Unmet Medical Needs in Chronic, Non-communicable Inflammatory Skin Diseases

Hideyuki Ujiie; David Rosmarin; Michael P. Schön; Sonja Ständer; Katharina Boch; Martin Metz; Marcus Maurer; Diamant Thaci; Enno Schmidt; Connor Cole; Kyle T. Amber; Dario Didona; Michael Hertl; Andreas Recke; Hanna Graßhoff; Alexander Hackel; Anja Schumann; Gabriela Riemekasten; Katja Bieber; Gant Sprow; Joshua Dan; Detlef Zillikens; Tanya Sezin; Angela M. Christiano; Kerstin Wolk; Robert Sabat; Khalaf Kridin; Victoria P. Werth; Ralf J. Ludwig

doi:10.3389/fmed.2022.875492

Unmet Medical Needs in Chronic, Non-communicable Inflammatory Skin Diseases

Hideyuki Ujiie, David Rosmarin, Michael P. Schön, Sonja Ständer, Katharina Boch, Martin Metz, Marcus Maurer, Diamant Thaci, Enno Schmidt, Connor Cole, Kyle T. Amber, Dario Didona, Michael Hertl, Andreas Recke, Hanna Graßhoff, Alexander Hackel, Anja Schumann, Gabriela Riemekasten, Katja Bieber, Gant SprowJoshua Dan, Detlef Zillikens, Tanya Sezin, Angela M. Christiano, Kerstin Wolk, Robert Sabat, Khalaf Kridin, Victoria P. Werth, Ralf J. Ludwig

Bar-Ilan University - Azrieli Faculty of Medicine

Research output: Contribution to journal › Review article › peer-review

90 Scopus citations

Abstract

An estimated 20–25% of the population is affected by chronic, non-communicable inflammatory skin diseases. Chronic skin inflammation has many causes. Among the most frequent chronic inflammatory skin diseases are atopic dermatitis, psoriasis, urticaria, lichen planus, and hidradenitis suppurativa, driven by a complex interplay of genetics and environmental factors. Autoimmunity is another important cause of chronic skin inflammation. The autoimmune response may be mainly T cell driven, such as in alopecia areata or vitiligo, or B cell driven in chronic spontaneous urticaria, pemphigus and pemphigoid diseases. Rare causes of chronic skin inflammation are autoinflammatory diseases, or rheumatic diseases, such as cutaneous lupus erythematosus or dermatomyositis. Whilst we have seen a significant improvement in diagnosis and treatment, several challenges remain. Especially for rarer causes of chronic skin inflammation, early diagnosis is often missed because of low awareness and lack of diagnostics. Systemic immunosuppression is the treatment of choice for almost all of these diseases. Adverse events due to immunosuppression, insufficient therapeutic responses and relapses remain a challenge. For atopic dermatitis and psoriasis, a broad spectrum of innovative treatments has been developed. However, treatment responses cannot be predicted so far. Hence, development of (bio)markers allowing selection of specific medications for individual patients is needed. Given the encouraging developments during the past years, we envision that many of these challenges in the diagnosis and treatment of chronic inflammatory skin diseases will be thoroughly addressed in the future.

Original language	English
Article number	875492
Journal	Frontiers in Medicine
Volume	9
DOIs	https://doi.org/10.3389/fmed.2022.875492
State	Published - 9 Jun 2022

Bibliographical note

Publisher Copyright:
Copyright © 2022 Ujiie, Rosmarin, Schön, Ständer, Boch, Metz, Maurer, Thaci, Schmidt, Cole, Amber, Didona, Hertl, Recke, Graßhoff, Hackel, Schumann, Riemekasten, Bieber, Sprow, Dan, Zillikens, Sezin, Christiano, Wolk, Sabat, Kridin, Werth and Ludwig.

Funding

This work has been financially supported by the Cluster of Excellence Precision Medicine in Chronic Inflammation (EXC 2167) and the Collaborative Research Center Pathomechanisms of Antibody-mediated Autoimmunity (SFB 1526), the Research Units PruSearch (FOR 2690) and PEGASUS (FOR 2497), the Individual Research Grant RI/1056-11, all from the Deutsche Forschungsgemeinschaft; the Schleswig-Holstein Excellence-Chair Program from the State of Schleswig Holstein, an EADV research fellowship grant 2019, the Department of Veterans Affairs Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development, National Institutes of Health (National Institute of Arthritis and Musculoskeletal and Skin Diseases) R01AR071653 (VPW) and R01AR076766 (VPW), and Sinergia Unravel principles of self-organization in injured tissue (CRSII5_202301/1) from the Swiss National Science Foundation. HU has received research grants from JB, Otsuka, Taiho, Boehringer Ingelheim, Kyowa Kirin, Kaken, Sun Pharma, Shionogi, Teijin, Mitsubishi Tanabe, Nihon Zoki, Eisai, Torii and Tokiwa, consultant fees from Ono, Nihon-Pharmaceutical, Sun Pharma, argenx and Ishin Pharma, and speaker's fees from Nihon-Pharmaceutical, Maruho, Eli Lilly, Abbie, Eisai, Sanofi, Janssen, Kyowa Kirin, Ono, UCB, Novartis, Sun Pharma, Torii, Taiho, Mitsubishi Tanabe, and Boehringer Ingelheim during the last 3 years, DR has received honoraria or research support from AbbVie, Abcuro, AltruBio, Amgen, Boehringer-Ingelheim, Bristol Meyers Squibb, Celgene, Concert, CSL Behring, Dermavant, Dermira, Galdrema, Incyte, Janssen, Kyowa Kirin, Lilly, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharmaceuticals, UCB, and VielaBio during the last 3 years, MS has received consulting/speakers' fees, or grant support from AbbVie, Almirall, Amgen, Biogen, BMS, Janssen, Novartis, and UCB during the last 3 years, SS has received funding and personal fees from Celldex, Clexio, Dermasence, Galderma, GSK, Kiniksa, Menlo, Trevi, Novartis, Sanofi (investigator all), Abbvie, Almirall, Beiersdorf, Bellus Health, Benevolent, Bionorica, Cara, Celgene, CelloHealth, Clexio, DS Biopharma, Eli Lilly, Escient, Galderma, Grünenthal, Kiniksa, Klinge Pharma, Menlo, Sanofi, Sienna, Trevi, P.G. Unna Academy, Perrigo, Pfizer, Vanda, Vifor, WebMD (Consultancy/Advisory board) and Almirall, Eli Lilly, Sanofi, Galderma, Menlo, Omnicuris, Beiersdorf, Leo Pharma, Novartis, P. G. Unna Academy, Pfizer, Pierre Fabre (speaker) during the last 3 years, MMe has received honoraria as a speaker and/or consultant for Amgen, Aralez, argenx, Bayer, Beiersdorf, Celgene, Escient, Galderma, GSK, Menlo, Moxie, Novartis, Pharvaris, Pfizer, Roche, Sanofi, Siennabio, and Uriach, MMa was a speaker and/or advisor for and/or has received research funding from Allakos, Amgen, Aralez, ArgenX, AstraZeneca, Celldex, Centogene, CSL Behring, FAES, Genentech, GIInnovation, Innate Pharma, Kyowa Kirin, Leo Pharma, Lilly, Menarini, Moxie, Novartis, Roche, Sanofi/Regeneron, Third HarmonicBio, UCB, and Uriach during the last 3 years, is a consultant, advisory board member, and/or investigator for AbbVie, Almirall, Amgen, Beiersdorf, BMS, Boehringer Ingelheim, Eli Lilly, Galapagos, Janssen-Cilag, LEO Pharma, MorphoSys, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Samsung, Sandoz, Sanofi, Sun Pharma, and UCB, ES has received research grants from UCB, Incyte, Biotest, ArgenX, Dompe, Fresenius Medical Care, Bayer, AstraZenca, and Euroimmun and honoraria from Biotest, Thermo Fisher, ArgenX, Fresenius Medical care, Topas, Leo, Chugai, AstraZenca, and Almirall during the last 3 years, MH has received honoraria from Novartis, Sanofi, Celgene, and unrestricted grants from Biotest, Janssen Cilag and Topas durimg the last 3 years, KBi has received research funds from ArgenX during the last 3 years, DZ has received support for research and development work, lecturing and consulting from Euroimmun AG, UCB Pharma, ArgenX, Biotest, Abbvie, Janssen, Sanofi in the last 3 years, KW has received research grants, travel grants, consulting honoraria or lecturer's honoraria from Amgen, Bristol Myers Squibb, Celgene, Charité Research Organization, Flexopharm, Janssen-Cilag, Novartis Pharma, Sanofi-Aventis, and Trial Form Support during the last 3 years, RS has received research grants or honoraria for participation in advisory boards, clinical trials, or as speaker for one or more of the following: AbbVie, Amgen, Bayer, Boehringer Ingelheim Pharma, Bristol Myers Squibb, Celgene, Charité Research Organization, CSL Behring, Dr. Willmar Schwabe, Flexopharm, Incyte, Janssen-Cilag, La Roche-Posay Laboratoire Dermatologique, Novartis Pharma, Parexel International, Sanofi–Aventis, TFS, and UCB Biopharma during the last 3 years, VW has received grants from Celgene, Amgen, Janssen, Biogen, Gilead, Viela; Horizon therapeutics, Pfizer, Corbus, CSL Behring, consulted Astra-Zeneca, Pfizer, Biogen, Celgene, Resolve, Janssen, Gilead, Lilly, BMS, Nektar, Abbvie, Viela, GSK, EMD Serona, Sanofi, Anaptysbio, Amgen, Merck, Pfizer, Janssen, Neovacs, Idera, Octapharma, CSL Behring, Corbus, Novartis, Romefor during the last 3 years, RL has received honoraria for speaking or consulting or has obtained research grants from Novartis, Lilly, Bayer, Dompe, Synthon, Argen-X, and Incyte during the last 3 years. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Funders	Funder number
AltruBio
Bellus Health
Charité Research Organization
Corbus
Department of Veterans Affairs Veterans Health Administration
EMD Serona
Euroimmun
Euroimmun AG
Ishin Pharma
State of Schleswig Holstein
UCB Biopharma
National Institutes of Health
National Institute of Arthritis and Musculoskeletal and Skin Diseases	R01AR076766, R01AR071653
Center for Information Technology
Boehringer Ingelheim
Amgen
Bristol-Myers Squibb
Eli Lilly and Company
Pfizer
AstraZeneca
Bayer
Genentech
GlaxoSmithKline
Novartis
Sanofi
Center for Scientific Review
Gilead Sciences
Biogen
Office of Research and Development
Celgene
AbbVie
Office of Extramural Research, National Institutes of Health
Biomedical Laboratory Research and Development, VA Office of Research and Development
CSL Behring
Boehringer Ingelheim
Novartis Pharma
Janssen Pharmaceuticals
UCB
Les Laboratories Pierre Fabre
UCB Pharma
Fresenius Medical Care North America
Cilag
Florida Agricultural Experiment Station
Office of Research Infrastructure Programs, National Institutes of Health
Incyte
Galápagos
Sanofi-Aventis Deutschland
Deutsche Forschungsgemeinschaft	FOR 2497, FOR 2690, SFB 1526, RI/1056-11
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung	CRSII5_202301/1
Kyowa Hakko Kirin
Shionogi
Sun Pharma

Keywords

alopecia areata
atopic dermatitis
chronic spontaneous urticaria
hidradenitis suppurativa
inflammation
medical need
psoriasis
skin

Access to Document

10.3389/fmed.2022.875492

Cite this

Ujiie, H., Rosmarin, D., Schön, M. P., Ständer, S., Boch, K., Metz, M., Maurer, M., Thaci, D., Schmidt, E., Cole, C., Amber, K. T., Didona, D., Hertl, M., Recke, A., Graßhoff, H., Hackel, A., Schumann, A., Riemekasten, G., Bieber, K., ... Ludwig, R. J. (2022). Unmet Medical Needs in Chronic, Non-communicable Inflammatory Skin Diseases. Frontiers in Medicine, 9, Article 875492. https://doi.org/10.3389/fmed.2022.875492

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title = "Unmet Medical Needs in Chronic, Non-communicable Inflammatory Skin Diseases",

abstract = "An estimated 20–25% of the population is affected by chronic, non-communicable inflammatory skin diseases. Chronic skin inflammation has many causes. Among the most frequent chronic inflammatory skin diseases are atopic dermatitis, psoriasis, urticaria, lichen planus, and hidradenitis suppurativa, driven by a complex interplay of genetics and environmental factors. Autoimmunity is another important cause of chronic skin inflammation. The autoimmune response may be mainly T cell driven, such as in alopecia areata or vitiligo, or B cell driven in chronic spontaneous urticaria, pemphigus and pemphigoid diseases. Rare causes of chronic skin inflammation are autoinflammatory diseases, or rheumatic diseases, such as cutaneous lupus erythematosus or dermatomyositis. Whilst we have seen a significant improvement in diagnosis and treatment, several challenges remain. Especially for rarer causes of chronic skin inflammation, early diagnosis is often missed because of low awareness and lack of diagnostics. Systemic immunosuppression is the treatment of choice for almost all of these diseases. Adverse events due to immunosuppression, insufficient therapeutic responses and relapses remain a challenge. For atopic dermatitis and psoriasis, a broad spectrum of innovative treatments has been developed. However, treatment responses cannot be predicted so far. Hence, development of (bio)markers allowing selection of specific medications for individual patients is needed. Given the encouraging developments during the past years, we envision that many of these challenges in the diagnosis and treatment of chronic inflammatory skin diseases will be thoroughly addressed in the future.",

keywords = "alopecia areata, atopic dermatitis, chronic spontaneous urticaria, hidradenitis suppurativa, inflammation, medical need, psoriasis, skin",

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Ujiie, H, Rosmarin, D, Schön, MP, Ständer, S, Boch, K, Metz, M, Maurer, M, Thaci, D, Schmidt, E, Cole, C, Amber, KT, Didona, D, Hertl, M, Recke, A, Graßhoff, H, Hackel, A, Schumann, A, Riemekasten, G, Bieber, K, Sprow, G, Dan, J, Zillikens, D, Sezin, T, Christiano, AM, Wolk, K, Sabat, R, Kridin, K, Werth, VP & Ludwig, RJ 2022, 'Unmet Medical Needs in Chronic, Non-communicable Inflammatory Skin Diseases', Frontiers in Medicine, vol. 9, 875492. https://doi.org/10.3389/fmed.2022.875492

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AU - Rosmarin, David

AU - Schön, Michael P.

AU - Ständer, Sonja

AU - Boch, Katharina

AU - Metz, Martin

AU - Maurer, Marcus

AU - Thaci, Diamant

AU - Schmidt, Enno

AU - Cole, Connor

AU - Amber, Kyle T.

AU - Didona, Dario

AU - Hertl, Michael

AU - Recke, Andreas

AU - Graßhoff, Hanna

AU - Hackel, Alexander

AU - Schumann, Anja

AU - Riemekasten, Gabriela

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AU - Dan, Joshua

AU - Zillikens, Detlef

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AU - Christiano, Angela M.

AU - Wolk, Kerstin

AU - Sabat, Robert

AU - Kridin, Khalaf

AU - Werth, Victoria P.

AU - Ludwig, Ralf J.

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PY - 2022/6/9

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N2 - An estimated 20–25% of the population is affected by chronic, non-communicable inflammatory skin diseases. Chronic skin inflammation has many causes. Among the most frequent chronic inflammatory skin diseases are atopic dermatitis, psoriasis, urticaria, lichen planus, and hidradenitis suppurativa, driven by a complex interplay of genetics and environmental factors. Autoimmunity is another important cause of chronic skin inflammation. The autoimmune response may be mainly T cell driven, such as in alopecia areata or vitiligo, or B cell driven in chronic spontaneous urticaria, pemphigus and pemphigoid diseases. Rare causes of chronic skin inflammation are autoinflammatory diseases, or rheumatic diseases, such as cutaneous lupus erythematosus or dermatomyositis. Whilst we have seen a significant improvement in diagnosis and treatment, several challenges remain. Especially for rarer causes of chronic skin inflammation, early diagnosis is often missed because of low awareness and lack of diagnostics. Systemic immunosuppression is the treatment of choice for almost all of these diseases. Adverse events due to immunosuppression, insufficient therapeutic responses and relapses remain a challenge. For atopic dermatitis and psoriasis, a broad spectrum of innovative treatments has been developed. However, treatment responses cannot be predicted so far. Hence, development of (bio)markers allowing selection of specific medications for individual patients is needed. Given the encouraging developments during the past years, we envision that many of these challenges in the diagnosis and treatment of chronic inflammatory skin diseases will be thoroughly addressed in the future.

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KW - alopecia areata

KW - atopic dermatitis

KW - chronic spontaneous urticaria

KW - hidradenitis suppurativa

KW - inflammation

KW - medical need

KW - psoriasis

KW - skin

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Unmet Medical Needs in Chronic, Non-communicable Inflammatory Skin Diseases

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Bibliographical note

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Keywords

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