis with polyp (CRS c polyp, group B), chronic rhinosinusitis without polyp (CRS s polyp, group C), and allergic rhinitis (AR, group D). We estimated and compared Beck Depression Inventory (BDI) scores among the 4 groups, and we investigated the relationship between depression index and nasal cavity area in patients with ENS. RESULTS: The ENS group (A) had depression prevalence of 71% with varying severity, which was much higher than group B (19%), group C (15%), and group D (27%). The correlation between nasal cavity volume and BDI score for the ENS group was not statistically significant. CONCLUSION: The degree and severity of depression in patients with ENS was higher than in patients with CRS or AR. Furthermore, there was no relationship between depression severity and nasal cavity volume in the patients with ENS. Thus, physicians should be careful not to dismiss the accompanying mental health problems of patients with ENS.

Eosinophilic Esophagitis with Angina Pectoris.

Eosinophilic esophagitis (EoE) is an immune or antigen-mediated chronic inflammatory esophageal disorder that is relatively rare in Asian countries. The main symptoms of EoE are dysphagia and food impaction. Although chest pain is a symptom of EoE, it is also a symptom of coronary heart disease. This paper reports a case of EoE with angina pectoris in a 45-year-old male who was referred to the authors' hospital for chest pain. He was diagnosed with angina pectoris because of mild stenosis in the left coronary artery on coronary angiography. On the other hand, the symptoms did not improve with angina medication therapy. Therefore, he underwent a chest CT scan, which revealed esophageal thickening. Esophagogastroduodenoscopy was performed. His endoscopic findings showed linear furrows with edema, and >90 eosinophils existed per high-power field on the histology findings. He was diagnosed with EoE. Through additional examinations, he was also diagnosed with asthma. The patient was treated with a proton pump inhibitor and a fluticasone inhaler. His symptoms and abnormal endoscopic findings disappeared after eight weeks of treatment. This case shows that physicians should consider the possibility of the symptoms for EoE when unexplained chest pain persists.

Anxiety, depression, and stress in Korean patients with chronic urticaria.

BACKGROUND/AIMS: Emotional distress is thought to cause or maintain chronic urticaria (CU). We aimed to investigate the presence of anxiety, depression, and stress in Korean adult CU patients and to explore their potential impact on treatment. METHODS: We enrolled 79 CU patients and a disease control group comprising 39 persistent asthma patients. The Hospital Anxiety and Depression Scale (HADS) was used to evaluate depression and anxiety. Stress and quality of life (QoL) were assessed by Stress Response Inventory and CU-QoL questionnaires. The sociodemographic and clinical data such as urticaria activity score (UAS-15, UAS-6) were obtained. RESULTS: The prevalence of depression and anxiety based on the HADS were 48.1% and 38.0%. Although the prevalence of anxiety didn't differ between the CU and asthma patients, depression was significantly more prevalent in the CU patients (48.1% vs. 28.2%). Stress tended to be lower in CU patients. Anxiety, depression, and stress exhibited negative correlations with QoL. Anxiety showed significant correlation with UAS-6 and pruritus-visual analog scale (VAS; r = 0.256, r = 0.272, p < 0.05, respectively); depression correlated with sleep difficulty-VAS (r = 0.261, p < 0.05). Stress was associated with UAS-15, UAS-6, pruritus-VAS, and sleep difficulty-VAS (r = 0.251, r = 0.317, r = 0.302, r = 0.258, p < 0.05, respectively). CONCLUSION: The current study first presented that Korean CU patients frequently have anxiety and depression, which affect their QoL and demonstrated that anxiety, depression, and stress had different effects on sleep difficulty, pruritus, and urticaria severity in Korean CU patients.

Prevalence and Risk Factors of Occupational Skin Disease in Korean Workers from the 2014 Korean Working Conditions Survey.

PURPOSE: Occupational skin disease (OSD) is a commonly known occupational disease. However, epidemiological data about this condition in Korea are limited. We aimed to estimate the prevalence and risk factors of OSD using nationally representative data. MATERIALS AND METHODS: We used data from the large-scale, cross-sectional, nationwide 4th Korean Working Conditions Survey conducted in 2014. OSD was defined as skin diseases caused or aggravated by working environments as indicated in a self-reported questionnaire. Factors affecting the occurrences of OSD were investigated using logistic regression analysis. RESULTS: The prevalence rates of OSD were 1.35% in all workers and 62.2% in workers with skin diseases. The workers with OSD were older, had lower educational levels, and had longer working times per week than those without OSD (p<0.001). Furthermore, OSDs occurred more frequently in self-employed workers (p=0.002), those with small-sized businesses (p=0.008), those with longer working durations (p<0.001), and manual and service workers (p<0.001). Although the workers with OSD had greater exposure to various hazardous factors, logistic multivariate analysis showed that high temperatures and skin contact with chemical products were significantly correlated (odds ratios: 2.096 and 2.326, respectively). High prevalence rates of OSD were observed in membership organizations/repair/other personal services (3.2%), agriculture/forestry/fishing (2.7%), manufacturing (2.0%), and construction (1.6%) industries. Additionally, depression/anxiety problems were significantly more prevalent in workers with OSD than in those without (p<0.001). CONCLUSION: This is the first study to present large-scale epidemiological data on OSD prevalence in Korean workers. Our results highlight modifiable factors contributing to the development of OSDs.

Role of clusterin/progranulin in toluene diisocyanate-induced occupational asthma.

Toluene diisocyanate (TDI) exposure induces oxidative stress and epithelial cell-derived inflammation, which affect the pathogenesis of TDI-induced occupational asthma (TDI-OA). Recent studies suggested a role for clusterin (CLU) and progranulin (PGRN) in oxidative stress-mediated airway inflammation. To evaluate CLU and PGRN involvement in airway inflammation in TDI-OA, we measured their serum levels in patients with TDI-OA, asymptomatic exposed controls (AECs), and unexposed healthy normal controls (NCs). Serum CLU and PGRN levels were significantly lower in the TDI-OA group than in the AEC and NC groups (P < 0.05). The sensitivity and specificity for predicting the TDI-OA phenotype were 72.4% and 53.4% when either CLU or PGRN levels were below the cutoff values (≤125 µg/mL and ≤68.4 ng/mL, respectively). If both parameters were below the cutoff levels, the sensitivity and specificity were 58.6% and 89.8%, respectively. To investigate CLU and PGRN function, we evaluated their production by human airway epithelial cells (HAECs) in response to TDI exposure and co-culturing with neutrophils. TDI-human serum albumin stimulation induced significant CLU/PGRN release from HAECs in a dose-dependent manner, which positively correlated with IL-8 and folliculin levels. Co-culturing with neutrophils significantly decreased CLU/PGRN production by HAECs. Intracellular ROS production in epithelial cells co-cultured with neutrophils tended to increase initially, but the ROS production decreased gradually at a higher ratio of neutrophils. Our results suggest that CLU and PGRN may be involved in TDI-OA pathogenesis by protecting against TDI-induced oxidative stress-mediated inflammation. The combined CLU/PGRN serum level may be used as a potential serological marker for identifying patients with TDI-OA among TDI-exposed workers.

Changes in skin reactivity and associated factors in patients sensitized to house dust mites after 1 year of allergen-specific immunotherapy.

BACKGROUND: Allergen-specific immunotherapy (SIT) can significantly improve symptoms and reduce the need for symptomatic medication. OBJECTIVE: The aim of this study was to investigate changes in skin reactivity to house dust mites (HDMs) as an immunologic response and associated factors after 1 year of immunotherapy. METHODS: A total of 80 patients with allergic airway diseases who received subcutaneous SIT with HDMs from 2009 to 2014 were evaluated. The investigated parameters were basic demographic characteristics, skin reactivity and specific IgE for HDM, serum total IgE level, blood eosinophil counts, and medication score. RESULTS: The mean levels of skin reactivity to HDMs, blood eosinophil counts, and medication scores after 1 year were significantly reduced from baseline. In univariate comparison of the changes in skin reactivity to HDMs, age ≤30 years, HDMs only as target of immunotherapy, and high initial skin reactivity (≥2) to HDMs were significantly associated with the reduction in skin test reactivity. In multivariate analysis, high initial skin reactivity and HDMs only as target allergens were significantly associated with changes in skin reactivity to HDMs. In the receiver operating characteristic curve of the initial mean skin reactivity to HDMs for more than 50% reduction, the optimal cutoff value was 2.14. CONCLUSION: This study showed significant reductions in allergen skin reactivity to HDMs after 1 year of immunotherapy in patients sensitized to HDMs. The extent of initial allergen skin reactivity and only HDMs as target allergen were important predictive factors for changes in skin reactivity.

The RIDA Allergy Screen Versus the Phadiatop Test in 430 Consecutive Patient Specimens.

OBJECTIVE: To compare the performances of the Phadiatop test and the RIDA qLine Allergy in specimens from the South Korean population. METHODS: We divided 430 consecutive patient specimens into 4 groups depending on the test results of the 2 assays. We evaluated the degree of agreement between the assays and used the ImmunoCAP sIgE test to identify the allergen-specific immunoglobulin E (IgE). RESULTS: Agreement between the 2 tests was significant (k = 0.614, P <.001). When tested with the ImmunoCAP allergen-specific immunoglobulin E (sIgE) test, 8 of 48 (16.7%) cases that tested RIDA qLine Allergy positive/Phadiatop negative yielded positive results and 34 of 35 (97.1%) RIDA qLine Allergy negative/Phadiatop positive cases yielded positive results in more than 1 of the 14 tested items. CONCLUSIONS: Our results suggest that the Phadiatop test is more accurate than the RIDA qLine Allergy in discrepant cases.

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.