Stories and lessons from thirty years as a clinical paediatrician

“Experiential learning is the process of making meaning from direct experience i.e. learning from experience”

Sir William Osler, the famous Canadian physician and one of the four founders of the Johns Hopkins Hospital in Baltimore, observed    “Medicine is to be learned by experience; and is not an inheritance; it cannot be revealed. Learn to see, learn to hear, learn to feel, learn to smell, and know that by practice alone can you become expert”.   

Detailed clinical evaluation is certainly essential in paediatrics to identify clinical problems and recognise areas where answers are required. As Dr. William Waring of New Orleans observed in relation to cystic fibrosis, “clinical research comes naturally as a result of the questions that arise from patient observations”.  This was exactly my experience. I recall, as a young tutor in paediatrics in the early Sixties sitting in  my office in the department in Blundell Street behind the Leeds Infirmary, wondering just what I should research on. However, as clinical experience increases, areas where management is unsatisfactory are identified and prompt a search for improvement. This is precisely what happened in my own clinic in relation to a number of conditions affecting children, particularly those with cystic fibrosis. Again it was the experience of seeing many children with a particular problem which then prompted research. 

During my years as a consultant it became increasingly apparent that experience was of central importance to becoming an effective clinical consultant.  So there follows a description of a number of clinical situations where lessons were learned.    Some of the solutions to the medical problems I will describe may seem obvious in hindsight, but I can assure you most did not appear so before the diagnosis was eventually made!  Following the eventual solution of most of these problems, it is unlikely, but not impossible, that one would be slow to make the diagnosis again.

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Dr.Peter Howdle
Prof. Monty Losowsky

I hope the following short clinical stories will prove of some interest – I certainly learned from the children, their problems and their parents.   Those readers who “stay the course” of these memoirs will note that as well as dedicated to clinical history and physical examination of the patient, I have always been keen on investigations be they the familiar blood counts and electrolytes etc but also new investigative techniques as they became available.  Hence I started small intestinal (jejunal) biopsies in 1968 (self taught) and upper gastrointestinal fibreoptic endoscopies in the early Eighties – the latter after tuition from my friend Professor Monty Losowsky who also taught me liver biopsy with a fine Menghini needle. Dr (subsequently Professor) Peter Howdle, then Senior Lecturer in Monty’s department,  from the late Seventies became a quite brilliant colonoscopist and developed a paediatric colonoscopy service (figure) working in our paediatric day our unit managed very efficiently by Nurse Jeanette Firth. I managed and regularly performed flexible sigmoidoscopies but never mastered full colonoscopies. 

Apparently in 1977 Monty Losowsky asked Peter Howdle to develop a colonoscopy service. It was predicted by experienced trainers that it would take about 50 colonoscopies before the colonoscopist could reliably reach the caecum. The hand-written record Peter kept shows he managed this in only 35 examinations (from A History of Specialities in Leeds Teaching Hospitals NHS Trust 1767-2018

Paediatric colonoscopy by Dr Peter Howdle in our day paediatric day unit at St James

Howdle P D, Littlewood J M,Firth J, Losowsky M S. Routine colonoscopy service. Arch Dis Child 1984;59:790-793.

So undoubtedly having my main base in St James University Hospital from 1980 in close proximity to the Monty Losowsky’s University Department with frequent contact with the many experts in that and many other departments in the hospital, was a major factor in the development of my paediatric service both with respect to gastroenterology and cystic fibrosis. 

A hazard of old houses

Early in the Sixties a comatose convulsing small child was admitted to the paediatric ward of the Leeds General Infirmary.  There was evidence of raised intracranial pressure and in view of the possibility of an intracranial tumour we sought the opinion of an experienced neurosurgeon; he also considered it was likely she had some form of intracranial tumour.  However, during the course of the early investigations, the haematology laboratory reported there  was a suggestion from the blood films that the red blood cells showed an abnormality known as punctate basophilia – a characteristic finding in lead poisoning and a number of other blood disorders  where numerous basophilic stained granules are present in some of the red blood cells (figure).  Certainly the clinical picture would do for lead encephalopathy.

Punctate basophilia of the red blood cells in lead poisoning 

So the long bones were X-rayed. The ends of the long bones did appear rather dense but we could not be sure if they were abnormal (figure).  The neurosurgeons did not consider that lead poisoning was a likely cause and virtually implied they were ready to operate when we had finished searching for obscure explanations for the child’s condition!  However, in view of the punctate basophilia the laboratory had reported, the paediatric team considered lead poisoning as a definite possibility to the extent of even requesting the opinion of a consultant radiologist in the middle of the night to decide if the long bones were abnormally dense as would be the case in chronic lead poisoning. He kindly came in and agreed that the  bones were rather denser than normal, supporting the diagnosis of lead poisoning (figure) .   

After all this day and night activity, if only we had X-rayed the abdomen we would have seen the radio opaque flecks of lead paint in the colon (figure).  Eventually, with treatment for the lead poisoning, the child slowly recovered consciousness over many weeks but unfortunately remained slightly mentally handicapped.  We saw further cases of lead poisoning over the years.  

Increased density of the ends of the long bones

In this particular case it transpired that the family lived in an old house in a poor area in the centre of Leeds.  The child had been in the habit of chewing the edge of an old gate covered with old lead paint, which had been placed across the top of the stairs for her safety! 

Fleckof ingested lead paint visible on X-ray of the abdomen in a similar case

After all this day and night activity, if only we had X-rayed the abdomen we would have seen the small opaque flecks of lead paint in the colon (figure)! Unfortunately it would not have affected the outlook.

 The WHO produced an excellent comprehensive document on lead poisoning  in 2010 describing how lead poisoning was still an important worldwide problem. “Although many countries have initiated programmes to lower the level of lead in the environment, human exposure to lead remains of concern tohealth care providers and public health officials worldwide. For over 35 years the World Health Organization and the International Programme on Chemical Safety have been concerned about the adverse effects on health of lead in the environment. The evaluation of human health risks arising from foodborne lead has been carried out by the World Health Organization on four occasions since 1972. In addition, health-based guidance values for lead in water, air and the workplace have been developed by various task groups convened by the World Health Organization.

Apparently lead poisoning was common in Roman times because of the use of lead in water pipes and in wine containers.  The problem became common among industrial workers in the 19th and 20th centuries, when workers were exposed to lead in smelting, painting, plumbing, printing, and many other industrial activities. Following the advent of motor vehicles at the beginning of the 20th century and the introduction of leaded gasoline, environmental lead contamination substantially increased.              

As long ago as 1904, the Australian physician and ophthalmologist  J. Lockhart Gibson concluded that lead paint in the home was responsible for poisoning children. The source of the poison was unknown until Gibson had the powdered paint from his own house analysed and lead carbonate was found. The paint on wooden Queensland houses dried and powdered in the hot sun. Most of the affected children were nail-biters or thumb-suckers who carried it on sweaty hands to the mouth. Gibson led the campaign to have lead paint replaced in the vulnerable parts of buildings; this was legally required in Australia by the Health Act of 1922. Despite Gibson’s work, and subsequent confirmation of it in the US medical literature, lead was not banned from US household paints until 1978. {Information from the Australian Dictionary of Biography, Volume 8, (MUP), 1981).

Too much of a good thing

An example of benign carotenaemia from dermatalas.org

During the 1970’s I was asked to see a young child who was noted to be slightly, but quite definitely,  yellow first noted soon after a transatlantic air flight.  I initially thought of the effects of altitude on children with thalassaemia and the haemolysis they may experience. Yet this child appeared very well although he was quite obviously yellow in the face, particularly in the nasolabial folds, but there was no yellow discoloration of the whites of his eyes. 

Full physical examination was normal as were the initial full blood count and liver function tests. However, at the time we were fortunate that Dr Jerry Kelleher, in the Department of Medicine at St James University Hospital, Leeds was a world expert on vitamins. He was prepared to estimate the blood carotene level and this was markedly elevated.  

Dr Jerry Kelleher

Once  I was aware of this condition of “hypercarotenaemia” I soon recognised other infants and young children with high levels of carotene but who were otherwise very well.  So we termed the condition ‘Benign Carotenaemia’ and published a report of six children where the initial serum carotene levels of 3 infants ranged from 320 to 510 ug/100ml (Normal <40 – 99 ug/100 ml) (Congdon et al, 1981)  

We suggested that the cause was a high intake of dietary carotene made available by the frequent use of carrots in proprietary infant weaning foods. Communication with the H J Heinz Company in 1980 confirmed that carrots are cheap and readily available and were added to most varieties of their strained savoury baby foods. Also the crushing and processing of the carrots in the foods was likely to enhance the release of the carotene.  

To this day I still notice infants who are obviously yellow and undoubtedly must have benign carotenaemia, but it does not seem to do them any harm and usually goes undiagnosed. I have included the illustration of a similar child from the internet (figure from dermatlas.org) who shows obvious yellow skin discolouration, particularly of the nose, when compared with the mother’s, but obviously has sparing of the sclera of the eyes.

The late Dr Peter Congdon (figure) was an excellent senior registrar with me at the time and was subsequently appointed consultant neonatologist at the Leeds General Infirmary.

Congdon PJ.  Kelleher J.  Edwards P.  Littlewood JM.  Benign carotenaemia in children. Arch Dis Child 1981; 56:292-294

The nose – an important aid in diagnosis

The sense of smell can often help the physician but it is a particular advantage if the doctor has experienced the particular odour on a previous occasion.  As with so many areas of medicine, having once experienced a particular odour one immediately recognises it on subsequent occasions (experiential learning!).  

In the late 1960’s we had a serious problem with a female infant born at the Leeds Maternity Hospital.  Following a normal pregnancy and delivery the infant became progressively more lethargic over the first 2 weeks to the extent that tube feeding was required – this was a most unusual and a very worrying sign for a  full term infant.  The infant was admitted to the neonatal special care baby unit at  the Leeds Maternity Hospital where all the usual tests for infection and intracranial problems were done – even to the extent of seeking a neurosurgical opinion and aspirating the subdural space and cerebral ventricles to rule out infection and haemorrhage.

Still undiagnosed by the third week, the drowsy infant was transferred to our general paediatric ward at Seacroft Hospital in Leeds for further investigation and long term care  

Soon after the infant’s arrival at Seacroft, our experienced paediatric Ward Sister, June Wilson, remarked cheerfully “You’ve sent us a right smelly infant here!”. As soon as June mentioned the unusual odour we all noticed the peculiar smell in the infant’s cubicle.  A urine was sent off for examination in the biochemical laboratory. As part of the investigation the biochemist estimated the amino acids present – a fashionable and relatively new test at that time. Two days later an excited biochemist Mr Alan Steel told us the infant had Maple Syrup Urine Disease (MSUD), a recently described condition we had not heard of at that time. However, with this knowledge the smell was now so blatantly obvious to everyone that it was hard to see how everyone could possibly have missed it for 3 weeks!  

Maple syrup urine disease is a very rare inherited metabolic disorder first described in 1954 and characterised by the onset of severe intracranial disturbance causing lethargy and drowsiness in the first weeks of life. There are markedly increased blood and urine concentrations of three amino acids – leucine, isoleucine and valine. Untreated the condition is fatal in early childhood.  

Although dietary treatment, with a major input from the dietitians and the biochemists, with restriction of the offending amino acids and monitoring plasma levels, improved this infant’s physical condition and conscious level, she remained severely developmentally retarded and died at the age of 4 years from a respiratory infection. The tragedy was that, although dietary treatment improved the general condition and comatose state, by the time the MSUD was diagnosed irreparable brain damage had occurred. 

Dickinson JP, Holton JB, Lewis GM, Littlewood JM, Steel AE. Maple syrup urine disease. Acta Paediatr Scand 1969; 58:341-351.

My experience  with a further infant with MSUD some years later demonstrates the great truth in the statement “Intelligence is learning by experience”.  It was some years after the first infant was treated, when a 3-week-old infant was brought to our weekly clinical paediatric meeting at Seacroft Hospital in Leeds by a consultant paediatrician from a neighbouring city. He sought help from his colleagues at the meeting as to the diagnosis.    After a normal pregnancy and delivery the infant had become progressively more lethargic during the first two weeks but all investigations were negative.  The experienced local paediatrician had brought the infant to the meeting to obtain the views of his paediatric colleagues as to the diagnosis. 

As I entered the infant’s cubicle I immediately recognised the strong odour of maple syrup, which I would stress in similar circumstances we had all missed for weeks some years before.  I said at once that I was sure the infant had maple syrup urine disease.  The infant’s paediatrician could not accept this initially as he and his colleagues had not noticed the characteristic smell until it was pointed out to them.  In fact the infant did have maple syrup urine disease.  I had experienced the smell and the clinical picture before – the infant’s paediatrician had not.  Of course I was recognising a disease pattern rather than showing great innate intelligence!  In fact the smell was so obvious I still find it difficult to see how we could possibly have failed to notice it in our first infant – but sadly fail to notice it we did.

Acute abdominal conditions

Acute surgical conditions are considered first in view of their importance and potential of serious complications. They are amongst the more important problems where  major disasters, even fatalities, can occur in paediatrics.  

Of all the conditions that can present to the doctor dealing with children, certain cases of intussusception must be one of the more difficult and fraught with potential problems.  Only a minority of children seem to have the classical textbook description of an ill child with severe colicky pain, an abdominal mass and blood in the stools (described as ‘red currant jelly stools’). Such children seem to present directly to accident and emergency and thence to the surgeons. However, most experienced paediatricians have been confronted with far more atypical cases of intussusception that by no means show the classical textbook symptoms and signs; the child may have ended up in a paediatric medical ward for investigation of abdominal pain and distension.

The doctor would be wise to consider any child, however well or ill they may appear, who has new and more than transient severe colicky abdominal pain to have an intussusception or some other important surgical emergency until proved otherwise.

Intussusception – marked intestinal gaseous distention in the upper abdomen.

I recall  one child with persisting abdominal distension admitted for investigation of possible malabsorption to a prestigious London children’s hospital who had subacute intussusception (I had previously seen a similar child in Leeds  admitted to our ward also for investigation of possible malabsorption).   The lesson is to always arrange radiological investigation, as a matter of urgency,  if a child has persisting severe unexplained colicky abdominal pain, particularly in young children when the pain persists without explanation.  

As a general working rule I have found it safer to regard all acute paediatric problems to be due to the most serious possible cause until proved otherwise!

Acute appendicitis is only a close second as a cause of diagnostic difficulties and potential disaster in children.  One particular child brought this home to me when I was a families’ medical officer in the Royal Army Medical Corps in Malta in 1958.  I visited the home of a small child who had been febrile and generally unwell for the past 24 hours. As was my usual practice I examined his ears, throat, chest, abdomen, eyes to check the optic fundi and checked for neck stiffness. He had obvious severe tonsillitis with livid red medium large tonsils and fresh yellow exudate; the tonsillar glands were slightly enlarged and very tender. It seemed obvious he had severe tonsillitis and I supplied a bottle of oral penicillin – which had just become available in Malta.  He could not produce a urine specimen (always part of the examination of an ill child) so I left a sterile bottle and arranged to call back later in the day for the specimen on my way back from a number of calls in the north end of the island.  

When I returned later in the afternoon for the specimen, his mother reported he was still unwell and now had developed some abdominal pain. His tonsils were unchanged but he was now very tender in the lower right abdomen. I admitted him to the Military Hospital, Mtarfa where an acutely inflamed appendix was removed that evening! 

Unfortunately children do not accept that double pathologies are very rare!  

This case also exemplifies the need to always ask the parents to contact the doctor again at any time if their ill child, from any cause, is worse or they are concerned by new signs and symptoms, whatever time it is, night or day. Children may deteriorate rapidly in a few hours.

Tonsillitis and meningococcal meningitis

Tonsillitis may be associated with other conditions, as we have seen with appendicitis, emphasising the importance of a general physical examination of every ill child.  Many years ago, when I was a house physician, an acutely ill child arrived in the casualty department with what appeared to be acute tonsillitis – fever, livid red tonsils with fresh yellow exudate, very tender tonsillar glands and no other signs.  He did not appear seriously ill; he was interested and cooperative and had warm peripheries. We sent him home with a bottle of sulphadimidene, which was the usual treatment for streptococcal tonsillitis at the time and arrangements were made for him to return to casualty for review the following morning.

Early meningococcal peticheal rash which does not fade on pressure from a glass

He returned the next morning to the casualty for follow-up and his mother reported he was generally very much better in himself but he seemed to have slight pain on moving his head; she had also noted a few small purple spots on his feet (figure).On examination, although definitely a little better than on the previous day, he now had  quite obvious neck stiffness highly suggestive of meningitis. I admitted him and a lumbar puncture revealed infected cerebrospinal fluid due to meningococcal meningitis!  Fortunately he made a full uninterupted recovery.

The infection had obviously been partly controlled by the sulphonamide prescribed the previous day for his tonsillitis; in fact sulphonamides were the treatment of choice of some paediatricians at that time for meningococcal meningitis.  I was even told in the Edinburgh Membership, by a notoriously very unpleasant Scots examiner, that sulphonamides alone were a quite adequate treatment for meningococcal meningitis! So it was fortunate that this child was started on treatment and that we asked to see him the following day.

Microscopy of fresh uncentrifuged urine

The examination of the throat, ears and urine should be the paediatrician’s Father, Son and Holy Ghost!  I have no doubt that the examination of a fresh urine specimen, both chemical and by microscopy for bacteria and white blood cells, should be part of the general paediatrician’s examination of any ill child – sadly this is now usually left to the laboratory.   I realise this does not seem to be common practice in 2018 when even the value of physical examination is questioned by some investigation orientated young doctors.

white blood (pus) cells in urine
strong>White blood cells and motile bacteria in urine specimen (x400)

I have never understood why the ability to diagnose urinary infection within seconds by visualising motile bacteria and pus cells in an unstained, uncentrifuged fresh urine on microscopy (figures) is now so rarely used by paediatricians and other doctors. One of my first consultants in Leeds, Dr Eric Allibone, always microscoped the urine of all new patients as did Dr Hughes Davies, the excellent senior registrar with whom I worked at Great Ormond Street in 1963;  so I developed the habit of a lifetime – even to the extent of incorporating the technique into my MD thesis on neonatal urinary tract infections

 A drop of fresh unstained uncentrifuged urine under a cover slip examined under high power (x 400) of even a modest student’s microscope will, with minimal experience, identify most instances of significant bacteriuria. Neither centrifugation nor staining is necessary. Although significant bacteriuria may occur without pus cells, the presence of pus cells will lend support to the significance of the bacteriuria.

Subsequent experience repeatedly proved the value of this simple examination which I eventually used in my MD thesis on urinary tract infection in the newborn. Performing routine microscopy of fresh, uncentrifuged urine from all new patients, both acutely ill and in the outpatients, over many years has solved many problems – from the more obvious abdominal pain to the less obvious chronic emotional problems and aches and pains related to chronic pyelonephritis. 

I  compared my results of urine microscopy in the clinic at St James’s and confirmed the value of routine microscopy in the outpatients (Littlewood et al, 1977).   The centrifuged deposits of  33/38 (87%) of  infected urine specimens contained more than 10 motile organisms per field on microscopy using x 400 magnification – 66% contained innumerable bacteria. Even using unspun specimens 29 (76%) of infected specimens were identified in the clinic.  Infection was excluded in 96% of specimens on microscopy of the deposit.

Littlewood JM. Jacobs SI. Ramsden CH. Comparison between microscopical examination of unstained deposits of urine and quantitative culture. Arch Dis Child 1977; 52 (11):894-6.

Littlewood JM. Kite P. Kite BA. Incidence of neonatal urinary tract infection. Arch Dis Child hood 1969; 44:617-620.  

Davies JM. Gibson GL. Littlewood JM. Meadow SR. Prevalence of bacteriuria in infants and preschool children. Lancet 1974; 2:7-10.                                                                 

Dr. David Vickers worked with me as an SHO at St James’s in Leeds in the Eighties where he learned the value of urine microscopy. I was pleased to see some years later he reported in a publication in the Lancet “Microscopy by a clinician represents a cheaper, quicker, and more reliable screening test for UTI in children than does routine culture in a microbiology laboratory.”

Vickers DAhmad TCoulthard MG. Diagnosis of urinary tract infection in children: fresh urine microscopy or culture? Lancet. 1991 Sep 28;338(8770):767-70

Urine microscopy saves the day

I make no apologies for re-stating my firm belief that any paediatrician, if involved in acute medical work, seeing an acutely ill child should always microscope the urine himself – he may be very grateful for taking the trouble to obtain and examine a specimen.  

During a serious influenza epidemic I was called out on a domiciliary visit by a family doctor to see an acutely ill 18 month old boy.  I examined the child thoroughly and agreed with the GP that the boy had flu’ and only anti-pyretics and, if necessary tepid, sponging were required.  No urine was available during the morning visit when I saw him so I left a sterile bottle and plastic urine-collecting bag for his mother to obtain a specimen.  Later in the day I collected the urine specimen on my way back to the nearby Seacroft hospital where I could microscope a drop of the urine.  On microscopy of the fresh urine it was quite obviously heavily infected showing numerous white blood cells  and motile bacteria. I admitted him to hospital at once for treatment. Subsequent investigation revealed the child had only one hydronephrotic kidney; this would have been missed without urine microscopy.

Encountering such cases every year or so confirmed my impression that examination of the ill child could not be regarded as complete without chemical testing and microscopy of a fresh urine specimen. I have to thank the senior registrar with whom I worked at Great Ormond Street in 1963, Dr Hughes-Davies, for teaching me the value of this simple technique, which I practised with all new and ill patients until I retired from clinical practice in 1997. 

Foreign bodies – an ever-present “banana skin” for the doctor

The recurring or non-resolving chest infection due to the presence of an inhaled foreign body is familiar to most experienced paediatricians. However, it is worth stressing that it is the patients who give no history of inhalation, such as choking on a peanut, even on direct questioning, that may prove a more difficult problem. 

Failure of a chest infection to resolve requires not only a chest X-ray but also a bronchoscopy to search for a foreign body and also to identify any unexpected or unusual pathogenic organisms present in the lower airways.  This is more readily arranged now that paediatric flexible fibreoptic bronchoscopy is generally available; in earlier days bronchoscopy required referral to the thoracic surgeon for examination using a rigid bronchoscope. 

I recall one older boy we had hospitalised for weeks in the Sixties with what was thought to be chronic uncontrollable asthma, difficult to control even with the use of large doses of oral corticosteroids. Although there was no history of inhalation of a foreign body, he was eventually bronchoscoped by the thoracic surgeon who found an inhaled peanut as the main cause of his worsening symptoms. he made an uneventful recovery.

A child may house a foreign body in any orifice

Foreign bodies are not restricted to the lungs of children.  I was called to a house of one young child as a matter of great urgency. The 5-year-old boy had been noted to have gradually developed an unpleasant smell to the extent that friends and neighbours had noticed it and commented to his mother. This was now causing great distress to his mother. The child seemed well in himself and full examination was negative.  The mother had noticed that the smell was worse when he was upset and crying.            Always keen on the obscure, I was at the time interested in amino acids and familiar with a recently recognised condition known as the “odour of sweaty feet syndrome” (isovaleric acidaemia due to an inability to metabolise leucine) which was characterised by the presence of an abnormal amino acid content of the sweat.  I therefore arranged for him to come to the outpatients after I had persuaded the always helpful biochemists to perform a sweat test and then examine the sweat for amino acids – which were normal!  So the puzzle remained – the smell persisted.

Sidbury JB Jr, Smith EK, Harlan W. An inborn error of short-chain fatty acid  metabolism. The odor-of-sweaty-feet syndrome. J Pediatr 1967; 70:8-15. 

The next week the child and his mother returned to my clinic to hear the result of the sweat test – which was normal! However, again on this occasion the smell around the child was still quite obvious – and definitely worse when I examined his throat.  Oh no! Could this possibly be a foreign body in the nose? Indeed it could and it was! Later the ENT surgeon removed a piece of stinking sponge rubber from well back in one nostril and the smell disappeared!  So much for the odour of sweaty feet disease, I suppose it is true. I learned yet again that common things actually do occur commonly!

Vaginal foreign bodies are usually associated with an offensive vaginal discharge for which the child is brought to the doctor. In a prepubertal child may be due to a foreign body in the vagina which may be revealed by an X-ray of the abdomen or may require an examination under anaesthesia by a paediatric surgeon. 

Ingested foreign bodies

 Swallowed foreign bodies are usually accompanied by a history of possible ingestion. They are commonly revealed by an X-ray of the chest and abdomen as was this 50p coin in the x-ray. 

The child whose X-ray shows a 50p coinwas having considerable pain and the coin was held up at the pylorus. It was removed using a flexible endoscope by Dr Richard Brown one of the gastroenterologists in the Department of Medicine. This 50p coin was removed by endoscopy but some foreign bodies may pass through the intestinal tract without a problem. It is important to be sure the FB has passed below the diaphragm into the stomach and is not lodged in the throat, oesophagus of even the airways.

Various foreign bodies removed from children at endoscopy

When the paediatric service moved from Seacroft to St James in the early Eighties Professor Monty Losowsky taught me the technique of fibreoptic endoscopy in adults. I eventually obtained a paediatric endoscope. Subsequently I provided a  paediatric fibreoptic upper GI endoscopy service at St James’s. The figure shows some examples of the type of the objects removed from the stomach or oesophagus of children using the our paediatric fibreoptic endoscope.  

Metabolic and endocrine disorders

Congenital adrenal hyperplasia (CAH) is group of inherited conditions that are present at birth (congenital) where the adrenal gland is larger than usual (hyperplasia). In CAH, the body is missing an enzyme (chemical substance) that stimulates the adrenal glands to release the cortisol hormone. The serum electrolytes should always be included in the investigations of infants who are “failing to thrive” i.e. who are failing to gain weight normally or who are generally unwell.  They may reveal a number of important disorders such as congenital adrenal hyperplasia (CAH) which is suggested by the finding of a low serum sodium and high potassium.

The paediatrician seeing many newborns and ill children will sooner or later encounter an infant with a serious rare metabolic disorder such as Maple Syrup Urine Disease, as I have already described above. 

Measurement of the serum electrolytes is a valuable, indeed one of the essential, initial investigations which may immediately suggest a variety of disorders – for example congenital adrenal hyperplasia, renal insufficiency or Bartter’s syndrome.

For example at the age of thirteen days the infant with congenital adrenal hyperplasia Dr Doug Addy and I reported in 1969 had a serum sodium 120 mEq/l, and a very high potassium of 9.4 mEq/l (normal not more than 6.5 mEq/l) and chloride of 90 mEq/l. The potassium was so high that it caused a cardiac abnormality in the form of ventricular tachycardia. This settled with appropriate treatment (detailed in our publication) and he was eventual discharged home at the age of 74 days at which time therapy consisted of oral cortisone acetate 7.5mg 3 times daily, fludrocortisone acetate 0.025mg twice daily and sodium chloride 1.0gm daily.

Addy D. Littlewood J. Ventricular tachycardia associated with hyperkalemia. Occurrence in an infant aged 13 days with adrenogenital syndrome. Am J Dis Child 1969; 117:706-709.

The diagnosis may give rise to problems in boys where the external genitalia are not obviously abnormal but is less of a problem in female infants due to the abnormal masculinised genitalia with enlargement of the clitoris. This may initially give rise to confusion as to the gender of the infant. 

Bartter’s syndrome

This is a rare condition first suspected by the finding of abnormal electrolytes with very low potassium and raised bicarbonate. In the early Seventies an infant who was failing to thrive was referred to me by Dr Olive Scott, our paediatric cardiologist. At the age of 9 months his weight of 6.75 kg was 1kg below the 3rd centile (lower end of the normal range) and length 70.5 cms (50th centile). His appearance was very similar to the infant with pseudo Bartter’s syndrome in the figure but he did not have cystic fibrosis.

Pseudo-Bartter’s syndrome from Devlin et al, 1989 (see below)

I first suspected he had Bartter’s syndrome purely on the results of first electrolytes done as part of the initial screening investigations for failure to thrive. The diagnosis had not crossed my mind, nor had I even heard of the condition, before the investigations returned and we had consulted the textbooks.  The syndrome is a very rare inherited defect in the thick ascending limb of the loop of Henle in the  kidney characterised by low potassium levels (hypokalemia),  increased blood pH (alkalosis), and normal to low blood pressure. 

Micael Lee

To help manage this infant I was fortunate to have the combined expertise of my friend and colleague Professor Roy Meadow with his paediatric renal expertise and Dr Michael Lee (figure) a physician and an authority on the condition. Michael Lee subsequently had a distinguished career and was at the time Senior Lecturer in Clinical Pharmacology at the University of Leeds Medical School from 1973 to 1984; between 1984 and 1995, he was Professor of Clinical Pharmacology and Therapeutics at the University of Edinburgh. He always maintained this infant was one of the most exciting cases he had seen in his career!. He actually knew Dr. Fred Bartter (figure), the distinguished endocrinologist who first described the condition in 1962! Mike Lee’s  expertise with the investigation and management of the infant were quite invaluable and he was a pleasure work with. After extensive investigation we treated the infant with prostaglandin synthetase inhibitors and subsequently he made excellent progress.

Fred Bartter

Littlewood JM. Lee MR. Meadow SR. Treatment of childhood Bartter’s syndrome with indomethacin. Lancet 1976; 2:795.  

Littlewood JM. Lee MR. Meadow SR. Treatment of Bartter’s syndrome in early childhood with prostaglandin synthetase inhibitors. Arch Dis Child 1978; 53:43-48. 

  Bartter FC. Pronove P, Gill JR, MacCardle,RC. Hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis. Amer J Med 1962; 33,811-82

Subsequently Pseudo Bartter’s syndrome was recognised as a complication of cystic fibrosis. For example  Devlin J, Beckett NS, David TJ. Elevated sweat potassium, hyperaldosteronism and pseudo-Bartter’s syndrome: a spectrum of disorders associated with cystic fibrosis. J R Soc Med 1989; 82 (Suppl 16):38-43. [PubMed].                   

John Devlin described these three cystic fibrosis infants with “pseudo-Bartter’s syndrome” (the term first used by these authors) from Prof. Tim David’s CF unit in Manchester and two further with related electrolyte disturbances with low potassium and sodium and alkalosis. They emphasise the importance of measuring the serum electrolytes at diagnosis and when unwell. They mention the first report of the syndrome in CF was by Rendle Short J (Arch Dis Child 1956; 31:28

Elsewhere I have reviewed the published reports of CF infants who have had Pseudo Bartter’s syndrome on the Leeds CF website –cysticfibrosis.online/history/topics/electrolytes.

Tonsils and adenoids

Enlarged infected tonsils obstructing the airway

Tonsils and adenoids, and whether they should be removed in some children, is a continuing source of discussion. The operation of tonsillectomy was condemned as long ago as in the 1930s as “one performed without clear indications and without obvious benefits”. Many doctors are against tonsillectomy and against antibiotics for inflamed tonsils.  However, I believe children who have repeated attacks of tonsillar inflammation with redness, swelling, exudate and enlarged tender glands are better off without their tonsils.  If their tonsils are not removed in childhood they will often continue to give trouble and require removal in adult life.

Also size really does matter with tonsils (figure).  The tonsils may be so large that they cause dangerous  obstruction and very noisy breathing particularly during sleep.   It is helpful to ask the parents if they can hear the child’s breathing when they are downstairs at night.  The parents will often describe breathing so noisy it can indeed be heard downstairs, often associated with short periods of apnoea (momentarily stopping breathing).  Such children should have overnight oximetry performed. The history that there are short periods of apnoea is usually associated with repeated falls in the blood oxygen saturation when this is measured.  Such children should have their tonsils removed no matter what their age – even during infancy as was the case in one of our patients where tonsillectomy had been decided against at one London hospital.  Post operative overnight oximetry is impressive and will show the alarming episodes of hypoxaemia have cleared and the child sleeps quietly through the night (figure)  There is often an impressive weight gain and an increase in daytime activity now that nights are more restful.

The illustration below is taken from the literature but the results are identical to those of the infant I have described above.

Overnight oximetry with episodes of hypoxia (reduced SaO2) due to obstructive episodes in the left hand recording

Summary of polysomnographic recording in a three-year-old boy with loud snoring, restless sleep, poor growth, and tonsillar enlargement. The hours from the start of the study are shown at the top; the study was terminated after 5 hours due to severe desaturation (second panel from top). The obstructive events (third panel) predominantly occurred in rapid eye movement sleep (sleep structure summarised in top panel). Hypercapnia developed over the course of the study with acute rises during periods of REM sleep associated obstructed breathing. The apnoea/hypopnoea index was 36 events/hour with a SaO2 nadir of 42%, a respiratory arousal index of 22/hour, and 89% of the study spent with a PCO2 above 6.6 kPa. (B) Polysomnography results in the same child 1 month after adenotonsillectomy showing complete resolution of OSA. The apnoea/hypopnoea index was 0 events/hour with a SaO2 nadir of 94% and 0% of the study spent with a PCO2 above 6.6 kPa.

Rarely exotic conditions may be encountered 

Diphtheria

It is unusual to see diphtheria in the UK;  I have only seen the condition on one occasion.  An Asian child was admitted as an acute to the paediatric ward at Seacroft with a high temperature, obvious sore throat, quite impressive soft, slightly enlarged tonsillar glands and also very quiet respiratory inspiratory stridor – indeed it was hardly audible but quite definite. The Asian house physician duty had telephoned me  to say she thought the child had early diphtheria. I thought this seemed very  unlikely having never having seen a case in the UK but nonetheless went in to see the patient with her. More probably it would be mild viral laryngeal stridor or early croup.  I asked the house physician if she had seen children with diphtheria previously. “Yes” she said, “many times”. So we asked the consultant in infectious diseases to come in and examine a throat smear. Sure enough it was diphtheria. The young doctor’s “experiential learning” in her home country had saved the day.

“Non-specific abdominal pain in childhood”

New developments and techniques have reduced the “Non-Specific” element of recurrent abdominal pain. Some 10% of school children have attacks of recurrent abdominal pain. A distinguished paediatrician, John Apley (figure) of Bristol, virtually made the subject his  own, attributing the majority of cases (19/20) to emotional/functional causes. His articles on the subject is regarded as a paediatric classics. 

John Apley

Certainly stress is an important factor in some children with recurrent abdominal pain but in my experience, as a busy general paediatrician from a different era in a northern city, stress is certainly not the prime cause in many.  John Apley, a widely respected Bristol paediatrician, did most of his writing on non-specific abdominal pain (NSAP) during the 1950s and 1960s before many of the present day gastrointestinal investigations were available e.g. jejunal biopsy, fibreoptic endoscopy, colonoscopy, hydrogen breath tests, Helicobacter pylori serology, reliable serological tests for coeliac disease and an awareness that of food allergy/intolerance as an important cause of gastrointestinal and other disorders.   Even the realisation that chronic constipation may cause chronic central abdominal pain without the patient complaining of hard, infrequent stools – the traditional definition of constipation. So many factors have certainly reduced the number of children thought to have a psychosomatic cause for their frequent abdominal discomfort.  I always made a habit of thinking “organic’ first!

Apley carried out a classic field survey of 1000 school children with recurrent abdominal pains.    A total of 10.8% of children (12.3% of girls and 9.5% of boys) of were affected.  Children were examined clinically, but ancillary investigations were not undertaken  Apley writes – “In our survey three subsidiary points were established: First, the high incidence of recurrent abdominal pain pains especially at certain ages and particularly in girls. Second: the high incidence of abdominal and other complaints in the families of affected children. Third: negative evidence of any physical associations with the pains and the frequent positive evidence of frequent emotional disturbances.  Children with abdominal pains tend to fall into certain categories as regards personality and emotional patterns so much so that often one can forecast which children are likely to develop the symptoms. Often when difficult situations are imminent as at the beginning of school terms examinations, the occurrence of pains can be correctly predicted. As compared with other children those with pains tend to be anxious timid fussy and over conscientious taking the ordinary difficulties of life (especially school life) too much to heart.”

There follows an account of some relevant information as to the causes of recurrent abdominal pain in children which have become apparent since Apley’s time. 

Helicobacter pylori as a cause of abdominal pain

Collected papers of John Apley Ed. A Graham Apley, Butterworth, 1984.

A 12-year-old girl was referred to me at St James for an upper GI endoscopy by a consultant paediatrician in a nearby city. He wanted to be sure there was no organic cause for her recurrent abdominal pain which had caused her to miss a great deal of school. The school was regarded as the main cause of her problem – in fact she already had an appointment to see a child psychiatrist after she had been to our unit at St James in Leeds for the endoscopy.

At endoscopy the gastric mucosa was obviously abnormal and typical of Helicobacter gastritis (vide infra); this was confirmed on the mucosal biopsies.  Within 48 hours of starting treatment for the H. pylori her symptoms of nausea and abdominal pain disappeared and she was able to return to school with no further problems!   

Mike Mahony

In collaboration with Professor Losowsky and other colleagues at St James’s and Dr Mike Mahony (figure) our excellent senior paediatric registrar at the time, we did further work on H. pylori in children (then known as Campylobacter pylori).    We knew that Campylobacter pylori colonisation of the stomach is strongly associated with type B non-autoimmune gastritis in adults. In a retrospective study of 38 gastric biopsy specimens taken during upper gastrointestinal endoscopy in children, we found C. pylori in nine (24%). Judy Wyatt, our pathologist colleague, found ten biopsy specimens showed histological evidence of gastritis and C. pylori was found in eight. We published our findings.

Mahony MJ, Wyatt JI, Littlewood JM. Campylobacter pylori gastritis. Arch Dis Child 1988; 63:654-655..  

Jean Crabtree

In a further study, Dr Jean Crabtree, (later Professor)(figure) examined the systemic immune response to Helicobacter pylori in 69 children with recurrent abdominal pain and upper gastrointestinal symptoms. Twenty-one (30%) children were histologically positive for H. pylori. Eighteen of the 21 positive subjects and two H. pylori negative subjects (one with normal mucosa, one with lymphocytic gastritis) were positive for H. pylori IgG antibodies by enzyme linked immunosorbent assay (ELISA) (86% sensitivity, 98% specificity).

Crabtree JE, Mahony MJ, Taylor JD, Heatley RV,. Littlewood JM,. Tompkins DS.  Immune responses to Helicobacter pylori in children with recurrent abdominal pain. J Clin Pathol 1991; 44:768-771. 

Gastritis associated with Helicobacter pylori was present in gastric biopsies from 24/95 (25%) children and adolescents undergoing endoscopy for recurrent abdominal pain and upper gastrointestinal symptoms at St James. H.  pylori associated gastritis occurred mainly in older children (8-16 years) and was significantly associated with low socioeconomic class and a family history of peptic ulcer disease. Antral nodularity (figure) was a common endoscopic finding in H. pylori positive children. Eighteen children, all over 5 years of age, were treated with tripotassium dicitratobismuthate (De-Nol) for two months and ampicillin for two weeks. In 12 children follow up gastric biopsies were obtained six weeks after completion of treatment. In 9/12 (75%) of children H. pylori was eradicated, and gastritis improved.

Antral gastritis

Mahony MJ, Wyatt JI, Littlewood JM. Management and response to treatment of Helicobacter pylori gastritis. Arch Dis Child 1992; 67:940-943.  

Mahony MJ, Littlewood JM. Helicobacter pylori in Paediatric Populations. In Rathbone BJ, Heatley RV. (eds). Campylobacter pylori and gastrointestinal disease. Blackwell Scientific Publications 1989 pp 167-175..

Mahony MJ, Littlewood JM. Helicobacter pylori in Paediatric Populations. In Rathbone BJ, Heatley RV. (eds). Helicobacter pylori and gastrointestinal disease. 2nd Ed.. Blackwell Scientific Publications 1992 pp 177-18

In the second of these chapters we summarised the present position regarding H. pylori in children as it was in 1992. I had been early in using the paediatric endoscope from the early Eighties as part of investigation of children with troublesome recurrent abdominal pain. Fortunately Helicobacter pylori was a major interest of Professor Monty Losowsky and members of his University Department of Medicine at St James. 

H. pylori was first discovered in the stomachs of patients with gastritis and ulcers in 1982 by Drs. Barry Marshall and Robin Warren of Perth, Australia (further detail below). At the time, the conventional thinking was that no bacterium could live in the acid environment of the human stomach. In recognition of their discovery, Marshall and Warren were awarded the 2005 Nobel Prize in Physiology or Medicine.

With the knowledge we have now it seems likely that some of Apley’s children with non-specific abdominal pain would have had H. pylori gastritis?   As a general paediatrician it is  always better to think “organic” before attributing a child’s problems to emotional causes. 

Barry Marshall, Robin Warren and Helicobacter pylori

(Information from Gastroenterology 2005; 129(6):1813-14)                              

The story of Campylobacter/helicobacter pylori is very interesting. The 2005 winners of the Nobel Prize for Physiology or Medicine were the Australian researchers Dr. Barry J. Marshall and Dr. J. Robin Warren (Figure). They won for their “remarkable and unexpected” discovery of the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease. Warren, Professor of Pathology at Royal Perth Hospital, in 1979 had observed small curved bacteria colonizing the lower part of the stomach (antrum) in about half of the patients from which biopsies had been taken. He then made the crucial observation that signs of inflammation were always present in the gastric mucosa close to where H pylori was observed.

 Opens large image
Robin Warren & Barry Marshall

Marshall, Senior Principal Research Fellow at the University of Western Australia, first teamed up with Warren in August 1981 to help prove the theory that bacteria, and not stress and lifestyle, cause most peptic ulcers. At the time, while at Royal Perth Hospital, Marshall was a gastroenterology research fellow in search of a project.   For the young research fellow, Warren’s work appealed partly because it went against conventional wisdom. In medical texts, the gastric environment was considered inhospitable to bacteria and therefore was viewed as sterile. Thus, Warren’s bacterium, one that had not been described in texts, should not have been in the stomach.  Initially in their collaboration, Marshall reviewed the clinical records of 25 patients in whom Warren had found the bacteria in gastric biopsies, describing the diseases the patients did or did not have. Not all had ulcers and not all had cancer, “so it was hard to see a pattern in those 25,” he has said. A subsequent blinded study of 100 patients, during which an independent gastroenterologist performed the endoscopies, was conducted from January to May 1982. The results established a link between the bacterium and peptic ulcer disease. During the study period, Marshall cultured and gave the microbe its name, one that included a new genus because it was similar to both Campylobacter and Vibrio-like cholera.

An abstract was submitted 1 year later to the Australian Gastroenterology Association and was flatly rejected. Still, the findings were published for the first time in The Lancet, June 1983, in 2 separate letters under the same title Unidentified curved bacilli on gastric epithelium in chronic active gastritis, one signed by Warren, the other Marshall. The letters preserved the separate contributions of each author: Warren’s observation of the bacteria and preliminary information on the link with gastritis; Marshall’s original culture and the observation that the bacteria were linked to peptic ulcer disease.

Also in 1983, Marshall discovered the in vitro sensitivity of H pylori to bismuth and, later, to metronidazole. Early in 1984, 11 patients with “difficult duodenal ulcer problems” were referred to him by a general practitioner friend. Marshall treated them with bismuth and metridonidazole, eradicating H pylori in 9 patients without further relapse and without further cimetidine therapy.

Marshall, who has been described as “unconventional” may have lived up to that adjective in July 1984 when he became his own guinea pig by swallowing a pure live culture of H pylori. The researcher, who was married with 4 children, became violently ill but had thus made his point to the world. “I did it out of frustration,” he has said. “Part of it was that when I presented at scientific meetings, the audience was always skeptical and was convinced that these bacteria infected the patient after the gastritis developed. So I did it prove that that did not have to be the case. That was the main reason.”

Another reason, he asserted, was the failure of his pig experiment. Despite Marshall’s attempts to do so, he was unable to infect the animals with Helicobacter. In addition, there were his clinical observations that many patients were asymptomatic or had minimal symptoms. Marshall also knew that in most of his cases he had eradicated the infection with antibiotic therapy; thus, it was a calculated risk. As it turned out, his own infection cured spontaneously, “so that by the time I had taken the antibiotics, the infection was already gone.” Biopsy after endoscopy at day 8 showed the infection. After a second endoscopy at day 14, biopsy showed the mucosa beginning to heal and no bacteria present. These findings confirmed his in vitro discovery that bismuth could kill H pylori, which meant that bismuth, long thought an antacid or coating agent, might actually be an antibiotic.

“One of the difficulties with the infection was that it was so difficult to treat, and we did not have successful therapies until 1992,” Marshall told an interviewer in October 2005. “That’s when the general opinion of the medical community changed, when they could actually test our hypothesis on their own with treatment that was available.”   “In treatment studies, Marshall and Warren as well as others showed that patients could be cured from their peptic ulcer disease only when the bacteria were eradicated from the stomach. Thanks to the pioneering discovery by Marshall and Warren, peptic ulcer disease is no longer a chronic, frequently disabling condition, but a disease that can be cured by a short regimen of antibiotics and acid secretion inhibitors.”

How I first became involved with H. pylori in children

During the mid-Eighties I was travelling to London on the morning train. Sitting opposite to me was a pleasant young lady. We started talking and it appeared she was a doctor and had recently been appointed as a consultant pathologist at St James University Hospital in Leeds. The lady in question was Dr Judy Wyatt (figure). I discovered that she was particularly interested in a new bacteria Campylobacter (soon Helicobacter) pylori that had recently been shown to be associated with gastritis and peptic ulcers. I mentioned that I worked at Jimmys and furthermore regularly performed gastric endoscopies and biopsies on children referred to me with abdominal pain by other consultants in the region. Judy offered to seek out and review these biopsies to check for H. pylori infection. So by the time we reached Kings Cross the plans for our first study of H.pylori had been agreed.

Judy Wyatt 

This was a very fortunate meeting as Judy Wyatt proved to be a very pleasant, knowledgeable and excellent colleague with whom we were fortunate to have a productive collaboration over the next decade.

Constipation – a cause of recurrent abdominal pain

Common disorders occur commonly and constipation is common in children both in those with recurrent abdominal pain and in those with faecal incontinence (encopresis).

gross overloading of the colon in child with constipation and pain

Children may have chronic central abdominal pain due to gross faecal overloading of the colon without any complaints of the infrequent passage of hard dry stools – the classical definition of constipation. 

In the child whose abdominal X-ray (figure) is shown there was chronic abdominal pain but the bowels were reported to be opened daily without problems and the stools were not reported as hard. Regular laxative treatment with Senokot (a commercial senna preparation) relieved the abdominal pain and gradually cleared the colon. Not infrequently substantial doses of Senokot may be required over prolonged periods.

So chronic constipation is a frequent, under-diagnosed, cause of recurrent abdominal pain in children.  An abdominal X-ray and a rectal examination are helpful investigations.

Coeliac disease and abdominal pain

Avril Crollick

In my published Leeds series of 108 children with coeliac disease seen and investigated over some 25 years, 16 (15%) complained of abdominal pain and in 5 (5%) it was the presenting symptom. In another series from elsewhere abdominal pain had been the main complaint in 36% (Maki, 1992). Dr Avril Crollick  performed many of the biopsies in later years.

Mary, aged 10 years, looked healthy and was well grown but had troublesome abdominal pain for 2 years diagnosed as “abdominal migraine” by an experienced consultant paediatrician. As the pain was so troublesome he eventually referred her to me for upper gastrointestinal endoscopy. This procedure included duodenal biopsies which suggested subtotal villous atrophy (figure) which we confirmed with a standard jejunal biopsy. The abdominal pain settled completely and permanently on a gluten free diet. Thus coeliac antibody blood tests (whichever ones are favoured at the time) should be included in the investigations of all children with unexplained recurrent abdominal pain. Current 2013 recommendations of BSPGHAN and Coeliac UK involve estimation of total IgA and IgA anti- tissue transglutaminase (tTG) antibodies. Findings of positive anti-tTG antibody or IgA deficiency require further diagnostic action—usually a small bowel biopsy.

 Intestinal mucosa. left- normal small intestinal villi. Right the flat mucosa of subtotal villous atrophy in coeliac disease

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

Littlewood JM.  Coeliac disease in childhood. Clin Gastroenterol. 1995; 9(2):295-327. A Review.  

Congdon PJ, Fiddler GI, Littlewood JM, Scott O. Coeliac disease in children with congenital heart disease. Arch Dis Child 1982; 57:78-79. 

Congdon P, Mason MK, Smith S, Crollick A, Littlewood J. Small bowel mucosa in asymptomatic children with celiac disease. Am J Dis Child 1981; 135:118-121.S

Food intolerance and abdominal pain/colic

In 1982 with Adrian Minford we published my experience of 68 children with food intolerance and food allergy of whom 48 (70%) presented with gastrointestinal symptoms and signs.(vomiting, diarrhoea, colic, abdominal pain, failure to thrive), 16 (24%) children had skin manifestations (eczema, urticaria, angioneurotic oedema, other rashes), and 4 (6%) children with wheeze. Twenty-one children had failed to thrive before diagnosis. A single food (most commonly cows’ milk) was concerned in 28 (41%) cases. Forty (59%) children had multiple food intolerance or allergy; eggs, cows’ milk, and wheat were the most common. Diagnosis was based on observing the effect of food withdrawal and of subsequent re-challenge. In many children food withdrawal will mean the use of an elimination diet which requires careful supervision by a dietitian experienced in this area. Laboratory investigations were often unhelpful in suggesting or confirming the diagnosis. 

Anita Macdonald

I was fortunate that we had Anita MacDonald, an outstanding paediatric dietitian working at St James and a co-author on some of our publications on food intolerance. Anita was an important co-author of a number of publications both on food intolerance and cystic fibrosis before she moved to Birmingham Children’s Hospital where she eventually became a professor and later was awarded an OBE.  Some dietitian!  We were very fortunate to have her at St James during the Eighties as our senior paediatric dietitian.

Cows milk protein intolerance is a common cause of “three month colic” in babies. Severe infantile colic driving the unfortunate parents to distraction was not an uncommon problem referred to me. The mother had usually been reassured by the family doctor (and sometimes by a consultant paediatrician!) that it would settle and the baby was healthy. A 48 hour trial on the hydrolysed protein feed Nutramigen usually settled the colic completely. The usual response from the relieved parents was – “Why didn’t my doctor put him on this feed?”

The relationship of severe 3-month colic and other gastrointestinal disorders to cows’ milk intolerance was a striking and not uncommon problem in my experience. Failure to recognise the association between gastrointestinal signs and cows’ milk intolerance at times resulted in unnecessary operations for gastro-oesophageal reflux before the cause of the infant’s symptoms was identified as in the infant illustrated.     

This infant who whose gastro-oesophageal reflux failed to respond to both medical treatment and then a fundoplication operation was cured on a cows’ milk free diet

The other variation on this problem was the breast fed infant who is also obtaining small amounts of cows’ milk protein antigens from the breast milk. Stopping breastfeeding and starting Nutramigen would cure the problem. Putting the mother on a cows’ milk free diet was another treatment option but always seemed rather involved for the family who were already stressed by their infant’s problems. I must confess I usually opted for Nutramigen.

The other really interesting aspect of this association of 3 month colic and cows’ milk intolerance was the refusal of many otherwise sensible consultant (and dare I say it academic) paediatricians (including a friendly Professor of Paediatrics!) to doubt the importance of the cows’ milk in these infants and fail to give trial to a cows’ milk free diet for a few days.   In all seriousness, I felt very strongly about failure to diagnose these infants as at a time for when the parents should have been enjoying the first months of the their new baby, they were made to feel inadequate and a failure in caring for their infant sadly often by their family doctor. At least one of my seven grand children did well on Nutramigen!

Minford A M B, MAcdonald A, Littlewood J M. Food intolerance and food allergy in children:a review of 68 cases. Arch Dis Child 1982; 57:742-747.

Littlewood JM, Macdonald A. Clinical aspects of food allergy and intolerance. In Heatley RV., Losowsky MS, Kelleher J. (eds.) Clinical Nutrition in Gastroenterology 1986  pp202-33.  Churchill Livingstone.

Littlewood JM, Macdonald A. Food Intolerance: Our Practice. Nutrition and Health 1987: 5 (3/4):119-135. A B Academic Publishers.

Littlewood JM. Allergy of the gastrointestinal tract. In Recognition and Management of Food Allergy in Children. Franklin A J (ed). 1988 pp 21-29. The Parthenon Publishing Group.

There may be more than one reason for a child’s poor growth and/or symptoms.  

Dr Olive Scott

Doctors are warned against “double pathologies” but this does not seem to apply to paediatrics. For example, an infant was referred by Dr Olive Scott, our distinguished paediatric cardiologist. Based on her extensive experience, there was more interference with the infant’s growth than they would expect from the severity of the cardiovascular abnormality.

As part of our investigations of the infant Olive Scott referred, a jejunal biopsy was performed which revealed subtotal villous atrophy and confirmed coeliac disease as an additional factor affecting growth. Following this experience we saw a further five children with congenital heart disease referred by the paediatric cardiologists in whom poor growth was found to be due to small-bowel villous atrophy; none was in heart failure and only one was severely cyanosed. Growth improved in all 6 on a gluten-free diet. We suggested that gluten enteropathy may be more common than is realised in children with congenital heart disease, and jejunal biopsy should be undertaken early in any patient with poor growth and no heart failure to exclude the coexistence of the condition. In recent times, of course, appropriate blood antibody tests would be the first step. 

Congdon PJ. Fiddler GI. Littlewood JM. Scott O.  Coeliac disease associated with congenital heart disease. Arch Dis Child 1982; 57(1):78-9.

Pancreatitis and severe abdominal pain

Pancreatitis is very rare in children and so not immediately diagnosed in many instances. I was asked to see a child in another city who had been admitted to hospital there with severe attacks of abdominal pain. These were accompanied by loud crying, screaming and severe extension of the trunk. It had been suggested that he was emotionally disturbed so violent were the outbursts of screaming and posturing.

As I had on many occasion recalled the advice of my friend, Professor Monty Losowsky, –  “the buck stops here” so fully investigate problems where the cause is not immediately obvious particularly if asked for a second opinion.  This is particularly important when the patient has been referred for another opinion on diagnosis. So, following this policy, the child was fully investigated and a raised plasma amylase led to a diagnosis of recurrent pancreatitis – a very rare condition in children.

“The buck stops here!”

Although originally attributed to President Harry S Truman, this is a good motto for the consultant in a tertiary referral centre who is asked to see patients with clinical problems which have not been solved elsewhere. My main base, St James University Hospital, with its numerous expert colleagues in so many different areas, was an ideal environment to provide such a service and over the years we received many such referrals. The following case history illustrates the rewards of such a policy in certain instances.

A 6 year old with progressive weakness 

Steve Conway was my registrar at the time

A Leeds family doctor asked if I would see a child whose parents had recently brought their 6 year old daughter from Bangladesh in view of a serious progressive illness. She had been well to the age of 3 years when her tongue became red and painful; she suffered unexplained episodes of severe anaemia despite repeated courses of iron and folic acid and there was a gradual onset of muscular weakness. From 5 years she developed a coarse tremor of the limbs and face.

On examination the child was weak and wasted (weight < 3rd  height 10th centile). She had difficulty swallowing, had slurred speech and saliva drooled from the side of her mouth. Her tongue was red, wasted and showed fasciculation. 

Initial assessment suggested a brain stem tumour but computed tomography showed unexplained mild hydrocephalus and a general decrease in size of other parts of the brainstem. Extensive metabolic investigations were also normal. However a second blood sample taken during a febrile episode was abnormal showing severe pancytopenia prompting bone marrow examination which was also very abnormal and megaloblastic (cells larger than normal). The serum B12 was only 55ng/l (low normal range 110ng/l. Further tests confirmed gross B12 deficiency which we showed was due to defective absorption.

Treatment with vitamin B12 1 mg daily brought about an almost miraculous improvement. There was rapid response in the anaemia and bone marrow. Growth and weight accelerated (Ht to 25th, Wt to more than 25th centile) over 4 months and she became an active child, able to run unaided.  The only residual abnormalities were some loss of peripheral sensation and absent tendon reflexes with slight reduction in power.

We concluded, by exclusion, that the condition was due to an inherited failure to absorb vitamin B12 from the small intestine.  This was really a remarkable case. The parents and referring doctor were obviously delighted. It was a good example of how many experts in a massive hospital, such as St James’s, working together solved a very serious and difficult problem. 

Conway SP. Gillies DR. Littlewood JM.   Vitamin B12 neuropathy in a 6 year old. Arch Dis Child 1984; 59(6):575-6. 

Intractable pruritus in a 2 yr old child

I was asked to see this child by the paediatrician in Harrogate Hospital. A 2 year old boy had been adopted at 9 days and had scratched intensely since that time. He did have transient neonatal jaundice. His general milestones and  growth had been normal.  He had extensive skin excoriations without evidence of eczema. His appearance was slightly unusual in that his forehead was prominent,  nose straight and small pointed chin with eyes set deeply and somewhat widely apart (figure of another child with syndrome). 

Alagille facies from Maha Saleh et al Appl Clin Genet 2016;9: 75-82 with 

There was an obvious systolic heart murmur audible over the whole chest. The liver was palpable one finger below the costal margin. Extensive investigations were normal apart from liver function tests – alkaline phosphate 71.4 (N 0-20 KA units), ALT 82 iu/l (N 0-40) and the plasma 25hydroxy vitamin D, 1,2ng/mi was very low in the rickets range.

I performed a needle biopsy of the liver which was initially considered normal but Dr Alex Mowat a colleague and national liver expert of King’s College Hospital, London considered it to be compatible with the diagnosis of arteriohepatic dysplasia (Alagille syndrome) showing intrahepatic bile duct hypoplasia and bile thrombi. Mild pulmonary stenosis was confirmed by Dr Gordon Williams our paediatric cardiologist. 

We tried various treatments for the pruritus. Three different regimens of antihistamines, topical corticosteroids and a cow’s milk free diet all failed. However, cholestyramine, reducing cholesterol and bile acid levels, produced a dramatic reduction in pruritus but this returned if ever the dose was less than 2.5g/day. Vitamins D and other fat soluble vitamins were also given.

In our article we reviewed previous patients described since 1949. There is now an extensive literature dealing with the condition including 91 liver transplantations eventually required in 20% to 50% of cases.

Ryatt KS. Cotterill JA. Littlewood JM.  Generalized pruritus in a baby as a presenting feature of the arteriohepatic dysplasia syndrome. Clin Exp Dermatol 1983; 8(6):657-61

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Edit “Some stories and lessons from thirty years in clinical paediatrics”

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