Da Woon Sim

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.

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, cows 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, cows 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.

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.

Ranitidine-induced anaphylaxis: clinical features, cross-reactivity, and skin testing

Histamine H2 receptor antagonists are commonly prescribed medications and are known to be well tolerated. However, 99 cases of ranitidine‐induced anaphylaxis occurred in Korea from 2007 to 2014.

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.

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.

Roflumilast Ameliorates Airway Hyperresponsiveness Caused by Diet-Induced Obesity in a Murine Model

Obese patients with asthma respond poorly to conventional asthma medications, resulting in severe symptoms and poor prognosis. Roflumilast, a phosphodiesterase-4 inhibitor that lowers the levels of various substances that are implicated in obese subjects with asthma, may be effective in the treatment of those subjects. We evaluated the potential of roflumilast as a novel therapeutic agent for obese subjects with asthma. We designed three models: diet-induced obesity (DIO); DIO with ovalbumin (OVA); and OVA. We fed C57BL/6J mice a high-fat diet for 3 months with or without OVA sensitization and challenge. Roflumilast or dexamethasone was administered orally three times at 2-day intervals in the last experimental week. Airway hyperresponsiveness resulting from DIO significantly improved in the roflumilast-treated group compared with the dexamethasone-treated groups. Although DIO did not affect the cell proliferation in bronchoalveolar lavage fluid, increased fibrosis was seen in the DIO group, which significantly improved from treatment with roflumilast. DIO-induced changes in adiponectin and leptin levels were improved by roflumilast, whereas dexamethasone aggravated them. mRNA levels and proteins of TNF-α, transforming growth factor-β, IL-1β, and IFN-γ increased in the DIO group and decreased with roflumilast. The reactive oxygen species levels were also increased in the DIO group and decreased by roflumilast. In the DIO plus OVA and OVA models, roflumilast improved Th1 and Th2 cell activation to a greater extent than dexamethasone. Roflumilast is significantly more effective than dexamethasone against airway hyperresponsiveness caused by DIO in the murine model. Roflumilast may represent a promising therapeutic agent for the treatment of obese patients with asthma.

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 (<2 months) and longer survival group (≥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.

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 Schnitzlers 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 Schnitzlers syndrome without monoclonal gammopathy. For an adult patient with refractory chronic urticaria and systemic inflammation, Schnitzlers syndrome could be considered as a possible differential diagnosis. Although the typical form of Schnitzlers 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.

Sensitization to various minor house dust mite allergens is greater in patients with atopic dermatitis than in those with respiratory allergic disease

Various allergenic proteins are produced by house dust mites (HDM). However, the allergenicity and clinical implications of these allergens are unknown.