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1. Hariharan S, et al. Kidney Int 2002;62:311

2. Kaplan B et al. Am J Transplant 2003, 3(12):1560-1565

Duplex Ultrasonography, An Alternative to Temporal Artery Biopsy? A Decision Analysis Model

Murtaza Amirali, Medical Student Faculty of Medicine, Undergraduate Medicine Education

ABSTRACT Temporal arteritis (TA) is an inflammatory disease affecting medium to large blood vessels of body. Prompt identification through biopsy of the temporal artery (TAB) and urgent treatment by high dose corticosteroids, is the gold standard, and is necessary as the one of the sinister complications of this disease is blindness. Temporal arteritis presents a complex clinical scenario and clinical uncertainty with regards to a definitive diagnosis through invasive biopsy or non-invasive ultrasound. To assist in the practice of evidence based clinical practice, a Markov model and clinical algorithm are proposed based on a literature review of the best evidence for the diagnosis of GCA. This will assist in providing the best evidence to determine how duplex ultrasonography can be used as a first-line investigation to temporal artery biopsy in the diagnosis of GCA. Future studies need to include a sensitivity and cost-effective analysis on the utility of ultrasound in the diagnostic algorithm of TA so that health resources can be used effectively and efficiently. INTRODUCTION Temporal arteritis/giant cell arteritis (GCA) is the most common systemic vasculitis to affect medium and large-sized arteries in patients over the age of 50 years. It peaks between the age of 70 and 80 years, is highest in northern European and Scandinavian population, and is more common in women than men. Temporal artery biopsy (TAB) is the current gold standard for the diagnostic workup for a temporal arteritis/giant cell arteritis (GCA). Due to the potential to prevent irreversible blindness and/or stroke treatment, treatment is often initiated, with glucocorticoids (i.e. steroid), prior to the results of biopsy. Thus treatment is largely based on clinical grounds and the 1990 American College of Rheumatology (ACR) criteria for positive GCA. Furthermore, TAB does not appear to change clinical management in 76.4% to 98% of patients who may have undergo a biopsy, thereby raising the question of its necessity in all cases of suspected GCA. Furthermore, studies are inconclusive to the value of a negative biopsy in terms of its useful to prevent unnecessary administration of steroids versus the prevention of vision loss and/or stroke. Imaging modalities (MRI, duplex ultrasound, PET-CT Scan) are currently being debated in the literature as an alternative to TAB in the diagnosis of GCA. Duplex ultrasound has been the modality studied the most and is being increasingly used for the diagnosis of GCA. The evidence in the literature suggests that TAB has lower sensitivity for diagnosis of GCA when compared to the halo sign on duplex imaging (i.e. ultrasound). A meta-analysis shows a sensitivity 75% (95% confidence interval (CI): 67-82%) and specificity 83% (95% CI: 78-88%) when ultrasound was compared to TAB. However, the literature is inconclusive with regards to the replacement of duplex ultrasound for TAB.

PURPOSE To propose a decision analysis model/decision tree/Markov model and a clinical algorithm based on a literature review of the best evidence for the diagnosis of GCA. This will assist in providing the best evidence to determine how duplex ultrasonography can be used as a first-line investigation to temporal artery biopsy in the diagnosis of GCA? METHODOLOGY The study was completed in three phases. Frist, the clinical question was further explored through a literature review to obtain information as to the possible consequences of the TAB versus Ultrasound. The likelihood ratios, specificity, sensitivity, and positive predictive value and negative predictive value where considered surrounding the topic of TA and the use of ultrasound and TAB in its diagnosis. Upon completion of the literature review, a Markov model was constructed. Using the Markov model, a proposed clinical diagnostic algorithm for TA was developed.

PROPOSED DIAGNOSTIC ALGORITHM CONCLUSION

Duplex ultrasonography should become the first-line investigation and an alternative diagnostic test to TAB in the diagnosis of temporal arteritis. TAB should be reserved for patients with a intermediate risk score and negative scan. FUTURE DIRECTIONS

To further determine the probability of outcomes to whether our clinical algorithm and Markov model can be used to make in clinical decisions, a decision analysis computer model should be used to identify the best strategy (Ultrasound vs. TAB) followed by a one-way sensitivity analysis to determine the preferred strategy. Furthermore, a cost-effective decision analysis could be conducted simultaneously to determine the most effective use of health care resources in the diagnosis of temporal arteritis. REFERENCES 1. Hisham, MH & Essa, AA. (2012). Color duplex ultrasonography of temporal arteries: role in diagnosis and follow-up of suspected cases of temporal arteritis. Clin Rheumatol, 31, 231-237. 2. Meisner, RJ, Labropoulos, N, Gasparis, AP, & Tassiopoulos, K. (2011). How to diagnose giant cell arteritis. Int Angiol,30, 58-63. 3. Quinn, EM, Kearny, DE, Kelly, J, Keohane, C, & Redmond, PR. (2012). Temporal Artery Biopsy is not Required in all Cases of Suspected Giant Cell Arteritis. Ann Vasc Surg, 26, 649-654. 4. Schmidt, WA. (2013). Imaging in vasculitis. Best Pract Res Clin Rheumatol, 27(1), 107-18. 5. Sears, ED, & Chung, KC. (2010). Decision Analysis in Plastic Surgery: A Primer. Plast Reconstr Surg, 126(4), 1373-1380. 6. Smetana, GW, Shmerling, RH, & Solomon, D.(2009). Update: temporal arteritis. In: Simel DL, Rennie D, eds. The Rational Clinical Examination: Evidence-Based Clinical Diagnosis. New York, NY: McGraw-Hill. 7. Younge, BR, Cook, BE, Bartley, GB, Hodge, DO, & Hunder GG. (2004). Initiation of glucocorticoid therapy before or or after temporal artery biopsy? Mayo Clin Proc, 79(4), 483-491.

ACKNOWLEDGEMENTS This project is a result of the support of the Markin Undergraduate Student Research Program (USRP) in Health & Wellness Studentship – Summer 2013. I would like to thank my research mentor Dr. Duncan Nickerson (University of Calgary , Faculty of Medicine, Department of Plastic Surgery) and Dr. Fiona Clement (University of Calgary, Faculty of Medicine, Department of Community Health Sciences) and Dr. Christopher Doherty (FRCSC – Plastic Surgery and Hand and Upper Extremity Surgery Fellow in London, Ontario).

RESULTS

Table 1 - Summary Likelihood Ratios (LR) of Symptoms, Signs, and the Erythrocyte Sedimentation Rate for Temporal Arteritis

Fig 5. Proposed diagnostic algorithm for suspected temporal arteritis using the current evidence

American College of Rheumatology Criteria for TA 3 out of 5 = Positive for TA

1. Age of disease at onset at least 50 years of age 2. New headache

3. Temporal artery abnormality (tenderness, diminished pulsation unrelated to atherosclerosis of cervical arteries)

4. Increased erythrocyte sedimentation rate (ESR) >50

5. Abnormal artery biopsy result (vasculitis with mononuclear cell predominance or granulomatous inflammation, usually with multinucleated giant cells)

Fig. 1 – Superficial Temporal Artery Biopsy Findings Showing Lymphocytic Infiltration and Multinucleated Giant Cells

Fig. 2 – Superficial Temporal Artery Findings of Duplex Ultrasound Showing Stenosis and Occlusion (Left Image is Normal Comparison)

Finding (# of Studies) LR+ (95% CI) LR– (95% CI)

Jaw claudication (17) 4.3 (3.0-6.1) 0.72 (0.66-0.79)

Diplopia (5) 3.5 (1.8-6.8) 0.96 (0.93-0.99)

Scalp tenderness (8) 1.7 (1.1-2.4) 0.73 (0.66-0.82)

Any headache (19) 1.7 (1.5-1.9) 0.67 (0.56-0.80)

Any vision symptoms (19) 1.1 (0.94-1.3) 0.97 (0.92-1.0)

"Abnormal" ESR (7) 1.1 (1.0-1.2) 0.2 (0.08-0.51)

ESR > 100 (4) 1.9 (1.1-3.3)

ESR 50-100 (5) 1.1 (0.87-1.5)

ESR < 50 (5) 0.55 (0.38-0.80)

Fig. 3 –Risk Stratification based on probability of TA according to 6 factors

Fig. 4 –Markov Decision Model of Ultrasound Diagnosis and Treatment of TA

Proposed Risk Stratification System:

1) Jaw Claudication (2 points) 2) Diplopia (2 points)

3) Elevated ESR >50 (1 point) 4) Localized Headache (1 point)

5) Age > 50 years (1 point) OR

Temporal Arteritis Score (TAS)

Low Risk 1-2 points TAS <-110

Ultrasound

- Consider

alternative diagnosis

+ Start high dose glucocorticoid

therapy

Intermediate Risk 3 points TAS -110 to 70

Ultrasound

- Consider Biopsy

+ Start high dose glucocorticoid

therapy

High Risk ≥ 4 points TAS >70

Start high dose glucocorticoid

therapy immediately