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• Author's Reply
  Jonathan M Rhodes
  Published on: 15 July 2004
• Inflammatory Markers in Crohn's Disease
  John N Gordon
  Published on: 30 June 2004

• Published on: 15 July 2004

  Author's Reply

  • Jonathan M Rhodes, Professor of Medicine
  • Other Contributors:
    • Manu Nayar

  Dear Editor,

  We think Gordon has been rather selective with his citation of the literature.[1] The issue here is whether serum C reactive protein estimation has acceptable sensitivity in undiagnosed patients presenting for the first time with symptomatic Crohn’s disease. It was first reported for this purpose by Shine et al who found that 19 of 19 newly presenting symptomatic Crohn’s disease patients had...

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  Dear Editor,

  We think Gordon has been rather selective with his citation of the literature.[1] The issue here is whether serum C reactive protein estimation has acceptable sensitivity in undiagnosed patients presenting for the first time with symptomatic Crohn’s disease. It was first reported for this purpose by Shine et al who found that 19 of 19 newly presenting symptomatic Crohn’s disease patients had elevated serum C reactive protein.[2] Beattie et al confirmed these findings in a paediatric population with 26 of 26 children with symptomatic Crohn’s disease having an elevated serum C reactive protein.[3] The 95% sensitivity we quoted was the result of an unpublished study done by one of us (JMR) some years ago in an adult population at the Royal Free Hospital.

  The three papers cited by Gordon do not really address the same issue. Boirivant et al describe a longitudinal study of patients with established Crohn's disease during follow-up.[4] Cellier et al again studied patients with established Crohn’s disease and present data for correlations between CRP measurement and disease activity that do not allow extrapolation of a value for sensitivity.[5] Tibble et al focus on faecal calprotectin. They provide data for serum CRP in 263 patients with various organic diseases of whom only 84 had Crohn’s disease and do not provide separate CRP data for the Crohn’s disease patients.[6]

  We accept that serum C reactive protein is not always elevated in symptomatic Crohn’s disease but 11.5% of the adult European population have irritable bowel syndrome [7] and it is not appropriate to investigate all such individuals by “appropriate endoscopic and radiological investigations” particularly if the patient is young, has no alarm symptoms or relevant family history and normal physical examination. In that setting, normal results for serum C reactive protein, coeliac disease antibodies and full blood count are very useful in helping to identify patients in whom a primary diagnosis of irritable bowel syndrome can safely be made. A recent study suggests that highly sensitive assay for serum C reactive protein, using a cut-off value of 2.3 mg/l, has a sensitivity of 100% in differentiating functional bowel disorders from new cases of inflammatory bowel disease [8].

  References

  (1) Gordon J N. Inflammatory markers in Crohn's disease [electronic response to Nayar M, Rhodes J M. Management of inflammatory bowel disease] postgradmedj.com 2004 http://pmj.bmjjournals.com/cgi/eletters/80/942/206#109

  (2) Shine B, Berghouse L, Jones LE, Landon J. C-reactive protein as an aid in the differentiation of functional and inflammatory bowel disorders. Clin Chim Acta 1985;148:105-9.

  (3) Beattie RM, Walker-Smith JA, Murch SH. Indications for investigation of chronic gastrointestinal symptoms. Arch Dis Child 1995;73:354-5.

  (4) Boirivant M, Leoni M, Tariciotti D, Fais S, Squarcia O, Pallone F. The clinical significance of serum C reactive protein levels in Crohn’s disease. Results of a prospective longitudinal study. J Clin Gastroenterol 1988;10:401-5.

  (5) Cellier C, Sahmoud T, Froguel E, Adenis A, Belaiche J, Bretagne JF, Florent C, Bouvry M, Mary JY, Modigliani R. Correlations between clinical activity, endoscopic severity, and biological parameters in colonic or ileo-colonic Crohn’s disease. A prospective multicentre study of 121 cases. The Groupe d’Etudes Therapeutiques des Affections Inflammatoires Digestives. Gut 1994;35:231-5.

  (6) Tibble JA, Sigthorsson G, Foster R, Forgacs I, Bjarnason I. Use of surrogate markers of inflammation and Rome criteria to distinguish organic from non-organic intestinal disease. Gastroenterology 2002;123:450-60.

  (7) Hungin AP, Whorwell PJ, Tack J, Mearin F. The prevalence, patterns and impact of irritable bowel syndrome: an international survey of 40,000 subjects. Aliment Pharmacol Ther 2003;17:643-50.

  (8) Poullis AP, Zar S, Sundaram KK, Moodie SJ, Risley P, Theodossi A, Mendall MA. A new, highly sensitive assay for C-reactive protein can aid the differentiation of inflammatory bowel disorders from constipation- and diarrhoea-predominant functional bowel disorders. Eur J Gastroenterol Hepatol 2002;14:409-12.

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  Conflict of Interest:
  None declared.

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• Published on: 30 June 2004

  Inflammatory Markers in Crohn's Disease

  • John N Gordon, Clinical Research Fellow

  Dear Editor

  I read with interest the review of the management of inflammatory bowel disease by Nayar et al, in which the authors elegantly highlight the major points for the general physician. However I was concerned by the potentially seriously misleading statement that serum C-reactive protein (CRP) concentration is raised in over 95% of patients with symptomatic Crohn's disease, and is useful in distingu...

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  Dear Editor

  I read with interest the review of the management of inflammatory bowel disease by Nayar et al, in which the authors elegantly highlight the major points for the general physician. However I was concerned by the potentially seriously misleading statement that serum C-reactive protein (CRP) concentration is raised in over 95% of patients with symptomatic Crohn's disease, and is useful in distinguishing it from irritable bowel syndrome. This is not the case.

  Crohn's disease can be difficult to diagnose and the non-specific symptoms mean that in many patients diagnosis is delayed with potentially hazardous consequences. Literature from the past fifteen years has clearly shown that inflammatory markers are neither sensitive nor specific in identifying patients with Crohn's disease and distinguishing them from those with irritable bowel syndrome. In a prospective longitudinal study of 101 patients by Boirivant et al, one-third of patients with clinically active Crohn's disease had normal CRP levels.[1] More recently Cellier et al. assessed the correlation between clinical activity, endoscopic severity, and biological parameters in 121 consecutive patients with Crohn's disease. They concluded that Crohn's disease clinical activity seems to be virtually independent of the severity of the mucosal lesions and biological activity.[2] Finally in a recent study by Tibble et al investigating the use of surrogate markers and Rome criteria to distinguish non-organic from organic disease CRP was shown to have a sensitivity of 50% and specificity of 68% for the presence of organic disease.[3] Thus, it should be emphasised that a normal CRP does not preclude the diagnosis of Crohn's disease, and that until better non- invasive tests emerge physicians will have to continue to rely on clinical judgment in conjunction with appropriate endoscopic and radiological investigations to distinguish inflammatory bowel disease from irritable bowel syndrome.

  References

  1. Boirivant M, Leoni M, Tariciotti D, Fais S, Squarcia O, Pallone F. The clinical significance of serum C reactive protein levels in Crohn's disease. Results of a prospective longitudinal study. J Clin Gastroenterol. 1988;10:401-5.

  2. Cellier C, Sahmoud T, Froguel E, Adenis A, Belaiche J, Bretagne JF, Florent C, Bouvry M, Mary JY, Modigliani R. Correlations between clinical activity, endoscopic severity, and biological parameters in colonic or ileocolonic Crohn's disease. A prospective multicentre study of 121 cases. The Groupe d'Etudes Therapeutiques des Affections Inflammatoires Digestives. Gut. 1994;35:231-5

  3. Tibble JA, Sigthorsson G, Foster R, Forgacs I, Bjarnason I. Use of surrogate markers of inflammation and Rome criteria to distinguish organic from nonorganic intestinal disease. Gastroenterology. 2002;123:450-60

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  Conflict of Interest:
  None declared.

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