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Apocytolysis, a proposed mechanism of blister formation in epidermolysis bullosa simplex

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Abstract

Epidermolysis bullosa simplex (EBS) is caused by keratin 5 and 14 mutations. In vitro studies revealed that susceptibility to caspase 8-mediated apoptosis is increased in keratin 14 mutated keratinocytes. We aimed to investigate the role of apoptotic/inflammatory pathways in the pathogenesis of EBS by studying the expression of caspase 8 in lesional and non-lesional skin compared to controls. Ten EBS patients proved by electron microscopy and five age and sex matched healthy volunteers were the subjects of this case control study. Caspase 8 expression was studied by immunohistochemistry. Caspase 8 expression in lesional and non-lesional skin was significantly higher than in controls (p < 0.01 and p = 0.013, respectively) with no significant difference between lesional and non-lesional skin. Lesional skin had significantly higher density of dermal infiltrate (p = 0.02). Caspase 8 expression in lesional skin was significantly correlated with the extent of the disease, rate of blistering, and density of dermal infiltrate (r = 0.835; p = 0.003, r = 0.889; p = 0.001 and r = 0.776; p = 0.008 respectively). Caspase 8-mediated apoptosis is an integral component of an orchestra of events conducted by keratin mutation. Apo-cytolysis is proposed to better describe the mechanism of blistering in EBS. The small number of cases is a limitation.

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Abbreviations

EBS:

Epidermolysis bullosa simplex

EB:

Epidermolysis bullosa

K:

Keratin

TNF-α:

Tumor necrosis factor alpha

TNFR1:

Tumor necrosis factor receptor type 1

TRADD:

Tumor necrosis factor receptor type1-associated DEATH domain

NFJS:

Naegeli–Franceschetti–Jadassohn syndrome

IL:

Interleukin

K5−/− :

Keratin 5 null

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Acknowledgments

We thank all the residents of the Dermatology Department for helping us in the collection of cases. We also thank Tarek Diab, MD, consultant of tropical medicine, Theodor Bilharz Research Institute, Cairo, Egypt for performing the statistical work.

Conflict of interest

The authors have no conflicts of interest to declare.

Ethical standard

The research was approved by the Department Ethical Committee.

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Authors and Affiliations

  1. Dermatology Department (Dermatopathology Unit), Faculty of Medicine, Cairo University, Kasr Al Aini Street, Cairo, 11562, Egypt

    Marwa S. El-Hawary, Mona R. E. Abdel-Halim & Heba A. Abdelkader

  2. Histology Department, Faculty of Medicine, Cairo University, Cairo, Egypt

    Safinaz S. Sayed

Authors
  1. Marwa S. El-Hawary
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  2. Mona R. E. Abdel-Halim
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  3. Safinaz S. Sayed
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  4. Heba A. Abdelkader
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Correspondence to Mona R. E. Abdel-Halim.

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El-Hawary, M.S., Abdel-Halim, M.R.E., Sayed, S.S. et al. Apocytolysis, a proposed mechanism of blister formation in epidermolysis bullosa simplex. Arch Dermatol Res 307, 371–377 (2015). https://doi.org/10.1007/s00403-015-1560-4

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  • DOI: https://doi.org/10.1007/s00403-015-1560-4

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