Objective.To assess longterm effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with psoriatic arthritis (PsA) registered in the Rheumatic Diseases Portuguese Register, exposed to at least 1 TNFi, prospectively followed between 2001 and 2017.Methods.Kaplan-Meier analysis was performed for first-, second-, and third-line TNFi. Responses included European League Against Rheumatism (EULAR) criteria, Disease Activity Index for Psoriatic Arthritis (DAPSA), minimal disease activity (MDA), and Ankylosing Spondylitis Disease Activity Score (ASDAS) at 3 and 6 months. Baseline predictors of discontinuation and response were studied using Cox and multivariable multinomial/logistic regression models.Results.The 750 patients with PsA showed drug retention of 4.1 ± 3.4 years (followup 5.8 ± 3.8 yrs) for first TNFi. Switching to a second (189 patients) or third (50 patients) TNFi further decreased survival by 1.1 years. Female sex, higher baseline 28-joint count Disease Activity Score, and infliximab were predictors of first TNFi discontinuation. After 6 months of the first TNFi, 48.7% of patients achieved a good EULAR criteria response and 20.9% were in DAPSA remission. There were 11.4% in MDA, and 56.4% had a good ASDAS. Responses to the second TNFi were significantly inferior compared to responses to the first TNFi. Female sex and higher baseline Health Assessment Questionnaire–Disability Index were negatively associated with good EULAR response at 3 months, and obesity decreased the chance of response at 6 months.Conclusion.In this study, switching to a second or third TNFi was associated with significantly lower drug survival and response rates for patients with axial and peripheral PsA subtypes. More successful therapeutic approaches will require considering the effect of sex and obesity on TNFi effectiveness.

The health-related QoL utilities of patients with premalignant conditions are similar to those without gastric diseases whereas patients with present cancer show decreased utilities. Moreover, women had consistently lower utilities than men. These results confirm that the use of a single standardized instrument such as the EQ-5D-5L for all stages of the gastric carcinogenesis cascade is feasible and that it captures differences between conditions and gender dissimilarities, being relevant information for authors pretending to conduct further cost-utility analysis.

CD4+ T cells mediate rheumatoid arthritis (RA) pathogenesis through both antibody-dependent and independent mechanisms. It remains unclear how synovial microenvironment impinges on CD4+ T cells pathogenic functions. Here, we identified a TLR4+ follicular helper T (Tfh) cell-like population present in the blood and expanded in synovial fluid. TLR4+ T cells possess a two-pronged pathogenic activity whereby direct TLR4+ engagement by endogenous ligands in the arthritic joint reprograms them from an IL-21 response, known to sponsor antibody production towards an IL-17 inflammatory program recognized to fuel tissue damage. Ex vivo, synovial fluid TLR4+ T cells produced IL-17, but not IL-21. Blocking TLR4 signaling with a specific inhibitor impaired IL-17 production in response to synovial fluid recognition. Mechanistically, we unveiled that T-cell HLA-DR regulates their TLR4 expression. TLR4+ T cells appear to uniquely reconcile an ability to promote systemic antibody production with a local synovial driven tissue damage program.

Mixed cryoglobulinemia is frequently secondary to hepatitis C virus infection. Diagnosis and therapeutic management are challenging, depending on the spectrum and severity of manifestations, as well as on the presence of comorbidities. We describe a case of a 79-year-old woman with a non-cirrhotic hepatitis C virus infection presenting with weakness, arthralgias, purpuric rash with left leg ulcerative lesions, bilateral peripheral sensorimotor polyneuropathy, renal impairment and cardiac failure. The investigation was compatible with a severe type II mixed cryoglobulinemia with multisystemic involvement, including a low-grade B cell lymphoma and concomitant intestinal tuberculosis. Initial management with immunosuppressive therapy with glucocorticoids to control symptoms and simultaneous tuberculosis treatment was required. Unavailability of adequate antiviral treatment led to the need to control the severity of systemic manifestations with rituximab, before the effective aetiological treatment with sofosbuvir and ledipasvir was possible, allowing the definitive resolution of the disease.

Tumor necrosis factor alpha (TNFα) antagonist is recognized as an effective treatment to achieve clinical remission and healing mucosal in patients with moderate to severe active Crohn’s disease. Considering that it plays a central role in immune-mediated modulation, there are some obvious concerns about its long-term safety. There is evidence that it may increase the risk of opportunistic infections such as tuberculosis, particularly reactivation of previous latent infection. Due to the global high incidence of tuberculosis and its frequent severity in immunocompromised patients, the exclusion of latent infection is currently part of the screening prior to anti-TNFα therapy. Only a few cases of life-threatening disseminated tuberculosis have been reported in immunocompromised patients probably related to widespread use of higher-accuracy screening tests, such as interferon-γ release assays. However, despite negative screening, the risk of active tuberculosis infection remains during treatment. In that instance, tuberculosis infection becomes considerably more difficult to diagnose due to its altered pattern presentation (extrapulmonary and disseminated infection) and is harder to treat because of the high rate of resistance and its associated relevant morbidity and mortality. We report an enigmatic case of a miliary tuberculosis despite negative latent infection screening, using interferon-γ release assays, in a Crohn’s disease patient undergoing treatment with infliximab and azathioprine, focusing on the screening and diagnostic and therapeutic challenge. This case enhances the awareness of anti-TNFα therapy management and the need for strategies to diagnose and treat tuberculosis in this context.