©1991 S. Karger AG, Basel 0028-2766/91 /0593 0493S2.75/0
Nephron 1991;59:493-496
Hemolytic-Uremic Syndrome with Anticardiolipin Antibodies Revealing Paraneoplastic Systemic Scleroderma A. Meyriera. L. Becquemonta. B. Weillh. P. Callardc, M. Rainfray a “Service de Néphrologie, Hôpital Avicenne, Bobigny; bLaboratoire d'immunologie Clinique, Hôpital Cochin, Paris; c Laboratoire d‘Anatomopathologie, Hôpital Jean Verdier, Bondy, France
KeyWords. Hemolytic-uremic syndrome • Cancer of the prostate • Acute renal failure • Systemic scleroderma • Lupus anticoagulant • Antiphospholipid antibodies Abstract. Lupus anticoagulant was present in this case of paraneoplastic scleroderma revealed by hemolyticuremic syndrome, suggesting that the autoantibody played a significant role in the sequence of events leading to anuria. Reviewing the literature we found several observations of paraneoplastic scleroderma, and in other series cases of scleroderma-linked (and in rare instances cancer-linked) antiphospholipid autoantibodies. Search for antiphospholipid antibodies should be considered in patients with systemic scleroderma as well as in patients with metastatic cancer. Presence of such procoagulant autoantibodies might predict future complications and should influence treatment strategy.
Diseases other than systemic lupus can elicit antiphos pholipid antibodies [1, 2], They can play a part in clinical manifestations, essentially characterized by thrombosis and thrombocytopenia. Thrombosis associated with the lupus anticoagulant mostly affects large vessels, includ ing veins and arteries [3-6]. Association of antiphospho lipid antibodies with the hemolytic-uremic syndrome (HUS) or renal thrombotic microangiopathy has rarely been observed, and was described only in cases of preg nancy [7] and in some patients with systemic lupus erythe matosus [8]. We report the case of a patient with cancer of the prostate in whom HUS with anuria revealed systemic scleroderma (SS) of recent onset, presumably paraneo plastic. Antiphospholipid antibodies (Ab) were found. Renal histology showed typical sclerodermic nephro
sclerosis and thrombotic microangiopathy. The patient remained anuric. This case is of particular interest in view of the relationship between cancer, scleroderma, anti phospholipid antibodies and HUS.
Case Report This 73-year-old white male presented with acute renal failure occurring 2 years after discovery of cancer of the prostate. He had been well until 1987 when consultation for pelvic pain revealed cancer of the prostate with metastases to the iliac bones and the spine. Blood pressure (BP) was 130/95 mm Hg, serum creatinine was 90 pmol/1 and intravenous pyelography was normal. Treatment was begun with cyproterone acetate and a luteinizing hormone-relea sing hormone analogue. Bone pain disappeared within I month. In July 1988 Raynaud's phenomenon was noted. In October 1988 the patient was admitted for confusion, oliguria and swollen legs. There was no recent history of infection or diar rhea. The patient looked acutely ill. Temperature was 37.9°C. BP
Downloaded by: Kings's College London 137.73.144.138 - 10/24/2017 3:31:21 AM
Introduction
494
Fig. 1. Renal biopsy. Typical features of malignant nephroscle rosis are visible on the artery shown on this sample. Note the wrinkled, ischemic appearance of the glomerulus on the left.
Fig. 2. Detail of a glomerulus with typical microangiopathic features and complete obliteration of most of the capillary loops by thrombi.
was 160/95 mm Hg. Funduscopy revealed grade III (Keith & We gener) hypertensive retinopathy. The prostate was clinically normal. The diagnosis of scleroderma was evident at inspection, with a taut appearance of the face, the trunk and the hands. It was later confirmed by (1) a typical aspect on skin biopsy, with fibrosis and microcalcification ; (2) microangiopathy observed on nail bed capillaroscopy. and (3) pulmonary function tests which disclosed restric tive disease and decreased CO diffusion capacity.
1 (ig/ml of purified anticardiolipin IgG or IgM kindly provided by Harris et al. [9] (the test is considered positive when the IgG or IgM anticardiolipin Ab are > 6 GPL or > 3 GML units, respectively). The assay was positive (IgG fraction, 17 GPL units). Antiplatelet Ab were de tected by Dixon’s test. Antinuclear Ab were present by immunofluorescence (1/100, speckled). Direct Coombs trest, search for single- and double-stranded anti-DNA Ab, anti-Sm, anti-Ro, anticentromere, anti-SCL-70, an tineutrophil cytoplasmic Ab and anticyproterone acetate Ab were all negative. Bone radiological survey showed progression of bone metastases. No other localization of cancer was found on pelvic and abdominal CT scan examination. Urinary tract was patent. Serum prostatic specific antigen (PSA) and acid phosphatase were elevated. Bone biopsy stud ied by light microscopy and with an anti-PSA mono clonal Ab confirmed the diagnosis of prostatic adenocar cinoma. The patient was treated with captopril, acetyl-salicylic acid, fresh-frozen plasma and maintenance hemodialy sis. One month later the microangiopathic process had disappeared. Antithrombin III, protein C and protein S levels were normal. Activated thromboplastin time was still abnormal. Despite disappearance of the microangio pathic process, diuresis did not resume. The findings of percutaneous renal biopsy, which was performed at the third month of anuria, are described in the legends to figure 1, 2. At the time of writing this report the patient is still anuric. Sclerodermic features have progressed.
Results Laboratory work-up disclosed the following abnor malities. Serum creatinine was 460 pmol/1 at admission and rose to 1,200 umol/1 4 days later. White blood cell count was 16,800/mm3 with 80% neutrophils. Hemoglobin was 7 g/dl, reticulocyte count was 400,000/mm3, numerous schistocytes were present, haptoglobin was 0.09 g/1, platelet count was 65,000/mm3, activated thromboplas tin time was 65" (normal 37"), prothrombin was 54%, clotting factors were low. Abundant fibrin degradation products were detected. Serum electrolytes were (mmol/ 1): Na 130, K 3.4, Cl 106, bicarbonate 19 and Ca 2.35. Total serum proteins were 5.7 g/dl (serum albumin 3.5). Liver tests were normal. Urine analysis revealed slight (0.6 g/1) proteinuria, no hematuria or leukocyturia. There were no cryoglobulins. Complement fractions were normal. Anticardiolipin Ab were sought using the enzymelinked immunoassay described by Harris et al. [9], GPL and GML units were defined as the Ab reactivity of
Downloaded by: Kings's College London 137.73.144.138 - 10/24/2017 3:31:21 AM
Meyrier/Becquemont/Weill/Callard/Rainfray
Antiphospholipid Antibodies and Scleroderma
In this patient HUS supervened in the course of metas tatic cancer of the prostate, led to the discovery of sclero derma of recent onset, and was associated with antiphos pholipid Ab. The three conditions can explain the devel opment of HUS; they are not exclusive and might have been mutually reinforcing. Paraneoplastic Scleroderma The succession of cancer and SS suggests that sclero derma was of paraneoplastic origin. This association has already been described, and we have found 15 reports of SS in patients already suffering from cancer [10-12], There were 14 females and 1 male with a mean age of 60 years. The tumors involved the breast in 6, the ovary in 3, the gastrointestinal tract in 3, the cervix in 2 and the thyroid gland in 1. In 4 of these patients, cancer and SS were diagnosed simultaneously, and the renal crisis of scleroderma was revealing in 2 of them. In one, the paraneoplastic origin of scleroderma was demonstrated by disappearance of skin lesions after surgical removal of the tumor [12]. Search for antiphospholipid Ab was not undertaken in these cases. Hemolytic-Uremic Syndrome Three possible etiologies of HUS, namely sclero derma, cancer and antiphospholipid Ab must be consid ered in the present case. The HUS of sclerodermic crisis has long been known. It is observed in 14% of patients with SS [13] but reveals SS in less than 1% of patients [14]. In some instances, anuria complicating sclerodermic crisis and HUS was followed by recovery of renal function after a protracted period of maintenance hemodialysis [15]. HUS may occasionally complicate cancer [16, 17], in cluding metastatic adenocarcinoma of the prostate. In such a case, it is usually ascribed to chemotherapy or estrogens. It may also reveal unsuspected prostatic cancer [18]. To the best of our knowledge the specific drugs taken by our patient have never been suspected of inducing HUS. Antiphospholipid Ah Lupus anticoagulants can be associated with venous and arterial thrombosis in patients with SLE [4], This is also the case with the germane 'anticardiolipin syn drome’ [5]. These procoagulant autoantibodies may also induce thromboses in glomerular capillaries [8] or be associated with the glomerular lesions of toxemia of
pregnancy [7], We doubt that metastatic cancer of the prostate was the source of antiphospholipid Ab in our patient, although a few cases of malignancy associated with lupus anticoagulant have been described [19,20], On the contrary, the immunological background of sclero derma would be a more likely explanation. Malia et al. [21] detected anticardiolipin Ab of IgG/IgM class in 7 of 28 patients with SS including 5 of 16 patients severely affected by extensive visceral disease. Such visceral in volvement was assessed by means of a disease score. In this essentially immunological paper, no details were given concerning possible renal manifestations of SS. However, Malia et al. suggested that presence of anticar diolipin Ab in SS is an indicator of severity. It would probably be worthwhile in future cases to determine whether such antibodies are more frequent in patients with scleroderma crisis ending in anuria. More generally, search for antiphospholipid Ab should probably be more systematic in patients suffering from conditions liable to be complicated with HUS. Presence of such Ab might indicate the necessity for antiplatelet therapy. It should perhaps also discourage prescription of such drugs as estrogens, mitomycin C or cyclosporin A.
References 1 Mackworth-Young CG, Loizou S, Walport MJ: Antiphospho lipid antibodies and disease. Q J Med 1989:72:767-777. 2 Asherson RA, Khamashta MA, Ordi-Ros J, et al: The ‘primary’ antiphospholipid syndrome: Major clinical and serological fea tures. Medicine (Baltimore) 1989;68:366-374. 3 Kant KS, Poliak VE, Weiss MA, Glueck HI, Miller MA, Hess EV: Glomerular thrombosis in SLE, prevalence and signifi cance. Medicine (Baltimore) 1981 ;60:71— 86. 4 Glueck HI. Kant KS, Weiss MA, Poliak VE, Miller MA, Coots M : Thrombosis in SLE in relation to the presence of circulating anticoagulants. Arch Intern Med 1985;145:1389-1395. 5 Hughes GRV. Harris NN, Gharavi AE: The anticardiolipin syndrome. J Rheumatol 1986;13:486-489. 6 Alarcon-Segovia D. Delezé M, Oria CV, et al : Antiphospholipid antibodies and the antiphospholipid syndrome in systemic lu pus erythematosus. A prospective analysis of 500 consecutive patients. Medicine (Baltimore) 1989:68:353-365. 7 Kincaid-Smith P, Fairley KF, Kloss M: Lupus anticoagulant associated with renal thrombotic microangiopathy and preg nancy related renal failure. Q J Med 1988;69:795-815. 8 Kleinknecht D. Bobrie G. Meyer O. Noël LH, Callard P, Ramdane M: Recurrent thrombosis and renal vascular disease in patients with a lupus anticoagulant. Nephrol Dial Transplant 1989:4:843-922. 9 Harris EN, Gharavi AE, Wasley GD, Hughes GRV: Use of an enzyme-linked immunosorbent assay and of inhibition studies to distinguish between antibodies to cardiolipin from patients
Downloaded by: Kings's College London 137.73.144.138 - 10/24/2017 3:31:21 AM
Discussion
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10 11 12
13
14
15
16 17
with syphilis or autoimmune disorders. J Infect Dis 1988; 157:23-32. Roumm AD, Medsger TA; Cancer and systemic sclerosis, an epidemiologic study. Arthritis Rheum 1985:28:1336-1340. Talbott JH, Barrocas M: PSS in malignancy, pulmonary and non-pulmonary. Medicine (Baltimore) 1979:58:182-207. Juliot AY.Vittori F, Allard C, Levrat R: Sclérodermie en plaques symptomatique d'un cancer du rectum. Nouv Presse Méd 1979:8:703. Steen YD, Medsger TA, Osial TA, Ziegler GL, Shapiro AP, Rodnan GP: Factors predicting development of renal involve ment in PSS. Am J Med 1984;76:779-786. Traub YM, Shapiro AP, Rodnan GP, et al: Hypertension and renal failure (scleroderma renal crisis) in PSS. Medicine (Balti more) 1983:62:335-352. Meyrier A, Becquemont L, Simon P, Laaban JP: Protracted anuria due to active vasoconstriction in primary or secondary malignant hypertension. Nephrol Dial Transplant 1990; 5:174-178. Multinovic J, Irly S, Fisher M : Hemolytic and uremic syndrome and metastatic malignancy. South Med J 1982;75:1409-1411. Sennesael JJ, Vanden Houte KM,Spapen H D ,de Bruyne RMG, Verbeelen DL: Recurrent hemolytic and uremic syndrome and metastatic malignancy. Am J Nephrol 1987;7:60-64.
Meyrier/Becquemont/Weill/Callard/Rainfray
18 Innés A, Bernard T, Cotton RE, Burden RP: Recurrent haemo lytic uraemic syndrome in the elderly associated with metastatic carcinoma. Nephrol Dial Transplant 1990;5:886-890. 19 Dührsen U, Paar D, Kölbel C, et al: Lupus anticoagulant asso ciated syndrome in benign and malignant systemic disease Analysis of 10 observations. Klin Wochenschr 1987 ; 65:852-859. 20 Kozlowski CL, Johnson MJ, Gorst DW, Willey RF: Lung cancer, immune thrombocytopenia and the lupus inhibitor. Postgrad Med J 1987;63:793-795. 21 Malia RG, Greaves M, Rowlands LN, et al: Anticardiolipin antibodies in systemic sclerosis: Immunological and clinical associations. Clin Exp Immunol 1988;73:456-460.
Accepted: January 18,1991 A. Meyrier, MD Service de Néphrologie Hôpital Avicenne 125, route de Stalingrad F-93009 Bobigny (France)
Downloaded by: Kings's College London 137.73.144.138 - 10/24/2017 3:31:21 AM
496
Nephron 1991;59:493-496
Hemolytic-Uremic Syndrome with Anticardiolipin Antibodies Revealing Paraneoplastic Systemic Scleroderma A. Meyriera. L. Becquemonta. B. Weillh. P. Callardc, M. Rainfray a “Service de Néphrologie, Hôpital Avicenne, Bobigny; bLaboratoire d'immunologie Clinique, Hôpital Cochin, Paris; c Laboratoire d‘Anatomopathologie, Hôpital Jean Verdier, Bondy, France
KeyWords. Hemolytic-uremic syndrome • Cancer of the prostate • Acute renal failure • Systemic scleroderma • Lupus anticoagulant • Antiphospholipid antibodies Abstract. Lupus anticoagulant was present in this case of paraneoplastic scleroderma revealed by hemolyticuremic syndrome, suggesting that the autoantibody played a significant role in the sequence of events leading to anuria. Reviewing the literature we found several observations of paraneoplastic scleroderma, and in other series cases of scleroderma-linked (and in rare instances cancer-linked) antiphospholipid autoantibodies. Search for antiphospholipid antibodies should be considered in patients with systemic scleroderma as well as in patients with metastatic cancer. Presence of such procoagulant autoantibodies might predict future complications and should influence treatment strategy.
Diseases other than systemic lupus can elicit antiphos pholipid antibodies [1, 2], They can play a part in clinical manifestations, essentially characterized by thrombosis and thrombocytopenia. Thrombosis associated with the lupus anticoagulant mostly affects large vessels, includ ing veins and arteries [3-6]. Association of antiphospho lipid antibodies with the hemolytic-uremic syndrome (HUS) or renal thrombotic microangiopathy has rarely been observed, and was described only in cases of preg nancy [7] and in some patients with systemic lupus erythe matosus [8]. We report the case of a patient with cancer of the prostate in whom HUS with anuria revealed systemic scleroderma (SS) of recent onset, presumably paraneo plastic. Antiphospholipid antibodies (Ab) were found. Renal histology showed typical sclerodermic nephro
sclerosis and thrombotic microangiopathy. The patient remained anuric. This case is of particular interest in view of the relationship between cancer, scleroderma, anti phospholipid antibodies and HUS.
Case Report This 73-year-old white male presented with acute renal failure occurring 2 years after discovery of cancer of the prostate. He had been well until 1987 when consultation for pelvic pain revealed cancer of the prostate with metastases to the iliac bones and the spine. Blood pressure (BP) was 130/95 mm Hg, serum creatinine was 90 pmol/1 and intravenous pyelography was normal. Treatment was begun with cyproterone acetate and a luteinizing hormone-relea sing hormone analogue. Bone pain disappeared within I month. In July 1988 Raynaud's phenomenon was noted. In October 1988 the patient was admitted for confusion, oliguria and swollen legs. There was no recent history of infection or diar rhea. The patient looked acutely ill. Temperature was 37.9°C. BP
Downloaded by: Kings's College London 137.73.144.138 - 10/24/2017 3:31:21 AM
Introduction
494
Fig. 1. Renal biopsy. Typical features of malignant nephroscle rosis are visible on the artery shown on this sample. Note the wrinkled, ischemic appearance of the glomerulus on the left.
Fig. 2. Detail of a glomerulus with typical microangiopathic features and complete obliteration of most of the capillary loops by thrombi.
was 160/95 mm Hg. Funduscopy revealed grade III (Keith & We gener) hypertensive retinopathy. The prostate was clinically normal. The diagnosis of scleroderma was evident at inspection, with a taut appearance of the face, the trunk and the hands. It was later confirmed by (1) a typical aspect on skin biopsy, with fibrosis and microcalcification ; (2) microangiopathy observed on nail bed capillaroscopy. and (3) pulmonary function tests which disclosed restric tive disease and decreased CO diffusion capacity.
1 (ig/ml of purified anticardiolipin IgG or IgM kindly provided by Harris et al. [9] (the test is considered positive when the IgG or IgM anticardiolipin Ab are > 6 GPL or > 3 GML units, respectively). The assay was positive (IgG fraction, 17 GPL units). Antiplatelet Ab were de tected by Dixon’s test. Antinuclear Ab were present by immunofluorescence (1/100, speckled). Direct Coombs trest, search for single- and double-stranded anti-DNA Ab, anti-Sm, anti-Ro, anticentromere, anti-SCL-70, an tineutrophil cytoplasmic Ab and anticyproterone acetate Ab were all negative. Bone radiological survey showed progression of bone metastases. No other localization of cancer was found on pelvic and abdominal CT scan examination. Urinary tract was patent. Serum prostatic specific antigen (PSA) and acid phosphatase were elevated. Bone biopsy stud ied by light microscopy and with an anti-PSA mono clonal Ab confirmed the diagnosis of prostatic adenocar cinoma. The patient was treated with captopril, acetyl-salicylic acid, fresh-frozen plasma and maintenance hemodialy sis. One month later the microangiopathic process had disappeared. Antithrombin III, protein C and protein S levels were normal. Activated thromboplastin time was still abnormal. Despite disappearance of the microangio pathic process, diuresis did not resume. The findings of percutaneous renal biopsy, which was performed at the third month of anuria, are described in the legends to figure 1, 2. At the time of writing this report the patient is still anuric. Sclerodermic features have progressed.
Results Laboratory work-up disclosed the following abnor malities. Serum creatinine was 460 pmol/1 at admission and rose to 1,200 umol/1 4 days later. White blood cell count was 16,800/mm3 with 80% neutrophils. Hemoglobin was 7 g/dl, reticulocyte count was 400,000/mm3, numerous schistocytes were present, haptoglobin was 0.09 g/1, platelet count was 65,000/mm3, activated thromboplas tin time was 65" (normal 37"), prothrombin was 54%, clotting factors were low. Abundant fibrin degradation products were detected. Serum electrolytes were (mmol/ 1): Na 130, K 3.4, Cl 106, bicarbonate 19 and Ca 2.35. Total serum proteins were 5.7 g/dl (serum albumin 3.5). Liver tests were normal. Urine analysis revealed slight (0.6 g/1) proteinuria, no hematuria or leukocyturia. There were no cryoglobulins. Complement fractions were normal. Anticardiolipin Ab were sought using the enzymelinked immunoassay described by Harris et al. [9], GPL and GML units were defined as the Ab reactivity of
Downloaded by: Kings's College London 137.73.144.138 - 10/24/2017 3:31:21 AM
Meyrier/Becquemont/Weill/Callard/Rainfray
Antiphospholipid Antibodies and Scleroderma
In this patient HUS supervened in the course of metas tatic cancer of the prostate, led to the discovery of sclero derma of recent onset, and was associated with antiphos pholipid Ab. The three conditions can explain the devel opment of HUS; they are not exclusive and might have been mutually reinforcing. Paraneoplastic Scleroderma The succession of cancer and SS suggests that sclero derma was of paraneoplastic origin. This association has already been described, and we have found 15 reports of SS in patients already suffering from cancer [10-12], There were 14 females and 1 male with a mean age of 60 years. The tumors involved the breast in 6, the ovary in 3, the gastrointestinal tract in 3, the cervix in 2 and the thyroid gland in 1. In 4 of these patients, cancer and SS were diagnosed simultaneously, and the renal crisis of scleroderma was revealing in 2 of them. In one, the paraneoplastic origin of scleroderma was demonstrated by disappearance of skin lesions after surgical removal of the tumor [12]. Search for antiphospholipid Ab was not undertaken in these cases. Hemolytic-Uremic Syndrome Three possible etiologies of HUS, namely sclero derma, cancer and antiphospholipid Ab must be consid ered in the present case. The HUS of sclerodermic crisis has long been known. It is observed in 14% of patients with SS [13] but reveals SS in less than 1% of patients [14]. In some instances, anuria complicating sclerodermic crisis and HUS was followed by recovery of renal function after a protracted period of maintenance hemodialysis [15]. HUS may occasionally complicate cancer [16, 17], in cluding metastatic adenocarcinoma of the prostate. In such a case, it is usually ascribed to chemotherapy or estrogens. It may also reveal unsuspected prostatic cancer [18]. To the best of our knowledge the specific drugs taken by our patient have never been suspected of inducing HUS. Antiphospholipid Ah Lupus anticoagulants can be associated with venous and arterial thrombosis in patients with SLE [4], This is also the case with the germane 'anticardiolipin syn drome’ [5]. These procoagulant autoantibodies may also induce thromboses in glomerular capillaries [8] or be associated with the glomerular lesions of toxemia of
pregnancy [7], We doubt that metastatic cancer of the prostate was the source of antiphospholipid Ab in our patient, although a few cases of malignancy associated with lupus anticoagulant have been described [19,20], On the contrary, the immunological background of sclero derma would be a more likely explanation. Malia et al. [21] detected anticardiolipin Ab of IgG/IgM class in 7 of 28 patients with SS including 5 of 16 patients severely affected by extensive visceral disease. Such visceral in volvement was assessed by means of a disease score. In this essentially immunological paper, no details were given concerning possible renal manifestations of SS. However, Malia et al. suggested that presence of anticar diolipin Ab in SS is an indicator of severity. It would probably be worthwhile in future cases to determine whether such antibodies are more frequent in patients with scleroderma crisis ending in anuria. More generally, search for antiphospholipid Ab should probably be more systematic in patients suffering from conditions liable to be complicated with HUS. Presence of such Ab might indicate the necessity for antiplatelet therapy. It should perhaps also discourage prescription of such drugs as estrogens, mitomycin C or cyclosporin A.
References 1 Mackworth-Young CG, Loizou S, Walport MJ: Antiphospho lipid antibodies and disease. Q J Med 1989:72:767-777. 2 Asherson RA, Khamashta MA, Ordi-Ros J, et al: The ‘primary’ antiphospholipid syndrome: Major clinical and serological fea tures. Medicine (Baltimore) 1989;68:366-374. 3 Kant KS, Poliak VE, Weiss MA, Glueck HI, Miller MA, Hess EV: Glomerular thrombosis in SLE, prevalence and signifi cance. Medicine (Baltimore) 1981 ;60:71— 86. 4 Glueck HI. Kant KS, Weiss MA, Poliak VE, Miller MA, Coots M : Thrombosis in SLE in relation to the presence of circulating anticoagulants. Arch Intern Med 1985;145:1389-1395. 5 Hughes GRV. Harris NN, Gharavi AE: The anticardiolipin syndrome. J Rheumatol 1986;13:486-489. 6 Alarcon-Segovia D. Delezé M, Oria CV, et al : Antiphospholipid antibodies and the antiphospholipid syndrome in systemic lu pus erythematosus. A prospective analysis of 500 consecutive patients. Medicine (Baltimore) 1989:68:353-365. 7 Kincaid-Smith P, Fairley KF, Kloss M: Lupus anticoagulant associated with renal thrombotic microangiopathy and preg nancy related renal failure. Q J Med 1988;69:795-815. 8 Kleinknecht D. Bobrie G. Meyer O. Noël LH, Callard P, Ramdane M: Recurrent thrombosis and renal vascular disease in patients with a lupus anticoagulant. Nephrol Dial Transplant 1989:4:843-922. 9 Harris EN, Gharavi AE, Wasley GD, Hughes GRV: Use of an enzyme-linked immunosorbent assay and of inhibition studies to distinguish between antibodies to cardiolipin from patients
Downloaded by: Kings's College London 137.73.144.138 - 10/24/2017 3:31:21 AM
Discussion
495
10 11 12
13
14
15
16 17
with syphilis or autoimmune disorders. J Infect Dis 1988; 157:23-32. Roumm AD, Medsger TA; Cancer and systemic sclerosis, an epidemiologic study. Arthritis Rheum 1985:28:1336-1340. Talbott JH, Barrocas M: PSS in malignancy, pulmonary and non-pulmonary. Medicine (Baltimore) 1979:58:182-207. Juliot AY.Vittori F, Allard C, Levrat R: Sclérodermie en plaques symptomatique d'un cancer du rectum. Nouv Presse Méd 1979:8:703. Steen YD, Medsger TA, Osial TA, Ziegler GL, Shapiro AP, Rodnan GP: Factors predicting development of renal involve ment in PSS. Am J Med 1984;76:779-786. Traub YM, Shapiro AP, Rodnan GP, et al: Hypertension and renal failure (scleroderma renal crisis) in PSS. Medicine (Balti more) 1983:62:335-352. Meyrier A, Becquemont L, Simon P, Laaban JP: Protracted anuria due to active vasoconstriction in primary or secondary malignant hypertension. Nephrol Dial Transplant 1990; 5:174-178. Multinovic J, Irly S, Fisher M : Hemolytic and uremic syndrome and metastatic malignancy. South Med J 1982;75:1409-1411. Sennesael JJ, Vanden Houte KM,Spapen H D ,de Bruyne RMG, Verbeelen DL: Recurrent hemolytic and uremic syndrome and metastatic malignancy. Am J Nephrol 1987;7:60-64.
Meyrier/Becquemont/Weill/Callard/Rainfray
18 Innés A, Bernard T, Cotton RE, Burden RP: Recurrent haemo lytic uraemic syndrome in the elderly associated with metastatic carcinoma. Nephrol Dial Transplant 1990;5:886-890. 19 Dührsen U, Paar D, Kölbel C, et al: Lupus anticoagulant asso ciated syndrome in benign and malignant systemic disease Analysis of 10 observations. Klin Wochenschr 1987 ; 65:852-859. 20 Kozlowski CL, Johnson MJ, Gorst DW, Willey RF: Lung cancer, immune thrombocytopenia and the lupus inhibitor. Postgrad Med J 1987;63:793-795. 21 Malia RG, Greaves M, Rowlands LN, et al: Anticardiolipin antibodies in systemic sclerosis: Immunological and clinical associations. Clin Exp Immunol 1988;73:456-460.
Accepted: January 18,1991 A. Meyrier, MD Service de Néphrologie Hôpital Avicenne 125, route de Stalingrad F-93009 Bobigny (France)
Downloaded by: Kings's College London 137.73.144.138 - 10/24/2017 3:31:21 AM
496
