TY - JOUR
AU - MD, Antonino Marino,
AB - To the Editor: Tumor necrosis factor-alpha (TNF-α) antagonists are successfully used in the treatment of Crohn's disease (CD). The treatment is generally well tolerated, and the most common side effects include reactions at the injection site (with the subcutaneous variety), dyspnea, urticaria, and headache. Severe infusion reactions, anaphylaxis, development of tuberculosis, and opportunistic infections have also been reported, as well as severe thrombocytopenia, both in patients with inflammatory bowel disease1 and others.2,3 A 75-year-old man, affected with ileal and right colonic CD since 2005, was admitted to our outpatient clinic for a clinical relapse characterized by bloody diarrhea (5–6 bowel movements per day), abdominal pain with mild tenderness, asthenia, and a 5-kg decrease in body weight. He weighed 80 kg. Laboratory tests showed an increase in C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), mild anemia (10 g/ dL), but normal white blood cell and platelet counts. Liver and renal function tests were normal. The patient was on azathioprine at a dosage of 2 mg/kg because of previous evidence of steroid-dependency (3 years prior). His family doctor had also added a high dose of prednisone (50 mg), although symptoms recurred during the dose reduction. An ileocolonoscopy showed extension of disease to the entire colon, as well as to the terminal ileum, with severe activity. On the basis of this finding, and after informing the patient of the risks and benefits related to the treatment, we decided to start infliximab at a dosage of 5 mg/kg (induction phase at 0, 2, and 6 weeks, with scheduled infusions every 8 weeks). Pretreatment screening was negative for infections, abscesses, or malignancies. The patient's symptoms improved dramatically after the induction phase, but laboratory tests after the fifth infusion showed a severe thrombocytopenia (35 x 109/L) with no signs of bleeding. Hemoglobin and white blood cell count were normal, as were liver and renal function tests. The patient had not been taking any other pharmaceuticals, so pharmaceutical side effect was ruled out as the cause. A further ileocolonoscopy showed a complete endoscopical remission. As a result, we decided to discontinue infliximab, while continuing to monitor the full blood count. One month later the platelet count increased to 150 x 109/L but with high values of CRP and ESR. Considering the complete mucosal healing and the risk of clinical recurrence we decided to switch to adalimumab (induction phase with 160/80 mg s.c. followed by 40 mg e.o.w). At the time of writing, the patient was doing well and at 3 months of follow-up his full blood count was normal, with normal values of CRP and ESR. As recently shown, advanced age is an independent risk factor for severe adverse event in patients given anti-TNF-α therapy,4 although there were no reports of thrombocytopenia. The exact mechanism of cytopenia as a result of TNF-α blocker therapy is unclear. Theoretically, TNF-α has the potential to block stem-cell differentiation, with resultant bone marrow failure through the regulation of some proinflammatory cytokines.5 Interestingly, there are some reports of a significant remission of an autoimmune thrombocytopenia in CD patients treated with anti-TNF-α antibodies.6 One case report,2 also, describes a safe switch to another TNF-α antagonist with no recurrence of thrombocytopenia. In our patient there was a highly likely relation between the anti-TNF-α antibodies and the onset of thrombocytopenia, given the absence of other drugs with potential thrombocytopenic effect, and the complete mucosal healing, which would seem to reflect the anti-TNF-α action. It is well known that the ultimate treatment goal in the management of CD should be to modify the clinical course of the disease, and mucosal healing has been shown to be linked with reductions in hospitalizations and surgeries, as well as with long-term remission.7 In our patient, considering the mucosal healing, the clinical remission, his previous clinical history, and according to the literature, we tried to switch to a second TNF-α antagonist treatment, maintaining a close follow-up, without thrombocytopenia recurrence. Nevertheless this therapeutic approach should be evaluated case by case. References 1. Salar A, Bessa X, Muñiz E, et al.  . Infliximab and adalimumab-induced thrombocytopenia in a woman with colonic Crohn's disease. Gut . 2007; 56: 1169– 1170. Google Scholar CrossRef Search ADS PubMed  2. Pathare SK, Heycock C, Hamilton J. TNFalpha blocker-induced thrombocytopenia. Rheumatology (Oxford) . 2006; 45: 1313– 1314. Google Scholar CrossRef Search ADS PubMed  3. Chen M, Holland MJ, Mir MR, et al.  . Frequency of thrombocytopenia in psoriasis patients treated with tumor necrosis factor-α inhibitors. J Drugs Dermatol.  2011; 10: 280– 284. Google Scholar PubMed  4. Cottone M, Kohn A, Daperno M, et al.  . Advanced age is an independent risk factor for severe infections and mortality in patients given anti-tumor necrosis factor therapy for inflammatory bowel disease. Clin Gastroenterol Hepatol . 2011; 9: 30– 35. Google Scholar CrossRef Search ADS PubMed  5. Rusten LS, Jacobsen FW, Lesslauer W, et al.  . Bifunctional effects of tumor necrosis factorα (TNFα) on the growth of mature and primitive human hematopoietic progenitor cells: involvement of p55 and p75 TNF receptors. Blood . 1994; 83: 3152– 3159. Google Scholar PubMed  6. de Rossi TM, Krauss N, Voll RE, et al.  . Long-term partial remission of autoimmune thrombocytopenia in a patient treated with the anti-tumor necrosis factor-alpha antibody infliximab for refractory fistulizing Crohn’s disease. Digestion . 2008; 78: 195– 200. Google Scholar CrossRef Search ADS PubMed  7. Danese S, Colombel JF, Reinisch W, et al.  . Review article: infliximab for Crohn’s disease treatment—shifting therapeutic strategies after 10 years of clinical experience. Aliment Pharmacol Ther . 2011; 33: 857– 869. Google Scholar CrossRef Search ADS PubMed  Copyright © 2013 Crohn's & Colitis Foundation of America, Inc.
TI - Infliximab-induced Thrombocytopenia in an Elderly Patient with Ileocolonic Crohn's Disease
JF - Inflammatory Bowel Diseases
DO - 10.1002/ibd.22989
DA - 2013-04-01
UR - https://www.deepdyve.com/lp/oxford-university-press/infliximab-induced-thrombocytopenia-in-an-elderly-patient-with-xKFTrrZzc6
SP - E52
EP - E53
VL - 19
IS - 4
DP - DeepDyve
ER -