Gut, 1969, 10, 285-292 Sclerodermatous involvement of the stomach and the small and large bowel R. D. G. PEACHEY, B. CREAMER, AND J. W. PIERCE From St Thomas' Hospital, London Although scleroderma was first described as a disease of the skin in the eighteenth century it was not until the early part of this century that it gradually became apparent that other organs could also be involved by the disease process. In 1944 Hale and Schatzki showed that barium swallow examination was abnormal in 13 of 22 patients with scleroderma. They also found four patients out of 18 whose duodenum and upper small intestine were dilated with marked delay in transit of barium. This they attributed to sclerodermatous involvement of the small bowel and could find only one previous similar case reported (Rake, 1931). In 1945 Goetz reported a further five cases with radiological evidence of dilatation of the duodenum and of loops of the small intestine. In recent years the high incidence of oesophageal involvement in scleroderma has become common knowledge. At the same time there have been increasing clinical reports of sclerodermatous involvement of the stomach and small and large bowel. Rosenthal (1957) was able to find 30 cases of small bowel scleroderma in the literature and added one case of his own with steatorrhoea. More recently a number of further cases have been reported and reviews of gastrointestinal involvement in this condition have been published by Goldgraber and Kirsner (1957), Monroe and Knauer (1962), Hoskins, Norris, Gottlieb, and Zamcheck (1962), Sackner (1966), and others. Although it is now apparent that clinical involve- ment of the small and large bowel in scleroderma is not uncommon, it is still regarded by many as a rare manifestation of the disease and the wide variation and typical features of the clinical picture have not been sufficiently emphasized in the liter- ature. We therefore reviewed the clinical mani- festations of scleroderma involving parts of the gastrointestinal tract other than the oesophagus as seen in 10 patients investigated at this hospital in recent years in order to illustrate some of the pre- dominant clinical features of this condition. CASES AND METHODS The 10 cases of scleroderma, nine of them in women, with evidence of gastric, small bowel, or large bowel involvement have all been investigated at this hospital in the last six years. Full haematological and biochemical investigations were carried out using conventional techniques. Small bowel meal examinations were performed on all the patients using a dilute barium technique (4 oz of Micro- paque made up to 1 pint with cold tap water). Barium enema examinations were carried out on five patients using routine methods. Delayed films of the small bowel meal showing barium outlining the colon were available in three other patients. Case E.N. has already been reported by McBrien and Lockhart Mummery (1962). RESULTS The clinical manifestations of gastrointestinal scleroderma and the results of investigation in the 10 cases are summarized in Tables I, II, and III. Of the 10 patients, the skin was involved in nine, eight suffered with Raynaud's phenomenon, and six had typical oesophageal changes on barium examination. One patient (case L.T.) had no manifestation of scleroderma other than malab- sorption and a grossly abnormal small bowel meal. Some degree of weight loss was present in all of the patients, and in several, especially those with diarrhoea, malabsorption, or vomiting, this was severe. The cause of death in the six patients who died is shown in Table I. In three of these scleroderma involving the gastrointestinal tract was directly or indirectly responsible for death. STOMACH Barium examination showed that al- though the rate at which the stomach began to empty was usually normal, in five of the 10 cases small amounts of barium remained in the stomach for a long time-in one case for over 24 hours. Gastric dilatation was not a marked feature and 285 on March 28, 2021 by guest. Protected by copyright. http://gut.bmj.com/ Gut: first published as 10.1136/gut.10.4.285 on 1 April 1969. Downloaded from
Transcript
Gut, 1969, 10, 285-292
Sclerodermatous involvement of the stomachand the small and large bowel
R. D. G. PEACHEY, B. CREAMER, AND J. W. PIERCE
From St Thomas' Hospital, London
Although scleroderma was first described as adisease of the skin in the eighteenth century it wasnot until the early part of this century that itgradually became apparent that other organs couldalso be involved by the disease process.
In 1944 Hale and Schatzki showed that bariumswallow examination was abnormal in 13 of 22patients with scleroderma. They also found fourpatients out of 18 whose duodenum and upper smallintestine were dilated with marked delay in transitof barium. This they attributed to sclerodermatousinvolvement of the small bowel and could find onlyone previous similar case reported (Rake, 1931).In 1945 Goetz reported a further five cases withradiological evidence of dilatation of the duodenumand of loops of the small intestine. In recent yearsthe high incidence of oesophageal involvement inscleroderma has become common knowledge.At the same time there have been increasing clinicalreports of sclerodermatous involvement of thestomach and small and large bowel. Rosenthal(1957) was able to find 30 cases of small bowelscleroderma in the literature and added one caseof his own with steatorrhoea. More recently anumber of further cases have been reported andreviews of gastrointestinal involvement in thiscondition have been published by Goldgraber andKirsner (1957), Monroe and Knauer (1962), Hoskins,Norris, Gottlieb, and Zamcheck (1962), Sackner(1966), and others.Although it is now apparent that clinical involve-
ment of the small and large bowel in sclerodermais not uncommon, it is still regarded by many as arare manifestation of the disease and the widevariation and typical features of the clinical picturehave not been sufficiently emphasized in the liter-ature. We therefore reviewed the clinical mani-festations of scleroderma involving parts of thegastrointestinal tract other than the oesophagus asseen in 10 patients investigated at this hospital inrecent years in order to illustrate some of the pre-dominant clinical features of this condition.
CASES AND METHODS
The 10 cases of scleroderma, nine of them in women,with evidence of gastric, small bowel, or large bowelinvolvement have all been investigated at this hospitalin the last six years.
Full haematological and biochemical investigationswere carried out using conventional techniques. Smallbowel meal examinations were performed on all thepatients using a dilute barium technique (4 oz of Micro-paque made up to 1 pint with cold tap water). Bariumenema examinations were carried out on five patientsusing routine methods. Delayed films of the smallbowel meal showing barium outlining the colon wereavailable in three other patients. Case E.N. has alreadybeen reported by McBrien and Lockhart Mummery(1962).
RESULTS
The clinical manifestations of gastrointestinalscleroderma and the results of investigation in the10 cases are summarized in Tables I, II, and III.Of the 10 patients, the skin was involved in nine,eight suffered with Raynaud's phenomenon, andsix had typical oesophageal changes on bariumexamination. One patient (case L.T.) had nomanifestation of scleroderma other than malab-sorption and a grossly abnormal small bowelmeal. Some degree of weight loss was present inall of the patients, and in several, especially thosewith diarrhoea, malabsorption, or vomiting, thiswas severe.The cause of death in the six patients who died
is shown in Table I. In three of these sclerodermainvolving the gastrointestinal tract was directlyor indirectly responsible for death.
STOMACH Barium examination showed that al-though the rate at which the stomach began toempty was usually normal, in five of the 10 casessmall amounts of barium remained in the stomachfor a long time-in one case for over 24 hours.Gastric dilatation was not a marked feature and
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was present only in E.J. who developed radiologicaland clinical pyloric stenosis.Of the five patients with radiological evidence
suggestive of gastric involvement three had noupper abdominal symptoms and it seems likelythat gastric involvement by itself may produce fewsymptoms. Involvement of the upper small bowelor of the oesophagus may cause prominent upperabdominal and epigastric symptoms and these mayeasily overshadow any symptoms of gastric involve-ment.
In case E.J., whose barium meal was originallynormal, changes of pyloric stenosis developed overa period of eight months, while she was alreadysuffering from small and large bowel scleroderma.At operation a partial gastrectomy was carried outand pathological examination showed severe sclero-dermatous involvement of the stomach and pylorus.Although there was an ulcer, 1 cm diameter, inthe stomach it was about 2 cm proximal to thepylorus, and on review of the macroscopic andmicroscopic appearances it appeared almost certainthat the pyloric stenosis was the result of sclero-derma rather than due to inflammation around theulcer.
SMALL BOWEL Small bowel meals were performedin all 10 patients.
In the duodenum, which was visualized in onlyeight cases, the most striking abnormality wasdilatation of the lumen which was present in fivecases and was very marked in three. In four patientsbarium persisted within the duodenum for anabnormally long time although the head of thebarium column traversed the duodenum at a normalrate and had reached the caecum in three of thefour cases within five to six hours. The duodenalcap in one patient presented a dilated and completelyunchanged outline on all the films in the series.
In all 10 cases the jejunum was dilated, especiallyin its upper part, and in four this appearance wasmost striking. A characteristic transverse barringof the mucosal pattern with prominent foldsrunning transversely across the whole width of thebowel was also present in all 10 cases (Figs. 1 and 2).In some parts of the jejunum where this appearancewas seen, the space between the folds was greater thanthe width of the folds and in other parts it was less.Another notable feature was that in five of the 10cases the small bowel tended to run in straightlengths for more than 3 to 4 in. between
286
Case Age andSex
F.C. 48M
+ Lung
+
+
E.N.
M.M.
E.M.
E.J.
C.D.
E.C.
I.M.
L.T.
L.C.
+
+
+
+
+
+
+
43F
67F40F44F
34F
49F
61F
67F75F
Heart,kidneys
+
+
+
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None None Episodes of diarrhoea, Presentlater alternatingdiarrhoea andconstipation
Nausea, vomiting, Lapartomy ior ? Chronic diarrhoea Presentdistension after meals, subacute small bowelborborygmi + + obstructionNone None None Present
None
Discomfort, pain, and Nonevomiting + +(pyloric stenosisfound at laparotomy)
Bowels open None2-3 times/dayEpisodes of diarrhoea Presentwith interveningconstipation
None None Episodes of diarrhoea Stool fat notwith intervening estimatedconstipation
Discomfort, Laparotomy for None Minimalvomiting episode of ? duodenal
obstructionDiscomfort, pain, None None Stool fat notdistension after estimatedmeals
None
None
None
None
Present
None
Severe constipation Inhalation of vomitbetween episodes of during Salmonelladiarrhoea: two episodes bredeney infectionof obstructionNone ? Hypokalaemia
None
None
Marrow failure(cause unknown)
Severe constipation Uraemiawith faecal massesimpacted on severaloccasionsConstipation, palpablefaecal masses in colon
None
Chronic severe Haemorrhage fromconstipation, episodes ulcer in oesophagusof large bowelobstruction by faecesNone
Intractable Rupture of aortaconstipation, severaepisodes of large bowelobstruction by faeces
TABLE IIRESULTS OF INVESTIGATIONS
Case Hb ESR Serum Serum Alkaline Serum Serum Serum Serum Stool Fat Figlu Other Abnormal(g %) (Westergren Fe Ca Phosphatase Albumin Globulin B1, Folate Excretion Excretion Investigations
abrupt changes of direction, and two or three of thestraight segments often lay adjacent and parallelto one another. A particularly clear-cut outline tothe jejunal shadow was also noticeable in sevenpatients, the edge of the bowel being particularlywell defined.
In three cases part of the ileum was dilated, andin one of these there was transverse barring andstraightened loops of bowel. In one further casethere was transverse barring.The overall time taken for the head of the small
bowel meal to reach the caecum was noted ineight patients, the longest time recorded beingfive to six hours.
Small intestinal involvement in this grouppresented several clinical pictures. In a number ofpatients, two or more of these manifestationswere present at the same time or developed inthe course of the disease.No gastrointestinal symptoms Of our 10 patients
four had no symptoms referable to the smallintestine although one (case E.M.) had her bowelsopen two to three times a day, and two others(cases M.M. and L.T.) were found to have steator-rhoea with a normal bowel habit.
Mainly upper abdominal symptoms Four pa-tients suffered from upper abdominal discomfort,pain, distension, bloating, increased borborygmiand flatulence, especially after meals. Intermittentcramping pains, nausea and vomiting also occurred,and anorexia was common. Weight loss was afeature in all of these patients and diarrhoea was
also present in two.Pseudo-obstruction of the small bowel Two
patients during the course of their illness hadepisodes of apparent small bowel obstructionwith severe and persistent vomiting, abdominalpain, marked abdominal distension, and x-rayevidence of fluid levels and dilatation in the duo-
denum or jejunum. In both cases a laparotomycarried out to exclude organic obstruction showedonly gross dilatation and atony of the upper smallbowel.
Chronic or intermittent diarrhoea Three patientshad severe episodes of diarrhoea lasting a few daysto a few weeks with alternating periods of morenormal stools or of constipation. One patient hadsevere chronic diarrhoea and another had herbowels open two to three times a day. Three ofthese five patients had evidence of steatorrhoea.
Malabsorption Steatorrhoea was present at sometime in six of the eight patients in whom stool fatexcretion was measured. One patient (case L.T.), whowas excreting 15.6 g of fat per day, presented withsevere osteomalacia but had no abdominal symptomsor change of bowel habit. Weight loss tended to bemost severe in these cases and several developedanaemia or other evidence of malabsorption.Results of these investigations are summarized inTable II.
LARGE BOWEL Barium films of the colon wereavailable in eight of the 10 cases and were judgedto be abnormal in five. In four patients the moststriking change was a loss of haustrations so thatthe colon appeared rather smooth in outline (Fig. 3).This appearance was confined to the descendingcolon in one patient but in the other three it waspresent throughout the length of the large bowel. Thecolon was dilated in four patients and in two thisappearance was very marked. In two cases kinking ofthe dilated bowel gave an erroneous impression ofareas of localized narrowing. 'Pseudo-diverticulae',as described by Kemp Harper and Jackson(1965), were present in only one case. One patient(case E.J.) showed a markedly narrowed, smoothand rather tube-like outline to the colon at the timeof her first barium examination but five years later
the colon, though still smooth and lacking inhaustrations, looked much more normal in calibre.The main symptom present in four of the five
patients with colonic involvement was severe.
intractable constipation or periods of constipationalternating with episodes of diarrhoea. In all fourpatients large faecal masses could be felt at timesin the colon and episodes of low colonic obstructionoccurred with severe pain and abdominal distension.These episodes of obstruction were due to faecalimpaction and could be relieved by enemata. Onepatient (case E.C.) with well marked x-ray changesof bowel involvement had no colonic symptoms.
DISCUSSION
Oesophageal involvement is common in sclerodermaand its clinical features are well known. This paper
deals with sclerodermatous involvement of theremainder of the gastrointestinal tract where theclinical presentations are protean and less commonlyrecognized. In the majority of cases in whichscleroderma involves the gastrointestinal tract,a history of Raynaud's phenomenon and some
evidence of skin involvement precedes the visceralinvolvement and is of great help in suggesting thecause of the gastrointestinal symptoms. Therehave, however, been a number of case reports ofbowel involvement in the presence of little or no skininvolvement by scleroderma (Hale and Schatzki,1944; Marshall, 1956; Sommerville, Bargen, andPugh, 1959; Herrington, 1959; Crown, 1961;McBrien and Lockhart Mummery, 1962).
It seems probable from x-ray and pathologicalstudies that scleroderma may involve the stomachin many cases in which gastric symptoms are
minimal or absent or where their presence may beovershadowed by the predominance of symptomsfrom other parts of the gastrointestinal tract. A
number of authors have described gastric atony,gastric dilatation, and delayed emptying of thestomach on barium meal examination (Rake, 1931;Goetz, 1945), and Gondos (1960) comments on onecase with thickening and marked irregularity of thegastric mucosal folds. In our cases gastric dilatationwas not a feature but in several cases a bariumresidue remained for an abnormal length of timein the stomach and in one true pyloric stenosisdeveloped. We have been unable to find any previousreports of pyloric stenosis occurring as a resultof sclerodermatous involvement of the stomach andpylorus.
Involvement of the small bowel by sclerodermawas first reported by Kraus (1924). Since thenincreasing numbers of reports of small bowelinvolvement have appeared and radiological studieshave shown that characteristic changes in the smallbowel are common. Reinhardt and Barry (1962)noted dilatation of the duodenal bulb and duodenalloop with retention of barium for up to 24 hoursafter ingestion. They also noted in five patients a
characteristic rather sharp margin extending down-wards and slightly laterally to the barium outlineofthe transverse portion of the duodenum. This 'loopsign' was interpreted as being a manifestation ofpressure from the superior mesenteric artery upon thestiffened and thickened wall of the duodenum.Changes in the small bowel mucosal pattern, in-effective peristalsis, and delay in transit of bariumand segmental or diffuse dilatation of the smallbowel are the most commonly reported radio-logical abnormalities in the jejunum and ileum(Sommerville et al, 1959; Reinhardt and Barry,1962).
In the present series dilatation of the duodenallumen and delay in complete emptying of theduodenum were striking features. The 'loop sign'was present in four cases but in all of these there
290 R. D. G. Peachey, B. Creamer, and J. W. Pierce
M .... ...... _ _2 ......~~~~~~~~~~~~~~~~~~~~~...................
5.~~ ..........
FIG. 1FIG. 2.FIG. 1. Small bowel meal (after gastrectomy) showing dilatation of the jejunum and characteristic transversebarring (case E.J).FIG. 2. Small bowel meal showing jejunal dilatation, transverse barring, and the tendency for the small bowelto lie in straight lengths between abrupt changes of direction (case M.M.).
Sclerodermatous involvement of the stomach and the small and large bowel
was marked dilatation of the duodenum. It seemslikely that the duodenal dilatation accentuates thisappearance because of the difference in contrastbetween the proximal dilated duodenum and therelatively flattened area beneath the superiormesenteric artery. In all of our cases the jejunumwas dilated. The characteristic transverse barringseen in all 10 patients was thought to be a conse-quence of jejunal dilatation and an apparent reori-entation of the usual feathery pattern of the mucosalfolds, so that they tended to lie in a transversealignment. The clear-cut outline to the small bowelseen in seven patients is possibly the result of morebarium reaching the periphery due to the transversealignment of the mucosal folds. A tendency forthe small bowel to lie in short straight lengths of afew inches between abrupt changes of directionwas a striking feature in five patients. This appear-ance does not seem to have been recorded beforebut is probably a mechanical effect of the dilatedbowel lumen.
Using the dilute barium technique (see above) thehead of the barium column reaches the caecumwithin four hours in 90% of normal subjects buttransit may take up to seven hours in occasionalinstances. The times taken in eight of our 10 pa-tients are shown in Table III, and all appear to bewithin the limits of normality. In spite of the factthat the head of the barium column passes throughthe small bowel at a normal speed there is a tendencyfor some of the barium to remain in parts of thesmall bowel and this is particularly noticeable inthe duodenum so that barium may still be presenthere many hours after ingestion. Flocculation ofbarium in the small bowel is not seen with the useof this technique.A review of clinical case reports in the literature
and our own experience in this condition indicatesthat scleroderma of the small intestine may presentany of the clinical pictures outlined previously, andthat any case may show one or more of these mainmanifestations during the course of the disease.
Cases with no symptoms but with radiologicalevidence of small bowel involvement have beenreported by a number of authors (Reinhardt andBarry, 1962; Sackner, 1966) and cases with mainlyupper abdominal symptoms have also been fre-quently described.
In occasional cases a clinical picture of apparentsmall bowel obstruction has been reported (Marshall,1956; Herrington, 1959). X-ray studies may showfluid levels and dilatation in the duodenum andjejunum, a few sparse bowel sounds may be heard,and the patient appears to have partial ileus orpossibly small bowel obstruction. A laparotomy maybe performed to exclude organic obstruction of the
small bowel but at operation no obstruction isapparent and the small bowel is found to be dilatedand atonic. The recognition of this clinical picturein a patient with scleroderma may prevent anunnecessary operation.
Chronic or intermittent diarrhoea may be aprominent feature of small bowel scleroderma.Diarrhoea may persist for months or years at a timeor, perhaps, rather more typically, may occurin shortlived episodes lasting from a few daysto a few weeks with intervening periods when thestools are more normal. Occasionally, periods ofconstipation alternate with the episodes of diarrhoeaand this pattern was seen in three of our patients,in all of whom the large bowel, as well as the smallbowel, was involved.
Malabsorption has been increasingly recognizedin recent years and occurs in many, but not in all,patients with diarrhoea. It may also be present inpatients with no abdominal symptoms (cases M.M.and L.T.) (Sonneveldt, van Leeuwen, and Blom,1962). Various explanations have been put forwardto explain the malabsorption in these patients butit now seems likely that a change of bowel flora,probably consequent upon stasis in the small bowel,is the most common cause (McBrien and LockhartMummery, 1962; Kahn, Jeffries, and Sleisenger,1966; Salen, Goldstein, and Wirts, 1966; Cliff,Herber, and Demis, 1966). A striking response ofdiarrhoea and steatorrhoea to broad-spectrumantibiotic therapy was seen in several of our cases,although the involvement was not always so obviousif subsequent courses of treatment were given.
Colonic involvement in scleroderma has usuallybeen reported in association with involvement ofthe small bowel and there are few reports detailingclinical cases where the colon has been mainly, orsolely, affected (Rake, 1931; Lushbaugh, Rubin, andRothman, 1948; Norton and Monroe, 1962; Hoskinset al, 1962). Kemp Harper and Jackson (1965)summarized the colonic x-ray changes in sclero-derma. They described wide-necked pseudo-divert-iculae, best seen on the antimesenteric border in thetransverse and descending colon, and in additionoccasional areas of rigidity due to fibrosis whichmay be present between the sacculations. They alsonoticed that in advanced cases the pseudo-divert-iculae might disappear over the years to be replacedby an atonic and dilated colon. According to theseauthors replacement of muscle in the colon may bepatchy, leading to distension of the fibrous andelastic tissue and the formation of pseudo-divert-iculae. As the disease advances the whole wall ofthe colon may be involved and the localized pseudo-diverticulae may disappear to be replaced bygeneralized dilatation of the colon.
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292 R. D. G. Peachey, B. Creamer, and J. W. Pierce
In the present series the most striking changesseen in the colon were a loss of haustration andlocalized or generalized dilatation. Pseudo-divert-iculae were present in only one patient. It seemsprobable that the severity of the colonic changesin our cases is, in general, greater than those seenin patients reported in purely radiological series.Although patients with radiological changes inthe large bowel do not necessarily have any symp-toms referable to the gastrointestinal tract, in caseswith severe colonic involvement there is commonlyconstipation which may be exceedingly chronicand intractable. This picture was seen in two of ourcases. In two other cases with radiological changesand, in one further case in which no barium studiesof the colon were available, there was severe chronicconstipation with occasional episodes of diarrhoea.Episodes of colonic obstruction due to faecalimpactation which could be relieved by enematawere a striking feature in several of our patients-a manifestation which has not been emphasizedin the literature.
Hoskins et al (1962) have shown that involvementof the colon results in marked decrease in motilityas measured by intraluminal pressure techniques.This lack of propulsion seems to be the main causeof the severe and intractable constipation seen inmany of these cases. Occasional episodes ofdiarrhoeaare possibly associated with change of bowel florasecondary to stasis in the small bowel or to obstruc-tion with spurious diarrhoea in patients withimpacted faeces in the colon.
Cullinan (1953) found that six of 10 patients withscleroderma who were examined by sigmoidoscopyhad a peculiar, pale, dry, rather rigid wall to therectum and lower sigmoid colon which he regardedas the characteristic appearance of sclerodermatousinvolvement. These typical sigmoidoscopic appear-ances were present in the only case in which sigmoid-oscopy was carried out in the present series and adeep rectal biopsy in this case (E.J.) showed sclero-dermatous changes to be severe.
SUMMARY
The results of investigation and the clinical featuresin 10 patients with scleroderma involving partsof the gastrointestinal tract other than the oeso-phagus are reviewed. Five patients had radiologicalevidence of gastric involvement and one of thesedeveloped true pyloric stenosis. Small bowelinvolvement presented a variety of clinical pictures,including upper abdominal symptoms, pseudo-obstruction, chronic or intermittent diarrhoea, andmalabsorption. Some cases were asymptomatic.
The large bowel was involved in five patients, andin four of these constipation, either chronic andintractable or alternating with episodes of diarrhoea,was a striking symptom. In all four cases impactedfaecal masses in the large bowel led to episodes ofpartial large bowel obstruction.
Our thanks are due to those members of the staff ofSt Thomas' Hospital who have kindly allowed us tostudy their patients.
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Cliff, I. S., Herber, R., and Demis, D. J. (1966). Control of malabsorp-tion in scleroderma. J. invest. Derm., 47, 475-483.
Crown, S. (1961). Visceral scleroderma without skin involvement.Brit. med. J., 2, 1541-1543.
Cullinan, E. R. (1953). Scleroderma (diffuse systemic sclerosis).Proc. roy. Soc. Med., 46, 507-51 1.
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Gondos, B. (1960). Roentgen manifestations in progressive sytemicsclerosis (diffuse scleroderma). Amer. J. Roentgenol., 84,235-247.
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Lushbaugh, C. C., Rubin, L., and Rothman, S. (1948). Scleroderma ofthe intestinal tract: first report of a fatal case. Gastroenterology,11, 382-387.
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Monroe, L. S., and Knauer, C. M. (1962). Gastro-intestinal mani-festations of systemic sclerosis (scleroderma). Amer. Practit.,13, 636-642.
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Rosenthal, F. D. (1957). Small intestinal lesions with steatorrheain diffuse systemic sclerosis (scleroderma). Gastroenterology,32, 332-342.
Sackner, M. A. (1966). Scleroderma. Grune and Stratton, New York.Salen, G., Goldstein, F., and Wirts, C. W. (1966). Malabsorption in
intestinal scleroderma. Relation to bacterial flora and treat-ment with antibiotics. Ann. intern. Med., 64, 834-841.
Sommerville, R. L. Bargen, J. A., and Pugh, D. G. (1959). Sclero-derma of the small intestine. Postgrad. Med., 26, 356-364.
Sonneveldt, H. A., van Leeuwen, P., and Blom, P. S. (1962). Malab-sorption in acrosclerosis (disseminated scleroderma). Acta,ned. scand., 171, 391-396.
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