Comparison of clinical features between patients with anti-synthetase syndrome and dermatomyositis: Results from the MYONET registry.

OBJECTIVES To compare clinical characteristics, including the frequency of cutaneous, extramuscular manifestations, and malignancy, between adults with anti-synthetase syndrome (ASyS) and dermatomyositis (DM). METHODS Using data regarding adults from the MYONET registry, a cohort of DM patients with anti-Mi2/-TIF1ɣ/-NXP2/-SAE/-MDA5 autoantibodies, and a cohort of ASyS patients with anti-tRNA synthetase autoantibodies (anti-Jo1/-PL7/-PL12/-OJ/-EJ/-Zo/-KS) were identified. Patients with DM sine dermatitis or with discordant dual autoantibody specificities were excluded. Sub-cohorts of patients with ASyS with or without skin involvement were defined based on presence of DM-type rashes (heliotrope rash, Gottron's papules/sign, violaceous rash, shawl sign, V sign, erythroderma, and/or periorbital rash). RESULTS In total 1,054 patients were included (DM, n = 405; ASyS, n = 649). In ASyS cohort, 31% (n = 203) had DM-type skin involvement (ASyS-DMskin). A higher frequency of extramuscular manifestations, including Mechanic's hands, Raynaud's phenomenon, arthritis, interstitial lung disease, and cardiac involvement differentiated ASyS-DMskin from DM (all p< 0.001), whereas higher frequency of any of four DM-type rashes: heliotrope rash (n = 248, 61% vs n = 90, 44%), violaceous rash (n = 166, 41% vs n = 57, 9%), V sign (n = 124, 31% vs n = 28, 4%), and shawl sign (n = 133, 33% vs n = 18, 3%) differentiated DM from ASyS-DMskin (all p< 0.005). Cancer-associated myositis (CAM) was more frequent in DM (n = 67, 17%) compared with ASyS (n = 21, 3%) and ASyS-DMskin (n = 7, 3%) cohorts (both p< 0.001). CONCLUSION DM-type rashes are frequent in patients with ASyS; however, distinct clinical manifestations differentiate these patients from classical DM. Skin involvement in ASyS does not necessitate increased malignancy surveillance. These findings will inform future ASyS classification criteria and patient management

P26 A case of B-cell lymphoma affecting the eye in a patient with rheumatoid arthritis following a reduction in the frequency of rituximab therapy

CASE REPORT - INTRODUCTION: Rheumatoid arthritis (RA) is a life-long systemic autoimmune inflammatory disease associated with numerous co-morbidities, one of which includes the increased risk of developing lymphoproliferative disorders. RA patients have been found to be at increased risk of developing lymphoma, with non-Hodgkin’s lymphomas (NHL), especially B-cell lymphoma, being the most common. Rituximab is a biologic disease modifying anti-rheumatic drug (bDMARD) that inhibits b cells used in oncology and rheumatology. In this case report, we present a middle-aged female with RA who developed B-cell lymphoma affecting her right eye after a reduction in the frequency of her rituximab therapy. CASE REPORT - CASE DESCRIPTION: A 43-year-old female was diagnosed with RA at age 27 and experienced dry eyes and corneal ulcers during her disease. Her RA was well controlled on adalimumab. She presented to clinic with right-sided eyelid and lacrimal gland swelling which had progressed over 4 months, with reduced eye motility and visual acuity (6/24). A CT scan revealed a mass lesion in the superolateral quadrant of the orbit involving the lacrimal gland. Histology from an incisional biopsy concluded that the diagnosis was “chronic idiopathic orbital inflammation”. The immunohistochemical report revealed a mixture of B- and T-cell populations, with no definite light chain restriction. The test for serum IgG4 was negative, ruling-out IgG4 disease. She was subsequently admitted to the hospital and received three 250mg infusions of methylprednisolone, followed by 6-monthly rituximab infusions. Following methylprednisolone therapy, her vision had improved 6/6 on the right, and 6/5 on the left. She went on to respond to the rituximab treatment, and the orbital mass shrank as her vision returned to baseline. After 7 years on 6-monthly rituximab cycles, her RA remained stable. Her immunoglobulins were normal, and she requested to be transferred to a local hospital for convenience of travel. At this centre, she received her rituximab infusions only when her disease would flare. After several years on this new regime frequency, she only received 1 treatment in 14 months when she presented with a flare in ocular symptoms. She presented with 2mm proptosis, and ptosis of the right eyelid, alongside a rapidly growing subcutaneous mass on her forehead. The mass was biopsied and determined to be a high-grade B-cell lymphoma. Following 12 months of chemotherapy, radiotherapy, and an autologous stem cell transplant, she went into remission. Her rituximab therapy was changed back to 6-monthly, and her RA remains stable with no further ocular complications. CASE REPORT - DISCUSSION: RA is associated with an increased risk of cancer; however, the aetiopathogenesis is unclear, though the role of chronic inflammation has been reported. A study by Wolfe et al. found that in patients with chronic inflammation, the risk of developing NHL was 9-times higher. Similarly, a Swedish study following 378 RA patients and 378 control patients reported that in patients with severe longstanding RA, the risk of developing cancer was significantly greater in those with higher disease activity. Furthermore, the role of immunomodulatory agents such as rituximab in altering the risk of malignancy is unclear. Rituximab inhibits B-cell activity, which may play a role in supressing the development of B-cell malignancies. A review of the literature found no studies about rituximab and reduced incidence of lymphoma in RA specifically; however, several studies in other diseases have reported a reduction in the incidence of lymphoma in patients taking rituximab. A study by Gérard et al. followed 113 patients with HIV-associated multicentric Castleman disease for 15 years, where 48 patients were given rituximab therapy and 65 patients were not. Only one patient in the rituximab cohort developed NHL, whereas 17 patients in the other cohort developed NHL. In another study using patient-derived xenografts, immunocompromised mice with high susceptibility of lymphoproliferative disease were implanted with gastric carcinomas. Over 30% of them developed human B-cell lymphomas; however, they found that if the mice were injected with rituximab upon implantation, lymphoma would cease to develop. CASE REPORT - KEY LEARNING POINTS: Several studies have demonstrated that rituximab therapy plays a significant role in reducing the incidence of lymphoma. In our case report, the development of lymphoma coincided in a reduction in the frequency of rituximab therapy. Therefore, it is possible that the loss of the suppressive effect of rituximab in our patient played a role in the development of lymphoma. Data from real-world drug registries such as the British Society of Rheumatology Biologics Registry for Rheumatoid Arthritis (BSRBR-RA) could provide insight into the incidence and age of onset of B-cell malignancies in patients taking rituximab, compared to those taking non-B-cell-modulating therapy. Similarly, these data could provide insight into whether this protective effect also applies to T-cell-modulating therapy and the risk of T-cell malignancies. Finally, rituximab was also integral in managing the ocular manifestations of her disease. Therefore, this case reinforces that rituximab remains a good treatment option for RA patients with ocular involvement. In conclusion, rituximab is an effective treatment option in managing the ocular manifestations of RA, and may play a role in suppressing the development of lymphoma

Septic arthritis caused by Mycoplasma hominis in a patient with systemic lupus erythematosus

Mycoplasma hominis is one of the most common commensal organisms of the genitourinary tract. Immunocompromised patients are susceptible to developing severe infections secondary to M. hominis, and rarely, septic arthritis. This case report describes the occurrence of septic arthritis secondary to M. hominis in a 27-year-old woman with systemic lupus erythematosus (SLE), who presented with a 2-week history of left elbow swelling and tenderness, elevated inflammatory markers and joint aspiration findings consistent with infection. Serial blood cultures were negative. She was treated with flucloxacillin; however, failed to respond and so doxycycline was added to cover for atypical organisms. Subsequently, PCR analysis from the joint aspirate found M. hominis on day 16. Fortunately, doxycycline was an effective treatment for this atypical organism. This case outlines the importance of considering atypical organisms such as M. hominis as a cause of septic arthritis in immunosuppressed patients especially those with SLE.</p

A case of IgG4-related disease and Membranous Nephropathy associated with Thrombospondin type-1 Domain-containing 7A

BACKGROUND: IgG4-related disease (IgG4-RD) is a systemic multi-organ inflammatory disorder which affects the kidney 20% of the time. Patients with intrinsic IgG4-related kidney disease (IgG4-RKD) often have tubulointerstitial nephritis (TIN) whereas glomerular lesions like membranous nephropathy (MN) are less common. Antibodies to thrombospondin type-1 domain-containing 7A (THSD7A) have been described in primary MN, but never in association with IgG4-RKD. CASE REPORT: We report the first case of IgG4-MN associated with THSD7A antibodies in serum and positivity on glomerular staining, in a 57-year-old Caucasian male with IgG4-RD affecting the pancreas, liver, lacrimal glands, extraocular muscles, and kidneys. This patient presented initially with glomerular disease including significant proteinuria consistent with MN. Glomerular staining for THSD7A antigen and serum THSD7A antibody titres was positive. Treatment with corticosteroids and cyclophosphamide successfully induced remission with resolution of proteinuria, and improvement in renal function. However, despite maintenance azathioprine, the patient relapsed 39 months later. On relapse, there was minimal proteinuria but a significant rise in creatinine. Subsequent renal biopsy showed less glomerular disease and instead a TIN pattern. Subsequent treatment with Rituximab and corticosteroids successfully induced remission. CONCLUSION: The role of THSD7A autoantibodies in MN is emerging, and as both IgG4-MN and presence of THSD7A antibody are rare occurrences in themselves, we speculate that there may be an undiscovered association between THSD7A and IgG4-MN. Routine testing for THSD7A in IgG4-MN may help to identify the link

Metabolic Syndrome and Psoriatic Arthritis:The Role Of Weight Loss As A Disease-Modifying Therapy

Psoriatic arthritis (PsA) is an inflammatory joint and entheseal disease associated with significant personal and public health burden. PsA has a prevalence of up to 1%, affecting ~20% of people suffering with psoriasis. PsA is frequently accompanied by metabolic syndrome (MetS), and both conditions are characterised by a chronic pro-inflammatory state, with several key cytokines in PsA (IL-17 and IL-23) also elevated in those with MetS. This narrative review aims to provide an update on MetS in PsA, focusing on its prevalence, pathogenesis, prognosis, treatment interactions and future therapeutic optionsMetS is particularly prevalent in PsA compared to other inflammatory arthritides. Cohort studies indicate a higher risk of PsA in individuals with obesity, while Mendelian randomization studies link childhood obesity, insulin resistance, and dyslipidaemia to PsA. Weight loss interventions have been shown to reduce disease activity in PsA. Additionally, MetS negatively impacts the efficacy of tumour necrosis factor inhibitor (TNFi) drugs in treating PsA.Drugs given for PsA may also affect the conditions constituting MetS. Leflunomide has been shown to reduce body weight but also increase blood pressure. TNFi drugs lead to weight gain but reduce cardiovascular risk. Janus kinase inhibitors (JAKi) increase lipid levels and cardiovascular risk among high-risk groups. Anti-IL-17 and anti-IL-12/IL-23 drugs may cause a short-term increase in cardiovascular risk, although the long-term effects have yet to be established.Weight loss represents an unexplored avenue for disease modification in PsA, alongside a plethora of general health benefits. Dietary and exercise modifications are the cornerstone of weight management but vary substantially across individuals. Novel therapies to treat weight loss, such as GLP-1 agonists and SGLT2 inhibitors, may prove useful alongside disease-modifying therapies for those with PsA and MetS and should be investigated as potential therapeutic adjuncts. <br/