Identification and characteristics of patients with potential difficult-to-treat Psoriatic Arthritis: exploratory analyses of the Greek PsA registry.

OBJECTIVE: To present the characteristics of patients with potential difficult-to-treat (D2T) psoriatic arthritis (PsA). METHODS: We used data from the Greek multicentre registry of PsA patients. D2T-PsA was defined as follows: patients with at least 6-months disease duration, who have failed to at least 1 csDMARD and at least 2 bDMARDs/tsDMARDs with a different mechanism of action and have either at least moderate disease activity (MODA) defined as DAPSA > 14, and/or are not at minimal disease activity (MDA). Demographic and clinical characteristics were compared between D2T and non-D2T PsA patients. In two sensitivity analyses, patients classified as D2T solely according to the MODA or MDA criterion were examined separately. RESULTS: Among 467 patients included, 77 (16.5%) were considered D2T and 390 non-D2T PsA. Compared with non-D2T, patients with D2T PsA presented more commonly with extensive psoriasis (p< 0.0001) and were more likely to have higher BMI (p= 0.023) and a history of inflammatory bowel disease (p= 0.026). In the MODA and MDA sensitivity analyses, 7.5% and 12.5% of patients were considered D2T, respectively. In both sensitivity analyses, extensive psoriasis was again identified as an independent variable for D2T PsA (p= 0.001 and p= 0.008, respectively). Moreover, female gender (p= 0.034) in the MODA analysis and axial disease (p= 0.040) in the MDA analysis were independent variables for D2T PsA. CONCLUSION: Despite the availability of therapies, D2T PsA is common in real-life cohorts of patients with PsA and extensive psoriasis. High BMI, female gender, axial-disease, and history of IBD were also associated with D2T PsA.

COVID-19 vaccine-associated myositis: a comprehensive review of the literature driven by a case report.

Several cases of vaccine-associated manifestations have been published including cases of inflammatory myositis. Herein, we comprehensively review the literature on the occasion of case of a woman with inflammatory myositis following COVID-19 vaccination. A 67-year-old woman presented with left arm edema, rash, and weakness after the 2nd dose of the BTN162b2 vaccine. Raised muscle enzymes and inflammatory markers with muscle edema on MRI and myositis findings on the electromyogram established the diagnosis. She was successfully treated with methylprednisolone pulses, intravenous immunoglobulin, methotrexate, and hydroxychloroquine. Cases of inflammatory myositis, dermatomyositis, or interstitial lung disease with myositis-specific autoantibodies or myositis-associated autoantibodies within 12 weeks from SARS-CoV-2 vaccination were included. Cases with malignancy, prior or subsequent COVID-19 infection, preexisting myositis/interstitial lung disease (ILD)/dermatomyositis (DM), or other connective tissue diseases were excluded. From our search, 49 cases were identified (mean age: 56.55 + 17.17 years), 59% were women, while 12 patients received the ChAdOx1 vaccine, 27 the BNT162b2, 8 the mRNA-1273, 1 the DB15806, and 1 the Ad26.COV2.S (overall, 70% received mRNA vaccines). Muscle involvement was the most common manifestation (79.5%), followed by skin involvement (53%) and ILD (34.6%), which were more common in the m-RNA vaccinees. Muscle biopsy, MRI findings, and autoantibody profile varied significantly, while successful immunosuppressive treatment was applied in most cases. Inflammatory myositis after COVID-19 vaccination has been well documented worldwide. Current evidence in support of a pathogenic link is challenging due to significant variation in clinical manifestations, radiological, histopathological, and immunological features.

Disease Profile and Achievement of Therapeutic Goals in a Modern, Nationwide Cohort of 923 Patients with Psoriatic Arthritis.

Background: Psoriatic arthritis (PsA) is a heterogenous chronic inflammatory disease affecting skin, joints, entheses, and spine with various extra-musculoskeletal manifestations and comorbidities. The reported patient, disease and treatment characteristics in the modern therapeutic era are limited. Methods: In this cross-sectional, multi-centre, nationwide study, we recorded the demographic, clinical, and therapeutic characteristics as well as the comorbidities of patients with PsA seen for 1 year (1/1/2022-31/12/2022). Results: 923 patients (55% females) with a median (IQR) age of 57 (48-65) years and a mean disease duration of 9.5 years were enrolled. Family history of psoriasis and PsA was noted in 28.3% and 6.3%, respectively. Most patients had limited psoriasis (BSA<3: 83%) while enthesitis, dactylitis, nail and axial involvement reported in 48.3%, 33.2%, 43% and 25.9% of patients, respectively. Regarding comorbidities, approximately half of patients had dyslipidaemia (42%) or hypertension (45.4%), 36.8% were obese and 17% had diabetes while 22.7% had a depressive disorder. Overall, 60.1% received biologics and among them more patients treated with anti-IL-17 or -12/23 agents were on monotherapy (64.2%) compared to those on TNFi monotherapy (49.4%, p=0.0001). The median PsA activity as assessed by the DAPSA score was 6 (IQR: 2.3 - 13.1) with 46% of patients reaching minimal disease activity status (MDA). Conclusion: In this large, real life, modern cohort of patients with PsA with frequent comorbidities who were treated mainly with biologics, almost half achieved minimal disease activity. These results show the value of existing therapeutic approaches while at the same time highlight the existing unmet needs.

Giant Hip Synovial Cyst Causing Deep Vein Thrombosis and Femoral Head Osteonecrosis in a Rheumatoid Arthritis Patient.

Hip synovial cysts are rare. However, in patients with Rheumatoid Arthritis (RA) they present in higher frequency than in general population. Herein, we present an unusual case of a 67-year-old man with RA that presented with unilateral leg oedema and Deep Vein Thrombosis (DVT). Computed tomography (CT) scan revealed a giant cystic lesion adjacent to the right hip joint with longitudinal diameter of 14 cm. Magnetic Resonance Imaging (MRI) confirmed the characteristics of the cyst. Interestingly enough, there was evidence of osteonecrosis of the femoral head. CT guided Fine Needle aspiration (FNA) of the fluid revealed fluid consistency similar to synovial fluid, while it excluded infectious process and malignancy. Patient was finally treated with total hip arthroplasty 3 months after the initiation of low molecular weight heparin (LMWH) in treatment dose.

Arthritis and Myositis in a Patient Treated with Programmed Cell Death-1 (PD-1) Inhibitor Pembrolizumab for Lung Cancer.

Immune checkpoint inhibitors (ICIs) are a new class of drug that have demonstrated efficacy across many cancer types. Because of their nature and mode of action, ICIs unleash immune activation raising concerns as to whether they can be used in patients with concomitant autoimmune or auto-inflammatory diseases. Their usage can lead to the development of autoimmune phenomena known as immune related adverse events (irAEs), virtually affecting every organ. As the use of ICIs is drastically increasing, evidence of irAEs has been accumulating. Herein, we report a case of inflammatory myositis and arthritis 6 months after pembrolizumab therapy, an anti-programmed death-1 (PD1) ICI in a patient with lung cancer, aiming at raising awareness of the diagnostic and clinical challenges clinicians may face when checkpoint inhibitors-related rheumatologic irAEs are developed.

Autoantibodies against specific nuclear antigens are present in psoriatic disease and are diminished by secukinumab.

Anti-nuclear antibodies (ANA) are frequently detected in patients with psoriasis (Ps) and psoriatic arthritis (PsA), but their target autoantigens remain unknown. We assessed antibody (ab) reactivity against 23 known nuclear antigens in patients with Ps and PsA and assess the effects of secukinumab (anti-IL17A) treatment on ANA levels. A total of 201 patients, 101 with Ps and 100 with PsA, and 50 ANA-negative healthy controls (HCs) were tested for ANAs by a line immunoassay testing reactivity to 23 nuclear antigens. Ab reactivity to at least 1 antigen was found in 20.4% psoriatic disease patients (25.7% Ps and 15% PsA) compared to 8% HCs (p = ns), the most frequent being against dense fine speckled 70 (DFS70) (6.5%). In Ps and PsA patients with secukinumab-induced remission, anti-DFS70 and other antigen-specific autoantibodies were diminished over time. No decline was noted for IgG abs against antigens from pathogens such as cytomegalovirus, Epstein-Barr virus and Helicobacter pylori. Autoantibody decrease was associated with significant reduction of plasmablasts, follicular B and follicular T cells. In conclusion, one third of antigen-specific ANA patients with psoriatic disease recognize DFS70. Secukinumab decreases nuclear antigen autoreactivity, plasmablasts, follicular B and follicular T cells, highlighting a new mechanism of its action.

Apremilast increases IL-10-producing regulatory B cells and decreases proinflammatory T cells and innate cells in psoriatic arthritis and psoriasis.

OBJECTIVES: Psoriatic arthritis (PsA) and psoriasis are immune-mediated inflammatory diseases sharing common immunological mechanisms. Regulatory B cells (Breg cells) producing IL-10 (B10 cells), a critical anti-inflammatory B-cell subset, were found to be decreased in both PsA and psoriasis. Apremilast, a phosphodiesterase-4(PDE4) inhibitor, increases IL-10 and therefore, we examined the effect of apremilast on Breg cells. METHODS: Fifty patients, including 20 with PsA and 30 with psoriasis, were included in the study. The effect of apremilast on Breg cells at 3, 6 and 12 months post-treatment, was examined by flow cytometry in ODN2006 (TLR9)-stimulated peripheral blood mononuclear cells and magnetically-isolated cells. Th1 cells, Th17 cells and NKT were also measured. RESULTS: Ex vivo stimulated cell analysis identified that post-apremilast (IL-10+CD19+) B10 cells were increased in all PsA and psoriasis patients and correlated with psoriatic skin and joint clinical improvement. Apremilast decreased IFNγ(+) T and NKT cells and IL-17(+)NKT cells. B10 cells also inversely correlated with Th1 cells, and IFNγ(+)NKT cells. CONCLUSION: These results suggest that Breg cells are a major target of apremilast in PsA and psoriasis and that apremilast-induced increase of Breg cells is associated with a decrease of Th1 cells, IFNγ-producing NKT cells and IL-17-producing NKT cells.

Immunotherapy of systemic sclerosis.

Systemic sclerosis (SSc) is a chronic systemic disease characterized by microvasculopathy, immune activation, and extensive collagen deposition. Microvasculopathy and immune activation occur very early in the disease process. Evidence from animal models and in vitro studies indicate that T-cells and B-cells activate fibroblasts to produce collagen. Traditional immunosuppressants, cyclophosphamide(CyP), methotrexate(MTX), and more recently mycophenolate mofetil(MMF), may prove more effective if used very early in the disease course. These drugs showed some benefit in skin (MTX, CyP, MMF) and lung function (CyP, MMF). Biologicals, such as intravenous immunoglobulin (IVIg), belimumab(Beli), tocilizumab(TCZ), abatacept(Aba), rituximab(RTX) and fresolimumab(Fresu) appear promising as they exhibited some benefit in skin (IVIg, Beli, TCZ, Aba, RTX, Fresu), hand function (IVIg), and joints (IVIg, TCZ, Aba). Autologous stem cell transplantation showed the best therapeutic efficacy on skin and internal organs, and looks very promising, as modification of transplantation immunosuppression is decreasing the early high mortality.

Inferior vena cava thrombosis as the initial presentation of IgG4-related retroperitoneal fibrosis: Case report and literature review.

IgG4-related disease is an immune-mediated deposition of fibro-inflammatory tissue with IgG4-positive plasma cells and dense fibrosis in a single or multiple organs. It often raises concern for malignancy requiring biopsy for diagnosis. Presentation may vary according to organ involved. IgG4-related retroperitoneal fibrosis accounts for two-thirds of the previously considered idiopathic retroperitoneal fibrosis cases. In IgG4-related retroperitoneal fibrosis, computed tomography scan or magnetic resonance imaging shows periaortic soft tissue that extends from below the kidneys to iliac arteries and entrap ureters causing hydronephrosis and renal failure. We present a rare case of IgG4-related retroperitoneal fibrosis presenting with leg swelling and pain due to inferior vena cava compression and thrombosis, and we review current concepts on disease pathogenesis, diagnosis and treatment.

Breg Cells Are Numerically Decreased and Functionally Impaired in Patients With Systemic Sclerosis.

OBJECTIVE: Breg cells, a regulatory cell subset that produces interleukin-10 (IL-10), play a significant role in suppressing autoimmune responses and preventing autoimmunity. This study was undertaken to examine the number and function of Breg cells in patients with systemic sclerosis (SSc), a disease with many autoantibodies. METHODS: Forty-five patients with SSc (12 with early SSc, 33 with established disease including 16 with SSc-associated pulmonary fibrosis [PF]), 12 healthy control subjects, and 10 patients with rheumatoid arthritis (RA)-associated PF were studied. The phenotypes of immature/transitional Breg cells (CD19+CD24(high) CD38(high) ) and memory Breg cells (CD19+CD27+CD24(high) ) were evaluated by flow cytometry. The function of Breg cells was assessed by measuring the production of IL-10 after B cell activation. In addition, activation of p38 MAPK and STAT-3 was measured following stimulation of the cells with B cell receptor (BCR) and Toll-like receptor 9 (TLR-9). RESULTS: Percentages of memory Breg cells were decreased in patients with early SSc (mean ± SEM 1.85 ± 0.38%), those with established SSc (1.6 ± 0.88%), those with SSc-associated PF (1.52 ± 0.17%), and those with RA-associated PF (1.58 ± 0.26%), compared to healthy controls (6.3 ± 0.49%; each P < 0.001). Percentages of transitional Breg cells were also decreased. Expression of IL-10 by Breg cells after stimulation with TLR-9 was impaired in patients with SSc, particularly those with SSc-associated PF. Activation of STAT-3 and p38 MAPK was impaired in naive and memory B cells from patients with SSc after stimulation with BCR and TLR-9. Expression of the stimulatory CD19 receptor was increased in B cells and also increased, to a lesser extent, in Breg cells from patients with SSc compared to healthy controls. Percentages of memory B cells were decreased in patients with SSc, particularly in those with SSc-associated PF. CONCLUSION: This is the first study to demonstrate that Breg cells are phenotypically and functionally impaired in patients with SSc. Furthermore, in SSc, B cells exhibit impaired p38 MAPK and STAT-3 activation upon stimulation with BCR and TLR-9. The findings of decreased numbers of Breg cells along with increased expression of CD19 support the idea of B cell autoaggression acting as an immunopathogenic mediator in SSc.

Enthesitis in psoriatic arthritis.

OBJECTIVES: It is increasingly recognized that enthesitis in patients with psoriatic arthritis (PsA) is of clinical importance. We review data on the detection, assessment, and treatment of enthesitis and its related dactylitis in PsA. METHODS: We searched Pubmed with the search terms psoriatic arthritis or psoriasis in combination with enthesitis, enthesopathy, and treatment, or enthesitis in combination with imaging. RESULTS: One hundred fifty-seven papers were selected. Enthesitis occurs frequently in PsA and may be asymptomatic or painful. It can also affect patient's function and quality of life. New imaging modalities, such as ultrasonography and magnetic resonance imaging, have revealed that enthesitis may be the initial osteoarticular inflammatory site in patients with PsA. Enthesitis indices have been developed and should be incorporated in clinical trials. Dactylitis, a characteristic and frequent manifestation of PsA can be tender or not tender and is prognostic of disease progression. Treatment of enthesitis includes non-steroidal anti-inflammatory drugs, classical DMARDs, and adjunctive local steroid injections. In inadequate response, TNFα inhibitors are used. CONCLUSIONS: Enthesitis and dactylitis are important manifestations of PsA, and their evaluation is increasingly used in drug trials and clinical practice.

Lipid metabolism and osteoarthritis: lessons from atherosclerosis.

Osteoarthritis (OA) is an age-related degenerative disease comprising the main reason of handicap in the Western world. Interestingly, to date, there are neither available biomarkers for early diagnosis of the disease nor any effective therapy other than symptomatic treatment and joint replacement surgery. OA has long been associated with obesity, mainly due to mechanical overload exerted on the joints. Recent studies however, point to the direction that OA is a metabolic disease, as it also involves non-weight bearing joints. In fact, altered lipid metabolism may be the underlying cause. First, adipokines have been shown to be key regulators of OA pathogenesis. Second, epidemiological studies have shown serum cholesterol to be a risk factor for OA development. Third, lipid deposition in the joint is observed at the early stages of OA before the occurrence of histological changes. Fourth, proteomic analyses have shown an important connection between OA and lipid metabolism. Finally, recent gene expression studies reveal a deregulation of cholesterol influx and efflux and in the expression of lipid metabolism-related genes. Interestingly, lipids and lipid metabolism are known to be implicated in the development and progression of another age-related degenerative disease, atherosclerosis (ATH). Thus, although it is tempting to speculate that the osteoarthritic chondrocyte has been transformed to foam cell, it has not been proven yet. However, this may be an intriguing theory linking ATH and OA, which may open new avenues to novel therapeutic interventions for OA taking advantage of previous knowledge from ATH.

A case report of osteomyelitis pubis in a hemodialysis patient with diabetes mellitus.

Osteomyelitis pubis is a rare form of osteomyelitis. Known risk factors are urogynecologic surgery, trauma caused by sport activities, pelvic malignancy and intravenous drug use. Immunocompromised patients, including hemodialysis patients, and those with diabetes are also susceptible to infection. Particularly in the hemodialysis population, the use of intravenous catheters frequently results in bacteremia and metastatic infectious complications such as osteomyelitis. We describe the first case of osteomyelitis pubis in a woman on chronic maintenance hemodialysis with diabetes mellitus.

Psoas abscess in a dialysis patient with dialysis-related amyloidosis.

Psoas abscess is an infrequent clinical entity which poses diagnostic and therapeutic challenges. Few cases have been reported in chronic hemodialysis patients. We describe a case of psoas abscess in a dialysis patient with dialysis-related amyloidosis, successfully treated with percutaneous drainage and parenteral antibiotics.