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Teppei Hagino,1 Risa Hamada,2 Mai Yoshida,2 Eita Fujimoto,3 Hidehisa Saeki,2 Naoko Kanda1 1Department of Dermatology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan; 2Department of Dermatology, Nippon Medical School, Tokyo, Japan; 3Fujimoto Dermatology Clinic, Funabashi, JapanCorrespondence: Teppei Hagino, Department of Dermatology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan, Tel +81 476 99 1111, Fax +81 476 99 1911, Email teppei-hagino@nms.ac.jpPurpose: To investigate the therapeutic effectiveness and safety of Janus kinase 1 inhibitor upadacitinib in adolescent patients with atopic dermatitis (AD).Patients and Methods: This study examined therapeutic effectiveness and safety of upadacitinib for 39 Japanese adolescent patients (aged 12– 17 years) diagnosed with moderate-to-severe AD from August 2021 to January 2023. The patients were treated with upadacitinib 15 mg/day plus twice daily topical corticosteroids. Total eczema area and severity index (EASI) or EASI on head and neck, upper limbs, lower limbs, and trunk or for erythema, edema/papulation, excoriation, or lichenification, atopic dermatitis control tool (ADCT), peak pruritus-numerical rating scale (PP-NRS), and laboratory indexes were assessed at weeks 0, 4, and 12 of treatment. Treatment-emergent adverse events were recorded.Results: Total EASI or EASI on 4 anatomical sites or for 4 rash types, ADCT, and PP-NRS were significantly reduced at week 4 and 12 compared to week 0. The achievement rates at weeks 4 or 12 were 64.1% or 62.5% for EASI 75, 93.5% or 73.1% for ADCT < 7-point, and 80.6% or 60% for PP-NRS ≥ 4-point improvement, respectively, indicating their peak at week 4 and slight decrease at week 12. The percent reduction of EASI for excoriation was higher than that for lichenification or edema/papulation at week 4 or week 12, respectively. The percent reductions of EASI for erythema and edema/papulation on head and neck were lower than those on lower limbs at week 12. Total eosinophil counts (TEC) and IgE reduced at week 4 compared to week 0 while TARC, IgE, TEC, and LDH increased at week 12 compared to week 4.Conclusion: These results suggest therapeutic effectiveness and tolerability of upadacitinib and support its therapeutic usefulness for adolescent AD patients.Keywords: atopic dermatitis, upadacitinib, adolescent, effectiveness, safety

Kei Hosoya,1 Taro Komachi,2,&ast; Katsunori Masaki,3,&ast; Isao Suzaki,4 Hidehisa Saeki,5 Naoko Kanda,6 Makoto Nozaki,7 Yosuke Kamide,8 Yoshinori Matsuwaki,9 Yoshiki Kobayashi,10 Eriko Ogino,11 Shin-Ichi Osada,12 Norihiro Usukura,13 Toshikazu Kurumagawa,14 Junya Ninomia,15 Mikiya Asako,16 Keitaro Nakamoto,17 Hidenori Yokoi,18 Manabu Ohyama,19 Keiji Tanese,3 Sho Kanzaki,3 Koichi Fukunaga,3 Motohiro Ebisawa,8 Kimihiro Okubo13 1Nippon Medical School, Musashi Kosugi Hospital, Kanagawa, Japan; 2Department of Otolaryngology, Nippon Medical School, Chiba Hokusoh Hospital, Inzai, Chiba, Japan; 3Keio Allergy Center, Keio University Hospital, Tokyo, Japan; 4Department of Otorhinolaryngology, Head and Neck Surgery, Showa University, School of Medicine, Tokyo, Japan; 5Department of Dermatology, Nihon Medical School, Tokyo, Japan; 6Department of Dermatology, Nippon Medical School, Chiba Hokusoh Hospital, Inzai, Chiba, Japan; 7Wakaba-Hifuka Clinic, Tokyo, Japan; 8National Hospital Organization Sagamihara National Hospital, Clinical Research Center for Allergy and Rheumatology, Kanagawa, Japan; 9Matsuwaki Clinic Shinagawa, Tokyo, Japan; 10Allergy Center, Kansai Medical University, Hirakata, Japan; 11Kyoto Nose and Allergy Clinic, Kyoto, Japan; 12Department of Dermatology, Nippon Medical School Tama Nagayama Hospital, Tokyo, Japan; 13Department of Otolaryngology, Head and Neck Surgery, Nippon Medical School Hospital, Tokyo, Japan; 14Minamiosawa Medical Plaza, Tokyo, Japan; 15Nagase Clinic of Dermatology, Tokyo, Japan; 16Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University, Osaka, Japan; 17Department of Respiratory Medicine, Kyorin University Faculty of Medicine, Tokyo, Japan; 18Department of Otolaryngology, Head and Neck Surgery, Kyorin University Faculty of Medicine, Tokyo, Japan; 19Department of Dermatology, Kyorin University Faculty of Medicine, Tokyo, Japan&ast;These authors contributed equally to this workCorrespondence: Kei Hosoya, Nippon Medical School, Musashi Kosugi Hospital, 1-383 Kosugimachi, Nakahara-ku, Kawasaki, Kanagawa, 211-8533, Japan, Tel +81-44-733-5181, Fax +81-44-711-8713, Email s00-073@nms.ac.jpPurpose: The status of dupilumab self-injection at home is not well understood. We therefore aimed to identify the barriers to adherence to dupilumab self-injection.Patients and Methods: This non-interventional open-label study was conducted between March 2021 and July 2021. Patients with atopic dermatitis, bronchial asthma, and chronic rhinosinusitis with nasal polyps receiving dupilumab, from 15 sites, were requested to complete a self-administered questionnaire regarding the frequency and effectiveness of dosing as well as their use and satisfaction with dupilumab. Barriers to adherence were assessed using the Adherence Starts with Knowledge-12.Results: We included 331 patients who used dupilumab for atopic dermatitis (n = 164), chronic rhinosinusitis with nasal polyps (n = 102), and bronchial asthma (n = 65). The median efficacy of dupilumab scored 9.3 on the visual analog scale. Overall, 85.5% of the patients self-injected dupilumab, and 70.7% perfectly complied with the established injection dates. The pre-filled pen was significantly superior to the conventional syringe in terms of usability, operability, ease of pushing the plunger, and patient satisfaction. However, the pre-filled pen caused more pain during self-injection than did the syringe. Multivariate logistic regression analysis showed that adherence decreased with longer dupilumab treatment duration (p = 0.017) and was not associated with age, sex, underlying disease, or device type. There was a difference in responses related to “inconvenience/forgetfulness” between the good and poor adherence groups.Conclusion: The pre-filled dupilumab pen was superior to the syringe in terms of usability, operability, ease of pushing the plunger, and satisfaction. Repetitive instructions are recommended for preventing poor adherence to dupilumab self-injection.Keywords: atopic dermatitis, biologics, bronchial asthma, chronic rhinosinusitis

Teppei Hagino,1 Hajime Nakano,2 Hidehisa Saeki,3 Naoko Kanda1 1Department of Dermatology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan; 2Department of Dermatology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan; 3Department of Dermatology, Nippon Medical School, Bunkyo-Ku, Tokyo, JapanCorrespondence: Teppei Hagino, Department of Dermatology, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamagari, Inzai, Chiba, 270-1694, Japan, Tel +81 476 99 1111, Fax +81 476 99 1911, Email teppei-hagino@nms.ac.jpAbstract: Darier’s disease (DD) is a rare autosomal dominant genodermatosis caused by mutations in the ATP2A2 gene, which encodes for the sarcoendoplasmic reticulum calcium ATPase type 2 isoform (SERCA2). In epidermal keratinocytes, the decrease in SERCA2 inhibits the transportation of desmosomal proteins to the plasma membrane, resulting in acantholysis and dyskeratosis. We present the first case of DD with a novel missense mutation in the ATP2A2 gene and successfully treated with calcipotriol/betamethasone dipropionate two-compound ointment. A 34-year-old Japanese woman presented with erythema and scales on the scalp and clusters of keratotic papules on the neck and groin. Similar symptoms were observed in her father, younger sister, and daughter. Histopathological examination revealed corps ronds in the granular layer and grains in the horny layer of the epidermis and acantholytic lacuna just above the basal layer. She was diagnosed with DD. A novel heterozygous missense mutation, c.616A>C (p.Asn206His), was detected in the ATP2A2 gene in both the patient and her daughter. The patient was treated with calcipotriol/betamethasone dipropionate two-compound ointment, which resulted in improvement of the skin eruption. This two-compound topical ointment may be a promising therapeutic strategy in the treatment for DD.Keywords: sarcoendoplasmic reticulum calcium ATPase type 2 isoform, corticosteroid, 1, 25-dihydroxyvitamin D3, p.Asn206His

Teppei Hagino,1,2 Shizuka Okazaki,1 Naotaka Serizawa,1 Kaori Suzuki,1 Mio Kaga,2 Yohei Otsuka,2 Erina Mikami,2 Toshihiko Hoashi,2 Hidehisa Saeki,2 Hiroki Matsuda,3 Hiroshi Mitsui,3 Naoko Kanda1 1Department of Dermatology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Chiba, Japan; 2Department of Dermatology, Nippon Medical School, Tokyo, Japan; 3Department of Dermatology, Tokyo Teishin Hospital, Tokyo, JapanCorrespondence: Naoko KandaDepartment of Dermatology, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamagari, Inzai, Chiba, 270-1694 JapanTel +81 476 99 1111Fax +81 476 99 1909Email n-kanda@nms.ac.jpPurpose: Alopecia areata (AA) is characterized by non-scarring, patchy hair loss caused by autoimmune reactions to anagen hair follicles. The pathogenesis of AA may be affected by the diet. However, the dietary habits of patients with AA have not been precisely examined. Therefore, the aim of this study was to investigate the dietary habits of patients with AA in comparison to those of healthy controls.Patients and Methods: We evaluated the dietary habits of 70 adult Japanese patients with AA using a brief-type self-administered diet history questionnaire and compared them to the habits of age- and sex-matched healthy controls.Results: Japanese patients with AA had a higher body mass index (BMI) and higher intakes of vitamin C and fruit than the controls. Logistic regression analysis showed that AA was associated with BMI. Retinol intake was positively correlated with severity of alopecia tool (SALT) score, and linear regression analysis revealed that retinol intake was a predictor of SALT score. Retinol intake among patients with moderate to severe AA (ie, a SALT score > 25) was higher than that in patients with mild AA (a SALT score ≤ 25). The mean age of AA patients with atopic dermatitis (AD) was lower than that of AA patients without AD; however, there were no differences in nutrient or food intake between these two groups. Logistic regression analysis showed that the comorbidity AD was negatively associated with age.Conclusion: AA was associated with a high BMI, and high retinol intake was a predictor of SALT score. Further studies should be conducted to clarify whether dietary intervention to reduce BMI or limit retinol intake can alter the development or severity of AA.Keywords: retinol, vitamin C, body mass index, atopic dermatitis