Gastrointestinal problems in children with Ehlers-Danlos syndrome

Mr Jonathan Sutcliffe, Consultant Paediatric Surgeon, Leeds Teaching Hospitals Trust & Mr David Crabbe, Consultant Paediatric Surgeon, Leeds Teaching Hospitals Trust & Angela Hunter, Speech and Language Therapist (retired) and trustee, EDS UK

Please note: The following text cannot and should not replace advice from the patient's healthcare professional(s). Any person who experiences symptoms or feels that something may be wrong should seek individual, professional help for evaluation and/or treatment. This information is for guidance only and is not intended to provide individual medical advice.

The information in this article is based on the experience and expertise of the authors.

Introduction

Gastrointestinal symptoms are common in children with Ehlers-Danlos syndrome (EDS) and a cause of major concern to many of their parents and carers. It can be difficult to decide whether the symptoms are related to the EDS or are symptoms seen in ‘normal’ children. Some types of EDS are associated with life-threatening gastrointestinal disorders. How do you tell whether the abdominal symptoms are serious or not? The aim of this article is to address some of the questions asked about the gastrointestinal symptoms children with EDS suffer.

The Ehlers-Danlos syndromes is a rare group of conditions. The exact incidence is not known, but is estimated to affect around 1 in 10,000 of the population. Because of the infrequency of EDS, scientific literature on clinical aspects of this intriguing condition remains in its infancy and to date the majority of research has focused on molecular genetics. Since most general practitioners and some paediatricians will have never seen the condition before, clinicians may be unfamiliar with the management of its associated problems. This lack of sufficiently detailed understanding by the medical profession is often a source of great frustration to parents, particularly when their children are poorly. The best way for parents to deal with this situation is to share any information they know or may have read about their child’s condition with the doctor at the outset. Most doctors will be grateful for this information not only because it helps them work out what is wrong but also because it alerts them to any specific concerns the parents may have.

What sort of symptoms do children with EDS suffer, how common are they and how can they be treated? Some of the more common symptoms children with EDS complain of include:

  • Pain and difficulty chewing and swallowing
  • Inflamed and bleeding gums, other dental problems
  • Heartburn and reflux symptoms
  • Bloating and excessive wind
  • Frequent hunger but quick satiation
  • Poor growth
  • Chronic abdominal pain
  • Constipation or constipation alternating with diarrhoea
  • Anal fissures
  • Rectal prolapse

 

Symptoms related to oral or gullet problems

Pain and difficulty chewing food is quite a common symptom in children with EDS. The temporomandibular joint (TMJ – between the jaw and the skull) suffers from the same problems of ligamentous laxity (loose ligaments) that affect other joints in the body. In the same way that aches and pains occur in other joints, so they can occur with the TMJ. Helpful supportive measures parents can offer include watching the texture of the food, avoiding particularly hard or chewy food in favour of softer food that separates more easily into lumps that can be swallowed. Do remember that cutting foods that are usually bitten (e.g. toast, apples) may also present the EDS child with a problem because holding a knife and fork can be difficult. Normal childhood activities like chewing toffee and gum may aggravate jaw problems.

The gums often become inflamed in children with EDS. Gentle but regular (morning and evening) brushing of the teeth is important to prevent tooth decay. Use a soft toothbrush or, better, an oscillating electric toothbrush. Avoid excessive sugary drinks. Cola drinks are particularly bad in this respect as they have the same damaging effect as rinsing teeth in concentrated phosphoric acid. Take your child for regular dental check-ups and make sure your dentist is aware of the EDS.

 

Symptoms related to abdominal problems

Heartburn is a common symptom in the healthy population. About 5% of the adult population experience heartburn on a regular basis and this becomes more frequent with age. Heartburn is less common in children but it still occurs. The stomach makes acid as part of the normal digestive process. The lining of the stomach is designed to withstand this acid, the lining of the oesophagus is not. Reflux, or gastrooesophageal reflux, occurs when stomach acid regurgitates into the oesophagus. The acid irritates the lining of the oesophagus and typically causes a burning pain in the upper abdomen or lower chest. Symptoms tend to be worse after a large meal, especially if this involves spicy food. Sometimes milk will help alleviate symptoms and this is a good source of protein and calcium. Proprietary antacids and indigestion remedies like Rennies® and Milk of Magnesia will also help. If symptoms are worse at night then avoid large meals late in the evening. Parents are often advised to raise the head of the bed but usually this just results in the child waking up at the bottom of the bed. Symptoms typically improve with age. Improvements are normally expected firstly when a baby is weaned onto solids and secondly when an infant becomes upright.

If symptoms fail to settle with these simple measures then a variety of medical treatments are available. Drugs to suppress stomach acid production are widely used in children. They include Ranitidine and Omeprazole. Omeprazole has a more profound effect on stomach acid production and it only has to be given once a day. However, this drug is not available as syrup, which sometimes makes administration more difficult. Other drugs used to treat reflux include Domperidone, which encourages the oesophagus and stomach to empty more rapidly, and Gaviscon which protects the lining of the oesophagus with a coating. In a tiny fraction of children the symptoms are so severe that surgical treatment of reflux is required.

Bloating and wind, which are common symptoms, are almost never serious. Usually all that is necessary is to offer small meals often (i.e. snacks between meals like milk and a biscuit) and to avoid a lot of fizzy drinks. Sometimes antacids will help.  Frequent hunger and quick satiation are desperately frustrating symptoms for many mothers. They are never serious but often occur in association with the other symptoms discussed above. The situation invariably improves as the child gets older. Some toddlers are avid drinkers of squash-type juices. These drinks are a good source of fluid (which is good for the bowels) but fill the stomach and provide a rapid surge in blood sugar. This can suppress appetite so the child doesn’t eat a meal. A short while later the child is then hungry. The same problem occurs with foods that rapidly break down to produce a surge in blood sugar. Foods that contain complex carbohydrates are digested more slowly and reduce this problem. Pasta is a particularly good example that is popular with most kids.

Poor growth is common in children with many types of chronic illness. The problem is that the nutritional intake is not sufficient for the child’s needs. Constant encouragement and praise for eating helps. Small snacks between meals can help. High calorie milk drinks are another option but sometimes these simply suppress appetite at meal times. Nutritional supplements bought over the counter (e.g. vitamins) are not generally helpful alone. Professional advice from a paediatric dietician can be invaluable and probably the best way to obtain this help is to ask your paediatrician.

In exceptional circumstances it may be necessary to resort to tube feeding as a method of increasing nutritional intake for a child who is not able to eat enough by mouth. This involves either a nasogastric tube or, if long term feeding becomes necessary, a gastrostomy. A nasogastric tube is a soft plastic tube that passes through the child’s nose down the oesophagus and into the stomach. The tube is taped to the side of the cheek. Special milk formulas can be given down the tube to supplement the oral intake.

Nasogastric tubes are fine for short-term use (up to a few months) but not really suitable for longer-term use because they block or get pulled out by accident and the tube and tape on the side of the child’s face is cosmetically unsightly. If longer term tube feeding becomes necessary then a gastrostomy is a better option. This involves an operation called a PEG – percutaneous endoscopic gastrostomy. The operation takes about 10 minutes and is performed under a general anaesthetic. Usually the child will need to stay in hospital for a few days after the PEG is inserted to establish feeds and make sure the parents are happy with care of the gastrostomy. PEG tubes are reliable, they cannot be pulled out easily by accident and they don’t interfere with oral feeding. PEG tubes generally last about 18 months before they need changing.

Chronic or recurrent abdominal pain is a symptom which drives many parents to despair. It is a very common problem both in children with EDS and in ‘normal’ children. Depending to some degree on how recurrent abdominal pain is defined, 10-25% of all children will suffer from these symptoms. In the 1950s Dr John Apley, a paediatrician from Bristol conducted a large study of otherwise healthy children with recurrent abdominal pain. Apley defined recurrent abdominal pain as three or more episodes of abdominal pain that occurred over at least a three-month period, severe enough to interfere with activities such as school attendance, social activities and participation in sports. Apley found that around 10% of school aged children suffered from recurrent abdominal pain. Other studies have shown that the figure rises to 20% in children in senior school. Long-term follow-up studies have shown that these symptoms eventually resolve spontaneously in the majority of children although some will go on to develop symptoms typical of irritable bowel syndrome in adult life.

How can you determine whether recurrent abdominal pain is serious or not? In general, recurrent episodes of pain that are vague and not localised consistently to any particular area of the abdomen, or are localised to the umbilicus, pains which are dull or crampy and pains which settle within an hour or so either spontaneously or after simple analgesics, are unlikely to be serious. In younger children it is very common for them to point to the umbilicus as the site for the pain. Nausea and vomiting are common in association with abdominal pain.

How can you help a child with recurrent abdominal pain? Sympathy and reassurance help. Lying down and resting with a hot-water bottle will often ease the pain. Paracetamol (Calpol®) may be useful. In the longer term coping strategies are necessary. Some help, others can make matters worse. Strategies that are termed accommodative are of proven benefit and these include acceptance, distraction and ‘positive thinking’. Strategies that are termed passive or disengagement generally make matters worse. These include denial and ‘wishful thinking’. Secondary gain for the child is, however, undesirable and may serve to reinforce and maintain pain behaviours. Examples of this include being excused from helping with the dishes or being allowed to stay off school or other special privileges.

Should you seek medical advice? If the symptoms persist despite these simple measures then the answer is yes. With chronic symptoms it is often helpful to keep a diary – record timing and duration of pain, associated symptoms like headache, nausea, the effects of any treatments and a brief note of any unusual circumstances or events that day. It can be very helpful to look back over a period of a few months to try and establish patterns that can provide useful clues to possible diagnoses. The general approach taken by most paediatric specialists to children with chronic abdominal pain starts with taking a careful history and then examining the child. Occasionally a clinical diagnosis can be made but usually this is not possible. A series of screening investigations may be necessary including blood tests and sometimes an ultrasound scan or X-rays. These investigations are designed to screen for serious diseases. If something turns up then a diagnosis can be made and treatment instituted but if no underlying cause is found then the child, their parents and the doctor can all be reassured that it is very unlikely that serious pathology is being missed. What next? The supporting measures and strategies discussed previously must come into play. With time either new symptoms will emerge to point in the direction of a diagnosis that can be treated or, more usually, symptoms slowly resolve. What is never helpful are continued investigations in search of some elusive diagnosis.

It is worth remembering that children lack the ability to communicate their feelings verbally to their parents. It is quite common for children of all ages to use a physical symptom, such as abdominal pain, as a method of eliciting a predictable response, i.e. sympathy, from their parents. This possibility needs to be considered alongside investigations for physical causes for the abdominal pain. The whole area needs to be handled carefully because parents can go away with the false impression that the child is fabricating the symptoms which makes resolving the problem even more difficult.

 

Constipation

Constipation affects about one child in ten. It is much more common in children with EDS. Symptoms are difficult to measure. Older children in particular may find symptoms embarrassing and fail to mention the problems unless specifically asked.

Our understanding of the causes of constipation is incomplete. The passage of digested food along the gastrointestinal tract requires co-ordinated contraction of the bowel wall, which is called peristalsis. Gut peristalsis is regulated by an intricate network of nerves (the enteric nervous system) which controls the way in which the bowel wall muscle contracts. One particular type of cell within the enteric nervous system – the Interstitial Cell of Cajal – is currently the focus of research in the study of bowel motility disorders. These cells act as pacemakers within the gut and as signal transmitters. Cajal cells appear to be responsible for controlling the resting ‘tone’ of the bowel by their pacemaker activity. This pacemaking activity is affected markedly by stretching the bowel. When bowel distension diminishes the pacemaking activity improves. This may be the explanation for one important strategy for treating children with constipation, which is to avoid letting the bowel become distended. The symptoms of gastrooesophageal reflux, bloating, failure of normal emptying of the stomach, gall bladder problems and constipation suggest that people with EDS may have a more generalised disorder of gut motility. There is a small amount of scientific evidence to support this and further research is needed in this area.

The National Institute for Clinical Excellent (NICE) has published guidelines for the management of constipation in childhood which is relevant for families with EDS. The guidelines include general and specific measures to manage constipation in children.

General measures include encouraging gentle exercise, a good fluid intake, a high fibre diet and patient education. It should be noted that it is very rare for a child to become constipated as a result of a poor diet although it is accepted that a high fibre diet does help constipation. Parents often report that their children become increasingly reluctant to eat or drink as they become more constipated, a situation which then improves after they have opened their bowels. Unfortunately, attempts to alter diet and increase fluid intake in isolation to combat constipation are invariably unsuccessful and laxatives are almost always needed.

Specific measures to treat constipation are considered in four steps:

  1. Faecal impaction: if hard stool has formed a blockage this should be cleared
  2. Different laxatives should be tried in different doses to work out how to keep the child stooling and prevent a further blockage.
  3. The importance of giving laxatives on a regular basis and adjusting the dose in response to changes in bowel function must be emphasised. Treatment with laxatives is usually required for a considerable period of time, rather than, for example, a five day course of antibiotics. Laxatives used to treat constipation in children do not cause problems even if given for long periods.
  4. The final stage in treatment is a careful withdrawal of medication once a normal bowel habit is re-established.

The main problems with laxatives in children are firstly the delay starting them and secondly finding a satisfactory dose. Stool in the small bowel is like diarrhoea and water is absorbed by the colon with the result to produce a formed stool which accumulates in the rectum. If the rectum does not evacuate once every 24-48 hours water will continue to be absorbed from the stool which then becomes progressively harder and larger. Laxatives work in the colon in one of two ways. Movicol® and other ‘softeners’ exert an osmotic effect in the colon, retaining water in the stools and making them softer. Movicol® is supplied in sachets which can be disguised in almost any drink and even jelly and yoghurt to suit the child’s taste. The other group are ‘stimulant laxatives’ such as Senokot or Sodium Picosulphate. These drugs irritate the colon and reduce the time it takes for bowel contents to pass through the colon. Senokot will almost always make a child open his/her bowels more frequently but may be associated with tummy ache and diarrhoea. Movicol® and Senokot are often used together. It is important to understand that treatment with laxatives usually needs to continue for months or even years. Attempts to stop laxatives too soon invariably end in relapse.

Enemas are never popular with children. They should be avoided in children with EDS because of the potential risk of colonic perforation. Occasionally children with a faecal impaction are taken to theatre to have the stool removed (manual evacuation) but, again, this is best avoided in EDS. Disimpaction with oral medication is usually successful if administered correctly. Effective drug regimes for disimpaction can be found in the NICE guidelines.

A fairly common complication of constipation in children is an anal fissure. Passage of a large hard stool causes a small tear in the lining of the anal canal – a fissure. This causes intense pain when the child tries to pass a stool. Often the fissure bleeds during defaecation. The blood is fresh and may be noticed on the toilet paper. Although anal fissures are very painful they are not dangerous. Anal fissures can usually be treated successfully by relieving the constipation to prevent the anal canal from being stretched and re-opening the fissure. In addition, application of specific ointments directly to the anus itself reduces painful spasm in the sphincter muscle and helps healing. The two types of ointment most commonly used are diltiazem 2% and GTN 0.1%. Surgery (anal dilatation or sphincterotomy) is best avoided although injection of Botox may be helpful in certain circumstances.

Rectal prolapse is associated with constipation. The child strains to pass a stool and manages to push out part of the lining of the bowel. This looks dramatic but is not dangerous. Almost always the prolapse will reduce spontaneously if the child lies down and relaxes. If it doesn’t then gentle pressure with a finger will push the bowel back inside without doing any harm. What about treatment? Again, prevention of constipation is important. In toddlers the potty should be banned – the child squats on the potty and is able to generate very high pressures straining. Sitting on a normal toilet seat or a child’s seat on the toilet stops them squatting and reduces the likelihood of prolapse. Limit the amount of time the child is allowed to spend on the toilet. If they don’t open their bowels then they can always go back later. Rarely surgery is necessary to treat a rectal prolapse. This involves injecting a substance called a sclerosant into the bowel wall under an anaesthetic. This works in a similar fashion to injecting piles by anchoring the wall in place. Sometimes more than one set of injections is needed. Rarely more complicated operations are necessary.

 

Serious gastrointestinal problems in EDS

How do you differentiate the common minor ailments from the major gastrointestinal (GI) problems seen in people with EDS? The short answer is that although major GI problems can occur in children with EDS they are very rare. The group at risk are individuals with vascular EDS (vEDS) but even in these children complications are uncommon before early adult life. Unfortunately at most serious risk are those who have unrecognised vEDS. So, for most children with EDS the discussion that follows does not apply.

Oesophageal diverticulae occur in some patients with vascular EDS. A diverticulum is an outpouching of the oesophagus through a weakness in the wall. They are very rare in children. They cause persistent difficulty swallowing associated with regurgitation. They can be identified on a Barium meal X-ray. Unless they are very large (which is unlikely) they are probably best managed without an operation unless the swallowing difficulties are very severe. Oesophageal rupture is another very rare but unfortunately potentially fatal complication in vascular EDS. If the oesophagus ruptures it will do so usually after a bout of prolonged retching and vomiting. Rupture is associated with excruciating chest pain, sweating and shortness of breath. Urgent surgery is necessary to repair the perforation.

Intestinal perforations can occur in vascular EDS. They may occur in both the small and large bowel, although they are more common in the latter. Perforation is associated with sudden onset of very severe abdominal pain, sweating, pallor, vomiting and fever. The pain inexorably worsens and is made worse by any movement. Perforations can occur at any age, but unlike many manifestations of EDS that decrease with age, perforations tend to be rare in childhood and occur predominantly in late teens to the fifth decade. Spontaneous perforation of the bowel may be the first sign of vEDS. Treatment involves emergency surgery. How the bowel is repaired depends in part on where the bowel perforates. Small bowel perforations in vEDS can usually be repaired successfully by closing the hole; large bowel perforation may need to be treated with a colostomy (a surgical procedure to divert one end of the large intestine, the colon, through an opening in the abdominal wall). Closing the colostomy requires a second operation but this is usually less risky than trying to repair the perforation because suture lines in the colon in the presence of infection from peritonitis have a nasty habit of leaking. If there have been previous perforations of the colon, then it may be necessary to remove all or part of the colon and sometimes a permanent colostomy is the safest option. Small bowel perforations cannot be prevented. Perforations of the large bowel may be associated with long-standing severe constipation, particularly if repeated enemas have been used. Enemas never go down well with children and certainly they are best avoided in children with EDS.

Vascular complications occur in people with vEDS although fortunately they are very rare in children. Complications include aneurysmal dilatation, rupture and dissection of major arteries. Individuals are often young adults and again this may be the first sign of vEDS. Aneurysms are swellings of the arteries and they are liable to burst without warning. This causes severe pain, pallor, clamminess and sweating. A dissecting aneurysm is a specific type of rupture where, instead of blood leaking out through a full thickness perforation, the perforation is only partial thickness with the result that blood tracks along the wall of the artery. This is no less dangerous and is associated with similar symptoms. A leaking aneurysm invariably requires urgent surgical repair but unfortunately this complication can be life-threatening.

If the patient knows they have vascular EDS then regular hospital check-ups may allow early detection of an aneurysm. Aneurysms of the thoracic aorta in the chest are common in people with Marfan syndrome and the progress of some of these aneurysms can be slowed down with medication to reduce blood pressure (Beta-blockers). If your child has vascular EDS it is probably wise to steer them away from rough contact sports although gentle exercise should be encouraged.

When surgery is required for the treatment of arterial or bowel complications or other health problems, it is more likely to be successful if the surgeon is aware of the diagnosis of EDS so that additional precautions can be taken when handling the fragile tissues.

Peer reviewed by: Dr Hanadi Kazkaz, Consultant Rheumatologist, University College London Hospital and Professor Qasim Aziz, Professor of Neurogastroenterology, Barts and The London School of Medicine and Dentistry

Date of last review: 01/03/2016

Date of next review: 01/03/2019

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