Dexamethasone in outpatients with SARS-COV-2 infection

Objetivo: Evaluar la evolución clínica de los pacientes ambulatorios con infección por SARS Cov-2, que recibieron dexametasona en nuestro Centro de Salud. Métodos: Se revisaron las historias clínicas de los pacientes a los que se les prescribió tratamiento con dexametasona desde Atención Primaria, en la fase aguda de la infección por SARS-CoV-2, sin criterios iniciales de gravedad. Describimos las características clínico-demográficas y los datos radiológicos y analíticos de tormenta de citoquinas, así como su evolución final. Resultados: se incluyeron un total de 9 pacientes, 6 mujeres y 3 hombres con una edad media de 56,6 (3474) años. El motivo de consulta fue en todos los casos fiebre, con un tiempo medio desde inicio de los síntomas hasta su consulta de 4 (2-7) días. Todos los pacientes presentaron una relación entre saturación de oxígeno y fracción inspirada de oxígeno mayor de 450. De ellos, 5 pacientes presentaron hallazgos radiológicos compatibles con COVID y en 4 no se observaron infiltrados. Ningún paciente presentaba datos analíticos de síndrome de tormenta de citoquinas. La dosis de dexametasona recomendad fue de 6mg/d durante 7 días. En tres casos se requirió ingreso hospitalario, dos al tercer día y uno al cuarto del inicio de la dexametasona, resolviéndose el proceso intrahospitalario con pulsos de corticoides y antibióticos, sin necesidad de oxigenoterapia de alto flujo, ni de ventilación mecánica. Conclusiones: el uso de dexametasona en pacientes con infección SARS-CoV-2 sin criterios de ingreso hospitalario no parece prevenir el riesgo de evolución a formas más graves. En ausencia de más datos, no parece recomendable el uso de dexametasona en esos casos, salvo que se requiera por otros motivos.Objective: To evaluate the clinical evolution of outpatients with SARS Cov-2 infection, who received dexamethasone in our Health Center. Methods: The medical records of the patients who were prescribed dexamethasone treatment from Primary Care, in the acute phase of the SARS-CoV-2 infection, were reviewed, without initial criteria of severity. We describe the clinical-demographic characteristics and the radiological and analytical data of the cytokine storm, as well as its final evolution. Results: a total of 9 patients were included, 6 women and 3 men with a mean age of 56.6 (34-74) years. The reason for consultation was fever in all cases, with a mean time of 4 (2-7) days from onset of symptoms to consultation. All patients presented a relationship between oxygen saturation and inspired oxygen fraction greater than 450. Out of these, 5 patients presented radiological findings compatible with COVID and no infiltrates were observed in 4. No patient had laboratory data for cytokine storm syndrome. The recommended dexamethasone dose was 6 mg/d for 7 days. In 3 cases, hospital admission was required, 2 on the third day and one on the fourth day after the start of dexamethasone. These patients resolved the in-hospital process with pulses of corticosteroids and antibiotics, without the need for high-flow oxygen therapy or mechanical ventilation. Conclusions: the use of dexamethasone in patients with SARS-CoV-2 infection without hospital admission criteria does not seem to prevent the risk of progression to more serious forms. In the absence of more data, the use of dexamethasone in these cases does not seem advisable, unless it is required for other reasons

Off-label use of rituximab for systemic lupus erythematosus in Europe

Objectives: Rituximab (RTX) is a biological treatment used off-label in patients with systemic lupus erythematosus (SLE). This survey aimed to investigate the off-label use of RTX in Europe and compare the characteristics of patients receiving RTX with those receiving conventional therapy. Methods: Data on patients with SLE receiving RTX were taken from the International Registry for Biologics in SLE retrospective registry and complemented with data on patients with SLE treated with conventional therapy. For nationwide estimates of RTX use in patients with SLE, investigators were asked to provide data through case report forms (CRFs). Countries for which no data were submitted through CRFs, published literature and/or personal communication were used, and for European countries where no data were available, estimates were made on the assumption of similarities with neighbouring countries. Results: The estimated off-label use of RTX in Europe was 0.5%-1.5% of all patients with SLE. In comparison with patients with SLE on conventional therapy, patients treated with RTX had longer disease duration, higher disease activity and were more often treated with immunosuppressives. The most frequent organ manifestations for which either RTX or conventional therapy was initiated were lupus nephritis followed by musculoskeletal and haematological. The reason for treatment was, besides disease control, corticosteroid-sparing for patients treated with conventional therapy. Conclusions: RTX use for SLE in Europe is restrictive and appears to be used as a last resort in patients for whom other reasonable options have been exhausted

Off-label use of rituximab for systemic lupus erythematosus in Europe

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Tocilizumab in visual involvement of giant cell arteritis: a multicenter study of 471 patients

Background: Visual involvement is the most feared complication of giant cell arteritis (GCA). Information on the efficacy of tocilizumab (TCZ) for this complication is scarce and controversial. Objective: We assessed a wide series of GCA treated with TCZ, to evaluate its role in the prevention of new visual complications and its efficacy when this manifestation was already present before the initiation of TCZ. Design: This is an observational multicenter study of patients with GCA treated with TCZ. Methods: Patients were divided into two subgroups according to the presence or absence of visual involvement before TCZ onset. Visual manifestations were classified into the following categories: transient visual loss (TVL), permanent visual loss (PVL), diplopia, and blurred vision. Results: Four hundred seventy-one GCA patients (mean age, 74 +/- 9 years) were treated with TCZ. Visual manifestations were observed in 122 cases (26%), of which 81 were present at TCZ onset: PVL (n = 60; unilateral/bilateral: 48/12), TVL (n = 17; unilateral/bilateral: 11/6), diplopia (n = 2), and blurred vision (n = 2). None of the patients without previous visual involvement or with TVL had new episodes after initiation of TCZ, while only 11 out of 60 (18%) patients with PVL experienced some improvement. The two patients with diplopia and one of the two patients with blurred vision improved. Conclusion: TCZ may have a protective effect against the development of visual complications or new episodes of TVL in GCA. However, once PVL was established, only a few patients improved

A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility

Introduction: A recent genome-wide association study (GWAS) comprising a French cohort of systemic sclerosis (SSc) reported several non-HLA single-nucleotide polymorphisms (SNPs) showing a nominal association in the discovery phase. We aimed to identify previously overlooked susceptibility variants by using a follow-up strategy.<p></p> Methods: Sixty-six non-HLA SNPs showing a P value <10-4 in the discovery phase of the French SSc GWAS were analyzed in the first step of this study, performing a meta-analysis that combined data from the two published SSc GWASs. A total of 2,921 SSc patients and 6,963 healthy controls were included in this first phase. Two SNPs, PPARG rs310746 and CHRNA9 rs6832151, were selected for genotyping in the replication cohort (1,068 SSc patients and 6,762 healthy controls) based on the results of the first step. Genotyping was performed by using TaqMan SNP genotyping assays. Results: We observed nominal associations for both PPARG rs310746 (PMH = 1.90 × 10-6, OR, 1.28) and CHRNA9 rs6832151 (PMH = 4.30 × 10-6, OR, 1.17) genetic variants with SSc in the first step of our study. In the replication phase, we observed a trend of association for PPARG rs310746 (P value = 0.066; OR, 1.17). The combined overall Mantel-Haenszel meta-analysis of all the cohorts included in the present study revealed that PPARG rs310746 remained associated with SSc with a nominal non-genome-wide significant P value (PMH = 5.00 × 10-7; OR, 1.25). No evidence of association was observed for CHRNA9 rs6832151 either in the replication phase or in the overall pooled analysis.<p></p> Conclusion: Our results suggest a role of PPARG gene in the development of SSc

Cross-disease Meta-analysis of Genome-wide Association Studies for Systemic Sclerosis and Rheumatoid Arthritis Reveals IRF4 as a New Common Susceptibility Locus

Objectives: Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that share clinical and immunological characteristics. To date, several shared SSc- RA loci have been identified independently. In this study, we aimed to systematically search for new common SSc-RA loci through an inter-disease meta-GWAS strategy. Methods: We performed a meta-analysis combining GWAS datasets of SSc and RA using a strategy that allowed identification of loci with both same-direction and opposingdirection allelic effects. The top single-nucleotide polymorphisms (SNPs) were followed-up in independent SSc and RA case-control cohorts. This allowed us to increase the sample size to a total of 8,830 SSc patients, 16,870 RA patients and 43,393 controls. Results: The cross-disease meta-analysis of the GWAS datasets identified several loci with nominal association signals (P-value < 5 x 10-6), which also showed evidence of association in the disease-specific GWAS scan. These loci included several genomic regions not previously reported as shared loci, besides risk factors associated with both diseases in previous studies. The follow-up of the putatively new SSc-RA loci identified IRF4 as a shared risk factor for these two diseases (Pcombined = 3.29 x 10-12). In addition, the analysis of the biological relevance of the known SSc-RA shared loci pointed to the type I interferon and the interleukin 12 signaling pathways as the main common etiopathogenic factors. Conclusions: Our study has identified a novel shared locus, IRF4, for SSc and RA and highlighted the usefulness of cross-disease GWAS meta-analysis in the identification of common risk loci

Impact of interstitial lung disease on the survival of systemic sclerosis with pulmonary arterial hypertension

To assess severity markers and outcomes of patients with systemic sclerosis (SSc) with or without pulmonary arterial hypertension (PAH-SSc/non-PAH-SSc), and the impact of interstitial lung disease (ILD) on PAH-SSc. Non-PAH-SSc patients from the Spanish SSc registry and PAH-SSc patients from the Spanish PAH registry were included. A total of 364 PAH-SSc and 1589 non-PAH-SSc patients were included. PAH-SSc patients had worse NYHA-functional class (NYHA-FC), worse forced vital capacity (FVC) (81.2 ± 20.6% vs 93.6 ± 20.6%, P &lt; 0.001), worse tricuspid annular plane systolic excursion (TAPSE) (17.4 ± 5.2 mm vs 19.9 ± 6.7 mm, P &lt; 0.001), higher incidence of pericardial effusion (30% vs 5.2%, P &lt; 0.001) and similar prevalence of ILD (41.8% vs. 44.9%). In individuals with PAH-SSc, ILD was associated with worse hemodynamics and pulmonary function tests (PFT). Up-front combination therapy was used in 59.8% and 61.7% of patients with and without ILD, respectively. Five-year transplant-free survival rate was 41.1% in PAH-SSc patients and 93.9% in non-PAH-SSc patients (P &lt; 0.001). Global survival of PAH-SSc patients was not affected by ILD regardless its severity. The multivariate survival analysis in PAH-SSc patients confirmed age at diagnosis, worse NYHA-FC, increased PVR, reduced DLCO, and lower management with up-front combination therapy as major risk factors. In conclusion, in PAH-SSc cohort risk of death was greatly increased by clinical, PFT, and hemodynamic factors, whereas it was decreased by up-front combination therapy. Concomitant ILD worsened hemodynamics and PFT in PAH-SSc but not survival regardless of FVC impairment

Impact of interstitial lung disease on the survival of systemic sclerosis with pulmonary arterial hypertension

To assess severity markers and outcomes of patients with systemic sclerosis (SSc) with or without pulmonary arterial hypertension (PAH-SSc/non-PAH-SSc), and the impact of interstitial lung disease (ILD) on PAH-SSc. Non-PAH-SSc patients from the Spanish SSc registry and PAH-SSc patients from the Spanish PAH registry were included. A total of 364 PAH-SSc and 1589 non-PAH-SSc patients were included. PAH-SSc patients had worse NYHA-functional class (NYHA-FC), worse forced vital capacity (FVC) (81.2 +/- 20.6% vs 93.6 +/- 20.6%, P < 0.001), worse tricuspid annular plane systolic excursion (TAPSE) (17.4 +/- 5.2 mm vs 19.9 +/- 6.7 mm, P < 0.001), higher incidence of pericardial effusion (30% vs 5.2%, P < 0.001) and similar prevalence of ILD (41.8% vs. 44.9%). In individuals with PAH-SSc, ILD was associated with worse hemodynamics and pulmonary function tests (PFT). Up-front combination therapy was used in 59.8% and 61.7% of patients with and without ILD, respectively. Five-year transplant-free survival rate was 41.1% in PAH-SSc patients and 93.9% in non-PAH-SSc patients (P < 0.001). Global survival of PAH-SSc patients was not affected by ILD regardless its severity. The multivariate survival analysis in PAH-SSc patients confirmed age at diagnosis, worse NYHA-FC, increased PVR, reduced DLCO, and lower management with up-front combination therapy as major risk factors. In conclusion, in PAH-SSc cohort risk of death was greatly increased by clinical, PFT, and hemodynamic factors, whereas it was decreased by up-front combination therapy. Concomitant ILD worsened hemodynamics and PFT in PAH-SSc but not survival regardless of FVC impairment

Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER), "A way of making Europe".Copy number (CN) polymorphisms of complement C4 play distinct roles in many conditions, including immune-mediated diseases. We investigated the association of C4 CN with systemic sclerosis (SSc) risk. Imputed total C4, C4A, C4B, and HERV-K CN were analyzed in 26,633 individuals and validated in an independent cohort. Our results showed that higher C4 CN confers protection to SSc, and deviations from CN parity of C4A and C4B augmented risk. The protection contributed per copy of C4A and C4B differed by sex. Stronger protection was afforded by C4A in men and by C4B in women. C4 CN correlated well with its gene expression and serum protein levels, and less C4 was detected for both in SSc patients. Conditioned analysis suggests that C4 genetics strongly contributes to the SSc association within the major histocompatibility complex locus and highlights classical alleles and amino acid variants of HLA-DRB1 and HLA-DPB1 as C4-independent signals

Effectiveness of Quinacrine (Mepacrine) in Photosensitive Autoimmune Diseases, Lupus Erythematosus, and Dermatomyositis: Report on 38 Cases and Literature Review

Objectives: This study aims to report our experience with photosensitive autoimmune diseases including lupus erythematosus and dermatomyositis (DM) treated with quinacrine (Qn) as either monotherapy or combination with other antimalarials, steroids, and immunosuppressive therapy in an add-on regimen in light of a review of the relevant literature.Patients and methods: The study included 38 patients (6 males, 32 females; mean age 45 +/- 8 years; range, 23 to 72 years) with systemic lupus erythematosus (SLE), cutaneous lupus or DM who had been treated with Qn. The following data were obtained from the records of each patient: sex, age, diagnosis, duration of the disease, duration of treatment, smoking behavior, antimalarial treatment, concomitant treatment, and clinical indications, as well as Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity before initiation, at the last visit, or when Qn treatment was completed. We carried out a MEDLINE search for previously reported cases that, together with our patients, served as the basis of this report.Results: Of the 38 patients, 34 were suffering from SLE or cutaneous lupus and four from DM. Qn was dosed at 50 or 100 mg in most of the patients. Twenty-seven patients received Qn as an add-on regimen therapy. Clinical response was analyzed in patients with SLE or cutaneous lupus. Of the patients, 25 responded (68.4%), 13 (52%) had improved CLASI activity and 12 (48%) had improved SLEDAI score. Fifty percent of the patients with DM responded. A total of 188 cases were identified from the literature. The most frequent diagnosis was cutaneous lupus (68.6%), followed by SLE (32.6%). Only 7.4% of the patients had DM. The majority of the patients received concomitant immunosuppressive medications. Treatment response was 73% in patients with SLE and/or cutaneous lupus and 35.7% in patients with DM. Side effects were scarce and the most frequent was yellow skin discoloration.Conclusion: Quinacrine may be an alternative for patients with poor response or those who are intolerant to other antimalarials. Thus, Qn may aid in controlling the activity of photosensitive autoimmune diseases