Pretreatment mortality risk prediction model in patients with polymyositis/dermatomyositis-associated interstitial lung disease.

OBJECTIVES: Risk prediction for patients with polymyositis/dermatomyositis-associated interstitial lung disease (PM/DM-ILD) is challenging due to heterogeneity in the disease course. We aimed to develop a mortality risk prediction model for PM/DM-ILD. METHODS: This prognostic study analysed patients with PM/DM-ILD admitted to Nanjing Drum Hospital from 2016 to 2021. The primary outcome was mortality within 1 year. We used a least absolute shrinkage and selection operator (LASSO) logistic regression model to identify predictive laboratory indicators. These indicators were used to create a laboratory risk score, and we developed a mortality risk prediction model by incorporating clinical factors. The evaluation of model performance encompassed discrimination, calibration, clinical utility and practical application for risk prediction and prognosis. RESULTS: Overall, 418 patients with PM/DM-ILD were enrolled and randomly divided into development (n=282) and validation (n=136) cohorts. LASSO logistic regression identified four optimal features in the development cohort, forming a laboratory risk score: C reactive protein, lactate dehydrogenase, CD3+CD4+ T cell counts and PO2/FiO2. The final prediction model integrated age, arthralgia, anti-melanoma differentiation-associated gene 5 antibody status, high-resolution CT pattern and the laboratory risk score. The prediction model exhibited robust discrimination (area under the receiver operating characteristic: 0.869, 95% CI 0.811 to 0.910), excellent calibration and valuable clinical utility. Patients were categorised into three risk groups with distinct mortality rates. The internal validation, sensitivity analyses and comparative assessments against previous models further confirmed the robustness of the prediction model. CONCLUSIONS: We developed and validated an evidence-based mortality risk prediction model with simple, readily accessible clinical variables in patients with PM/DM-ILD, which may inform clinical decision-making.

Long-term secular trends in dermatomyositis and polymyositis mortality in the USA from 1981 to 2020 according to underlying and multiple cause of death mortality data.

BACKGROUND: People with dermatomyositis (DM) or polymyositis (PM) often die from cancer, pulmonary, cardiac complications, or infections. In such cases, DM or PM might not be designated as the underlying cause of death (UCD) for mortality tabulation. In this study, we investigated DM/PM mortality trends in the USA from 1981 to 2020 with respect to UCD and multiple causes of death (MCD) data. METHODS: We used the MCD data to identify all deaths with DM or PM mentioned anywhere on the death certificate and as the UCD in the USA from 1981-1982 to 2019-2020. We calculated age-adjusted mortality rates (AAMRs) and annual percentage changes (APCs) based on joinpoint regression analysis. RESULTS: We identified 12,249 (3985 with DM and 7097 with PM) and 23,608 (8264 with DM and 15,344 with PM) people who died between 1981 and 2020 according to the UCD and MCD data, respectively. For DM, the APC was - 6.7% (from 1981-1982 to 1985-1986), - 0.1% (from 1985-1986 to 2003-2004), and - 1.9% (from 2003-2004 to 2019-2020) according UCD and was - 1.2% (from 1981-1982 to 2003-2004), - 2.5% (from 2003-2004 to 2015-2016), and 2.8% (from 2015-2016 to 2019-2020) according MCD. For PM, the APC was 1.9% (from 1981-1982 to 1989-1990), - 2.3% (from 1989-1990 to 2005-2006), and - 5.2% (from 2005-2006 to 2019-2020) according UCD and was 1.3% (from 1981-1982 to 1991-1992) and - 4.1% (from 1991-1992 to 2019-2020) according MCD. CONCLUSION: We identified two times as many DM/PM deaths using the MCD as those identified using the UCD. Similar downward DM/PM mortality trends were noted according to UCD and MCD. However, the year of significant decline in PM mortality was about 10 years earlier according to MCD than those according to UCD.

Persistent premature mortality gap in dermatomyositis and polymyositis: a United Kingdom general population-based cohort study.

OBJECTIVE: DM and PM are associated with substantial morbidity and mortality. We aimed to examine recent trends. METHODS: Using The Health Improvement Network, we identified patients with incident DM/PM (defined by ≥1 Read diagnosis code) aged 18-89 years with ≥1 year of continuous enrolment prior to the cohort entry date and up to 10 comparators matched on age, sex and entry year. The cohort was divided in two based on the year of DM/PM diagnosis: the early cohort (1999-2006) and late cohort (2007-2014). We calculated multivariable hazard ratios (HR) for death using a Cox-proportional hazards model and multivariable rate differences (RD) using an additive hazard model. RESULTS: We identified 410 DM cases (mean age: 58 years, 66% female) and 407 PM cases (mean age: 59 years, 61% female). Both DM cohorts had excess mortality compared with the comparison cohorts (71.5 vs 12.9 deaths/1000 person-years [PY] in the early cohort and 49.1 vs 10.4 deaths/1000 PY in the late cohort). The multivariable HRs were 7.51 (95% CI: 4.20, 13.42) in the early cohort and 5.42 (95% CI: 3.11, 9.45) in the late cohort (P-value for interaction = 0.59), and multivariable RDs were 56.2 (95% CI: 31.8, 81.2) in the early cohort and 36.3 (95% CI: 19.6, 53.0) in the late cohort (P-value for interaction = 0.15). A similar trend existed in PM. CONCLUSION: The premature mortality gap in DM/PM has not considerably improved in recent years, highlighting an unmet need for therapeutic improvement.

Ultra-low dose rituximab as add-on therapy in anti-MDA5-positive patients with polymyositis /dermatomyositis associated ILD.

OBJECTIVES: To evaluate the efficacy and safety of ultra-low dose (100 mg) rituximab (RTX) administration in anti-melanoma differentiation-associated gene 5 (MDA5) positive patients with polymyositis/dermatomyositis (PM/DM) associated interstitial lung disease. METHODS: This retrospective study included anti-MDA5 antibody positive ILD subjects in the First Affiliated Hospital of Guangzhou Medical University from November 2017 to March 2019. Independent predictors for 180-day mortality were measured by Cox regression analysis. Patients were divided into 3 groups: Group 1 (non-cyclophosphamide (CTX)/RTX) (n = 10), Group 2 (CTX only) (n = 19) and Group 3 (RTX with/without CTX) (n = 11). The 180-day mortality was compared among 3 groups with Kaplan-Meier analysis. Post-RTX serological parameters as well as adverse events were evaluated. RESULTS: Forty patients were included with the mean age of 51.3 years. Elevated IL-10 level and CD4+/8+ ratio were considered as risk factors of 180-day mortality. Kaplan-Meier analysis showed a trend toward decrease, albeit non-significant, in 180-day mortality in Group 3 (P = 0.26). The administration of 100 mg RTX brought down B cell within 7 days that lasted for 180 days. There were 7 and 6 infection events observed within 2 months of CTX/RTX treatment in Group 2 and 3, with 5 and 2 fatal cases respectively. Cytomegalovirus infection accounted for half infection events in Group 3. CONCLUSION: We found a pronounced and prolonged B cell depletion following 100 mg RTX infusion and RTX add-on may be effective in anti-MDA5 positive ILD patients. However, infection, especially opportunistic infection, should be concerned during the treatment.

Mortality in Patients with Polymyositis and Dermatomyositis in an Israeli Population.

BACKGROUND: The reported mortality rates of patients with polymyositis and dermatomyositis are highly variable worldwide. The excess mortality of patients with polymyositis/dermatomyositis has not been evaluated in an Israeli population. OBJECTIVES: To investigate the overall mortality in a large and well-established cohort of patients with polymyositis/dermatomyositis as compared to the mortality expected in the matched general population in a tertiary medical center. METHODS: In this retrospective cohort study, the mortality of 166 patients with polymyositis/dermatomyositis was compared to age- and sex-matched control subjects in the general population. All-cause standardized mortality ratios (SMRs) were estimated. RESULTS: Overall, 47 (28.3%) deaths were observed among patients with polymyositis/dermatomyositis during a mean follow-up period of 5.8 ± 4.8 years, which was 7 times higher than in the control group (SMR 7.4, 95% confidence interval [95%CI] 5.5-9.8). The SMRs were comparable in patents with polymyositis (7.7, 95%CI 4.8-12.3) and dermatomyositis (7.2, 95%CI 5.0-10.3). The 1-, 5-, 10-, and 15-year overall survival rates were 90.0%, 82.8%, 51.5%, and 26.1%, respectively, in patients with polymyositis, and 80.3%, 59.6%, 40.0%, and 17.1%, respectively, in patients with dermatomyositis. CONCLUSIONS: The overall mortality among Israeli patients with polymyositis/dermatomyositis is 7.4 times greater than for the general population. Although long-term mortality was comparable between patients with dermatomyositis and polymyositis, patients in the former group died at a notably earlier stage.

Mortality of Chinese patients with polymyositis and dermatomyositis.

OBJECTIVE: To investigate the mortality and the causes of death in Chinese patients with polymyositis (PM) and dermatomyositis (DM). METHODS: The clinical data of all consecutive adult PM/DM patients in Rheumatology and clinical immunology department of Peking University First Hospital from January 2007 to Apr2016 were collected. The primary causes of death were identified, the standardized mortality ratio (SMR) and years of life lost (YLL) were calculated based on the National Bureau of Statistics of China for the general population, the survival in the first decade was performed using Kaplan-Meier analysis, and the predictors of mortality were evaluated by multivariable cox regression. RESULTS: A total of 85 PM and226 DM cases were included and 68 patients died. Infection (52.3%) was the leading cause of death. The overall age and sex adjusted SMR was 6.0(95%CI 3.5-8.5) for PM, and 9.0(95%CI 6.8-11.2) for DM. The YLL of women and men were 12.2 and 18.3 years respectively for PM, and 37.5 and 28.4 years respectively for DM. The 10-year survival of patients with ILD, malignancy or infection was significantly worse than those without, respectively. The independent predictors of mortality for PM/DM patients were age at disease onset, malignancy and infection. CONCLUSIONS: Mortality of PM/DM patients in China is substantial, especially in females, and those with ILD, malignancy or infection. Infection was the leading cause of death. Patients with older age at onset, infection, ILD, and malignancy need to be paid more attention. Key Points • This is the first comprehensive report about the mortality situation with a large population in PM/DM patients in China including SMR, YLL, and cause of death, Kaplan-Meier survival analysis and Cox regression analysis for mortality risk factors. • The specific SMRs for PM/DM patients with malignancy and interstitial lung disease were also reported in this study. To our knowledge, only two studies worldwide reported SMRs in PM/DM patients and no figure about YLL was reported so far. • Overall, the mortality figures in this study were higher than those from the western countries, and the leading cause of death was different from the western countries.

Integrated therapy decreases the mortality of patients with polymyositis and dermatomyositis: A Taiwan-wide population-based retrospective study.

ETHNOPHARMACOLOGICAL RELEVANCE: The issue of whether integrated treatment with conventional medicine (CM) and herbal medicine (HM) can reduce mortality in patients with polymyositis/dermatomyositis (PM/DM) had not been addressed. AIM OF THE STUDY: In this study, we investigated the effect of integrated therapy on mortality in a retrospective PM/DM cohort in the Taiwan National Health Insurance Research Database (NHIRD). MATERIALS AND METHODS: Patients with PM/DM were retrospectively enrolled from the PM/DM Registry of Catastrophic Illnesses cohort in the Taiwan NHIRD between 1997 and 2011. The patients were divided into an integrated medicine (IM) group that received CM and HM and a non-IM group that received CM alone. The Cox proportional hazards regression model and Kaplan-Meier method were used to evaluate the hazard ratio (HR) for mortality. RESULTS: Three hundred and eighty-five of 2595 patients with newly diagnosed PM/DM had received IM and 99 had received non-IM. The adjusted HR for mortality was lower in the IM group than in the non-IM group (0.42, 95% confidence interval 0.26-0.68, p < 0.001). The adjusted HR for mortality was also lower in the IM group that had received CM plus HM than in the group that received CM alone (0.48, 95% confidence interval 0.28-0.84, p < 0.05). The core pattern of HM prescriptions integrated with methylprednisolone, methotrexate, azathioprine, or cyclophosphamide to decrease mortality included "San-Qi" (Panax notoginseng), "Bai-Ji" (Bletilla striata), "Chen-Pi" (Citrus reticulata), "Hou-Po" (Magnolia officinalis), and "Dan-Shan" (Salvia miltiorrhiza). CONCLUSION: Integrated therapy has reduced mortality in patients with PM/DM in Taiwan. Further investigation of the clinical effects and pharmaceutical mechanism involved is needed.

Long-term follow-up of 76 Iranian patients with idiopathic inflammatory myopathies.

AIM: This study aimed to follow up patients with polymyositis (PM) and/or dermatomyositis (DM) to determine survival rate, pattern of disease, response to treatment, malignancy incidence and poor prognostic factors (PPFs). METHOD: A total of 76 patients with PM (n = 47) and/or DM (n = 29) based on Bohan and Peter diagnostic criteria referred to the Imam-Reza Hospital were followed up from 2004 to 2016. The follow-up period was considered from diagnosis to patient's death or last visit. All patients underwent physical examinations and data including age, sex, disease duration, disease subtype, pattern of disease, PPFs and malignancy incidence were collected. RESULTS: Mean age at diagnosis was 45.49 ± 10.88 years and women were predominant (84.2%). Course of disease in the majority of patients (52.6%) was polyphasic, followed by monophasic (31.6%) and chronic-progressive (5.3%). The 1-, 5- and 10-year survival rates were 96%, 93% and 92%, respectively. Delay in treatment and dysphagia were common PPFs in the present study. The majority of patients responded to treatment (88.2%) and there were significant differences in cancer and dysphagia between responders and non-responders to treatment (P < 0.05). The most common cause of death was cancer in four of eight deaths. There was significant difference in survival rates between patients with and without pulmonary involvement (P = 0.001). Moreover, the survival rates were significantly lower in patients with malignancy (P = 0.001). CONCLUSION: Presence of dysphagia and cancer were associated with poor response to treatment. Pulmonary involvement and cancer incidence significantly affect survival rate. Furthermore, since cancer is the most common cause of death, so this study emphasizes the importance of careful cancer screening in these patients.

MicroRNA-381 reduces inflammation and infiltration of macrophages in polymyositis via downregulating HMGB1.

The downregulation of microRNA (miR)-381 has been detected in various diseases. The present study aimed to investigate the effects, and underlying mechanisms of miR-381 on inflammation and macrophage infiltration in polymyositis (PM). A mouse model of experimental autoimmune myositis (EAM) was generated in this study. Hematoxylin and eosin staining was conducted to detect the inflammation of muscle tissues. In addition, ELISA and immunohistochemistry were performed to determine the expression levels of associated factors, and reverse transcription-quantitative polymerase chain reaction and western blotting were used to detect the expression levels of related mRNAs and proteins. A luciferase activity assay was used to confirm the binding of miR-381 and high mobility group box 1 (HMGB1) 3' untranslated region. Transwell assays were also performed to assess the migratory ability of macrophages. The results demonstrated that serum creatine kinase (s-CK), HMGB1 and cluster of differentiation (CD)163 expression in patients with PM were increased compared within healthy controls. Conversely, the expression levels of miR-381 were downregulated in patients with PM. Furthermore, high HMGB1 expression was associated with poor survival rate in patients with PM. In the mouse studies, muscle inflammation and CD163 expression were decreased in the anti-IL-17 and anti-HMGB1 groups, compared with in the EAM model group. The expression levels of s-CK, HMGB1, IL-17 and intercellular adhesion molecule (ICAM)-1 were also downregulated in response to anti-IL-17 and anti-HMGB1. These findings indicated that HMGB1 was closely associated with inflammatory responses. In addition, the present study indicated that transfection of macrophages with miR-381 mimics reduced the migration of inflammatory macrophages, and the expression levels of HMGB1, IL-17 and ICAM-1. Conversely, miR-381 inhibition exerted the opposite effects. The effects of miR-381 inhibitors were reversed by HMGB1 small interfering RNA. In conclusion, miR-381 may reduce inflammation and the infiltration of macrophages; these effects were closely associated with the downregulation of HMGB1.

Clinical Heterogeneity of Interstitial Lung Disease in Polymyositis and Dermatomyositis Patients With or Without Specific Autoantibodies.

BACKGROUND: The aim of this study was to compare the heterogeneity of interstitial lung disease (ILD) in patients with polymyositis and dermatomyositis (PM/DM) according to serological type. METHODS: A total of 182 patients with PM/DM-ILD were observed retrospectively. Antiaminoacyl-tRNA synthetase (ARS) and antimelanoma differentiation-associated gene5 (MDA5) antibodies were screened using immunoblotting approach. The patients with ILD were divided into 3 groups: MDA5 (with anti-MDA5 antibody), ARS (with anti-ARS antibody) and MSN (without anti-MDA5 or anti-ARS antibody) group. Pulmonary features, treatment responses and prognoses were compared among the groups. RESULTS: A higher percentage of rapidly progressive ILD (RP-ILD) occurrences (55.8% versus 25% versus 16.9%, P < 0.001) was observed in the MDA5 group compared to ARS and MSN groups. The MSN group experienced lower dyspnea (48.2% versus 79% versus 71.4%, P = 0.001) and fever (18.1% versus 39.5% versus 37.5%, P = 0.01) frequencies compared to MDA5 and ARS groups. Response to 6-month treatment among 95 patients showed highest deterioration ratio (70%, P = 0.001) of ILD in the MDA5 group. Additionally, the highest frequency of ILD improvement (60%, P = 0.04) was observed in the ARS group. During the observation period, 24 patients died of respiratory failure. The 5-year survival rates were significantly lower in MDA5 group (50.2%) compared to ARS group (97.7%) or the MSN group (91.4%) (P < 0.001). CONCLUSIONS: MDA5-ILD was associated with severe pulmonary manifestations, poor response to treatment and aggravated prognosis. The ARS-ILD group had favorable treatment response and prognosis. MSN-ILD patients had relatively worse treatment response and prognosis compared to the ARS group, even though they expressed milder pulmonary manifestation.

Patients with Systemic Sclerosis/polymyositis Overlap Have a Worse Survival Rate Than Patients Without It.

OBJECTIVE: Studies on mortality associated with patients with systemic sclerosis (SSc) and myopathy have been limited by heterogeneous definitions of muscle involvement. The objective of this study is to determine whether homogeneous-defined SSc/polymyositis overlap (SSc-PM overlap) is associated with a worse survival rate compared with SSc without PM. METHODS: Data from the Nijmegen Systemic Sclerosis cohort were used. Incidence rates were calculated from the observed number of deaths and followup time. Survival analysis using Cox proportional hazard modeling was performed to compare survival among patients with SSc and patients with SSc-PM overlap, including controlling for confounders. All patients with SSc-PM fulfilled the Bohan and Peter criteria for PM. RESULTS: There were 24 patients with SSc-PM (5.7%) and 396 patients with SSc (94.2%). The 5- and 10-year cumulative survival rates from diagnosis were 82% and 68% for the SSc-PM group and 93% and 87% for the SSc group, respectively. Multivariate survival analysis revealed an adjusted HR of 2.34 (95% CI 1.09-5.02) for SSc-PM compared with SSc, with age at diagnosis, modified Rodnan skin score, diffuse cutaneous subtype, and male sex included as confounders. The most common cause of death among patients with SSc-PM overlap was cardiopulmonary involvement (63%), which was similar to the patients with SSc (51%). CONCLUSION: Patients with SSc-PM overlap have a worse survival rate compared with patients with SSc.

Long-term follow-up of 124 patients with polymyositis and dermatomyositis: Statistical analysis of prognostic factors.

OBJECTIVES: The aims of this study were to clarify the long-term outcome of patients with polymyositis and dermatomyositis (PM/DM) and to elucidate prognostic factors using statistical analysis. METHODS: We enrolled patients with PM/DM who visited our department between 1990 and 2014. Diagnoses of PM/DM and clinically amyopathic DM were based on the definitions of Bohan and Peter, and Sontheimer, respectively. We also obtained clinical data, such as age of onset, sex, medications, and presence of interstitial lung disease and malignancies, as well as laboratory tests, including the values of creatine kinase, KL-6, and ferritin. The follow-up was conducted until June 2014. RESULTS: A total of 124 patients (PM: 46, DM: 78) were enrolled. The mean age of onset was 53.5 years, and females were predominant (64.5%). Overall survival rates were 93%, 86%, and 78% for 1, 5, and 10 years, respectively. The survival rates were significantly lower in patients with higher age of onset, with malignancies, and with hyperferritinemia in univariate analysis; however, multivariate analysis identified age of onset and serum ferritin as the most significant prognostic factors. CONCLUSIONS: Our study indicates that when age of onset and serum ferritin are used in combination, we can predict prognosis of patients with PM/DM.

Prognostic significance of anti-aminoacyl-tRNA synthetase antibodies in polymyositis/dermatomyositis-associated interstitial lung disease: a retrospective case control study.

BACKGROUND: In polymyositis/dermatomyositis (PM/DM), anti-aminoacyl-tRNA synthetase (ARS) antibodies are closely associated with interstitial lung disease (ILD), a frequent pulmonary complication. However, the clinical significance of anti-ARS antibodies is not well established. OBJECTIVE: We aimed to evaluate the clinical significance of anti-ARS antibodies in PM/DM-ILD patients. METHODS: Forty-eight consecutive PM/DM-ILD patients were studied retrospectively. Anti-ARS antibodies were screened by ELISA and confirmed by RNA immunoprecipitation test. Medical records, high-resolution computed tomography images, and surgical lung biopsy specimens were compared between ARS-positive (ARS group) and ARS-negative patients (non-ARS group). RESULTS: Anti-ARS antibodies were detected in 23 of 48 patients (48%). Radiologically, nonspecific interstitial pneumonia (NSIP) pattern was observed more frequently in the ARS group than in the non-ARS group (73.9% vs. 40%, P = 0.02). Pathologically, NSIP was the most frequent in both groups. Ten-year survival rate was also significantly higher in the ARS group than in the non-ARS group (91.6% vs. 58.7%, P = 0.02). Univariate Cox hazards analysis revealed that the presence of anti-ARS antibodies was associated with better prognosis (HR = 0.34, 95% CI 0.08-0.80; P = 0.01). CONCLUSIONS: The presence of anti-ARS antibodies is a possible prognostic marker in patients with PM/DM-ILD.

A population-based study of infection-related hospital mortality in patients with dermatomyositis/polymyositis.

OBJECTIVE: Dermatomyositis (DM) and polymyositis (PM) are debilitating inflammatory myopathies associated with significant mortality. We evaluated the relative contribution of infection to hospital mortality in a large population-based study of individuals with PM/DM. METHODS: Data derive from the 2007 to 2011 Healthcare Cost and Utilization Project National Inpatient Samples and include all hospital discharges that met a validated administrative definition of PM/DM. The primary outcome was hospital mortality. Variables for infections and comorbidities were generated from discharge diagnoses using validated administrative definitions. Logistic regression was used to investigate the relationship between infection and mortality in individuals with PM/DM, adjusting for sociodemographics, utilization variables, and comorbidities. Relative risks (RRs) were calculated to compare the overall prevalence of specific infections and associated mortality in PM/DM hospitalizations with those seen in the general hospitalized population. RESULTS: A total of 15,407 hospitalizations with PM/DM met inclusion criteria for this study and inpatient mortality was 4.5% (700 deaths). In adjusted logistic regression analyses, infection (odds ratio [OR] 3.4, 95% confidence interval [95% CI] 2.9-4.0) was the strongest predictor of hospital mortality among individuals with PM/DM. Bacterial infection (OR 3.5, 95% CI 3.0-4.1), comprised primarily of pneumonia and bacteremia, and opportunistic fungal infections (OR 2.5, 95% CI 1.5-4.0) were independently associated with hospital mortality. The overall burden of infection in hospitalizations with PM/DM was significantly increased in comparison with the general hospitalized population (RR 1.5, 95% CI 1.4-1.6). CONCLUSION: Among hospitalized individuals with PM/DM, infection is the leading cause of mortality. Strategies to mitigate infection risk in both the clinic and hospital settings should be evaluated to improve disease outcomes.

Impact of treatment on survival in polymyositis and dermatomyositis. A single-centre long-term follow-up study.

OBJECTIVE: To assess the long-term outcome in polymyositis (PM) and dermatomyositis (DM), with a particular emphasis on mortality and influence of treatment. METHODS: Diagnosis was based according to the Bohan and Peter's criteria. Patients have been followed up by a standardised protocol. Deaths were registered and causes of death were ascertained. Survival probability at 5 and 10years was estimated according to the Kaplan-Meier method, in the overall series and by a diagnostic group and an initial treatment. Mortality hazard ratios (95% CI) for major clinical and demographic features were estimated through univariate and multivariate Cox proportional hazard models. RESULTS: 91 patients (43 PM and 48 DM) were available for the study. Baseline characteristics were not different from those previously reported. Twenty-two patients (24%) died after a median follow-up of 8.7years. As for idiopathic myositis, the survival probabilities at 5 and 10years from the diagnosis were 96.2% and 88.8% for PM respectively; and 93.9% for DM, whereas a higher mortality was documented for cancer-associated myositis and overlap myositis. Male sex [HR=2.4, 95% CI 1.0 to 5.6], heart involvement (HR=1.8), interstitial lung disease (HR=2.3) and arthritis (HR=1.8) increased the risk of mortality, these risk excesses were confirmed in the multivariate analysis. Independent of these features, a higher mortality was documented for patients treated with glucocorticoids (HR=2.3) or immunosuppressants (HR=2.1) when compared to patients treated with immunoglobulins. CONCLUSION: Our study, with longitudinal and statistical analyses, suggests that survival has considerably increased in patients with PM/DM. Prognostic factors for mortality are male sex, and heart and lung involvement. Immunoglobulin treatment, intravenously or subcutaneously, is associated with a better survival.

Smoldering multiple myeloma requiring treatment: time for a new definition?

Smoldering multiple myeloma (SMM) bridges the gap between monoclonal gammopathy of undetermined significance (a mostly premalignant disorder) and active multiple myeloma (MM). Until recently, no interventional study in patients with SMM showed improved overall survival (OS) with therapy as compared with observation. A report from the PETHEMA-GEM (Programa Español de Tratamientos en Hematologica) group described both fewer myeloma-related events and better OS among patients with high-risk SMM who were treated with lenalidomide and dexamethasone. This unique study prompted us to review current knowledge about SMM and address the following questions: (1) Are there patients currently defined as SMM who should be treated routinely? (2) Should the definitions of SMM and MM be reconsidered? (3) Has the time come when not treating is more dangerous than treating? (4) Could unintended medical harm result from overzealous intervention? Our conclusion is that those patients with the highest-risk SMM (extreme bone marrow plasmacytosis, extremely abnormal serum immunoglobulin free light chain ratio, and multiple bone lesions detected only by modern imaging) should be reclassified as active MM so that they can receive MM-appropriate therapy and the paradigm of careful observation for patients with SMM can be preserved.

Clinical manifestations and outcome of anti-PL7 positive patients with antisynthetase syndrome.

BACKGROUND: The aims of the present study were to determine both clinical manifestations and outcome of anti-PL7 patients with antisynthetase syndrome (ASS). METHODS: The medical records of 15 consecutive anti-PL7 patients with biopsy proven ASS were retrospectively analyzed without prior selection. RESULTS: Anti-PL7 patients exhibited polymyositis (n=14) and dermatomyositis (n=1); extra-pulmonary manifestations of ASS included: Raynaud's phenomenon (40%), mechanic's hands (33.3%), joint impairment (26.7%), pericardial effusion (20%) and esophageal/gastrointestinal involvement (20%). The outcome of myositis was as follows: remission/improvement (91.7%) and deterioration (8.3%). Fourteen patients (93.3%) experienced interstitial lung disease (ILD). ILD preceded ASS diagnosis (n=5), was identified concomitantly with ASS (n=8) and occurred after ASS diagnosis (n=1). Patients could be divided into 3 groups according to their presenting lung manifestations: acute onset of lung disease (n=1), progressive onset of lung signs (n=11) and asymptomatic patients exhibiting abnormalities consistent with ILD on PFT and HRCT-scan (n=2). No patient had resolution of ILD, whereas 64.3% and 35.7% experienced improvement and deterioration of ILD, respectively. ILD resulted in respiratory insufficiency requiring O2 therapy in 14.3% of cases. Two patients died. Predictive parameters of ILD deterioration were: DLCO<45% at ILD diagnosis and HRCT-scan pattern of usual interstitial pneumonia (UIP). CONCLUSION: Our series mainly underscores that ILD is frequent in anti-PL7 patients, leading to high morbidity. Our study further suggests that patients with predictive factors of ILD deterioration may require more aggressive therapy, especially the group of patients with DLCO<45% at ILD diagnosis and UIP pattern on HRCT-scan.

Hematological malignancy associated with polymyositis and dermatomyositis.

The aims of this present study were to: 1) assess the characteristics of hematological malignancies in polymyositis/polymyositis (PM/DM) patients; and 2) determine predictive variables of hematological malignancies in PM/DM patients. We retrospectively reviewed the medical records of 32 patients (14 PM, 18 DM) associated with hematological malignancies. In our 32 PM/DM patients, hematological malignancy was concurrently identified (18.8%) or occurred during the course of PM/DM (31.2%); although, PM/DM more often preceded hematological malignancy onset (50%). We observed that the types of hematological malignancies varied, consisting of: B-cell lymphoma (n=20), T-cell lymphoma (n=4), Hodgkin's disease (n=2), multiple myeloma (n=1), myelodysplastic syndrome without excess of blasts (n=3), hairy cell (n=1) and acute lymphocytic leukemia (n=1). In 21 patients of our 32 patients with PM/DM-associated hematological malignancy (65.6% of cases), PM/DM paralleled the course of hematological malignancy. Finally, we observed that patients with PM/DM-associated hematological malignancies had a poor prognosis, the survival status ranging from 96.9%, 78.1% and 51.4% at 1, 3 and 5years, respectively. Interestingly, we found that patients with hematological malignancies, compared with those without were older and more frequently had DM; on the other hand, these patients less commonly exhibited: joint involvement (p=0.017), interstitial lung disease (p=0.06) and anti-Jo1 antibody (p=0.001). Taken together, our study underscores that the association between PM/DM and hematological malignancy, especially lymphoma, should not be ignored. Our findings also suggest that antisynthetase syndrome may be a protective factor of hematological malignancy in PM/DM patients.