From Bispebjerg Hospital, Medical Depl . B. ( P r o f . E . Meulengracht, M . D.) and Pathologicul Instititle (Prosecior Bj. Vinztriip, M . D.), Copenhagen, Denmark.

A RAPIDLY PROGRESSING SPRUE-LIKE SYNDROME W I T H HITHERTO UNDESCRIBED PATHOLOGICAL CHANGES

BY

M. Faber, E . Meulengracht and B j . Vimtrirp.

We have observed a case of a rapidly progressive sprue-like syndrome, in which t h e post mor ten i examinat ion revealed pathological changes of the inesenteric l y m p h nodes, the small intestine, t h e duodenum, the panc reas and t h e liver. To our knowledge s imi la r changes have not lieen described before, so that i t is difficult to classify t h e case unde r any previously known well defined disease.

CLINICAL REPORT E. H. E. L. 39 years o/ age, Manager. Bispebjerg Hospital Medical I lept . B.

Admitted Jan. 1, 1950. Died April 29, 1950. The patient had never been in the tropics, and, in fact, had never been out of

Denmark. The only previous riiseaw seemed to have been sciatica 10 years ago. The present illness began in January 1949 with light yellow diarrhoea, once

o r twice daily, without blood or mucus and presumably without fever. As the diarrhoea continued he was admitted to the Municipal Hospital, Dept. 111, where he remained from 21. 111. 49 to 29. 111. 49. The clinical history records that nothing worth noting wa\ found on routine examination of the organs. Recto- scopy showed a normal niticous membrane. An X-ray photograph of the colon after a barium enema dirclosed nn irregular pattern of the mucous membrane of thc transverse and descending portions, pointing to a diagnosis of colitis. While in hospital there were 1 or 2 motion4 daily. The faeces were thin and yellowish. They gave a negative benzitiinr reaction, and on cultivation no pathogenic in- t e~ t ina l bacteria were found. A por& diet WRS given and the condition improved to some extent. The clinical diagnosis was chronic colitis.

Since his first stay in hospital there have been periods of diarrhoea with 1 or 2 thin, light-coloured motions a da!,. The last period persisted for 6 weeks. During this time there was a loss in weight of 10 kgm., the last week, before again being admitted to hospital, alonc accounting for 5 kgm.

011 admission to the Medical Dept. B of Bispebjerg Hospital the patient was cmaciated (height 177 cm., weight (id kgm.), but otherwise looked lively and healthy,-not anaemic nor jaundiced. ’Thcre was a moderate degree of dark diffuse cutaneous pigmentation. The tongue was normal with natural papillae, not inflanied or red, and without white patches. Compareld with the rest of the emaciated body the abdomen was a trifle large, but not due to subcutaneous fat,

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Submitted for publication June 29, 1951.

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which was extremely scanty, nor to ascites, but obviously caused by slight diffuse distension of the intestines. No abnormal swellings were felt. The ingvinal glands ]seemed to be slightly enlarged, up to the size of an almond. Nothing of note was brought to light by further objective investigation, i n particular therc were no sSgnis of heart disease or joint affection.

While the patient was in hospital the most striking signs were the tendency to diarrhoea and the characteristic faeces. Defaecation occurreld once o r twice a day, usually in the morning. There was some churning and rumbling in the intestfines, but no pain or tenesmus. The faeces were mostly quite watery, somc- times, however, of the consistence of thin gruel, but for a short period only, towards the end, when opiates were freely administered they became formed, almost hard, even giving rise to a large accumulation in the rectum. Thcy werr very copious. When they were watery a single motion could completely fill n hrtl pan and weigh from 1500 to 2000 g; when a little Ihicfker in consistenrc the volume was rather less. The colour was a light yellowish drab. There was 21 scum on the surface. On cooling the scum became coagulated and would not liquefy again on heating, Typical macroscopic fat was not observed. On the other hand there were many macroscopic particles consisting of food elements containing cellulose. On microscopic examinatlion numerous fatty acid needles were seen. On staining with Sudan I11 typical neutral fat globules werc not detected, but there was some diffuse reddening of the intestinal contents. When the preparation was heated, howcver, innunicrablc minute red globules made their appearance, becoming more amorphous on cooling, No starch grains were identified. A chemical analysis of the faeces gave 19.6 g total fat per 100 I: substance, consisting of 7.6 g ‘free fatty acids and soap, and 12.0 g neutral fat. A determination of the daily excretion and a balance test were not undertakcn.

The benzidine reaction of the faeces was constantly negative. Rectoscopy was impossilble on account of the watery nature of the faeces. An X-ray photograph of the colon after a barium enema showed a rather ”shaggy” picture, witmh a

0. zap

Fig. 1 . Blood sugar curves during thr progression of thr disease.

”blurred” distribution of the contrast material at the ileo-coecal junction. Ewald test meal 9/4 hour: 107 cc; congo red, 33; phenolphthalein, 56. At first the blood picture was fairly normal: Icteric index 5, Hgb., 115 %; red cells, 5,385000; leucocytes, 13700; polymorphs, 78 %; mononuclears, 8 %, lymphocytes, 13 %; undctcrrnined, 1 %, sedimentation reaction, 7 mm. in 1 hour. Later, Hbg, 79 %; red cells, 3,605000. Still later, Hbg, 56 76; W.R. negative; 3 blood sugar curves after the administration of 70 g glucose in 500 cc water are shown in Fig. 1.

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IJrine: sugar negative, albumin negative. The electrolytes showed the character- istic picture for the chronic diarrhoeas, viz. low serum cloride values, almost constant, low serum potassium figures right down to 9.4 mgm %, and periods of inarked alkalosis.

A biopsy of the skin showed some accumulation of an iron-free pigment in the basal layer of the epithelium (melanin). Biopsy of a lymph node from the right groin revealed fibrosis in the centre of the node. There was some proliferation of reticulum cells, lymphocytes were numerous and the germ centres were small.

While in hospital the patient grew steadily worse and worse. Vomiting occurred occasionally, but never pain. The appetite was fair, the

patient eating moderately well, but the weight went consistently downwards. During the 4 months he was in hospital he lost 15-20 kgm. and finally he was all skin and bone, his weight being ultimately atbout 43 kgm. One gained the impression that all the nutritive material passed through him. At no time did he have glossitis or symptoms of tetany.

Dieting had n o influence on the condition. Pancreas enzymes (tablet zymopan MCO, 2 tablets 3 times daily), fol’ic acid (15 mg., 3 times daily), complex B vita- min preparations, chalk and bismuth preparations were useless. On the whole opiates acted best.

For about a month an attempt was made to ‘replenish the salt loss by intra- vmoiiq injections. Thus he received U D to 8 g potassium chloride intravenously for a long time, but it was not possible to raise the ”post absorbtive” serum potassium up to the normal values. As a guide to the potassium treatment the electrocardiogram was chiefly used.

In spitc. of the inanition and extreme emaciation sensation was preserved in a remarkable degree. The very day that death occurred the patient smoked a cigarette with satisfaction. The inanition probably caused death, which took place suddenly .

The tentative clinicul diagnosis was sprue syndrome from blocking of the lymph nodes in the mesentery (tuberculosis, lymphogranulorna o r other lymph nodes disease), or sprue syndrome from lipodystrophia intestinalis (Whipple). The latter diagnosis was rendered the more likely by reason of the patient’s sex, agc, the rapidly fatal course and the pigmentation.

A formalin injection into the abdomen was made immediately after death.

PATHOLOGICAL ANATOMICAL REPORT Macroscopic Investigation.

The body is very emaciated. The skin is browniish, dry and a little scaly. The upper part of the abdomen is sunken in, below it bulges forward. The cervical lymph nodes are slightly enlarged, up to 1.5 cm in diameter. In

the upper lobe of the right lung there is a small pneumonic infiltration posteriorly, and the pleura over it is fibrosed and adherent to the thoracic wall.

The thoracic lymph nodes measure 4-8 mm in diameter and show some hyperplasia.

The heart is small, 230 g in weight. The myocardium is brown. There is no valvular disease. The endocardium and pericardium are normal.

On opening tllie abdomen it is noted that some olf the intestines are greatly distended while others are collapsed. Formalin was injected immediately after death. The omentum is thin and the fat scanty. Extraordinarily little fat is present in the mesentery, so that the blood vessels atand out, and all the arterial arcades can be clearly seen, as illustrated by fig. 2.

At the junction of the jejunum and ileum there is an invagination free from fibrin or haemorrhagc. The intestines form a large mass lying in the lowest part of the abdomen and partly in the pelvis, but they are not matted together. The intestinal wall appears to be considerably thickened, which may result from the formallin fixation.

In the upper part of the small intestines the valvulae conniventes are extremely prominent. In the colon the mucous membrane is smooth. There are no tumors in the gut.

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In the mucous membrane of the small intestine a number of small reddish spots up to 2 mm in diameter are seen. There is no haemorrhage here nor in the deeper layers of the intestinal wall.

The stomach is a little diilated, but its mucous membrane is somewhat foldsed. No ulcera,tionls, cicatrices or tumors are present. The duodenum appears normal.

The liver is large, measuring 27 X 23 X 10 cm. It is dark brown with a bluish tinge anid blackish brown patches. Its consistence is fairly firm. The cut surface shows a dark blue pattern and a network of lighter tissue, possibly with small infiltrations along the vessels, especially around branches of the portal vein. The hepatic lymph nodes are not appreciably enlarged.

Fig. 2. Small intestine and mesentery almost devoid o/ fat . The bloodvessels are remarkable outstanding. Lymph

nodes considerably enlarged.

The pancreas appears to be of normal siize. The tissue is fairly hard and has a distinct glandular structure everywhere. No pathological changes can be detected by the ordinary macroscopic examination, in particular, no tumors o r fat necrosis.

Very large lymph nodes are present along the pancreas and around the large vcssels and aorta extending down into the pelvis, and i n the hilum of the right kidney. Some af them are the size of peas, but the majority are as large or larger than acorns, the largest attaining the size of olives. At the base of the mesentery also, such lymph nodes occur in very great numbers. On sections they present a bulging surface, which is moist and fairly light coloured with reddish dots, The normal pattern cannot be distinguished, and the tissue is much softer than normal. There is no marked thickening of the capsule and no coalescence.

The spleen is a characteristic congested spleen. In the inferior vena cava there is a parietal non-obstructive adherent thrombus 2 % X 1% em in size at the point where i t is crossed by the right common iliac artery.

The remaining organs display nothing abnormal. The brain was not examined.

Microscopic Examination. In the enlarged mesenteric lginph nodes only a very few germ centres are

to be seen, and on the whole there are few lymphocytes. The sinuses are mostly of considerable width, while inside them as well as between them, in the retic- ulating cords of the medulla, there are enormous numbers of large roundish cells whose nuclei are a little darker than those of reticulum cells usually are. These large cells usually have a single nucleus, but some have several, either as 2 distinct nuclei or they contain phagocytized nuclei in their cytoplasm. In ordinary staining the cytoplasm often appears homogeneous, but in haematoxylin

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- azur I1 - eosin stained slides it can be demonstrated that the cytoplasm of many of these cells contains remnants of red blood cells. The cytoplasm may also contain small vacuoles, or it may have an inidistinct reticular structure. The cells mostly lie separatcly, but very close together, they may, however, also be found in compact masses. They are present in hoth thc border sinus and the intermediate sinus, as well as in thc lymphoid tissue itself, which is almost

Fig. 4. Peripheral part of mesenteric lymph node. Lym- ph0cytt.s are spurse, no germ centers. Endothelial und reticulum cells are nurnc'rous and of a considerable size.

Fig. h. Lymph node w i th a multi tude o f large rounded presumably endotheliul rells w i th inclusions in their

cytoplasm. Hematoxylin-Azur IZ-Eosin.

depleted of lymphocytes. The great majority of the lymph nodes in the abdomen present changes of this naturc and the said cells are encountered in the lymph nodes of the thorax and the root of the neck as well. Similar cells occur in the lymphatic vcssels hctween groups of 15 mph nodcs. Leucocytcs, often eosinophilic, can also be found, mostly restricted to small areas in some of the lymph nodes.

Staining with Sudan 111 failed to reveal any fat in the lymph nodes. Nor do the cells contain any mucin which can be stained with mucicarmine, Mallory's haematoxylin, Delafield's haematoxylin or thionine. It is difficult Lo decide what role these cells play, but they are the overall prevailing cells of all the lymph nodes. Mitosis have not been detected in the cells in question. As stated above

385 2s Uarburg \nm,e,.,,r, 1 I , l l l",C

the nucleus is fairly dark, having a distinct chromatin network with rather large irregular chromatin granules which are scattered throughout the nuclear sub- stance.

I t is presumablg most reasonable to assume that we are dealing with f r e e reticulum cells or endothelial cells which are much swollen and act as phagocytes, but beyond the fact that some of them contain red blood cells and a few remain-

F i g . 5 . Part o f lymph node and a l ymph vessel w i th large rounded cells. Hematoxylin-Eosin.

Fig. 6. Mucous membrane o f ileum. No proliferation o f reticulum cells, no l ipids in the cells. Hematoxylin-Eosin.

ders of nuclei it is impossible, with the methods employed, to determine what kind of material they engulf.

There is no necrosis in the lymph nodes, no sign of tuberculosis or Hodgkins disease. The picture does not resemble any genuine inflammatory lesion or any kind of true tumour formation.

The examination of the intestines shows that the mucous membrane is relatively well preserved and of a fairly normal structure. The Lieberkiihn’s crypts in the jejunum and ileum are normal. The surface epithelium is also normal in character, it is of normal height and the cell nuclei are well preserved in the parts that were fixed immediately after death. There are a good many lymphocytes in the tunica propria at the base of the villi, It is possible that the height of the villi is less than usual. In the deepest zone of the mucous membrane there are

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jyiiiphocytes and a fair number of fibroblasts. No specially large cells can be ilcmonstrated, particularly no cells containing fat that can be stained with Sudan 111. There is no eosinophilia.

I n the duodenum the mucous membrane is seen to be rather thickened, and 111c valvulae connivcntcs, especially, are of a considerable height. There is some iriotlcrate autolysis of the superficial zone of the mucous membrane, resulting ~ I I loss of the epithelium of ihe villi. Thc crypts of Lieberkiihn are normal with numerous cells of Paneth in the bottom. The tunica propria is very rich in cells, and there is considerable infiltration in the muscularis mucosae reaching far tlown into the submucosa.

The infiltrating cells are mostly lymphocytes and mononuclear cells of medium \ i n ' with rountlrd nuclei.

Fig. 7. Duodmum. Infiltration amongst the submueosal glands of Brunners. Ironhernatoxylin, acidfuchsin-picric

cicitl.

Besides the infiltrations there are also hyperacmia and local accumulations of Icucocytes along the vessels in the submucosa. h few of the largc mononuclear cells which occur in the lymphatic vessels and lymph nodes arc seen here too. There is no ulceration or necrosis in the miicosa or submucosa. KO cells contain- ing fat a re observed.

In sections of the pancreas large regions appear normal. But in numerous small areas often restricted to single lobiiles or portions of lobules conspicuous simple chronic reactive inflammatory changes, sometimes with adenoma forma- t ion :ire cncountered. The inflammation is interstitial, accompanied o r followed by atrophy of the exocrine glandular apparatus. Only remnants of the pancreatic iicini with some few centro-acinous cells remain. The zymogen granules do not \tain, and a large proportion of the iiucllei are pycnotic. There is a considerable interstitial infiltration with lymphocytes and other monuclear cells with a com- pact nucleus rich in chromatin; likewise a great numbcr of fibroblasts and a modcrate amount of collagen fibrils.

The islands of Langerhans in these areas are mostly small and show dilatation of the blood capillaries, although well preserved islands are also present. They are not cncapsuled, and they are nornlally distributed. In larger areas of inflamed tissue large encapsulated adenomata occur, which may measure 1-2 nim in dia- meter. The encapsulation may, however, be due to an accumulation of connective tissue during the growth of thc adenoma. In many of the adenomata there seem to be glandular formations with centro-acinar cells and zymogen granules, but in others only island-cells and no exocrine cells are discerned. The adenomata always contain a number of fibroblasts. The blood capillaries show proliferation of the endothelium; they are wide, but contain only moderate numbers of red blood cells. The adenomata occur in all stages of development, viz. as islnnds of Langerhans just beginning to hypertrophy or as small adenomata consisting of

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Langerhans islands and some exocrine glands partially encapsulated by fibrous tissue with fibroblasts in large numbers, and finally as large adenomata with a definite capsule. These large adenomata are often placed fairly close together and occur in the areas of most marked inflammation.

It can not be excluded that the adenomas consist to a large extent of islet-cell5 which are hypertrophied and increased in numbers, but it might well be possible that they are chiefly composed of exocrine glandular elements wilhout zyniogenle granules in combination with definite groups of islet-cells. In the great majonity of regions in the pancreas a perfectly normal appearance is seen, and the num- ber and size of the islands of Langerhans do not seem to encroach beyond the physiological boundarics. No abscesses are prcwnt. There is considcrahle fatty infiltration in thc pathologically changed areas, but only rarely in the pancreatic

Fig. 8 . Pancreas w i th a characteristic adenonia in an area o f well pronounced inflammatory altcrations and

utrophg of acini.

cells themselves, being most pronounced in the interstitial Connective tissue. Destruction of the normal tissue is found especially in the periphery of thc areas with marked inflammatory infiltration, where there is an abundant development of connective tissue with total disappearance of the exocrine and th r endocrine glandular elements, and here occur many cclls containing fat globule5 which stain distinctly with Sudan 111.

The lesion of the pancreas thus consists morphologically of strictly localized processes which, however, are present in very large numbers distributed through- out the pancreas. The changes do not appcar to be located to any spccial part of the organ. The excretory ducts possess a normal epithelium which reacts positively to mucin-staining dycs. There is no inflammatory infiltration around the ducts.

In sections of the l iuer very pronounced changes in the parenchyma and in the interstitial tissue are found. Along the interlobular portal veins there occurs abundant connective tissue rich in cells and with lymphocytic infiltration and fat cells or cells which give the fat reaction. The liver lobules are smaller than normal. The sinusoids are dilated and filled with blood. The liver cells are some- what atrophic and arranged in quite narrow and richly branching cords. The nuclei of some of the liver cclls are well preserved, but many nuclei are pycnotic. The cell boundaries are indistinct, Nearly all the liver cells contain small fat globules. The intralohular central vein is dilated, its wall a little thickened, and there is a considerable dilatation of the sinusoids most marked in the neighbour- hood of the central vein. There are no large areas of necrosis or marked infiltra- tion of leucocytes. No abscesses are present. Summarizing we thus find a con- siderable increase and lymphocytic infiltration of the interlobular connective tissue, and in addition, atrophy of the liver cells and dilatation of the sinusoidis, but no increase of intralobular connective tissue. The changes are evenly dis-

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pcrsed throughout the liver. Bile pigment in the liver cells is scanty. There is no thrombosis in the portal vein or hepatic artery, and n o concrements in the bile dL1cts.

In sections of the myocardium the muscle .fibres are rather thin, and rich in lipofuscin, while fatty degeneration occurs only sparingly in individual muscle fibres. On the other hand i t is observed that both the small arteries and the very small arterioles are the seat of diffuse fatty infiltration in the intima, which is particularly distinct in sections stained with Sudan 111. The interstitial ronnective tissue is slightly increased but there is no inflammatory infiltration. In the kidneys, also, fatty infiltration i n the intima of the small blood vessels of the medullary substance can be detected, especially close up to the apex of a pyramid. Nothing else definitely pathological can be demonstrated in the kid- ncys, which are richly vascularised.

The spleen present the common ehararterislic features of chronic congestion, with abundant blood pigment in the cells. The germ centres are small and exhibit some fibrosis and hyaline transformation in the walls of the central arteries. A number of elongatrd cells containing blood pigment arc present in the pulp. Therc are also many red blood cells and remnants of blood cells in the sinuses. Thrrc is no necrosis and no abscesse~ i n the spleen. No giant cells and no myelopoiesis are present.

Provisiorial pulhological ariatomicd diagnosis: Extreme emaciation. Enlarge- ment of the lymph nodes in the mesentery. Accumulation of reticuloendothelial cells in the mcsenteric lymph nodes and lymph vessels. Changes resembling an inflammatory lesion in the duodenum. Scattered foci of an inflammatory nature and small adenomata in the pancreas. Predominantly interlobular infiltration of an inflammatorv nature in the liver.

DISCUSSION

Clinically the case cannot be classified beyond saying tha t it WIS a rapidly progressing sprue-like syndrome with diarrhoea, with demonstrated diminished fat and glucose absorption, with extreme emaciation and fatal termination despite therapeutic measures of the most varied description. This does not admit of more than the tentative diagnosis advanced a t the end of the clinical report.

Nor from the pathological anatomical standpoint does the case fall into any definite category. The pathological anatomical changes do not corre- spond with those which have been described as occurring in tropical sprue or in ”idiopathic” non-tropical sprue, where the characteristic features on the contrary seem to be the lack of changes in the intestine and the normal lymph nodes in the mesentery, although it must be remembered tha t in some cases slight ulceration of the intestine and a mild degree of swelling of the lymph nodes in the mesentery have been observed (1).

Pathological anatomical changes of a known character, which may be accompanied by ”secondary sprue”, were not found. Thus there was no sign of terminal ileitis, tuberculosis, lymphogranulomatosis, carcinomatosis, or other lesion resembling a tumour in the intestine. Nor was there any evidence of such lesions in the mesenteric lymph nodes resulting in their blocking and prevention of absorption from the intestine; the lymphatic vessels in the mesentery were neither dilated nor full of fat.

The pathological anatomical changes, again, do not resemble the findings in Whipple’s lipodystrophy. This disease is characterised anatomically by

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large mesenteric lymph nodes containing great quantities of fat, presuni- ably chiefly fatty acids, often in cavities therein, and by the accuinulatiou of large cells in the intestinal mucous membrane, at times accompanied hy pericarditis and articular changes. But in our case no storing of Cat i n the mesenteric lymph nodes was detected microscopically, there were no cavities, and the chemical analysis of a mesenteric lymph node gave only 3.3 %, total fat. Nor were the characteristic large cells found in the intestinal mucous membrane. If it really was a case of Whipple’s disease, thereforc, it murt be assumed to be an early and atypically developed one.

There are grounds for questioning whether some of the pathological m a - tomical changes might be of a secondary nature resulting from the con- siderable functional disturbances evoked by the disease, especially the intestinal disturbances and the inanition. This may possibly be truc fo r the changes in the duodenum and liver. Jensenius ( 2 ) may he cited as having experimentally produced syndromes resembling sprue by extensive intestinal resections and finding secondary lymphocylic infiltration in the intestines. A similar problem arises in the case of the scattered lesions resembling inflammation seen in the pancreas. Thus Ball and his collabor- ators found inflammatory changes in half their cases of ulcerative colitis, and Dauies detected frequent fibrosis in the pancrcas in :I disease presum- ably of nutritional origin in Africa (Kwashiorkor). Rut there also seems to be the possibility that the changes in the pancreas may have played a definite part, secondarily, in the later development of the disease. Within the scattered areas of inflammatory appearance, small adenoniata and atrophy of the exocrine glandular elements with a diminished amount of zymogen granules occur. The lesions are so dispersed that it seems hardly likely they could have any primary effect on the development of the disease, but it seems possible that they may have exerted a secondary in- fluence. In this connection we may refer to the three glucose tolerhnce curves which have been carried out, and which have a curious appearance. The first began with a normal blood sugar, rose rather quickly up to 150 mgm. %, only to fall immediately to normal: therefore an entirely normal curve. When it was repeated a fortnight later, the initial valuc was unchanged, but a steady rise was observed so that after the lapse ot one hour the blood sugar value was 150 mgm. %, and after a further hour and a half it was 195 mgm. %, at which time the test was ended. Oiicc more a blood sugar tolerance curve was undertaken, about 3 weeks before death. There was then a slight fasting hyperglycaernia of 125 mgm. %, and the blood sugar rose nearly to 270 mgm. % in the course of 2% hours, but the rise was rather slowly initiating. After half an hour the value was only 135 mgm. %, and after one hour, 160 mgm. $4.

The finding is difficult to interpret, but the following explanation may be justified. The first curve is very much what would be expected in the case of a simple sprue syndrome. The two others, on the other hand, more resemble diabetic curves. Both of them, especially the last, however, arc

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characterised by a very prolonged course particularly at the outset. The middle curve does not rise to pathological heights, which is the case with the other one. The rise of the last curve cannot be explained as an indic- ation of hunger diabetes because intravenous injections of glucose and amino-acids were given for a long time, until the day before the tolcrancc test. The curves must undoubtedly be interpreted on the assumption that from the beginning there was obstruction to the absorption o f glucose. This condition persisted all the time he was in hospital, but, gradually. as the internal secreting system of the pancreas became deficient, a diabetic state was established which caused the high rise. That in actual fact :I re- straining action on the absorption of glucose does occur in sprue was proved by Maegraifh among others, by introducing glucose into the duodenum. Some of his cases gave a flat curve; others clearly showed a depressed ab- sorption which pointed to a well pronounced latent period beforc the hlood glucose rose.

If one is resolved to include the case in any hitherto recognised disease category, Whipple’s lipodystrophy would probably be the most appropriate. Sex and age class fit in, and so do the rapid and fatal course and the en- tirely ineffectual therapeutic measures. Macroscopically, the pathological anatomical picture is also in agreement, but microscopically it diverges in :i decisive manner. The large cells in the intestinal mucous membrane are absent. It is true that there is an accumulation of large phagocytic cells in the lymph nodes, but an accumulation of fat in the latter is lacking, while there are the hitherto unrecorded findings of foci resembling inflammatory lesions in the duodenum, pancreas and liver.

SUMMARY A case of a rapidly progressing syndrome resembling sprue in a man of

39 years is reported. The clinical symptoms were diarrhoea, diminished fat absorption, diminished glucose absorption and extreme emaciation. The provisional clinical diagnosis was a sprue syndrome due to obstruction of the lymph nodes in the mesentery (Tuberculosis, lymphogranulomatosis or other disease of the lymph nodes?), or a sprue syndrome due to lipodystrophy of the intestine (Whipple).

The post mortem investigation showed.: severe emaciation, enlarged lymph nodes in the mesentery, accumulation of reticuloendothelial cells in the mesenteric lymph nodes and lymph vessels, changes resembling in- flammatory lesions in the duodenum, scattered foci of a similar nature and small adenomata in the pancreas, and predominantly interlobular infiltra- tion of an inflammatory nature in the liver.

Similar pathological anatomical changes do not appear to have been previously described.

It is difficult to classify the case under any hitherto recognised clinical entity.

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REFERENCES 1. Boels, W. and Tvedy, G.: Acta Gastro-Enterol. Belgica. Vol. 13, Suppl. I, p. 83, 1950. 2. Jensenius, Hans: Results of experimental resections of the small intestine on dogs.

(Experimental enteroprival sprue) . Arhus, Denmark, 1945. 3. Ball, Ph., Baggenstoss, A. H. and Bargen, J. A.: Proc. Staff Meet. Mayo-Clin. 25,256, 1950. 4. Davies, I. P. N.: Lancet 1, 317, 1948. 5. Maegraith: 1st Internat. Congr. Biochem. Abstracts 1949, p. 190.

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