The third original observation

Littlewood JM, Crollick AJ, Richards IDG. Childhood coeliac disease is disappearing. Lancet 1980; ii: 1359.

During the Seventies paediatric consultants in the Yorkshire Region increasingly referred children to Seacroft for our biochemist’s (Mr Alan Steel) reliable sweat tests and my paediatric jejunal biopsy service which I had started in the late Sixties. When I returned to Leeds from Great Ormond Street in 1964 , having observed the new iontophoresis sweat tests there, I persuaded our Prof. Craig to approve the purchase of Gibson and Cooke sweat testing apparatus. Alan Steel used this equipment to perform very accurate sweat test from 1964 that soon became a well-established service that most paediatricians from Leeds and surrounding general hospitals used for their patients.

Paedaitric intestins biopsy capsule

Per oral jejunal biopsy was the other new major gastrointestinal investigation. Prof. John Walker Smith regards per oral intestinal biopsy as being the basis of paediatric gastroenterology developing as a speciality. In 1968 I obtained a paediatric sized Crosby intestinal biopsy capsule (Watson capsule) and after a steep learning curve, started a paediatric jejunal biopsy service; this facility soon attracted referrals from paediatricians in the region to confirm or exclude coeliac disease (CD) in their children. We eventually changed to the twin port Kilby modification of the Crosby capsule to use one specimen for histology and the other for biochemical (disaccharide) estimation (Kilby, 1976).

Figures : Small bowel mucosa obtained by jejunal biopsy. on the left -normal mucosa, centre – subtotal villous atrophy of coeliac disease, right – biopsy capsule in the small bowel

Margot Shiner
Charlotte Anderson

The characteristic histological small bowel appearance of subtotal villous atrophy of gluten induced coeliac disease was first identified in 1954 by Paulley, a physician in Ipswich, in laparotomy specimens from four adults with idiopathic steatorrhoea (coeliac disease). In 1957 Margot Shiner was the first clinician to obtain specimens by per oral small bowel biopsy from an 8-year old child; soon a series of small bowel biopsies in children was reported by Charlotte Anderson.
In contrast to the subtotal villous atrophy in coeliac disease, in people with CF the intestinal villi are of normal height – in some children with CF whom we biopsied the intestinal villi appeared to be even taller than normal.

Paulley J W. Observations on the aetiology of idiopathic steatorrhoea. Jejunal and lymph node biopsies. BMJ 1954; 173:1318-1321. [PubMed]
Sakula J, Shiner M. Coeliac disease with atrophy of the small intestine mucosa. Lancet 1957; ii: 876-877. [PubMed]
Anderson CM. Histological changes in the duodenal mucosa in coeliac disease. Reversibility during treatment with a wheat gluten free diet. Arch Dis Child 1960; 35:419-427. [PubMed]
Kilby A. Pediatric small intestinal biopsy capsule with two ports. Gut 1976; 17:158-15

In this venture I had the invaluable help of my friend and colleague Dr. Sidney Smith, our paediatric radiologist, who was responsible for the rapid X-ray screening of the capsule into the duodenum. Sydney was a good friend of paediatrics and helped us with many studies and clinical problems over the years. Dr Mike Mason, again avery helpful pathologist from St James’s, provided histology reports for many years.

Avril Crollick

Later Dr. Avril Crollick was appointed as my Clinical Assistant and she eventually performed many of the biopsies until I started using the paediatric endoscope for the purpose during the Eighties. The ability to obtain jejunal mucosa for histological and biochemical examination from children was a relatively recent but one of the really major advances in the Seventies.

Jejunal biopsy with a paediatric sized Crosby capsule was a relatively new technique in the Sixties. Initially Sir Wilfred Sheldon (the senior consultant paediatrician at Great Ormond Street) and a senior registrar at GOS at the time, Dr. Eddie Tempany, (who was subsequently Professor of Paediatrics in Dublin), considered the investigation to be “outside the scope of routine investigations in children” due to the increased difficulty and risk of perforation reported in small children.

Eddie tempany

It is true there were a number of reports of intestinal perforation. On one occasion, when I was working at GOS and observing Eddie performing a biopsy, the capsule could not be retrieved until the next day. So I admit it was with some trepidation that I started the jejunal biopsy service at Seacroft.  However, as with many practical procedures when restricted to a few experienced individuals complications were less likely.

Subsequently, elsewhere, I have published in detail our experience with over 1000 jejunal biopsies and 108 children with coeliac disease in my friend Professor Peter Howdle’s book (Howdle PD, 1997). Peter, was a major friend of paediatrics in St James’s, eventually succeeded Monty Losowsky as professor  of medicine at St James’s. He was an excellent and helpful colleague in many areas of gastroenterology where his expertise and kind approach benefited many of our young patients including those with cystic fibrosis

Peter Howdle

However, my delay in starting jejunal biopsies in Leeds was mainly related to the fact that Sir Wilfred Sheldon and our Professor Stuart Craig were old friends and, as I was then a new lecturer in Craig’s department, he would not approve of my performing jejunal biopsies. So I had to wait until 1968 when I became an NHS consultant.  Over the next 25 years we had no serious complications from over 1000 jejunal biopsies in children aged down to 3 months.

Incidentally, from our experience with performing jejunal biopsies for many paediatric colleagues around the Yorkshire region, over 11 years we observed that coeliac disease appeared to be becoming less common in young children (Littlewood et al, 1980). (see also pages below on original observations for details)

Sheldon W, Tempany E. Small intestine per oral biopsy in coeliac children. Gut 1966; 7:481-489.
Howdle PD, Littlewood JM, Firth J, Losowsky MS. Routine colonoscopy service. Arch Dis Child 1984; 59:790-3
Walker-Smith JA. Historic notes in pediatric gastroenterology. J Pediatr Gastroenterol Nutr 1997; 25: 316
Littlewood JM. Coeliac disease in childhood. In: Howdle PD (Ed.). Clinical Gastroenterology. International Practice and Research. Bailliere l, London. 1995; 9: 295-328.
Littlewood JM, Crollick AJ, Richards IDG. Childhood coeliac disease is disappearing. Lancet 1980; ii: 1359.

As I have observed on a number of occasions, the more patients one sees and carefully evaluates and treats, the more likely is one to observe some new phenomenon. This occurred in relation to the falling incidence of coeliac disease in children in our region.

Gerald Richards

Avril Crollick and I were co-authors of this letter to the Lancet and we sought the advice of Professor Gerald Richards, the distinguished head of of the Department of Community Medicine and General Practice at Leeds University.

So for the past 11 years we had been providing a jejunal biopsy service for paediatricians in Leeds and many of the surrounding hospitals. During this period 113 children had been diagnosed as having CD. Approximately half of these children were being followed up in my outpatients first at Seacroft then from 1980 at St James’s. The remainder were under the care of their referring consultant paediatricians. There was no doubt about the diagnosis of these children. All had mucosal biopsy changes compatible with CD i.e. either subtotal villous atrophy or severe partial villous atrophy (figure above); all had a definite positive response to the withdrawal of gluten from their diet. Most of those with a normal jejunal biopsy after two years were challenged with gluten powder (5-15 g per day for 3 months) after which a third biopsy was performed to demonstrate a deterioration of the intestinal mucosa. Those who failed to show any deterioration (5%) were not included in the series. Children who were less than 2 years at the time of diagnosis were usually challenged with gluten in the third or fourth year to confirm the permanence of the gluten intolerance by deterioration of the jejunal mucosa.

Sue Wolfe
Anita MacDonald

In the dietary treatment and investigation of these children were were fortunate to have the long term close collaboration of a number of expert paediatric dietitians particularly Sue Wolfe and Anita MacDonald at St James’s – both of whom achieved an international reputation.

We had noted previously that over the past three years fewer young patients had been diagnosed as having coeliac disease. The number children by year of birth is shown in the figure. The rising incidence from 1958 o 1968 reflects increasing referral of patients by colleagues sometimes for confirmation of the diagnosis some years after the initial presentation and treatment. Since we introduced the jejunal biopsy service in 1968the number of sasses diagnosed remained reasonably constant until 1975.

The fall in the number of young CD patients we observed occurred without major changes in referral habits of our colleagues. There was no reduction in the number of biopsies done annually in our unit (around 55) over the past ten years. Furthermore there had been a steady increase in the number of children referred with a variety of other gastrointestinal problems.

Paediatric colleagues in the Yorkshire region who do not refer children to us for biopsy confirm our impression that fewer infants have been diagnosed as having CD in the past two years. Enquires amongst adult gastroenterologists have failed to reveal any notable reduction in the number of adults with CD. Although no definite prevalence figures for CD in the Yorkshire region were available, hospital admissions for CD at all ages at all ages had fallen dramatically fro 588 in 1978 to 102 in 1979. As many of these patients were children it may reflect the falling incidence of CD in infants and children. With the increasing use of diagnostic gluten challenges and repeat biopsies one might have even expected the admission rate to increase rather than this clear cut fall. So for these reasons we believed that we were observing a fall in the incidence of coeliac disease in children in our region.

What was the cause of this fall in incidence? A number of changes in infant feeding practices that occurred around 1971 and may have been relevant to the observed fall in incidence of CD. In 1974 advice from the DHSS on infant feeding advocated later introduction of cereals, avoidance of hyper solar feeds and encouragement f breast feeding. Since then there hd been a definite increase in the number of women breast feeding their infants and also some delay (to around 3 months) in the introduction of cereals. Furthermore a number of infant cereals were now gluten free.

We had recently reviewed the clinical aspects of the children in our series. Of 89 in whom the early feeding history was known, 72 had only had cows’s milk preparations and only five had been breast fed for more than a month. Most had had cereals introduced before the age of 3 months. Cow’s milk protein intolerance had been shown by Walker-Smith to follow gastroenteritis causing secondary damage to the mucosa and secondary lactose intolerance. It was our impression that CD may well be initiated by an attack of gastroenteritis in infancy. However, our virologist Dr Peter Hambling assured us there there was no change in virological factors since the early seventies that could have been responsible for the fall incidence of CD.

So we concluded that the incidence of CD was falling in childhood and that this was directly related to infant feeding practice occurring in the mid 1970s. The increased prevalence of breast feeding , the consequent reduction in gastroenteritisand /or early immunological challenge from cow’s milk protein and the later introduction of gluten into the diet all seemed to be factors.

Subsequently our first report of the falling incidence of CD from the mid 1970s was confirmed by many other centres in the UK (for example Challacombe & Baylis 1980; Logan et al, 1986; Stevens et al, 1987) including Prof John Walker Smith’s unit at the QE Hospital for Children in London (Kelley D A et al, 1989); also in a number of reports from abroad. One exception was Sweden where there had been an increase from 1.7 per 1000 before 1982 to to 3.52 per 1000 in 1987. A sudden increase between 1983 and 1985 was attributed to the Swedish manufacturers doubling the amount of gluten in infant cereal preparations.

Logan RFA, Rifkiind EA, Buttil A et al. Prevalence and ‘incidence’ of celiac disease in Edinburgh and the Lothian region of Scotland. Gastroenterology 1986;90:334-342 Logan RFA Descriptive epidemiology of celiac disease. Frontiers of Gastroenterology Research, 1992;19:1-14. Stevens F M, Egan-Mitchell, Cryan E et al 1987 Decreasing incidence of coeliac disease Arch Dis Child 1987;62:465-468. Maki M, Holm K. Incidence and prevalence of coeliac disease in Tampere. Acta Paediatr Scand 1980;79:980-982 Kelly DA, Phillips AD, Elliott EJ et al. Rise and fall of coeliac disease. Arch Dis Child 1989;64:1157-1160 Cavell B, Senhammar L, Ascher H et al. Incidence of childhood coeliac disease in Sweden. Results of a national study. Acta Paediatr Scand 1992; 81:589-592.

At the time of writing in 2019, searching PubMed for “Incidence of childhood coeliac disease” retrieves no less than 287 references; the majority recognise our letter to the Lancet in December 1980 as the first report of this occurrence – the third significant observation!

Addendum: For some reason the reference to our original Lancet letter on Medline does not include our (the authors’) names, only the journal reference. I have no idea why this occurred except a letter from David Challacombe was published a short time after ours and I presume there must have been some confusion there – apparently not unusual at that journal at the time. It is interesting that I had discussed our findings only a short time before the additional letter from David Challacombe was published following ours in the Lancet!

Littlewood JM, Crollick AJ, Richards IDG. Childhood coeliac disease is disappearing. Lancet 1980; ii: 1359.

Challacombe DN, Baylis JM. Childhood coeliac disease is disappering. Lancet 1980;ii:1360