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Volume 2 Number 5
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Gastrointestinal Perforation in Childhood Lupus: A Case Report and Discussion Rohit Kohli MD, Hisham Abdel-Azim MD and Sarla Inamdar
MD, FAAP Department of Pediatrics, Keywords Systemic lupus erythematosus, children, gastrointestinal
perforation, management, cyclophosphamide Correspondence: Sarla Inamdar, MD,
FAAP Professor of Clinical Pediatrics, Department of Pediatrics, Room # 523, 1901 First Avenue, Telephone (212)
423-6228 Fax
(212) 423-8450 Email: drkohlirohit@hotmail.com Abstract Perforation from intestinal vasculitis in systemic lupus
erythematosus (SLE) is a rare but high mortality complication. It is
a challenging condition both to identify and manage. We present a case
report of a 13-year-old female child with SLE complicated with small
bowel perforations. The child failed to respond to a regimen of high
dose steroid therapy and required repeated surgical intervention. The
patient subsequently responded to cyclophosphamide showing regression
of clinical symptoms including closure of fistulae. We therefore encourage
clinicians to aggressively utilize this emerging management option for
SLE bowel vasculitis. Introduction Bowel vasculitis is one of the most devastating complications
of systemic lupus erythematosus (SLE). Secondary complications from
bowel wall vasculitis and mesenteric arteritis include bowel hemorrhage,
infarction and perforation (1, 2). Amongst these consequences of bowel
vasculitis, perforation is the most ominous and has been shown in the
past to be a leading cause of death in SLE patients with acute abdominal
events (3, 4). The mortality rate in the largest published series of
bowel wall perforation in SLE was greater than 50 percent (5). Figure
1 is an example of severe small intestinal vasculitis.
Hematoxylin
and eosin medium power (200 x) view of small intestine. Endarteritis
obliterans and periadventitial inflammation in submucosal vessel. Arrow
at fibrinoid necrosis. The most commonly used treatment for bowel vasculitis
is a high dose steroid regimen (2, 6). If high dose steroids fail to
control the progression of symtomatology, early recognition of the regimen’s
failure and prompt initiation of other aggressive disease modifying
agents is necessary to prevent the more morbid complications of bowel
vasculitis including perforation (7). We report a case of repeated bowel perforations in a
pediatric patient with SLE who responded well to pulse cyclophosphamide
therapy. Case Report A 13-year- old African-American girl was diagnosed with
SLE associated with nephritis, hypertension and depression. The patient
achieved remission with oral prednisone 60 mg daily and was maintained
on prednisone 40 mg every other day and hydroxychloroquine 200mg twice
daily. The patient also received fluoxetine 20 mg a day and enalapril
2.5 mg a day. The patient presented four months after diagnosis to
the pediatric rheumatology clinic with a one week history of incapacitating
generalized muscle aches, severe arthralgias, low-grade fevers, malar
erythema and multiple mucosal oral and labial ulcers. The patient denied
any gastrointestinal symptoms at that time. Laboratory analysis revealed
a normal white blood cell and platelet count. The patient’s hemoglobin
9.5 gm/dl was low and serum creatinine was 0.9 mg/dl (0.3-0.6 mg/dl).
A rheumatologic work up revealed elevated antinuclear antibody (ANA)
(>1: 640) and anti DNA (>1: 80) titers. The patient’s C3 {36mg/dl
(80-175mg/dl)} and C4 {6.6 mg/dl (15-45 mg/dl)} levels were low. The patient was admitted and the dose of prednisone
was increased to 40 mg daily with slow improvement of her musculoskeletal
symptoms and mucosal ulcers. The patient further developed a painful
erythematous bullous rash which on biopsy showed IgG and C1q linear
staining of the basement membrane consistent with a diagnosis of bullous
SLE. The patient responded well to the pulse corticosteroid
therapy of 1 gm methylprednisolone infusion daily for three consecutive
days; as manifested by resolution of the rash and musculoskeletal symptoms.
Subsequently the patient complained of the onset of
diarrhea and abdominal pain. Physical exam revealed marked abdominal
guarding and distension with hypoactive bowel sounds. Roentological
films (x-rays) showed both large and small bowel distension. An emergency
exploratory laparotomy showed diffuse peritonitis and four distal ileal
perforations. A 6-cm segment of the distal ileum was resected and ileostomy
was performed. Histopathology of the resected bowel showed chronic lupus
vasculitis as evidenced by endarteritis obliterans and periadventitial
inflammation in submucosal vessels including areas of fibrinoid necrosis
(Fig 1). The patient was started with oral feeding on the sixth
postoperative day but soon developed an acute exacerbation of musculoskeletal
symptoms and an entero-cutaneous fistula. Additional imaging studies
revealed bilateral pleural and pericardial effusions. The C3 and C4
as well as the ANA titers at this time remained unchanged. The enteral
feedings were discontinued and a second pulse of steroids was initiated.
The patient improved and underwent surgery for resection of the fistula,
small bowel re-anastomosis and ileostomy closure. The patient’s second postoperative course was again
complicated by two entero-cutaneous fistulae. Her C3 and C4 remained
low and the ANA was 1:640. At this point the patient was started on
intravenous cyclophosphamide (500 mg / m2) therapy which
resulted in regression of musculoskeletal symptoms and improvement in
C3 (62 mg/dl) and C4 (7.8 mg/dl) levels. The patient received six more
monthly pulses of intravenous cyclophosphamide (750 mg / m2)
and the entero-cutaneous fistulae closed after the third pulse. The
patient did not require further surgical intervention and has been symptom
free for the last eighteen months on low dose oral prednisone and intravenous
cyclophosphamide pulse therapy every three months. Discussion Acute abdominal pain is a common feature of SLE and
can be secondary to symptoms of gastro-esophageal reflux disease from
esophageal dysmotility, pseudo-obstruction from gastric or intestinal
dysmotility, mesenteric arteritis, peritonitis, acute pancreatitis,
biliary tract disease, sterile serositis, intestinal perforation or
other surgical causes. The acute abdomen in patients with SLE is thus
a diagnostic challenge (3, 5, 8, 9). Intestinal vasculitis remains a
relatively uncommon complication involving only 2% of all SLE patients
(7) but is associated with a very high morbidity rate and mortality
rate of up to 50% in cases of perforation (5). Other signs of lupus
vasculitis, which may accompany patients with gut vasculitis, such as
skin and peripheral nervous system involvement may be helpful in diagnosing
intestinal vasculitis. This was
demonstrated by our patient who presented with severe musculoskeletal
and mucocutaneous vasculitis prior to clinically evident intestinal
vasculitis (3). A study by Zizic et al reported that the majority of
patients with bowel perforation had gastrointestinal symptoms including
diarrhea and all patients had fever prior to the abdominal crisis (5).
Abdominal x-rays revealed evidence of small bowel perforation in only
25% of patients in the same study. Computerized tomography (CT) scans
have been shown to offer direct observation of the thickness of the
intestinal wall and Si-Hoe et al reported such small bowel wall thickening
in 30 out of 54 SLE patients who underwent abdominal CT scans for various
complaints. The characteristic finding in small bowel vasculitis has
been reported as wall thickening with prominence of the mesenteric vessels
though these findings are by no means specific to this condition(6).
The abdominal ultrasound ( Treatment of lupus-induced abdominal vasculitis has
been difficult; nearly all reported cases have been treated with high
dose steroids and surgery. Despite these measures, symptoms usually
recur when steroids are tapered (5, 8, 9). Our patient had bowel vasculitis
which failed to respond to high dose steroid therapy and surgery. Early trials of intravenous cyclophosphamide for lupus
nephritis and cerebritis have been promising (11,12). Laing and Grimbacher have reported successful
treatment of SLE induced gastrointestinal vasculitis with pulse intravenous
cyclophosphamide while Eberhard reported a similar failed attempt in
a 13 yr old girl (9,13,14). Our patient showed marked clinical improvement
of gut vasculitis to intravenous cyclophosphamide pulse therapy as evidenced
by closure of the enterocutaneous fistulae, resolution of her cutaneous
and systemic symptoms of SLE, and improvement of her complement levels. Conclusion There exists a need to decrease the high morbidity and
the mortality arising from bowel vasculitis induced by SLE and its secondary
complications. There is no single definitive clinical, laboratory or
imaging modality available for early detection of SLE induced bowel
vasculitis. CT scans or US of the abdomen may be used as non invasive
methods of evaluating for small bowel vasculitis in this population,
but it is our belief that not tests and scans but a high index of suspicion
towards SLE patients with gastrointestinal symptoms is the most important
factor that may lead to early identification of bowel vasculitis. The results of steroid therapy in bowel vasculitis are
not very encouraging. The option of pulse cyclophosphamide therapy has
been used successfully in adults and needs to be encouraged in the pediatric
SLE population. We would recommend that pulse cyclophosphamide therapy
be considered early in active SLE patients with gastrointestinal involvement,
especially if the child is not responding to high dose parenteral steroid
therapy. Acknowledgement The
authors would like to thank B.U.K. Li, MD; Director of Gastroenterology,
Children's |
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