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Intestinal Lymphangiectasia: A Reappraisal


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A Reappraisal

Peter A. Vardy, M.B., D.C.H., Emanuel Lebenthal, M.D., and Harry Shwachman, M.D.

From the Departments of Pediatrics, Ba,Zilai Medical Center, Ashkelon, israel and Harvard Medical School and the Childrens Hospital Medical Center, Boston, Massachusetts

ABSTRACT. Intestinal lymphangiectasia (IL) may vary widely in its manifestations and severity. Fifteen children seen between 1960 and 1974 with histologically proven IL are analyzed by clinical, laboratory, radiologic, and histo-logic criteria. Remissions occurred in most patients and none died. Exacerbations occurred in five children.

Diarrhea was present in 14 patients and in 13 appeared before the age of 3 years. Vomiting occurred in nine patients and growth retardation in seven. Four children had asso-ciated peripheral lymphedema and two of these had a family history of lymphedema, both had affected fathers and one had affected siblings and paternal cousins. Seven had hypo-proteinemic edema, and, of these, four suffered from hype-calcemic seizures. Chylous effusions were present in five. Hypoproteinemia was present in 12 although five had no hypoalbuminemic edema. Six had lymphopenia which was

related to the severity of the disease and was the last

abnormality to disappear after clinical remission. Lympho-penia may first appear years after the protein loss begins. Upper gastrointestinal tract series were performed in 13 children and had diagnostic supportive value in seven. Six children had two or more small-intestinal biopsies done. They all showed great variation from one examination to the other, ranging from a normal appearance to severe changes.

Lymphatic block may occur at different sites-in the lamina propria only, generalized (lamina pmpria, submu-cosa, semsa, and mesentery), or conversely in the mesentery

alone with minimal changes in the lamina propria. In three

patients intravenous hyperalimentation was necessary. Specific treatment with a high-protein, low-fat diet with added medium-chain triglyceride (MCT) is valuable. Surgi-cal resection was of benefit in one patient, and anastomosis

of mesenteric to para-aortic lymph nodes in another.

Pedia-trics, 55:842, 1975, irsrni LYMPHANCIECTASIA,


Intestinal lymphangiectasia (IL) has been

clas-sically described as a disease entity characterized

by dilated intestinal, submucosal, and subserosal

lymphatics, protein-losing enteropathy,

hypoal-buminemia, hypoproteinemic edema, and

lym-phopenia.’8 It has been considered a rare

condi-lion, and after Waldmann’s review article in


where 40 cases in adults and children are

recorded, only another nine with histologic proof

have been reported in the literature.96 It is the

purpose of this paper to suggest that the clinical,

laboratory, and radiologic spectrum of this

condi-lion is more protean than has been suspected.

Furthermore, its rarity is called in question. The

disease may be severe or mild, chronic or

transi-tory, and, on occasion, none of the classical signs

or symptoms may be manifest.


Fifteen children admitted to The Children’s

Hospital Medical Center (CHMC), Boston, from


through 1974, were studied retrospectively.

No patient with this disorder came to post

mortem during this period. There were nine boys

and six girls and age at onset of symptoms ranged

from 1 week to 15 years. Peripheral lymphatic

edema was present in four patients and two had a

positive family history of lythphedema. All 15

patients were proven to have histologic IL, 1 1 by

per-oral duodenal biopsy alone, 2 by per-oral

duodenal biopsy and laparotomy, and 2 by

lapa-(Receivedjune 24; revision accepted for publication October 15, 1974.)

Supported by grants from the Ullmann Foundation and from the World Health Organization. Dr. Vardy is a Fellow of the World Health Organization.



FIG. 1. Duodenal biopsy: marked dilatation of the lymphatic channels in the lamina propria with distortion of villi

(patient 4).

notomy alone. A pediatric 8-mm Crosby-Kuglen capsule with two 3-mm ports were used. Contrast radiology of the upper gastrointestinal tract was performed using Easy-Paque with 1% sorbital as a

suspending agent. Thirteen children had one or

more upper gastrointestinal series performed. Case 2 will be presented in detail as a “classical”

example of intestinal lymphangiectasia with

many points of interest.


This white girl of Italian parentage was born weighing 3,330 gm after a normal gestation and delivery. A brawny constant swelling of the left arm was noted at birth. The family history is noncontributory.

She was well until 3 years of age when she fell ill with abdominal pain, nausea, vomiting, diarrhea, and a distended abdomen. At 5 years she again fell ill with the same complaints, this time accompanied by fever. An appendec-tomy was performed. Her third episode of similar complaints was some three months later. The diagnosis was “viral gastroenteritis.” On this occasion a left-sided abdominal mass was felt. Three years later, for the same complaints, a laparotomy was performed which showed lymph nodes the



:i 2

FIG. 2. Specimen shows (1) jejunal fold thickening, (2) spiculation, (3) punctate lucencies (arrows), and (4)

jejuniza-tion of ileum (patient 2).




Clinical Features (Age at Onset)


AgeIL and/or Hypo

pro-- teinemia Growth

Patient Born Sex Diagnosed Diarrhea Vomiting Edema Retardation

1 1957 M 15 yr 15 yr 15 yr 15 yr 0

2 1958 F 10 yr 3 yr 3 yr 12 yr 0

3 1967 F 9 mo 10 mo 0 9 mo 0

4 1961 M 6wk 3yr 0 6wk

-5 1966 M 2yr 2mo 4mo 0 4mo

6 1968 F 2yr 0 0 0 0

7 1969 F 4 me 1 wk 3 me 0 1 wk

8 1972 M 3 yr 2#{189}me 3 me 0 3 me

9 1968 M 4 me 1 me 3 yr 10 me 0 2 me

10 1970 F 9 wk 6 wk 6 wk 8 wk 0

11 1968 M 2 yr - 0 0 2 yr

12 1968 M 2 yr - 0 0 3 me

13 1969 M 4 yr 2 me 0 0 3 me

14 1969 F 8 me 4 me 4 me 5 me 0

15 1945 M 18 yr 1 yr Birth 11 yr 0

Frequency 14 of 15 9 of 15 7 of 15 7 of 15

size of golf balls throughout the mesentery of the small bowel. Histologically there was “severe lymphangiectasis.” At the age of 10 years she was again hospitalized because of abdominal pain and loose bowel movements which had persisted since the age of 3 years. Her sixth admission at 11 years of age was for severe diarrhea of one month’s duration and abdominal pain. A severe hypoproteinemia and lympho-penia was then found and the child was transferred to the CHMC at 1 1 years of age.

On admission she appeared chronically ill with a protu-berant abdomen and a swollen left upper limb with no pitting. Pitting edema was present over both pretibial areas. Her weight was below the 25th percentile and her height on the 50th percentile for her age. A mobile 3 x 4-cm mass was palpated in the left lower quadrant of her abdomen and a smaller mass above it.

Laboratory Data

Laboratory tests gave the following values: total protein, 3.06 gm/100 ml; albumin, 1.56 gm/100 ml; lgG, 360 mg/ 100 ml; IgA, 110 mg/100 ml; 1gM, 160 mg/100 ml; C3 protein, 130 mg/100 ml; haptoglobin, 98 mg/100 ml; transferrin, 106 mg/100 ml; a,-antitrypsin, 390 mg/100 ml, and orosomu-coid, 142% of normal. The complete blood cell count (and specifically the lymphocyte count) was normal. Serum calcium concentration was 7 mg/100 ml; total lipids, 500 mg/100 ml; phospholipids, 119 mg/100 ml; and cholesterol, 133 mg/100 ml.

Duodenal biopsy revealed vacuolizatien of some mucosal cells, slightly flattened viii, and marked lymphangiectasia in the lamina propria, submucosa, and subserosa (Fig. 1). Disaccharidase assay of small-intestine mucosa showed no

lactase activity with normal sucrase, maltase, and palatinase.

A lactose tolerance test showed a flat curve. She responded well to a low-milk, fat-free, high-protein diet with added medium-chain triglycerides (MCT). The abdominal pain disappeared and the abdominal mass was no longer palpable. Over the next four years she was asymptomatic. She reached the 50th percentile of weight for her age, (a gain of 8 kg) and had one formed, brown stool per day. Total plasma pretein rose gradually to 5.8 gm/100 ml with an albumin of 3.18 gm/100 ml. However, on routine follow-up an abdom-inal mass was again felt and she was readmitted to CHMC at the age of 16 years. Investigation revealed a lymphopenia of 680/cu mm with no ether abnormalities. Other values were: total protein, 5.7 gm/100 ml; albumin, 3.51 gm/100 ml; and calcium, 9.5 mg/100 ml. Protein electrepheresis showed: a’, 0.12 gm/100 ml; a2, 0.83 gm/100 ml; fi, 0.77 gm/100 ml; and


0.42 gm/100 ml. IgG and IgA were 450 and 25 mg/100 ml respectively and 1gM was normal.

Skin testing to PPD, and SKSD was negative and positive to mumps. During this period of clinical remission 5’Cr-labeled albumin was given and showed a half-life of one day (normal, four to seven days); stool excretion was 0.29% (normal, 0.1% to 0.7%); and plasma volume, 1,371 ml or 40.6 ml/kg (mean normal, 45 mI/kg). Barium enema showed evidence of a mass indenting the sigmoid and barium swallow and follow-through showed jejunal thickening with marked spiculation, “jejunization” of the ileal pattern, and general disorganization of small bowel pattern. Small punc-tate lucencies were also seen. Technetium scan and echo scanning revealed a left lower quadrant mass. Laparatomy showed the whole of the small gut mesentery to be a huge, yellowish plaque encompassing a mass of lymph-engorged



Course & Treatment

Full recovery on high-protein, fat-free diet with MCT Partial remission on high-protein, fat-free diet with MCT Complete remission on high-protein, fat-free diet with MCT

Partial remission, intermittent diarrhea, and chronic hypoproteinemia despite diet (nonadherence)

Complete recovery (normal diet)

Normal diet and added iron; no diarrhea

Occasional loose stools on normal diet; well but height is below third percentile and weight is at tenth percentile

No apparent symptoms relating to IL; child also has cystic fibrosis

Occasional diarrhea; normal diet; doing well

Complete remission on high-protein, fat-free diet with MCT

Lost to follow-up

Incomplete follow-up; weight and height responded well to fat-free diet with MCT

No diarrhea (also has DiGeorge syndrome); doing wellon normal diet

Recovery after resection of 43 inches of small gut; is on high-protein, fat-free diet with MCT

Partial remission, remains lymphopenic; low-fat diet

showed numerous dilated lymph channels interspersed with smooth muscle and lymphoid aggregates. The lesion was called a “lymphangiohamartoma.” No section was per-formed.

Her postoperative course was uneventful and she was discharged on a high-protein, fat-free diet with added MCT (20 gm/day). On follow-up three months later at age 16, she was asymptomatic and her height and weight were on the 50th percentile. Total protein was 6.2 gm/100 ml; albumin, 3.51 gm/100 ml; a,, 0.18 gm/100 ml; a,, 0.82 gm/100 ml;


0.99 gm/100 ml; and y, 0.20 gm/100 ml. She had 1,152 lymphocytes per cubic centimeter (normal for age, 1,200 to 5,800).


The main clinical features in each of the 15

patients are shown in Table I. The frequency of

occurrence is noted at the bottom of each


The most constant finding is diarrhea at some

time in the course of the disease, accompanied by

nausea and/or vomiting in nine children and

followed in frequency by growth retardation in

seven children. The diarrhea was first noted in all

the 14 patients in whom it occurred by the age of

3 years, but only in case 2 was it the most severe

of the clinical problems, both because of its

degree and its chronicity over a period of more

than eight years until relieved by a fat-free diet

with added MCT. In patients 9, 10, and 14 the

diarrhea was also severe enough to necessitate

intravenous hyperalimentation at the ages of 4

months, 12 months, and 5 months respectively

and may well have continued to be a major

problem had these children remained

undiag-nosed. Growth retardation, as determined by

height and weight records and/or bone age, can

be related to the lymphatic anomaly in five

patients out of seven where this was present. Of

the remaining two children, patient 8 had cystic

fibrosis and patient 13 suffered from a Di George

Syndrome with multiple congenital anomalies.

Patient 12 also showed spasticity and severe

psychomotor retardation following an episode of hypertonic dehydration at the age of 3 years,

although his failure to thrive was already evident

by 3 months of age.

An attempt was made in all the cases to

differentiate between peripheral lymphatic

ede-ma and hypoproteinemic edema. No difficulty

was encountered in this differentiation.

Hypoproteinemic edema was present in seven

children in three of whom lymphedema was also

present. In patients 4 and 10 the hypoproteinemic

edema was evident during the neonatal period

and in all cases tended to be symmetrical,

gener-alized, pitting, and fluctuating with changes in



Constituent ill Remission

Patient2 Patient 3

Ill issi#{176} Ill Remission

Total protein (gm/i#{174} ml) 2.60 6.60 3.06 6.20 4.40 7.10

Albumin (gm/i#{174} ml) 1.15 3.59 1.56 3.51 2.86 4.20

a1(gm/lOOml) 0.18 0.17 0.18 0.18 0.17 0.28

a2 (gm/i#{174}ml) 0.67 1.09 0.48 0.82 0.40 0.92

/ (gm/100 ml) 0.42 0.75 0.36 0.99 0.53 0.85

a (m/1O0 ml) 0.18 1.00 0.42 0.70 0.44 0.78

IgG (mg/i#{174}ml) 200 480 360 450 N 1,140

IgA (mg/i#{174}ml) 25 100 110 25 N 155

1gM (gm/100 ml) 28 94 160 60 N 144

C3 protein (mg/100 ml) 124 110 130 116 ND 134

Haptoglobin (mg/i#{174} ml) 200 190 98 68 ND 140

Transferrin (mg/i#{174} ml) 130 155 106 112 ND 340

a-antitrypsin (%N) 108 120 290 315 ND 124

Orosomucoid (%N) ND 92 .142 140 ND 136

#{176}Clinicaland laboratoly remission incomplete. tClinical remission only.

tN - recorded as normal; ND - not done.



for the relatively sudden appearance of all his

symptoms, including severe hypoproteinemia, at

the age of 15 years, and his rapid and complete

recovery within a matter of weeks after the

initiation of a high-protein, fat-free diet with

added MCT.

In three children lymphedema was present at

birth, was asymmetrical, constant, and

nonpit-ting, and all these characteristics were present in

the fourth child (patient 5), although the

lymphedema only appeared at the age of 17

months. In this patient the father, two siblings,

and two cousins also suffered from lymphedema.

A positive family history was also present in

patient 4, whose father manifested scrotal

lymphedema at 30 years ofage.

Chylous effusions, both pleural and pentoneal;

were present in five children, and in one child

(patient 3) were the main clinical problem and

necessitated bilateral pleurectomy. This last child

also suffered from hypocalcemic tetany as did

patients 4, 13, 14, and 15, although in patient 13

the mechanism of the hypocalcemia may well

have been associated with parathyroid

dysfunc-tion rather than the intestinal lymphangiectasia.

Abdominal swelling in patient 4 was due to

chylous ascites but in patient 2, to massive

enlargement of the mesenteric lymph nodes of the

small gut caused by lymphangiectasia, but with

no chylotth effusion. She was also the only child

who suffered from abdominal pain to any

appre-ciable degree. Five children out of 13 who were

followed-up had from three to more than ten

exacerbations. Patient 3 had in addition repeated

exacerbations of her pleural chylous effusions. All

four children who had peripheral lymphedema

were in this group.


Although only seven children manifested

hypo-proteinemic edema, 12 had hypoproteinemia

(range: total protein, 3.4 to 5.5


ml and

albumin, 1.1 to 2.7 gm/i#{174} ml). The serum

proteins and immunoglobulin status during the

acute illness and in remission were available in

five patients and are recorded in Table II. In

addition to the five children who suffered from

hypocalcemic seizures, patients 1 and 2 also had

hypocalcemla (7.6 to 7.0 mg/i#{174} ml) but with no

clinical manifestation. Lymphocytopenia was

found in six children at some time in the course of

their disease. In four, it appeared at the same time

as the hypoproteinemia but in one child it was 16

months and in the fourth child (patient 2) five

years after hypoproteinemia was first noted. Its

presence and severity tended to be related to the


Patient4 Patientl3 Patient 14

Ill Remission Normal Values Ill Remissiont

Ill Remissiont

2.80 4.10 3.50 4.30 2.70 6.50 6.5 to 8.0

1.26 2.16 1.40 1.40 0.95 3.89 3.5 to 4.5

0.28 0.32 0.30 ND 0.49 0.33 0.15 to 0.45

0.61 1.79 0.43 ND 0.70 1.17 0.40 to 0.80

0.48 0.66 0.43 ND 0.35 0.72 0.65 to 1.50

0.17 0.72 0.90 ND 0.13 0.39 0.80 to 1.60

ND 360 220 230 Very low ND 600 to 1.500

ND 30 100 175 Very low ND 60 to 290

ND 70 32 100 Very low ND 50 to 200

ND 138 190 200 ND ND 100 to 200

ND 144 59 141 44 ND 30 to 160

ND 225 185 170 Low ND 205 to 374

ND 126 25 38 59 ND 47 to 153

ND 66 111 280 ND ND 38 to 142



Of the 15 patients, 13 had one or more upper

gastrointestinal tract series performed. The films

were reviewed and the findings recorded, using

criteria based on those developed by Shimkin et

al.6 and Werbeloff


al.17 These findings (Figs. 2

to 4) were:

Mucosal detail of small bowel

(1) Thickened jejunal folds 2 mm;

(2) Spiculation; (3) Disorganization; (4) Punctate lucencies;

(5) Jejunization of ileum

Distal dilution of barium (hypersecretion)

Djlatation of lumen

(1) Jejunum 3 cm;

(2) Ileum ; 2.5 cm

The frequency of occurrence of the radiological

findings is shown in Table IV. Lymphangiograms

were performed in three children. In patient 1,

who had no peripheral lymphedema although he

suffered from chylous pleural effusions as well as

chylous ascites, a lymphangiogram was

per-formed on the right leg. This showed normal leg

lymphatics and normal iliac lymph nodes, but no

channels or nodes were visualized at the aortic

level, nor was the thoracic duct seen. In patient 3,

lymphedema of both feet was present at birth and

lymphangiography at the age of 1. year, using the



Lymphocyte Count (per cu mm)

Patient ill Clinical Remission

1 80 1,240

2t 1,380 680

3 122 1,323

4 205 855

14 324 2,318

15 No good remission; count remained in the region of 700/cu mm

#{176}Lowestrange of normal for all ages, 1,000/cu mm (Geigy Tables, ed. 7, Ciba-Geigy, p. 619).

tLymphocytopenia first appeared five years after onset of clinical symptoms and hypoproteinemia.

inguinal region as the site of entry for the contrast

media, showed markedly dilated and ectatic

abdominal lymphatics with abnormal back flow

and proximal obstruction. The contrast media

never entered the para-aortic region but some

reached the axilla. None was seen in the pleural

space or thoracic duct. It will be noted that this

child presented with severe and repeated pleural

chylous effusions. Later in the course of her

disease a dorsal, pedal lymphangiography was




.--*_‘_ .



FIG. 4. Enlargement of arrowed area in Fig. 2., showing punctate lucencies (patient 2).

scrotal and right lower limb lymphedema present

at birth. Lymphangiography was performed at 6

years of age; no lymphatics could be demon-strated in the right (lymphedematous) leg while in the left leg the lymph channels were irregular and more tortuous than usual. The thoracic duct was normal but dermal back flow was present in the region of the left hip. There was good opacifica-tion of the inguinal and abdominal nodes but the para-aortic channels were enlarged.


Intestinal lymphangiectasia in the pediatric age group may vary widely in its manifestation

and severity. These manifestations range from

severe hypoproteinemia with gross anasarca and

complete recovery as in patient 1, through

chronic diarrhea with protein loss as in case 2, chylous effusions as in patient 3, iron deficiency anemia as in patient 6, and growth retardation accompanying diarrhea in patients 5, 7, 9, and 13

and accompanying hypocalcemia in patient 12.

Similarly, complete remission may occur with a














,‘tr:L\ ‘


I,‘, : -



FIG. 5. Lymphangiectasia in subserosa with no involvement of lamina propria (patient 14).

high-protein, low-fat diet with added MCT as in

patient 1, or remission may never occur as in

patients 4, 13, and 15. Parfitt’5 considered that those cases in which hypoproteinemia occurred at or shortly after birth and was associated with a “positive family history” represent a genetically determined subgroup. Bookstein et al.’8 and Stoe-linga et al.’9 suggested, and our study leads us to suspect, that we are dealing with a single disease

entity with a wide spectrum of clinical and

laboratory manifestations determined by the

anatomical location and extent of the lymphatic

anomaly. This supports the view put forward by

Mistilis et al.,2#{176}Bookstein et al.,’8 Stoelinga et al.,’9 and Pomerantz and Waldmann3 that intes-tinal lymphangiectasia is part of a congenital disorder of the lymphatic system as a whole. If the lymphatic anomaly is peripheral it is usually referred to as congenital hereditary lymphedema

and studies by Esterling2’ and Wood et al.22

suggest that this is determined by a “simple





Jejunal Fold

Thickening Spiculation Disorganization

Punctate Lucencies



Dilation of

Lumen Jejunization

1 + 0 0 + 0 0 +

2 + + + + 0 0 +

4 + 0 + 0 0 + 0

7 +. 0 0 0 + 0 0

13 + + 0 0 0 + 0

14 + 0 0 0 + 0 0

15 + + + + + + +

Frequency 7 of 13 3 of 13 3 of 13 3 of 13 3 of 13 3 of 13 3 of 13

trance and variable expressivity.” Patterson and

colleagues23’24 in studies of congenital hereditary

lymphedema in the dog observed a wide range of

severity and also suggested a dominant type of

inheritance. It is of interest that on autopsy of 30

offspring of a lymphedematous dog, 7 had clinical

lymphedema while 17 had histologic

lymphede-ma and lymph channel abnormalities.

Abnormal-ities of lymph vessels also occurred in organs and tissues of body cavities and many dilated lymph vessels appeared ruptured. Vallet et al.’#{176}report an autopsy finding of lymph channel abnormalities

in various tissues in a child in whom intestinal

lymphangiectasia had been found on per-oral

small bowel biopsy, ante mortem. This lends

support to our thesis that intestinal

lymphangiec-tasia is one possible result of a congenital

lymphatic anomaly. It seems probable that cases

of asymptomatic intestinal lymphangiectasia exist

and that symptoms are precipitated by an

exoge-nous trigger. This may have been the mechanism

suggested by Kobayashi and Ohbe9 in their report

of a case of protein-losing enteropathy associated

with arsenic poisoning where intestinal

lymphan-giectasia was found on biopsy. Patterson’s24

histo-logic finding of ruptured lymphatic vessels lends

support to the view that this may be an important

mechanism in determining gastrointestinal

pro-tein loss as has been suggested by Herskovic et

al.,2 Waldman25 and Shimkin et al.6 In our series,

hypoproteinemia was severe in those children

who evidenced clinical peripheral lymphedema.

This would suggest that the intestinal protein loss

was augmented by trapping of albumin in the

peripheral lymphangiectatic areas. It also seems

reasonable to assume that clinically evident

lymphedema associated with intestinal

lymphan-giectasia indicates a more severe form of the

condition and that larger areas of gut are

involved, thus increasing the protein loss by this

route. Salazar de Sousa et al.26 found intestinal

lymphangiectasia in four out of seven intestinal biopsies performed on children with nephrotic syndrome. Similarly, Vallet et al.1#{176}found

intes-tinal lymphangiectasia in a child with Noonan’s

syndrome, Haddad and Wilkins27 found it

asso-ciated with a case of Turner’s syndrome, and

Dobbins28 described its presence in a case of

hypo-$-lipoproteinemia. It seems highly unlikely

that such disparate conditions should have

anything more than a coincidental relationship

with intestinal lymphangiectasia, except in the

case of Turner’s syndrome where the relationship

is well recognized. This strengthens our

supposi-tion that intestinal lymphangiectasia may be

relatively common and asymptomatic.

Sham et al.29 reported on a family of two

sibships in whom 8 of 28 children were affected

by edema, growth retardation, diarrhea,

abdom-inal pain, and clubbing in various combinations.

Five were proven to have intestinal protein loss

but dilated lacteals were found on per oral jejunal

biopsy in three cases only.

Six of our patients had more than one per-oral

biopsy and showed no histologic uniformity. To

illustrate this point, patient 3 had three biopsies

showing lymphangiectasia and one without.

Patient 9 also had four biopsies performed, of

which the first two showed moderate and mild

lymphangiectasia, the third, marked dilatation,

and the fourth, one day later, none. It seems likely

that the site of biopsy and possibly the preceding

dietary regime may be the cause. Shwachman et

al.3#{176}reported the histological findings in 11

duo-denal biopsies performed during intravenous

hyperalimentation for protracted diarrhea in

infancy and dilated lymphatics were noted in five.


hypoalbuminemia although the mechanism seems somewhat obscure. Repeat biopsies after clinical

recovery were done in four of the patients where

dilated lymphatics were found and all “had

reverted to normal.” These findings should be

used to support the thesis that there are two types

of intestinal lymphangiectasia-one genetic in

origin and the other acquired and transitory.

However, in one of the abovementioned patients,

no dilatation of the lymphatics was found on a

biopsy specimen taken only 24 hours after a

specimen in which marked dilatation was

evident. It seems unlikely that a disease process

could change so rapidly so that, therefore, the

biopsy site is most probably the determining


Lymphatic block may occur at different

sites.36 15. 16. 18 Lymphangiectasia may be present

in the lamina propria only and this is well shown

in the case described by Shani et al.29 where

marked lymphangiectasia was found in the

lamina propria on per-oral biopsy, whereas no

dilated lymphatics were seen on the small bowel

serosa at laparotomy and postmortem

lymphan-giography of the small bowel mesentery was

completely normal. Conversely, patient 14 in our

series shows marked dilatation of lymphatics in

the subserosa and mesentery with minimal

changes in the lamina propria (Fig. 5).

Lymphocytopenia may only manifest years

after the symptoms of protein loss appear, as in

patient 2 of our series, and may never be found.

There is evidence to suggest that not merely is

there a lymphocyte loss in IL, either by intestinal

loss from ruptured or “permeable” lymphatics or by “trapping” in lymphangiectatic areas, but that this loss is a differential one affecting mainly the

T lymphocytes.5 It would, therefore, be of interest

to know, in those patients with IL with a normal lymphocyte count, whether these lymphocytes

are all or mainly B cells and whether there is any

disturbance of delayed skin hypersensitivity. This is currently being investigated.

Treatment of IL with a high-protein, fat-free

diet with added MCT,3’ while supposedly having no effect on the underlying pathology, is usually effective in preventing or alleviating the diarrhea

and hypoproteinemia. It seems reasonable to

assume that the absence of fat in the diet prevents

engorgement of the intestinal lymphatics with

chyle, thus preventing their rupture with its

concomitant T cell and protein loss. MCT, being

absorbed directly into the portal system, provides

nutrient fat but avoids lacteal engorgement.

In the few cases where the lymph channel

anomaly is limited to a segment of the small

bowel, as in patient 14, resection may provide a


In view of the relative success of therapy, it

seems to us that the realizations that IL is a more

common condition than has been considered in

the past and that its manifestations may vary

widely should lead to a high index of suspicion

and vigorous attempts to confirm or exclude this



1. Waldmann, T. A.: Protein-losing enteropathy. Gastroen-terology, 50:422, 1966.

2. Herskovic, T., Winawer, S. J., Goldsmith, R., Klein, R., and Zamcheck, N.: Hypoproteinemia in intestinal lymphangiectasia. Pediatrics, 40:345, 1962. 3. Pomerantz, M., and Waldmann, T. A.: Systemic

lymphatic abnormalities associated with gastroin-testinal protein loss secondary to intestinal lymphangiectasia. Gastroenterology, 45:703, 1963.

4. MiStiliS, S. P., and Skyring, A. P.: Intestinal lymphan-giectasia. Am. J. Med., 40:634, 1966.

5. Weiden, P. L., Blaese, R. M., Strober, W., Block, B. J., and Waldmann, T. A.: Impaired lymphecyte trans-formation in intestinal lymphangiectasia: Evidence for at least two functionally distinct lymphocyte populations in man. J. Chin. Invest., 51:1319, 1972.

6. Shimkin, P. M., Waldmann, T. A., and Krugman, R. L.: Intestinal lymphangiectasia. Am. J. Radiol., 110:827, 1970.

7. Strober, W., Wochner, R. D., Carbone, P. P., and Waldmann, T. A.: Intestinal lymphangiectasia: A protein-losing enteropathy with hypogammaglobu-linemia, lymphocytopenia and impaired homograft rejection. J. Chin. Invest., 46:1643, 1967.

8. Kowlessar, D. 0.: Intestinal lymphangiectasia and A-Beta-lipoproteinemia. In, Sleisinger, M. H., and Fordtran, J. S. (eds.): Gastrointestinal Disease. Philadelphia: W. B. Saunders Company, 1973, p.


9. Kobayashi, A., and Ohbe, Y.: Protein-losing enteropathy associated with arsenic poisoning. Am. J. Dis. Child., 121:515, 1971.

10. Vallet, H. L., Holtzapple, P. C., Eberlein, W. R., Yakovac, W. C., Moshang, T., and Bengiovanni,

A. M.: Noonan syndrome with intestinal lymphan-giectasia. J. Pediatr., 80:269, 1972.

11. McGuigan, J. E., Purkerson, M. L., Trudeau, N. L., and Peterson, M. L.: Studies of the immunologic defects associated with intestinal lymphangiectasia. Ann. Intern. Med., 68:398, 1968.

12. Muzaffar, K., Block, M. A., and Fox, T. A.: Primary intestinal lymphangiectasia; Surgical implications. Am. Surg., 38:288, 1972.

13. Eisner, J. W., and Bralow, S. P.: Intestinal lymphangiec-tasia with immunoglobulin A deficiency. Am. J. Dig. Dis., 13:1055, 1968.

14. Amirhakimi, G. H., Samloff, I. M., Brysen, M. F., and Forbes, G. B.: Intestinal lymphangiectasia. Am. J. Dis. Child., 117:178, 1969.

15. Parfitt, A. M.: Familial neonatal hypoproteinemia with exudative enteropathy and intestinal lymphangiec-tasia. Arch. Dis. Child., 41:54, 1966.


diarrhea of infancy. Am. J. Dis. Child., 127:416, 1974.

17. Werbeloff, L., Bank, S., and Marks, I. N.: Radiological findings in protein-losing gastroenteropathy. Br. J. Radio!., 42:605, 1969.

18. Bookstein, J. J., French, A. B., and Pollard, H. M.: Protein-losing gastroenteropathy: Concepts derived from lymphangiography. Am. J. Dig. Dis., 10:573,


19. Stoelinga, C. B. A., Van Muster, P. J. J., and Sloff, J. R.:

Chylous effusions into the intestine in a patient with protein-losing gastroenteropathy. Pediatrics,

31:1011, 1963.

20. Mistilis, S. P., Skyring, A. P., and Stephen, D. D.: Intestinal lymphangiectasia: Mechanism of enteric loss of plasma-protein and fat. Lancet, 1:77, 1965. 21. Esterling, J. R.: Congenital hereditary lymphedema. J.

Med. Genet., 2:93, 1965.

22. Wood, J. E., Esterling, J. R., and McKusick, Y. A.: Genetic, clinical and physiologic observations in Milroy’s disease. Circulation, 22:834, 1960.

23. Patterson, D. F., Medway, W., and Luginbuhl, H.: Congenital hereditary lymphedema in the dog: I. Clinical and genetic studies. J. Med. Genet., 4:142,


24. Patterson, D. F.: Congenital hereditary lymphedema in the dog: II. Pathologic studies. J. Med. Genet., 4:153, 1967.

25. Waldmann, T. A.: Gastrointestinal protein loss demon-strated by”Cr- labelled albumin. Lancet, 2:121,


26. Salazar-De Sousa, J., Guerreiro, 0., Cunha, A., and Araujo, J.: Association of nephrotic syndrome with intestinal lymphangiectasia. Arch. Dis. Child., 43:425, 1968.

27. Haddad, H. M., and Wilkins, L.: Congenital abnermali-ties associated with gonadal aplasia. Pediatrics, 23:885, 1959.

28. Dobbins, W. 0.: Hypo-beta-lipoproteinemia and intes-final lymphangiectasia. Arch. Intern. Med., 122:31,


29. Shani, M., Theodor, E., Frand, M., and Goldman, B.: A family with protein-losing enteropathy. Gastroen-terology, 66:433, 1974.

30. Shwachman, H., Uoyd-Still, J. D., Khaw, K-T., and

Antonowicz, I.: Protracted diarrhea of infancy

treated by intravenous hyperalimentation. Am. J.

Dis. Child., 125:365, 1973.

31. Holt, P. R.: Dietary treatment of protein loss in intes-tinal lymphangiectasia. Pediatrics, 34:629, 1964.





Peter A. Vardy, Emanuel Lebenthal and Harry Shwachman

Intestinal Lymphangiectasia: A Reappraisal


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Intestinal Lymphangiectasia: A Reappraisal


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