Today, physicians around the world are diagnosing an increasing number of patients with coeliac disease. Does this mean the condition is becoming more common, or is it a result of increased awareness? CARA BOATSWAIN looks at coeliac disease through the ages.
When it comes to autoimmune conditions, coeliac disease is considered by researchers to be the one best understood. “In coeliac disease, we are lucky enough to know the trigger, so we know what is harmful,” explains paediatric gastroenterologist Dr Alina Popp. “There is no other autoimmune disease where the trigger is so well defined, where we can prevent or reverse the damage that has been done.”
Today we know that the gluten proteins found in wheat, barley and rye provoke an abnormal immune response in people with coeliac disease. Before we knew a strict gluten-free diet was necessary, coeliac disease was considered terminal.
Ancient Greek Physician Arateus of Cappadocia reported the first known cases of coeliac disease in 250 AD. In his writings, he describes incidents of diarrhoea, weight loss and general malaise in patients, especially children and young adults. He used the Greek word “koiliakos,” (belly or abdomen) to refer to these patients. When Francis Adams translated the writings into English in 1856, he adopted the word “coeliac” as an English derivative of “koiliakos” to describe these patients.
It wasn’t until 1888 that the first modern description of coeliac disease was recorded. Samuel Gee, a physician at the Children’s Hospital on Great Ormond Street in London, noted that the condition could occur at any age but was most common in children between one and five. Gee was also the first to comment that diet might play a role in treatment. “If the patient can be cured at all, it must be by means of diet,” he wrote.
In 1908, American physician Christian Archibald Herter published a book on children with coeliac disease titled, Infantalism from Chronic Intestinal Infection. In addition to highlighting his patients’ failure to thrive, Herter notes that the children he studied tolerated fats better than carbohydrates.
In reference to the significant contribution made by these researchers, coeliac disease was known as Gee-Herter syndrome until mid-way through the 20th century.
Bananas are delicious and packed with nutrients, but did you know they were once considered a treatment for coeliac disease? In 1927 American paediatrician Dr Sidney Haas published a paper titled, “The Value of the Banana in the Treatment of Celiac Disease.
Dr Sidney Haas thought he had discovered a remedy for the illness in the 1920s: the banana diet. The diet was effective for people with coeliac disease because it (unintentionally) did not contain gluten.[/caption]
In the paper, Haas reports on 10 patients diagnosed with coeliac disease. Eight patients follow a strict diet of bananas and milk, supplemented with broth, gelatine and a little meat; the other two patients continue to eat as usual. According to Haas, the eight following the banana diet were ‘cured.’ Sadly the two patients not treated by the diet passed away.
A War-Time Discovery
In the lead-up to World War Two (WW2), doctors treating coeliac disease tried various diets on their patients. Carbohydrate, milk and even mussel diets have been recorded in studies from that time.
Dutch paediatrician, Willem Dicke began trialling a wheat-free diet as a treatment for coeliac disease in the 1930s. “He was quite clear in his conversation with me that it was a young mother’s statement that her coeliac child’s rash improved if she removed bread from the diet that first alerted his interest. And that was when he was a paediatrician in the Hague in 1936,” recalled gastroenterologist Sir Christopher Booth in a letter to the British Medical Journal in 1989.
Dicke’s first report was published in 1941 and addressed the food shortages in Europe due to the war. “In recent literature it is stated that the diet of Haas (Banana-diet) and Fanconi (fruit and vegetables) gives the best results in the treatment of patients suffering from coeliac disease. At present (WW2) these items are not available,” he wrote. “Therefore, I give a simple diet, which is helping these children at this time of rationing. The diet should not contain any bread or rusks. A hot meal twice a day is also well tolerated. The third meal can be sweet or sour porridge (without any wheat flour).”
As diets returned to normal after the conclusion of WW2 and bread was again readily available, Dicke became certain that cereals were putting the lives of his young patients at risk. He believed eating fewer cereals and more unique food products (including tulip bulbs) improved patient outcomes.
The Fabulous 50s and 60s
As the world was recovering from war, researchers made discoveries that significantly contributed to a better understanding of coeliac disease. In 1954 UK physician Dr John W Paulley, described villous atrophy for the first time. He was able to conclusively show the loss of normal villi by studying biopsies taken from coeliac patients who were undergoing abdominal surgery.
1956, paediatric gastroenterologist Dr Margo Shiner made a significant development. She devised a quick, safe and non-invasive biopsy technique to examine the small intestine of patients diagnosed with coeliac disease. The method became even easier to perform a few years later when American Lieutenant Colonel Crosby invented a capsule that could attach to the inserted flexible tube.
It was Paulley’s discovery combined with Shiner’s technique that enabled doctors to diagnose coeliac disease and distinguish it from other conditions producing similar gastrointestinal symptoms. However, it wasn’t until 1960 that the exact cause of the damage was identified.
Australian physician Dr Charlotte Anderson published a paper in 1960 that established the gluten component of wheat (and other grains) as the cause of the villous atrophy present in coeliac disease. Her study proved that the villi would return to normal once patients adopted a gluten-free diet. During the 60s, villous atrophy was thought to be caused by a number of conditions (including a milk protein allergy), so for a coeliac disease diagnosis to be made, doctors needed to prove that gluten was the cause.
The 60s concluded with experts from the European Society for Pediatric Gastroenterology establishing the first diagnostic criteria for coeliac disease. It came to be known as the Interlaken Criteria due to the location of the meeting in the Swiss town of Interlaken. For the next 20 years, this criteria were universally accepted as the diagnostic standard.
According to the criteria, doctors were required to conduct three small bowel biopsies to diagnose coeliac disease. The initial biopsy was necessary to determine the extent of damage before implementing a gluten-free diet, and the patient’s villi must be completely flattened to meet the Interlaken criteria.
After adopting a gluten-free diet, a second biopsy was performed, and the villi needed to show signs of repair to continue to fulfill the Interlaken criteria.
Finally, the patient reintroduced gluten before having a third biopsy, which had to demonstrate that the villi had deteriorated again, confirming gluten as the trigger. Only then could a diagnosis of coeliac disease be established.
Reviewing The Criteria
As with any disease criteria, exceptions to the rules can exist. In 1977, 53 European Society for Pediatric Gastroenterology members completed a survey reviewing elements of the Interlarken Criteria that had been established for almost 10 years.
The respondents questioned the requirement for completely flattened villi at the initial biopsy, noting that some patients presented with damaged, but not completely flat, villi. It was another 10 years before the need for the third biopsy and the re-introduction of gluten was questioned.
The diagnosis criteria established at Interlaken in 1969 also overlooked the important discovery of anti-gliadin antibodies made by German researchers in 1964. Gliadin, one of the proteins found in wheat, contains gluten polymers. The researchers discovered that people with coeliac disease produce anti-gliadin antibodies (AGA) to attack the protein.
The subsequent big discovery came in 1984 when antiendomysium antibodies were discovered. Italian researchers showed that by relying on strict clinical and laboratory criteria, coeliac disease could be diagnosed in 95 percent of cases with just one biopsy. As a result, changes to the diagnostic guidelines were made in 1985.
The Link To Other Diseases
During the 1980s the link between coeliac disease and other conditions became apparent. Links were found to other autoimmune conditions, such as Type 1 Diabetes. The link between coeliac disease and the skin condition dermatitis herpetiformis was also made.
Today, it is widely understood that coeliac disease can present with a range of symptoms and sometimes none at all. However, in the 1980s, researchers were only just recognising this and started questioning the classical gastrointestinal symptoms associated with the disease.
The 80s concluded with a discovery by immunologist Ludvig Sollid and his team that narrowed the genetic risk factors associated with coeliac disease. The researchers from Oslo were the first to identify the two versions of histocompatibility leukocyte antigen (HLA) as the primary genetic risk factors of the disease.
Blood screening for coeliac disease
As the world welcomed the final decade of the 20th Century, a greater understanding of coeliac disease had been achieved, but there was still much to learn. Coeliac disease was now widely accepted as an autoimmune condition associated with HLA gene structure (DQ2 or DQ8).
In 1997, German gastroenterologist Detlef Schuppan linked tissue transglutaminase (tTG) to the immune response that triggers coeliac disease. He found that the transglutaminase enzyme released by the small intestine when gluten passes the intestinal wall was actually impaired in people with coeliac disease. From this, he developed a blood-screening test to diagnose the disease.
Zonulin and Leaky Gut
In 2010 Dr Alessio Fasano discovered zonulin while trying to develop a vaccine for cholera. Zonulin is a protein that regulates the permeability of the intestine. Fasano and his team found increased zonulin levels in patients with coeliac disease. “Zonulin works like the traffic conductor or the gatekeeper of our body’s tissues,” explains Fasano. “Our largest gateway is the intestine with its billions of cells. Zonulin opens the spaces between cells allowing some substances to pass through while keeping harmful bacteria and toxins out.”
While strict adherence to the gluten-free diet remains the only treatment option for people diagnosed with coeliac disease, the future looks bright. A number of therapies are currently being developed and tested with the hope of making life easier for those medically diagnosed with the condition.