Tsukane Kobayashi

A New Reliable Method for Detecting Specific IgE Antibodies in the Patients with Immediate Type Wheat Allergy due to Hydrolyzed Wheat Protein: Correlation of Its Titer and Clinical Severity

BACKGROUND Immediate-type wheat allergy caused by a specific hydrolyzed wheat protein (HWP-IWA), Glupearl 19S (GP19S), typically develops food-dependent exercise-induced anaphylaxis (FDEIA), but is different from conventional FDEIA, or simple wheat allergy in many aspects. The skin prick test (SPT) is considered to be the most effective method for diagnosis of HWP-IWA. As SPT is a relatively qualitative method, we developed quantitative and high-throughput test method for HWP-IWA. METHODS An enzyme-linked immunosorbent assay (ELISA)-based GP19S-specific IgE assay was tested using sera from 14 HWP-IWA and five conventional wheat-dependent exercise-induced anaphylaxis (CO-WDEIA) patients, as well as five healthy subjects. Then a validation study at five different institutions was carried out using sera from 10 HWP-IWA and five CO-WDEIA patients, as well as five healthy subjects different from the previous studies. RESULTS The mean unit values converted from measured absorbance of ELISA were 68.3, 1.3 and 1.1 respectively. Furthermore, the validation study revealed reproducible results across all five institutions, with the standard deviation (SD) being 0.3-0.4 for the healthy group, 0.2-0.6 for the CO-WDEIA group, and 3.8-9.6 for HWP-IWA group except for one case. One case of HWP-IWA was excluded from analysis due to the high SD of 53.3 units, indicating that samples with a unit value > 100.0 will affect inter-laboratory reproducibility. CONCLUSIONS Our findings suggest that the ELISA-based GP19S-specific IgE assay can be used to test HWP-IWA using venous blood samples, except for those with a unit value > 100.0.

Clinical utility of loop-mediated isothermal amplification assay for the diagnosis of common alpha herpesvirus skin infections.

Loop‐mediated isothermal amplification (LAMP) is a nucleic acid amplification method with a high specificity, efficiency and speed. No reports exist regarding the usefulness of LAMP for clinically suspected skin infections caused by herpes simplex virus (HSV) or varicella zoster virus (VZV). The aim of this study was to evaluate the clinical usefulness of LAMP in the diagnosis of common cutaneous alpha herpesvirus (HSV type 1 and 2, and VZV) infections. LAMP and real‐time polymerase chain reaction (PCR) were performed using swab samples collected from 106 patients with clinically suspected alpha herpesvirus skin infections. The results of LAMP performed with DNA extraction did not differ from those performed without DNA extraction. The sensitivity of LAMP tested against real‐time PCR was 96% in herpes simplex, 78% in eczema herpeticum, 93% in herpes zoster and 100% in varicella. No viral DNA was detected by LAMP in all negative real‐time PCR samples. Viral DNA load was significantly lower in samples with false‐negative LAMP results than in the LAMP‐positive samples. LAMP enables confirmation of clinically suspected cutaneous HSV and VZV infections. However, the sensitivity of LAMP is lower than real‐time PCR. The accuracy of LAMP may increase if sufficient viral DNA is obtained from lesions. LAMP performed without DNA extraction remains sensitive; thus, LAMP represents a quick and economical method for the diagnosis of common alpha herpesvirus skin infections.

Effect of related donor availability on outcome of AML in the context of related and unrelated hematopoietic cell transplantation.

Although allogeneic hematopoietic cell transplantation (HCT) from a related donor is effective therapy for younger patients with AML, it remains unknown how the availability of a related donor affects the outcome when unrelated HCT is a treatment option for patients without a related donor. To address this issue, we retrospectively analyzed 605 cytogenetically non-favorable AML patients younger than 50 years for whom a related donor search was performed during first CR (CR1). The 4-year OS was 62% in 253 patients with a related donor and 59% in 352 patients without a related donor (P=0.534). Allogeneic HCT was performed during CR1 in 62% and 41% of patients with and without a related donor, respectively. Among patients transplanted in CR1, the cumulative incidence of non-relapse mortality was significantly higher in patients without a related donor (P=0.022), but there was no difference in post-transplant OS between the groups (P=0.262). These findings show the usefulness of unrelated HCT in younger patients with cytogenetically non-favorable AML who do not have a related donor. The extensive use of unrelated HCT for such patients may minimize the potential disadvantage of lacking a related donor.

Severe hepatitis associated with varicella zoster virus infection in a patient with diffuse large B cell lymphoma treated with rituximab-CHOP chemotherapy.

Severe disseminated varicella zoster virus (VZV) infection rarely occurs in patients who are not recipients of hematopoietic stem cell transplantation. This report concerns severe disseminated VZV infection in a diffuse large B cell lymphoma (DLBCL) patient treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). The patient was an 82-year-old male with DLBCL who had a history of type II diabetes mellitus. He incurred VZV infection with severe hepatitis and disseminated intravascular coagulopathy after three courses of R-CHOP. When the VZV infection occurred, anti-VZV IgG was not detected and lymphopenia was observed. We initiated treatment with acyclovir, immunoglobulin, and thrombomodulin alpha, and rescued this patient. We suggest that the use of chemotherapy for immune-suppressed elderly lymphoma patients may involve the risk of severe VZV infection.

Evaluation of the cross-reactivity of antigens in Glupearl 19S and other hydrolysed wheat proteins in cosmetics.

In Japan, over 2000 users of a facial soap containing Glupearl 19S (GP19S), a hydrolysed wheat protein (HWP), developed immediate‐type systemic wheat allergy (HWP‐IWA), and ∼70% of them developed associated contact urticaria.

Rhododendrol-induced leukoderma accompanied by allergic contact dermatitis caused by a non-rhododendrol skin-lightening agent, 5,5′-dipropylbiphenyl-2,2′-diol

Dear Editor, In 2013, a number of consumers who used rhododendrol-containing cosmetics developed leukoderma at the site of application of the cosmetic in Japan and Taiwan. Here, we report the first case of rhododendrol (4-[4-hydroxyphenyl]-2-butanol; C10H14O2, Chemical Abstracts Service [CAS] no. 501-96-2, molecular weight [MW] = 166.22)-induced leukoderma accompanied by allergic contact dermatitis caused by 5,50-dipropylbiphenyl-2,20diol (C18H22O2, CAS no. 20601-85-8, MW = 270.37). A 64-year-old housewife suffered from itchy erythema on the face for 2 years and noticed leukoderma at the same sites. The leukoderma gradually extended to her neck and forearms. For 2 years, she had been using skin-lightening cosmetics that contained 5,50-dipropylbiphenyl-2,20-diol or rhododendrol. When she presented at our hospital, she had leukoderma surrounded by pigmentation and itchy erythema on her face. The leukoderma was prominent on the face, and also affected her neck and forearms. Because we initially suspected allergic contact dermatitis caused by the cosmetics, we performed patch testing using her cosmetics and patch test allergens related to cosmetics after obtaining written informed consent. Finn Chambers (Smart Practice, Phoenix, AZ, USA) were used for the test, and the results were read according to the International Contact Dermatitis Research Group standards. On days 3, 4 and 7, the patient showed a positive reaction (+) to her skin lotion (as is) containing 5,50-dipropylbiphenyl-2,20-diol. In the ingredient patch test of this skin lotion, she also showed positive reactions ([+?] on day 4 and [+] on day 7) to 5,50-dipropylbiphenyl-2,20-diol (0.5% pet.) and negative reactions to rhododendrol (2% pet). All three healthy control subjects did not react to 5,50-dipropylbiphenyl-2,20-diol and rhododendrol. Rhododendrol was synthesized in Japan as a new skinlightening agent that suppresses melanogenesis formation. Cosmetics that contained 2% rhododendrol had been sold in 10 Asian countries. The symptoms of depigmentation had been confirmed in approximately 16 000 (2%) of 800 000 estimated users of cosmetic products containing rhododendrol (The Japanese Dermatological Association Special Committee on the Safety of Cosmetics Containing Rhododendrol, 2014 [in Japanese]). On the other hand, Suzuki et al. reported the first case of allergic contact dermatitis caused by the skin-lightening agent, 5,50-dipropylbiphenyl-2,20-diol. Because 5,50-dipropylbiphenyl-2,20-diol was a skin lightening agent as well as rhododendrol, we could not deny the possibility that the leukoderma of our patient’s face and neck was caused by 5,50-dipropylbiphenyl-2,20-diol. However, based on the sites of her lesions of leukoderma, we reached the diagnosis of rhododendrol-induced leukoderma accompanied by allergic contact dermatitis from 5,50-dipropylbiphenyl-2,20-diol. After discontinuing the cosmetics containing 5,50-dipropylbiphenyl-2,20-diol and rhododendrol, her erythema and leukoderma improved (Fig. 1). Sasaki et al. elucidated that rhododendrol Figure 1. Clinical course of leukoderma in the patient. (Top) Clinical appearance of her neck at the first visit to our department. There was leukoderma surrounded by pigmentation on her neck. (Bottom) Clinical appearance of the neck 1 year after the first visit. The leukoderma had gradually improved.

Case of anaphylactic reaction to soy following percutaneous sensitization by soy‐based ingredients in cosmetic products

1 Aihara Y, Kotoyori T, Takahashi Y, Osuna H, Ohnuma S, Ikezawa Z. The necessity for dual food intake to provoke food-dependent exercise-induced anaphylaxis (FEIAn): a case report of FEIAn with simultaneous intake of wheat and umeboshi. J Allergy Clin Immunol 2001; 107: 1100–1105. 2 Komoto K, Kimura Y, Horio T. A case of umeboshi-dependent exercise-incudes anaphylaxis. Jpn J Dermatoallergol 2003; 11: 62–66. (in Japanese). 3 Inomata N, Okazaki F, Moriyama T et al. Identification of peamaclein as a marker allergen related to systemic reactions in peach allergy. Ann Allergy Asthma Immunol 2014; 112: 175–177. 4 Bianchi A, Rienzo Businco AD, Bondanini F, Mistrello G, Carlucci A, Tripodi S. Rosaceae-associated exercise-induced anaphylaxis with positive SPT and negative IgE reactivity to Pru p 3. Eur Ann Allergy Clin Immunol 2011; 43: 122–124. 5 Miceli Sopo S, Monaco S, Giorgio V, Calvani M, Mistrello G, Onesimo R. Food-dependent exercise-induced anaphylaxis (FDEIA) by nectarine in a paediatric patient with weakly positive nectarine prick-byprick and negative specific IgE to Pru p3. Allergol Immunopathol 2013; 41: 201–203.

Occupational food allergy due to parvalbumin and phaseolin induced by epicutaneous sensitization

Sensitization in food allergy is traditionally thought to occur via the intestinal tract. In recent years, it has been proposed that the primary mechanism for the development of food allergies is epicutaneous sensitization.1,2 In Japan, numerous cases of wheat allergy that developed from epicutaneous sensitization to hydrolyzed wheat protein (Glupearl 19S) in soap (sold by Yuuka Co., Ltd., Fukuoka, Japan) have been reported; this finding suggests that food allergies may be caused by epicutaneous sensitization.3 A 25-year-old man with atopic dermatitis (LDH: 321 U/L, TARC level: 2208 pg/ml, SCORAD index: 24) and pollinosis visited our hospital for investigation of food allergy and hand eczema. He had worked as a sushi chef and handled raw fish with his bare hands. After one year, he experienced itchiness in his hands after touching multiple types of fish, and intraoral itchiness, respiratory difficulty, diarrhea and abdominal pain occurred after consuming them. Consequently, he changed his job and become a Japanese sweets maker. He touches white bean paste (white kidney beans) with his bare hands for making Japanese sweets in daily work. After 6 months in this job, he felled itchy on his hands after touching white bean paste, and the hand eczema had worsened. When he consumed white bean paste, he began to experience the same symptoms as consuming fish. He had no history of food allergy before working in the aforementioned occupations. We considered the possibility that his food allergies were induced by epicutaneous sensitization. The total IgE level was 841 IU/mL. The levels of specific IgE antibodies by ImmunoCAP (Phadia Inc., Tokyo, Japan) were: class 2 for codfish, flatfish, salmon, mackerel, sardine and horse mackerel, class 3 for soybeans and class 4 for kidney beans. On the other hand, specific IgE antibodies for wheat, gluten, u-5 gliadin, latex and anisakis were not detected. In skin prick test, he showed positive reactions for several kinds of fish (raw, as is) such as young yellowtail, horse mackerel, salmon roe, flatfish, sardine and white kidney bean.4 The tests for prawns, octopus, spiral shellfish, anisakis and black bean paste with azuki beans were negative. The positive control (1% of histamine dihydrochloride, Wako Pure Chemical Industries, Ltd., Osaka, Japan) exhibited a reaction of 3 3 mm. The negative control (physiological saline) exhibited no reaction. The skin prick test reaction was considered positive if a wheal 3 mm diameter appeared after 15e20 min of application. The fluorescence intensities of specific IgE antibodies to

A varicella outbreak in B-cell lymphoma patients receiving rituximab-containing chemotherapy

Varicella, characterized by a vesicular rash, occurs primarily in young children. Although older individuals can also be affected or vaccinated, outbreaks among adults are rare. We investigated a small outbreak of varicella in B-cell lymphoma patients for elucidation of risk factor of the disease. We experienced four cases of varicella after an index herpes zoster case. All varicella cases were confirmed varicella zoster virus (VZV) infection by PCR. All varicella cases occurred in diffuse large B-cell lymphoma patients receiving rituximab-containing chemotherapy. On the other hand, only three of the 18 non-varicella patients in the same room were receiving rituximab-containing chemotherapy (P = 0.005). All varicella patients had detectable serum anti-varicella zoster virus IgG antibodies before chemotherapy. Even in the presence of neutralizing antibodies to the virus, lymphoma patients treated with rituximab-containing chemotherapy can possibly become re-infected with varicella. These findings suggest that zoster patients should be strictly isolated in hematology and oncology ward, and prophylactic acyclovir should be considered for such patients when exposed to zoster/varicella.

Concurrent Reactivation of Herpes Simplex and Varicella Zoster Viruses Confirmed by the Loop-Mediated Isothermal Amplification Assay

Concurrent reactivation of herpes simplex and varicella zoster viruses is rare. Here, we describe the case of an elderly patient with herpes labialis and herpes zoster manifesting as a right-side facial eruption with vesicles and crusting. The loop-mediated isothermal amplification (LAMP) assay demonstrated the presence of both herpes simplex virus type 1 and varicella zoster virus in swab samples taken from the face, which was confirmed by real-time PCR, suggesting concurrent reactivation of both viruses. The use of the LAMP assay in the present case indicates its usefulness in the diagnosis of atypical herpes infections.