Lymphoprolipherative skin reactions induced by anti-TNFα: an open question.
抗tnf α 诱导的淋巴滞留性皮肤反应: 一个悬而未决的问题。
- 作者列表："Nikolaou V","Gerochristou M","Marinos L","Economidi A","Voudouri D","Rigopoulos D","Stratigos AJ
:Although anti-TNFα agents have revolutionized the treatment of many inflammatory diseases, various concerns have been reported regarding the risks of cancer development, as well as acceleration of the progression of subclinical, preexisting malignancies. In this case series, we investigated the provocative effect of anti-TNFα drugs in the development of cutaneous mycosis fungoides (MF)-like lymphoproliferative reactions. We describe five patients aged between 25-63 diagnosed with autoimmune disorders (psoriatic arthritis - one patient, Crohn's disease - one patient and ankylosing spondylitis - three patients) who received anti-TNFα agents before the development of a cutaneous lymphoproliferative reaction. Histological and immunophenotypical analysis was typical for mycosis fungoides in all of them. Anti-TNFα agents were stopped with regression of the skin rash. A direct effect of anti-TNFα agents in the development of lymphoproliferative reactions (including MF) is suggested and further analyzed. Treatment cessation can be therapeutic.
虽然抗tnf α 药物已经彻底改变了许多炎症性疾病的治疗，但已经报道了关于癌症发展风险以及加速亚临床、先前存在的恶性肿瘤进展的各种担忧。在本病例系列中，我们研究了抗tnf α 药物在皮肤蕈样肉芽肿 (MF) 样淋巴增生反应发生中的激发作用。我们描述了 5 例年龄在 25-63 岁之间诊断为自身免疫性疾病的患者 (银屑病关节炎-1 例患者，克罗恩病-1 例患者和强直性脊柱炎-3 例患者) 在发生皮肤淋巴增生反应之前接受了抗tnf α 药物。所有患者的蕈样肉芽肿的组织学和免疫表型分析都是典型的。随着皮疹消退，停用抗tnf α 药物。建议并进一步分析抗tnf α 药物在淋巴增生反应 (包括MF) 发展中的直接作用。停止治疗可以是治疗性的。
METHODS:OBJECTIVE:Patients with immune-mediated inflammatory diseases such as rheumatoid arthritis or systemic lupus erythematosus are at increased risk of cardiovascular disease. However, the cardiovascular risk of patients with primary Sjögren's syndrome (SS) remains poorly studied. We aimed to investigate the association between primary SS and cardiovascular morbidity and mortality. METHODS:We performed a systematic review of articles in Medline and the Cochrane Library and recent abstracts from US and European meetings, searching for reports of randomized controlled studies of cardiovascular morbidity and cardiovascular mortality in primary SS. The relative risk (RR) values for cardiovascular morbidity and mortality associated with primary SS were collected and pooled in a meta-analysis with a random-effects model by using Review Manager (Cochrane collaboration). RESULTS:The literature search revealed 484 articles and abstracts of interest; 14 studies (67,124 patients with primary SS) were included in the meta-analysis. With primary SS versus control populations, the risk was significantly increased for coronary morbidity (RR 1.34 [95% confidence interval (95% CI) 1.06-1.38]; P = 0.01), cerebrovascular morbidity (RR 1.46 [95% CI 1.43-1.49]; P < 0.00001), heart failure rate (odds ratio 2.54 [95% CI 1.30-4.97]; P < 0.007), and thromboembolic morbidity (RR 1.78 [95% CI 1.41-2.25]; P < 0.00001), with no statistically significant increased risk of cardiovascular mortality (RR 1.48 [95% CI 0.77-2.85]; P = 0.24). CONCLUSION:This meta-analysis demonstrates that primary SS is associated with increased cardiovascular morbidity, which suggests that these patients should be screened for cardiovascular comorbidities and considered for preventive interventions, in a multidisciplinary approach with cardiologists.
METHODS:OBJECTIVE:We aimed to evaluate the comparative risk of hospitalized infection among patients with rheumatoid arthritis (RA) who initiated abatacept versus a tumor necrosis factor inhibitor (TNFi). METHODS:Using claims data from Truven MarketScan database (2006-2015), we identified patients with RA ages ≥18 years with ≥2 RA diagnoses who initiated treatment with abatacept or a TNFi. The primary outcome was a composite end point of any hospitalized infection. Secondary outcomes included bacterial infection, herpes zoster, and infections affecting different organ systems. We performed 1:1 propensity score (PS) matching between the groups in order to control for baseline confounders. We estimated incidence rates (IRs) and hazard ratios (HRs) with 95% confidence intervals (95% CIs) for hospitalized infection. RESULTS:We identified 11,248 PS-matched pairs of patients who initiated treatment with abatacept and TNFi with a median age of 56 years (83% were women). The IR per 1,000 person-years for any hospitalized infection was 37 among patients who initiated treatment with abatacept and 47 in those who initiated treatment with TNFi. The HR for the risk of any hospitalized infection associated with abatacept versus TNFi was 0.78 (95% CI 0.64-0.95) and remained lower when compared to infliximab (HR 0.63 [95% CI 0.47-0.85]), while no significant difference was seen when compared to adalimumab and etanercept. The risk of secondary outcomes was lower for abatacept for pulmonary infections, and similar to TNFi for the remaining outcomes. CONCLUSION:In this large cohort of patients with RA who initiated treatment with abatacept or TNFi as a first- or second-line biologic agent, we found a lower risk of hospitalized infection after initiating abatacept versus TNFi, which was driven mostly by infliximab.
METHODS:OBJECTIVE:Reducing pain is one of the main health priorities for children and young people with juvenile idiopathic arthritis (JIA); however, some studies indicate that pain is not routinely assessed in this patient group. The aim of this study was to explore health care professionals' (HCPs) beliefs about the role of pain and the prioritization of its assessment in children and young people with JIA. METHODS:Semi-structured interviews were conducted with HCPs who manage children and young people with JIA in the UK (including consultant and trainee pediatric rheumatologists, nurses, physical therapists, and occupational therapists). Data were analyzed qualitatively following a framework analysis approach. RESULTS:Twenty-one HCPs participated. Analyses of the data identified 6 themes, including lack of training and low confidence in pain assessment, reluctance to engage in pain discussions, low prioritization of pain assessment, specific beliefs about the nature of pain in JIA, treatment of pain in JIA, and undervaluing pain reports. Assessment of pain symptoms was regarded as a low priority and some HCPs actively avoided conversations about pain. CONCLUSION:These findings indicate that the assessment of pain in children and young people with JIA may be limited by knowledge, skills, and attitudinal factors. HCPs' accounts of their beliefs about pain in JIA and their low prioritization of pain in clinical practice suggest that a shift in perceptions about pain management may be helpful for professionals managing children and young people with this condition.