How Does Previous Corticosteroid Treatment Affect the Biopsy Findings in Giant Cell (Temporal) Arteritis?

Giant cell (temporal) arteritis is a common systemic vasculitis with no known cause. It affects persons older than 50 years and often occurs with symptoms such as headache, loss of vision, jaw claudication, and polymyalgia rheumatica [1-4]. Physicians can diagnose this condition by recognizing its clinical manifestations and finding the characteristic granulomatous inflammation in temporal artery biopsy specimens. With suspected cases of giant cell arteritis, often physicians must decide whether to begin corticosteroid treatment immediately to prevent complications, such as blindness [3], or to wait for the results of a temporal artery biopsy to avoid possibly obscuring the histologic diagnosis and to prevent unnecessary corticosteroid treatment. This is important because one study reported that histologic evidence of arteritis is usually masked after 1 week of corticosteroid treatment [5]. Other studies [6-8], however, suggested that histologic evidence of arteritis may persist despite longer courses of corticosteroid treatment. These previous investigations, which yielded conflicting results, included only patients who were later treated for giant cell arteritis regardless of biopsy result [5] and who had few bilateral biopsies [6-8], which may increase false-negative results [9-11]. To define further the effect of previous corticosteroid treatment on temporal artery biopsy results, we reviewed the clinical and histologic findings in a consecutive cohort of 535 patients who had temporal artery biopsy at Mayo Clinic during a 4-year period. We compared biopsy positivity rates among those who received corticosteroid therapy before temporal artery biopsy with rates among those who did not, adjusting for clinical and laboratory characteristics. Methods Patients We reviewed the medical records and histologic temporal artery biopsy specimens of all patients who had temporal artery biopsy at the Mayo Clinic, Rochester, Minnesota, between 1 January 1988 and 31 December 1991. During this time, 545 patients had temporal artery biopsy. Ten patients were excluded for the following reasons: unavailable records (n = 1), unavailable slides (n = 4), systemic non-giant cell arteritis (n = 3), juvenile (at age 8 years) temporal arteritis with dissection (n = 1), and first temporal artery biopsy done at the Mayo Clinic before 1 January 1988 (n = 1). Therefore the study sample consisted of 535 patients. We used a standardized data collection form to record information, including the date of biopsy and the dose and duration of corticosteroid treatment received before biopsy. Information recorded from the history included age, sex, duration of symptoms, and the presence (during the month preceding temporal artery biopsy) of general malaise, fever, chills, sweats, weight loss, new headache, jaw or tongue claudication, blurred vision, amaurosis fugax, diplopia, polymyalgia rheumatica, morning stiffness, arthralgias, sore throat, and cough. Information recorded from the physical examination included the presence of ischemic optic neuritis, optic atrophy, decreased visual acuity, tender temporal artery, decreased or absent temporal artery pulse, scalp nodules or tenderness, synovitis, and large-vessel bruits. Recorded laboratory information included the erythrocyte sedimentation rate, hemoglobin concentration, platelet count, and the aspartate aminotransferase, alkaline phosphatase, albumin, and serum -2 globulin levels. Temporal Artery Biopsies The usual practice at the Mayo Clinic is to biopsy the temporal artery in patients with suspected giant cell arteritis when that diagnostic question arises. A 3- to 4-cm specimen of the more clinically suspicious temporal artery is removed and frozen sections are examined at multiple levels. If frozen sections of this temporal artery show no vasculitis, a biopsy specimen from the opposite temporal artery is usually taken at the same time and examined at multiple levels. Permanent sections are also examined 24 hours later. An experienced pathologist who was blinded to the clinical data, previous corticosteroid treatment information, and the original pathologic diagnosis re-examined all biopsy slides. We classified the biopsy results as negative (no evidence of arteritis) or positive (histologic evidence of arteritis). We further classified positive biopsy results as typical temporal arteritis or atypical temporal arteritis [12, 13]. Typical temporal arteritis (Figure 1) denotes granulomatous arteritis with one or more giant cells present in a cross section of the artery. The inflammatory infiltrate is a mixed cell type with mononuclear cells (lymphocytes, histiocytes, and plasma cells) predominating. Atypical temporal arteritis (Figure 2) denotes the presence of inflammation (consistent with giant cell arteritis) but with atypical features such as the absence of giant cells or the occurrence of the inflammatory infiltrate mainly in the adventitia rather than in the media, the more typical location. Figure 1. Photomicrograph of typical granulomatous temporal arteritis (left) with giant cells (arrow) seen in a close view (right) (hematoxylin and eosin; left, 64; right, 400). Figure 2. Hematoxylin and eosin (top left) and elastic stain (top right) photomicrographs of a positive temporal artery biopsy specimen without identifiable giant cells. bottom Statistical Analysis We assessed the reliability of the histologic interpretation by comparing the repeated histologic interpretation used in the study with that of the original pathologist using the statistic [14]. We used a chi-square analysis (or Fisher exact test in cases of small cell sizes) to compare the biopsy positivity rates among patients with various doses and durations of corticosteroid therapy before temporal artery biopsy. To assess the influence of multiple independent variables, univariably and multivariably, we used logistic regression, incorporating the temporal artery biopsy result (positive or negative) as the dependent variable [15]. We analyzed all recorded clinical and laboratory variables univariably. We used stepwise methods to develop a final logistic model in which only statistically significant (P < 0.05) independent variables and interactions among them were retained. Then we used the final best logistic model to test the null hypotheses that previous corticosteroid treatment does not affect the temporal artery biopsy positivity rate, adjusting for the influence of the independent variables in the model. Results Study Sample Of 535 patients who had biopsies, 345 (64%) were women and 190 (36%) were men. Their mean age was 71.7 years (range, 31 to 93 years). The study sample included 46 (9%) patients from Olmsted County, Minnesota (local), and 489 (91%) patients from other areas. Many patients had been given corticosteroid therapy before referral to the Mayo Clinic, especially those receiving treatment for longer periods before temporal artery biopsy. There were 286 (53%) untreated patients and 249 (47%) patients who received corticosteroid therapy before temporal artery biopsy. Patients in the study generally had some clinical indication suggesting arteritis that prompted the clinician to order a temporal artery biopsy. For example, 60% (322 of 535 patients) had a new headache, and 73% (393 of 535 patients) satisfied American College of Rheumatology Criteria for classification as giant cell arteritis [16]. Patients who did not satisfy these criteria generally had symptoms and findings of a systemic illness that suggested possible giant cell arteritis. Table 1 shows clinical and laboratory features present in corticosteroid-treated and untreated patients before temporal artery biopsy. Many features occurred frequently among both corticosteroid-treated and untreated patients, including headache, visual symptoms or ocular findings, temporal artery abnormalities, polymyalgia rheumatica, and an erythrocyte sedimentation rate greater than 40 mm/h. Patients who received more than 15 mg/d of prednisone for more than 14 days before temporal artery biopsy, when compared with untreated patients, had equal or higher frequencies of many symptoms, including headache (69% compared with 55%) and visual symptoms or ocular findings (63% compared with 25%). Patients in this corticosteroid subgroup had slightly less frequent temporal artery abnormalities (38% compared with 49%) and a lower median erythrocyte sedimentation rate (40 mm/h compared with 72 mm/h) than did untreated patients. Table 1. Presenting Features in Patients Who Had Temporal Artery Biopsy: Classification according to Corticosteroid Therapy Received before Biopsy Overall Biopsy Results Positive biopsy results were found in 175 (33%) patients, and negative results were found in 360 (67%) patients. Of the 175 patients with positive biopsy results, 86 (49%) had typical temporal arteritis and 89 (51%) had atypical temporal arteritis according to histologic examination. The reviewed histologic diagnosis used in the study correlated with the original pathologist's interpretation in 94% of cases (estimated = 0.87). Mean biopsy specimen length was similar in patients with positive (3.7 cm) and negative (3.6 cm) results. Bilateral temporal artery biopsy specimens were taken in 314 (59%) patients. Relation between Previous Corticosteroid Treatment and Biopsy Results Table 2 shows the relation between corticosteroid treatment before temporal artery biopsy and biopsy results. The biopsy results were positive for 31% (89 of 286) of patients who did not receive corticosteroids before biopsy and for 35% (86 of 249) of those who did receive corticosteroids before biopsy (P = 0.4; 95% CI for the difference, 4.7% to 11.5%). We grouped patients treated with more than 15 mg/d of prednisone or an equivalent dose of a different corticosteroid (n = 149) according to treatment duration before biopsy, and biopsy results were positive in 43% at 1 to 7 days (46 of 107 patients), 30% at 8 to 14 days (3