I just started learning about atopic dermatitis (AD), a chronic inflammatory skin disease that occurs in approximately 17% of children. I came across this genetic disorder in my research for my honors thesis because stress plays a role in its onset and severity. AD is characterized by rashes that arise from bacteria and viruses. Individuals with AD cannot safely be vaccinated against smallpox with vaccine virus (VV) because this could give rise to an adverse skin reaction called eczema vaccinatum. Therefore, researchers have been trying to figure out how to clinically prevent this from happening.
Patients with AD have a compromised immune response to the bacteria and viruses that cause rashes. This partially occurs because AD individuals have a decreased expression of macrophage inflammatory protein 3α (MIP-3α), an important chemokine that recruits Langerhans cells (a type of antigen-presenting cell). Therefore, this chemokine helps kill pathogens in the epidermis. Byung et al. (2007) collected skin biopsies from normal subjects and from patients with AD and psoriasis. They found that MIP-3α gene expression was 50% lower in AD skin than in psoriasis skin. This suggests that patients with AD don’t have enough MIP-3α to prevent a disseminated VV infection. Also, they found that cytokines from a certain type of T helper cell, called TH2, down-regulate MIP-3α gene expression. The authors propose that increasing MIP-3α or neutralizing TH2 cytokines could help against eczema vaccinatum.
Furthermore, Howell, Streib and Leung (2007) researched a type of antimicrobial peptide called human β-defensin (HBD)-3. Infection with VV induced the expression of HBD-3 in keratinocytes. Similar to the previous study, these authors suggest that a shortage of HBD-3 in AD patients makes them more susceptible to systemic VV infection after smallpox vaccination.
I don’t know about you, but oftentimes I take normally-functioning skin for granted. Because normal levels of MIP-3α and HBD-3 strengthen our barrier against pathogens, I hope that our growing understanding of the immune response to VV will give rise to new therapies to alleviate AD symptoms and prevent eczema vaccinatum.
Byung, E.K. et al. (2007). Macrophage inflammatory protein 3α deficiency in atopic dermatitis skin and role in innate immune response to vaccinia virus. Journal of Allergy and Clinical Immunology, 119(2), 457-463.
Howell, M.D., Streib, J.E., & Leung, D.Y.M. (2007). Antiviral activity of human β-defensin 3 against vaccinia virus. Journal of Allergy and Clinical Immunology, 119(4), 1022-1025.
Is eczema vaccinatum really a big concern for many people, it is a good reason to not get vaccines from deadly diseases? I have eczema and have lived with it my whole life and it doesn’t interrupt my life at all. Also I read an article that stated that Eczema Vaccinatum isn’t common and that there are no confirmed cases in the United States that getting the vaccine caused ev (Vellozzi). I guess I am just curious as to how serious this disease is. Would your proposed research help other skin diseases as well? There are a lot of skin diseases out there and if this one cure could help a lot of them it would be really good research that could potentially help a lot of people.
ReplyDeleteVellozzi, C., etal. (2005). Generalized Vaccinia, Progressive Vaccinia, and Eczema Vaccinatum Are Rare following Smallpox (Vaccinia) Vaccination: United States Surveillance, 2003. Clinical Infectious Diseases, 41(5), 689-697. Retrieved from EBSCOhost.