Preliminary Study on Pulse Wave Changes in Patients with Inflammatory Arthropathies Treated with bDMARDs.

Background: Patients with inflammatory arthropathies exhibit an increased cardiovascular disease (CVD) risk as compared to the general population, which is not fully quantified by the conventional CVD risk scores. Biotechnological disease-modifying drugs (bDMARDs) have proved beneficial to reduce the overall CVD risk in these patients, although CVD remains a major cause of increased mortality. Since it has been shown that pulse wave parameters and in particular carotid-femoral pulse wave velocity (cfPWV) are predictors of CVD risk, the aim of this study was to evaluate their changes in patients with inflammatory arthropathies before and after bDMARD therapy. Methods: Pulse wave parameters were evaluated with applanation tonometry in patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA), and rheumatoid arthritis (RA), before and after two years of bDMARD therapy. Results: At baseline, cfPWV was significantly associated with age (p < 0.001) and, among pulse wave parameters, the subendocardial viability ratio was negatively associated with C-reactive protein (CRP) (p = 0.04) and the HAQ-disability index (p = 0.03). At baseline, PsA patients showed a higher percentage of male subjects, higher CRP, and the highest cfPWV values (p = 0.048). After two years, pulse wave parameters improved in the AS and RA groups, but not in the PsA group. Conclusions: Our data confirm that pulse wave parameters are potentially reversible after bDMARD therapy, as they improved in AS and RA patients. In PsA patients, there were no changes, which may be due to the higher percentage of male subjects and higher baseline cfPWV values.

Clinical Characterization and Predictive Factors for Progression in a Cohort of Patients with Interstitial Lung Disease and Features of Autoimmunity: The Need for a Revision of IPAF Classification Criteria.

Background and Objectives: The "interstitial pneumonia with autoimmune features" (IPAF) criteria have been criticized because of the exclusion of usual interstitial pneumonia (UIP) patients with a single clinical or serological feature. To classify these patients, the term UIPAF was proposed. This study aims to describe clinical characteristics and predictive factors for progression of a cohort of interstitial lung disease (ILD) patients with at least one feature of autoimmunity, applying criteria for IPAF, specific connective tissue diseases (CTD), and a definition of UIPAF when possible. Methods: We retrospectively evaluated data on 133 consecutive patients with ILD at onset associated with at least one feature of autoimmunity, referred by pulmonologists to rheumatologists from March 2009 to March 2020. Patients received 33 (16.5-69.5) months of follow-up. Results: Among the 101 ILD patients included, 37 were diagnosed with IPAF, 53 with ILD-onset CTD, and 11 with UIPAF. IPAF patients had a lower prevalence of UIP pattern compared to CTD-ILD and UIPAF patients (10.8% vs. 32.1% vs. 100%, p < 0.01). During the follow-up, 4 IPAF (10.8%) and 2 UIPAF (18.2%) patients evolved into CTD-ILD. IPAF patients presented features not included in IPAF criteria, such as sicca syndrome (8.1%), and were more frequently affected by systemic hypertension (p < 0.01). Over one year, ILD progression (greater extent of fibrosis on HRCT and/or decline in PFTs) was less frequent in the IPAF group compared to CTD-ILD and UIPAF (32.3% vs. 58.8% vs. 72.7, p = 0.02). A UIP pattern and an IPAF predicted a faster (OR: 3.80, p = 0.01) and a slower (OR: 0.28, p = 0.02) ILD progression, respectively. Conclusions: IPAF criteria help identify patients who might develop a CTD-ILD, even though a single clinical or serological feature is respected. Future revisions of IPAF criteria should include sicca syndrome and separate UIP-pattern into a different definition (UIPAF), given its association with a different prognosis, independently from ILD classification.

The Combined Use of Tocilizumab and Hemoadsorption in a Patient with SARS-COV-2-19-Associated Pneumonia: A Case Report.

The SARS-COV-2-19-associated respiratory involvement is caused by the massive release of inflammatory cytokines ultimately leading to interstitial pneumonia and acute respiratory distress syndrome (ARDS). In the absence of an effective antiviral treatment, a reasonable causal approach could be constituted by the neutralization of these substances. The authors describe the clinical course of a patient with SARS-COV-2-19 interstitial pneumonia treated with the combination of an anti-interleukin 6 (IL-6) agent (tocilizumab) and hemoadsorption (HA). This combination was used to abate the surge of inflammatory mediators leading to the lung damage. Blood levels of IL-6 and C-reactive protein (CRP) were measured before the initiation of the treatment and in the following 3 days. At the end of the treatment, the values of IL-6 and CRP decreased from 1,040 to 415 pg/mL and from 229 to 59 mg/L, respectively. The gas exchanges and the chest imaging rapidly improved, and the patient was extubated 10 days later. The combination of tocilizumab and HA could be valuable in the treatment of SARS-COV-2-19-associated pneumonia and ARDS that are caused by the release of inflammatory mediators.

Sudden hearing loss and Crohn disease: when Cogan syndrome must be suspected.

Cogan's syndrome is a rare systemic vasculitis of unknown origin. It is characterized by the presence of worsening audiovestibular and ocular symptoms that may manifest simultaneously or sequentially. No specific diagnostic laboratory tests or imaging studies exist. The diagnosis is clinical and should be established as early as possible so as to initiate prompt treatment with steroids and prevent rapid progression to deafness or blindness and potentially fatal systemic involvement. We report a case of association between Cogan's syndrome and ileal Crohn's disease which we believe deserves attention since, after an accurate review of the literature, we have found approximately 250 reports of patients with Cogan's syndrome, only 13 of whom with concurrent chronic inflammatory bowel disease; of these 13 cases, none experienced improvement after therapy. In the light of the good outcome obtained in our case, we proposed a valid treatment option with boluses of steroids, combined with early systemic immunosuppression and intra-tympanic steroid injections.

Tumour necrosis factor alpha inhibitor therapy and rehabilitation for the treatment of ankylosing spondylitis: a systematic review.

OBJECTIVES: To systematically review the evidence for a synergistic effect of combining rehabilitation with biological anti-tumour necrosis factor (TNF) therapy in patients with ankylosing spondylitis (AS). METHODS: Data were analysed to identify the most effective rehabilitation programmes, the best endpoints for effectiveness, and patient subgroups most likely to benefit from combination therapy. Systematic MEDLINE and Embase searches were performed to identify studies evaluating rehabilitation programmes and biological therapy in patients with AS. Evidence was categorised by study type, and efficacy, adverse effects and other outcomes were summarised. RESULTS: Of the 75 studies identified, 13 investigated the combination of a rehabilitation programme with TNF inhibitor therapy, while the remainder studied rehabilitation with standard therapy (often not specified). Data from these few studies suggest that combined rehabilitation plus anti-TNF therapy is more effective in terms of symptom severity, disease activity, disability and quality-of-life indices versus biologic alone or rehabilitation with standard medical therapy, or, in non-comparative studies, compared with baseline. The most effective rehabilitation appears to be supervised or in-patient programmes with an educational component. Available data do not provide guidance on most appropriate endpoints or identify patients most likely to benefit from combination therapy. Combined, TNF inhibitor and rehabilitation therapy appear to have a synergistic effect, possibly due to increased adherence to exercise. Exercise regimes are more effective if supervised and include an education component. CONCLUSIONS: Further randomized, controlled trials comparing endpoints and investigating longer-term benefits of combining TNF inhibitors with rehabilitation in different AS subgroups are needed.

The 158VV Fcgamma receptor 3A genotype is associated with response to rituximab in rheumatoid arthritis: results of an Italian multicentre study.

OBJECTIVE: The polymorphism 158V/F of Fc fragment of IgG (FCGR) type 3A may influence the response to rituximab (RTX) in rheumatoid arthritis (RA). We investigated the FCG3A polymorphism in a large cohort of RA patients treated with RTX, also by considering the possible loss of response from month +4 to +6 after RTX and the presence of established predictors of response. METHODS: The study analysed 212 RA patients. European League Against Rheumatism (EULAR) response was evaluated at months +4 and +6 after the first RTX infusion. The FCGR3A polymorphism was analysed by PCR followed by Sanger sequencing. RESULTS: The FCGR3A genotypes were associated with EULAR response (good or moderate) at month +6 (response in 34/38 (89.5%) VV vs 70/106 (66%) VF and in 51/77 (66.2%) FF patients; p=0.01), but not at month +4 (response in 32/37 (86.5%) VV vs 69/102 (67.6%) VF and 53/73 (72.6%) FF patients; p=0.09). Loss of response was observed only in VF and FF carriers ((VV vs VF vs FF: 0/37 (0%) vs 11/102 (10.8%) vs 12/73 (16.4%); p=0.02)). Probability of response at month +6 was very high when at least two of the three following items selected by multivariate analysis were present: positive rheumatoid factor and/or anticyclic citrullinated peptide antibodies, previous treatment with ≤ 1 anti-tumor necrosis factor (TNF) agent, and 158VV FCGR3A genotype (p<0.0001; OR 7.9, 95% CI 4.1 to 15.1). CONCLUSIONS: The 158VV FCGR3A genotype was associated with response to RTX in a large cohort of RA patients. Patient genotyping may be helpful to plan RTX treatment, and may be integrated with clinical predictors.

Mononuclear cell response to lipopolysaccharide in patients with rheumatoid arthritis: relationship with tristetraprolin expression.

OBJECTIVE: To analyze tumor necrosis factor-alpha (TNF-alpha) synthesis by mononuclear cells stimulated with lipopolysaccharide (LPS) in patients with rheumatoid arthritis (RA). METHODS: TNF-alpha molecular expression and extracellular release were assessed in the peripheral blood mononuclear cells (PBMC) of 27 RA patients and 16 healthy blood donor controls during 8 hours of LPS stimulation. We also analyzed the mRNA expression of tristetraprolin (TTP), the major TNF-alpha mRNA destabilizing factor. TNF receptor p75 (TNFR 2) plasma concentrations were also tested in all patients. RESULTS: Controls and patients demonstrated a comparable wide range of TNF-alpha release capability, but patients achieved the peak value of protein release more quickly. Defining the median TNF-alpha release in controls as the cutoff value to distinguish high and low LPS-induced TNF-alpha-releasing phenotypes, patients with early RA (disease duration < 1 yr) belonged mainly to the low TNF-alpha producer subgroup, whereas patients with long-standing RA (> 1 yr) were prevalently high TNF-alpha producers. TTP molecular expression was higher in patients with shorter, than in patients with longer, disease duration. The profile of TNF-alpha release in patients with early RA changed significantly when retested after 6 months of therapy, while patients with long-standing disease maintained the same behavior as at baseline. Finally, a baseline low TNF-alpha-producer phenotype predisposed to a better responsiveness to disease modifying antirheumatic drugs. CONCLUSION: The LPS-induced TNF-alpha-releasing phenotype differs between cells obtained from RA patients with different disease durations and seems to influence the therapeutic outcome.