, Volume 78, Issue 15, pp 1527–1548 | Cite as

Targeted Therapies for Autoimmune Bullous Diseases: Current Status

  • Kyle T. Amber
  • Roberto Maglie
  • Farzan Solimani
  • Rüdiger Eming
  • Michael Hertl
Leading Article


Autoimmune bullous skin disorders are rare but meaningful chronic inflammatory diseases, many of which had a poor or devastating prognosis prior to the advent of immunosuppressive drugs such as systemic corticosteroids, which down-regulate the immune pathogenesis in these disorders. Glucocorticoids and adjuvant immunosuppressive drugs have been of major benefit for the fast control of most of these disorders, but their long-term use is limited by major side effects such as blood cytopenia, osteoporosis, diabetes mellitus, hypertension, and gastrointestinal ulcers. In recent years, major efforts were made to identify key elements in the pathogenesis of autoimmune bullous disorders, leading to the identification of their autoantigens, which are mainly located in desmosomes (pemphigus) and the basement membrane zone (pemphigoids). In the majority of cases, immunoglobulin G, and to a lesser extent, immunoglobulin A autoantibodies directed against distinct cutaneous adhesion molecules are directly responsible for the loss of cell-cell and cell-basement membrane adhesion, which is clinically related to the formation of blisters and/or erosions of the skin and mucous membranes. We describe and discuss novel therapeutic strategies that directly interfere with the production and regulation of pathogenic autoantibodies (rituximab), their catabolism (intravenous immunoglobulins), and their presence in the circulation and extravascular tissues such as the skin (immunoadsorption), leading to a significant amelioration of disease. Moreover, we show that these novel therapies have pleiotropic effects on various proinflammatory cells and cytokines. Recent studies in bullous pemphigoid suggest that targeting of immunoglobulin E autoantibodies (omalizumab) may be also beneficial. In summary, the introduction of targeted therapies in pemphigus and pemphigoid holds major promise because of the high efficacy and fewer side effects compared with conventional global immunosuppressive therapy.


Compliance with Ethical Standards


The preparation of this review was funded by grants from the German Research Foundation (Deutsche Forschungsgemeinschaft; He 1602/13-1 to Michael Hertl and FOR 2497 PEGASUS to Rüdiger Eming, and Michael Hertl; BD LSRFortessa: INST 160/666-1 FUGG).

Conflict of interest

Kyle T. Amber, Roberto Maglie, and Farzan Solimani have no conflicts of interest that are directly relevant to the contents of this article. Michael Hertl and Rüdiger Eming have been speakers for and have received unrestricted grants from Fresenius and Biotest. Michael Hertl has been an advisor to Roche Inc.


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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Department of DermatologyUniversity of Illinois at ChicagoChicagoUSA
  2. 2.Department of DermatologyPhilipps UniversityMarburgGermany
  3. 3.Department of Surgery and Translational Medicine, Section of DermatologyUniversity of FlorenceFlorenceItaly

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