Background: Relapse is common in patients with giant cell arteritis (GCA). A clinically relevant question for both patients and providers is whether the initial symptoms at GCA diagnosis will be present at time of relapse or whether other clinical features may manifest. Given most cohorts describe both baseline and relapse symptoms in aggregate, evaluation of patient level concordance between initial symptoms and relapse symptoms has not been delineated. Objectives: To evaluate symptom concordance from initial presentation to first relapse and from first relapse to second relapse across a cohort of patients with GCA. Methods: A 510-patient aggregate of three previously described GCA cohorts was analyzed [1-3]. Clinical symptoms at diagnosis and relapse were grouped into five categories: constitutional, musculoskeletal (MSK), cranial (non-visual), visual, and large vessel (LV). Patients could have more than one category present at each time point. Odds ratios and conditional probabilities were calculated. Results: 303/510 (59%) patients had at least one relapse and 160/510 (31%) had at least two relapses. 20% of patients presented with a symptom category on first relapse that was not present at baseline. At first relapse, 68% of patients had symptoms in a single category, versus 10% at baseline. At second relapse, 64% of patients had symptoms in a single category. Odds ratios for presence of symptoms at first relapse associated with presence of given symptoms at baseline (1A) and presence of symptoms at second relapse associated with given symptoms at first relapse (1B) are shown in Table 1. In 1A, patients with cranial symptoms at baseline were near 6 times less likely to develop LV at first relapse. There was a 15-fold increased risk of visual symptoms at first relapse if visual symptoms were present at baseline and a 25-fold increased risk of LV symptoms at first relapse if LV symptoms were present at baseline. In 1B, visual symptoms at first relapse resulted in a 30-fold increased risk for visual symptoms on second relapse. LV symptoms on first relapse resulted in a 15.5-fold increased risk for LV symptoms on second relapse. Conditional probabilities of symptoms at first relapse according to presence or absence of baseline symptoms (2A) and conditional probabilities of given symptom category at second relapse according to presence or absence of first relapse symptom category (2B) are shown in Table 2. In 2A, no patient without cranial symptoms at baseline developed visual symptoms at first relapse. The probabilities of specific symptom categories repeating themselves on first relapse if present at baseline were: 27% for constitutional, 57% for MSK, 56% for cranial, 13% for visual, and 44% for LV. In 2B, the probabilities of specific symptom categories repeating themselves on second relapse if present at first relapse were: 64% for constitutional, 78% for MSK, 59% for cranial, 29% for visual, and 45% for LV. Conclusion: In our study, approximately 1 in 5 patients reported a new symptom domain at first relapse that was not present at baseline. Visual symptoms on first relapse were overall uncommon, but risk was higher if visual symptoms were present at baseline. Providers should educate patients on the spectrum of GCA symptoms to be aware of, even beyond those present at a patient's diagnosis. The significance of this study lies in its potential to aid clinicians in providing patient-level data regarding relapsing GCA that will ultimately translate into better patient education and overall better monitoring of the disease. REFERENCES: [1] Predictors of relapse and treatment outcomes in biopsy-proven giant cell arteritis: a retrospective cohort study. Rheumatology (Oxford). 2016;55(2):347-56. [2] Giant cell arteritis and its mimics: A comparison of three patient cohorts. Semin Arthritis Rheum. 2020;50(5):923-9. [3] Relapse Risk and Safety of Long-Term Tocilizumab Use Among Patients With Giant Cell Arteritis: A Single-Enterprise Cohort Study. J Rheumatol. 2023;50(10):1310-7. Acknowledgements: NIL. Disclosure of Interests: None declared.

OBJECTIVE:We aimed to characterize presentation and care pathways of patients with systemic lupus erythematosus (SLE), and delays in access to SLE-specialized care. METHODS:We included patients with incident SLE from the Lupus Midwest Network registry. Time from the first medical encounter for SLE clinical manifestation to access to SLE-specialized care, physician diagnosis, and treatment was estimated. Delays were defined as ≥6 months to access specialized care. We compared SLE manifestations, disease activity, and Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage indexes (SDI) between patients with and without delays. Logistic regression models assessed associations with delays. RESULTS:The study included 373 patients with SLE. The median time to access SLE-specialized care was 1.1 (95% confidence interval [CI] 0.9-1.5) months, time to diagnosis was 30.6 (95% CI 18.9-48.1) months, and time to treatment initiation was 4.7 (95% CI 3.9-8.4) months. Approximately 25% of patients (93 out of 373) experienced delays accessing specialized care, which were associated with fewer SLE manifestations at first SLE-related encounter (fewer than two SLE domains; 92% vs 72%, P < 0.001). Patients with mucocutaneous or musculoskeletal manifestations were less likely to experience delays, whereas hematologic (odds ratio [OR] 1.71, 95% CI 1.03-2.84) or antiphospholipid antibodies domains (OR 6.05, 95% CI 2.46-14.88) were associated with delays. Delays were associated with damage at first access to SLE-specialized care (SDI ≥1; 30% vs 7%, P < 0.001). CONCLUSION:Patients follow a heterogeneous pathway to receive care. One-fourth of patients experienced delays accessing SLE-specialized care, which was associated with disease-related damage. Fewer manifestations, hematologic manifestations, or antiphospholipid antibodies were associated with delays.

OBJECTIVES:To examine the clinicopathologic features of patients with polymyalgia rheumatica (PMR) who had thoracic aorta repair surgery. Findings were compared with those of a cohort of patients with giant cell arteritis (GCA) requiring thoracic aorta repair. METHODS:All patients evaluated at Mayo Clinic in Rochester, MN, with Current Procedural Terminology (CPT) codes for thoracic aorta repair surgery between 2000-2021 were identified. All patients were screened for prior PMR diagnosis. Patients with PMR and no signs of GCA were categorized as clinically isolated PMR. The medical records of all patients were manually reviewed, and pathologists re-examined all the aortic tissues. RESULTS:Of the 4621 patients with at least one CPT code for thoracic aorta repair surgery, 43 patients were diagnosed with clinically isolated PMR before the surgery. Detailed histopathological examination of the aortic tissues revealed active inflammation in 30/43 (70%) patients after a median (IQR) of 10.0 (4.7-13.3) years from the PMR diagnosis. When compared with aortic tissue from patients with a prior diagnosis of GCA, the aorta of patients with PMR had more severe inflammation (Grade 3: 15/30 [50%] vs 5/34 [15%], P = 0.002). Patients with PMR and thoracic aorta repair may experience a 40% increased risk of mortality compared with the general population, but this did not reach statistical significance (standardized mortality ratio: 1.40; 95% CI: 0.91-2.07). CONCLUSIONS:Some patients with PMR have subclinical aortic inflammation that is detectable many years after initial diagnosis and may contribute to the development of aortic aneurysm.

OBJECTIVES:To investigate the clinicopathologic features of patients with giant cell arteritis (GCA) who had thoracic aorta aneurysm or dissection surgery.METHODS:Patients who had thoracic aorta surgery between January 1, 2000, and December 31, 2021, at the Mayo Clinic, Rochester, Minnesota, were identified with current procedural terminology (CPT) codes. The identified patients were screened for a prior diagnosis of GCA with diagnostic codes and electronic text search. The available medical records of all the patients of interest were manually reviewed. Thoracic aorta tissues obtained during surgery were re-evaluated in detail by pathologists. The clinicopathologic features of these patients were analyzed. Overall observed survival was compared with lifetable rates from the United States population.RESULTS:Of the 4621 patients with a CPT code for thoracic aorta surgery, 49 had a previous diagnosis of GCA. Histopathologic evaluation of the aortic tissue revealed active aortitis in most patients with GCA (40/49, 82%) after a median (IQR) of 6.0 (2.6-10.3) years from GCA diagnosis. All patients were considered in clinical remission at the time of aortic surgery. The overall mortality compared to age and sex-matched general population was significantly increased with a standardized mortality ratio of 1.55 (95% CI, 1.05-2.19).CONCLUSION:Histopathologic evaluation of the thoracic aorta obtained during surgery revealed active aortitis in most patients with GCA despite being considered in clinical remission several years after GCA diagnosis. Chronic, smoldering aortic inflammation likely contributes to the development of aortic aneurysm and dissection in GCA.

OBJECTIVE:To evaluate the safety and efficacy of tocilizumab (TCZ) in giant cell arteritis (GCA) in a large North American cohort. METHODS:Patients with GCA treated with TCZ between January 1, 2010, and May 15, 2020, were retrospectively identified. Kaplan-Meier methods were used to estimate time to TCZ discontinuation and time to first relapse after TCZ discontinuation. Poisson regression models were used to compare annualized relapse rates before, during, and after TCZ use. Age- and sex-adjusted risk factors associated with relapse on and off TCZ and development of adverse events of significant interest (AESIs) were examined using Cox models. RESULTS:One hundred fourteen patients (60.5% female) were included with mean (SD) age 70.4 (8.2) years. Median duration from GCA diagnosis to TCZ start was 4.5 months. Median overall duration of TCZ treatment was 2.3 years. Relapse rate prior to TCZ start (0.84 relapses/person-year) was 3-fold reduced while on TCZ (0.28 relapses/person-year; P < 0.001) but increased to 0.64 relapses/person-year after TCZ discontinuation. Fifty-two patients stopped TCZ after a median of 16.8 months; 27 relapsed after discontinuation (median: 8.4 months; 58% relapsed within 12 months). Only 14.9% of patients stopped TCZ because of AESIs. Neither dose/route of TCZ, presence of large-vessel vasculitis, nor duration of TCZ therapy prior to discontinuation predicted relapse after TCZ stop. CONCLUSION:TCZ is well tolerated in GCA, with low rates of discontinuation for AESIs. However, relapse occurred in > 50% despite median treatment > 12 months. Since the duration of TCZ prior to discontinuation did not significantly affect subsequent risk of GCA recurrence, further research is needed to determine the optimal duration of therapy.

Objectives ANCA-associated vasculitis (AAV) is currently categorized under the small vessel vasculitides. There is limited knowledge about large vessel involvement in AAV (L-AAV), mainly described in case reports and small series. L-AAV can involve temporal arteries (TA-AAV), aorta (A-AAV), and periaortic soft tissue (PA-AAV). We sought to characterize the features of patients with L-AAV.Methods Patients older than 18 years at diagnosis of TA-AAV, A-AAV and PA-AAV seen at the Mayo Clinic, Rochester between 1 January 2000 and 31 December 2021 were identified through a proprietary medical text search algorithm. Patients were included if diagnosed with L-AAV, fulfilled 2022 ACR/EULAR classification criteria for GPA, MPA or EGPA, had positive ANCA test results, and had more than one outpatient or inpatient visit.Results The study cohort consists of 36 patients with L-AAV. Of those, 23 had p-ANCA and/or MPO-ANCA, and 13 had c-ANCA and/or PR3-ANCA. Mean (s.d.) age at AAV diagnosis was 63.4 (12.79) years; 20 (56%) were male. Seventeen patients had TA-AAV, 10 had A-AAV and 9 had PA-AAV. Most patients (n = 25, 69%) were diagnosed with large vessel vasculitis and AAV within a 1-year timespan. Twenty-five (69%) patients had histopathological confirmation of AAV diagnosis in a location other than temporal artery, aorta or periaortic soft tissue. Glucocorticoids (36/36), rituximab (19/36) and methotrexate (18/36) were the most frequent treatments.Conclusion This is the largest single-centre cohort of patients with L-AAV to date. AAV can involve large arteries, albeit infrequent. AAV-targeted therapy should be considered in patients with L-AAV.

OBJECTIVES:Clinically isolated aortitis (CIA) refers to inflammation of the aorta without signs of systemic vasculitis or infection. Population-based data on the epidemiology of CIA in North America is lacking. We aimed to investigate the epidemiology of pathologically confirmed CIA.METHODS:Residents of Olmsted County, Minnesota were screened for thoracic aortic aneurysm procedures with current procedural terminology codes between January 1, 2000, and December 31, 2021, using the resources of the Rochester Epidemiology Project. The medical records of all patients were manually reviewed. CIA was defined as histopathologically confirmed active aortitis diagnosed by evaluation of aortic tissue obtained during thoracic aortic aneurysm surgery in the absence of any infection, rheumatic disease, or systemic vasculitis. Incidence rates were age and sex adjusted to the 2020 United States total population.RESULTS:Eight incident cases of CIA were diagnosed during the study period; 6 (75%) of them were female. Median (IQR) age at diagnosis of CIA was 78.3 (70.2-78.9) years; all were diagnosed following ascending aortic aneurysm repair. The overall age and sex adjusted annual incidence rate of CIA was 8.9 (95% CI, 2.7-15.1) per 1,000,000 individuals over age 50 years. The median (IQR) duration of follow-up was 8.7 (1.2-12.0) years. The overall mortality compared to the age and sex matched general population did not differ (standardised mortality ratio: 1.58; 95% CI, 0.51-3.68).CONCLUSIONS:This is the first population-based epidemiologic study of pathologically confirmed CIA in North America. CIA predominantly affects women in their eighth decade and is quite rare.

Background The most common extraarticular manifestation of rheumatoid arthritis (RA) is the rheumatoid nodule, which is reported to affect about 30% of patients with RA.[1] The development of rheumatoid nodules has been associated most strongly with high disease activity, seropositive status, and more rapid progression of joint destruction. Despite significant changes in RA treatment and decreasing incidence of seropositive RA, no recent population-based studies have assessed the epidemiology of rheumatoid nodules. Objectives We aim to investigate changes in rheumatoid nodule incidence over time. Methods This study evaluated rheumatoid nodule incidence trends using an inception cohort that included all adult patients from a geographically well-defined area who met the 1987 American College of Rheumatology criteria for RA between 1/1/1985 and 12/31/2014. Patients were followed until the earlier of death, migration from the region, or 12/31/2000 (for patients with incident RA in 1985-1994) or 12/31/2008 (for 1995-2007 patients) or 10/15/2022 (for 2008-2014 patients). Patients were divided into two cohorts based on the incidence date of RA, an early cohort from 1985-1999 and a later cohort from 2000-2014. Medical records were reviewed manually, and the incidence date of rheumatoid nodules was recorded if determined to be present either by clinical judgment and/or histopathology. The 10-year cumulative incidence of rheumatoid nodules was estimated in each cohort. Cox proportional hazard models adjusted for age, sex and calendar year were used to determine associations between specific demographic and RA disease data with rheumatoid nodules. Results 907 patients were included in this study, 296 (67% female) in the 1985-1999 cohort and 611 (70% female) in the 2000-2014 cohort. The mean follow-up period between these cohorts, respectively, was 9.1 and 7.4 years. Baseline characteristics (earlier cohort, latter cohort) included rheumatoid factor (RF) positive (70%, 59%), joint erosions in the first year of RA (24%, 29%), and ever smoker (57%, 47%). The 10-year cumulative incidence of rheumatoid nodules was 31% in the 1985-1999 cohort and 16% in the 2000-2014 cohort (hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.39-0.70). Identified risk factors for the development of rheumatoid nodules included RF positivity (HR 4.38, 95%CI 2.37-8.09), erosions (HR 2.53, 95%CI 1.64-3.91), current smoker (HR 2.09, 95%CI 1.30-3.37), male sex (HR 1.77, 95%CI 1.14-2.73), methotrexate use (HR 1.77, 95%CI 1.09-2.86) and other DMARDs (HR 2.07, 95%CI 1.14-3.74) (Table 1). Conclusion The incidence of rheumatoid nodules has decreased substantially over time. More research is needed to understand the drivers of this improvement and implications on RA disease outcomes. Reference [1] Myasoedova E, Crowson CS, Turesson C, Gabriel SE, Matteson EL. Incidence of extraarticular rheumatoid arthritis in Olmsted County, Minnesota, in 1995-2007 versus 1985-1994: a population-based study. J Rheumatol. 2011;38(6):983-989. Acknowledgements: NIL. Disclosure of Interests None Declared.

Background: Antiphospholipid syndrome (APS) is a systemic autoimmune disease clinically associated with thrombotic and obstetric events. Additional manifestations have been associated with APS, like diffuse alveolar hemorrhage (DAH). We aimed to summarize all the evidence available to describe the presenting clinical fea-tures, their prognostic factors, and short-and long-term outcomes.Methods: We performed a mixed-method approach combining a multicenter cohort with a systematic literature review (SLR) of patients with incident APS-associated DAH. We described their clinical features, treatments, prognostic factors, and outcomes (relapse, mortality, and requirement of mechanical ventilation [MV]). Kaplan-Meier methods were used to estimate relapse and mortality rates, and Cox and logistic regression models were used to assess the factors associated as appropriate.Results: We included 219 patients with incident APS-associated DAH (61 from Mayo Clinic and 158 from SLR). The median age was 39.5 years, 51% were female, 29% had systemic lupus erythematosus, and 34% presented with catastrophic APS (CAPS). 74% of patients had a history of thrombotic events, and 26% of women had a history of pregnancy morbidity; half of the patients had a history of thrombocytopenia, and a third had val-vulopathy. Before DAH, 55% of the patients were anticoagulated. At DAH onset, 65% of patients presented hemoptysis. The relapse rate was 47% at six months and 52% at one year. Triple positivity (HR 4.22, 95% CI 1.14-15.59) was associated with relapse at six months. The estimated mortality at one and five years was 30.3% and 45.8%. Factors associated with mortality were severe thrombocytopenia (< 50 K/mu L) (HR 3.10, 95% CI 1.39-6.92), valve vegetations (HR 3.22, 95% CI 1.14-9.07), CAPS (HR 3.80, 95% CI 1.84-7.87), and requirement of MV (HR 2.22, 95% CI 1.03-4.80). Forty-two percent of patients required MV on the incident DAH episode. Patients presenting with severe thrombocytopenia (OR 6.42, 95% CI 1.77-23.30) or CAPS (OR 4.30, 95% CI 1.65-11.16) were more likely to require MV.Conclusion: APS-associated DAH is associated with high morbidity and mortality, particularly when presenting with triple positivity, thrombocytopenia, valvular involvement, and CAPS.

Objectives Vasculitis in patients with sarcoidosis is rare and can affect any sized blood vessel. Limited information describing this association is available. Methods A single-institution medical records review study was performed reviewing all patients with a diagnosis code for sarcoidosis and vasculitis between January 1, 1998, and December 31, 2019. Data were abstracted regarding diagnosis, treatment, and outcomes from medical records. Patients were diagnosed with vasculitis based on biopsy and/or arterial imaging. Comparison between patients presenting with large and/or medium vessel vasculitis (L/MVV) versus patients with only small vessel vasculitis (SVV) was performed. Results Seventeen patients were identified during the study period. Nine patients (56% female) had L/MVV, and 8 (50% female) had SVV. Sarcoidosis preceded vasculitis in 4 (44%) L/MVV and 3 (38%) SVV. The mean ± SD age at sarcoidosis diagnosis was 53.2 ± 17.8 and 51.9 ± 11.4 years, and the mean ± SD age at vasculitis diagnosis was 57.4 ± 19.6 and 59.0 ± 13.4 years in L/MVV and SVV, respectively. Number of organ systems involved by sarcoidosis was similar (median [interquartile range], 3 [1–4] L/MVV vs 2.5 [1.75–3.25] SVV). The mean length of follow-up was 11.5 ± 12.8 in L/MVV and 13.1 ± 14.3 years in SVV. Complete response to therapy for vasculitis was observed in 8 of 9 with L/MVV and 7 of 8 with SVV. Four patients with SVV were able to stop all immunosuppression as compared with only 1 patient with L/MVV at the last follow-up. Conclusions This series observed a comparable number of patients with L/MVV and SVV. Although a variety of treatments were used, most patients achieved remission regardless of vessel size affected. Clinicians should be aware of the overlap between sarcoidosis and vasculitis.

Vasculitis in patients with sarcoidosis is rare and can affect blood vessels of any size. Limited information describing this association is available.To describe a large, single-institution case-series of patients with sarcoidosis and vasculitis.A single-institution retrospective study was performed reviewing all patients with a diagnosis code for sarcoidosis and vasculitis between January 1, 1998 and December 31, 2019. Medical records were individually reviewed, and data regarding diagnosis, treatment, and outcomes were abstracted. Sarcoidosis was diagnosed based on histologic, radiographic, and clinical data with exclusion of alternative diagnoses. Diagnosis for small vessel vasculitis (SVV) required biopsy confirmation. Patients with large or medium-vessel vasculitis (L/MVV) required biopsy and/or arterial imaging. Comparison between patients presenting with L/MVV versus patients with only SVV was performed.Seventeen patients were identified during the study period. Nine patients (56% female) had L/MVV and 8 (50% female) had SVV. Sarcoidosis preceded the diagnosis of vasculitis in 4 (44%) patients in the L/MVV group compared to 3 (38%) patients in the SVV group. Mean±SD age at sarcoidosis diagnosis was 53.2±17.8 and 51.9±11.4 years and mean±SD age at vasculitis diagnosis was 57.4±19.6 and 59.0±13.4 years in L/MVV and SVV groups, respectively. Number of organ systems involved by sarcoidosis was similar [median (IQR) 3 (1,4) L/MVV vs. 2.5 (1.75, 3.25) SVV]. Sarcoid organ involvement and vasculitis vessel distributions are noted in Table 1. Mean length of follow-up was 11.5±12.8 years in L/MVV and 13.1±14.3 years in SVV. All patients were treated with glucocorticoids for vasculitis. More patients with L/MVV were treated with at least one DMARD/biologic (8/9, 89%) compared to SVV (3/8, 38%, p=0.05). Complete response to therapy for vasculitis was observed in 8/9 L/MVV and 7/8 in SVV. Four patients in SVV group were able to stop all immunosuppression but only one patient with L/MVV was off all therapy at last follow-up.CaseSexAge Sarcoid / Vasculitis Dx, yrWASOG Organ Involvement*Vessel sizeArterial involvementon imaging†¥ or biopsy**1M44/44B-J, ET-LN, SkLVV, MVVAA (e), Ant Tib (s), Ax (s), Br (o), V (s), Ca (s), CF (b), I (b), Innom (b), Mes (b, o, s), Per (b), Pop (a), Re (b), SF (b), Sub (o, pa, wt), TA (a)2F66/68BM, ET-LN, Li, Lu, NS, SLVVTA (hm)3F55/55Lu, SpMVVIMA (a, s, o, wt), Sp (a)4M81/80LuLVVAA (hm), Car (hm), Innom (hm), Sub (hm), TA (hm)5F72/72Eye, NS, LuLVV, MVVACA (b), ICA (b, en, s), MCA (b), SMA (wt)6M43/45LuLVV, MVVBr (o, s), Ce (s), SMA (s), Sp (s), TA (wt)7F53/54B-J, Eye, Lu, SkMVVSkin – medium vessel**8M24/20Eye, Li, Lu, SpMVVHep (a), Sp (a)9F40/79LuLVVTemporal artery**10M55/57Li, Lu, NSSVVSural nerve**11F53/50ET-LN, Lu, SkSVVSkin**12M60/62LuSVVSkin**13F67/82ET-LN, LuSVVSkin**14F52/56Eye, Lu, NS, SkSVVSkin**15M39/37Eye, Lu, NS, SkSVVSkin**16F57/56Lu, SkSVVSkin**17M32/71LuSVVSkin***WASOG Organ Involvement: B-J, bone-joint; BM, bone marrow; ET-LN, extra-thoracic lymph node; Li, liver; Lu, lung; NS, nervous system; Sk, skin; Sp, spleen† a, aneurysm; b, beaded irregularities; e, ectasia; en, enhancement; hm, hypermetabolism (on positive emission tomography); o, occlusion; pa, pseudoaneurysm; s, stenosis; wt, wall thickening¥ AA, abdominal aorta; ACA, anterior cerebral artery; Ant Tib, anterior tibial; Ax, axial; Br, brachial; Ca, carotid; Ce, celiac; CF, common femoral; Hep, hepatic; I, iliac; ICA, internal carotid artery; IMA, inferior mesenteric artery; Innom, innominate; MCA, middle cerebral artery; Mes, mesenteric branch; PCA, posterior cerebral artery; Per, peroneal; Pop, popliteal; Re, renal; SF, superficial femoral; Sp, splenic; Sub, subclavian; TA, thoracic aorta; V, vertebralVasculitis in patients with sarcoidosis is uncommon. Variability exists in the vessels involved and the treatments utilized. Overall this series observed favorable outcomes with a high percentage achieving complete response, regardless of vessel size affected.None declared