Newly diagnosed dermatomyositis in the elderly as predictor of malignancy

Abstracts

OBJETIVO: Os sintomas da dermatomiosite (DM) podem ser um indício da existência de um câncer oculto. Melhorar a detecção precoce é essencial, porém não há estudos avaliando em curto prazo os fatores preditivos para a doença. MÉTODO: Estudo retrospectivo, monocêntrico, incluindo pacientes com DM definida (pelo menos quatro dos cinco critérios de Bohan e Peter, 1975), no período entre 1991 e 2011. A presença de malignidade foi limitada a um período de até 12 meses após o diagnóstico da doença. RESULTADOS: Houve 12 casos de neoplasias em 139 pacientes (pele, trato gastrintestinal, próstata, tireoide, mama, pulmão e trato geniturinário). Os pacientes com neoplasia tiveram maior média de idade que os controles (56,8 ± 15,7 vs. 40,3 ± 13,1 anos, respectivamente, P = 0,004; odds ratio 1,09; intervalo de confiança de 95%: 1,04-1,14). Não foram observadas diferenças estatísticas em relação a gênero, etnia, frequência de sintomas constitucionais, envolvimento de órgãos e sistemas e/ou alterações laboratoriais. CONCLUSÃO: Na DM recém-diagnosticada, a idade tardia ao diagnóstico foi um fator preditivo de malignidade.

dermatomiosite; miosite; fatores de risco; neoplasias; envelhecimento

ORIGINAL ARTICLE

^IAssistant Physician of the Rheumatology Service, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo - HC-FMUSP

^IIPhD in Sciences; Assistant Physician of the Rheumatology Service, HC-FMUSP; Collaborating Professor of the Discipline of Rheumatology, FMUSP

Correspondence to

ABSTRACT

OBJECTIVE: Dermatomyositis (DM) symptoms may be a clue to the existence of a hidden cancer. Enhancing early detection is essential, but there are no studies evaluating short-term predictive factors in this disease.

METHODS: This is a singlecenter retrospective study, including patients diagnosed with DM meeting at least four of the five Bohan and Peter's criteria (1975), from 1991 to 2011. This study assessed malignancies occurring in up to 12 months after the diagnosis of DM.

RESULTS: Neoplasm was found in 12 out of 139 patients (skin, gastrointestinal tract, prostate, thyroid, breast, lungs, and genitourinary tract). Patients with neoplasm had a higher mean age than controls (56.8 ± 15.7 vs. 40.3 ± 13.1 years, respectively, P = 0.004, odds ratio 1.09; 95% confidence interval: 1.04-1.14). No statistical differences were observed regarding gender, ethnicity, frequency of constitutional symptoms, organ and systemic involvements, and/or laboratory alterations.

CONCLUSION: In newly diagnosed DM, age at disease diagnosis was a predictive factor of malignancy.

Keywords: dermatomyositis, myositis, risk factors, neoplasms, aging.

INTRODUCTION

Dermatomyositis (DM) is an idiopathic inflammatory myopathy characterized by clinical findings such as progressive, symmetric proximal muscle weakness in the four limbs, in addition to the presence of typical cutaneous changes, such as heliotrope rash and Gottron's papules.

The risk of developing neoplasias in idiopathic inflammatory myopathies is greater than that in the general population,^1-23 mainly in DM^{1,4-7,12,15-17} and in the first years following the disease diagnosis.^{1-6,8,10,13,21} The risk factors described in the literature are as follows: atypical cutaneous manifestations;^12,16-18,21 persistently high erythrocyte sedimentation rate (ESR);^12,17 refractoriness to treatment in the elderly;^20,21 rapid progression to muscle weakness;^12,16-22 presence of myositis-specific autoantibodies (anti-p155 or anti-p155/p140 antibodies);²³ cutaneous necrosis or periungual erythema;^12,16,17,21 dysphagia;²⁴ no lung impairment;²⁴ gender;^4,5,10,19,21 and advanced age on the occasion of disease diagnosis.^5,7,19,21,24

However, those studies have analyzed predictive factors of malignancy in a general population of inflammatory myopathies^{1-8,10,14-16,19,21} and/or independently of disease duration at the time of cancer diagnosis.^{1-3,5,7,10,12-19,21,23}

This study assesses the prevalence and possible factors associated with neoplasias in a population constituted only by patients with DM diagnosed in the preceding year (newly diagnosed).

PATIENTS AND METHODS

This retrospective study assessed 139 patients diagnosed with DM, meeting at least four of the five criteria proposed by Bohan and Peter.^25,26 Those patients were on an outpatient clinic follow-up at our tertiary service from 1991 to 2011. Patients with amyopathic DM or diagnosed with possible or probable DM were not included. This study was approved by the local Ethics Committee [HC 0039/10].

Demographic, clinical, and laboratory data were obtained from a systematic review of the patients' medical records. The manifestations assessed were limited to up to one year after the diagnosis of DM. The following parameters were assessed: constitutional symptoms; cutaneous changes (heliotrope rash, Gottron's papules, ulcers, rash, calcinosis); joint involvement (arthralgia and/or arthritis); dysphagia; dysphonia; dyspnea; and muscle strength of the limbs (grade 0: no muscle contractility; grade I: signs of discrete contractility; grade II: range of motion that does not overcome gravity; grade III: normal range of motion that overcomes gravity; grade IV: full motion against gravity and certain degree of resistance; grade V: full motion against marked resistance and gravity).²⁷ The serum level of creatine kinase measured at the time of the initial diagnosis of DM by use of the automated kinetic method was also assessed. Complementary tests (electroneuromyography, muscle biopsy - brachial biceps or vastus lateralis muscles), when performed, were requested as routine in the fi rst medical consultations. Electroneuromyography was considered positive in the presence of inflammatory proximal myopathy of the limbs with no neuropathy associated. The muscle biopsy was considered diagnostic when perifascicular atrophy with or without infl ammatory infiltrate was evidenced.

This study assessed neoplasias occurring in up to one year after the diagnosis of DM and confirmed by anatomopathological analysis. In our service, screening for neoplasia in all patients suspected of having initial DM is routine, with assessment of breasts, genitourinary and gastrointestinal tracts, lungs, hematologic system (particularly lymphoma), and skin.

The results were expressed as mean ± standard deviation (SD) or percentage. The Student t test was used for the statistical analysis of parametric data, and the Fisher exact test for categorical data. The 95% confidence interval (95% CI) was calculated by use of binomial distribution. The disease duration and adjusted age, odds ratio (OR), and 95% CI were calculated by using a non-conditional logistic model. Those calculations were performed by using the version 7.0 of the STATA software (STATA, College Station, TX, USA). Values of P < 0.050 were considered statistically significant.

RESULTS

In the period studied, 139 patients diagnosed with DM, meeting at least four of the five Bohan and Peter's criteria, were assessed, 12 of whom (8.6%) had a history of neoplasia in the first 12 months of disease.

Chart 1 lists the types of cancer found in the patients, which were in the following sites: breasts, genitourinary and gastrointestinal tracts, lungs, prostate, thyroid, and skin. Metastasis was identified in four (33.3%) patients at the time neoplasia was diagnosed. Of the 12 patients affected, 11 (91.7%) were females and 10 (83.3%) were white (Table 1).

Patients who had neoplasia (group A) were compared with those who did not (group B) (Table 1). The mean age at the time DM was diagnosed in group A was 56.8 ± 15.7 years (35-84 years), and, in group B, 40.3 ± 13.1 years (20-78 years) (P = 0.004). Even after analyzing age quartiles, statistical difference was observed between the groups (OR, 1.09; 95% CI: 1.04-1.14).

However, no differences were found in the groups regarding clinical laboratory manifestations and complementary tests (electroneuromyography and muscle biopsy) (Table 1).

DISCUSSION

This study found an 8.6% prevalence of neoplasia in individuals with newly-diagnosed DM, age being a risk factor associated with malignancy in that population.

Differently from the studies available in the literature,^{1-8,10,14-16,20} we assessed the prevalence and possible predictive factors of cancer in a population comprising only DM. In addition, we restricted our sample to patients diagnosed with DM, whose disease duration did not exceed one year, unlike other studies.^{1-3,5,7,10,12-19,21,23} That restriction is important because patients with a longer disease duration can have other parameters related to cancer development, such as the chronic use of immunosuppressive drugs.

András et al.⁸ have reported that malignancy may precede myopathy by two years, while Maoz et al.¹⁶ have described neoplasias in DM even after five years of disease. In general, the prevalence and incidence of neoplasias in the general population of DM ranges from 9.4%-28%.^3,4,13,15 Considering that cancer is more frequent in the first year of disease,^1-3,5,6,10 in this study, it was found in 8.6% of the patients, representing, thus, a prevalence within the expected range.

The sites of neoplasia usually found in DM are as follows: pulmonary,^2,3,5,16 ovarian,^2,3,5,16,28 nasopharyngeal,^16,29 pancreatic,³ gastric,^3,16 colorectal,^3,16 uterine,^3,5 breast,^8,16 thyroidal,¹⁶ and hematological, including lymphomas.^2,3,16 In this study they were in accordance with those reported in the literature and were as follows: pulmonary, ovarian, uterine, thyroidal, hematological, colorectal, cutaneous, and prostatic. In addition, one third of the patients already had metastasis at the time cancer was diagnosed.

In our study we observed that age at the time of disease diagnosis was a predictive factor of the development of malignancy in DM, in accordance with other studies in the literature.^{5,7,10,20-22,24} In addition, similarly to Sigurgeirsson et al.⁴ and Stockton et al.,⁵ we showed that the neoplasias affected predominantly women, although other studies have reported a higher incidence among men.^10,19,21

Other risk factors reported in the literature are as follows: cutaneous necrosis or periungual erythema,^12,16,17,21 persistently high ESR values,^12,17 refractoriness to treatment in elderly patients,^20,21 presence of myositis-specific autoantibodies, such as anti-p155 and anti-p155/140 antibodies,²³ no pulmonary involvement,²⁴ dysphagia,²⁴ and amyopathic DM.³⁰

In this study neither cutaneous necrosis nor refractoriness to treatment was observed. Regarding pulmonary involvement and presence of dysphagia, the same distribution was found in patients with and without neoplasias. In amyopathic DM, the incidence of neoplasias is higher than in classic DM.³⁰ In the presence of neoplasia, it is difficult to differentiate whether the patients really have amyopathic DM or whether the manifestations are paraneoplastic; thus, we limited our analysis only to DM meeting at least four of the five Bohan and Peter's criteria.

Because this was a retrospective study, we had some limitations such as unavailability to some laboratory tests (ESR, C-reactive protein, aldolase) of some patients. In addition, the possible autoantibodies related to the neoplasias were not assessed in this study.

Our study emphasizes the concept that patients with DM should be routinely screened for neoplasias, mainly those with newly diagnosed DM. Among other predictive factors of cancer, DM initiating at advanced age should be considered, when a more extensive assessment for cancer is recommended.

In conclusion, we showed that age was a factor associated with malignancy in newly-diagnosed DM.

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Newly diagnosed dermatomyositis in the elderly as predictor of malignancy

Fernando Henrique Carlos de Souza^I; Samuel Katsuyuki Shinjo^II

Publication Dates

• Publication in this collection
  19 Oct 2012
• Date of issue
  Oct 2012

History

• Received
  28 Oct 2011
• Accepted
  27 June 2012