intestinal involvement in wegener’s granulomatosis
TRANSCRIPT
219
□ CASE REPORT □
Intestinal Involvement in Wegener’s GranulomatosisDiagnosed and Followed up by Double
Balloon Enteroscopy
Kazuko Beppu, Taro Osada, Kanako Inoue, Kenshi Matsumoto, Tomoyoshi Shibuya,
Naoto Sakamoto, Masato Kawabe, Akihito Nagahara, Tatsuo Ogihara and Sumio Watanabe
Abstract
Wegener’s granulomatosis (WG) is a multisystemic disease of unknown etiology characterized by necrotiz-
ing vasculitis and granulomatous inflammation (1-3). The disease typically involves the upper airways, lungs
and kidneys, and gastrointestinal involvement is uncommon. Described here is a 33-year-old man who pre-
sented at the hospital with abdominal pain. Colonoscopy revealed multiple ulcers, including round ulcers,
throughout the large intestine. Small bowel ulcers were detected by double balloon enteroscopy (DBE). Fur-
ther study confirmed that these ulcers were caused by gastrointestinal complications of WG. The patient was
administered prednisolone and cyclophosphamide and remains in remission. This case indicates the impor-
tance of considering a gastrointestinal complication of WG as the potential cause of abdominal symptoms
among WG patients as well as the use of DBE in detecting such a complication.
Key words: Wegener’s granulomatosis, double balloon enteroscopy, small intestinal ulceration
(Intern Med 50: 219-222, 2011)(DOI: 10.2169/internalmedicine.50.4188)
Introduction
Wegener’s granulomatosis (WG) is a multisystemic ne-
crotizing vasculitis of unknown etiology with distinct clini-
cal and histological features (1-3). Histologically, it consists
of necrotizing vasculitis, affecting mainly small and
medium-sized arteries (4). The disease typically involves the
upper airways, lungs and kidneys. Gastrointestinal involve-
ment is very rare and has been previously detected almost
entirely by autopsy studies.
Double balloon enteroscopy (DBE) enables examination
of the entire small intestine and simultaneous tissue sam-
pling, along with a variety of therapeutic interven-
tions (5, 6). We present here the first reported case of intes-
tinal involvement in WG that was detected and followed up
by DBE.
Case Report
The patient was a 33-year-old Japanese man who was di-
agnosed in 2007 with WG at the age of 32 when he pre-
sented with recurrent upper respiratory tract infections, he-
maturia, polyarticular joint pain, nasal bleeding and sus-
tained low-grade fever. This diagnosis was made according
to the criteria of the American College of Rheumatology
(ACR) (4) based on radiological evidence of pulmonary
cavities and the presence of granulomatous inflammation
with giant cells on nasal biopsies, in addition to positivity
for antineutrophil cytoplasmic antibody (C-ANCA). At that
time, he was administered oral medication (60 mg/day pred-
nisolone), which alleviated his symptoms.
In 2008, one year after the diagnosis, the patient, who
had been receiving treatment with prednisolone 1 mg/kg,
was admitted to the hospital due to abdominal pain. Physi-
cal examination revealed a body temperature of 38.8℃.
Blood pressure and pulse rate were 148/90 mmHg and 116
Department of Gastroenterology, Juntendo University, School of Medicine, Japan
Received for publication July 8, 2010; Accepted for publication October 6, 2010
Correspondence to Dr. Kazuko Beppu, [email protected]
Intern Med 50: 219-222, 2011 DOI: 10.2169/internalmedicine.50.4188
220
Figure 1. Colonoscopic examination shows round ulcers in the cecum.
Table 1. Laboratory Findings on Admission
Peripheral bloodWBC 23000 /LRBC 3.54×1012 /LHb 9.3 g/dLHct 29.1 % Plt 295×109 /L
Blood chemistryTP 4.9 g/dLAlb 1.8 g/dLNa 135 mM/LK 4.4 mM/LCl 96 mM/LGlu106 mg/dLFe 10 μg/dLFerritin 2234 mg/mL
C3 124 mg/dLC4 15 mg/dLCH50 50 URF 310 IU/mLANA 20 ×anti-DNA (-)C-ANCA (-)P-ANCA (-)C7-HARP (-)
UrinalysisPH 8.0Glucose 1.2 g/dayProtein 1.2 g/dayOccult blood 1(+)
TIBC 188 μg/dLHbA1c 5.4 %CRP 11.8 mg/dLALP 578 IU/LAST 23 IU/LALT 58 IU/LLDH 275 IU/Lγ-GTP 100 IU/LT-Bil 1.07 mg/dLBUN 21 mg/dLCr 0.45 mg/dL
SerologyIgG 746 mg/dLIgA 176 mg/dLIgM 110 mg/dL
per minute, respectively. Findings of chest and abdominal
radiographs were unremarkable. Laboratory evaluation on
admission revealed a white blood cell count of 23,000/mm3,
C-reactive protein of 11.8 mg/dL and hemoglobin of 9.3 g/
dL. Although creatinine levels were normal, very slight he-
maturia and proteinuria were observed. In addition, C-
ANCA, which had been positive previously, was negative
(Table 1).
Colonoscopy showed round ulcers in the transverse colon,
cecum and terminal ileum (Fig. 1). A double-contrast bar-
ium study of the small intestine was performed and revealed
a ragged and narrow ileal colon (Fig. 2A). On the basis of
these results, retrograde double balloon enteroscopy (DBE)
(Fujinon EN-450T5/20; Fujinon Corp., Saitama, Japan) was
performed, which identified round ulcers in the ileal colon
(Fig. 2B). Multiple biopsies were performed; lesional biop-
sies showed inflammatory cells and fibrosis to the lamina
propia. Angiography revealed that multiple areas of stenosis
and irregular walls of the anterior and inferior mesenteric ar-
teries were caused by vasculitis (Fig. 3). Based on these
data, the final diagnosis was established as gastrointestinal
complications associated with WG.
The patient was switched from an ordinary diet to total
parenteral nutrition. In addition, the dosage of prednisolone
was increased to 2 mg/kg/day and 1 mg/kg/day of cyclo-
phosphamide was administered. The abdominal pain imme-
diately resolved, and after two subsequent weeks of treat-
ment, white blood cell count and C-reactive protein levels
normalized. Retrograde DBE performed two months after
the start of treatment indicated scarring from the initially de-
tected multiple ulcers and no new ulcerations in the ileum,
colon or rectum (Fig. 4A). Angiography revealed improve-
ment in the stenosis and irregular walls of the superior and
inferior arteries that had been initially observed (Fig. 4B).
The patient then resumed an ordinary diet and was given
oral systemic steroidal therapy; subsequently, symptoms
have been under control and the patient remains in remis-
sion.
Discussion
First described by Friedrich Wegener in 1936 (7), WG is
a form of vasculitis that affects various organs, particularly
the lungs and kidneys. The incidence of WG is 10 cases per
million per year, and it mainly occurs among the middle
aged. This disease can be effectively treated by daily ad-
ministration of prednisolone and cyclophosphamide. More-
over, because WG causes end-organ damage, long-term im-
Intern Med 50: 219-222, 2011 DOI: 10.2169/internalmedicine.50.4188
221
Figure 2. A double contrast barium study of the small intestine shows a ragged and narrow ileal colon (A) and DBE image shows round ulcers located in the ileum (B).
A B
Figure 3. Angiography image of the superior mesenteric ar-tery showing diffuse stenosis and irregular walls of the branches.
munosuppression is required (8). It is accompanied by long
periods of remission and relapse; hence, it is a critical ill-
ness.
Although focal necrotizing arteriolitis of the intestine has
been detected by necropsy in 24% of the 56 WG cases for
whom data are available (9), reports of significant clinical
manifestations of intestinal involvement are rare. Between
1982 and 2009, only 5 cases with severe intestinal involve-
ment were detected by emergency surgery due to perfora-
tion (10-14). In addition, 2 cases were detected by colono-
scopy (15, 16). The affected regions were in the terminal il-
eum, cecum and rectum in one of these patients and in the
terminal ileum and ascending colon in the other patient. En-
doscopic intestinal findings in these patients included small
ulcers and multiple ulcerations with bleeding and elevated
lesions. With regard to the present case, multiple round ul-
cers in the ileum could be detected by DBE in addition to
the colonic involvement found by colonoscopy.
The cause of ulcer formation in WG is generally consid-
ered to be vasculitis that obstructs blood flow to the intes-
tine. However, histological confirmation through examina-
tion of biopsy specimens obtained by endoscopy is not al-
ways possible, as biopsy specimens are generally too small
for a proper examination. This was true in the case reported
here. Although there was no detectable histological evidence
of vasculitis, intestinal involvement could be diagnosed by
ruling out other potential causes of small intestinal ulcers,
such as Crohn’s disease or tuberculosis, and on the basis of
the patient’s history, laboratory findings, including negative
fecal culture, and angiography results. As this case and pre-
vious reports suggest, endoscopic characteristics of intestinal
involvement in WG can be predicted by the presence of
multiple, small, round and clear ulcers associated with ob-
structed blood flow.
In summary, most significant is that this is the first re-
ported case of WG with intestinal involvement in which
DBE was used both to detect intestinal involvement and to
confirm non-recurrence. Also noteworthy is that although in-
testinal involvement is uncommon in WG, if left untreated,
it could be fatal. Therefore, when WG patients complain of
abdominal pain or exhibit abdominal symptoms without ap-
parent cause, intestinal complications due to vasculitis
should be strongly suspected and might be scrutinized using
DBE, the most optimal and up-to-date method for such a
purpose.
Intern Med 50: 219-222, 2011 DOI: 10.2169/internalmedicine.50.4188
222
Figure 4. DBE examination revealing scarring from the initially detected multiple ulcers in the il-eum (A) and angiography image of the superior mesenteric artery shows multiple normal walls of the branches (B).
A B
The authors state that they have no Conflict of Interest (COI).
References
1. Goodman GC, Churg J. Wegener’s granulomatosis: pathology and
review of the literature. Arch Pathol 58: 533-553, 1954.
2. Fahey JL, Leonard E, Churg J, Goodman GC. Wegener’s granulo-
matosis. Am J Med 17: 168-179, 1954.
3. Fauci AS, Haynes BF, Katz P, Wolff SM. Wegener’s granulomato-
sis: prospective clinical and therapeutic experience with 85 pa-
tients for 21 years. Ann Intern Med 98: 76-85, 1983.
4. Leavitt RY, Fauci AS, Bloch DA, et al. The American College of
Rhematology 1990 criteria for the classification of Wegener’s
granulomatosis. Arthritis Rheum 33: 1101-1107, 1990.
5. Beppu K, Osada T, Nagahara A, et al. Malignant lymphoma in the
ileum diagnosed by double-balloon enteroscopy. World J Gastro-
enterol 13: 3388-3391, 2007.
6. Shibuya T, Osada T, Asaoka D, et al. Double-balloon enteroscopy
for treatment of long-term abdominal discomfort due to small
bowel penetration by an eel bone. Med Sci Monit 14: CS107-CS
109, 2008.
7. Wegener F. Uber generalisierte, septishe Gefasserkrankungen. Verh
Dtsch Ges Pathol 29: 202-210, 1936 (in German).
8. Seo P, Stone JH. The antineutrophil cytoplasmic antibody-
associated vasculitides. Am J Med 117: 39-50, 2004.
9. Wolton EW. Giant cell granuloma of the respiratory tract
(Wegener’s granulomatosis). Br Med J 2: 265-270, 1958.
10. Tokuda M, Kurata N, Daikuhara H, et al. Small intestinal perfora-
tion in Wegener’s granulomatosis. J Rhumatol 16: 547-549, 1989.
11. Geraghty J, Mackay IR, Smith DC. Intestinal perforation in
Wegener’s granulomatosis. Gut 27: 450-451, 1986.
12. McNabb MR, Lennox MS, Wedzicha JA. Small intestinal perfora-
tion in Wegener’s granulomatosis. Postgrad Med J 58: 123-125,
1982.
13. Storesund B, Gran JT, Koldingsnes W. Severe intestinal involve-
ment in Wegener’s granulomatosis: report of two cases and review
of the literature. Br J Rheumatol 37: 387-390, 1998.
14. Deniz K, Ozseker HS, Balas S, Akpýnar E, Sökmensüer C. Intes-
tinal involvement in Wegener’s granulomatosis. J Gastrointestin
Liver Dis 16: 329-331, 2007.
15. Haworth SJ, Pusey CD. Severe intestinal involvement in
Wegener’s granulomatosis. Gut 25: 1296-1300, 1984.
16. Kitamura N, Matsukawa Y, Takei M, et al. Wegener’s granuloma-
tosis complicated with intestinal ulceration. Mod Rheumatol 14:
480-484, 2004.
Ⓒ 2011 The Japanese Society of Internal Medicine
http://www.naika.or.jp/imindex.html