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Rheumatoid arthritis associated with jejunoileal bypass.

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The jejunoileal bypass operation has produced
numerous enteric and extraintestinal complications.
Among the latter, an arthritis-arthralgia syndrome was
one of the commonly observed side effects (1-7). The
disorder tended to resemble early features of rheumatoid arthritis (RA) but it never progressed to the
classic, manifest disease. Bypass arthritis was therefore considered a distinct entity and, if RA was ever
seen in a bypass patient, it was regarded as a coexistent and independent illness.
This case suggests that the generally benign
arthritic syndrome following jejunoileal bypass can
evolve into RA, or a disorder indistinguishable from
Case report. A 31-year-old woman, obese all
her adult life, underwent a jejunoileal bypass in 1973,
at a weight of 120.5 kg. The operation was unconventional in that it created 2, rather than 1, nonfunctioning
segments. The excluded long segment of jejunum and
ileum was fashioned as usual. However, the 25-cm
functioning jejunal segment extended as an additional
20-cm blind loop segment beyond a side-to-side jejunoileal anastomosis. The usual diarrhea, bloating, and
abdominal discomfort indicated “bypass enteropathy.”
From the Medical, Research, and Laboratory Services,
Wadsworth VA Medical Center and the Departments of Medicine,
Pathology, and Radiology, UCLA Medical School, Los Angeles,
Supported by VA Medical Research funds.
E. J. Drenick, MD; L. W. Bassett, MD; T. M. Stanley,
Address reprint requests to Ernst J . Drenick, MD, Wadsworth VA Medical Center, 691/11 IG, Wilshire and Sawtelle Blvds.,
Los Angeles, CA 90073.
Submitted for publication December 19, 1983; accepted in
revised form May 21, 1984.
Arthritis and Rheumatism, Vol. 27, No. 11 (November 1984)
Preoperatively, the patient had never experienced joint pains. Within 6 months after the operation,
she developed transient and migratory arthritic symptoms. These included pain, stiffness, and swelling
which affected various joints. Until 1979, these manifestations were considered typical of the arthralgiaarthritis bypass syndrome. No redness, deformities,
joint effusions, pathologic radiographic findings, or
serologic abnormalities were noted.
Starting in July 1979, the syndrome gradually
changed. Pain, stiffness, and swelling affected large
and small joints symmetrically, and the periods of
active arthritis became progressively longer. With
exacerbations of the enteropathy , pleuritic pain occurred intermittently. Her weight had decreased to
54.6 kg. No fever or skin eruptions were noted.
Nodules developed over several joints and extensor
tendons, namely, the left shoulder, 2 nodules on the
left elbow and 1 on the right, 1 each on the dorsal and
volar aspects of the right wrist, 1 on the second finger
of the left hand, 2 over the left knee, 1 on each Achilles
tendon, and 1 on the first toe of the right foot. In
September of 1979, radiographs of the hands, wrists,
ankles, and feet revealed only soft tissue swelling and
juxtaarticular osteoporosis in affected joints. Serum
IgG was 619 mg/dl (normal 566-1,313 mg/dl), but
antinuclear antibody (ANA) and latex fixation results
were negative. Complement C3 was 187 mg/dl (normal
68-143 mg/dl). No tests were performed for the presence of cryoglobulins or circulating immune complexes. A node wds removed from the right wrist and
another from the left elbow in May 1980. Both specimens exhibited features consistent with rheumatoid
nodules (Figure 1).
The patient was treated in the rheumatology
Figure 1. Histologic examination of the tissue from the left elbow,
revealing a rheumatoid nodule characterized by fibroblastic and
histiocytic proliferation surtounding zones of necrosis with fibrinous
exudates (lower right) (hematoxylin and eosin stained, original
magnification x 310).
clinic, receiving, at various times, ibuprofen, indomethacin, tolmetin sodium, sulindac, gold, and penicillamine; all provided only temporary or limited benefit. However, during 2 pregnancies, in 1976 and 1980,
all symptoms spontaneously remitted.
In early 1982, symptoms became more severe
and chronic. Swelling, stiffness, and pain were present
in both second metacarpophalangeal joints, in the
proximal interphalangeal joints of the second, third,
and fourth fingers of the right hand, and the second
finger of the left hand. Similar manifestations involved
the third, fourth, and fifth (right hand) and fourth (left
hand) metatarsophalangeal (MTP) joints. Synovitis of
the right elbow and right knee was noted. Motion was
restricted and painful in most major joints such as the
shoulders, elbows, and hips. Intermittent rcdrless and
heat in the elbows, wrists, knees, and ankles were
reported by the patient.
Test results for rheumatoid factors had remained negative until March 1983, when an ANA titer
determination was positive at a dilution of 1:40. The
sedimentation rate was elevated to 53 mdhour. Complement C3 had decreased to 69 mg/dl. Radiographs
demonstrated periarticular osteoporosis of all joints in
both hands and at the MTP joints of the feet. Multiple
marginal erosions at symmetric interphalangeal joints
of the first toes and both fifth MTPjoints were seen.
There was also marginal erosion of the second metacarpal head (left hand). The radiographic features were
thought to be consistent with rheumatoid arthritis. The
sequence of progressive erosive changes and dislocation of the fifth MTPjoint (left) is illustrated in Figures
In July 1982 the patient was started on a regimen of metronidazole, 500 mg 3 times a day. All joint
pain subsided within a few days. Bowel frequency
diminished. The offensive odor of flatus and stools
subsided. General well-being improved and the patient
gained 1.5 kg. Her symptoms promptly recurred when
metronidazole treatment was discontinued. A second
remission occurred with resumption of antibiotic treatment. However, after 4 months of metronidazole use,
joint symptoms gradually returned and indications of
mild peripheral neuritis, presumably a side effect of
the medication, developed.
The impression at this stage was that the patient
had 2 diseases: the bypass-related arthralgia syndrome
and, independently, rheumatoid arthritis.
In March 1983, because of disabling arthritis,
the bypass was dismantled and normal intestinal continuity reestablished. A biopsy specimen from the bypassed ileum segment revealed nonspecific chronic
inflammatory changes consistent with “bypass enteropathy .
Arthralgias subsided within 4 days and did not
recur. Synovial swelling receded simultaneously and
was no longer notable after 2 weeks. Two months after
the operation, all rheumatoid nodules had disappeared. No antiinflammatory agents had been administered prior to or after this operation. The patient was
once again active and feeling well. She had gained 7.4
kg. Followup radiographic studies 6 and 12 months
later revealed no progression, and possibly some recalcification, of cystic bone lesions, as shown in
Figure 5. Twelve months later, the sedimentation rate
was 7 mmlhour.
Discussion. We have described a case of rheumatoid arthritis in a woman with a jejunoileal bypass.
The clinical diagnosis of RA was confirmed by histo”
Figure 2. Anteroposterior radiographs of the left (A) and right (B)feet, taken 6 years .after jejunoileal bypass surgery. No
abnormalities are shown, although the patient complained of chronic, symmetric, small and large joint arthritis and nodules.
Figure 3. Anteroposterior radiographs of the left (A) and right (B)feet, taken 9 years afterjejunoilealbypass surgery. There are
soft tissue swelling and erosions of the interphalangeal joint of the first toe on the right, and bilateral symmetric erosions of the
fifth metatarsophalangeal joints. Nodules and chronic joint pain were still present.
Figure 4. Radiographs of the left (A) and right (B) feet, taken immediately prior to surgical reestablishment of normal bowel
continuity. The patient now has severe arthropathy and malnutrition. The first interphalangeal joint erosions on the right have
progressed and there is a new erosion at the first interphalangeal joint on the left. Dislocation of the fifth metatarsophalangeal
joint on the left is more severe.
pathologic findings typical of rheumatoid nodules and
by radiographic evidence of characteristic lesions involving bones, joints, and soft tissues. The positive
response to dismantling the bypass strongly suggested
a causal relationship. Joint symptoms subsided within
days. Rheumatoid nodules disappeared within 2
months, and 12 months later bone lesions had not
Post-bypass polyarthralgias and polyarthritis
have been described in detail since the original report
by Shagrin et a1 in 1971 (1). Erosive bone lesions were
minimal and were rarely seen (5,7). No joint deformities were noted. The lack of bone involvement, despite
a prolonged course and often disabling joint manifestations, led to the generally accepted conclusion that the
disorder was not RA, but a separate entity. This view
was supported by several observations. The joint
manifestations were usually transient, asymmetric,
and subsided promptly following re-anastomosis. Similarly, various antibiotics had effectively relieved the
syndrome. In contrast, RA would persist after antibiotic treatment and dismantling of the bypass. Rheumatoid or antinuclear factors were almost universally
absent, while RA is serologically positive in at least
70% of patients. Test results for HLA-B27 were
positive on rare occasions ( 5 , 8 ) . Therefore, this association seemed of questionable significance.
In our patient, the American Rheumatism Association criteria for RA (9) were fulfilled, since 8 of 11
manifestations were observed. Although she had positive ANA, rheumatoid factor test results remained
negative, although they are usually positive in the
presence of rheumatoid nodules.
The progression from the arthritis-arthralgia
syndrome to RA remains unexplained. The unconventional anastomosis probably did not play a role. A
particular host susceptibility may be required for RA
to evolve. Additionally, only certain bacteria or specific by-products may be capable of inducing RA.
Admittedly, alternative interpretations should
Figure 5. Radiographs of the left (A) and right
(B)feet, taken 12 months after dismantling of bypass. Patient is now totally
asymptomatic. Radiographs show no lesion progression and some recalcification of the erosion in the left first interphalangeal
be considered. Bypass arthritis may, on rare occasions, assume an erosive pattern resembling RA. Also,
a fortuitous coexistence and simultaneous remission of
bypass arthritis and RA cannot, with finality, be ruled
out on the basis of observations in a single case,
although such a coincidence would be rather unusual.
Although a variety of antiinflammatory agents
had been helpful to a degree, they were largely ineffective in this patient, perhaps as a result of the continuing production of antigenic stimuli. The disorder did
respond to metronidazole and to dismantling of the
bypass, implicating bacterial overgrowth. The transient remissions during her 2 pregnancies also suggested a role for immune mechanisms which were altered
during gestation. Wands et a1 (3) demonstrated that
bacterial overgrowth can produce the arthralgia syndrome, mediated by immune complexes. Whether the
arthritic changes in this instance were caused or
mediated by immune complexes cannot be established.
Additional extraintestinal manifestations, including connective tissue syndromes (10) and vasculitides (1 1) have been described as complications of the
bypass. Our patient’s case may be added to this
spectrum of disorders, The course of illness favors the
interpretation that, in this instance, the arthritis-arthralgia bypass syndrome and RA may not have been
distinct entities, but different stages of a pathologic
Acknowledgments. We are grateful to Drs. R. L.
Lesonsky for the sections and descriptions of the rheumatoid nodules and James B. Peter for immunologic and
serologic tests, and to Mrs. Dolores K . Shapiro for her
assistance in the preparation of the manuscript.
1. Shagrin JW, Frame B, Duncan H: Polyarthritis in obese
patients with intestinal bypass. Ann Intern Med 75:377-
380, 1971
2. Drenick EJ, Ament ME, Finegold SM, Corrodi P,
Passaro E: Bypass enteropathy: intestinal and systemic
manifestations following small bowel bypass. JAMA
236:269-272, 1976
Wands JR, LaMont JT, Mann E, Isselbacher KF: Arthritis associated with intestinal-bypass procedure for
morbid obesity. N Engl J Med 294:121-124, 1976
Rose E, Espinosa LR, Osterland CK: Intestinal bypass
arthritis: association with circulating immune complexes
and HLA B27. J Rheumatol4:129-134, 1977
Fernandez-Herlihy L: Arthritis after jejunoileostomy for
intractable obesity. J Rheumatol4: 135-138, 1977
Zapanta M, Aldo-Benson M, Biegel A, Madura J: Arthritis associated with jejunoileal bypass: clinical and
immunologic evaluation. Arthritis Rheum 22:711-717,
7. Utsinger PD: Systemic immune complex disease following intestinal bypass surgery: bypass disease. J Am
Acad Dermatol2:488-495, 1980
8. Stein HB, Schlappner OLA, Boyko W, Gourlay RH,
Reeve CE: The intestinal bypass arthritis-dermatitis
syndrome. Arthritis Rheum 24:684-690, 1981
9. Ropes MW, Bennett GA, Cobb S, Jacox R, Jessar RA:
1958 revision of diagnostic criteria for rheumatoid arthritis. Bull Rheum Dis 9:175-176, 1958
10. Persellin SC, Griffing WL, Michet CJ Jr, Schroeder
KW, Luthra HS: Polymyositis associated with jejunoileal bypass. J Rheumatol 10:637-639, 1983
11. Drenick EJ, Ahmed AR, Greenway F, Olerud JE:
Cutaneous lesions after intestinal bypass. Ann Intern
Med 93557-559, 1980
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associates, arthritis, bypass, jejunoileal, rheumatoid
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