Performance of 4 methods for screening of latent tuberculosis infection in patients with chronic inflammatory arthritis under TNFα inhibitors: a 24-month prospective study

Background The reactivation rate of tuberculosis in patients with chronic inflammatory arthritis (CIA) on TNFα inhibitors (TNFi) and baseline negative screening for latent tuberculosis infection (LTBI) is higher than in the general population. Aim To compare the performance of tuberculin skin test (TST), TST-Booster, ELISPOT (T-SPOT.TB) and QuantiFERON-TB Gold in tube (QFT-IT) to detect LTBI in patients with CIA on TNFi. Patients and methods A total of 102 patients with CIA [rheumatoid arthritis (RA), n = 40; ankylosing spondylitis (AS), n = 35; psoriatic arthritis (PsA), n = 7; and juvenile idiopathic arthritis (JIA), n = 20] were prospectively followed-up for 24 months to identify incident LTBI cases. Epidemiologic data, TST, T-SPOT.TB, QFT-IT and a chest X-ray were performed at baseline and after 6 months of LTBI treatment. Results Thirty six percent (37/102) of patients had positive TST or Interferon Gamma Release Assays (IGRAs) tests. Agreement among TST and IGRAs was moderate (k = 0.475; p = 0.001), but high between T-SPOT.TB and QFT-IT (k = 0.785; p < 0.001). During the 24-Month follow-up, 15 (18.5%) incident cases of LTBI were identified. In comparison to TST, the IGRAs increased the LTBI diagnosis power in 8.5% (95% CI 3.16–17.49). TST-Booster did not add any value in patients with negative TST at baseline. After 6-Month isoniazid therapy, IGRAs results did not change significantly. Conclusions Almost 20% of CIA patients had some evidence of LTBI, suggesting higher conversion rate after exposition to TNFi. TST was effective in identifying new cases of LTBI, but IGRAs added diagnostic power in this scenario. Our findings did not support the repetition of IGRAs after 6-Month isoniazid therapy and this approach was effective to mitigate active TB in 2 years of follow-up.

Ex vivo Demonstration of Functional Deficiencies in Popliteal Lymphatic Vessels From TNF-Transgenic Mice With Inflammatory Arthritis

Background: Recent studies demonstrated lymphangiogenesis and expansion of draining lymph nodes during chronic inflammatory arthritis, and lymphatic dysfunction associated with collapse of draining lymph nodes in rheumatoid arthritis (RA) patients and TNF-transgenic (TNF-Tg) mice experiencing arthritic flare. As the intrinsic differences between lymphatic vessels afferent to healthy, expanding, and collapsed draining lymph nodes are unknown, we characterized the ex vivo behavior of popliteal lymphatic vessels (PLVs) from WT and TNF-Tg mice. We also interrogated the mechanisms of lymphatic dysfunction through inhibition of nitric oxide synthase (NOS).Methods: Popliteal lymph nodes (PLNs) in TNF-Tg mice were phenotyped as Expanding or Collapsed by in vivo ultrasound and age-matched to WT littermate controls. The PLVs were harvested and cannulated for ex vivo functional analysis over a relatively wide range of hydrostatic pressures (0.5–10 cmH2O) to quantify the end diastolic diameter (EDD), tone, amplitude (AMP), ejection fraction (EF), contraction frequency (FREQ), and fractional pump flow (FPF) with or without NOS inhibitors Data were analyzed using repeated measures two-way ANOVA with Bonferroni’s post hoc test.Results: Real time videos of the cannulated PLVs demonstrated the predicted phenotypes of robust vs. weak contractions of the WT vs. TNF-Tg PLV, respectively. Quantitative analyses confirmed that TNF-Tg PLVs had significantly decreased AMP, EF, and FPF vs. WT (p &lt; 0.05). EF and FPF were recovered by NOS inhibition, while the reduction in AMP was NOS independent. No differences in EDD, tone, or FREQ were observed between WT and TNF-Tg PLVs, nor between Expanding vs. Collapsed PLVs.Conclusion: These findings support the concept that chronic inflammatory arthritis leads to NOS dependent and independent draining lymphatic vessel dysfunction that exacerbates disease, and may trigger arthritic flare due to decreased egress of inflammatory cells and soluble factors from affected joints.

PsAID High-impact Disease in Psoriatic Arthritis: A Component Weighting Analysis of the Assessment of SpondyloArthritis international Society Health Index

Psoriatic arthritis (PsA) is a chronic inflammatory arthritis that affects almost one-third of patients with psoriasis. PsA is a relatively common inflammatory condition in rheumatology clinics. In fact, a recent epidemiological study raised the prevalence of PsA to almost 0.6% in the general population in Spain.1

AB0821 PSYCHOMETRIC PROFILE OF PATIENTS WITH CHRONIC INFLAMMATORY ARTHRITIS

Background:Psoriatic Arthritis (PsA) is a chronic inflammatory disease characterized by a condition of inflammation of joint and periarticular tissues with progressive destruction of bone and cartilage tissues and consequent disability. Numerous studies suggest that the systemic inflammation that characterizes this disease is the basis of the onset of numerous comorbidities, including anxiety and depression.Objectives:This prospective study aims to examine the psychometric profile of patients with chronic inflammatory arthritis to investigate possible correlations with psychiatric comorbidities and disease status.Methods:from October 2018 to March 2019, consecutive out-patients with PsA (according to CASPAR criteria) referred to the Rheumatology Unit of the University of Rome Tor Vergata, were evaluated by a dedicated psychiatrist for attachment style (Relationship Questionnaire - RQ), alexithymia (Toronto Alexithymia Scale - TAS20), perceived stress (Perceived Stress Scale - PSS) and depressive symptoms (Beck Depression Inventory - BDI). These indices were then correlated with clinimetric indices, indices of inflammation and therapy taken by the patient. Statistical analysis was performed using Fisher’s exact test and Pearson’s correlation coefficient.Results:33 patients affected by PsA and 40 healthy individuals as control group were enrolled. The RQ test showed that in patients an insecure “avoidant” attachment style prevails (51.5%) compared to the control group (10%) (p<0.0008)[Figure 1]. This result correlates with the presence of alexithymia and with the duration of illness, showing that patients with an “insecure” profile at the RQ test are those who have higher scores on the TAS-20 scale (p=0.035) and a longer duration of illness (p<0.0001). Regarding the perception of stress, at the PSS test women have mean values (18.12±7.31) statistically superior to the values of the male population (11.69±7.79)(p=0.0015). PSS values of the overall study population were directly proportional to RQ values (p<0.0068) and TAS-20 values (p<0.0001). The correlation between PSS and TAS-20 was further confirmed in the analysis of the individual subgroups “patients” (p<0.0001) and control group (p<0.0001)[Figure 2]. No correlation was shown with phlogosis and clinimetric indices.Conclusion:This study suggests how PsA patients are a more vulnerable subtype of patient from the psychological point of view, with an avoidant attachment style, characterized by the difficulty to express emotions and to rely on others in times of need. These characteristics can influence the adherence to pharmacological therapies and the doctor-patient relationship. This profile is manifested more frequently in female patients, with long duration of illness, high perception of stress. The state of disease activity does not influence these elements, suggesting that the insecure attachment style is not related to the single inflammatory flare, but is the result of years of illness and long-standing disease. Our results support the relevance of early diagnosis in PsA.Disclosure of Interests:None declared

Mechanisms and Mediators of Pain in Chronic Inflammatory Arthritis

Purpose of the review Pain in chronic inflammatory joint diseases is a common symptom reported by patients. Pain becomes of absolute clinical relevance especially when it becomes chronic, i.e., when it persists beyond normal healing times. As an operational definition, pain is defined chronic when it lasts for more than 3 months. This article aims to provide a review of the main mechanisms underlying pain in patients with chronic inflammatory joint diseases, discussing in particular their overlap. Recent findings While it may be intuitive how synovial inflammation or enthesitis are responsible for nociceptive pain, in clinical practice, it is common to find patients who continue to complain of symptoms despite optimal control of inflammation. In this kind of patients at the genesis of pain, there may be neuropathic or nociplastic mechanisms. Summary In the context of chronic inflammatory joint diseases, multiple mechanisms generally coexist behind chronic pain. It is the rheumatologist’s task to identify the mechanisms of pain that go beyond the nociceptive mechanisms, to adopt appropriate therapeutic strategies, including avoiding overtreatment of patients with immunosuppressive drugs. In this sense, future research will have to be oriented to search for biomarkers of non-inflammatory pain in patients with chronic inflammatory joint diseases.

Impact of corticosteroids and immunosuppressive therapies on symptomatic SARS-CoV-2 infection in a large cohort of patients with chronic inflammatory arthritis

Background: Prevalence and outcomes of Coronavirus Disease (COVID)-19 in relation to immunomodulatory medications are still unknown. The aim of the study is to investigate the impact of glucocorticoids and immunosuppressive agents on COVID-19 in a large cohort of patients with chronic immune-mediated inflammatory arthritis.Methods: The study was conducted in the arthritis outpatient clinic at two large Academic Hospitals in the COVID-19 most endemic area of Northern Italy (Lombardy). We circulated a cross-sectional survey exploring the prevalence of Severe Acute Respiratory Syndrome-Coronavirus-2 nasopharyngeal swab positivity and the occurrence of acute respiratory illness (fever and/or cough and/or dyspnea), administered face-to-face or by phone to consecutive patients from 25th February to 20th April 2020. COVID-19 cases were defined as confirmed or highly suspicious according to the World Health Organization criteria. The impact of medications on COVID-19 development was evaluated. Results: The study population included 2050 adults with chronic inflammatory arthritis receiving glucocorticoids, conventional-synthetic (cs), or targeted-synthetic/biological (ts/b) disease-modifying drugs (DMARDs). Laboratory-confirmed COVID-19 and highly suspicious infection were recorded in 1.1% and 1.4% of the population, respectively. Treatment with glucocorticoids was independently associated with increased risk of COVID-19 (adjusted OR [95% CI] ranging from 1.23 [1.04-1.44] to 3.20 [1.97-5.18] depending on the definition used). Conversely, patients treated with ts/bDMARDs were at reduced risk (adjusted OR ranging from 0.46 [0.18-1.21] to 0.47 [0.46-0.48]). No independent effects of csDMARDs, age, sex, and comorbidities were observed.Conclusions: During the COVID-19 outbreak, treatment with immunomodulatory medications appears safe. Conversely, glucocorticoids, even at low-dose, may confer increased risk of infection.Trial registration: retrospectively registered

Impact of corticosteroids and immunosuppressive therapies on symptomatic SARS-CoV-2 infection in a large cohort of patients with chronic inflammatory arthritis

Background Prevalence and outcomes of coronavirus disease (COVID)-19 in relation to immunomodulatory medications are still unknown. The aim of the study is to investigate the impact of glucocorticoids and immunosuppressive agents on COVID-19 in a large cohort of patients with chronic immune-mediated inflammatory arthritis. Methods The study was conducted in the arthritis outpatient clinic at two large academic hospitals in the COVID-19 most endemic area of Northern Italy (Lombardy). We circulated a cross-sectional survey exploring the prevalence of severe acute respiratory syndrome-coronavirus-2 nasopharyngeal swab positivity and the occurrence of acute respiratory illness (fever and/or cough and/or dyspnea), administered face-to-face or by phone to consecutive patients from 25 February to 20 April 2020. COVID-19 cases were defined as confirmed or highly suspicious according to the World Health Organization criteria. The impact of medications on COVID-19 development was evaluated. Results The study population included 2050 adults with chronic inflammatory arthritis receiving glucocorticoids, conventional-synthetic (cs), or targeted-synthetic/biological (ts/b) disease-modifying drugs (DMARDs). Laboratory-confirmed COVID-19 and highly suspicious infection were recorded in 1.1% and 1.4% of the population, respectively. Treatment with glucocorticoids was independently associated with increased risk of COVID-19 (adjusted OR [95% CI] ranging from 1.23 [1.04–1.44] to 3.20 [1.97–5.18] depending on the definition used). Conversely, patients treated with ts/bDMARDs were at reduced risk (adjusted OR ranging from 0.46 [0.18–1.21] to 0.47 [0.46–0.48]). No independent effects of csDMARDs, age, sex, and comorbidities were observed. Conclusions During the COVID-19 outbreak, treatment with immunomodulatory medications appears safe. Conversely, glucocorticoids, even at low-dose, may confer increased risk of infection. Trial registration Retrospectively registered. Not applicable.