Achalasia May Be Associated With Salivary Varicella Zoster Virus DNA

Varicella zoster (chickenpox) virus, illustration. The virus consists of a lipid membrane envelope with glycoproteins, a protective capsid holding the nucleic acid. VZV is a virus from the Herpesviridae family, the causative agent of chickenpox and shingles. In severe cases VZV may cause complications, such as pneumonia and encephalitis.
Researchers investigated whether varicella zoster virus is linked to achalasia.

Varicella zoster virus (VZV) may have a causal role in achalasia, researchers reported in Gastroenterology.

The study included 9 men and 6 women (age range, 18.0-81.0 years) with the following achalasia phenotypes: type I (n=3), type II (n=8), and type III (n=4). No patients had received a varicella vaccine. The investigators also obtained saliva from 2 healthy men and 3 healthy women (aged 70.5-81.0 years).

A total of 12 patients (80%) had detectable salivary VZV DNA, while no control participants had detectable salivary VZV (P <.004). In addition, 13 patients (87%) had transcripts encoding VZV late gene products (open reading frame [ORF] 40 or ORF67) in surgically excised esophageal tissue, similar to the proportion with salivary VZV DNA.

Transcripts encoding VZV gene products were observed in the esophagus of all but 1 patient with salivary VZV DNA, and salivary VZV DNA was observed in all but 1 patient in whom transcripts were detected. The proportion of patients who had detectable VZV DNA in resected esophageal tissue was not significantly different from that of VZV transcripts (7 patients; 44%).

The study authors also found immunoreactivity of gE in cells, confirmed as neurons with antibodies to b3-tubulin, as well as immunoreactivities of gH and ORF40p in esophageal neurons identified with antibodies to peripherin. Many of the nerve fiber bundles had bulbous swellings and strictures, and multinucleated giant cells were also found.

The findings suggest that reactivation of VZV from latency in esophageal neurons may lead to chronic VZV infection that impairs the functional regulation of esophageal motility and control of the lower esophageal sphincter in achalasia, according to the investigators.

“The current study has made the hypothesis that VZV plays a causal role in achalasia plausible, but further evidence of causality is needed,” stated the researchers. “Given the large number of ganglia in the body that harbor latent VZV, it seems unlikely that a stochastic process could lead to reactivation exclusively in esophageal neurons; therefore, an additional, possibly genetic, factor is probably involved.”


Naik RD, Vaezi MF, Gershon AA, et al. Association of achalasia with active varicella zoster virus infection of the esophagus. Gastroenterol. Published online April 28, 2021. doi: 10.1053/j.gastro.2021.04.057