Diagnosis and management of pemphigus: Recommendations of an international panel of experts

doi:10.1016/j.jaad.2018.02.021

. 2020 Mar;82(3):575-585.e1.

doi: 10.1016/j.jaad.2018.02.021. Epub 2018 Feb 10.

Diagnosis and management of pemphigus: Recommendations of an international panel of experts

Dedee F Murrell¹, Sandra Peña², Pascal Joly³, Branka Marinovic⁴, Takashi Hashimoto⁵, Luis A Diaz⁶, Animesh A Sinha⁷, Aimee S Payne⁸, Maryam Daneshpazhooh⁹, Rüdiger Eming¹⁰, Marcel F Jonkman¹¹, Daniel Mimouni¹², Luca Borradori¹³, Soo-Chan Kim¹⁴, Jun Yamagami¹⁵, Julia S Lehman¹⁶, Marwah Adly Saleh¹⁷, Donna A Culton⁶, Annette Czernik¹⁸, John J Zone¹⁹, David Fivenson²⁰, Hideyuki Ujiie²¹, Katarzyna Wozniak²², Ayşe Akman-Karakaş²³, Philippe Bernard²⁴, Neil J Korman²⁵, Frédéric Caux²⁶, Kossara Drenovska²⁷, Catherine Prost-Squarcioni²⁸, Snejina Vassileva²⁷, Ron J Feldman²⁹, Adela Rambi Cardones³⁰, Johann Bauer³¹, Dimitrios Ioannides³², Hana Jedlickova³³, Francis Palisson³⁴, Aikaterini Patsatsi³⁵, Soner Uzun²³, Savas Yayli³⁶, Detlef Zillikens³⁷, Masayuki Amagai¹⁵, Michael Hertl³⁸, Enno Schmidt³⁷, Valeria Aoki³⁹, Sergei A Grando⁴⁰, Hiroshi Shimizu²¹, Sharon Baum⁴¹, Guiseppe Cianchini⁴², Claudio Feliciani⁴³, Pilar Iranzo⁴⁴, Jose M Mascaró Jr⁴⁴, Cezary Kowalewski²², Russell Hall³⁰, Richard Groves⁴⁵, Karen E Harman⁴⁶, M Peter Marinkovich⁴⁷, Emanual Maverakis⁴⁸, Victoria P Werth⁴⁹

Affiliations

¹ Department of Dermatology, St. George Hospital, University of New South Wales, Sydney, Australia. Electronic address: d.murrell@unsw.edu.au.
² Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania; Department of Dermatology at the Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
³ Department of Dermatology, Rouen University Hospital, Rouen, France.
⁴ Department of Dermatology and Venereology, Zagreb University Hospital Center and School of Medicine, Zagreb, Croatia.
⁵ Kurume University Institute of Cutaneous Cell Biology, Kurume, Japan.
⁶ Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
⁷ Department of Dermatology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York.
⁸ Department of Dermatology at the Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
⁹ Department of Dermatology, Autoimmune Bullous Diseases Research Center, Tehran University of Medical Sciences, Tehran, Iran.
¹⁰ Department of Dermatology and Allergology, University Hospital, Philipps-Universität Marburg, Marburg, Germany.
¹¹ University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
¹² Department of Dermatology, Rabin Medical Center, Beilinson Campus, Petach Tikva, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
¹³ Department of Dermatology, University Hospital of Bern, Bern, Switzerland.
¹⁴ Department of Dermatology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
¹⁵ Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
¹⁶ Department of Dermatology, Mayo Clinic College of Medicine, Rochester, Minnesota.
¹⁷ Department of Dermatology, Faculty of Medicine, Cairo University, Cairo, Egypt.
¹⁸ Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York.
¹⁹ Department of Dermatology, School of Medicine, University of Utah, Salt Lake City, Utah.
²⁰ St. Joseph Mercy Health System, Department of Dermatology, Ann Arbor, Michigan.
²¹ Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
²² Department of Dermatology and Immunodermatology, Medical University of Warsaw, Warsaw, Poland.
²³ Department of Dermatology and Venereology, Faculty of Medicine, Akdeniz University, Antalya, Turkey.
²⁴ Department of Dermatology, Reims University Hospital, University of Champagne-Ardenne, Reims, France.
²⁵ Department of Dermatology and the Murdough Family Center for Psoriasis, University Hospitals Case Medical Center, Cleveland, Ohio.
²⁶ Department of Dermatology, Avicenne Hospital, University Paris 13, Bobigny, France.
²⁷ Department of Dermatology and Venereology, Medical Faculty, University of Medicine, Sofia, Bulgaria.
²⁸ Department of Dermatology, Department of Histology, Reference Center for Autoimmune Bullous Diseases, Avicenne Hospital, University Paris 13, Bobigny, France.
²⁹ Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia.
³⁰ Dermatology, Duke University Medical Center, Durham.
³¹ Division of Molecular Dermatology, Department of Dermatology, Paracelsus Medical University Salzburg, Salzburg, Austria.
³² First Department of Dermatology, Aristotle University, Thessaloniki, Greece.
³³ Department of Dermatovenereology, St. Anna University Hospital, Masaryk University, Brno, Czech Republic.
³⁴ Facultad de Medicina, Clínica Alemana, Santiago, Chile.
³⁵ Second Dermatology Department, Aristotle University School of Medicine, Papageorgiou General Hospital, Thessaloniki, Greece.
³⁶ Dermatology Department, School of Medicine, Karadeniz Technical University, Trabzon, Turkey.
³⁷ Department of Dermatology, University of Lubeck, Lubeck, Germany.
³⁸ Department of Dermatology, University Hospital, Marburg, Germany.
³⁹ Departamento de Dermatologia, Universidade de Sao Paulo, Sao Paulo, Brazil.
⁴⁰ Department of Dermatology, University of California, Irvine, California; Department of Biological Chemistry Cancer Center, University of California, Irvine, California; Research Institute, Institute for Immunology, University of California, Irvine, California.
⁴¹ Sheba Medical Center, Dermatology Department, Tel-Hashomer, Ramat-Gan, Israel.
⁴² Department of Immunodermatology, Istituto Dermopatico dell'Immacolata, IRCCS, Rome, Italy; Laboratory of Molecular and Cell Biology, Istituto Dermopatico dell'Immacolata, IRCCS, Rome, Italy.
⁴³ Clinica Dermatologica, Universita' Di Parma, Parma, Italy.
⁴⁴ Department of Dermatology, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
⁴⁵ St. John's Institute of Dermatology, Guy's & St. Thomas' Hospitals, London, United Kingdom.
⁴⁶ University Hospitals Leicester, Leicester Royal Infirmary, Leicester, United Kingdom.
⁴⁷ Department of Dermatology, Stanford University School of Medicine, Stanford, California; Center for Clinical Sciences Research, Palo Alto, California; Division of Dermatology, Department of Veterans Affairs Palo Alto Healthcare System, Palo Alto, California.
⁴⁸ Department of Dermatology, School of Medicine, University of California, Davis, California.
⁴⁹ Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania; Department of Dermatology at the Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: werth@pennmedicine.upenn.edu.

PMID: 29438767
PMCID: PMC7313440
DOI: 10.1016/j.jaad.2018.02.021

Diagnosis and management of pemphigus: Recommendations of an international panel of experts

Dedee F Murrell et al. J Am Acad Dermatol. 2020 Mar.

. 2020 Mar;82(3):575-585.e1.

doi: 10.1016/j.jaad.2018.02.021. Epub 2018 Feb 10.

Authors

Affiliations

¹ Department of Dermatology, St. George Hospital, University of New South Wales, Sydney, Australia. Electronic address: d.murrell@unsw.edu.au.
² Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania; Department of Dermatology at the Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
³ Department of Dermatology, Rouen University Hospital, Rouen, France.
⁴ Department of Dermatology and Venereology, Zagreb University Hospital Center and School of Medicine, Zagreb, Croatia.
⁵ Kurume University Institute of Cutaneous Cell Biology, Kurume, Japan.
⁶ Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
⁷ Department of Dermatology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York.
⁸ Department of Dermatology at the Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
⁹ Department of Dermatology, Autoimmune Bullous Diseases Research Center, Tehran University of Medical Sciences, Tehran, Iran.
¹⁰ Department of Dermatology and Allergology, University Hospital, Philipps-Universität Marburg, Marburg, Germany.
¹¹ University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
¹² Department of Dermatology, Rabin Medical Center, Beilinson Campus, Petach Tikva, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
¹³ Department of Dermatology, University Hospital of Bern, Bern, Switzerland.
¹⁴ Department of Dermatology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
¹⁵ Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
¹⁶ Department of Dermatology, Mayo Clinic College of Medicine, Rochester, Minnesota.
¹⁷ Department of Dermatology, Faculty of Medicine, Cairo University, Cairo, Egypt.
¹⁸ Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York.
¹⁹ Department of Dermatology, School of Medicine, University of Utah, Salt Lake City, Utah.
²⁰ St. Joseph Mercy Health System, Department of Dermatology, Ann Arbor, Michigan.
²¹ Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
²² Department of Dermatology and Immunodermatology, Medical University of Warsaw, Warsaw, Poland.
²³ Department of Dermatology and Venereology, Faculty of Medicine, Akdeniz University, Antalya, Turkey.
²⁴ Department of Dermatology, Reims University Hospital, University of Champagne-Ardenne, Reims, France.
²⁵ Department of Dermatology and the Murdough Family Center for Psoriasis, University Hospitals Case Medical Center, Cleveland, Ohio.
²⁶ Department of Dermatology, Avicenne Hospital, University Paris 13, Bobigny, France.
²⁷ Department of Dermatology and Venereology, Medical Faculty, University of Medicine, Sofia, Bulgaria.
²⁸ Department of Dermatology, Department of Histology, Reference Center for Autoimmune Bullous Diseases, Avicenne Hospital, University Paris 13, Bobigny, France.
²⁹ Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia.
³⁰ Dermatology, Duke University Medical Center, Durham.
³¹ Division of Molecular Dermatology, Department of Dermatology, Paracelsus Medical University Salzburg, Salzburg, Austria.
³² First Department of Dermatology, Aristotle University, Thessaloniki, Greece.
³³ Department of Dermatovenereology, St. Anna University Hospital, Masaryk University, Brno, Czech Republic.
³⁴ Facultad de Medicina, Clínica Alemana, Santiago, Chile.
³⁵ Second Dermatology Department, Aristotle University School of Medicine, Papageorgiou General Hospital, Thessaloniki, Greece.
³⁶ Dermatology Department, School of Medicine, Karadeniz Technical University, Trabzon, Turkey.
³⁷ Department of Dermatology, University of Lubeck, Lubeck, Germany.
³⁸ Department of Dermatology, University Hospital, Marburg, Germany.
³⁹ Departamento de Dermatologia, Universidade de Sao Paulo, Sao Paulo, Brazil.
⁴⁰ Department of Dermatology, University of California, Irvine, California; Department of Biological Chemistry Cancer Center, University of California, Irvine, California; Research Institute, Institute for Immunology, University of California, Irvine, California.
⁴¹ Sheba Medical Center, Dermatology Department, Tel-Hashomer, Ramat-Gan, Israel.
⁴² Department of Immunodermatology, Istituto Dermopatico dell'Immacolata, IRCCS, Rome, Italy; Laboratory of Molecular and Cell Biology, Istituto Dermopatico dell'Immacolata, IRCCS, Rome, Italy.
⁴³ Clinica Dermatologica, Universita' Di Parma, Parma, Italy.
⁴⁴ Department of Dermatology, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
⁴⁵ St. John's Institute of Dermatology, Guy's & St. Thomas' Hospitals, London, United Kingdom.
⁴⁶ University Hospitals Leicester, Leicester Royal Infirmary, Leicester, United Kingdom.
⁴⁷ Department of Dermatology, Stanford University School of Medicine, Stanford, California; Center for Clinical Sciences Research, Palo Alto, California; Division of Dermatology, Department of Veterans Affairs Palo Alto Healthcare System, Palo Alto, California.
⁴⁸ Department of Dermatology, School of Medicine, University of California, Davis, California.
⁴⁹ Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania; Department of Dermatology at the Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: werth@pennmedicine.upenn.edu.

PMID: 29438767
PMCID: PMC7313440
DOI: 10.1016/j.jaad.2018.02.021

Abstract

Background: Several European countries recently developed international diagnostic and management guidelines for pemphigus, which have been instrumental in the standardization of pemphigus management.

Objective: We now present results from a subsequent Delphi consensus to broaden the generalizability of the recommendations.

Methods: A preliminary survey, based on the European Dermatology Forum and the European Academy of Dermatology and Venereology guidelines, was sent to a panel of international experts to determine the level of consensus. The results were discussed at the International Bullous Diseases Consensus Group in March 2016 during the annual American Academy of Dermatology conference. Following the meeting, a second survey was sent to more experts to achieve greater international consensus.

Results: The 39 experts participated in the first round of the Delphi survey, and 54 experts from 21 countries completed the second round. The number of statements in the survey was reduced from 175 topics in Delphi I to 24 topics in Delphi II on the basis of Delphi results and meeting discussion.

Limitations: Each recommendation represents the majority opinion and therefore may not reflect all possible treatment options available.

Conclusions: We present here the recommendations resulting from this Delphi process. This international consensus includes intravenous CD20 inhibitors as a first-line therapy option for moderate-to-severe pemphigus.

Keywords: CD20 inhibitor; consensus; guidelines; pemphigus foliaceus; pemphigus vulgaris; treatment.

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Figures

**Fig 1.**
Diagnosis of pemphigus. Diagnosis requires clinical presentation and histopathology that are consistent with pemphigus and either a positive direct immunofluorescence (DIF) microscopy result or serologic detection of autoantibodies against epithelial cell surface antigens. *ELISA,* Enzyme-linked immunosorbent assay; *PF,* pemphigus foliaceus; *PV,* pemphigus vulgaris; *WOCBP,* women of childbearing potential.

**Fig 2.**
Treatment options. The principal objective is to promote the healing of blisters and erosions, prevent development of new lesions, and minimize serious side effects of treatment.

See this image and copyright information in PMC

Comment in

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References

1. Mimouni D, Nousari C, Cummins D, Kouba D, David M, Anhalt G. Differences and similarities among expert opinions on the diagnosis and treatment of pemphigus vulgaris. J Am Acad Dermatol. 2003;49(6):1059–1062. - PubMed
1. Venugopal S, Murrell D. Diagnosis and clinical features of pemphigus vulgaris. Immunol Allergy Clin North Am. 2012; 32(2):233–243. - PubMed
1. Joly P, Bernard P, Bedane C, Prost C, Ingen-Housz-Oro S. Pemphigus. Guidelines for the diagnosis and treatment. Centres de reference des maladies bulleuses auto-immunes. Societe Francaise de Dermatologie. Ann Dermatol Venereol. 2011;138:252–258. - PubMed
1. Committee for Guidelines for the Management of Pemphigus Disease, Amagai M, Tanikawa A, Shimizu T, et al. Japanese guidelines for the management of pemphigus. J Dermatol. 2014;41:471–486. - PubMed
1. Eming R, Sticherling M, Hofmann SC, et al. S2k guidelines for the treatment of pemphigus vulgaris/foliaceus and bullous pemphigoid. J Dtsch Dermatol Ges. 2015;13:833–844. - PubMed

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[1] Mimouni D, Nousari C, Cummins D, Kouba D, David M, Anhalt G. Differences and similarities among expert opinions on the diagnosis and treatment of pemphigus vulgaris. J Am Acad Dermatol. 2003;49(6):1059–1062. - PubMed

[2] Mimouni D, Nousari C, Cummins D, Kouba D, David M, Anhalt G. Differences and similarities among expert opinions on the diagnosis and treatment of pemphigus vulgaris. J Am Acad Dermatol. 2003;49(6):1059–1062. - PubMed

[3] Venugopal S, Murrell D. Diagnosis and clinical features of pemphigus vulgaris. Immunol Allergy Clin North Am. 2012; 32(2):233–243. - PubMed

[4] Venugopal S, Murrell D. Diagnosis and clinical features of pemphigus vulgaris. Immunol Allergy Clin North Am. 2012; 32(2):233–243. - PubMed

[5] Joly P, Bernard P, Bedane C, Prost C, Ingen-Housz-Oro S. Pemphigus. Guidelines for the diagnosis and treatment. Centres de reference des maladies bulleuses auto-immunes. Societe Francaise de Dermatologie. Ann Dermatol Venereol. 2011;138:252–258. - PubMed

[6] Joly P, Bernard P, Bedane C, Prost C, Ingen-Housz-Oro S. Pemphigus. Guidelines for the diagnosis and treatment. Centres de reference des maladies bulleuses auto-immunes. Societe Francaise de Dermatologie. Ann Dermatol Venereol. 2011;138:252–258. - PubMed

[7] Committee for Guidelines for the Management of Pemphigus Disease, Amagai M, Tanikawa A, Shimizu T, et al. Japanese guidelines for the management of pemphigus. J Dermatol. 2014;41:471–486. - PubMed

[8] Committee for Guidelines for the Management of Pemphigus Disease, Amagai M, Tanikawa A, Shimizu T, et al. Japanese guidelines for the management of pemphigus. J Dermatol. 2014;41:471–486. - PubMed

[9] Eming R, Sticherling M, Hofmann SC, et al. S2k guidelines for the treatment of pemphigus vulgaris/foliaceus and bullous pemphigoid. J Dtsch Dermatol Ges. 2015;13:833–844. - PubMed

[10] Eming R, Sticherling M, Hofmann SC, et al. S2k guidelines for the treatment of pemphigus vulgaris/foliaceus and bullous pemphigoid. J Dtsch Dermatol Ges. 2015;13:833–844. - PubMed

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Diagnosis and management of pemphigus: Recommendations of an international panel of experts

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Diagnosis and management of pemphigus: Recommendations of an international panel of experts

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