Digestive Diseases and Sciences

, Volume 53, Issue 8, pp 2079–2082 | Cite as

RETRACTED ARTICLE: Gastric Changes Following Colchicine Therapy in Patients with FMF

  • Wael Ismail Al-Daraji
  • Riham M. W. Al-Mahmoud
  • Mohammed Ilyas
Original Paper


Background Familial Mediterranean fever (FMF) is also called recurrent polyserositis. The salient features of this disease include brief recurrent episodes of peritonitis, pleuritis, and arthritis, which are usually associated with fever. Colchicine is highly effective in the treatment of FMF and in preventing the development of recurrent attacks and amyloidosis, and it is essential to make the correct diagnosis and institute daily therapy with colchicine (0.5–0.6 mg bid). Colchicine is used to treat a variety of conditions but it is known to have gastrointestinal (GI) side effects. In this study, effects of colchicines on the gastrointestinal tract were evaluated in patients with FMF treated with colchicine. Methods Biopsies were reviewed from 43 patients attending Ain Shams University Hospital (Egypt) who were diagnosed with FMF and treated with colchicine. One-hundred and twelve GI biopsies, obtained over a 14-year period, were reviewed. This included biopsies from stomach body (38), stomach antrum (50), and colon (24). In addition, gastric biopsies were reviewed from 17 control patients who did not have FMF and were not on colchicine. Results Three patients known to have FMF and on colchicine therapy showed typical histological features of colchicine (metaphase mitoses, epithelial pseudoproliferation, mucin depletion, and frequent apoptosis). These features were seen only in gastric antral biopsies and not in colonic biopsies. None of the control group showed the characteristic morphological features of colchicine toxicity. Conclusion This is the first report of histological changes seen in the stomach following colchicine therapy. In contrast with previous reports, we did not find any definitive change in the large intestine. Our data show that gastric changes can be encountered in symptomatic patients who have recently had colchicine. If these finding are seen histologically, they merit correlation with the clinical impression and should not be interpreted as toxicity in isolation.


Colchicine GI effects FMF Ring mitoses Antrum 



The authors thank Professor M.S. Zaki (Head of Surgery at Aim Shams University Hospitals) for his continuous help and support.


  1. 1.
    Cazeneuve C, Ajrapetyan H, Papin S et al (2000) Identification of MEFV-independent modifying genetic factors for familial Mediterranean fever. Am J Hum Genet 67:1136–1143PubMedGoogle Scholar
  2. 2.
    Cazeneuve C, Hovannesyan Z, Genevieve D et al (2003) Familial Mediterranean fever among patients from Karabakh and the diagnostic value of MEFV gene analysis in all classically affected populations. Arthritis Rheum 48:2324–2331CrossRefPubMedGoogle Scholar
  3. 3.
    Dode C, Hazenberg BP, Pecheux C et al (2002) Mutational spectrum in the MEFV and TNFRSF1A genes in patients suffering from AA amyloidosis and recurrent inflammatory attacks. Nephrol Dial Transplant 17:1212–1217CrossRefPubMedGoogle Scholar
  4. 4.
    Booth DR, Gillmore JD, Booth SE et al (1998) Pyrin/marenostrin mutations in familial Mediterranean fever. Qjm 91:603–606CrossRefPubMedGoogle Scholar
  5. 5.
    Booth DR, Gillmore JD, Lachmann HJ et al (2000) The genetic basis of autosomal dominant familial Mediterranean fever. Qjm 93:217–221CrossRefPubMedGoogle Scholar
  6. 6.
    Booth DR, Lachmann HJ, Gillmore JD et al (2001) Prevalence and significance of the familial Mediterranean fever gene mutation encoding pyrin Q148. Qjm 94:527–531CrossRefPubMedGoogle Scholar
  7. 7.
    Chen X, Bykhovskaya Y, Tidow N et al (2000) The familial Mediterranean fever protein interacts and colocalizes with a putative Golgi transporter. Proc Soc Exp Biol Med 224:32–40CrossRefPubMedGoogle Scholar
  8. 8.
    Al-Alami JR, Tayeh MK, Najib DA et al (2003) Familial Mediterranean fever mutation frequencies and carrier rates among a mixed Arabic population. Saudi Med J 24:1055–1059PubMedGoogle Scholar
  9. 9.
    Livneh A, Aksentijevich I, Langevitz P et al (2001) A single mutated MEFV allele in Israeli patients suffering from familial Mediterranean fever and Behcet’s disease (FMF-BD). Eur J Hum Genet 9:191–196CrossRefPubMedGoogle Scholar
  10. 10.
    Livneh A, Langevitz P, Shinar Y et al (1999) MEFV mutation analysis in patients suffering from amyloidosis of familial Mediterranean fever. Amyloid 6:1–6PubMedGoogle Scholar
  11. 11.
    Settin A, El-Baz R, Abd Rasool M et al (2007) Clinical and molecular diagnosis of familial Mediterranean fever in Egyptian children. J Gastrointestin Liver Dis 16:141–145PubMedGoogle Scholar
  12. 12.
    Andreu JM, Timasheff SN (1982) Interaction of tubulin with single ring analogues of colchicine. Biochemistry 21:534–543CrossRefPubMedGoogle Scholar
  13. 13.
    Anilkumar TV, Sarraf CE, Hunt T et al (1992) The nature of cytotoxic drug-induced cell death in murine intestinal crypts. Br J Cancer 65:552–558PubMedGoogle Scholar
  14. 14.
    Stern N, Kupferschmidt H, Meier-Abt PJ (1997) [Follow-up and therapy of acute colchicine poisoning]. Schweiz Rundsch Med Prax 86:952–956Google Scholar
  15. 15.
    Webb DI, Chodos RB, Mahar CQ et al (1968) Mechanism of vitamin B12 malabsorption in patients receiving colchicine. N Engl J Med 279:845–850PubMedCrossRefGoogle Scholar
  16. 16.
    Ben-Chetrit E (2003) Familial Mediterranean fever (FMF) and renal AA amyloidosis-phenotype-genotype correlation, treatment and prognosis. J Nephrol 16:431–434PubMedGoogle Scholar
  17. 17.
    Ben-Chetrit E, Cohen R, Chajek-Shaul T (2002) Familial Mediterranean fever and Behcet’s disease—are they associated? J Rheumatol 29:530–534PubMedGoogle Scholar
  18. 18.
    Ben-Chetrit E, Lerer I, Malamud E et al (2000) The E148Q mutation in the MEFV gene: is it a disease-causing mutation or a sequence variant? Hum Mutat 15:385–386CrossRefPubMedGoogle Scholar
  19. 19.
    Ben-Chetrit E, Levy M. Colchicine: 1998 update. Semin Arthritis Rheum (1998)28:48–59Google Scholar
  20. 20.
    Ben-Chetrit E, Levy M (2001) Enigmas in familial Mediterranean fever (FMF). Clin Exp Rheumatol 19: S1–S5PubMedGoogle Scholar
  21. 21.
    Ben-Chetrit E, Urieli-Shoval S, Calko S et al (2002) Molecular diagnosis of FMF: lessons from a study of 446 unrelated individuals. Clin Exp Rheumatol 20: S25–S29PubMedGoogle Scholar
  22. 22.
    Iacobuzio-Donahue CA, Lee EL, Abraham SC et al (2001) Colchicine toxicity: distinct morphologic findings in gastrointestinal biopsies. Am J Surg Pathol 25:1067–1073CrossRefPubMedGoogle Scholar
  23. 23.
    Parfitt JR, Driman DK (2007) Pathological effects of drugs on the gastrointestinal tract: a review. Hum Pathol 38:527–536CrossRefPubMedGoogle Scholar
  24. 24.
    Hruban RH, Yardley JH, Donehower RC et al (1989) Taxol toxicity. Epithelial necrosis in the gastrointestinal tract associated with polymerized microtubule accumulation and mitotic arrest. Cancer 63:1944–1950CrossRefPubMedGoogle Scholar
  25. 25.
    Tishler RB, Lamppu DM, Park S et al (1995) Microtubule-active drugs taxol, vinblastine, and nocodazole increase the levels of transcriptionally active p53. Cancer Res 55:6021–6025PubMedGoogle Scholar
  26. 26.
    Debernardis D, Sire EG, De Feudis P et al (1997) p53 status does not affect sensitivity of human ovarian cancer cell lines to paclitaxel. Cancer Res 57:870–874PubMedGoogle Scholar
  27. 27.
    Woods CM, Zhu J, McQueney PA et al (1995) Taxol-induced mitotic block triggers rapid onset of a p53-independent apoptotic pathway. Mol Med 1:506–526PubMedGoogle Scholar
  28. 28.
    Torres K, Horwitz SB (1998) Mechanisms of Taxol-induced cell death are concentration dependent. Cancer Res 58:3620–3626PubMedGoogle Scholar
  29. 29.
    Haldar S, Chintapalli J, Croce CM (1996) Taxol induces bcl-2 phosphorylation and death of prostate cancer cells. Cancer Res 56:1253–1255PubMedGoogle Scholar
  30. 30.
    Stemmermann GN, Hayashi T (1971) Colchicine intoxication. A reappraisal of its pathology based on a study of three fatal cases. Hum Pathol 2:321–332CrossRefPubMedGoogle Scholar
  31. 31.
    Hart J, Lewin KJ, Peters RS et al (1993) Effect of long-term colchicine therapy on jejunal mucosa. Dig Dis Sci 38:2017–2021CrossRefPubMedGoogle Scholar
  32. 32.
    Race TF, Paes IC, Faloon WW (1970) Intestinal malabsorption induced by oral colchicine. Comparison with neomycin and cathartic agents. Am J Med Sci 259:32–41CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Wael Ismail Al-Daraji
    • 1
  • Riham M. W. Al-Mahmoud
    • 2
  • Mohammed Ilyas
    • 1
  1. 1.Department of Pathology, School of Molecular MedicineUniversity of NottinghamNottinghamUK
  2. 2.Department of MedicineAin Shams University HospitalCairoEgypt

Personalised recommendations