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Prevalence of clinical and subclinical spondyloarthropathy in patients with inflammatory bowel disease
April 1998 • G3947 PREVALENCE OF CLINICAL AND SUBCLINICAL SPONDYLOARTHROPATHY IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE. M. De Vos, K. De Vlam, D. Elewant, H. Mielants, E. Cesmeli, F. De Keyser, C. Cuvelier, E. Veys. Depts. of Gastroenterology, Rheumatology and Pathology, University Hospital Ghent, Belgium. Data about the prevalence of spondyloarthropathy (SPA) and subclinical sacroiliitis in IBD are scarce and disparate. Study design: We performed a prospective study including 65 consecutive patients (CDIUC=50/15) consulting at GI unit. Thirty eight patients (58 %) had a history of IBD longer than 5 years. Clinical evaluation was performed by the rheumatologist. Radiology assessment included anteroposterior views of the pelvis and oblique views of the sacroiliac joints. Results: Clinical diagnosis of spondyloarthropathy (SPA) including inflammatory low back pain and/or peripheral synovitis was found in 15 patients (23%) (criteria EESG). Uni- or bilateral sacroiliitis >_stage 2 (New York criteria) was present in 17 patients (25%). Sch6berindex was abnormal in 22 patients (34%). Diagnosis of ankylosing spondylitis (AS) including inflammatory back pain and bilateral sacroiliitis stage 2 was found in 4 patients (6 %) (Rome criteria). Globally, articular involvement including SpA or sacroiliitis was found in 28 patients (43 %). No differences in prevalences were found between patients with long or short bowel history.
N % CD UC
Intl. Enthesitis Synovitis SpA Sacroiliitis AS SpA or >_Stage 2 sacroiliitis back pain Clinical 15 17 4 28 14 5 3 (23 %) (25 %) (6 %) (43 %) (22 %) (8 %) (5 %) 20 % 26 % 4% 42 % 18 % 8% 4% 33 % 26 % 12 % 47 % 33% 6% 6%
CONCLUSIONS: Articular involvement is a much more common extraintestinal manifestation of IBD than generally believed and present in 43 % of the patients. In 23 % of the patients clinical symptoms are present and diagnosis of SpA made. Moreover, subclinical sacroiliitis is a very common finding in IBD and present as the only manifestation of the articular disease in 25 % of the patients. Longterm follow-up is necessary to evaluate the clinical significance of these findings. • G3948
INTRAVENOUS CYCLOSPORINE (CyA) MONOTHERAPY VERSUS INTRAVENOUS METHYLPREDNISOLONE (MP) MONOTHERAPY IN SEVERE ULCERATIVE COLITIS: A RANDOMIZED, DOUBLE BLIND CONTROLLED TRIAL. G. D'Haens. L. Lemmens, M. Hiele, L. Vandeputte, F. Nevens, M. Peeters, S. Vermeire, F. Baert, K. Geboes, P. Rutgeerts, Depts. of Gastroenterologyand Pathology, University of Leuven, Belgium. Severe attacks of ulcerative colitis (UC) are usually treated with intravenous (IV) corticosteroids. Refractory cases often improve when high dose IV CyA is added to this treatment. We conducted a randomized controlled double blind trial in which pts with severe attacks of UC (at least up to the splenic flexure) admitted to the hospital were started on either IV CyA (Sandimmun ®, Sandoz, Switzerland) 4 mg/kg/day alone (adjusted to serum levels between 250 and 350 ng/ml by a clinician not involved in the pts' care) or IV MP (Solumedrol ®, Upjohn, Belgium) 40 mg/d (50 mg prednisolone equivalent), both in continuous infusion for 8 days. Oral steroids (used maximally 2 weeks without improvement) were discontinued at the start of the trial; pts already on IV steroids were not included. During the study period both physicians and pts were blinded to the treatment. Twenty pts with a severe attack of UC (Lichtiger symptom score >10, NEJM June 1994) were included. Ten pts (8M/2F age 40.7 -+ 16.7) received MP, 10 (5M/5F age 38.7-+ 8.2) received CyA. Over the 8 days they received 2.83_+0.5 mg/kg CyA/day. At day 8, 7/10 pts treated with CyA had responded to the therapy (score from 12.7 _+2.6 to 6.5 _+2.7) versus 6/10 pts treated with MP (score from 11.4 _+1.1 to 5.4-+ 1.5). In the responders CRP serum levels dropped from 4.2 _+4.3 to 1.4 _+ 1.6 mg/dl with CyA and from 6.8 _+3.5 to 1.8 _+1.9 mg/dl with MP. Of the non-responders, 1/3 MP-pt and 1/3 CyA-pt improved when CyA and MP were combined. 2/10 pts in the MP group and 1/10 in the CyA group underwent colectomy. All nonoperated pts were discharged from the hospital on the same therapy given orally (Neoral ® or Medrol ®) with or without azathioprine. No serious toxicity was observed. We conclude that CyA monotherapy started IV and continued orally appears an effective and safe alternative to glucocorticosteroid treatment in patients with severe attacks of UC.
Immunology, Microbiology, and Inflammatory Disorders A963 G3949
PROCTITIS: A PARTICULAR TYPE OF CROHN'S RECURRENCE FOLLOWING ILEAL RESECTION. G. D'Haens F. Sels, M. Peeters, F. Baert, K. Geboes, P. Rutgeerts, Dept. of Gastroenterology and Pathology, University of Leuven, Belgium. Postoperative recurrence of ileal Crohn's disease is almost always located in the neoterminal ileum, proximally to the ileocolonic anastomosis. We describe a series of 18 pts who underwent an ileal resection, in whom Crohn's disease postoperatively appeared in the rectum or the rectosigmoid, whereas preoperatively no signs of Crohn's disease had been observed in this location. Eighteen patients (12 female, 6 male, mean age 44.2 _+ 12.8 yrs) underwent an ileal resection for Crohn's disease (flrst:14/18, second: 3/18, third: 1118) and developed typical Crohn's proctitis a mean of 64 _+ 12.2 (2-251) months after this surgery. The symptoms began in 4 pts without recurrence in the ileum, in 4 pts 8 to 48 months prior to clinical recurrence in the ileum, in 4 pts simultaneously with ileal recurrence and in 6 pts 2 to 122 months following ileal recurrence. None of the patients had had rectal Crohn's disease prior to surgery, but 4 pts had suffered from anal fissures and 4 from abscesses and/or fistulae. Only two pts had positive p-ANCA antibodies. Symptoms consisted of tenesmus, bloody and mucus discharge and urgency. On endoscopy 1 pt had only aphthous ulcers, while all other pts had diffuse inflammation with erosions and ulcerations, up to a distance of 15 _+10.4 cm above the anal margin. Fifteen of the eighteen pts had varying degrees of bile acid diarrhea, most often successfully treated with cholestyramine. Rectal inflammation and symptoms improved with topical 5-ASA alone (n=7), topical corticosteroids (n=5), systemic imidazole antibiotics (n=3) or corticosteroids (n=3). Two pts required azathioprine as maintenance therapy. Conclusion: Crohn's proctitis is a particular type of postoperative recurrence possibly related to bile acid diarrhea, which in most instances can be treated successfully with topical therapy alone. • G3950
THE PRESENCE AND SEVERITY OF NEURAL INFLAMMATION PREDICT SEVERE POSTOPERATIVE RECURRENCE OF CROHN'S DISEASE. G. D'Haens, S. Colpaert, M. Peeters, F. Baert, F. Penninckx, P. Rutgeerts, K. Geboes, depts of Gastroenterology, Surgery and Histopathology, University of Leuven, Belgium. Structural and inflammatory changes of the enteric nervous system are characteristic for Crohn's disease (CD) and have been observed in otherwise uninflamed surgical section margins from CD pts. We investigated the link between neural changes in resected Crohn's ileitis and postoperative recurrence. The presence of neural hyperplasia and hypertrophy, the proportion of inflamed ganglia and the nature of the (peri)neural inflammation were examined microscopically in resection specimens and section margins from 40 CD pts (21F/19M, mean age 28 _+7 yrs) undergoing ileal resection. The findings were then correlated with CD recurrence diagnosed endoscopically and histologically three months following surgery, using standardized scores. All pts used placebo-medication in recurrence prevention trials. Resection specimens from UC-pts (n=10, 8M/2F, mean age 38.2 _+10.4) and cecal carcinoma-pts (n=10, 5M/5F, mean age 73.0 -+ 12.8) served as controls. Neural lesions were found in the ileal section margins in 22/40 CD cases. Auerbach's ganglia were more frequently inflamed than submucosal ganglia (4-44% vs 10-14%); the inflammatory infiltrate consisted of eosinophils in 50%, of lymphocytes in 27% and of a mixture of both in 23% of inflamed ganglia. 20•32 pts with endoscopic recurrence had neuritis in the ileal section margins vs 2/8 pts without endoscopic recurrence at 3 months (Odd's ratio 8.75 (1.7-45.4), p<0.01). Moreover, the proportion of inflamed ganglia was correlated with the severity of endoscopic (p<0.001) and histologic (p<0.01) recurrence. Neural inflammation was also frequently found in Crohn's ileal resection specimens (in 37140 CD pts, both in Auerbach's (33/40) and submucosal (30/40) plexuses), while it was uncommon in colonic section margins. Neural hyperplasia and/or hypertrophy were frequently seen in resection specimens (19/40) and ileal section margins (7/40), but appeared unrelated to recurrence. In the controls, neural inflammation was rarely observed in UC-specimens (1 ganglion in 2/10 UC-cases) and absent in carcinoma specimens. We conclude that neural inflammation frequently occurs in ileal CD. Its presence in the ileal section margin appears to be predictive for early postoperative recurrence. This supports the hypothesis that the neural network may provide a pathway for the spreading of inflammation in CD.
N % CD UC
Intl. Enthesitis Synovitis SpA Sacroiliitis AS SpA or >_Stage 2 sacroiliitis back pain Clinical 15 17 4 28 14 5 3 (23 %) (25 %) (6 %) (43 %) (22 %) (8 %) (5 %) 20 % 26 % 4% 42 % 18 % 8% 4% 33 % 26 % 12 % 47 % 33% 6% 6%
CONCLUSIONS: Articular involvement is a much more common extraintestinal manifestation of IBD than generally believed and present in 43 % of the patients. In 23 % of the patients clinical symptoms are present and diagnosis of SpA made. Moreover, subclinical sacroiliitis is a very common finding in IBD and present as the only manifestation of the articular disease in 25 % of the patients. Longterm follow-up is necessary to evaluate the clinical significance of these findings. • G3948
INTRAVENOUS CYCLOSPORINE (CyA) MONOTHERAPY VERSUS INTRAVENOUS METHYLPREDNISOLONE (MP) MONOTHERAPY IN SEVERE ULCERATIVE COLITIS: A RANDOMIZED, DOUBLE BLIND CONTROLLED TRIAL. G. D'Haens. L. Lemmens, M. Hiele, L. Vandeputte, F. Nevens, M. Peeters, S. Vermeire, F. Baert, K. Geboes, P. Rutgeerts, Depts. of Gastroenterologyand Pathology, University of Leuven, Belgium. Severe attacks of ulcerative colitis (UC) are usually treated with intravenous (IV) corticosteroids. Refractory cases often improve when high dose IV CyA is added to this treatment. We conducted a randomized controlled double blind trial in which pts with severe attacks of UC (at least up to the splenic flexure) admitted to the hospital were started on either IV CyA (Sandimmun ®, Sandoz, Switzerland) 4 mg/kg/day alone (adjusted to serum levels between 250 and 350 ng/ml by a clinician not involved in the pts' care) or IV MP (Solumedrol ®, Upjohn, Belgium) 40 mg/d (50 mg prednisolone equivalent), both in continuous infusion for 8 days. Oral steroids (used maximally 2 weeks without improvement) were discontinued at the start of the trial; pts already on IV steroids were not included. During the study period both physicians and pts were blinded to the treatment. Twenty pts with a severe attack of UC (Lichtiger symptom score >10, NEJM June 1994) were included. Ten pts (8M/2F age 40.7 -+ 16.7) received MP, 10 (5M/5F age 38.7-+ 8.2) received CyA. Over the 8 days they received 2.83_+0.5 mg/kg CyA/day. At day 8, 7/10 pts treated with CyA had responded to the therapy (score from 12.7 _+2.6 to 6.5 _+2.7) versus 6/10 pts treated with MP (score from 11.4 _+1.1 to 5.4-+ 1.5). In the responders CRP serum levels dropped from 4.2 _+4.3 to 1.4 _+ 1.6 mg/dl with CyA and from 6.8 _+3.5 to 1.8 _+1.9 mg/dl with MP. Of the non-responders, 1/3 MP-pt and 1/3 CyA-pt improved when CyA and MP were combined. 2/10 pts in the MP group and 1/10 in the CyA group underwent colectomy. All nonoperated pts were discharged from the hospital on the same therapy given orally (Neoral ® or Medrol ®) with or without azathioprine. No serious toxicity was observed. We conclude that CyA monotherapy started IV and continued orally appears an effective and safe alternative to glucocorticosteroid treatment in patients with severe attacks of UC.
Immunology, Microbiology, and Inflammatory Disorders A963 G3949
PROCTITIS: A PARTICULAR TYPE OF CROHN'S RECURRENCE FOLLOWING ILEAL RESECTION. G. D'Haens F. Sels, M. Peeters, F. Baert, K. Geboes, P. Rutgeerts, Dept. of Gastroenterology and Pathology, University of Leuven, Belgium. Postoperative recurrence of ileal Crohn's disease is almost always located in the neoterminal ileum, proximally to the ileocolonic anastomosis. We describe a series of 18 pts who underwent an ileal resection, in whom Crohn's disease postoperatively appeared in the rectum or the rectosigmoid, whereas preoperatively no signs of Crohn's disease had been observed in this location. Eighteen patients (12 female, 6 male, mean age 44.2 _+ 12.8 yrs) underwent an ileal resection for Crohn's disease (flrst:14/18, second: 3/18, third: 1118) and developed typical Crohn's proctitis a mean of 64 _+ 12.2 (2-251) months after this surgery. The symptoms began in 4 pts without recurrence in the ileum, in 4 pts 8 to 48 months prior to clinical recurrence in the ileum, in 4 pts simultaneously with ileal recurrence and in 6 pts 2 to 122 months following ileal recurrence. None of the patients had had rectal Crohn's disease prior to surgery, but 4 pts had suffered from anal fissures and 4 from abscesses and/or fistulae. Only two pts had positive p-ANCA antibodies. Symptoms consisted of tenesmus, bloody and mucus discharge and urgency. On endoscopy 1 pt had only aphthous ulcers, while all other pts had diffuse inflammation with erosions and ulcerations, up to a distance of 15 _+10.4 cm above the anal margin. Fifteen of the eighteen pts had varying degrees of bile acid diarrhea, most often successfully treated with cholestyramine. Rectal inflammation and symptoms improved with topical 5-ASA alone (n=7), topical corticosteroids (n=5), systemic imidazole antibiotics (n=3) or corticosteroids (n=3). Two pts required azathioprine as maintenance therapy. Conclusion: Crohn's proctitis is a particular type of postoperative recurrence possibly related to bile acid diarrhea, which in most instances can be treated successfully with topical therapy alone. • G3950
THE PRESENCE AND SEVERITY OF NEURAL INFLAMMATION PREDICT SEVERE POSTOPERATIVE RECURRENCE OF CROHN'S DISEASE. G. D'Haens, S. Colpaert, M. Peeters, F. Baert, F. Penninckx, P. Rutgeerts, K. Geboes, depts of Gastroenterology, Surgery and Histopathology, University of Leuven, Belgium. Structural and inflammatory changes of the enteric nervous system are characteristic for Crohn's disease (CD) and have been observed in otherwise uninflamed surgical section margins from CD pts. We investigated the link between neural changes in resected Crohn's ileitis and postoperative recurrence. The presence of neural hyperplasia and hypertrophy, the proportion of inflamed ganglia and the nature of the (peri)neural inflammation were examined microscopically in resection specimens and section margins from 40 CD pts (21F/19M, mean age 28 _+7 yrs) undergoing ileal resection. The findings were then correlated with CD recurrence diagnosed endoscopically and histologically three months following surgery, using standardized scores. All pts used placebo-medication in recurrence prevention trials. Resection specimens from UC-pts (n=10, 8M/2F, mean age 38.2 _+10.4) and cecal carcinoma-pts (n=10, 5M/5F, mean age 73.0 -+ 12.8) served as controls. Neural lesions were found in the ileal section margins in 22/40 CD cases. Auerbach's ganglia were more frequently inflamed than submucosal ganglia (4-44% vs 10-14%); the inflammatory infiltrate consisted of eosinophils in 50%, of lymphocytes in 27% and of a mixture of both in 23% of inflamed ganglia. 20•32 pts with endoscopic recurrence had neuritis in the ileal section margins vs 2/8 pts without endoscopic recurrence at 3 months (Odd's ratio 8.75 (1.7-45.4), p<0.01). Moreover, the proportion of inflamed ganglia was correlated with the severity of endoscopic (p<0.001) and histologic (p<0.01) recurrence. Neural inflammation was also frequently found in Crohn's ileal resection specimens (in 37140 CD pts, both in Auerbach's (33/40) and submucosal (30/40) plexuses), while it was uncommon in colonic section margins. Neural hyperplasia and/or hypertrophy were frequently seen in resection specimens (19/40) and ileal section margins (7/40), but appeared unrelated to recurrence. In the controls, neural inflammation was rarely observed in UC-specimens (1 ganglion in 2/10 UC-cases) and absent in carcinoma specimens. We conclude that neural inflammation frequently occurs in ileal CD. Its presence in the ileal section margin appears to be predictive for early postoperative recurrence. This supports the hypothesis that the neural network may provide a pathway for the spreading of inflammation in CD.