Treatment Strategies in Neutrophilic Dermatoses: A Comprehensive Review.

Neutrophilic dermatoses (NDs) are a group of noninfectious disorders characterized by the presence of a sterile neutrophilic infiltrate without vasculitis histopathology. Their physiopathology is not fully understood. The association between neutrophilic dermatoses and autoinflammatory diseases has led some authors to propose that both are part of the same spectrum of diseases. The classification of NDs depends on clinical and histopathological features. This review focuses on the recent developments of treatments in these pathologies.

Ocular involvement in adult and paediatric patients with monogenic autoinflammatory diseases: a Spanish multicentre retrospective study.

OBJECTIVES: Ophthalmologic involvement in monogenic autoinflammatory diseases has been explored mainly in paediatric patients. The aim of this study is to characterise ophthalmologic manifestations, therapeutic management and visual outcomes in a Spanish (UVESAI) cohort of adult/paediatric patients with monogenic autoinflammatory diseases. METHODS: Multicentre and retrospective study of patients with monogenic autoinflammatory diseases and ocular involvement. Eye manifestations, structural complications, treatments used and visual outcomes were analysed, and compared with previous studies. RESULTS: Forty-six patients (44/2 adults/children; 21/25 adult/paediatric-onset) with monogenic autoinflammatory diseases [cryopyrin associated periodic syndromes (n=13/28.3%), mainly Muckle-Wells syndrome (MWS) (n=11/24%); familial Mediterranean fever (FMF) (n=12/26%); TNF receptor-associated periodic syndrome (TRAPS); (n=9/20%); Blau syndrome (n=8/17%); hyperimmunoglobulin D syndrome (HIDS) (n=2/4.3%), deficiency of adenosine deaminase-2 and NLRC4-Autoinflammatory disease] (one each) were included. Conjunctivitis (n=26/56.5%) and uveitis (n=23/50%) were the most frequent ocular manifestations. Twelve (26.1%) patients developed structural complications, being cataracts (n=11/24%) and posterior synechiae (n=10/22%) the most frequent. Conjunctivitis predominated in TRAPS, FMF, MWS and HIDS (mainly in adults), and uveitis, in Blau syndrome. Seven (8%) eyes (all with uveitis) presented with impaired visual acuity. Local and systemic treatment led to good visual outcomes in most patients. Compared with previous studies mainly including paediatric patients, less severe ocular involvement was observed in our adult/paediatric cohort. CONCLUSIONS: Conjunctivitis was the most common ocular manifestation in our TRAPS, FMF, MWS and HIDS patients, and uveitis predominated in Blau syndrome. Severe eye complications and poor visual prognosis were associated with uveitis. Adults with monogenic autoinflammatory diseases seem to exhibit a less severe ophthalmologic presentation than paediatric patients.

Spanish cohort of VEXAS syndrome: clinical manifestations, outcome of treatments and novel evidences about UBA1 mosaicism.

BACKGROUND: The vacuoles, E1-enzyme, X linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease (AID) due to postzygotic UBA1 variants. OBJECTIVES: To investigate the presence of VEXAS syndrome among patients with adult-onset undiagnosed AID. Additional studies evaluated the mosaicism distribution and the circulating cytokines. METHODS: Gene analyses were performed by both Sanger and amplicon-based deep sequencing. Patients' data were collected from their medical charts. Cytokines were quantified by Luminex. RESULTS: Genetic analyses of enrolled patients (n=42) identified 30 patients carrying UBA1 pathogenic variants, with frequencies compatible for postzygotic variants. All patients were male individuals who presented with a late-onset disease (mean 67.5 years; median 67.0 years) characterised by cutaneous lesions (90%), fever (66.7%), pulmonary manifestations (66.7%) and arthritis (53.3%). Macrocytic anaemia and increased erythrocyte sedimentation rate and ferritin were the most relevant analytical abnormalities. Glucocorticoids ameliorated the inflammatory manifestations, but most patients became glucocorticoid-dependent. Positive responses were obtained when targeting the haematopoietic component of the disease with either decitabine or allogeneic haematopoietic stem cell transplantation. Additional analyses detected the UBA1 variants in both haematopoietic and non-haematopoietic tissues. Finally, analysis of circulating cytokines did not identify inflammatory mediators of the disease. CONCLUSION: Thirty patients with adult-onset AID were definitively diagnosed with VEXAS syndrome through genetic analyses. Despite minor interindividual differences, their main characteristics were in concordance with previous reports. We detected for the first time the UBA1 mosaicism in non-haematopoietic tissue, which questions the previous concept of myeloid-restricted mosaicism and may have conceptual consequences for the disease mechanisms.

Expert consensus on the integrated diagnosis of idiopathic multicentric Castleman disease / Consenso de expertos sobre el diagnóstico integrado de la enfermedad de Castleman idiopática multicéntrica

Idiopathic multicentric Castleman disease (iMCD) is rare. The differential diagnosis includes inflammatory, autoimmune and neoplastic disease. The identification of the histopathological features of Castleman disease in the lymph node is the main diagnostic criterion.Fifty-three experts from three medical societies (SEMI, SEHH and SEAP) have created a multi-disciplinary consensus document in order to standardise the diagnosis of Castleman disease. Using the Delphi method, specific recommendations for the initial clinical, laboratory and imaging studies have been made for an integrated diagnosis of iMCD as well as for the best way to obtain samples for histopathological confirmation, correct laboratory procedure and interpretation and reporting of results.(AU)

La enfermedad de Castleman multicéntrica idiopática (ECMi) es una patología infrecuente. El diagnóstico diferencial incluye patología inflamatoria, autoinmune y neoplásica. El estudio anatomopatológico del ganglio linfático y la identificación de las características histopatológicas de la enfermedad de Castleman constituyen un criterio principal para el diagnóstico.Con el objetivo de estandarizar el proceso diagnóstico de esta patología, se ha desarrollado un documento de consenso multidisciplinario con la participación de 53 expertos de tres sociedades médicas (Sociedad Española de Medicina Interna [SEMI], Sociedad Española de Hematología y Hemoterapia [SEHH] y Sociedad Española de Anatomía Patológica [SEAP]). Mediante el método Delphi se han validado las recomendaciones específicas para el diagnóstico integrado de la ECMi con respecto a los estudios clínicos, de laboratorio y de imagen necesarios en el abordaje inicial del paciente y las recomendaciones acerca de la mejor obtención de muestras para confirmación histopatológica, así como procedimientos de laboratorio para el estudio de las muestras, interpretación de resultados y emisión de un informe anatomopatológico.(AU)

Mortality risk factors in primary Sjögren syndrome: a real-world, retrospective, cohort study.

Background: What baseline predictors would be involved in mortality in people with primary Sjögren syndrome (SjS) remains uncertain. This study aimed to investigate the baseline characteristics collected at the time of diagnosis of SjS associated with mortality and to identify mortality risk factors for all-cause death and deaths related to systemic SjS activity measured by the ESSDAI score. Methods: In this international, real-world, retrospective, cohort study, we retrospectively collected data from 27 countries on mortality and causes of death from the Big Data Sjögren Registry. Inclusion criteria consisted of fulfilling 2002/2016 SjS classification criteria, and exclusion criteria included chronic HCV/HIV infections and associated systemic autoimmune diseases. A statistical approach based on a directed acyclic graph was used, with all-cause and Sjögren-related mortality as primary endpoints. The key determinants that defined the disease phenotype at diagnosis (glandular, systemic, and immunological) were analysed as independent variables. Findings: Between January 1st, 2014 and December 31, 2023, data from 11,372 patients with primary SjS (93.5% women, 78.4% classified as White, mean age at diagnosis of 51.1 years) included in the Registry were analysed. 876 (7.7%) deaths were recorded after a mean follow-up of 8.6 years (SD 7.12). Univariate analysis of prognostic factors for all-cause death identified eight Sjögren-related variables (ocular and oral tests, salivary biopsy, ESSDAI, ANA, anti-Ro, anti-La, and cryoglobulins). The multivariate CPH model adjusted for these variables and the epidemiological features showed that DAS-ESSDAI (high vs no high: HR = 1.68; 95% CI, 1.27-2.22) and cryoglobulins (positive vs negative: HR = 1.72; 95% CI, 1.22-2.42) were independent predictors of all-cause death. Of the 640 deaths with available information detailing the specific cause of death, 14% were due to systemic SjS. Univariate analysis of prognostic factors for Sjögren-cause death identified five Sjögren-related variables (oral tests, clinESSDAI, DAS-ESSDAI, ANA, and cryoglobulins). The multivariate competing risks CPH model adjusted for these variables and the epidemiological features showed that oral tests (abnormal vs normal results: HR = 1.38; 95% CI, 1.01-1.87), DAS-ESSDAI (high vs no high: HR = 1.55; 95% CI, 1.22-1.96) and cryoglobulins (positive vs negative: HR = 1.52; 95% CI, 1.16-2) were independent predictors of SjS-related death. Interpretation: The key mortality risk factors at the time of SjS diagnosis were positive cryoglobulins and a high systemic activity scored using the ESSDAI, conferring a 2-times increased risk of all-cause and SjS-related death. ESSDAI measurement and cryoglobulin testing should be considered mandatory when an individual is diagnosed with SjS. Funding: Novartis.

Expert consensus on the integrated diagnosis of idiopathic multicentric Castleman disease.

Idiopathic multicentric Castleman disease (iMCD) is rare. The differential diagnosis includes inflammatory, autoimmune and neoplastic disease. The identification of the histopathological features of Castleman disease in the lymph node is the main diagnostic criterion. Fifty-three experts from three medical societies (SEMI, SEHH and SEAP) have created a multi-disciplinary consensus document in order to standardise the diagnosis of Castleman disease. Using the Delphi method, specific recommendations for the initial clinical, laboratory and imaging studies have been made for an integrated diagnosis of iMCD as well as for the best way to obtain samples for histopathological confirmation, correct laboratory procedure and interpretation and reporting of results.

Idiopathic multicentric Castleman disease and associated autoimmune and autoinflammatory conditions: practical guidance for diagnosis.

Idiopathic multicentric Castleman disease (iMCD) is an infrequent and life-threatening disorder characterized by systemic inflammatory symptoms, generalized lymphadenopathy, polyclonal lymphocyte proliferation and organ dysfunction caused by a hyperinflammatory state. It accounts for one-third to one-half of all multicentric Castleman disease (MCD) cases. iMCD is often associated with autoimmune manifestations that may precede the iMCD diagnosis, be identified at the same time or follow it. In addition, iMCD may also coincide with a number of autoimmune diseases (such as psoriasis or myasthenia gravis) or autoinflammatory diseases (such as familial Mediterranean fever). Moreover, diverse inflammatory disorders, such as rheumatoid arthritis, systemic lupus erythematosus, adult-onset Still disease, systemic juvenile idiopathic arthritis, immunoglobulin (IgG4) related disease, or the recently described VEXAS syndrome, can present clinical features or lymphadenopathy with histopathological 'Castleman-like' findings compatible with those of iMCD. Given the iMCD clinical heterogeneity and the overlap with other autoimmune or autoinflammatory disorders, iMCD diagnosis can be challenging. In this review, we explore the overlap between iMCD and inflammatory diseases and provide practical guidance on iMCD diagnosis in order to avoid misdiagnosis and confusion with other autoimmune or autoinflammatory conditions.

Current clinical spectrum of common variable immunodeficiency in Spain: The multicentric nationwide GTEM-SEMI-CVID registry.

Common variable immunodeficiency (CVID) constitutes a heterogenic group of primary immunodeficiency disorders with a wide-ranging clinical spectrum. CVID-associated non-infectious morbidity constitutes a major challenge requiring a full understanding of its pathophysiology and its clinical importance and global variability, especially considering the broad clinical, genetic, and regional heterogeneity of CVID disorders. This work aimed to develop a nationwide, multicenter, retrospective study over a 3-year period describing epidemiological, clinical, laboratory, therapeutic, and prognostic features of 250 CVID patients in Spain. The mean diagnostic delay was around 10 years and most patients initially presented with infectious complications followed by non-infectious immune disorders. However, infectious diseases were not the main cause of morbimortality. Non-infectious lung disease was extraordinarily frequent in our registry affecting approximately 60% of the patients. More than one-third of the patients in our cohort showed lymphadenopathies and splenomegaly in their follow-up, and more than 33% presented immune cytopenias, especially Evans' syndrome. Gastrointestinal disease was observed in more than 40% of the patients. Among biopsied organs in our cohort, benign lymphoproliferation was the principal histopathological alteration. Reaching 15.26%, the global prevalence of cancer in our registry was one of the highest reported to date, with non-Hodgkin B lymphoma being the most frequent. These data emphasize the importance of basic and translational research delving into the pathophysiological pathways involved in immune dysregulation and diffuse lymphocytic infiltration. This would reveal new tailored strategies to reduce immune complications, and the associated healthcare burden, and ensure a better quality of life for CVID patients.

Hereditary Hemorrhagic Telangiectasia: Genetics, Pathophysiology, Diagnosis, and Management.

Hereditary hemorrhagic telangiectasia is an inherited disease related to an alteration in angiogenesis, manifesting as cutaneous telangiectasias and epistaxis. As complications, it presents vascular malformations in organs such as the lung, liver, digestive tract, and brain. Currently, diagnosis can be made using the Curaçao criteria or by identifying the affected gene. In recent years, there has been an advance in the understanding of the pathophysiology of the disease, which has allowed the use of new therapeutic strategies to improve the quality of life of patients. This article reviews some of the main and most current evidence on the pathophysiology, clinical manifestations, diagnostic approach, screening for complications, and therapeutic options, both pharmacological and surgical.

Standardized incidence ratios and risk factors for cancer in patients with systemic sclerosis: Data from the Spanish Scleroderma Registry (RESCLE).

AIM: Patients with systemic sclerosis (SSc) are at increased risk of cancer, a growing cause of non-SSc-related death among these patients. We analyzed the increased cancer risk among Spanish patients with SSc using standardized incidence ratios (SIRs) and identified independent cancer risk factors in this population. MATERIAL AND METHODS: Spanish Scleroderma Registry data were analyzed to determine the demographic characteristics of patients with SSc, and logistic regression was used to identify cancer risk factors. SIRs with 95% confidence intervals (CIs) relative to the general Spanish population were calculated. RESULTS: Of 1930 patients with SSc, 206 had cancer, most commonly breast, lung, hematological, and colorectal cancers. Patients with SSc had increased risks of overall cancer (SIR 1.48, 95% CI 1.36-1.60; P < 0.001), and of lung (SIR 2.22, 95% CI 1.77-2.73; P < 0.001), breast (SIR 1.31, 95% CI 1.10-1.54; P = 0.003), and hematological (SIR 2.03, 95% CI 1.52-2.62; P < 0.001) cancers. Cancer was associated with older age at SSc onset (odds ratio [OR] 1.22, 95% CI 1.01-1.03; P < 0.001), the presence of primary biliary cholangitis (OR 2.35, 95% CI 1.18-4.68; P = 0.015) and forced vital capacity <70% (OR 1.8, 95% CI 1.24-2.70; P = 0.002). The presence of anticentromere antibodies lowered the risk of cancer (OR 0.66, 95% CI 0.45-0.97; P = 0.036). CONCLUSIONS: Spanish patients with SSc had an increased cancer risk compared with the general population. Some characteristics, including specific autoantibodies, may be related to this increased risk.

Left ventricular diastolic dysfunction in systemic sclerosis: Clinical, immunological and survival differences in the Spanish RESCLE registry.

OBJECTIVES: Left ventricular diastolic dysfunction (LVDD) remains poorly studied in Systemic Sclerosis (SSc). To determine the prevalence and to define factors associated with LVDD and survival in a large cohort of patients with SSc. METHODS: An observational study was conducted with data from the multicentre Spanish Scleroderma Registry (RESCLE) to identify factors associated with LVDD and estimate survival. RESULTS: Out of 1517 patients, 319 (21.0%) had LVDD. The subset of sine scleroderma SSc was associated to LVDD (14.7% vs. 10.6%, p =0.048), whilst diffuse cutaneous SSc was more prevalent in non-LVDD (16.0 % vs. 21.2%, p =0.041). Multivariable analysis identified that LVDD was associated with older age at diagnosis of SSc (OR 1.05; 95% CI 1.04 to 1.06), longer time from diagnosis (OR 1.04; 95% CI 1.03 to 1.06), presence of telangiectasia (OR 1.42; 95% CI 1.08 to 1.88), treatment with calcium channel blockers (CCB) (OR 1.51; 95% CI 1.16 to 1.96), and inversely related to angiotensin-converting-enzyme inhibitors (ACEi) use (OR 0.59; 95% CI 0.44 to 0.80). SSc patients with LVDD had increased mortality (23.8 vs. 17.4%, p =0.010) and shortened survival from the first SSc symptom (p =0.040), even though it was not found to be an independent risk factor for death. CONCLUSIONS: LVDD is relatively common in SSc patients, and it is associated with worst prognosis, older age, longer time from diagnosis of SSc, presence of telangiectasia and vasodilator treatment.

In-hospital mortality among immunosuppressed patients with COVID-19: Analysis from a national cohort in Spain.

BACKGROUND: Whether immunosuppressed (IS) patients have a worse prognosis of COVID-19 compared to non-IS patients is not known. The aim of this study was to evaluate the clinical characteristics and outcome of IS patients hospitalized with COVID-19 compared to non-IS patients. METHODS: We designed a retrospective cohort study. We included all patients hospitalized with laboratory-confirmed COVID-19 from the SEMI-COVID-19 Registry, a large multicentre national cohort in Spain, from March 27th until June 19th, 2020. We used multivariable logistic regression to assess the adjusted odds ratios (aOR) of in-hospital death among IS compared to non-IS patients. RESULTS: Among 13 206 included patients, 2 111 (16.0%) were IS. A total of 166 (1.3%) patients had solid organ (SO) transplant, 1081 (8.2%) had SO neoplasia, 332 (2.5%) had hematologic neoplasia, and 570 (4.3%), 183 (1.4%) and 394 (3.0%) were receiving systemic steroids, biological treatments, and immunosuppressors, respectively. Compared to non-IS patients, the aOR (95% CI) for in-hospital death was 1.60 (1.43-1.79) for all IS patients, 1.39 (1.18-1.63) for patients with SO cancer, 2.31 (1.76-3.03) for patients with haematological cancer and 3.12 (2.23-4.36) for patients with SO transplant. The aOR (95% CI) for death for patients who were receiving systemic steroids, biological treatments and immunosuppressors compared to non-IS patients were 2.16 (1.80-2.61), 1.97 (1.33-2.91) and 2.06 (1.64-2.60), respectively. IS patients had a higher odds than non-IS patients of in-hospital acute respiratory distress syndrome, heart failure, myocarditis, thromboembolic disease and multiorgan failure. CONCLUSIONS: IS patients hospitalized with COVID-19 have a higher odds of in-hospital complications and death compared to non-IS patients.

Clinical characterization and outcomes of 85 patients with neurosarcoidosis.

To analyze the frequency and clinical phenotype of neurosarcoidosis (NS) in one of the largest nationwide cohorts of patients with sarcoidosis reported from southern Europe. NS was evaluated according to the Diagnostic Criteria for Central Nervous System and Peripheral Nervous System Sarcoidosis recently proposed by Stern et al. Pathologic confirmation of granulomatous disease was used to subclassify NS into definite (confirmation in neurological tissue), probable (confirmation in extraneurological tissue) and possible (no histopathological confirmation of the disease). Of the 1532 patients included in the cohort, 85 (5.5%) fulfilled the Stern criteria for NS (49 women, mean age at diagnosis of NS of 47.6 years, 91% White). These patients developed 103 neurological conditions involving the brain (38%), cranial nerves (36%), the meninges (3%), the spinal cord (10%) and the peripheral nerves (14%); no patient had concomitant central and peripheral nerve involvements. In 59 (69%) patients, neurological involvement preceded or was present at the time of diagnosis of the disease. According to the classification proposed by Stern et al., 11 (13%) were classified as a definite NS, 61 (72%) as a probable NS and the remaining 13 (15%) as a possible NS. In comparison with the systemic phenotype of patients without NS, patients with CNS involvement presented a lower frequency of thoracic involvement (82% vs 93%, q = 0.018), a higher frequency of ocular (27% vs 10%, q < 0.001) and salivary gland (15% vs 4%, q = 0.002) WASOG involvements. In contrast, patients with PNS involvement showed a higher frequency of liver involvement (36% vs 12%, p = 0.02) in comparison with patients without NS. Neurosarcoidosis was identified in 5.5% of patients. CNS involvement prevails significantly over PNS involvement, and both conditions do not overlap in any patient. The systemic phenotype associated to each involvement was clearly differentiated, and can be helpful not only in the early identification of neurological involvement, but also in the systemic evaluation of patients diagnosed with neurosarcoidosis.

Effect of Canakinumab vs Placebo on Survival Without Invasive Mechanical Ventilation in Patients Hospitalized With Severe COVID-19: A Randomized Clinical Trial.

Importance: Effective treatments for patients with severe COVID-19 are needed. Objective: To evaluate the efficacy of canakinumab, an anti-interleukin-1ß antibody, in patients hospitalized with severe COVID-19. Design, Setting, and Participants: This randomized, double-blind, placebo-controlled phase 3 trial was conducted at 39 hospitals in Europe and the United States. A total of 454 hospitalized patients with COVID-19 pneumonia, hypoxia (not requiring invasive mechanical ventilation [IMV]), and systemic hyperinflammation defined by increased blood concentrations of C-reactive protein or ferritin were enrolled between April 30 and August 17, 2020, with the last assessment of the primary end point on September 22, 2020. Intervention: Patients were randomly assigned 1:1 to receive a single intravenous infusion of canakinumab (450 mg for body weight of 40-<60 kg, 600 mg for 60-80 kg, and 750 mg for >80 kg; n = 227) or placebo (n = 227). Main Outcomes and Measures: The primary outcome was survival without IMV from day 3 to day 29. Secondary outcomes were COVID-19-related mortality, measurements of biomarkers of systemic hyperinflammation, and safety evaluations. Results: Among 454 patients who were randomized (median age, 59 years; 187 women [41.2%]), 417 (91.9%) completed day 29 of the trial. Between days 3 and 29, 198 of 223 patients (88.8%) survived without requiring IMV in the canakinumab group and 191 of 223 (85.7%) in the placebo group, with a rate difference of 3.1% (95% CI, -3.1% to 9.3%) and an odds ratio of 1.39 (95% CI, 0.76 to 2.54; P = .29). COVID-19-related mortality occurred in 11 of 223 patients (4.9%) in the canakinumab group vs 16 of 222 (7.2%) in the placebo group, with a rate difference of -2.3% (95% CI, -6.7% to 2.2%) and an odds ratio of 0.67 (95% CI, 0.30 to 1.50). Serious adverse events were observed in 36 of 225 patients (16%) treated with canakinumab vs 46 of 223 (20.6%) who received placebo. Conclusions and Relevance: Among patients hospitalized with severe COVID-19, treatment with canakinumab, compared with placebo, did not significantly increase the likelihood of survival without IMV at day 29. Trial Registration: ClinicalTrials.gov Identifier: NCT04362813.

Coexistence of immune-mediated diseases in sarcoidosis. Frequency and clinical significance in 1737 patients.

OBJECTIVE: To analyze whether immune-mediated diseases (IMDs) occurs in sarcoidosis more commonly than expected in the general population, and how concomitant IMDs influence the clinical presentation of the disease. METHODS: We searched for coexisting IMDs in patients included in the SARCOGEAS-cohort, a multicenter nationwide database of consecutive patients diagnosed according to the ATS/ESC/WASOG criteria. Comparisons were made considering the presence or absence of IMD clustering, and odds ratios (OR) and their 95% confidence intervals (CI) were calculated as the ratio of observed cases of every IMD in the sarcoidosis cohort to the observed cases in the general population. RESULTS: Among 1737 patients with sarcoidosis, 283 (16%) patients presented at least one associated IMD. These patients were more commonly female (OR: 1.98, 95% CI: 1.49-2.62) and were diagnosed with sarcoidosis at an older age (49.6 vs. 47.5years, P<0.05). The frequency of IMDs in patients with sarcoidosis was nearly 2-fold higher than the frequency observed in the general population (OR: 1.64, 95% CI: 1.44-1.86). Significant associations were identified in 17 individual IMDs. In comparison with the general population, the IMDs with the strongest strength of association with sarcoidosis (OR>5) were common variable immunodeficiency (CVID) (OR: 431.8), familial Mediterranean fever (OR 33.9), primary biliary cholangitis (OR: 16.57), haemolytic anemia (OR: 12.17), autoimmune hepatitis (OR: 9.01), antiphospholipid syndrome (OR: 8.70), immune thrombocytopenia (OR: 8.43), Sjögren syndrome (OR: 6.98), systemic sclerosis (OR: 5.71), ankylosing spondylitis (OR: 5.49), IgA deficiency (OR: 5.07) and psoriatic arthritis (OR: 5.06). Sex-adjusted ORs were considerably higher than crude ORs for eosinophilic digestive disease in women, and for immune thrombocytopenia, systemic sclerosis and autoimmune hepatitis in men. CONCLUSION: We found coexisting IMDs in 1 out of 6 patients with sarcoidosis. The strongest associations were found for immunodeficiencies and some systemic, rheumatic, hepatic and hematological autoimmune diseases.

Inappropriate antibiotic use in the COVID-19 era: Factors associated with inappropriate prescribing and secondary complications. Analysis of the registry SEMI-COVID.

BACKGROUND: Most patients with COVID-19 receive antibiotics despite the fact that bacterial co-infections are rare. This can lead to increased complications, including antibacterial resistance. We aim to analyze risk factors for inappropriate antibiotic prescription in these patients and describe possible complications arising from their use. METHODS: The SEMI-COVID-19 Registry is a multicenter, retrospective patient cohort. Patients with antibiotic were divided into two groups according to appropriate or inappropriate prescription, depending on whether the patient fulfill any criteria for its use. Comparison was made by means of multilevel logistic regression analysis. Possible complications of antibiotic use were also identified. RESULTS: Out of 13,932 patients, 3047 (21.6%) were prescribed no antibiotics, 6116 (43.9%) were appropriately prescribed antibiotics, and 4769 (34.2%) were inappropriately prescribed antibiotics. The following were independent factors of inappropriate prescription: February-March 2020 admission (OR 1.54, 95%CI 1.18-2.00), age (OR 0.98, 95%CI 0.97-0.99), absence of comorbidity (OR 1.43, 95%CI 1.05-1.94), dry cough (OR 2.51, 95%CI 1.94-3.26), fever (OR 1.33, 95%CI 1.13-1.56), dyspnea (OR 1.31, 95%CI 1.04-1.69), flu-like symptoms (OR 2.70, 95%CI 1.75-4.17), and elevated C-reactive protein levels (OR 1.01 for each mg/L increase, 95% CI 1.00-1.01). Adverse drug reactions were more frequent in patients who received ANTIBIOTIC (4.9% vs 2.7%, p < .001). CONCLUSION: The inappropriate use of antibiotics was very frequent in COVID-19 patients and entailed an increased risk of adverse reactions. It is crucial to define criteria for their use in these patients. Knowledge of the factors associated with inappropriate prescribing can be helpful.

Cardiometabolic Therapy and Mortality in Very Old Patients With Diabetes Hospitalized due to COVID-19.

BACKGROUND: The effects of cardiometabolic drugs on the prognosis of diabetic patients with COVID-19, especially very old patients, are not well known. This work was aimed to analyze the association between preadmission cardiometabolic therapy (antidiabetic, antiaggregant, antihypertensive, and lipid-lowering drugs) and in-hospital mortality among patients ≥80 years with type 2 diabetes mellitus (T2DM) hospitalized for COVID-19. METHOD: We conducted a nationwide, multicenter, observational study in patients ≥80 years with T2DM hospitalized for COVID-19 between March 1 and May 29, 2020. The primary outcome measure was in-hospital mortality. A multivariate logistic regression analysis was performed to assess the association between preadmission cardiometabolic therapy and in-hospital mortality. RESULTS: Of the 2 763 patients ≥80 years old hospitalized due to COVID-19, 790 (28.6%) had T2DM. Of these patients, 385 (48.7%) died during admission. On the multivariate analysis, the use of dipeptidyl peptidase-4 inhibitors (adjusted odds ratio [AOR] 0.502, 95% confidence interval [CI]: 0.309-0.815, p = .005) and angiotensin receptor blockers (AOR 0.454, 95% CI: 0.274-0.759, p = .003) were independent protectors against in-hospital mortality, whereas the use of acetylsalicylic acid was associated with higher in-hospital mortality (AOR 1.761, 95% CI: 1.092-2.842, p = .020). Other antidiabetic drugs, angiotensin-converting enzyme inhibitors, and statins showed neutral association with in-hospital mortality. CONCLUSIONS: We found important differences between cardiometabolic drugs and in-hospital mortality in older patients with T2DM hospitalized for COVID-19. Preadmission treatment with dipeptidyl peptidase-4 inhibitors and angiotensin receptor blockers could reduce in-hospital mortality; other antidiabetic drugs, angiotensin-converting enzyme inhibitors, and statins seem to have a neutral effect; and acetylsalicylic acid could be associated with excess mortality.