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.

The Psychological Relieving Effect of Drug Provocation Test in Drug Hypersensitivity.

Purpose: Drug hypersensitivity is an adverse drug reaction mediated by immunological mechanisms and is accompanied by a significant socioeconomic burden. The drug provocation test (DPT) is the gold standard for drug allergy diagnosis; however, a standardized protocol does not exist. This study aimed to investigate the effects of psychological relief from DPT in patients with drug hypersensitivity. Patients and Methods: A total of 46 patients who had experienced drug hypersensitivity were administered DPT after admission to our clinic at Dong-A University Hospital and asked to complete the questionnaires before and after DPT. Anxiety and depressive symptom levels were assessed using the Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI)-II, respectively. Results: There was a significant decrease in the BAI and BDI-II scores after DPT than before DPT, respectively (BAI: 10.22 ± 10.75 vs 7.26 ± 6.95, P=0.025; BDI-II: 13.00 ± 7.92 vs 11.17 ± 7.80, P = 0.019). Twenty-two patients with non-anaphylactic drug hypersensitivity showed a significant decrease in the BDI-II scores after DPT (11.50 ± 7.60 vs 9.50 ± 5.98, P = 0.009), but not in the BAI scores (8.45 ± 7.41 vs 6.18 ± 4.58, P = 0.127). However, there were no statistically significant differences in the BDI-II and BAI scores before and after DPT (BAI: 11.83 ± 13.05 vs 8.25 ± 8.56, P = 0.664; BDI-II: 14.38 ± 8.11 vs 12.71 ± 9.01, P = 0.215) in 24 patients with anaphylaxis. Conclusion: DPT may reduce the psychological burden in patients with drug hypersensitivity, especially in those without anaphylaxis.

Emerging Biomarkers Beyond Leukotrienes for the Management of Nonsteroidal Anti-inflammatory Drug (NSAID)-Exacerbated Respiratory Disease.

Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD) is a unique condition characterized by aspirin/NSAID hypersensitivity, adult-onset asthma, and/or chronic rhinosinusitis with nasal polyps. Arachidonic acid metabolism dysregulation and intense eosinophilic/type 2 inflammation are central mechanisms in NERD. Studies have been conducted on various biomarkers, and urinary leukotriene E4 is considered the most available biomarker of NERD. However, the pathophysiology of NERD is heterogeneous and complex. Epithelial cells and platelets can interact with immune cells in NERD, and novel biomarkers related to these interactions have recently been investigated. We summarize emerging novel biomarkers of NERD and discuss their roles in the management of NERD.

Successful induction treatment of bullous pemphigoid using reslizumab: a case report.

BACKGROUND: Bullous pemphigoid (BP) is a potentially life-threatening autoimmune blistering disease which is characterized by autoantibodies against hemidesmosomal proteins of the skin and mucous membranes. In recent years, the role of eosinophil and immunoglobulin E autoantibodies have been further elucidated in BP, and have been considered potential therapeutic targets. CASE PRESENTATIONS: A 67-year-old male presented with erythematous bullous eruption. The skin eruption was located on whole body, and suggested BP. Peripheral blood eosinophil count and total immunoglobulin E markedly elevated in initial laboratory findings. Topical and systemic steroid (methylprednisolone 2 mg/kg/day) treatment was started, and his skin symptoms worsened repeatedly, whenever systemic steroid were reduced. On admission day 29, reslizumab (anti-interleukin-5) 3.5 mg/kg was administered intravenously to the patients. The bullous skin lesion began to improve rapidly, and methylprednisolone (8 mg/day) was reduced without any worsening of symptoms during two doses of reslizumab. CONCLUSIONS: We report a case of successful treatment response to reslizumab administration in a patient with BP. Further studies are needed to confirm the role of anti-interleukin-5 as a treatment for BP in the future.

Cefaclor-induced hypersensitivity: Differences in the incidence of anaphylaxis relative to other 2nd and 3rd generation cephalosporins.

Cefaclor, a second-generation oral cephalosporin, is the most frequently prescribed cephalosporin in Korea. Studies, however, have yet to analyze the incidence of cefaclor-associated adverse drug reactions (ADRs), including hypersensitivity (HS), according to total national usage rates. This study aimed to investigate the incidence rates and clinical features of cefaclor ADRs reported to the Korean Adverse Event Reporting System (KAERS) and Health Insurance Review and Assessment Service (HIRA) database for the most recent 5 years. Reviewing the HIRA database, which contains information on all insurance claims, including prescribed medications and patient demographics, we identified the total number of individuals who had been prescribed cefaclor and other cephalosporins including 2nd generation without cefaclor and 3rd generation antibiotics from January 2014 to December 2018. Additionally, we retrospectively analyzed all ADRs reported to the KAERS for these drugs over the same study period. Incidence rates for ADRs, HS, and anaphylaxis to cefaclor were 1.92/10,000 persons, 1.17/10,000 persons, and 0.38/10,000 persons, respectively, lower than those to other 2nd and 3rd cephalosporins. Among all ADRs, HS (60.9% vs. 43.6% vs. 44.8%, P <0.001) and anaphylaxis (19.8% vs. 4.6% vs. 4.7%, P <0.001) were more common for cefaclor than for other 2nd and 3rd cephalosporins. Females, individuals under 65 years of age, concomitant use of drugs, and serious ADRs were more strongly associated with HS to cefaclor than with HS to other 2nd and 3rd cephalosporins. In a nationwide database for the Korean population, the incidence of cefaclor-induced ADRs, particularly HS and anaphylaxis, was high. Female sex, age younger than 65 years, and concomitant use of drugs may be associated with HS to cefaclor.

Association Between Olfactory Function and Asthma in Adults.

PURPOSE: Chronic rhinosinusitis (CRS) and allergic rhinitis (AR) are common asthma-associated upper airway diseases. Olfactory dysfunction, a common symptom among these patients, is an increasingly recognized condition that is associated with a reduced quality of life and major health outcomes. However, there are few studies on the association between olfactory function and asthma. We investigated the relationship between asthma and olfactory function. PATIENTS AND METHODS: A total of 146 patients with asthma aged >18 years were retrospectively analyzed from August 2019 to February 2020. Olfactory function was assessed using the Sniffin' stick test or the YSK olfactory function test. We compared the clinical parameters of patients with olfactory dysfunction and patients with normosmia. RESULTS: Of the total participants, 68 (46.6%) showed olfactory dysfunction (hyposmia, n=31; anosmia, n=37). The patients with olfactory dysfunction were older, had longer durations of asthma, and a higher proportion of those with poor general health, CRS, and nasal polyps compared to patients with normosmia. However, there were no significant differences in the socioeconomic status, lung function, asthma severity, and use of inhaled corticosteroids or intranasal steroids between the two groups. Age (odds ratio: 1.044, 95% confidence interval: 1.009-1.081, P=0.012), poor general health (3.304, 1.231-8.863, P=0.018), CRS (2.589, 1.155-5.804, P=0.021), and nasal polyps (3.306, 1.1-9.94, P=0.033) were significantly associated with olfactory dysfunction. CONCLUSION: Olfactory dysfunction was quite frequently observed in adults with asthma. Age, poor general health, CRS, and nasal polyps were significantly associated with olfactory dysfunction.

Clinical characteristics and risk factors for cefaclor-induced immediate hypersensitivity: a retrospective observation at two university hospitals in Korea.

BACKGROUND: Cefaclor, a second-generation oral cephalosporin, is widely prescribed to treat infectious diseases. Immediate hypersensitivity (HS) reactions to cefaclor have continuously been reported and are expected to increase with its greater use. This study aimed to investigate the clinical characteristics and risk factors of immediate HS to cefaclor over the most recent 5 years. METHODS: This retrospective study investigated 521 adverse drug reactions (ADRs) to cefaclor at pharmacovigilance centers at two tertiary hospitals from January 2014 to December 2018. In total, 459 patients with immediate HS to cefaclor were reviewed. RESULTS: A total of 459 cases of cefaclor immediate HS were included among 521 cefaclor ADRs, and anaphylaxis was recorded in 61.2%. Female sex (odds ratio 2.917, 95% confidence interval 2.397-3.550, P < 0.001), age under 65 years (4.225, 3.017-5.916, P < 0.001), hypertension (2.520, 1.875-3.388, P < 0.001), liver diseases (2.189, 1.208-3.967, P = 0.010), asthma (8.075, 5.301-12.302, P < 0.001), and concomitant use of nonsteroidal anti-inflammatory drugs (1.888, 1.554-2.294, P < 0.001) were significantly associated with cefaclor immediate HS. CONCLUSIONS: Cefaclor was found to elicit high proportions of immediate HS and anaphylaxis. Physicians ought to be cautious with prescribing cefaclor to females, individuals with hypertension, liver diseases, or asthma, and patients taking nonsteroidal anti-inflammatory drugs. TRIAL REGISTRATION: This study was retrospectively registered.

Association between cognitive function and asthma in adults.

BACKGROUND: Cognitive deficits are associated with asthma globally; however, the association between cognitive function and asthma has not been fully elucidated. OBJECTIVE: To assess the relationship between asthma and cognitive function. METHODS: A total of 202 patients with asthma aged older than 18 years were analyzed retrospectively from August 2019 to February 2020. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) test. We compared the associations of clinical parameters with cognitive function (MoCA, ≥23 vs <23) and lung function (forced expiratory volume in 1 second [FEV1], ≥70% vs <70%). RESULTS: Of the total participants, 89 (44.1%) indicated cognitive impairment, of whom 23.1% were aged less than 65 years and 72.9% were aged 65 years or older. MoCA scores were significantly different according to age (24.91 ± 3.89 for ages <65 years vs 19.11 ± 5.11 for ages ≥65 years, P < .001) and lung function (23.29 ± 5.17 for FEV1 ≥70% vs 21.23 ± 5.21 for FEV1 <70%, P = .006), but not according to asthma control (22.35 ± 5.38 for nonsevere asthma vs 22.88 ± 4.91 for severe asthma, P = .55). Age (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.014-1.13; P = .01), educational status (OR, 6.068; CI, 2.175-16.927; P = .001), and asthma duration (OR, 1.007; CI, 1.001-1.013; P = .02) were significantly associated with cognitive impairment. CONCLUSION: Cognitive impairment was largely observed in adults (44.1%) with asthma and was more prevalent in older adults than in younger adults. Longer asthma duration and lower lung function were more associated with cognitive dysfunction.

Predictive factors of response to inhaled corticosteroids in newly diagnosed asthma: A real-world observational study.

BACKGROUND: Asthma is characterized by chronic airway inflammation, and inhaled corticosteroids (ICSs) have been recommended as first-line treatment. However, response to ICS treatment is various, and the prediction of response to ICSs is still difficult, especially in individuals with newly diagnosed asthma. OBJECTIVE: To assess the clinical factors and biomarkers associated with response to ICSs in newly diagnosed asthma. METHODS: A total of 150 ICS-naive patients with newly diagnosed asthma in the allergy clinic of a single tertiary hospital in Korea from January 2014 to January 2019 were included in this study. All patients initially received moderate-dose ICSs and were treated for more than 1 year. We compared the clinical characteristics and parameters between patients with and without acute exacerbation (AE) during the study period. RESULTS: In this study, 99 patients had no AE (stable asthma group), and 51 patients presented with more than 1 AE (unstable asthma group). The mean (SD) blood eosinophil count (635.7 [780.3] × 103/µL vs 373.4 [266.8] × 103/µL, P = .003) and sputum eosinophil count (15.2% [23.9%] vs 8.3% [15.4%], P = .051) were higher and the sputum neutrophil count (42.9% [35.1%] vs 61.3% [35.1%], P = .057) was lower in the stable asthma group than in the unstable asthma group. CONCLUSION: High blood and sputum eosinophil counts can predict a good response to ICS treatment in terms of prevention of AE in individuals with newly diagnosed asthma. The sputum neutrophil count may be an effective predictor of response to ICSs, even though additional studies must be conducted.

Efficacy of Allergen Immunotherapy for Allergic Asthma in Real World Practice.

PURPOSE: Allergen immunotherapy (AIT) induces immunological tolerance, and there is increasing evidence of the clinical efficacy of AIT in the treatment of allergic asthma. However, the optimal parameters for asthma control in clinical trials are still unclear. We investigated the efficacy of AIT with respect to changes in the inhaled corticosteroid (ICS) dose in patients with allergic asthma. METHODS: A total of 117 adults with allergic asthma who had used ICS for more than 1 year in a single tertiary hospital in Korea were included in this retrospective study. We compared the clinical parameters and outcomes between the AIT group (ICS with AIT, n = 48) and the non-AIT group (ICS without AIT, n = 69) by applying an inverse probability of treatment weighting method. The patients in the AIT group had received subcutaneous AIT monthly as a maintenance treatment for more than 1 year. The changes in the ICS dose from baseline were evaluated in the 2 groups for 3 years. RESULTS: The proportion of responders who discontinued or decreased in the ICS dose with achieving control status of asthma was significantly higher in the AIT group than in the non-AIT group throughout the study period (at 6 months, 52.1% vs. 24.6%; at 1 year, 70.8% vs. 34.7%; at 2 years, 89.5% vs. 35.6%; at 3 years, 96.3% vs. 51.2%). Treatment responses did not differ significantly by type of allergen (single- or multi-allergens or 3 different products) used throughout the study period. CONCLUSIONS: Irrespective of the type of allergen, long-term maintenance AIT helps to spare ICS dose and achieve better control in patients with allergic asthma in real-world clinical practice.

Proper Cut-off Levels of Serum Specific IgE to Cefaclor for Patients with Cefaclor Allergy.

PURPOSE: Cefaclor, a second-generation oral cephalosporin, is known to cause IgE-mediated hypersensitivity. Assays of serum-specific IgE (sIgE) to cefaclor are commercially available via the ImmunoCAP system (Thermo Fisher Scientific). While serum levels of sIgE >0.35 kU/L are considered indicative of an allergy, some patients with cefaclor allergy show low serum IgE levels. This study aimed to evaluate the proper cut-off levels of sIgE in the diagnosis of immediate hypersensitivity to cefaclor. MATERIALS AND METHODS: A total of 269 patients with drug allergy history, who underwent assays of sIgE to cefaclor at Ajou University hospital and Dong-A University Hospital, were reviewed retrospectively. Among them, 193 patients exhibited cefaclor-induced immediate hypersensitivity with certain or probable causality of an adverse drug reaction according to the WHO-UMC (the World Health Organization-the Uppsala Monitoring Centre) algorithm, and 76 controls showed delayed hypersensitivity reactions to non-antibiotics. RESULTS: In total, 126 of the 193 patients (65.3%) experienced anaphylaxis; they had higher serum sIgE levels than patients with immediate hypersensitivity who did not experience anaphylaxis (6.36±12.39 kU/L vs. 4.28±13.61 kU/L, p<0.001). The best cut-off value for cefaclor-induced immediate hypersensitivity was 0.11 kU/L, with sensitivity of 80.2% and specificity of 81.6%. A cut-off value of 0.44 kU/L showed the best sensitivity (75.4%) and specificity (65.7%) for differentiating anaphylaxis from immediate hypersensitivity reactions. CONCLUSION: Patients with cefaclor anaphylaxis exhibit high serum IgE levels. A cut-off value of 0.11 kU/L of sIgE to cefaclor is proper for identifying patients with cefaclor allergy, and 0.44 kU/L may be useful to detect anaphylaxis.

Clinical factors associated with the development of atrial fibrillation in the year following STEMI treated by primary PCI.

BACKGROUND: Advanced age, poor left ventricular function, and congestive heart failure are known predictors of atrial fibrillation (AF) in acute myocardial infarction (AMI) patients. Recent advances in AMI treatment may have changed the occurrence of new-onset AF. Thus, we investigated the factors associated with the development of new-onset AF in ST elevation myocardial infarction (STEMI) patients. METHODS: This study included 527 STEMI patients [mean age, 60.6±12.8 years; 102 (19.4%) women] who underwent primary percutaneous coronary intervention (PCI) in the previous 7 years. New-onset AF was evaluated following STEMI treated by primary PCI. Patients who developed AF during this follow-up period were compared with those who did not develop AF to identify factors that were associated with the development of AF. RESULTS: New-onset AF was documented in 81 patients (15.4%) at 1 year after STEMI. Patients with new-onset AF (n=81) tended to be older (p<0.001); were more often female (p=0.009); had more congestive heart failure (p=0.015); had less use of beta-blockers (p=0.001); had more often used antiarrhythmic drugs (p<0.001); experienced cardiogenic shock more frequently (p=0.038); had lower left ventricular ejection fraction (p=0.024); and had higher E velocity (p<0.001), E/e' (p=0.011), and left atrial volume index (LAVI; p=0.029) than the 446 patients with no AF. Multivariate regression analysis revealed that cardiogenic shock, LAVI, and age were predictors of new-onset AF in STEMI patients (OR 2.823, 1.254, and 1.124; p=0.005, <0.001, and 0.028, respectively). CONCLUSION: Cardiogenic shock was a new predictor of new-onset AF in STEMI patients.

A Rare Cause of Secondary Hypertension in A Young Adult.

Reninoma is a rare, renin-secreting, benign renal neoplasm that can cause secondary hypertension. We report a case of a 21-year-old man who suffered from progressively worsening headache for 2 months with a history of hypertension for 7 years. Laboratory studies showed normal potassium level, increased basal plasma renin activity, and normal serum aldosterone level. Abdominal computed tomography and magnetic resonance imaging revealed a small mass in the middle region of the right kidney. Partial nephrectomy was performed; immunohistochemical results demonstrated typical features of reninoma. Postoperatively, blood pressure and potassium level were normal at the 2-month follow-up.

Ventricular Septal Rupture in a Case Suspected as Stress Induced Cardiomyopathy.

An 87-year-old woman with continuous chest discomfort was referred to our hospital. ST-segment elevation in lead V1-4 was detected on electrocardiography and ventricular septal rupture (VSR) was observed on echocardiography. Post-acute myocardial infarction (AMI) VSR was suspected and she underwent emergency cardiac catheterization. However, coronary angiography showed normal coronary artery. On the fourth day after admission, the patient died. We suspect that VSR was developed by stress induced cardiomyopathy, not by AMI.

Rapidly aggravated skeletal muscle metastases from an intrahepatic cholangiocarcinoma.

We present a rare case of intrahepatic cholangiocarcinoma (ICC) with multiple skeletal muscle metastases. The patient was a 55-year-old Asian woman presenting with abdominal pain; abdominal and pelvic computed tomography and magnetic resonance cholangiopancreatography revealed an unresectable ICC with hepatic metastasis and metastastatic lymphadenopathy in the porto-caval area. After 3 mo of treatment with palliative radiotherapy and chemotherapy, magnetic resonance imaging of the thoracolumbar spine detected right psoas muscle and paraspinous muscle metastases. We performed an ultrasound-guided percutaneous fine-needle biopsy that confirmed a similar pattern of poorly differentiated adenocarcinoma. The patient treated with palliative chemotherapy and achieved 10 mo of survival. Here we report the first case quickly spread to multiple sites of muscle even though the three-month treatment, compare to the other cases reported muscle metastases at diagnosis.