Int J Colorectal Dis DOI 10.1007/s00384-014-1903-1
LETTER TO THE EDITOR
A role of colectomy in immune thrombocytopenic purpura associated with ulcerative colitis: a case report and a review of the literature Ayako Negoro & Tomoko Takano & Hitoshi Tajiri & Riichiro Nezu & Nohisa Kawamura & Stephen Brooks
Accepted: 2 May 2014 # Springer-Verlag Berlin Heidelberg 2014
Dear Editor: We report our experience with a 13-year-old girl with ulcerative colitis associated with chronic immune thrombocytopenic purpura (ITP). Since ulcerative colitis had become steroiddependent in this patient, a total colectomy was performed. The platelet count has normalized after the colectomy, suggesting that a colectomy performed for ulcerative colitis was also effective against ITP in this case. We suggest that colectomy may be indicated in patients with refractory ITP associated with ulcerative colitis. Ulcerative colitis is associated with extra-intestinal manifestations in various target tissues [1]. However, the concurrence of ulcerative colitis and ITP is rare. There has been no established treatment for ulcerative colitis-associated ITP, which is often difficult to manage and may be fatal in some cases. An 11-year-old girl visited our center with a 2-month history of frequent bloody diarrhea and anemia. She had no remarkable past personal or family medical history. She was diagnosed with ulcerative colitis on the findings of colonoscopy and histopathological examination. The patient was treated with mesalasine (5-aminosalicylic acid, 5-ASA), A. Negoro : T. Takano (*) : H. Tajiri Department of Pediatrics, Osaka General Medical Center, 3-1-56 Bandaihigashi, Sumiyoshi-ku, Osaka, Japan e-mail: [email protected] R. Nezu Department of Surgery, Osaka Rosai Hospital, 1179-3 Nakasone-chou, Kita-ku, Sakai, Ōsaka 591-8025, Japan N. Kawamura Department of Pediatrics, Osaka Rosai Hospital, 1179-3 Nakasone-chou, Kita-ku, Sakai, Ōsaka 591-8025, Japan S. Brooks Department of Microbiology/Immunology, State University of New York at Buffalo, 3435 Main St, Buffalo, NY 14214, USA
prednisolone, and azathiopurine, and an endoscopic confirmed remission was achieved after 3 months of treatment. Prednisolone was stopped and 5-ASA and azathiopurine were maintained. The patient’s symptoms recurred 6 months after the first remission. Her symptoms were ameliorated by steroid administration but repeatedly recurred with the withdrawal of prednisolone. When the sixth recurrence was observed at the age of 13.8 years, oral administration of tacrolimus (0.25 mg/kg/day) was introduced to induce a remission. Tacrolimus therapy was effective, and remission was achieved after 1 month of tacrolimus therapy; however, the platelet count decreased from 18.9 to 2.5×104/μl after 2 months of tacrolimus therapy. Blood examinations showed WBC counts 3,500/μl and hemoglobulin 11.3 g/dl. Bone marrow examination revealed a normocellular marrow with a normal number of megakaryocytes. Platelet-associated IgG (PAIgG) was slightly elevated to 25.4 ng/107 cells (normal range, 5–25), and no splenomegaly was found on abdominal ultrasonography. Immune thrombocytopenic purpura associated with ulcerative colitis was diagnosed based on these findings. Tacrolimus therapy was stopped and prednisolone administration was resumed, resulting in the resolution of bloody diarrhea and the increase of the platelet count to 21.2×104/μl. When taking both tacrolimus and prednisolone, the patient developed drug-induced diabetes mellitus and insulin therapy was introduced. At the age of 14.4 years, bloody stools and abdominal pain appeared after cessation of steroid therapy, and the patient was admitted. On admission, the height was 150.5 cm (−1.17 SD) and body weight was 37.6 kg (−1.61 SD), and there was mild tenderness in the right lower abdomen. Abdominal ultrasonography revealed mild thickening of the bowel wall that extended from the rectum to the descending colon. The platelet count had decreased to 2.0 × 104/μl and PAIgG was 43.3 ng/107 cells. Treatment with intravenous administration of cyclosporine (2 mg/kg/day), mizoribin, 5-ASA, and
Int J Colorectal Dis
probiotics was initiated but was not successful in controlling symptoms. Since the total dose of steroid exceeded 10 g at that time and there was no effective maintenance therapy of ulcerative colitis for this patient, surgical treatment was considered. Immunoglobulin (IVIG, 1 g/kg/day×two times) was intravenously administrated as part of the preparation for subsequent colectomy. The platelet count increased to 12.1×104/μl, and total colectomy without splenectomy was performed at the age of 14.5 years. The platelet count increased to 20.6×104/μl at 14 days after surgery and has remained within normal ranges during the following 1 year. Ulcerative colitis is known to have various extra-intestinal manifestations. Among them, ITP is considered to be a rare manifestation. It has been observed in 0.5 % of adult ulcerative colitis patients [1]. In recent reviews, there are very few descriptions of ITP as IBD-related extra-intestinal manifestations [2]. Until now, a literature survey has shown 29 cases with ulcerative colitis and ITP [3]. The median age at diagnosis of ulcerative colitis in those cases was 20.0 years old (range 5–63 years old), and the male/female ratio was 15/14. The median age at onset of ITP was 21.5 years old (range 6–63 years old); 10 of the 29 patients were children and adolescents. The demographic data suggest that this complication tends to occur in a younger population of ulcerative colitis patients. Ulcerative colitis was treated with steroids in 28 patients, 5ASA acid in 25, azathiopurine in four, cyclosporine in two, leukocyte aphresis in one, and anti-tumor necrosis factor-α preparations in one. Complicated ITP was successfully managed with medical treatment in 15 of the 29 patients; prednisolone in seven, IVIG in four, a combination of prednisolone and IVIG in two, anti-Rh (D) antibodies in one, and cyclosporine in one. In 12 of the 29 patients, ITP was not controlled by medical treatment and was cured or ameliorated by surgical treatment; including splenectomy in six and colectomy in six patients. Of note, for the six patients who underwent colectomy, the surgical treatment eventually improved both ITP and ulcerative colitis. On the other hand, the remaining two patients who had persistent ITP associated with refractory ulcerative colitis and failed to response to medical treatment against ITP eventually died due to cerebral hemorrhage [3]. Our preliminary review suggests that when ITP complicated with ulcerative colitis cannot be controlled by medical
treatment, colectomy should be immediately indicated for the control of this condition. Although the pathogenesis of thrombocytopenia associated with ulcerative colitis has not yet be clarified, PAIgG were positive in 14 of 16 patients who were tested for this antibody among the 29 patients with ITP associated with ulcerative colitis. ITP often occurs during periods when ulcerative colitis is in the active condition and is resolved after the successful control of ulcerative colitis by medical or surgical treatment in the reported cases, including ours. These findings suggest that ITP with ulcerative colitis might be considered to have an autoimmune mechanism and also to be dependent on the activity of ulcerative colitis. Zlatanic et al. have proposed that antibodies to the glycoproteins of intestinal bacteria are produced in patients with ulcerative colitis who have had a disruption of the mucosal barrier in the colon. The putative antibodies in turn cross-react with surface antigens on platelets and continuously promote increased phagocytosis of platelets as long as the disrupted mucosal barrier remains due to active disease in the colon of ulcerative colitis patients [4]. Since ITP is a rare complication of ulcerative colitis and may be fatal in cases with refractory ITP, a further accumulation of such cases is necessary to establish a role for surgery in treatment of refractory ITP complicated with ulcerative colitis.
References 1. Edwards FC, Truelove SC (1964) The course and prognosis of ulcerative colitis. III. Complications. Gut 5:1–22 2. Larsen S, Bendtzen K, Nielsen OH (2010) Extraintestinal manifestations of inflammatory bowel disease: epidemiology, diagnosis, and management. Ann Med 42:97–114 3. Mares WG, Gerver J, Masclee AA, Pierik M (2011) Anti-TNF treatment of ulcerative colitis associated with idiopathic thrombocytopenic purpura. Inflamm Bowel Dis 17:864–865 4. Zlatanic J, Korelitz BI, Wisch N, Kim P, Ammirati M, Schwarz S, Gruenstein S, Lipsey L (1997) Inflammatory bowel disease and immune thrombocytopenic purpura: is there a correlation? Am J Gastroenterol 92:2285–2288
LETTER TO THE EDITOR
A role of colectomy in immune thrombocytopenic purpura associated with ulcerative colitis: a case report and a review of the literature Ayako Negoro & Tomoko Takano & Hitoshi Tajiri & Riichiro Nezu & Nohisa Kawamura & Stephen Brooks
Accepted: 2 May 2014 # Springer-Verlag Berlin Heidelberg 2014
Dear Editor: We report our experience with a 13-year-old girl with ulcerative colitis associated with chronic immune thrombocytopenic purpura (ITP). Since ulcerative colitis had become steroiddependent in this patient, a total colectomy was performed. The platelet count has normalized after the colectomy, suggesting that a colectomy performed for ulcerative colitis was also effective against ITP in this case. We suggest that colectomy may be indicated in patients with refractory ITP associated with ulcerative colitis. Ulcerative colitis is associated with extra-intestinal manifestations in various target tissues [1]. However, the concurrence of ulcerative colitis and ITP is rare. There has been no established treatment for ulcerative colitis-associated ITP, which is often difficult to manage and may be fatal in some cases. An 11-year-old girl visited our center with a 2-month history of frequent bloody diarrhea and anemia. She had no remarkable past personal or family medical history. She was diagnosed with ulcerative colitis on the findings of colonoscopy and histopathological examination. The patient was treated with mesalasine (5-aminosalicylic acid, 5-ASA), A. Negoro : T. Takano (*) : H. Tajiri Department of Pediatrics, Osaka General Medical Center, 3-1-56 Bandaihigashi, Sumiyoshi-ku, Osaka, Japan e-mail: [email protected] R. Nezu Department of Surgery, Osaka Rosai Hospital, 1179-3 Nakasone-chou, Kita-ku, Sakai, Ōsaka 591-8025, Japan N. Kawamura Department of Pediatrics, Osaka Rosai Hospital, 1179-3 Nakasone-chou, Kita-ku, Sakai, Ōsaka 591-8025, Japan S. Brooks Department of Microbiology/Immunology, State University of New York at Buffalo, 3435 Main St, Buffalo, NY 14214, USA
prednisolone, and azathiopurine, and an endoscopic confirmed remission was achieved after 3 months of treatment. Prednisolone was stopped and 5-ASA and azathiopurine were maintained. The patient’s symptoms recurred 6 months after the first remission. Her symptoms were ameliorated by steroid administration but repeatedly recurred with the withdrawal of prednisolone. When the sixth recurrence was observed at the age of 13.8 years, oral administration of tacrolimus (0.25 mg/kg/day) was introduced to induce a remission. Tacrolimus therapy was effective, and remission was achieved after 1 month of tacrolimus therapy; however, the platelet count decreased from 18.9 to 2.5×104/μl after 2 months of tacrolimus therapy. Blood examinations showed WBC counts 3,500/μl and hemoglobulin 11.3 g/dl. Bone marrow examination revealed a normocellular marrow with a normal number of megakaryocytes. Platelet-associated IgG (PAIgG) was slightly elevated to 25.4 ng/107 cells (normal range, 5–25), and no splenomegaly was found on abdominal ultrasonography. Immune thrombocytopenic purpura associated with ulcerative colitis was diagnosed based on these findings. Tacrolimus therapy was stopped and prednisolone administration was resumed, resulting in the resolution of bloody diarrhea and the increase of the platelet count to 21.2×104/μl. When taking both tacrolimus and prednisolone, the patient developed drug-induced diabetes mellitus and insulin therapy was introduced. At the age of 14.4 years, bloody stools and abdominal pain appeared after cessation of steroid therapy, and the patient was admitted. On admission, the height was 150.5 cm (−1.17 SD) and body weight was 37.6 kg (−1.61 SD), and there was mild tenderness in the right lower abdomen. Abdominal ultrasonography revealed mild thickening of the bowel wall that extended from the rectum to the descending colon. The platelet count had decreased to 2.0 × 104/μl and PAIgG was 43.3 ng/107 cells. Treatment with intravenous administration of cyclosporine (2 mg/kg/day), mizoribin, 5-ASA, and
Int J Colorectal Dis
probiotics was initiated but was not successful in controlling symptoms. Since the total dose of steroid exceeded 10 g at that time and there was no effective maintenance therapy of ulcerative colitis for this patient, surgical treatment was considered. Immunoglobulin (IVIG, 1 g/kg/day×two times) was intravenously administrated as part of the preparation for subsequent colectomy. The platelet count increased to 12.1×104/μl, and total colectomy without splenectomy was performed at the age of 14.5 years. The platelet count increased to 20.6×104/μl at 14 days after surgery and has remained within normal ranges during the following 1 year. Ulcerative colitis is known to have various extra-intestinal manifestations. Among them, ITP is considered to be a rare manifestation. It has been observed in 0.5 % of adult ulcerative colitis patients [1]. In recent reviews, there are very few descriptions of ITP as IBD-related extra-intestinal manifestations [2]. Until now, a literature survey has shown 29 cases with ulcerative colitis and ITP [3]. The median age at diagnosis of ulcerative colitis in those cases was 20.0 years old (range 5–63 years old), and the male/female ratio was 15/14. The median age at onset of ITP was 21.5 years old (range 6–63 years old); 10 of the 29 patients were children and adolescents. The demographic data suggest that this complication tends to occur in a younger population of ulcerative colitis patients. Ulcerative colitis was treated with steroids in 28 patients, 5ASA acid in 25, azathiopurine in four, cyclosporine in two, leukocyte aphresis in one, and anti-tumor necrosis factor-α preparations in one. Complicated ITP was successfully managed with medical treatment in 15 of the 29 patients; prednisolone in seven, IVIG in four, a combination of prednisolone and IVIG in two, anti-Rh (D) antibodies in one, and cyclosporine in one. In 12 of the 29 patients, ITP was not controlled by medical treatment and was cured or ameliorated by surgical treatment; including splenectomy in six and colectomy in six patients. Of note, for the six patients who underwent colectomy, the surgical treatment eventually improved both ITP and ulcerative colitis. On the other hand, the remaining two patients who had persistent ITP associated with refractory ulcerative colitis and failed to response to medical treatment against ITP eventually died due to cerebral hemorrhage [3]. Our preliminary review suggests that when ITP complicated with ulcerative colitis cannot be controlled by medical
treatment, colectomy should be immediately indicated for the control of this condition. Although the pathogenesis of thrombocytopenia associated with ulcerative colitis has not yet be clarified, PAIgG were positive in 14 of 16 patients who were tested for this antibody among the 29 patients with ITP associated with ulcerative colitis. ITP often occurs during periods when ulcerative colitis is in the active condition and is resolved after the successful control of ulcerative colitis by medical or surgical treatment in the reported cases, including ours. These findings suggest that ITP with ulcerative colitis might be considered to have an autoimmune mechanism and also to be dependent on the activity of ulcerative colitis. Zlatanic et al. have proposed that antibodies to the glycoproteins of intestinal bacteria are produced in patients with ulcerative colitis who have had a disruption of the mucosal barrier in the colon. The putative antibodies in turn cross-react with surface antigens on platelets and continuously promote increased phagocytosis of platelets as long as the disrupted mucosal barrier remains due to active disease in the colon of ulcerative colitis patients [4]. Since ITP is a rare complication of ulcerative colitis and may be fatal in cases with refractory ITP, a further accumulation of such cases is necessary to establish a role for surgery in treatment of refractory ITP complicated with ulcerative colitis.
References 1. Edwards FC, Truelove SC (1964) The course and prognosis of ulcerative colitis. III. Complications. Gut 5:1–22 2. Larsen S, Bendtzen K, Nielsen OH (2010) Extraintestinal manifestations of inflammatory bowel disease: epidemiology, diagnosis, and management. Ann Med 42:97–114 3. Mares WG, Gerver J, Masclee AA, Pierik M (2011) Anti-TNF treatment of ulcerative colitis associated with idiopathic thrombocytopenic purpura. Inflamm Bowel Dis 17:864–865 4. Zlatanic J, Korelitz BI, Wisch N, Kim P, Ammirati M, Schwarz S, Gruenstein S, Lipsey L (1997) Inflammatory bowel disease and immune thrombocytopenic purpura: is there a correlation? Am J Gastroenterol 92:2285–2288
