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NIHR Signal Ultrasound could help diagnose giant cell arteritis

Published on 14 February 2017

doi: 10.3310/signal-000382

Ultrasound may aid giant cell arteritis diagnosis in people referred from the community. It is less invasive than biopsy and might provide quicker results than a biopsy, but its role and place in the diagnostic pathway remain unclear.

Giant cell arteritis is a disease of medium to large sized arteries and can lead to a range of eye, brain and other complications. Sudden or gradual blindness is a real risk and anyone with suspected giant cell arteritis is referred to hospital for a biopsy and started on high dose steroids.

This NIHR-funded study found that ultrasound correctly picks up more cases than biopsies, but also falsely identifies some people who do not have the condition. Biopsies falsely diagnose giant cell arteritis in fewer people without the condition than ultrasound.

Testing all patients by ultrasound gave similar results to a combination of clinical assessment plus biopsy, and overall is £485 cheaper per patient.

The study highlights that diagnosis remains difficult and that careful clinical diagnosis is still required.

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Why was this study needed?

About one in every 4,500 people in the UK develops giant cell arteritis each year. It leads to total or partial loss of vision in up to 20% of people with the condition. Diagnosis is based on careful patient history, blood testing for markers of inflammation, eye examination and biopsy of an affected artery. Because of the real risk of blindness, people with suspected giant cell arteritis are usually given high doses of corticosteroid drugs while awaiting the test results. Early diagnosis is important to decide whether people should continue with the drugs.  

A positive biopsy confirms the diagnosis. But biopsy isn’t a completely reliable test for diagnosis - many patients (between 9 and 61%) with negative results are later found to have the condition.

Ultrasound is an emerging alternative test for giant cell arteritis, and this study aimed to assess its accuracy.

What did this study do?

This diagnostic accuracy study included 381 people aged over 50 with suspected giant cell arteritis. Most participants (72%) were female and the average age was 71 years. Each person had a full clinical assessment, and then both an ultrasound and a biopsy within seven days of being referred to hospital. Ultrasound training was provided, so that the process was the same at each hospital. The ultrasound result was not revealed to the treating clinician unless at two weeks they were considering stopping the steroid.

Clinical assessments after two weeks and six months were used as the reference diagnosis for the study, along with the opinion of an expert review panel. The diagnosis was changed in a few cases. The results of the ultrasound and biopsy were compared against the reference clinical diagnosis which included biopsy. Although this is a practical approach, as there is no unequivocal diagnostic standard, it presents some limitation to the interpretation of test accuracy, and may favour biopsy.  The cost-effectiveness of the different tests was also assessed.

What did it find?

  • Ultrasound was more sensitive than biopsy at identifying people who did have giant cell arteritis: 54% identified using ultrasound (95% confidence interval [CI] 48% to 60%) versus 39% identified from biopsy alone (95% CI 33% to 46%). This sensitivity for biopsy was lower than previously thought and suggests that without a clinical diagnosis, many people with the condition might be missed by biopsy alone.
  • Biopsy was more specific than ultrasound and therefore better at identifying people who did not have giant cell arteritis, generating fewer false positives. None of those without arteritis had a positive biopsy compared to 19% with a positive scan.
  • If scans were performed first in all suspected patients and biopsies reserved for negative cases, sensitivity increased to 65% and the number of false positives were maintained at 19%. This could reduce the need for biopsies by 43%. A third of people (35%) with giant cell arteritis had both a negative scan and negative biopsy and using this testing sequence would still rely on clinical diagnosis to override the test suggestions in these cases.
  • The most cost-effective strategy for diagnosis was to give all people with suspected giant cell arteritis an ultrasound test, largely because of its lower cost (£58 for ultrasound compared with £514 for biopsy). The ultrasound strategy resulted in a net benefit of £485 per person.

What does current guidance say on this issue?

The British Society for Rheumatology and the British Health Professionals in Rheumatology has produced a joint guideline for the management of giant cell arteritis. It lists five criteria for classifying the disease and states that a diagnosis should be given if someone shows at least three of these. The criteria are age above 50, new headache, tenderness or reduced pulsation in the temporal artery, increased erythrocyte sedimentation rate (measured with a simple blood test), and an abnormal artery biopsy. It does not recommend that ultrasound be used instead of biopsy because, unlike a biopsy, it is not able to give information on prognosis.

What are the implications?

This study suggests that ultrasound could have a role to play in the diagnosis of giant cell arteritis. Ultrasound is a less invasive procedure than biopsy, so may be preferred by patients. However, there may be issues for implementation in terms of training for those carrying out the ultrasound procedure and the quality of the scans performed, as this is not currently a widely-used procedure.

At what point in the care pathway and in which groups of patients ultrasound may be useful remains uncertain. The researchers analysed numerous models of care, from only performing biopsies in people with a negative ultrasound scan to just giving an ultrasound without biopsy to people highly likely to have the condition. No model was convincing enough to warrant a change in practice.

Citation and Funding

Luqmani R, Lee E, Singh S, et al. The Role of Ultrasound Compared to Biopsy of Temporal Arteries in the Diagnosis and Treatment of Giant Cell Arteritis (TABUL): a diagnostic accuracy and cost-effectiveness study. Health Technol Assess. 2016;20(90):1-238.

This project was funded by the National Institute for Health Research Health Technology Assessment Programme (project number 08/64/01).

Bibliography

Barraclough K, Mallen CD, Helliwell T, et al. Diagnosis and management of giant cell arteritis. Br J Gen Pract. 2012;62(599):329-30.

Dasgupta B, Borg FA, Hassan N, et al. BSR and BHPR Guidelines for the management of giant cell arteritis. Rheumatology. 2010;49(8):1594-7.

NHS Choices. Giant cell arteritis. London: Department of Health; 2015.

NICE CKS. Giant cell arteritis. London: National Institute for Health and Care Excellence Clinical Knowledge Summaries; 2014.

Smeeth L, Cook C, Hall AJ. Incidence of diagnosed polymyalgia rheumatica and temporal arteritis in the United Kingdom, 1990-2001. Ann Rheum Dis. 2006;65(8):1093-98.

Why was this study needed?

About one in every 4,500 people in the UK develops giant cell arteritis each year. It leads to total or partial loss of vision in up to 20% of people with the condition. Diagnosis is based on careful patient history, blood testing for markers of inflammation, eye examination and biopsy of an affected artery. Because of the real risk of blindness, people with suspected giant cell arteritis are usually given high doses of corticosteroid drugs while awaiting the test results. Early diagnosis is important to decide whether people should continue with the drugs.  

A positive biopsy confirms the diagnosis. But biopsy isn’t a completely reliable test for diagnosis - many patients (between 9 and 61%) with negative results are later found to have the condition.

Ultrasound is an emerging alternative test for giant cell arteritis, and this study aimed to assess its accuracy.

What did this study do?

This diagnostic accuracy study included 381 people aged over 50 with suspected giant cell arteritis. Most participants (72%) were female and the average age was 71 years. Each person had a full clinical assessment, and then both an ultrasound and a biopsy within seven days of being referred to hospital. Ultrasound training was provided, so that the process was the same at each hospital. The ultrasound result was not revealed to the treating clinician unless at two weeks they were considering stopping the steroid.

Clinical assessments after two weeks and six months were used as the reference diagnosis for the study, along with the opinion of an expert review panel. The diagnosis was changed in a few cases. The results of the ultrasound and biopsy were compared against the reference clinical diagnosis which included biopsy. Although this is a practical approach, as there is no unequivocal diagnostic standard, it presents some limitation to the interpretation of test accuracy, and may favour biopsy.  The cost-effectiveness of the different tests was also assessed.

What did it find?

  • Ultrasound was more sensitive than biopsy at identifying people who did have giant cell arteritis: 54% identified using ultrasound (95% confidence interval [CI] 48% to 60%) versus 39% identified from biopsy alone (95% CI 33% to 46%). This sensitivity for biopsy was lower than previously thought and suggests that without a clinical diagnosis, many people with the condition might be missed by biopsy alone.
  • Biopsy was more specific than ultrasound and therefore better at identifying people who did not have giant cell arteritis, generating fewer false positives. None of those without arteritis had a positive biopsy compared to 19% with a positive scan.
  • If scans were performed first in all suspected patients and biopsies reserved for negative cases, sensitivity increased to 65% and the number of false positives were maintained at 19%. This could reduce the need for biopsies by 43%. A third of people (35%) with giant cell arteritis had both a negative scan and negative biopsy and using this testing sequence would still rely on clinical diagnosis to override the test suggestions in these cases.
  • The most cost-effective strategy for diagnosis was to give all people with suspected giant cell arteritis an ultrasound test, largely because of its lower cost (£58 for ultrasound compared with £514 for biopsy). The ultrasound strategy resulted in a net benefit of £485 per person.

What does current guidance say on this issue?

The British Society for Rheumatology and the British Health Professionals in Rheumatology has produced a joint guideline for the management of giant cell arteritis. It lists five criteria for classifying the disease and states that a diagnosis should be given if someone shows at least three of these. The criteria are age above 50, new headache, tenderness or reduced pulsation in the temporal artery, increased erythrocyte sedimentation rate (measured with a simple blood test), and an abnormal artery biopsy. It does not recommend that ultrasound be used instead of biopsy because, unlike a biopsy, it is not able to give information on prognosis.

What are the implications?

This study suggests that ultrasound could have a role to play in the diagnosis of giant cell arteritis. Ultrasound is a less invasive procedure than biopsy, so may be preferred by patients. However, there may be issues for implementation in terms of training for those carrying out the ultrasound procedure and the quality of the scans performed, as this is not currently a widely-used procedure.

At what point in the care pathway and in which groups of patients ultrasound may be useful remains uncertain. The researchers analysed numerous models of care, from only performing biopsies in people with a negative ultrasound scan to just giving an ultrasound without biopsy to people highly likely to have the condition. No model was convincing enough to warrant a change in practice.

Citation and Funding

Luqmani R, Lee E, Singh S, et al. The Role of Ultrasound Compared to Biopsy of Temporal Arteries in the Diagnosis and Treatment of Giant Cell Arteritis (TABUL): a diagnostic accuracy and cost-effectiveness study. Health Technol Assess. 2016;20(90):1-238.

This project was funded by the National Institute for Health Research Health Technology Assessment Programme (project number 08/64/01).

Bibliography

Barraclough K, Mallen CD, Helliwell T, et al. Diagnosis and management of giant cell arteritis. Br J Gen Pract. 2012;62(599):329-30.

Dasgupta B, Borg FA, Hassan N, et al. BSR and BHPR Guidelines for the management of giant cell arteritis. Rheumatology. 2010;49(8):1594-7.

NHS Choices. Giant cell arteritis. London: Department of Health; 2015.

NICE CKS. Giant cell arteritis. London: National Institute for Health and Care Excellence Clinical Knowledge Summaries; 2014.

Smeeth L, Cook C, Hall AJ. Incidence of diagnosed polymyalgia rheumatica and temporal arteritis in the United Kingdom, 1990-2001. Ann Rheum Dis. 2006;65(8):1093-98.

The Role of Ultrasound Compared to Biopsy of Temporal Arteries in the Diagnosis and Treatment of Giant Cell Arteritis (TABUL): a diagnostic accuracy and cost-effectiveness study

Published on 5 December 2016

Luqmani R, Lee E, Singh S, Gillett M, Schmidt WA, Bradburn M et al.

Health Technology Assessment Volume 20 Issue 90 , 2016

Background Giant cell arteritis (GCA) is a relatively common form of primary systemic vasculitis, which, if left untreated, can lead to permanent sight loss. We compared ultrasound as an alternative diagnostic test with temporal artery biopsy, which may be negative in 9–61% of true cases. Objective To compare the clinical effectiveness and cost-effectiveness of ultrasound with biopsy in diagnosing patients with suspected GCA. Design Prospective multicentre cohort study. Setting Secondary care. Participants A total of 381 patients referred with newly suspected GCA. Main outcome measures Sensitivity, specificity and cost-effectiveness of ultrasound compared with biopsy or ultrasound combined with biopsy for diagnosing GCA and interobserver reliability in interpreting scan or biopsy findings. Results We developed and implemented an ultrasound training programme for diagnosing suspected GCA. We recruited 430 patients with suspected GCA. We analysed 381 patients who underwent both ultrasound and biopsy within 10 days of starting treatment for suspected GCA and who attended a follow-up assessment (median age 71.1 years; 72% female). The sensitivity of biopsy was 39% [95% confidence interval (CI) 33% to 46%], which was significantly lower than previously reported and inferior to ultrasound (54%, 95% CI 48% to 60%); the specificity of biopsy (100%, 95% CI 97% to 100%) was superior to ultrasound (81%, 95% CI 73% to 88%). If we scanned all suspected patients and performed biopsies only on negative cases, sensitivity increased to 65% and specificity was maintained at 81%, reducing the need for biopsies by 43%. Strategies combining clinical judgement (clinician’s assessment at 2 weeks) with the tests showed sensitivity and specificity of 91% and 81%, respectively, for biopsy and 93% and 77%, respectively, for ultrasound; cost-effectiveness (incremental net monetary benefit) was £485 per patient in favour of ultrasound with both cost savings and a small health gain. Inter-rater analysis revealed moderate agreement among sonographers (intraclass correlation coefficient 0.61, 95% CI 0.48 to 0.75), similar to pathologists (0.62, 95% CI 0.49 to 0.76). Limitations There is no independent gold standard diagnosis for GCA. The reference diagnosis used to determine accuracy was based on classification criteria for GCA that include clinical features at presentation and biopsy results. Conclusion We have demonstrated the feasibility of providing training in ultrasound for the diagnosis of GCA. Our results indicate better sensitivity but poorer specificity of ultrasound compared with biopsy and suggest some scope for reducing the role of biopsy. The moderate interobserver agreement for both ultrasound and biopsy indicates scope for improving assessment and reporting of test results and challenges the assumption that a positive biopsy always represents GCA. Future work Further research should address the issue of an independent reference diagnosis, standards for interpreting and reporting test results and the evaluation of ultrasound training, and should also explore the acceptability of these new diagnostic strategies in GCA. Funding The National Institute for Health Research Health Technology Assessment programme.

Giant cell arteritis is also called temporal arteritis. It is a common type of vasculitis, which is the term for inflammation of the arteries and veins. In this condition, the medium and large arteries, usually in the head and neck, become inflamed. It tends to affect people over the age of 50. It is three times more common in women than in men, and seven times more common in white people than black people.

A temporal artery biopsy enables the lining of the artery to be checked for damage and inflammation. A small section of the artery is removed and then examined under a microscope.

Expert commentary

Giant cell arteritis is not common and can be tricky to diagnose. It is important because unless treated it can cause blindness. Currently most patients are sent for a surgical procedure called a temporal artery biopsy. While no single test is perfect, this study suggests that an ultrasound of the temporal artery may be a "good enough" test for giant cell arteritis - and crucially, unlike a biopsy, an ultrasound doesn’t involve any operating theatres, cutting or stitching. This could allow faster treatment decisions to be made without needing a biopsy. As the saying goes: "a stitch in time saves nine".

Dr Sarah Mackie, Associate Clinical Professor and Honorary Consultant Rheumatologist, University of Leeds