About Epidermolysis Bullosa


What Causes EBS?

Epidermolysis bullosa simplex (EBS) is a genetic keratin disorder which involves the formation of keratin proteins and their polymerization into keratin intermediate filaments (KIFs). The formation of these KIFs within the keratinocytes (epidermal or upper layer skin cells) is important for cell shape and structural support.

The most commonly involved genes for EBS are KRT5 and KRT14 which make the proteins keratin 5 and 14.1,2 EBS is typically inherited in an autosomal dominant fashion (where one bad gene causes the disease). Autosomal recessive inheritance is possible but is extremely rare. For the KRT5 and KRT14 genes, both alleles (one from each parent) are expressed, generating both wild type (“healthy”) and mutant (“unhealthy”) keratins. The combination of mutant and wild type keratins creates mechanically unstable KIFs.3-5

Imagine making a net out of thick rope (wild type) and string (mutant). If we pull-on or hang weight from the net, the rope will hold but the string will break causing the net to collapse into a ball of rope and broken string. Stress (pulling) on these KIF “nets” causes them to collapse into keratin aggregates (balled up or broken string). Breaking and collapse of these KIF “nets” causes damaged keratinocyte cells to die. Dying cells then cause inflammation, leading to pain and itch, and more damaged keratinocytes die creating the epicenter for a blister to form.

References arrow-up arrow-down

  1. Mariath LM, Santin JT, Frantz JA, Doriqui MJR, Schuler-Faccini L, Kiszewski AE. Genotype-phenotype correlations on epidermolysis bullosa with congenital absence of skin: A comprehensive review. Clin Genet. 2021;99(1):29-41. doi:10.1111/cge.13792
  2. Fuchs E, Coulombe P, Cheng J, et al. Genetic bases of epidermolysis bullosa simplex and epidermolytic hyperkeratosis. J Invest Dermatol. 1994;103(5 Suppl):25S-30S. doi:10.1111/1523-1747.ep12398924
  3. Chamcheu JC, Lorié EP, Akgul B, et al. Characterization of immortalized human epidermolysis bullosa simplex (KRT5) cell lines: Trimethylamine N-oxide protects the keratin cytoskeleton against disruptive stress condition. J Dermatol Sci. 2009;53(3):198-206. doi:10.1016/j.jdermsci.2008.11.003
  4. Spörrer M, Prochnicki A, Tölle RC, et al. Treatment of keratinocytes with 4-phenylbutyrate in epidermolysis bullosa: Lessons for therapies in keratin disorders. EBioMedicine. 2019;44:502-515. doi:10.1016/j.ebiom.2019.04.062
  5. Anton-Lamprecht I, Schnyder UW. Epidermolysis bullosa herpetiformis Dowling-Meara. Report of a case and pathomorphogenesis. Dermatologica. 1982;164(4):221-235.