Immune checkpoint inhibitors (ICIs) have revolutionized anticancer therapy due to their long-term clinical benefits and immune boosting mechanisms. However, despite their consistent therapeutic effects, the use of ICIs is associated with a spectrum of adverse events due to their autoimmune and auto-inflammatory actions. These adverse events can affect any organ system, including the endocrine, neurologic, gastrointestinal, cardiac, skin, pulmonary, and musculoskeletal systems. Of the immune-related adverse events (irAEs), rheumatic complications are common and appear to be distinct from irAEs in other organs in terms of variability of onset time, capacity for persistence, and relationship with pre-existing autoimmune rheumatologic diseases. In this article, we review the mechanisms of the anti-cancer effects of ICIs, the irAEs of immuno-oncology drugs, and the general recommendations for managing irAEs. In particular, we focus on rheumatologic irAEs and discuss their prevalence, clinical characteristics, and management.

Ankylosing spondylitis (AS) is a chronic, progressive, and inflammatory disorder and causes chronic back pain. It is not unusual for patients with AS to have symptoms similar to neuropathic pain. We aimed to investigate the neuropathic pain (NeP) component in patients with AS using the painDETECT questionnaire (PD-Q) and to assess the relation between NeP and the disease characteristics of AS. A single-center prospective study was performed, including 105 patients. Patients with AS completed three questionnaires: PD-Q, Beck Depression Inventory (BDI), and Euro Quality of Life (EQ-5D) questionnaires. Patients were classified into three groups according to the PD-Q scores: nociceptive pain (NoP) (score ≤ 12), mixed pain (MP) (score 13-18), and NeP pain (score ≥ 19). Fifteen patients (14.2%) were classified into the NeP group, 22 (21.0%) in the MP group, and 68 (64.8%) in the NoP group. The questionnaires and clinical and radiographic findings were analyzed. Patients with NeP and MP scored worse on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI); BDI; modified Stoke Ankylosing Spondylitis Spine Score; pain-visual analog scale (VAS); and EQ-5L index and showed an increased prevalence of enthesitis and peripheral arthritis. There were no differences in objective inflammatory markers. PD-Q scores were positively correlated with pain-VAS, BASDAI, BDI, and inversely correlated with EQ-5D index. Age, BASDAI, presence of current enthesitis, and BDI score were independently associated with PD-Q scores. The findings showed that NeP component in AS was associated with age, high disease activity, presence of current enthesitis, and depression.

Background The present study aimed to evaluate the suppressive role of interleukin (IL)-25 in IL-22-induced osteoclastogenesis and receptor activator of nuclear factor κB ligand (RANKL) expression in rheumatoid arthritis (RA). Methods Serum from patients with RA and osteoarthritis (OA), and healthy controls, and synovial fluid from patients with RA and OA were collected, and the levels of IL-22 and IL-25 were measured. RA and OA synovial tissues were stained against IL-25. Fibroblast-like synoviocytes (FLSs) of patients with RA were cultured with IL-22, in the presence or absence of IL-25, and RANKL expression was measured by real-time PCR and enzyme-linked immunosorbent assay (ELISA). Human peripheral blood monocytes were cultured under IL-22/RANKL + M-CSF, with or without IL-25, and tartrate-resistant acid phosphatase (TRAP)-positive cells and osteoclast-related markers were investigated to determine osteoclastogenesis. Results Serum and synovial IL-25 levels in RA were upregulated compared to those in OA and healthy control, and elevated expression of IL-25 in RA synovial tissue was re-confirmed. IL-25 and IL-22 levels showed significant correlation in serum and synovial fluid. Pre-treatment of FLS with IL-25 reduced IL-22-induced RANKL expression at the RNA level. The suppressive effects of IL-25 were confirmed to occur through the STAT3 and p38 MAPK/IκBα pathways. IL-25 reduced osteoclast differentiation and suppressed the expression of osteoclast-related markers. Conclusion In the current study, we demonstrated the regulatory effect of IL-25 on IL-22-induced osteoclastogenesis. Therapeutic approach involving augmentation of IL-25 regulatory response may serve as a novel treatment option for RA, especially by suppressing osteoclastogenesis.

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This study identified the distribution and prevalence of MRI-detected bone erosion, BME, synovitis, and tenosynovitis of the wrist and MCP joints in RA patients. The patterns of the MRI-detected abnormalities may help to select sites for the application of MRI protocols in clinical trials and practice.

IgA RF should be the predictive and diagnostic marker in patients with pSS.

We aimed to evaluate the changes over time in salivary gland (SG) abnormalities by ultrasound (US) in patients with primary Sjögren's syndrome (pSS). Patients with pSS (n = 70) and idiopathic sicca syndrome (n = 18) underwent baseline salivary gland ultrasound (SGUS) scans, and follow-up scans two years later. The semi-quantitative SGUS score (0-48) and intraglandular power Doppler signal (PDS) were assessed. We found that in the pSS group, the SGUS scores for total SGs and bilateral parotid glands significantly increased after the median 23.4-months follow-up. SGUS scores either worsened, improved, or were stable in 18.6%, 2.9%, and 78.6% of patients with pSS, respectively. The median changes from baseline in SGUS scores for total and parotid glands were +1.0 and +0.5, respectively. None of the SGUS scores changed significantly in the controls. The variables of homogeneity and hypoechoic showed a statistically significant progression of SGUS scores. In pSS patients, the baseline and follow-up PDS scores were significantly higher in the "worsening" group than in the "no change/improvement" group. Overall, the structural abnormalities in major SGs assessed using SGUS remained stable in patients with pSS. At the 2-year follow-up, SGUS scores worsened in 18.6% of patients with pSS. Intra-glandular hypervascularity was associated with the worsening of SG abnormalities.

Aim To evaluate the ability of the trabecular bone score (TBS) to discriminate vertebral fracture (VF) and fragility fracture (FF) in patients with chronic inflammatory rheumatic diseases on long‐term and low‐dose glucocorticoid (GC) treatment and those without exposure to GC. Methods This study assessed TBS and bone mineral density (BMD) in chronic GC users, defined as ≥2.5 mg/d of prednisone for >3 months (n = 89, mean age: 62.5 ± 11 years), and in controls (n = 59, mean age: 60.3 ± 9.6 years). Osteoporosis risk factors, radiographs of the thoracolumbar spine, non‐VF history, osteoporosis drugs, and current/cumulative GC doses were collected. Patients were classified as high (TBS <1.23), intermediate (1.23‐1.31), or low risk (>1.31), according to the fracture risk based on a recent meta‐analysis. Results The mean current dose and duration of GC treatment were 3.9 ± 1.9 mg/d and 3.9 ± 4.2 years, respectively. The prevalence of VF was significantly higher in chronic GC users than in controls (20.2% vs 5.1%, P = .010), although the prevalence of non‐VF was similar (11.2% vs 5.1%). The GC group had significantly lower L1‐L4 TBS and femur total BMD than did the controls (all with P < .01) without significantly different lumbar BMD. TBS (<1.31) showed a higher sensitivity for patients with VF and FF (83.3% and 81.8%, respectively) than with densitometric osteoporosis in the GC group (61.1% and 59.1%, respectively). Using the receiver operating characteristic curve, TBS <1.31 showed better diagnostic accuracy than TBS <1.23 and BMD in chronic GC users. Conclusion TBS is more sensitive than BMD in detecting VF and FF in chronic GC users, even at a lower dose.