Incidences of different cancer types in dermatomyositis, polymyositis and dermatopolymyositis: results of a registry analysis
Authors: M. Zidane, C. Dressler, A. Nast, A. Egeberg
Journal: British Journal of Dermatology (2020)

Dear Editor, Studies confirming dermatomyositis/polymyositis/dermatopolymyositis (DM/PM/DPM) as a paraneoplastic disease have found cancer incidence rates elevated at the timepoint of diagnosis and remaining elevated over time.1 Guidelines promote cancer screening in patients with newly diagnosed myositis.2 Data on the incidence of cancer types in patients with DM and PM are insufficient to guide targeted screening.3-5 We conducted a retrospective registry analysis using data from the Danish National Patient Register (NPR). The NPR, established in 1977, is an administrative registry that provides individual-level linkage. Cancers that were diagnosed before and after the onset of myositis were studied. Patients with DM/PM/DPM were identified by their first outpatient or inpatient consultation for DM/PM/DPM using the International Classification of Diseases 8th Revision (ICD-8) codes 716·00 and 716·10, and ICD-10 codes M33·0, M33·1, M33·2 and M33·9. The primary endpoint was the development of any type of cancer (ICD-8: 140–209; ICD-10: C00–97, B21). Secondary endpoints were the occurrence of the most frequent cancer types during the predefined time period (colon–rectum–anus, ICD-8: 153–4; ICD-10: C18–21), lung (ICD-8: 162; ICD-10: C33–34), bladder (ICD-8: 188; ICD-10: C67), female breast (ICD-8: 174; ICD-10: C50), ovary (ICD-8: 183; ICD-10: C56) and prostate cancer (ICD-8: 185; ICD-10: C61), as well as non-Hodgkin lymphoma (NHL) (ICD-8: 200, 202; ICD-10: C82–86, C96) and multiple myeloma (MM) (ICD-8: 203; ICD-10: C88, C90). We calculated the cancer incidence rates (IRs) of these individuals and compared them with general-population values (matched for age and sex). The general population was sampled using the Civil Registration System (for detailed information see Schmidt et al.).6 To assess the cancer risk after diagnosis of DM/PM/DPM we calculated IRs for four periods: 0–1, 1–2, 2–5 and ≥ 5 years. Individuals were followed up until death from any cause, migration or occurrence of another type of cancer, whichever happened first. To assess the cancer risk before diagnosis of DM/PM/DPM we calculated IRs for three periods: ≤ 2, 2–5 and ≥ 5 years. The initial cohort of patients with DM/PM/DPM, aged ≥ 18 years, identified from 1 January 1977 to 31 December 2017, comprised 2825 individuals. In total, 249 had a cancer diagnosis prior to DM, PM and/or DPM (n = 96, 108 and 45, respectively). Table 1 illustrates cancers after diagnosis of DM, PM and DPM (n = 127, 218 and 57, respectively). In the first year after diagnosis, the risk of any type of cancer was significantly higher for DM/DPM [IR 126·6 per 100 person-years, 95% confidence interval (CI) 100·5–159·5; P < 0·001] than for the general population. After that the effects were not sustained. The adjusted level of significance was P ≤ 0·0019. PM did not reach statistical significance at any point in time. With regard to cancers arising before DM, the majority (57·3%) preceded DM and one-third preceded PM by > 2 years before diagnosis. In contrast, most diagnoses of DPM (60·0%) and PM (38·3%) were made ≥ 5 years before cancer. Analysis by type of cancer in patients with DM/DPM showed a significantly higher risk of diagnosis of lung cancer (incidence rate ratio (IRR) 8·93, 95% CI 5·24–15·2; P < 0·001) and ovarian cancer (IRR 27·1, 95% CI 8·49–86·3; P < 0·001) than in the general population during the first year after diagnosis. In the same period, patients with PM had higher incidences of NHL (IRR 3·18, 95% CI 1·81–5·60; P < 0·001) and MM (IRR 4·50, 95% CI 1·93–10·5; P < 0·001) in comparison with general-population values (IR per 100 person-years 0·7, 95% CI 0·3–1·5 for NHL; IR 0·2, 95% CI 0·1–0·9 for MM). The different rates in terms of cancer type and extent for all cancer types 1 year after diagnosis of DM/DPM and PM emphasize the differences in pathophysiology of these diseases. We did not identify significantly elevated risks for specific cancer types over time to justify specific screening recommendations. This study has several limitations. Firstly, although statistical testing was performed, it remains controversial whether or not to adjust for multiple comparisons.7 Secondly, the clinical validity of the diagnostic codes was not addressed in this study. Hence, it remains unclear which characteristics were used to assigned patients to DPM in the ICD-10 classification. An additional coding validation study may further strengthen the validity of the results. Thirdly, the IRRs were adjusted only for age and sex. Other confounders (e.g. deprivation) were not adjusted for. In line with previous work, we found an increased risk of malignancy, with strong emphasis on the first year after diagnosis. This close temporal association is consistent with a paraneoplastic mechanism. In contrast to Hill et al.,1 we were not able to detect an effect that persisted more than 1 year after DM diagnosis. Detection bias due to cancer screening at the timepoint of diagnosis of DM/PM/DPM, and possibly ascertainment bias need to be taken into consideration as a cause of the elevated rate of cancer diagnosis during the first year, rather than an increased propensity for malignancy in patients with autoimmune disease. Diagnosis of DM/PM/DPM often leads to high patient concerns due to its described paraneoplastic nature. Specific autoantibodies like anti-p155/14M may assist in differentiating between paraneoplastic and nonparaneoplastic DM/PM/DPM. Analyses linking anti-p155/140 antibodies and a routine myositis panel to cancer incidence rates may help to investigate further the paraneoplastic nature of DM/PM/DPM and to consult patients with regard to their cancer risk and provide appropriate screening and follow-up measures.