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Background: 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., Methods: 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., Results: 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/mm 3 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., Conclusions: 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., (© 2024 The Author(s). International Journal of Dermatology published by Wiley Periodicals LLC on behalf of the International Society of Dermatology.)

Clinical trials of biologics have frequently excluded elderly patients, resulting in inadequate data on their safety and efficacy. Additionally, evidence of their safety and efficacy remains limited, despite some real-world studies. To assess the safety and efficacy of biologics in elderly patients with psoriasis, we compared these outcomes in younger patients using data from the West Japan Psoriasis Registry (WJPR). The WJPR consists of approximately 30 facilities in Western Japan, including various healthcare settings. This study enrolled 1395 patients who participated in the 2022 follow-up survey of the WJPR and were either using or had used biologics during the survey. These included 456 patients in the elderly group (≥65 years) and 939 patients in the younger group (<65 years). Treatment-ending adverse events (TEAEs) occurred in 15.8% and 11.3% of elderly and younger patients, respectively. The incidence rate per 1000 patient-years (PY) for TEAEs was significantly higher in elderly patients than in younger patients (32.9 vs 23.2, p = 0.0234). Infectious diseases were more prevalent in the elderly group than the younger group; however, no significant difference in the frequency of infectious diseases was found between the two groups (p = 0.0807). Malignant neoplasms occurred significantly more frequently in the elderly group than in the younger group (p = 0.0169). Our results indicate a few concerns about infection when prescribing biologics to elderly patients. Biologics were effective for both elderly and younger patients. We found no significant differences in the proportion of patients with a body surface area score ≤3%, Physician's Global Assessment score 0/1, or Patient's Global Assessment score 0/1, as well as in the mean Dermatology Life Quality Index and the Itch Numerical Rating Scale between the younger and the elderly groups. Overall, our results confirm the appropriateness of using biologics in elderly patients with regard to safety and efficacy., (© 2024 Japanese Dermatological Association.)

α-Gal syndrome (AGS) is an allergic reaction to galactose-α-1,3-galactose (α-gal) found in the salivary glands of ticks, mammalian meat excluding primates, and some antibody preparations, such as cetuximab. We report two cases of AGS diagnosed after ingestion of wild boar meat. Patient 1, a male in his 70s, developed anaphylactic shock about 3 h after eating wild boar meat. He was transported to our acute and critical care center in Nagasaki University Hospital because he had difficulty in moving. Patient 2, a female in her 60s, developed a skin rash about 2.5 h after ingesting wild boar meat. After visiting our department to investigate the cause of the disease, the sera of both patients were found to be positive for α-gal specific IgE antibody and were diagnosed with AGS caused by ingestion of wild boar meat. Reports of AGS diagnosed after ingestion of wild boar meat are rare in Japan. Compared with other prefectures, the consumption of wild boar meat in Nagasaki is relatively high in Japan. In the past 10 years, four cases of AGS were diagnosed at our department, half of which were caused by the ingestion of wild boar meat, the ratio is possibly higher than that in other prefectures in Japan.

Background: In patients with wheat-dependent exercise-induced anaphylaxis (WDEIA), anaphylactic shock occurs frequently, therefore avoidance of wheat products is recommended. We aimed to evaluate efficacy and safety of long-term omalizumab treatment for adult patients with WDEIA., Methods: In this phase 2, multicentre single-arm trial, 20 adult patients with WDEIA were enrolled (UMIN 000019250). All patients were administered 150-600 mg of omalizumab subcutaneously and evaluations (basophil activation and blood examination) were performed at regular intervals during administration period (0-48 weeks) and observation period (48-68 weeks). Primary endpoint was proportion of the patients who achieved a basophil activation rate below 10% with fractionated wheat preparations, and secondary endpoint was proportion of the patients with no allergic reactions after wheat products ingestion., Results: During the omalizumab treatment, more than 80% of the patients achieved the basophil activation rate less than 10% against all fractionated wheat preparations, and 68.8% of the patients who achieved the primary endpoint experienced no allergic reaction. During the observation period, the proportion of the patients who achieved a basophil activation rate below 10% decreased gradually, and the proportion of patients with positive allergic reactions increased gradually thereafter and reached maximum of 46.7%. Severe adverse events were not observed during the study., Conclusions: Long-term omalizumab treatment is safe and effective for adult patients with WDEIA when assessed by basophil activation rate with wheat allergens as well as allergic reactions after lifting of restrictions on wheat intake. However, this is not enough to achieve desensitization., (Copyright © 2023 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Sensitization to galactose-α-1,3-galactose (α-Gal) leads to the development of α-Gal syndrome, which includes red meat allergy and cetuximab-induced anaphylaxis. Since tick bites represent the main cause of α-Gal sensitization, it was speculated that sensitization to α-Gal occurs throughout Japan. However, few cohort studies have investigated α-Gal sensitization in Japan. Therefore, we aimed to elucidate the subclinical sensitization rate to α-Gal in Japan. Sera were obtained from 300 participants without food or cetuximab allergy at Shimane University Hospital (Shimane prefecture), Tokyo Medical and Dental University Hospital (Tokyo metropolis), and Tohoku University Hospital (Miyagi prefecture). ImmunoCAP-bovine thyroglobulin (BTG), ImmunoCAP-beef, and IgE immunoblotting with cetuximab were performed to detect α-Gal-specific IgE. Clinical information was collected from participants using a questionnaire. The overall positivity rate of ImmunoCAP-BTG was 4.0% without significant inter-institute differences, whereas that for ImmunoCAP-beef was 9.7% with a significant inter-institute difference. Tokyo Medical and Dental University Hospital (19.0%) had the highest positivity rate. The positivity rate based on cetuximab IgE immunoblotting was 2.7%, without any significant inter-institute differences. The overall positivity rate for both ImmunoCAP-BTG and cetuximab immunoblotting was 2.0%, with a significant inter-institute difference; 5.0% of Shimane University Hospital was the highest. Two cases showed sensitization against the non-α-Gal epitope of cetuximab. The overall positivity rate for both ImmunoCAP-beef and cetuximab immunoblotting was 1.3%, without significant inter-institute differences. Male sex was associated with positive beef-specific IgE. The prevalence of subclinical sensitization to α-Gal is estimated at 2.0%-4.0% in Japan and may be higher in rural areas, supporting an association between tick bites and α-Gal sensitization. In contrast, the prevalence of subclinical sensitization to beef is 9.7% in Japan and is highest in Tokyo Metropolis, suggesting the presence of another IgE-binding epitope apart from α-Gal and another sensitization route in the sensitization to beef IgE., (© 2022 Japanese Dermatological Association.)

Background: Autoantibodies (AAbs) against immunoglobulin E (IgE) antibodies (Abs) and their high-affinity receptor alpha subunits (FcεRIα) are key factors in the elicitation of type IIb autoimmune chronic spontaneous urticaria (type IIb aiCSU). In this study, we aimed to develop a new method to detect functional anti-FcεRIα and anti-IgE AAbs, which can crosslink the plural FcεRІα molecules and IgE Abs on the surface of mast cells and basophils, in sera from aiCSU patients using the amplified luminescence proximity homogeneous assay (Alpha)., Methods: Sera were obtained from 14 aiCSU patients, as diagnosed by recurrent chronic spontaneous urticaria episodes and positive results for the autologous serum skin test and/or histamine release test (HRT). The AAbs to FcεRIα and IgE Abs were determined in sera from aiCSU patients using enzyme-linked immunosorbent assay (ELISA) and Alpha by cross-linking (AlphaCL) of IgE Abs and/or FcεRІα., Results: Serum anti-FcεRIα and anti-IgE AAb levels were not significantly different between aiCSU patients and healthy subjects in ELISA. Anti-FcεRIα AAbs were detected in 10 of 14 aiCSU patients who displayed positive (5/5) and negative (5/9) results in the HRT for anti-FcεRIα AAbs by AlphaCL, whereas no signals were observed in healthy subjects. Additionally, anti-IgE AAbs were detected in two of four aiCSU patients who displayed positive results in the HRT for anti-IgE AAbs., Conclusions: A new assay method using AlphaCL can detect anti-FcεRIα and anti-IgE AAbs with FcεRIα- and IgE-crosslinking abilities in sera from aiCSU patients. This simple and practical assay method may be available as a diagnostic tool for urticaria patients., (Copyright © 2021 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Loss-of-function mutations of filaggrin (FLG) gene (FLG) are the strongest known genetic risk factor for atopic dermatitis (AD). It is still debatable how FLG gene mutations and the resulting abnormal amount of FLG protein contribute to skin barrier function and symptoms of AD. In this study, we examined the effects of loss-of-function mutations of FLG gene on the severity of skin lesions and skin barrier function in 55 patients with AD by evaluating eight patients with AD with FLG gene mutations and 47 patients with AD without mutations. The results showed that the FLG gene mutation did not affect the duration of AD, severity of AD, degree of local inflammatory symptoms, skin water content and trans-epidermal water loss of the lesions. Next, in these eight mutation carriers and the 47 non-carriers, stratum corneum was collected from the three site of skin lesions using tape-stripping method, and the amounts of FLG protein and total amino acid contained in the stratum corneum was measured to investigate the effect of the FLG gene mutation on the amount of FLG gene product in the local lesion. FLG abnormalities had little effect on FLG protein and total amino acid content in the stratum corneum in the lesional skin. The amount of the FLG products, especially amino acids derived from FLG, in the stratum corneum of AD lesional skin is influenced by development of dermatitis. The results obtained from this study supports that the activation of Th2-dominant inflammatory cells, together with FLG abnormality, plays a role in suppressing the production of FLG in skin lesions., (© 2021 Japanese Dermatological Association.)

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a life-threatening food allergy triggered by wheat in combination with the second factor such as exercise. The identification of potential genetic risk factors for this allergy might help high-risk individuals before consuming wheat-containing food. We aimed to identify genetic variants associated with WDEIA. A genome-wide association study was conducted in a discovery set of 77 individuals with WDEIA and 924 control subjects via three genetic models. The associations were confirmed in a replication set of 91 affected individuals and 435 control individuals. Summary statistics from the combined set were analyzed by meta-analysis with a random-effect model. In the discovery set, a locus on chromosome 6, rs9277630, was associated with WDEIA in the dominant model (OR = 3.95 [95% CI, 2.31-6.73], p = 7.87 × 10 -8 ). The HLA-DPB1 ∗ 02:01:02 allele displayed the most significant association with WDEIA (OR = 4.51 [95% CI, 2.66-7.63], p = 2.28 × 10 -9 ), as determined via HLA imputation following targeted sequencing. The association of the allele with WDEIA was confirmed in replication samples (OR = 3.82 [95% CI, 2.33-6.26], p = 3.03 × 10 -8 ). A meta-analysis performed in the combined set revealed that the HLA-DPB1 ∗ 02:01:02 allele was significantly associated with an increased risk of WDEIA (OR = 4.13 [95% CI, 2.89-5.93], p = 1.06 × 10 -14 ). Individuals carrying the HLA-DPB1 ∗ 02:01:02 allele have a significantly increased risk of WDEIA. Further validation of these findings in independent multiethnic cohorts is needed., (Copyright © 2021 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Cetuximab is mainly used for the treatment of advanced and metastatic colorectal cancer. Owing to the oligosaccharide galactose-α-1,3-galactose (α-gal) in its heavy chain, cetuximab can induce severe IgE-dependent anaphylaxis. α-Gal is also the antigen responsible for α-gal syndrome, known as mammalian meat allergy. Patients with α-gal syndrome may suffer from cetuximab-induced anaphylaxis at the first administration because of developed α-gal-specific IgE antibodies. A male patient in his 50 s with metastatic colon cancer was receiving chemotherapy involving scheduled cetuximab administration. However, he died soon after the first administration. Forensic autopsy confirmed rectal cancer, metastatic rectal cancer in the liver, and renal cancer. Laboratory blood tests revealed the presence of cetuximab- and beef-specific IgE antibodies before cetuximab administration and an extremely high level of tryptase after administration. Thus, we determined that the death was caused by cetuximab-induced anaphylaxis due to the preexisting α-gal syndrome. To the best of our knowledge, this is the first autopsy case report in forensic medicine of fatal anaphylaxis after initial cetuximab administration., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Some patients with wheat-dependent exercise-induced anaphylaxis (WDEIA) or wheat allergy showed negative ω-5 gliadin-specific IgE test and high level of grass pollen-specific IgE. It was presumed that these patients developed allergic reaction upon cross-reaction of their IgE antibodies raised against grass pollen allergens to wheat allergens. This study aimed to clarify clinical characteristics and wheat allergens of this phenotype of WDEIA/wheat allergy, which were tentatively diagnosed as grass pollen-related wheat allergy (GPWA)., Methods: A total of six patients with GPWA were enrolled, and controls were 17 patients with grass pollen allergy but no episode of wheat allergy, and 29 patients with other wheat allergies: 18 with conventional WDEIA and 11 with hydrolyzed wheat protein allergy. Sensitization to wheat proteins was determined by basophil activation test (BAT). IgE-binding proteins in wheat flour were identified by immunoblotting followed by mass spectrometry. Wheat allergen-specific IgE tests were established by CAP-FEIA system., Results: All the six patients with GPWA were sensitized to water-soluble wheat proteins in BAT and IgE-immunoblotting, and peroxidase-1 (35 kDa) and beta-glucosidase (60 kDa) were identified as specific IgE-binding wheat proteins. The binding of patient IgE to these proteins was inhibited by pre-incubation of patient sera with grass pollen. The peroxidase-1- and beta-glucosidase-specific IgE tests identified three and four of six patients with GPWA, respectively, but only two of 29 controls, indicating high specificity of these tests., Conclusions: Peroxidase-1 and beta-glucosidase are specific wheat allergens for GPWA among grass pollen allergy and other types of wheat-induced food allergies., (Copyright © 2020 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Shrimp is a causative food that elicits food-dependent exercise-induced anaphylaxis (FDEIA). In this study, we sought to identify IgE-binding allergens in patients with shrimp-FDEIA. Sera were obtained from eight patients with shrimp-FDEIA and two healthy control subjects. Proteins were extracted from four shrimp species by homogenization in Tris buffer. Immunoblot analysis revealed that IgE from patient sera bound strongly to a 70-kDa and a 43-kDa protein in a preparation of Tris-soluble extracts from Litopenaeus vannamei. Mass spectrometry identified the 70-kDa and 43-kDa proteins as a P75 homologue and fructose 1,6-bisphosphate aldolase (FBPA), respectively. To confirm that the putative shrimp allergens were specifically recognized by serum IgE from shrimp-FDEIA patients, the two proteins were purified by ammonium sulfate precipitation followed by reversed-phase HPLC and/or anion-exchange hydrophobic interaction chromatography and then subjected to immunoblot analysis. Purified P75 homologue and FBPA were positively bound by serum IgE from one and three, respectively, of the eight patients with shrimp-FDEIA, but not by sera from control subjects. Thus, P75 homologue and FBPA are identified as IgE-binding allergens for shrimp-FDEIA. These findings could be useful for the development of diagnostic tools and desensitization therapy for shrimp-FDEIA patients.

Linear immunoglobulin A dermatosis (LAD) is rarely complicated in patients with ulcerative colitis (UC), though the long-term prognosis in those with concurrent LAD and UC is not fully understood. Here, we report findings obtained in follow-up examinations performed over a 10-year period of a UC patient initially complicated with LAD. We treated an 18-year-old male for relapse of UC with deteriorating blisters diagnosed as LAD. Following successful induction therapy for both UC and LAD with oral prednisolone, the patient was followed for 10 years. Skin condition remained good at each examination, even with second and third relapses of UC. Our findings in this case indicate that LAD is rarely complicated with UC, while it has no association with colitis disease activity. Furthermore, adequate treatment following an initial diagnosis of LAD is important for management of affected UC patients.

Background: Fish roe allergy is a common health problem in countries where sea food is a major part of the diet, such as Japan. β'-component (β'-c) in fish roe has been identified as a major antigen for patients who show hypersensitivity to various fish roes. However, little is known about causative antigens for patients reactive to fish roe of specific species., Methods: Serum and basophils were obtained from patients who had reactivity to roes of Gadus chalcogrammus (GC) and/or other fish species. GC roe specific antigens were analyzed by immunoblotting, histamine release assay (HRA) and mass spectrometry. Recombinant-fragments of vitellogenin (Vg) were obtained by the Escherichia coli expression system., Results: Serum IgE of a patient with specific reactions to GC roe bound to 15, 28, 40 and 70 kDa-proteins in GC roe extract. Mass spectrometry analysis revealed that proteins in these bands contained fragments corresponding to Vg. Immunoblotting of Vg immunoprecipitated by rabbit anti-Vg antiserum from the extract revealed 15, 28 and 54 kDa fragments bound by the patient's IgE. These bindings were inhibited by the pretreatment of recombinant phosvitin (rPv) and β'-c (rβ'-c). Fractions obtained by native gel electrophoresis containing 15, 28 and 54 kDa proteins, but not the other fractions, induced significant histamine release from the patient's basophils. Sera of the other patients with GC roe specific-IgE showed IgE binding to rPv and/or rβ'-c., Conclusions: The 15, 28 and 54 kDa-fragments of Vg which include structures of Pv and β'-c, could be antigens for GC roe specific type-I-hypersensitivity., (Copyright © 2019 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Food allergy is a growing health problem worldwide because of its increasing prevalence, life-threatening potential, and shortage of effective preventive treatments. In an outbreak of wheat allergy in Japan, thousands of patients had allergic reactions to wheat after using soap containing hydrolyzed wheat protein (HWP)., Objectives: The aim of the present study was to investigate genetic variation that can contribute to susceptibility to HWP allergy., Methods: We conducted a genome-wide association study of HWP allergy in 452 cases and 2700 control subjects using 6.6 million genotyped or imputed single nucleotide polymorphisms. Replication was assessed by genotyping single nucleotide polymorphisms in independent samples comprising 45 patients with HWP allergy and 326 control subjects., Results: Through the genome-wide association study, we identified significant associations with the class II HLA region on 6p21 (P = 2.16 × 10 -24 for rs9271588 and P = 2.96 × 10 -24 for HLA-DQα1 amino acid position 34) and with the RBFOX1 locus at 16p13 (rs74575857, P = 8.4 × 10 -9 ). The associations were also confirmed in the replication data set. Both amino acid polymorphisms (HLA-DQβ1 amino acid positions 13 and 26) located in the P4 binding pockets on the HLA-DQ molecule achieved the genome-wide significance level (P < 5.0 × 10 -8 )., Conclusions: Our data provide the first demonstration of genetic risk for HWP allergy and show that this genetic risk is mainly represented by multiple combinations of HLA variants., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Cetuximab, the IgG1 subclass chimeric mouse-human monoclonal antibody biologic that targets the epidermal growth factor receptor (EGFR), is used worldwide for the treatment of EGFR-positive unresectable progressive/recurrent colorectal cancer and head and neck cancer. Research has shown that the principal cause of cetuximab-induced anaphylaxis is anti-oligosaccharide IgE antibodies specific for galactose-α-1,3-galactose (α-Gal) oligosaccharide present on the mouse-derived Fab portion of the cetuximab heavy chain. Furthermore, it has been revealed that patients who are allergic to cetuximab also develop an allergic reaction to mammalian meat containing the same α-Gal oligosaccharide owing to cross-reactivity, and the presumed cause of sensitization is tick bites: Amblyomma in the United States, Ixodes in Australia and Europe, and Haemaphysalis in Japan. The α-Gal-specific IgE test (bovine thyroglobulin-conjugated ImmunoCAP) or CD63-expression-based basophil activation test may be useful to identify patients with IgE to α-Gal in order to predict risk for cetuximab-induced anaphylactic shock. Investigations of cetuximab-related anaphylaxis have revealed three novel findings that improve our understanding of immediate-type allergy: 1) oligosaccharide can serve as the main IgE epitope of anaphylaxis; 2) because of the oligosaccharide epitope, a wide range of cross-reactivity with mammalian meats containing α-Gal similar to cetuximab occurs; and 3) tick bites are a crucial factor of sensitization to the oligosaccharide. Nonetheless, taking a medical history of tick bites and beef allergy may be insufficient to prevent cetuximab-induced anaphylaxis, and therefore blood testing with an α-Gal-specific IgE test, with high sensitivity and specificity, is necessary to detect sensitization to α-Gal., (Copyright © 2019 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

We present a case of early childhood-onset pork-cat syndrome possibly due to sensitization by both cats and dogs. A 6-year-old girl was referred to our hospital because of repetitive episodes of urticaria when she consumed pork meat. The patient lived with a dog and the ground floor of her house was a veterinary clinic run by her veterinarian parents. Blood tests demonstrated high specific IgE (≥50UA/ml) against cat dander, dog dander, pork, Sus s 1, Fel d 2, Can f 1, Can f 2, and Can f 3. The skin prick test was positive for raw pork and beef. Western blotting analysis detected hot spots on 67-kDa proteins in pork meat and cat dander extract. Cross-reactivity between these two proteins was confirmed by an inhibition test. Furthermore, crossreactivity between pork meat and dog dander extract was also noted. Taken together, the diagnosis of porkcat syndrome was made, and both cats and dogs were suggested to have led to the sensitization. The patient was advised to only eat well-cooked pork, and has been followed thereafter without additional reactions. The previously reported cases of this syndrome developed during adolescence and young adulthood because a considerable period from the sensitization to the development cross-reactivity with pork meat is required. To our best knowledge, this is the youngest reported case of pork-cat syndrome among English and Japanese literatures. The nomenclature of this syndrome as pet animal-meat syndrome improves the understanding of the underlying pathogenesis of cross-reactivity between animal albumins and meat albumins.

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., (Copyright © 2018 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: In severe drug eruptions, precise evaluation of disease severity at an early stage is needed to start appropriate treatment. It is not always easy to diagnose these conditions at their early stage. In addition, there are no reported prognostic biomarkers of disease severity in drug eruptions. The aim of this study was to test whether the thymus and activation-regulated chemokine (TARC) level in serum at an early stage of a drug eruption can serve as a prognostic biomarker of systemic inflammation., Methods: Study participants included 76 patients who received a diagnosis of a drug eruption, one of the following: drug rash with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome, maculopapular exanthema, and erythema multiforme. Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) was eliminated in this study because scoring system for evaluating the severity was established. Correlation coefficients between serum TARC levels and indicators of systemic inflammation, including the neutrophil-to-lymphocyte ratio, Glasgow prognostic score, modified systemic inflammatory response syndrome (mSIRS) score, and C-reactive protein in serum were evaluated., Results: Serum TARC levels positively correlated with the neutrophil-to-lymphocyte ratio, Glasgow prognostic score, mSIRS score, C-reactive protein, albumin, white blood cell count, body temperature, and pulse rate. TARC levels negatively correlated with systolic blood pressure. Among these parameters, the mSIRS score showed strong correlation (correlation coefficient: 0.68)., Conclusions: Serum TARC levels correlate well with indicators of systemic inflammation and of disease severity among patients with a drug eruption except SJS/TEN. Serum TARC may be a prognostic biomarker of severity of inflammation in drug eruptions., (Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

A 79-year-old Japanese woman had clinical and histopathological features of bullous pemphigoid, while direct immunofluorescence test revealed C3 and immunoglobulin G depositions in the lower cell surfaces of the epidermis in addition to those in the dermoepidermal junction. Chemiluminescent enzyme immunoassays were positive for desmoglein-1 and -3 antibodies in addition to anti-BP180 antibodies. In an immunoblotting study, antibodies against both 180-kDa bullous pemphigoid antigen and 130-kDa pemphigus vulgaris antigen were detected. Based on these results, bullous pemphigoid coexisting with anti-desmoglein autoantibodies was diagnosed in this case., (© 2017 Japanese Dermatological Association.)

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 300mg, 150mg, 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 300mg, 150mg 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 300mg, 150mg, 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., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: This study aims to evaluate the relationship between serum thymus and activation-regulated chemokine (TARC) levels with various clinicopathological conditions in patients with drug eruptions. The value of TARC in diagnosing drug-induced hypersensitivity syndrome (DIHS) was also examined., Methods: Study participants included 84 patients who presented with generalized eruptions suspected to be drug-related, including DIHS, Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), maculopapular exanthema (MPE), erythema multiforme (EM), erythroderma, and toxicoderma. The correlation coefficients between serum TARC levels and clinical parameters in peripheral blood samples were calculated., Results: Serum TARC levels in patients with DIHS were higher than those found in patients with SJS/TEN, MPE, EM, and toxicoderma. TARC levels had 100% sensitivity and 92.3% specificity in diagnosing DIHS, with a threshold value of 13,900 pg/mL. Serum TARC levels positively correlated with age, white blood cell (WBC) count, neutrophil count, eosinophil count, monocyte count, atypical lymphocyte (Aty-ly) count, serum blood urea nitrogen (BUN) levels, and creatinine (Cr) levels. It negatively correlated with serum total protein (TP), albumin (Alb), and estimated glomerular filtration rate (eGFR). Among these clinical parameters, blood eosinophil counts were most strongly correlated with serum TARC levels, with a correlation coefficient of 0.53., Conclusions: Serum TARC levels are well correlated with blood eosinophil counts in patients with generalized drug eruptions, indicating that Th2-type immune reactions underlie TARC production. Serum TARC measurements also have potent diagnostic value for DIHS, with high sensitivity and specificity., (Copyright © 2016 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Invasive cases of extramammary Paget's disease have a poor prognosis, owing to its rapid progression and resistance to irradiation and chemotherapy. Morton et al. introduced a technique to identify sentinel lymph nodes by local injection of vital dyes and reported its benefit for managing the progress of malignant melanoma., Objectives: Since the rate of lymph node metastasis of extramammary Paget's disease is not uncommon (reported from 8.5% to 26%), this study tested the hypothesis that sentinel lymph node biopsy would be useful to detect lymph node metastasis in the clinically early stage of extramammary Paget's disease., Materials & Methods: Eighteen patients with primary extramammary Paget's disease were enrolled in the study. The precise location of sentinel lymph nodes was visualized using either intraoperative patent blue dye injection or indocyanine green dye injection in combination with a hand-held gamma-detecting probe after a 99mTc phytate injection., Results: Of the 18 patients, sentinel lymph node metastasis was identified in 2 (Cases 2 and 15) of the 2 patients with deep invasion and in 1 (Case 12) of the 7 patients with minimal dermal invasion, however, it was absent in 9 patients who had been categorized into the intraepidermal group., Conclusion: This study demonstrates that extramammary Paget's disease possibly causes metastasis via regional lymphatic systems to which the lesion belongs, even in the early stages of no nodule or tumor formation, and that sentinel lymph node biopsy is useful to detect lymph node metastasis.

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.