key: cord-0038313-tyfube0t authors: Gorbach, Sherwood L. title: Viral Infections and Inflammatory Bowel Disease date: 2020-02-14 journal: Gastroenterology DOI: 10.1016/s0016-5085(82)80147-9 sha: 352897cf2af8db2328f0d0ba28cb974805d646e5 doc_id: 38313 cord_uid: tyfube0t nan When our Pax Intestinum is disturbed, our bowels react in a few stereotyped patterns. They can increase grinding or decrease grinding; they can cramp or they can snort from either end. Considering the enormous variety of potential insults-bacteria, viruses, fungi, parasites, hormones, toxins, poisons, heavy metals, and various intrinsic diseases-it is not surprising that the clinical features of so many diseases overlap. This problem is highlighted by the provocative article in this issue by Gebhard et al. (1) . They studied patients with established inflammatory bowel disease and asked how many relapses were associated with viral infections, specifically rotavirus, Norwalk virus, and adenovirus. Because diarrhea is the common pathway for viral enteritis and exacerbations of inflammatory bowel disease (IBD), neither the investigators nor the patients could distinguish between these processes by clinical features. It turned out that only 10% of relapses (5 of 56) in IBD patients could be explained by a documented viral infection. When the eight viral infections among the IBD patients were examined specifically, it was noted that five in fact were associated temporally with clinical relapse. Compared with our knowledge of bacteria in the intestine, viruses remain in relative obscurity. With-in the normal microflora, over 400 types of anaerobic bacteria, as well as many aerobic bacteria, have already been identified. Many bacterial pathogens have been catalogued, and studies of their epidemiology, natural habitat, incubation period, and clinical expression in volunteers have been made. By contrast, we know almost nothing about the viral flora of the intestinal tract. The list of common viral pathogens is rather small, and most of these have defied in vitro cultivation, so their biology is largely unexplored. Rotavirus is perhaps the best studied of the viruses that invade the human intestine. Its clinical impact is largely in children under the age of 2 years. Although older children and adults may excrete the virus, it is usually as an asymptomatic carrier, but it may occasionally produce mild symptoms. Hence, this virus would be an uncommon cause of exacerbation of IBD in adults. The Norwalk agent has been described mainly in epidemics of "winter vomiting disease," as in Norwalk, Ohio, which contributed its name to the agent. It can cause endemic gastroenteritis as well. Other viruses are known to cause gastroenteritis. The classic enteroviruses such as ECHO virus and Coxsackievirus are rather rare causes of intestinal infections; they tend to cause diarrhea in association with other organ involvement such as respiratory, central nervous system, and myocardial. Cytomegalovirus (CMV) has been recognized as the cause of diarrhea in some patients. Intestinal x-rays have shown punctate ulcerations in the stomach and small intestine, especially the ileum. Calicivirus has been identified by electronmicroscopy in several outbreaks of gastroenteritis among children. Certain structural features bear resemblance to the Norwalk agent, although this point remains disputed. There have been reports of astrovirus and coronavirus causing infections in humans, but because these viruses cannot be propagated in tissue culture or in experimental animals, a feature common to many of the viral pathogens of diarrheal disease, there is a paucity of information on their overall significance. Even using the best methodology, as was used in the study of Gebhard et aI., it is obvious that many infections that are presumably viral in origin cannot be related to a specific pathogen. Indeed, it is estimated that two-thirds of epidemics of gastroenteritis that are clinically and epidemiologically viral in origin cannot be diagnosed by the available techniques. In endemic diarrheal disease, ~30%-50% of cases are not assigned to a specific pathogen, and the majority of these infections are probably caused by as yet undiscovered viral pathogens. Thus, because 10% of exacerbations of IBD were recognized with the available techniques, and because only one-third of putative viral infections can be diagnosed by these methods, one could estimate that up to 30% of such exacerbations could be caused by viruses, were it possible to identify all such agents. It has been suggested that Salmonella infections are more common in patients with IBD. Although there have been no reports to implicate Campylobacter and Shigella infections as causes of exacerbation of IBD, these patients are not immune to such common pathogens. In New England, we have seen a great increase in locally acquired Giardia infections, even in such pristine beauty spots as the White Mountains. Patients with IBD receive antimicrobial drugs for a variety of reasons, just like many other members of our society. These drugs can trigger an attack of antibiotic-associated diarrhea caused by Clostridium difticile. Even sulfonamides, such as contained in salazopyrine, can cause this condition. We should not forget that attacks of diarrhea, EDITORIALS 1319 presumably infectious in origin, are among the commonest ills of mankind. Diarrhea is one of the major complaints that brings patients to a doctor's office or causes them to lose time from school or work. It is the estimate of most experts that these diarrhea attacks are caused, in the main, by viral agents as yet unrecognized. When a patient with established IBD has an exacerbation of diarrhea, we tend to blame the underlying disease without looking for an intercurrent cause. Some of these attacks could be treated by a specific drug, if the pathogen was known, i.e., the bacterial pathogens and C. difticile. Viral agents cannot be treated at the present time; however, we might be willing to temporize with relatively mild symptomatic therapies before going on to steroids and antimetabolites, if we knew the process was intrinsically self-limited. Whether caused by a viral infection or "spontaneous," the clinical features of an exacerbation of IBD are similar. It is clear that even the injured intestine has a stereotyped range of responses. A viral infection apparently can even trigger a prolonged exacerbation of symptoms. Herein may lie one of the secrets of IBD itself, for it is possible that all exacerbations of IBD are exogenous insults, caused by a virus or perhaps another pathogen, which are inflicted on an abnormal bowel, unable to cope with the environmental stresses to which we are all subjected. If we could understand how the healthy bowel repairs itself after a viral or bacterial infection, we might understand why the patient with IBD goes on with grinding diarrhea and associated symptoms after a seemingly trivial event. 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