Aplastic Anemia in an HIV Infected Child
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《美国医学杂志》
Department of Perinatal and Pediatric HIV Clinic and Pathology Department, B.J. Wadia Hospital for Children, Parel, Mumbai, India
Abstract
Hematologic manifestations of HIV in children are common and include anemia, neutropenia, lymphocytopenia, thrombocytopenia that may occur due to many reasons. However, aplastic anemia due to HIV infection is rare and even more so in children. Though anemia is seen with advanced disease and associated with poor prognosis it is treated with various therapeutic modalities. Our patient with aplastic anemia due to HIV infection responded to antiretroviral therapy.
Keywords: Aplastic anemia; HIV; AIDS; Antiretroviral therapy, ART
Anemia is a frequent hematological manifestation of human immunodeficiency virus (HIV) infection. The causes of HIV related anemia are multifactorial.[1] The prevalence of anemia in patients with acquired immunodeficiency syndrome (AIDS) has been estimated to be 63-95%.[2],[3] Treatment of HIV related anemia requires correction of nutritional deficiencies, blood transfusion, recombinant human erythropoietin and modification of offending medications.[4] Here is reported a case of aplastic anemia in a child secondary to HIV infection who responded very amenably to antiretroviral therapy.
Case Report
A 13-year-old female child presented to the Pediatric HIV Clinic, Mumbai with bleeding from gums and weight loss since 3 months. There was no history of fever or any rash. She had received antituberculous therapy for 9 months in view of Pulmonary Kochs at the age of 4 years. She had also received a blood transfusion at the age of 5 years for anemia. On examination, she was malnourished with a weight of 25 kg and had severe pallor. She had insignificant cervical lymphadenopathy with hepatomegaly (liver span = 10 cm) and splenomegaly. Other systemic examination was normal. Her diet was sufficient in iron and multivitamins with a poor calorie intake of only 1000 calories/day. Her hemogram showed hemoglobin of 5.8 gm%, with a total leucocyte count of 2,500 cells/cumm and platelet count of 14,000 cells/cumm. Her absolute neutrophil count was 300 cells/cumm. Her reticulocyte count was 0.5%. Thus in view of the pancytopenia and low reticulocyte count, a bone marrow aspiration and biopsy was done which showed overall hypocellularity with patches of cellularity composed of megakaryocytes, erythroid cells and relative reduction in myeloid cell. There were no parasites, granulomas, blast cell excess or myxomatous degeneration. Minimal focal fibrosis was seen Figure1. She was screened for secondary causes of aplastic anemia and was found to be HIV positive by the 3rd generation ELISA test [DETECT-HIV MC (V.2)] and her HIV status was confirmed by the Western blot test. Both the parents were screened for HIV infection and were negative, so most likely the HIV infection was acquired through blood transfusion that she had received at 5 years of age, as there was no evidence of sexual abuse. Her other viral markers such as HBsAg and Anti HCV were negative. Her immunological workup showed CD4 count of 211 cells/cumm with CD4 percent of 19.1%. Her total CD8 count was 856 cells/cumm with CD8 percent of 77.6% and CD4:CD8 ratio = 0.24. In view of bone marrow suppression due to HIV infection and immunological category II, she was started on antiretroviral therapy in form of stavudine (d4T), Lamivudine (3TC) and Nevirapine (NVP). Zidovudine was avoided in view of anemia and efavirenz and protease inhibitors could not be started in view of the cost. She was followed up regularly and a detailed clinical examination and hemogram was done monthly table1.
On the completion of 6 months after starting antiretroviral therapy, her weight had increased by 6 kg to 30 kg and the hepatosplenomegaly had regressed with her hemogram being normal and she was clinically asymptomatic with no bleeding. She showed no side effects to antiretroviral therapy and her liver enzymes and serum amylase remained normal. A repeat bone marrow was not done in view of hematological and clinical response to antiretroviral therapy and thus an invasive procedure that would not change the course of the therapy was avoided. Thus, this HIV positive child with aplastic anemia responded very well to antiretroviral therapy.
Discussion
HIV causes anemia due to a number of probable mechanisms. There is increased production of cytokines especially in advanced disease which may block marrow production of red cells, decreased erythropoietin production, opportunistic infections such as Mycobacterium avium complex and Parvovirus B-19, administration of drugs such as zidovudine, ganciclovir and trimethoprim - sulfamethoxazole and myelophthisis caused by malignancies such as lymphoma.[1] Other uncommon mechanisms for HIV associated anemia postulated are autoimmune destruction of red blood cells,[5] vitamin B12 deficiency[6] and direct infection of marrow precursor cells.[7] In the present patient since the bone marrow did not show any parasites or granulomas, opportunistic infections causing the aplastic anemic would be unlikely. Also since there were no excess blasts and the child was not on any drugs prior to the bone marrow suppression, malignancy and drug induced anemia seems unlikely. Since the child responded very well to the antiretroviral therapy with normal hemogram at the end of 4 months (antiretrovirals themselves are known to be hematotoxic agents), it is most likely that the cause of bone marrow suppression in this child would most likely be due to direct effect of the HIV virus on the marrow cells. Thus introduction of the antiretroviral therapy must have decreased the viral invasion of the bone marrow leading to improvement as was seen in the patient.
Aplastic anemia has rarely been reported in literature as a complication of HIV with only 1 pediatric case being reported and none from India.[8] Bone marrow changes in HIV disease are non-specific and not pathognomic, however, erythroid hypoplasia is found to be a distinctive feature associated with mycobacterium avium infection.[9] Anemia has also been associated with progression towards AIDS[10] and shorter survival times for HIV infected patients.
Treatment of HIV related anemia addresses correction of underlying causes such as modification of offending medications, correction of nutritional deficiencies and parvovirus infection. For anemia that is not amenable to correction, therapeutic modalities such as blood transfusion and recombinant human erythropoietin are recommended.[4] Bone marrow transplant is not very useful in aplastic anemia with HIV infection.[11] However, there have been reports of improvement of anemia due to parvovirus B19 infection with antiretroviral therapy in patients with AIDS.[12] In the patient, the author observed saw an excellent response to combined antiretroviral therapy with aplastic anemia due to HIV infection. Thus, we would recommend that every patient with aplastic anemia should be screened for HIV infection as HIV itself may lead to bone marrow suppression that may respond to antiretroviral therapy.
Acknowledgement
The authors thank Dr. Dod, CSE of B. J. Wadia Hospital for Children for giving permission to publish this article.
References
1. Doukas MA. Human Immunodeficiency virus associated anemia. Med Clin North AM 1992; 76; 699 -700.
2. Groopman JE. Management of hematologic complications of human immunodeficiency virus infection. Rev Infect Dis 1990; 12: 931.
3. Mir N, Costello C, Luckit J, Lindley R. HIV disease and bone marrow changes: A study of 60 cases. Eur J Haematol 1989; 42: 339-340.
4. Claster S. Biology of anemia, differential diagnosis and treatment options in human immunodeficiency virus infection. J Infect Dis 2002; 185 (Suppl 2): 105-109.
5. Ciaffoni S, Luzzali R, Roata C, Turrini A, Antonello O, Aprili G. Presence and significance of cold agglutinins in patients with HIV infection. Haematologica 1992; 77: 233-234.
6. Remacha AF, Riera A, Cadafalch J, Gimferrer E. Vitamin B12 abnormalities in HIV infected patients. Eur J Haematol 1991; 41: 60-61.
7. Cleveland RP, Liu YC. CD4 expression by erythroid precursor cells in human bone marrow. Blood 1996; 87: 2275-2278.
8. Morad AB, Steuber CP, Mahoney DH, Hurwitz RL. Hypoplastic anemia in an infant with human immuno-deficiency virus (HIV) infection. Am J Hematol 1993; 42(2): 236.
9. Mir N. Costello C, Luckit J, Lindley R. HIV-disease and bone marrow changes: a study of 60 cases. Eur J Haematol 1989; 42: 339-343.
10. Ellaurie M, Burns ER, Rubinstein A. Hematologic manifestations in pediatric HIV infection: Severe anemia as a prognostic factor. Am J Pediatr Hematol Oncol 1990; 12:449-450.
11. Giri N, Vowels MR, Ziegler JB. Failure of allogenic bone marrow transplantation to benefit HIV infection. J Paediatr Child Health 1992; 28: 331-333.
12. Scapellato PG, Palumbo AM, Del Valle S. Improvement of anemia induced by parvovirus B19 in a patient with AIDS after combined antiretroviral therapy. Mayo Clin Proc 2000;75:215-216.(Shah Ira, Murthy Anuradha)
Abstract
Hematologic manifestations of HIV in children are common and include anemia, neutropenia, lymphocytopenia, thrombocytopenia that may occur due to many reasons. However, aplastic anemia due to HIV infection is rare and even more so in children. Though anemia is seen with advanced disease and associated with poor prognosis it is treated with various therapeutic modalities. Our patient with aplastic anemia due to HIV infection responded to antiretroviral therapy.
Keywords: Aplastic anemia; HIV; AIDS; Antiretroviral therapy, ART
Anemia is a frequent hematological manifestation of human immunodeficiency virus (HIV) infection. The causes of HIV related anemia are multifactorial.[1] The prevalence of anemia in patients with acquired immunodeficiency syndrome (AIDS) has been estimated to be 63-95%.[2],[3] Treatment of HIV related anemia requires correction of nutritional deficiencies, blood transfusion, recombinant human erythropoietin and modification of offending medications.[4] Here is reported a case of aplastic anemia in a child secondary to HIV infection who responded very amenably to antiretroviral therapy.
Case Report
A 13-year-old female child presented to the Pediatric HIV Clinic, Mumbai with bleeding from gums and weight loss since 3 months. There was no history of fever or any rash. She had received antituberculous therapy for 9 months in view of Pulmonary Kochs at the age of 4 years. She had also received a blood transfusion at the age of 5 years for anemia. On examination, she was malnourished with a weight of 25 kg and had severe pallor. She had insignificant cervical lymphadenopathy with hepatomegaly (liver span = 10 cm) and splenomegaly. Other systemic examination was normal. Her diet was sufficient in iron and multivitamins with a poor calorie intake of only 1000 calories/day. Her hemogram showed hemoglobin of 5.8 gm%, with a total leucocyte count of 2,500 cells/cumm and platelet count of 14,000 cells/cumm. Her absolute neutrophil count was 300 cells/cumm. Her reticulocyte count was 0.5%. Thus in view of the pancytopenia and low reticulocyte count, a bone marrow aspiration and biopsy was done which showed overall hypocellularity with patches of cellularity composed of megakaryocytes, erythroid cells and relative reduction in myeloid cell. There were no parasites, granulomas, blast cell excess or myxomatous degeneration. Minimal focal fibrosis was seen Figure1. She was screened for secondary causes of aplastic anemia and was found to be HIV positive by the 3rd generation ELISA test [DETECT-HIV MC (V.2)] and her HIV status was confirmed by the Western blot test. Both the parents were screened for HIV infection and were negative, so most likely the HIV infection was acquired through blood transfusion that she had received at 5 years of age, as there was no evidence of sexual abuse. Her other viral markers such as HBsAg and Anti HCV were negative. Her immunological workup showed CD4 count of 211 cells/cumm with CD4 percent of 19.1%. Her total CD8 count was 856 cells/cumm with CD8 percent of 77.6% and CD4:CD8 ratio = 0.24. In view of bone marrow suppression due to HIV infection and immunological category II, she was started on antiretroviral therapy in form of stavudine (d4T), Lamivudine (3TC) and Nevirapine (NVP). Zidovudine was avoided in view of anemia and efavirenz and protease inhibitors could not be started in view of the cost. She was followed up regularly and a detailed clinical examination and hemogram was done monthly table1.
On the completion of 6 months after starting antiretroviral therapy, her weight had increased by 6 kg to 30 kg and the hepatosplenomegaly had regressed with her hemogram being normal and she was clinically asymptomatic with no bleeding. She showed no side effects to antiretroviral therapy and her liver enzymes and serum amylase remained normal. A repeat bone marrow was not done in view of hematological and clinical response to antiretroviral therapy and thus an invasive procedure that would not change the course of the therapy was avoided. Thus, this HIV positive child with aplastic anemia responded very well to antiretroviral therapy.
Discussion
HIV causes anemia due to a number of probable mechanisms. There is increased production of cytokines especially in advanced disease which may block marrow production of red cells, decreased erythropoietin production, opportunistic infections such as Mycobacterium avium complex and Parvovirus B-19, administration of drugs such as zidovudine, ganciclovir and trimethoprim - sulfamethoxazole and myelophthisis caused by malignancies such as lymphoma.[1] Other uncommon mechanisms for HIV associated anemia postulated are autoimmune destruction of red blood cells,[5] vitamin B12 deficiency[6] and direct infection of marrow precursor cells.[7] In the present patient since the bone marrow did not show any parasites or granulomas, opportunistic infections causing the aplastic anemic would be unlikely. Also since there were no excess blasts and the child was not on any drugs prior to the bone marrow suppression, malignancy and drug induced anemia seems unlikely. Since the child responded very well to the antiretroviral therapy with normal hemogram at the end of 4 months (antiretrovirals themselves are known to be hematotoxic agents), it is most likely that the cause of bone marrow suppression in this child would most likely be due to direct effect of the HIV virus on the marrow cells. Thus introduction of the antiretroviral therapy must have decreased the viral invasion of the bone marrow leading to improvement as was seen in the patient.
Aplastic anemia has rarely been reported in literature as a complication of HIV with only 1 pediatric case being reported and none from India.[8] Bone marrow changes in HIV disease are non-specific and not pathognomic, however, erythroid hypoplasia is found to be a distinctive feature associated with mycobacterium avium infection.[9] Anemia has also been associated with progression towards AIDS[10] and shorter survival times for HIV infected patients.
Treatment of HIV related anemia addresses correction of underlying causes such as modification of offending medications, correction of nutritional deficiencies and parvovirus infection. For anemia that is not amenable to correction, therapeutic modalities such as blood transfusion and recombinant human erythropoietin are recommended.[4] Bone marrow transplant is not very useful in aplastic anemia with HIV infection.[11] However, there have been reports of improvement of anemia due to parvovirus B19 infection with antiretroviral therapy in patients with AIDS.[12] In the patient, the author observed saw an excellent response to combined antiretroviral therapy with aplastic anemia due to HIV infection. Thus, we would recommend that every patient with aplastic anemia should be screened for HIV infection as HIV itself may lead to bone marrow suppression that may respond to antiretroviral therapy.
Acknowledgement
The authors thank Dr. Dod, CSE of B. J. Wadia Hospital for Children for giving permission to publish this article.
References
1. Doukas MA. Human Immunodeficiency virus associated anemia. Med Clin North AM 1992; 76; 699 -700.
2. Groopman JE. Management of hematologic complications of human immunodeficiency virus infection. Rev Infect Dis 1990; 12: 931.
3. Mir N, Costello C, Luckit J, Lindley R. HIV disease and bone marrow changes: A study of 60 cases. Eur J Haematol 1989; 42: 339-340.
4. Claster S. Biology of anemia, differential diagnosis and treatment options in human immunodeficiency virus infection. J Infect Dis 2002; 185 (Suppl 2): 105-109.
5. Ciaffoni S, Luzzali R, Roata C, Turrini A, Antonello O, Aprili G. Presence and significance of cold agglutinins in patients with HIV infection. Haematologica 1992; 77: 233-234.
6. Remacha AF, Riera A, Cadafalch J, Gimferrer E. Vitamin B12 abnormalities in HIV infected patients. Eur J Haematol 1991; 41: 60-61.
7. Cleveland RP, Liu YC. CD4 expression by erythroid precursor cells in human bone marrow. Blood 1996; 87: 2275-2278.
8. Morad AB, Steuber CP, Mahoney DH, Hurwitz RL. Hypoplastic anemia in an infant with human immuno-deficiency virus (HIV) infection. Am J Hematol 1993; 42(2): 236.
9. Mir N. Costello C, Luckit J, Lindley R. HIV-disease and bone marrow changes: a study of 60 cases. Eur J Haematol 1989; 42: 339-343.
10. Ellaurie M, Burns ER, Rubinstein A. Hematologic manifestations in pediatric HIV infection: Severe anemia as a prognostic factor. Am J Pediatr Hematol Oncol 1990; 12:449-450.
11. Giri N, Vowels MR, Ziegler JB. Failure of allogenic bone marrow transplantation to benefit HIV infection. J Paediatr Child Health 1992; 28: 331-333.
12. Scapellato PG, Palumbo AM, Del Valle S. Improvement of anemia induced by parvovirus B19 in a patient with AIDS after combined antiretroviral therapy. Mayo Clin Proc 2000;75:215-216.(Shah Ira, Murthy Anuradha)