Microbiota and arthritis: cause or consequence?

The relationship between intestinal microbiota and arthritis has garnered significant attention, with emerging evidence suggesting a potential association between dysbiosis and various forms of inflammatory arthropathies. While observational studies have provided valuable insights into microbiota alterations in patients with arthritis, establishing causality remains challenging. Observational data, influenced by multiple confounders such as environmental factors, medication effects, and dietary habits, are insufficient to conclusively determine whether microbiota changes are somehow causally linked to arthritis. The heterogeneity of results across independent studies further complicates interpretation. To further support this hypothesis, interventional randomised trials are deemed necessary, yet their implementation in this area presents significant technical limitations. Experimental animal models offer insights into potential pathogenic mechanisms linking dysbiosis to arthritis, including compromised intestinal barrier function, the role of microbiota-derived metabolites and molecular mimicry. However, conflicting findings underscore the complexity of hostmicrobiota interactions and the challenges in establishing causality.Efforts to modulate the microbiota for arthritis treatment or prevention have shown promise, yet efficacy and applicability remains uncertain. Antibacterial drugs, dietary interventions, probiotics, and faecal microbiota transplantation have been explored, but their clinical utility awaits further validation. In conclusion, while the association between intestinal microbiota and arthritis is increasingly recognised, establishing causality remains elusive.

Sjögren's syndrome: one year in review 2023.

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disorder characterised by the T-cell-mediated hyperactivation of B-cells and cytokine production. The condition may evolve from an asymptomatic, indolent course, with glandular involvement, to extra-glandular systemic manifestations up to lymphoma development. On tissue level, the typical feature is the lymphocytic infiltration of the salivary gland by B-, T- and antigen presenting cells, as mirrored by the diagnostic cornerstone role of minor salivary gland (MSG) biopsy. Recently, increasing research focused on the investigation of mechanisms underlying the complex pathogenesis of the disease and highlighted the multi-factorial nature of SS consisting of concomitant involvement of environmental, genetic, neuroendocrine and immune factors. In particular, many aspects have been investigated regarding genetic and epigenetics, the role of specific B- and T-cell phenotypes and the investigation of disease-specific biomarkers as predictors of disease development, activity, and lymphomagenesis. Surely, a deeper understanding of these multiple mechanisms may facilitate earlier diagnosis, enable subphenotyping of patients and open novel therapeutic possibilities to address the unmet needs of the disease in the upcoming years.In this review, following the others of this series, we will summarise the most recent literature on pSS pathogenesis and clinical features focusing in particular on new insights into pSS molecular stratification and therapeutic advances in the era of precision medicine.

Rituximab for rapidly progressive juvenile systemic sclerosis.

OBJECTIVE: Juvenile systemic sclerosis (JSSc) with rapidly progressive course is a life-threatening condition associated with a poor prognosis. Recently, rituximab (RTX) has been shown to be a promising treatment for adult patients with SSc. We present a series of four patients with rapidly progressive JSSc successfully treated with RTX. METHODS: Clinical, laboratory and functional parameters were collected from four patients with rapidly progressive JSSc treated with RTX for at least 1 year. All patients underwent four yearly courses of i.v. RTX 375 mg/m2 on day 0 and 14, at 3-month intervals. Low dose oral prednisone and MMF were also administered. Data were recorded at baseline and every 6 months and included pulmonary and myocardial function parameters, muscular, vascular and skin changes. The Juvenile Systemic Sclerosis Severity Score (J4S) estimated the overall disease severity over time. RESULTS: Four patients (three males, one female), aged 8-17 years, entered the study. Three patients presented with prevalent cardiac involvement, one with severe pulmonary involvement. After 1 year of RTX treatment, all patients showed significant improvement of J4S, Raynaud's phenomenon and cutaneous involvement. Among those with prevalent cardiac involvement, two showed an improvement of the myocardial function (left ventricular ejection fraction [EF] +37% and +19%, respectively) and in the third arrhythmias disappeared. The patient with severe pulmonary involvement showed a significant improvement of the respiratory function (forced vital capacity +46%, forced expiratory volume in 1 s +33%, diffusing capacity of the lung for carbon monoxide [DLCO] +30%). No major side effects were reported. CONCLUSIONS: Our data suggest that a combination of RTX and MMF is effective in arresting the rapid progression of JSSc.

Salivary gland biopsy as a prognostic tool in Sjögren's syndrome.

INTRODUCTION: Primary Sjögren's syndrome (pSS) is an autoimmune disorder primarily affecting salivary and lacrimal glands, although about 40% of patients experience systemic complications. In this setting, the identification of patient phenotypes characterized by increased risk of extra-glandular involvement still represents an unmet need. AREAS COVERED: The aim of this paper is to review the scientific evidence on the utility of salivary gland biopsies in pSS, emphasizing their role in defining prognosis. In latest years, research focused on disease-specific clinical, serological, or histological features able to categorize patient prognosis. Among histopathological features, focus score and ectopic germinal centers exhibit associations with glandular and extraglandular manifestations, including higher rates of lymphomagenesis. EXPERT OPINION: Pathological characterization of salivary glands provides information that go beyond a mere diagnostic or classification utility, providing insights for a stratification of disease severity and for predicting systemic manifestations. Thus, a salivary gland biopsy should be offered to all patients and included in routine practice, even when not strictly required for diagnostic purposes. More advanced analysis techniques of the tissue, including immunohistochemistry and 'omics' should be further explored in longitudinal studies to boost the ability to further stratify and predict disease evolution.

Rational approach to the prescription of anti-rheumatic drugs in rheumatoid arthritis: a product leaflet-based strategy in Italy.

The treatment of patients with rheumatoid arthritis (RA) has dramatically changed in the past 30 years. Currently, numerous conventional, biologic, and targeted synthetic DMARDs have been licensed and used following recommendations provided by international and national scientific societies. However, the availability of biosimilars and the increasing necessity of savings impacted on the local/national prescription of these drugs. The information provided by data sheet of every single drug is a decisive factor on the choice of a certain treatment merged with the patient's profile. Thus, our purpose was to construct a rational algorithm for the treatment strategy in RA according to costs and the product leaflet of the biologic and targeted-synthetic DMARDs currently licensed in Italy. We used the most recent available recommendations and then we performed a review of the literature considering all the factors that are known to influence drug safety/effectiveness. All these factors were considered in the context of the data sheets of currently available originators and biosimilars.