Hye-Soo Yoo

Increased Level of Basophil CD203c Expression Predicts Severe Chronic Urticaria

Increased FcεR1α expression with upregulated CD203c expression on peripheral basophils is seen in patients with chronic urticaria (CU). However, there has been no published report on the association between CD203c expression level and clinical disease activity in CU patients. To investigate whether the increase of basophil activation is associated with the disease activity of CU, we measured basophil CD203c expression using a tricolor flow cytometric method in 82 CU patients and 21 normal controls. The relationship between the percentage of CD203c-expressing basophils and clinical parameters was analyzed. The mean basophil CD203c expression was significantly higher in CU patients than in healthy controls (57.5% vs 11.6%, P < 0.001). The basophil CD203c expression in severe CU patients was significantly higher than in non-severe CU (66.5% ± 23.3% vs 54.0% ± 23.3%, P = 0.033). Multiple logistic regression analysis indicated that both ≥ 72% basophil CD203c expression and urticaria activity score (UAS)≥ 13 were significant predictors of severe CU (P = 0.005 and P = 0.032, respectively). These findings suggest that the quantification of basophil activation with CD203c at baseline may be used as a potential predictor of severe CU requiring another treatment option beyond antihistamines.

Clinical significance of immunoglobulin E responses to staphylococcal superantigens in patients with aspirin-exacerbated respiratory disease.

Background: Previous studies have reported a higher prevalence of immunoglobulin E (IgE) specific for staphylococcal superantigens (SAg) in the nasal mucosa of patients with aspirin-exacerbated respiratory disease (AERD), associated with eosinophilic inflammation and leukotriene production. However, the role of SAg-specific IgE in the pathogenesis of AERD is not well understood. We evaluated the clinical significance of serum IgE specific for three types of SAg, namely staphylococcal enterotoxins A and B (SEA and SEB) and toxic shock syndrome toxin-1 (TSST-1) in AERD. Methods: We enrolled 147 patients with AERD confirmed by a lysine-acetyl salicylic acid bronchoprovocative test and compared them with 147 patients with aspirin-tolerant asthma (ATA) and 141 healthy controls (NC). The levels of serum total IgE and SAg-specific IgE were measured using an ImmunoCAP system. Other clinical parameters were analyzed retrospectively. Results: The prevalences of SEA-, SEB- and TSST-1-specific IgE in the AERD and ATA groups were significantly higher than those in the NC group (p < 0.05, respectively). The total IgE level was significantly higher in patients with AERD with high levels of SEA-specific IgE than in those with lower levels (p < 0.05), with significant positive correlations between total and SAE-specific IgE levels (p < 0.05). The PC20 methacholine level was significantly lower in patients with AERD with high levels of SEA-specific IgE, while a significantly higher eosinophil count was noted in patients with AERD with high levels of SEB-specific IgE (p < 0.05, respectively). Conclusions: Specific IgE responses to SAg may increase the serum total IgE level, airway hyperresponsiveness and eosinophil activation, leading to more severe clinical symptoms in AERD.

Elevated platelet activation in patients with chronic urticaria: a comparison between aspirin-intolerant and aspirin-tolerant groups

BACKGROUND Platelets are actively involved in immune inflammatory processes that release inflammatory mediators. Platelet activation has been reported in various inflammatory diseases; however, few studies have described platelet involvement in chronic urticaria (CU). OBJECTIVE To investigate platelet-activation markers, namely P2Y12 receptor and P-selectin expression, and soluble P-selectin level in patients with aspirin-intolerant CU (AICU) and aspirin-tolerant CU (ATCU). METHODS Forty-eight patients with CU and 25 normal controls were enrolled in this study. Aspirin intolerance in patients with CU was confirmed by an oral provocation test. P2Y12 and P-selectin expressions on platelets were measured using flow cytometry; soluble P-selectin level in plasma was measured by enzyme-linked immunosorbent assay. To study the functional effects of aspirin, platelets were treated with aspirin (2 mmol/L) and the expressions of P2Y12 and P-selectin were compared between the AICU and ATCU groups. RESULTS The expression of P2Y12 was significantly higher in patients with CU compared with controls, whereas no significant difference was noted in the expression of P-selectin level. The levels were not significantly different according to urticaria symptom score, symptom control status, and aspirin intolerance. Soluble P-selectin level was significantly higher in the AICU group than in the ATCU group compared with controls. Aspirin did not significantly suppress P2Y12 and P-selectin expressions on platelets in the AICU group, whereas significant suppression was noted in the ATCU group. CONCLUSION These findings suggest that increased platelet activation contributes to skin inflammation in patients with AICU and those with ATCU. The functional difference of platelets in response to aspirin may contribute to persistent skin inflammation in patients with AICU.

Clinical features of elderly chronic urticaria

Background/Aims Chronic urticaria (CU) is defined as itchy wheals lasting 6 weeks or more. As the aged population increases worldwide, it is essential to identify the specific features of this disease in the elderly population. Methods We investigated the prevalence and clinical features of CU in elderly patients. Medical records of 837 CU patients from the outpatient Allergy Clinic of Ajou University Hospital, Korea were analyzed retrospectively. Patients with chronic spontaneous urticaria according to the EAACI/GA2LEN/EDF/WAO guidelines were included. Patients older than 60 years were defined as elderly. Results Of the 837 patients, 37 (4.5%) were elderly. In elderly versus nonelderly CU patients, the prevalence of atopic dermatitis (AD) was significantly higher (37.8% vs. 21.7%, respectively; p = 0.022), while that of aspirin intolerance was lower (18.9% vs. 43.6%, respectively; p = 0.003) in terms of comorbid conditions. The prevalences of serum specific immunoglobulin E antibodies to staphylococcal enterotoxin A and staphylococcal enterotoxin B were considerably higher in elderly CU patients with AD than in those without AD (37.5% vs. 0%, respectively). Conclusions Elderly patients with CU had a higher prevalence of AD. Therefore, there is a need to recognize the existence of AD in elderly CU patients.

A Case of Codeine Induced Anaphylaxis via Oral Route

Codeine is widely prescribed in clinical settings for the relief of pain and non-productive coughs. Common adverse drug reactions to codeine include constipation, euphoria, nausea, and drowsiness. However, there have been few reports of serious adverse reactions after codeine ingestion in adults. Here, we present a case of severe anaphylaxis after oral ingestion of a therapeutic dose of codeine. A 30-year-old Korean woman complained of the sudden onset of dyspnea, urticaria, chest tightness, and dizziness 10 minutes after taking a 10-mg dose of codeine to treat a chronic cough following a viral infection. She had previously experienced episodes of asthma exacerbation following upper respiratory infections, and had non-atopic rhinitis and a food allergy to seafood. A skin prick test showed a positive response to 1-10 mg/mL of codeine extract, with a mean wheal size of 3.5 mm, while negative results were obtained in 3 healthy adult controls. A basophil histamine release test showed a notable dose-dependent increase in histamine following serial incubations with codeine phosphate, while there were minimal changes in the healthy controls. Following a CYP2D6 genotype analysis, the patient was found to have the CYP2D6*1/*10 allele, indicating she was an intermediate metabolizer. An open label oral challenge test was positive. To the best of our knowledge, this is the first report of a patient presenting with severe anaphylaxis after the ingestion of a therapeutic dose of codeine, which may be mediated by the direct release of histamine by basophils following exposure to codeine.

Letter to the Editor: Two Major Phenotypes of Sulfite Hypersensitivity: Asthma and Urticaria

The sulfites are widely used as anti-browning agents and preservatives in food, cosmetics and medicine. The use and amount of sulfites in products have recently been regulated by the Food and Drug Administration (FDA) and the Korean FDA; however, sulfite hypersensitivity reactions, ranging from bronchoconstriction,1 urticaria,2 contact dermatitis3 to life threatening anaphylaxis,4 are still being reported.5 To date, this is the first study to compare two major phenotypes of sulfite hypersensitivity, asthma and urticaria, in this country. Moreover, we carefully analyzed the clinical features of sulfite sensitive asthma, and compared them with those of sulfite tolerant asthma. We retrospectively analyzed the medical records of 26 sulfite hypersensitivity subjects confirmed by a sulfite oral provocation test (OPT). As a control group, 61 asthmatic patients negative to sulfite OPT were enrolled from Ajou University Hospital, Suwon, Korea. We performed sulfite oral provocation test on the subjects who were resistant to conventional treatment of asthma/urticaria or who had histories of allergy to sulfite containing food such as wine, dried fruits, or salads from buffet. To confirm sulfite sensitivity, we conducted single blind placebo controlled provocation test. After the asthmatic patients showed no response to gelatin capsule (EMBO CAPS lot. 051A51-22306, Suheung Capsule, Seoul, Korea) with 2 hours observation, they were administered sodium metabisulfite (Na2S2O5; Sigma Co., St. Louis, MO, USA) starting from 40 mg and increasing to 100-200 mg via gelatin capsule vehicle. The reactions were observed for 2 hours each until the hypersensitivity reactions developed,1 maximally 6 hours. Especially for bronchoconstriction reaction, 1) a decline in FEV1 of 20% or greater, or 2) a decline in FEV1 of 15% to 20% compared to the baseline with definite symptoms/signs of sulfite hypersensitivities (such as wheezing, cough or dyspnea) were considered positive. Pulmonary function tests were repeated at 30 minute intervals.6 In the case of urticarial reaction, sulfite OPT was defined as positive when hives arise; however, it was classified as negative if subjective pruritus developed. Subjects were classified into group I: sulfite sensitive asthma, group II: sulfite sensitive urticaria and group III: sulfite tolerant asthma according to their sulfite OPT reaction. In addition, group I included two patients with concurrent sulfite anaphylaxis. Sulfite sensitive asthma was a more common phenotype of sulfite hypersensitivity than sulfite sensitive urticaria (69.2% vs. 30.8%). Chronic asthma was more common in group I, as previously reported;6 however, chronic urticaria was more common in group II. Group II subjects required significantly higher provocative dosage of sulfite (187.5±35.4 mg vs. 114.4±60.0 mg, p=0.006) and a longer time (100±37.4 min vs. 54.2±34.8 min, p=0.008) to induce hypersensitivity reactions compared with group I subjects. A previous history of adverse reactions was found in 44.4% of group I and 62.5% of group II, being different from previous studies that enrolled subjects with a history of sulfite hypersensitivities (Table 1).1,7 Table 1 Comparison of Clinical Characteristics between Group I and II There were no significant differences in asthma-related parameters-such as atopic status, total IgE level, peripheral eosinophil count, FEV1% and metacholine PC20 level when the clinical characteristics were compared between group I and group III. The prevalence of severe asthma according to American Thoracic Society guidelines was significantly higher in group I than as previously reported in group III (44% vs. 16%, p=0.023).1,8 The asthma exacerbation related hospitalization rate (≥1 times/yr), emergency room visit (≥1 times/yr) and oral steroid burst (≥3 times/yr) were significantly higher in group I than in group III (66.7% vs. 24.6%, p=0.001; 66.7% vs. 24.6%, p=0.001; 55.6% vs. 17.3%, p=0.003). Many potential mechanisms of sulfite hypersensitivity have been postulated. Sulfite oxidase deficiency has been suggested as one of the mechanisms.5 Most asthmatic patients could show a sensitivity to SO2 exposure due to bronchial hypersensitivity.9 However, not all asthmatic patients with severe clinical symptoms presented sulfite hypersensitivity in this study, due to their higher prevalence of severe asthma and more frequent episodes of acute exacerbation compared to sulfite tolerant asthma. We speculate that these findings are due to individual variability of sulfite oxidase inactivity.1 It would, therefore, be helpful to investigate individual factors, including genetic factors, in order to better understand the mechanism of sulfite hypersensitivity. We report herein two major phenotypes of sulfite hypersensitivity, asthma and urticaria in Korea. Considering high prevalence of severe asthma and frequent health care utilization rate in patients with sulfite sensitive asthma, sulfite OPT can be considered as a screening test to identify exacerbating factors for severe asthma patients regardless of history of hypersensitivity reaction.

A case of IgG4-related disease with bronchial asthma and chronic rhinosinusitis in Korea.

IgG4-related disease (IgG4-RD) is characterized by a systemic involvement of tumor-like lesions with IgG4-positive plasmacytes. We experienced a case of IgG4-RD developed in a patient with bronchial asthma (BA) and chronic rhinosinusitis (CRS). A 55-yr-old female patient with BA and CRS complained of both eyes and neck swelling as well as a recurrent upper respiratory infection in recent 1 yr. The serum levels of IgG4, creatinine, and pancreatic enzymes were elevated. A biopsy of the submandibular gland showed an abundant infiltration of IgG4-positive plasmacytes. Her symptoms remarkably improved after the treatment of a systemic steroid that has been maintained without recurrence. We report a rare case of IgG4-RD developed in a patient with BA and CRS. Graphical Abstract

Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis Associated with Acetaminophen Use during Viral Infections

An association between drug treatment for viral infections and severe cutaneous adverse reactions has been noted. We investigated six patients diagnosed with Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) after being prescribed acetaminophen for suspected viral illnesses. Multiplex analysis was performed to measure cytokine levels in sera before and after treatment. IL-2Rα levels significantly decreased during the convalescence phase. Although acetaminophen is relatively safe, the drug can trigger SJS/TEN in patients with suspected viral infections. T-cells and monocytes may be key components of the link between viral infection and acetaminophen-induced SJS/TEN.

Clinical Characteristics of Angioedema With Eosinophilia

Angioedema with eosinophilia (AE) is a very rare allergy disease, case reports of which have been published sporadically since 1984. Here, we retrospectively analyzed the clinical features of 10 AE patients in Korea. Nine of the 10 subjects were young females, ranging from 23 to 38 years old. Twenty percent of the subjects had episodic-type AE with high serum IgM and eosinophil counts, while 80% were non-episodic type with normal serum IgM levels but high eosinophil counts. All patients had used systemic corticosteroids to control AE. One patient with refractory episodic-type AE was treated with anti-IgE antibody. This is the first study to evaluate the clinical characteristics of AE in a Korean population.

Immunologic Evaluation of Immediate Hypersensitivity to Cefaclor

Purpose Cefaclor is widely prescribed for various infectious diseases. As its consumption increases, the number of hypersensitivity reactions to cefaclor has increased. This study aimed to evaluate the immunologic findings of immediate hypersensitivity to cefaclor. Materials and Methods We enrolled 47 patients with immediate hypersensitivity to cefaclor from Ajou University Hospital and Asan Medical Center. Serum specific IgE, IgG1, and IgG4 antibodies to cefaclor-human serum albumin (HSA) conjugate were measured by enzyme-linked immunosorbent assay (ELISA). Results The most common phenotype was anaphylaxis (Group I, 78.7%), followed by urticaria (Group II, 21.3%). The detection of specific IgE, IgG1, and IgG4 to cefaclor-HSA conjugate by ELISA tended to be higher in Group I (40.5%, 41.7%, 21.6%) than in Group II (20.0%, 20.0%, 0%) with no statistical significance. Significant associations were found between specific IgE and IgG1 or IgG4 (p<0.001, p=0.019). ELISA inhibition tests showed significant inhibitions by both free cefaclor and cefaclor-HSA conjugate. For basophil activation tests in patients having no specific IgE antibody, the CD63 expression level on basophils increased with incubations of free cefaclor. Conclusion The most common manifestation of immediate hypersensitivity to cefaclor was anaphylaxis, most of which was mediated by IgE; however, a non-IgE mediated direct basophil activation mechanism was suggested in a subset of anaphylaxis patients.