Faculty Profiles - TAKEICHI Takuya

ANCA-associated neuropathy in systemic sclerosis: A case report and review of literature Reviewed

Kayo Takenaka, Takuya Takeichi, Ryoji Nishi, Masashi Suzuki, Haruki Koike, Masahisa Katsuno, Mariko Ogawa-Momohara, Yoshinao Muro, Masashi Akiyama

JOURNAL OF CUTANEOUS IMMUNOLOGY AND ALLERGY Vol. 4 ( 2 ) page： 34 - 36 2021.4

Language：English Publisher：JOHN WILEY & SONS LTD

Systemic sclerosis (SSc) is a multi-system autoimmune disease. Anti-neutrophil cytoplasmic antibodies (ANCA) are autoantibodies directed against enzymes found within primary granules of neutrophils and lysosomes in monocytes. Although up to 12% of SSc patients have ANCA, only a minority of these patients develop an overlap syndrome with ANCA-associated vasculitis. We summarize previous reports on SSc patients with ANCA-associated neuropathy. In all the reported cases, the SSc diagnosis preceded the ANCA-associated neuropathy diagnosis. Seven of the eight patients with limited cutaneous SSc had interstitial lung disease (ILD). Thus, patients with ANCA-associated neuropathy in lSSc may be prone to complication with ILD.

DOI： 10.1002/cia2.12153

Acute generalized exanthematous pustulosis triggered by acetaminophen in an IL36RN variant heterozygote. Reviewed International journal

Chiaki Murase, Takuya Takeichi, Kazumitsu Sugiura, Masashi Akiyama

The Journal of dermatology Vol. 48 ( 4 ) page： E186 - E187 2021.4

Identification of a novel causative mutation in KRT1 in diffuse palmoplantar keratoderma, facilitated by whole-exome sequencing. Reviewed International journal

So Takeuchi, Takuya Takeichi, Yasutoshi Ito, Kana Tanahashi, Yoshinao Muro, Tomoo Ogi, Masashi Akiyama

European journal of dermatology : EJD Vol. 31 ( 2 ) page： 264 - 265 2021.3

Two Cases of Porokeratosis with MVD Mutations, in Association with Bullous Pemphigoid. Reviewed International journal

Yuki Arisawa, Yasutoshi Ito, Kana Tanahashi, Yoshinao Muro, Tomoo Ogi, Takuya Takeichi, Masashi Akiyama

Acta dermato-venereologica Vol. 101 ( 3 ) page： adv00423 2021.3

A case with overlapping features of IgG4-related autoimmune pancreatitis, Sjögren's syndrome and anti-aminoacyl-tRNA synthetase syndrome. Reviewed International journal

Masato Yoshikawa, Yoshinao Muro, Mariko Ogawa-Momohara, Satoru Ito, Takuya Takeichi, Masashi Akiyama

Modern rheumatology case reports Vol. 5 ( 1 ) page： 82 - 86 2021.1

Language：English Publishing type：Research paper (scientific journal) Publisher：TAYLOR & FRANCIS LTD

A 55-year-old man who had been diagnosed with autoimmune pancreatitis five years earlier was referred to our department because of finger swelling, finger stiffness and the presence of interstitial lung disease (ILD). The patient was diagnosed with Sjögren's syndrome according to the pathological findings of minor salivary glands and positive anti-SS-A antibodies. Later, at age 58, he was hospitalised due to the exacerbation of the ILD. Serum IgG4 level was checked and was found to be elevated (417 mg/dL). After the introduction of cyclosporine in addition to the prednisolone, at age 60, the ILD disease activity stabilised. However, at age 62, fever, myalgia and mechanic's hands appeared. His serum creatine kinase level was high, and magnetic resonance imaging showed inflammatory findings of muscle. In-house ELISA clarified that his serum carried anti-PL-7 antibody among anti-aminoacyl-tRNA synthetase antibodies. This is a unique case who had overlapping features of IgG4-related autoimmune pancreatitis, Sjögren's syndrome and anti-synthetase syndrome. Although the aetiology of the complications in this patient is obscure, autoimmunity might have played a significant role in the disease conditions and prognosis of the present case with IgG4-related disease.

DOI： 10.1080/24725625.2020.1816675

A patient with CARD14-associated papulosquamous eruptions showing atopic dermatitis-like features. Reviewed International journal

Takuya Takeichi, Shiho Terawaki, Yumiko Kubota, Yasutoshi Ito, Kana Tanahashi, Yoshinao Muro, Masashi Akiyama

Journal of the European Academy of Dermatology and Venereology : JEADV Vol. 35 ( 1 ) page： E58 - E59 2021.1

Language：English

Caspase recruitment domain family member 14 (CARD14) is an activator of nuclear factor kappa-light-chain-enhancer in activated B cells (NF-κB) and contributes to inflammatory responses within the epidermis. CARD14 mutations are associated with autoinflammatory keratinization diseases, such as psoriasis and familial pityriasis rubra pilaris (PRP). Recently, Craiglow et al. proposed CARD14-associated papulosquamous eruption (CAPE), a spectrum that includes clinical features of psoriasis and PRP. Characteristic features of patients with CAPE include early onset, prominent facial involvement, and favorable response to ustekinumab therapy. Here, we describe a unique CAPE patient with atopic dermatitis (AD)-like features and extend the spectrum of CAPE.

DOI： 10.1111/jdv.16799

Generalized pustular psoriasis associated with systemic lupus erythematosus successfully treated with secukinumab. Reviewed International journal

Kazuya Akaji, Yukinobu Nakagawa, Kasumi Kakuda, Madoka Takafuji, Eiji Kiyohara, Chiaki Murase, Takuya Takeichi, Masashi Akiyama, Manabu Fujimoto

The Journal of dermatology Vol. 48 ( 1 ) page： E43 - E44 2021.1

Systemic inflammatory diseases due to germ line EGFR mutations, with features suggestive of autoinflammatory keratinization diseases. Reviewed International journal

Takuya Takeichi, Masashi Akiyama

The Journal of dermatology Vol. 48 ( 1 ) page： E24 - E25 2021.1

Morphea in a Crohn's disease patient undergoing ustekinumab treatment. Reviewed International journal

Misako Makihara-Inukai, Takuya Takeichi, Mariko Ogawa-Momohara, Yoshinao Muro, Masashi Akiyama

European journal of dermatology : EJD Vol. 31 ( 1 ) page： 96 - 97 2021.1

A heterozygous SERPINB7 mutation is a possible modifying factor for epidermolytic palmoplantar keratoderma. Reviewed International journal

Takenori Yoshikawa, Takuya Takeichi, Tomoo Ogi, Yasushi Suga, Yoshinao Muro, Masashi Akiyama

Journal of dermatological science Vol. 100 ( 2 ) page： 148 - 151 2020.11

Anti-Zo antibodies in Japanese myositis patients detected by a newly developed ELISA. Reviewed International journal

Yoshinao Muro, Takako Hashimoto, Shinyu Izumi, Mariko Ogawa-Momohara, Takuya Takeichi, Hiroyuki Yamashita, Hidekata Yasuoka, Masashi Akiyama

Clinical and experimental rheumatology Vol. 40 ( 2 ) page： 219 - 223 2020.10

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: The myositis-specific autoantibodies that characterise certain forms of idiopathic inflammatory myopathy (IIM) are useful for diagnosing dermatomyositis (DM) / polymyositis (PM) and predicting its prognosis. The autoantibody to phenylalanyl-tRNA synthetase (anti-Zo) has been identified as a disease marker antibody for anti-synthetase syndrome only in a UK cohort. Here we aim to establish an ELISA for the measurement of anti-Zo and to characterise the clinical features of Japanese patients who have this autoantibody. METHODS: Anti-Zo was investigated by immunoprecipitation with recombinant phenylalanyl-tRNA synthetase α/β proteins. The results were confirmed by immunoprecipitation-Western blotting with cell extract. Sera from patients with DM/PM (n=224) were screened by an ELISA with the recombinant proteins. Medical records were retrospectively reviewed to obtain detailed information on the clinical phenotypes of the anti-Zo-positive patients. RESULTS: Only two male patients were confirmed to have anti-Zo. Both patients had fever, myopathy, interstitial lung disease, and mechanic's hands, and these clinical features are consistent with those of anti-synthetase syndrome. Another patient's serum showed a higher level than the cut-off value for anti-phenylalanyl-tRNA synthetase α by our in-house ELISA, but was judged to be negative for anti-Zo by immunoprecipitation-Western blotting. CONCLUSIONS: This is the first report of anti-Zo-positive IIM patients from Asia. Although Japanese patients with anti-Zo have a clinical phenotype similar to that of Caucasian patients, further large cohort studies are necessary to confirm the frequency of anti-Zo in Japanese IIM patients. Our newly developed ELISA should be validated for sensitivity and specificity in large cohorts.

DOI： 10.55563/clinexprheumatol/q70vmh

Reducing immunosuppressant use in patients with chronic inflammation during the COVID-19 pandemic: Risks versus benefits

Acquired reactive perforating collagenosis with chondrodermatitis nodularis chronica helicis. International journal

Yuya Murase, Takuya Takeichi, Kana Tanahashi, Hiroyuki Takama, Masashi Akiyama

The Journal of dermatology Vol. 47 ( 10 ) page： E362 - E364 2020.10

Mariko Ogawa-Momohara, Yoshinao Muro, Takuya Takeichi, Masashi Akiyama

JOURNAL OF CUTANEOUS IMMUNOLOGY AND ALLERGY Vol. 3 ( 5 ) page： 120 - 121 2020.10

Language：English Publisher：JOHN WILEY & SONS LTD

During the COVID-19 pandemic, clinicians are facing a difficult but important question: Should we try to reduce immunosuppressant use or postpone immunosuppressant therapies for newly diagnosed autoimmune disease patients with mild to moderate symptoms? We would like to alert your readership that although potential chronic inflammation itself is not always critical, it can trigger a hyper-inflammatory condition in patients who become infected with COVID-19. We should be careful when reducing immunosuppressant use.

DOI： 10.1002/cia2.12132

Clinical and serological features of dermatomyositis and systemic lupus erythematosus patients with autoantibodies to ADAR1. International journal

Yoshinao Muro, Mariko Ogawa-Momohara, Takuya Takeichi, Shusaku Fukaya, Hidekata Yasuoka, Michihiro Kono, Masashi Akiyama

Journal of dermatological science Vol. 100 ( 1 ) page： 82 - 84 2020.10

Classical Vohwinkel syndrome with heterozygous p.Asp66His mutation in GJB2 gene: Second Asian case. International journal

Kenta Ikeda, Takuya Takeichi, Yasutoshi Ito, Yoshio Kawakami, Yuki Nakagawa, Seiko Naito, Osamu Yamasaki, Masashi Akiyama, Shin Morizane

The Journal of dermatology Vol. 47 ( 10 ) page： E352 - E354 2020.10

Association of Topical Minoxidil With Autosomal Recessive Woolly Hair/Hypotrichosis Caused by LIPH Pathogenic Variants. Reviewed International journal

Tomoki Taki, Kana Tanahashi, Takuya Takeichi, Takenori Yoshikawa, Yuya Murase, Kazumitsu Sugiura, Masashi Akiyama

JAMA dermatology Vol. 156 ( 10 ) page： 1030 - 1032 2020.10

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER MEDICAL ASSOC

This nonrandomized clinical trial evaluates the association of topical minoxidil with hypotrichosis in patients with autosomal recessive woolly hair/hypotrichosis carrying LIPH pathogenic variants.

DOI： 10.1001/jamadermatol.2020.2195

Exploration of biomarkers to predict clinical improvement of atopic dermatitis in patients treated with dupilumab: A study protocol. Reviewed International journal

Takeshi Nakahara, Kenji Izuhara, Daisuke Onozuka, Satoshi Nunomura, Risa Tamagawa-Mineoka, Koji Masuda, Susumu Ichiyama, Hidehisa Saeki, Yudai Kabata, Riichiro Abe, Mamitaro Ohtsuki, Koji Kamiya, Tatsuro Okano, Tomomitsu Miyagaki, Yozo Ishiuji, Akihiko Asahina, Hiroshi Kawasaki, Keiji Tanese, Hiroshi Mitsui, Tatsuyoshi Kawamura, Takuya Takeichi, Masashi Akiyama, Emi Nishida, Akimichi Morita, Kyoko Tonomura, Yukinobu Nakagawa, Koji Sugawara, Chiharu Tateishi, Yoko Kataoka, Rai Fujimoto, Sakae Kaneko, Eishin Morita, Akio Tanaka, Michihiro Hide, Natsuko Aoki, Shigetoshi Sano, Haruna Matsuda-Hirose, Yutaka Hatano, Motoi Takenaka, Hiroyuki Murota, Norito Katoh, Masutaka Furue

Medicine Vol. 99 ( 38 ) page： e22043 2020.9

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Atopic dermatitis (AD) is a common eczematous skin disorder that profoundly reduces the quality of life due to intractable pruritus. Excellent therapeutic success of the anti-interleukin 4 receptor-α antibody dupilumab in clinical trials and a real-world clinical context indicates the crucial roles of interleukin (IL)-4 and IL-13 in the pathogenesis of AD. Along with the clinical improvement in skin scores and pruritus, dupilumab significantly and progressively reduces and normalizes the upregulated expression of T helper type 2 signatures such as Chemokine (C-C motif) ligand (CCL)17, CCL18, CCL22, and CCL26 in the lesional skin of AD. However, no blood/serum biomarkers are known to predict good or poor outcome in patients with AD treated with dupilumab. METHODS: Patients are at least 18 years of age and have moderate-to-severe AD with Eczema Area and Severity Index (EASI) ≥16, Investigator's Global Assessment ≥3, and body surface area ≥10%. We are going to enroll more than 130 subjects from 18 medical facilities. Clinical objective findings will be evaluated by EASI. Subjective symptoms will be assessed by Patient-Oriented Eczema Measure, Numerical Rating Scale for Pruritus (Pruritus-NRS), Skin Comfort-NRS, and Treatment Satisfaction-NRS. We will measure 18 blood/serum biomarkers including % eosinophils in blood cell count, lactate dehydrogenase, total IgE, soluble interleukin 2 receptor, CCL17, CCL18, CCL22, CCL26, CCL27, IL-13, IL-22, IL-24, IL-25, IL-31, IL-33, thymic stromal lymphopoietin, periostin, and squamous cell carcinoma antigen-2. The clinical evaluation and biomarker sampling will be performed at 0, 2, 4, 8, and 16 weeks of dupilumab treatment. We will also perform proteomic analysis (of roughly 300 proteins) of the patients' sera obtained at 0 and 2 weeks of treatment. The primary endpoint is the association between "baseline levels of 18 biomarkers" and "% change from baseline of EASI at 16 weeks of dupilumab treatment." DISCUSSION: This is the first clinical trial to explore the biomarkers, including potential proteomic markers, most strongly associated with improvement in EASI in patients with moderate-to-severe AD treated with dupilumab for 16 weeks (B-PAD study). A limitation is that we will only enroll Japanese patients.

DOI： 10.1097/MD.0000000000022043