A Brief History of Celiac Disease Stefano Guandalini, MD
Long, long ago, man was a simple hunter/gatherer. His diet consisted of fruits, nuts, perhaps tubers and the occasional feast of meat. But eventually, he learned to cultivate plants, and the agricultural revolution began. Soon, the hunter/gatherer way of life was replaced by domestication of crops and animals.
As habits changed, some unanticipated problems arose. The human gut had developed, over more than 2 million years, into a sophisticated organ that could tolerate food antigens that were staples of the human diet over hundreds of thousands of years. But how would it react to new antigens, suddenly appearing in the diet? The agricultural revolution of the Neolithic period generated a whole battery of food antigens previously unknown to man, including protein from cow, goat, and donkey milk, as well as birds’ eggs and cereals. Most individuals were able to adapt. Among those who could not, food intolerances appeared and Celiac Disease was born.
Some 8,000 years after its onset, celiac disease was identified and named. A clever
Greek physician named Aretaeus of Cappadocia, living in the first century AD, wrote about “The Coeliac Affection.” In fact, he named it “koiliakos” after the Greek word “koelia” (abdomen). His description: “If the stomach be irretentive of the food and if it pass through undigested and crude, and nothing ascends into the body, we call such persons Coeliacs”.
Another 17 centuries went by, and in the early 19th century a Dr. Mathew Baillie, probably unaware of Aretaeus, published his observations on a chronic diarrheal disorder of adults causing malnutrition and characterized by a gas-distended abdomen. He even went on to suggest dietetic treatment, writing: “ Some patients have appeared to derive considerable advantage from living almost entirely upon rice.” Baillie’s observations, however, went practically unnoticed, and it was for the English doctor Samuel Gee, a leading authority in pediatric diseases, to take full credit for the modern description of celiac disease some 75 years later, when he gave a lecture to medical students on the “Celiac Affection,” the milestone description of this disorder in modern times.
Like Baillie, Gee sensed that “if the patient can be cured at all, it must be by means of diet.” He added that “the allowance of farinaceous food must be small”, and also described “a child who was fed upon a quart of the best Dutch mussels daily, throve wonderfully, but relapsed when the season for mussels was over; next season he could not be prevailed upon to take them.” Thus he documents the improvement following the introduction of a gluten-free diet, and the relapse after reintroduction of gluten.
As the decades passed, there was still no clue as to what could be causing Celiac Disease and no hint (in spite of autopsies frequently performed given the high mortality rate) of the damage to the intestinal mucosa. Yet some of the present-day findings, which we tend to consider as recent advances, were indeed well known long ago, including that Celiac Disease could be present without diarrhea, the protective role of breast-feeding in the development and severity of Celiac Disease, only recently documented, and the increased incidence in families, particularly twins.
In the 1920s a new dietetic treatment erupted on the scene and for decades established itself as the cornerstone of therapy: The Banana Diet. In 1924 Sidney Haas described his successful treatment of eight children whom he had diagnosed with Celiac Disease. Based on his previous success in treating a case of anorexia with a banana diet, he elected to try to experiment with the same diet in these eight children who were also anorexic. He published ten cases, eight of them treated (“clinically cured”) with the banana diet, whilst the two untreated died. This paper encountered enormous success and for decades and the banana diet enjoyed wide popularity. Indeed it benefited a large number of Celiac children and probably prevented many deaths. The diet specifically excluded bread, crackers, potatoes, and all cereals, and it’s easy to argue that its success was based on the elimination of gluten containing grains.
Haas was very proud of his insight that carbohydrates were the culprit and he was highly resistant to other viewpoints, no matter how well documented. Indeed, even as late as forty years later, well after Dicke, a Dutch pediatrician, had convincingly shown that wheat protein, not starch, was the only culprit, Haas still insisted that with his banana diet “all patients are cured by the specific carbohydrate diet, a cure which is permanent without relapse.”
The breakthrough that Haas chose to downplay was to change forever our view of Celiac Disease. Dicke had noticed that during bread shortages in the Netherlands caused by World War II, children with Celiac Disease improved. He also saw that when Allied planes dropped bread into the Netherlands, they quickly deteriorated. A few years later, working with others, he produced a series of seminal papers, documenting for the first time the role that gluten from wheat and rye plays in Celiac Disease.
The next major breakthrough came in the mid-50s, when Margot Shiner described a new jejunal biopsy apparatus with which she successfully reached and biopsied the distal duodenum. This – and the development of the less cumbersome capsule developed shortly after by the American Lieutenant Colonel Crosby -- finally allowed doctors to link the disease with a specific, recognizable pattern of damage to the proximal small intestinal mucosa.
Thus, at the dawn of the 60’s we had three important elements: the knowledge that gluten is the triggering agent for Celiac Disease; the notion that there was a remarkable and easy identifiable mucosal lesion; and finally the availability of an instrument to obtain biopsies and begin to unravel the mystery of Celiac Disease pathogenesis.
In the mid to late 60’s, it had become clear that Celiac Disease could be diagnosed with the Jejunal Biopsy showing atrophy of the villi. However, since that lesion could have other causes, the medical community urged doctors not to diagnose Celiac Disease until it could be proven that gluten was indeed the cause of the mucosal atrophy.
The steps were manifold: First, a complete clinical remission on a gluten-free diet, followed by the documentation of the normalization of the lesion, and finally by its recurrence once gluten was reintroduced into the diet. These criteria were formalized in 1969 by a panel of experts in the newly born European Society for Pediatric Gastroenterology (today ESPGHAN) as the “Interlaken Criteria” which for over 20 years served worldwide as the accepted diagnostic standard.
The Interlaken Criteria, however, overlooked an important discovery made a few years earlier: that Celiac children presented in their blood antibodies caused by the ingestion of gluten. The first category to be discovered were the anti-gliadin antibodies, detected and reported by Berger in 1964. Seven years later Seah et al. identified for the first time not an anti-food protein, but an actual auto-antibody in the serum of Celiac children: the antireticulins, although it took, however, several years before their diagnostic utility was fully appreciated.
During the 1980’s it became increasingly clear that Celiac Disease could be associated with other conditions, mostly autoimmune disorders such as type 1 diabetes, but also some syndromes such as Down. It was also apparent that Celiac Disease was changing patterns of presentation, becoming less an intestinal disorder, and more a variety of extra-intestinal symptoms and signs.
In the late 80’s, a large multicenter Italian study demonstrated that by relying on strict clinical and laboratoristic criteria, a correct diagnosis of Celiac Disease could be reached in 95% of cases by limiting to the one initial biopsy, and new diagnostic guidelines were published in 1990 by ESPGHAN, guidelines that stand to this day.
After 1990, Celiac Disease was increasingly accepted as an example of an autoimmune disease, associated with a specific gene (either DQ2 or DQ8) and the missing autoantigen was finally identified in the enzyme “tissue transglutaminase”. At long last, there was universal acceptance that Celiac Disease is an autoimmune condition whose trigger (gluten) and autoantigen (tissue transglutaminase) are known.
