We conducted a retrospective study in patients with dermatomyositis and polymyositis admitted to Kyungpook National University Hospital between 1999 and 2013. The diagnoses of polymyositis and dermatomyositis were based on the criteria of Bohan and Peter [11]: (1) symmetric muscle weakness, (2) increased serum muscle enzymes, (3) myopathic changes on EMG, (4) typical histological findings on a muscle biopsy, and (5) characteristic dermatological manifestations. Two patients were diagnosed with amyopathic dermatomyositis (ADM) according to the criteria of Sontheimer [12]. Patients were divided into those with and without malignancies, and comparisons were made between the two groups in terms of their demographic factors, clinical findings, laboratory results, and EMG findings.

In this study, patients with hallmark cutaneous manifestations of dermatomyositis but for whom muscle testing did not reveal any abnormality were classified as having ADM, according to Sontheimer's criteria [12]. We included a total of 61 patients with dermatomyositis/polymyositis after excluding four patients with juvenile dermatomyositis, and two with ADM. We reviewed the medical records of these patients. The diagnosis of malignancy-associated IIM was retained if IIM occurred in the context of a recently diagnosed malignancy, or if a malignancy was diagnosed during the 2 years following the diagnosis of IIM (three patients were followed for less than 2 years after the diagnosis of IIM: two for 6 months and one for 9 months). Malignancy screening was performed in all patients, based on our institution's guidelines. All patients were screened for malignancy with laboratory tests including carcinoembryonic antigen, α-fetoprotein, carbohydrate antigen (CA 19-9), cancer antigen (CA-125), neuron-specific enolase, and β-human chorionic gonadotropin for females or prostate-specific antigen for males, radiographic imaging, including abdominal and chest computed tomographies (CTs), upper and lower endoscopic examinations, and positron emission tomography-CT if available. A muscle biopsy was performed in most cases. A nerve conduction study and needle EMGs were performed according to basic principles by one of two experienced electromyographers (JKS and HSS, Neurologist) with Medelec Synergy (VIASYS, London, UK). The classic triad of EMG findings of IIM (1) polyphasic, short duration motor unit potentials, (2) fibrillation, positive sharp waves, increased insertional activity, and (3) complex repetitive discharge (CRD) were evaluated [10,11].

Baseline characteristics were compared between groups using Student t test and the chi-square test, or Fisher exact test for categorical variables. An age-adjusted analysis was performed to compare malignancy-associated and nonmalignancy-associated IIM, using univariate logistic regression analysis. We calculated the odds ratios (ORs) and 95% confidence intervals (CIs) of the factors associated with malignancies in patients with IIM. The factors with a p value < 0.05 in the univariate analysis were subjected to a multivariate analysis. Multivariate logistic regression analysis was used to identify the relationship between the malignancy and predictor variables. The multivariate analysis used a step-wise backward regression model. The relative excess risk due to interaction (RERI) that was attributable to the interaction between the two variables [13] was calculated to estimate the excess risk. All statistical calculations were performed using the SPSS version 20 (IBM Co., Armonk, NY, USA). p values < 0.05 were considered to indicate statistical significance.

Each patient was followed from the time of the initial diagnosis at our institute to either the date of death or the date of the latest follow-up. We excluded patients with a preceding malignancy who had been in remission for more than 3 years at the time of IIM diagnosis. Among 61 the patients, dermatomyositis was the most common type (n = 30, 49%), followed by polymyositis (n = 25, 41%), juvenile dermatomyositis (n = 4, 7%), and ADM (n = 2, 3%). Demographic and clinical data on these patients are presented in Table 1. The mean age at diagnosis was 45.3 years for dermatomyositis (including ADM/juvenile dermatomyositis) and 49.3 years for polymyositis. Patients with IIM were predominantly women (60.7%). Distributions of age at diagnosis, gender, and frequency of ILD were not significantly different between the two groups.

Malignancies were present in 16.4% of all patients (10/61). These included eight of the 36 patients with dermatomyositis (including ADM and juvenile dermatomyositis) (22.2%) and two of the 25 with polymyositis (8.0%). No patient with ADM or juvenile dermatomyositis had a malignancy. There was no significant difference in the risk of malignancy between dermatomyositis and polymyositis patients. Gastric cancer was the most frequent malignancy observed (two patients), followed by bladder cancer, nasopharyngeal cancer, ovarian cancer, prostate cancer, thyroid cancer, lung cancer, gallbladder cancer, and invasive thymoma (one patient each). Adenocarcinoma was the predominant histological type (50%). A comparison of the clinical findings of the 10 patients with malignancies and 51 without is presented in Table 2.

Patients with malignancies showed a significantly higher incidence of dysphagia (OR, 21.50; 95% CI, 3.84 to 120.49; p < 0.001) and a lower incidence of ILD (OR, 0.12; 95% CI, 0.01 to 0.98; p = 0.034), compared with those without. After adjustment for age, dysphagia remained significant, while ILD showed a trend for a difference but was not statistically significant. Serum concentrations of muscle enzymes, such as creatine phosphokinase, aldolase, and myoglobin, and the frequency of autoantibodies, including antinuclear, and anti-Jo-1, -Ro, and -La antibodies, showed no significant difference between IIM patients with and without malignancies.

EMG was performed in 42 patients, including five with malignancy. The number of abnormal EMG findings was significantly higher in patients with malignancies (OR, 9.05; 95% CI, 1.08 to 75.57; p = 0.044). Patients with malignancies showed an increased incidence of CRD (OR, 26.25; 95% CI, 2.67 to 258.52; p = 0.008), versus those without, which remained significant after adjustment for age.

In the next step, interactions among the three predictive factors that were statistically significantly associated with a higher risk of malignancy in patients with IIM were investigated. We chose these significant factors for multivariate logistic regression to determine the independent predictive factors for malignancies (Table 3). The presence of CRD on the EMG conferred an OR of 25.99 (95% CI, 1.27 to 531.86; p = 0.034) for developing a malignancy. We found that CRD was another independent factor associated with malignancy in IIM, while dysphagia showed marginal statistical significance (p < 0.1). Furthermore, we found that an increase in the number of these risk factors was associated with a higher malignancy incidence. Patients with three risk factors showed a significantly higher incidence of malignancies, compared with those with zero (p = 0.007) or one (p = 0.014) (Fig. 1). RERI was calculated to determine the synergistic interaction between two variables among the three risk factors. There was no statistically significant excess risk attributable to an interaction between any two variables.