Mortality and risk factors on admission in toxic epidermal necrolysis: A cohort study of 59 patients.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening disorders characterized by widespread epidermal necrosis of the skin and mucosa. The severity-of-illness scoring system for TEN (SCORTEN) was widely used since 2000 as a standard prognostic tool consisting of seven clinical values. METHODS: To evaluate the prognosis using current treatments and risk factors for mortality, we retrospectively analyzed 59 cases of TEN, including SJS/TEN overlap treated in two university hospitals from January 2000 to March 2020. RESULTS: The mortality rate of TEN was 13.6% (8/59). All patients treated with high-dose steroid administration in combination with plasma exchange and/or immunoglobulin therapy recovered. Logistic regression analysis showed nine clinical composite scores, namely: heart rate (≧120 bpm), malignancy present, percentage of body surface area with epidermal detachment (>10%), blood urea nitrogen (>28 mg/dL), serum bicarbonate level (<20 mEq/L), serum glucose level (>252 mg/dL), age (≧71 years), the interval between disease onset and treatment initiation at the specialty hospital (≧8 days), and respiratory disorder within 48 h after admission. The receiver operating characteristic curves confirmed a high potential for predicting the prognosis of TEN. CONCLUSIONS: Recent developments in treatment strategies have contributed to the improved prognosis of TEN patients. A modified severity scoring model composed of nine scores may be helpful in the prediction of TEN prognosis in recent patients. Further large-scale studies are needed to confirm mortality findings to improve prognostication in patients with TEN.

[A LONG PROSPECTIVE OBSERVATIONAL STUDY ON PREVALENCE OF ATOPIC DERMATITIS IN EARLY CHILDHOOD TO ADOLESCENCE].

BACKGROUND: There are few prospective observational studies on the prevalence of atopic dermatitis (AD) in children. We aimed to prospectively investigate the dynamics of change in the prevalence of AD from early childhood to adolescence. METHODS: We conducted a survey with a modified questionnaire to diagnose AD based on The International Study of Asthma and Allergies in Childhood questionnaire with 1230 13-year-old children who were born in the Minami ward, Yokohama City between May 2004 and June 2005 and had undergone physical examinations by dermatologists at 3 years of age. Among the 422 children who answered the questionnaire, 210 had undergone periodic physical examinations by dermatologists from 4 months to 3 years of age (Cohort 1), whereas 212 had undergone physical examinations only at 3 years of age (Cohort 2). RESULTS: The prevalence of AD was 16.9% in 422 children at 13 years of age, with 22.9%, 16.6%, 20.0% and 18.3% prevalence at 4 months, 18 months, 3 years and 13 years of age, respectively, in children who were followed up long-term. The frequency of AD occurrence per year decreased after the age of 3 years; a history of AD at this age was significantly related to AD at 13 years of age (Fisher's exact test, p<0.001). CONCLUSION: In conclusion, it was suggested that AD in 3-year-old children is one of the risk factors for the development of AD in 13-year-old children.

Skin rash following Administration of Apalutamide in Japanese patients with Advanced Prostate Cancer: an integrated analysis of the phase 3 SPARTAN and TITAN studies and a phase 1 open-label study.

BACKGROUND: A higher incidence of apalutamide-related skin rash has been observed in Japanese patients with prostate cancer (PC). METHODS: This integrated analysis of data of Japanese patients from 2 global Phase 3 studies, SPARTAN ( NCT01946204 ; patients with non-metastatic castration-resistant PC [nmCRPC]) and TITAN ( NCT02489318 ; patients with metastatic castration-sensitive PC [mCSPC]), and the Phase 1 study 56021927PCR1008 ( NCT02162836 ; patients with metastatic CRPC [mCRPC]), assessed clinical risk factors of apalutamide-related skin rash as well as the potential correlation with plasma exposure to apalutamide. Kaplan-Meier method was used for time-to-event analyses. Clinical risk factors for skin rash were assessed using odds ratio. RESULTS: Data from 68 patients (SPARTAN: n = 34, TITAN: n = 28, 56021927PCR1008: n = 6) receiving apalutamide 240 mg orally once-daily were analyzed. Rash (13 [19.1%]) and maculo-papular rash (11 [16.2%]) were the most frequently reported skin rash. All Grade and Grade 3 skin rash occurred in 35 (51.5%) and 10 (14.7%) patients, respectively. Most (85.7%) skin rash occurred within 4 months of apalutamide initiation and resolved in a median time of 1 month following the use of antihistamines, topical or systemic corticosteroids, with/without apalutamide dose interruptions/reductions. Median time-to-remission of first incidence of rash and maximum grade incidence of rash were 1.0 month (IQR: 0.36-1.81) and 1.0 month (IQR: 0.30-2.43), respectively. No significant clinical risk factors for the incidence of skin rash were observed. Areas under the curve (0-24 h) (AUC0-24, ss) at steady-state of plasma apalutamide concentration were numerically slightly higher in patients with skin rash than those without. CONCLUSIONS: No clinical risk factors for rash could be detected. There is a potential correlation between incidence of skin rash and plasma exposure to apalutamide. In general, apalutamide-related skin rash is easily managed, with appropriate treatment with or without dose adjustment. TRIAL REGISTRATION: Retrospective pooled analysis of NCT01946204 , NCT02489318 , and NCT02162836 .

Correction to: Skin rash following Administration of Apalutamide in Japanese patients with Advanced Prostate Cancer: an integrated analysis of the phase 3 SPARTAN and TITAN studies and a phase 1 open-label study.

An amendment to this paper has been published and can be accessed via the original article.

[Case of Gastric Malignant Lymphoma Invading Other Organs with Bleeding Treated by Surgery].

A female in her late 50s experienced dyspnea and was transported by an ambulance. Her hemoglobin score was low, and CT imaging showed a giant tumor in her stomach. The tumor perforated her liver and invaded the abdominal wall and duodenum around the Treitz ligament. She required surgery because of the massive hemorrhage due to the tumor. Total gastrectomy with lateral segmentectomy of the liver and resection of the duodenum and the ileum around the Treitz ligament were performed. At 1.5 months after surgery, chemotherapy for malignant lymphoma was successfully initiated.

Serum levels of squamous cell carcinoma antigens 1 and 2 reflect disease severity and clinical type of atopic dermatitis in adult patients.

BACKGROUND: Recent studies have indicated that serum levels of squamous cell carcinoma antigen (SCCA) 1 and 2 induced by type 2 cytokines such as IL-4 and IL-13, are increased in patients with atopic dermatitis (AD). However, no clinical studies have analyzed serum levels of SCCA2 in larger series of AD patients or their association with various clinical characteristics. This study was performed to clarify whether serum levels of SCCA2 are associated with disease severity and clinical phenotypes of adult AD patients. METHODS: An enzyme-linked immunosorbent assay was performed to examine serum SCCA2 levels in 240 adult patients with AD and 25 healthy controls in this study. Serum SCCA2 levels were analyzed with clinical characteristics and laboratory parameters including thymus and activation-regulated chemokine (TARC), lactate dehydrogenase (LDH), blood eosinophils, total IgE, and specific IgE (Japanese cedar pollen, Dermatophagoides farina, Candida, malassezia, Staphylococcal enterotoxin B). Expression of SCCA2 in AD eruption was examined by immunohistochemistry. The effect of treatment on serum SCCA2 was also assessed. RESULTS: Serum SCCA2 level showed a positive correlation with disease severity, levels of TARC, LDH, eosinophil counts, and IgE levels. Robust expression of SCCA2 was detected in the supra basal keratinocytes in the epidermis of AD patients. Serial measurements of serum SCCA2 revealed decreased levels of SCCA2 after treatment for AD. CONCLUSIONS: Serum SCCA2 levels reflected disease severity and clinical type of AD. Serum SCCA2 may thus be a relevant biomarker for AD.

Retrospective analysis of Stevens-Johnson syndrome and toxic epidermal necrolysis in 87 Japanese patients--Treatment and outcome.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe adverse drug reactions with high mortality. METHODS: To present the clinical characteristics of SJS and TEN in Japan and evaluate the efficacy of treatments, we retrospectively analyzed cases of SJS and TEN treated in 2 university hospitals during 2000-2013. RESULTS: Fifty-two cases of SJS (21 males and 31 females; average age, 55.1 years) and 35 cases of TEN (17 males and 18 females; average age, 56.6 years) were included in this study. Twenty-eight cases of SJS (53.8%) and all cases of TEN were caused by drugs. Hepatitis was the most common organ involvement in both SJS and TEN. Renal dysfunction, intestinal disorder, and respiratory disorder were also involved in some cases. The major complication was pneumonia and sepsis. All cases except for 3 cases were treated systemically with corticosteroids. Steroid pulse therapy was performed in 88.6% of TEN. Plasmapheresis and/or immunoglobulin therapy was combined with steroid therapy mainly in TEN after 2007. The mortality rate was 6.9% and the rates for SJS and TEN were 1.9% and 14.3%, respectively. These were much lower than predicted mortality according to a severity-of-illness scoring system for TEN prognosis (SCORTEN) score. When comparing the mortality rate between 2000-2006 and 2007-2013, it was decreased from 4.5% to 0.0% in SJS and from 22.2% to 5.3% in TEN. CONCLUSIONS: Treatment with steroid pulse therapy in combination with plasmapheresis and/or immunoglobulin therapy seems to have contributed to prognostic improvement in SJS/TEN.

[HER2-Positive Advanced Gastric Cancer with Disseminated Intravascular Coagulation and Diffuse Bone Marrow Carcinomatosis Successfully Treated with S-1/Trastuzumab Chemotherapy--A Case Report].

Trastuzumab, a humanized monoclonal antibody against human epidermal growth factor receptor 2 (HER2), has been proven to result in a survival benefit for the treatment of patients with HER2-positive advanced gastric cancer (AGC). However, data are lacking for the treatment of those with disseminated intravascular coagulation (DIC) and diffuse bone marrow carcinomatosis. A 77-year-old woman presented with back pain and fatigue since 2 months. Esophagogastroduodenoscopy showed a scirrhous lesion in the gastric corpus, which was biopsied and identified as signet-ring cell carcinoma with HER2 overexpression on immunohistochemistry. Laboratory testing, bone scintigraphy, and bone marrow biopsy were conducted, and she was diagnosed with HER2-positive AGC with DIC and diffuse bone marrow carcinomatosis. She underwent chemotherapy with the following regimen: oral administration of 80 mg/m2 S-1 for 2 weeks and 6 mg/kg trastuzumab infusion on day 6 every 3 weeks, which significantly improved the DIC. She was discharged from the hospital 73 days after admission and survived for 438 days after diagnosis. To the best of our knowledge, this is the first case report in which HER2-positive AGC complicated by DIC with diffuse bone marrow carcinomatosis was successfully treated with combined chemotherapy consisting of S-1 plus trastuzumab.

Effects of oral administration of Lactobacillus acidophilus L-92 on the symptoms and serum cytokines of atopic dermatitis in Japanese adults: a double-blind, randomized, clinical trial.

OBJECTIVES: Several studies on lactobacilli have demonstrated they are effective against atopic dermatitis (AD) in children, but there are very few reports of their effects in adults. We investigated the changes in AD symptoms in adults after the ingestion of the Lactobacillus acidophilus strain L-92 (L-92), which has been shown to have a curative effect on AD in children. METHODS: A double-blind, parallel-group, placebo-controlled comparison was performed on 49 AD patients aged ≥16 years using heat-killed L-92. Skin lesions were assessed using the SCORing AD (SCORAD) index before the start of L-92 ingestion and 4 and 8 weeks after ingestion. Serum cytokine and blood marker levels were measured 8 weeks after the start of L-92 ingestion. RESULTS: The group that ingested L-92 had lower SCORAD scores than the controls (p = 0.002). The L-92 group also had decreased ratios of change for eosinophil count (p = 0.03) and increased ratios of change for serum TGF-ß (p = 0.03). Ratios of change for serum TGF-ß rose significantly (p = 0.04) in patients showing mitigated symptoms with L-92 administration. CONCLUSIONS: Administration of heat-killed L-92 was effective for AD symptoms in adults. L-92 may contribute to the suppression of Th2-dominant inflammation. Our preliminary trial is the first to report the effects of L-92 on adult AD.

Decreased expression of semaphorin-3A, a neurite-collapsing factor, is associated with itch in psoriatic skin.

Pruritus is a common symptom of psoriasis, which affects quality of life. This symptom accompanies the hyper-innervation of sensory C-fibres in psoriatic lesions. Two extracellular molecules, nerve growth factor (NGF) and semaphorin-3A, regulate C-fibre extension. In this study, the expression levels of these 2 molecules in biopsy specimens from psoriatic and healthy skin were quantified by immunohistochemistry and quantitative reverse-transcription PCR. Semaphorin-3A expression was lower in the psoriatic samples compared with the healthy samples, whereas NGF was higher. C-fibre innervation in the epidermis was also increased in psoriatic skin. Semaphorin-3A mRNA expression was negatively correlated with itch intensity and severity of psoriasis. We propose that decreased semaphorin-3A and increased NGF expression levels may trigger the outgrowth of C-fibres, leading to pruritus.

Clinical features and antimicrobial treatment of skin infections caused by Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus.

Skin infections caused by Panton-Valentine leukocidin (PVL)-positive methicillin-resistant Staphylococcus aureus (MRSA), especially the USA300 clone, have been increasing in Japan. To prevent an epidemic of PVL-positive MRSA, rapid diagnosis and effective antimicrobial therapy are essential. However, the clinical features of, and antimicrobial efficacy against, these skin infections are not well understood in Japan. Here, we report 10 cases of skin infections caused by PVL-positive MRSA that presented over a two-year period in our clinic. Genetic analyses revealed that 90% of the PVL-positive MRSA strains were identified as USA300 and its related clones. Notably, 70% of the patients had atopic dermatitis (AD) as an underlying disease. Average durations of antimicrobial therapy for AD patients (10.6 weeks) were 2.9-fold longer than those for non-AD patients (3.7 weeks). However, all cases were improved by a long-term course of fosfomycin, minocycline, doxycycline, and/or rifampicin. Our data suggest that AD may be an important risk factor for intractable skin infections caused by PVL-positive MRSA.

Phenotypes of atopic dermatitis up to 36 months of age by latent class analysis and associated factors in Japan.

BACKGROUND: Atopic dermatitis (AD) in early childhood is the first allergic manifestation in the atopic march. Recently, latent class analysis (LCA) has revealed the presence of AD subgroups in childhood. OBJECTIVE: This study aimed to elucidate different AD phenotypes up to 36 months of age and identify factors associated with a particular AD phenotype in early childhood. METHODS: Pediatric allergists or dermatologists examined children who visited local public health centers in Chiba or Yokohama city at 4, 18, and 36 months of age for regular health checkups between 2003 and 2005. LCA was used to identify AD subtypes on the basis of the course of skin symptoms and comorbidity of other allergic diseases. After LCA, the association between genetic and environmental factors and AD phenotypes was assessed. RESULTS: A total of 1,378 children who underwent the 3 checkups were included. Complete data were available for 515 children up to 36 months of age. Of 515 children, 183 were diagnosed with AD at least at one out of the 3 time points. The LCA model of these children with AD separated 4 AD phenotypes: early-persistent (EP), early-transient (ET), late-onset (LO), and variable (V). Antibiotic use by 4 months of age was significantly higher in EP group than in other 3 groups. Mother's allergy was significantly higher in EP and LO groups than in other 2 groups. Passive smoking at 18 months of age was higher in LO group than in other groups. Furthermore, >80% of V group was born in spring-summer. CONCLUSION: We identified 4 AD phenotypes using LCA on the basis of the onset/course of AD and comorbidity of other allergic diseases and also identified several factors related to the particular phenotypes, which may be useful markers for the prediction of prognosis of AD in early childhood.

Plectin deficiency leads to both muscular dystrophy and pyloric atresia in epidermolysis bullosa simplex.

Plectin is a cytoskeletal linker protein which has a long central rod and N- and C-terminal globular domains. Mutations in the gene encoding plectin (PLEC) cause two distinct autosomal recessive subtypes of epidermolysis bullosa: EB simplex (EBS) with muscular dystrophy (EBS-MD), and EBS with pyloric atresia (EBS-PA). Previous studies have demonstrated that loss of full-length plectin with residual expression of the rodless isoform leads to EBS-MD, whereas complete loss or marked attenuation of expression of full-length and rodless plectin underlies the more severe EBS-PA phenotype. However, muscular dystrophy has never been identified in EBS-PA, not even in the severe form of the disease. Here, we report the first case of EBS associated with both pyloric atresia and muscular dystrophy. Both of the premature termination codon-causing mutations of the proband are located within exon 32, the last exon of PLEC. Immunofluorescence and immunoblot analysis of skin samples and cultured fibroblasts from the proband revealed truncated plectin protein expression in low amounts. This study demonstrates that plectin deficiency can indeed lead to both muscular dystrophy and pyloric atresia in an individual EBS patient.

Optimal Criteria for G3 (Poorly Differentiated) Stage II Colon Cancer: Prospective Validation in a Randomized Controlled Study (SACURA Trial).

Grade 3 (G3, poorly differentiated) is an important treatment-decision factor in stage II colon cancer, but no unified diagnostic criteria are established. According to previous studies, an intratumoural poorly differentiated area with no glandular formation (POR) that fills the microscopic field of a ×40 objective lens was an essential factor that defined G3. We aimed to prospectively validate this in a randomized controlled study of adjuvant chemotherapy (SACURA trial). We enrolled 991 patients with stage II colon cancer. POR was graded according to the ×40 objective lens rule and the intensity of poorly differentiated clusters (Grade), and its prognostic power was compared with that of the conventional tumor grade on the basis of predominant histology rule (Grade). According to Grade, 313, 526, and 152 tumors were classified as G1, G2, and G3, respectively, and the 5-year relapse-free survival (RFS) rates were 91.1%, 82.9%, and 74.7%, respectively (P<0.0001). When G3 and G3 were alternatively added to the prognostic model consisting of 8 conventional factors, only G3 was a significant factor for RFS (P=0.040, Wald test). The adverse impact of G3 on RFS was greater in the microsatellite stable/microsatellite instability-low subset than that in the full analysis set. In the microsatellite stable/microsatellite instability-low subset, the 5-year RFS rate of patients with G3 tumors in the chemotherapy group achieved greater improvement (9.1%) than the surgery-alone group. The least differentiation policy with the ×40 objective lens rule may be highlighted as the diagnostic criterion for G3 because of its validated prognostic value.

Quantitative analysis of nerve growth factor (NGF) in the atopic dermatitis and psoriasis horny layer and effect of treatment on NGF in atopic dermatitis.

BACKGROUND AND OBJECTIVE: The expression of nerve growth factor (NGF) is known to increase in the skin of patients with atopic dermatitis (AD) and is related to disease aggravation. In the present study, we measured skin NGF levels in AD patients and determined whether they correlate to AD severity as well as treatment effects. METHODS: NGF in the horny layer (horn NGF) of skin lesions found on the cubital fossa of AD patients was collected via tape stripping and measured using ELISA before and after 2 and 4 weeks following initiation of treatments. Itching and eruptions on the lesions were also evaluated. Peripheral blood eosinophil count, serum LDH level and total serum IgE level were also examined. RESULTS: The level of NGF was significantly higher in AD patients than in healthy controls, and correlated with the severity of itch, erythema, scale/xerosis, eosinophil count, and LDH level. The NGF level decreased significantly at 2 and 4 weeks of treatment with olopatadine, a histamine H(1) receptor antagonist, and/or topical steroid. The reduction in NGF correlated with the decrease in the severity of itching and erythema, papule, scale/xerosis and lichenification of the lesion, eosinophil count, and LDH level. In psoriatic lesional skin with itch, the horn NGF was significantly higher than in non-lesional skin of psoriasis, but the value was lower than NGF in atopic skin. CONCLUSIONS: The level of horn NGF was found to reflect the severity of itching and eruptions in AD. Therefore, quantification of NGF in the samples collected directly from the horny layer appears to be useful in assessing severity and therapeutic effects in AD.

A multi-institution phase II study of docetaxel and S-1 in combination with trastuzumab for HER2-positive advanced gastric cancer (DASH study).

BACKGROUND: Trastuzumab when combined with fluoropyrimidine and cisplatin was proven to improve survival in patients with human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC) in the ToGA study. The safety and efficacy of trastuzumab in combination with docetaxel and S-1 have not yet been evaluated. METHODS: This study was a multicenter, phase II study. Patients with chemotherapy-naïve HER2-positive advanced or metastatic GC were eligible. Trastuzumab was administered intravenously on day 1 of the first cycle at 8 and 6 mg/kg in subsequent cycles. Docetaxel was administered intravenously at 40 mg/m2 on day 1 of each cycle. S-1 was administered at a dosage based on body surface area for 14 days in a 3-weekly cycle. The primary endpoint was progression-free survival (PFS). RESULTS: A total of 23 patients were enrolled. Median PFS was 6.7 months (95% CI 4.1-10.1). The response rate (RR) was 39.1%. Median overall survival (OS) and time to treatment failure (TTF) were 17.5 and 4.4 months, respectively. Major grade 3-4 adverse events were neutropenia (39.1%), leukopenia (30.4%), and febrile neutropenia (8.7%). CONCLUSION: Trastuzumab in combination with docetaxel and S-1 showed effective antitumor activity and manageable toxicities as first-line treatment for patients with HER2-positive GC.

Microsatellite instability and clinicopathological features in esophageal squamous cell cancer.

Since multiple genetic alterations are involved in the molecular pathogenesis of esophageal squamous cell cancer (ESCC), the role of microsatellite instability (MSI) in its carcinogenesis is not well defined. The reported frequency of MSI in ESCC ranges from 2 to 66.7% but the majority of the results are derived from relatively small studies. Therefore, we carried out a precise MSI analysis on a large number of ESCC samples to clarify the significance of MSI in the ESCC tumorigenesis. The MSI status of the DNA extracted from 62 ESCC samples and 62 counterpart-normal esophageal epitheliums were studied with five NCI panel markers and ten microsatellite markers located in 17q24-25. Forty-four paraffin-embedded samples and 18 frozen samples from the ESCC patients who underwent surgery were studied. The MSI status was classified as MSS (microsatellite stable), MSI-L (low-level MSI; <30% of markers examined showed instability) and MSI-H (high-level MSI; >30% of markers reported instability). Among the 62 ESCC cases analyzed by the 15 microsatellite markers, 38 out of 62 cases (61.3%) showed MSS, 19 out of 62 cases (30.6%) showed MSI-L and 5 out of 62 cases (8.1%) showed MSI-H. Although the MSI status was not associated with the status of lymph node metastasis or a histological type of cancer, the depth of cancer invasion was significantly associated with the frequency of MSS status and the levels of MSI-L were inversely correlated with the depth of invasion (T1/T2 vs. T3/4; P=0.0007). However, MSI status was not associated with the prognosis of the ESCC patients. This is the first large scale MSI analysis of the ESCC in comparison with the clinicopathological features. Relatively high frequency of MSI-L was observed in ESCC and the frequency of MSI-L was inversely correlated with the depth of invasion.

Safety of selective cyclooxygenase-2 inhibitors and a basic non-steroidal anti-inflammatory drug (NSAID) in Japanese patients with NSAID-induced urticaria and/or angioedema: Comparison of meloxicam, etodolac and tiaramide.

The identification of a safe and reliable alternative for patients with non-steroidal anti-inflammatory drug (NSAID)-induced urticaria/angioedema is a frequent problem for dermatologists and other practitioners. Cyclooxygenase-2 (COX-2) inhibitors have been reported to be safe for NSAID-intolerant patients from the US and Europe but not all of them have yet been approved for use in Japan. It was our objective to investigate the clinical manifestations of oral NSAID challenges in Japanese patients with histories of urticaria and/or angioedema after the intake of NSAIDs and to find safe alternative drugs, including COX-2 inhibitors and a basic anti-inflammatory drug. Twenty subjects suspected NSAID-induced urticaria/angioedema from histories were included in a double-blind or single-blind, placebo-controlled oral challenge protocol using NSAIDs. Skin prick tests using NSAIDs, which were dissolved in saline, were conducted. The mean age of the patients was 37.3 years; 14 patients were female. The results of other challenge tests showed that the most frequently intolerated drugs was loxoprofen (100%), followed by acetyl salicylic (94.4%), etodolac (53.3%), dicrofenac (50%), acetaminophen (38.5%), meloxicam (33%), and tiaramide (21.4%). Urticaria and angioedema were induced after aspirin intake in 83.3% and 22.2% of patients, respectively, whereas an asthmatic response was seen in 5.6%. Skin prick tests with NSAIDs were 100% negative. This study showed that among the NSAIDs that are available in Japan and that were investigated in this study, tiaramide, which does not inhibit COX, is the relatively safe alternative drug for Japanese patients with NSAID-induced urtiacaria and/or angioedema. Furthermore, meloxicam seems to be better tolerated than etodolac between two selective COX-2 inhibitors.