Authors: Mike Butterfield, MD, MS, MPH1 and Lauren Jeang, MD2 (University of South Florida Departments of Emergency Medicine1 and Ophthalmology2) // Edited by: Alex Koyfman, MD (@EMHighAK) and Brit Long, MD (@long_brit, EM Chief Resident at SAUSHEC, USAF)
A 70-year-old woman presents to the ED for worsening left-sided headache. She has not had headaches in the past, but doesn’t have any other “red-flag” symptoms (fever, thunderclap, etc). Her vitals are normal, and she has some tenderness over the left temple. Her visual acuity, fields, and the rest of her exam are normal. The CT of her head returns without acute findings, and her lab markers are notable for an ESR of 41. The ibuprofen you give her improves the headache somewhat. By this time, it is 2am. Given her age and scalp tenderness, you have considered giant cell arteritis (GCA), but not everything in her history matches up. You are reluctant to page the ophthalmology resident on call or empirically start steroids with this muddled picture.
You wonder: Is there a good way to rule out GCA myself in the ED?
Giant cell arteritis (also: “temporal arteritis”) is the most common large vessel vasculitis, primarily affecting the cranial arteries and aorta. Risk of disease increases steadily in patients after age 50, but is very rare before then. Women are twice as likely as men to develop the disease (lifetime incidence 1% vs. 0.5%), and disease prevalence is highest among northern Europeans.1,2
GCA causes transmural vessel inflammation leading to both stenosis of the cranial arteries and mural weakening of the proximal aorta. GCA is most feared for its potential to cause monocular or binocular blindness in untreated individuals, which happens 13-50% of the time. Visual loss is often irreversible, and patients presenting with this complaint are treated in hopes of preserving vision in an unaffected eye.3,4
Clinical Signs and Symptoms
GCA is associated with an array of both local and systemic symptoms. The former include headache, jaw claudication, scalp tenderness, and vision changes, while the latter include more protean manifestations such as fever, fatigue, and weight loss. About 30% will have polymyalgia rheumatica, characterized by proximal muscle pain, weakness, and morning stiffness. On physical exam, abnormalities of the temporal artery, scalp tenderness, and synovitis may be observed.
Unfortunately, none of these classic findings accurately separates those with disease from those without it.
Smetana et al. (2002) have written the most comprehensive review on this subject for JAMA’s series, the Rational Clinical Examination. Pooling together 2680 patients with suspected GCA from 21 studies, they found that none of the 27 most commonly reported symptoms and signs had a sensitivity greater than 76% (any headache), a positive likelihood ratio greater than 4.6 (a beaded temporal artery), or a negative likelihood ratio of less than 0.53 (any temporal artery abnormality). Perhaps the most useful finding from Smetana’s review was demographic – only 2/1435 patients with positive biopsies were under the age of 50.5
The poor performance of the history and physical in predicting GCA diagnosis leads to the thorny issue of diagnosis of GCA itself.
Hunder et al. published the American College of Rheumatology’s (ACR) criteria for GCA in 1990, the most widely referenced paper on this subject. They determined that fulfilling 3 of 5 criteria – age 50+, new headache, temporal artery tenderness (or decreased pulse), ESR > 50 mm/h, or a positive biopsy – had a sensitivity of 93.5% and a specificity of 91.2% for disease.6
But the problem with the ACR criteria has been their misapplication – as Hunder and others have pointed out, the ACR criteria were meant to distinguish GCA from other vasculidities for research studies and actually perform poorly when applied in clinical practice.7–9
So regarding GCA, we as clinicians are still left with an amorphous syndrome without well-defined features that can accurately rule out disease – except for age.
Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP)
Diagnosis of GCA has been traditionally associated with an ESR. However, the literature is replete with cases in which GCA is diagnosed in patients with an ESR less than 50 or even normal. To a lesser extent, CRP has also been examined as a screening method for GCA. 10
Parikh et al. (2006) offered encouraging results in a series of 119 patients diagnosed biopsy-positive GCA. Sensitivities for GCA were 76-86% (depending on the formula used) for ESR, 97.5% for CRP (< 0.5 mg/dL), and 99.2% (118/119) for an elevation in either marker.11
Kermani et al. (2012), however, did not reproduce those findings in a subsequent large retrospective case series (n = 177). In their study, sensitivities were 84.2% for ESR, 86.4% for CRP, and 89.8% for either (96% if patients taking steroids at the time of testing were excluded). Notably, the authors used a cutoff of 8mg/L (ie 0.8mg/dL) for CRP, which is higher than that used by Parikh.12
Additionally, Hegg et al. (2011) have shown that ESR was significantly reduced in GCA patients taking anti-inflammatory medications such as statins and NSAIDS.13
All of these studies are limited by their retrospective nature, incomplete information, and focus on only biopsy-proven GCA patients. Even so, they do not support the idea that lab tests can rule out GCA.
Ultrasound and Magnetic Resonance Imaging (MRI)
Over the last 10 years, imaging studies gained importance in the diagnostic evaluation of GCA. In particular, ultrasound of the temporal arteries has been endorsed as a potential replacement for temporal artery biopsy, given its high specificity, non-invasiveness, and ability to evaluate both arteries over time.
Schmidt et al.’s (1997) prospective cohort study compared 30 patients diagnosed with GCA with 82 controls. Even though 22/30 had gotten steroids within 10 days of examination, 22/30 had a positive “halo sign” on ultrasound, indicating edema in and surrounding the wall of the temporal artery, compared to 0/82 of the controls.14
Ball et al. (2010), a decade later, conducted a meta-analysis of 9 studies comparing the halo sign to temporal artery biopsy, finding the halo sign to have a weighted sensitivity and specificity of 75% and 85%. Another metaanalysis found similar results.15,16
Aschwanden et al. (2012), recognizing the technical difficulty of ultrasound examination, examined whether an abnormal “compression sign” of the temporal artery (continued visualization despite compression) might perform better than the halo sign alone. The compression sign was just as sensitive (79 vs. 80%) as the halo sign in the 43 patients with GCA, and none of the patients without GCA had either ultrasound finding.17
MRI has also shown promise in detecting GCA, albeit with less clinical investigation than ultrasound. Contrast-enhanced studies are capable of detecting signs of inflammation in the superficial cranial and other arteries.18,19
Bley et al. (2007) used a contrast-enhanced MRI protocol in 64 consecutive patients with suspected GCA, looking for abnormalities in vessel lumen diameter, wall enhancement, and wall thickening. Overall sensitivity and specificity were 80.6% and 97.0%, with improved sensitivity (85.7%) if only patients with less than 10 days of steroid treatment were included.20
Klink et al. (2014), in a larger prospective study (n = 185) using the same MRI criteria as Bley et al., estimated sensitivities and specificities between 78.4-83.3% and 85.5-90.4%, respectively. Notably, in this study only patients with an ESR >50 were included.21
In summary, imaging studies are emerging as useful, noninvasive tools for supporting and confirming diagnosis of GCA – for rheumatologists. Unfortunately, these tests do not possess sufficient sensitivity/negative predictive value beyond ESR/CRP to comfortably rule out serious disease. Neither do most ED physicians, technicians, or even radiologists likely have enough experience with these modalities to perform them with a high degree of accuracy, at least at this moment. While ED physicians have demonstrated proficiency in performing many kinds of bedside ultrasonography, evaluation of the temporal arteries is entirely new, esoteric, territory.
Clinical Bottom Line
Given its protean manifestations, the insufficient sensitivity of biomarkers, and unavailability of highly accurate imaging modalities, GCA will be difficult, if not impossible to rule out in the ED. Emergency physicians should have a low threshold for making a presumptive diagnosis of GCA and managing accordingly. One exception to this rule might be patients under 50 years old with an unconvincing presentation and another plausible reason for abnormal biomarkers (if elevated), as only about 40 cases of GCA have ever been reported in this age group.22 Another might be patients with an atypical presentation, normal ESR and CRP, who have been counseled on the risks of GCA, and have reliable follow-up (a lot of “ifs” in that statement).
For all others, consultants should be called, and if unavailable, steroid treatment should be started until follow-up. Patients without visual symptoms should be started on 40-60 mg of prednisone daily, while those with visual impairment need to start with 1 g of intravenous methylprednisolone for 3 days, according to the British Society for Rheumatology guidelines.23
References / Further Reading
- Lindor RA, Laughlin MJ, Sadosty AT. Elderly woman with headache. Giant cell arteritis/temporal arteritis. Ann Emerg Med 2015;65(5):614, 622.
- Watts RA, Lane S, Scott DGI. What is known about the epidemiology of the vasculitides? Best Pract Res Clin Rheumatol 2005;19(2):191–207.
- Azhar SS, Tang RA, Dorotheo EU. Giant cell arteritis: diagnosing and treating inflammatory disease in older adults. Geriatrics 2005;60(8):26–30.
- Danesh-Meyer H, Savino PJ, Gamble GG. Poor prognosis of visual outcome after visual loss from giant cell arteritis. Ophthalmology 2005;112(6):1098–103.
- Smetana GW, Shmerling RH. Does this patient have temporal arteritis? JAMA 2002;287(1):92–101.
- Hunder GG, Bloch DA, Michel BA, et al. The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum 1990;33(8):1122–8.
- Hunder GG. The use and misuse of classification and diagnostic criteria for complex diseases. Ann Intern Med 1998;129(5):417–8.
- Rao JK, Allen NB, Pincus T. Limitations of the 1990 American College of Rheumatology classification criteria in the diagnosis of vasculitis. Ann Intern Med 1998;129(5):345–52.
- Jhun P, Aguilera P, Shoenberger J, Bright A, Herbert M. Giant cell arteritis: read the fine print! Ann Emerg Med 2015;65(5):615–7.
- Ciccarelli M, Jeanmonod D, Jeanmonod R. Giant cell temporal arteritis with a normal erythrocyte sedimentation rate: report of a case. Am J Emerg Med 2009;27(2):255.e1–3.
- Parikh M, Miller NR, Lee AG, et al. Prevalence of a normal C-reactive protein with an elevated erythrocyte sedimentation rate in biopsy-proven giant cell arteritis. Ophthalmology 2006;113(10):1842–5.
- Kermani TA, Schmidt J, Crowson CS, et al. Utility of erythrocyte sedimentation rate and C-reactive protein for the diagnosis of giant cell arteritis. Semin Arthritis Rheum 2012;41(6):866–71.
- Hegg R, Lee AG, Tagg NT, Zimmerman MB. Statin or nonsteroidal anti-inflammatory drug use is associated with lower erythrocyte sedimentation rate in patients with giant cell arteritis. J Neuro-Ophthalmol Off J North Am Neuro-Ophthalmol Soc 2011;31(2):135–8.
- Schmidt WA, Kraft HE, Vorpahl K, Völker L, Gromnica-Ihle EJ. Color duplex ultrasonography in the diagnosis of temporal arteritis. N Engl J Med 1997;337(19):1336–42.
- Ball EL, Walsh SR, Tang TY, Gohil R, Clarke JMF. Role of ultrasonography in the diagnosis of temporal arteritis. Br J Surg 2010;97(12):1765–71.
- Karassa FB, Matsagas MI, Schmidt WA, Ioannidis JPA. Meta-analysis: test performance of ultrasonography for giant-cell arteritis. Ann Intern Med 2005;142(5):359–69.
- Aschwanden M, Daikeler T, Kesten F, et al. Temporal artery compression sign–a novel ultrasound finding for the diagnosis of giant cell arteritis. Ultraschall Med Stuttg Ger 1980 2013;34(1):47–50.
- Geiger J, Ness T, Uhl M, et al. Involvement of the ophthalmic artery in giant cell arteritis visualized by 3T MRI. Rheumatol Oxf Engl 2009;48(5):537–41.
- Khan A, Dasgupta B. Imaging in Giant Cell Arteritis. Curr Rheumatol Rep 2015;17(8):52.
- Bley TA, Uhl M, Carew J, et al. Diagnostic value of high-resolution MR imaging in giant cell arteritis. AJNR Am J Neuroradiol 2007;28(9):1722–7.
- Klink T, Geiger J, Both M, et al. Giant cell arteritis: diagnostic accuracy of MR imaging of superficial cranial arteries in initial diagnosis-results from a multicenter trial. Radiology 2014;273(3):844–52.
- Nesher G, Oren S, Lijovetzky G, Nesher R. Vasculitis of the temporal arteries in the young. Semin Arthritis Rheum 2009;39(2):96–107.
- Dasgupta B, Borg FA, Hassan N, et al. BSR and BHPR guidelines for the management of giant cell arteritis. Rheumatol Oxf Engl 2010;49(8):1594–7.