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Human immunodeficiency virus-associated thrombocytopenic purpura
CORRESPONDENCE
Shaare
BARUCH HLMCH, M.D. Zedeh Medical Center
PO% 3235 Submitted
April
91-031 Jerusalem,
Israel
20. 1989.
May
and accepted
18. 1989
HUMAN IMMUNODEFICIENCY VIRUS-ASSOCIATED THROMBOCYTOPENIC PURPURA To the Editor: We read with interest the review by Ratner (Am J Med 1989; 86: 194198). As he suggested in the last paragraph, high-dose immunoglobulin followed by zidovudine (formerly called azidothymidine [AZT]) may be considered for patients with severe human immunodeficiency virus (HIV)-associated thrombocytopenic purpura. However, this alternative has not been included in his schemein Figure 1. We wish to illustrate this therapeutic approach with the following brief case report. A 33-year-old white woman, married to a bisexual, HIV-positive man (who later developed acquired immunodeficiency syndrome and died), gave birth to an HIV-positive female infant in July 1986. At that time, she was found to have a group IIA (Centers for Disease Control classification) HIV infection. Six months later, her platelet count was 101 X log/L. In May 1987, she experienced an episode of fever, purpura, and ecchymoses,with a low platelet count (value not available). On September 4, 1987, her white blood cell count was 2.8 X log/L, hemoglobin level was 105 g/L, and platelet count was 21 X log/L (or 21,000/ mm:‘). A bone marrow examination confirmed the peripheral origin of thrombocytopenia. Also, a high level (more than four times the upper-normal limit) of platelet-associated IgG antibodies was found. Treatment with prednisone (60 mg/day) was started by her physician and a prompt elevation in platelet count occurred. The prednisone dose was then reduced to 50 mg/day, and the platelet count decreased progressively from 137 X log/L to 121 X log/L (September 30, 1987), 108 X log/L (October 1987), and 82 X log/L (November 1987). Becauseof edema, acne, and hirsutism, the prednisone dosewas further reduced to 25 mg and 12.5 mg on alternate days. With this dosage, her platelet count decreased to 33 X log/L in a month;
the prednisone dose was therefore elevated to 25 mglday. In January 1988 (platelet count 182 X log/L), another tentative reduction of prednisone was followed by a decline in thrombocyte number (58 X log/L in February 1988 and 7 X log/L in March 1988) with exacerbation of purpura and ecchymoses. Despite a higher prednisone dose (50 mg/day), her platelet count remained between 21 X log/L and 33 X lOs/L. Splenectomy was proposed by her physician but the patient refused and asked for alternative therapy. After being fully informed, she consented to receive high-dose intravenous immunoglobulins (20 g/day for five days) followed by zidovudine. The intravenous immunoglobulins were very well tolerated and her platelet count increased progressively to 183 X log/L at the end of the fiveday courseof therapy. At that time, zidovudine was initiated (600 mg/ day orally) and treatment with prednisone tapered off and stopped in five days. Her platelet count again decreased, to 49 X lOe/L in three weeks. The zidovudine dose was then increased to 1,200 mglday, which led to a progressive elevation in thrombocyte values, reaching 141 X log/L in January 1989. Currently, 16 months since the diagnosis of HIV-associated thrombocytopenia and more than 10 months since the administration of intravenous immunoglobulins followed by zidovudine, the patient is well, asymptomatic, free of purpura and ecchymoses, and has a normal platelet count. The transient elevation in platelets, achieved with intravenous immunoglobulins (Pollak AN, Janinis J, Green D: Successful intravenous immune globulin therapy for human immunodeficiency virus-associated thrombocytopenia. Arch Intern Med 1988; 148: 659-697), should therefore be targeted before institution of zidovudine therapy in patients with severe thrombocytopenia. At our institution, we currently recommend this approach for severe HIV-associated thrombocytopenia (less than 20 X log/L). Steroids and splenectomy should be avoided in these patients. However, it would be of interest to undertake a controlled study comparing prednisone with intravenous immunoglobulins given for two to three days and followed by zidovuAugust
1989
dine, in HIV-associated thrombocytopenic purpura. EMIL TOMA, M.D., D.s~., F.R.C’.P.ICJ DENIM PHANEUF, M.D., MA. GRBCOIRE NOEL, M.D., M.s~. HBtel-Dieu de MontrCal and University of Montreal 3840 St-Urbain Street Montreal, Quebec H2 W 1 T8, Canada Submdted
March
27, 1989.
and accepted
May 18. 1989
The Reply: The letter by Toma and colleagues supports previously published data about the efficacy of zidovudine for thrombocytopenic purpura in HIV-l-infected persons [1,2]. It is questioned, however, whether their patient could have been treated with zidovudine alone at the initial presentation of thrombocytopenia, or at the time of recurrence. For patients with more severe thrombocytopenia, associatedwith platelet counts of less than 10,000 to 20,00O/mm~’or with clinically significant bleeding, treatment with steroids, splenectomy, high-dose immunoglobulins, anti-Rh immunoglobulins, cytotoxic agents, or danazol, followed by zidovudine when at least a partial responseis achieved, may be a reasonable course of action. Insufficient data are available to justify the use of zidovudine alone in these situations. Investigation of the long-term responsesof thrombocytopenia to zidovudine as reported here in a larger cohort of patients will be important to assessthe risk-benefit ratio of zidovudine for this indication. Furthermore, the optimal dose of zidovudine for this indication remains to be determined.
LEE RATNER, M.D., Ph.0 Washington University St. Louis, Missouri 1. SWISS Group for Cknfcal Studfes on AIDS: Zidovudfne for the treatment of thrombocytopenia assocfated wdh human immunodekcfency virus (HIV) Ann Intern Med 1988: 109: 718-721. 2. Oksendhandler E. Bier@ P. Ferchal F. Clauvel J-P. Sekgman M: Zfdovudine lor thrombocytopenfc purpura related to human mmunodefictency wus WI’0 miecbon Ann Intern Med 1989: 110: 365-368.
AMINOGLYCOSIDE NEPHROTOXICITY IN OBSTRUCTIVE JAUNDICE: POSSIBLE CONTRIBUTION BY CONCOMITANTLY ADMINISTERED CORTICOSTEROIDS To the Editor: Although the report of Desai and Tsang (Am J Med 1988; 85: 47-50)
The American
Journal
of Medicine
Volume
87
245
Shaare
BARUCH HLMCH, M.D. Zedeh Medical Center
PO% 3235 Submitted
April
91-031 Jerusalem,
Israel
20. 1989.
May
and accepted
18. 1989
HUMAN IMMUNODEFICIENCY VIRUS-ASSOCIATED THROMBOCYTOPENIC PURPURA To the Editor: We read with interest the review by Ratner (Am J Med 1989; 86: 194198). As he suggested in the last paragraph, high-dose immunoglobulin followed by zidovudine (formerly called azidothymidine [AZT]) may be considered for patients with severe human immunodeficiency virus (HIV)-associated thrombocytopenic purpura. However, this alternative has not been included in his schemein Figure 1. We wish to illustrate this therapeutic approach with the following brief case report. A 33-year-old white woman, married to a bisexual, HIV-positive man (who later developed acquired immunodeficiency syndrome and died), gave birth to an HIV-positive female infant in July 1986. At that time, she was found to have a group IIA (Centers for Disease Control classification) HIV infection. Six months later, her platelet count was 101 X log/L. In May 1987, she experienced an episode of fever, purpura, and ecchymoses,with a low platelet count (value not available). On September 4, 1987, her white blood cell count was 2.8 X log/L, hemoglobin level was 105 g/L, and platelet count was 21 X log/L (or 21,000/ mm:‘). A bone marrow examination confirmed the peripheral origin of thrombocytopenia. Also, a high level (more than four times the upper-normal limit) of platelet-associated IgG antibodies was found. Treatment with prednisone (60 mg/day) was started by her physician and a prompt elevation in platelet count occurred. The prednisone dose was then reduced to 50 mg/day, and the platelet count decreased progressively from 137 X log/L to 121 X log/L (September 30, 1987), 108 X log/L (October 1987), and 82 X log/L (November 1987). Becauseof edema, acne, and hirsutism, the prednisone dosewas further reduced to 25 mg and 12.5 mg on alternate days. With this dosage, her platelet count decreased to 33 X log/L in a month;
the prednisone dose was therefore elevated to 25 mglday. In January 1988 (platelet count 182 X log/L), another tentative reduction of prednisone was followed by a decline in thrombocyte number (58 X log/L in February 1988 and 7 X log/L in March 1988) with exacerbation of purpura and ecchymoses. Despite a higher prednisone dose (50 mg/day), her platelet count remained between 21 X log/L and 33 X lOs/L. Splenectomy was proposed by her physician but the patient refused and asked for alternative therapy. After being fully informed, she consented to receive high-dose intravenous immunoglobulins (20 g/day for five days) followed by zidovudine. The intravenous immunoglobulins were very well tolerated and her platelet count increased progressively to 183 X log/L at the end of the fiveday courseof therapy. At that time, zidovudine was initiated (600 mg/ day orally) and treatment with prednisone tapered off and stopped in five days. Her platelet count again decreased, to 49 X lOe/L in three weeks. The zidovudine dose was then increased to 1,200 mglday, which led to a progressive elevation in thrombocyte values, reaching 141 X log/L in January 1989. Currently, 16 months since the diagnosis of HIV-associated thrombocytopenia and more than 10 months since the administration of intravenous immunoglobulins followed by zidovudine, the patient is well, asymptomatic, free of purpura and ecchymoses, and has a normal platelet count. The transient elevation in platelets, achieved with intravenous immunoglobulins (Pollak AN, Janinis J, Green D: Successful intravenous immune globulin therapy for human immunodeficiency virus-associated thrombocytopenia. Arch Intern Med 1988; 148: 659-697), should therefore be targeted before institution of zidovudine therapy in patients with severe thrombocytopenia. At our institution, we currently recommend this approach for severe HIV-associated thrombocytopenia (less than 20 X log/L). Steroids and splenectomy should be avoided in these patients. However, it would be of interest to undertake a controlled study comparing prednisone with intravenous immunoglobulins given for two to three days and followed by zidovuAugust
1989
dine, in HIV-associated thrombocytopenic purpura. EMIL TOMA, M.D., D.s~., F.R.C’.P.ICJ DENIM PHANEUF, M.D., MA. GRBCOIRE NOEL, M.D., M.s~. HBtel-Dieu de MontrCal and University of Montreal 3840 St-Urbain Street Montreal, Quebec H2 W 1 T8, Canada Submdted
March
27, 1989.
and accepted
May 18. 1989
The Reply: The letter by Toma and colleagues supports previously published data about the efficacy of zidovudine for thrombocytopenic purpura in HIV-l-infected persons [1,2]. It is questioned, however, whether their patient could have been treated with zidovudine alone at the initial presentation of thrombocytopenia, or at the time of recurrence. For patients with more severe thrombocytopenia, associatedwith platelet counts of less than 10,000 to 20,00O/mm~’or with clinically significant bleeding, treatment with steroids, splenectomy, high-dose immunoglobulins, anti-Rh immunoglobulins, cytotoxic agents, or danazol, followed by zidovudine when at least a partial responseis achieved, may be a reasonable course of action. Insufficient data are available to justify the use of zidovudine alone in these situations. Investigation of the long-term responsesof thrombocytopenia to zidovudine as reported here in a larger cohort of patients will be important to assessthe risk-benefit ratio of zidovudine for this indication. Furthermore, the optimal dose of zidovudine for this indication remains to be determined.
LEE RATNER, M.D., Ph.0 Washington University St. Louis, Missouri 1. SWISS Group for Cknfcal Studfes on AIDS: Zidovudfne for the treatment of thrombocytopenia assocfated wdh human immunodekcfency virus (HIV) Ann Intern Med 1988: 109: 718-721. 2. Oksendhandler E. Bier@ P. Ferchal F. Clauvel J-P. Sekgman M: Zfdovudine lor thrombocytopenfc purpura related to human mmunodefictency wus WI’0 miecbon Ann Intern Med 1989: 110: 365-368.
AMINOGLYCOSIDE NEPHROTOXICITY IN OBSTRUCTIVE JAUNDICE: POSSIBLE CONTRIBUTION BY CONCOMITANTLY ADMINISTERED CORTICOSTEROIDS To the Editor: Although the report of Desai and Tsang (Am J Med 1988; 85: 47-50)
The American
Journal
of Medicine
Volume
87
245