MUC5B Promoter Variant and Rheumatoid Arthritis with Interstitial Lung Disease.

BACKGROUND: Given the phenotypic similarities between rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) (hereafter, RA-ILD) and idiopathic pulmonary fibrosis, we hypothesized that the strongest risk factor for the development of idiopathic pulmonary fibrosis, the gain-of-function MUC5B promoter variant rs35705950, would also contribute to the risk of ILD among patients with RA. METHODS: Using a discovery population and multiple validation populations, we tested the association of the MUC5B promoter variant rs35705950 in 620 patients with RA-ILD, 614 patients with RA without ILD, and 5448 unaffected controls. RESULTS: Analysis of the discovery population revealed an association of the minor allele of the MUC5B promoter variant with RA-ILD when patients with RA-ILD were compared with unaffected controls (adjusted odds ratio, 3.8; 95% confidence interval [CI], 2.8 to 5.2; P=9.7×10-17). The MUC5B promoter variant was also significantly overrepresented among patients with RA-ILD, as compared with unaffected controls, in an analysis of the multiethnic case series (adjusted odds ratio, 5.5; 95% CI, 4.2 to 7.3; P=4.7×10-35) and in a combined analysis of the discovery population and the multiethnic case series (adjusted odds ratio, 4.7; 95% CI, 3.9 to 5.8; P=1.3×10-49). In addition, the MUC5B promoter variant was associated with an increased risk of ILD among patients with RA (adjusted odds ratio in combined analysis, 3.1; 95% CI, 1.8 to 5.4; P=7.4×10-5), particularly among those with evidence of usual interstitial pneumonia on high-resolution computed tomography (adjusted odds ratio in combined analysis, 6.1; 95% CI, 2.9 to 13.1; P=2.5×10-6). However, no significant association with the MUC5B promoter variant was observed for the diagnosis of RA alone. CONCLUSIONS: We found that the MUC5B promoter variant was associated with RA-ILD and more specifically associated with evidence of usual interstitial pneumonia on imaging. (Funded by Société Française de Rhumatologie and others.).

Methotrexate and rheumatoid arthritis associated interstitial lung disease.

QUESTION ADDRESSED BY THE STUDY: Methotrexate (MTX) is a key anchor drug for rheumatoid arthritis (RA) management. Fibrotic interstitial lung disease (ILD) is a common complication of RA. Whether MTX exposure increases the risk of ILD in patients with RA is disputed. We aimed to evaluate the association of prior MTX use with development of RA-ILD. METHODS: Through a case-control study design with discovery and international replication samples, we examined the association of MTX exposure with ILD in 410 patients with chronic fibrotic ILD associated with RA (RA-ILD) and 673 patients with RA without ILD. Estimates were pooled over the different samples using meta-analysis techniques. RESULTS: Analysis of the discovery sample revealed an inverse relationship between MTX exposure and RA-ILD (adjusted OR 0.46, 95% CI 0.24-0.90; p=0.022), which was confirmed in the replication samples (pooled adjusted OR 0.39, 95% CI 0.19-0.79; p=0.009). The combined estimate using both the derivation and validation samples revealed an adjusted OR of 0.43 (95% CI 0.26-0.69; p=0.0006). MTX ever-users were less frequent among patients with RA-ILD compared to those without ILD, irrespective of chest high-resolution computed tomography pattern. In patients with RA-ILD, ILD detection was significantly delayed in MTX ever-users compared to never-users (11.4±10.4 years and 4.0±7.4 years, respectively; p<0.001). ANSWER TO THE QUESTION: Our results suggest that MTX use is not associated with an increased risk of RA-ILD in patients with RA, and that ILD was detected later in MTX-treated patients.

Timing of umbilical cord occlusion, delayed vs early, in preterm babies: A randomized controlled trial (CODE-P Trial).

INTRODUCTION: Our hypothesis was that delayed cord clamping (DCC) (not earlier than 30 s; at 30-60 s) in premature neonates (born between 26.0 and 32.6 weeks of gestation), as compared with the usual early cord clamping (ECC), significantly reduces the need for blood transfusions and incidence of intraventricular haemorrhage (IVH) without an increased rate of maternal postpartum haemorrhage. MATERIAL AND METHODS: A prospective, open-label, randomized, controlled trial was conducted at Vall d'Hebron Hospital from July 2014 to December 2018. All pregnant women at risk of impending preterm birth (≥26.0-<33.0 weeks of gestation) who were admitted to the obstetrics emergency department were evaluated for eligibility. If they met the eligibility criteria, they were invited to participate in the study and, if they agreed, they signed an informed consent. Patients were randomly assigned to one of two groups: ECC group and DCC group. RESULTS: Our study included a total of 57 patients: 30 in the ECC group and 27 in the DCC group. Due to a lack of funding and low recruitment rates, the study was discontinued in 2018. Maternal characteristics and obstetric outcomes were similar between both groups. The intention-to-treat analysis did not reveal any differences between groups for neonatal red blood cell transfusions, neonatal IVH or maternal postpartum haemorrhage. There were no differences for secondary outcomes. Similarly, no differences were observed in the as-treated analysis. CONCLUSION: The primary and secondary outcomes of our study were not achieved. Therefore, more meta-analysis and trials are needed to evaluate the appropriate timing of cord clamping in preterm birth.

Clinical risk factors in patients with interstitial lung disease associated with anti-MDA5 autoantibodies.

INTRODUCTION: The anti-MDA5-associated autoimmune disease represents a poorly understood entity. The study's objectives were to describe a cohort of interstitial lung disease (ILD) patients who were positive for anti-MDA5 autoantibody and identify clinical risk factors associated with survival. METHODS: This single-center cohort study included ILD patients positive for anti-MDA5 autoantibody. Baseline clinical features were registered, and survival analysis was performed to identify risk factors associated with worse survival. RESULTS: Fifty-three ILD-MDA5 positive patients were included; twelve died during follow-up due to rapidly progressive interstitial lung disease (RP-ILD). Dermatological signs of anti-MDA5 (Gottron papules, Gottron sign, palmar papules, V-neck sign, facial dermatomyositis rashes, and skin ulcers) were strongly associated with death secondary to RP-ILD (HR: 3.7, 95% CI: 1.02-13.35). Patients with dermatological signs were younger, had higher anti-MDA5 autoantibodies titers, more frequent inflammatory patterns in HRCT evaluation, and less fibrosis extent in HRCT. CONCLUSION: Dermatological manifestation in ILD patients to anti-MDA5 autoantibodies are associated with RP-ILD and short-term fatal outcomes. Dermatological signs may identify a subgroup of ILD-positive to anti-MDA5 patients with a high risk of RP-ILD.

Enhanced Activity of NLRP3 Inflammasome in the Lung of Patients with Anti-Synthetase Syndrome.

Anti-synthetase syndrome (ASSD) is an autoimmune disorder characterized by inflammatory interstitial lung disease (ILD). The main objective of this work was to quantify the concentrations of cytokines and molecules associated with inflammasome activation in bronchoalveolar lavage (BAL) of patients with ASSD and a comparison group of systemic sclerosis (SSc) patients. Cytokines and lactate dehydrogenase (LDH) were determined using the concentrated BAL protein. The activity of caspase-1 and concentration of NLRP3 with the protein purified from the cell pellet in each group of patients. We found higher caspase-1 levels in ASSD vs. SSc, 1.25 RFU vs. 0.75 RFU p = 0.003, and LDH levels at 0.15 OD vs. 0.09 OD p < 0.001. A significant difference was observed in molecules associated with inflammasome activation, IL-18: 1.42 pg/mL vs. 0.87 pg/mL p = 0.02 and IFN-γ: 0.9 pg/mL vs. 0.86 pg/mL, p = 0.01. A positive correlation was found between caspase-1 and LDH in the patients with ASSD Rho 0.58 (p = 0.008) but not in the SSc group. In patients with ASSD, greater caspase-1 and higher LDH activity were observed in BAL, suggesting cell death due to pyroptosis and activation of the inflammasome pathway.

Interstitial lung disease progression in patients with anti-aminoacyl transfer-RNA-synthetase autoantibodies is characterized by higher levels of sCD163.

BACKGROUND: Patients with anti-tRNA autoantibodies are characterized by arthritis, mechanic´s hands, fever, Raynaud´s phenomenon, and interstitial lung disease (ILD), in at least two clinical scenarios: the antisynthetase syndrome (ASSD) and interstitial pneumonia with autoimmune features (IPAF). The anti-tRNA-ILD treatment is centered on the administration of corticosteroids and a wide variety of immunosuppressive drugs; however, the effectiveness of the treatment depends on factors not fully understood. This research work aimed to quantify the serum levels of two molecules related to pulmonary fibrosis and explore their relationship with the progression of ILD associated with ASSD METHODOLOGY: Serum levels of sCD163 and TGF-ß1 from baseline and after six months of treatment of ILD patients' positives to anti-tRNA were included in the current study. At six months, patients were classified as with or without ILD progression RESULTS: Forty patients were included (anti-Jo1, anti-PL7, anti-PL12, and anti-Ej). Five patients (12.5%) had ILD progression and were characterized by higher levels of sCD163 at baseline. Baseline sCD163 serum levels showed good discriminatory capacity in patients with ILD progression. On the other hand, at follow-up, serum TGF-ß1 levels significantly increased in both patients' groups, with and without progression CONCLUSION: Basal levels of sCD163 were higher in patients who later developed ILD progression and kinetics of both molecules suggests the participation of M2 macrophages in the development of ILD.

Single Nucleotide Polymorphism in the IL17A Gene Is Associated with Interstitial Lung Disease Positive to Anti-Jo1 Antisynthetase Autoantibodies.

Antisynthetase syndrome (ASSD) is a rare multisystemic connective tissue disease affecting the skin, joints, muscles, and lungs, characterized by anti-aminoacyl transfer-RNA-synthetases (anti-tRNA) autoantibodies production, being anti-Jo1 the most frequent. We included one-hundred twenty-one ASSD patients and 340 healthy subjects (HS), and also, we divided the case group into anti-Jo1 and non-anti-Jo1. Two single nucleotide polymorphisms (SNPs) in the IL17A gene were evaluated. Anti-Jo1 was the most common anti-tRNA antibody in our cohort, and the most frequent tomographic pattern was non-specific interstitial pneumonia (NSIP). Anti-Jo1 ASSD patients had higher levels of creatine phosphokinase than the non-anti-Jo1 group. Significant differences in genotype frequencies with rs8193036/CC between anti-Jo1 vs. non-anti-Jo1 ASSD patients (p < 0.001), maintaining the association after Bonferroni correction (p = 0.002). Additionally, in the anti-Jo1 group vs. HS comparison, we found a statistically significant difference with the same SNP (p = 0.018, OR = 2.91, 95% CI = 1.15-7.35), maintaining the association after Bonferroni correction (p = 0.036). The rs8193036/CC genotype in IL17A is associated with ASSD patients with anti-Jo1. Also, anti-Jo1 and non-anti-Jo1 patients display differences in genotype frequencies.

MUC5B promoter variant rs35705950 and rheumatoid arthritis associated interstitial lung disease survival and progression.

BACKGROUND: The major risk factor for idiopathic pulmonary fibrosis (IPF), MUC5B rs35705950, was found to be associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Whilst the MUC5B rs35705950 T risk allele has been associated with better survival in IPF, its impact on RA-ILD prognosis remains to be determined. Our objective was to explore the influence of MUC5B rs35705950 on survival and progression in RA-ILD. METHODS: Through an international retrospective observational study, patients with RA-ILD were genotyped for the MUC5B rs35705950 variant and consecutive pulmonary function tests (PFTs) findings were collected. Longitudinal data up to a 10-year follow-up were considered and analyzed using mixed regression models. Proportional hazards and joint proportional hazards models were used to analyze the association of baseline and longitudinal variables with lung transplant-free survival. Significant progression of RA-ILD was defined as at least an absolute or relative 10% decline of forced vital capacity at 2 years from baseline. RESULTS: Out of 321 registered patients, 261 were included in the study: 139 women (53.3%), median age at RA-ILD diagnosis 65 years (interquartile range [IQR] 57 to 71), 151 ever smokers (59.2%). Median follow-up was 3.5 years (IQR 1.3 to 6.6). Mortality rate was 32% (95%CI 19 to 42) at 10 years. The MUC5B rs35705950 variant did not impact lung transplant-free survival (HR for the T risk allele carriers=1.26; 95%CI 0.61 to 2.62; P=0.53). Decline in pulmonary function at 2 years was not influenced by MUC5B rs35705950 (OR=0.95; 95%CI 0.44 to 2.05; P=0.89), irrespective of the HRCT pattern. CONCLUSION: In this study, the MUC5B rs35705950 promoter variant did not influence transplant- free survival or decline in pulmonary function in patients with RA-ILD.

Anti-Aminoacyl Transfer-RNA-Synthetases (Anti-tRNA) Autoantibodies Associated with Interstitial Lung Disease: Pulmonary Disease Progression has a Persistent Elevation of the Th17 Cytokine Profile.

Anti-tRNA autoantibodies are associated with interstitial lung disease (ILD), in at least two clinical scenarios: the anti-synthetase syndrome (ASSD) and interstitial pneumonia with autoimmune features (IPAF). Under pathological conditions, cytokines indicate the participating elements and the course of inflammatory phenomena. We aimed to quantify serum concentrations of different inflammatory cytokines profiles in patients with anti-tRNA associated ILD (anti-tRNA-ILD) and estimate the association between these and ILD improvement and progression. Serum levels of 18 cytokines from baseline and after six months of treatment of ILD patients' positives to anti-tRNA were included in the current study. At six months, patients were classified as with or without ILD progression. A total of 39 patients were included (10 anti-Jo1, eight anti-PL7, 11 anti-PL12, and 10 anti-Ej). Three patients (7.6%) had ILD progression (progressors patients, PP) and showed statistically higher levels in IL-4, IL-10, IL-17A, IL-22, GM-CSF, IL-1ß, IL-6, IL-12, IL-18, and TNF-α, compared to patients without disease progression (no progressors patients, NPP). IL-17A, IL-1ß, and IL-6 (T-helper-lymphocyte (Th)17 inflammatory cytokine profile) were elevated and had a high discriminatory capacity in distinguishing ILD PP of those NPP at follow-up. Overall, there is an association between the cytokines of the Th17 inflammatory profile and the ASSD progression.

Genetic Susceptibility to Antisynthetase Syndrome Associated With Single-Nucleotide Variants in the IL1B Gene That Lead Variation in IL-1ß Serum Levels.

The antisynthetase syndrome (ASSD) is an autoimmune disorder characterized by myositis, arthritis, mechanic's hands, fever, Raynaud phenomenon, and interstitial lung disease (ILD). We aimed to evaluate single-nucleotide polymorphisms in the interleukin 1B (IL1B) gene and their association between ILD with antisynthetase autoantibodies, as well as IL-1ß serum levels. The most frequent antisynthetase autoantibody was anti-Jo1. The most frequent tomographic pattern was non-specific interstitial pneumonia, whereas in the anti-Jo1 subjects, it was organized pneumonia. Anti-Jo1 patients tend to have more significant arthritis, and Raynaud phenomenon have higher levels of creatinine phosphokinase. In the IL1B gene, the GG genotype and G allele of rs1143634 [odds ratio (OR) = 2.21 and OR = 2.60, respectively, p < 0.05] are associated with an increased risk, as well as with the dominant and recessive models (p < 0.05). This finding is maintained after logistic regression analysis adjusting for potential confounding variables (p < 0.05). Subjects with the rs16944/AG heterozygous genotype had higher serum levels of IL-1ß compared to homozygous (p < 0.05). In conclusion, rs1143634 is associated with a higher risk of ASSD. Also, the GA genotype is associated with higher levels of IL-1ß in ASSD patients.

[Revision of carcinomas in paranasal sinuses]. / Revisión de los carcinomas de senos paranasales.

The annual incidence rate for paranasal sinus cancer is quite low in Europe at approximately 1 case a year per 100 000 inhabitants. The most frequent site is the maxillary sinus; in some countries such as Spain, however, carcinomas of the ethmoidal sinus complex are more prevalent. Squamous cell carcinoma is the most frequent histological type and adenocarcinoma is the one with the best prognosis. In general terms, the association of surgery and radiotherapy continues to be the optimal therapeutic option. The inclusion of an endoscopic endonasal approach for the treatment of these lesions must be considered in very selective cases. Most authors currently accept invasion of the fat and muscles of the orbital apex and infiltration of the conjunctiva and/or sclera as an absolute indication for orbital exenteration. Lymph node involvement at diagnosis or in the course of the disease is infrequent, so prophylactic lymph node treatment would therefore not be indicated.

[Is it possible to improve the preventive usefulness of workers' health surveillance in the current regulatory framework?] / ¿Es posible mejorar la utilidad preventiva de la vigilancia de la salud de los trabajadores en el actual marco normativo?

OBJECTIVE: In Spain, the limited preventive usefulness of health surveillance is determined by the indiscriminate use of nonspecific "generic" health examinations aimed at producing a "fitness for work list", presumably allowing companies to comply with health and safety regulations. This study aimed to produce a technical interpretation of the Spanish Prevention of Risks at Work Act and propose a new conceptual framework to favour greater preventive usefulness of health surveillance within the current regulatory framework. METHODS: Using qualitative techniques of content analysis, the text of the Law was studied, the key concepts that impeded the fulfilment of the preventive objectives of health surveillance were identified, and a technical interpretation adjusted to regulations was made in order to propose a new conceptual framework RESULTS: This conceptual framework would include: clearly differentiating health surveillance from health examinations (one of its instruments) and from fitness for work evaluations (an independent concept in itself); restricting mandatory health surveillance to situations in which it is "imperative" to carry it out because of the existence of a substantial risk to workers or third parties, including potentially vulnerable workers; and communicating the results of health surveillance through preventive recommendations to the company, reserving fitness for duty certificates -always based on clear, pre-established and justified criteria in relation to risk- for mandatory surveillance. CONCLUSIONS: The proposed new conceptual framework falls within the scope of the Spanish Prevention of Risks at Work Act, and its implementation could contribute to improving the preventive usefulness of health surveillance without the need to reform the legislation.

Epidemiologic evidence of transmission of donor-related bacterial infection through a transplanted heart.

This study describes a patient who had fulminant infectious myocarditis as a result of methicillin-resistant Staphylococcus aureus after receiving a heart transplant from an infected donor. There was complete concordance of typing results between donor and recipient strains that were different from the 20 isolates with which they were compared. Molecular epidemiologic study provided compelling evidence that a transplanted organ can transmit a bacterial infection from the donor to the recipient.

[Successful fibrinolytic treatment in a patient with acute mitral prosthetic thrombosis]. / Tratamiento fibrinolítico resolutivo en un paciente con trombosis protésica mitral aguda.

A case is described of a 50 year-old man with an acute prosthetic dysfunction due to valve thrombosis and cardiogenic shock, on a prosthesis in the mitral position (Bjork-Shiley). The patient was promptly treated with a streptokinase in two infusions 1.5 x 10(6) UI over 180 and 90 minutes, respectively. Early clinical, fluoroscopy and echocardiography improvement was observed. The authors comment the present role of the thrombolytic therapy in front of surgery of prosthetic valve thrombosis.

[Application of molecular epidemiology techniques in the study of food poisoning caused by Staphylococcus aureus]. / Aplicación de las técnicas de epidemiología molecular en el estudio de una toxiinfección alimentaria por Staphylococcus aureus.

BACKGROUND: The use of molecular epidemiology techniques has provided better knowledge as to the clonal organization of bacterian populations and thus allows better follow up of epidemics. An alimentary toxiinfection in a Barcelona school produced by Staphylococcus aureus was analyzed by the combination of epidemiologic, phenotype and genotype markers with the aim of determining the source of the alimentary contamination. METHODS: Nine strains of Staphylococcus aureus isolated in 6 food manipulators and 3 patients were studied with the following markers: biotype, antibiotype, phagotype, plasmid profile, polymorphism of the size of the restriction fragments of total DNA and ribotype. RESULTS: Epidemiologic study of the strains analyzed showed that both the phenotype markers and the plasmid profile are thecniques of little discriminatory value. The only clearly discriminatory technique used was ribotyping which defined 3 clones in the 9 strains of Staphylococcus aureus studied. CONCLUSIONS: Molecular study of isolated strains of Staphylococcus aureus was able to identify the causal origin of the alimentary toxiinfection in one of the 6 food manipulators studied.

[Pregnancy and thrombophilia in women with congenital deficit of antithrombin III, protein C, protein S or plasminogen: analysis of 39 cases]. / Embarazo y trombofilia en mujeres con déficit congénito de antitrombina III, proteína C, proteína S o plasminógeno: análisis de 39 caso.

BACKGROUND: Pregnancy, delivery and puerperium are situations which increment the risk of thromboembolic complications in women who are carriers of congenital heterozygotic deficits of type I antithrombin III (ATIII), protein C (PC) or protein S (PS). The aim of this study was to analyze the experience of the authors and propose therapeutic conduct in each case. Furthermore, the spontaneous losses of pregnancy related with these deficits were studied. METHODS: Thirty-nine women, seventeen with ATIII deficit, fifteen with PC deficit and four with a deficit of PS and three with a plasminogen (Pg) deficit totalling 79 pregnancies and 51 thrombotic episodes sixteen of which were related with the pregnancy, delivery or puerperium were studied. The antigenic and functional activity of ATIII, PC, PS and Pg were determined. RESULTS: The incidence of thrombosis for the ATIII deficit during pregnancy was 39%, which was greater, of statistical significance (p = 0.046), than the 15% observed during puerperium. In women with a deficit of PC, the incidence of thrombosis was 4.5% during pregnancy and 14% during puerperium with no significant difference between the two situations. The incidence of thrombosis during pregnancy and postpartum in the deficit of ATIII was significantly higher (p < 0.025) than that observed for the deficit of PC. For women with a deficit of PS and Pg the incidence of thrombosis was nul in pregnancy and puerperium. CONCLUSIONS: Pregnancy and puerperium are situations which trigger thrombotic phenomena and increase the risk of the same in women with a deficit of antithrombin III and protein C and, to a lesser degree, the deficit of protein S or plasminogen. A strict control of these situations and individualized treatment is required according to the type of deficit, presence of previous thromboembolic history and anticoagulant history at the time of pregnancy. No increase in the risk of loss of pregnancy in any of the deficits studied was observed.

El mito de Sísifo y la vigilancia de la salud / El mite de Sísif i la vigilància de la salut / No disponible

No disponible

Clinical risk factors in patients with interstitial lung disease associated with anti-MDA5 autoantibodies / Factores de riesgo clínicos en pacientes con enfermedad pulmonar intersticial con anticuerpos anti-MDA5

Introduction The anti-MDA5-associated autoimmune disease represents a poorly understood entity. The study's objectives were to describe a cohort of interstitial lung disease (ILD) patients who were positive for anti-MDA5 autoantibody and identify clinical risk factors associated with survival. Methods This single-center cohort study included ILD patients positive for anti-MDA5 autoantibody. Baseline clinical features were registered, and survival analysis was performed to identify risk factors associated with worse survival. Results Fifty-three ILD-MDA5 positive patients were included; twelve died during follow-up due to rapidly progressive interstitial lung disease (RP-ILD). Dermatological signs of anti-MDA5 (Gottron papules, Gottron sign, palmar papules, V-neck sign, facial dermatomyositis rashes, and skin ulcers) were strongly associated with death secondary to RP-ILD (HR: 3.7, 95% CI: 1.02–13.35). Patients with dermatological signs were younger, had higher anti-MDA5 autoantibodies titers, more frequent inflammatory patterns in HRCT evaluation, and less fibrosis extent in HRCT. Conclusion Dermatological manifestation in ILD patients to anti-MDA5 autoantibodies are associated with RP-ILD and short-term fatal outcomes. Dermatological signs may identify a subgroup of ILD-positive to anti-MDA5 patients with a high risk of RP-ILD (AU)

Introducción La enfermedad autoinmune asociada a los anticuerpos anti-MDA5 es una entidad poco estudiada. Los objetivos de este estudio son describir una cohorte de sujetos con enfermedad pulmonar intersticial (EPI) positivos al anticuerpo anti-MDA5 e identificar los factores clínicos de riesgo asociados con la supervivencia. Métodos Estudio de cohorte de un solo centro de pacientes con EPI y positivos al anticuerpo anti-MDA5. Se registraron las características clínicas basales y se realizó un análisis de supervivencia para identificar los factores de riesgo asociados con la supervivencia. Resultados Se incluyeron 53 pacientes con EPI y positivos a anti-MDA5; 12 pacientes fallecieron por una enfermedad intersticial rápidamente progresiva (EPI-RP). Los signos dermatológicos asociados a anti-MDA5 (pápulas de Gottron, signo de Gottron, pápulas palmares, signo de la V del escote, eritema facial de dermatomiositis y úlceras cutáneas) se asociaron fuertemente con la EPI-RP (HR: 3,7, IC 95%: 1,02-13,35). Los pacientes con manifestaciones dermatológicas eran más jóvenes, tenían mayores títulos de anticuerpos anti-MDA5, tenían mayor frecuencia de patrones inflamatorios en la tomografía de tórax de alta resolución y menor extensión de la fibrosis en la TCAR. Conclusión Las manifestaciones dermatológicas en los pacientes con EPI positivos a anticuerpos anti-MDA5 están asociados a EPI-RP y a desenlaces fatales al corto plazo. Los signos dermatológicos pueden identificar un subgrupo de pacientes positivos a anti-MDA5 con mayor riesgo de EPI-RP (AU)