Abstract
Pemphigus consists of a group of rare and severe autoimmune blistering diseases mediated by pathogenic autoantibodies mainly directed against two desmosomal adhesion proteins, desmoglein (Dsg)1 and Dsg3 (also known as DG1 and DG3), which are present in the skin and surface-close mucosae. The binding of autoantibodies to Dsg proteins induces a separation of neighbouring keratinocytes, in a process known as acantholysis. The two main pemphigus variants are pemphigus vulgaris, which often originates with painful oral erosions, and pemphigus foliaceus, which is characterised by exclusive skin lesions. Pemphigus is diagnosed on the basis of either IgG or complement component 3 deposits (or both) at the keratinocyte cell membrane, detected by direct immunofluorescence microscopy of a perilesional biopsy, with serum anti-Dsg1 or anti-Dsg3 antibodies (or both) detected by ELISA. Corticosteroids are the therapeutic mainstay, which have recently been complemented by the anti-CD20 antibody rituximab in moderate and severe disease. Rituximab induces complete remission off therapy in 90% of patients, despite rapid tapering of corticosteroids, thus allowing for a major corticosteroid-sparing effect and a halved number of adverse events related to corticosteroids.
| Original language | English |
|---|---|
| Journal | The Lancet |
| Volume | 394 |
| Issue number | 10201 |
| Pages (from-to) | 882-894 |
| Number of pages | 13 |
| ISSN | 0140-6736 |
| DOIs | |
| Publication status | Published - 07.09.2019 |
Funding
ES reports personal fees from Roche, grants from the German Research Foundation and Euroimmun, and grants and personal fees from Fresenius Medical Care, Biotest, Union Chimique Belge, and argenx, during the conduct of the Review. ES also reports grants and personal fees from Novartis, TxCell, True North Therapeutics, Incyte, and Amryt Pharma, and personal fees from Genetech, outside of the submitted work. PJ reports personal fees from Principia Biopharma, argenx, Lilly, Novartis, Abbvie, Amgen, and Uriage, personal fees and non-financial support from Roche, Janssen, Bristol-Myers Squibb, and Pierre Fabre, outside of the submitted work. MK declares no competing interests. No authors within the past 3 years had stocks or shares, equity of a relevant company, a contract of employment or a named position on a company board. No organisation other than The Lancet has asked the authors to write, be named on, or submit the paper. This Seminar is dedicated to Marcel F Jonkman, Groningen, Netherlands, who contributed enormously to the field of research on pemphigus and who passed away at the height of his career after a short and severe illness. We miss his vast clinical knowledge, sharp intellect, clear concepts, and strong beliefs in scientific discussions. This work was supported by the German Research Foundation under Germany's Excellence Strategy (grant number EXC 2167 ). We acknowledge researchers who have contributed to this field whose work was not cited directly but through review articles because of space limitation. We thank Stephanie Goletz, Florian Heck, Sabrina Tofern, and Marina Kongsbak-Reim for their help with the immunofluorescence and histopathological photographs, and Carolin Mahlerwein for the graphical design of figure 2 .
Research Areas and Centers
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)
