Anti-TNF treatment of ulcerative colitis associated with idiopathic thrombocytopenic purpura.

To the Editor: Crohn’s disease (CD) and ulcerative colitis (UC) are associated with a variety of extraintestinal manifestations for which anti-tumor necrosis factor (TNF) therapy is usually an effective treatment. Previous reports have described immune thrombocytopenic purpura (ITP) in patients with UC and hypothesized that it represents an immunologically mediated extraintestinal manifestation. In 10 out of 18 published cases the ITP and/or UC were refractory to medical treatment (corticosteroids, mesalazine, cyclosporine, intravenous immunoglobulins) and patients eventually received surgical treatment (either splenectomy or colectomy) (Table 1). Surgical treatment proved to be effective in these published cases. We report for the first time a case of active UC and coexistent ITP that both responded well to infliximab therapy. In 2002 a 32-year-old man presented with a 4-week history of bloody diarrhea. Sigmoidoscopy showed a leftsided colitis with erythematous mucosa, exudates and frank hemorrhage (Mayo endoscopic subscore 2). Colonic biopsies showed significant inflammation with crypt abscesses and atrophy of glands, compatible with UC. The patient was successfully treated with oral and local mesalazine. In July 2008 he presented with loose stools with hematochezia, passage of mucus, urgency, and abdominal cramps. He did not use any medication between 2003 and 2008. The patient was admitted to the hospital since the whole blood count revealed severe thrombocytopenia (thrombocytes 15*10/L, normal values 130–350*10/L). The hemoglobin and inflammation parameters were normal (hemoglobin 8.5 mmol/L, leukocytes 5.2*10/L, C-reactive protein 7.3 mg/L). Endoscopy showed a severe pancolitis (Mayo endoscopic subscore 3). Colonic biopsies showed active inflammation compatible with UC and did not show cytomegalovirus inclusions (CMV). The patient was treated with prednisolone 60 mg once daily intravenously. Within 1 week the thrombocytes count increased to 97*10/L, after which the patient was discharged with prednisolone orally and we planned to start 6-mercaptopurine. After 1 week the patient was readmitted with severe thrombocytopenia (thrombocytes 10*10/L). Prednisolone was restarted. Because of a lack of response, immunoglobulins 1 g/ kg intravenously were administered on 2 consecutive days (days 17 and 18). A bone marrow aspiration was performed which showed reactive changes with an increase of megakaryocytes with an abnormal morphology, pointing to peripheral thrombocytopenia. Viral serology including human immunodeficiency virus (HIV), hepatitis C virus (HCV), and CMV was negative. Therefore, the thrombocytopenia was considered secondary to UC. Because of a lack of clinical response of the colitis, infliximab (5 mg/kg body weight) was added on day 21. After this infusion his clinical condition improved within a few days; the frequency of loose bloody stools decreased. The thrombocyte count increased to 224*10/L on day 25. The infliximab infusions were repeated at week 2 and week 6. On day 39 the thrombocyte count was 152*10/L. On day 64, right before the third infliximab infusion, the thrombocyte count had decreased to 113*10/L (Fig. 1). Because the thrombocyte count decreased after several weeks the interval between two infliximab infusions was set at 6 weeks. Platelet counts decreased after tapering prednisolone below 15 mg per day until dose attenuation of the infliximab to 10 mg/ kg. The prednisolone could be tapered and discontinued within 6 weeks. The patient has remained in clinical remission ever since. Infliximab has proven efficacy in moderate-to-severe UC refractory to conventional treatment. ITP is presumed to be related to the combination of increased platelet destruction along with inhibition of megakaryocyte platelet production via the production of specific IgG autoantibodies by the patient’s B cells, most often directed against platelet membrane glycoproteins such as GPIIb/IIIa. Bowel inflammation results in an increased permeability and subsequent translocation of gut microbiota through the mucosa that might result in platelet antibody formation through crossreactivity; furthermore, the inflammatory process of UC might induce degradation of platelet glycoproteins and subsequent antibody formation. In our patient medical treatment with high-dose prednisolone failed to control the colonic inflammation and the ITP. To prevent colectomy rescue therapy with infliximab was added successfully. Possible mechanisms of action of infliximab are: the effect on the inflammatory disease itself and the induction of mucosal healing. We suggest infliximab might be an interesting option in UC-related ITP refractory to steroids.