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Postgastrectomy blind loop syndrome and the arthritis-dermatitis syndrome.

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BRIEF REPORT
POSTGASTRECTOMY BLIND LOOP SYNDROME AND THE
ARTHRITIS-DERMATITIS SYNDROME
ALICE V . KLINKHOFF, HOWARD B. STEIN, OTTO L A. SCHLAPPNER, and WILLIAM B. BOYKO
The arthritisdermatitis syndrome is a complication of intestinal bypass surgery in 6-24% of patients. It is related to the overgrowth of bacteria in the
excluded segment of the intestine (1-3). Antigenic
components of these bacteria probably lead to the
formation of immune complexes which then deposit in
the target tissues. This theory is partly supported by
the occurrence of the arthritis-dermatitis syndrome in
4 patients with a blind loop syndrome not caused by
intestinal bypass surgery (4). We report another case
of blind loop syndrome resulting from previous gastric
surgery.
Case report. A 51-year-old woman complained
of pain in the shoulders, lateral epicondyles of the
elbows, anterior rib cage, low back, groin, knees, and
toes for 6 months. There was no joint swelling, deformity, or morning stiffness. For 2 years she had episodes of pruritic, pustular skin lesions over the shoulders, arms, hands, legs, and feet. These lesions,
initially single and subsequently in groups, would
begin as vesicles, turn into pustules, umbilicate, become crusted, and heal within 7 days.
From the Departments of Medicine and Pathology, St.
Paul’s Hospital, and the Divisions of Rheumatology and Dermatology, University of British Columbia, Vancouver, British Columbia,
Canada.
Alice V. Klinkhoff, MD: Canadian Arthritis Society Fellow; Howard B. Stein, MD: Clinical Associate Professor of Medicine; Otto L. A. Schlappner, MD: Clinical Associate Professor of
Medicine; William B. Boyko, MD: Clinical Assistant Professor of
Pathology.
Address reprint requests to Dr. H . B. Stein, 507-1160
Burrard Street, Vancouver, BC, V6Z 2E8, Canada.
Submitted for publication May 21, 1984; accepted in revised
form August 13, 1984.
Arthritis and Rheumatism, Vol. 28, No. 2 (February 1985)
She had several episodes of purplish, tender,
swollen nodules on the lower legs and ankles. The skin
lesions were accompanied by polyarthralgia, malaise,
fever, chills, and sweats. These episodes occurred
monthly. An episode of pleurisy had occurred 4
months previously. She had had Raynaud’s phenomenon for 2 years.
A subtotal gastrectomy had been performed 10
years previously for a perforated peptic ulcer. For the
last 2 years she had diarrhea 3-4 times daily with
loose, beige, floating, and foul-smelling stools. She
had lost 7 pounds over a 3-month period, and noted
easy bruising.
She was thin and had a midline abdominal
surgical scar, but no abdominal tenderness or hepatosplenomegaly . Several ecchymoses were present on
her extremities but there were no other skin lesions.
There was tenosynovitis of the left peroneal tendon
with redness, swelling, and tenderness. Muscle
strength was normal except for grade 4/5 strength in
the neck flexors and quadriceps. The remainder of the
physical findings were unremarkable.
The hemoglobin level was 12.7 gm/dl, white
blood cell count 7,000/mm3, platelet count 440,000/
mm3, Westergren erythrocyte sedimentation rate 36
mmlhour, creatinine 1 . 1 mg/dl, calcium 7.6 mg/dl
(normal 8.6-10.3), albumin 3.1 gm/dl (normal 3.3-5.3),
alkaline phosphatase 346 units/liter (normal 35-105),
and phosphate 2.8 mg/dl (normal 2.5-4.4). Prothrombin time was 27.7 seconds (normal 11-13) and partial
thromboplastin time was 47 seconds (normal 25-39),
but both corrected to normal following an intramuscular injection of 10 mg of vitamin K. Serum vitamin B12
and folate values were normal. Her serum ferritin level
was low at 7 ng/ml (normal >20) and carotene was
BRIEF REPORTS
0.30 pmoles/liter (normal 0.95-3.8). Serum 25-OH
vitamin D was markedly reduced at 3 nglml (normal
>17). A 72-hour fat collection measured 3.8 gm (normal 2.3-7.7). Antinuclear antibody, rheumatoid factor, and cryoglobulins were not detected and C3 and
C4 complement levels were normal. Immune complexes measured by C l q binding were 4% (normal <6).
Chest radiograph results were unremarkable.
Radiographs of the pelvis and hands showed osteopenia with undisplaced fractures of the left femoral
neck and distal phalanx of the right middle finger. A
bone scan revealed multiple areas of increased activity
involving the ribs, the left femoral head, distal phalanx
of the right middle finger, and both feet, consistent
with multiple fractures. An upper gastrointestinal series with small bowel follow-through showed a partial
gastrectomy and a localized stricture of the efferent
loop of the bowel distal to the stoma. Endoscopy
revealed a large pouch of small bowel with a very
narrow outlet beyond the anastamosis. The mucosa of
the afferent loop appeared inflamed. A small bowel
biopsy of the afferent loop showed acute and chronic
inflammation. Cultures of the small bowel aspirate
grew >60,000 coliforms and > lo5 lactobacilli. I4Cglycine cholate breath analysis was consistent with
bacterial overgrowth at 12% (normal <1%). An iliac
crest bone biopsy showed severe osteomalacia with
active bone resorption consistent with osteitis fibrosa.
While in the hospital she had an attack of the
arthritis-dermatitis syndrome with papulovesicles
over the arms, shoulders, and right foot (Figure I),
which resolved over a 4-day period. C3 and C4 complement tests repeated during this episode remained at
normal levels; C l q binding was unchanged at 4% and
cryoglobulins were absent. Microscopic examination
of a skin biopsy showed necrosis of the upper dermis
with adjacent vasculitis characterized by endothelial
swelling, necrosis, and neutrophilic and mononuclear
cell infiltration. Direct iminunofluorescence showed
deposition of IgM, IgA, and C3 in the vessels of the
reticular dermis (Figure 2).
At laparotomy, a stricture was found at the site
of the previous Billroth I anastamosis and a second
stricture was found in the second part of the duodenum. Between these strictures was a blind loop which
was dilated to 10 cm in diameter. The distal bowel was
normal. The duodenal stricture was opened and sutured longitudinally and a gastrojejunostomy was performed. When discharged from the hospital, she was
prescribed vitamin D, 50,000 1U twice weekly and
elemental calcium, 1,500 mg daily.
215
Figure 1. Close-up photograph of the forearm, showing vesiculopustular skin lesions, with crusting apparent on the upper lesion.
Over the subsequent 9 months, there were no
further episodes of the arthritis-dermatitis syndrome
and no bone pain. She gained 12 pounds. Laboratory
data 9 months postoperatively included normal serum
calcium, phosphate, and alkaline phosphatase levels.
Discussion. A blind loop syndrome developed in
our patient 8 years after a Billroth I gastrectomy. She
had malabsorption of carotene, iron, calcium, and
vitamins D and K, which resulted in weight loss,
osteomalacia with multiple fractures, and bruising.
Bacterial overgrowth was proven by the culture of the
jejunal aspirate and the elevated ''C-glycine cholate
breath analysis. Coincident with the development of
this malabsorption syndrome, she experienced episodes of papulovesicular skin lesions, erythema nodosum-like lesions, fever, chills, malaise, Raynaud's
phenomenon, polyarthralgia, and tenosynovitis. Biopsy of a fresh skin lesion showed necrosis and vasculitis
with immune deposits, although circulating immune
complexes were not found by our tests. This picture
was similar to that previously described in the arthri-
216
BRIEF REPORTS
Figure 2. Skin biopsy showing necrosis of papillary and upper reticular dermis (magnification x 100). Left insert, Small
vessels surrounded by lymphocytes, and intact and degenerating neutrophils (magnification x 400). Right insert, Direct
immunofluorescent preparation demonstrating coarse granular deposition of IgM in dermal vessels. Vascular IgA and C3
deposition is also present.
tis-dermatitis syndrome associated with intestinal bypass surgery (1-4).
An association between the intestinal bypass
procedure and arthritis was first recognized by Payne,
who reported polyarthritis and tenosynovitis in 32% of
jejunocolostomy patients (1). The incidence of this
complication has been diminished to 6-24% by the
modification of the procedure to jejunoileostomy (59). The syndrome consists of recurrent episodes of
arthralgia, nondeforming polyarthritis, tenosynovitis,
and cutaneous vasculitis. Skin lesions are typically
vesiculopustular or erythema nodosum-like. Paresthesias and Raynaud’s phenomenon are common. Antibiotics such as tetracycline or clindamycin can sometimes improve symptoms of the syndrome. In resistant
cases, prednisone may be necessary (10). Surgical
reconstitution of normal bowel anatomy is curative
( 1 1,12).
This syndrome appears to be caused by the
overgrowth of bowel bacteria in the blind loop created
by the intestinal bypass. Bacterial antigens may then
enter the circulation, leading to the formation of
antibodies and immune complexes. Such complexes,
containing IgG, IgA, IgM, and complement, have been
detected during episodes of arthritis (13,14). The finding of antibodies to Escherichia coli and Bacterioides
fragilis in the cryoglobulins of these patients further
supports the role of intestinal bacteria in this syndrome (15).
The presence of the syndrome in association
with bacterial overgrowth in the bowel and its disappearance with the eradication of the bacterial overgrowth and the finding of immune deposits in skin
lesions in our patient partially supports this theory.
However, we did not find immune complexes, cryoglobulins, or complement abnormalities in the circulation of our patient during an active phase of the
syndrome.
The intestinal bypass arthritis-dermatitis syndrome has recently been described in 4 patients who
BRIEF REPORTS
did not have bowel bypass (4). T w o patients, both with
previous partial gastrectomy, developed diarrhea followed by cutaneous pustules, arthritis, arthralgia, and
fever. Skin biopsy specimens showed features consistent with the intestinal bypass arthritis-dermatitis syndrome, including the deposition of IgG and C3 in the
upper dermis. T w o other patients in the same series, 1
with Crohn’s disease and the other with ulcerative
colitis, had episodic fever, arthralgia, and papulovesicular skin lesions, pathologically indistinguishable
from those seen complicating bypass surgery. T he skin
lesions and arthralgia responded t o prednisone.
T h e finding of the arthritis-dermatitis syndrome
in patients with a blind loop syndrome not caused by
intestinal bypass surgery supports the notion that the
bacterial overgrowth is the initiating event. Blind loop
syndrome occurring after gastrectomy and with inflammatory bowel disease has now been associated
with the arthritis-dermatitis syndrome. It is unclear
why this syndrome has escaped notice in these patients in the past. It may be that the quantities of
bacteria which inhabit the small bowel after intestinal
bypass are greater than after gastrectomy, or that
different organisms are involved. Furthermore, the
liver disease which complicates obesity and the intestinal bypass procedure may impair the clearance of
immune complexes by the reticuloendothelial system.
Acknowledgment. The authors wish to thank Ruth
Minchington for typing the manuscript.
REFERENCES
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12. Leff RD, Aldo-Benson MA, Madure JA: The effect of
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13. Utsinger PD, Farber N , Shapiro RF, Ely PH, McLaughlin GE, Weisner KB: Clinical and immunologic study of
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14. Rose E, Espinoza LR, Osterland CK: Intestinal bypass
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15. Wands JR, LaMont JT, Mann E, Isselbacher KJ: Arthritis associated with intestinal bypass procedure for morbid obesity: complement activation and characterization
of circulating cryoproteins. N Engl J Med 294:121-124,
1976
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