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Keywords
Mesenteritis, panniculitis, retractile mesenteritis,
sclerosing mesenteritis
Introduction
Inflammatory and fibrotic diseases of the
mesentery are rare, and detailed reports of response to their
treatment are few. We here report two patients with sclerosing
mesenteritis who responded dramatically to treatment with
prednisone or with prednisone plus azathioprine.
Case/Body
PATIENT 1
A 37-year old Moroccan national, who has lived in
the United States for the past twelve years, complained of
nausea, vomiting, and weight loss for three months. He had
been in generally good health except for complex partial seizures
since 1991 (treated with valproic acid) and depression (treated
with sertraline). He was unemployed but had worked in food
preparation and sales. He recalled no serious illness while
living in Morocco and had no other foreign travel, known exposure
to toxic agents, or abdominal operations.
The only physical examination abnormality was a distended,
firm abdomen.
His laboratory values are given in Table 1. A computer tomogram
(CT) image of the abdomen is shown in Figure 1.
| Test |
Patient
1 (normal range) |
Patient
2 (normal range) |
| Hematocrit |
38.9%
(38.0-52.0) |
22.5%
(42-45) |
| Mean
corpuscular volume |
87.9
mum^3 (80-100) |
77
mum^3 (80-100) |
| White
blood cell count |
10.6/mm^-3
(4.5-10) |
12.5/mm^-3
(4.5-11) |
| Eosinophils |
0.3%
(0-5) |
0.1%
(0-6) |
| Platelet
count |
304
x 10^3/muL (150-400) |
300
x 10^3/muL (150-400) |
| Erythrocyte
sedimentation rate |
ND
|
144
mm/hr (0-13) |
| C-reactive
protein |
ND
|
180
mg/L ( 0-8) |
| Serum
protein, total |
6.7
g/dL (6.0-8.2) |
6.3
g/dL (6.8-8.6) |
| Serum
albumin |
3.8
g/dL (3.4-5.5) |
1.6
g/dL (3.4-5) |
| Serum
pre-albumin |
ND |
9
mg/dL (18-45) |
| Serum
alkaline phosphatase |
76
IU/L (40-117) |
532
IU/L (50-136) |
| Alanine
aminotransferase |
15
IU/L (5-40) |
53
IU/L (20-65) |
| Serum
bilirubin, total |
0.4
mg/dL (0.2-1.2) |
0.9
mg/dL (0-1.2) |
| Serum
glucose |
75
mg/dL (60-115) |
160-204
mg/dL (70-100) |
| Urinary
protein |
0-2+
(negative) |
977
mg/24 h (10-150) |
| Fecal
a1-Antitrypsin |
ND |
5.0
mg/g wet weight (<2.6) |
| Serum
immunoglobulin A |
ND |
1060
mg/dL (79-356 |
| Anti-nuclear
antibody |
Negative
(negative) |
Negative
(negative) |
| Serum
iron |
42
mug/dL (40-160) |
12
mg/dL (40-150) |
| Serum
iron binding capacity |
274
mug/dL (220-420) |
138
mg/dL (275-4000) |
| Iron
saturation |
15%
(16-55) |
8.7%
(16-55) |
| Serum
lipase |
43
U/L (16-63) |
165
U/L (115-285) |
Table
1: Laboratory Values
(ND indicates Test not Done)
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An upper gastrointestinal and small bowel
radiographic series demonstrated delayed transit through the
ileum and sharp angulation and fixation of ileal loops, suggestive
of an adhesive or fibrotic process. Upper gastrointestinal
endoscopy revealed thick folds in the gastric body and diffuse
gastritis. At enteroscopy, the small bowel to the mid-jejunum
appeared normal. Histologically, gastric biopsies had chronic
gastritis, with mixed T-cell and B-cell populations identified
by immunohistochemical stains for CD20 and CD3 markers, and
negative Congo red stain; Helicobacter pylori were present.
The small bowel biopsies had a few areas of intestinal lymphangiectasia.
Eosinophilia was not present in any of the biopsies.
Laparoscopy was attempted. An umbilical port was placed but
only after the peritoneum was incised sharply because of its
"thickness and toughness". Abdominal exploration
was impossible because of inflammatory adhesions (Figure 2).
The characteristics of the ascitic fluid obtained at laparoscopy
are given in Table 2. The serum albumin-ascitic fluid albumin
gradient was 1.4, consistent with a transudative effusion.
|
| Patient
1 |
Patient
2 |
| Appearance |
Serosanguinous |
Yellow,
clear-hazy |
| Erythrocytes |
49,680/
muL |
100/muL |
| Leukocytes |
30/muL
|
230/muL |
| Eosinophils |
2% |
1/muL |
| Glucose |
21
mg/dL |
118
mg/dL |
| Albumin |
2.4
g/dL* |
1.2-1.4
g/dL** |
| Total
protein |
4.0
g/dL |
5.2
g/dL |
| Amylase
|
ND |
ND |
| Triglyceride |
40
mg/dL |
ND |
| Lactic
dehydrogenase |
244
IU/L |
74
IU/L |
Table
2: Ascitic Fluid Analyses
(ND indicates Test Not Done)
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*
Serum albumin/ascitic fluid albumin gradient 1.4
**Serum albumin/ascitic fluid albumin gradient 0.2-0.4
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| Note:
Multiple cytopathologic examinations for malignant cells;
cultures for fungi, acid-fast bacilli, aerobic bacteria
and anaerobic bacteria; and stains for acid-fast bacilli
were negative in both patients' fluids. In addition, viral
cultures were negative in the fluid of Patient 1, and
no Mycobacterium tuberculosis complex RNA was detected
by polymerase chain reaction in the fluid of Patient 2.
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Next, laparotomy was attempted. The peritoneum was extremely
(5-mm) thick, and extensive digital dissection was required
to separate it from what appeared to be the bowel. No visible
landmarks could be identified on the bowel surface, and no
motility was seen. Nodular adhesions that were very difficult
to separate prevented any further dissection.
Histopathologically, the peritoneal biopsies were characterized
by extensive areas of hyalinized connective tissue, scattered
foci of mixed inflammatory cells, and spindle cells (Figures
3A and 3B). No granulomas or foreign-body reactions were present.
In immunohistochemical stains, a few of the spindle cells
were positive for CD117 (c-kit proto-oncogene product) but
negative for CD34 (1,2); mitoses and cellular atypia were
not seen. Thus, it was concluded that the patient did not
have a gastrointestinal stromal tumor (1). Stains for acid-fast
bacilli and fungi were negative. By flow cytometric analysis,
a polyclonal population of plasma cells was found, and the
CD15 stain for Reed-Sternberg cells of Hodgkin’s lymphoma
was negative (3). The histologic findings were felt most consistent
with the diagnosis of sclerosing mesenteritis.
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|
 |
| Figure
3A |
Figure
3B |
Figure
4 |
Prednisone orally at 40 mg per day was begun. Within a few
days the patient’s appetite and tolerance for food had
markedly improved, and his sense of well being returned. Taking
his current dose of prednisone, 5 mg per day, he has no abdominal
symptoms. He has not been treated for H. pylori infection.
An abdominal CT scan performed four weeks after the initiation
of prednisone revealed that the ascites was absent, but some
signs of mesenteritis persisted (Figure 4).
PATIENT 2
A 54-year old Vietnam War veteran had a four-month history
of right upper quadrant abdominal pain, early satiety, vomiting
and 35-pound weight loss. He had non-insulin-dependent diabetes
mellitus; coronary artery disease, with coronary artery by-pass
grafts; hypertension; ankylosing spondylitis; bilateral hip
prostheses for degenerative joint disease; an umbilical hernia
repair in the remote past; and hyperlipidemia. About 30 years
previously he was told he had Crohn’s disease of the
proximal colon and had taken sulfasalazine regularly until
the past year, with no symptomatic recurrence of disease.
He had worked at various labor jobs without sustained toxic
exposures, had no foreign travel except infrequent trips to
Mexico border towns, and used alcohol moderately. Currently,
he was taking docusate, indomethacin, lisinopril, tramadol,
hydrocodone/acetaminophen, lovastatin, lansoprazole, atenolol
and glyburide.
The physical examination revealed general ill appearance;
pallor; firm, distended and diffusely tender abdomen; splenomegaly;
questionable hepatomegaly; 3+ edema to the thighs.
His laboratory values are given above in
Table 1. A CT image of the abdomen is illustrated in Figure
5. Upper gastrointestinal endoscopy showed increased folds
and decreased motility in the gastric antrum, suggestive of
a malignancy. A H. pylori urease test was negative. Endoscopic
ultrasound examination of the stomach confirmed thickening
of the gastric wall (Figure 6). Cytologic and flow cytometric
analysis of gastric wall material obtained by fine-needle
aspiration revealed a mixed population of lymphocytes and
granulocytes, with no malignant or monoclonal B-cells. Enteroscopy
showed a normal-appearing small intestine to the mid-jejunum.
The colonoscopy could not be completed because of poor preparation
but was normal to the hepatic flexure.
Histologic evaluation of biopsies obtained at endoscopy revealed
mild, chronic gastritis and fundic gland hyperplasia, without
features suggestive of Menetrier’s disease or the presence
of H. pylori; the small intestinal and rectal morphology was
normal. No evidence of amyloidosis, eosinophilia, lymphoma,
granulomatous disease or acid-fast bacilli was present in
any of the biopsies. The serum IgA concentration was elevated,
but this was considered to be a monoclonal IgA-kappa gammopathy
of undetermined clinical significance on the basis of histologic,
flow cytometric and immunohistologic examination of bone marrow
biopsy material. Abdominal ultrasound examination demonstrated
hepatosplenomegaly and normal blood flow in all hepatic vessels.
Liver tissue obtained via transjugular biopsy was normal except
for mild cholestatsis, and the portal pressure/hepatic vein
gradient was normal.
Laparoscopy was attempted, but a grossly thickened peritoneum
and loculated septations surrounding yellow ascitic fluid
were encountered; a pneumoperitoneum could not be achieved
and the procedure was abandoned. The characteristics of the
ascitic fluid are given above in Table 2.
Next, laparotomy was attempted. The omentum, mesentery and
bowel were encased in a thick peel. All structures were densely
adherent and impossible to dissect safely. The adhesions were
felt much different from those usually encountered in a postoperative
patient or associated with other intra-abdominal pathology.
No free planes were found, and it was impossible to see the
liver or other abdominal organs.
The histologic features of the operative biopsies are illustrated
in Figures 7A and 7B. Various stains for microorganisms, including
acid-fast bacilli and a Congo red stain for amyloid were negative.
A pancytokeratin stain revealed proliferation of spindled
mesothelial cells, but no evidence of malignancy. The findings
were felt consistent with the diagnosis of sclerosing mesenteritis;
peer review of the sections by the Armed Forces Institute
of Pathology concurred.
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Figure
7A |
Figure
7B |
Postoperatively, the patient was treated
with prednisone orally (initially, 60 mg per day, then tapered
to 6 mg per day) and azathioprine, 50 mg per day. His appetite,
sense of well being and tolerance of food improved markedly,
beginning 3-4 weeks after starting the immunosuppressive treatment.
After a few months he had gained weight from 110 to 170 pounds
despite losing all leg edema and clinically appreciable ascites.
Azathioprine has been continued at 50 mg per day. Attempts
to reduce the prednisone dosage below 6 mg/day have resulted
in a recurrence of abdominal symptoms. The serum albumin has
risen to 2.8 mg/dL. Several months after his laparotomy his
abdominal aneurysm ruptured, and because his mesenteritis
prevented surgical repair, endograft placement of a stent
graft was performed. A CT scan of his abdomen taken 15 months
after his laparatomy showed much resolution of ascites, but
changes resulting from the ruptured aortic aneurysm made other
comparison with earlier CT scans difficult.
Discussion/Summary
Statement
Chronic inflammatory and fibrotic conditions
of the mesentery are rare (4,5). They have a spectrum of overlapping
clinical and histologic features, and have been designated
by many different names (4,5). So-called retractile mesenteritis,
also known as sclerosing mesenteritis, represents the fibrotic
end of the spectrum, whereas the inflammatory end has been
called mesenteric panniculitis, mesenteric lipodystrophy and
other names (4). Histologically, our patients have predominantly
a fibrotic form of mesenteritis, although inflammatory features
also are present; they lack a characteristic feature of mesenteric
panniculitis, i.e., multinucleated giant cells (6). A wide
variety of constitutional and abdominal symptoms and signs
may be associated with the various mesenteritides; our patients
manifested principally inability to eat or to retain food,
weight loss, abdominal pain and large-volume ascites. Gastrointestinal
protein loss, a reported feature in sclerosing mesenteritis
(7), was documented in Patient 2 by the presence of increased
loss of fecal a1-anti-trypsin.
The cause of chronic mesenteritis is unknown, as in our cases.
Neither patient had known exposure to toxic agents or the
use of medications that have been causally linked to retroperitoneal
fibrosis, i.e., methysergide and ergotamine (4). Abdominal
trauma or previous abdominal surgery could not be implicated.
Our exhaustive search for malignancies or infectious diseases
was negative, and the patients’ favorable response to
immunosuppressive therapy belies the possibility that such
diseases were undetected. We have found no reports of sclerosing
mesenteritis associated with chronic inflammatory bowel disease
(which Patient 2 was reputed to have had but could not be
confirmed), ankylosing spondylitis, autoimmune diseases, or
the use of the medications our patients were taking. Patient
1 had gastric H. pylori infection, but Patient 2 did not,
so infection with that organism cannot be implicated. Despite
the many similarities in our patients’ illnesses, we
can find no common etiologic link; they are markedly dissimilar
in nationality, ethnicity, occupation and military experience.
The natural history and treatment of chronic, fibrotic forms
of mesenteritis are not well documented. Although mesenteric
panniculitis seems to have a good prognosis and may regress
spontaneously (4,5), the outcome in sclerosing mesenteritis
seems less favorable. We believe it unlikely that our patients’
diseases would have resolved without medical treatment since
both men had been ill for months, and their disease was progressing.
Their response to treatment with immunosuppressive agents
was dramatic and prompt. Although similar improvement has
been recorded among a few such patients treated with cyclophosphamide
(8), corticosteroids alone (7), corticosteroids together with
colchicine (9) or azathioprine (10,11), the reported experience
with these agents still is small. Moreover, radiologic resolution
or improvement of the ascites or fibrosis, as in our patients,
has been documented infrequently (8,12). Thus, the outcome
in our two patients is a significant addition to the literature
on this subject. On the basis of recorded experience it seems
reasonable that immunosuppressive agents be tried in the pharmacologic
treatment of idiopathic chronic mesenteritides, although some
patients have not responded to the agents and a few have responded
to other categories of drugs, i.e., oral progesterone (12)
and tamoxifen (13). The impressive responses of idiopathic
mesenteritis to immunosuppressive agents suggest that the
condition has an immunologic pathogenesis, but that possibility
awaits verification.
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