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Gastric bleeding in a patient with rheumatoid arthritis complicated by immune thrombocytopenic purpura
Available online at www.sciencedirect.com
Joint Bone Spine 75 (2008) 350e352 http://france.elsevier.com/direct/BONSOI/
Case report
Gastric bleeding in a patient with rheumatoid arthritis complicated by immune thrombocytopenic purpura Istva´n Ga´l a,*,1, Lajos To´th b,1, La´szlo´ Szegedi a, Gyula G. Kiss a a
2nd Department of Internal Medicine, Kene´zy Gyula Teaching Hospital, Barto´k B. u. 2-26, H-4043 Debrecen, Hungary b Department of Surgery, Kene´zy Gyula Teaching Hospital, Barto´k B. u. 2-26, H-4043 Debrecen, Hungary Accepted 6 June 2007 Available online 28 January 2008
Abstract Rheumatoid arthritis, in common with other systemic autoimmune diseases, can involve several other organs presenting with complex immunological manifestations. Immune thrombocytopenic purpura caused by an autoimmune reaction against platelets is an infrequent haematological complications. A female patient with rheumatoid arthritis rapidly developed extremely severe immune thrombocytopenic purpura upon suspending oral corticosteroid therapy. Besides the involvement of the mucosa of the coecum, ascending colon and the gastric antrum, the situation was further complicated by bleeding of a gastric polyp, at the nadir of the thrombocytopenic crisis. The bleeding was managed by endoscopic intervention and platelet count recovered upon high dose corticosteroid treatment within a couple of days. Ó 2008 Published by Elsevier Masson SAS. Keywords: Immune thrombocytopenic purpura; Rheumatoid arthritis; Gastrointestinal bleeding
1. Introduction Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease which can involve the musculoskeletal system and various organs such as the cardiovascular, respiratory, nervous, urogenital and haematopoietic system. The principal of RA therapy is immunosuppression in order to diminish the augmented autoimmune reaction against target organs. The course of the disease is characterized by eventual flare-ups which necessitate thorough follow-up of patients and precise dosage adjustment of immunosuppressants. Dose reduction of these drugs requires strict medical supervision in order to prevent a flare-up episode. We present the case of a female RA patient who arbitrarily abandoned corticosteroid therapy. Within 2 months her disease started to show signs of activity, then within 2 weeks she developed extremely severe immune thrombocytopenic purpura
* Corresponding author. Tel.: þ36 30 209 3460; fax: þ36 52 511 755. E-mail address: [email protected] (I. Ga´l). 1 These authors contributed equally to this work. 1297-319X/$ - see front matter Ó 2008 Published by Elsevier Masson SAS. doi:10.1016/j.jbspin.2007.06.010
(ITP), presenting with severe hematochesia. Sources of bleeding included suffusions in coecal, ascending colon and the gastric antrum mucosa, and a gastric polyp. 2. Clinical report A 64-year-old Caucasian female was admitted to our gastroenterology unit with a 1-day history of massive hematochesia, weakness and dizziness on 7 January 2006. She was diagnosed with RA in 1996, and had been taking a weekly dose of 7.5 mg methotrexate and a daily dose of 8 mg methylprednisolone for her disease. Worrying about the side effects of the drug, she decided to discontinue oral steroid therapy in October 2005. In December 2005, she developed arthralgia of both knees and reported morning stiffness in her metacarpophalangeal and proximal interphalangeal joints. Blood tests on 20 December 2005 showed a mild thrombocytosis with a platelet count of 560 000/ml, a haemoglobin concentration of 110 g/ l, leukocyte count of 5600/ml, C-reactive protein serum level of 74 mg/l, and physical examination revealed unilateral swelling and tenderness of knees, wrists and metacarpophalangeal and proximal interphalangeal joints.
I. Ga´l et al. / Joint Bone Spine 75 (2008) 350e352
On 6 January 2006, within 1 day, she developed hematochesia and weakness, necessitating her urgent admission to our department. Physical examination revealed pale skin, tachycardia, low systolic blood pressure, confluent purpura of the lower limbs and haematomas all over her body. Blood tests upon admission showed severe anaemia with a haemoglobin concentration of 65 g/l and an extremely low platelet count of 2000/ml with a normal leukocyte count. Serum electrolytes, liver and kidney function, and blood coagulation tests were normal. Immunoserology revealed high titres of rheumatoid factor of IgM type, polyclonal hypergammaglobulinaemia, a strong anti-cyclic citrullinated peptide antibody positivity and anti-nuclear factor positivity, although anti-platelet antibodies were not present. C-reactive protein level and erythrocyte sedimentation rate were both elevated. Bone marrow analysis did not show reduction in megakaryocyte counts which suggested a peripheral damage of platelets, further supporting the diagnosis of ITP. Colonoscopy revealed oedema and petechiae of coecal and ascending colon mucosa (Fig. S1g,h: see the Supplementary material associated with this article online); the terminal ileum had normal appearance, however. Biopsy samples were taken following correction of platelet count; histological analysis showed no signs of inflammation and was not suggestive for inflammatory bowel diseases. Gastroscopy revealed suffusions of the antral mucosa with a striated pattern (Fig. S1a,b), and a small polyp with a dangling coagulum (Fig. S1c,d). An endoloop was immediately applied to ligate the polyp in order to prevent further bleeding (Fig. S1e); the position of the loop was checked 12 h after the application (Fig. S1f). The patient received transfusions of blood and fresh frozen plasma in order to stabilize her haemodynamic status and thrombocyte transfusions to increase platelet counts. Also, the haemostatic agent etamsylate was administered intravenously to promote platelet aggregate formation. Intravenous methylprednisolone at a dose of 125 mg daily was applied to attenuate the ardent autoimmune inflammation. Protection of gastric mucosa and control of acid production was achieved by intravenous use of the proton pump inhibitor pantoprazole, administered in a continuous infusion. As the result of this therapy, within 3 days, platelet counts started to increase steeply, up to 205 000/ ml by day 10. Purpuras on the lower limbs started to fade, gastrointestinal bleeding ceased and no other haemorrhagic complications occurred. Due to the striking therapeutic response, use of plasmapheresis or administration of intravenous immunoglobulines was not necessary. The patient’s general status and platelet counts continued to show distinct improvement and control gastroscopy at week 2 revealed regression of mucosal suffusions in the antrum (Fig. S2a,b) and necrosis and disappearance of the bleeding polyp with an intact stub left behind (Fig. S2c). In order to decrease risk of bleeding, the patient was instructed to continue 40 mg/day oral pantoprazole therapy. 3. Discussion ITP is an autoimmune thrombocytopenia characterized by presence of anti-platelet antibodies. The disease can either develop in a primary form or may coexist with autoimmune
351
[1e3] or haematological [4e6] diseases or several infections, such as those caused by Helicobacter pylori. In contrast to children, ITP in adults is a chronic disease, however, with a usually benign course [7] and with a low risk of fatal haemorrhage, mainly that of intracranial origin. In the case of untreated disease, the outcome and course are uncertain; spontaneous remission of chronic ITP is infrequent. Since the introduction of newer therapeutic modalities, current mortality rates may be less than 5%. Patients usually present with hemorrhagic complications including purpura, petechiae, hemorrhagic bullae on mucous membranes, or gingival bleeding. More perilous symptoms are gastrointestinal bleeding in some 5% of patients [8] or intracranial bleeding, which can occur spontaneously when platelet count drops to <20 000/ml. In case of gastrointestinal bleeding in ITP, identification of its source is usually problematic because of diffuse mucosal involvement. Nevertheless, amending platelet counts in these situations is a sine qua non for the control of bleeding. Standard therapy for ITP includes use of platelet transfusions, corticosteroids, intravenous immunoglobulins, plasmapheresis, H. pylori eradication in positive cases, or use of cytostatic drugs such as cyclophosphamide. Splenectomy is maintained for cases of failure of standard therapy. An estimated 10e125/1 000 000 patients develop ITP each year. Certainly, those associated with another autoimmune disease occur with a lower frequency. Coexistence of ITP with RA is a rarity: only a few case reports have been published [9e11]. Here we present the case of a patient who, after suspending immunosuppressive therapy, developed ITP supposedly associated with her RA. Her urgent admission was necessitated by severe gastrointestinal bleeding, caused by the very low platelet count accompanying the disease. Beside diffuse bleeding from mucosal petechiae in the colon and stomach, the situation was aggravated by a haemorrhage from a gastric polyp which required immediate endoscopic intervention. The therapeutic response to immunosuppressants, co-administered with the proton pump inhibitor pantoprazole, was very good, platelet count normalized in a couple of days and gastrointestinal bleeding ceased. This is the first case report on a patient who developed ITP after discontinuing oral corticosteroid therapy at her own risk and presented severe gastrointestinal bleeding as a complication. We believe that autoimmune disease patients should be made aware of possible increased susceptibility of serious relapse of their disease upon altering therapy without medical attendance.
Supplementary material Supplementary material (Figs. S1 and S2) associated with this article can be found, at http://www.sciencedirect.com, at doi:10.1016/j.jbspin.2007.06.010. References [1] Baudard M, Molina T, Benfiguig K, et al. Idiopathic thrombocytopenic purpura associated with Crohn’s disease. Haematologica 1998;83:92e3.
352
I. Ga´l et al. / Joint Bone Spine 75 (2008) 350e352
[2] Kurata Y, Miyagawa S, Kosugi S, et al. High-titer antinuclear antibodies, anti-SSA/Ro antibodies and anti-nuclear RNP antibodies in patients with idiopathic thrombocytopenic purpura. Thromb Haemost 1994;71:184e7. [3] Stasi R, Stipa E, Masi M, et al. Prevalence and clinical significance of elevated antiphospholipid antibodies in patients with idiopathic thrombocytopenic purpura. Blood 1994;84:4203e8. [4] Kedar A, Khan AB, Mattern JQ, et al. Autoimmune disorders complicating adolescent Hodgkin’s disease. Cancer 1979;44:112e6. [5] Shibuya A, Satomich A, Nagaba S, et al. Thrombotic thrombocytopenic purpura in autoimmune hepatitis. J Gastroenterol 2001;36:569e73. [6] Noda M, Mori N, Nomura K, et al. Regression of idiopathic thrombocytopenic purpura after endoscopic mucosal resection of gastric mucosa associated lymphoid tissue lymphoma. Gut 2004;53: 1698e700.
[7] Cohen YC, Djulbegovic B, Shamai-Lubovitz O, et al. The bleeding risk and natural history of idiopathic thrombocytopenic purpura in patients with persistent low platelet counts. Arch Intern Med 2000;160:1630e8. [8] Wong GC, Lee LH. A study of idiopathic thrombocytopenic purpura (ITP) patients over a ten-year period. Ann Acad Med Singapore 1998;27:789e93. [9] Yamada Y, Kuroe K. A case of rheumatoid arthritis complicated with idiopathic thrombocytopenic purpura and Hashimoto’s disease. Ryumachi 1991;31:413e9. [10] Horino T, Sasaoka A, Takao T, et al. Immune thrombocytopenic purpura associated with rheumatoid arthritis: case report. Clin Rheumatol 2005;24:641e4. [11] Lin SJ, Jaing TH. Thrombocytopenia in systemic-onset juvenile chronic arthritis: report of two cases with unusual bone marrow features. Clin Rheumatol 1999;18:241e3.
Joint Bone Spine 75 (2008) 350e352 http://france.elsevier.com/direct/BONSOI/
Case report
Gastric bleeding in a patient with rheumatoid arthritis complicated by immune thrombocytopenic purpura Istva´n Ga´l a,*,1, Lajos To´th b,1, La´szlo´ Szegedi a, Gyula G. Kiss a a
2nd Department of Internal Medicine, Kene´zy Gyula Teaching Hospital, Barto´k B. u. 2-26, H-4043 Debrecen, Hungary b Department of Surgery, Kene´zy Gyula Teaching Hospital, Barto´k B. u. 2-26, H-4043 Debrecen, Hungary Accepted 6 June 2007 Available online 28 January 2008
Abstract Rheumatoid arthritis, in common with other systemic autoimmune diseases, can involve several other organs presenting with complex immunological manifestations. Immune thrombocytopenic purpura caused by an autoimmune reaction against platelets is an infrequent haematological complications. A female patient with rheumatoid arthritis rapidly developed extremely severe immune thrombocytopenic purpura upon suspending oral corticosteroid therapy. Besides the involvement of the mucosa of the coecum, ascending colon and the gastric antrum, the situation was further complicated by bleeding of a gastric polyp, at the nadir of the thrombocytopenic crisis. The bleeding was managed by endoscopic intervention and platelet count recovered upon high dose corticosteroid treatment within a couple of days. Ó 2008 Published by Elsevier Masson SAS. Keywords: Immune thrombocytopenic purpura; Rheumatoid arthritis; Gastrointestinal bleeding
1. Introduction Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease which can involve the musculoskeletal system and various organs such as the cardiovascular, respiratory, nervous, urogenital and haematopoietic system. The principal of RA therapy is immunosuppression in order to diminish the augmented autoimmune reaction against target organs. The course of the disease is characterized by eventual flare-ups which necessitate thorough follow-up of patients and precise dosage adjustment of immunosuppressants. Dose reduction of these drugs requires strict medical supervision in order to prevent a flare-up episode. We present the case of a female RA patient who arbitrarily abandoned corticosteroid therapy. Within 2 months her disease started to show signs of activity, then within 2 weeks she developed extremely severe immune thrombocytopenic purpura
* Corresponding author. Tel.: þ36 30 209 3460; fax: þ36 52 511 755. E-mail address: [email protected] (I. Ga´l). 1 These authors contributed equally to this work. 1297-319X/$ - see front matter Ó 2008 Published by Elsevier Masson SAS. doi:10.1016/j.jbspin.2007.06.010
(ITP), presenting with severe hematochesia. Sources of bleeding included suffusions in coecal, ascending colon and the gastric antrum mucosa, and a gastric polyp. 2. Clinical report A 64-year-old Caucasian female was admitted to our gastroenterology unit with a 1-day history of massive hematochesia, weakness and dizziness on 7 January 2006. She was diagnosed with RA in 1996, and had been taking a weekly dose of 7.5 mg methotrexate and a daily dose of 8 mg methylprednisolone for her disease. Worrying about the side effects of the drug, she decided to discontinue oral steroid therapy in October 2005. In December 2005, she developed arthralgia of both knees and reported morning stiffness in her metacarpophalangeal and proximal interphalangeal joints. Blood tests on 20 December 2005 showed a mild thrombocytosis with a platelet count of 560 000/ml, a haemoglobin concentration of 110 g/ l, leukocyte count of 5600/ml, C-reactive protein serum level of 74 mg/l, and physical examination revealed unilateral swelling and tenderness of knees, wrists and metacarpophalangeal and proximal interphalangeal joints.
I. Ga´l et al. / Joint Bone Spine 75 (2008) 350e352
On 6 January 2006, within 1 day, she developed hematochesia and weakness, necessitating her urgent admission to our department. Physical examination revealed pale skin, tachycardia, low systolic blood pressure, confluent purpura of the lower limbs and haematomas all over her body. Blood tests upon admission showed severe anaemia with a haemoglobin concentration of 65 g/l and an extremely low platelet count of 2000/ml with a normal leukocyte count. Serum electrolytes, liver and kidney function, and blood coagulation tests were normal. Immunoserology revealed high titres of rheumatoid factor of IgM type, polyclonal hypergammaglobulinaemia, a strong anti-cyclic citrullinated peptide antibody positivity and anti-nuclear factor positivity, although anti-platelet antibodies were not present. C-reactive protein level and erythrocyte sedimentation rate were both elevated. Bone marrow analysis did not show reduction in megakaryocyte counts which suggested a peripheral damage of platelets, further supporting the diagnosis of ITP. Colonoscopy revealed oedema and petechiae of coecal and ascending colon mucosa (Fig. S1g,h: see the Supplementary material associated with this article online); the terminal ileum had normal appearance, however. Biopsy samples were taken following correction of platelet count; histological analysis showed no signs of inflammation and was not suggestive for inflammatory bowel diseases. Gastroscopy revealed suffusions of the antral mucosa with a striated pattern (Fig. S1a,b), and a small polyp with a dangling coagulum (Fig. S1c,d). An endoloop was immediately applied to ligate the polyp in order to prevent further bleeding (Fig. S1e); the position of the loop was checked 12 h after the application (Fig. S1f). The patient received transfusions of blood and fresh frozen plasma in order to stabilize her haemodynamic status and thrombocyte transfusions to increase platelet counts. Also, the haemostatic agent etamsylate was administered intravenously to promote platelet aggregate formation. Intravenous methylprednisolone at a dose of 125 mg daily was applied to attenuate the ardent autoimmune inflammation. Protection of gastric mucosa and control of acid production was achieved by intravenous use of the proton pump inhibitor pantoprazole, administered in a continuous infusion. As the result of this therapy, within 3 days, platelet counts started to increase steeply, up to 205 000/ ml by day 10. Purpuras on the lower limbs started to fade, gastrointestinal bleeding ceased and no other haemorrhagic complications occurred. Due to the striking therapeutic response, use of plasmapheresis or administration of intravenous immunoglobulines was not necessary. The patient’s general status and platelet counts continued to show distinct improvement and control gastroscopy at week 2 revealed regression of mucosal suffusions in the antrum (Fig. S2a,b) and necrosis and disappearance of the bleeding polyp with an intact stub left behind (Fig. S2c). In order to decrease risk of bleeding, the patient was instructed to continue 40 mg/day oral pantoprazole therapy. 3. Discussion ITP is an autoimmune thrombocytopenia characterized by presence of anti-platelet antibodies. The disease can either develop in a primary form or may coexist with autoimmune
351
[1e3] or haematological [4e6] diseases or several infections, such as those caused by Helicobacter pylori. In contrast to children, ITP in adults is a chronic disease, however, with a usually benign course [7] and with a low risk of fatal haemorrhage, mainly that of intracranial origin. In the case of untreated disease, the outcome and course are uncertain; spontaneous remission of chronic ITP is infrequent. Since the introduction of newer therapeutic modalities, current mortality rates may be less than 5%. Patients usually present with hemorrhagic complications including purpura, petechiae, hemorrhagic bullae on mucous membranes, or gingival bleeding. More perilous symptoms are gastrointestinal bleeding in some 5% of patients [8] or intracranial bleeding, which can occur spontaneously when platelet count drops to <20 000/ml. In case of gastrointestinal bleeding in ITP, identification of its source is usually problematic because of diffuse mucosal involvement. Nevertheless, amending platelet counts in these situations is a sine qua non for the control of bleeding. Standard therapy for ITP includes use of platelet transfusions, corticosteroids, intravenous immunoglobulins, plasmapheresis, H. pylori eradication in positive cases, or use of cytostatic drugs such as cyclophosphamide. Splenectomy is maintained for cases of failure of standard therapy. An estimated 10e125/1 000 000 patients develop ITP each year. Certainly, those associated with another autoimmune disease occur with a lower frequency. Coexistence of ITP with RA is a rarity: only a few case reports have been published [9e11]. Here we present the case of a patient who, after suspending immunosuppressive therapy, developed ITP supposedly associated with her RA. Her urgent admission was necessitated by severe gastrointestinal bleeding, caused by the very low platelet count accompanying the disease. Beside diffuse bleeding from mucosal petechiae in the colon and stomach, the situation was aggravated by a haemorrhage from a gastric polyp which required immediate endoscopic intervention. The therapeutic response to immunosuppressants, co-administered with the proton pump inhibitor pantoprazole, was very good, platelet count normalized in a couple of days and gastrointestinal bleeding ceased. This is the first case report on a patient who developed ITP after discontinuing oral corticosteroid therapy at her own risk and presented severe gastrointestinal bleeding as a complication. We believe that autoimmune disease patients should be made aware of possible increased susceptibility of serious relapse of their disease upon altering therapy without medical attendance.
Supplementary material Supplementary material (Figs. S1 and S2) associated with this article can be found, at http://www.sciencedirect.com, at doi:10.1016/j.jbspin.2007.06.010. References [1] Baudard M, Molina T, Benfiguig K, et al. Idiopathic thrombocytopenic purpura associated with Crohn’s disease. Haematologica 1998;83:92e3.
352
I. Ga´l et al. / Joint Bone Spine 75 (2008) 350e352
[2] Kurata Y, Miyagawa S, Kosugi S, et al. High-titer antinuclear antibodies, anti-SSA/Ro antibodies and anti-nuclear RNP antibodies in patients with idiopathic thrombocytopenic purpura. Thromb Haemost 1994;71:184e7. [3] Stasi R, Stipa E, Masi M, et al. Prevalence and clinical significance of elevated antiphospholipid antibodies in patients with idiopathic thrombocytopenic purpura. Blood 1994;84:4203e8. [4] Kedar A, Khan AB, Mattern JQ, et al. Autoimmune disorders complicating adolescent Hodgkin’s disease. Cancer 1979;44:112e6. [5] Shibuya A, Satomich A, Nagaba S, et al. Thrombotic thrombocytopenic purpura in autoimmune hepatitis. J Gastroenterol 2001;36:569e73. [6] Noda M, Mori N, Nomura K, et al. Regression of idiopathic thrombocytopenic purpura after endoscopic mucosal resection of gastric mucosa associated lymphoid tissue lymphoma. Gut 2004;53: 1698e700.
[7] Cohen YC, Djulbegovic B, Shamai-Lubovitz O, et al. The bleeding risk and natural history of idiopathic thrombocytopenic purpura in patients with persistent low platelet counts. Arch Intern Med 2000;160:1630e8. [8] Wong GC, Lee LH. A study of idiopathic thrombocytopenic purpura (ITP) patients over a ten-year period. Ann Acad Med Singapore 1998;27:789e93. [9] Yamada Y, Kuroe K. A case of rheumatoid arthritis complicated with idiopathic thrombocytopenic purpura and Hashimoto’s disease. Ryumachi 1991;31:413e9. [10] Horino T, Sasaoka A, Takao T, et al. Immune thrombocytopenic purpura associated with rheumatoid arthritis: case report. Clin Rheumatol 2005;24:641e4. [11] Lin SJ, Jaing TH. Thrombocytopenia in systemic-onset juvenile chronic arthritis: report of two cases with unusual bone marrow features. Clin Rheumatol 1999;18:241e3.