Review
Immunology
Mohammad I. Fardos, Rohan Singh, Patrick O. Perche, Katherine A. Kelly, Steven R. Feldman
Summary: Atopic dermatitis is a chronic inflammatory skin condition mediated by cytokines using the JAK-STAT signaling cascade. Topical JAK inhibitors are emerging as a promising alternative treatment option for AD with good efficacy and safety profiles.
EXPERT REVIEW OF CLINICAL IMMUNOLOGY
(2022)
Article
Dermatology
Masataka Suehiro, Tomofumi Numata, Emi Murakami, Masakazu Takahashi, Ryo Saito, Satoshi Morioke, Akiko Kamegashira, Shunsuke Takahagi, Michihiro Hide, Akio Tanaka
Summary: The topical Janus kinase inhibitor, delgocitinib (DEL) ointment, has been shown to be effective in treating atopic dermatitis (AD). It is as effective as topical corticosteroids in maintaining remission, especially for patients with dry skin.
DERMATOLOGIC THERAPY
(2022)
Review
Allergy
Martin Steinhoff, Fareed Ahmad, Atul Pandey, Angeliki Datsi, Ayda AlHammadi, Sara Al-Khawaga, Aysha Al-Malki, Jianghui Meng, Majid Alam, Joerg Buddenkotte
Summary: Atopic dermatitis is a common chronic inflammatory skin disease, and its pathogenesis involves the dysregulation of neuroimmune circuits. Abnormal neuroimmune circuits can lead to inflammation, pruritus, pain, and skin barrier dysfunction. Understanding neuroimmune circuits and neuronal signaling is crucial for controlling the pathological mechanisms of atopic dermatitis.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Review
Medicine, General & Internal
Michelle Le, Melissa Berman-Rosa, Feras M. Ghazawi, Marc Bourcier, Loretta Fiorillo, Melinda Gooderham, Lyn Guenther, Sameh Hanna, H. Chih-Ho Hong, Ian Landells, Perla Lansang, Danielle Marcoux, Marni C. Wiseman, Jensen Yeung, Charles Lynde, Ivan V. Litvinov
Summary: Oral JAK inhibitors have shown significant clinical efficacy and reassuring safety profile in the treatment of moderate-to-severe atopic dermatitis, providing rapid symptom control and serving as a reliable systemic treatment option for patients unresponsive to topical treatments.
FRONTIERS IN MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Agnieszka Kaczmarska, Dominika Kwiatkowska, Katarzyna Konstancja Skrzypek, Zbigniew Tadeusz Kowalewski, Kamila Jaworecka, Adam Reich
Summary: Pruritus, an unpleasant sensation that elicits a desire to scratch, is widely observed in various inflammatory skin diseases. The pathogenesis of pruritus in conditions like atopic dermatitis and psoriasis involves complex interactions between biochemical mediators, enzymes, and pathways. Although the exact mechanisms remain elusive, considerable progress has been made in recent years.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Allergy
Chisa Nakashima, Shigeto Yanagihara, Atsushi Otsuka
Summary: Atopic dermatitis is a chronic, eczematous skin condition characterized by severe itchiness. Th2 cell-mediated immunity, skin barrier dysfunction, and pruritus contribute to the development of atopic dermatitis. The JAK/STAT pathway is involved in various inflammatory diseases, including atopic dermatitis. JAK inhibitors show promise as potential treatments for severe atopic dermatitis.
ALLERGOLOGY INTERNATIONAL
(2022)
Review
Allergy
Raj Chovatiya, Amy S. Paller
Summary: Atopic dermatitis (AD) is a chronic inflammatory skin disorder with limited treatment options. Recent studies have shown that both topical and systemic Janus kinase (JAK) inhibitors hold promise in treating AD, with further research needed to fully understand their efficacy and safety.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2021)
Article
Medicine, General & Internal
Franz J. Legat
Summary: Atopic dermatitis is a common inflammatory skin disease affecting up to 20% of children and 10% of adults in higher income countries, with chronic pruritus as a major symptom causing significant impact on quality of life. New systemic and topical treatments targeting specific cytokines and receptors have ushered in a new era in atopic dermatitis and pruritus therapy.
FRONTIERS IN MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Laura Calabrese, Andrea Chiricozzi, Clara De Simone, Barbara Fossati, Alessandra D'Amore, Ketty Peris
Summary: Atopic dermatitis (AD) is the most common inflammatory skin disorder with limited therapeutic options. The JAK/STAT signaling pathway plays a significant role in the pathogenesis of AD, and JAK inhibitors have shown promise as effective drugs for treating AD.
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
(2022)
Article
Immunology
Pei-Yun Shih, Chia-Jung Li, Su-Boon Yong
Summary: Atopic dermatitis is a chronic inflammatory skin disease characterized by immune function imbalance and impaired epidermal barrier function. The JAK/STAT signaling pathway plays a critical role in its pathogenesis, and JAK inhibitors offer a novel therapeutic approach.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Medicine, General & Internal
Alice Plant, Michael R. Ardern-Jones
Summary: Atopic dermatitis is a common inflammatory skin disease characterized by itch, which can significantly impact quality of life and persist into adulthood. General physicians must recognize the disease to differentiate acute flares from other conditions, such as eczema herpeticum and allergic reactions. While current treatments focus on broad spectrum immunomodulation, advancements in understanding the disease's pathophysiology have expanded treatment options, with promising new drugs offering potential for more effective and safe therapies in the future.
Review
Dermatology
Timo Buhl, Thomas Werfel
Summary: In recent years, there have been significant advancements in understanding the pathophysiology, concomitant diseases, and therapeutics of atopic dermatitis (AD). Although numerous studies have been conducted on AD diagnosis and subtypes, there is still no established diagnostic biomarker or clinical predictor of treatment response. Topical treatments, such as Janus kinase (JAK) inhibitors, are in advanced stages of clinical trials and have been approved in some countries, indicating potential availability in Europe in the near future. Systemic therapies in Europe currently include antibodies for interleukin (IL)-4/13 signaling inhibition and oral JAK inhibitors with varying efficacy and safety profiles. Promising new targets for AD antibody therapies include IL-31, neurokinin-1 receptor, and the OX40/OX40L axis. Future research on AD will focus on primary prevention, modulation of disease progression, and the impact of early therapeutic intervention on concomitant diseases.
JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT
(2023)
Review
Dermatology
Timo Buhl, Thomas Werfel
Summary: In recent years, new insights and advancements in the understanding of atopic dermatitis (AD) have been made. However, there is still no established diagnostic biomarker or clinical predictor for treatment response. Topical treatment options such as Janus kinase (JAK) inhibitors are currently in clinical trials or approved in some countries. Systemic therapies in Europe include IL-4/13 signaling cascade inhibitors and oral JAK inhibitors with varying efficacy and safety profiles. Promising new targets for AD treatment include IL-31 blockade, neurokinin-1 receptor blockade, and OX40/OX40L axis inhibition.
JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT
(2023)
Article
Pharmacology & Pharmacy
Egidio Freitas, Melinda Gooderham, Tiago Torres
Summary: Atopic dermatitis is a common chronic inflammatory skin disease that is mainly treated with topical medications. However, long-term use of these medications may have safety concerns. Several new topical compounds are being developed and show promising results in treating mild to moderate disease. Further research is needed to evaluate their long-term efficacy and safety compared to current treatments.
Review
Pharmacology & Pharmacy
Carlos Alves, Ana Penedones, Diogo Mendes, Francisco Batel Marques
Summary: This study compared the relative safety of topical Janus kinase (JAK) inhibitors in patients with mild to moderate atopic dermatitis. The results showed that tofacitinib was associated with a reduced risk of any adverse event compared to ruxolitinib (OR 0.18). However, due to limited data and heterogeneity between studies, there is no robust evidence indicating clinically important differences in the safety profiles of existing topical JAK inhibitors. Further pharmacovigilance activities are needed to confirm the safety profile of these drugs.
INTERNATIONAL JOURNAL OF CLINICAL PHARMACY
(2023)
Article
Infectious Diseases
Takamitsu Ohnishi, Shinichi Watanabe, Tetsuya Matsumoto, Hiroshi Yotsuyanagi, Junko Sato, Intestu Kobayashi, Shin Iinuma, Takashi Nagayama, Shuichiro Shibuya, Natsuki Ogawa, Ken Iozumi, Yasuyuki Nakajima, Yukiko Kurikawa, Motoko Kobayashi, Koma Matsuo, Hideyuki Ishikawa, Tadamichi Shimizu, Kiyohiro Tsutsui, Tatsuyoshi Kawamura, Ryuhei Okuyama, Mariko Seishima, Yoichi Akita, Chikatoshi Kasugai, Katsuaki Yano, Yasuhiko Tamada, Kimihiko Mizutani, Kenji Kabashima, Nanako Yamada, Masami Ikeda
Summary: The present study compared trends in antimicrobial resistance patterns in pathogens isolated from skin and soft-tissue infections (SSTIs) in Japan with those of a nationwide survey conducted in 2013. The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) did not differ significantly between the present study and the 2013 survey. However, the prevalence of methicillin-resistant coagulase-negative staphylococci (MRCNS) was higher in the present study compared to the 2013 survey. The susceptibility profiles of MRSA and MRCNS to various antibiotics were not significantly different between the two surveys. Continuous monitoring is important for guiding the appropriate treatment of SSTIs.
JOURNAL OF INFECTION AND CHEMOTHERAPY
(2023)
Letter
Dermatology
Takayoshi Komatsu-Fujii, Corrine Sison de Jesus, Takashi Nomura, Kenji Kabashima
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
(2023)
Article
Dermatology
Annelie H. Musters, Conor Broderick, David Prieto-Merino, Andrea Chiricozzi, Giovanni Damiani, Ketty Peris, Sandipan Dhar, Abhishek De, Esther Freeman, Bernd W. M. Arents, Tim Burton, Angela Leigh-Ann L. Bosma, Ching-Chi Chi, Godfrey Fletcher, Aaron M. Drucker, Kenji Kabashima, Emilie F. de Monchy, Maitreyee Panda, Dmitri Robert Wall, Christian Vestergaard, Emmanuel Mahe, Laura Bonzano, Leila Kattach, Maddalena Napolitano, Maria Fernanda Ordonez-Rubiano, Eva Haufe, Cataldo Patruno, Alan D. Irvine, Phyllis Spuls, Carsten Flohr
Summary: Limited data suggest that patients with atopic dermatitis (AD) receiving systemic immunomodulatory treatments have a lower risk of severe COVID-19 complications. Monotherapy with dupilumab is associated with lower hospitalization rates compared to other therapies. However, combination systemic treatments, particularly those including systemic corticosteroids, have the highest risk of severe COVID-19.
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
(2023)
Article
Dermatology
Hidehisa Saeki, Masashi Akiyama, Masatoshi Abe, Atsuyuki Igarashi, Shinichi Imafuku, Yukihiro Ohya, Norito Katoh, Hideto Kameda, Kenji Kabashima, Yuichiro Tsunemi, Michihiro Hide, Mamitaro Ohtsuki
Summary: This guidance provides information on the use of oral JAK inhibitors for the treatment of atopic dermatitis. It explains the role of oral JAK inhibitors in inhibiting the signal transduction of cytokines involved in the pathogenesis of atopic dermatitis. It also highlights the authorized oral JAK inhibitors for atopic dermatitis in Japan and emphasizes the importance of considering disease factors, treatment factors, and patient backgrounds in the selection of treatment options.
JOURNAL OF DERMATOLOGY
(2023)
Review
Dermatology
R. Bissonnette, L. F. Eichenfield, E. Simpson, D. Thaci, K. Kabashima, J. P. Thyssen, E. Guttman-Yassky, F. P. Nunes, M. Gamalo, F. Ahmad, M. Kuligowski, K. Sun, C. Pipper, A. W. Christensen, P. D'Angelo, M. Milutinovic, A. Guettner, J. I. Silverberg
Summary: Despite the lack of guidelines for analyzing clinical trial data in atopic dermatitis (AD), using the estimand framework can help standardize the analysis and incorporate intercurrent events. Intercurrent events, such as rescue therapy and sleep deprivation, frequently occur in AD trials and their inconsistent handling limits result interpretation. Applying the estimand framework, as guided by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH), can improve AD trial design and analysis by providing more reflective and informative results for clinicians to make treatment selection.
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
(2023)
Article
Medicine, General & Internal
Emma Guttman-Yassky, Eric L. Simpson, Kristian Reich, Kenji Kabashima, Ken Igawa, Tetsuya Suzuki, Hirotaka Mano, Takeshi Matsui, Ehsanollah Esfandiari, Masutaka Furue
Summary: This study evaluated the efficacy and safety of the anti-OX40 antibody rocatinlimab in patients with moderate-to-severe atopic dermatitis. The results showed significant reductions in EASI score at week 16 in patients receiving rocatinlimab compared to placebo. The treatment led to progressive improvements in atopic dermatitis, which were maintained in most patients after treatment discontinuation, and it was well tolerated.
Article
Dermatology
Amy S. Paller, Jonathan I. Silverberg, Michael J. Cork, Emma Guttman-Yassky, Benjamin Lockshin, Alan D. Irvine, Moon Bum Kim, Kenji Kabashima, Zhen Chen, Yufang Lu, Ashish Bansal, Ana B. Rossi, Arsalan Shabbir
Summary: This study assessed the efficacy and safety of dupilumab in patients with severe erythrodermic atopic dermatitis (AD). The results showed that dupilumab significantly improved AD signs and symptoms, including affected body surface area, Eczema Area and Severity Index (EASI) score, and Pruritus Numerical Rating Scale (PP-NRS) score. The treatment also led to reductions in serum biomarker levels.
Article
Allergy
Riko Takimoto-Ito, Naotomo Kambe, Toshiaki Kogame, Takashi Nomura, Kazushi Izawa, Tomoyasu Jo, Yasuhiro Kazuma, Hajime Yoshifuji, Yuya Tabuchi, Hiroyasu Abe, Mayuko Yamamoto, Kimiko Nakajima, Ozumi Tomita, Yosuke Yagi, Kazumoto Katagiri, Yuki Matsuzaka, Yohei Takeuchi, Miho Hatanaka, Takuro Kanekura, Sora Takeuchi, Takafumi Kadono, Yuya Fujita, Kiyoshi Migita, Takahiro Fujino, Takahiko Akagi, Tomoyuki Mukai, Tohru Nagano, Mitsuhiro Kawano, Hayato Kimura, Yukari Okubo, Akimichi Morita, Michihiro Hide, Takahiro Satoh, Akihiko Asahina, Nobuo Kanazawa, Kenji Kabashima
Summary: Schnitzler syndrome is a rare disorder characterized by chronic urticaria. A nationwide survey was conducted in Japan to determine the current status of the disease. Clinical information of 36 diagnosed cases was collected, providing insights into the clinical features and treatment of the syndrome. Continuous collection and long-term follow-up of clinical information are crucial for the appropriate management and further understanding of Schnitzler syndrome.
ALLERGOLOGY INTERNATIONAL
(2023)
Review
Immunology
Yuki Honda Keith, Gyohei Egawa, Tetsuya Honda, Kenji Kabashima
Summary: Mast cells (MCs) are immune cells that play important roles in maintaining homeostasis and inflammatory states in tissues. They are involved in the pathogenesis of type 2 skin inflammation in atopic dermatitis (AD) through both pro- and anti-inflammatory effects. The activation of skin MCs by environmental factors like Staphylococcus aureus can lead to AD inflammation, while MCs also contribute to pruritus through IgE-dependent and -independent degranulation. On the other hand, MCs can suppress type 2 skin inflammation by promoting Treg expansion and enhancing skin barrier function.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Review
Immunology
Tetsuya Honda, Kenji Kabashima, Jun Kunisawa
Summary: Lipid mediators act through specific receptors on cell surfaces and play physiological roles locally at their production sites. Recent research has shed light on the roles of these mediators in various diseases, including inflammatory skin conditions. They not only signal themselves, but also enhance the signaling of other chemical mediators. Manipulating their signaling has the potential to be a novel therapeutic approach for human skin diseases.
IMMUNOLOGICAL REVIEWS
(2023)
Article
Dermatology
Kenji Kabashima, Takayo Matsumura, Hiroshi Komazaki, Makoto Kawashima
Summary: This study investigated the impact of nemolizumab on the quality of life in patients with atopic dermatitis. The results showed that nemolizumab treatment improved sleep quality, interpersonal relationships, and work activities.
DERMATOLOGY AND THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Azusa Saika, Prabha Tiwari, Takahiro Nagatake, Eri Node, Koji Hosomi, Tetsuya Honda, Kenji Kabashima, Jun Kunisawa
Summary: Mead acid can suppress retinol-induced irritant contact dermatitis and prevent keratinocyte hyperproliferation and the expression of neutrophil chemoattractants through the PPAR-alpha pathway.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Review
Immunology
Toshiaki Kogame, Gyohei Egawa, Kenji Kabashima
Summary: Recent studies have shown that Janus kinase (JAK) plays a crucial role in signal transduction for inflammatory diseases like atopic dermatitis (AD). Clinical trials using JAK inhibitors and biologic reagents have been successful in treating AD, indicating the efficacy of molecular-based therapies. However, there are concerns about the safety of JAK inhibitors, including severe heart disease. This article provides an overview of the molecular mechanisms of AD and discusses JAK-related biology as a target for AD treatment.
IMMUNOLOGICAL MEDICINE
(2023)
Letter
Dermatology
Yui Hirano-Lotman, Toshiaki Kogame, Yo Kaku, Takayoshi Komatsu-Fujii, Yuichiro Endo, Takashi Nomura, Kenji Kabashima
JOURNAL OF DERMATOLOGY
(2023)
Article
Dermatology
Hitomi Nakaizumi, Naotomo Kambe, Hiroyuki Irie, Yo Kaku, Masakazu Fujimoto, Hajime Yoshifuji, Yasuhiro Kazuma, Kazumoto Katagiri, Takuro Kanekura, Kenji Kabashima
Summary: Schnitzler syndrome (SchS) is a rare autoinflammatory disease characterized by bone pain, recurrent fever, and other symptoms. A key feature of the syndrome is the presence of a persistent urticarial-like rash. Histopathological data suggests that neutrophilic epitheliotropism, or the tendency of neutrophils to infiltrate and affect epithelial tissue, can be a useful marker for diagnosing SchS and differentiating it from conventional urticaria. Understanding this characteristic is crucial for early diagnosis and appropriate treatment.
JOURNAL OF DERMATOLOGY
(2023)