Case Reports © 1990 S. Karger AG. Basel 0001-5792/90/0841-0038 $ 2.75/0
Acta Haematol 1990;84:38-39
Chronic Lymphocytic Leukemia in a Patient with Systemic Lupus erythematosus Michael Lishner, Gillian Hawker, Dominick Amato Department of Medicine, Mount Sinai Hospital and University of Toronto, Canada
Key Words. Autoimmunity and malignancy • Chronic lymphocytic leukemia • Systemic lupus erythematosus Abstract. We report the development of chronic lymphocytic leukemia in a 48-year-old woman with sys temic lupus erythematosus of 5 years’ duration. Although the association of autoimmunity and lymphoreticular malignancy is well known, this particular association has only rarely been reported. Possible mechanisms of pathogenesis are discussed.
Case Report A 48-year-old woman was diagnosed as having SLE by stan dard criteria. She was treated with nonsteroidal anti-inflammatory drugs because of arthralgias. Five years later, she developed a spi nal cord infarct and was treated at another hospital with high-dose steroids and pulses of cyclophosphamide. Three months later, she was transferred to the Rehabilitation Service of our hospital. Physi cal examination was unremarkable except for slightly reduced strength and sensation (pinprick and light touch) in the lower limbs. There was no lymphadenopathy or hepatosplenomegaly. Blood counts revealed a hemoglobin of 72 g/1, white cell count of U.7xlOVl (76% lymphocytes, frequent smudge cells), and platelets of 7 9 x l0 9/l. Biochemistries, including renal function tests, were normal. Antinuclear antibodies were positive at > 1:320, and LE cell preparation was positive. The levels of anti-ds and anti-ss DNA antibodies were 0.980 and 0.639, respectively (positive range 0.300-2.000). C3 and C4 were borderline low. Direct and in direct antiglobulin tests were negative, but platelet-associated IgG was increased. Immunoglobulin levels were normal. Bone marrow
aspiration and biopsy (performed after cyclophosphamide and ste roid treatment) showed mild hypocellularity with a slight increase in mature-appearing lymphocytes. Immunophenotyping of peri pheral blood lymphocytes demonstrated an expansion of a B cell population with the phenotype B1 + (60%), B4+ (81%), HLA-DR+ (69%), and predominantly surface immunoglobulin-negative, com patible with B-cell CLL. With continued steroid treatment and intensive physiotherapy, the patient’s neurological status improved. She was discharged and followed in her home city. Over the next 10 months, her white cell count rose to >500x lO’/l, and she developed shotty adenopathy but no splenomegaly. She was treated with leukapheresis and sub sequently chlorambucil, but with little response. She died 14 months after diagnosis of CLL.
Discussion The association between SLE and malignancy is well known [1,2], but the information concerning the relationship of SLE to lymphoproliférative diseases (LPDs) is scattered and not well established. Green et al. [3] reviewed 14 cases from the literature, added 4 of their own, and suggested that the frequency of ne oplasia and specifically non-Hodgkin’s lymphoma in SLE may be exaggerated. Agudelo et al. [4] estimated that the ratio of 4 patients with lymphoma that they observed in 130 SLE patients is increased, compared to the estimate of the general population. However,
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The association between autoimmune diseases and malignancy is well known [1, 2]. Although there is a well-recognized association between systemic lupus erythematosus (SLE) and malignant lymphoma, the true incidence of this occurrence is not well estab lished [2]. However, the occurrence of chronic lym phocytic leukemia (CLL) in patients with SLE is only rarely reported.
C L L and SLE
References 1 Canosso JJ, Cohen AS: Malignancy in a series of 70 patients with systemic lupus erythematosus. Arthritis Rheum 1974;17: 383-388. 2 Lewis RB, Castor CW, Knisley RE, Bole GG: Frequency of neoplasia in systemic lupus erythematosus and rheumatoid ar thritis. Arthritis Rheum 1976;19:1256-1260. 3 Green JA, Dawson AA, Walker W: Systemic lupus erythemato sus and lymphoma. Lancet 1978;ii:753— 758. 4 Agudelo CA, Schumacher R, Glick JH, Molina J: Non-Hodgkin’s lymphoma in systemic lupus erythematosus. J Rheumatol 1981;8:69-78. 5 Miller DG: The association of immune disease and malignant lymphoma. Ann Intern Med 1967;66:507-521. 6 Ho C, Chiang Y, Chong L, Lin H, Hwang T: Development of chronic lymphocytic leukemia in a case of Sjogren’s syndrome with systemic lupus erythematosus. Scand J Haematol 1985; 35:246-248. 7 Steinberg AB, Klinman DM: Pathogenesis of systemic lupus erythematosus. Rheum Dis Clin North Am 1988;14:25-42. 8 Houssian RA, Devogelaer JP, Gerard R, et al: Systemic lupus erythematosus and concomitant malignant lymphoma. A case report. Acta Clin Belg 1987;42:445-449. 9 Schwartz RS: Immunoregulation, oncogenic viruses and malig nant lymphomas. Lancet 1972;i: 1266-1269. 10 Hehir ME, Sewell JR, Hughes GRV: Reticulum cell sarcoma in azathioprine-treated systemic lupus erythematosus. Ann Rheum Dis 1979;38:94-95.
Received: May 31, 1989 Accepted: November 22, 1989 Dr. D. Amato Department of Medicine Mount Sinai Hospital 600 University Avenue Toronto, Ont. M5G 1X5 (Canada)
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Lewis et al. [2] found only 1 case of LPD (Hodgkin’s disease) among 484 SLE patients hospitalized in a large teaching hospital over 20 years. Thus the true in cidence is not yet clear [4], In most of the cases in which SLE and malignant lymphoma are well documented, the lymphoma deve loped months to years after the diagnosis of SLE [3]. Most of the patients were women and the mean age at diagnosis of lymphoma was 46 years, approximately 5 years after the diagnosis of SLE [3]. However, the occurrence of CLL in association with SLE has only rarely been reported. The few cases that we could find in the literature were reported before 1970 [5]. Re cently, Ho et al. [6] described the development of CLL in a case of Sjogren’s syndrome with SLE, but in this case the Sjogren’s syndrome may have been the major determining factor, since its relationship to LPDs is well known. There are several possible explanations for the de velopment of LPDs in patients with SLE. These in clude: immune regulatory defects in SLE [7], which may allow the emergence of clonal B cell prolifera tion [8]; genetic susceptibility to both autoimmunity and lymphoid proliferation [5]; activation of latent oncogenic viruses in patients with SLE and poorly re gulated immune systems [9], and immunosuppressive drugs (used to treat the SLE) leading to development of a LPD [10]. Finally, the concurrence of SLE and CLL may be interpreted as the coexistence of two rel atively common diseases in the same patient. Before this last explanation is accepted, however, more de finitive epidemiological studies are needed to deter mine the true frequency of the coincidence of SLE with CLL and other LPDs.
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