abdominal pain in cystic fibrosis

JOURNAL OF THE ROYAL SOCIETY OF MEDICINE Supplement No. 25 Volume 88 1995

Abdominal pain in cystic fibrosisJ M Littlewood MD FRCP

J R Soc Med 1995;88(Suppl. 25):9-17 PAPER READ TO SECTION OF PAEDIATRICS, 25 OCTOBER 1994

Keywords: cysticfibrosis; abdominal pain

GENERAL OBSERVATIONS ONABDOMINAL PAIN IN CHILDREN

Abdominal pain, both acute and recurrent, is a relativelycommon problem in childhood. Even in infancy the wellknown 'three month colic' affects some 15% of healthyinfants and is the most likely explanation for recurrent andexcessive crying in the first year; cow's milk proteinintolerance appears to be a major causel. Cow's milkintolerance is well documented in infants who have cysticfibrosis (CF)2. In some infants the bowel abnormality persistsinto the second year and the so-called 'toddler diarrhoea' maybe associated with abdominal pain as a manifestation of theircolonic irritability.

The usual cause for an isolated bout of abdominal pain ina school child is an acute gastrointestinal or systemicinfection which may also be responsible for more importantsymptoms and signs e.g. high fever, diarrhoea or chestinfection.

However, some 10% of school children havetroublesome recurrent attacks of abdominal pain; the typeof pain and other clinical features of this 'recurrentabdominal pain syndrome' have been well described bythe late Dr John Apley. He described these children as

having three or more attacks of abdominal pain occurring

within the year before evaluation; the pain was severe

enough to interfere with the child's normal activities34.Recurrent abdominal pain syndrome was considered byApley to be primarily a psychosomatic disorder-anapproach still adopted by some paediatricians. Provokingand relieving factors are variable but certainly stress is an

important factor in many children while not being alwaysthe primary cause. The frequent association of other physicalsigns of pallor (38%), lethargy (26%), vomiting (22%),fever (11%) and headache (11%) suggest that some degreeof autonomic instability is present. In addition to Apley'sobservations the infrequent effect on appetite (which makesa gastric cause unlikely), the lack of nocturnal pain sufficientto wake the child (suggesting a daytime motility problem),the presence of a parental gastrointestinal motility problemand migraine and a personal history of infant colic are further

St James's Univemity Hospial, Beckett Street, Leeds 1.59 7TE, UK

valuable evidence for recurrent abdominal pain syndrome inthe child who does not have cystic fibrosis.

It is relevant that Apley's early clinical studies of childrenwith recurrent abdominal pain syndrome were carried outbetween the 1950s and 1960s i.e. before many of thepresent-day gastroenterological investigations wereavailable5. These include jejunal biopsy, fibre opticendoscopy, hydrogen breath tests, tests for Helicobacterpylori, reliable serological tests for coeliac disease and anawareness of food allergy and intolerance as an importantcause of gastrointestinal and other disorders6.

At all ages, acute surgical conditions, acute infections ofall types and constipation are considered as alternativeexplanations for abdominal pain even when the child doesnot appear particularly unwell and even when the patient hashad previous episodes of recurrent abdominal pain syndromeor, in the case of an individual who has CF, previousepisodes of distal intestinal obstruction syndrome (DIOS).

ABDOMINAL PAIN IN CHILDRENWHO HAVE CYSTIC FIBROSIS

It is important to emphasize that although there areparticular circumstances which may result in children withCF having abdominal pain (e.g. inadequately controlledintestinal malabsorption), their pains should not immediatelybe attributed to one or other of these complications.

In our paediatric CF clinic approximately 11% of,individuals report having occasional abdominal pain-interestingly, a similar prevalence to that reported innormal school children by Apley4. Regular abdominal pain isreported to occur in 31% of children who are referred fromgeneral paediatric clinics to our unit for assessment of theirCF7. Prior to referral only a minority of these patients havehad their intestinal absorption monitored by regular dietaryassessments and faecal fat estimations. Thereforemalabsorption, which has not given rise to significantgastrointestinal symptoms, has not been identified and theenzyme dose has not been increased. As a result the patientsare receiving relatively smaller doses of pancreatic enzymesthan patients whose absorption is checked every year.

The prevalence of recurrent abdominal pain differs withthe mode of presentation e.g. meconium ileus 38%,respiratory 39%, malabsorption 47%, presence of CFsibling 30% and in those diagnosed by neonatal screening

JOURNAL OF THE ROYAL SOCIETY OF MEDICINE

Table 1 Investigation of recurrent abdominal pain in cystic fibrosis

Urine-chemical, microscopy and culture

Faeces-ova, cysts, parasites, pathogens. Blood, fat microscopy,faecal fat, chymotrypsinFull blood count, ESR, plasma viscosity

Acute phase reactants, e.g. C-reactive protein

Amylase, immunoreactive trypsinLiver function tests

Helicobacter pylori ELISA (or breath test)

Coeliac serology

X-ray chest and abdomen

Ultrasound (GI, liver, renal)Contrast studies

Endoscopies (with biopsies)Surgical opinion

only 4%8. It is interesting, but not understood, whygastrointestinal symptoms are more likely to persist in thoseindividuals who were not diagnosed in early infancy.

All individuals who have CF already have a variabledegree of pancreatic damage at birth and in our clinic, wherethe majority of the patients come from the North ofEngland, 95% have pancreatic insufficiency of a degree tocause intestinal malabsorption from early infancy. Pancreaticsecretion of bicarbonate is affected early and the duodenaland upper jejunal pH is abnormally low; however, most ofthe small bowel is at a pH of 6 or more9 which permits thesatisfactory release of the enzymes from acid-resistantmicrosphere pancreatin preparationsl'. Also the smallbowel transit time is prolonged in CF compared tocontrols9. If the patient does not receive appropriate dosesof pancreatic enzymes taken in a correct manner, theresulting intestinal malabsorption is likely to causeunpleasant gastrointestinal symptoms and signs indudingacute and recurrent abdominal pain, distention, abnormalstools, malnutrition and growth failure.

With modern pancreatic enzyme replacement therapyand dietary advice, the symptoms of intestinal malabsorptionare completely controlled in the majority and a normalnutritional state can be achieved11. Most adequately treatedpatients will have considerable, if not complete, control oftheir intestinal malabsorption as judged by subsequent fatabsorption studies12.

However, a minority of individuals who have CF willcomplain of persisting gastrointestinal problems indudingabdominal pain, distension and abnormal stools even thoughthey are taling substantial doses of acid-resistant pancreaticenzymes in a correct manner. Some, but not all, will also

have persisting significant intestinal malabsorption (absorbingless than 85% of their dietary fat intake).

Abdominal pain is best considered as an acute isolatedevent or as a recurring problem. The recurrences may bemild or severe. Most causes which need to be consideredaffect children who do not have CF as well as those who do.

IMPORTANT CAUSES OFACUTE ABDOMINAL PAIN

Acute gastrointestinal infection

Some form of gastroenteritis is a common cause of acuteabdominal pain in a previously well child and will, of coursealso affect children who have cystic fibrosis. The acutenature of the illness, the occurrence in friends or otherfamily members and the presence of diarrhoea soon after theonset of the pain are helpful in distinguishing gastrointestinalinfections from more serious conditions. The differentiationfrom an acute surgical condition may be difficult if the childis seen before the onset of the diarrhoea when onlyabdominal pain and vomiting are the main symptoms.

Gastrointestinal infections, both acute and chronic,should be exduded as far as possible in CF individualswho have persisting or acute gastrointestinal symptoms. Inone North American series of CF patients a cross-sectionalstudy identified 28% of CF patients were positive for Lambliagiardia compared to 6% of controls13. Although theprevalence is unlikely to be so high in the UnitedKingdom (UK), there have been isolated reports ofgiardiasis affecting CF patients in this country'4.

Acute surgical conditions

In any child who complains of significant abdominal pain, thepossibility of an acute surgical condition should beconsidered even if they have previously had recurrentepisodes of abdominal pain diagnosed as recurrent abdominalpain syndrome or DIOS in the case of cystic fibrosis.

Acute appendicitis

Appendicitis is notoriously difficult to diagnose particularlyin young children. Pain in the right iliac fossa and areluctance to move about are important symptoms and signsin young children; tenderness in the right iliac fossa remainsthe most important physical sign in children of all ages. It isimportant for the doctor to review children with significantabdominal pain frequently, to request that any deteriorationis reported immediately and to recognize that a surgicalcause is increasingly probable if the child is not improvingwithin 24 h.

In a recent review of 1220 CF patients, a total of 60(4.9%) patients had previously had an appendicectomy. Thespectrum of appendiceal disease varied from simple mucusdistention to classical acute appendicitis with perforationl5.10

Supplement No. 25 Volume 88 1 9 9 5


In a series of 51 autopsied CF patients, in 49 the mucosa ofthe appendix was hyperplastic and the glands distended witheosinophilic material16. The diagnosis is certainly delayed insome CF patients; in nine patients with appendicitis from theToronto clinic, eight had abscesses and in four operation wasdelayed for more than three days'7. Pain from a non-inflamed distended appendix is a distinct syndrome in CFpatients and even intussusception of the appendix has beendescribed as causing cramping lower abdominal pain'8.

Thus, appendicitis should be considered in any CF patientwith suggestive symptoms and signs particularly if thebarium enema, perhaps performed to excludeintussusception, shows extrinsic compression of thecaecum. Other investigations including ultrasound, CT andgallium scans are of limited value19'20. It is re-emphasizedthat even when sophisticated present-day investigations areavailable, persisting and/or increasing local tenderness in theright iliac fossa remains one of the most important signs ofappendicitis and abscess formation.

Intussusception

The diagnosis of intussusception is also difficult in the earlystages. Particularly in young children there may be almostnormal behaviour between the bouts of severe intestinalcolic, vomiting and pallor. The diagnosis must always beconsidered in any child who develops an acute attack ofsevere colicky abdominal pain. The presence of rectalbleeding is a late sign and the abdominal mass is oftenimpalpable.

Intussusception is even more difficult to diagnose inpatients who have CF who may have had previous episodesof abdominal pain associated with inadequately controlledintestinal malabsorption or DIOS. In every patient withcolicky abdominal pain the possibility of intussusceptionshould be considered even if there has been previous painassociated with DIOS. It has been estimated that 1% of CFpatients have an intussusception but this report was beforethe more effective acid-resistant microsphere pancreaticenzyme preparations were available21. Recent experiencesuggests that the frequency is lower since the control of theintestinal malabsorption has improved. The main clinicalfeatures reported in the CF patientfs were colicky abdominalpain (77%), a palpable mass (68%), vomiting (57%) andrectal bleeding (23%).

Ultrasound examination may reveal typical appearancesof a doughnut or bull's eye22 but not all would agree thatultrasound is 'a reliable non-invasive method to confirm orexclude intussusception'23. In our experience abdominalultrasound has failed to identify intussusception in a CFpatient; therefore a contrast enema should be performed atan early stage and will usually suggest the diagnosis21'24'25.

The intussusception may be chronic in CF patients as in onecase reported23.

Thus, the CF individual who has severe colickyabdominal pain and a right iliac fossa mass and tendernessshould have a contrast enema at an early stage in an attemptto rule out intussusception. The enema may be therapeutic ifDIOS or constipation or even intussusception is the cause(vide infra). Increasing local tenderness and deterioration inthe patient's general condition are also of paramountimportance in deciding on the need for surgical intervention.

Structural abnormalities

Complications of previous abdominal surgery should beconsidered in CF patients who have previously hadmeconium ileus or other previous abdominal surgerywhich may have been followed by adhesions, leading tovolvulus and obstruction. Early recognition and surgicalintervention may prevent further loss of bowel. Strictures atthe site of previous bowel anastomosis following operativetreatment of meconium ileus are a well recognizedcomplication8; improved surgical techniques have reducedthe likelihood of their occurrence. Other anatomicalproblems include unrelated structural abnormalities eithercongenital or acquired including malrotation, volvulus,Meckel's diverticulum and strangulated hernia.

Primary peritonitis

This is a rare cause of acute abdominal pain and fever inchildren but has been described in adults with cystic fibrosispatients who have ascites secondary to hepatic cirrhosis26.Ascitic fluid should be obtained for culture at an early stage-when abdominal pain and fever occur in such patients.

Liver and biliary disease

Although abnormalities of liver function tests and ultrasoundexamination of the liver, bile ducts and gall bladder arerelatively common in CF, liver disease rarely causes acuteabdominal pain in those with a clinically abnormal liver and/or spleen on abdominal examination. The pre-icteric phaseof hepatitis is a rare but at times confusing cause of acuteabdominal pain in a previously healthy child. Such childrenusually have some localized tenderness over the liver butjaundice may not be apparent for some days. Acutepresentation of CF liver disease as an apparent non-A/non-B hepatitis has been described in two patients27.

Although bile duct and gall bladder abnormalities arerelatively common in individuals who have CF, they are nota common cause of symptoms28. The suggestion thatabdominal pain was commonly related to the presence ofdistal bile duct stenosis29 has not been confirmed insubsequent studies30'31 nor in our own patients32 and


appear to be a manifestation of more general abnormalitywith the cholangiographic features of sclerosing cholangitis.Radiolucent gallstones are common in older CF patients(approximately 15%) but less than 5% develop pain or othersymptoms which require operative treatment33.

In CF patients who have splenomegaly splenic infarctionsmay result in pain and tenderness in the left upper abdomen.The area of tenderness may be obviously localized to thesurface of the enlarged spleen on palpation.

Constipation

This may be the only abnormality found in many childrenwho are admitted to hospital with an attack of acuteabdominal pain. It is also relatively common in patients whohave cystic fibrosis. Constipation as a cause as suggested by ahistory of constipation earlier in childhood is helpful insupporting the diagnosis for many parents are unfamiliarwith the bowel habits of their older children. On clinicalexamination there may be faecal masses palpable in theabdomen and on rectal examination. Abdominal X-ray ishelpful in demonstrating excessive faecal shadowing in thecolon. In some CF patients the differentiation betweenconstipation and DIOS becomes somewhat blurred as will bediscussed (vide infra).

Other possible causes

Other possible causes of abdominal pain which must beconsidered in any child with acute symptoms, whether ornot they have CF, include referred pleuritic pain associatedwith a chest infection, urinary tract infection, abdominaltrauma, ingested foreign bodies, Henoch-Schonlien purpurabefore the appearance of the rash, referred pain from spinaldisease and dietary indiscretions or food allergy, intoleranceor poisoning.

RECURRENT ATTACKS OF ABDOMINAL PAIN

Chronic colonic faecal overloading with variable abdominalpain occurs in CF patients and is a relatively frequent causeof chronic intermittent pain with episodes of more acutepain. These patients may not complain of constipation(defined as the infrequent, painful passage of hard stools) andthey may report having their bowels opened daily withoutmajor problems. In a patient who has CF and more acuteepisodes of pain, the colonic overloading may be moresevere and extensive leading to the signs of lower intestinalobstruction. At this stage the clinical syndrome of distalintestinal obstruction is likely to be diagnosed.

Distal intestinal obstruction syndrome (DIOS)

This is dharacterized by recurrent attacks of abdominal painresulting from complete or partial intestinal obstruction34-36.

Figure 1 Colonic overloading causing chronic abdominal pain in achild with cystic fibrosis

Inspissated intestinal contents present in the distal ileum andproximal colon can often be palpated as masses in the right iliacfossa. In some patients there are the dassical signs ofsmall bowelobstruction with pain, abdominal distension, constipation andbilious vomiting.

In those patients who have recurrent episodes of DIOS itmay be particularly difficult to identify other intra-abdominalconditions if and when they occur. These includeappendicitis, peritonitis, intussusception, intestinalvolvulus, Crohn's disease, small bowel perforation, afistula or ovarian conditions22'36. It is essential that thesealternative causes for the episode of abdominal pain arealways considered.

The prevalence of DIOS differs between CF clinics and isreported to affect 10-47% of CF individuals. It is no morecommon in those who had neonatal meconium ileus35,37. Inour clinic 11% of patients complain of occasional mildabdominal pain but troublesome DIOS is rare. The varyingprevalence of DIOS is interesting and supports the view thatvariations in treatment regimens, particularly the dose andmethod of administration of pancreatic enzymes, areimportant in pathogenesis38. Although DIOS is morecommon in patients whose malabsorption is inadequatelycontrolled, it can occur when adequate doses of enzymes arebeing taken to achieve good control of the malabsorption.12


The incidence of DIOS does not appear to have increasedfollowing the gradual relaxation of fat restriction after theintroduction of acid-resistant pancreatic supplements in 1983.The condition is certainly more prevalent in older patients whotake relatively less enzyme per kg body weight as they growolder39. Compliance with enzyme treatment appears to be amajor factor in some patients but occasionally there is noobvious explanation for the recurrent attacks of pain andobstruction. In one series the diabetes mellitus present in someof the patients and possibly mild dehydration may have been acontributory factor40. Opiate addiction has been implicated as acontributory factor4l.

In patients with DIOS, there may be a history of previousepisodes, increasing constipation and inadequate intake ofpancreatic supplements suggested by a significantly less thanaverage dose for age or by evidence of poor compliance withother treatments. A low faecal chymotrypsin level in thepresence of an allegedly reasonable dose of pancreaticenzymes suggests poor compliance with taking the enzymes.

Investigations in patients who are prone to attacks ofDIOS should include a serum amylase and abdominalX-rays. If the condition is not responding to medicaltreatment a contrast enema should be performed (vide infra).CT scan has been recommended to reduce likelihood ofunnecessary surgery and to monitor the treatment of thecondition42. Ultrasound may be helpful in identifying theobstructing masses and may, but cannot be relied upon to,exclude other causes of pain and obstruction such asintussusception.

Patients with more resistant and prolonged symptoms ofDIOS may be ill and dehydrated; they require urgentintravenous rehydration and thorough investigation as it isessential to exclude surgical conditions. For patients withmild symptoms of colicky pain perhaps with an abdominalmass but a soft non-tender abdomen, one or more doses oforal gastrografin (diatrizoate) with additional fluid usuallyrelieves the situation in hours38. We use the recommendeddoses of 100 ml of gastrografin in 400 ml of water or fruitjuice for patients over eight years and 50 ml gastrografin and200 ml fluid for younger patients; then half doses can begiven daily until clear. Gastrografin can be used as an enemausing 100 ml up to three times daily. Some prefer to useoral N-acetylcysteine using a solution of10-20 gm in 100 ml and giving 10 ml three times daily oras an enema using 50 ml of the solution with 50 ml ofwater. It is important to maintain adequate hydration at alltimes.

A particularly effective treatment is the oraladministration of large volumes of a balanced electrolyteintestinal lavage solution41,43A44. Klean-Prep is a convenientready mixed preparation. Adults and older children maydrink the solution but children usually require a nasogastrictube to achieve the 20-30 ml/kg body weight per hour

required (max I l/h) although more protractedadministration seems to be effective. Usually 2-3 1 of thesolution are required for a child and 5-6 1 for an adult.

After an episode of DIOS there should be a review of theadequacy of and compliance with pancreatic replacementtherapy-often the dose of enzymes is increased. Regulardoses of oral gastrografin (perhaps every weekend) or otherlaxatives have proved effective in some patients with morechronic low grade symptoms which persist even afterimproving intestinal absorption. Cisapride is helpful inpatients having recurrent attacks of DIOS and/orconstipation45.

Episodes of DIOS are relatively infrequent in a clinicpopulation if intestinal absorption is monitored regularly byannual dietary assessments and faecal fat estimationspermitting calculation of the percentage of dietary fatabsorbed. Those with significant steatorrhoea (less than 85%absorption of dietary fat intake) have their dose of pancreaticenzyme gradually increased even if they have nosymptoms'2.

CONSTIPATION AND ACQUIRED MEGACOLONIN CF PATIENTS

Although some CF patients have recurrent and acuteabdominal pain due to inspissated material in the lower smallintestine and colon, some patients have an acquiredmegacolon syndrome with chronic faecal retention andcolonic pain37 similar to that which occurs in chronicallyconstipated patients who do not have cystic fibrosis. Chronicconstipation, acquired megacolon and DIOS may, at times,be present in the same individual and it is helpful to considerthese complications as variants of the same motility problemwhich leads to slow intestinal transit time. Important in thecausation are abnormal mucosal transport, mucusabnormalities and intestinal malabsorption primarily due topancreatic insufficiency. All these factors may contribute tothe abnormal and excessive intestinal contents which mayresult in blockage and DIOS.

Much abdominal pain, both in those who have CF and inotherwise healthy individuals, is undoubtedly colonic inorigin. In fact, the late Dr Still, a distinguished paediatricianearlier this century, considered constipation to be one of themore common causes of abdominal pain particularly inyoung children46 even though it received no mention in arecent review of the subject in a leading paediatric journal47.

A overloaded colon is easily seen on abdominal X-ray butmay not be identified by abdominal palpation (Figure 1). Theincreasing colicky central abdominal pain caused byincreasing distension of the colon is typically central orlower abdominal and relieved or improved by defaecation.There may or may not be associated persisting intestinalmalabsorption. There may be either reduced bowel 13


frequency and occasionally severe rectal overloading evenresulting in soiling from overflow incontinence. Distalcolonic obstruction severe enough to require laparotomy hasbeen described48.

Many patients with continuing abdominal symptoms haveoften been diagnosed late or received inadequate treatmentwith pancreatic enzymes. If such patients are suddenly givenincreased doses of pancreatic enzymes or changed to a moreeffective enzyme preparation to control their chronicmalabsorption, they may develop severe constipationwhich requires vigorous laxative treatment.

In non-acute cases where there is troublesome chronicdiscomfort and evidence of colonic faecal overloading,management should include checking that absorption isadequately controlled by gradually increasing the pancreaticenzyme supplement until the faecal fat absorption isreasonable (more than 85% and ideally more than 90%).If the symptoms persist laxatives are indicated-eitherregular lactulose, Senokot (senna), gastrografin (diatrizoate)or even balanced electrolyte intestinal lavage solution.Abdominal X-ray provides useful additional information tothe history and physical examination in determining thedegree of faecal overloading. Cisapride has proved helpful insome of these patients45, as it is in treating constipation inchildren who do not have cystic fibrosis49.

Colonic strictures

The recent description of colonic strictures in CF children,most of whom have been taking large doses of the newhigher lipase pancreatic enzyme preparations, has promptedearlier investigation of patients who have troublesomepersisting abdominal symptoms50. The subject is reviewedelsewhere in this volume51. Two children of the 130receiving all their care at our CF unit have developed colonicstrictures, one mild and one severe requiring ileostomy52.All our other patients who have any abdominal symptoms atall and who have taken higher lipase enzyme preparations,either now or in the past, have been shown to have normalcolonic anatomy. Abdominal X-rays one, three and fivehours after giving a therapeutic dose of oral gastrografin willoften permit adequate visualization of the colon; others havehad contrast enemas. The details of ultrasound and contrastinvestigations are discussed elsewhere in this volume53.

OTHER CAUSES OF RECURRENT OR CHRONICABDOMINAL PAIN

Gastro-oesophageal reflux

There is an increased frequency of gastro-oesophagael reflux(GOR) in CF individuals5456. A recent study identifiedinappropriate relaxation of the gastro-oesophageal sphincteras the major cause of their reflux55. Gastro-oesophagealreflux is more prevalent and troublesome in young CF

infants but improves with increasing age. In the younginfants the tendency to regurgitation and vomiting iscommonly associated with more severe chest symptoms.Treatment of the GOR, particularly with cisapride, not onlyimproves the vomiting but frequently improves therespiratory symptomsS6.

Severe GOR and associated symptomatic oesophagitiscausing severe pain may prove a major problem at any age.In the rare CF patient with reflux and vomiting sufficient tointerfere with weight gain, a fundoplication operation maybe required. In patients with symptoms of GOR who havesignificant chest involvement, a more aggressive approach tothe chest infection with high doses of intravenous antibiotics,in addition to standard anti-reflux treatment, may lead toimprovement of the oesophagitis and significant reduction inthe pain and vomiting.

GASTRITIS AND PEPTIC ULCER

A peptic ulcer was present in 12 (8%) of one autopsy seriesof 146 CF patients some years ago57. In the children andadults attending our CF clinics peptic ulcer does not appearas a significant problem or cause of abdominal pain; thisseems to be general experience nowadays.

Helicobacter pylor (HP) gastritis is an important cause ofupper abdominal pain in children who do not have CF in ourexperience58 although this relationship has beenquestionedS9. Infection with HP has been reported to beno more common in 279 CF individuals (11% positive) than170 controls (16% positive)60. However, in a recent studyfrom Greece HP antibodies were detected in 27.2% of CFindividuals, compared to 20.2% of patients with epigastricpain and 7.4% of controls; infection was more common inthose homozygous for the d508 mutation61. The prevalenceof HP does vary with locality and social conditions inchildhood but the possibility of HP gastritis should beconsidered in both children and adults who have cysticfibrosis who have persisting abdominal pain, particularly ifthis is epigastric and associated with nausea and vomiting.

The adverse effects of multiple drugs on the gastricmucosa should be considered in patients where epigastricpain and vomiting are problems. Certainly in patients withupper abdominal symptoms the possibility that they arerelated to oral drugs should be considered. Gastroscopy mayreveal a nonspecific gastritis.

PANCREATITIS

Histological abnormalities of the pancreas are present in allCF infants at birth and progressive throughout life62.Chronic and acute pain due to pancreatitis is a well describedcomplication in CF patients particularly those who havesome residual pancreatic function63'64. Conversely, CFshould be considered in all patients with acute or relapsing14


pancreatitis even if there are no other features suggesting thediagnosis. Pancreatic serum enzymes, amylase, iso-amylaseand immunoreactive trpsin are usually low in CF after thenewborn period and virtually always after the age of 10years65 but are raised in those patients who have pancreatitis.Pancreatic ultrasound is usually abnormal by mid-childhood,but may be normal in pancreatic sufficient patients66. Serumamylase is measured by all laboratories and should bemeasured on a number of occasions, preferably at the timeof symptoms, in individuals who have CF and who havetroublesome recurrent abdominal pain to identify those withpancreatitis.

COWS' MILK INTOLERANCE

Vomiting, failure to thrive or persisting abdominal pain anddiarrhoea in a CF infant may be due to cows' milk proteinintolerance (CMI). Cows' milk intolerance has been provedby serial jejunal biopsies in CF infants and it is important toconsider this possibility in any who have persistingabdominal symptoms2. However, we have found thatsymptoms due to food allergy and intolerance are unusualin older CF patients even though many are atopic. The lowerfrequency of specific IgE to foods was considered to berelated to impaired antigen absorption67.

COELIAC DISEASE

Abdominal pain may be the main presenting feature of CF inolder children68. In a recent series of 1100 CF patients, five(0.45%) also had coeliac disease. Coeliac disease wasdiagnosed by the usual criteria following investigation ofpersisting clinical and biochemical evidence of malabsorptiondespite apparently adequate pancreatic supplements69. Ofapproximately 500 CF patients having a comprehensiveassessment at our unit, two also had coeliac disease-asimilar prevalence (0.4%) to that reported from Italy69.

Although anti-gliadin, anti-reticulin and anti-endomysialantibodies are of value in identifying CF individuals at riskfor coeliac disease, a jejunal biopsy should be performed inany CF patient who has significant persisting bowelsymptoms and malabsorption despite apparently adequatepancreatic enzyme treatment and is still required whenantibody tests suggest the diagnosis. Alternatively, duodenalbiopsies should be obtained if the patient has an endoscopy asthese may be adequate to demonstrate a normal villouspattern and thus exclude coeliac disease.

CROHN'S DISEASE

Crohn's disease in CF patients has been reported on anumber of occasions and recurrent pain has been aprominent clinical symptom70. The diagnosis ofinflammatory bowel disease can be difficult beforelaparotomy, which may itself be delayed, the symptoms

having been attributed to distal intestinal obstructionsyndrome. It has been suggested that inflammatory boweldisease is more likely to develop after meconium ileus andthe increased survival of these infants in recent years may berelevant. It is sound advice that 'any patient with CF whodoes not have an obvious explanation for failure to thrive orgrowth failure as a result of advanced pulmonary disease orwho fails to respond to treatment for pancreatic insufficiencyneeds a full work-up that includes demonstration of theanatomical status of the intestinal tract'70. In addition toradiological investigations to demonstrate the anatomy of thegastrointestinal tract, there should also be biopsies of thegastric, duodenal and colonic mucosa for histology.

There has been no CF patient recognized as havingCrohn's disease in the 500 CF patients thoroughlyinvestigated at our CF unit.

INTRA-ABDOMINAL MALIGNANCY

As the survival of CF individuals improves, there have been anumber of reports of malignant disease of thegastrointestinal tract which may present with symptomsinduding abdominal pain. Adenocarcinoma of the ileum hasbeen reported in four patients71. Another presented asclostridial myonecrosis72. Bowel carcinoma may presentwith abdominal pain and mimic meconium ileusequivalent73. Carcinoma74 and adenocarcinoma75 of thepancreas have also been described. The increasing frequencyof these reports have been advanced as a reason for theimportance of routine postmortem examination of all CFindividuals to determine the exact prevalence of suchmalignancies.

CONCLUSION

Abdominal pain is a frequent complaint in people who haveCF whose intestinal malabsorption is not well controlled.The CF patient may, of course, suffer from any of the intra-abdominal conditions which occur in the non-CF individual.It is important that these are considered both as the maincause of the patient's symptoms and also as an additionalcomplication of an existing CF-related disorder. Appendicitisor intussusception may also occur in a patient who alreadyhas distal intestinal obstruction syndrome.

The improved survival of individuals who have CF andthe better control of their malabsorption, and its associatedsymptoms, have permitted the more frequent recognition ofother gastrointestinal complications and additional disorders.

Since the introduction of more effective acid-resistantpancreatic enzymes, 90% of individuals who have CF haveno distressing or indeed any abdominal symptoms. Thepresence of troublesome abdominal symptoms and signs,despite adequate doses of pancreatic enzymes, deserves fullgastrointestinal investigation to exclude the many other 15


disorders which may or may not be unrelated to the CF yetmay be amenable to appropriate treatment.

Thorough gastroenterological investigation of all CFpatients with persisting abdominal pain and other bowelsymptoms at an early stage, rather than assuming they havemalabsorption and progressively increasing the pancreaticenzyme dose, is particularly important in view of the recentreports of colonic strictures.

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