Crohn's disease is a near-universal ailment from hell.
It owes its name to two European father and son gastroenterologists - Archibald Crohn (1791-1881) and Burrill Crohn (1884?-1983). The fundamental cause of Crohn's disease (CD) remains unknown since Burrill Crohn described its medical manifestations in 1932.
Cigarette smoke, or smoking, seems to be the sole etiological suspect of CD, although other environmental, dietary or bacterial agents are strongly suspected. Yersinia pestis causes plague in humans, rodents and many other mammalian species. They are transmitted from rat to rat and from rat to humans by the rat flea Xenopsylla. The most popular causal theory is that the body's immune system reacts to a virus or bacterium by causing ongoing inflammation in the intestine. People with the disease tend to have abnormalities of the immune system, but physicians do not know whether these aberrations are a cause or an effect of the disease. (It is not caused by emotional distress.)
A mutated gene called CARD15 occurred during plague outbreaks in the Middle Ages. Scientists suggest that carriers of the gene mutation have a selective advantage against Y. pestis. The link between bacterial components and Crohn's disease was lent strong support by the discovery that mutations in CARD15 - a gene involved in innate immunity - predispose people to the disease.
Crohn's disease affects men and women equally and seems to run in some families. Most CD cases begin in patients under 30 years of age and peak between ages 14 and 24. Suspicion arises in patients with obstruction or obstructive symptoms in the gut, with unexplained arthritis, erythema nodosum - sudden formation of painful nodes on the outer portions of the lower extremities. Those lesions are self-limiting but tend to recur, marked by arthralgia (joint pain), fever and stunted growth in kids. The commonest symptoms of Crohn's disease are abdominal pain (often in the lower right area), diarrhea, rectal bleeding and weight loss. CD also may cause sores or ulcers that tunnel through the affected area into surrounding tissues, such as inflammation in eyes or mouth, kidney or gallstones, bladder, skin or vagina. Gastrointestinal cancer of the colon and intestine is the leading cause of death in Crohn's disease. Seventy percent of patients will require excising affected regions of diseased intestine, surgery that might be done more than once. The changing pattern of CD cannot always tell when a treatment has helped. Predicting when a remission may occur, or when symptoms will recur, is not possible.
Corticosteroids Vs. Gut Inflammation
Some patients take corticosteroids to control inflammation. The drugs are the most effective for active Crohn's disease, but they can cause serious side effects, including greater susceptibility to infection. The FDA has approved the drug infliximab (Remicade, Centocor Inc.) to treat moderate to severe CD.
"In addition to the temporal coincidence in Crohn's disease," observed French gastroenterologist Jean-Pierre Hugot, "a geographical relationship can also be noted: yersinia are more common in northern countries. This finding can be related to the North-South gradient seen for Crohn's disease in Europe and America. Finally, seasonal variations have been reported for both yersinia infections and relapses of Crohn's disease - and that finding warrants further investigation. Crohn's disease is common in Europe and North America," Hugot noted, "where incidence has risen in the second half of the 20th century. Thus," he continued, "environmental factors probably related to the modern occidental way of life might have a role in Crohn's disease.
"Many crucial changes occurred with respect to food, housing, transport, leisure and clothing," he continued. "In view of the observation that Crohn's disease is linked to a familial, environmental risk factor related to modern western lifestyles, domestic hygiene, diet and infectious agents, we propose a specific candidate for the development of Crohn's disease: the refrigerator."
Surprise Crohn Etiology: The Refrigerator
"The first refrigerating machines," he went on, "were built around 1875, and during the first parts of the 20th century, refrigeration methods were more widespread in the U.S. than in other countries. By 1937, 49 percent of Americans had a refrigerator. In Sweden, just over half of families had a refrigerator developed by Electrolux. Although difficult to define precisely, population-based data suggest that the increase in prevalence of Crohn's disease was in the 1940s in the U.S. and in the 1950s or before in Sweden. If our hypothesis is valid," Hugot proposed, "it points to the existence of bacteria capable of surviving or developing at low temperatures. Such psychotrophic bacteria have optimum growth at temperatures higher than 30 C but are able to grow, at a slower rate, at temperatures minus 1 C and 10 C - i.e., the temperature inside refrigerators. Yersinia species are commonly found in humans and in foods such as milk, beef, pork, chicken, sausages, hamburgers, cheese and lettuce."
Hugot is lead author of an article in The Lancet, dated Dec. 13, 2003, and titled "Crohn's disease: the cold chain hypothesis." The paper noted: "Crohn's disease lesions occur predominantly where there is a high density of lymphoid follicles in the small bowel where the follicles form Peyer's patches (on the intestinal wall where they facilitate antigens)."
Summing up, Hugot made the point that, "Additional features are relevant for Crohn's disease. Yersinia produces a urease enzyme essential in gastritis formation, a finding that could explain the high frequency of enhanced gastritis in CD.
"We propose a link," Hugot volunteered. "Our model provides structures and unified explanation, based on biological evidence. However, much more testing is needed before our model can be retained or discarded. It cannot elucidate the clinical heterogeneity seen between patients with Crohn's disease. The cold chain has produced many benefits for western societies, including the prevention of enteric infections, allowing more people to have a well-balanced diet, and the economic development of agriculture and fishing. These advantages clearly outweigh the putative risks discussed here, and, in the absence of experimental evidence, practical conclusions should not be drawn.
"Finally," he concluded, "antibiotics active against Yersinia species, such as ciprofloxacin [the Cipro anti-anthrax antibiotic], have a limited effect in Crohn's disease."