Clinical features of patients with paucigranulocytic asthma classified based on the induced sputum test

Purpose@#Asthma phenotypes are often defined by relative cell counts of airway granulocytes. Induced sputum test results enable clinicians to determine the inflammatory phenotype of asthma based on the eosinophil and neutrophil counts. This study aimed to investigate clinical characteristics of patients with asthma according to the inflammatory phenotype of their condition. @*Methods@#Data from 107 patients with asthma reported at a single tertiary allergy center in Korea during October 2016 to January 2019 were obtained. Patients were categorized into 4 asthma phenotypes based on the cell counts on the induced sputum test: eosinophilic, neutrophilic, mixed, and paucigranulocytic types. Blood eosinophil count, total IgE level, eosinophil cationic protein, spirometric measurements, fractional exhaled nitric oxide, atopy based on the skin prick test, PC20 (provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 second) in methacholine provocation test, type of asthma controller used, frequency of exacerbation, and use of systemic corticosteroids were examined. @*Results@#The frequency of phenotype is as follows: eosinophilic (21.4%), neutrophilic (34.8%), mixed (13.4%), and paucigranulocytic types (30.4%). During the observation period, the proportion of patients who experienced an exacerbation and received systemic glucocorticosteroids were significantly lower in patients with the paucigranulocytic type of asthma than in those with the mixed type of asthma (6.3% vs. 40.0%; P = 0.007 and 5.9% vs. 40.0%; P = 0.004, respectively). @*Conclusion@#Paucigranulocytic asthma may be associated with lower incidence rates of asthma exacerbation and systemic corticosteroid use than the other phenotypes, classified according to induced sputum test results.

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.

Effects of Air Purifiers on Patients with Allergic Rhinitis: a Multicenter, Randomized, Double-Blind, and Placebo-Controlled Study

Purpose@#Exposure to particulate matter (PM) is a well-known risk factor in the triggering and exacerbation of allergic airway disease. Indoor environments, where people spend most of their time, are of utmost importance. To assess the effects of air purifiers [equipped with high-efficiency particulate air (HEPA) filters] on allergic rhinitis (AR) in adult patients, we performed a multicenter, randomized, double-blind, and placebo-controlled study. @*Materials and Methods@#Patients with house dust mite (HDM)-induced AR were randomly assigned to either active or mockup (placebo) air-purification groups. Two air purifiers (placed in living room and bedroom) were operated for 6 weeks in each home environment. The primary study endpoint was to achieve improvement in AR symptoms and medication scores. Secondary endpoints were to achieve improvement in the quality of life (QoL) and visual analog scale (VAS) scores, as well as in the indoor (bedroom and living room) concentrations of PM2.5 and PM10. @*Results@#After 6 weeks of air purifier use, medication scores improved significantly in the active (vs. placebo) group, although subjective measures (symptoms, VAS, and QoL scores) did not differ. Bedroom PM2.5 concentrations initially exceeded living room or outdoor levels, but declined (by up to 51.8%) following active purifier operation. Concentrations of PM2.5 in living room and PM10 in bedroom and living room were also significantly reduced through active purification. @*Conclusion@#The use of air purifiers with HEPA filters significantly reduced medication requirements for patients with HDM-induced AR and significantly lowered indoor PM2.5 concentrations, regardless of room placement. Active intervention to reduce household air pollutants may help improve allergic airway disease (clinicaltrials.gov NCT03313453).

A case of toxic epidermal necrolysis induced by cytomegalovirus infection followed by DRESS (drug reaction with eosinophilia and systemic symptoms)

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions. Although viral reactivation is associated with DRESS syndrome, its role in TEN remains unclear. An 80-year-old woman visited our hospital because of fever and skin eruption. DRESS syndrome was diagnosed and was thought to caused by the use of the drug allopurinol. She was treated by discontinuation of the drug and administration of systemic steroids. She recovered from DRESS syndrome and was discharged from the hospital with tapering doses of steroids prescribed. One week after discharge, she visited our hospital again as the skin rash recurred and oral pain as well as oral and ocular mucosal lesions developed. In addition to the skin rash, blisters and Nikolsky's sign that were different from the skin lesions present in the previous DRESS syndrome were observed. Unlike those in DRESS syndrome, the viral serological test results were positive for anti-cytomegalovirus (CMV) IgM and CMV polymerase chain reaction. Therefore, it was thought that TEN was due to reactivation of CMV and she was treated this with ganciclovir and intravenous immunoglobulin. Here, we report a case of TEN caused by viral reactivation after DRESS syndrome developed after use of allopurinol which recovered after steroid treatment.

What Are the Clinical Features and Etiology of Eosinophilic Liver Infiltration?

BACKGROUND/AIMS: Although eosinophilic liver infiltration (ELI) is not rare, few data exist regarding its clinical characteristics and etiology. Therefore, we evaluated these aspects to better understand the clinical implications of this lesion type, which is reasonably common in Korea. METHODS: Patients suspected of having ELI, based on abdominal computed tomography results obtained between January 2010 and September 2017, were enrolled in this retrospective study. The presumptive etiologies of ELI were categorized as parasite infections, hypereosinophilic syndrome (HES), eosinophilic granulomatosis with polyangiitis (EGPA), malignancies, and unidentified. Clinical courses and treatment responses were also evaluated. RESULTS: The mean age of the enrolled patients (male, 237/328) was 62 years. Most patients (63%) were diagnosed incidentally and had peripheral eosinophilia (90%). Only 38% of the enrolled patients (n=126) underwent further evaluations to elucidate the etiology of the suspected ELI; 82 (25%) had parasite infections, 31 (9%) had HES, five (2%) had EGPA, and five (2%) had drug reactions in conjunction with eosinophilia and systemic symptoms. Almost half of the other enrolled patients had cancer. Radiologic resolution was achieved in 191 patients (61%; median time to radiologic resolution, 185 days). Resolution of peripheral eosinophilia was achieved in 220 patients (79%). In most cases, the course of ELI was benign. CONCLUSIONS: This large ELI study is unique in that the incidence rate, underlying diseases, and clinical courses were comprehensively evaluated. Clinicians should investigate the etiology of ELI, as several of the underlying diseases require intervention rather than observation.

Etiologies and differential markers of eosinophilia-associated diseases in the Allergy Department of a single university hospital

PURPOSE: We aimed to analyze the frequency of eosinophilia-associated diseases and to search for possible markers that may be useful for their differential diagnosis. METHODS: We retrospectively reviewed the medical records of 148 patients with peripheral blood eosinophil count of more than 500/µL who visited the Allergy Department of Chonnam National University Hospital for the first time from January to December 2016. Blood eosinophilia was categorized as mild (5,000/µL). RESULTS: Blood eosinophilia was mostly caused by allergic diseases (41.9%), parasitic infestation (23.6%), and drug allergy (19.6%). Eosinophil count was higher in patients with parasitic infestation (P<0.01), drug allergy (P<0.01), hypereosinophilic syndrome (HES, P<0.001), or eosinophilic granulomatosis with polyangiitis (EGPA, P<0.001) than in those with allergic diseases. The eosinophilic cationic protein level was higher in patients with HES than in those with allergic diseases (P<0.05) and parasitic infestation (P<0.05). The total IgE level was lower in patients with HES than in those with parasitic infestation (P<0.05) and EGPA (P<0.05). The vitamin B12 level was higher in patients with HES than in those with parasitic infestation (P<0.05). There was no statistically significant difference in tryptase levels between the groups. The most common cause of mild eosinophilia was allergic diseases (59.8%), followed by parasitic infestation (22.7%) and drug allergy (13.4%). The common causes of moderate eosinophilia were drug allergy (37.8%), parasitic infestation (29.7%), and allergic diseases (10.8%). The common causes of severe eosinophilia were EGPA (28.6%), HES (21.4%), parasitic infestation (14.3%), and drug allergy (14.3%). CONCLUSION: Common causes of blood eosinophilia in patients who visit the allergy department are allergic diseases, parasitic infestation, and drug allergy. Several markers, including eosinophil count, total IgE, and vitamin B12, may be useful for the differential diagnosis of eosinophilia-associated diseases.

Comparison between Newly Developed and Commercial Inhalant Skin Prick Test Reagents Using In Vivo and In Vitro Methods

BACKGROUND: We developed skin prick test (SPT) reagents for common inhalant allergens that reflected the real exposure in Korea. The study aim was to evaluate diagnostic usefulness and allergen potency of our inhalant SPT reagents in comparison with commercial products. METHODS: We produced eight common inhalant allergen SPT reagents using total extract (Prolagen): Dermatophagoides farinae, Dermatophagoides pteronyssinus, oak, ragweed, mugwort, Humulus japonicus pollens, as well as cat and dog allergens. We compared the newly developed reagents with three commercially available SPT reagents (Allergopharma, Hollister-Stier, Lofarma). We measured total protein concentrations, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), major allergen concentration, and biological allergen potencies measured by immunoglobulin E (IgE) immunoblotting and ImmunoCAP inhibition test. RESULTS: Diagnostic values of these SPT reagents were expressed as positivity rate and concordance rate of the results from ImmunoCAP allergen-specific IgE test in 94 allergic patients. In vitro analysis showed marked differences in protein concentrations, SDS-PAGE features, major allergen concentrations, and biological allergen potencies of four different SPT reagents. In vivo analysis showed that positive rates and concordance rates of Prolagen® SPT reagents were similar compared to the three commercial SPT reagents. CONCLUSION: The newly developed Prolagen® inhalant SPT reagents are not inferior to the commercially available SPT reagents in allergy diagnosis.

A Case of Schnitzler's Syndrome without Monoclonal Gammopathy-Associated Chronic Urticaria Treated with Anakinra

Chronic urticaria may often be associated with interleukin (IL)-1-mediated autoinflammatory disease, which should be suspected if systemic inflammation signs are present. Here, we report a case of Schnitzler's syndrome without monoclonal gammopathy treated successfully with the IL-1 receptor antagonist anakinra. A 69-year-old man suffered from a pruritic urticarial rash for 12 years. It became aggravated episodically and was accompanied by high fever, arthralgia, leukocytosis, and an elevated C-reactive protein and erythrocyte sedimentation rate. The episodes each lasted for over one week. Neutrophilic and eosinophilic inflammation was found on skin biopsy. However, serum and urine electrophoresis showed no evidence of monoclonal gammopathy. The cutaneous lesions were unresponsive to various kinds of anti-histamines, systemic glucocorticoids, colchicine, cyclosporine, dapsone, and methotrexate, which were administered over a span of 3 years immediately preceding successful treatment. A dramatic response, however, was observed after a daily administration of anakinra. This observation suggests that the correct diagnosis of this case is Schnitzler's syndrome without monoclonal gammopathy. For an adult patient with refractory chronic urticaria and systemic inflammation, Schnitzler's syndrome could be considered as a possible differential diagnosis. Although the typical form of Schnitzler's syndrome exhibits the presence of monoclonal gammopathy as a diagnostic criterion, monoclonal gammopathy may be absent in an atypical form. In such a situation, an IL-1 antagonist should be effective for the management of chronic urticaria.

Clinical Features of Serious Adverse Drug Reactions in a Tertiary Care Hospital in Korea / 대한내과학회지

BACKGROUND/AIMS: Several studies have reported on the clinical aspects of adverse drug reactions (ADRs). To date, no study has evaluated serious adverse drug reactions (SADRs) in Korea. The current study evaluates the clinical expression of SADRs in a Korean hospital. METHODS: We reviewed a total of 3,386 cases of SADR occurring between March 2012 and November 2015 in a single tertiary care institution (Regional Pharmacovigilance Center). RESULTS: When classified by organ system, the most common SADRs were white cell and reticuloendothelial system disorders (n = 511). Skin/appendage (n = 296) and gastrointestinal (n = 216) disorders were the fourth- and eighth-most common SADRs, respectively. The three most common single symptoms were leukopenia (n = 499 events), hypotension (n = 444) and anaphylaxis (n = 215). Leukopenia was mainly caused by anti-tumor drugs, followed by piperacilin/tazobactam (n = 28), vancomycin (n = 10) and methimazole (n = 6). Hypotension was most often caused by propacetamol injection (n = 145), while anaphylaxis was mainly caused by cefaclor (n = 19), ranitidine (n = 12), iopamidol (n = 10) and multi-vitamin infusion (n = 9). CONCLUSIONS: Significant differences were noted in the clinical aspects of ADRs and SADRs. Additional studies are warranted to further assess SADRs in response to frequently used causative drugs.

A Case of Type 2 Hereditary Angioedema With SERPING1 Mutation

Hereditary angioedema is a disease of congenital deficiency or functional defect in the C1 esterase inhibitor (C1-INH) consequent to mutation in the SERPING1 gene, which encodes C1-INH. This disease manifests as recurrent, non-pitting, non-pruritic subcutaneous, or submucosal edema as well as an erythematous rash in some cases. These symptoms result from the uncontrolled localized production of bradykinin. The most commonly affected sites are the extremities, face, gastrointestinal tract, and respiratory system. When the respiratory system is affected by hereditary angioedema, swelling of the airway can restrict breathing and lead to life-threatening obstruction. Herein, we report a case of a 24-year-old woman with type 2 hereditary angioedema who presented with recurrent episodic abdominal pain and swelling of the extremities. She had no family history of angioedema. Although her C4 level was markedly decreased (3.40 mg/dL; normal range: 10-40 mg/dL), she presented with a very high C1-INH level (81.0 mg/dL; normal range: 21.0-39.0 mg/dL) and abnormally low C1-INH activity (less than 25%; normal range: 70%-130%). The SERPING1 gene mutation was confirmed in this patient. She was treated with prophylactic tranexamic acid, as needed, and subsequently reported fewer and less severe episodes. To our knowledge, this is the first reported case of type 2 hereditary angioedema in Korea that was consequent to SERPING1 mutation and involved a significantly elevated level of C1-INH as well as a low level of C1-INH activity.

Comparison of the ImmunoCAP Assay and AdvanSure™ AlloScreen Advanced Multiplex Specific IgE Detection Assay

PURPOSE: The AdvanSure™ AlloScreen assay is an advanced multiplex test that allows for simultaneous detection of specific IgE (sIgE) against multiple allergens. For precise identification of causative allergens in allergic patients, we compared this new multiplex sIgE assay with the ImmunoCAP assay, which is currently the gold-standard method for sIgE detection. MATERIALS AND METHODS: Serum samples from 218 Korean allergic disease patients were used to compare the ImmunoCAP and AlloScreen assays with respect to the following 13 allergens: Dermatophagoides pteronyssinus, Dermatophagoides farinae, cat and dog dander, Alternaria, birch, oak, ragweed, mugwort, rye grass, and food allergens (egg white, cow's milk, peanuts). RESULTS: A total of 957 paired tests using the 13 allergens were compared. The total agreement ratio ranged from 0.74 (oak) to 0.97 (Alternaria). With respect to class association analyses, the gamma index ranged from 0.819 (rye grass) to 0.990 (Alternaria). The intra-class correlation coefficients for house dust mites, cat and dog dander, Alternaria, birch, ragweed, egg white, cow's milk, and peanut sIgE titers were >0.8. CONCLUSION: The AlloScreen and ImmunoCAP assays exhibited similar diagnostic performance. However, due to methodological differences between the two systems, careful interpretation of their results is needed in clinical applications.

Soluble CD93 in Serum as a Marker of Allergic Inflammation

PURPOSE: CD93 is receiving renewed attention as a biomarker of inflammation. We aimed to evaluate the potential for serum sCD93 to serve as a novel biomarker for allergic inflammation. MATERIALS AND METHODS: We enrolled 348 subjects with an allergic disease [allergic rhinitis (AR), chronic spontaneous urticaria (CSU), or bronchial asthma (BA)], including 14 steroid-naïve BA patients who were serially followed-up. RESULTS: The serum sCD93 levels (ng/mL) in patients with exacerbated AR (mean±standard deviation, 153.1±58.4) were significantly higher than in patients without AR (132.2±49.0) or with stable AR (122.3±42.1). Serum sCD93 levels in exacerbated CSU (169.5±42.8) were also significantly higher than those in non-CSU (132.4±51.6) and stable CSU (122.8±36.2). This trend was also seen in BA. Serum levels in patients with ICS-naïve BA (161.4±53.1) were significantly higher than those in healthy controls without BA (112.2±30.8), low- and medium-dose ICS users. Serum sCD93 levels in high-dose ICS users (72.2±20.6) were significantly lower than those in low- and medium-dose users. The serum sCD93 levels in steroid-naïve patients with BA (195.1±72.7) decreased after ICS use for 4 weeks (134.4±42.8) and 8 weeks (100.7±13.4), serially. CONCLUSION: Elevated serum sCD93 levels reflected exacerbated status of allergic diseases, including CSU, AR, and asthma. ICS use significantly diminished serum sCD93 levels in steroid-naïve patients with BA. This result may suggest sCD93 in serum as a therapeutic marker for allergic inflammation.

Biomarkers of adult asthma and personalized medicine

The concept of personalized medicine for disease diagnosis, treatment, and management, considering individual variability, including susceptibility, clinical manifestations, and drug responsiveness, is a global emerging trend in medicine, which is also inevitable. However, clinical applications of personalized medicine in the real-world practice have been limited to certain cancers so far. Furthermore, this new concept to the diagnosis and treatment of adult asthma has not been applied to clinical use. Asthma is a multifactorial and heterogeneous disease. It seems to encompass a broad spectrum of clinical manifestations with different underlying pathophysiological mechanisms. Thus, it is not easy to categorize by their clinical features alone. Endotypical categorization that considering specific pathophysiological mechanisms will be more helpful in applying the concept of personalized medicine. The success of personalized medicine depends on patient selection for precise prescription of asthma medications. In the recent years, many investigators and physicians have devoted a lot of effort to the discovery of reliable biomarkers in asthmatic patients, which will be able to actualize the personalized medicine in near future. Despite such great efforts toward investigation of good biomarkers, few things have turned out to be practical in the clinic. Easily interpretable biomarkers of asthma are necessary to assess early detection, determination of treatment, prognosis prediction, and monitoring of exacerbation. Herein, we review recent studies regarding disease classifications and biomarkers of asthma.

Clinical Significance of Component Allergens in Fagales Pollen-Sensitized Peanut Allergy in Korea

PURPOSE: Clinical features of peanut allergy can range from localized to systemic reactions. Because peanut and birch pollen have cross-reactivity, peanut can lead to localized allergic reaction in Fagales pollen-sensitized oral allergy syndrome (OAS) patients without peanut sensitization per se. The purpose of this study was to discriminate true peanut food allergy from cross-reactive hypersensitivity in birch-sensitized peanut allergy. METHODS: Birch-sensitized (n=81) and peanut anaphylaxis patients (n=12) were enrolled. Peanut-related allergic reactions and sensitization profiles were examined. Specific IgE to Fagales tree pollens (birch, oak), peanut, and their component allergens (Bet v 1, Bet v 2, Ara h 1, Ara h 2, Ara h 3, Ara h 8, and Ara h 9) were evaluated. Based on these specific IgEs and clinical features, the patients were classified into 4 groups: group 1 (Fagales pollen allergy without OAS), group 2 (Fagales pollen allergy with OAS), group 3 (OAS with peanut anaphylaxis), and group 4 (peanut anaphylaxis). RESULTS: After peanut consumption, one-third of OAS patients experienced oral symptoms not associated with peanut sensitization. Ara h 1 or Ara h 2 was positive in peanut anaphylaxis patients, whereas Ara h 8 was positive in OAS patients. There were 4 patients with both peanut anaphylaxis and OAS (group 3). Both Ara h 2 and Ara h 8 were positive in these patients. Foods associated with OAS in Korea showed unique patterns compared to Westernized countries. CONCLUSIONS: Ara h 2 and Ara h 8 may be important component allergens for discriminating peanut allergy.

Different Responses in Induction of Allergen Specific Immunoglobulin G4 and IgE-Blocking Factors for Three Mite Subcutaneous Immunotherapy Products

PURPOSE: Specific immunoglobulin G4 (sIgG4) and immunoglobulin E (IgE)-blocking factors produced by subcutaneous immunotherapy (SCIT) play a critical role in the induction of allergen tolerance. However, comparative studies of available SCIT reagents on the induction of sIgG4 are limited. We compared increases in sIgG4 for three different house dust mite (HDM) SCIT reagents. MATERIALS AND METHODS: Seventy-two HDM sensitized allergic patients were enrolled and classified into four groups: 1) control (n=27), 2) SCIT with Hollister-Stier® (n=19), 3) Tyrosine S® (n=16), and 4) Novo-Helisen® (n=10). Levels of specific IgE (sIgE), sIgG4, and IgE blocking factor to Dermatophagoides farinae (D. farinae) were measured using ImmunoCAP (sIgE, sIgG4) and enzyme-linked immunosorbent assay (ELISA) (IgE-blocking factors). Levels were measured before and 13.9±6.6 months after the SCIT. The allergen specificity and the induction levels of sIgE and sIgG4 were confirmed by immunoblot analysis. RESULTS: After SCIT, sIgG4 levels to D. farinae increased significantly; however, the increases differed significantly among the SCIT groups (p<0.001). Specific IgG4 levels to D. farinae were highest in Hollister-Stier® (3.7±4.1 mg/L), followed by Novo-Helisen® (2.2±2.3 mg/L) and Tyrosine S® (0.7±0.5 mg/L). In addition, patients who were administered using Hollister-Stier® showed the most significant decrease in IgE/IgG4 ratio (p<0.001) and increase in blocking factor (p=0.009). Finally, according to IgE immunoblot results, the Hollister-Stier® group showed the most significant attenuation of IgE binding patterns among others. CONCLUSION: Currently available SCIT reagents induce different levels of specific IgG4, IgE/IgG4 ratio, and IgE-blocking factor.

Different Responses in Induction of Allergen Specific Immunoglobulin G4 and IgE-Blocking Factors for Three Mite Subcutaneous Immunotherapy Products

PURPOSE: Specific immunoglobulin G4 (sIgG4) and immunoglobulin E (IgE)-blocking factors produced by subcutaneous immunotherapy (SCIT) play a critical role in the induction of allergen tolerance. However, comparative studies of available SCIT reagents on the induction of sIgG4 are limited. We compared increases in sIgG4 for three different house dust mite (HDM) SCIT reagents. MATERIALS AND METHODS: Seventy-two HDM sensitized allergic patients were enrolled and classified into four groups: 1) control (n=27), 2) SCIT with Hollister-Stier® (n=19), 3) Tyrosine S® (n=16), and 4) Novo-Helisen® (n=10). Levels of specific IgE (sIgE), sIgG4, and IgE blocking factor to Dermatophagoides farinae (D. farinae) were measured using ImmunoCAP (sIgE, sIgG4) and enzyme-linked immunosorbent assay (ELISA) (IgE-blocking factors). Levels were measured before and 13.9±6.6 months after the SCIT. The allergen specificity and the induction levels of sIgE and sIgG4 were confirmed by immunoblot analysis. RESULTS: After SCIT, sIgG4 levels to D. farinae increased significantly; however, the increases differed significantly among the SCIT groups (p<0.001). Specific IgG4 levels to D. farinae were highest in Hollister-Stier® (3.7±4.1 mg/L), followed by Novo-Helisen® (2.2±2.3 mg/L) and Tyrosine S® (0.7±0.5 mg/L). In addition, patients who were administered using Hollister-Stier® showed the most significant decrease in IgE/IgG4 ratio (p<0.001) and increase in blocking factor (p=0.009). Finally, according to IgE immunoblot results, the Hollister-Stier® group showed the most significant attenuation of IgE binding patterns among others. CONCLUSION: Currently available SCIT reagents induce different levels of specific IgG4, IgE/IgG4 ratio, and IgE-blocking factor.

Oral allergy syndrome associated with weed pollinosis

Oral allergy syndrome (OAS) is caused by cross-reactivity between certain pollens and plant foods, including vegetables, nuts, or fruits. Here, we experienced 2 cases of OAS patients associated with mugwort pollinosis without sensitization to Fagales. A 54-year-old female repeatedly experienced skin rashes, perioral edema, nasal obstruction after eating fresh vegetables (celery, lettuce, chicory, radish sprouts, ginseng, etc.). She had suffered from allergic rhinitis worsening in autumn for 5 years. Specific IgE (sIgE) titers to ragweed and mugwort were elevated to 54.1 and 24.9 kU/L, respectively. With regard to the allergen component of pollens, sIgE to Art v 1 (mugwort) and Amb a 1 (ragweed) were elevated to 21.9 and 36.1 kU/L, respectively. Birch sIgE (including Bet v 1 and Bet v 2) was not detected. A 35-year-old male suffered from abdominal pain, skin rashes after eating mango and kiwi. In addition, systemic allergic reaction developed after consumption of tomato and ginseng. He had chronic rhinitis. The sIgE levels to ragweed, mugwort, and tomato were elevated to 0.55, 6.39, and 0.78 kU/L, respectively. The sIgE test results were all negative for Amb a 1, Bet v 1, and Bet v 2 sIgE. Specific IgE levels to Art v 1, Art v 2 sIgE were 3.51 and 4.46 kU/L, respectively. Based on the history and sIgE test results, 2 cases OAS were related to mugwort. We experienced 2 cases of weed pollinosis related to OAS. Culprit foods of OAS can vary depending on their cuisine cultures.

ERRATUM: Table Correction. Suppressive effects of long-term treatment with inhaled steroids on hypothalamic-pituitary-adrenal axis in asthma

Some parts of Tables 1 and 2 in this paper was described incorrectly.

Suppressive effects of long-term treatment with inhaled steroids on hypothalamic-pituitary-adrenal axis in asthma

PURPOSE: Long-term treatment with inhaled steroids (ICS), especially fluticasone that developed lately, may suppress the hypothalamic-pituitary-adrenal (HPA) axis. This study investigated the relationship between ICS use and HPA axis suppression in asthmatics under ICS treatment for average 4.5 years. METHODS: The medical records of 129 adult asthmatics who received ICS treatment for 6 months or more and underwent a corticotropin stimulation test from January 2005 to August 2013 were retrospectively reviewed. RESULTS: The patients received ICS only (n=87) were found to have an abnormal response to the corticotropin test in as high as 32.2%, and those received ICS in combination with oral steroids (n=42) had a significantly higher prevalence of the response (71.4%, P<0.001). Abnormal responses to corticotropin occurred depending on ICS daily doses (low, n=8, 12.5%; medium, n=19, 36.8%; high, n=102, 49.0%; chi2=4.384, P=0.036). Among the subjects received ICS only, nasal steroid doses (P=0.016) but not ICS doses (P=0.159) were significantly higher in those with abnormal responses than the others. Among all the subjects, oral steroid use (odds ratio [OR], 4.27; 95% confidence interval [CI], 2.35-11.80; P<0.001) and nasal steroid dose (OR, 1.02; 95% CI, 1.00-1.04; P=0.015) were significant risk factors for HPA axis suppression. CONCLUSION: One-third of asthmatics under long-term treatment with ICS showed a suppression of the HPA axis in a dose-dependent manner. Oral or nasal steroid use may be a risk factor for the suppression. However, since our results may have been overestimated due to subject selection bias, further prospective case-control studies are warranted.

Risk Factors for Patients with Stage IVB Hepatocellular Carcinoma and Extension into the Heart: Prognostic and Therapeutic Implications

PURPOSE: To evaluate the risk factors of hepatocellular carcinoma (HCC) extension into the right atrium (RA) and determine poor prognostic factors for HCC extension to the heart. MATERIALS AND METHODS: A total of 665 patients who were newly diagnosed with HCC were analyzed retrospectively from January 2004 to July 2012. The patients were divided into two groups: 33 patients with HCC extending into the RA and 632 HCC patients during the same period. The patients with HCC extending into the RA were subdivided into shorter survival group ( or =2 months). RESULTS: The prevalence of HCC extending to the RA was 4.96%. In multivariate analysis, a modified Union Internationale Contre le Cancer (UICC) stage higher than IVA, hepatic vein invasion, concomitant inferior vena cava and portal vein invasion, and multinodular tumor type were risk factors for HCC extending to the RA. In multivariate analysis, Cancer of the Liver Italian Program (CLIP) score >3 (p=0.016, OR: 13.89) and active treatment (p=0.024, OR: 0.054) were associated with prognostic factors in patients HCC extending into the RA. Active treatment such as radiation (n=1), transcatheter arterial chemoembolization (TACE) (n=11), Sorafenib (n=1), and combined modalities (n=2) were performed. CONCLUSION: Modified UICC stage higher than IVA, vascular invasion and multinodular tumor type are independent risk factors for HCC extending to the RA. Active treatment may prolong survival in patients HCC extending into the RA.