Intestinal
Lymphangiectasia:
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,
c.s-TROINTESTINAL PROTEIN LOSS, LYMPHEDEMA, HYPOPROTEIN-EMIC EDEMA, MEDIUM-CHAIN TRIGLYCERIDE.
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
1966,
where 40 cases in adults and children arerecorded, 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.
MATERIAL AND METHODS
Fifteen children admitted to The Children’s
Hospital Medical Center (CHMC), Boston, from
1960
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.
S
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.
CASE REPORT
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).
TABLE I
ACE AT DIAGNosIs AND CLINICAL FEATURES IN 15 PATIENTS WITH INTESTINAL LYMPHANGIECTASIA
Clinical Features (Age at Onset)
Nausea
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
.1’
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
TABLE I(CONTINUED
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;
/3,
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).CLINICAL SIGNS AND SYMPTOMS
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
column.
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
Patienti
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.
TABLE II
SERUM PROTEIN ANALYSIS DURING ACUTE ILLNESS AND REMIssIoN
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.
LABORATORY FINDINGS
Although only seven children manifested
hypo-proteinemic edema, 12 had hypoproteinemia
(range: total protein, 3.4 to 5.5
gm/100
ml andalbumin, 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
TABLE III TABLE II (CONTINUED
RADIOLOGY
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
et
al.17 These findings (Figs. 2to 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
RELATIONSHIP OF LYMPHOCYTE COUNT
TO CLINICAL STATE
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
I
-,
.--*_‘_ .
..,-‘
0
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.
DISCUSSION
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
:
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:
L:
ii“#{149}A
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.-.
.
:‘.‘c
\--.‘.:i
,‘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
pene-TABLE IV
RADIOLOGICAL FINDINGS AND FREQUENCY
Patient
Jejunal Fold
Thickening Spiculation Disorganization
Punctate Lucencies
Barium
Dilution
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
factor.
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
cure.
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
diagnosis.
REFERENCES
1. Waldmann, T. A.: Protein-losing enteropathy. Gastroen-terology, 50:422, 1966.
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ACKNOWLEDGMENT
