“Appendicitis may be triggered by a viral infection,” reported the Daily Mail. The newspaper said that the same researchers who made this claim also suggested that non-perforated appendicitis (where the appendix has not burst) may not always warrant surgery. This news story is based on a study of hospital discharge records for patients with influenza, rotavirus and appendicitis over a 36-year period in the US. The number of viral infections and perforated and non-perforated cases of appendicitis were analysed to see if they had similar enough patterns of prevalence to suggest an association between the two. Although influenza and appendicitis showed similar year-on-year prevalence patterns, there were no similarities in the seasonal variations of the two diseases. This is not enough evidence to suggest that appendicitis is caused by a virus. There is also not enough evidence to suggest that untreated non-perforated appendicitis can resolve itself. At present, it is not known why some people’s appendixes burst while others’ do not, and the research does not give any reason to change standard treatments for appendicitis. Where did the story come from? This research was carried out by Dr Adam Alder and colleagues from the University of Texas. The study was published in the (peer-reviewed) medical journal: Archives of Surgery. Sources of funding were not given. In addition to commenting on the data on viral infections and appendicitis, the Daily Mail says other evidence from the study suggests that appendicitis does not always warrant surgery. This claim is based on the finding that year-on-year trends for the numbers of people with a burst appendix do not match the pattern of cases where the appendix has not burst. However, this difference was not explored and no evidence was given to suggest that untreated non-perforated appendicitis can resolve itself. At present, it is not known why some people’s appendixes burst while others’ do not, and the research does not give any reason to change standard treatments for appendicitis. What kind of research was this? This is an epidemiological study examining trends in hospital discharge data for factors that may be associated with appendicitis. The researchers say that the cause of appendicitis is not known, but the most popular theory is that the appendix is initially obstructed by a hard mass of faecal matter or enlarged lymph tissues. This blockage stops the mucus defence systems from working properly, which leads to the infection that causes appendicitis. The researchers suggest that viruses may be involved in this process, and that many viral infections are associated with lymph tissue enlargement or they can cause ulcerations resulting in bacterial infection. Their research investigated whether there is a link between rates of selected infectious diseases (such as influenza, rotavirus and intestinal infections) and rates of appendicitis. This type of observational study can look for patterns in large amounts of data. These patterns can then be used to suggest plausible associations. However, it cannot establish whether these associated factors cause disease. What did the research involve? The researchers used data from the National Hospital Discharge Survey in the US, from 1970 to 2006. This database contains hospital discharge information for about 300,000 patients that receive hospital treatment annually. This sample is designed to represent the rest of the 35 million people who receive hospital treatment in the US each year. The database contains information on some inpatient surgical procedures that are performed, such as appendectomies, and data on diseases that have been diagnosed, such as influenza and rotavirus rates. The researchers compared data for flu infections between outpatients and inpatients to ensure that inpatient influenza rates could be used to estimate flu rates in the general population. The researchers then looked at whether the incidence of both perforated (burst) and non-perforated appendicitis paralleled the rates of flu and rotavirus between seasons and over the 36-year survey period. What were the basic results? There was a similar year-on-year, parallel pattern of non-perforating appendicitis and influenza. Both decreased in frequency from 1970 to 1995, after which both increased in frequency. This pattern did not appear for rotavirus infections and non-perforating appendicitis, nor between flu and perforating appendicitis. There was also no parallel pattern of incidence between non-perforating and perforating appendicitis, which surprised the researchers. When the seasonal incidence of all the diseases across one year were examined, appendicitis was found to occur throughout the year, with a small increase in the summer months. Rotavirus infections occurred throughout the year and were more common in winter. Flu tended to occur in the winter, and was less common in the summer months. How did the researchers interpret the results? The researchers conclude that “neither influenza nor rotavirus are likely proximate causes of appendicitis, given the lack of a seasonal relationship between these diseases”. Despite this, the year-on-year parallel patterns between influenza and appendicitis indicate that it is possible that the diseases share “common etiologic determinates, pathogenetic mechanisms or environmental factors that similarly affect their incidence.” They also conclude that the, “incidence of perforated appendicitis did not correlate with non-perforating appendicitis or with the other infectious diseases”. They say this suggests that the causes of perforated appendicitis are more complex than simply delayed treatment of acute appendicitis. Conclusion This study has a few limitations: This type of epidemiological study can highlight factors (such as viral infections) that may be associated with a disease, but cannot determine whether such factors cause the disease. The researchers estimated the prevalence of influenza from hospital records. Although they showed that this mirrored outpatient influenza rates, it may not accurately represent everyone who suffered from flu but did not consult a doctor. The researchers limited the intestinal infections that were studied to rotavirus because this was the only one with enough data for analysis. In addition, they did not study subclinical viral infections (that have either no outward symptoms or symptoms that required hospital admissions). This research found some evidence of a similar incidence pattern of flu and appendicitis over the last 36 years in the US, but this is not enough to suggest that a virus causes appendicitis. One finding that merits further research is the different incidence patterns between perforated appendicitis and non-perforating appendicitis.