Rho Kinase Expression in Giant Cell Arteritis Validating pERM Intensity Score as a Method of Increasing Sensitivity of Temporal Artery Biopsy

2021 ◽  
Author(s):  
Lindsay Lally ◽  
Navneet Narula ◽  
Nicola Goodfellow ◽  
Raashid Luqmani ◽  
David Pisapia ◽  
...  
Keyword(s):  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Rho Kinase ◽  
Temporal Artery ◽  
Staining Intensity ◽  
Vasa Vasorum ◽  
Temporal Artery Biopsy ◽  
Diagnostic Significance ◽  
Intensity Score ◽  
Rock Activity

Abstract Background: Aberrant rho-kinase (ROCK) activity is implicated in pathogenesis of several vascular and immunologic disorders. We previously demonstrated evidence of increased ROCK activity in histopathologically negative temporal artery biopsies (TAB) of subjects with clinical Giant Cell Arteritis (GCA) compared to those without GCA. This study aimed to examine ROCK activity in a larger cohort of biopsy-negative GCA subjects and to validate the prior findings. Methods: Subjects were categorized into 2 groups based on clinical data 6-months after TAB: biopsy-negative GCA and controls without GCA. Paraffin-embedded TAB were stained for phosphorylated ezrin/radixin/moesin (pERM), a surrogate of ROCK activity, and scored by two pathologists blinded to clinical diagnosis using a previously derived scoring system. Three areas of the vessel (intima, adventitial and vasa vasorum) were scored for staining intensity on a scale of 0–2, with a maximum possible score of 6 for each TAB. As determined a priori, scores ³4 were considered a high pERM intensity score correlating with ROCK activity. TAB sections were also stained for unphosphorylated ERM, the inactive protein. Results: Thirty six subjects with biopsy-negative GCA and 43 controls were analyzed. There were no differences between groups in age, sex and corticosteroid dose. The mean pERM intensity score in non-GCA subjects was 3.9 ± 1.4 (compared to 5.0 ± 1.4 in those with GCA, p = 0.002). Using the predetermined cut-off of 4 to define high pERM intensity, subjects with GCA were significantly more likely to have a high pERM intensity score compared to non-GCA, OR 3.67, 95%CI :1.19,11.36; p= 0.019. The sensitivity of high pERM intensity score for diagnosis of GCA in histologically negative TAB was 86%, 95%CI: 70,95. Conclusions:. In this well characterized cohort, those with GCA and negative biopsies had significantly higher pERM intensity scores in TAB specimens compared to subjects without GCA. pERM staining has diagnostic significance in enhancing the sensitivity of TAB, and helps to define the clinically important group of biopsy-negative GCA. The ROCK pathway warrants further investigation in GCA and may be a potential therapeutic target

scholarly journals Full-field optical coherence tomography for the diagnosis of giant cell arteritis

2020 ◽  
Author(s):  
Thomas Maldiney ◽  
Hélène Greigert ◽  
Laurent Martin ◽  
Emilie Benoit ◽  
Catherine Creuzot-Garcher ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Temporal Artery ◽  
Machine Intelligence ◽  
Vasa Vasorum ◽  
Temporal Artery Biopsy ◽  
Optical Coherence ◽  
Gabor Filtering ◽  
Full Field

AbstractHistopathological examination of temporal artery biopsy (TAB) remains the gold standard for the diagnosis of giant cell arteritis (GCA) but is associated with essential limitations that emphasize the need for an upgraded pathological process. This study pioneered the use of full-field optical coherence tomography (FF-OCT) for rapid and automated on-site pathological diagnosis of GCA. Sixteen TABs (12 negative and 4 positive for GCA) were selected according to major histopathological criteria of GCA following hematoxylin-eosin-saffron-staining for subsequent acquisition with FF-OCT to compare structural modifications of the artery cell wall and thickness of each tunica. Gabor filtering of FF-OCT images was then used to compute TAB orientation maps and validate a potential automated analysis of TAB sections. FF-OCT allowed both qualitative and quantitative visualization of the main structures of the temporal artery wall, from the internal elastic lamina to the vasa vasorum and red blood cells, unveiling a significant correlation with conventional histology. FF-OCT imaging of GCA TABs revealed destruction of the media with distinct remodeling of the whole arterial wall into a denser reticular fibrous neo-intima, which is distinctive of GCA pathogenesis and accessible through automated Gabor filtering. Rapid on-site FF-OCT TAB acquisition makes it possible to identify some characteristic pathological lesions of GCA within a few minutes, paving the way for potential machine intelligence-based or even non-invasive diagnosis of GCA.

scholarly journals OP0150 WHAT IS THE ROLE OF TEMPORAL ARTERY BIOPSY IN GIANT CELL ARTERITIS FAST-TRACK PATHWAYS WHEN TEMPORAL ARTERY ULTRASOUND IS NEGATIVE?

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 95.3-95
Author(s):  
A. Sachdev ◽  
S. Dubey ◽  
C. Tiivas ◽  
M. George ◽  
P. Mehta
Keyword(s):  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Sensitivity And Specificity ◽  
Fast Track ◽  
Temporal Artery ◽  
Clinical Findings ◽  
Specimen Size ◽  
Temporal Artery Biopsy ◽  
Duration Of Treatment ◽  
Relevant Role

Background:A number of centres are now running fast track pathways for diagnosis and management of Giant cell arteritis with ultrasound as the first port of call for diagnosis1. Temporal artery biopsies (TABs) have become the second line of investigation, and it is unclear how useful TAB is in this setting.Objectives:This study looked at accuracy of Temporal artery biopsy (TAB) in patients with suspected Giant Cell arteritis (GCA) with negative/inconclusive ultrasound (U/S) and how duration of treatment on steroids prior to these investigations and arterial specimen size affected it.Methods:Prospective study of all patients with suspected GCA referred for TAB when U/S was negative or inconclusive, as part of the local fast-track pathway (Coventry). Database included clinical findings, serological work up, U/S and TAB results and treatment. Sensitivity and specificity of U/S and TAB was calculated and compared based on duration of treatment with steroids.Results:One hundred and nine patients were referred for TAB via Coventry fast-track-pathway. The sensitivity of U/S in this cohort of patients was 9.08% and specificity was 93.33%. After 3 days of steroid this was 0% and 100% respectively. For TAB when done within 10 days of starting steroids, this was 65% and 87.5% respectively. After 20 days of steroids this was 0 % and 100%. The sensitivity and specificity was 20% and 85% when arterial specimen size was 11-15mm and 47% and 100% when specimen size was 16 mm or more. Sensitivity and specificity of U/S of 644 suspected GCA patients was 48% and 98%.Conclusion:Our study demonstrates that TAB plays a relevant role in GCA fast-track-pathways, when U/S is negative/inconclusive. TAB was more sensitive than U/S in this cohort of patients, but overall sensitivity of U/S was higher when calculated for all patients suspected with GCA. Both remain useful tests if performed early. TAB specimen size should ideally be 16mm or more and done within 10 days of starting steroids.References:[1]Jonathan Pinnell, Carl Tiivas, Kaushik Chaudhuri, Purnima Mehta, Shirish Dubey, O38 The diagnostic performance of ultrasound Doppler in a fast-track pathway for giant cell arteritis,Rheumatology, Volume 58, Issue Supplement_3, April 2019, kez105.036,https://doi.org/10.1093/rheumatology/kez105.036Disclosure of Interests:None declared

Evaluating the Usefulness and Timing of the Temporal Artery Biopsy for the Diagnosis of Giant Cell Arteritis

2011 ◽  
Vol 121 (S5) ◽  
pp. S264-S264
Author(s):  
Stephen V. Tornabene ◽  
Raymond Hilsinger ◽  
Raul M. Cruz
Keyword(s):  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Temporal Artery ◽  
Temporal Artery Biopsy

The sensitivity of temporal artery biopsy in the detection of giant cell arteritis is independent of tissue length

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S28-S29
Author(s):  
H J Hurley ◽  
P Q Deb
Keyword(s):  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Average Length ◽  
Statistical Significance ◽  
Temporal Artery ◽  
Temporal Artery Biopsy ◽  
Temporal Arteries ◽  
Biopsy Specimens ◽  
Two Samples ◽  
Left And Right

Abstract Introduction/Objective Giant cell arteritis (GCA) is the most common vasculitis of the elderly, and the most common primary systemic vasculitis overall, with an annual incidence of 200/million. The long term sequelae, namely vision loss and stroke, are permanent and devastating. While GCA is often treated empirically based on clinical presentation, panarteritis on temporal artery biopsy is required for diagnosis. However, these biopsies have the tendency to be falsely negative due to skip lesions, a common feature of GCA. Therefore, we set out to determine whether longer biopsy specimens were more sensitive in the detection of GCA. Methods/Case Report A census of temporal artery biopsies performed with the indication of clinical symptoms of GCA was taken at our institution. The patient age, sex, biopsy laterality, biopsy length, and pathological diagnosis were recorded for each cataloged sample. Statistical significance of difference in biopsy length was tested using an unpaired t-test in R 4.1.0. Results (if a Case Study enter NA) A total of 114 temporal artery specimens were biopsied from 94 different patients with the indication of GCA and assigned a definitive positive or negative diagnosis. Of the 94 patients, 54 were female and 40 were male. Of the total pathological specimens, 11 were positive and 103 were negative. The overall average length of biopsy specimens was 2.13 cm with a standard deviation of 0.65 cm. The average positive biopsy was 2.26 cm long, and the average negative was 2.12 cm, an insignificant difference (0.14 cm, t = 0.7, p = 0.43). In 25 patients, biopsies were taken from both the left and right temporal arteries. Of those patients, 2 were positive for GCA and the remaining 23 were negative. Interestingly, the biopsy result in every case was identical between the left and right samples; we found no instances of pathological evidence of GCA in only one of the two samples from the same patient. Conclusion According to data taken at our institution, there is no indication to lengthen the biopsy requirements from the existing 1.5 cm. However, we have demonstrated evidence that it may be unnecessary to biopsy both temporal arteries in a single patient. Larger studies would be required to confirm our findings.

scholarly journals The impact of Temporal Artery Biopsy for the diagnosis of Giant Cell Arteritis in clinical practice in a tertiary University Hospital

2019 ◽  
Author(s):  
E Kaltsonoudis ◽  
E Pelechas ◽  
A Papoudou-Bai ◽  
E.T. Markatseli ◽  
M Elisaf ◽  
...  
Keyword(s):  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Laboratory Data ◽  
Unknown Origin ◽  
Temporal Artery ◽  
University Hospital ◽  
Temporal Artery Biopsy ◽  
Acute Phase Reactants ◽  
Anemia Of Chronic Disease ◽  
The Impact

ABSTRACTBackgroundTemporal artery biopsy (TAB) is useful in assisting with giant cell arteritis (GCA) diagnosis but lacks sensitivity. The aim of our study was to assess the diagnostic impact of TAB histology in patients with suspected GCA on hospital admission.MethodsA prospectively maintained database was queried for all TABs performed between 1-1-2000 until 31-12-2017 at the University Hospital of Ioannina. Thus, inclusion criteria were made on the grounds of every patient that underwent a TAB during the above-mentioned period, regardless of demographic, clinical and laboratory data.ResultsTwo hundred forty-five TABs were included (149 females and 96 males), with a mean age of 64.5 (±3.5) years. The mean symptoms duration until admission to the hospital was 8.6 (±1.3) weeks and all had elevated acute phase reactants on admission. The reasons of admission were fever of unknown origin (FUO) in 114 (46.5%) patients, symptoms of polymyalgia rheumatica (PMR) in 84 (34.3%), new headache in 33 (13.5%), anemia of chronic disease (ACD) in 8 (3.32%) and eye disturbances in 6 (2.5%) patients. Positive results were found in 49 (20%) TABs. More specifically, in 14% of patients with FUO, 21% in those with PMR, while in patients with a new headache the percentage was 27%. Finally, 5 out of 6 (83.3%) of patients with ocular symptoms and only one (12.5%) of those suffering from ACD. Visual manifestations and FUO are correlated with a positive TAB.ConclusionIt seems that TAB is useful in assisting with GCA diagnosis, but lacks sensitivity.

Temporal artery biopsy for giant cell arteritis: an audit of 471 cases – what have we learnt?

2015 ◽  
Vol 53 (10) ◽  
pp. e44
Author(s):  
J. Sloane ◽  
N. Rice ◽  
E. Kergozou ◽  
P. Chanyarungrojn ◽  
S. Walsh
Keyword(s):  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Temporal Artery ◽  
Temporal Artery Biopsy

Temporal Artery Biopsy is not Required in all Cases of Suspected Giant Cell Arteritis

2012 ◽  
Vol 26 (5) ◽  
pp. 649-654 ◽  
Author(s):  
Edel Marie Quinn ◽  
David E. Kearney ◽  
Justin Kelly ◽  
Catherine Keohane ◽  
Henry Paul Redmond
Keyword(s):  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Temporal Artery ◽  
Temporal Artery Biopsy

THU0309 UNILATERAL TEMPORAL ARTERY BIOPSY IS SUFFICIENT FOR DIAGNOSING GIANT CELL ARTERITIS IF THE SERUM C-REACTIVE PROTEIN LEVEL IS 10 MG/DL OR HIGHER

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 383-384
Author(s):  
T. Kise ◽  
E. Takamasu ◽  
Y. Miyoshi ◽  
N. Yokogawa ◽  
K. Shimada
Keyword(s):  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Temporal Artery ◽  
High Dose ◽  
Temporal Artery Biopsy ◽  
C Reactive Protein ◽  
Positive Group ◽  
Reactive Protein ◽  
Discordance Rate ◽  
Serum Crp

Background:Temporal artery biopsy (TAB) is the gold standard for diagnosing giant cell arteritis (GCA). However, previous studies have reported that the discordance rate of TAB is 3-45%,i.e., in unliteral TAB, GCA may be overlooked in one in five patients, approximately. Evidence as to whether bilateral TAB should be performed initially or one-sided TAB is sufficient for diagnosing GCA is lacking.Objectives:To investigate the predictors of patients with GCA in whom one-sided TAB is sufficient.Methods:The present study was a cross-sectional, single center study conducted from April 1, 2011 to July 31, 2019 at Tokyo Metropolitan Tama Medical Center. Of all consecutive GCA cases for which bilateral TAB was performed, bilaterally positive cases and unilaterally positive cases were extracted as bilateral positive group (BPG) and unilateral positive group (UPG), respectively. GCA was defined in accordance with the classification criteria of the 1990 American College of Rheumatology, and GCA was diagnosed if no other etiology was found within six months after beginning of high-dose glucocorticoid treatment. Demographic, clinical and laboratory data were obtained from the medical records, and the BPG and the UPG were compared statistically in each variable. Statistical significance was defined asp< 0.05.Results:During study, 264 biopsies were performed for 145 cases, who suspected GCA and underwent TAB. The pathological positivity rate was 26.1% (68 / 264 biopsies). Of these, 53 cases had final diagnosis of GCA, in which 43 cases were biopsy proven GCA. Thirty-seven biopsy proven GCA with bilateral TAB were enrolled; 64.9% women; mean (SD) age 75 (8.9) years; median [IQR] TAB length 17.5 [13.0,20.0] mm; headache 54.1%; jaw claudication 45.9%; scalp tenderness 16.2%; temporal artery (TA) tenderness 32.4%; TA engorgement 32.4%; TA pulse abnormality 5.4%; visual symptoms 2.7%; a fever of 38.5°C or higher 40.5%; shoulder girdle pain 48.6%; imaging of aortitis or arteritis 40.5%; median [IQR] white blood cell 9,100 [7200, 12050] /μl; median [IQR] platelet cell 37.5 [27.0, 46.3] ×104/μl; median [IQR] C-reactive protein (CRP) 10.1 [3.9, 16.5] mg/dL; erythrocyte sedimentation rate [IQR] 105 [66, 129] mm/h. Thirty-one in 37 cases were positive bilaterally while 6 in 37 cases were positive unilaterally; and the discordance rate was 16.2%. The median sample length after formalin fixation was 19.0 mm for the BPG and 14.5 mm for the UPG (p= 0.171). The parameters above were compared between UPG and BPG. Of these, only the serum CRP value (mg/dL) differed statistically between groups, and the median value of the two groups was 10.6 and 6.5, respectively (median test:p= 0.031). To predict BPG, in whom unilateral TAB is sufficient for diagnosing GCA, the cut-off value of serum CRP with a specificity of 100% and a sensitivity of 61.3% was set at 9.3 mg/dL (ROC analysis: AUC 0.726).Conclusion:When the serum CRP level is 10 mg/dL or higher in GCA suspected patients, an unilateral TAB alone was sufficient for an accurate diagnosis.References:[1]Hellmich, B, et al.Ann Rheum Dis2020;79(1):19-30.[2]Breuer, GS, et al.J Rheumatol. 2009;36(4):794-796.[3]Czyz CN, et al.Vascular2019;27(4):347-351.[4]Durling B, et al.Can J Ophthalmol2014;49(2):157-161.Figure.Comparison of median CRP levels between unilaterally positive group and bilaterally positive group.Disclosure of Interests:None declared

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