Double Trouble

Double Trouble

Cassidy Myhre

Atopic Dermatitis (AD) isn’t just about dealing with itchy, painful, cracked skin. It’s an inflammatory skin disorder associated with many other allergic conditions, as well as non-atopic entities like T1D. AD is a heterogeneous disease, meaning there are multiple factors involved in pathogenesis, including gene interactions, environmental factors, impaired barrier skin integrity and immune deregulation.  

Research comparing these different interactions found:

  • The most significant factor associated with genetic variants for AD were mutations in Filaggrin (FLG), a key protein in the differentiation of the epidermis and formation of the skin barrier.
  • FLG mutations lead to epidermal barrier defects, increasing skin permeability and subsequent allergic sensitization, which promotes the Th2 inflammatory response.
  • Certain genes associated with AD have been connected to innate immune system pathways. 
  • The structure of the extracellular matrix is important in the development of AD and in the integrity of the skin barrier and collagen formation.
  • Epigenetic regulation plays a key role in the development of AD and other allergic diseases. 

While it has been determined that epidermal barrier defects promote Th2 immunologic abnormalities, it has also been proposed that the barrier abnormality is not just a secondary phenomenon, but the “driver” of disease activity in AD. Here’s why:

  • The extent of the abnormalities in the permeability barrier correlate with the severity of disease phenotype in AD. 
  • Clinically-uninvolved skin sites and skin cleared of inflammation for less than five years display barrier abnormalities.
  • Emollient therapy comprises effective ancillary therapy for AD.
  • Specific lipid replacement therapy, which targets the lipid abnormalities that account for the barrier abnormality, corrects the barrier abnormality and ameliorates inflammation in AD.

These discoveries provide insight towards new developments in genetics and epigenetics technology that will offer opportunities to improve the diagnosis of AD and develop more efficient therapy methods.

Sources

  • Martin, Maria J, et al. “Genetics and Epigenetics of Atopic Dermatitis: An Updated Systematic Review.” Genes, MDPI, 18 Apr. 2020, www.ncbi.nlm.nih.gov/pmc/articles/PMC7231115/. 
  • PM;, Elias. “Therapeutic Implications of a Barrier-Based Pathogenesis of Atopic Dermatitis.” Annals of Dermatology, U.S. National Library of Medicine, pubmed.ncbi.nlm.nih.gov/20711259/. 

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