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OBJECTIVES: N-acetylcysteine (NAC) is used in Sjögren's disease (SjD) based on limited evidence. The aim of this study was to assess the efficacy of NAC for relieving dryness symptoms in SjD. METHODS: In this placebo-controlled double-blind trial, 60 adult SjD females (with low disease activity) were randomised to receive NAC (1,200 mg/day orally) or placebo. At baseline (D0), 30 days (D30) and 90 days (D90), all participants underwent the following evaluations: EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI), Ocular Surface Disease Index (OSDI), Xerostomia Inventory (XI), Leicester Cough Questionnaire (LCQ), unstimulated/stimulated salivary flow, Schirmer's test, and plasma levels of thiobarbituric acid reactive substances (TBARS), glutathione and NAC. RESULTS: At inclusion, both groups were balanced for age, ethnicity, disease duration, ESSPRI, OSDI, XI, Schirmer's test, salivary flow, ESSDAI and topical/systemic treatments (p>0.05). No significant differences were observed between NAC and placebo groups on D30 and D90 regarding ESSPRI, XI, OSDI, LCQ, Schirmer's test, stimulated salivary flow, ESSDAI and topical/systemic treatments (p>0.05). Unstimulated salivary flow was significantly higher in the placebo group on D90 (p=0.018). NAC blood concentrations were significantly higher in the NAC group on D30 (p=0.018) and D90 (p<0.001), however, no differences were found in TBARS and glutathione. Further analysis showed decrease≥1 in ESSPRI in the NAC compared with placebo group on D30 (p=0.045), a result not found on D90 (p=0.696). CONCLUSIONS: NAC is recommended as a rescue therapy for SjD. However, our well-designed study provides novel evidence demonstrating its inefficacy for improving dryness symptoms or reducing oxidative stress. CLINICALTRIALS: gov-NCT04793646.
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Enfermedades del Sistema Nervioso Central , Sarcoidosis , Síndrome de Sjögren , Humanos , Rituximab/efectos adversos , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/tratamiento farmacológico , Enfermedades del Sistema Nervioso Central/diagnóstico , Enfermedades del Sistema Nervioso Central/tratamiento farmacológico , Sarcoidosis/tratamiento farmacológicoRESUMEN
The determination of durability and vaccine-associated protection is essential for booster doses strategies, however data on the stability of SARS-CoV-2 immunity are scarce. Here we assess anti-SARS-CoV-2 immunogenicity decay and incident cases six months after the 2nd dose of Sinovac-CoronaVac inactivated vaccine (D210) in 828 autoimmune rheumatic diseases patients compared with 207 age/sex-balanced control individuals. The primary outcome is the presence of anti-S1/S2 SARS-CoV-2 IgG at 6 months compared to 6 weeks after 2nd vaccine dose for decay evaluation. Secondary outcomes are presence of neutralizing antibodies, percent inhibition by neutralizing, geometric mean titers and cumulative incident cases at 6 months after 2nd dose. Anti-S1/S2 IgG positivity and titers reduce to 23.8% and 38% in patients (p < 0.001) during the six-month follow up and 20% and 51% in controls (p < 0.001), respectively. Neutralizing antibodies positivity and percent inhibition declines 41% and 54% in patients (p < 0.001) and 39.7% and 47% in controls (p < 0.001). Multivariate logistic regression analysis show males (OR = 0.56;95% CI0.40-0.79), prednisone (OR = 0.56; 95% CI0.41-0.76), anti-TNF (OR = 0.66;95% CI0.45-0.96), abatacept (OR = 0.29; 95% CI0.15-0.56) and rituximab (OR = 0.32;95% CI0.11-0.90) associate with a substantial reduction in IgG response at day 210 in patients. Although cellular immunity was not assessed, a decrease of COVID-19 cases (from 27.5 to 8.1/100 person-years; p < 0.001) is observed despite the concomitant emergence and spread of the Delta variant. Altogether we show a reduction in immunity 6-months of Sinovac-CoronaVac 2nd dose, particularly in males and those under immunosuppressives therapies, without a concomitant rise in COVID-19 cases. (CoronavRheum clinicaltrials.gov:NCT04754698).
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COVID-19 , Enfermedades Reumáticas , Vacunas Virales , Abatacept , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19 , Humanos , Inmunoglobulina G , Incidencia , Masculino , Prednisona , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/epidemiología , Rituximab/uso terapéutico , SARS-CoV-2 , Inhibidores del Factor de Necrosis Tumoral , Vacunas de Productos InactivadosRESUMEN
BACKGROUND: Coronary artery aneurysm (CAA) in an uncommon condition usually associated with atherosclerosis, but systemic vasculitides constitute important differential diagnoses. A less recognized cause of CAA, tuberculosis (TB) has also been noted to occur simultaneously in patients with such vascular abnormalities. CASE REPORT: A 60-year-old female presented to the Emergency Department with a non-ST segment elevation myocardial infarction. Angiography demonstrated segmental aneurysms of the left anterior descending coronary artery. Shortly after, she was also diagnosed with cutaneous TB, and treatment was promptly initiated. Reevaluation conducted several months later demonstrated that levels of inflammation markers had significantly decreased. New catheterization of coronary arteries evidenced complete resolution of coronary aneurysm images. CONCLUSION: Due to the clinical and radiologic resolution with only TB treatment, as well as lack of evidence supporting atherosclerotic or vasculitic etiologies, TB can be considered a possible contributor to aneurysm formation in this case. Prospective studies are necessary to reliably demonstrate causality between TB infection and CAA.
RESUMEN
Periodontal disease (POD) may affect rheumatic diseases severity, but there are no data regarding the effect of its treatment on disease activity in SLE patients under immunosuppressive therapy. Forty-nine consecutive SLE patients (SLEDAI ≥ 2) with POD and under corticosteroid and cyclophosphamide pulse therapy (IVCYC) were selected. Periodontal assessment included bleeding gingival index (BGI), probing depth (PD), and probing attachment level (PAL). At entry, POD was defined as BGI > 1 and patients were assigned to groups according to the availability of odontological intervention in TREATED (n = 32) and NOT TREATED (n = 17). SLEDAI and POD parameters were determined at entry and after 3 months. Age, female gender, and race were alike among TREATED and NOT TREATED (p > 0.05). Both groups had also comparable disease duration (10.7 ± 6.8 vs. 11.0 ± 6.6, p = 0.83), IVCYC number (5.8 ± 4.8 vs. 4.5 ± 4.8, p = 0.17), and SLEDAI (5.9 ± 4.2 vs. 6.3 ± 4.3, p = 0.73) as well as POD parameters [BGI (40.8 ± 31.0 vs. 40.7 ± 36.2 %, p = 0.89), PD (1.7 ± 1.8 vs. 1.5 ± 0.60 mm, p = 0.80), and PAL (2.5 ± 1.9 vs. 1.9 ± 1.1 mm, p = 0.18)]. At the end of the study, TREATED group had a significant improvement in SLEDAI (5.9 ± 4.2 vs. 3.4 ± 3.3, p = 0.04) with a paralleled reduction in BGI (40.8 ± 31.0 vs. 15.2 ± 17.2 %, p < 0.01), PD (1.7 ± 1.8 vs. 1.1 ± 0.3 mm, p < 0.01), and PAL (2.5 ± 1.9 vs. 1.7 ± 0.9 mm, p < 0.01). In contrast, SLEDAI (6.3 ± 4.3 vs. 6.0 ± 5.5, p = 0.40) and POD parameters [BGI (p = 0.33), PD (p = 0.91), and PAL (p = 0.39)] remained largely unchanged in NOT TREATED group. Periodontal disease treatment seems to have a beneficial effect in controlling disease activity in SLE patients under immunosuppressive therapy. Therefore, management of this modifiable risk factor is recommended.
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Raspado Dental , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Periodontitis/terapia , Aplanamiento de la Raíz , Adulto , Ciclofosfamida/uso terapéutico , Femenino , Humanos , Lupus Eritematoso Sistémico/complicaciones , Masculino , Periodontitis/complicaciones , Prednisona/uso terapéutico , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto JovenRESUMEN
Avaliação comparativa da qualidade de vida dos pacientes com lúpus eritematoso sistêmico (LES) nas diferentes manifestações clínicas da doença, por meio do questionário SF-36. Métodos - Participaram do estudo 21 sujeitos saudáveis, denominado grupo controle, e 75 pacientes com diagnóstico de LES, agrupados como articular (n=15), renal (n=21), outro (n=17), e remissão (n=22). A qualidade devida foi avaliada pelo questionário SF-36 nos escores Capacidade Funcional (CF), Limitação por Aspecto Físico (LAF), Dor (DOR), Estado Geral de Saúde (EGS), Vitalidade (VIT), Aspectos Sociais (AS), Limitações por Aspectos Emocionais (LAE) e Saúde Mental (SM). Na inclusão foi avaliado o escore do SLEDAI (Systemic Lupus Erythematosus Disease Activity Index). Resultados - O grupo articular apresentou os menores valores em todos os escores e o controle os maiores. No escore CF o grupo articular apresentou valores significativamente menores em relação ao grupo renal (p=0,001) e grupo controle (p=0,001). Na LAF, o grupo articular apresentou escore menor que o controle(p=0,003). Na Dor, o grupo articular esteve menor em relação ao renal (p=0,023), remissão (p=0,041), e controle (p=0,003). No SM o grupo articular esteve menor que o controle (p=0,036). No EGS, o grupo controle se diferenciou do articular (p=0,037), outros (p=0,029), e remissão(p=0,036). Nos itens VIT e LAE não houve diferença entre os grupos. Conclusão - O LES interfere na qualidade de vida dos pacientes avaliados através do SF-36. A manifestação articular é o principal fator de piora comparativamente às demais manifestações...
To compare the quality of life of systemic lupus erythematosus (SLE) patients in different clinical manifestations of disease by means of the SF-36. Methods - The study invited 21 healthy subjects, called the control group and 75 patients with SLE, grouped as articular (n=15), renal (n=21), other (n=17) and remission (n=22). The quality of life was assessed by SF-36 scores in the Functional Capacity (FC), limitations due to Physical Aspect (LAF), Pain (PAIN), General Health (EGS), Vitality (VIT), Social Aspects (AS) , Limitations on the emotional aspects (LAE) and Mental Health (MH). In addition we evaluated the SLEDAI score. Results - The joint group had the lowest values in all control and the highest scores. Score in the CF group had significantly less articulate in relation to the renal group (p = 0.001) and control group (p=0.001). In LAF, the joint group had lower scores than the control (p=0.003). Pain in the joint group was lower than in the kidney (p=0.023), remission (p=0.041) and control (p=0.003). In the SM group was less articulate them the control (p=0.036). In EGS, the control group differed from the joint (p=0.037), other (p=0.029) and remission (p=0.036). In items VIT and LAE no difference between groups. Conclusion - SLE alters the quality of life of patients assessed by the SF-36. The joint demonstration is the main factor in the worsening compared to other events...
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Humanos , Masculino , Lupus Eritematoso Sistémico , Calidad de VidaRESUMEN
OBJECTIVE: To assess the efficacy and safety of pandemic 2009 influenza A (H1N1) in SLE under different therapeutic regimens. METHODS: A total of 555 SLE patients and 170 healthy controls were vaccinated with a single dose of a non-adjuvanted preparation. According to current therapy, patients were initially classified as SLE No Therapy (n = 75) and SLE with Therapy (n = 480). Subsequent evaluations included groups under monotherapy: chloroquine (CQ) (n = 105), prednisone (PRED) ≥20 mg (n = 76), immunosuppressor (IS) (n = 95) and those with a combination of these drugs. Anti-H1N1 titres and seroconversion (SC) rate were evaluated at entry and 21 days post-vaccination. RESULTS: The SLE with Therapy group had lower SC compared with healthy controls (59.0 vs 80.0%; P < 0.0001), whereas the SLE No Therapy group had equivalent SC (72 vs 80.0%; P = 0.18) compared with healthy controls. Further comparison revealed that the SC of SLE No Therapy (72%) was similar to the CQ group (69.5%; P = 0.75), but it was significantly reduced in PRED ≥20 mg (53.9%; P = 0.028), IS (55.7%; P = 0.035) and PRED ≥20 mg + IS (45.4%; P = 0.038). The concomitant use of CQ in each of these later regimens was associated with SC responses comparable with SLE No Therapy group (72%): PRED ≥20 mg + CQ (71.4%; P = 1.00), IS + CQ (65.2%; P = 0.54) and PRED ≥20 mg + IS + CQ (57.4%; P = 0.09). CONCLUSION: Pandemic influenza A H1N1/2009 vaccine response is diminished in SLE under immunosuppressive therapy and antimalarials seems to restore this immunogenicity. Trial registration. www.clinicaltrials.gov, NCT01151644.
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Antimaláricos/administración & dosificación , Subtipo H1N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/administración & dosificación , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Lupus Eritematoso Sistémico/inmunología , Adulto , Antiinflamatorios/administración & dosificación , Cloroquina/administración & dosificación , Estudios de Cohortes , Quimioterapia Combinada , Femenino , Humanos , Sistema Inmunológico/efectos de los fármacos , Sistema Inmunológico/inmunología , Huésped Inmunocomprometido/inmunología , Vacunas contra la Influenza/efectos adversos , Gripe Humana/inmunología , Lupus Eritematoso Sistémico/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Estudios Prospectivos , Adulto JovenRESUMEN
BACKGROUND: Reduced response to pandemic (2009) H1N1 (pH1N1) vaccine in patients with rheumatoid arthritis (RA) was recently reported. OBJECTIVES: To evaluate the contribution of age, disease activity, medication and previous antibody levels to this reduced response. METHODS: 340 adult RA patients and 234 healthy controls were assessed before and 21 days after adjuvant-free influenza A/California/7/2009 (pH1N1) vaccine. Disease activity (DAS28), current treatment and pH1N1 antibody titres were collected. Seroprotection, seroconversion and factor increase in geometric mean titre (GMT) were calculated and adverse events registered. RESULTS: RA and controls showed similar (p>0.05) prevaccination GMT (8.0 vs 9.3) and seroprotection (10.8% vs 11.5%). After vaccination a significant reduction (p<0.001) was observed in all endpoints: GMT and factor increase in GMT, seroprotection and seroconversion rates. Disease activity did not preclude seroconversion or seroprotection and remained unchanged in 97.4% of patients. Methotrexate was the only disease-modifying antirheumatic drug associated with reduced responses (p=0.001). Vaccination was well tolerated. CONCLUSIONS: The data confirmed both short-term anti-pH1N1 vaccine safety and, different from most studies with seasonal influenza, reduced seroprotection in RA patients, unrelated to disease activity and to most medications (except methotrexate). Extrapolation of immune responses from one vaccine to another may therefore not be possible and specific immunisation strategies (possibly booster) may be needed. Clinicaltrials.gov no NCT01151644.
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Artritis Reumatoide/inmunología , Subtipo H1N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Adyuvantes Inmunológicos , Adulto , Anciano , Anticuerpos Antivirales/sangre , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Estudios de Casos y Controles , Femenino , Humanos , Inmunosupresores/uso terapéutico , Vacunas contra la Influenza/efectos adversos , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Despite the WHO recommendation that the 2010-2011 trivalent seasonal flu vaccine must contain A/California/7/2009/H1N1-like virus there is no consistent data regarding its immunogenicity and safety in a large autoimmune rheumatic disease (ARD) population. METHODS: 1668 ARD patients (systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic sclerosis, psoriatic arthritis (PsA), Behçet's disease (BD), mixed connective tissue disease, primary antiphospholipid syndrome (PAPS), dermatomyositis (DM), primary Sjögren's syndrome, Takayasu's arteritis, polymyositis and Granulomatosis with polyangiitis (Wegener's) (GPA)) and 234 healthy controls were vaccinated with a non-adjuvanted influenza A/California/7/2009(H1N1) virus-like strain flu. Subjects were evaluated before vaccination and 21 days post-vaccination. The percentage of seroprotection, seroconversion and the factor increase in geometric mean titre (GMT) were calculated. RESULTS: /st> After immunisation, seroprotection rates (68.5% vs 82.9% p<0.0001), seroconversion rates (63.4% vs 76.9%, p<0.001) and the factor increase in GMT (8.9 vs 13.2 p<0.0001) were significantly lower in ARD than controls. Analysis of specific diseases revealed that seroprotection significantly reduced in SLE (p<0.0001), RA (p<0.0001), PsA (p=0.0006), AS (p=0.04), BD (p=0.04) and DM (p=0.04) patients than controls. The seroconversion rates in SLE (p<0.0001), RA (p<0.0001) and PsA (p=0.0006) patients and the increase in GMTs in SLE (p<0.0001), RA (p<0.0001) and PsA (p<0.0001) patients were also reduced compared with controls. Moderate and severe side effects were not reported. CONCLUSIONS: The novel recognition of a diverse vaccine immunogenicity profile in distinct ARDs supports the notion that a booster dose may be recommended for diseases with suboptimal immune responses. This large study also settles the issue of vaccine safety. (ClinicalTrials.gov #NCT01151644).
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Enfermedades Autoinmunes/inmunología , Subtipo H1N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Enfermedades Reumáticas/inmunología , Adyuvantes Inmunológicos , Adulto , Anticuerpos Antivirales/biosíntesis , Métodos Epidemiológicos , Femenino , Humanos , Tolerancia Inmunológica , Huésped Inmunocomprometido , Vacunas contra la Influenza/efectos adversos , Masculino , Persona de Mediana Edad , Vacunación/efectos adversos , Vacunación/métodos , Adulto JovenRESUMEN
BACKGROUND: The incidence and outcome of Herpes zoster (HZ) in systemic lupus erythematosus (SLE) are not completely defined as well as the relevance to HZ of disease and therapy factors. OBJECTIVE: To determine HZ features in SLE. PATIENTS AND METHODS: SLE patients (1997 update of the American College of Rheumatology classification criteria) with definitive HZ infection were identified from our Lupus Clinic computerized database of 1145 patients. RESULTS: HZ was diagnosed in 51 SLE patients (4.45%) with an annual incidence rate of 6.4 events/1000 patient-years. At HZ diagnosis, mean disease duration was 9.78 +/- 8.37 years, median Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) was 1, and only 17.6% had SLEDAI >or=8. Frequency of manifestations and immunosuppressor use were similar between patients with and without HZ. Forty-two patients (82.5%) with HZ were under prednisone with concomitant immunosuppressive therapy in 66.7%. Thirty-five patients (68.6%) were using immunosuppressors: azathioprine (39.2%), cyclophosphamide (9.8%), and mycophenolate mofetil (9.8%). The mean lymphocyte count was 1219 +/- 803/mm3 (43.1% <1000/mm3 and 17.6% <500/mm3). Only patients using azathioprine and cyclophosphamide had lymphocyte counts <500/mm3 (15% and 40%).All patients received acyclovir, 19.6% had postherpetic neuralgia, and recurrence occurred in only 7.8%. Thoracic nerves were the most involved site (56.8%) followed by lumbar (23.5%). Bacterial suprainfection occurred in 11.7% but was not associated with therapy, lymphocyte count, or SLEDAI scores (P > 0.05). CONCLUSION: This is the largest cohort to determine that HZ is a late SLE complication with some peculiar features, such as good prognosis and typical dermatomal distribution. In addition, we have identified that the major trigger factor for this viral infection in SLE is therapy, particularly the concomitant use of corticosteroid and immunosuppressors, and not active disease.