Increased Neutrophil-to-Lymphocyte Ratio as a Marker of Systemic Immunity in Lichen Sclerosus Alessia Paganelli, Alessandra Corrente, Roberta Priori, Giovanni Di Zenzo, Francesco Moro, et al. Dermatology Practical and Conceptual, 2026 Introduction: Lichen sclerosus (LS) is a chronic inflammatory dermatosis traditionally considered a localized condition, yet associations with autoimmune comorbidities and circulating autoantibodies suggest possible systemic immune involvement. The neutrophil-to-lymphocyte ratio (NLR) is an inexpensive biomarker of systemic inflammation and frailty, but its role in LS has not been investigated. Aims: To evaluate NLR values in patients with LS and assess whether LS is associated with systemic inflammatory changes. Methods: This single-center retrospective observational study analyzed anonymized laboratory data from patients diagnosed with LS at IDI-IRCCS (Rome, Italy) between January 2020 and January 2025. Full blood count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), age, and sex were collected. Patients were subdivided into three age groups (<65, 65–74, ≥75 years). Welch’s ANOVA and t-tests assessed group differences; chi-square tests examined NLR frailty-range distribution; Pearson correlations evaluated associations with CRP and ESR. Results: A total of 631 samples were included. Mean NLR was 2.34 ±1.36, increasing significantly with age (P=0.02). Approximately one third of patients fell within frailty-associated NLR ranges. Among adults <65 years, mean NLR (2.17 ±1.00) was significantly higher than in two healthy control cohorts (1.85 ± 0.64 and 1.65 ± 1.96; both P<0.01). NLR correlated moderately with ESR (r=0.47) and modestly with CRP (r=0.36). Conclusions: LS is associated with higher NLR values than those observed in healthy controls, indicating mild systemic inflammation. These findings support the concept that LS may not be exclusively localized but may involve broader immune dysregulation. NLR may help identify LS patients with potential systemic involvement, although prospective validation is required.
Heat-not-burn tobacco induces protein post-translational modifications and apoptosis in bronchial cells: possible role in rheumatoid arthritis Claudia Ciancarella, Federica Maria Ucci, Valeria Manganelli, Tina Garofalo, Elena Fasciolo, et al. Rmd Open, 2026 Objectives Smoking is recognised as one of the strongest environmental risk factors for the development of rheumatoid arthritis (RA). Cigarette smoke increases protein post-translational modifications (PTMs), including citrullination and carbamylation, involved in the pathogenetic mechanisms of RA. Recently, tobacco companies developed new products, such as iQOS, a heat-not-burn cigarette (HNBC), which are becoming increasingly used. To date, only two epidemiological studies have been conducted in the rheumatology field. However, no studies are available on the effects of HNBCs on the pathogenic mechanisms involved in rheumatic diseases. We aimed to evaluate whether HNBCs are associated with an increase in PTMs and their effects on cell death mechanisms, such as apoptosis. Methods Human bronchial cells (BEAS-2B) were treated with cigarette smoke extracts from traditional cigarettes (TC) and HNBC. Western blot was performed to assess protein citrullination and carbamylation, while apoptosis was assessed by flow cytometry, after staining with annexin V-FITC/PI and western blot through enzyme Parp1 evaluation. Results The exposure of BEAS-2B to HNBC or TC extracts causes significantly increased citrullination and carbamylation of proteins, compared with untreated cells. Furthermore, it leads to an augmentation of apoptosis, evaluated through annexin V-FITC/PI and enzyme Parp1 levels. Conclusion Our results show that the extracts of HNBC and TC increase citrullination, carbamylation and influence cell death, causing an activation of apoptosis. This is the first study showing the effects of HNBC on PTMs and cell death mechanisms, raising alarm about the safety of these smoking alternatives in rheumatology. These data allow us to speculate that HNBC, like TC, could represent a risk factor for the development of RA in genetically susceptible individuals.
PASSing to the patient side: early achieving of an acceptable symptom state in patients with rheumatoid arthritis treated with Janus kinase inhibitors C. Garufi, S. Mancuso, F. Ceccarelli, L. Caruso, C. Alessandri, et al. Reumatismo, 2025 Objective. Patients Acceptable Symptom State (PASS) is a single dichotomized question assessing health satisfaction. We aimed to investigate PASS achievement within 4 weeks of treatment with Janus kinase (JAK) inhibitors (Jakinibs) and its association with treatment response after 4 and 12 weeks in rheumatoid arthritis (RA) patients. Methods. We recruited consecutive RA patients starting baricitinib or tofacitinib. At baseline, 4 and 12 weeks, we calculated disease activity [Disease Activity Score on 28 joints (DAS28), Clinical Disease Activity Index, Simplified Disease Activity Index], disease status [remission and low-disease activity (LDA)], percentage of patients achieving PASS, and the time to attain PASS. We assessed the impact of clinically relevant variables on PASS achievement by logistic regression analysis. Results. We enrolled 113 patients [98 (86.7%) females; median age 59.6 (interquartile range 16.9), median disease duration 144 (132) months]. 90 (79.6%) patients achieved PASS after 10 (8) days. A similar percentage of PASS achievers and non-achievers was in remission/LDA at weeks 4 and 12, but the reduction of disease activity was significantly greater in PASS achievers. All patients achieving Boolean remission at weeks 4 and 12 had achieved PASS within 4 weeks. The impact of Patients Global Assessment (PGA) on DAS28 was significantly greater in PASS non-achievers compared to PASS achievers; inversely, the impact of C-reactive protein was more relevant in PASS achievers. At multivariate analysis, pain and PGA were significantly associated with PASS. Conclusions. In our cohort, Jakinibs allowed an early achievement of PASS in a great percentage of RA patients. PASS is strictly dependent on PGA and pain and could suggest, early in the management of RA patients, therapeutic success.
Adherence to vaccination against SARS-CoV-2 and vaccine safety in patients with IgG4-related disease Linda Mastromanno, Federico Giardina, Angelica Gattamelata, Serena Colafrancesco, Simona Truglia, et al. Reumatismo, 2025 Objective. To assess the adherence to the vaccination campaign against SARS-CoV-2 in patients with IgG4-related disease (IgG4-RD) and to evaluate the development of local and systemic adverse events (AEs) following vaccination. Additionally, to investigate the rate and outcome of SARS-CoV-2 infection in IgG4-RD patients. Methods. Patients with IgG4-RD in follow-up before the onset of the SARS-CoV-2 pandemic were contacted by telephone and asked to answer an ad hoc questionnaire regarding their vaccination status against SARS-CoV-2 and related AEs following vaccination. The occurrence and the outcome of SARS-CoV-2 infection were also recorded. The same questionnaire was proposed to healthy controls (HC). Results. 20 patients and 40 HC were enrolled. In the patient’s cohort, 90% were vaccinated with at least one dose; among them, 11 reported AEs: 61.1% systemic and 22.2% local. Within the HC group, 100% were vaccinated with at least one dose. 20 out of 40 HC had systemic AEs (50%), and 27 (67.5%) reported local AEs. Neither in IgG4-RD nor in HC, serious adverse reactions were observed. Among the patient’s cohort, 60% contracted SARS-CoV-2 infection, and 41.67% were on immunosuppressants at the time of the infection. One patient presented with severe COVID-19. No disease flares following vaccination or infection were reported. Conclusions. Results from our study indicate good adherence to the vaccination campaign against SARS-CoV-2 in patients with IgG4-RD and support a relatively good safety profile of this vaccine. Compared to controls, patients with IgG4-RD reported slightly more systemic AEs and fewer local AEs. A similar rate of COVID-19 development was observed between IgG4-RD patients and HC.
Exposure to air pollution as an environmental determinant of how Sjögren’s disease is expressed at diagnosis Clinical and Experimental Rheumatology, 2023
