ChloroquineV1, Istex, Corpus, bibRecord, 000831

The Association of Malignancy with SLE: An Analysis of 150 Patients Long-Term Review

Identifieur interne : 000831 ( Istex/Corpus ); précédent : 000830; suivant : 000832

The Association of Malignancy with SLE: An Analysis of 150 Patients Long-Term Review

Auteurs : S. Menon ; M. L. Snaith ; D. A. Isenberg

Source :

Lupus [ 0961-2033 ] ; 1993-06.

RBID : ISTEX:913950C1D11D2F1FCB1102270229E1083FF3B40C

English descriptors

Teeft :
- Arch intern, Arthritis, Arthritis rheum, Breast carcinoma, Carcinoma, Case histories, Cervical atypia, Chest radiograph, Cytotoxic agents, Erythematosus, Female patient, Lupus, Lupus patients, Lymphoma, Malignancy, Malignant, Malignant lymphoma, Prednisolone, Relative risk, Rheum, Rheumatic diseases, Rheumatoid arthritis, Speckled pattern, Syndrome, Systemic, Systemic lupus erythematosus, Tumour.

Abstract

We describe seven patients who developed malignancy before, after or at the onset of systemic lupus erythematosus (SLE). They comprise three cases of breast adenocarcinoma, two cases of Hodgkin's lymphoma, and one each of cholangiocarcinoma and thymoma. Only one of this group had been treated with cytotoxic agents, and five have subsequently died. They belonged to a group of 150 SLE patients, many of whom had been treated with steroids and cytotoxic agents, under long-term follow-up at a specialized lupus clinic. We discuss the reported association of malignancy in patients with SLE.

Url:

https://api.istex.fr/ark:/67375/M70-7TGBPKDJ-9/fulltext.pdf

DOI: 10.1177/096120339300200309

Links to Exploration step

ISTEX:913950C1D11D2F1FCB1102270229E1083FF3B40C

Le document en format XML

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<abstract><p>We describe seven patients who developed malignancy before, after or at the onset of systemic lupus erythematosus (SLE). They comprise three cases of breast adenocarcinoma, two cases of Hodgkin's lymphoma, and one each of cholangiocarcinoma and thymoma. Only one of this group had been treated with cytotoxic agents, and five have subsequently died. They belonged to a group of 150 SLE patients, many of whom had been treated with steroids and cytotoxic agents, under long-term follow-up at a specialized lupus clinic. We discuss the reported association of malignancy in patients with SLE.</p>
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<meta-value>177 The Association of Malignancy with SLE: An Analysis of 150 Patients Long-Term Review SAGE Publications, Inc.1993DOI: 10.1177/096120339300200309 S. Menon Department of Rheumatology Research, University College & Middlesex School of Medicine, London WIP 9PG M.L. Snaith Sheffield Centre for Rheumatic Diseases, Nether Edge Hospital, Sheffield S11 9EL, UK D.A. Isenberg Department of Rheumatology Research, University College & Middlesex School of Medicine, London WIP 9PG We describe seven patients who developed malignancy before, after or at the onset of systemic lupus erythematosus (SLE). They comprise three cases of breast adenocarcinoma, two cases of Hodgkin's lymphoma, and one each of cholangiocarcinoma and thymoma. Only one of this group had been treated with cytotoxic agents, and five have subsequently died. They belonged to a group of 150 SLE patients, many of whom had been treated with steroids and cytotoxic agents, under long-term follow-up at a specialized lupus clinic. We discuss the reported association of malignancy in patients with SLE. Systemic lupus erythematosus Sjögren's syndrome Malignancy Hodgkin's lymphoma Introduction The appearance of malignancy in patients with systemic lupus erythematosus (SLE) has been documented by a variety of case reports in the literature. Although lym- phomas have been cited frequently'-', myeloma,' and leukaemia' are also described. Of the solid malignancies, uterine' and breast tumours5.7.9 are the types most commonly reported. It has been suggested that malignancies may occur more commonly in patients with SLE than in the general population, either as a consequence of the disease or as a result of treatment. The development of neoplasia in SLE patients has been reported to vary from 2.6,070 to 11.40, although in two large studies", " fewer than 1070 of deaths were as a consequence of malignancy. We report our experience of following cohort of 150 lupus patients in a dedicated clinic for periods varying between 6 months and 14 years. We detail the case histories of seven (4.7%) patients who developed a malignancy, of whom five (3.3Vo) have died. Malignancy presented first in two cases, coincident with the onset of SLE in one, and after several years of follow-up in the remaining four patients. There was no apparent difference in either the age or the treatment of those patients who did or did not develop a malignancy. Since many of the patients have been treated with steroids (69%) and cytotoxic agents (31%), the low frequency of malignant change is notable. Case reports The study population from which the seven case histories are obtained consists of 147 women and three men with SLE treated at the Bloomsbury Rheumatology Unit from 1978 to 1992. Over a half of the patients have been seen regularly for at least 5 years of follow-up, and SLE was classified according to the 1982 revised criteria of the American Rheumatism Association". Table I illustrates the criteria that the seven patients with malignancy fulfilled, and Table II summarizes the main features of their case histories. Case I A 47-year-old female was diagnosed as having SLE in 1968 at the age of 27. Initial investigations included a positive diffuse-pattern antinuclear antibody (ANA) at a titre of 1;4tI, a positive lupus anticoagulant, hypocomplementaemia, renal impairment ~I~B'A clearance 52 ml/min) and proteinuria. She developed thrombo- cytopenia in 1977 and was treated thereafter with prednisolone, and in 1987 azathioprine was added at a dose of 100 mg/day. In May 1988 her platelet count fell to 16 x I4'll; she became resistant to Sandoglobulin (Sandoz Pharmaceuticals) infusions and developed jaundice. At endoscopic retrograde cholangiopancreatography, a stricture of the porta hepatis was found and passed with a stent, and histology confirmed a cholangiocarcinoma. She later had a splenectomy but postoperatively deteriorated with intermittent per rectum bleeding. After several 178 Table I Classification of seven SLE patients with malignancy according to the 1982 American Rheumatism Association (ARA) criteria for SLE'2. Table ~I Case histories of seven SLE patients with malignancy. F: female; DXT: radiotherapy. ' blood transfusions further resuscitation was abandoned and the patient died in August 1988. Postmortem examination found multiple non-malignant colonic ulcers up to 2 cm in diameter and a 4-cm ulcer in the first part of the duodenum. The common hepatic duct was narrowed at its origin with tumour extending for a distance of 1.5 cm. Case 2 A 38-year-old female was referred in January 1986 with a 1-year history of polyarthritis, myalgia and lethargy. She was being treated with prednisolone (5mg/day), and blood tests revealed a positive ANA ~1:128~, speckled pattern), anti-RNP and Crithidia-positive anti-DNA antibodies, and hypocomplementaemia. A diagnosis of SLE was made and treatment with hydroxychloroquine was started. She later developed dry eyes and mouth and a labial biopsy confirmed Sj6gren's syndrome. In February 1987 clinical examination revealed an 8-cm lump in the right breast with a 3-cm lymph node palpable in the axilla. The patient was given radiotherapy to the breast and started on tamoxifen. In May 1987 she developed severe back pain and breathlessness. A chest radiograph showed a marked change in the right lung with loss of volume and ill-defined shadowing with sclerotic metastases of the ribs; liver ultrasound confirmed multiple liver metastases. Chemotherapy was instituted but the patient deteriorated rapidly and died 4 months after the diagnosis of breast cancer had been established. 179 Case 3 In 1980 a 53-year-old female presented with a facial rash, photosensitivity and dry eyes. She had a positive ANA (1:320, speckled pattern) and positive-Ro and anti-La antibodies, and the immunofluorescence appearance of a skin biopsy was typical of SLE. In her previous medical history, she had had bilateral upper lobectomies in 1953 following pulmonary tuberculosis, and sero-positive rheumatoid arthritis in 1971, which settled with gold and prednisolone. On this occasion she was treated successfully with hydroxychloroquine. In April 1983 she developed weight loss, night sweats and groin pain, and examination revealed lymphadenopathy and splenomegaly. Lymph-node biopsy confirmed lymphocyte-depleted subtype Hodgkin's disease, and her disease was classed at stage IIlb. Her haemoglobin dropped to 6.1 g~dl, she was transfused and chemotherapy was started with vincristine, etoposide, chlorambucil and prednisolone. Her condition steadily deteriorated, and after an episode of leg cellulitis she developed septicaemia and died in hospital, 3 months after the diagnosis of lymphoma. Case 4 At 26 years of age this female patient was diagnosed as having SLE after presenting with pleural effusions and a photosensitive rash. A positive lupus band was found on uninvolved skin and she also had a positive ANA (1:1~8fl, diffuse pattern), antibodies to Sm and RNP, hypocomplementaemia and raised anti-DNA antibodies. She was treated with non-steroidal anti-inflammatory medication, hydroxychloroquine and prednisolone. She felt well and in June 1991 was weaned off steroids. In December 1991, when the patient was aged 50, an adenocarcinoma of the breast was confirmed after a right segmental mastectomy. Local lymph nodes were dissected and found to be free of tumour, and treatment with tamoxifen and 6 weeks of local radiotherapy followed. A repeat mammography in June 1992 shows no evidence of tumour recurrence and she remains well. Case 5 . At the age of 17 this female patient was treated for stage IIIa nodular sclerosing Hodgkin's disease after presentation with generalized lymphadenopathy. Mantle irradiation was followed by inverted Y wide-field irradiation in 1978 and she remained disease free on follow-up. Four years later, in 1980, a diagnosis of SLE was made after the patient developed evidence of arthritis, polymyositis and Raynaud's phenomenon. Her erythrocyte sedimentation rate was 95 mm/h, and a positive ANA (I:25f0, speckled pattern) and anti-RNP and anti-DNA antibodies were found. She later had proteinuria and in May 1982 an echocardiogram confirmed a small peri- cardial effusion, which was not drained. Treatment consisted of non-steroidal anti-inflammatory drugs, rr~epacrine and prednisolone, up to a dose of 15 mg/day. Unexpectedly in December 1982 she had a cardiac arrest and although initially resuscitated died in the intensive care unit 36 h later. Post-mortem showed multiple areas of left ventricular myocardial necrosis, haemorrhagic pleural effusions and a purulent lung exudate indicative of pneumonia. Case 6 A 32-year-old female had an excision biopsy of a left- breast lump in 1984, which revealed an intraductal carcinoma. A left Patey mastectomy was performed and axillary lymph nodes were dissected, none of which showed tumour infiltration. In June 1987 she developed arthralgia and photosensitivity, with a positive ANA (1:320, speckled pattern) and antibodies to Sm and RNP. She was started on hydroxychloroquine and then prednisolone, which she took for only 2 months. She became pregnant in July 1987 but, after myo- clonic seizures affecting the right hand in October 1987, a computerized tomography (CT) scan revealed cerebral metastases, and these soon spread to involve the lungs: Her baby was electively delivered at 31 weeks. In spite of radiotherapy to the brain and several courses of chemotherapy, the patient deteriorated and died in October 1988, 4 years after the original diagnosis of breast carcinoma. Case 7 In 1982 a 62-year-old lady described general malaise, depression, arthralgias, Raynaud's phenomenon and pleuritic chest pain. A positive ANA (1:2560, homogenous pattern) and Crithidia-positive anti-DNA antibodies were found, and a chest radiograph also revealed a large shadow, which on CT scanning was shown to be a mass separate from the ascending aorta. A median sternotomy was performed and an anterior mediastinal tumour dissected free. It measured 10 x 5.5 x 3.5 cm and weighed 130g. On histologicai examination the features were compatible with a thymoma. Muscle- strength testing postoperatively was normal with no evidence of fatiguability. Since then the patient has also had an angioplasty of the right common iliac artery for leg claudication but otherwise remains well on hydroxychloroquine. 180 Results In our group of I ~0 SLE patients, seven (representing 4.7~'u of the total) had a malignancy. Two had Hodgkin's lympoma, three had carcinoma of the breast and there was one case each of cholangiocarcinoma and thymoma. The age at diagnosis of malignancy varied between 17 and 62 years. All patients were female, and five ~3.3~'0) have died, although in only four (2.7 Vo ; cases 1,2,3 and 6) was death directly attributable to carcinoma. In four of these cases, malignancy developed in patients with a prior diagnosis of SLE (made 1-24 years before). Both cases of breast carcinoma (cases 3 and 4) had been treated with steroids and hydroxychloroquine; in only one of the patients (case 1, cholangiocarcinoma) had azathioprine been administered. In case 6, the breast tumour recurred in disseminated form after the patient had taken only 2 months of prednisolone. From a careful evaluation of the 150 case notes, 121 (81 1 ~fo) patients received non-steroidal anti-inflammatory drugs at some point in their illness: 67 (45%) antimalarials, 103 ~~~~7~) steroids (with 83 (55%) at a dose of > 10 mg/day), and 46 (31Vo) cytotoxics (azathioprine and cyclophosphamide). In this last group, all had azathioprine in doses up to 2 mg/kg/day but 24o also had cyclophosphamide, either by daily oral regimes or by intermittent intravenous pulsing. Over the 14-year follow-up period, 17 { 1 I . ~ ~In ) have died of various causes including three (2~70) with renal failure and four ~2.~~70) with infection, with death directly associated with malignancy contributing to 4/17 (2~.5%). Discussion A recent report has suggested that there is an increased risk of carcinoma in patients with SLE'. In a follow-up of 205 patients, 15 cancers were diagnosed against an expected 5.7 (relative risk 2.6), of which non-Hodgkin's lymphoma (six), soft tissue sarcoma (two) and breast carcinoma (two) occurred more frequently than expected. There was no increased risk of cancer with the use of cytotoxic agents, which were in fact given to fewer patients in the group that developed cancer, but rather it appeared that development of cancer was directly related to the SLE itself. In a previous study of 484 SLE patients!3, 18 (3.7o) ultimately developed some kind of malignancy in comparison with U.6~T~ of 2867 patients with the diagnosis of rheumatoid arthritis. In a series of 70 patients with SLE 7, eight (11.4o) developed carcinoma. However, half of the cases in this group had superficial epithelial lesions - 3/8 were carcinoma of the cervix `in situ' and 1/8 was a Bowen's carcinoma of the skin. Two were squamous cell lesions of the cervix and one case of multiple myeloma was seen. These studies contrast with other published series in which the frequency of malignancy and subsequent death was noted less frequently. In a group of 609 SLE patients'°, renal disease (32~10~ and sepsis (23~~) were the most common causes of death, with malignant neoplasms responsible only for four deaths (~.7~~). These were not described in detail, nor was it mentioned whether any tumours had occurred that had been successfully treated. In another study'~, only one case (2~.6~1~~ of malignant melanoma was found in 39 SLE patients, although, in contrast, there did appear to be an increased risk of cancer in women with polymyositis. A multicentre study of outcome in 1,103 SLE patients" found no deaths from malignancy despite a total of 222 patients (20%) dying, and concluded that death, at least, from carcinoma is not increased in these patients. Nonetheless, numerous anecdotal reports of malignancy are found in the literature and, in particular, over 100 cases of coincident SLE and lymphoma have been recorded". Of these, less than a dozen cases are described of Hodgkin's lymphoma and SLE in the same patient, and in the majority of these SLE preceded the onset of lymphoproliferative disease', ','6-". In this study we report a further two cases (patients 3 and 5), one 3 years after, and the other 4 years before, the diagnosis of SLE. Although a variety of clinical and laboratory stigmata of autoimmunity may be found in patients with lymphoma, including fever, rashes, arthralgias and autoantibodies22 , these patients clearly fulfilled the criteria for SLE, and in both cases several years had elapsed between diagnosis of lupus and malignancy. Interestingly, patients 2 and 3 had both SLE and Sj6gren's syndrome, and were associated with adenocarcinoma of the breast and Hodgkin's disease, respectively. The relative risk for primary Sj6gren's syndrome patients of developing lymphoma has been estimated to be approximately 40-fold higher than age-and sex- matched control subjects by investigators at the National Institutes of Health3~. However, some feel that this risk may have been overestimated~' ° ~~, and there are no reports to suggest that other malignancies are more common in Sj6gren's syndrome. As reported elsewhere", 22 out of 100 of our SLE patients developed Sj6gren's syndrome. There was no statistically increased risk of developing malignancy in our SLE patients if they also had Sj6gren's syndrome (chi-square P<0.05). In our group of 150 lupus patients, malignancy has occurred in seven (4.7Vo). Four deaths (2.7%) were directly as a consequence of the tumour, and these represented 23.5% of the total deaths in these patients over a 14-year period. A link has been made with the use of cytotoxics in SLE patients, with cyclophosphamide blamed for cases of bladder cancer", and an increased incidence of cervical atypia has perhaps been associated 181 with the use of azathioprine28. No significant difference was found in either the age of onset of SLE or treatment of the disease, between these cases and patients who remain free of cancer. Moreover, over two-thirds of this cohort have been treated with steroids and 31 ~7o have been prescribed cytotoxic drugs. Despite this, no cases of bladder or cervical carcinoma have occurred and it seems in particular that our frequent use of azathioprine (at doses of up to 2 mg/kg/day) does not appear to confer an increased malignant potential. We would nevertheless recommend vigilance in these patients, and persistent abnormal clinical findings should be investigated further. In particular, checking for breast lumps, persistent lymphadenopathy and splenomegaly is advisable, and biopsies should be taken where clinical suspicion is aroused. Awareness of the possibility of bladder carcinoma after treatment with cyclophosphamide might necessitate a urine screening policy, and patients should be encouraged to have regular cervical smear tests. References Green JA, Dawson AA, Walker W. Systemic lupus erythematosus and lymphoma. Lancet 1987; ii: 753-6. Efremidis A. , Eiser AR, Grishman E., Rosenberg V. Hodgkin's lymphoma in an adolescent with systemic lupus erythematosus. Cancer 1984; 53: 142-6. 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<mods version="3.6"><titleInfo lang="en"><title>The Association of Malignancy with SLE: An Analysis of 150 Patients Long-Term Review</title>
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<titleInfo type="alternative" lang="en" contentType="CDATA"><title>The Association of Malignancy with SLE: An Analysis of 150 Patients Long-Term Review</title>
</titleInfo>
<name type="personal"><namePart type="given">S.</namePart>
<namePart type="family">Menon</namePart>
<affiliation>Department of Rheumatology Research, University College & Middlesex School of Medicine, London WIP 9PG</affiliation>
</name>
<name type="personal"><namePart type="given">M.L.</namePart>
<namePart type="family">Snaith</namePart>
<affiliation>Sheffield Centre for Rheumatic Diseases, Nether Edge Hospital, Sheffield S11 9EL, UK</affiliation>
</name>
<name type="personal"><namePart type="given">D.A.</namePart>
<namePart type="family">Isenberg</namePart>
<affiliation>Department of Rheumatology Research, University College & Middlesex School of Medicine, London WIP 9PG</affiliation>
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<typeOfResource>text</typeOfResource>
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<originInfo><publisher>Sage Publications</publisher>
<place><placeTerm type="text">Sage CA: Thousand Oaks, CA</placeTerm>
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<dateIssued encoding="w3cdtf">1993-06</dateIssued>
<copyrightDate encoding="w3cdtf">1993</copyrightDate>
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<language><languageTerm type="code" authority="iso639-2b">eng</languageTerm>
<languageTerm type="code" authority="rfc3066">en</languageTerm>
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<abstract lang="en">We describe seven patients who developed malignancy before, after or at the onset of systemic lupus erythematosus (SLE). They comprise three cases of breast adenocarcinoma, two cases of Hodgkin's lymphoma, and one each of cholangiocarcinoma and thymoma. Only one of this group had been treated with cytotoxic agents, and five have subsequently died. They belonged to a group of 150 SLE patients, many of whom had been treated with steroids and cytotoxic agents, under long-term follow-up at a specialized lupus clinic. We discuss the reported association of malignancy in patients with SLE.</abstract>
<subject><genre>keywords</genre>
<topic>Systemic lupus erythematosus</topic>
<topic>Sjögren's syndrome</topic>
<topic>Malignancy</topic>
<topic>Hodgkin's lymphoma</topic>
</subject>
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<identifier type="ISSN">0961-2033</identifier>
<identifier type="eISSN">1477-0962</identifier>
<identifier type="PublisherID">LUP</identifier>
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<part><date>1993</date>
<detail type="volume"><caption>vol.</caption>
<number>2</number>
</detail>
<detail type="issue"><caption>no.</caption>
<number>3</number>
</detail>
<extent unit="pages"><start>177</start>
<end>181</end>
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The Association of Malignancy with SLE: An Analysis of 150 Patients Long-Term Review

The Association of Malignancy with SLE: An Analysis of 150 Patients Long-Term Review

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