Search

H1-antihistamines are widely used in the treatment of various allergic diseases. Particularly, a cornerstone of the management of chronic idiopathic urticaria is treatment with H1-antihistamines. However, a few cases of H1-antihistamine-induced urticaria have been reported. A 34-year-old woman presented with a 4-month history of recurrent urticaria, which was prominently exacerbated by the administration of H1-antihistamines. The patient consented to a provocation test of fexofenadine among drugs including cetirizine and hydroxyzine, which were suspected of inducing severe symptoms in episodes. One hour after challenge with 12 mg fexofenadine (one-fifth of the therapeutic dose), a urticarial reaction rapidly developed on nearly the entire body with remarkably increased levels of plasma histamine (190 nmol/L) and plasma leukotriene B4 (150 pg/mL). In challenge tests with other antihistamines, generalized urticaria occurred 5 and 1 h after intake of 10 mg loratadine and 10 mg bepotastine, respectively, whereas challenges with chlorpheniramine, mequitazine and azelastine were all negative. Skin prick tests with H1-antihistamines used in the challenges were all negative, indicating that the urticarial reactions after challenges with the causative drugs might not be immunoglobulin E-mediated. Among the causative drugs in our case, cetirizine and hydroxyzine are the piperazine derivatives, whereas fexofenadine, bepotastine, ebastine and loratadine are the piperidine derivatives. The chemical structures of both derivatives are very similar. Therefore, in this case, H1-antihistamine-induced urticaria may have been due to cross-reactivity between metabolites of these drugs, but not to drugs before metabolization. Hypersensitivity to H1-antihistamines should be considered when urticarial lesions worsen after H1-antihistamine treatment. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Chronic spontaneous urticaria (CSU) exhibits notable responsiveness to omalizumab (OMA). The prognosis and subsequent therapeutic strategies warrant comprehensive exploration in cases exhibiting inadequate responses to OMA.We conducted a multicenter retrospective analysis to investigate the 12‐month prognosis of patients inadequately responding to three injections of OMA. The endpoints encompassed identifying predictive factors for a favorable prognosis and assessing interventions related to an ameliorated prognostic outlook.The study involved 48 patients who met the inclusion criteria. After three OMA administrations, therapeutic interventions included the continuation of OMA in 34 patients, systemic corticosteroids in seven patients, and immunosuppressants in 12 patients. After 12 months, 28 of the 48 patients exhibited a good prognosis, whereas the remaining 20 displayed a less favorable prognosis. Good prognostic determinants encompassed the duration of CSU within 51 weeks, the presence of angioedema, IgE levels ≤100 IU/mL pre‐OMA, blood eosinophil counts ≥100/mm3 post‐OMA, and urticaria control test (UCT) scores ≥5 pre‐OMA and ≥6 post‐OMA. Following the third OMA injection, the implementation of immunosuppressants presented an association with a good prognosis, while the employment of systemic corticosteroids correlated with an unfavorable prognosis.More than half of patients inadequately responding to OMA achieved a good prognosis 12 months later. Several clinical variables appear to be predictive of prognosis, and certain therapeutic agents can be associated with prognostic outcomes. [ABSTRACT FROM AUTHOR]

Background Omalizumab, a humanized anti-IgE monoclonal antibody, proved efficacious and well tolerated in patients with chronic spontaneous urticaria (CSU) refractory to H 1 antihistamines (H 1 AH) in the POLARIS study ( NCT02329223 ), a randomized, double-blind, placebo-controlled trial in East Asian patients. However, data in Japanese patients, who have specific baseline characteristics (e.g., low angioedema incidence, different background medications) that may impact clinical outcomes, are lacking. This pre-specified analysis presents additional patient-level data over time, pharmacokinetic and pharmacodynamics data for omalizumab and IgE, and efficacy and safety data for omalizumab in Japanese patients. Methods Japanese patients (N = 105) were randomized 1:1:1 to omalizumab 300 mg, 150 mg, or placebo by subcutaneous injection every 4 weeks. Efficacy and safety were assessed primarily based on changes from baseline to Week 12 in weekly itch-severity scores (ISS7) and weekly urticaria activity scores (UAS7), and incidence of adverse events (AEs), respectively. Patient-level UAS7 data over time were also reviewed. Results At Week 12, least squares mean (LSM) changes from baseline in ISS7 were greater with omalizumab vs. placebo (−9.54 and −7.29 for omalizumab 300 mg and 150 mg, respectively, vs. placebo [−5.17]). Corresponding LSM changes from baseline in UAS7 were −21.61 and −15.59 (vs. placebo [−10.88]). Most responders in the omalizumab 300 mg group displayed improvement of disease activity within 2–4 weeks and had well-controlled symptoms during the treatment period. Overall AE incidence was similar across treatment arms. Conclusions This subgroup analysis demonstrated that omalizumab is a well-tolerated, beneficial option for treatment of CSU in H 1 AH-refractory Japanese patients. [ABSTRACT FROM AUTHOR]

Background Many patients with chronic spontaneous/idiopathic urticaria (CSU/CIU) do not respond adequately to treatment with non-sedating H1 antihistamines (H1AH). There are limited studies on use of omalizumab as add-on therapy for treatment of CSU in an Asian population. Objective The POLARIS study (NCT02329223), representing the first randomized, double-blind, placebo-controlled phase III trial of omalizumab for CSU in an Eastern Asian population, evaluated efficacy and safety of omalizumab as add-on therapy for treatment of CSU. Methods This 26-week multicenter (41 Japanese/Korean sites) study enrolled patients (12–75 years) who were symptomatic despite H1AH treatment. Eligible participants (N = 218) were randomized 1:1:1 to receive three subcutaneous injections of omalizumab 300 mg, 150 mg, or placebo every 4 weeks, followed by 12 weeks of follow-up. Primary outcome was change from baseline to Week 12 (Wk12) in weekly itch severity score (ISS7). Safety was assessed through the summary of adverse events (AEs). Results Baseline demographics and disease characteristics were generally well balanced across treatment groups. At Wk12, statistically significant decreases from baseline were observed in ISS7 with omalizumab vs placebo (mean changes −10.22, −8.80, and −6.51 for omalizumab 300 mg, 150 mg and placebo; p < 0.001 and p = 0.006 vs placebo, respectively). Overall AE incidence was similar across treatment groups (54.8%, 57.7%, and 55.4% in omalizumab 300 mg, 150 mg, and placebo groups, respectively); nasopharyngitis was the most frequently reported AE in all treatment arms. Conclusion The POLARIS study demonstrates that omalizumab is an efficacious and well-tolerated add-on therapy in Japanese and Korean H1AH-refractory patients with CSU. [ABSTRACT FROM AUTHOR]

Background Patients’ high adherence to medication is indispensable for the management of skin diseases including atopic dermatitis. We previously showed poor medication adherence in Japanese dermatological patients. Objective This study was conducted to determine the level of adherence to oral or topical medication in Japanese patients with atopic dermatitis, attempting to characterize the socioeconomic status of those patients with poor adherence. Methods A web questionnaire survey on demographic data as well as adherence level was conducted on patients registered in the monitoring system. Adherence level was assessed with Morisky Medication Adherence Scale-8 (MMAS-8). Among a total of 3096 respondents with dermatological disorders, data of 1327 subjects with atopic dermatitis were extracted and analyzed. Results More than 80% of subjects felt that both oral and topical medications were safe and efficacious, while less than 60% of them were satisfied with their treatment. Levels of adherence to oral and topical treatments were evaluated with MMAS-8, giving scores of 4.6 and 4.2, respectively. Demographic factors such as gender, marital status, state of employment, alcohol consumption, frequency of hospital visits, and experience of drug effectiveness had a significant impact on the degree of adherence to treatment. Conclusion Medication adherence level in Japanese subjects with atopic dermatitis was relatively low compared with that of other chronic diseases. Our survey has characterized patients with poor adherence, who are good targets for interventions to maximize potentially limited healthcare resources. [ABSTRACT FROM AUTHOR]

Background: For treating patients with refractory chronic spontaneous urticaria (CSU) resistant to standard doses of 2 nd generation H1-antihistamines (H1AH) the International and Japanese guidelines recommend increasing H1AH dose. The latter also recommends switching to a different H1AH. This study explored if the efficacy of the standard dose of bilastine 20 mg is non-inferior to that of double-dose of H1AH in patients with refractory CSU., Methods: This phase IV, multicenter, open-label, randomized, parallel-group trial evaluated the efficacy and safety of switching treatment to bilastine compared to treatment with a 2-fold dose of H1AH in patients with CSU refractory to standard dose H1AH. The primary endpoint was the mean total symptom score (TSS) at Day 5-7 after the start of administration., Results: Treatment efficacy and safety were evaluated in 128 patients (bilastine, n=64; 2-fold dose of H1AH, n=64). The mean TSS at Day 5-7 after the start of administration was smaller than the non-inferiority margin of 0.8, demonstrating non-inferiority of the bilastine switching group to the double-dose H1AH group (0.17 (95% CI -0.32, 0.67)). No difference in Japanese version of Epworth Sleepiness Scale (JESS), DLQI, and urticaria activity score over 7 consecutive days (UAS7) was observed between the two groups. There were no serious adverse events in either group. H1AH-related adverse events occurred in 5 subjects (8 cases) and 2 subjects (3 cases) in the double-dose H1AH and bilastine groups, respectively., Conclusions: Switching treatment to bilastine demonstrated non-inferiority to a double-dose of H1AH in terms of efficacy in patients with CSU refractory to standard dose H1AH with a favorable safety profile., Clinical Trial Registration: https://jrct.niph.go.jp/latest-detail/jRCTs051180105, identifier jRCTs051180105., Competing Interests: AF reports study grants and honoraria from Novartis and Taiho, and honoraria as a speaker from Sanofi, Kyowa Kirin, Kyorin, Mitsubishi-Tanabe, and Kaken Pharmaceutical. KM reports speaking fees from Sanofi, Eli Lilly Japan K.K. Maruho Co. Ltd, Mitsubishi Tanabe Pharma Corporation, and honoraria as an investigator of Eli Lilly Japan K.K. MJ reports study grants from Sanofi. KW reports speaking fee from Sanofi, Novartis, Eli Lilly, Pfizer, Kyowa Kirin, Otsuka Pharmaceutical, Mitsubishi-Tanabe, Kyorin, and Taiho. HA declares receiving consulting fees and speaker fees from Taiho. ST reports research grant from Sanofi, Maruho, Tanabe-Mitsubishi, Eli Lilly, Torii and Taiho Pharmaceutical, honorarium from Tanabe-Mitsubishi, Taiho Pharmaceutical, CSL Behring, Kaken, Maruho, Otsuka and Abbvie, advisory fees from Sanofi, and gift of a medication for a clinical study from Takeda. NIs reports study grants from Maruho. KH reports study grants and honoraria from Kaken Pharmaceutical, Kyowa Kirin, Meiji Seika Pharma, Mitsubishi-Tanabe, and Taiho, and honoraria as a speaker from Kyorin, and honoraria as a speaker and advisory fees from Novartis and Sanofi. NIn reports study grants and honoraria from Taiho, and honoraria as a speaker from Sanofi, Novartis, Kyowa Kirin, Mitsubishi-Tanabe, and Kaken Pharmaceutical. MH has received lecture and/or consultation fees from Kaken Pharmaceutical, Kyorin Pharmaceutical, Kyowa-Kirin, Mitsubishi Tanabe Pharma, Novartis, Sanofi/Regeneron, TAIHO Pharmaceutical, and Teikoku Seiyaku. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Fukunaga, Kakei, Murakami, Kan, Masuda, Jinnin, Washio, Amano, Nagano, Yamamoto, Otsuka, Takahagi, Takenaka, Ishiguro, Hayama, Inomata, Nakagawa, Sugiyama and Hide.)

Carmine is an aluminium and/or calcium-chelated complex form of carminic acid (CA), which is derived from the Dactylopius coccus extract (cochineal), and is globally used as a red-colourant in foods and cosmetics. Although several allergens in carmine allergies, such as CC38K, have been reported, it remains unknown whether chelation affects the allergenicity of carmine. We report a case of Japanese fish sausage ( Gyoniku Sausage ) anaphylaxis induced by epicutaneous sensitization to carmine contained in eyeshadows. In addition, we report on the effect of chelation on carmine allergy. A 32-year-old woman had experienced itching, wheals, and swelling of her eyelids immediately after applying pink eyeshadows, which contained carmine, on several occasions for 3 years. Two months ago, she developed itching, wheals, and swelling on her whole body, especially her eyelids, and dyspnea immediately after ingesting fried pink fish sausages, which contained cochineal. In skin prick tests (SPTs) with all ingredients ingested in the two episodes of anaphylaxis, only fish sausage was positive. SPT was also positive for carmine. In IgE-immunoblotting using the eyeshadow and fish sausage, the patient serum IgE was bound to three protein bands at approximately 86, 114, and 130 kDa. In addition, IgE-immunoblotting using the carmine showed a broad band at 86-130 kDa, which were consistent with those using the eyeshadow and fish sausage, whereas there is no band using CA. Interestingly, the protein bands using the eyeshadow and carmine were diminished by preincubation in the presence of ethylenediaminetetraacetic acid (EDTA) as a chelating agent. The results indicated that the causative allergens of carmine contained in the eyeshadows could be dechelated by EDTA, reducing its allergenicity. In conclusion, carmine contained in cosmetics can cause epicutaneous sensitisation and consequently can induce food anaphylaxis. To prevent sensitisation in carmine allergy, the effect of chelation on allergenicity of carmine should be considered., Competing Interests: The authors declare that they have no conflicts of interest associated with this manuscript., (Copyright © 2024 Maiko Yamaura et al.)

Cutaneous squamous cell carcinoma is usually treated with surgery; however, locoregionally advanced cutaneous squamous cell carcinoma can be difficult to resect. Although recent guidelines from Western countries recommend using anti-programmed cell death protein 1 (PD-1) antibodies, including cemiplimab and pembrolizumab, there are no approved anti-PD-1 antibodies for locoregional cutaneous squamous cell carcinoma in Asian countries. S-1 is an oral drug with a low incidence of severe toxicity that can be used for head and neck cancers, including head and neck locoregional cutaneous squamous cell carcinoma, in Japan. We retrospectively evaluated patients with head and neck locoregional cutaneous squamous cell carcinoma treated with S-1 at two Japanese institutions (2008-2022). The initial dosage was determined by the body surface area (<1.25 m 2 : 80 mg/day, 1.25-1.5 m 2 : 100 mg/day, ≥1.5 m 2: 120 mg/day) for 28 consecutive days. The outcome measures were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Fourteen patients were included. The ORR was 78%, and the complete response (CR) rate was 64.3%. The median PFS and OS were not reached (NR) (95% confidence interval [CI], 5.9 months-NR) and NR (95% CI, 13.8 months-NR), respectively. The 12-month PFS and OS rates were 51% and 85%, respectively. Six of the nine patients who achieved CR showed no recurrence during the follow-up period (median follow-up, 24.7 months). After CR, three patients experienced recurrence. Among these, two resumed S-1 treatment and subsequently underwent salvage surgery, resulting in a sustained absence of recurrence. One patient developed lung metastasis and died, although S-1 therapy was resumed. Only one patient (7.1%) developed grade 3 anemia. S-1 showed favorable efficacy and low toxicity in patients with head and neck locoregionally advanced cutaneous squamous cell carcinoma. S-1 may be a good alternative to the anti-PD-1 antibody for treating head and neck locoregionally advanced squamous cell carcinoma., (© 2023 Japanese Dermatological Association.)

Background: Cold urticaria (ColdU), that is, the occurrence of wheals or angioedema in response to cold exposure, is classified into typical and atypical forms. The diagnosis of typical ColdU relies on whealing in response to local cold stimulation testing (CST). It can also manifest with cold-induced anaphylaxis (ColdA). We aimed to determine risk factors for ColdA in typical ColdU., Methods: An international, cross-sectional study COLD-CE was carried out at 32 urticaria centers of reference and excellence (UCAREs). Detailed history was taken and CST with an ice cube and/or TempTest ® performed. ColdA was defined as an acute cold-induced involvement of the skin and/or visible mucosal tissue and at least one of: cardiovascular manifestations, difficulty breathing, or gastrointestinal symptoms., Results: Of 551 ColdU patients, 75% (n = 412) had a positive CST and ColdA occurred in 37% (n = 151) of the latter. Cold-induced generalized wheals, angioedema, acral swelling, oropharyngeal/laryngeal symptoms, and itch of earlobes were identified as signs/symptoms of severe disease. ColdA was most commonly provoked by complete cold water immersion and ColdA caused by cold air was more common in countries with a warmer climate. Ten percent (n = 40) of typical ColdU patients had a concomitant chronic spontaneous urticaria (CSU). They had a lower frequency of ColdA than those without CSU (4% vs. 39%, p = .003). We identified the following risk factors for cardiovascular manifestations: previous systemic reaction to a Hymenoptera sting, angioedema, oropharyngeal/laryngeal symptoms, and itchy earlobes., Conclusion: ColdA is common in typical ColdU. High-risk patients require education about their condition and how to use an adrenaline autoinjector., (© 2021 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Gibberellin-regulated proteins (GRPs)/GASA proteins are members of cysteine-rich antimicrobial peptide families and are conserved in a broad range of plants. Some GRPs in fruits and pollens have been identified as allergens including peach Pru p 7, Japanese apricot Pru m 7, orange Cit s 7, pomegranate Pun g 7, and cypress pollen GRP. The clinical features of fruit-derived GRP allergies frequently include systemic reactions, multiple fruit allergies regardless of plant kingdom classifications and, less frequently, cofactor-dependence. Multiple fruit allergies might be related to cross-reactivity between GRPs. Clinical cross-reactivity, at least between the four fruit-derived GRPs, has been proven. In addition, GRP allergy induces peculiar clinical symptoms, such as laryngeal tightness and facial swelling, especially eyelid edema, which was proposed to be a predictive factor for Pru p 7 allergy. Fruit-derived GRPs have an unusually high content of cysteine, resulting in high stability to heat and resistance to digestive enzymes. Therefore, GRPs are considered "true" food allergens that induce severe allergic reactions. As an alternative mechanism of fruit-derived GRP allergies, cross-reactivity between fruit GRP and cypress pollen GRP, which might play a role as a sensitizer, is suspected. Taken together, these characteristics indicate GRPs are clinically relevant plant allergens. This review article summarizes our current knowledge of the clinical features and important aspects of GRP sensitization and allergy., (Copyright © 2019 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Poly(γ-glutamic acid) (PGA) is an allergen in natto, fermented soybeans, which causes late-onset anaphylaxis. We hypothesized that jellyfish stings sensitize adults to PGA because a surfer had allergies to both natto and jellyfish, whose sting contains PGA. The aim of the study was to identify behavioral factors, such as marine sports, associated with PGA sensitization., Methods: Outpatients diagnosed with food allergies based on relevant clinical history, positive skin test and/or food challenge test answered a questionnaire during a regular visit in 2016., Results: Questionnaire data from 140 outpatients were analyzed. These patients were divided into two groups: natto allergy group (13 patients, M:F = 10:3, mean age 40.6 years) and non-natto allergy group (127 patients, M:F = 46:81, mean age 44.5 years). All patients with natto allergy had positive results in skin prick test and basophil activation test with PGA. Of these, 92.3% had a marine sport hobby, especially surfing (84.6%). PGA sensitization was independently associated with marine sports (odds ratio, 278.0, 95 percent confidence interval, 36.9-6315.9, p < 0.001) adjusted for male sex and sea bathing, but not with male sex or sea bathing. In addition, although there was no significant difference in the experience of marine sports between natto and non-natto allergy groups, the natto allergy group participated significantly more frequently in marine sports than the non-natto allergy group (p < 0.001). There was no significant difference between natto consumption amount and PGA sensitization., Conclusions: Surfing is a risk factor for PGA sensitization in those with allergy to natto., (Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Poor adherence to medication is a major public health challenge. Here, we aimed to determine the adherence to oral and topical medications and to analyze underlying associated factors using the translated Japanese version of Morisky Medication Adherence Scale-8 regarding urticaria treatment. Web-based questionnaires were performed for 3096 registered dermatological patients, along with a subanalysis of 751 registered urticaria patients in this study. The adherence to oral medication was significantly associated with the frequency of hospital visits. Variables that affected the adherence to topical medication included age and experience of drug effectiveness. The rate of responses that "It felt like the symptoms had improved" varied significantly among the dermatological diseases treated with oral medications. Dermatologists should be aware that adherence to the treatment of urticaria is quite low. Regular visits and active education for patients with urticaria are mandatory in order to achieve a good therapeutic outcome by increasing the adherence., (© 2015 The Authors. The Journal of Dermatology published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Dermatological Association.)

Previously we assessed the medication adherence for oral and topical remedies by a translated Japanese version of the Morisky Medication Adherence Scale-8 (MMAS-8) together with socioeconomic backgrounds in 3096 Japanese dermatological patients, and found the medication adherence, especially to topical drugs, was poor in these patients. In order to elucidate the disease-specific sociomedical factors, we further sub-analyzed the medication adherence in 237 psoriasis patients and compared it with that in other dermatological diseases such as atopic dermatitis, urticaria or tinea. This study was conducted among patients registered in monitoring system and 3096 eligible patients were enrolled. Our web-based questionnaire included the following items such as age, sex, annual income, main health-care institution, experience of effectiveness by oral or topical medication, overall satisfaction with treatment, and MMAS-8 for oral or topical medication. Mean adherence score by MMAS-8 was 5.2 for oral and 4.3 for topical medication. More patients with psoriasis used a university hospital and fewer used a private clinic compared with those with the other skin disease patients. Experience of drug effectiveness by oral medication and overall satisfaction with treatment was lower in psoriasis patients than in other patients. In oral medication, significantly better adherence was observed in those of higher age and with higher annual income. The adherence to medication, especially to topical drugs, was poor in 237 psoriasis patients. We speculated that some severe psoriasis patients were not sufficiently treated systemically and were resistant to topical therapy, leading to poor adherence., (© 2015 Japanese Dermatological Association.)

We report here a 20-year old woman who referred to our clinic for identify the responsible antigen of anaphylaxis. Five days before the reaction, she had a cold and had taken a gel capsule cold medicine, Stona IB Gel®. On the day of the reaction, she took a dose of Stona IB Gel® after eating yogurt. Five minutes after oral administration, she developed a heat sensation and pruritus on her neck, with flushing, abdominal pains, breathing difficulties, and syncope. The specific IgE antibodies measured by ImmunoCAP® were all negative except for gelatin. Prick-prick skin testing revealed positive responses to Stona IB Gel®, gelatin KS and gelatin RP600, of which the latter two were included in the Stona IB Gel® capsule. From these test results, she was diagnosed with anaphylaxis due to gelatin, and to date she has had no further allergic symptoms since avoiding foods containing gelatin. In infancy she had received four vaccinations against diphtheria, pertussis and tetanus, which contained gelatin as a stabilizer. However, she had not developed allergic symptoms until this time. We hypothesize that she might be sensitized to gelatin by taking Stona IB Gel® during the preceding 4 days. This is the first case of anaphylaxis from the ingestion of an oral medication containing gelatin in Japan. Allergic reactions to gelatin are comparatively rare, but according to the past reports, the reactions were severe. Since many kinds of foods, cosmetics, pharmaceutical products, and medication contain gelatin, it is important to be aware of gelatin allergy.

A 29-year-old woman had an episode of urticaria at the age of 17 while exercising after eating fried cuttlefish. For years thereafter, she experienced several episodes of urticaria after eating seafood. At the age of 29, she ate grilled seafood, including cuttlefish for supper after taking loxoprofen for lumbago. One hour later, she developed generalized urticaria accompanied by nausea, abdominal pain, swelling of the lips, and dyspnea while walking; she was taken to a hospital. She was then referred to us for further examination of the etiology of her anaphylactic reactions. The level of specific IgE measured using Immuno CAP was negative for all kinds of foods, including cuttlefish. However, a skin prick test was positive for raw and cooked cuttlefish. Provocation tests were performed on admission by combining the intake of cuttlefish and aspirin under the suspicion of cuttlefish allergy enhanced by nonsteroidal anti-inflammatory drugs and exercise. As a result, she developed no symptoms except for slight itching of the oral mucosa after eating 20 g or 100 g of cuttlefish with or without concomitant administration of 0.5 g of aspirin. Finally, generalized urticaria appeared after challenge with cuttlefish and 1.5 g of aspirin. She was diagnosed with food-dependent exercise-induced anaphylaxis (FDEIA) caused by cuttlefish. She has not developed urticaria since she started to avoid eating cuttlefish. Our results indicated that in provocation tests for the diagnosis of FDEIA, allergic reactions could not only be induced by food intake but could also be enhanced by aspirin in a dose-dependent manner.

A 75-year-old man ingested salted fish guts made of Sagittated calamari which he caught in the daytime, with alcohol and then dozed. Five hours later, he woke up due to itching over his entire body and noticed generalized urticaria and a swollen tongue, which was too large for him to close his mouth. Serum total IgE was 456 IU/ml and ImmunoCAP was positive for anisakis, but negative for squid, shrimp, and ascaris. A skin prick test (SPT) was positive for anisakis extract (10 mg/ml) and house dust mites, but negative for squid and shrimp. He was diagnosed with IgE-mediated allergy due to Anisakis simplex after the ingestion of salted fish guts made of Sagittated calamari, which had been parasitized by Anisakis simplex. Furthermore, we performed SPT with six extracts of purified or recombinant allergens (Ani s 1, 3, 4, 5, 6, and 8) to identify the causative allergens in this case. Only Ani s 3 (tropomyosin) was positive, indicating that Ani s 3 was the causative allergen in this case. Third stage larvae of the nematode Anisakis simplex often parasitize not only marine fish but also invertebrates, including squid. It is necessary to consider Anisakis simplex allergy for urticarial reactions that develop after the ingestion of squid.

We report two cases of anaphylactic reactions to peach with negative result of ImmunoCAP to peach. Case 1 is a 35-year-old man, who felt an itch in his oral cavity immediately after ingesting a whole fresh peach. He rapidly developed generalized urticaria, dyspnea, vomiting, and loss of consciousness. He recovered after treatment at a local hospital, thereafter he was referred to our hospital because ImmunoCAP conducted for screening allergens revealed a negative test result to peach and the cause of anaphylaxis remained unclear. He had a history of pollinosis. He reported that he previously felt an itch on his oral cavity after ingesting melon, watermelon, apple, and strawberry. Serum total IgE was 436 IU/ml. CAP-RAST revealed negative results to peach, strawberry and kiwi. Skin prick tests (SPTs) with raw peach pulp, canned peach pulp, strawberry and kiwi were positive. Case 2 is a 30-year-old woman who felt an itch on her oral cavity accompanied by blepharedema, rhinorrhea, generalized urticaria, nausea, abdominal pain and diarrhea after eating peach. She had a history of pollinosis. She reported that she previously developed urticaria after ingesting an apple. Serum total IgE was 85 IU/ml. ImmunoCAP revealed negative results to peach and apple. SPTs with canned yellow peach, strawberry and apple were positive. Consequently, the two patients were diagnosed with anaphylaxis due to peach, and allergic symptoms have never recurred since they avoided ingesting peach. Furthermore, in two patients ImmunoCAP to rPru p 1, rPru p 3, and rPru p 4 were negative. However, in IgE-immunoblotting of peach, serum IgE antibodies of two patients were bound to approximately 10 kDa proteins. Meanwhile, the cross-reactivity between Rosaceae fruits, such as peach, apple, apricot, and plum, has been reported. These results suggest that in patients, who are suspected of having peach anaphylaxis and show a negative ImmunoCAP result to peach, the additional testing, such as SPT with peach, should be performed for diagnosis.

Background/aim: Oral allergy syndrome (OAS) to plant foods is often caused by cross-reactivity to pollen. We investigated whether there was any significant correlation between sensitization to the pollen of alder and Japanese cedar flying off in spring and prevalence of OAS in Yokohama region., Methods: We measured specific IgE antibodies (CAP-FEIA: CAP) against alder and Japanese cedar in 337 outpatients with skin allergy in 2005 (M:F=167:170, 33.4 years of age, on the average). In the patients who showed positive response to CAP against alder and Japanese cedar, we also tested response to CAP against rBet v 1 and rBet v 2. In addition, we statistically analyzed whether there was any correlation between prevalence of OAS and sensitization to the pollen., Results: Ratio of positive response to CAP against alder was 23.4% (79 cases) while that to CAP against Japanese cedar was 73.7% (244 cases). Response to CAP against rBet v 1 and rBet v 2 was tested in 55 cases, and the ratio of positive response to CAP against rBet v 1 was 43.6% (24 cases) while that to CAP against rBet v 2 was 27.3% (15 cases). Prevalence of OAS showed a significant positive correlation (p<0.001) with sensitization to alder, but no correlation with sensitization to Japanese cedar., Conclusion: It was suggested that sensitization to alder pollen would be involved in prevalence of OAS in Yokohama region.

Background: The clinical features of many patients with oral allergy syndrome (OAS) due to plant-derived foods have rarely been reported in Japan., Objectives: We aimed to determine the causative foods of OAS due to plant-derived foods based on clinical features and skin prick tests (SPTs). Furthermore, we aimed to elucidate the association between causative foods and sensitized pollens in patients with OAS due to plant-derived foods., Methods: SPTs and specific IgE measurements (CAP-FEIA: CAP) were performed in relation to foods and pollens in 118 patients with positive histories of OAS due to plant-derived foods. Patients with positive histories and with positive skin test responses were identified as having type I allergy to the causative foods., Results: The mean age of 63 patients with positive histories and positive skin test responses was 29.2 years (range, 2-61 years), and there were twice as many females as male. The most frequent causative foods were found to be apple, peach, kiwi, and melon in 13, 12, 12, and 11 patients, respectively. CAP frequency was shown to be similar to that of SPT regarding apple, whereas it was less than that of SPT regarding melon, peach, and kiwi. A significant correlation between the frequencies of SPT and CAP was found regarding apple (r=0.39, p<0.05) but not peach, kiwi, and melon. Forty-one of 63 patients with OAS (66.1%) had pollinosis and/or allergic rhinitis. In patients with OAS due to apple, the positive ratio of CAP response against alder pollen was higher than that in patients with OAS due to melon. In patients with OAS due to melon, the positive ratio of CAP responses against ragweed pollen, grass pollen, and mugwort pollen was higher than that in patients with OAS due to apple., Conclusion: In this study, positive ratios of SPT and CAP tended to differ according to the causative food, showing a smaller potential for reaction than might be suggested by patient history. Therefore, for the time being it would be more accurate to use a skin test for the diagnosis of OAS due to plant-derived foods.

A 20-year-old woman was referred for evaluation after about 2 years of recurrent episodes of localized urticaria during handling of several kinds of raw fish in a sushi shop, where she had worked part-time for 2 years. She had also experienced allergic symptoms such as itching and swelling of her lips, generalized urticaria, laryngeal tightness, stridor and dyspnea immediately after ingestion of raw and cooked seafood, including sole, horse mackerel, sea eel and shellfish, over the previous 1 year before referral. Skin prick tests and blood test for specific IgE antibodies were positive for many kinds of seafood, including sole, horse mackerel, sea eel, eel, crab, and abalone, which belonged to different taxonomic phyla, including Chordata, Arthropoda, and Mollusca. A challenge with a piece of broiled sole induced swelling of the lips, obstruction of the larynx, difficulty with deglutition, and abdominal pain. In addition, serum-specific IgE antibodies to two major fish allergens, parvalbumin and collagen, were detected by ELISA, suggesting that allergic symptoms could be induced by many kinds of seafood in the present patient. She was therefore diagnosed with occupational contact urticaria and oral allergy syndrome due to seafood. At the time of this report, the present patient had been followed for one year and no reactions have occurred since she started to avoid the causative types of seafood.

Background: Aspirin has been known to be an enhancer to wheat allergy, including wheat-dependent, exercise-induced anaphylaxis., Objective: To investigate whether nonsteroidal, anti-inflammatory drugs (NSAIDs) other than aspirin would enhance allergic reactions after wheat ingestion and whether antihistamines and disodium cromoglycate would prevent these reactions., Methods: Seven cases, whose reactions after wheat ingestion were enhanced by aspirin on challenge tests, were enrolled. Skin prick tests (SPT) and CAP-RAST were undergone for wheat and gluten. We used challenge tests of wheat after pretreatment of NSAIDs and preventive drugs., Results: Four cases were diagnosed with wheat allergy, 3 cases had wheat-dependent, salicylic acid-induced anaphylaxis. SPT and CAP-RAST were positive for wheat and gluten in 5 of 7 cases and 4 of 7 cases, respectively. Dicrofenac enhanced the allergic reactions after wheat ingestion in 1 of 2 cases, whereas etodolac failed to enhance the symptoms in all 5 cases performed. Furthermore, disodium cromoglycate could not completely prevent the allergic reaction in all 4 cases and even enhanced the reaction in 1 case of them. To see an inhibitory effect of antihistamines on the symptoms, fexofenadine (in 2, 1 and 1 case, respectively), olopatadine, and chlorpheniramine were administrated before the challenge test, and as a result these drugs were found to have inhibitory effects on the allergic reaction., Conclusion: In this study, it was suggested that etodolac might be a relatively safe anti-inflammatory drug on wheat allergy and antihistamines could prevent allergic reactions more than DSCG in patients with wheat allergy.

A 26-year-old woman felt tingling on her tongue and itching both in the throat and on the face immediately after she put a cashew nut on her tongue. She had a history of atopic dermatitis and bronchial asthma, but not of pollinosis. CAP-FEIA and skin prick test (SPT) were positive for cashew nuts. The results showed negative for peanuts and other tree nuts than cashew nuts. Consequently, she was diagnosed with oral allergy syndrome due to cashew nuts. In addition, the result of skin prick test with cashew nuts normalized one year after she began avoiding cashew nuts, indicating that cashew nuts allergy would be due to sensitization by itself rather than to cross-reactivity between cashew nuts and pollens in this case.

A 23-year-old woman experienced generalized urticaria and loss of consciousness during walking after ingestion of wheat. Skin prick test and CAP-RAST were positive for gluten. An oral challenge test using 100g wheat was positive without exercise. The patient was given diagnosis of wheat allergy. In addition, not only exercise but also administration of 500mg aspirin were found to exacerbate her symptoms after the ingestion of wheat, suggesting that acetylsalicylic acid could be an augmentation factor in wheat allergy. Etodorac failed to enhance the symptoms. Further, oral administration of Fexofenadine could prevent allergic reactions induced by ingestion of 100g wheat, but sodium cromoglycate partially reduced the reactions.

We report a case of leprosy. A 31-old-phillippine female present with 5 month history of an erythematous plaqe on her right neck. Examination showed 4 erythematous plaques with her. A histological examination of the skin lesion of hir thigh revealed granulomas around nerve and skin appendages which consist of lymphocytes, epidermoid cells and giant cells. Although no acid fast bacilli were not demonstrated by skin biopsy with Ziehl-Neelsen staining, the Mycobacterium leprae-specific DNA was detected by polymerase chain reaction method. A diagnosis of paucibacillary leprosy had made. We started treatment with ofloxacin but she return to philippine soon.