scholarly journals AB0353 ADRENAL INSUFFICIENCY AFTER GLUCOCORTICOID TREATMENT OF GIANT CELL ARTERITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1201.2-1201
Author(s):  
A. Hočevar ◽  
R. Jese ◽  
J. Kramarič ◽  
M. Tomsic ◽  
Z. Rotar

Background:Adrenal insufficiency is frequently neglected and underappreciated, potentially severe complication of systemic glucocorticoid therapy.Objectives:We aimed to evaluate the prevalence of glucocorticoid induced adrenal insufficiency in giant cell arteritis (GCA).Methods:We analysed adrenal function data in a cohort of GCA patients diagnosed between July 2014 and July 2019, in whom discontinuation of methylprednisolone therapy was planned. Adrenal function was tested by Corticotropin stimulation test (CST). To perform the CST, methylprednisolone was substituted with hydrocortisone (20mg qd in three divided doses) for one to four weeks before the test. Adrenal insufficiency was defined as cortisol level <450 nmol/l measured 30 minutes after the corticotropin injection; additionally, the result of the CST was defined as borderline when the cortisol level 30 minutes after corticotropin injection was between 450 nmol/l and 500 nmol/l.Results:Adrenal function was tested in 74/215 GCA patients before definite methylprednisolone withdrawal (after a median 13.5 (12.9 – 22.4) months of glucocorticoid therapy). The mean (SD) methylprednisolone dose, prior to substitution with hydrocortisone and subsequent CST, was 3.1 (1.6) mg. Adrenal insufficiency was detected in 36/74 patients (48.6%); additionally, 10/74 patients (13.5%) had a borderline CST result. Seventeen patients with either adrenal insufficiency or borderline CST result, had a repeated CST after median (IQR) 11.6 (8.9; 12.6) months. Adrenal insufficiency persisted in 11/17 (64.7%) patients, and 1/17 patients had a borderline CST. A third CST was performed in 4/12 patients with abnormal second CST after median (IQR) 8.3 (6.9; 10.6) months. Adrenal function recovered in one patient, while the adrenal insufficiency persisted in the remaining 3 patients.Conclusion:Adrenal insufficiency is a common and potentially long-lasting glucocorticoid induced adverse event in GCA patients.Disclosure of Interests:None declared

Rheumatology ◽  
2020 ◽  
Vol 59 (10) ◽  
pp. 2764-2773 ◽  
Author(s):  
Stina W Borresen ◽  
Toke B Thorgrimsen ◽  
Bente Jensen ◽  
Linda Hilsted ◽  
Else M Bartels ◽  
...  

Abstract Objectives Glucocorticoid treatment is fundamental in polymyalgia rheumatica (PMR) and giant cell arteritis (GCA), but carries a risk of glucocorticoid-induced adrenal insufficiency. Adrenal insufficiency can cause reluctance to stop glucocorticoid treatment after disease remission as symptoms can resemble PMR/GCA flare. We aimed to determine the prevalence of adrenal insufficiency in prednisolone-treated patients with PMR/GCA. Methods We included 47 patients with PMR (n = 37), GCA (n = 1) or both (n = 9), treated with prednisolone for ≥5.4 months, current dose 2.5–10 mg/day. Adrenal function was evaluated using a corticotropin (Synacthen®) stimulation test following 48 h prednisolone pause. Two years’ clinical follow-up data are provided. Results Seven patients (15%) had adrenal insufficiency, 4 (11%) of the 37 patients with PMR alone, and 3 (30%) of the 10 patients with GCA. Corticotropin-stimulated P-cortisol was significantly associated with current prednisolone dose, mean daily dose the last 3 and 6 months before testing, and basal P-cortisol, but not with total dose or treatment duration. Adrenal insufficiency occurred with all current prednisolone doses (2.5–10 mg/day). Five (71%) of the glucocorticoid-insufficient patients could discontinue prednisolone treatment; two of them recovered glucocorticoid function, whereas three still needed hydrocortisone replacement 2 years later. Two patients experienced in total four acute hospital admissions with symptoms of adrenal crises. Conclusion Glucocorticoid-induced adrenal insufficiency occurred in 15% of patients with PMR/GCA. Mean prednisolone dose the last 3 months and basal P-cortisol were the best and simplest predictors of adrenal function. Most of the glucocorticoid-insufficient patients could discontinue prednisolone with appropriate treatment for adrenal insufficiency.


BMJ ◽  
2021 ◽  
pp. n1380
Author(s):  
Alessandro Prete ◽  
Irina Bancos

ABSTRACTSynthetic glucocorticoids are widely used for their anti-inflammatory and immunosuppressive actions. A possible unwanted effect of glucocorticoid treatment is suppression of the hypothalamic-pituitary-adrenal axis, which can lead to adrenal insufficiency. Factors affecting the risk of glucocorticoid induced adrenal insufficiency (GI-AI) include the duration of glucocorticoid therapy, mode of administration, glucocorticoid dose and potency, concomitant drugs that interfere with glucocorticoid metabolism, and individual susceptibility. Patients with exogenous glucocorticoid use may develop features of Cushing’s syndrome and, subsequently, glucocorticoid withdrawal syndrome when the treatment is tapered down. Symptoms of glucocorticoid withdrawal can overlap with those of the underlying disorder, as well as of GI-AI. A careful approach to the glucocorticoid taper and appropriate patient counseling are needed to assure a successful taper. Glucocorticoid therapy should not be completely stopped until recovery of adrenal function is achieved. In this review, we discuss the factors affecting the risk of GI-AI, propose a regimen for the glucocorticoid taper, and make suggestions for assessment of adrenal function recovery. We also describe current gaps in the management of patients with GI-AI and make suggestions for an approach to the glucocorticoid withdrawal syndrome, chronic management of glucocorticoid therapy, and education on GI-AI for patients and providers.


Author(s):  
Yvan Jamilloux ◽  
Eric Liozon ◽  
Gregory Pugnet ◽  
Sylvie Nadalon ◽  
Kim Heang Ly ◽  
...  

PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e68713 ◽  
Author(s):  
Yvan Jamilloux ◽  
Eric Liozon ◽  
Gregory Pugnet ◽  
Sylvie Nadalon ◽  
Kim Heang Ly ◽  
...  

2021 ◽  
Vol 8 ◽  
Author(s):  
Annette D. Wagner ◽  
Ulrike Wittkop ◽  
Jessica Thalmann ◽  
Tina Willmen ◽  
Vega Gödecke ◽  
...  

Giant cell arteritis (GCA) is a systemic granulomatous vasculitis clinically characterized by a prompt response to glucocorticoid therapy. Dendritic cells (DCs) play a central role in the pathogenesis of the disease and are increased in temporal arteries from GCA patients. The aim of this study was to determine the effects of glucocorticoid therapy on granulomatous infiltrates and on peripheral DCs of GCA patients. Immunohistochemical staining of temporal artery specimens from 41 GCA patients revealed a rapid reduction of the number of DCs after initiation of glucocorticoid treatment. TUNEL staining was performed to quantify apoptotic S100+ DC, CD3+ T cells, and CD68+ macrophages in the granulomatous infiltrates. An increase of apoptotic cells up to 9 ± 2% after 4–5 days of glucocorticoid therapy and up to 27 ± 5% (p &lt; 0.001, compared to earlier timepoints) after 6–10 days was detected. A decrease of CCL19 and CCL21 expression was observed after starting glucocorticoid therapy. Granulocyte-macrophage colony-stimulating factor (GM-CSF) expression also significantly decreased under glucocorticoid therapy. No GM-CSF expression was detected in the control specimens. Glucocorticoid therapy leads to a rapid, time-dependent reduction of DCs in temporal arteries from GCA patients and reduction of mediators for cell migration. Our data suggest GM-CSF as a novel therapeutic target of GCA.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 34.1-34
Author(s):  
R. S. Andev ◽  
N. Ahmad ◽  
A. Verdiyeva ◽  
R. Luqmani ◽  
S. Dubey

Background:Aortitis, a rare form of large vessel vasculitis, may occur in the context of a primary systemic vasculitis, as a part of systemic autoimmune disease or in isolation. The evidence and guidelines to diagnose, manage and monitor aortitis remain limited. However, PET CT and vascular MRI scans have facilitated our ability to make the diagnosis more readily. The optimal management strategy and complication rates remain uncertain.Objectives:Our aim was to explore the clinical, laboratory and radiological features of aortitis. We sought to review the management and complications of this illness by collecting detailed information on the outcomes and treatments used, including disease modifying agents (DMARDs) and biologics.Methods:Patients diagnosed with aortitis since 2006 that had been managed in a single tertiary centre were identified using the Rheumatology Assessment Database Innovation in Oxford (RHADIO). Their medical notes were retrospectively reviewed using a local electronic patient record system and the following information was obtained: demographics, underlying risk factors, imaging and laboratory results (including biopsy reports if available), management and outcome.Results:We identified 155 patients who met the inclusion criteria. There was a female preponderance of 57.4% (n=89). At the time of diagnosis, the average age was 69 (range 30-92) and the mean symptomatology length prior to diagnosis was 12 months (range 0-120). The majority of patients (60.4%, n=94) had aortitis secondary to giant cell arteritis (GCA), isolated aortitis was identified in 29.7% (n=46) and IgG4-related disease aortitis was uncommon (2.6%, n=4). Those with cranial GCA-like symptoms were diagnosed on average 3.9 months before those who presented differently (10.1 months versus 14.0 months).Common presentations comprised: systemic inflammatory response syndrome (49.0%, n=76), cranial GCA-like symptoms (26.5%, n=41) and unexplained weight loss (24.5%, n=38). Importantly, 18.7% (n=29) of patients presented with ischaemic symptoms that included angina, TIAs/strokes and claudication. Aortic dissection was the primary presentation for 6.5% (n=10) of patients.At presentation, the mean CRP was 84 mg/L (range 1-249) and the ESR was 72 mm/hr (range 2-164). Most (73.5%, n=114) had diagnostic PET CT changes. For those patients with GCA, diagnostic ultrasound changes were seen in 27.7% (n=26).Nearly all were treated with prednisolone (92.3%, n=143) and all but 8 (5.1%) received a DMARD at some point. Methotrexate was the most commonly used DMARD (93.9%, n=138), followed by leflunomide (22.3%, n=35) and azathioprine (19.1%, n=28). Cyclophosphamide was used in 23.8% of patients (n=38) and 15 patients (9.7%) received tocilizumab.Around a third (34.1% n=53/155) had received at least two DMARDs during their treatment course. On average, patients required 3.46 drugs to manage their aortitis. Those who relapsed (43.2%, n=67) were more likely to have GCA (65.7%, n=44).Vascular sequelae were present in 37.4% (n=58). The most common complications were ischaemic in nature with stroke/TIA and claudication reported in 16.8% (n=26). Aortic aneurysms were recorded in 11.6% (n=18) of cases and 5.1% (n=8) developed dissections despite being on treatment for their aortitis. One patient developed renal infarcts and ischaemic bowel leading to intestinal failure because of florid vasculitis.Conclusion:Aortitis has a varied presentation with systemic inflammatory response syndrome being the most common. Delayed diagnosis remains a problem and especially for those with non-GCA related aortitis, which is likely to contribute to the risk of subsequent vascular complications. Vascular events including dissection are common, many of which could be preventable, emphasising the importance of early diagnosis and good disease control.References:[1]Koster M et al. Large-vessel giant cell arteritis: diagnosis, monitoring and management. Rheumatology [Internet]. 2018 Feb 1;57(suppl_2):ii32–42. Available from: https://doi.org/10.1093/rheumatology/kex424Disclosure of Interests:None declared


Rheumatology ◽  
2021 ◽  
Author(s):  
Verena Schönau ◽  
Jessica Roth ◽  
Koray Tascilar ◽  
Giulia Corte ◽  
Bernhard Manger ◽  
...  

Abstract Objectives Efficacy evaluation of giant cell arteritis (GCA) treatment is primarily based on non-specific symptoms and laboratory markers. We aimed to assess the change in vascular inflammation in patients with large vessel (LV)-GCA under different treatments using [18F]FDG PET/CT. Methods Observational study on patients with new-onset, active LV-GCA starting treatment with either prednisolone monotherapy (PRED) or combination with methotrexate (MTX) or tocilizumab (TOC). All patients underwent baseline and follow-up PET/CT. The aorta and its major branches were assessed using PET vascular activity score (PETVAS) by independent readers. Cumulative glucocorticoid doses and cessation of glucocorticoid treatment were documented in all patients. Results We included 88 LV-GCA patients, 27 were treated with PRED, 42 with MTX, and 19 with TOC. PETVAS decreased from 18.9–8.0 units at follow-up in the overall population (p&lt; 0.001). PETVAS changes were numerically higher in patients receiving MTX (-12.3 units) or TOC (-11.7 units) compared with PRED (-8.7). Mean cumulative prednisolone dosages were 5637, 4418, and 2984 mg in patients treated with PRED, MTX, and TOC (p= 0.002). Risk ratios for glucocorticoid discontinuation at the time of follow-up PET/CT were 6.77 (95%CI 1.01–45.29; p= 0.049) and 16.25 (95%CI 2.60–101.73; p= 0.003) for MTX and TOC users compared with PRED users. Conclusion Treatment of LV-GCA inhibits vascular inflammation in the aorta and its major branches. While similar control of vascular inflammation was achieved with PRED, MTX, and TOC treatments, TOC showed a strong glucocorticoid sparing effect, supporting the concept of initial combination therapy.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 93.2-94
Author(s):  
L. C. Burg ◽  
P. Brossart ◽  
K. I. Reinking ◽  
R. P. Finger ◽  
C. Behning ◽  
...  

Background:Giant cell arteritis (GCA) is the most common form of systemic vasculitis in patients aged 50 years and older.1Visual symptoms such as amaurosis, diplopia, temporary or permanent visual field loss secondary to optic nerve ischemia are common manifestations.2The value of vascular ultrasound of extra-ocular vessels in diagnosing GCA is well established.3However, the role of transocular ultrasound of the central retinal artery in GCA patients has not yet been established.Objectives:To identify changes in flow velocities of the central retinal artery in GCA patients with visual symptoms and controls with transocular high resolution ultrasound.Methods:Prospective analysis of GCA patients with visual symptoms and controls. Ultrasound of the central retinal artery was performed in 18 newly diagnosed consecutive GCA patients with visual symptoms (GCA-group) and 25 controls without ocular pathology. Visual symptoms included amaurosis, diplopia and temporary or permanent visual field loss. For each eye, peak systolic values (PS) and end diastolic values (ED) were recorded. Furthermore, the resistance index of each central retinal artery was measured.Results:Twenty-one of 36 eyes of 18 GCA patients were affected. Therefore 21 central retinal were measured. The control group consisted of 50 central retinal arteries of 25 eye-healthy individuals. The mean age and gender distribution of the GCA-group were 75.6 years (SD± 8.1) with eight females (44 %) and 67 years (SD± 8.9) with twelve females (48%) in the control group. The mean flow velocity of the central retinal artery was PS 12.2 cm/s (SD± 3.5) and ED 3.7 cm/s (SD± 1.2) in the GCA group and PS 14.4 cm/s (SD± 3.2) and ED 5.1 cm/s (SD± 1.6) in the control group. The mean RI was 0.9 (SD± 0.3) in the GCA group and 0.8 (SD± 0.3) in the control group. Mean reduction in flow velocity in the GCA-group was PS 2.1 cm/s (p= 0.039) and ED 1.4 (p= 0.0004) cm/s, while the RI was increased by 0.14 (p= 0.077). The results for PS and ED measurements were statistically significant, while the results for RI were not significant.Conclusion:In GCA patients with ocular symptoms, a reduction of flow velocities of the central retinal artery compared to the eye-healthy control group was found. Results for PS and ED were significant. There seems to be a trend for decreased flow velocities in coexistence with visual symptoms in patients with GCA.References:[1]Warrington KJ, Matteson EL. Management guidelines and outcome measures in giant cell arteritis (GCA). Clin Exp Rheumatol 2007;25:137–41.[2]Chean CS, Prior JA, Helliwell T, et al. Characteristics of patients with giant cell arteritis who experience visual symptoms. Rheumatol Int 2019;39:1789–96.[3]Dejaco C, Ramiro S, Duftner C, et al. EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice. Ann Rheum Dis 2018;77:636–43Figure 1.Transocular ultrasound of an affected eye in giant cell arteritis with reduced flow velocities and increased resistance index.Disclosure of Interests:None declared


Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Owen Cronin ◽  
Neil D McKay ◽  
Hannah Preston ◽  
Helen Harris ◽  
Barbara Hauser

Abstract Background/Aims  Giant cell arteritis with large vessel vasculitis (LV-GCA) represents a distinct, less researched sub-category of giant cell arteritis (GCA). In comparison to cranial GCA, the patient’s diagnostic pathway is less well described and it is thought that LV-GCA is underdiagnosed, including in patients with polymyalgia rheumatica and cranial-GCA. Advances in imaging (e.g. PET-CT) and treatment (tocilizumab), have provided additional options in the diagnosis and management of LV-GCA. The aim was to describe the contemporary clinical journey for patients diagnosed with LV-GCA. Methods  The electronic patient health record system in NHS Lothian (TrakCare) was used to collect relevant data. Patients with imaging-confirmed large vessel vasculitis, diagnosed with GCA after 1 January 2017 were included. Follow-up was until August 2020. Results  Eighteen patients with LV-GCA were included. The mean age was 65 years and 66.7% were female. Two patients had known cranial-GCA but 89% of patients were diagnosed exclusively with large vessel involvement. The most common symptoms were malaise (55%), weight loss (55%), polymyalgia rheumatica (55%) and limb claudication (44%). Pyrexia of unknown origin was a feature in only 17% of patients. Two patients were asymptomatic and were investigated on the basis of raised inflammatory markers. Mean CRP at baseline was 99mg/L and ESR 85mm/hour. The mean time from symptom-onset to diagnosis was 6.8 months (range 1 to 15 months). Sixteen patients (89%) were reviewed by at least one other secondary care specialist. One third of patients were referred from General Medicine followed by Vascular Surgery (16%) and General Practice (16%). 7/18 patients were inpatients at the time of referral. 56% of patients required two modalities of imaging to confirm large vessel involvement. The most commonly used imaging techniques (in descending order) were CT-Chest/Abdomen/Pelvis, CT-angiogram, PET-CT and Vascular Ultrasound. 50% of patients underwent follow-up imaging, most commonly MR- or CT-angiography. Mean follow-up was for 1.6 years. The mean prednisolone dose at 3 months (n = 18) was 24mg daily and 8mg at 12 months (n = 12). 28% of patients relapsed during the follow-up period at 4, 5, 8, 9 and 24 months post-diagnosis. 7/18 patients were commenced on methotrexate for steroid-side effects or for relapse. 8/18 received subcutaneous tocilizumab in combination with methotrexate in two cases. Three patients were started on azathioprine but only one continued. Conclusion  In modern-day clinical practice, patients with LV-GCA experience a longer time to diagnosis than those with cranial symptoms. Patients with LV-GCA can experience an array of constitutional symptoms. Frequently, more than one imaging modality is required to confirm LV-GCA and the majority of patients will have seen other hospital specialists or have been admitted to hospital before diagnosis. Methotrexate and tocilizumab are the most frequently-used and effective steroid-adjunct in this single-centre cohort. Disclosure  O. Cronin: None. N.D. McKay: Consultancies; Gilead. Other; Has received support for conference attendance from Pfizer and Gilead, Has received educational support from UCB, Gilead, Celgene, Biogen, Sanofi, Abbvie, Novartis, Pfizer. H. Preston: None. H. Harris: None. B. Hauser: None.


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