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Show Journal of Neuro- Ophthalmology 20( 3): 216- 218, 2000. © 2000 Lippincott Williams & Wilkins, Inc., Philadelphia Concordance of Bilateral Temporal Artery Biopsy in Giant Cell Arteritis Misha Pless, MD, Joseph F. Rizzo III, MD, Jeffrey C. Lamkin, MD, and Simmons Lessell, MD Objective: To determine whether the diagnostic sensitivity of bilateral temporal artery biopsy is superior to that of unilateral biopsy in cases of suspected temporal arteritis. Materials and Methods: A retrospective analysis of the results of 60 bilateral temporal artery biopsies examined in an ophthalmic pathology laboratory. Results: The histopathologic diagnosis in 13% of the biopsy pairs was discordant. There was a 5% chance of obtaining a positive biopsy result on the side opposite an initially negative biopsy result. Conclusions: Bilateral temporal artery biopsy is 5% more likely than unilateral biopsy to detect the characteristic histopathologic findings in patients with temporal arteritis. Key Words: Giant cell arteritis- Temporal arteritis- Temporal artery biopsy. The role of temporal artery biopsy in the diagnosis of giant cell arteritis is well established. In most cases, a unilateral biopsy is thought to be sufficient. Studies have shown that a unilateral temporal artery biopsy is over 90% accurate in all patients undergoing biopsy ( 1- 3). Some investigators have argued that bilateral biopsies increase sensitivity, which would be true only if there are cases in which the results from the two sides are discordant ( 4,5). Bilateral biopsies would offer no advantage over unilateral biopsy if there is an extraordinarily high incidence of concordance ( 6). We investigated a series of patients suspected to have temporal arteritis who underwent bilateral biopsies. The primary aim was to learn how often the biopsy diagnoses were discordant. We also wanted to learn how often a unilateral biopsy would have sufficed. Finally, we wanted to determine whether the laterality of symptoms and signs correlated witb biopsy results. Manuscript received October 25, 1999; accepted May 1, 2000. From The Eye and Ear Institute ( MP), University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; the Department of Ophthalmology ( JFR, SL), Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts; and private practice ( JCL), Akron, Ohio. Address correspondence and reprint requests to Misha Pless, MD, Department of Ophthalmology, Eye and Ear Institute, 203 Lothrop Street, Allsburgh, PA 15221. METHODS Between January 1980 and October 1990, 510 temporal artery biopsy specimens from 450 patients were received at the ophthalmic pathology laboratory of the Massachusetts Eye and Ear Infirmary. Review of the records showed that 60 patients had bilateral biopsies. Thirty- one biopsies were performed simultaneously ( at the same surgery), and 29 biopsies were performed sequentially. Thirteen of the patients underwent biopsy in locations other than the Massachusetts Eye and Ear Infirmary; only microscopic sections of their biopsies were available for examination. In the remaining cases, each specimen was divided into ten segments, nine of which were subsectioned and stained with hematoxylin and eosin. The tenth segment was stained using the Verhoff modified technique. All slides were examined by one or more of the senior ophthalmic pathologists. A positive diagnosis was based solely on the presence of epithelioid giant cells and granulomas. We reviewed the clinical records of all 60 of the study patients and abstracted information concerning the laterality of symptoms, age, gender, length of specimen, history of polymyalgia rheumatica, and erythrocyte sedimentation rate. RESULTS The results ( Table 1) are presented separately for the simultaneous and sequential biopsy groups. The positive and negative concordance between histopathologic diagnosis on the two sides is very high. Twenty- nine of 31 of the simultaneous and 23 of 29 of the sequential biopsies revealed the same diagnosis. There were two and six discordant results for the simultaneous and sequential biopsies, respectively. In 12 of the 31 simultaneous biopsies, the side that initially underwent biopsy was positive, and in 19 of 31 simultaneous biopsies, the side that initially underwent biopsy was negative. Of the patients undergoing sequential biopsies, one patient had bilaterally positive biopsies. The contralateral artery underwent biopsy because the first specimen was interpreted as " equivocal but probably negative"; on fur- 276 UNILATERAL VERSUS BILATERAL TEMPORAL ARTERY BIOPSY 217 1 >• TABLE 1. Summary of biopsy findings Simultaneous biopsies ( 31 total) Sequential biopsies ( 29 total) 18 bilaterally negative 11 bilaterally positive 2 discordant 22 bilaterally negative 1 bilaterally positive 6 discordant ther review, the first specimen was interpreted as positive. In 18 of 19 patients whose first artery was negative ( 95%), the second artery was negative. Therefore, the probability of finding a negative artery contralateral to a negative artery was 95%. The probability of finding a positive artery contralateral to a negative artery was 5%. Comparison between the two subgroups of patients with at least one positive biopsy ( that is, bilaterally positive and discordant biopsies) did not detect significant differences for age, gender, length of specimen, sedimentation rate, presence of polymyalgia rheumatica, or the laterality of pain or headache ( Table 2). Among the patients with giant cell arteritis, those with unilateral pain or headache were more likely to have discordant results on bilateral biopsy than were those with bilateral pain or headache ( P < 0.05). There was a trend among patients with discordant results toward localization of symptoms and signs ipsilateral to the side with the positive artery. Of the seven patients with unilateral symptoms and discordant biopsy results, five patients had symptoms ipsilateral to the positive biopsy. DISCUSSION A temporal artery biopsy showing the characteristic epithelioid giant cells lesions is 100% specific for the disease. However, temporal artery biopsy is less than 100% sensitive and is variously estimated to be 65% to 95% sensitive ( 7). Studies with well- defined patient populations and comprehensive follow- up estimate the sensitivity at 85% to 91% ( 2,8). Because giant cell arteritis affects vessels focally and segmentally, increasing the length of the biopsy specimen is one method of increasing the sensitivity ( 9). Another method of increasing sensitivity is to perform bilateral biopsies. A report in the ophthalmic literature stated that the apparent high rate of concordance of bilateral biopsy in active arteritis is high enough to justify unilateral biopsy ( 6). Unilateral biopsy has also been advocated in the medical and rheumatologic literature ( 3). Several studies claimed that unilateral biopsy is accurate in over 90% of patients undergoing biopsy and in over 85% of patients with giant cell arteritis ( 4,6). It is worth noting that the biopsy specimens on which their data were based were, on average, longer than those reported iri other studies. Our study confirms recent observations by Boyev et al. ( 10), who reported that performing bilateral simultaneous or sequential temporal artery biopsy improves the diagnostic yield in at least 3% of cases of giant cell arteritis. With comparable conclusions, in our study, we identified a group of patients who underwent simultaneous bilateral temporal artery biopsies, and we found that 92% of arteries contralateral to a positive biopsy were positive. Ninety- five percent of arteries contralateral to a negative biopsy were negative. At our institution, an earlier study established that 5% of all patients with negative temporal artery biopsy nonetheless eventually would be diagnosed with giant cell arteritis on clinical grounds ( 8). We show that bilateral biopsies appear to enhance the diagnostic accuracy in our population by 14.9% among patients with arteritis. Comparison of patients who had unilateral versus simultaneous bilateral temporal artery biopsy by age, gender, presence of symptoms, specimen length, presence of polymyalgia rheumatica, and sedimentation rate did not to reveal any group differences. This may not be valid, however, because patients who underwent simultaneous bilateral biopsy may have had a higher probability of giant cell arteritis than those in whom a unilateral biopsy was thought to be adequate. If this bias is present, probabilities from the bilateral group may not be directly applicable to the unilateral group. If either of these assumptions is incorrect, the accuracy of unilateral biopsy may be higher than we have estimated. However, the 13% discordance rate among patients undergoing bilateral biopsy shows the enhanced diagnostic sensitivity afforded by the second biopsy. No clinical parameter, except laterality, was predictive of concordance or discordance. Discordance might have been attributable to shorter specimen lengths, thereby leading to falsely negative results. Our analysis, however, did not show an association between discordance and shorter specimens. The statistical power of this review was limited by the relatively small numbers of patients in each group. We cannot exclude the possibility of TABLE 2. Gender ( M/ F) Age ( yr) Mean deviation Polymyalgia rheumatica (%) Pain/ headache ESR, mm/ h Standard deviation Specimen length mm Standard deviation Summary of clinical features in Bilaterally positive 3/ 9 79 8.9 25 5 unilateral, 7 bilateral 86.2 38.2 17.3 8.56 relation 7 uni to biopsy results Discordant 3/ 5 78.6 7.3 13 lateral, 1 bilateral 99 3.7 14 3.7 P value P> 0.10 P> 0.10 P> 0.10 P > 0.05 P> 0.10 P> 0.50 ESR, erythrocyte sedimentation rate. J Neuro- Ophthalmol, Vol. 20, No. 3, 2000 218 M. PLESSETAL. an association that we are unable to detect ( i. e., a type II error). Symptoms and signs proved to be limited predictors of biopsy outcome. Twelve patients had unilateral symptoms, and eight patients had bilateral symptoms or non-localizing findings. Among the latter, only one patient had discordant results, while seven patients with unilateral symptoms had discordant biopsies. Therefore, patients with giant cell arteritis and unilateral symptoms and signs were significantly more likely to have discordant biopsy results. Among discordant pairs, there was a trend for the positive biopsy to be ipsilateral to symptoms and signs ( five of seven patients). In the final analysis, the diagnosis of giant cell arteritis is usually made on the basis of the symptoms and signs. It helps to have a confirmatory biopsy, but there are experts who omit biopsy in patients with classical symptoms and signs. We favor biopsy, even in cases that have definite clinical features, because without histopathologic proof, physicians may not persevere with adequate long- term treatment when, as is sometimes the case, undesirable side- effects of corticosteroid therapy develop. Because temporal artery biopsy is a safe procedure with low morbidity, it is reasonable to biopsy both sides at the same session in order to increase the likelihood of achievement of a correct diagnosis. Conversely, sequential bilateral biopsy is recommended if symptoms are suggestive of the presence of temporal arteritis and the first biopsy is negative. REFERENCES 1. Hall S, Lie JT, Kurland LT, et al. The therapeatic impact of temporal artery biopsy. Lancet 1983; 8361: 1217- 20. 2. Hall S, Hunder GG. Is temporal biopsy prudent? Mayo Clin Proc 1984; 59: 793- 5. 3. Fernandez- Herlihy L. Temporal arteritis: clinical aids to diagnosis. J Rheumatol 1988; 15: 1797- 801. 4. Nadeau SE. Temporal arteritis: a decision- analytic approach to temporal artery biopsy. Acta Neurol Scand 1988; 78: 90- 100. 5. Ponge T, Barrier JH, Grolleau JV, et al. The efficacy of selective unilateral temporal artery biopsy versus bilateral biopsies for diagnosis of giant cell arteritis. J Rheumatol 1988; 15: 997- 1000. 6. McDonnell PJ, Moore GW, Miller NR, et al. Temporal arteritis. A clinicopathologic study. Ophthalmology 1986; 93: 518- 30. 7. Bengtsson B, Malmvall B. Giant cell arteritis. Acta Med Scand 1982; 658( suppl): l- 102. 8. Hedges TR, Geiger GL, Albert DM. The clinical value of negative temporal artery biopsy specimens. Arch Ophthalmol 1983; 101: 1251- 4. 9. Albert DM, Ruchman MC, Keltner JL. Skip areas in temporal arteritis. Arch Ophthalmol 1976; 94: 2072- 7. 10. Boyev LR, Miller NR, Green WR. Efficacy of unilateral versus bilateral temporal artery biopsies for the diagnosis of giant cell arteritis. Am J Opthalmol 1999; 129: 211- 8. J Neuro- Ophthalmol, Vol. 20, No. 3, 2000 |