[JAPANESE TRANSLATION AND LINGUISTIC VALIDATION OF THE RECAP OF ATOPIC ECZEMA (RECAP)].

BACKGROUND: The Recap of atopic eczema (RECAP), a new core outcome of the atopic dermatitis trial, was translated into Japanese and linguistically validated. METHODS: Translation into Japanese was accomplished according to the ISPOR (International Society for Pharmacoeconomics and Outcome Research) guidelines and the basic guidelines for scale translation. The translation process included two forward translations, reconciliation with native English speakers, third-party back translation, cognitive debriefing, review and harmonization by the original authors. Twenty-seven atopic dermatitis and pediatric specialists from 21 centers in Japan participated in the translation process. Cognitive debriefing was conducted through face-to-face interviews using a think-aloud method with the interview guide including questions about comprehensibility, relevance, comprehensiveness, recall period and suggested improvements, based on the COSMIN methodology. RESULTS: No linguistic or cultural problems were encountered in the translation into Japanese. Cognitive debriefings were conducted with 10 adult patients and 10 parents of pediatric patients. Some minor modifications were made following discussion and approval by the research team and the original authors. The Japanese version of RECAP was considered to be understandable, comprehensive and relevant for adult patients and families of pediatric patients. CONCLUSION: The Japanese version of the RECAP, which has been validated as linguistically equivalent to the original version, is now available. Further evaluation of the measurement properties is needed in the future.

Computational Simulation Model to Predict Behavior Changes in Inflammatory Bowel Disease Patients during the COVID-19 Pandemic: Analysis of Two Regional Japanese Populations.

Managing inflammatory bowel disease (IBD) is a major challenge for physicians and patients during the COVID-19 pandemic. To understand the impact of the pandemic on patient behaviors and disruptions in medical care, we used a combination of population-based modeling, system dynamics simulation, and linear optimization. Synthetic IBD populations in Tokyo and Hokkaido were created by localizing an existing US-based synthetic IBD population using data from the Ministry of Health, Labor, and Welfare in Japan. A clinical pathway of IBD-specific disease progression was constructed and calibrated using longitudinal claims data from JMDC Inc for patients with IBD before and during the COVID-19 pandemic. Key points considered for disruptions in patient behavior (demand) and medical care (supply) were diagnosis of new patients, clinic visits for new patients seeking care and diagnosed patients receiving continuous care, number of procedures, and the interval between procedures or biologic prescriptions. COVID-19 had a large initial impact and subsequent smaller impacts on demand and supply despite higher infection rates. Our population model (Behavior Predictor) and patient treatment simulation model (Demand Simulator) represent the dynamics of clinical care demand among patients with IBD in Japan, both in recapitulating historical demand curves and simulating future demand during disruption scenarios, such as pandemic, earthquake, and economic crisis.

A Computational Platform Integrating a Mechanistic Model of Crohn's Disease for Predicting Temporal Progression of Mucosal Damage and Healing.

INTRODUCTION: Physicians are often required to make treatment decisions for patients with Crohn's disease on the basis of limited objective information about the state of the patient's gastrointestinal tissue while aiming to achieve mucosal healing. Tools to predict changes in mucosal health with treatment are needed. We evaluated a computational approach integrating a mechanistic model of Crohn's disease with a responder classifier to predict temporal changes in mucosal health. METHODS: A hybrid mechanistic-statistical platform was developed to predict biomarker and tissue health time courses in patients with Crohn's disease. Eligible patients from the VERSIFY study (n = 69) were classified into archetypical response cohorts using a decision tree based on early treatment data and baseline characteristics. A virtual patient matching algorithm assigned a digital twin to each patient from their corresponding response cohort. The digital twin was used to forecast response to treatment using the mechanistic model. RESULTS: The responder classifier predicted endoscopic remission and mucosal healing for treatment with vedolizumab over 26 weeks, with overall sensitivities of 80% and 75% and overall specificities of 69% and 70%, respectively. Predictions for changes in tissue damage over time in the validation set (n = 31), a measure of the overall performance of the platform, were considered good (at least 70% of data points matched), fair (at least 50%), and poor (less than 50%) for 71%, 23%, and 6% of patients, respectively. CONCLUSION: Hybrid computational tools including mechanistic components represent a promising form of decision support that can predict outcomes and patient progress in Crohn's disease.

Dietary habits in Japanese patients with chronic spontaneous urticaria.

BACKGROUND: Chronic spontaneous urticaria (CSU) is defined as the spontaneously appearing weals and/or angioedema for more than 6 weeks. Dietary habits can modulate the pathogenesis of CSU. However, dietary intakes of nutrients or food in CSU patients, compared with healthy controls, have not been examined in quality and quantity. METHODS: We evaluated dietary habits in adult Japanese patients with chronic spontaneous urticaria using a validated, brief-type self-administered diet history questionnaire and compared the results to those of age- and sex-matched healthy controls. The severity of CSU was evaluated using the Urticaria Control Test. RESULTS: Japanese CSU patients showed higher body mass indices, higher intakes of eggs, vegetables other than green/yellow vegetables/mushrooms/algae, cholesterol, folic acid, dietary fibres, vitamin D, vitamin K, Cu, Fe, Pi, Ca, Mg, Na and salt, and lower intake of alcohol, compared to controls. The logistic regression analysis showed that CSU was associated with high body mass index and high intake of eggs. The intake of beverages was higher in uncontrolled CSU patients (Urticaria Control Test ≦11 points) than in controlled patients. The logistic regression analysis showed that uncontrolled CSU was associated with high intake of beverages. The intake of coffee, caffeine-rich and non-alcohol beverage, in uncontrolled CSU patients was higher than that in controlled patients. CONCLUSIONS: Chronic spontaneous urticaria was associated with high body mass index and high intake of eggs. Uncontrolled CSU was associated with high intake of beverages. Further studies should elucidate the relationships of these results with the development or exacerbation of CSU.

Dietary habits in Japanese patients with psoriasis and psoriatic arthritis: Low intake of meat in psoriasis and high intake of vitamin A in psoriatic arthritis.

Psoriasis is characterized by T-helper 17 cell-dominant abnormal immunity, and hyperproliferation and abnormal differentiation of epidermal keratinocytes. Some patients are associated with arthritis. Dietary habits can modulate the pathogenesis of psoriasis. Previous studies in Western countries showed higher body mass indices, higher intake of fat and lower intake of fish or vegetables in psoriatic patients compared with the reference groups. We evaluated dietary habits in adult Japanese psoriatic patients, using a validated brief-type self-administered dietary history questionnaire, and compared the results to those of age- and sex-matched healthy controls. The results in psoriatic patients with arthritis were compared with those in the patients without. Japanese psoriatic patients showed higher body mass indices, higher intake of fish/shellfish, pulses, sugar/sweeteners, vitamin B12 and vitamin D, and lower intake of meat, compared with those of healthy controls. The logistic regression analysis showed that psoriasis was associated with high body mass index and low intake of meat. The intake of confection in patients with high Psoriasis Area and Severity Index was higher than that in those with low index. The intake of ß-carotene, vitamin A and green/yellow vegetables in psoriatic patients with arthritis were higher than those in the patients without. The dietary habits in Japanese psoriatic patients are rather different from those in Western patients. This is the first study showing the differences in dietary habits between psoriatic patients with arthritis and those without. Further studies should elucidate the relationships of these results with skin and joint lesions in psoriatic patients.

Dietary habits in adult Japanese patients with atopic dermatitis.

Dietary habits can modulate the pathogenesis of atopic dermatitis. We evaluated these habits in adult Japanese patients with atopic dermatitis using a validated, brief-type self-administered diet history questionnaire and compared the results to those of age- and sex-matched healthy controls. Patients with atopic dermatitis showed higher intakes of carbohydrate and potatoes and lower intakes of alcohol, niacin, meat and oils/fats compared with those of the healthy controls. The results of logistic regression analysis showed that the intake of alcohol was negatively associated with atopic dermatitis (odds ratio, 0.905; 95% confidence interval, 0.832-0.983; P = 0.0181). The intakes of vitamin B6 and fruit were positively correlated with the severity scoring of atopic dermatitis. Multiple regression analysis revealed that vitamin B6 intake was a predictor of the severity scoring of atopic dermatitis (ß = 26.98508709, t = 2.3995292, P = 0.01933781). The intakes of vegetable fat, n-6 polyunsaturated fatty acid, and confections were lower in the severe atopic dermatitis group (severity scoring of atopic dermatitis, ≥33) than those in the mild group. Atopic dermatitis is negatively associated with alcohol intake, and intake of vitamin B6 is a predictor of severity scoring of atopic dermatitis. The intake of n-6 polyunsaturated fatty acid is lower in the severe atopic dermatitis group than that in the mild group. Further study is warranted on the relationships of these results with abnormal immune responses, impaired skin barrier or pruritus in atopic dermatitis.

Intralymphatic histiocytosis in a patient with lung adenocarcinoma treated with pembrolizumab: a case report.

BACKGROUND: Pembrolizumab, an anti-programmed cell death-1 protein monoclonal antibody, is effective for patients with advanced non-small-cell lung cancer. However, immune checkpoint inhibitors such as pembrolizumab induce various immune-related adverse events, involving the lung, liver, gastrointestinal, endocrine system, and skin. Intralymphatic histiocytosis (ILH) is a rare, chronic cutaneous disorder with a reactive inflammatory component, which often occurs in patients with rheumatoid arthritis. CASE PRESENTATION: We present a 67-year-old man with lung adenocarcinoma who developed ILH associated with pembrolizumab treatment. He was treated with palliative thoracic radiotherapy for superior vena cava syndrome. Subsequently, he received four cycles of pembrolizumab. Approximately 2.5 months after the initiation of pembrolizumab, he developed erythema on the trunk of his body. Based on findings of skin biopsies, he was diagnosed with pembrolizumab-induced ILH. Moreover, the upregulation of tumor necrosis factor-α was observed during pembrolizumab therapy. CONCLUSIONS: This is the first report of ILH induced by pembrolizumab in a patient with lung adenocarcinoma.

Epidermoid Cyst Arising on the Body of the Tongue: Case Report and Literature Review.

BACKGROUND: Epidermoid cysts of the body of the tongue are rare. Only 12 cases of such lesions have been reported in the English literature. CASE: A 14-year-old boy had a 7×5-mm-sized cystic lesion with a yellowish-white surface on the ventral aspect of his tongue. The cystic wall was composed of squamous epithelium containing keratinous material. No skin appendages were attached to the wall. These findings were consistent with a diagnosis of an epidermoid cyst. LITERATURE REVIEW: For the thirteen cases, including ours, the average age was 18.0 years. The highest incidence was found in the first decade of life. Eight of the patients were male and five were female. The size varied from several millimeters to several centimeters. There may be a left side predilection of the occurrence. There is no evidence for malignant transformation of epidermoid cysts of the tongue, though two cases were reported as carcinoma arising from an epidermoid or dermoid cyst of another oral area. DISCUSSION: Epidermoid cysts of the body of the tongue are congenital or acquired. The congenital type can arise due to a failure of surface ectoderm separation or invagination of the surface ectoderm along the embryologic fusion sites. The acquired type is caused by trauma, with implanting of an epithelial element into the deeper tissue. In the present case, it was difficult to determine whether the pathogenesis was congenital or acquired because there are no clinical or histopathological differences between the two types.

Immunoglobulin G4-related disease and its skin manifestations.

Immunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory condition characterized by tissue infiltration with IgG4+ plasma cells and an elevated serum IgG4 level. It usually occurs in middle-aged or older patients, with male predominance, and can involve multiple organs synchronously or metachronously. Patients with IgG4-RD generally respond to steroid therapy. IgG4-related skin lesions are typically erythematous and itchy plaques, subcutaneous nodules, or papules like prurigo nodularis located on the head and neck areas. Histologically, lymphoplasmacytic infiltrates with abundant IgG4+ plasma cells are seen in the dermis and/or subcutaneous tissue. The skin condition of IgG4-RD does not necessarily exhibit infiltration of IgG4+ plasma cells, which is a prerequisite for IgG4-related skin disease, but such skin lesions without infiltration by IgG4+ plasma cells can be included in the skin manifestations of IgG4-RD.

Hobnail Hemangioma: A Case Report.

Hobnail hemangioma is a small, solitary, benign vascular tumor that shows a biphasic histological pattern of dilated vascular spaces in the superficial dermis and narrow vascular structures in the deeper dermis. In the superficial dermis, dilated, irregular, thin-walled vascular spaces are lined by plump endothelial cells with large nuclei which protrude into the lumina like hobnails. A 43-year-old Japanese man presented with an 11×8-mm bluish-red macule surrounding a 6×3-mm violaceous, slightly elevated papule of the lumbar region of 6 months' duration. Total resection was performed under local anesthesia. Microscopic examination revealed a biphasic pattern with dilated superficial vessels whose endothelial cells were plump with intraluminal papillary projections, showing a "hobnail" appearance, in the papillary layer and upper dermis, and vascular spaces forming slitlike spaces, some of them dissecting collagen fibers, in the deeper dermis. Neither true atypia nor mitotic figures were present. The findings were consistent with those of hobnail hemangioma. Immunohistochemical analysis of the endothelia of the superficial vessels showed that CD31 and D2-40 were expressed, factor VIII was focally expressed, and CD34 and α-SMA were not expressed. In the endothelia of the deeper vessels, CD31, CD34, factor VIII, and α-SMA were expressed, but D2-40 was not expressed. These findings suggest that hobnail hemangioma also shows a biphasic immunohistochemical pattern because of its origin from both lymphatic vessels and blood vessels.

Expression of lumican in hidroacanthoma simplex and clonal-type seborrheic keratosis as a potent differential diagnostic marker.

Lumican, a member of the small leucine-rich proteoglycan family, regulates the assembly and diameter of collagen fibers in the extracellular matrix of various tissues. The lumican expression correlates with pathological conditions and the growth and metastasis of various malignancies. In cutaneous neoplasms, the lumican expression is lower in advanced-stage malignant melanomas that invade the dermis than in early-stage melanomas. Furthermore, we have recently reported that the expression pattern of lumican is different from that of actinic keratosis and the Bowen disease. Lumican is positive in the poroid cells of intraepidermal sweat ducts; therefore, we examined the expression patterns of lumican in acanthotic-type seborrheic keratosis and Pinkus-type poroma followed by clonal-type seborrheic keratosis and hidroacanthoma simplex. The neoplastic cells of acanthotic-type seborrheic keratosis exhibited positive immunostaining in only 1 of 31 cases (3.23%), whereas the poroid cells of Pinkus-type poroma exhibited positive immunoreactivity in 26 of 28 patients (92.8%). In the hidroacanthoma simplex cases, lumican was expressed in poroid cells forming intraepidermal nests in 22 of 28 patients (78.6%), whereas the neoplastic cells in most cases of clonal-type seborrheic keratosis were negative for lumican. In some seborrheic keratosis cases that were positive for lumican in neoplastic cells, lumican was observed in squamoid cells but not in basaloid cells. Therefore, it is necessary to evaluate the immunoreactivity of lumican in seborrheic keratosis and in basaloid cells. These findings suggest that lumican is a potent differential diagnostic marker that distinguishes hidroacanthoma simplex from clonal-type seborrheic keratosis.

Lumican as a novel marker for differential diagnosis of Bowen disease and actinic keratosis.

Lumican, a member of the small leucine-rich proteoglycan family, regulates the assembly and diameter of collagen fibers in the extracellular matrix of various tissues. Lumican expression correlates with pathological conditions, including skin fragility, corneal opacification, and corneal and cardiac wound healing. Lumican is overexpressed in tumor cells, including in the breast, colorectal, neuroendocrine cell, uterine cervical, and pancreatic cancers. Lumican expression also correlates with the growth and metastasis of various malignancies. For example, lumican expression is lower in the dermis of malignant melanoma cases than in early-stage melanomas. However, the expression patterns and roles of lumican in nonmelanoma skin cancer have not been elucidated. In this study, we used immunohistochemistry and in situ hybridization to examine the expression patterns of lumican in normal skin, Bowen disease, and actinic keratosis. In normal skin, lumican was expressed in the collagen fibers in the dermis, acrosyringium, follicular epithelium, and sebocytes but not in epidermal keratinocytes. In Bowen disease, lumican was expressed in 34 (91.8%) of 37 patients. Notably, all cases of actinic keratosis were negative for lumican. These findings suggest that lumican plays an important role in the pathogenesis of Bowen disease and actinic keratosis and might be useful as an adjunct to the diagnosis for subtypes of 2 diseases: bowenoid actinic keratosis and Bowen disease in sun-exposed areas.

Tenosynovial giant cell tumor arising on the scapular region.

Tenosynovial giant cell tumor (TSGCT) is a benign soft tissue tumor arising from the synovial membrane that composes the lining of joints, tendons and bursae. TSGCT is a common tumor occurring in the hands and fingers, and also consecutively in the knees, ankles, feet and hips. It is rarely found in the scapular region. To the best of our knowledge, only 2 cases arising on the upper back have been reported. This report presents the case of a 44-year-old Japanese female with a TSGCT arising on her right scapular region.

Ber-EP4 is a useful marker for follicular germinative cell differentiation of cutaneous epithelial neoplasms.

Ber-EP4 is a monoclonal antibody that recognizes 34-kDa and 39-kDa non-covalently linked glycopolypeptides expressed by most human epithelial cells and carcinomas. In this study, we performed immunohistochemical staining of 31 cases of basal cell carcinoma (BCC); 20 cases of trichoblastoma (TB), including ten cases of nodular type, eight cases of cribriform type (trichoepithelioma) and two cases of columnar type (desmoplastic trichoepithelioma); 16 cases of actinic keratosis (AK); and 10 cases each of Bowen's disease, poroma and seborrheic keratosis. Six cases of BCC and AK were co-lesions of both neoplasms. In normal skin tissue, Ber-EP4 reacted positively with the secretory portion of eccrine glands and follicular germinative cells at the lower end of catagen hairs. Neoplastic cells in 97% of cases with BCC reacted positively with Ber-EP4 in at least 5% of neoplastic cells. Those in 90% with nodular type TB and 50% with trichoepithelioma also reacted positively in at least 5% of neoplastic cells. No cases of poroma, seborrheic keratosis, AK or Bowen's disease were immunohistochemically positive for Ber-EP4 in neoplastic cells. In all six cases with co-lesions of BCC and AK, neoplastic cells of BCC reacted positively with Ber-EP4 and those of AK were negative. Immunohistochemical examination using the Ber-EP4 antibody is a useful tool for diagnosing neoplasms with follicular germinative differentiation, such as TB, TE or BCC, and for differentiating those from squamous cell carcinoma in situ, poroma or seborrheic keratosis.