The main objectives of the REMICAM are to describe and characterize IIM patients, who usually managed in the rheumatology departments of the Community of Madrid, for the purpose of:

• 1.

  Describing the sociodemographic and clinical characteristics

• 2.

  Studying the rate of comorbidity and the cumulative incidence, and possible differences among distinct types of myopathies

• 3.

  Calculating the mortality rate in the overall series and by clinical subgroups

As secondary objectives, the registry proposes a multicenter collaborative study to subsequently examine specific aspects of autoimmune inflammatory myopathies.

Retrospective multicenter registry of patients with IIM from units or departments of rheumatology in the Community of Madrid, using a hospital-based cross-sectional registry, recording retrospective information on clinical data, mortality and cause of death.

Through SORCOM, the invitation to participate in the present study was sent to the different departments or units of rheumatology of public hospitals in the Community of Madrid, as well as the rheumatology department of Hospital Madrid Norte in Sanchinarro, a borough of Madrid. We included unselected consecutive patients with a diagnosis of IIM (dermatomyositis, polymyositis, inclusion body myositis and immune-mediated necrotizing myositis), who had undergone follow-up in the above departments at some time during the period between January 1980 and December 2014, without taking into account their age at onset of the process. The patients ultimately selected met the criteria of Bohan and Peter7,8 and/or Tanimoto's classification criteria,9 and we excluded toxic and infectious myopathies and myopathies secondary to neuromuscular disease. The patients were classified into 7 subgroups: idiopathic polymyositis (PM), idiopathic dermatomyositis (DM), juvenile myositis (JM), IIM associated with another connective tissue disease (overlap syndrome), cancer-associated IIM, inclusion body myositis10 and immune-mediated necrotizing myositis.11 Patients with overlap syndrome had to meet criteria for IIM and criteria for the following connective tissue diseases: rheumatoid arthritis,12 systemic sclerosis,13 systemic lupus erythematosus,14 mixed connective tissue disease15 or Sjögren's syndrome.16 We defined myositis as being cancer-associated in those cases in which cancer was diagnosed during the 3 years prior to or after the development of the myopathy, similar to the approach used in previous studies.17 For the comparison of the different subgroups, we only took into account the first 5 of those mentioned above, given the low prevalence of inclusion body myositis and immune-mediated necrotizing myositis.

In all, 313 variables were included for each patient, and were grouped in terms of their relation to sociodemographic characteristics, classification, mortality, comorbidity, clinical manifestations and analytical data, as well as information regarding treatments. All of these data were retrieved from the medical history of each patient. Exhaustive monitoring for inconsistencies in the data was performed by an external company.

The sociodemographic data included information on sex, race, age at disease onset, age at the last visit (age of the patient at the time of the last visit available or age at the time of death), disease duration (time since the diagnosis and the last visit).

General symptoms included weight loss >10% or fever not explained by causes other than the rheumatic disease. Skin manifestations included Gottron's papules, heliotrope rash, Gottron's sign, cutaneous vasculitis (established by a compatible biopsy), photosensitivity, mechanic's hands, nonspecific pruritus, skin ulcers, ischemic ulcers in fingertips, periungual erythema and/or macroscopic dilatation of nailfold capillaries, hand edema and sclerodactyly. The hematologic manifestations included anemia, leukopenia or thrombocytopenia attributed to the disease, after ruling out drug-related and infectious causes, among others. We took into account gastrointestinal manifestations such as: dysphagia, gastroesophageal reflux (defined as suggestive clinical signs and upper gastrointestinal tract endoscopy and/or pH-metry and/or esophageal manometry showing evidence of gastrointestinal tract dysmotility, after ruling out other causes), upper/lower gastrointestinal bleeding attributed to the disease (defined as hematemesis, melena or rectal bleeding, after ruling out other causes) and diarrhea or constipation attributed to the disease (defined by compatible clinical signs, after ruling out other causes). As cardiovascular disease, we included: arterial or venous or pulmonary thromboembolic disease, ischemic cardiomyopathy, arrhythmias, stroke and pulmonary hypertension. Pulmonary hypertension was defined by echocardiogram (estimated systolic pulmonary artery pressure [sPAP] ≥40mmHg) and/or cardiac catheterization (measured sPAP ≥25mmHg). Interstitial lung disease was diagnosed on the basis of compatible clinical signs (recent onset dyspnea on exertion and/or dry cough and/or fever with no other origin) and diagnostic chest radiographic images, high-resolution computed tomography of the lungs and/or compatible lung biopsy, and/or compatible respiratory function tests, once other causes had been ruled out. Interstitial lung disease was classified, when possible, depending on the result of the lung biopsy and/or the radiologic image and, in the case of disagreement, a consensus was reached between the radiologist and the pathologist to define the following subtypes: nonspecific interstitial pneumonia, usual interstitial pneumonia, bronchiolitis obliterans organizing pneumonia, diffuse alveolar damage and cryptogenic pneumonia. An infection was considered to be serious if it required hospital admission or led to death.

The cause of death of patients in routine follow-up in their referral hospital was recorded in terms of the data on the medical history or the death certificate. When a patient was lost to follow-up, the attempt was made to make contact by telephone to determine the status of the patient, as well as the cause and date of death. The causes of death were classified according to 5 subgroups depending on the underlying cause: infections, cardiovascular event (arrhythmia, ischemic cardiomyopathy, acute ischemic or hemorrhagic stroke, pulmonary hypertension, heart failure and pulmonary thromboembolism), cancer, interstitial lung disease and miscellaneous.

A significance level α of .05 was assumed for all of the statistical analyses. Sociodemographic factors, classification subgroups, comorbidity and survival were assessed by basic descriptive statistical analysis. For the description of the sample, we used central tendency measures (mean and median) and dispersion (standard deviation and interquartile range), as well as frequency tables and percentage distribution for continuous and categorical variables, respectively. The comparison of the distinct types of myopathies was done using mean difference tests, with analysis of variance, comparison of proportions by means of chi-square test, and Fisher's exact test in cases of cell sizes less than 5. All of the analyses were performed with Stata 12.

The most widespread myopathy subgroups were the primary forms (PM and DM), followed by overlap syndrome, juvenile myositis and cancer-associated myositis. Moreover, there were 6 cases of inclusion body myositis and 6 patients with immune-mediated necrotizing myositis (Fig. 1). Of the 6 patients with immune-mediated necrotizing myositis, only 1 had undergone treatment with statins and 3 had not. It was not possible to obtain this information for the other 2 patients. The connective tissue disease most frequently associated with IIM in overlap syndrome was mixed connective tissue disease, followed by systemic sclerosis, systemic lupus erythematosus, Sjögren's syndrome and rheumatoid arthritis (Fig. 2). In all, 99.6% met the criteria of Bohan and Peter, 97.3% Tanimoto's criteria, and 96.9% both. According to the classification criteria proposed by Bohan and Peter, 99.6% of the patients would have a possible disease, 94.1% a probable disease and 67.4% a definite disease. All of the patients but 1 with a diagnosis of overlap syndrome had a muscle biopsy compatible with myositis or electromyographic study with a typical myopathic pattern. That patient was diagnosed with systemic sclerosis and had muscle weakness and a baseline creatine kinase (CK) level of 748IU/L, but later improved with treatment.

Fig. 1.

Clinical subgroups.

CAM, cancer-associated myositis; DM, idiopathic dermatomyositis; IBM, inclusion body myopathy; IMNM, immune-mediated necrotizing myositis; JM, juvenile myositis; PM, idiopathic polymyositis; OS, overlap syndrome.

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Fig. 2.

Connective tissue diseases associated with overlap syndrome.

MCTD, mixed connective tissue disease; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; SS, Sjögren's syndrome; SSc, systemic sclerosis.

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Most of the patients in our series were women (74.1%) and Caucasian (93.5%). The remaining sociodemographic data are shown in Table 2. With regard to clinical manifestations, there was a marked prevalence of interstitial lung disease (29.9%), mainly usual interstitial pneumonia (28.2%) and nonspecific interstitial pneumonia (23.4%), followed by bronchiolitis obliterans organizing pneumonia (4%), diffuse alveolar damage (2.4%) and cryptogenic pneumonia (0.8%); it was not possible to identify the subtype of the remainder of the patients. The CK levels in 11.6% of the patients were higher than normal at the end of follow-up, and the follow-up period was longer in patients with normal CK levels (10.3±8.5 years vs 5.9±5.2 years; P<.001).

Patients with DM experienced a greater number of general symptoms when compared with those with PM, and mechanic's hands and typical skin manifestations were more frequent. Juvenile myositis was characterized by more frequent typical skin manifestations than was observed in dermatomyositis, but Raynaud's phenomenon, extramuscular manifestations, malignant neoplasms and serious infections were less common. On the other hand, overlap syndrome was more frequently accompanied by arthritis, Raynaud's phenomenon, hematologic manifestations, interstitial lung disease, and systemic, neuropsychiatric and renal manifestations. Paraneoplastic myositis had a shorter follow-up and the patients had lower CK levels at the end of follow-up when compared to the other subgroups. The most common myositis specific antibodies were anti-Jo-1 (77 cases), followed by anti-RNP, anti-Mi-2, anti-PM-Scl and others less frequent (Fig. 3). The remaining clinical manifestations are shown in Table 2.

Fig. 3.

Myositis specific antibodies.

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Overall, 54.6% of the patients had some cardiovascular risk factor, mostly dyslipidemia, hypertension, diabetes mellitus and active tobacco use, and 22.3% of the cases were complicated by one or more cardiovascular events (Table 3).

In all, 25% of the patients had complications in the form of serious infections, mainly lower respiratory tract infections (63%), followed by urinary tract (14%), gastrointestinal (10%) and others that were less common. In 30% of the cases of serious infections, the outcome was death. Serious infections developed more frequently in patients with overlap syndrome and myopathy associated with a malignant neoplasm. With regard to cancer-associated myositis, the tumors most frequently involved were lung and skin cancer (8 cases each), lymphoma (n=7) and breast cancer (n=6). In 2 cases, the origin of the cancer had not been determined.

During the study period, there were 114 deaths, representing 28% of the analysis sample. The major causes were cancer, infections and cardiovascular events (Fig. 4). Patients with cancer-associated myositis had the worst prognosis, followed by overlap syndrome, whereas the patients with juvenile myositis had the best prognosis.

Fig. 4.

Causes of death in the overall series.

ILD, interstitial lung disease.

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With regard to treatment, a substantial number of the patients had received, at some time, glucocorticoids, either intravenously (15%) or orally (99%), and half of them (50.3%) still required oral steroids when they visited their physician for the last time. They were taking a dose of less than 30mg/day in 95% of the cases at the end of follow-up. In all, 13.2% of the patients required more than 1 cycle of oral steroids over the course of the disease. Immunosuppressive agents were utilized in 74.1% of those patients, 30.5% of whom required the use of 2 or more drugs over the course of the disease (with an average of 2.4±0.9 immunosuppressive drugs in those cases). The nonbiologic therapies most widely utilized, in cumulative percentage, were methotrexate (48%), azathioprine (40%), hydroxychloroquine (16%) and cyclophosphamide (9%). In all, 9% were treated with intravenous immunoglobulin and 12% received biological therapy at some time (the drug most frequently used was rituximab in 9% of the cases) (Fig. 5).

Fig. 5.

Cumulative and current treatment.

Anti-TNFα, anti-tumor necrosis factor α; AZA, azathioprine; CP, cyclophosphamide; CyA, cyclosporine A; HCQ, hydroxychloroquine; IVIG, intravenous immunoglobulins; LEF, leflunomide; MMF, mycophenolate mofetil; MTX, methotrexate; PRED, prednisone; RTX, rituximab.

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The authors declare that no experiments were performed on humans or animals for this study.

The authors declare that they have followed the protocols of their work center on the publication of patient data.

The authors have obtained the written informed consent of the patients or subjects mentioned in the article. The corresponding author is in possession of this document.