Data Resource Profile of Shizuoka Kokuho Database (SKDB) Using Integrated Health- and Care-insurance Claims and Health Checkups: The Shizuoka Study.

BACKGROUND: Analyzing real-world data, including health insurance claims, may help provide insights into preventing and treating various diseases. We developed a database covering Shizuoka Prefecture (Shizuoka Kokuho Database [SKDB]) in Japan, which included individual-level linked data on health- and care-insurance claims and health checkup results. METHODS: Anonymized claims data on health insurance (National Health Insurance [age <75 years] and Latter-Stage Elderly Medical Care System [age ≥75 years]), care insurance, subscriber lists, annual health checkups, and all dates of death were collected from 35 municipalities in Shizuoka Prefecture. To efficiently link claims and health checkups, unique individual IDs were assigned using a novel procedure. RESULTS: From April 2012 to September 2018, the SKDB included 2,230,848 individuals (men, 1,019,687; 45.7%). The median age (min-max) of men and women was 60 (0-106) and 62 (0-111) years, respectively. During the study period, the median subscription time was 4.4 years; 40.8% of individuals continuously subscribed for the 6.5 years; 213,566 individuals died. Health checkup data were available for 654,035 individuals, amounting to 2,469,648 records. Care-service recipient data were available for 283,537 individuals; they used care insurance to pay for care costs. CONCLUSION: SKDB, a population-based longitudinal cohort, provides a comprehensive dataset covering health checkups, disorders, medication, and care service. This database may provide a robust platform to identify epidemiological problems and generate hypotheses for preventing and treating disorders in the elderly.

JAK inhibitor JTE-052 regulates contact hypersensitivity by downmodulating T cell activation and differentiation.

BACKGROUND: Using JAK inhibitors to inhibit cytokine signaling is presumed to be a possible means of treating skin inflammatory disorders such as contact dermatitis. OBJECTIVE: To clarify the action site of JAK inhibitors in skin inflammatory disorders. METHODS: We analyzed the mechanism of action of the JAK inhibitor JTE-052 using murine skin inflammation models, including contact hypersensitivity (CHS) and irritant contact dermatitis. Cells isolated from ear tissue or lymph node (LN) were analyzed by flow cytometry. The amounts of cytokines in the culture medium were measured by ELISA or bead array system. Proliferation of LN cells was evaluated by measurement of tritiated thymidine incorporation. RESULTS: Oral administration of JTE-052 during both sensitization and elicitation phase attenuated CHS, but did not affect croton oil-induced irritant contact dermatitis. JTE-052 potently inhibited T cell proliferation and activation by antigen presentation in vitro, and attenuated skin inflammation in a sensitized-lymphocyte transfer model without suppressing T cell migration. JTE-052 did not affect hapten-induced cutaneous dendritic cell migration into draining lymph nodes or their costimulatory molecule expressions. CONCLUSION: The JAK inhibitor JTE-052 exerts an inhibitory effect on antigen-specific T cell activation and subsequent inflammation in acquired skin immunity, such as CHS.

Eosinophilic pustular folliculitis: A published work-based comprehensive analysis of therapeutic responsiveness.

Eosinophilic pustular folliculitis (EPF) is a non-infectious inflammatory dermatosis of unknown etiology that principally affects the hair follicles. There are three variants of EPF: (i) classic EPF; (ii) immunosuppression-associated EPF, which is subdivided into HIV-associated (IS/HIV) and non-HIV-associated (IS/non-HIV); and (iii) infancy-associated EPF. Oral indomethacin is efficacious, especially for classic EPF. No comprehensive information on the efficacies of other medical management regimens is currently available. In this study, we surveyed regimens for EPF that were described in articles published between 1965 and 2013. In total, there were 1171 regimens; 874, 137, 45 and 115 of which were applied to classic, IS/HIV, IS/non-HIV and infancy-associated EPF, respectively. Classic EPF was preferentially treated with oral indomethacin with efficacy of 84% whereas topical steroids were preferred for IS/HIV, IS/non-HIV and infancy-associated EPF with efficacy of 47%, 73% and 82%, respectively. Other regimens such as oral Sairei-to (a Chinese-Japanese herbal medicine), diaminodiphenyl sulfone, cyclosporin and topical tacrolimus were effective for indomethacin-resistant cases. Although the preclusion of direct comparison among cases was one limitation, this study provides a dataset that is applicable to the construction of therapeutic algorithms for EPF.

Basophils regulate the recruitment of eosinophils in a murine model of irritant contact dermatitis.

BACKGROUND: Although eosinophils have been detected in several human skin diseases in the vicinity of basophils, how eosinophils infiltrate the skin and the role of eosinophils in the development of skin inflammation have yet to be examined. OBJECTIVE: Using murine irritant contact dermatitis (ICD) as a model, we sought to clarify the roles of eosinophils in ICD and the underlying mechanism of eosinophil infiltration of the skin. METHODS: We induced croton oil-induced ICD in eosinophil-deficient ΔdblGATA mice with or without a reactive oxygen species (ROS) inhibitor. We performed cocultivation with fibroblasts and bone marrow-derived basophils and evaluated eosinophil migration using a chemotaxis assay. RESULTS: ICD responses were significantly attenuated in the absence of eosinophils or by treatment with the ROS inhibitor. ROS was produced abundantly by eosinophils, and both basophils and eosinophils were detected in human and murine ICD skin lesions. In coculture experiments, basophils attracted eosinophils, especially in the presence of fibroblasts. Moreover, basophils produced IL-4 and TNF-α in contact with fibroblasts and promoted the expression of eotaxin/CCL11 from fibroblasts in vitro. CONCLUSION: Eosinophils mediated the development of murine ICD, possibly through ROS production. Recruitment of eosinophils into the skin was induced by basophils in cooperation with fibroblasts. Our findings introduce the novel concept that basophils promote the recruitment of eosinophils into the skin through fibroblasts in the development of skin inflammation.

Acne management in Japan: study of patient adherence.

Obtaining good adherence to acne therapy is a challenge for all dermatologists. We studied 428 acne patients in Japan to determine the likelihood of good adherence and factors associated with medication-taking. This study utilized a simple validated questionnaire to assess risk of poor adherence; information about patient and treatment characteristics was also collected. There was an overall rate of poor adherence in 76% of subjects. Adherence to topical medication was poor in 52% of those treated with a topical agent only (n = 123). Among those taking combination therapies (n = 275), adherence to the topical portion of therapy was poor in 49% of subjects. The likelihood of poor adherence to oral medication was higher, both when administered alone (n = 30, 93% poor adherence) and when given as part of a combination regimen (n = 275, 86%). Factors with an impact on adherence included satisfaction with treatment (p = 0.023) and the experience of side effects (p = 0.027). Patients who felt they had a good understanding of acne and its treatment were more likely to have good adherence. These data suggest that there is significant room for improvement in acne adherence in Japan, as in other areas of the world, and that improved education may enhance adherence.

New insights into the management of acne: an update from the Global Alliance to Improve Outcomes in Acne group.

The Global Alliance to Improve Outcomes in Acne published recommendations for the management of acne as a supplement to the Journal of the American Academy of Dermatology in 2003. The recommendations incorporated evidence-based strategies when possible and the collective clinical experience of the group when evidence was lacking. This update reviews new information about acne pathophysiology and treatment-such as lasers and light therapy-and relevant topics where published data were sparse in 2003 but are now available including combination therapy, revision of acne scarring, and maintenance therapy. The update also includes a new way of looking at acne as a chronic disease, a discussion of the changing role of antibiotics in acne management as a result of concerns about microbial resistance, and factors that affect adherence to acne treatments. Summary statements and recommendations are provided throughout the update along with an indication of the level of evidence that currently supports each finding. As in the original supplement, the authors have based recommendations on published evidence as much as possible.

Large cell transformation mimicking regional lymphomatoid papulosis in a patient with mycosis fungoides.

A 57-year-old Japanese man with tumor-stage mycosis fungoides suddenly presented multiple small papules on the right chest. Histopathology of a biopsy specimen from the papules revealed medium-to-large pleomorphic lymphoid cells throughout the entire dermis but not in the epidermis, and the large cells expressed CD30 antigen. These newly-developed papules underwent spontaneous remission in the following 3 months. We reviewed the reported cases of mycosis fungoides, which showed CD30-positive large cell transformation and those of CD30-positive lymphoproliferative disorders associated with mycosis fungoides.

Dendritic cell immunoactivating receptor, a novel C-type lectin immunoreceptor, acts as an activating receptor through association with Fc receptor gamma chain.

An increasing number of C-type lectin receptors are being discovered on dendritic cells, but their signaling abilities and underlying mechanisms require further definition. Among these, dendritic cell immunoreceptor (DCIR) induces negative signals through an inhibitory immunoreceptor tyrosine-based inhibitory motif (ITIM) in its cytoplasmic tail. Here we identify a novel C-type lectin receptor, dendritic cell immunoactivating receptor (DCAR), whose extracellular lectin domain is highly homologous to that of DCIR. DCAR is expressed similarly in tissues to DCIR, but its short cytoplasmic portion lacks signaling motifs like ITIM. However, a positively charged arginine residue is present in the transmembrane region of the DCAR, which may explain its association with Fc receptor gamma chain and its stable expression on the cell surface. Furthermore, cross-linking of DCAR in the presence of gamma chain activates calcium mobilization and tyrosine phosphorylation of cellular proteins. These signals are mediated by the immunoreceptor tyrosine-based activating motif (ITAM) of the gamma chain. Thus, DCAR is closely related to DCIR, but it introduces activating signals into antigen-presenting cells through its physical and functional association with ITAM-bearing gamma chain. The identification of this activating immunoreceptor provides an example of signaling via a dendritic cell-expressed C-type lectin receptor.

Seventeen cases of alopecia areata: combination of SADBE topical immunotherapy with other therapies.

Topical immunotherapy is effective for severe alopecia areata. However, there are patients with alopecia areata refractory to topical immunotherapy alone. We tried SADBE (squaric acid dibutylester) topical immunotherapy combined with topical dry ice cryotherapy, carpronium chloride (a parasympathetic nerve stimulant) and/or oral cepharanthin (a biscoclaur alkaloid) in alopecia areata refractory to topical SADBE. Seventeen patients with alopecia areata (3 multiple, 3 ophiasis, 5 totalis and 6 universalis) were treated with SADBE in our department in 1999 to 2001. In 3 cases (2 multiple and 1 universalis) out of the 17 cases, cosmetically acceptable regrowth of hair was observed in several months with topical SADBE alone. In the other 14 cases, the SADBE therapy alone for several months (mean: 6.9 months) resulted in no or poor regrowth of hair. However, with subsequent combination therapy of topical SADBE for several months (mean: 7.6 months), satisfactory regrowth of hair was observed in 6 of the 14 cases. Our cases indicate that combination therapy of topical SADBE with other therapies can be a choice for alopecia areata which is refractory to topical SADBE therapy alone.