characteristic ballooning in the prickle-cell layer of the epidermis.2 The lesions do not respond to antifungal therapy, even though surface cultures often yield ...
characteristic ballooning in the prickle-cell layer of the epidermis.2 The lesions do not respond to antifungal therapy, even though surface cultures often yield Candida.' Papillomavirus and EpsteinBarr virus have been detected in the affected epithelial cells, and an interaction of these viruses may account for the lesions.3 There is a strong association between this form of leukoplakia and previous exposure to HIV-I in homosexual men. Of 79 serum samples obtained from such men with these lesions, 78 had HIV-I antibody.4 In San Francisco 20 of 80 homosexual men acquired AIDS within 1 to 33 months (mean 7.5 months) of the diagnosis of oral "hairy" leukoplakia.4 The positive serologic results in our case allowed us to recommend that appropriate precautions be taken to avoid exposure to potentially infectious material. In addition, the patient's family was advised accordingly.5 The patient will have to be monitored closely because of the high risk for AIDS. This is the first report of oral "hairy" leukoplakia associated with exposure to HIV-I after blood transfusion. It occurred almost 1 year before the Canadian Red Cross Blood Transfusion Service began screening all blood products for HIV anti-
body; the number of future cases attributed to blood transfusion should be small. Addendum Since this paper was accepted for publication a similar case has been reported in which the leukoplakia is believed to have occurred secondary to a blood transfusion.6
References 1. Greenspan JS, Greenspan D, Lennette ET et al: Oral viral leukoplakia - a new AIDS-associated condition. Adv Exp Med Biol 1985; 187: 123-128 2. Greenspan D, Greenspan JS, Conant M et al: Oral ''hairy" leucoplakia in male homosexuals: evidence of association with both papillomavirus and a herpes-group virus. Lancet 1984; 2: 831-834 3. Greenspan JS, Greenspan D, Lennette ET et al: Replication of Epstein-Barr virus within the epithelial cells of oral "hairy" leukoplakia, an AIDS-associated lesion. N Engl J Med 1985; 313: 1564-1571 4. Oral viral lesion (hairy leukoplakia) associated with acquired immunodeficiencv svndrome. MMWR 1985; 34: 549-550 5. Guidelines for household contacts of HTLV-III/LAV-reactive persons and AIDS patients. Can Dis Wkly Rep 1986; 12: 6567 6. Greenspan D, Hollander H, Friedman-Kien A et al: Oral hairy leucoplakia in two women, a haemophiliac, and a transfusion recipient [C]. Lancet 1986; 2: 978-979
Aplastic anemia complicating infectious mononucleosis Carol A. Sawka, MD Jo-Anne Bessette, MD Bruce Furie, MD Jane F. Desforges, MD A
plastic anemia is a rare complication of infectious mononucleosis.1 Isolated cytopenias, such as immune thrombocytopenia and cold agglutinin-mediated hemolysis, are more common. Case report
Pharyngitis, cervical lymphadenopathy and fatigue developed in a previously healthy 17-year-old girl. One week later petechiae and epistaxis developed. She was taking no medications and had no prior history of blood dyscrasias, hepatitis or other medical problems. Pertinent From the Division of Hematology-Oncology, Department of Medicine, New England Medical Center, Boston Reprint requests to: Dr. Carol A. Sawka, Division of Hematology-Oncology, Department of Medicine, St. Michael's Hospital, 30 Bond St., Toronto, Ont. M5B 1 W8 730
CMAJ, VOL. 136, APRIL 1, 1987
physical findings included multiple petechiae and ecchymoses on the skin and palate and bilateral tender cervical lymphadenopathy. There was no hepatosplenomegaly. Laboratory evaluation gave the following results: hemoglobin concentration 100 g/L, reticulocyte count 30 X 109/L, leukocyte count 7.3 X 109/L (50% lymphocytes, 35% neutrophils, 8% atypical lymphocytes, 5% monocytes and 2% eosinophils) and platelet count 3 X 109/L. A Coombs' test gave negative results. A Monospot test (Ortho Diagnostics, Raritan, New Jersey) gave positive results, and the titres of antibody to Epstein-Barr virus (EBV) capsid antigen were elevated (acute titre 1:640, convalescent titre 1:2560). The ratio of helper to suppressor T cells was low, at 0.45. Bone marrow studies showed decreased cellularity, a markedly decreased number of megakaryocytes and a decreased number of erythroid precursor cells, the myeloid:erythroid ratio being 20:1.
The patient's clinical course is shown in Fig. 1. Therapy with prednisone, 100 mg/d given orally, was begun but was stopped because of continuing epistaxis and gastrointestinal bleeding. Platelet and packed red blood cell transfusions were given. Therapy with danazol, 200 mg given orally twice a day, was started on the 14th hospital day to suppress menstruation. Bone marrow studies on the 8th hospital day showed virtual absence of megakaryocytes and erythroid precursors. The reticulocytopenia and thrombocytopenia persisted, and by the 25th hospital day neutropenia was also evident (absolute neutrophil count 0.6 X 109/L). HLA typing was done, but the patient did not have a haploidentical sibling. On the 30th hospital day therapy was begun with antithymocyte globulin (ATG) (Upjohn Corporation, Kalamazoo, Michigan), 40 mg/kg per day for 4 days. Serum sickness, as manifested by fever, chills, rash and pruritus, was controlled with antihistamines and antipyretics. Several weeks after treatment with ATG the platelet count returned to normal and the reticulocyte count rose to 170 X 109/L; subsequently the hematocrit and the leukocyte count increased to normal. At the time of writing, 3 years after the onset of the illness, the patient is still in complete clinical remission without therapy. In-vitro methylcellulose culture of erythroid progenitor cells (burst-forming unit-erythroid [BFU-E]) from the patient and from a normal control was performed before blood transfusion, as previously described.2 The results were consistent with an immune-mediated mechanism of the aplastic anemia: the patient's T lymphocytes inhibited formation of both autologous and allogeneic BFU-E, while normal T lymphocytes supported formation of BFU-E from both the patient and the normal control. (The mean numbers [and standard 0 .1
deviations] of BFU-E in cultures of non-T cells plus T cells were as follows: patient non-T + patient T, 15 [2]; patient non-T + control T, 132 [13]; control non-T + patient T, 219 [18]; control non-T + control T, 407 [26]; patient non-T + [patient + control]T, 42 [3]; and control non-T + [patient + control]T, 156 [12].) This pattern of colony formation has previously been described in immunemediated aplastic anemia.3 Comments
Although aplastic anemia has been described in association with aberrant responses to EBV infection in immunologically compromised boys with the X-linked lymphoproliferative syndrome,4 it rarely follows infectious mononucleosis in immunocompetent hosts. Lazarus and Baehner1 reviewed 10 cases, but in only 4 was aplastic anemia proven to be the cause of peripheral pancytopenia. Shadduck and colleagues5 reported one case and showed that coculture of patient and normal marrow cells resulted in suppression of myeloid progenitors. This finding is consistent with cellmediated inhibition of hematopoiesis. Aplastic anemia due to immune-mediated suppression of hematopoietic progenitor cells is well described.36 Some cases are thought to be mediated by suppressor T lymphocytes.3 The restriction of the inhibitory activity in our patient to the T-lymphocyte population is consistent with this mechanism. Therefore, both the clinical response to ATG7 and the in-vitro culture results support the hypothesis that immune-mediated inhibition of hematopoiesis was the cause of bone marrow aplasia in our patient. This study was supported in part by grants 5T32HL07437-05 and HL15157-11 from the National Institutes of Health, Bethesda, Maryland, and by the Alberta Heritage Foundation for Medical Research.
rt
References P.
t
j
-'t tt LC ~~~~~
0 ~~~~~~~~
F
.++r
t
S
t
'
;
9
rows rersn trnsuson ofx^ pltele>t{s} and packed red,,bood_ cells.. AT
Fig. 1
e globulin. . antithymocyt}
Clinical course of patient with infectious
1. Lazarus KH, Baehner RL: Aplastic anemia complicating infectious mononucleosis: a case report and a review of the literature. Pediatrics 1981; 67: 907-910 2. Sawka CA, Desforges JF: Target cell for prostaglandin E in the stimulation of in vitro human erythroid (BFU-E) progenitor cells: correlation of Ia antigen expression with the stimulatory effect. Exp Hematol 1986; 14: 873-877 3. Bacigalupo A, Podesta M, Mingari MC et al: Immune suppression of hematopoiesis in aplastic anemia: activity of T-'y lymphocytes. J Immunol 1980; 125: 1449-1453 4. Purtilo DT, Sakamoto K, Barnabei V et al: Epstein-Barr virus induced diseases in boys with the X-linked lymphoproliferative syndrome (XLP). Am J Med 1982; 75: 49-56 5. Shadduck RK, Winkelstein A, Zeigler Z et al: Aplastic anemia following infectious mononucleosis: possible immune etiology. Exp Hematol 1979; 7: 264-271 6. Singer JW, Doney KC, Thomas ED: Coculture studies of 16 untransfused patients with aplastic anemia. Blood 1979; 54: 180-185 7. Amare M, Abdou NL, Robinson MG et al: Aplastic anemia associated with bone marrow suppressor T-cell hyperactivity: successful treatment with antithymocyte globulin. Am J Hematol 1978; 5: 28-32
CMAJ, VOL. 136, APRIL 1, 1987
731
