Targeted Therapy for The Treatment of Autoimmune Blistering Diseases

This article is based on an article titled “Skin Barrier and Autoimmunity—Mechanisms and Novel Therapeutic Approaches for Autoimmune Blistering Diseases of the Skin”

Original written by: Stevens et al., 2019

By: Murielle Nsiela 

The skin is divided into three layers and each layer has its function. The first layer is the skin's outermost layer, called the epidermis.[1] The skin has multiple essential functions including: regulating body temperature, protecting against UV radiation, preventing moisture loss, forming a barrier against the external environment to prevent foreign substances from entering the skin, and preventing infections. All of these functions occur in the epidermis. Hence, autoimmune blistering disease (ABD) is a group of skin disorders whereby the body’s immune system produces antibodies that attack healthy skin tissue on the epidermis layer. 

This leads to blister-like lesions visible on the skin.[2] The blisters disrupt the epidermis layer, disturbing several of its functional properties. Although autoimmune disease generally occurs in the elderly, the condition clinically occurs in different forms, making the diagnosis process difficult.[3] Autoimmune blistering diseases can be classified into four main groups: pemphigoid, pemphigus diseases and dermatitis herpetiformis.[4] Each type of autoimmune blistering disorder has specific autoantibodies that target certain antigens on the epidermis. 

There are multiple mechanisms by which autoimmune blistering diseases cause skin disruption and blistering. Therefore, the development of targeted therapies and the management of patients affected are often complex due to the frequent relapses, the number of adverse events and the lack of efficacy for some treatments.[5][6] Current treatment options mostly rely on non-specific therapies that stop the immune system from targeting the body’s skin tissue. However, this is not as effective, highlighting the importance of developing a targeted therapeutic approach.[7][8] Therefore, this article focuses on the mechanisms of developing the disease and the latest approach for developing targeted therapy for treating blistering autoimmune diseases.

The different mechanisms in developing autoimmune blistering diseases 

It has been suggested that the development of the disease is divided into three phases: the induction phase, maintenance phase and effector phase. The induction phase involves the initiation of the body producing an immune response against its tissues to the target antigen. Subsequently, the maintenance phase is a stage where there is a constant production of autoantibodies. The final phase is the effector phase whereby the body's autoantibodies cause tissue damage. In addition, autoimmune blistering diseases have also been associated with certain diabetic drugs, such as DPP-4 inhibitors.[9][10]

Targeted approach for treating autoimmune blistering diseases

The targeted system can be divided into two groups: the traditional approach and topical therapies. The table outlines the different therapeutic approaches that are currently available and some which are in the development stage.

Treatment Approach: Corticosteroids
Treatment Agent: Prednisolone
Development Stage: Standard choice of treatment (First line)
Class of autoimmune blistering disease being treated: Treats most classes of the disease including pemphigus diseases, dermatitis herpetiformis, epidermolysis bullosa acquista

Treatment Approach: Immuno-suppressant
Treatment Agent: Azathioprine
Development Stage: Used when the standard choice has failed (Second line)
Class of autoimmune blistering disease being treated: Treats most classes of the disease including pemphigus diseases and dermatitis herpetiformis

Treatment Approach: Anti-body removal
Treatment Agent: Plasma exchange
Development Stage: Used when second-line therapy has failed
Class of autoimmune blistering disease being treated: Treats dermatitis herpetiformis and epidermolysis bullosa acquista

Treatment Approach: Immunomodulatory
Treatment Agent: Vitamin D
Development Stage: In pre-clinical phase
Class of autoimmune blistering disease being treated: Treats epidermolysis bullosa acquista and pemphigus diseases

In summary, although there are treatments already available and some being under the development process for blistering autoimmune diseases, there are still unmet medical needs due to side effects and unresolved blistering that tends to remain on the skin. This can affect individuals' quality of life and increases the risk of bleeding, infections and the growth of tumours. It is crucial to have optimal healing of blisters (especially for individuals with extensive blistering of the mouth) which can affect feeding, digestion and potentially other organs. In addition, it is as important to restore the skin’s barrier function to normal; therefore, new therapies need to cover both aspects, restoration of skin barrier function and complete healing of blisters. 


  1. HSE - Skin at work: Work-related skin disease – Skin structure and function [Internet]. 2022 [cited 13 May 2022]. Available from:
  2. Autoimmune Blistering Diseases [Internet]. UCF Health. 2022 [cited 13 May 2022]. Available from: 
  3. Amber KT, Murrell DF, Schmidt E, Joly P, Borradori L. Autoimmune subepidermal bullous diseases of the skin and mucosae: clinical features, diagnosis, and management. Clin Rev Allergy Immunol. (2018) 54:26–51. 
  4. Vorobyev A, Ludwig RJ, Schmidt E. Clinical features and diagnosis of epidermolysis bullosa acquisita. Expert Rev Clin Immunol. (2017) 13:157–69. 
  5. Murrell DF. Autoimmune diseases of the skin. Immunol Allerg Clin North Am. (2012) 32:xiii–iv. 10.1016/j.iac.2012.04.015 
  6. Kasprick A, Bieber K, Ludwig RJ. Drug discovery for pemphigoid diseases. Curr Protoc Pharmacol. (2019) 84:e55. 
  7. Koga H, Prost-Squarcioni C, Iwata H, Jonkman MF, Ludwig RJ, Bieber K. Epidermolysis bullosa acquisita: the 2019 update. Front Med (Lausanne). (2018) 5:362.
  8. Kasperkiewicz M, Schmidt E, Zillikens D. Current therapy of the pemphigus group. Clin Dermatol. (2012) 30:84–94. 
  9. Kridin K, Bergman R. Association of bullous pemphigoid with dipeptidyl-peptidase 4 inhibitors in patients with diabetes: estimating the risk of the new agents and characterizing the patients. JAMA Dermatol. (2018) 154:1152–8. 
  10. Stevens N, Cowin A, Kopecki Z. Skin Barrier and Autoimmunity—Mechanisms and Novel Therapeutic Approaches for Autoimmune Blistering Diseases of the Skin. Frontiers in Immunology. 2019;10. 
  11. Tukaj S, Bieber K, Witte M, Ghorbanalipoor S, Schmidt E, Zillikens D, et al. . Calcitriol treatment ameliorates inflammation and blistering in mouse models of epidermolysis bullosa acquisita. J Invest Dermatol. (2018) 138:301–9. 
  12. Venning VA, Taghipour K, Mohd Mustapa MF, Highet AS, Kirtschig G. British Association of Dermatologists' guidelines for the management of bullous pemphigoid 2012. Br J Dermatol. (2012) 167:1200–14. 


  1. Bullous pemphigoid - Symptoms and causes [Internet]. Mayo Clinic. 2022 [cited 13 May 2022]. Available from: 
  2. Pemphigus - Symptoms and causes [Internet]. Mayo Clinic. 2022 [cited 13 May 2022]. Available from: 
  3. Epidermolysis bullosa acquisita | DermNet NZ [Internet]. 2022 [cited 13 May 2022]. Available from: 
  4. Dermatitis Herpetiformis | Celiac Disease Foundation [Internet]. Celiac Disease Foundation. 2022 [cited 13 May 2022]. Available from: 
  5. NCI Dictionary of Cancer Terms [Internet]. National Cancer Institute. 2022 [cited 13 May 2022]. Available from: 
  6. NCI Dictionary of Cancer Terms [Internet]. National Cancer Institute. 2022 [cited 13 May 2022]. Available from: 
This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

Get our health newsletter

Get daily health and wellness advice from our medical team.
Your privacy is important to us. Any information you provide to this website may be placed by us on our servers. If you do not agree do not provide the information.

Murielle Nsiela

MSc Graduate in Medical Engineering - Bachelor's degree, Pharmaceutical Science, Keele University, Staffordshire UK

MSc in Medical Engineering Design, Keele University Modules included: Advanced engineering applications, Engineering for medical applications report, Bioreactors and Growth environment, Creative engineering design, Experimental research methodology and research projects

BSc (Hons) Pharmaceutical Science, Technology and Business, Keele University Modules included: Core topics in pharmaceutical science, Laboratory studies - tabletting and liposomes report, applied Pharmaceutical Science 2, Pharmaceutical research project

Leave a Reply

Your email address will not be published. Required fields are marked * presents all health information in line with our terms and conditions. It is essential to understand that the medical information available on our platform is not intended to substitute the relationship between a patient and their physician or doctor, as well as any medical guidance they offer. Always consult with a healthcare professional before making any decisions based on the information found on our website.
Klarity is a citizen-centric health data management platform that enables citizens to securely access, control and share their own health data. Klarity Health Library aims to provide clear and evidence-based health and wellness related informative articles. 
Klarity / Managed Self Ltd
Alum House
5 Alum Chine Road
Westbourne Bournemouth BH4 8DT
VAT Number: 362 5758 74
Company Number: 10696687

Phone Number:

 +44 20 3239 9818