What is the pathophysiology of diphtheria?

Updated: Jan 18, 2019
  • Author: Bruce M Lo, MD, MBA, CPE, RDMS, FACEP, FAAEM, FACHE; Chief Editor: Jeter (Jay) Pritchard Taylor, III, MD  more...
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C diphtheria adheres to mucosal epithelial cells where the exotoxin, released by endosomes, causes a localized inflammatory reaction followed by tissue destruction and necrosis. The toxin is made of two joined proteins. [2] The B fragment binds to a receptor on the surface of the susceptible host cell, which proteolytically cleaves the membrane lipid layer enabling segment A to enter. [1] Molecularly, it is suggested that the cellular susceptibility is also due to diphthamide modification, dependent on human leukocyte antigen (HLA) types predisposing to more severe infection. The diphthamide molecule is present in all eukaryotic organisms and is located on a histidine residue of the translation elongation factor 2 (eEF2). eEF2 is responsible for the modification of this histidine residue and is the target for the diphtheria toxin (DT).

Fragment A inhibits an amino acid transfer from RNA translocase to the ribosomal amino acid chain, thus inhibiting protein synthesis is required for normal host cell functioning. [1] DT causes a catalytic transfer of NAD to diphthamide, which inactivates the elongation factor, resulting in the inactivation eEF2, which results in protein synthesis blockage and subsequent cell death. [9, 2]

Local tissue destruction enables the toxin to be carried lymphatically and hematologically to other parts of the body. Elaboration of the diphtheria toxin may affect distant organs such as the myocardium, kidneys, and nervous system. Nontoxigenic strains tend to produce less severe infections; however, since widespread vaccination, case reports of nontoxigenic strains of C diphtheria causing invasive disease have been documented. [1]

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