Adenovirus-Associated Acute Appendicitis: An Under-Recognized Relationship?

Abstract

Acute appendicitis (AA) is one of the most common causes of a surgical abdomen worldwide, occurring most frequently in those age 10 to 29 years. Adenovirus (ADV) is a rare but reported cause of AA in children and a well-recognized cause of intussusception in infants and young children. Annually, about 36,000 basic military trainees (BMTs) undergo initial training at Joint Base San Antonio Lackland, Texas. Before reintroduction of the ADV 4/7 vaccine in November 2011, one-third of BMTs developed an adenoviral upper respiratory tract infection (URI) during the 8.5 weeks of training. We hypothesized that ADV may be a common cause of AA in the BMT population given their young age and high incidence of adenoviral URIs. The objective of this study was to determine the frequency with which ADV, cytomegalovirus (CMV), Epstein-Barr virus (EBV), and enterovirus were associated with AA in a population of young adults. This study was a retrospective review of patient charts and existing pathological tissue specimens of all BMTs who underwent appendectomy at the Wilford Hall Medical Center from January 1, 2003, to August 31, 2011. Pathological tissue samples from 112 BMTs were assayed by quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC) for viral targets. ADV DNA was detected in 16 of 112 samples (14%) via qPCR: ADV 4 in 13 cases, ADV B14 in 1 case, and nontypable ADV in 2 cases. IHC was positive in only the ADV B14 case (0.9%). All cases were negative for CMV, EBV, and enterovirus. By using qPCR, this study demonstrated an association between ADV and AA higher than has been previously reported: ADV was detected in 14% of AA cases in this series versus in only 0.23% of AA cases in previous studies (p < 0.01). There was no evidence of CMV, EBV, or enterovirus association with AA in this study. Comparison of qPCR to IHC shows that histologic analysis may overlook evidence of ADV in appendiceal tissue: qPCR is significantly more sensitive than light microscopy and IHC for detecting ADV in this setting. Because ADV 4 was detected in 81% of those with positive qPCR, the recently licensed live oral ADV vaccine might be useful for primary prevention against AA. Prospective studies evaluating young adults presenting with AA for evidence of infection with ADV are needed to determine if a causal relationship exists.