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Is there an association of malignancy with systemic lupus erythematosus? An analysis of 276 patients under long‐term review

Identifieur interne : 001314 ( Istex/Corpus ); précédent : 001313; suivant : 001315

Is there an association of malignancy with systemic lupus erythematosus? An analysis of 276 patients under long‐term review

Auteurs : S. M. Sultan ; Y. Ioannou ; D. A. Isenberg

Source :

Rheumatology [ 1462-0324 ] ; 2000.

RBID : ISTEX:B17672D66D0AB7CECEA918F5589E1D53938BC77D

Abstract

Objective. To estimate the risk of malignancy in a UK cohort of patients with systemic lupus erythematosus (SLE) under long‐term review. Method. The University College London Lupus Clinic Database was used to identify a cohort of 276 patients followed up prospectively between 1978 and 1999. Standardized incidence ratios and 95% confidence intervals for all cancers were calculated using age and sex‐specific cancer incidence rates for the southeast of England. Results. In total, 16 malignancies were diagnosed in 15 patients. However, five malignancies were diagnosed before the diagnosis of SLE and were therefore excluded from the final statistical analysis. One case of basal cell carcinoma was also identified, but this was also excluded from the final analysis as no comparable figures were available for the general population. Death as a direct consequence of the malignancy occurred in six (2.3%) patients, accounting for 22.6% of the deaths in our cohort of SLE patients. Compared with the general population, the overall estimated risk for all cancers was not increased in the lupus cohort (standardized incidence rate 1.16 (95% confidence interval 0.55–2.13). Hodgkin's lymphoma was the only individual cancer that was increased in our cohort of patients [standardized incidence rate 17.82 (95% confidence interval 0.45–99.23)]. Conclusions. In our cohort of patients with SLE we did not show an overall increased risk of malignancy. However, SLE was associated with an increased risk of Hodgkin's lymphoma compared with the general population. From our cohort of 276 patients, none of those treated with cyclosporin (3%) developed malignancy, and out of 49 (18%) patients treated with cyclophosphamide only one patient developed malignancy. Out of the 10 patients in the final analysis who developed malignancy, six had treatment with prednisolone, four with azathioprine, five with hydroxychloroquine and only one with cyclophosphamide. No statistical difference in the above cytotoxic therapy was observed between those patients who developed malignancy and those who did not.

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https://api.istex.fr/ark:/67375/HXZ-0KPR161B-M/fulltext.pdf

DOI: 10.1093/rheumatology/39.10.1147

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ISTEX:B17672D66D0AB7CECEA918F5589E1D53938BC77D

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<front><div type="abstract" xml:lang="en">Objective. To estimate the risk of malignancy in a UK cohort of patients with systemic lupus erythematosus (SLE) under long‐term review. Method. The University College London Lupus Clinic Database was used to identify a cohort of 276 patients followed up prospectively between 1978 and 1999. Standardized incidence ratios and 95% confidence intervals for all cancers were calculated using age and sex‐specific cancer incidence rates for the southeast of England. Results. In total, 16 malignancies were diagnosed in 15 patients. However, five malignancies were diagnosed before the diagnosis of SLE and were therefore excluded from the final statistical analysis. One case of basal cell carcinoma was also identified, but this was also excluded from the final analysis as no comparable figures were available for the general population. Death as a direct consequence of the malignancy occurred in six (2.3%) patients, accounting for 22.6% of the deaths in our cohort of SLE patients. Compared with the general population, the overall estimated risk for all cancers was not increased in the lupus cohort (standardized incidence rate 1.16 (95% confidence interval 0.55–2.13). Hodgkin's lymphoma was the only individual cancer that was increased in our cohort of patients [standardized incidence rate 17.82 (95% confidence interval 0.45–99.23)]. Conclusions. In our cohort of patients with SLE we did not show an overall increased risk of malignancy. However, SLE was associated with an increased risk of Hodgkin's lymphoma compared with the general population. From our cohort of 276 patients, none of those treated with cyclosporin (3%) developed malignancy, and out of 49 (18%) patients treated with cyclophosphamide only one patient developed malignancy. Out of the 10 patients in the final analysis who developed malignancy, six had treatment with prednisolone, four with azathioprine, five with hydroxychloroquine and only one with cyclophosphamide. No statistical difference in the above cytotoxic therapy was observed between those patients who developed malignancy and those who did not.</div>
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<profileDesc><abstract xml:lang="en"><p><hi rend="italic">Objective</hi>
. To estimate the risk of malignancy in a UK cohort of patients with systemic lupus erythematosus (SLE) under long‐term review.</p>
<p><hi rend="italic">Method</hi>
. The University College London Lupus Clinic Database was used to identify a cohort of 276 patients followed up prospectively between 1978 and 1999. Standardized incidence ratios and 95% confidence intervals for all cancers were calculated using age and sex‐specific cancer incidence rates for the southeast of England.</p>
<p><hi rend="italic">Results</hi>
. In total, 16 malignancies were diagnosed in 15 patients. However, five malignancies were diagnosed before the diagnosis of SLE and were therefore excluded from the final statistical analysis. One case of basal cell carcinoma was also identified, but this was also excluded from the final analysis as no comparable figures were available for the general population. Death as a direct consequence of the malignancy occurred in six (2.3%) patients, accounting for 22.6% of the deaths in our cohort of SLE patients. Compared with the general population, the overall estimated risk for all cancers was not increased in the lupus cohort (standardized incidence rate 1.16 (95% confidence interval 0.55–2.13). Hodgkin's lymphoma was the only individual cancer that was increased in our cohort of patients [standardized incidence rate 17.82 (95% confidence interval 0.45–99.23)].</p>
<p><hi rend="italic">Conclusions</hi>
. In our cohort of patients with SLE we did not show an overall increased risk of malignancy. However, SLE was associated with an increased risk of Hodgkin's lymphoma compared with the general population. From our cohort of 276 patients, none of those treated with cyclosporin (3%) developed malignancy, and out of 49 (18%) patients treated with cyclophosphamide only one patient developed malignancy. Out of the 10 patients in the final analysis who developed malignancy, six had treatment with prednisolone, four with azathioprine, five with hydroxychloroquine and only one with cyclophosphamide. No statistical difference in the above cytotoxic therapy was observed between those patients who developed malignancy and those who did not.</p>
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  <front>

    <journal-meta>

      <journal-id journal-id-type="hwp">rheumatology</journal-id>

      <journal-id journal-id-type="nlm-ta">Rheumatology (Oxford)</journal-id>

<journal-id journal-id-type="publisher-id">brheum</journal-id>

      <journal-title>Rheumatology</journal-title>

      <abbrev-journal-title abbrev-type="publisher">Rheumatology</abbrev-journal-title>

      <issn pub-type="ppub">1462-0324</issn>

      <issn pub-type="epub">1462-0332</issn>

      <publisher>

        <publisher-name>Oxford University Press</publisher-name>

      </publisher>

    </journal-meta>

    <article-meta>

      <article-id pub-id-type="other">391147</article-id>

<article-id pub-id-type="doi">10.1093/rheumatology/39.10.1147</article-id>

      <article-id pub-id-type="pii">1460-2172</article-id>

      <article-categories>

        <subj-group subj-group-type="heading">

          <subject>Original Papers</subject>

        </subj-group>

      </article-categories>

      <title-group>

        <article-title>Is there an association of malignancy with systemic lupus erythematosus? An analysis of 276 patients under long‐term review</article-title>

      </title-group>

      <contrib-group>

        <contrib contrib-type="author">

          <name>

            <surname>Sultan</surname>

            <given-names>S. M.</given-names>

          </name>

        </contrib>

        <contrib contrib-type="author">

          <name>

            <surname>Ioannou</surname>

            <given-names>Y.</given-names>

          </name>

        </contrib>

        <contrib contrib-type="author">

          <name>

            <surname>Isenberg</surname>

            <given-names>D. A.</given-names>

          </name>

          <xref rid="FN1"></xref>

        </contrib>

        <aff>Centre for Rheumatology, Bloomsbury Rheumatology Unit, Department of Medicine, University College London, London W1P 9PG, UK</aff>

      </contrib-group>

      <pub-date pub-type="ppub">

        <month>10</month>

        <year>2000</year>

      </pub-date>

      <volume>39</volume>

      <issue>10</issue>

      <fpage>1147</fpage>

      <lpage>1152</lpage>

      <history>

        <date date-type="received">

          <day>28</day>

          <month>05</month>

          <year>1999</year>

        </date>

        <date date-type="rev-recd">

          <day>15</day>

          <month>05</month>

          <year>2000</year>

        </date>

      </history>

      <permissions>

        <copyright-statement>© British Society for Rheumatology</copyright-statement>

        <copyright-year>2000</copyright-year>

      </permissions>

      <abstract xml:lang="en">

        <p><italic>Objective</italic>
. To estimate the risk of malignancy in a UK cohort of patients with systemic lupus erythematosus (SLE) under long‐term review.</p>

        <p><italic>Method</italic>
. The University College London Lupus Clinic Database was used to identify a cohort of 276 patients followed up prospectively between 1978 and 1999. Standardized incidence ratios and 95% confidence intervals for all cancers were calculated using age and sex‐specific cancer incidence rates for the southeast of England.</p>

        <p><italic>Results</italic>
. In total, 16 malignancies were diagnosed in 15 patients. However, five malignancies were diagnosed before the diagnosis of SLE and were therefore excluded from the final statistical analysis. One case of basal cell carcinoma was also identified, but this was also excluded from the final analysis as no comparable figures were available for the general population. Death as a direct consequence of the malignancy occurred in six (2.3%) patients, accounting for 22.6% of the deaths in our cohort of SLE patients. Compared with the general population, the overall estimated risk for all cancers was not increased in the lupus cohort (standardized incidence rate 1.16 (95% confidence interval 0.55–2.13). Hodgkin's lymphoma was the only individual cancer that was increased in our cohort of patients [standardized incidence rate 17.82 (95% confidence interval 0.45–99.23)].</p>

        <p><italic>Conclusions</italic>
. In our cohort of patients with SLE we did not show an overall increased risk of malignancy. However, SLE was associated with an increased risk of Hodgkin's lymphoma compared with the general population. From our cohort of 276 patients, none of those treated with cyclosporin (3%) developed malignancy, and out of 49 (18%) patients treated with cyclophosphamide only one patient developed malignancy. Out of the 10 patients in the final analysis who developed malignancy, six had treatment with prednisolone, four with azathioprine, five with hydroxychloroquine and only one with cyclophosphamide. No statistical difference in the above cytotoxic therapy was observed between those patients who developed malignancy and those who did not.</p>

      </abstract>

      <kwd-group kwd-group-type="KWD" xml:lang="en">

        <kwd>Systemic lupus erythematosus (SLE)</kwd>

        <kwd>Malignancy</kwd>

        <kwd>Cytotoxic therapy</kwd>

        <kwd>Hodgkin's lymphoma.</kwd>

      </kwd-group>

      <custom-meta-wrap>

        <custom-meta>

          <meta-name>hwp-legacy-fpage</meta-name>

          <meta-value>1147</meta-value>

        </custom-meta>

        <custom-meta>

          <meta-name>hwp-legacy-dochead</meta-name>

          <meta-value>Original Papers</meta-value>

        </custom-meta>

      </custom-meta-wrap>

    </article-meta>

  </front>

  <body>

    <p>There has been interest in the association of autoimmune rheumatic disease with malignancy for many years. It has been shown that there is an increased risk of haematological malignancies, particularly from non‐Hodgkin's lymphoma, in patients with rheumatoid arthritis (RA) [<xref rid="R1">1</xref>
]. A twofold risk of malignancy in patients with systemic sclerosis (SSc) has been shown [<xref rid="R2">2</xref>
], as well as an increased risk of lung cancer in patients with SSc who have underlying pulmonary fibrosis [<xref rid="R3">3</xref>
]. Sjögren's syndrome has been linked to an increased risk of developing non‐Hodgkin's lymphoma [<xref rid="R4">4</xref>
]. It has been suggested that malignancy in patients with SLE may occur more commonly than in the general population, either as a consequence of their disease or as a result of treatment. The occurrence of neoplasia has been reported to vary between 3.2 and 11.4% [<xref rid="R2">2</xref>
, <xref rid="R5">5</xref>
–<xref rid="R10">10</xref>
]. We have reviewed the available literature and analysed the risk of developing a malignancy in a UK cohort, which has not been documented before. We have looked previously at the risk of malignancy in a cohort of 150 patients [<xref rid="R11">11</xref>
]. Our cohort has since expanded by over 100 patients and the period of follow‐up has increased substantially. In the present study we analyse the occurrence of malignancy in 276 patients with SLE who were followed up prospectively over a 20‐yr period. This study was designed to assess the risk of malignancy in our cohort of patients with SLE and a comparable age‐ and sex‐adjusted rate for the general population from the same geographical location. In addition, we sought data to assess whether there was an increased risk of malignancy after the use of immunosuppressive drugs in patients with lupus.</p>

    <sec>

      <title>Patients and methods</title>

      <sec>

        <title>Patients</title>

        <p>The University College London Lupus Clinic Database was used to identify patients with SLE who were diagnosed as having cancer. Two hundred and seventy‐six patients with SLE were identified who had been followed up prospectively from 1978 to 1999; only 39 (14.1%) of patients were lost to follow‐up and 31 (11.2%) died during this period. All patients fulfilled the revised American Rheumatism Association (ARA) criteria for the classification of SLE [<xref rid="R12">12</xref>
] (all patients with discoid lupus and drug‐induced lupus were excluded). We analysed retrospectively, from the medical records, the data recording age, sex, date of diagnosis of SLE, time of follow‐up, date of diagnosis of malignancy, and immunosuppressive therapy. The follow‐up period was defined as the interval from the date of diagnosis of SLE until the last review date or the date of death. The zero point for the calculation of person‐years at risk was the date of diagnosis of SLE and ended on 30 April 1999 or at the date of cancer diagnosis or death. The total number of person‐years in each age category was calculated as the sum of the individual contributions to each age group. An individual at risk for an entire age interval contributed years towards the entire interval. An individual at risk for only part of the age interval contributed time proportional to the years in the interval that they were at risk.</p>

      </sec>

      <sec>

        <title>Statistical analysis</title>

        <sec>

          <title>Observed cancers.</title>

          <p>All cancers were identified by review of the medical notes. In all cases neoplasia was diagnosed after the onset of clinical features suggestive of malignant disease and not through a screening programme (excluding the case of cervical carcinoma, which was found on routine screening appropriate to that age group, which is currently available to the general population). The diagnosis of cancer was ascertained by histological examination or autopsy report. A total of 16 malignancies were identified in 15 patients in our cohort. However, five malignancies predated the diagnosis of SLE and were therefore excluded from the study. A case of basal cell carcinoma was excluded, as no comparable data were available for the general population. The Thames Cancer Registry [<xref rid="R13">13</xref>
] excluded basal cell carcinoma from their database. This is because skin lesions are now often treated by general practitioners or in out‐patients clinics, where data capture facilities are poor or non‐existent. The Registry data for the basal cell carcinoma were substantially incomplete and therefore of limited value.</p>

        </sec>

        <sec>

          <title>Expected number of malignancies.</title>

          <p>Five‐year annualized age and gender‐specific cancer incidence rates per 100 000 population for the southeast of England were used. The expected number of malignancies (<italic>E</italic>
) was calculated as the sum of all person‐years at risk in age group <italic>i</italic>
 from the study cohort (<italic>ni</italic>
) multiplied by the age‐ and sex‐specific cancer rates for the southeast of England in age group <italic>i (Ri</italic>
) using the expression <italic>E</italic>
 = <italic>Σ</italic>
 (<italic>ni) × Ri</italic>
 [<xref rid="R14">14</xref>
].</p>

          <p>The expected numbers of cancers for men and women were calculated separately and then the total expected number of malignancies was calculated. The expected number of malignancies for individual cancers was also calculated using the available age‐standardized rates for the southeast of England for breast cancer, lung cancer, Hodgkin's lymphoma, cervix cancer and prostate cancer from the Thames Cancer Registry [<xref rid="R13">13</xref>
].</p>

        </sec>

        <sec>

          <title>Standardized incidence rate.</title>

          <p>The standardized incidence rate (SIR) was calculated to estimate the risks for the overall and age‐specific cancers. It was calculated as the ratio of the observed number of cancers to the expected number of cancers. The 95% confidence intervals (CI) for the SIR were obtained by regarding the observed number of cancers as a Poisson variable and finding its related interval from tables based on the Poisson distribution [<xref rid="R14">14</xref>
].</p>

        </sec>

        <sec>

          <title>Differences in therapy.</title>

          <p>To study whether the incidence of cancer was influenced by treatment with cytotoxic drugs, a comparison was made between patients who developed malignancies and had been treated and those patients with SLE who did not develop malignancies but had also been treated with the same drugs. Statistical analysis was made using the exact method for the 2 × 2 contingency tables.</p>

        </sec>

      </sec>

    </sec>

    <sec>

      <title>Results</title>

      <p>The total number of patient‐years of follow‐up was 1695, and the median follow‐up period was 4.8 yr. Of the total SLE population, females constituted 93.5%, males 6.5%, Caucasians 67.4%, Afro‐Caribbeans 17.4%, Asians 9.4%, Orientals 3.6% and others 2.2%.</p>

      <p>In total, 16 malignancies were diagnosed in 15 patients. There were five cases of breast carcinoma, two cases of non‐Hodgkin's lymphoma, and one each of carcinoma of the prostate, cholangiocarcinoma, cervical carcinoma, vulval carcinoma, small cell carcinoma of the lung, squamous cell carcinoma of the anal canal, carcinoma of the colon, thymoma and basal cell carcinoma. However, five malignancies (one non‐Hodgkin's lymphoma, two breast carcinomas, one thymoma and one carcinoma of the colon) were diagnosed before the diagnosis of SLE and were therefore excluded from the final statistical analysis. Basal cell carcinoma was also excluded from the final analysis, as no comparable figures were available for the general population. All patients were Caucasians, comprising one male and 15 females. Death as a direct result of malignancy occurred in six (2.3%) patients, accounting for 22.6% of deaths in our cohort of SLE patients. The mean age of diagnosis of SLE was 34.7 yr and the mean time between diagnosis of SLE and the occurrence of malignancy was 7.4 yr. Table 1<xref rid="T1"></xref>
 shows the observed number of cancers in patients with SLE, patient‐years at risk for females and the overall sex‐ and age‐specific estimated risks of cancer in female patients. There was only one male patient in our cohort who developed prostate cancer in the age group 75–79 yr (a total of 147 male patient‐years at risk was calculated to estimate the expected number of cancers). The SIR was 7.7 (0.19–42.89) (the <italic>P</italic>
 value was not statistically significant). The overall estimated risk for developing a malignancy was SIR 1.16 (95% CI 0.56–2.13, <italic>P</italic>
 < 0.05).</p>

      <p>The SIRs for the individual malignancies are shown in Table 2<xref rid="T2"></xref>
. For all cancer types except Hodgkin's lymphoma, the observed number of malignancies was not statistically significantly different from the expected number. There was a 17‐fold increase for Hodgkin's lymphoma (SIR 17.82, 95% CI 0.45–99.23, <italic>P</italic>
 < 0.05).</p>

      <p>We also analysed whether there was a difference in treatment between those patients with SLE who developed malignancy and those who did not. We found that treatment with azathioprine, hydroxychloroquine or prednisolone did not constitute an additional risk factor. Only one patient treated with cyclophosphamide developed a malignancy out of a total of 49 patients treated in the cohort; again we did not find a statistically significant difference between the two groups.</p>

    </sec>

    <sec>

      <title></title>

      <p>

        <table-wrap id="T1" position="float">

          <label>T<sc>able</sc>
 1.</label>

          <caption>

            <p>Risk estimates for cancer (SIR) in the female SLE patients compared with the population of the southeast of England</p>

          </caption>

          <table>

            <tbody>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">Age (yr)<hr></hr>
</td>

                <td colspan="1" rowspan="1" align="left" valign="top">Patient‐years at risk<hr></hr>
</td>

                <td colspan="1" rowspan="1" align="left" valign="top">Observed number of malignancies<hr></hr>
</td>

                <td colspan="1" rowspan="1" align="left" valign="top">SIR<hr></hr>
</td>

                <td colspan="1" rowspan="1" align="left" valign="top">95% CI<hr></hr>
</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">0–4</td>

                <td colspan="1" rowspan="1" align="left" valign="top">0</td>

                <td colspan="1" rowspan="1" align="left" valign="top"> 0</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">5–9</td>

                <td colspan="1" rowspan="1" align="left" valign="top">1</td>

                <td colspan="1" rowspan="1" align="left" valign="top"> 0</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">10–14</td>

                <td colspan="1" rowspan="1" align="left" valign="top">10</td>

                <td colspan="1" rowspan="1" align="left" valign="top"> 0</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">15–19</td>

                <td colspan="1" rowspan="1" align="left" valign="top">123</td>

                <td colspan="1" rowspan="1" align="left" valign="top"> 0</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">20–24</td>

                <td colspan="1" rowspan="1" align="left" valign="top">313</td>

                <td colspan="1" rowspan="1" align="left" valign="top"> 0</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">25–29</td>

                <td colspan="1" rowspan="1" align="left" valign="top">437</td>

                <td colspan="1" rowspan="1" align="left" valign="top"> 1</td>

                <td colspan="1" rowspan="1" align="left" valign="top">7.04</td>

                <td colspan="1" rowspan="1" align="left" valign="top">0.18–39.2</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">30–34</td>

                <td colspan="1" rowspan="1" align="left" valign="top">570</td>

                <td colspan="1" rowspan="1" align="left" valign="top"> 0</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">35–39</td>

                <td colspan="1" rowspan="1" align="left" valign="top">559</td>

                <td colspan="1" rowspan="1" align="left" valign="top"> 1</td>

                <td colspan="1" rowspan="1" align="left" valign="top">1.48</td>

                <td colspan="1" rowspan="1" align="left" valign="top">0.04–8.24</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">40–44</td>

                <td colspan="1" rowspan="1" align="left" valign="top">486</td>

                <td colspan="1" rowspan="1" align="left" valign="top"> 2</td>

                <td colspan="1" rowspan="1" align="left" valign="top">2.17</td>

                <td colspan="1" rowspan="1" align="left" valign="top">0.26–7.83</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">45–49</td>

                <td colspan="1" rowspan="1" align="left" valign="top">365</td>

                <td colspan="1" rowspan="1" align="left" valign="top"> 2</td>

                <td colspan="1" rowspan="1" align="left" valign="top">1.82</td>

                <td colspan="1" rowspan="1" align="left" valign="top">0.22–6.57</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">50–54</td>

                <td colspan="1" rowspan="1" align="left" valign="top">261</td>

                <td colspan="1" rowspan="1" align="left" valign="top"> 1</td>

                <td colspan="1" rowspan="1" align="left" valign="top">0.72</td>

                <td colspan="1" rowspan="1" align="left" valign="top">0.02–4.01</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">55–59</td>

                <td colspan="1" rowspan="1" align="left" valign="top">195</td>

                <td colspan="1" rowspan="1" align="left" valign="top"> 1</td>

                <td colspan="1" rowspan="1" align="left" valign="top">0.84</td>

                <td colspan="1" rowspan="1" align="left" valign="top">0.02–4.68</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">60–64</td>

                <td colspan="1" rowspan="1" align="left" valign="top">123</td>

                <td colspan="1" rowspan="1" align="left" valign="top"> 0</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">65–69</td>

                <td colspan="1" rowspan="1" align="left" valign="top">75</td>

                <td colspan="1" rowspan="1" align="left" valign="top"> 1</td>

                <td colspan="1" rowspan="1" align="left" valign="top">1.47</td>

                <td colspan="1" rowspan="1" align="left" valign="top">0.04–8.19</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">70–74</td>

                <td colspan="1" rowspan="1" align="left" valign="top">45</td>

                <td colspan="1" rowspan="1" align="left" valign="top"> 0</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">75–79</td>

                <td colspan="1" rowspan="1" align="left" valign="top">20</td>

                <td colspan="1" rowspan="1" align="left" valign="top"> 0</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">80–84</td>

                <td colspan="1" rowspan="1" align="left" valign="top">10</td>

                <td colspan="1" rowspan="1" align="left" valign="top"> 0</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">85 + </td>

                <td colspan="1" rowspan="1" align="left" valign="top">2</td>

                <td colspan="1" rowspan="1" align="left" valign="top"> 0</td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">Overall (including data</td>

                <td colspan="1" rowspan="1" align="left" valign="top">3742</td>

                <td colspan="1" rowspan="1" align="left" valign="top">10</td>

                <td colspan="1" rowspan="1" align="left" valign="top">1.16</td>

                <td colspan="1" rowspan="1" align="left" valign="top">0.56–2.13</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">   for one male patient)</td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

              </tr>

            </tbody>

          </table>

        </table-wrap>

      </p>

      <p>

        <table-wrap id="T2" position="float">

          <label>T<sc>able</sc>
 2.</label>

          <caption>

            <p>Risk estimates for the various types of cancers compared for the population of the southeast of England. Risks for the other malignancies were not calculated as there are no comparable data for the general population</p>

          </caption>

          <table>

            <tbody>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">Cancer type<hr></hr>
</td>

                <td colspan="1" rowspan="1" align="left" valign="top">Observed number of malignancies<hr></hr>
</td>

                <td colspan="1" rowspan="1" align="left" valign="top">SIR<hr></hr>
</td>

                <td colspan="1" rowspan="1" align="left" valign="top">95% CI<hr></hr>
</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">Hodgkin's lymphoma</td>

                <td colspan="1" rowspan="1" align="left" valign="top">1</td>

                <td colspan="1" rowspan="1" align="left" valign="top">17.82</td>

                <td colspan="1" rowspan="1" align="left" valign="top">0.45–99.23*</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">Lung</td>

                <td colspan="1" rowspan="1" align="left" valign="top">1</td>

                <td colspan="1" rowspan="1" align="left" valign="top">1.31</td>

                <td colspan="1" rowspan="1" align="left" valign="top">0.03–7.30</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">Breast</td>

                <td colspan="1" rowspan="1" align="left" valign="top">3</td>

                <td colspan="1" rowspan="1" align="left" valign="top">1.06</td>

                <td colspan="1" rowspan="1" align="left" valign="top">0.21–5.9</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">Cervix</td>

                <td colspan="1" rowspan="1" align="left" valign="top">1</td>

                <td colspan="1" rowspan="1" align="left" valign="top">4.19</td>

                <td colspan="1" rowspan="1" align="left" valign="top">0.11–23.33</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">Carcinoma of the</td>

                <td colspan="1" rowspan="1" align="left" valign="top">1</td>

                <td colspan="1" rowspan="1" align="left" valign="top">0.69</td>

                <td colspan="1" rowspan="1" align="left" valign="top">0.02–3.84</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">   anal canal</td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">Prostate</td>

                <td colspan="1" rowspan="1" align="left" valign="top">1</td>

                <td colspan="1" rowspan="1" align="left" valign="top">1.34</td>

                <td colspan="1" rowspan="1" align="left" valign="top">0.03–7.46</td>

              </tr>

            </tbody>

          </table>

          <table-wrap-foot>

            <fn>

              <p>*<italic>P</italic>
 < 0.05.</p>

            </fn>

          </table-wrap-foot>

        </table-wrap>

      </p>

    </sec>

    <sec>

      <title>Discussion</title>

      <p>We analysed the occurrence of malignancy in a large group of patients with SLE in the UK. Malignancy occurred in 5.4% of our 276 patients with SLE. However, to address the question whether SLE is an additional risk factor for the development of malignancy, we defined the at‐risk period strictly as the time to onset after the diagnosis of SLE. Within this definition of the at‐risk period, the incidence of malignancy fell to 3.6%. The overall age and sex‐standardized incidence rate was not different from that of the general population (SIR 1.16, 95% CI 0.56–2.13). Similarly, the estimated risk for cancer (SIR) was not increased in any of the age‐specific groups. We did find an increased risk from Hodgkin's lymphoma, which was 17‐fold above what would be expected (SIR 17.82, 95% CI 0.45–99.23, <italic>P</italic>
 < 0.05). However, this was based on only one case and consequently the confidence intervals are wide.</p>

      <p>Table 3<xref rid="T3"></xref>
 outlines the major published series to date. We selected large cohort studies rather than reviewing individual case reports. In summary, four large studies have indicated an overall increased risk when compared with the general population [<xref rid="R5">5</xref>
, <xref rid="R6">6</xref>
, <xref rid="R8">8</xref>
, <xref rid="R9">9</xref>
.</p>

      <p>Ramsey‐Goldman <italic>et al</italic>
. [<xref rid="R5">5</xref>
] found a twofold increased risk from all malignancies (SIR 2.0, 95% CI 1.4–2.9). They also found that lung cancer was the only individual cancer that was increased in all women (SIR 3.1, 95% CI 1.3–7.9), and the risk of breast carcinoma was also increased in Caucasian women with lupus (SIR 2.9, 95% CI 1.4–6.4). Mellemkjœr <italic>et al</italic>
. [<xref rid="R6">6</xref>
] also suggested that there was an increased risk of developing non‐Hodgkin's lymphoma [relative risk (RR) 5.2], lung carcinoma (RR 1.9) and liver cancer. However, there were multiple potential errors that may have exaggerated this risk. They used the Hospital Discharge Registry to establish their lupus cohort, which may represent the more severe cases of SLE. Also, when the medical case notes were reviewed for some of the patients, it was found that not all of the patients fulfilled the ARA criteria for SLE. They also found that some patients represented in their cohort actually had a diagnosis of discoid lupus.</p>

      <p>Petterson <italic>et al</italic>
. [<xref rid="R8">8</xref>
] suggested that there was an increased risk for all malignancies but found a dramatically increased risk (RR 44, 95% CI 11.9–111) based on four cases of non‐Hodgkin's lymphoma. Lewis <italic>et al</italic>
. [<xref rid="R9">9</xref>
] also suggested an increased risk. He also used hospital admission records to identify the patients with SLE. Again, this may have exaggerated the risk as they may have included patients with more severe SLE. Canoso and Cohen [<xref rid="R10">10</xref>
] suggested that there was perhaps an increased frequency, 11.4% of their cohort of 70 patients with SLE developing a malignancy. However, they had an excess of superficial epithelial lesions (three cervical intraepithelial neoplasias and one Bowen's carcinoma of the skin).</p>

      <p>Abu‐Shakra <italic>et al</italic>
. [<xref rid="R2">2</xref>
] noted that the overall risk of cancer was not increased in their cohort of SLE patients, but there was a 4.1‐fold increased risk for haematological malignancies, and only non‐Hodgkin's lymphoma (three cases) was significantly associated with an increased risk (SIR 5.4). This association is far smaller than that reported by Pettersson <italic>et al</italic>
. [<xref rid="R8">8</xref>
] (SIR 44) (based on four cases). The general impression from these studies remains that there may be an increased risk, particularly from haematological malignancies and breast and lung carcinomas.</p>

      <p>Series looking into the cause of death in cohorts of patients with lupus do not give a true incidence of malignancy, as they do not mention whether any tumours had been treated successfully (as not all malignancies cause death) [<xref rid="R15">15</xref>
–<xref rid="R18">18</xref>
]. Therefore these series may underestimate the incidence of malignancies.</p>

      <p>There are numerous anecdotal reports of haematological malignancies in patients with SLE; in the majority of patients SLE precedes the diagnosis of lymphoproliferative disease. Patients with lymphoma may present with clinical and laboratory features suggestive of autoimmunity, including fever, rashes, arthralgias and autoantibodies. Our patients certainly fulfilled the revised ARA criteria for the classification of SLE [<xref rid="R12">12</xref>
], and several years had lapsed between the diagnosis of SLE and malignancy.</p>

      <p>It has been shown previously that patients with RA are at increased risk of haematological malignancies [<xref rid="R1">1</xref>
]. Abu‐Shakra [<xref rid="R2">2</xref>
] compared the risk of cancer in their cohort of SLE patients with RA and SSc. It was found that the overall risk of cancer was not increased in RA compared with the general population, but a twofold increased risk was observed in patients with SSc compared with the general population. The overall SIR in the SLE cohort was significantly lower compared with that in patients with RA (SIR 0.65, 95% CI 0.41–0.96) and patients with SSc (SIR 0.4, 95% CI 0.26–0.60). None of the 248 patients in the SSc cohort developed haematological malignancies. Of the 1426 RA patients, four had lymphoma, two had leukaemia and one developed a myeloma. The prevalences reported in two studies for patients with rheumatoid arthritis in the absence of immunosuppressive treatment were 0.08 and 1.56% respectively [<xref rid="R20">20</xref>
, <xref rid="R21">21</xref>
].</p>

      <p>Interestingly, both the patients who developed lymphoma in our study had both SLE and Sjögren's syndrome. The relative risk for primary Sjögren's syndrome patients developing non‐Hodgkin's lymphoma has been estimated to be approximately 40‐fold higher than that for age‐ and sex‐matched control subjects in investigations at the National Institute of Health [<xref rid="R19">19</xref>
]. However, this may be a slight overestimate. We have also found that patients with Sjögren's syndrome have an increased risk of developing non‐Hodgkin's lymphoma [<xref rid="R4">4</xref>
]. The prevalence of malignant non‐Hodgkin's lymphoma in Sjögren's syndrome patients was estimated to be 4.3%, whereas the prevalence in two studies for patients with RA in the absence of immunosuppressive treatment was 0.08 and 1.56% respectively [<xref rid="R22">22</xref>
, <xref rid="R23">23</xref>
].</p>

      <p>The reason lymphoma occurs more commonly in patients with SLE than in the general population is unknown. A side‐effect of immunosuppression is a possibility, as is intercurrent viral infection due to, for example, Epstein–Barr, herpes simplex, herpes zoster and polyoma viruses, which are potentially oncogenic. Patients who have had a renal transplant are known to have an increased risk of cancer [<xref rid="R22">22</xref>
]. They are, however, treated with much higher doses of immunosuppressive agents than patients with lupus. In the studies of Pettersson <italic>et al</italic>
. [<xref rid="R8">8</xref>
] and Abu‐Shakra [<xref rid="R2">2</xref>
] and in our study, the use of cytotoxic agents was not related to the occurrence of malignancy. It may be that the disease itself confers an increased risk. Patients with SLE have defects in both their cellular and humoral immune systems. Prolonged stimulation of B lymphocytes together with defective immune surveillance could result in the formation of autonomous B‐cell clones. It is possible that malignant lymphoma, RA and SLE are manifestations of the same underlying disturbance, and may be ascribed to chronic antigenic stimulation [<xref rid="R23">23</xref>
].</p>

      <p>Two studies have found an increased risk of breast carcinoma [<xref rid="R4">4</xref>
, <xref rid="R7">7</xref>
]. Oestrogenic hormones have been suggested as a possible causal factor in the development of SLE. Risk factors such as low parity or nulliparity and large body size with truncal obesity are well‐known risk factors for the development of breast cancer [<xref rid="R24">24</xref>
, <xref rid="R25">25</xref>
].</p>

      <p>However, large multicentre studies are required to address adequately the risk of developing malignancies in large cohorts of patients with SLE and to address issues such as associated risk factors and additional confounding factors, such as deprivation and exposure to therapy. The chance of detection of a malignancy may vary due to factors such as access to health services, which vary widely and are not uniformly available (cf. the USA), and may therefore underestimate the risk of malignancy.</p>

      <p>In conclusion, we did not observe an overall increased risk for the development of malignancies in our cohort of patients when compared with the population of the southeast of England. However, we found that SLE was associated with an increased risk of Hodgkin's lymphoma. There was no statistically significant difference in therapy with cytotoxic agents between those patients who developed a malignancy and those that did not. We recommend vigilance in dealing with patients with SLE during long‐term follow‐up, checking in particular for persistent lymphadenopathy, splenomegaly and breast lumps.</p>

    </sec>

    <sec>

      <title></title>

      <p>

        <table-wrap id="T3" position="float">

          <label>T<sc>able</sc>
 3.</label>

          <caption>

            <p>Summary of series of malignancy in SLE</p>

          </caption>

          <table>

            <tbody>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">Reference<hr></hr>
</td>

                <td colspan="1" rowspan="1" align="left" valign="top">Year<hr></hr>
</td>

                <td colspan="1" rowspan="1" align="left" valign="top">Location<hr></hr>
</td>

                <td colspan="1" rowspan="1" align="left" valign="top">No of patients in cohort<hr></hr>
</td>

                <td colspan="1" rowspan="1" align="left" valign="top">Patient‐yr of follow‐up<hr></hr>
</td>

                <td colspan="1" rowspan="1" align="left" valign="top">No. of deaths<hr></hr>
</td>

                <td colspan="1" rowspan="1" align="left" valign="top">No. of deaths due to malignancy<hr></hr>
</td>

                <td colspan="1" rowspan="1" align="left" valign="top">Observed no. of malignancies<hr></hr>
</td>

                <td colspan="1" rowspan="1" align="left" valign="top">SIR/RR (95% CI)<hr></hr>
</td>

                <td colspan="1" rowspan="1" align="left" valign="top">Association with cytotoxic drugs<hr></hr>
</td>

                <td colspan="1" rowspan="1" align="left" valign="top">Comments<hr></hr>
</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">Present</td>

                <td colspan="1" rowspan="1" align="left" valign="top">1999</td>

                <td colspan="1" rowspan="1" align="left" valign="top">London,</td>

                <td colspan="1" rowspan="1" align="left" valign="top">276</td>

                <td colspan="1" rowspan="1" align="left" valign="top">1695</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

                <td colspan="1" rowspan="1" align="left" valign="top">10 (3.6%)</td>

                <td colspan="1" rowspan="1" align="left" valign="top">SIR 1.18 (0.56–2.13); no increased risk of</td>

                <td colspan="1" rowspan="1" align="left" valign="top">No</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">paper</td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">UK</td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">development of malignancy</td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">SIR 17.82 (0.45–99.23); ↑ risk of Hodgkin's lymphoma</td>

                <td colspan="1" rowspan="1" align="left" valign="top"> No</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">5</td>

                <td colspan="1" rowspan="1" align="left" valign="top">1999</td>

                <td colspan="1" rowspan="1" align="left" valign="top">Chicago,</td>

                <td colspan="1" rowspan="1" align="left" valign="top">616</td>

                <td colspan="1" rowspan="1" align="left" valign="top">4051</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

                <td colspan="1" rowspan="1" align="left" valign="top">30 (4.9%)</td>

                <td colspan="1" rowspan="1" align="left" valign="top">SIR 2.0 (1.4–2.9); ↑ risk from all malignancies</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

                <td colspan="1" rowspan="1" align="left" valign="top">No comment about whether cancers</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">USA</td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">SIR 3.1 (1.3–7.9); ↑ risk for lung carcinoma</td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">predating onset of SLE</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">SIR 2.9 (1.4–6.4); ↑ risk for breast carcinoma in</td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">Caucasian females</td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">6</td>

                <td colspan="1" rowspan="1" align="left" valign="top">1997</td>

                <td colspan="1" rowspan="1" align="left" valign="top">Denmark</td>

                <td colspan="1" rowspan="1" align="left" valign="top">1585</td>

                <td colspan="1" rowspan="1" align="left" valign="top">10 807</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

                <td colspan="1" rowspan="1" align="left" valign="top">102 (6.4%)</td>

                <td colspan="1" rowspan="1" align="left" valign="top">RR 1.3 (1.06–1.58); ↑ risk from all malignancies</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

                <td colspan="1" rowspan="1" align="left" valign="top">Linkage using hospital discharge</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">RR 5.2 (2.2–10.3); ↑ risk from NHL (3 cases)</td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">registry. Therefore may represent</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">RR 1.9 (1.1–3.1); ↑ risk from lung cancer</td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">the more severe cases of SLE.</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">RR 8 (2.6–18.6); ↑ risk from liver cancer</td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">Some carcinomas diagnosed before</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">the onset of SLE included.</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">Not all patients fulfilled ACR</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">criteria when hospital notes were</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">analysed.</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">Included patients with discoid lupus</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">2</td>

                <td colspan="1" rowspan="1" align="left" valign="top">1996</td>

                <td colspan="1" rowspan="1" align="left" valign="top">Canada</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

                <td colspan="1" rowspan="1" align="left" valign="top">7233</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

                <td colspan="1" rowspan="1" align="left" valign="top">23 (3.2%)</td>

                <td colspan="1" rowspan="1" align="left" valign="top">SIR 1.08 (0.7–1.62); no overall increased risk</td>

                <td colspan="1" rowspan="1" align="left" valign="top">No</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">SIR 5.38 (1.11–15.70); ↑ risk from NHL</td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">7</td>

                <td colspan="1" rowspan="1" align="left" valign="top">1993</td>

                <td colspan="1" rowspan="1" align="left" valign="top">Spain</td>

                <td colspan="1" rowspan="1" align="left" valign="top">96</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

                <td colspan="1" rowspan="1" align="left" valign="top">18 (19%)</td>

                <td colspan="1" rowspan="1" align="left" valign="top">2 (2%)</td>

                <td colspan="1" rowspan="1" align="left" valign="top">5 (5.2%)</td>

                <td colspan="1" rowspan="1" align="left" valign="top">No comparison made with general population</td>

                <td colspan="1" rowspan="1" align="left" valign="top"> No</td>

                <td colspan="1" rowspan="1" align="left" valign="top">Concluded no increased risk, but no</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">comparison with general population</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">8</td>

                <td colspan="1" rowspan="1" align="left" valign="top">1992</td>

                <td colspan="1" rowspan="1" align="left" valign="top">Finland</td>

                <td colspan="1" rowspan="1" align="left" valign="top">205</td>

                <td colspan="1" rowspan="1" align="left" valign="top">2340</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

                <td colspan="1" rowspan="1" align="left" valign="top">15 (7.3%)</td>

                <td colspan="1" rowspan="1" align="left" valign="top">RR 2.6 (1.5–4.4); overall increased risk from all</td>

                <td colspan="1" rowspan="1" align="left" valign="top">No</td>

                <td colspan="1" rowspan="1" align="left" valign="top">Used 1971 criteria for the diagnosis</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">malignancies</td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">of SLE</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">RR 44 (11.9 –111); ↑ risk from NHL (4 cases)</td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">RR 2.7 (0.7–6.8); ↑ risk from breast carcinoma</td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">(4 cases)</td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">9</td>

                <td colspan="1" rowspan="1" align="left" valign="top">1976</td>

                <td colspan="1" rowspan="1" align="left" valign="top">Michigan,</td>

                <td colspan="1" rowspan="1" align="left" valign="top">484</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

                <td colspan="1" rowspan="1" align="left" valign="top">18 (4%)</td>

                <td colspan="1" rowspan="1" align="left" valign="top">Comparison of the occurrence of malignancy in a hospital</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

                <td colspan="1" rowspan="1" align="left" valign="top">Looked at patients admitted to</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">USA</td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">cohort of patients admitted with hypertension (<italic>n</italic>
 = 3295),</td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">hospital with a diagnosis of SLE.</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">only 1.6% developing a malignancy. Statistical</td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">No cases of lymphoproliferative</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">comparison using χ<sup>2</sup>
 analysis: <italic>P</italic>
 < 0.0005.</td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">disorders</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">Concluded exaggerated risk of malignancy in SLE</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">patients.</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top">10</td>

                <td colspan="1" rowspan="1" align="left" valign="top">1974</td>

                <td colspan="1" rowspan="1" align="left" valign="top">Boston,</td>

                <td colspan="1" rowspan="1" align="left" valign="top">70</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

                <td colspan="1" rowspan="1" align="left" valign="top">8 (11.4%)</td>

                <td colspan="1" rowspan="1" align="left" valign="top">No comparison with general population; highlighted</td>

                <td colspan="1" rowspan="1" align="left" valign="top">–</td>

                <td colspan="1" rowspan="1" align="left" valign="top">Excess of superficial epithelial</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">USA</td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">perhaps increased frequency of malignancy in patients</td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">lesions (3 CIN and1 Bowen's</td>

              </tr>

              <tr>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">with SLE</td>

                <td colspan="1" rowspan="1" align="left" valign="top"></td>

                <td colspan="1" rowspan="1" align="left" valign="top">carcinoma)</td>

              </tr>

            </tbody>

          </table>

          <table-wrap-foot>

            <fn>

              <p>CIN, cervical intraepithelial neoplasia; NHL, non‐Hodgkin's lymphoma; ↑ increased.</p>

            </fn>

          </table-wrap-foot>

        </table-wrap>

      </p>

      <p>

        <fn id="FN1" xml:lang="en">

          <p>Correspondence to: D. Isenberg, Centre for Rheumatology, 4th Floor, Arthur Stanley House, 40–50 Tottenham Street, London W1P 9PG, UK.</p>

        </fn>

      </p>

    </sec>

  </body>

  <back>

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<mods version="3.6"><titleInfo lang="en"><title>Is there an association of malignancy with systemic lupus erythematosus? An analysis of 276 patients under long‐term review</title>
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<titleInfo type="alternative" lang="en" contentType="CDATA"><title>Is there an association of malignancy with systemic lupus erythematosus? An analysis of 276 patients under long‐term review</title>
</titleInfo>
<name type="personal"><namePart type="given">S. M.</namePart>
<namePart type="family">Sultan</namePart>
<affiliation>Centre for Rheumatology, Bloomsbury Rheumatology Unit, Department of Medicine, University College London, London W1P 9PG, UK</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Y.</namePart>
<namePart type="family">Ioannou</namePart>
<affiliation>Centre for Rheumatology, Bloomsbury Rheumatology Unit, Department of Medicine, University College London, London W1P 9PG, UK</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">D. A.</namePart>
<namePart type="family">Isenberg</namePart>
<affiliation>Centre for Rheumatology, Bloomsbury Rheumatology Unit, Department of Medicine, University College London, London W1P 9PG, UK</affiliation>
<affiliation>Centre for Rheumatology, Bloomsbury Rheumatology Unit, Department of Medicine, University College London, London W1P 9PG, UK</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
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<originInfo><publisher>Oxford University Press</publisher>
<dateIssued encoding="w3cdtf">2000-10</dateIssued>
<copyrightDate encoding="w3cdtf">2000</copyrightDate>
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<language><languageTerm type="code" authority="iso639-2b">eng</languageTerm>
<languageTerm type="code" authority="rfc3066">en</languageTerm>
</language>
<abstract lang="en">Objective. To estimate the risk of malignancy in a UK cohort of patients with systemic lupus erythematosus (SLE) under long‐term review. Method. The University College London Lupus Clinic Database was used to identify a cohort of 276 patients followed up prospectively between 1978 and 1999. Standardized incidence ratios and 95% confidence intervals for all cancers were calculated using age and sex‐specific cancer incidence rates for the southeast of England. Results. In total, 16 malignancies were diagnosed in 15 patients. However, five malignancies were diagnosed before the diagnosis of SLE and were therefore excluded from the final statistical analysis. One case of basal cell carcinoma was also identified, but this was also excluded from the final analysis as no comparable figures were available for the general population. Death as a direct consequence of the malignancy occurred in six (2.3%) patients, accounting for 22.6% of the deaths in our cohort of SLE patients. Compared with the general population, the overall estimated risk for all cancers was not increased in the lupus cohort (standardized incidence rate 1.16 (95% confidence interval 0.55–2.13). Hodgkin's lymphoma was the only individual cancer that was increased in our cohort of patients [standardized incidence rate 17.82 (95% confidence interval 0.45–99.23)]. Conclusions. In our cohort of patients with SLE we did not show an overall increased risk of malignancy. However, SLE was associated with an increased risk of Hodgkin's lymphoma compared with the general population. From our cohort of 276 patients, none of those treated with cyclosporin (3%) developed malignancy, and out of 49 (18%) patients treated with cyclophosphamide only one patient developed malignancy. Out of the 10 patients in the final analysis who developed malignancy, six had treatment with prednisolone, four with azathioprine, five with hydroxychloroquine and only one with cyclophosphamide. No statistical difference in the above cytotoxic therapy was observed between those patients who developed malignancy and those who did not.</abstract>
<subject lang="en"><genre>KWD</genre>
<topic>Systemic lupus erythematosus (SLE)</topic>
<topic>Malignancy</topic>
<topic>Cytotoxic therapy</topic>
<topic>Hodgkin's lymphoma.</topic>
</subject>
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<titleInfo type="abbreviated"><title>Rheumatology</title>
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<identifier type="ISSN">1462-0324</identifier>
<identifier type="eISSN">1462-0332</identifier>
<identifier type="PublisherID">brheum</identifier>
<identifier type="PublisherID-hwp">rheumatology</identifier>
<identifier type="PublisherID-nlm-ta">Rheumatology (Oxford)</identifier>
<part><date>2000</date>
<detail type="volume"><caption>vol.</caption>
<number>39</number>
</detail>
<detail type="issue"><caption>no.</caption>
<number>10</number>
</detail>
<extent unit="pages"><start>1147</start>
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Is there an association of malignancy with systemic lupus erythematosus? An analysis of 276 patients under long‐term review

Is there an association of malignancy with systemic lupus erythematosus? An analysis of 276 patients under long‐term review

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