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INTRODUCTION: Osteoarthritis (OA) is a chronic, degenerative, and debilitating disease associated with significant long-term morbidity and disability. The pathogenesis of OA is not completely understood but involves an interplay between environmental risk factors, joint mechanics, abnormal pain pathways and upregulation of inflammatory signaling pathways. Current therapeutic options for patients are limited to conservative management, minimal pharmacological options or surgical management, with significant caveats to all approaches. AREAS COVERED: In this review, we have set out to investigate current phase II/III clinical trials by undertaking a PubMed search. Examined clinical trials have explored a myriad of potential therapeutics from conventional disease-modifying anti-rheumatic drugs and biologics usually used in the treatment of inflammatory arthritides, to more novel approaches targeting inflammatory pathways implicated in OA, cartilage degeneration or pain pathways. EXPERT OPINION: Unfortunately, most completed phase II/III clinical trials have shown little impact on patient pain scores, with the exception of the traditional DMARD methotrexate and Sprifermin. Methotrexate has been shown to be beneficial when used in the correct patient cohort (MRI proven synovitis). Sprifermin has the longest follow-up data of 5 years and has been shown to reduce loss of MRI-measured cartilage thickness and pain scores.
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Background In the United Kingdom, diagnostic delay remains a challenge in axial spondyloarthritis (axSpA). Psoriasis is a frequently identified extra-musculoskeletal manifestation associated with axSpA. In this study, we aimed to determine the prevalence of inflammatory back pain (IBP) in psoriasis patients at a specialized psoriasis dermatology clinic in a London NHS Trust. Our primary goal was to identify psoriasis patients with IBP who were not referred to a rheumatologist, potentially leading to axSpA diagnostic delays. Additionally, we aimed to investigate factors contributing to these delays and strategies to address them. Methodology A patient survey consisting of 22 questions was used to assess the prevalence of IBP among 66 psoriasis patients attending a weekly specialized psoriasis dermatology clinic within a London NHS Trust between May and July 2023. The survey comprised patient demographic information along with inquiries about the existence of back pain exceeding three months. The Berlin Criteria was utilized to identify IBP among patients who reported experiencing back pain for over three months. Additionally, the survey sought information on prior diagnosis of axSpA and whether participants had consulted healthcare professionals regarding their back pain. Results Of the 66 patients invited, 51 (77%) completed the survey. The average age of the patients was 50 years (range = 19-74 years), with 58.8% being female. The mean duration of psoriasis was 15.7 years (range = 2-44 years). Overall, 45% (23/51) reported back pain lasting over three months. Among the patients who reported back pain for more than three months, 13 met the Berlin Criteria for IBP (25% of the total surveyed), and only four of these patients had a diagnosis of axSpA. Notably, seven patients (14% of the total surveyed) potentially had undiagnosed axSpA. General practitioners (GPs) were commonly consulted for back pain, yet only 39% of those with prolonged back pain had seen a rheumatologist. Despite experiencing prolonged back pain, 17% of patients had not sought healthcare advice for their symptoms. Conclusions This study highlights that IBP is a common yet underdiagnosed comorbidity in psoriasis patients. Dermatologists, GPs, and other allied healthcare professionals play a crucial role in detecting early axSpA. However, limited awareness of IBP hinders its identification in psoriasis patients and subsequent referral to rheumatologists. This highlights the need for improving awareness and education regarding axSpA among dermatologists and allied healthcare professionals as well as the public and patients to ensure timely diagnosis. The development of simple and easy-to-administer screening questionnaires to aid non-rheumatologists in identifying patients with IBP together with simplified referral pathways would increase onward referrals of appropriate patients to rheumatologists.
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Systemic sclerosis (SSc) is a multisystem connective tissue disease characterised by pathological processes involving autoimmunity, vasculopathy and resultant extensive skin and organ fibrosis. Recent studies have demonstrated activation and aberrant wound healing responses in the epithelial layer of the skin in this disease, implicating the epithelial keratinocytes as a source of pro-fibrotic and inflammatory mediators. In this paper, we investigated the role of Immunoglobulin G (IgG) autoantibodies directed against epithelial cells, as potential initiators and propagators of pathological keratocyte activation and the ensuing SSc fibrotic cascade. A keratinocyte cell-based ELISA is used to evaluate the binding of SSc IgG. SSc skin biopsies were stained by immunofluorescence for the presence of IgG in the keratinocyte layer. Moreover, IgG purified from SSc sera was evaluated for the potential to activate keratinocytes in tissue culture and to induce TLR2 and 3 signalling in reporter cell lines. We demonstrate enhanced binding of SSc IgG to keratinocytes and the activation of these cells leading to the release of IL-1α, representing a potential initiating pathway in this disease.