OBJECTIVE:To identify risk of serious infections (SI) according to initial conventional synthetic DMARDs (csDMARD) and CS, in patients recruited to the National Early Inflammatory Arthritis Audit. METHODS:An observational cohort study was used, including adults in England and Wales with new diagnoses of RA between 2018 and 2023. The main outcome was SI events, defined as infections requiring hospitalization/or resulting in death. Secondary analyses evaluated SI-related mortality alone. Hazard ratios (HR) were calculated using cox proportional hazards models. Primary predictor was initial treatment strategy, with confounder adjustments. RESULTS:A total of 17 472 patients were included, of whom 10 997 were on MTX-based strategies, 4540 on other csDMARDs and 13 680 received CS. There were 1307 SI events, corresponding to incidence rates (IR) per 100 person-years of 3.02 (95% CI 2.86-3.19) and 311 cases of SI-related mortality (IR 0.69, 95% CI 0.61-0.77). MTX-based strategies were associated with reduced risk of SI events compared with other csDMARDs (adjusted HR 0.72, 95% CI 0.63-0.82). In unadjusted models, CS was associated with higher risk of SI events, but in adjusted models this association was no longer significant (adjusted HR 0.99, 95% CI 0.87-1.12). Increasing age, being a current/or ex-smoker (relative to non-smoker), having a comorbidity, being seropositive and having high DAS based on 28 joint count (DAS28) were all associated with increased incidence of SI. One unit increase in baseline DAS28 increases the risk of SI event by 10%. CONCLUSION:MTX-based regimens associated with a reduced risk of SI compared with other strategies. Patient-level and disease-related factors at diagnosis are important predictors of SI in individuals with new RA.

Journal Article Corrected proof Does reduced cathepsin activity contribute to skin and lung fibrosis in patients with systemic sclerosis and related disorders? Get access Mark Garton, Mark Garton Department of Medicine, Royal Shrewsbury Hospital, Shrewsbury, UK Correspondence to: Mark Garton, Department of Medicine, Royal Shrewsbury Hospital, Mytton Oak Road, Shrewsbury, Shropshire SY3 8XQ, UK. E-mail: m.garton@nhs.net Search for other works by this author on: Oxford Academic PubMed Google Scholar Clive Kelly Clive Kelly Departments of Rheumatology and Chest Medicine, James Cook University Hospital, Middlesbrough, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Rheumatology, kead549, https://doi.org/10.1093/rheumatology/kead549 Published: 13 October 2023 Article history Accepted: 02 October 2023 Published: 13 October 2023 Corrected and typeset: 23 October 2023

Interstitial lung disease (ILD) is a significant complication of many systemic autoimmune rheumatic diseases (SARDs), although the clinical presentation, severity and outlook may vary widely between individuals. Despite the prevalence, there are no specific guidelines addressing the issue of screening, diagnosis and management of ILD across this diverse group. Guidelines from the ACR and EULAR are expected, but there is a need for UK-specific guidelines that consider the framework of the UK National Health Service, local licensing and funding strategies. This article outlines the intended scope for the British Society for Rheumatology guideline on the diagnosis and management of SARD-ILD developed by the guideline working group. It specifically identifies the SARDs for consideration, alongside the overarching principles for which systematic review will be conducted. Expert consensus will be produced based on the most up-to-date available evidence for inclusion within the final guideline. Key issues to be addressed include recommendations for screening of ILD, identifying the methodology and frequency of monitoring and pharmacological and non-pharmacological management. The guideline will be developed according to methods and processes outlined in Creating Clinical Guidelines: British Society for Rheumatology Protocol version 5.1.

Background: There is little evidence available that specifically assesses morbidity and mortality in early RA. Most evidence is derived from people with well-established disease and a substantial burden of comorbidities [*]. Objectives: To identify the risk of serious infections (SI) admissions and SI mortality according to the initial treatment strategy, using conventional synthetic disease modifying anti-rheumatic drugs (csDMARD) and corticosteroids, in patients recruited to the National Early Inflammatory Arthritis Audit (NEIAA). Methods: An observational cohort study design was used. The population included adults in England with a new onset RA, fulfilling ACR/EULAR 2010 criteria, between April 2018-April 2021. Outcomes studied were SIs, defined by infections requiring hospitalisation (primary admission diagnosis/nosocomial acquisition) or death (SI stated on death certificate), identified using NHS Digital linkage. Patients characteristics were tabulated by treatment strategies. Hazard ratios (HR) were calculated using single failure Cox proportional-hazards models, with confounders-adjusted models (age, gender, smoking status, comorbidities, social deprivation) and fully-adjusted models including disease factors (seropositivity, DAS28). Individuals were considered at risk from the date of RA diagnosis, and censored at SI event, death, or April 2021 (whichever was earliest). Results: Initial DMARD therapy was known for 9,591 patients, of whom 5,887 were on methotrexate/MTX based strategies (mono or combo), 2,457 on csDMARD strategies other than MTX (of which 1,375 on combo and 1,082 on mono non-MTX strategies) and 1,247 on no DMARD strategy. 7,501 patients were on corticosteroids at baseline. Mean age 59.3 years (+/-15); 63% female; smoking status (20% current; 30% ex-smokers); comorbidities (21% hypertension; 9% diabetes; and 11% lung disease). Rheumatoid Factor/CCP antibodies were positive in 68%. At presentation, median diseases scores were 5.0 (interquartile range (IQR): 4.0-5.9) for DAS28, 1.1 (IQR: 0.6-1.6) for health assessment questionnaire (HAQ) and 24 (IQR: 16.0-33.0) for musculoskeletal health questionnaire (MSKHQ) where higher score indicate butter MSK health. In our cohort there were 523 SI admissions with 158.74 patients years of follow up, and 18 SI deaths with 159.40 years of follow up. Corresponding to an incidence rates per 100 person-years for SI admissions: 3.29 [95% CI: 3.02-3.58] and SI deaths: 0.11 [95% CI: 0.07-0.17]. In fully-adjusted models, increasing age predicted both SI admissions and deaths. Being a current smoker, having a comorbidity, higher disease activity (DAS28), symptom burden (MSKHQ) and disability (HAQ) at presentation associated with more SI admissions. For each 1 unit increase in DAS28, the risk of SI admissions increased by 8% (HR 1.09 [95% CI:1.02-1.17]). Seropositivity did not associate with SI. MTX-based strategies (0.76 [95% CI:0.63-0.91]) and csDMARD combination therapy (0.72 [95% CI:0.55-0.95]) associated with fewer SI admissions compared to no DMARD. Mono non-MTX strategies were not correlated with SI admissions. In unadjusted models, corticosteroid associated with more SI admissions (1.28 [95% CI:1.02 -1.61]); however, in fully-adjusted models this relation was no longer statistically significant (1.08 [95% CI: 0.83-1.39]). All csDMARD strategies were not associated with SI deaths in any of the models. Conclusion: Patient and disease factors at diagnosis appear to be important predictors of admissions and mortality for serious infections in early RA. Infection risk appears to be greatest in those with higher RA disease activity. An important limitation is that NEIAA does not capture data on treatment changes over time and steroids use beyond baseline. REFERENCES: [1] Black RJ, Lester S, Tieu J, Sinnathurai P, Barrett C, Buchbinder R, Lassere M, March L, Proudman SM, Hill CL. Mortality estimates and excess mortality in rheumatoid arthritis. Rheumatology. 2023 Mar 15:kead106. Acknowledgements: NIL. Disclosure of Interests: Maryam A. Adas: None declared, Katie Bechman: None declared, Benjamin Zuckerman: None declared, Mark Russell Has received honoraria from Lilly, Galapagos, Biogen and Menarini, and support for attending meetings from Lilly, Pfizer, Janssen and UCB., Samir Patel: None declared, Deepak Nagra: None declared, Ioasaf Karafotias: None declared, Mark Gibson: None declared, Sarah Gallagher: None declared, Elizabeth Price: None declared, Mark Garton: None declared, Andrew Rutherford: None declared, Andrew Cope: None declared, Sam Norton: None declared, James Galloway Has received honoraria from AbbVie, Biovitrum, BMS, Celgene, Chugai, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi and UCB.

Acute and chronic toxicity during low-dose methotrexate is common and deserves improved recognition and mitigation.

Background/Aims To identify the risk of serious infections (SI) according to initial treatment strategy, using conventional synthetic disease modifying anti-rheumatic drugs (csDMARD) and corticosteroids, in patients recruited to the National Early Inflammatory Arthritis Audit (NEIAA). Methods An observational cohort study design was used. The population included adults in England with a new onset rheumatoid arthritis (RA), fulfilling ACR/EULAR 2010 criteria, between April 2018-March 2021. Outcomes studied were SI, defined by infections requiring hospitalisation (primary admission diagnosis/nosocomial acquisition) or death (SI stated on death certificate), identified using NHS Digital linkage. Patients' characteristics were tabulated by treatment strategies. Hazard ratios (HR) were calculated using single failure Cox proportional-hazards models, with confounders-adjusted models (age, gender, smoking status, comorbidities, social deprivation) and fully-adjusted models including disease factors (seropositivity, DAS28). Individuals were considered at risk from the date of RA diagnosis, and censored at SI event, death, or March 2021 (whichever was earliest). Results 20,060 patients with RA were included. Initial DMARD therapy was known for 19,572 patients, of whom 11,966 were on methotrexate/MTX based strategies (mono or combo), 5,059 on csDMARD combination strategies (other than MTX) and 2,547 on no DMARD strategy. 15,319 patients were on corticosteroids at baseline. Mean age 59.5 years (+/-15); 63% female; smoking status (20% current; 30% ex-smokers); comorbidities (21% hypertension; 10% diabetes; and 12% lung disease). Rheumatoid Factor/CCP antibodies were positive in 68%. At presentation, median disease scores were 5.1 (interquartile range [IQR]: 4.0-5.9) for DAS28, 1.1 (IQR: 0.6-1.7) for health assessment questionnaire (HAQ) and 24 (IQR: 16.0-33.0) for musculoskeletal health questionnaire (MSKHQ).There were 519 SI admissions and 17 SI deaths, corresponding to incidence rates per 100 person-years for admissions: 3.19 (95% CI: 2.93-3.48) and deaths: 0.10 (95% CI: 0.06-0.16). In fully-adjusted models, increasing age predicted both SI admissions and deaths. Being a smoker, having a comorbidity, higher disease activity (DAS28), symptom burden (MSKHQ) and disability (HAQ) at presentation associated with more SI admissions. For each 1 unit increase in DAS28, the risk of SI increased by 8% (HR 1.08 [95% CI:1.01-1.16]). Seropositivity did not associate with SI. MTX-based strategies 0.75 (95% CI:0.62-0.91) and csDMARD combination therapy 0.70 (95% CI:0.53-0.94) associated with fewer SI admissions compared to no DMARD. In unadjusted models, corticosteroid associated with more SI admissions 1.29 (95% CI:1.10 -1.62); however, in fully-adjusted models this association was no longer statistically significant. csDMARD strategies did not associated with SI deaths in any of the models. Conclusion Patient and disease factors at diagnosis appear to be important predictors of admissions and mortality for serious infections. Infection risk appears to be greatest in those with higher RA disease activity. An important limitation is that NEIAA does not capture data on treatment changes over time and steroid use beyond baseline. Disclosure M. Adas: None. K. Bechman: None. M. Russell: Honoraria; Lilly and Menarini. Other; upport for attending conferences from Lilly, Pfizer, Janssen, and UCB, and advisory board fees from Biogen.. I. Karafotias: None. D. Nagra: None. S. Patel: None. S. Gallagher: None. E. Price: None. M. Garton: None. A. Rutherford: None. A. Cope: None. S. Norton: None. J. Galloway: Honoraria; from Abbvie, Biovitrum, Bristol Myers Squib (BMS), Celgene, Chugai, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi, and UCB.

Interstitial lung disease is a leading complication of rheumatoid arthritis (RA). However, no drugs are yet available to treat these pulmonary and articular diseases together, although several agents show promise. Janus kinase inhibitors have found increasing favour among rheumatologists in the treatment of active RA because they can rapidly reduce articular disease activity and because they have a simple oral dosing regime and good patient acceptability. There are many plausible reasons to believe that Janus kinase inhibitors may delay the onset and improve the outcomes of RA-associated interstitial lung disease, in tandem with their beneficial articular effects. This editorial describes the rationale for exploring this possibility further.

report favourable effects of ultrasound guided intra-articular lidocaine with or without triamcinolone in patients with moderate to severe pain from primary hip osteoarthritis. A strong Ultimately, however, the of repeated intra-articular steroid administration careful scrutiny, and even remote intra-muscular delivery suggesting some systemic treatment Paskins and colleagues’ data also suggest that in patients without significant secondary inflammation, lidocaine alone might confer equal benefit with respect to the main outcome measure at least. Indeed, if lidocaine does possess significant short to medium term immunomodulatory activity, 4 then ultrasound guided intra-articular delivery of local anaesthesia (without steroids) might be safer and non-inferior to triamcinolone in this patient group; a placebo controlled trial of such a strategy would be worthwhile, and might permit evaluation of exploratory explanatory variables. For those patients whose degenerative hip disease is complicated by ultrasonic evidence of inflammation, where steroid treatment might be expected to provide superior short term benefit, a comparative trial of intra-muscular steroids versus intra-articular delivery might show similar efficacy at substantially lower cost.

Introduction: Case presentation of 61 year old female patient who developed BRONJ (bisphosphonate related osteonecrosis of the jaw) and a pathological triple fracture of the anterior mandible. She had underlying vitamin D deficiency and secondary hypoparathyroidism. She also suffers from anca positive rheumatoid arthritis and is under the active care of rheumatology.

Stress fractures, that is fatigue and insufficiency fractures, of the pelvis and lower limb come in many guises. Most doctors are familiar with typical sacral, tibial or metatarsal stress fractures. However, even common and typical presentations can pose diagnostic difficulties especially early after the onset of clinical symptoms. This article reviews the aetiology and pathophysiology of stress fractures and their reflection in the imaging appearances. The role of varying imaging modalities is laid out and typical findings are demonstrated. Emphasis is given to sometimes less wellappreciated fractures, which might be missed and can have devastating consequences for longer termpatient outcomes. In particular, atypical femoral shaft fractures and their relationship to bisphosphonates are discussed. Migrating bone marrow oedema syndrome, transient osteoporosis and spontaneous osteonecrosis are reviewed as manifestations of stress fractures. Radiotherapy-related stress fractures are examined in more detail. An overview of typical sites of stress fractures in the pelvis and lower limbs and their particular clinical relevance concludes this review.Teaching PointsStress fractures indicate bone fatigue or insufficiency or a combination of theseRadiographic visibility of stress fractures is delayed by 2 to 3 weeksMRI is the most sensitive and specific modality for stress fracturesStress fractures are often multiple; the underlying cause should be evaluatedInfratrochanteric lateral femoral fractures suggest an atypical femoral fracture (AFF); endocrinologist referral is advisable.