Análisis de factores implicados en el desarrollo de respuesta humoral a la vacunación frente a SARS-CoV-2 en pacientes con enfermedad reumática en tratamiento biológico / Analysis of factors involved in the development of humoral response to vaccination against SARS-CoV-2 in patients with rheumatic pathology under biological treatment

Antecedentes y objetivo: En el contexto de la pandemia por SARS-CoV-2 el desarrollo de nuevas vacunas y su eficacia en pacientes con enfermedades reumáticas inmunomediadas ha sido motivo de estudio. El objetivo de este trabajo es evaluar la tasa de respuesta vacunal en pacientes con enfermedades reumáticas inmunomediadas en tratamiento con inmunomoduladores, incluyendo el rituximab (RTX), así como la influencia de posibles factores implicados en la respuesta vacunal en estos pacientes. Material y métodos: Se realizó un estudio de cohortes prospectivo, unicéntrico, en 130 pacientes con enfermedad reumática inmunomediada en tratamiento con inmunomoduladores, incluyendo RTX, que recibieron la pauta completa de vacunación frente a SARS-CoV-2 con BioNTech/Pfizer, Moderna/Lonza, AstraZeneca o Janssen entre abril y octubre de 2021. Se analizaron factores demográficos como la edad, el sexo, el tipo de enfermedad inmunomediada, el tratamiento inmunomodulador y el tipo de vacuna, así como marcadores serológicos incluyendo los niveles de anticuerpos anti-SARS-CoV-2 IgG al mes y a los 6 meses desde la vacunación, niveles de linfocitos CD19+ y la presencia o no de hipogammaglobulinemia. Se realizó un análisis estadístico para evaluar la influencia en los títulos de anticuerpos de las diferentes variables recogidas en el estudio. Resultados: Se obtuvo una muestra de 130 pacientes, 41 en tratamiento con RTX y 89 con otros inmunomoduladores. Se observó una menor tasa de respuesta vacunal en los pacientes con RTX (12/34, 36,7%) al mes de la primovacunación con respecto al 96,5% (82/85) de pacientes que no recibieron este fármaco y sí alcanzaron respuesta. En el análisis de variables secundarias la hipogammaglobulinemia se asoció de forma significativa a la ausencia de desarrollo de respuesta vacunal. La administración del último RTX en los 6 meses previos a la vacunación y niveles bajos de CD19+ (<20mg/dl) también influyeron de forma negativa en el desarrollo de...(AU)

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...(AU)

Analysis of factors involved in the development of humoral response to vaccination against SARS-CoV-2 in patients with rheumatic pathology under biological treatment.

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 (<20 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.

Immunoglobulins in systemic sclerosis management. A large multicenter experience.

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.

[ANALYSIS OF FACTORS INVOLVED IN THE DEVELOPMENT OF HUMORAL RESPONSE TO VACCINATION AGAINST SARS-COV-2 IN PATIENTS WITH RHEUMATIC PATHOLOGY UNDER BIOLOGICAL TREATMENT.] / ANÁLISIS DE FACTORES IMPLICADOS EN EL DESARROLLO DE RESPUESTA HUMORAL A LA VACUNACIÓN FRENTE A SARS-COV-2 EN PACIENTES CON PATOLOGÍA REUMÁTICA EN TRATAMIENTO BIOLÓGICO.

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.

Snyder-Robinson syndrome: differential diagnosis of osteogenesis imperfecta.

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.

Pulse wave velocity and augmentation index are not independently associated with carotid atherosclerosis in patients with rheumatoid arthritis.

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.

Replication of PTPRC as genetic biomarker of response to TNF inhibitors in patients with rheumatoid arthritis.

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.

Terapias hormonales, fertilidad y embarazo en el síndrome Antifosfolipídico / Hormone therapy, fertility and pregnancy in antiphospholipid syndrome

Debido al riesgo trombótico, y a sus implicaciones en la fertilidad, el síndrome antifosfolipídico (SAF) conlleva consideraciones particulares respecto a cualquier tipo de terapia hormonal y a la gestación. En el presente artículo, se procede a revisar ampliamente todos estos aspectos. Se desglosa lo referente a anticoncepción, terapia hormonal sustitutiva y moduladores selectivos de los receptores de estrógenos en el SAF. Se revisa la fertilización in vitro/transferencia embrionaria y la inducción ovárica en estas pacientes. Por último, se detallan las posibles complicaciones fetales y maternas durante la gestación, y basándose en la bibliografía, se indica una posible guía para el manejo del embarazo en mujeres con SAF(AU)

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 inwomen with APS are provided(AU)

[Hormone therapy, fertility and pregnancy in antiphospholipid syndrome]. / Terapias hormonales, fertilidad y embarazo en el síndrome antifosfolipídico.

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.

Bursitis: análisis clínico de 52 casos / Bursitis: clinical analysis of 52 patients

Estudio retrospectivo longitudinal que evalúa las características clínicas de los pacientes diagnosticados de bursitis durante un año en una sección de reumatología de un hospital terciario, comparándolos con resultados previos de la bibliografía. Se incluyó a 52 pacientes, diagnosticados todos de bursitis según criterios clínicos y ecográficos. De ellos, 19 pacientes (36,5 por ciento) presentaban bursitis superficial, y 33 (63,5 por ciento) bursitis profunda. La mayoría de las bursitis superficiales ocurrieron en varones (84,2 por ciento), con una media de 49,2 años de edad. En cambio, las bursitis profundas se dieron predominantemente en mujeres (78,8 por ciento) con una edad media de 53,8 años. Entre los factores predisponentes para las bursitis superficiales encontramos diferentes profesiones (albañil, fontanero, carpintero y ama de casa), frente a las profundas, en que los pacientes eran predominantemente sedentarios (el 100 por ciento de las bursitis glúteas). Las radiografías simples fueron normales, excepto en un 18,8 por ciento de las bursitis superficiales, en las que se observó un aumento de partes blandas. El diagnóstico clínico fue confirmado ecográficamente en todos los casos. Se obtuvo líquido de las bursas en 17 de las bursitis superficiales (89,4 por ciento), y en todos ellos se practicó examen en fresco y cultivo. En ningún caso se observaron cristales. El cultivo fue positivo en 8 pacientes (47 por ciento), y Staphylococcus aureus fue el germen aislado con más frecuencia (75 por ciento). Otros microorganismos aislados fueron: Streptoccus piogenes y Staphylococcus epidermidis. Sólo en cinco (15,1 por ciento) de las bursitis profundas se obtuvo líquido bursal: el cultivo fue negativo en todos los casos, detectándose la presencia de cristales de hidroxiapatita en un caso. El tratamiento más empleado en las bursitis superficiales consistió en la administración de antibióticos (89,5 por ciento); en cambio, en las bursitis profundas, predominó el uso de la infiltración local de esteroides (57,5 por ciento).Conclusiones: Las diferencias etiológicas encontradas entre las bursitis superficiales y las profundas pueden ser de utilidad a la hora de escoger el tratamiento correcto desde el inicio (AU)

Dorsalgia aguda en mujer de 74 años / Acute back pain in a 74 year old woman

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Complete heart block in an adult with systemic lupus erythematosus and recent onset of hydroxychloroquine therapy.

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.

Septic arthiritis due to Prevotella bivia in a patient with rheumatoid arthritis.

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.

Sudden cochlear hearing loss in a patient with Behçet's disease.

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.