Decoding clinical and molecular pathways of liver dysfunction in Psoriatic Arthritis: Impact of cumulative methotrexate doses.

BACKGROUND: The occurrence of liver abnormalities in Psoriatic Arthritis (PsA) has gained significant recognition. Identifying key factors at the clinical and molecular level can help to detect high-risk patients for non-alcoholic fatty liver disease in PsA. OBJECTIVES: to investigate the influence of PsA and cumulative doses of methotrexate on liver function through comprehensive in vivo and in vitro investigations. METHODS: A cross-sectional study involving 387 subjects was conducted, 200 patients with PsA, 87 NAFLD-non-PsA patients, and 100 healthy donors (HDs), age and sex-matched. Additionally, a retrospective longitudinal study was carried out, including 83 PsA patients since initiation with methotrexate. Detailed clinical, and laboratory parameters along with liver disease risk were analyzed. In vitro, experiments with hepatocyte cell line (HEPG2) were conducted. RESULTS: PsA patients present increased liver disease risk associated with the presence of cardiometabolic comorbidities, inflammatory markers, onychopathy, and psoriasis. The treatment with PsA serum on hepatocytes encompassed inflammatory, fibrotic, cell stress, and apoptotic processes. At the molecular level, methotrexate impacts liver biology, although the cumulative doses did not affect those alterations, causing any potential damage to liver function at the clinical level. Finally, anti-PDE-4 or anti-JAK decreased the inflammatory profile induced by PsA serum on hepatocytes. CONCLUSION: 1)This study identifies the complex link between liver disease risk, comorbidities, and disease-specific features in PsA patients. 2)Methotrexate dose in PsA patients had no significant effect on liver parameters, confirmed by hepatocyte in vitro studies. 3)Anti-PDE-4 and anti-JAK therapies show promise in reducing PsA serum-induced hepatocyte activation, potentially aiding liver complication management.

Clinical features of late onset psoriatic arthritis.

The aim of this work is to compare the clinical and radiological manifestations of patients presenting late onset psoriatic arthritis (PsA) with early onset PsA. An overall of 96 consecutive PsA patients were studied over an 8-month-period. Clinical, laboratory and radiographic signs were assessed. Of the 96 patients studied, 84 had their earliest symptoms before the age of 60 (Group I) and 12 after it (Group II). In Group II the mean age was 65.7 years (range 60-73), the sex ratio (male/female) was 9/3. All patients were HLA-B27 negative; the clinical forms observed were: polyarticular (6 patients; 50%), oligoarticular (4 patients; 33%) and spondyloarthropathy (SpA) (2 patients; 17%). Only two patients had asymmetric sacroiliitis and three had history of dactylitis episodes. In conclusion, we found distinct clinical manifestations in late onset PsA. Peripheral affection was found predominant. The male/female ratio was higher than other age groups.