Celiac disease—What is it?

Celiac disease—What is it?

The Journal of Pediatrics VOL. 46 APRIL, 1955 CELIAC DISEASE- NO. 4 W t I A T IS ITS. L. E ~ 5 ~ r HoL'r, JR., M.D. N~w Yo~K, N. Y. H E t e r m " ...

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The Journal of Pediatrics VOL. 46

APRIL, 1955 CELIAC DISEASE-

NO. 4

W t I A T IS ITS.

L. E ~ 5 ~ r HoL'r, JR., M.D. N~w Yo~K, N. Y. H E t e r m " celiac disease" is of comp a r a t i v e l y recent origin, so far as the American literature is concerned. Samuel Gee 1 of St. Bartholomew's Hospital wrote his original description of the "coeliae a f f e c t i o n " in 1888, a designation followed by English writers, but American and most Continental E u r o p e a n writers continued to describe the condition under the term " c h r o n i c intestinal indigest i o n . " It was only in 1932 when the late Sit" L e o n a r d Parsons visited this country and delivered the R a c h f o r d Lectures that the term "celiac" came into general use here, and almost simultaneously in Continental Europe. Since then, it has been increasingly popular with doctors and parents as well. I t is easier to say " h e ' s a celiac" than "he's suffering from chronic intestinal indigestion." It has a learned sound and conveys an a i r of mystery which impresses parents far more than the simple word indigestion. All of us who knew Leonard Parsons admired him greatly and were only too h a p p y to nse his term. As it became clear t h a t more than one e n t i t y was included in this picture, the group as a whole came to

T

This paper was presented at the Annual M e e t i n g of t h e N [ i e h i g a n S t a t e M e d i c a l Society, S e p t e m b e r 30, 1954, A d d r e s s : :New Y o r k U n i v e r s i t y C o l l e g e of lVledieine, D e p a r t m e n t of P e d i a t r i c s .

be known as the celiac syndrome, one m e m b e r of which was idiopathic

celiac disease. The term "celiac" seems destined to stay with us. It is too late to abandon it. Nevertheless, I believe it has done us a disservice. Oee's concept has been distorted by his successors who like his term but find difficulty in defining it. Attempts to apply specific l a b o r a t o r y criteria have added to the confusion. A specific response to a "celiac d i e t " helps to define the disease for many, but unf o r t u n a t e l y there is little agreement as to what a celiac diet is. In Switzerland it is one thing, in Holland another. In this c o u n t r y it depends upon whom one f o l l o w s - - t h e advocates of the banana, the advocates of fat restriction, or those who stress restriction of certain forms of carbohydrate. Several recent writers have stressed the need for avoiding polysaccharides and the desirability of supplying all c a r b o h y d r a t e s as monosaeeharide, but in the early part of this c e n t u r y careful students of the disease took precisely the opposite view. I should like to give you the following' quotation from Christian H e r t e r ' s a classic m o n o g r a p h on the disease : From a eonslderable experience with various

369

but not exhaustive carbohydrate foods

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I have reached the conclusion that such carbohydrate food as can be taken by these patients is best given in the form of starchholding preparations and not in any ordinary form of sugar.

It is interesting that Hcrter favored the use of rice or arrowroot flour, though he used wheat flour to some extent in the form of Huntley and Palmer biscuits. Herter's experience was indeed considerable. He turned the top floor of his large New York house into a ward for the study of the disease, and for the better part of two years he and his associates, Wakeman and Kendall, carried on extensive clinical, metabolic, and bacteriological studies--all at his own expense. The tIerter diet, quite different from the Haas, the Andersen, or the Fanconi diet, produced satisfactory results in its day. All celiac diets, no matter how diverse, appear to have produced excellent results, which, after all, is not too surprising in a condition with a tendency to spontaneous improvement, even though it be slow and punctuated by relapses. My purpose in calling attention to the many and diverse celiac diets is to point out the fallacy in assuming that a condition which responds to a particular celiac diet is ipso facto a form of celiac disease. It would be as logical to conclude that because pneumococcus pneumonia and amebic dysentery both respond to Terramycin, both are forms of the same ailment. Nevertheless, it is just such reasoning which has been used to expand our concept of celiac disease to include clinical phenomena that bear very little resemblance to what Gee originally described.

Having criticized other people's definitions, I shall now put dowh my own for what may be called idiopathic celiac disease : a state of malnutrition induced by a poorly understood chronic functional disorder of intestinal assimilation. With our present knowledge, we can interpret, but need not abandon, the clinical picture painted by Gee--the body contour due to loss of fat, the bulging abdomen due to loss of muscle tone and abdominal fat coupled with some measure of fermentation in the intestine, the pale bulky stools due to an excess of unabsorbed fat, their frothy character due to carbohydrate fermentation, and the cranky disposition, attributable chiefly to the somatic disorder. "We may obtain added evidence of malabsorption of lipid from the vitamin A absorption curve, or of defective sugar absorption from the glucose tolerance eurve, a n d less frequently some degree of hypoproteinemia perhaps due to defective protein assimilation. The fundamental absorption mechanisms and how they are affected here still defy us, but the original definition still stands. My present remarks were stimulated by our efforts a few years ago to study genuine idiopathic celiac disease, as part of a study of steatorrheas of all kinds. Although we ourselves saw these cases very infrequently, it seemed as if they must be very prevalent in the city in general. One pediatric colleague had just written a book describing 600 personally observed cases. At another medical center in the city, an active clinic for celiaes and cystic fibrosis of the pancreas was apparently well attended. But to get

HOLT:

CELIAC D I S E A S E - - W H A T

a case to s t u d y p r o v e d not so easy. Our colleague who had w r i t t e n the book was most cooperative, but it seemed that most of his cases were in the past, the present ones being private patients, not v e r y sick and not anxious to enter a hospital for study. The clinic in our neighboring institution p r o v e d to have few classical celiac patieuts, the present clientele consisting largely of cases showing no significant clinical malnutrition, the diagnosis having been made by l a b o r a t o r y tests, such as undigested starch or stainable fat in the stool or a low concentration of stool amylase. W e tried an appeal to the public, inspiring an article in the New York Times which described the great interest the doctors in Bellevue had in s t u d y i n g this disease. This brought results, but not w h a t we expected. The telephone r a n g frequently the next day with calls from mothers of celiacs, all i n t e r e s t e d in having their children studied at Beller u e - - s o m e twelve of them in all. Appointments were made and we examined all the candidates, but there was not a celiac among them. The diagnosis had been made on the basis of a single a t t a c k of indigestion from which the child had made a complete clinical recovery, but the banana-low fat-high protein diet had been continued, and, with it, the state of faroily apprehension and the f r e q u e n t visits to the doctor. In one or two instances the diagnosis had been made by the discovery of stainable fat or starch in the stools. I n v a r i a b l y the child was a healthy, rosy looking y o u n g s t e r in an excellent state of nutrition. W e ended up b y waiting patiently f o r a few real eeliacs that came our way, although on one occa-

IS I T .~

371

sion impatience got the better of us and we made a trip to Toronto to s t u d y some classical examples there. I submit, and I t h i n k you will agree, t h a t it is not good medicine to put the label of a chronic disease on a child who has had one acute attack or to create needless dietary restrictions or apprehensions. i should like to leave two thoughts with you t o d a y - - ( 1 ) what celiac disease is not and (2) what, according to the best of our knowledge, it is. D o r o t h y A n d e r s e n has made valuable contributions to our knowledge and her w o r k is always stimulating. Nevertheless, I must f r a n k l y disagree with her thesis 4 that starch intolerance as revealed by starch granules in the stools represents an early stage of celiac disease, which, if u n t r e a t e d by her d i e t a r y regimen, will develop into the more serious f o r m of the disease with steatorrhea. A n d I must likewise disagree as to the reliability of stainable fat in the stoop as an index of the presence of steatorrhea. Most of us are not familiar with the b a c k g r o u n d and the shortcomings of these two l a b o r a t o r y tests which are not new; they were developed, t h o r o u g h l y tested, and abandoned by a generation ahead of ours. Techniques for staining stool fat, including differential stains to determine fat partition, were developed by the Germans t o w a r d the end of the last century. An accurate description of accepted technique and references to the earlier l i t e r a t u r e will be found in the review article b y F. B. Talbot G w r i t t e n in 1911. The method was used at t h a t time in a n u m b e r of our leading hospitals. It was abandoned when chemical measurements of fecal fat were developed, because it so fre-

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quently led to a false conclusion. I t is t r u e as Andersen has pointed out t h a t there is a reasonable correlation between stainable f a t and the perTABLE I.

S~J~JEO~ D.T. P.L. 2 P. L. 3 V. 1~. P. L. 5 J.M. J. F.

sorption. D a t a published b y I-lolt a n d associates ~ in 1919 bear eloquent witness to / this fact as is shown in Tables I to I I I .

]=~REAST-]~'EDINFANTS \VIT/~ 7-~OF~MAL STOOLS FAT INTAKE

[ [~ATABSORPTION

A~E

(~./DAY)

1

6 wk. 3 wk. 3i~ wk. 3 too. 9 wk. 4 too. 10 too.

9.8 37.7 41.9 19.8 31.1 10.6 33.0

TABLE I I . AGE (MO.) 5 7 5 5 11 10 101//2 7 51~ 10 10 12 71~ 4 4 89 31~ 14 3 13 11

TABLE SUBJECT S.J. V. C. 2 V. C. 1 W. S, 1 F. }t. 1 B. S. 3

AGE (IV[O.) 9 5 5 4 10 13

61.1 52.0 41.0 30.8 29.3 14.4 12.4

FAT ABSOEPTION

(GS]I./DAY) 30.2 39.7 22.2 17.0 25.2 16.8 23.4 30.7 15.0 27.1 33.6 15.5 25,.4 14.0 24.4 15.8 18.4 13.2 20.6 20.0

III.

STOOL

90.3 94.8 94.5 93.9 94.9 94.2 99.2

INFANTS WITH MILD D[AgBHEA FAT INTAKE

SUBJECT V. C. 3 J. G. 1 D. W. 2 J.D. A.H. E. R. 1 E. 1% 3 J. @. 2 P.V. E. 1~. 2 F. H. 2 B. S. 2 J . G. 3 D. F. 2 I. P. 2 D. F. 1 W. 14. 3 R. B. 1 F. It. 10 F. H, 4

% FAT IN DR,Y

(%)

INFANTS

WITH

FAT I N T A K E (G]~[./DAY) 29.1 23.6 23.6 17.0 32.4 11.6

e e n t a g e of f a t in a stool. A chain is, however, no s t r o n g e r t h a n its weakest link a n d the w e a k link here is the v e r y p o o r correlation b e t w e e n percentage of f a t in the stool a n d f a t ab-

(%) 77.7 80.3 75.7 64.7 83.2 80.1 78.7 84.5 70.6 86.2 86.3 80.2 84.3 77.0 87.8 80.5 88.6 79.8 89.9 91.1 Average 77.3

O~ F A T I N D R Y STOOLS 54.2 49.9 48.9 48.0 45.9 44.1 39.4 33.8 32.2 31.6 29.5 29.5 27.3 26.2 25.4 24.0 22.3 16.6 16.4 14.2 34.2

~EVEI~E DIARRHEA ABSOI~PTi0N (%) 50.0 56.1 75.7 49.4 78.6 12.9 Average 53.7 FAT

%

FAT IN DRY

STOOL 57.5 49.5 43.6 36.6 34.7 27.0 39.9

It is apparent from these data and from the experiences of many other w o r k e r s ineluding ourselves t h a t the p e r c e n t a g e of f a t in the stool is not to be relied on as a m e a s u r e of ab-

HOLT:

CELIAC D I S E A S E - - W H A T IS IT .~

sorption. I t m a y be high or low in conditions of excellent absorption and may be low when much f a t is being' lost. A test which leads one into error at least one-third of the time is, in m y opinion, best omitted. We have at present no simple clinical method for measuring fat absorption and m a y as well admit it. W h a t about the significance of undigested starch in the stools? The literature on this 8 goes back more than seventy-five years. The iodine test w a s a simple one to c a r r y out and was studied p a r t i c u l a r l y during the era when cereals and gruels were used to dilute raw milk, b u t when we began to control the curd problem by heating the milk r a t h e r than by starch diluents, interest in this subjeer waned. JcIowever, the facts in r e g a r d to starch digestion have been reasonably well established some years ago. B y means of the iodine test applied to stools it was shown: 1. T h a t cooked starch is more digestible t h a n raw starch. 2. T h a t the tolerance for cooked starch is limited in the n e w b o r n inf a n t but increases with age. 3. T h a t the tolerance is improved b y the administration of starch, often within a m a t t e r of a few days. 4. T h a t a mild digestive upset may be associated with the appearance of starch in the stools, at times without steatorrhea. 5. Finally, that the iodine test, taken by itself, i.e., in the absence of symptoras, has no diagnostic or prognostic significance and is often shown by infants in the best of health, gaining weight normally. In the face of the long and v e r y considerable experience with the iodine test I think we are justified in awMting valid statistical evidence before accepting the conclusion that

373

starch intolerance represents mild or early celiac disease with specific therapeutic indications. So much for what, in my opinion, is not celiac disease. Now as to what is, and, more important, what we should do about it. The problem which bothered us is the same one t h a t had bothered us in other states of intestinal intolerance, namely, should a poorly tolerated foodstuff be given or should it be withheld? Current feeding policies have, in general, been based on tile view that food intolerance to a particular food was induced by an excess of that food. Such :food was to be avoided with the expectation that rest would predispose to recovery of the disordered function. On the other hand, our experiences with intestinal intolerance in acute diarrhea 9 have led us to a different view, namely, that the state of intolerance was not induced by the food but by some exogenous f a c t o r such as an infection which in some unknown w a y impaired the mechanism for absorption; the increased fecal loss caused by giving the p o o r l y tolerated food merely demonstrated rather than induced the intolerance. I n support of this view in diarrhea was the finding that giving the poorly tolerated food increased its absolute absorption, failed to affect the percentage absorption, and had no influence on the rate of recovery. W e were interested to see if a similar situation prevailed in the case of idiopathic celiac disease. W e carried out balance studies on three typical celiac patients on a s t a n d a r d milk diet which was then supplemented by additional fat, given in the form of melted b u t t e r b y spoon. Tables IV, V, and VI illustrate the

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F a v o r a b l e clinical results were rep o r t e d b y H a a s ~~ f r o m a generous f a t supplement. Maerae a n d Morris ~ in Glasgow carried out seven balance studies on f o u r celiac p a t i e n t s with findings a l t o g e t h e r similar to ours, which are s u m m a r i z e d in Table VII. D a t i n g f r o m an earlier p e r i o d were e x p e r i m e n t s carried out in Vienna in 1921 b y Schick and Wagner, ~2 a typical one of which is reproduced in Table V I I I . Their c o m m e n t s are of

results of this experiment. I t m a y be seen t h a t the a d m i n i s t r a t i o n of a sizeable f a t supplement, a l t h o u g h it increases the loss of fecal fat, b r o u g h t ./ about a s u b s t a n t i a l increase m the a m o u n t of f a t absorbed. 0 n l y favorable reactions were noted clinically, even with continuation of the generous f a t i n t a k e for m a n y weeks, and, b a r r i n g one m i n o r exception,* the absorption of other food m a t e r i a l s was not affected. TABLE I V .

EFFECT OF INCREASING }PAT INTAKE ON FAT A.BSORPTION

(Celiac P a t i e n t D. C., A g e d 20 M o n t h s ) PERIOD 1

F a t intake (Gm./day) ~ a t in feces (Gm./day) :Pat a b s o r b e d (Gm./day) P e r cent intake absorbed Periods ten days each.

I

PERIOD II

I

PERIOD IIl

I

PERIOD IV

36.0

36.0

45.0

92.7

5.3

8.5

6.7

10.0

30.7

27.5

38.3

82.7

85.1%

76.5%

85.0%

89.1%

TABLE V. EF]~EOT OF INCREASING FAT INTAKE (Celiac P a t i e n t , A g e d 71/_o Y e a r s )

%

~5 z5

~d Control diet

Control diet +85.4 Gm. butter/day

Bold-face

Intake 1920 Urine 525 Feces 186 Absorbed 1734 % Intake 90 absorbed Intake 1920 Urine 679 Feces 272 Absorbed 1648 % Intake 86 absorbed type is for emphasis.

~N

14.84 5.40 5.35 9.49 64

50.0 33.3 4.7 45.3 91

79.0 48.4 7.0 72.0 91

168.0 0.6 81.5 86.5 52

52.6 12.5 19.1 33.5 64

46.0 25.8 0.9 45.1 98

76.80

16.04 7.26 6.50 10.14 61

78.2 48.6 8.2 70.0 90

79.8 45.5 9.2 70.6 89

172.3 0.7 84.5 87.8 51

52.9 12.8 21.0 31.9 60

74.8 40.5 2.1 72.7 97

153.60

These observations on the beneficiM effect of giving f a t in idiopathic celiac disease arc not unique. *It m a y be noted t h a t the patient shown in Table l I I showed an unfavorable calcium balance for a time, associated with the increased fat intake. With continuation of the d~et this did not, however, p e r s i s t ; hence, it does not a p p e a r to us a phenomenon to oecasion concern,

41.50 35.25 46

89.40 64.20 42

8.06 2.98 1.53 6.53 81

20.6

8.06 3.38 1.54 6.52 81

20.6

interest. Questioning the p r e v a l e n t view t h a t the m a t e r i a l lost in excess in the stool was the " m a t e r i a pecc a n s " which should be restricted in the diet, they a r g u e d t h a t the res t r i c t e d diet, t h r o u g h lack of use, m a y h a v e discouraged the f o r m a t i o n

HOLT:

CELIAC DISEASE--WHAT IS I T .~

375

TABLE VI. EFISECX,01~ INCREASING FAT INTAKE (Celiac P a t i e n t , A g e d 8 M o n t h s )

g5 ~5 Control diet

Intake 1080 6.70 21.9 33.4 52.5 23.0 24.8 33.50 4.62 8.0 Urine 293 1.92 5.7 24.4 0.3 7.9 23.4 2.45 Feces 189 4.00 0.8 4.2 46.5 17.0 1.2 14.20 0.74 891 2.70 21.1 29,2 6.0 6.0 23.6 Absorbed 19.30 3.88 % Intake 82 40 99 88 11 26 95 58 84 absorbed Control diet Intake 1260 7.32 31.8 34.1 54.0 23.1 34.9 59.60 4.62 8.0 +30 Gm. Urine 425 3.06 19.5 29.8 0.3 8.2 31.4 ].85 butter/day Feces 236 4.07 2.3 4.6 51.0 14.1 2.8 28.50 0.67 Absorbed 1024 3.25 29.5 29.5 3.0 9.0 32.1 31.10 3.95 % Intake 81 44 93 87 6 39 92 52 86 absorbed Control diet Intake 1050 8.59 51.6 34.3 57.0 23.3 54.8 1.11.70 4.62 8.1 +90 Gm. Urine 446 2.96 26.2 30.0 0.6 6.8 41.5 ].30 butter/day Feces 293 4.65 5.2 5.8 74.9 21.8 2.1 60.50 0.72 757 3.94 46.4 28.5 - ] 7 . 9 1.5 52.7 51.20 3.90 Absorbed 72 46 90 86 -31 6 97 46 85 % Intake absorbed Control diet Intake 1280 10.62 66.8 49.5 57.3 25.5 60.7 111.70 8.88 8.8 +90 Gin. Urine 430 3.80 28.2 36.8 0,2 14.3 44.8 2.42 b u t t e r +170 Feces 224 5.90 15.7 12.8 51,0 10.8 2.6 34.00 1.46 Gm. m e a t / Absorbed ]056 4.72 51.] 36.7 6,3 14.7 58.1 77.70 7.42 day % Intake 83 45 77 74 11 58 96 67 84 absorbed The metabolism periods in this and other patients here reported were four days in duration, stools being marked with carmine. The patients were with 1 exception (Case 2) placed on metabolism f r a m e s to permit separate collections of urine and feces, The analytic methods employed were as described in a previous publication. 2 The basal diets were prepared from evaporated milk and sugar, providing approximately 100 calories per kilogram of which approximately 15 per cent of the calories were from protein, 50 per cent from carbohydrate, and 35 per cent from fat. The supplementary fat w a s supplied as melted butter, fed by spoon. A complete report of these experiments was published by Cbung and associates, Pediatrics 7: 491, 1951.

TABLE

VII.

EFFECT

OF FAT

II FAT INTAKE DIET I (G~./DAY) Case 1 Normal 29.4 High fat 99.2 Normal 24.2 High fat 97.0 Normal 24.0 High fat 104.3 Case 2 Normal 34.1 High fat 99.9 Normal 38.4 Higl~ f a t 75.1 Case 3 Normal 28.2 H i g h fat 114,7 Case 6 Normal 38.8 High fat 115.0 *Data of Macrae and Morris, 1931.11

SUPPLEI~ENT

CELIAC

FAT EXCRETION (a~./BAY) 3.77 5.98 7.99 18.53 2.94 12.11 4.45 4.56 12.08 11.37 7.46 22.20 9.91 9.62

DISEASE ~

FAT ABSORBED (~./.AV) 25.61 93.22 16.21 78.47 21.1 92.2 29.6 95.3 26.4 63.7 20.7 92,7 28.9 105.4

~ II~TAKE ABS0~ED 87.2 94.2 67.0 80.9 87.6 88.4 87.2 95.4 68.7 84.8 73.6 80.8 74.4 91,6

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THE JOURNAL OF PEDIATRICS

of some digestive secretions, a process t h e y a t t e m p t e d to reverse b y giving fat. Clinical as well as chemical findings were favorable. Although the stools continued to show an excess of f a t for some time, the children put on weight and felt well and lively. Their concluding c o m m e n t m a y be q u o t e d : These f i n d i n g s show w h y we believ e t h a t the therapy of avoidance can be h a r m f u l i n such cases a n d t h a t as f a r as a r e t u r n to h e a l t h is concerned much more is to be exp e t t e d f r o m the therapy of use.

The t h e r a p y of use has received s u p p o r t in other quarters. I n a d u l t sprue, t h o u g h t by most to be an analogous if not an identical condition with celiac disease, metabolic observations both in this c o u n t r y 1~ and in E n g l a n d 1~ have shown i m p r o v e d f a t a b s o r p t i o n resulting f r o m f a t administration. TABLE

.AY 4/12/21 4/13/21 4/14/21 4/15/21 4/16/21 4/17/21

VIII.

EFFECT

OF ADDING

and associates 1~ a d o p t the principle of giving more of the p o o r l y absorbed r m t r i e n t b y m o u t h w h e n it comes to giving potassium in diarrhea, but t a k e the opposite point of view in the ease of foods which s u p p l y calories. One wonders w h y the t h e r a p y of use has had so little a c c e p t a n c e and w h y the evidence in its f a v o r has been so consistently i g n o r e d in this country. The answer would seem to be t h a t increased stool loss on giving, the p o o r l y absorbed food is obvious, whereas the a c c o m p a n y i n g increased r e t e n t i o n requires either a chemist or a p r o l o n g e d clinical o b s e r v a t i o n to demonstrate. T r e a t m e n t has been aimed at the stools r a t h e r t h a n at the child himself. L e t us t u r n now to the second foodstuff t h o u g h t to be p o o r l y tolerated b y the celiac--carbohydrate. Does

]~AT IN CHRONIC

DIET C ont rol Control 34 Gin. b u t t e r Control 34 Gm. b u t t e r C ont rol C ont rol C ont rol

INTESTINAL

INDIGESTION

~"

STOOL FAT (~./DAY) 4.4 6.6 6.7 11.7 10.4: 6.0

Of 34 Gin. f a t added, a p p r o x i m a t e l y 5 Gin. w e re e x t r a c t e d a n d 29 Gm, a b s o r b e d by the p atient. * D a t a from Schiek and W a g n e r . 12

I m i g h t point out t h a t some of our most vocal opponents of the t h e r a p y of use in states of oral intolerance h a v e shown a certain a m o u n t of inconsistency. Thus Andersen has rep e a t e d l y held out for f a t r e s t r i c t i o n in celiac disease, yet w h e n it comes to v i t a m i n A, a substance which is p r o b a b l y absorbed b y an identical meehanism, she does not hesitate to give increased quantities of v i t a m i n A b y m o u t h in order to insure adequate absorption. Likewise, D a r r o w

the t h e r a p y of use a p p l y here, too? The thesis is more difficult to demons t r a t e b y a balanee study. W e can m e a s u r e u n a b s o r b e d f a t and calculate f a t a b s o r p t i o n w i t h o u t difficulty, but we cannot do this with sugar. Undigested sugars f e r m e n t in the intestine and b r e a k d o w n into p r o d u c t s not r e a d i l y m e a s u r a b l e as being derived f r o m sugar. To be sure, we have the s u g a r absorption curve to guide us, b u t it is a m o s t u n s a t i s f a c t o r y guide. A fiat s u g a r

ttOLT :

CELIAC D I S E A S E - - W H A T

curve m a y mean only that sugar is being more slowly absorbed, not that it is less completely absorbed. It occurred to us t h a t sugar absorption could be a c c u r a t e l y measured by using isotopical]y tagged sugar in which e v e r y carbon atom was so tagged. The unabsorbed degraded material could t h e n be identified by the fecal isotopic carbon and the absorbed sugar d e t e r m i n e d by difference. I shall not go into the details of the p r o c e d u r e except to say that it involved a great deal of work on the p a r t of a n u m b e r of people. We were f o r t u n a t e in obtaining the cooperation of the B r o o k h a v e n Laboratories in the preparation of one isotopic sugar and of Dr. Sidney Weinhouse of the L a n k e n a u Research Institute and Dr. Leon Hellman of Memorial Hospital in New Y o r k for making some of the measurements. Much of the work was done by Dr. 011i Somersalo, a visiting fellow from Finland. The absorption of sugars in normal infants and children p r o v e d surprisingly complete, more t h a n 99.8 per cent of glucose or sugar being absorbed. Two subjects with celiac disease * studied on two occasions showed absorption figures for glucose absorption of 99.2 per cent, 99.5 per cent, 99.8 per cent, and 99.9 per cent - - i n other words, not appreciably below the normals. H o w do we explain the f r o t h y stools which these patients have even on simple sugars? The answer would seem to be t h a t it takes very little sugar to make a lot of gas. I have calculated that 1 Gin. of sugar is capable of forming 745 c.c. of CO2. The few bubbles of gas noticed in the 9 S t u d i e d t h r o u g h t h e c o u r t e s y of I ) r s . E b b s and Chute at the Hospital for Sick Children in T o r o n t o .

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stool represent amounts of sugar which are infinitesimal and which from the point of view of nutrition can be completely ignored. W h a t about starch? Our own studies with starch are as yet incomplete. Using the iodine reaction Andersen and di Sant'Agnese ~ have f o u n d that as much as 85 per cent of the ingested starch appears to be absorbed by cellars. Can we ignore this defect and feed starch with impunity.9 A t the present time such a blanket recommendation cannot be made. Although polysaccharide itself appears to be safe to give, Dicke and his co-workers 16 have presented evidence now confirmed 17 that the cereal protein associated with flour may initiate a relapse. W h e a t and, mor.e particularly, w h e a t gluten have been blamed, and it has been claimed that idiopathic celiac disease is by and large a manifestation of idiosyncrasy to wheat gluten. I f we are dealing with a condition of food allergy, the " t h e r a p y of u s e " does not a p p l y - - a t least it requires qualification, g r a d e d dosage of the offending food being perhaps given. But granting t h a t allergy to wheat protein can produce the picture, how often is this the ease.9 I do not think we have adequate data to answer this question at the present time. I certainly do not have it. But from a perusal of the literaure, the old as well as the new, I find it difficult to believe that sensitivity to wheat gluten accounts for more t h a n a small percentage of these cases. Sensitivity to other food proteins, such as potato, may, in some instances, be at fault. It is quite certain, as H e r t e r and others since him have pointed out, that some children tolerate wheat protein well.

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THE ,JOURNAL OF PEDIATRICS

H o w l a n d , TM a firm believer in the disastrous results of giving polysaceharide, w a s f r a n k to admit that some patients in w h o m his advice had been disregarded, and w h o had been given farina, came back thriving. Front published eases it is often difficult to decide w h e t h e r a relapse f o l l o w i n g the addition of a cereal was due to sensitivity to that food or to a coincident flare-up of infection, i n the present state of our k n o w l e d g e , it w o u l d seem that the cereal grains and particularly w h e a t should be used with caution. More than a single trial is, however, needed to establish the presence of food allergy and we certainly need more data before we can a c c u r a t e l y assess the role of allergy in this disorder. In concluding m y c o m m e n t s on the d i e t o t h e r a p y of celiac disease, I feel on safe ground in stating that w e do not need to exclude either fats or sugars from the diet. No one questions the need of adequate protein and vitamins. The question of sensitivity to particular foods needs to be studied carefully in every ease and only those starchy foods excluded in w h i c h sensitivity to the associated protein has been clearly demonstrated. A p a r t front dietotherapy, antibiotics, prophylactic as well as therapeutic, are indicated. There is no question that intereurrent infections are responsible for most relapses. The possibility that agammaglobulinemia exists in some of these eases remains to be further explored. I k n o w of at least one instance in w h i c h this condition w a s found to be present. REFERENCES

1. Gee, S.: On the Coeliac Affection, St. ]3arthol. Hosp. Rep. 24: 17, 1888.

2. Parsons, L. G.: Celiac Disease, Am. J. Dis. Child. 43: 1293, 1932. 3. Herter, C. A.: Intestinal Infantilism, New York, 1908~ The Macmillan Co., p. 87. 4. Andersen, D. It.: Celiac Syndrome; tgel a t i o n s h i p - o f Celiac Disease, S t a r c h Intolerance and Steatorrhea, J. PEmAT. 30: 564, 1947. 5. Andersen, D. H., and di S a n t ' A g n e s e , P.A.: The Celiac Syndrome in Brenn e m a n n ' s Pediatrics, edited b y I. McQuarrie, IIagerstown, 1952, chap. 20, p. 6, W. F. Prior Co. 6. Talbot, F . B . : Physiology and Pathology of the Digestion of F a t in Infancy. Am. J. Dis. Child. 1: 173, 1911. 7. Holt, L. E., Courtney, A. M., and Fales, t{. L.: A Study of the F a t Metabolism of I n f a n t s and Young Children, Am. J. Dis. Child. 17: 241, 423: 1919. 8. E a r l i e r refercnces to s t a r c h indigestion will be found in: (a) I~eeht, A. F.: Die Faeces des Siiuglings und des Kindes, Berlin and Vienna, 1910, Urban & Schwartzenberg. (b) Czerny, A., and Keller, A.: Des Kindes Erniihrung. Ern:~ihrungstSrungen a n d Erniihrungstherapie, ed. 2 Leipzig, 1928, F r a n z Deuticke. Subsequent papers of i n t e r e s t are the following : (e) Simehen, H.: Studien iiber Mehlverdauung, Arch. Kinderheilk. 75: 6, 1924. (d) Andrejew, S., and Georgiewsky, S.: U e b e r die Abhiingigkeit der fermerttivers Fiihigkeit des D a r m s a f t e s yon der A r t der Ni~hrung; das amylolytische Ferment, Arch. ges. Physiol. 230: 33, 1932. (e) Bespaloff, M.: Etude de la digestion des F a r i n e a u x chez le Nourrisson, Nourrisson 20: 352, 1932. (f) Armand-de-Lille, P. F.: tIarben Lectures; Problems of N u t r i t i o n and Growth: Digestion of Starch; Role of V i t a m i n s ; L i g h t and Itelio therapy in Nutrition, J. S t a t e 3zfed. 43: 683, 1935. 9. (a) Chung, A. W.: The Effect of Oral Feeding at Different Levels on the Absorption of Foodstuffs in I n f a n tile Diarrhea, J. PEDIAT. 33: 1, 1948. (b) Chung, A. ~ r and Viseorova, B.: The Effect of E a r l y Oral Feeding versus E a r l y 0 r a l S t a r v a t i o n on the Course of I n f a n t i l e Diarrhea, J. PEDIAT. 33: 14, 1948. (C) Chung, A. W , and Holt, L. E , Jr.: The Role of 0 r a l F e e d i n g in I n f a n tile Diarrhea, P e d i a t r i c s 5: 421, 1950. 10. Haas, S. V.: Celiac Disease, J. PEDIA~. 13: 390, 1938. 11. )/[acrae, O., and 2v[orris, IN.: Metabolism Studies in Celiac Disease, Arch. Dis. Childhood 6: 75, 1931.

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CELIAC DISEASE--WHAT IS IT.~

]2. Schick, B., and Wagner, R.: Ueber eine VerdauungstSrung jenseits des I
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16. Dicke, W. K., Weijers, H. A., and Van de Kamer, J. t{.: Celiac Disease. II. The Presence of a W h e a t Factor t I a w lug a Deleterious Effect in Cases of Celiac Disease, Acta paediat. 42: 34, 1953. 17. Sheldon, W., and Lawson, D.: The ]YIanagement of Celiac Disease, Lancet 2: 902, 1952. 18. I~owland, J.: Prolonged Intolerance to Carbohydrates, Tr. Am. Pod. Soc. 33: 11, 1921.

An ~4ecount of an Hemorrhagic Disposition existing in certain Families. By John C. Otto, M.D., of Philadelphia About seventy or eighty years ago, a woman by the name of Smith, settled in the vicinity of Plymouth, New ttampshire, and transmitted tile following idiosyncrasy to her descendants. I t is one, she observed, to which her family is unfortunately subject, and had been the source not only of great solicitude, but frequently the cause of death. I f the least scratch is made on the skin of some of them, as mortal a hemorrhagy will eventually ensue as if the largest wound is inflicted. The divided parts, in some instances, have had the appearance of uniting, and have shown a kind disposition to heal; and, in others, cicatrization has abnost been perfect, when, generally about a week from the injury, an hemorrhagy takes place from the whole surface of the wound, and continues several days, and is then succeeded by effusions of serous fluid; the strength and spirits of the person become rapidly prostrate; the countenance assumes a pale and ghastly appearance; the pulse loses its force, and is increased in frequency; and death, from me~e debility, then soon closes the scene. Dr. Rogers attended a lad, who had a slight cut on his foot~ whose pulse ~'was full and f r e q u e n t " in the commencement of the complaint, and whose blood '~seemed to be in a high state of efferverscence." So assured are the members of this family of the terrible consequences of the least wound, that they will not suffer themselves to be bled on any consideration, having lost a relation by not being able to stop the discharge occasioned by this operation. I t is a surprising circumstance that the males only are subject to this strange affectlon~ and that all of them are not liable to it. ~ome persons, who are curious, suppose they can distinguish the bleeders (for this is the name giveu to them) even in infancy; but as yet the characteristic marks are not ascertained sufficiently definite. Although the females are exempt, they are still capable of transmitting it to their male children, as is evidenced by its introduction~ and other instances, an account of which I have received from the IIon. Judge Livcrmore, who was polite enough to communicate to me many particulars upon this subject. This :fact is confirmed by Drs. Rogers and Porter, gentlemen of character residing in the neighbourhood, to whom I am indebted for some information upon this curious disposition. When the cases shall become more numerous, it may perhaps be found that the female sex is not entirely exempt, but, as far as my knowledge extends, there has not been an instance of their being attacked. Dr. Rush has informed me, he has been consulted twice in the course of his practice upon this disease. The first time, by a family in York, and the second, by one in Northampton county, in this state. THE MEDICAL ~EPOSITOaY, VOL. V~, ~EW "~rOI~K, ]803.