683
BRIEF REPORT
SUCCESSFUL MANAGEMENT OF CATASTROPHIC
GASTROINTESTINAL INVOLVEMENT IN POLYARTERITIS NODOSA
DAVID R. KARP, OWEN S. KANTOR, JOHN D. HALVERSON, and JOHN P. ATKINSON
A patient with polyarteritis nodosa developed
necrotizing enterocolitis, as indicated by pneumatosis
intestinalis seen on computed tomographic scans of the
abdomen. Despite immunosuppressivetherapy and con-
comitant resolution of the intramural and portal venous
gas and general clinical improvement, on 2 occasions
(between 20 and 30 days later) the patient developed
bowel infarctions and perforations that necessitated
bowel resection. Leaks developed at anastomotic sites,
but were not closed surgically. However, these sites and
the lower quadrants of the abdomen were drained, and
the patient was given total parented nutrition. Over a
2-month period the patient completely recovered from
this nearly always fatal gastrointestinal complication of
polyarteritis nodosa. The medical, surgical, and radio-
graphic approach we used may be applicable to the
management of similar cases in the future.
Gastrointestinal tract involvement is a common
cause of morbidity and mortality in polyarteritis no-
dosa (PAN). Necrotizing enterocolitis and bowel in-
farction with perforation are among the most feared
complications and usually are fatal. We describe a
patient with these manifestations whose survival
prompted us to report the medical, surgical, and
radiologic management that was used.
From the Departments of Medicine and Surgery, Washing-
ton University School of Medicine, St. Louis, Missouri.
David R. Karp, MD, PhD (current address: Laboratory of
Immunogenetics, NIAID, NIH, Bethesda, MD); Owen S. Kantor,
MD; John D. Halverson, MD; John P. Atkinson, MD.
Address reprint requests to John P. Atkinson, MD, Divi-
sion of Rheumatology, Box 8045, Washington University School of
Medicine, St. Louis, MO 63110.
Submitted for publication August 13, 1987; accepted in
revised form October 26, 1987.
Arthritis and Rheumatism, Vol. 31, No. 5 (May 1988)
Case report. The patient, a 48-year-old white
man, was well until 1 year prior to admission, when he
noted burning pain on the soles of his feet while
jogging. Over the next 4 months, he experienced a
crampy pain in the backs of his calves and thighs
during exercise. Nonsteroidal antiinflammatory drugs
provided no relief.
Six months later, he noted stiffness and myal-
gias in his neck, shoulders, and upper arms. No
weakness was found on physical examination. A 1-
month course of oral prednisone (15 mg/day) resulted
in transient improvement.
Three months prior to admission, he noted
intermittent bouts of crampy, right upper quadrant
abdominal pain and fevers of 38.5"C. Results of an
ultrasonographic examination of the gall bladder and
biliary tract and an upper gastrointestinal tract radio-
graphic series were normal. Because of more severe
musculoskeletal complaints, he was again started on
the prednisone regimen (15 mg/day). There was a
slight improvement in his symptoms.
Two weeks before admission to Barnes Hospi-
tal, he was evaluated at another hospital, where results
of the physical examination were normal, except for
the presence of multiple splinter hemorrhages. During
that hospitalization, he experienced daily temperature
elevations to -38C. The hemoglobin level was 12.3
gmldl, and the erythrocyte sedimentation rate (ESR)
was 93 mdhour. A test for rheumatoid factor (RF)
was positive at a titer of 1:160. Hypergammaglobuli-
nemia (4.0 gm/dl) of a polyclonal nature was demon-
strated by serum protein electrophoresis. Hepatitis B
surface antigen and antibody were absent. Results of a
computed tomographic (CT) scan of the abdomen
were unremarkable. Nerve conduction tests demon-
684 BRIEF REPORTS

strated a severe bilateral peroneal neuropathy. The

patient was placed on a daily regimen of 30 mg of
prednisone for presumed polymyalgia rheumatica.
Two days later, a left foot drop developed, and the
prednisone dosage was increased to 50 mg/day. How-
ever, the patient then developed a right foot drop and
was transferred to Barnes Hospital.
When admitted (October 21, 1986), the patient
appeared ill and hiccoughed continuously. His oral
temperature was 36.9C, the pulse rate was 100/
minute, and blood pressure was 170/100mm Hg. Since
his illness began, he had lost 10 kg. In addition to the
splinter hemorrhages, there was a 3-cm ecchymotic
lesion on the lateral aspect of the right foot. There
were no oral or nasal lesions. Results of a cardiopul-
monary examination were normal. The peripheral
pulses were strong and equal. The abdomen was soft,
and bowel sounds were hypoactive. There was mild
upper right quadrant tenderness without rebound or
guarding. Hepatosplenomegaly , abdominal masses,
testicular abnormalities, and lymphadenopathy were
not present. Joint examination results were normal.
Neurologic findings included a high-stepping gait, loss
of sensation on the lateral surfaces of both calves and
soles, and an inability to dorsiflex or evert the feet.
Otherwise, muscle strength was normal, and there was
no muscle wasting or tenderness.
The following serum levels were determined:
creatinine (0.9 mgldl), total serum protein (5.6 g d d l ,
with a globulin fraction of 3.3 gm/dl and an albumin
fraction of 2.3 gm/dl), alkaline phosphatase (166
IU/liter, normal <loo), aspartate aminotransferase (55
IUfliter, normal <40), and lactate dehydrogenase (224
IUfliter, normal <200). Creatine kinase, amylase, and
bilirubin levels were normal. The white blood cell
count was 26,100/mm3, hemoglobin level was 11.0
gm/dl, and platelet count was 595,000/mm3. Wester-
gren ESR was 90 mm/hour. Urinalysis (24-hour collec-
tion) revealed a creatinine clearance of 136 ml/minute
and 2.1 gm of protein. No red blood cells or red cell
casts were seen. The R F titer was 1:1,280. Antinuclear
antibodies and cryoglobulins were absent. Total hemo-
lytic complement, C3, and C4 determinations were
normal. Other tests for immune complexes were not
performed.
A presumptive diagnosis of PAN was made. On Figure 1. Computed tomographic scans of the patients abdomen
October 22, 1986 he began receiving Solu-Medrol (500 after the administration of oral contrast material. A, The small bowel
is thickened and there are numerous gas bubbles in the bowel wall
mg/every 12 hours) and was given an intravenous
(arrows). B,Gas is demonstrated within the portal system of the left
Of cyclophosphamide t5Oo mdm2)*The patients lobe of the liver (arrows). C, A repeat scan, obtained 7 days after
symptoms were nausea, diffuse dXbminal pain, and that shown in A and B, demonstrating clearing of the gas in the
constant hiccoughing. A radiographic series to deter- portal system.
BRIEF REPORTS
mine whether there was any obstruction demonstrated
the presence of an adynamic ileus, but no free intra-
peritoneal air. A CT scan of the abdomen revealed
thickened small bowel walls with widespread intramu-
ral gas bubbles (Figures 1A and B). Gas was present
within the wall of the stomach and in the portal venous
system. These findings were consistent with diffuse
vasculitis of the bowel. Because the patient did not
appear gravely ill and had relatively benign findings on
abdominal examination, it was not believed that the
problem needed to be corrected surgically; therefore,
prophylactic broad-spectrum parenteral antibiotic
therapy was initiated. The steroid pulse therapy was
continued for 5 days.
On the fourth day of hospitalization, the patient
underwent a sural nerve biopsy and adjacent muscle
biopsy, which demonstrated infiltration of the walls of
the small arteries of the muscle and nerve by neutro-
phils and mononuclear cells, and occlusion of the
vessels by intraluminal thrombi (Figure 2). There was
replacement of myelinated nerve fibers and muscle
fibers with connective tissue. This biopsy was inter-
preted as showing an acute arteritis with fibrinoid
necrosis, consistent with a diagnosis of PAN.
The patient continued to have diffuse abdominal
pain and began to pass guaiac-positive stool. However,
a repeat CT scan of the abdomen, performed 7 days
after the first, demonstrated resolution of intramural
and portal venous gas (Figure 1C). The patient devel-
oped atrial fibrillation, which converted to sinus rhythm
when digoxin was administered. On October 29 and
Figure 2. Photomicrograph of a histologic section from the patients
sural nerve, demonstrating loss of myelinated nerve fibers, organiz-
ing thrombi in the epineural arteries, and marked perivascular
mononuclear cell infiltrate (original magnification x 140).
685
November 2, his ESR was 18 mdhour and 25 m d
hour, respectively. By November 3, the steroid dosage
had been tapered to 50 mg of oral prednisone. No
additional cyclophosphamide was administered during
the hospitalization. From October 28 to November 9,
the patient gradually regained strength and appetite, but
the neurologic deficit did not improve. On November 9,
he developed anorexia and loose, watery bowel move-
ments. Chest and abdominal radiographs demonstrated
free intraabdominal air, and an emergency laparotomy
was performed. Free pus was found in the pelvis. Three
1-cm perforations within a focally necrotic bowel were
seen in a 14-cm section of the mid-jejunum. The remain-
der of the small bowel was pale but appeared viable.
The affected bowel was resected and an end-to-end
anastomosis was performed. Sections of the small
bowel showed ulceration of the mucosa, with granula-
tion tissue and acute and chronic inflammatory infiltrate
occupying the mucosa and extending through both
layers of the muscularis. Peritonitis was present. The
findings were consistent with ischemic bowel second-
ary to a prior vasculitic process; however, no active
vasculitis was seen.
The patient recuperated from the operation,
and oral feedings were gradually resumed. On the
ninth postoperative day, he developed left lower quad-
rant pain and guaiac-positive emesis. His white blood
cell count was 29,000/mm3.A CT scan of the abdomen
demonstrated a large amount of both free air and
peritoneal fluid. He underwent exploratory surgery,
and 2 focal perforations of the ileum and massive
peritoneal soilage were found. The perforations were
in a 21-cm section of small bowel, which was resected
en bloc, and a primary anastomosis was performed.
Following this resection, enteric contents were noted
to be coming from the right upper quadrant. The
source was the anastomosis performed at the first
operation. This hole was drained with a mushroom
catheter. The pelvis was also drained from each lower
quadrant with a sump drain and a Penrose drain.
Pathologic examination of this second surgical
specimen revealed extensive ulceration of the mucosa,
with granulation tissue and acute and chronic inflam-
mation, which was focally transmural. Microscopic
analysis revealed mild atherosclerosis, intimal thick-
ening, and intraluminal thrombi, but no active vascu-
litis. The margins of the resection were involved in the
inflammatory ulcerative process. Bacterial coloniza-
tion of the serosal surface was present.
Following the second operation, the patient was
placed on complete bowel rest and total parenteral
686
nutrition. The steroid dosage was gradually decreased
to 50 mg of Solu/Cortef twice a day. Enteric material
drained for 1 week after the operation, and a fistulo-
gram revealed a leak at the first anastomotic site.
However, the abdomen was believed to be adequately
drained, and no further operative intervention was
undertaken. During the ensuing 2 months, the pa-
tients clinical course steadily improved, including
improved nutrition, return of bowel function, and
absence of signs of sepsis. Though the drainage from
the fistula in the lower abdomen continued, the midline
wound healed well. Serial dye injections through the
mushroom catheter revealed a diminishing leak around
that catheter, suggesting intraabdominal healing.
Ultimately, the mushroom catheter was re-
moved, and there was no further drainage from above.
Similar serial injections at the drain sites in the lower
quadrants revealed a decrease in size of the cavity in
which the drains rested, and the lower right quadrant
drain was removed uneventfully. By that time, a
decrease in the size of the fistula at the second
anastomotic site could be demonstrated radiographi-
cally. The lower left quadrant sump was accordingly
advanced and ultimately removed uneventfully. Oral
feedings were begun on the sixtieth hospital day. He
also received physical therapy and became ambula-
tory. On the eighty-first hospital day, the patient was
discharged.
One year later, he had returned to work and
regained his weight. He had a residual bilateral foot
drop. His medications at that time consisted of pred-
nisone (10 mg every morning) and cyclophosphamide
( 1.5 mg/kg/day).
Discussion. This patients symptoms began with
dysesthesias in the lower extremities and progressed
over a 1-year period to include musculoskeletal, gas-
trointestinal, and further neurologic problems. Sural
nerve biopsy established a diagnosis of PAN. Treat-
ment with corticosteroids and intravenous cyclophos-
phamide was instituted, and an episode of pneumat-
osis intestinalis resolved. However, on 2 subsequent
occasions, the patient developed multiple small bowel
perforations, as well as anastomotic leaks. Necrotic
bowel was resected twice, the abdomen and an anasto-
matic leak were drained, total parenteral nutrition was
instituted, and after a prolonged disease course, the
patient made a remarkable recovery from extensive
vasculitis of the gastrointestinal tract.
The presence of severe gut involvement, such
as that seen in our patient, is a poor prognostic sign
(1-10). With catastrophic gastrointestinal tract in-
BRIEF REPORTS
volvement, such as infarction, hemorrhage, or perfo-
ration, mortality is 75-100% ( 1 1 ) . If the patient sur-
vives, resection may leave little or no functional
bowel. Loss of mucosal integrity predisposes the
patient to sepsis, especially during therapy with immu-
nosuppressive drugs. In our patient, the initial bowel
symptoms were relatively mild, although the signs and
symptoms of an acute abdomen could have been
masked, in part, by the corticosteroids.
Intractable hiccoughs, usually a sign of diaphrag-
matic irritation, along with nausea and anorexia, led to
the decision to perform the CT scan that demonstrated
pneumatosis intestinalis. This finding has been reported
in PAN and several other collagen vascular diseases
(12-14). In scleroderma, for example, pneumatosis in-
testinalis commonly takes the form of cystic intramural
collections of gas in the large colon. This is usually a
benign condition diagnosed incidentally during routine
radiographs. This is in contrast with the linear collec-
tions of submucosal gas seen in vasculitis. These linear
collections are presumed to be evidence of necrotizing
enterocolitis, which is seen in 6% of the cases of PAN
(1). Ischemic or infarcted areas of bowel lose their
mucosal integrity. Intraluminal gas and gas-forming
bacteria enter the bowel wall and gain access to the
portal venous system, leading to infarction of the liver
or sepsis. Mortality in reported cases of frank intestinal
infarction has approached loo%, regardless of treat-
ment (1 1).
Because the incidence of gut involvement is
high, a patient who is known to have systemic necro-
tizing vasculitis and abdominal symptoms should be
presumed to have vasculitic involvement of the gas-
trointestinal tract. Since the outcome of gut involve-
ment in PAN is poor, frequent radiographic examina-
tions for perforation or obstruction and early surgical
consultation are required. Even though there was
radiographic evidence of gut vasculitis, our patient
was initially hemodynamically stable, still able to eat,
and had no clinical evidence of a perforated bowel or
intraabdominal sepsis. Therefore, early management
of his illness was medical rather than surgical.
The significance of the resolution of the pneu-
matosis intestinalis in this patient is unclear. Two
explanations were considered. First, it may represent
early healing of the mucosal surface that was damaged
by the vasculitis. Second, the use of antibiotics may
have suppressed the growth of gas-producing enteric
bacteria, thus allowing clearance of the intramural and
portal venous gas collections. The finding of a severely
necrotic bowel, but no active vasculitis, at the time of
BRIEF REPORTS
the operation demonstrates that even though clinical,
pathologic, and radiographic improvement may be
seen, this does not always correlate with resolution
and healing of the ischemic bowel. In addition, it is
known that the gastrointestinal complications of poly-
arteritis can develop while the patient is undergoing
therapy. As in this patient, bowel perforation and
infarction may occur relatively late.
Pathologic specimens from both laparotomies
performed on our patient demonstrated an ischemic
process, but no evidence of active vasculitis. In par-
ticular, microscopic examination of the vessels re-
vealed mild atherosclerosis, acute and remote thrombi,
and intimal thickening, with fibrous and hyaline
changes. Similar changes, which probably represented
the result of prior vascular damage and a healing
process, were described in 1951 in the first 2 patients
with PAN who were treated with cortisone (15). This
healing process may have secondarily led to occlusion
of the bowel wall vessels and further mucosal ischemia,
and may explain the delayed appearance of the bowel
lesions (15). Because of these facts, the medical treat-
ment was thought to be effective, and was continued
while the abdomen was drained and a catheter was
placed in the leak. The bowel was rested, and healing
was eventually documented. The patient completely
recovered from what is nearly always a fatal gastroin-
testinal complication of PAN. One year later, he re-
mained well except for a residual partial bilateral foot
drop. The medical, surgical, and radiographic approach
we used may be applicable to the management of
similar patients.
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