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Snyder-Robinson syndrome is an extremely rare genetic disorder, caused by mutations of the spermine synthase gene. We report a novel case of Snyder-Robinson syndrome, caused by a de novo mutation and first misdiagnosed with osteogenesis imperfecta. Clinical features, course, and genetic analysis are presented. The patient was treated with bisphosphonates for a decade, until developing an atypical femoral fracture. Teriparatide was then administered for 2 years and then changed to denosumab every 6 months, improving his bone density mass and preventing further fractures.
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Discapacidad Intelectual Ligada al Cromosoma X , Osteogénesis Imperfecta , Espermina Sintasa , Diagnóstico Diferencial , Humanos , Discapacidad Intelectual Ligada al Cromosoma X/diagnóstico , Discapacidad Intelectual Ligada al Cromosoma X/genética , Osteogénesis Imperfecta/diagnóstico , Osteogénesis Imperfecta/tratamiento farmacológico , Osteogénesis Imperfecta/genética , Espermina Sintasa/genéticaRESUMEN
Genetic biomarkers could be useful for orienting treatment of patients with rheumatoid arthritis (RA), but none has been convincingly validated yet. Putative biomarkers include 14 single nucleotide polymorphisms that have shown association with response to TNF inhibitors (TNFi) in candidate gene studies and that we assayed here in 755 RA patients. Three of them, in the PTPRC, IL10 and CHUK genes, were significantly associated with response to TNFi. The most significant result was obtained with rs10919563 in PTPRC, which is a confirmed RA susceptibility locus. Its RA risk allele was associated with improved response (B=0.33, P=0.006). This is the second independent replication of this biomarker (P=9.08 × 10(-8) in the combined 3003 RA patients). In this way, PTPRC has become the most replicated genetic biomarker of response to TNFi. In addition, the positive but weaker replication of IL10 and CHUK should stimulate further validation studies.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Quinasa I-kappa B/genética , Interleucina-10/genética , Antígenos Comunes de Leucocito/genética , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab/uso terapéutico , Artritis Reumatoide/genética , Femenino , Estudios de Asociación Genética , Marcadores Genéticos , Humanos , Infliximab/uso terapéutico , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , RiesgoRESUMEN
BACKGROUND AND OBJECTIVE: In the context of the SARS-CoV-2 pandemic, the development of new vaccines and their efficacy in patients with immune-mediated rheumatic diseases has been a target to investigate. The objective of this study is to evaluate the vaccine response rate in patients with immune-mediated rheumatic diseases under treatment with immunomodulators, including rituximab (RTX), as well as the influence of possible factors involved in the vaccination response in these patients. MATERIAL AND METHODS: A single-centre, prospective cohort study was conducted in 130 patients with immune-mediated rheumatic disease on treatment with immunomodulators, including RTX, who received the full course of vaccination against SARS-CoV-2 with BioNTech/Pfizer, Moderna/Lonza, AstraZeneca, or Janssen between April and October 2021. Demographic factors such as age, sex, type of immune-mediated disease, immunomodulatory treatment and type of vaccine were analysed, as well as serological markers including anti-SARS-CoV-2 IgG antibody levels measured one and six months after vaccination, CD19+ lymphocyte levels and the presence or absence of hypogammaglobulinemia. A statistical analysis was performed to assess the influence of the different variables collected in the study on the antibody titres. RESULTS: A sample of 130 patients was studied, 41 under treatment with RTX and 89 with other immunomodulators. A lower vaccination response rate was observed in patients with RTX (12/34, 36.7%) one month after the primary vaccination compared to 96.5% (82/85) of patients who did not receive this drug and did respond. In the analysis of secondary variables, hypogammaglobulinemia was significantly associated with lack of development of a vaccine response. The administration of the last RTX cycle in the 6 months prior to vaccination and low CD19+ levels (<20mg/dL) also had a negative influence on the development of a vaccine response. In the group of patients who were not receiving RTX treatment, the vaccination response was like that observed in the general population. We did not observe statistically significant differences in the vaccine response based on immunomodulatory treatment other than RTX, concomitant corticosteroid treatment, type of immune-mediated pathology, age, or sex. DISCUSSION AND CONCLUSIONS: In patients with rheumatic diseases receiving immunomodulatory treatment, the response to vaccination against SARS-CoV-2 is comparable to the general population, except in the case of patients receiving RTX, who have a lower response rate (around 36.7%) which is associated with factors such as hypogammaglobulinemia, pre-vaccination CD19+ lymphocyte levels, and a period between vaccination and the last dose of RTX of less than 6 months. It is important to take these factors into consideration to optimize vaccination in these patients.
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BACKGROUND AND OBJECTIVE: In the context of the SARS-CoV-2 pandemic, the development of new vaccines and their efficacy in patients with immune-mediated rheumatic diseases has been a target to investigate. The objective of this study is to evaluate the vaccine response rate in patients with immune-mediated rheumatic diseases under treatment with immunomodulators, including rituximab (RTX), as well as the influence of possible factors involved in the vaccination response in these patients. MATERIAL AND METHODS: A single-centre, prospective cohort study was conducted in 130 patients with immune-mediated rheumatic disease on treatment with immunomodulators, including RTX, who received the full course of vaccination against SARS-CoV-2 with BioNTech/Pfizer, Moderna/Lonza, AstraZeneca, or Janssen between April and October 2021. Demographic factors such as age, sex, type of immune-mediated disease, immunomodulatory treatment and type of vaccine were analysed, as well as serological markers including anti-SARS-CoV-2 IgG antibody levels measured one and six months after vaccination, CD19+ lymphocyte levels and the presence or absence of hypogammaglobulinemia. A statistical analysis was performed to assess the influence of the different variables collected in the study on the antibody titres. RESULTS: A sample of 130 patients was studied, 41 under treatment with RTX and 89 with other immunomodulators. A lower vaccination response rate was observed in patients with RTX (12/34, 36.7%) one month after the primary vaccination compared to 96.5% (82/85) of patients who did not receive this drug and did respond. In the analysis of secondary variables, hypogammaglobulinemia was significantly associated with lack of development of a vaccine response. The administration of the last RTX cycle in the 6 months prior to vaccination and low CD19+ levels (<20â¯mg/dL) also had a negative influence on the development of a vaccine response. In the group of patients who were not receiving RTX treatment, the vaccination response was like that observed in the general population. We did not observe statistically significant differences in the vaccine response based on immunomodulatory treatment other than RTX, concomitant corticosteroid treatment, type of immune-mediated pathology, age, or sex. DISCUSSION AND CONCLUSIONS: In patients with rheumatic diseases receiving immunomodulatory treatment, the response to vaccination against SARS-CoV-2 is comparable to the general population, except in the case of patients receiving RTX, who have a lower response rate (around 36.7%) which is associated with factors such as hypogammaglobulinemia, pre-vaccination CD19+ lymphocyte levels, and a period between vaccination and the last dose of RTX of less than 6 months. It is important to take these factors into consideration to optimize vaccination in these patients.
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Agammaglobulinemia , COVID-19 , Enfermedades Reumáticas , Vacunas , Humanos , Lactante , SARS-CoV-2 , Estudios Prospectivos , COVID-19/prevención & control , Vacunación , Rituximab/uso terapéutico , Factores Inmunológicos , Enfermedades Reumáticas/tratamiento farmacológicoRESUMEN
OBJECTIVE: To analyze the effectiveness and safety of intravenous immunoglobulin (IVIG) given in routine care to patients with systemic sclerosis (SSc). METHODS: A retrospective multicenter observational study was conducted in SSc patients treated with IVIG. We collected data on epidemiological parameters and clinical outcomes. Firstly, we assessed changes in organ manifestations during IVIG treatment. Secondly, we analyzed the frequency of adverse effects. The following parameters were collected from baseline to the last follow-up: the patient's weight, modified Rodnan Skin Score (mRSS), modified manual muscle strength scale (MRC), laboratory test(creatine kinase(CK), hemoglobin and protein levels), The University of California Los Angeles Scleroderma Clinical Trials Consortium gastrointestinal tract 2.0 (UCLA GIT 2.0) questionnaire, pulmonary function tests, and echocardiography. RESULTS: Data were collected on 78 patients (82% females; 59% with diffuse SSc). Inflammatory idiopathic myopathy was the most frequent concomitant overlap disease (41%). The time since Raynaud's phenomenon and SSc onset were 8.8 ± 18 and 6.2 ± 6.7 years respectively. The most frequent IVIG indication was myositis (38/78), followed by gastrointestinal (27/78) and cutaneous (17/78) involvement. The median number of cycles given were 5. 54, 53 and 9 patients have been treated previously with glucocorticoids, synthetic disease-modifying antirheumatic drugs and biologic therapies respectively. After IVIG use we found significant improvements in muscular involvement (MRC ≥ 3/5 92% IVIG, p = 0.001 and CK levels from 1149 ± 2026 UI to 217 ± 224 UI, p = 0.02), mRSS (15 ± 12.4 to 13 ± 12.5, p = 0.015) and improvement in total score of UCLA GIT 2.0 (p = 0.05). None Anti-RNA polymerase III patients showed an adequate response in gastrointestinal involvement (0/7) in comparison with other antibodies (0 vs. 25, p = 0,039). Cardiorespiratory involvement remained stable. A total of 12 adverse events were reported with only one withdrawn due to serious adverse effect. CONCLUSIONS: this study suggest that IVIG may improve myositis, gastrointestinal and skin involvement in SSc patients treated in routine care and seems to have a good safety profile.
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Miositis , Esclerodermia Sistémica , Femenino , Humanos , Masculino , Inmunoglobulinas Intravenosas/uso terapéutico , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/tratamiento farmacológico , Estudios Retrospectivos , Piel , Miositis/tratamiento farmacológico , Estudios Multicéntricos como Asunto , Estudios Observacionales como AsuntoRESUMEN
Arterial stiffness can enhance cardiovascular risk by increasing atherogenesis or adverse hemodynamic effects. We examined whether the arterial stiffness markers of aortic pulse wave velocity (PWV) and the augmentation index (AIx) are independently associated with carotid artery intima-media thickness (IMT) and plaque in patients with rheumatoid arthritis (RA). PWV and AIx were determined by brachial oscillometry using the Mobil-O-Graph® system and carotid IMT and plaque by ultrasound in 194 consecutive RA patients without established cardiovascular disease, chronic kidney disease, and diabetes at disease onset. In crude analysis, PWV was associated with IMT (ß (95% CI) = 0.04 (0.03 to 0.05), p value < 0.0001) and plaque (OR (95% CI) = 1.69 (1.40 to 2.04), p value < 0.0001). Upon adjustment for the confounders of age, sex, mean blood pressure, body height, and cardiovascular risk factors comprising smoking, the atherogenic index, and diabetes, PWV was not related to IMT (ß (95% CI) = 0.01 (-0.02 to 0.04), p value = 0.5) or plaque (OR (95% CI) = 0.99 (0.96 to 1.01), p value = 0.3). AIx was not associated with IMT in crude (ß (95% CI) = -0.002 (-0.004 to 0.007), p value = 0.2) and adjusted analyses (ß (95% CI) = -0.002 (-0.004 to 0.000), p value = 0.06). AIx was also unrelated to carotid plaque in crude (OR (95% CI) = 1.04 (0.60 to 1.82), p value = 0.9) and adjusted analyses (OR (95% CI) = 0.97 (0.94 to 1.01), p value = 0.1). PWV and AIx are not independently associated with subclinical carotid atherosclerosis in RA.
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Artritis Reumatoide/fisiopatología , Aterosclerosis/fisiopatología , Velocidad del Flujo Sanguíneo/fisiología , Enfermedades de las Arterias Carótidas/fisiopatología , Factores de Edad , Anciano , Artritis Reumatoide/complicaciones , Artritis Reumatoide/diagnóstico por imagen , Aterosclerosis/complicaciones , Aterosclerosis/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/complicaciones , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Arteria Carótida Común/diagnóstico por imagen , Grosor Intima-Media Carotídeo , Femenino , Hemodinámica/fisiología , Humanos , Masculino , Persona de Mediana Edad , Análisis de la Onda del Pulso , Factores de Riesgo , Factores Sexuales , UltrasonografíaRESUMEN
Prevotella bivia is a gram-negative anaerobic bacteria traditionally classified in the genus Bacteroides, and usually reported in obstetric and gynecologic infections. To date, there has been only one description of infectious arthritis secondary to this germ. We report the first case of septic arthritis due to Prevotella bivia in a patient with severe, long-lasting rheumatoid arthritis (RA) treated with low doses of corticosteroids. RA is a well-known predisposing factor to septic arthritis, whose causes are multifactorial (general immunosuppression induced by the disease and its therapy, presence of prosthetic joints, etc.). However, infectious arthritis due to anaerobic bacteria is rarely observed. In general, clinical presentation varies widely: insidious onset, apyrexia, and lack of inflammatory signs or systemic disturbance are frequent features. Joint infection is generally secondary to hematogenous spread, the Bacteroides fragilis group being the most commonly isolated pathogens. Early diagnosis and prompt treatment, with drainage and debridement of the affected joint and specific antimicrobial treatment with Metronidazole are essential for a successful outcome.
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Artritis Infecciosa/microbiología , Artritis Reumatoide/complicaciones , Infecciones por Bacteroidaceae/complicaciones , Infecciones por Bacteroidaceae/etiología , Prevotella/aislamiento & purificación , Prevotella/fisiología , Corticoesteroides/efectos adversos , Anciano , Artritis Infecciosa/diagnóstico , Artritis Infecciosa/tratamiento farmacológico , Infecciones por Bacteroidaceae/tratamiento farmacológico , Humanos , Masculino , Metronidazol/administración & dosificaciónRESUMEN
Antiphospholipid syndrome (APS) carries a risk of thrombosis and infertility. Consequently the use of any type of hormone therapy and pregnancy in APS requires special considerations. The present article provides a broad review of all these issues. The use of contraception, hormone replacement therapy and selective estrogen receptor modulators in APS are described. In vitro fertilization/embryo transfer and ovarian induction in these patients are reviewed. Lastly, the possible fetal and maternal complications that can occur during pregnancy are described and, based on the literature, recommendations for the management of pregnancy in women with APS are provided.
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A Behçet's disease patient developed sudden cochlear hearing loss during a flare of her disease. Prednisone and cyclosporin therapy was ineffective, probably because it was initiated late. Sensorineural hearing loss is a rare but underrecognized complication of various forms of vasculitis such as Wegener's granulomatosis, polyarteritis nodosa, giant cell arteritis and Behçet's disease. Its importance lies in the need for an early diagnosis, since prompt treatment with steroids and immunosuppressive agents may lead to restoration of hearing.
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Síndrome de Behçet/complicaciones , Enfermedades Cocleares/etiología , Trastornos de la Audición/etiología , Síndrome de Behçet/tratamiento farmacológico , Síndrome de Behçet/fisiopatología , Femenino , Humanos , Persona de Mediana Edad , Prednisona/uso terapéuticoRESUMEN
Complete heart block (CHB) is a rare complication of systemic lupus erythematosus (SLE), mainly seen during an acute flare-up of the disease or after high-dose long-term treatment with antimalarial drugs, although anti-Ro and anti-RNP antibodies have also been implied by some authors. A 40-y-old woman developed CHB in the context of an acute flare-up of SLE, first diagnosed three years ago, having recently commenced hydroxychloroquine (HCQ) treatment. Anti-Ro and anti-RNP antibodies were also positive. No features of myocarditis were found. A temporary pacemaker was required and complete resolution was achieved on steroid therapy with withdrawal of antimalarial therapy. The characteristics of previous cases are well publicised and discussion focuses on the possible aetiology and pathogenesis of the present case.