234

QUANTITATIVE SACROILIAC SCINTIGRAPHY IN PATIENTS WITH

CROHN’S DISEASE

PAUL DAVIS, ALAN B. R . THOMSON, and BRIAN C. LENTLE

Sixty patients with Crohn’s disease have been assessed radiologically and by quantitative sacroiliac scintigraphy for evidence of sacroilitis and/or ankylosing spondylitis. The incidence of radiologic sacroiliitis ( 11%) and ankylosing spondylitis (5%) was no greater in our series than previously reported. However, the incidence of increased uptake of radiotracer at the sacroiliac joints was 52%. There was no correlation in the group as a whole between radiologic and/or scintigraphic evidence of sacro- iliitis and the tissue antigen HLA-B27.

One of the well recognized nonenteric manifesta- tions of Crohn’s disease is the presence of sacroiliitis on plain films of the pelvis. This has a reported prevalence of between 11 and 18% and may be associated with the clinical symptoms and signs of classic ankylosing spondylitis in approximately 6% of patients with Crohn’s disease (1) . It has recently been shown that sacroiliitis can be accurately and objectively assessed by

From the Divisions of Rheumatology and Gastroenterology, Department of Medicine, University of Alberta, and the Dr. W. W. Cross Cancer Institute, Edmonton, Alberta, Canada.

Paul Davis, F.R.C.P., M.R.C.P.: Assistant Professor of Med- icine, University of Alberta, and Associate, Canadian Arthritis and Rheumatism Society: A.B.R. Thornson, M.D.. F.R.C.P.: Assistant Professor of Medicine, University of Alberta; B.C. Lentle. M.D., F.R.C.P.: Director, Department of Nuclear Medicine, and Assistant Clinical Professor of Medicine, University of Alberta.

Address reprint requests to: Dr. Paul Davis, 9-1 12 Clinical Sciences Building, University of Alberta, Edmonton, Alberta, Canada T6G 2G3.

Submitted for publication July 1 I , 1977; accepted in revised form October 3, 1977.

quantitative sacroiliac scintigraphy (QSS) and that some patients with low back pain may have scintigraphic evi- dence of sacroiliitis in the absence of changes demon- strable on routine x-rays (2,3). Particular attention was paid to this feature in the present study which was undertaken to determine the prevalence of axial skeletal abnormalities in 60 consecutive patients with Crohn’s disease seen either as inpatients or outpatients in a gas- troenterology unit. Patients were evaluated for ankylos- ing spondylitis and sacroiliitis by x-rays of the pelvis and QSS. Each method of assessment was measured “blind” without prior cross reference. In addition, because of the known association between the tissue antigen HLA-B27 and classic ankylosing spondylitis, all patients had their HLA antigens characterized.

MATERIALS AND METHODS Sixty patients with Crohn’s disease were examined

consecutively in this study. Clinical, radiologic, and histologic features were used to confirm the diagnosis of Crohn’s disease (4). The male to female ratio was 1 : 1 with an age range of 14 to 62 (mean age 36). Most patients were receiving Azulfidine and/or prednisone, but no other antiinflammatory agents were administered during the course of this study. The activity of the underlying bowel disease ranged from quiescent to moder- ately severe.

X-ray films of the sacroiliac (SI) joints and of the lumbar spine were obtained and graded for sacroiliitis and ankylosing spondylitis according to the New York criteria (5). Bone scanning was performed using 88mTechnetium labeled stannous pyrophosphate (6). A profile scan of the sacroiliac joints was obtained by a method (previously reported in detail)

Arthritis and Rheumatism, Vol. 21, No. 2 (March 1978)

SACROILIAC SCINTIGRAPHY IN CROHN’S DISEASE 23 5

Table I. C‘linical and Radiological A bnormaliries in 60 Parienrs wirh C’rohn’s Disease

% of Number of Patients

Abnormal Findings Patients Studied

Abnormal quantitative sacroiliac scintigraphy 31 52%

Radiological sacroiliitis 7 1 1 % Classic ankylosing spondylitis 3 5%

using a count density of 2,000 counts/cm2. An uptake ratio at the SI joint in relation to central sacrum of greater than 1.3: 1 .O was considered abnormal. These figures are based on the results in 54 age-matched patients scanned for isolated bone tumors or trauma (age range: 21 to 45, mean age 31; scan results: SI:S ratios-ratio uptake over SI joints compared to normal bone-0.96-1.34; mean f2 SD = 0.93-1.27). Similar results were seen in an older age group of patients scanned for nonmetastatic malignant disease. Abnormally high ratios have been reported at the sacroiliac joints in association with Rei- ter’s syndrome (7 ) , psoriatic spondylitis (8), and classic anky- losing spondylitis (3). HLA antigen typing was carried out using a technique based on the microcytotoxicity method of Mittal el a/ (9).

R ESU LTS Clinical and Radiological Examination (Table 1 ).

Three patients had classic ankylosing spondylitis on the basis of the New York diagnostic criteria ( 5 ) . Peripheral large joint synovitis was detected clinically in 4 (10%) patients. I n 2 of these patients there was clinical evi- dence of sacroiliitis. None of the patients had clinical or radiologic evidence of other spinal disease, for example degenerative disease. Radiologic changes of the sacro- iliac joints were present in 7 of the patients studied. The prevalence of radiologic sacroiliitis and classic ankylos- ing spondylitis was no different from that reported in previous studies.

Quantitative Sacroiliac Scintigraphy. In patients over the age of 20, sacroiliac to sacral ratios (SI: S) of 1.30: 1 or above a re 2 standard deviations outside the range of normal. Thirty-one of the 60 patients had ratios in excess of this value, giving presumptive evidence of inflammatory disease of the sacroiliac joints. Assess- ment of the sacroiliac joints by this technique in patients under the age of 20 is more difficult because younger persons may normally have higher (SI: S) ratios. This factor did not interfere with our study since the 3 pa- tients below age 20 examined had SI : S ratios within the normal adult range. Because it is not possible at the present time to objectively quantitate increased uptake

in the lumbar spine on bone scintigraphy, we were un- able to correlate the bone scintiscan directly with evi- dence of extrapelvic inflammatory disease. Increased up- take in the peripheral joints was noticed in the 4 patients with clinical evidence of synovitis. I n addition, bone scintiscan evidence of increased uptake at periph- eral joints was seen in a further 3 patients in whom there was n o correlation between abnormal SI joints and pe- ripheral joints on scintiscan.

Correlation Between Radiological Sacroiliitis and Quantitative Sacroiliac Scintigraphy. Of those patients who had abnormal sacroiliac joints on bone scanning, 6:31 also had some radiologic change in their sacroiliac joints, and of those with positive x-rays, 6: 7 had abnor- mal scans (Table 2).

HLA Antigens (Table 3). The frequency of the tissue antigen HLA-B27 was higher in our 60 patients with Crohn’s disease (20%) than in 295 normal local controls (9.2%), but this difference was not statistically significant. There was no significant difference in other antigen frequencies between patients and controls, as reported in earlier studies (10). HLA-B27 was present in the 3 patients with classic ankylosing spondylitis but was absent i n the other 4 patients with radio- logic sacroiliitis. HLA-B27 was found in 8 patients with bone scan evidence of sacroiliitis but was absent in a further 23. HLA-B27 was also present in 2 apparently normal patients. The frequency of HLA-B27 was not sta- tistically higher in Crohn’s disease patients with radi- ologic or bone scan evidence of sacroiliitis compared to those patients without such evidence. However, of the 12 patients with HLA-B27, 10 had evidence of sacroiliitis.

DISCUSSION Bone scanning has previously been used in the

assessment of patients with low back pain and ankylos- ing spondylitis and has been proved useful in assessing evidence of inflammatory disease of the spine (3 , l l ) . Assessment of increased uptake over the sacroiliac joints is measured objectively using a ratio of counts of emis- sions from gsmTe~hnetium obtained over normal bone compared to counts obtained over the sacroiliac joints. Our results suggest that with radiology and bone scan-

Table 2. Relarionship Betnwn Radiographic and Bone Scinriscun Evidence oJ Sacroiliitis in 60 Parienrs with Crohn’s Disease

Q S S positive Q S S negative

X-ray positive 6 X-ray negative 25

1 28

DAVIS ET AL 236

Table 3. Frequency o/ HLA-B27 in Study Groups

Ratio of % of HLA-B27 to HLA-B27 in

Study Groups Group Studied Group Studied

Control population 27 : 295 9.2%

Crohn’s disease and radiologic

Crohn’s disease and bone

Crohn’s disease and classic

Crohn’s disease patients 12:60 20%

sacroiliitis 3:7 43%

scintiscan sacroiliitis 8:31 26%

anklosing spondylitis 3:3 loo%

ning the prevalence of sacroiliitis in patients with Crohn’s disease is much higher than previously reported ( I ) . These earlier reports were based on radiologic changes that can reliably diagnose sacroiliitis only in advanced disease. When similar radiologic criteria were used, a comparable incidence was observed in this study. A high degree of correlation between radio- logic and bone scan evidence of sacroiliitis was noted, but a number of patients were seen with abnormal scans and normal x-rays. This is in accord with previous observations in ankylosing spondylitis (3). One patient with abnormal x-rays had a normal scan. Since abnor- mal scan sites probably represent areas of increased osteoblastic activity ( 12), the scan was possibly negative in this instance, due to either lack of currently active disease or the antiinflammatory effects of concurrent steroid therapy of inflammatory bowel disease. This is supported by the recent report of Namey et al. (2) which showed that antiinflammatory drugs will influence QSS. It is probable that a bone scan is a more sensitive in- dicator of active sacroiliac disease, whereas routine radiologic investigation may reflect a more advanced stage of the disease process. The prevalence of classic ankylosing spondylitis in our group is similar to that previously reported.

These results support the hypothesis that either sacroiliitis in inflammatory bowel disease is a distinct clinical entity or that subclinical or minor forms of ankylosing spondylitis are much more common in pa- tients with Crohn’s disease than previously reported.

antigen HLA-B27. Previous reports of tissue typing in patients with inflammatory bowel disease demonstrated that there is no increased frequency in HLA-B27 (17- 19). However, in the previous report from our Unit (17) 10 of 1 1 patients studied with Crohn’s disease and clas- sic ankylosing spondylitis did have this antigen. Our present results support those from other series (20) that there is a poor correlation between HLA-B27 and isolated radiographic sacroiliitis in patients with inflam- matory bowel disease. In addition the presence of HLA- B27 failed to correlate with bone scan evidence of sacro- iliitis. Ten of 12 patients with Crohn’s disease and HLA- B27 antigen did have evidence of sacroiliitis; this is a higher frequency than would be expected in normal subjects with HLA-B27. All patients with classic anky- losing spondylitis were HLA-B27 positive. Such results support the suggestion that the possession of HLA-B27, in addition to other environmental factors, may influ- ence the frequency or severity of the resultant axial arthropathy (21).

Our study has shown that the prevalence of in- flammatory disease of the sacroiliac joints is higher than has been previously reported. Although good correla- tion was seen between bone scanning and x-ray, these two investigations probably reflect different stages of the disease process. Thus both procedures may prove to be useful in the assessment of back pain in patients with inflammatory bowel disease. The presence of the tissue antigen HLA-B27 in patients with back symptoms and inflammatory bowel disease may be associated with the presence of classic ankylosing spondylitis, or an abnor- mal bone scan, but the absence of the tissue antigen does not exclude the diagnosis of sacroiliitis in these individ- uals. In addition, our study does not establish whether the B27 antigen is a marker of a potentially severe sacroiliitis that will eventually progress to classic anky- losing spondylitis; only long-term follow-up studies will establish this point.

It is recommended that all patients with inflam- matory bowel disease should be carefully assessed for axial arthropathy since the frequency of sacroiliitis is much higher than previously reported, and treatment for i t is so readily available.

ACKNOWLEDGMENTS Therefore, the results of tissue typing are of interest. The increased frequency of HLA-B27 in patients with anky- losing spondylitis has been previously reported (1 3,14) and has been well substantiated by a number of other investigators. In addition, the SpOndYlitis associated with Reiter’s syndrome (15) and Psoriasis (16) has also

We are grateful for the cooperation of Dr. R.H. Wen- sel and Dr. R.W. Sherbaniuk in allowing us access to patients under their care. We would also like to acknowledge the assistance of Ms. J . Schlaut who performed the tissue typing. We would like to thank Dr. D. Barraclough for reading the x-

been shown to be linked with the histocompatibility rays and Dr. A S . Russell for his helpfulcornrnents. -

SACROILIAC SCINTIGRAPHY IN CROHN’S DISEASE 237

REFERENCES 1. Ansel BM, Wigley RAD: Arthritic manifestations in re-

gional enteritis. Ann Rheum Dis 23:64-72, 1964 2. Namey TC, McIntyre J , Buse M, LeRoy EC: Nucle-

ographic studies of axial spondarthritides. Quantitative sacroiliac scintigraphy in early HLA-B27 associated sac- roiliitis. Arthritis Rheum 20:1058-1064, 1977

3. Russell AS, Lentle BC, Percy JS: Investigation of sacro- iliac disease: Comparative evaluation of radiological and radionuclide techniques. J Rheumatol 245-51, 1975

4. Lennard-Jones JE, Lockhart-Mummay HE, Morson BC: Clinical and pathological differentiation of Crohn’s dis- ease and proctocolitis. Gastroenterology 54:1162-1170, 1968

5. Bennett RHJ, Burch TA: New York symposium on popu- lation studied in the rheumatic disease-new diagnostic criteria. Bull Rheum Dis 17:453-458, 1967

6. Lentle BC, Russell AS, Percy JS: Bone scintiscanning updated. Ann Intern Med 84:297-303, 1976

7. Russell AS, Davis P, Percy JS: The sacro-iliitis of acute Reiter’s syndrome. J Rheumatol 4:293-296, 1977

8. Barraclough D, Russell AS, Percy JS: Psoriatic spondy-

11. Lentle BC, Russell AS, Percy JS, et al: The scintigraphic investigation of sacro-iliac disease. J Nucl Med 18529- 533, 1977

12. Weber DA, Greenberg EJ, Dimich A, et al: Kinetics or radionuclides used for bone studies. J Nucl Med 103-17. 1969

13. Brewerton DA, Caffrey M, Hart FD, et al: Ankylosing spondylitis and HLA B27. Lancet 1:904-907, 1973

14. Schlosstein L, Terasaki PI, Bluestone R: High association of an HLA antigen B27 with ankylosing spondylitis. N Engl J Med 288:704-706, 1973

15. Brewerton DA, Caffrey M, Nicholls A, et al: Reiter’s disease and HLA B27. Lancet 2:996-998, 1973

16. Brewerton DA, Caffrey M, Nicholls A, et al: HLA antigen 27 and arthropathies associated with ulcerative colitis and psoriasis. Lancet 1:956-957, 1974

17. Russell AS, Percy JS, Schlaut J, et al: Transplantation antigens in Crohn’s disease. Am J Dig Dis 20:359-361, 1975

18. Gleeson MH, Walker JS, Wentzel J, et al: Human leuco- cyte antigens in Crohn’s disease and ulcerative colitis. Gut 13~438-440. 1972 - - -

litis: A clinical, radiological and scintiscan survey. J Rheumatol 4:282-287, 1977

9. Mittal KK, Mickey MR, Singal DP, et al: Serotyping for the homotransplantation XVIII. Refinement of the micro- droplet lymphocyte toxicity test. Transplantation 6:912- 927, 1968

19, Jakoby RK, Jayson MIV: HLA 27 in Crohn’s disease. Ann Rheum Dis 33:422-425, 1974

20. Hyla JF , Franck WA, Davis JS: Lack of association of HLA-B27 with radiographic sacro-iliitis in inflammatory bowel disease. J Rheumatol 3:196-200, 1976

10. Mallas EG, Mackintosh P, Asquith P, et al: Histocom- patibility antigens in inflammatory bowel disease. Gut 17:906-910, 1976

21. Russell AS, Lentle BC, Schlaut J: Radiologic and scinti- sc’an findings in HLA B27 negative patients with ankylos- ing spondylitis. J Rheumatol 3:321-323, 1976