Symptoms Of Giant Cell Arteritis Research Articles

OP0059 MAVRILIMUMAB (ANTI GM-CSF RECEPTOR Α MONOCLONAL ANTIBODY) REDUCES RISK OF FLARE AND INCREASES SUSTAINED REMISSION IN A PHASE 2 TRIAL OF PATIENTS WITH GIANT CELL ARTERITIS

Background:T helper (Th)1 and Th17 lymphocytes play a role in the pathogenesis of giant cell arteritis (GCA). Current treatments primarily target the Th17 axis, possibly leaving residual Th1 activity. Granulocyte macrophage colony stimulating factor (GM-CSF), a mediator of Th1 and Th17 cells, is a pathogenic factor in GCA.Objectives:To evaluate the efficacy and safety of the GM-CSF inhibitor mavrilimumab in patients with GCA.Methods:Randomized, double-blind, placebo-controlled phase 2 trial enrolling patients with active, biopsy- or imaging-proven new onset (N/O) or relapsing refractory (R/R) GCA. Active disease: GCA symptoms and erythrocyte sedimentation rate (ESR) (>30 mm/hr) and/or C-reactive protein (CRP) (≥1 mg/dL) elevation within 6 weeks from randomization. Corticosteroid-induced remission (resolution of GCA symptoms and CRP <1 mg/dL or ESR <20 mm/hr) was required by baseline. 3:2 randomization to mavrilimumab 150 mg or placebo subcutaneously every 2 weeks and protocol-defined 26-week prednisone taper starting at 20-60 mg/day.Primary efficacy endpoint: time to first adjudicated flare (ESR ≥30 mm/hr and/or CRP ≥1 mg/dL and GCA symptoms or new/worsening vasculitis on imaging) by Week 26 in all treated patients. Key secondary endpoint: sustained remission through Week 26. Safety up to Week 38 was assessed.Results:70 patients (35 N/O, 35 R/R) were enrolled (mavrilimumab [N=42] or placebo [N=28]). Mean (SD) age was 69.7 (7.48) years and 71.4% were female. Flare by Week 26 occurred in 8 (19%) and 13 (46.4%) patients receiving mavrilimumab and placebo, respectively (27.4 percentage points reduction). Median time to flare by Week 26 could not be estimated in the mavrilimumab group due to too few events (Not Estimable) and was 25.1 weeks [95% CI: (16.0, NE)] in the placebo group (HR [95% CI] 0.38 [0.15, 0.92]; p=0.0263) (Figure). Sustained remission at Week 26 occurred in 83.2% of patients receiving mavrilimumab and 49.9% of those receiving placebo (33.4 percentage points increase; p=0.0038). Results were consistent across disease type subgroups (HR for flare: N/O 0.29 [95% CI: 0.06, 1.31; nominal p= 0.0873]; R/R 0.43 [95% CI: 0.14, 1.30]; nominal p=0.1231), although not powered for significance (Table). Adverse events (AEs), mostly mild to moderate, were comparable between groups. There were 5 serious AEs (mavrilimumab 2 [4.8%], placebo 3 [10.7%]), none drug-related. No deaths or vision loss occurred. No adjudicated cases of pulmonary alveolar proteinosis were observed.Table 1.Efficacy at Week 26All Patients [1]SubgroupsN/OR/RMavrilimu-mab (N=42)Placebo (N=28)Mavrilimu-mab (N=24)Placebo (N=11)Mavrilimu-mab (N=18)Placebo (N=17)Patients with Flare, n (%)8 (19.0)13 (46.4)3 (12.5)4 (36.4)5 (27.8)9 (52.9)Time to Flare (weeks) [2]Median, 95% CINE (NE, NE)25.1 (16.0, NE)NE (NE, NE)NE (11.7, NE)NE (16.4, NE)22.6 (16.0, NE)HR (Mavrilimumab vs Placebo), 95% CI [3]0.38 (0.15, 0.92)0.29 (0.06, 1.31)0.43 (0.14, 1.30)P-value [4] [5]0.02630.08730.1231Sustained Remission (%), 95% CI [6]83.2 (67.9, 91.6)49.9 (29.6, 67.3)91.3 (69.3, 97.7)62.3 (27.7, 84.0)72.2 (45.6, 87.4)41.7 (17.4, 64.5)Difference in Proportions (95% CI) [7]33.3 (10.7, 55.8)28.9 (-2.7, 60.5)30.6 (-2.1, 63.2)P-value [5] [7]0.00380.07270.0668NE = Not estimable. [1] Total mITT population. Stratified by randomization strata. [2] Kaplan-Meier. [3] Cox proportional-hazards model; treatment as covariate. [4] Log-rank test. [5] N/O and R/R subgroups not powered for significance; nominal p values reported. [6] Kaplan-Meier Survival Estimates with standard error. [7] Two-sided p-value for the difference in sustained remission between 2 arms using normal approximation. Placebo arm is reference.Conclusion:Mavrilimumab was superior to placebo on the primary and secondary efficacy endpoints of time to flare and sustained remission at week 26 in patients with GCA. Mavrilimumab was well tolerated, and no new safety signals were observed.Disclosure of Interests:Maria C. Cid Speakers bureau: meeting attendance support from Roche and Kiniksa, Paid instructor for: educational from GSK and Vifor, Consultant of: consulting for Janssen, GSK, and Abbvie, Grant/research support from: research grant from Kiniksa, Sebastian Unizony Consultant of: consulting for Janssen and Kiniksa, Grant/research support from: research support from Genentech, Lara Pupim Shareholder of: Kiniksa Pharmaceuticals, Employee of: Kiniksa Pharmaceuticals, Fang Fang Shareholder of: Kiniksa Pharmaceuticals, Employee of: Kiniksa Pharmaceuticals, Joseph Pirrello Shareholder of: Kiniksa Pharmaceuticals, Employee of: Kiniksa Pharmaceuticals, Ai Ren Shareholder of: Kiniksa Pharmaceuticals, Employee of: Kiniksa Pharmaceuticals, Manoj Samant Shareholder of: Kiniksa Pharmaceuticals, Employee of: Kiniksa Pharmaceuticals, Teresa Zhou Shareholder of: Kiniksa Pharmaceuticals, Employee of: Kiniksa Pharmaceuticals, John F. Paolini Shareholder of: Kiniksa Pharmaceuticals, Employee of: Kiniksa Pharmaceuticals

AB0370 UTILITY OF CRP AND ESR IN THE DIAGNOSIS OF GIANT CELL ARTERITIS RELAPSE IN A PHASE 2 TRIAL OF MAVRILIMUMAB

Background:No universally accepted definition of flare currently exists in giant cell arteritis (GCA). Although relapses are defined mostly on clinical grounds (recurrence of GCA-related signs/symptoms), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) help clinicians assess disease activity. In fact, >70% of patients on glucocorticoids (GCs) alone have increased CRP or ESR when the disease is active. In contrast, tocilizumab, given its IL-6-blockade effect in the liver, rapidly reduces CRP and ESR levels, rendering them unreliable for disease activity monitoring. Mavrilimumab – a GM-CSF receptor α inhibitor with demonstrated efficacy in a Phase 2 GCA trial1 – downregulates inflammation upstream of IL-6. We hypothesized that mavrilimumab would not interfere with the utility of CRP and ESR in monitoring disease activity and in identifying GCA relapse.Objectives:To analyze the relationship between CRP/ESR and clinical disease activity in GCA patients treated with mavrilimumab.Methods:New-onset and relapsing GCA patients with active disease were recruited. GC-induced remission (no GCA symptoms and CRP <1 mg/dL or ESR <20 mm/hr) was required by baseline. Patients were randomized 3:2 to mavrilimumab 150 mg or placebo subcutaneously every 2 weeks plus a protocol-defined 26-week prednisone taper. The primary efficacy endpoint was time to relapse by Week 26. Relapse (adjudicated) was defined as recurrent GCA-related signs/symptoms, including new/worsening vasculitis on imaging, concurrent with CRP ≥1 mg/dL and/or ESR ≥30 mm/hr. CRP and ESR were also measured periodically during the trial.This post hoc analysis assessed the association of recurrent GCA-related signs/symptoms with concurrent CRP or ESR elevation post-randomization by treatment arm. We also assessed the proportion of patients with CRP or ESR elevation without GCA-related signs/symptoms up to Week 26.Results:Seventy patients were enrolled (mavrilimumab, N=42; placebo, N=28). The association of CRP or ESR elevation with unequivocal GCA-related signs/symptoms post-randomization was consistent regardless of treatment arm: 8/8 in the mavrilimumab group and 13/13 in the placebo group (Table 1). During relapse, median (range) CRP was 1.8 (1.4 – 8.4) mg/dL (mavrilimumab group) and 1.8 (1.1 – 9.0) mg/dL (placebo group). Corresponding ESR values were 39.5 (30 – 102) mm/hr (mavrilimumab group) and 49 (31 – 101) mm/hr (placebo group). Four mavrilimumab recipients had self-limited, equivocal GCA-related signs/symptoms without concurrent CRP or ESR elevation; all 4 completed the prespecified GC taper by Week 26 without need for rescue GCs, so relapse was not confirmed. At least 1 elevated CRP or ESR value in the absence of GCA-related signs/symptoms was observed in 58.8% of mavrilimumab recipients and 93.3% of placebo recipients by Week 26.Conclusion:The observed association of CRP or ESR elevation with GCA-related signs/symptoms is consistent with the upstream mechanism and supports the utility of the stringent protocol definition of relapse. The frequency and magnitude of CRP and ESR elevations at relapse were similar in both treatment groups, suggesting that CRP and ESR remain useful in assessments of disease activity in mavrilimumab-treated patients. CRP and ESR elevations without GCA-related signs/symptoms occurred more often in placebo recipients.

Giant cell arteritis presenting as a stroke in the internal carotid artery territory: a case-based review.

Giant cell arteritis (GCA) is a large-vessel vasculitis, typically affecting the aorta and its branches. The involvement of vertebral and internal carotid arteries occurs in a limited number of cases, and stroke as a presenting symptom of GCA is extremely unusual: this subset of the disease has a poor prognosis and rarely responds to immunosuppression.We report the case of a 70-year-old woman, who presented to the Emergency Department for ischemic stroke, which appeared to be the first and only symptom of GCA. The prompt administration of steroids and tocilizumab (TCZ) led to clinical and radiological resolution, with no residual disability at 6-month follow-up.Our case-based review, highlighting the rarity of a large vessel vasculitis presenting only with a cerebrovascular accident, provides new evidence for the efficacy of TCZ even in more unusual varieties of GCA: in these cases, TCZ should be immediately prescribed, in order to prevent mortality and severe long-term morbidity.

A Review of the Dermatological Complications of Giant Cell Arteritis.

Giant cell arteritis (GCA) is characterized by granulomatous inflammation of large and medium-sized vessels. It is the most common vasculitis among elderly people in Europe and North America. GCA usually presents with ischemic cranial manifestations such as headache, scalp tenderness, visual manifestations, and claudication of the tongue and jaw. Thickness and tenderness of temporal arteries are the most recognizable signs of GCA on physical examination. Laboratory tests usually show raised acute phase reactants. Skin manifestations are uncommon in GCA and are rarely found as a presenting symptom of GCA. Necrosis of the scalp and tongue is the most common ischemic cutaneous manifestation of GCA. Although infrequent, when present it reflects severe affection and poor prognosis of GCA. Panniculitis-like lesions have been reported in the setting of GCA, with nodules being the most common finding. Other entities, such as generalized granuloma annulare or basal cell carcinoma have been occasionally described in GCA patients. Prompt recognition and initiation of therapy are crucial to prevent serious complications of GCA. When high suspicion of GCA exists, immediate administration of glucocorticoids is recommended. It is advisable to refer the patient to a specialist GCA team for further multidisciplinary assessment.

Clinical Experience With a Multidisciplinary Model of Vascular Ultrasound for the Evaluation for Giant Cell Arteritis

ObjectiveVascular ultrasound (VUS) is a first‐line test for giant cell arteritis (GCA) in Europe but has been of limited use in the United States. We report clinical experience with a multidisciplinary model of VUS for the evaluation of GCA at a large US medical center.MethodsPatients who underwent VUS for evaluation of GCA between 2013 and 2017 were reviewed. Trained vascular technologists followed a standardized protocol to visualize bilateral temporal, carotid, subclavian, and axillary arteries. Vascular medicine physicians interpreted VUS as no arteritis, hyperechoic wall thickening, or acute arteritis. Characteristics of patients with versus without acute arteritis (no arteritis or hyperechoic wall thickening) were compared. Among patients with suspected new‐onset GCA, the treating physician’s pretest and posttest suspicion for GCA were compared.ResultsOf 530 patients, 10.6% had prior‐onset GCA, 31.7% had polymyalgia rheumatica, and 57.6% were taking glucocorticoids. Most patients had no arteritis on VUS (84.3%); 10.6% had acute arteritis, and 5.1% had hyperechoic wall thickening. Typical GCA symptoms, such as jaw claudication and scalp tenderness, were significantly more frequent in patients with acute arteritis. For all 42 patients with suspected new‐onset GCA and acute arteritis, posttest suspicion was unchanged or increased. Of 415 patients with suspected new‐onset GCA and VUS without acute arteritis, suspicion decreased (76.4%) or was unchanged (20.2%).ConclusionWe describe a multidisciplinary model for incorporating VUS into GCA care. When pretest suspicion was low and VUS did not reveal acute arteritis, posttest suspicion typically decreased, whereas when pretest suspicion was high and VUS revealed acute arteritis, posttest suspicion was reinforced.

Dry Nonproductive Cough as the Presenting Symptom of Giant Cell Arteritis.

Dry Nonproductive Cough as the Presenting Symptom of Giant Cell Arteritis.

Large-vessel involvement is predictive of multiple relapses in giant cell arteritis.

Background:Giant cell arteritis (GCA) is the most common systemic vasculitis. Relapses are frequent. The aim of this study was to identify relapse risk factors in patients with GCA with complete large-vessel imaging at diagnosis.Methods:Patients with GCA followed in our institution between April 1998 and April 2018 were included retrospectively. We included only patients who had undergone large vascular imaging investigations at diagnosis by computed tomography (CT)-scan and/or positron emission tomography (PET)-scan and/or angio-magnetic resonance imaging (MRI). Clinical, biological, and radiological data were collected. Relapse was defined as the reappearance of GCA symptoms, with concomitant increase in inflammatory markers, requiring treatment adjustment. Relapsing patients (R) and non-relapsing patients (NR) were compared. Relapse and multiple relapses (>2) risk factors were identified in multivariable Cox analyses.Results:This study included 254 patients (73.2% women), with a median age of 72 years at diagnosis and a median follow up of 32.5 months. At diagnosis, 160 patients (63%) had an inflammatory large-vessel involvement on imaging, 46.1% (117 patients) relapsed at least once, and 21.3% (54 patients) had multiple relapses. The median delay of first relapse after diagnosis was 9 months. The second relapse delay was 21.5 months. NR patients had more stroke at diagnosis than R (p = 0.03) and the brachiocephalic trunk was involved more frequently on CT-scan (p = 0.046), as carotids (p = 0.02) in R patients. Multivariate Cox model identified male gender [hazard ratio (HR): 0.51, confidence interval (CI) (0.27–0.96), p = 0.04] as a relapse protective factor, and peripheral musculoskeletal manifestations [HR: 1.74 (1.03–2.94), p = 0.004] as a relapse risk factor. Peripheral musculoskeletal manifestations [HR: 2.78 (1.23–6.28), p = 0.014], negative temporal artery biopsy [HR: 2.29 (1.18–4.45), p = 0.015], large-vessel involvement like upper limb ischemia [HR: 8.84 (2.48–31.56), p = 0.001] and inflammation of arm arteries on CT-scan [HR: 2.39 (1.02–5.58), p = 0.04] at diagnosis were risk factors of multiple relapses.Conclusion:Male gender was a protective factor for GCA relapse and peripheral musculoskeletal manifestations appeared as a relapsing risk factor. Moreover, this study identified a particular clinical phenotype of multi-relapsing patients with GCA, characterized by peripheral musculoskeletal manifestations, negative temporal artery biopsy, and large-vessel involvement with upper limb ischemia or inflammation of arm arteries.Plain language Summary At giant cell arteritis diagnosis, large-vessel inflammatory involvement is predictive of multiple relapses 46.1% of patients with GCA relapse, and 21.3% undergo multiple relapses;Male gender appears as a protective factor for relapsing in GCA;Peripheral musculoskeletal manifestations are a relapse and multiple relapses risk factor;A negative temporal artery biopsy is predictive of multiple relapses;Large-vessel involvement is predictive of multiple relapses.

Temporal Arteritis Revealing Antineutrophil Cytoplasmic Antibody-Associated Vasculitides: A Case-Control Study.

Temporal arteritis (TA) is a typical manifestation of giant cell arteritis (GCA). Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are rarely revealed by TA manifestations, leading to a risk of misdiagnosis of GCA and inappropriate treatments. This study was undertaken to describe the clinical, biologic, and histologic presentations and outcomes in cases of TA revealing AAV (TA-AAV) compared to controls with classic GCA. In this retrospective case-control study, the characteristics of patients with TA-AAV were compared to those of control subjects with classic GCA. Log-rank test, with hazard ratios (HRs) and 95% confidence intervals (95% CIs), was used to assess the risk of treatment failure. Fifty patients with TA-AAV (median age 70 years) were included. Thirty-three patients (66%) presented with atypical symptoms of GCA (ear, nose, and throat involvement in 32% of patients, and renal, pulmonary, and neurologic involvement in 26%, 20%, and 16% of patients, respectively). Blood samples were screened for ANCAs at the time of disease onset in 33 patients, and results were positive in 88%, leading to a diagnosis of early TA-AAV in 20 patients. The diagnosis of AAV was delayed a median interval of 15 months in 30 patients. Compared to controls with GCA, patients with TA-AAV were younger (median age 70 years versus 74 years), were more frequently men (48% versus 30%), and had high frequencies of atypical manifestations and higher C-reactive protein levels (median 10.8 mg/dl versus 7.0 mg/dl). In patients with TA-AAV, temporal artery biopsy (TAB) showed fibrinoid necrosis and small branch vasculitis in 23% of patients each, whereas neither of these characteristics was evident in controls with GCA. Treatment failure-free survival was comparable between early TA-AAV cases and GCA controls, whereas those with delayed TA-AAV had a significantly higher risk of treatment failure compared to controls (HR 3.85, 95% CI 1.97-7.51; P < 0.0001). TA-AAV should be considered diagnostically in cases of atypical manifestations of GCA, refractoriness to glucocorticoid treatment, or early relapse. Analysis of TAB specimens for the detection of small branch vasculitis and/or fibrinoid necrosis could be useful. Detection of ANCAs should be performed in cases of suspected GCA with atypical clinical features and/or evidence of temporal artery abnormalities on TAB.

Bilateral cilioretinal artery occlusions in giant cell arteritis

An 82-year-old man presented with painless sequential vision loss of his right eye (OD). Ten days earlier, he presented to another hospital for left eye (OS) vision loss. His vision was Light perception only OD and No light perception OS. Fundoscopy demonstrated bilateral cilioretinal artery occlusions with chalky white optic disc swelling OS (Fig. A, B). Although he denied symptoms of giant cell arteritis (GCA) and had normal inflammatory markers, his clinical examination was suspicious for GCA, which was confirmed by temporal artery biopsy.

SAT0256 THE ROLE OF FAST-TRACK ULTRASOUND IN PREVENTING EARLY COMPLICATIONS AND RELAPSES IN GIANT CELL ARTERITIS

Background:Giant Cell Arteritis (GCA) is the most common form of primary systemic vasculitis, mainly affecting adults over 50 years old. Permanent visual loss (PVL) is one of the most feared complications, occurring in about 20% of cases, typically prior to initiation of high-dose glucocorticoid (GC) therapy. Color-duplex sonography (CDS) of temporal arteries (TAs) and large vessels (LVs) is recognized as a first-line diagnostic tool for patients with suspected GCA. A fast track approach (FTA), incorporating CDS has been associated to a significant reduction of PVL in two retrospective studies1,2.Objectives:To assess the impact of FTA on PVL and risk of relapses during follow-up compared to conventional care prior to the introduction of the FTA in our rheumatology clinic.Methods:Patients with new-onset GCA evaluated in our department from January 1998 to September 2019 were included in the study. The FTA approach for GCA was implemented since October 2016. The diagnosis of GCA was based on positive TAs and/or LVs CDS and/or a positive TA biopsy and clinical signs and symptoms of GCA. All patients were clinically examined by the same rheumatologist who performed the CDS. PVL was defined as total visual impairment in one or both eyes. Data on baseline clinical features and later outcomes were collected.Results:153 patients were included: 115 females (75.2%), mean age at diagnosis 71.6±8.2 years. Of these, 112 patients (73%) were evaluated conventionally and 41 (27%) with FTA. Patients in the FTA group were older (P=0.0002), presented more frequently with polymyalgia rheumatica symptoms, weight loss, jaw or tongue claudication and scalp tenderness (P&lt;0.05 for all comparisons). The median duration of follow-up in the FTA group was shorter compared with the conventional group (1.5 vs 5.8 years). PVL occurred in 22 (19.6%) patients in the conventional group compared to 5 patient (12.2%) in the FTA, leading to a reduction of 37.9% in the relative risk of PVL with the FTA approach. Cumulative incidence of relapses and time to first relapse did not change after FTA introduction (P&gt;0.05) (Fig. 1).Conclusion:The application of a FTA in GCA resulted in a significant reduction of PVL. However, the relapse rate did not seem to be influenced by the FTA, highlighting the need to implement further management strategies, besides earlier diagnosis and prompt initiation of GC, that would impact the course of the disease during long-term follow-up

Should Tocilizumab Be Used Routinely in New Patients With a Diagnosis of Giant Cell Arteritis?

Should Tocilizumab Be Used Routinely in New Patients With a Diagnosis of Giant Cell Arteritis?

Investigation and management of giant cell arteritis

Early recognition of the symptoms of giant cell arteritis (GCA), followed by urgent referral and treatment are important in order to prevent possible sight loss. This article discusses the clinical presentation of GCA, the investigations needed to aid diagnosis, and recommended management.

29. Management of GCA and RA in patients with chronic suppurative lung disease

IntroductionThe diagnosis and management guidelines for giant cell arteritis (GCA) are relatively straightforward. However the diagnosis can be challenging when it is hidden under other inflammatory conditions and management is difficult when affected patient has other co- morbidities especially in the background of chronic suppurative infection. This article demonstrates the challenges in diagnosing and managing such case.Case descriptionOur patient is an 83-year-old lady who was referred to rheumatology. She has complex medical history of chronic suppurative lung disease with pseudomonas infection. In addition she had previous ESBL urinary tract infection (UTI), deep vein thrombosis and pulmonary embolism. Management of infection is severely limited by her multiple antibiotic intolerances (gentamycin, tobramycin, colomycin, fluoroquinolones, doxycycline, cefaclor, amoxicillin, co-amoxiclav, meropenem, tazobactam/piperallin and ceftazidime). She is on prophylactic cefradine for UTI and prophylactic amoxicillin for lung infection.On presentation, she had inflammatory polyarthritis which was subsequently diagnosed as seronegative rheumatoid arthritis (RA). She had limited therapeutic options owing to chronic suppurative lung disease. She was advised against methotrexate and leflunomide by chest physician. She could not tolerate sulfasalazine twice during the course of her illness due to gastrointestinal side effects and had to stop hydroxychloroquine because of headache and nausea. Therefore, she had to be managed with tapering doses of prednisolone and intraarticular knee injection during flairs.Nearly two years after her first presentation, she developed recurrent headache. However, there were no other symptoms of giant cell arteritis. On clinical examination her temporal arteries were prominent, thickened and tender to touch but pulsatile. CRP was 88. Ultrasound of temporal arteries showed evidence of inflammation. Biopsy of temporal artery was not performed.She was treated with prednisolone 20 mg daily. She continued treatment for six weeks and showed clinical improvement with normalization of CRP. Her prednisolone dose continued to be tapered successfully. However, she developed complications from treatment, in form of worsening cataract and recurrent urinary tract infections. At the time of article submission, her GCA and RA remain in remission while her prednisolone had been tapered to 9 mg daily.DiscussionBased on NICE guidelines, the treatment of GCA is 60mg of prednisolone for patients with visual symptoms and 40mg of prednisolone for patients without visual symptoms. The risk of infections in high-dose glucocorticoids is well-established. A study using administrative data found that GCA patients, when compared with a matched historical cohort, had increased rates of lower respiratory tract infections, UTI, and other serious infections, which are defined as pneumonias, upper urinary tract infections, and sepsis. The rate of infection is the highest in the first six months of treatment during the greatest glucocorticoid exposure.Due to her pre-existing chronic suppurative lung disease, it was deemed to be of too high risk to commence on the standard dose of prednisolone and to adhere to the recommended length of tapering. We have decided to opt for a lower dose (20mg) of prednisolone for 6 weeks and taper after that. The dose was selected based on the risk and benefit assessment of her underlying chronic infection. There may be difficulties in future management because usual steroid-sparring agents (DMARDs and biologics) would be contra-indicated.According to NICE guidelines, the diagnosis of GCA should be confirmed on temporal artery biopsy (TAB). We have decided that the clinical and imaging evidences were sufficient to diagnose her GCA. We felt that temporal artery biopsy would not add or change her therapeutic management.Key learning pointsThis case highlights the difficulty in managing multiple inflammatory conditions in the presence of complex chronic infections. In case in which all recommended treatments are contraindicated, we have to be prepared to deviate from the recommended guidelines and make decision based on patient tailored risk benefit assessment.This case also serves as a reminder of the importance of shared decision-making and multi-disciplinary approach in managing complex clinical case. She is at risk of developing complications from prolonged glucocorticoid use, and therefore we have involved the local respiratory team and discussed the case in the rheumatology multi-disciplinary (MDT) meeting.Conflicts of interestThe authors have declared no conflicts of interest.

18. An unusual PET project: large vessel vasculitis presenting as lower limb claudication in the absence of aortitis

IntroductionRheumatologists are increasingly aware of extracranial giant cell arteritis (GCA), namely large vessel vasculitis (LVV) involving the aorta and its branches. It is uncommon for patients to present with claudication as their initial complaint. We present an unusual case of femoral arteritis presenting with lower limb claudication. PET-CT demonstrated increased uptake bilaterally in the femoral arteries with typical hypoechoic haloes on Doppler ultrasound. There was no evidence of aortitis. We also illustrate the diagnostic challenge differentiating between vasculitis and atherosclerosis on PET-CT and how steroid-therapy reduces the sensitivity PET imaging.Case descriptionA 57-year-old lady with known hypertension presented to her local hospital with a 3-year history of worsening claudication in her lower limbs. Her exercise tolerance was limited to 50 metres over the past 2 months and she had rest pain. Other symptoms included widespread musculoskeletal pain, chest pain, headaches and jaw pain on mastication. Lower limb Doppler ultrasound demonstrated significant stenosis of the distal femoral arteries bilaterally with hypoechoic haloes typical for vasculitis. Immunology tests were all negative but inflammatory markers were raised (ESR 43 mm/h, CRP 14 mg/L). In view of the Doppler findings and GCA symptoms she was started on prednisolone 60mg. The prednisolone was held 2 days before a PET-CT which demonstrated mild uptake in both femoral arteries with no evidence of aortitis. Her CT angiogram showed significant diffuse atheromatous disease in the superficial femoral and popliteal arteries bilaterally. In view of this, the PET-CT uptake was thought to be in keeping with atherosclerosis rather than vasculitis. Her prednisolone was therefore stopped and she was transferred to a tertiary vascular centre for further management. The vascular team at our hospital were still concerned about the possibility of vasculitis and a second rheumatology opinion was sought. Her inflammatory markers continued to rise (ESR 76 mm/h, CRP 29 mg/L). It was felt that the PET-CT results may have been affected by high-dose prednisolone which was temporarily held. The PET-CT was therefore repeated having been off steroids for 4 weeks. This demonstrated increased uptake in the superficial femoral and profunda arteries when compared to her previous scan. All her images were reviewed and the diagnosis was felt to be in keeping with LVV. Furthermore, she had a good clinical response to 40mg prednisolone and methotrexate was subsequently added.DiscussionClassical GCA typically presents with cranial symptoms. Extracranial symptoms such claudication can occur although only 4% of patients fall into this category. In our patient, femoral arteritis presented with lower limb claudication. Peripheral limb ischaemia and/or aorta involvement is associated with a slightly younger demographic of LVV (<60 years). Initially, there was diagnostic uncertainty given her raised inflammatory markers and hypoechoic femoral artery haloes on Doppler ultrasound, yet diffuse atherosclerosis on the CT angiogram. Hypoechoic haloes and multiple short segment occlusions are more typically seen in vasculitis rather than atherosclerotic disease. Accelerated atherosclerosis is common in primary vasculitides. Despite establishing the diagnosis of LVV by ultrasound in this case, the sensitivity for this in the common femoral artery is < 17%, and PET-CT is preferred. EULAR recommendations for LVV diagnosis include ultrasound and PET-CT. PET-CT was performed twice in this patient because the initial scan was performed following temporary cessation of high-dose steroids, which can decrease the sensitivity of PET-CT. The first PET-CT showed only mild uptake in the femoral arteries which could be consistent with atherosclerosis. Interestingly, PET-CT has been used to identify plaques vulnerable to rupture bed on FDG-avidity. Recent studies have utilised PET-CT to quantify the burden of atherosclerotic disease to help risk stratify patients accurately. This potential diagnostic ambiguity between vasculitis and atherosclerosis on PET-CT reinforces the importance of remaining off steroids around the time of PET imaging where possible.Key learning pointsThis case sheds light on LVV through several interesting perspectives. Firstly, it is unusual for LVV to present with claudication in the lower limbs in the absence of aortitis, demonstrating the variety of ways in which the same pathophysiological mechanism can present clinically. We also highlight the initial diagnostic challenge, as mild uptake in the femoral arteries on PET-CT can be consistent with atherosclerosis. However, with typical findings of hypoechoic haloes on Doppler ultrasound and raised inflammatory markers, clinically this was in keeping with LVV. Interestingly, a repeat PET-CT off steroids demonstrated increased FDG-avidity in the affected areas. This is important as even holding steroids for 2 days before a PET-CT affected the results of the study. This case adds to the growing number of atypical extracranial presentations of LVV and provides useful insight for future possible cases.Conflict of interestThe authors declare no conflicts of interest.

51. An atypical case of GCA: an innocuous presentation ending with ophthalmic complications and cerebral vasculitis

IntroductionDespite being the most common form of primary systemic vasculitis in adults, giant cell arteritis (GCA) remains a difficult diagnosis to make due to the breadth and versatility of presenting symptoms and signs. Many patients present with a myriad of symptoms which don’t fit neatly into the American College of Rheumatology criteria (1990) often with a negative or absent temporal artery biopsy. Here we describe an atypical and aggressive presentation of a patient with GCA.Case descriptionA 77-year old male with a background of pertussis was initially referred to the medical take with 2 weeks of lethargy, raised C-reactive protein (343) and white cell count (27.8). He admitted to fevers, myalgia and sweats but denied any GCA symptoms. Examination revealed no abnormalities. He was treated for an infection of unknown source with broad spectrum antibiotics. A CT chest, abdomen and pelvis showed bibasal consolidation in the lungs with small effusions. He went on to have negative blood, sputum and urine cultures. Despite antibiotic escalations, his inflammatory markers remained high. An echocardiogram showed no vegetations. His pleural effusions were aspirated and revealed a transudative lymphocytic fluid with no acid-fast bacilli. He was then referred to rheumatology. He denied GCA or connective tissue disease symptoms. He had a persistently raised CRP (>150) and WCC (>15) with no fevers. Examination revealed present temporal artery pulses and no abnormalities. Immunology was negative (ANA, ENA, ANCA and CCP). A PET scan showed no changes consistent with a malignancy, large vessel vasculitis or infection. He was labelled as an undifferentiated autoimmune disorder by the medical team and given a trial of prednisolone 30mg to which his CRP fell from 265 to 41. He was discharged with general medical follow-up and a prednisolone weaning regime. After 1 month he re-presented to the medical take with acute bilateral visual loss (on 15mg prednisolone). This was preceded by a 2-week history of bitemporal headaches. There was no history of polymyalgia, jaw claudication or scalp tenderness. Ocular examination revealed bilateral swollen optic discs. He was admitted and treated with pulsed intravenous methylprednisolone. An MRA of his head and neck showed intracranial irregularities consistent with a cerebral vasculitis. He was started on methotrexate alongside prednisolone and referred to the regional GCA centre for tocilizumab therapy. DiscussionThe frequency of ophthalmic complications in GCA is quoted to be as high as 30%. The case above presented with non-specific symptoms and extremely raised inflammatory markers. Despite numerous investigations including a PET scan, a definitive diagnosis was not made without the final presentation of permanent bilateral visual loss. The patient had appropriate and timely investigations for his symptoms at initial admission (blood tests, cultures, CT and PET imaging). Positive findings were appropriately investigated further. Ultimately, he was trialled with prednisolone when infection and malignancy were excluded by the medical team and discharged with follow up. Unfortunately, he was then readmitted with a dramatic relapse. The British Society for Rheumatology recommends starting methotrexate following recurrent relapses in GCA, but we decided to start methotrexate due to the aggressive nature of his disease (sudden onset visual loss and cerebral vasculitis on MRA).Few randomised controlled studies, case-control studies and meta-analyses have looked at the efficacy and steroid-sparing effects of methotrexate introduction at diagnosis of GCA to conflicting results. Jover et al. (2001) showed that low dose methotrexate (10mg) was effective in controlling GCA disease activity. This was supported by a meta-analysis (Mahr et al., 2007) and most recently in a retrospective case-control study (Koster et al., 2019). The larger and well-designed Hoffman et al. (2002) trial showed a small benefit from methotrexate introduction but no statistical significance. There has been no large-trial convincing evidence of methotrexate efficacy in GCA at introduction or for relapses and this is reflected in the national guidance. However, the trials above used relatively low doses of methotrexate. Some of the trial also had short follow-up times and with slow steroid weans possibly masking a positive methotrexate effect. Key learning pointsDespite the vague and nondescript presentation of this patient, focusing on subtleties from the history and having a high index of suspicion are vital to making a diagnosis of GCA.The patient had a negative PET scan despite progression to severe disease within 1 month. PET studies have shown high sensitivity and specificity values for the diagnosis of large vessel inflammation in GCA (90% and 98% respectively – Soussan et al., 2015). However, the lack of large vessel involvement on this scan was falsely reassuring. Conflicts of interestThe authors have declared no conflicts of interest.

Central Retinal Artery Occlusion as the Initial Manifestation of Occult Giant Cell Arteritis - A Diagnostic Enigma

Giant cell arteritis (GCA) is a systemic vasculitis with a myriad of ocular manifestations such as Anterior Ischaemic Optic Neuropathy (AION), Central Retinal Artery Occlusion (CRAO), choroidal infarction, occipital lobe infarction and ocular motor nerve palsies. The predominant systemic features include fever, polymyalgia rheumatica, jaw claudication, weight loss and fatigue. Occult GCA accounts for a minority of cases presenting without systemic symptoms. It is a potential cause of bilateral blindness unless a high index of suspicion is contemplated. A 60 year old female presented with CRAO with no systemic symptoms of GCA. Cardiovascular examination, electrocardiography, echocardiography and carotid doppler were unremarkable. Erythrocyte Sedimentation Rate (ESR), C Reactive Protein (CRP) and platelets were normal. Bilateral prominent temporal arteries were noted but were non tender with subtle pulsations, leading to a suspicion of GCA. Temporal artery biopsy disclosed transmural granulomatous inflammation and fragmentation of internal elastic lamina, ascertaining the diagnosis. Systemic steroids were administered promptly. Although an unusual etiology of CRAO, GCA must be ruled out with utmost priority in patients older than 50 years. The diagnosis can be elusive in occult GCA and CRAO may be the inceptive manifestation, further compounding the diagnostic enigma. Urgent temporal artery biopsy is warranted in occult cases of GCA and substantiates the diagnosis in dubious cases. Occult GCA constitutes an ophthalmic emergency and the imperativeness of urgent systemic steroid therapy to prevent visual loss in the other eye cannot be overemphasized.

Myasthenia Gravis Associated With Orbital Marginal Zone Lymphoma

Myasthenia Gravis Associated With Orbital Marginal Zone Lymphoma

Differences in clinical manifestations and prognosis of Chinese giant cell arteritis patients with or without polymyalgia rheumatica

BackgroundThe symptoms of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) frequently overlap in the elderly. Whether there are differences in clinical features or prognosis between GCA patients with or without PMR remains unknown.AimsTo identify differences in clinical manifestation and prognosis between Chinese GCA patients with or without PMR.MethodsA retrospective study of patients diagnosed with GCA in Peking Union Medical College Hospital (PUMCH) during the last 20 years was conducted. Clinical data was collected and analyzed accordingly, and follow-up was performed.ResultsA total of 50 patients had PMR, while 41 patients did not, with no significant differences in age, gender, and disease course between the two groups. GCA patients with PMR presented with higher risks of family history of malignancy (p = 0.048). Patients without PMR had higher proportion of hearing loss (p = 0.006), ANCA positive (p = 0.024), and abnormal imaging findings illustrating the involvement of arteries under aortic arch (p = 0.018). Before treatment, total lymphocyte counts in patients without PMR were lower than those with PMR, and monocyte counts in both groups were higher than normal. Acute phase reactants in patients without PMR were higher than the other group. No significant differences were found in prognosis during follow-up.ConclusionsGCA patients with or without PMR have different clinical characteristics. Patients with PMR present myalgia or arthralgia more frequently, while those without PMR have higher inflammatory markers, lower lymphocyte counts, and wider involvement of arteries under aortic arch.

Identification of Herpes Zoster–Associated Temporal Arteritis Among Cases of Giant Cell Arteritis

PURPOSETo examine whether herpes zoster antigen (also called varicellazoster virus antigen) was detectable in temporal artery biopsies taken from individuals with giant cell arteritis (GCA).DESIGNRetrospective comparative case series.METHODSSections of formalin-fixed paraffin-embedded temporal arteries were examined first by hematoxylin-eosin (H&E) staining to establish the diagnosis of GCA. Adjacent sections of the same biopsy were then examined by immunohistochemistry, using 2 different monoclonal antibodies against a major antigen of varicella-zoster virus called gE. Pathologic specimens were obtained from patients cared for at the University of Iowa and Washington University in St. Louis ophthalmology clinics.RESULTSThe study included biopsies from 25 patients with symptoms of GCA as well as positive H&E pathology and 25 patients with symptoms compatible with GCA but negative H&E pathology. Among the GCA-positive group, 3 patients had positive staining for herpes zoster antigen. Among the GCA-negative group, herpes zoster antigen was not detected in any biopsy. In both groups of patients, false-positive staining for herpes zoster antigen was detected in the presence of calcifications in the arteries. False-positive staining was also detected on some extra-arterial skeletal muscle and erythrocytes.CONCLUSIONHerpes zoster antigen was detected in 3 of 25 temporal arteries from patients with biopsy-proven GCA. One of the 3 positive cases was noteworthy because the patient had had herpes zoster ophthalmicus diagnosed 3 weeks before the onset of GCA symptoms. False-positive staining for herpes zoster antigen was detected on several temporal artery biopsies.

Possible giant cell arteritis symptoms are common in newly diagnosed patients with Polymyalgia Rheumatica: results from an incident primary care PMR cohort

BackgroundTo examine the frequency of possible giant cell arteritis (GCA) symptoms (including headache, temporal/scalp tenderness, jaw claudication and visual symptoms) in newly diagnosed polymyalgia rheumatica (PMR) patients in UK primary care.MethodsThe PMR Cohort Study is a primary care inception cohort of 652 adults with newly diagnosed polymyalgia rheumatica (PMR). At baseline, participants were asked to report (yes/no) on the presence of seven potential GCA symptoms: sudden headache, tender scalp, disturbed/double vision, jaw claudication, fever, appetite loss and unintentional weight loss.ResultsOf the 652 patients, 405 (62%) were female, with a mean (SD) age of 72.5 (8.9) years. Sudden headache was the commonest symptom in 161 patients (24.7%). The least commonly reported symptom was jaw claudication in 66 (10.1%) patients. Females had a higher prevalence of headache, tender scalp and jaw pain. Sudden onset headache and fever were commoner in younger patients, (OR (95% CI) per 10 year age band increase: headache 0.76 (0.62–0.92), fever 0.63 (0.49, 0.79)). In those reporting sudden headache (n = 161), 19.9% (n = 32) also reported double/disturbed vision and a tender scalp, whilst 11.8% (n = 19) reported double/disturbed vision and jaw pain.ConclusionThe data suggests possible GCA symptoms are common in PMR patients, particularly sudden headache, appetite loss and weight loss. These symptomatic PMR patients warrant careful monitoring and consideration for early referral to specialist services.