Aging Clin Exp Res DOI 10.1007/s40520-014-0310-3
LETTER TO THE EDITOR
Pure red cell aplasia due to anti-erythropoietin antibodies or isoniazid? A case report from a 94-year-old man Guang Yang • Qingli Cheng • Sheng Liu Xiaoying Zhang
•
Received: 26 November 2014 / Accepted: 26 December 2014 Ó Springer International Publishing Switzerland 2015
To the Editor, PRCA is a rare disease characterized by selective reduction or elimination of the erythropoietic cell line in the bone marrow. Acquired PRCA is often secondary to drug exposure. At present nearly 30 drugs have been confirmed or suspected to induce PRCA [1]. The following case is an advanced age patient who had been initially misdiagnosed as anti-EPO antibody-mediated PRCA, but the isoniazidinduced PRCA was diagnosed finally. A 94-year-old Chinese male was admitted to our hospital on December 4, 2004 for repeated low-grade fever, intermittent bloody sputum, and debility for 2 months. The patient’s laboratory analysis showed hemoglobin (Hb) was 102 g/L, white cell count 9.9 9 109/L, platelets 149 9 109/L. While the patient was admitted, pulmonary infection also occurred due to aspiration. Antibiotics were administered but did not control the infection well, the Hb level of the patient was lower to 78 g/L (December 31, 2004). Then, the recombinant human erythropoietin-b (rHuEpo-b, Roche), 6000U, was injected subcutaneously, three times per week and supplemented with iron, folic acid, and vitamins. However, there were not any positive effects after EPO treatment. Furthermore, the patient required weekly red blood cells (RBC) infusions to maintain his Hb level between 70 and 85 g/L. On August 23, 2005, bone marrow biopsy and smears were performed. The results showed the generation of the erythrocyte series decreased markedly, and there were no other abnormal cells. The results of bone marrow smear showed the
G. Yang Q. Cheng (&) S. Liu X. Zhang Department of Geriatric Nephrology, Chinese PLA General Hospital, 28 Fuxing Rd, Beijing 100853, China e-mail: [email protected]
myeloid to erythroid ratio of 72.3:1. Pure red cell aplasia (PRCA) was diagnosed. As the patient presented the PRCA during the treatment of EPO, anti-EPO antibody-induced PCRA was initially suspected, but the diagnosis didn’t be confirmed because the result of EPO antibody test can’t available at that time. From September 2, 2005, the EPO treatment was stopped and the patient was treated with androgen, human immune globulin, and intermittent infusions of RBC. However, the patient’s Hb level still fluctuated around 66–87 g/L. The patient had been diagnosed with pulmonary tuberculosis (TB) in 1962. Two months prior to this admission he was administered isoniazid (0.2 qd), ethambutol (0.5 qd), and levofloxacin (0.2 bid) for the testing positive for acid-fast bacillus in his sputum smear. On October 9, 2005, all of the anti-TB drugs were stopped after multiple negative results in sputum TB smear and TB antibody tests. One week later, the patient’s Hb levels could be maintained at 90 g/L without any blood transfusion, and the count of reticulated corpuscles (RC) gradually increased to the normal range. However, 1 month later, the patient’s cough, sputum, and other symptoms reappeared and gradually became more serious. An acid-fast bacilli sputum smear was positive and the patient received the previous anti-TB drug therapy program again. Surprisingly, his Hb levels declined rapidly after the anti-TB therapy. Thus, the isoniazid was suspected the cause of PRCA in the patient. After consultation with the TB treatment specialist, the patient was changed to other anti-TB drug program excluding isoniazid, and the rHuEPO-b treatment was started again. Twenty days later, the patient’s Hb level increased to 101 g/L, and gradually increased to 113 g/ L on January 12 2006. RBC counts were in the normal range and EPO treatment was stopped. Two years later, the patient’s Hb level and RC count were still in the normal range without EPO treatment or blood infusion.
123
Aging Clin Exp Res
There are only 14 case reports about isoniazid-induced PRCA [2]. The exact mechanism for isoniazid-induced PRCA remains unclear. Suggested mechanisms include a direct toxic effect or its metabolic interference affecting erythrocyte production, or immune-mediated inhibition of marrow erythroid progenitors [3, 4]. The treatment of druginduced PRCA should include the following: first, discontinue or avoid the use of drugs that can lead to this disease. Second, if there are no signs of recovery after drug discontinuation, the specific treatment should be instituted. Immunosuppressive agents may be used, including corticosteroids (CS), cyclosporine A, cyclophosphamide (CY) plus CS, and others [5]. In the present case, the patient was the most advanced age patient of all those reported in the world. The patient’s general condition was poor and included several complicated diseases with multiple drug treatments. In this case, EPO-mediated PRCA was initially considered because the patient’s anemia progressed after administration of EPO. However, after stopping EPO treatment, the Hb level did not increase and blood transfusions were still required. Upon comprehensive review of the patient’s medication history, there was a close relationship between the decreased Hb levels and the use of isoniazid. Thus, we conclude that PRCA was induced by isoniazid.
123
Drug-induced PRCA is not a common disease and their diagnosis is not easy, especially in the elderly with multiple diseases and multiple risk factors for PRCA. EPO-induced PRCA is very serious and rare, and the most patients need intermittent RBC transfusion to keep their basic normal life. Therefore, other possible causes should be considered when EPO-treated patients develop PRCA, as evidenced by this case. Conflict of interest On behalf of all authors, the corresponding author states that there is no conflict of interest.
References 1. Fisch P, Handgretinger R, Schaefer HE (2000) Pure red cell aplasia. Br J Haematol 111:1010–1022 2. Nakamura H, Okada A, Kawakami A et al (2010) Isoniazid-triggered pure red cell aplasia in systemic lupus erythematosus complicated with myasthenia gravis. Rheumatol Int 30(12):1643–1645 3. Marseglia GL, Locatelly F (1998) Isoniazid induced pure red cell aplasia in two siblings. J Pediatr 132:898–900 4. Johnsson R, Lommi J (1990) A case of isoniazid-induced red cell aplasia. Respir Med 84:171–174 (PubMed: 2115192) 5. Sawada K, Fujishima N, Hirokawa M (2008) Acquired pure red cell aplasia: updated review of treatment. Br J Haematol 142(4):505–514
LETTER TO THE EDITOR
Pure red cell aplasia due to anti-erythropoietin antibodies or isoniazid? A case report from a 94-year-old man Guang Yang • Qingli Cheng • Sheng Liu Xiaoying Zhang
•
Received: 26 November 2014 / Accepted: 26 December 2014 Ó Springer International Publishing Switzerland 2015
To the Editor, PRCA is a rare disease characterized by selective reduction or elimination of the erythropoietic cell line in the bone marrow. Acquired PRCA is often secondary to drug exposure. At present nearly 30 drugs have been confirmed or suspected to induce PRCA [1]. The following case is an advanced age patient who had been initially misdiagnosed as anti-EPO antibody-mediated PRCA, but the isoniazidinduced PRCA was diagnosed finally. A 94-year-old Chinese male was admitted to our hospital on December 4, 2004 for repeated low-grade fever, intermittent bloody sputum, and debility for 2 months. The patient’s laboratory analysis showed hemoglobin (Hb) was 102 g/L, white cell count 9.9 9 109/L, platelets 149 9 109/L. While the patient was admitted, pulmonary infection also occurred due to aspiration. Antibiotics were administered but did not control the infection well, the Hb level of the patient was lower to 78 g/L (December 31, 2004). Then, the recombinant human erythropoietin-b (rHuEpo-b, Roche), 6000U, was injected subcutaneously, three times per week and supplemented with iron, folic acid, and vitamins. However, there were not any positive effects after EPO treatment. Furthermore, the patient required weekly red blood cells (RBC) infusions to maintain his Hb level between 70 and 85 g/L. On August 23, 2005, bone marrow biopsy and smears were performed. The results showed the generation of the erythrocyte series decreased markedly, and there were no other abnormal cells. The results of bone marrow smear showed the
G. Yang Q. Cheng (&) S. Liu X. Zhang Department of Geriatric Nephrology, Chinese PLA General Hospital, 28 Fuxing Rd, Beijing 100853, China e-mail: [email protected]
myeloid to erythroid ratio of 72.3:1. Pure red cell aplasia (PRCA) was diagnosed. As the patient presented the PRCA during the treatment of EPO, anti-EPO antibody-induced PCRA was initially suspected, but the diagnosis didn’t be confirmed because the result of EPO antibody test can’t available at that time. From September 2, 2005, the EPO treatment was stopped and the patient was treated with androgen, human immune globulin, and intermittent infusions of RBC. However, the patient’s Hb level still fluctuated around 66–87 g/L. The patient had been diagnosed with pulmonary tuberculosis (TB) in 1962. Two months prior to this admission he was administered isoniazid (0.2 qd), ethambutol (0.5 qd), and levofloxacin (0.2 bid) for the testing positive for acid-fast bacillus in his sputum smear. On October 9, 2005, all of the anti-TB drugs were stopped after multiple negative results in sputum TB smear and TB antibody tests. One week later, the patient’s Hb levels could be maintained at 90 g/L without any blood transfusion, and the count of reticulated corpuscles (RC) gradually increased to the normal range. However, 1 month later, the patient’s cough, sputum, and other symptoms reappeared and gradually became more serious. An acid-fast bacilli sputum smear was positive and the patient received the previous anti-TB drug therapy program again. Surprisingly, his Hb levels declined rapidly after the anti-TB therapy. Thus, the isoniazid was suspected the cause of PRCA in the patient. After consultation with the TB treatment specialist, the patient was changed to other anti-TB drug program excluding isoniazid, and the rHuEPO-b treatment was started again. Twenty days later, the patient’s Hb level increased to 101 g/L, and gradually increased to 113 g/ L on January 12 2006. RBC counts were in the normal range and EPO treatment was stopped. Two years later, the patient’s Hb level and RC count were still in the normal range without EPO treatment or blood infusion.
123
Aging Clin Exp Res
There are only 14 case reports about isoniazid-induced PRCA [2]. The exact mechanism for isoniazid-induced PRCA remains unclear. Suggested mechanisms include a direct toxic effect or its metabolic interference affecting erythrocyte production, or immune-mediated inhibition of marrow erythroid progenitors [3, 4]. The treatment of druginduced PRCA should include the following: first, discontinue or avoid the use of drugs that can lead to this disease. Second, if there are no signs of recovery after drug discontinuation, the specific treatment should be instituted. Immunosuppressive agents may be used, including corticosteroids (CS), cyclosporine A, cyclophosphamide (CY) plus CS, and others [5]. In the present case, the patient was the most advanced age patient of all those reported in the world. The patient’s general condition was poor and included several complicated diseases with multiple drug treatments. In this case, EPO-mediated PRCA was initially considered because the patient’s anemia progressed after administration of EPO. However, after stopping EPO treatment, the Hb level did not increase and blood transfusions were still required. Upon comprehensive review of the patient’s medication history, there was a close relationship between the decreased Hb levels and the use of isoniazid. Thus, we conclude that PRCA was induced by isoniazid.
123
Drug-induced PRCA is not a common disease and their diagnosis is not easy, especially in the elderly with multiple diseases and multiple risk factors for PRCA. EPO-induced PRCA is very serious and rare, and the most patients need intermittent RBC transfusion to keep their basic normal life. Therefore, other possible causes should be considered when EPO-treated patients develop PRCA, as evidenced by this case. Conflict of interest On behalf of all authors, the corresponding author states that there is no conflict of interest.
References 1. Fisch P, Handgretinger R, Schaefer HE (2000) Pure red cell aplasia. Br J Haematol 111:1010–1022 2. Nakamura H, Okada A, Kawakami A et al (2010) Isoniazid-triggered pure red cell aplasia in systemic lupus erythematosus complicated with myasthenia gravis. Rheumatol Int 30(12):1643–1645 3. Marseglia GL, Locatelly F (1998) Isoniazid induced pure red cell aplasia in two siblings. J Pediatr 132:898–900 4. Johnsson R, Lommi J (1990) A case of isoniazid-induced red cell aplasia. Respir Med 84:171–174 (PubMed: 2115192) 5. Sawada K, Fujishima N, Hirokawa M (2008) Acquired pure red cell aplasia: updated review of treatment. Br J Haematol 142(4):505–514
