A survey on subtypes and clinical characteristics of 1061 patients with urticaria in the primary care institutes in Japan.

The prevalence of urticaria has been reported mostly in Europe and North America. However, precise information regarding its subtypes and clinical characteristics in primary care practice, especially in Asian countries, are scant. Patients with urticaria and/or angioedema who visited nine primary clinics of accredited dermatologists and allergologists in Japan were recruited from October to November 2020. The information of age, sex, disease duration, urticaria control test (UCT), and concomitant urticaria subtypes were collected. A total of 1061 patients participated. The number of patients was high in the 20 to 50 age groups with a peak in the 40s. The most frequent urticaria subtype was chronic spontaneous urticaria (CSU) followed by dermographism, acute spontaneous urticaria (ASU), angioedema, and cholinergic urticaria (CholU) (66.8%, 22.7%, 18.9%, 14.1% and 5.7% in all patients with urticaria). CSU development increased with age from the 20s to 50s, especially in females. Dermographism had a peak in the 40s. ASU had bimodal peaks in childhood and in the 30s. CholU was common in males in the 10-20s. Most angioedema patients were female with an increase in their 30s. Angioedema was solely present in 14 of 1061 participants (1.3%), while 136 (12.8%) had angioedema concomitant with urticaria. UCT showed poorly controlled urticaria with lower scores in patients with concomitant CSU and other subtypes than in those with CSU alone. Urticaria tends to develop in young to middle-aged females. The most common urticaria subtype is CSU, while the number of patients with CholU is high and that of angioedema is low in Japan.

A randomized double-blind trial of intravenous immunoglobulin for bullous pemphigoid.

BACKGROUND: Patients with steroid-resistant bullous pemphigoid (BP) require an appropriate treatment option. OBJECTIVE: A multicenter, randomized, placebo-controlled, double-blind trial was conducted to investigate the therapeutic effect of high-dose intravenous immunoglobulin (IVIG; 400mg/kg/day for 5days) in BP patients who showed no symptomatic improvement with prednisolone (≥0.4mg/kg/day) administered. METHODS: We evaluated the efficacy using the disease activity score on day15 (DAS15) as a primary endpoint, and changes in the DAS over time, the anti-BP180 antibody titer, and safety for a period of 57days as secondary endpoints. RESULTS: We enrolled 56 patients in this study. The DAS15 was 12.5 points lower in the IVIG group than in the placebo group (p=0.089). The mean DAS of the IVIG group was constantly lower than that of the placebo group throughout the course of observation, and a post hoc analysis of covariance revealed a significant difference (p=0.041). Furthermore, when analyzed only in severe cases (DAS≥40), the DAS15 differed significantly (p=0.046). The anti-BP180 antibody titers showed no difference between the two groups. CONCLUSION: IVIG provides a beneficial therapeutic outcome for patients with BP who are resistant to steroid therapy.

Balloon Cell Malignant Melanoma in a Young Female: A Case Report and Review of the Literature.

Balloon cell malignant melanoma (BCMM) is a very rare malignant melanoma subtype. The clinical appearance of BCMM varies; it may be nodular, ulcerated, polypoid, papillomatous and often non-pigmented. The tumor cells histologically appear large, polygonal or round and contain abundant granular or vacuolated cytoplasm. We herein report the case of a 32-year-old female who presented with a focal eccentric pigmented mass in the left lumbar region of 15 mm in diameter that had been present for several years. She underwent tumor excision. The histopathological analysis showed epithelioid melanocytes with clear cytoplasm. An immunohistochemical analysis revealed that the cells were positive for HMB-45 and S-100 protein and negative for cytokeratin. The balloon cell component stained negative for Fontana-Masson. A month later, the patient underwent excision of the bilateral inguinal lymph nodes and metastatic BCMM was revealed. The lymph node metastases showed the complete replacement of lymph nodes by balloon cells. A diagnosis of BCMM (Breslow depth 10 mm, Clark level V) without ulcer was rendered. Staining with Ki-67 was positive in almost 44% of the balloon cells.

Dermoscopic insight into skin microcirculation--Burn depth assessment.

To investigate the effectiveness of dermoscopic observation of skin microcirculation, the dermal capillary integrity of burn wounds was evaluated by dermoscopy according to a proposed algorithm that is designed to distinguish burn wounds between superficial dermal burns: SDB, and deep dermal burns: DDB. As the gold standard for comparison, two widely accepted endpoints of primary healing within 21 days (SDB) or over 21 days after injury (DDB) were used. A number of dermatologists conducted diagnostic imaging by dermoscopy. Comparison among polarized noncontact dermoscopy (PNCD), polarized contact dermoscopy (PCD) and nonpolarized contact dermoscopy (NPD) was also conducted. Images from the three modalities were evaluated for color, pattern and qualitative differences among them. The results of dermoscopy measurements according to the proposed algorithm showed accuracy of 96.7%, sensitivity of 100.0% and specificity of 94.4%. Dermoscopy measurements were significantly more accurate than clinical assessment (p<0.05). The recognition of dots increased for NPD, vessels were most clearly observed under PCD and colours tended to be more distinctly recognized under polarized light. Dermoscopy is a useful and simple tool to evaluate not only epidermal and superficial dermal skin components but also the skin microcirculation.

Grade 3 lymphomatoid granulomatosis in a patient receiving methotrexate therapy for rheumatoid arthritis.

Lymphomatoid granulomatosis (LyG) is a rare, B-cell derived, lymphoproliferative disorder that often presents as pulmonary nodular lesions with a histopathology of lymphatic invasion of the vascular wall. The development of LyG may be associated with reactivation of the Epstein-Barr virus under an immunosuppressive state. We herein report a case of Grade 3 LyG that developed during methotrexate therapy for rheumatoid arthritis and regressed following the withdrawal of the drug.

The sensitivity and clinical course of patients with wheat-dependent exercise-induced anaphylaxis sensitized to hydrolyzed wheat protein in facial soap - secondary publication.

BACKGROUND: Recently, an increasing number of patients with wheat-dependent exercise-induced anaphylaxis (WDEIA) have been reported in Japan. Most of them had developed this condition during or after using hydrolyzed wheat protein (HWP)-containing soap (HWP-WDEIA). METHODS: To clarify the relation between WDEIA and HWP-containing soap and their prognosis, we retrospectively studied the patients who visited Hiroshima University Hospital and were diagnosed as WDEIA from January 2010 to June 2011. We took detailed clinical histories, performed skin prick tests, serum immunoassays for antigen-specific IgE and basophil histamine release test, and followed up their clinical courses after the diagnosis. RESULTS: Among 36 patients with WDEIA, 30 patients had used only one type of HWP-soap. The patients with HWP-WDEIA were mainly women and had developed facial symptoms and angioedema. They suffered from blood pressure reductions less frequently than patients with conventional WDEIA. The levels of gluten-specific IgE were higher than those of omega-5 gliadin in patients with HWP-WDEIA (P < 0.05, One-way ANOVA). All patients with HWP-WDEIA were positive against HWP in histamine release test. Among the conventional wheat antigens, glutenins induced the highest histamine release from basophils of patients with HWP-WDEIA. The sensitivities of patients against glutens and glutenins were reduced over months along with the discontinuance of HWP-soap. CONCLUSIONS: The development of HWP-WDEIA is associated with the use of HWP-soap. The sensitivity to HWP that cross reacts with non-processed wheat may be reduced or possibly cured after the discontinuation of HWP-soap.

Histamine release-neutralization assay for sera of patients with atopic dermatitis and/or cholinergic urticaria is useful to screen type I hypersensitivity against sweat antigens.

We previously reported that about 80 % of patients with atopic dermatitis and 60 % with cholinergic urticaria revealed type I allergy against sweat, by means of skin test against autologous sweat and/or histamine-release test for peripheral blood basophils with semi-purified sweat antigen. In this study, we developed an assay for sera to neutralize histamine-releasing activity of semi-purified sweat antigen. The semi-purified sweat antigen was pre-incubated with serially diluted sera for 30 min at 37 °C and was subjected to histamine-release activity. Histamine release-neutralization (HRN) activities were calculated by measuring the amount of histamine release from basophils in the presence or absence of semi-purified sweat antigen. Of 62 subjects, 39 showed positive histamine release (≥5 %) from their basophils in response to semi-purified sweat antigen, and sera of 34 out of 39 subjects (87.2 %) were also positive in HRN activity (≥10 %). The specificity of the HRN assay was 0.522. Moreover, HRN activities in sera were largely correlated with degrees of histamine release from peripheral blood basophils of the same donors in response to sweat antigen. To identify the substance that neutralizes histamine-release activity, we removed IgE and IgG from the sera of HRN (+) subjects by column chromatography. The HRN activities in 30 out of 42 sera were largely reduced by the removal of IgG. On the other hand, sera of four subjects lost HRN activity by the removal of IgE, suggesting that the majority of HRN (+) subjects have serum IgG against the sweat antigen as well as IgE bound to peripheral basophils. Thus, the HRN assay maybe useful for the screening of type I allergy against sweat antigen.

Early depth assessment of local burns by dermoscopy: a new frontier of dermoscopic evaluation.

UNLABELLED: This article has been retracted. See Notice of Retraction. OBJECTIVE: To investigate the effectiveness of early depth assessment of local burns, the depth of which is difficult to assess with the naked eye, by dermoscopy. DESIGN: The morphological findings of burn wounds were prospectively evaluated by dermoscopy and videomicroscopy. Prior to dermoscopic and videomicroscopic measurement, clinical assessment was performed. All patients received conservative treatment for 21 days after injury. SETTING: A burns unit at a primary care hospital. PARTICIPANTS: Thirty-two patients with 41 intermediate-depth local burn wounds were included. Inclusion criteria were time to presentation greater than 24 hours after injury and total burn size greater than 1% and less than 10% of the total body surface area. MAIN OUTCOME MEASURES: Primary healing within 21 days (superficial partial thickness) and failure of primary healing within 21 days (deep partial thickness). The accuracy, sensitivity, and specificity of the assessment according to the algorithm proposed in this study were evaluated by dermoscopy, and the accuracy of the dermoscopic measurements was compared with videomicroscopic measurements and clinical assessments. RESULTS: The results of dermoscopic measurements according to the proposed algorithm showed an accuracy of 93%, sensitivity of 86%, and specificity of 100%. The dermoscopic measurements were significantly more accurate compared with clinical assessment (P = .01). CONCLUSIONS: Dermoscopy is a noninvasive, portable, relatively inexpensive, and effective approach for assessment of the burn wound healing potential. It is more accurate if compared with clinical observation in burn depth assessment. It has a broader utility and is equally or more accurate compared with the more expensive videomicroscopy.

Early depth assessment of local burns by videomicroscopy: a novel proposed classification.

PURPOSE: Videomicroscopy is very useful for burn depth assessment in an early phase; however, there is no practical classification that includes complicated anatomic, pathologic, and morphologic findings of burn wounds. The aim of this study was to propose a novel classification to assess burn depth in its early phase easily and reliably by videomicroscopy. METHODS: Forty-four patients with 56 intermediate-depth burn wounds were included. Burn depth was divided into each grade according to our proposed classification, which is composed of five categories based on dermal capillary integrity patterns. The intrarater and interrater reliabilities of the assessment by the second and third authors were evaluated by Cohen's unweighted κ-value. RESULTS: The results of the measurements according to the proposed classification showed an accuracy of 92.9%, sensitivity of 81.8%, and specificity of 100.0%. The intrarater reliability of the second and third authors showed substantial agreement (κ=0.719 and 0.729, respectively). The interrater reliability of the sum of each observer's variable also showed substantial agreement (κ=0.636). CONCLUSION: This pattern analysis system is easy to use even for inexperienced personnel, and is reliable with high accuracy and specificity. Intrarater and interrater statistics also support its reliability and reproducibility.

Early depth assessment of local burns by videomicroscopy: 24 h after injury is a critical time point.

PURPOSE: Videomicroscopy has simple and prompt operability, and useful in the burn depth assessment in its early phase. A burn wound is, however, a dynamic environment in the first few days and the critical time to assess a burn wound by videomicroscopy has not been investigated. The aim of this study is to investigate the critical time point to assess the burn depth by videomicroscopy. METHODS: Forty one patients with 44 intermediate depth burns admitted within 7 days after injury were included. Accuracies were assessed by comparison with clinical outcome: healing within 21 days after injury or not with conservative treatment. We prospectively evaluated and compared the accuracy of the videomicroscopy measurements with the clinical assessments. All findings were serialized in order of time after injury and divided into three groups, and we compared the appreciation of burn depth by videomicroscopy findings among groups. RESULTS: The videomicroscopy measurements is significantly accurate compared with clinical assessments (p=0.001). The accuracy of videomicroscopy measurements was significantly lower in the post-injury <24 h group compared with post-injury ≥24 h group (p=0.004). CONCLUSION: Videomicroscopy is effective tool in assessment of early burn depth and the critical time point to assess the burn depth by videomicroscopy is 24 h after injury.

[Efficacy of sweat-antigen-inactivating skin care products on itching of patients with atopic dermatitis].

BACKGROUND: Many patients with atopic dermatitis showed immediate-type hypersensitivity against sweat antigen. Therefore, to deal with sweating is important to prevent itching and aggravations of dermatitis of patient with atopic dermatitis. We had searched a substance that inactivated sweat antigen adopting histamine release test. And we found that tannic acid which selected by screening various natural products inactivated sweat antigen. METHODS: We evaluate skin care products (spray, after-bathing water and aerosol-spray) containing tannic acid for patients with atopic dermatitis. We administered in a tannic acid-containing spray and after-bathing water on 17 patients with atopic dermatitis. RESULTS: After treatment, total clinical assessment score and itching in the afternoon had significantly decreased from that on day 0. To evaluate the effect of tannic acid containing-aerosol spray on itching of patients with AD, we assessed symptoms of atopic dermatitis patients who used a tannic acid containing-aerosol spray every day for 4 weeks in a cross-over, double-blind study. Clinical severity of atopic dermatitis and degrees of itching in daily life of patients were evaluated by physicians and patients themselves, respectively. Degrees of itching in morning and those at night were significantly more largely improved by the use of tannic acid-containing aerosol spray than those by the use of placebo control aerosol spray. The overall efficacy of tannic acid-containing aerosol sprays was also significantly higher than those of tannic acid free spray. CONCLUSION: Sweat antigen inactivating skin care products may be effective to reduce itching of patients with atopic dermatitis.

[The sensitivity and clinical course of patients with wheat-dependent exercise-induced anaphylaxis sensitized to hydrolyzed wheat protein in facial soap].

BACKGROUND: Recently an increasing number of patients with wheat-dependent exercise-induced anaphylaxis (WDEIA), developed during or after using hydrolyzed wheat protein (HWP)-containing soap (HWP-WDEIA), were reported in Japan. METHODS: To clarify the relation between WDEIA and HWP-containing soap and their prognosis, we investigated the patients who visited Hiroshima University Hospital and were diagnosed as WDEIA from January 2010 to June 2011. We took detailed clinical histories, performed skin prick tests, serum immunoassays for antigen-specific IgE and basophil histamine release test, and followed up their clinical courses after the diagnosis. RESULTS: Among 36 patients with WDEIA, 30 patients had used only one type of HWP-soap. The patients with HWP-WDEIA were mainly women and had developed facial symptoms and angioedema. They suffered from blood pressure reductions less frequently than patients with conventional WDEIA. The levels of glutens-specific IgE were higher than those of ω-5 gliadin in patients with HWP-WDEIA (p<0.05, One-way ANOVA). All patients with HWP-WDEIA were positive against HWP in histamine release test. Among the conventional wheat antigens, glutenins induced highest histamine release from basophils of patients with HWP-WDEIA. The sensitivities of patients against glutens and glutenins were reduced over months along with the discontinuance of HWP-soap. CONCLUSIONS: The development of HWP-WDEIA is associated with the use of HWP-soap. The sensitivities to HWP that cross reacts with non-processed wheat may be reduced or possibly cured after the discontinuation of HWP-soap.

Pressure challenge test and histopathological inspections for 17 Japanese cases with clinically diagnosed delayed pressure urticaria.

Delayed pressure urticaria (DPU) is characterized by deep dermal wheals that appear in response to a local continuous pressure. Although it has been reported to complicate as many as 40% of cases of Caucasian patients with chronic urticaria, no definitive cases of Asian/Japanese patients have been reported in English literature. Here, we identified 17 cases of DPU, among 540 Japanese patients with urticaria (3.1%), based on careful history taking, pressure challenge test and, ideally, skin biopsy. Twelve out of 17 patients (70.5%) who undertook pressure challenge test developed wheal and erythema in the area of pressure 1-12 h later. Six out of 15 patients (40%) were positive for the autologous serum skin test. All cases were complicated with ordinary chronic urticaria, and all specimens of skin biopsies performed for 12 patients showed substantial eosinophil infiltration. All cases were resistant to antihistamines with or without other non-steroidal medications and eventually treated with 0.25-1.5 mg/day of betamethasone. However, 12 of them (70.6%) were able to cease steroid use because of cure or remission. For those cured or in remission, the duration of steroid administration and that from the onset to diagnosis was 11.2 +/- 11.0 and 54.8 +/- 60.2 months (mean +/- SD), respectively. DPU may be identified as a relatively rare complication of Japanese patients with chronic idiopathic urticaria. A proper diagnosis and a small amount of steroid may be beneficial for the treatment of DPU.

Metastatic extramammary Paget's disease treated with paclitaxel and trastuzumab combination chemotherapy.

In the treatment of metastatic breast cancer, trastuzumab, a recombinant monoclonal antibody against human epidermal growth factor receptor 2 (HER2), is effective when tumor cells overexpress HER2 protein. Although some cases of extramammary Paget's disease (EMPD) also express HER2 protein, no case of EMPD has been reported to be treated with trastuzumab. A 75-year-old man who suffered from EMPD of the scrotum and inguinal region underwent a local excision and lymph node dissection. Tumor cells invaded the dermis and lymph nodes. Although he was postoperatively treated with adjuvant chemotherapies, metastatic skin lesions appeared and spread over his left thigh, rapidly and widely. Tumor cells disseminated along lymph vessels in the dermis and overexpressed HER2 protein. We administered paclitaxel and trastuzumab according to a protocol for HER2-positive metastatic breast cancers. The skin metastasis dramatically decreased during the regimen and a histopathological examination showed that most of HER2-positive tumor cells diminished. Six months later, metastases were found in the central nervous system (CNS), but no other metastases were found in the skin, visceral organs or lymph nodes. Trastuzumab and paclitaxel-combination with the assessment of central nervous system lesions should be considered as an option for the treatment of HER2-positive EMPD.