Early Crohn's diagnosis

In addition to usual barium Upper GI series( X-ray ), colonoscopy with biopsy and erythrocyte sedimentation rate( blood test ), there are other tests proven to reflect inflammatory disease activity, and used to predict disease relapse. These tests can be used for early detection, as well as for monitoring effectiveness of conventional and experimental treatment.

(1) Relapses of Crohn’s disease appear to be almost random. If these attacks could be reliably predicted, it might be possible to abort them with early treatment. The clinical indices and the serum C-reactive protein, orosomucoid, alpha 1-antitrypsin, and iron were increased at the time of the attack as compared to three months earlier, while only the clinical indices, orosomucoid and alpha 1-antitrypsin increased between three months and one month prior to the attack.

(2) As approximately 50% of patients in remission [Crohn’s disease activity index (CDAI) less than 150] show some laboratory abnormalities, we inquired whether these alterations might be of value for predicting relapse. We prospectively studied 41 patients with Crohn’s disease who had been showing CDAI less than 150 for at least 6 mo before entering the study and who were not receiving any long-term treatment. The 41 patients were studied at the ninth and at the 18th month after inclusion in the study. Disease activity was monitored by CDAI calculation and by measurement of erythrocyte sedimentation rate, white blood cell count, hemoglobin, albumin, alpha 2-globulin, serum iron, C-reactive protein, alpha 1-glycoprotein, and alpha 2-antitrypsin. Seventeen of the 41 patients had a clinical relapse during follow-up. At the beginning of the study the patients who later relapsed showed a remarkable alteration of acid alpha 1-glycoprotein (p less than 0.0001), alpha 2-globulin (p less than 0.0003), and erythrocyte sedimentation rate (p less than 0.0006), in comparison with the patients who remained in remission. By discriminant analysis a prognostic index with these laboratory investigations provided a high percentage(88%) of accuracy according to the outcome at the 18th month.

(3) Among the 32 variables tested, interleukin-6 serum level had the greatest ability to predict the time-to-relapse, with 17-fold chance of relapse over a 1-year period for patients with an interleukin-6 serum level greater than 20 pg/ml than for patients with a lower level (P < 0.001). A high serum level of the soluble TNF receptors p55 and p75 also had significant predictive value, in contrast to TNF-alpha serum levels. An interleukin-6 serum level greater than 20 pg/ml and either an acid alpha-1-glycoprotein level greater than 1.1 g/l or a soluble interleukin-2 receptor serum level greater than 95 pM/l were risk factors selected by a stepwise multivariate analysis.

(4) The current study compared decision-making strategies on the basis of a combination of disease indices and serum concentrations of orosomucoid (strategy A) and disease indices only (strategy B) for the tapering of prednisolone. By means of multiple regression analysis a high serum concentration of orosomucoid and previous disease activity were identified as predictors of relapse. A therapeutic end-point of normalization of an increased level of S-orosomucoid in addition to clinical remission may be difficult to use, as serum concentrations may be continuously increased in spite of clinical remission. However, this goal may still be relevant, as a trend towards higher risk of relapse was found in patients with increased orosomucoid concentrations after completing therapy.

(5) Aim of the study was to evaluate [99mTc]hexamethyl-propylamine-oxime (HMPAO) leukocyte scintigraphy for the assessment of disease activity and extent in inflammatory bowel disease patients. Sensitivities for active disease at 1 and 3 hr were 98% and 98% and specificities were 100% and 83%, respectively. [99mTC]HMPAO leukocyte scintigraphy is superior to the activity index and the gastroenterologists’ clinical assessment of active inflammation in IBD patients. Scintigraphy allows assessment of the existence, extent, and intensity of active inflammation in IBD patients in one examination with high accuracy.

(6) Patients with Crohn’s disease exhibit marked changes in intestinal permeability that can be assessed by lactulose and mannitol. Sucrose is a novel marker for gastric permeability. We combined these three sugars to investigate whether patients with Crohn’s disease demonstrate changes in gastric permeability and if so, whether these changes are matched with altered intestinal permeability. Patients with Crohn’s disease showed higher gastric and intestinal permeability compared with healthy control subjects. Gastric permeability was correlated with intestinal permeability. Patients with granuloma had more pronounced changes in both gastric and intestinal permeability than patients with various endoscopic and histological lesions. Patients with normal mucosa had normal permeability. Alterations in gastric mucosa caused by Crohn’s disease are reflected by changes in gastric permeability and can be used to noninvasively screen for Crohn’s disease involvement of the upper GI tract.

(7) Identification of patients with IBD in clinical remission who have ongoing inflammation may be of clinical-therapeutic relevance. The novel leukocyte adhesiveness/aggregation test( LAAT ) is a simple, rapid, very sensitive and convenient test. Similar results were obtained when other acute phase reactants like the erythrocyte sedimentation rate, white blood cell count, differential count, and C-reactive protein level were examined. However, in a linear regression analysis, LAAT was the only significant (P < 0.0006) variable that could classify correctly each subject to the appropriate category of control and IBD in remission or relapse.

Different other coagulation parameters were shown to be altered in Crohn's disease( increased fibrinogen, platelet count, serum von Willebrand factor, factor V, factor VII and decreased factor XIII ). Valuable standard blood tests are also haemoglobin, iron, albumin, cholesterol, biliary( GGT, AP, bilirubin ) and liver( ALT, AST )  tests.
 

References:

1. PREDICTORS OF ACUTE RELAPSE OF CROHN’S DISEASE. A LABORATORY AND CLINICAL STUDY.
Wright JP; Young GO; Tigler-Wybrandi N; Dig Dis Sci, 1987 Feb, 32:2, 164-70

2. A LABORATORY INDEX FOR PREDICTING RELAPSE IN ASYMPTOMATIC PATIENTS WITH CROHN’S DISEASE.      Brignola C; Campieri M; Bazzocchi G; Farruggia P; Tragnone A; Lanfranchi GA
Gastroenterology, 1986 Dec, 91:6, 1490-4

3. A HIGH SERUM CONCENTRATION OF INTERLEUKIN-6 IS PREDICTIVE OF RELAPSE IN QUIESCENT CROHN’S    Louis E; Belaiche J; van Kemseke C; Franchimont D; de Groote D; Gueenen V; Mary JY; Department of Gastroenterology, CHU of LiÄege, Belgium.  Eur J Gastroenterol Hepatol, 1997 Oct, 9:10, 939-44

4. SERUM CONCENTRATIONS OF OROSOMUCOID: IMPROVED DECISION-MAKING FOR TAPERING PREDNISOLONE THERAPY IN PATIENTS WITH ACTIVE INFLAMMATORY BOWEL DISEASE?
Kjeldsen J; Lauritsen K; De Muckadell OB; Dept. of Medical Gastroenterology, Odense University Hospital, Denmark.  Scand J Gastroenterol, 1997 Sep, 32:9, 933-41

5. IBD ACTIVITY ASSESSMENT USING TECHNETIUM-99M-HMPAO LEUKOCYTES.
Arndt JW; Grootscholten MI; van Hogezand RA; Griffioen G; Lamers CB; Pauwels EK;  Department of Diagnostic Radiology and Nuclear Medicine, University Hospital Leiden, The Netherlands. Dig Dis Sci, 1997 Feb, 42:2, 387-93

6. INCREASED GASTRIC AND INTESTINAL PERMEABILITY IN PATIENTS WITH CROHN’S DISEASE.
Wyatt J; Oberhuber G; Pongratz S; Püspök A; Moser G; Novacek G; Lochs H; Vogelsang H; Department of Gastroenterology, Allgemeines Krankenhaus, University of Vienna, Austria.  Am J Gastroenterol, 1997 Oct, 92:10, 1891-6

7. INCREASED LEUKOCYTE ADHESIVENESS/AGGREGATION IN PATIENTS WITH IBD DURING REMISSION. FURTHER EVIDENCE FOR SUBCLINICAL INFLAMMATION. Arber N; Hallak A; Dotan I; Bujanover Y; Liberman E; Santo M; Moshkowitz M; Tiomny E; Aronson M; Berliner S; Gilat T;  Department of Gastroenterology, Tel-Aviv Medical Center Ichilov Hospital, Sackler Faculty of Medicine, Tel-Aviv University, Israel. Dis Colon Rectum, 1996 Jun, 39:6, 632-5

Go back to the front page