Flares in Biopsy-Proven Giant Cell Arteritis in Northern Italy: Characteristics and Predictors in a Long-Term Follow-Up Study

Abstract

This study evaluated the frequency, timing, and characteristics of flares in a large cohort of Italian patients with biopsy-proven giant cell arteritis (GCA) and to identify factors at diagnosis able to predict the occurrence of flares. We evaluated 157 patients with biopsy-proven transmural GCA diagnosed and followed at the Rheumatology Unit of Reggio Emilia Hospital (Italy) for whom sufficient information was available from the time of diagnosis until at least 4 years of follow-up. Fifty-seven patients (36.5%) experienced ≥1 flares. Fifty-one (46.4%) of the 110 total flares (88 relapses and 22 recurrences) were experienced during the first 2 years after diagnosis. The majority of relapses occurred with doses of prednisone ≤ 10 mg/day (82.9%), whereas only 3.4% of relapses occurred for doses ≥ 25 mg/day. Polymyalgia rheumatica (46.5%) and cranial symptoms (41.9%) were the most frequent manifestations at the time of the first relapse. Cumulative prednisone dose during the first year and total cumulative prednisone dose were significantly higher in flaring patients compared with those without flares (7.8 ± 2.4 vs 6.7 ± 2.4 g, P = 0.02; 15.5 ± 8.9 vs 10.0 ± 9.2 g, P = 0.0001, respectively). The total duration of prednisone treatment was longer in flaring patients (58 ± 44 vs 30 ± 30 months, P = 0.0001).Patients with disease flares had at diagnosis more frequently systemic manifestations (P = 0.02) and fever ≥ 38°C (P = 0.02), significantly lower hemoglobin levels (P = 0.05), more frequent presence at temporal artery biopsy (TAB) specimens of giant cells (P = 0.04) and intraluminal acute thrombosis (P = 0.007), and more moderate/severe arterial inflammation (P = 0.009) compared with those without flares. In the multivariate model fever ≥ 38 °C (hazard ratio 2.14; 95% confidence interval, 1.06-4.32, P = 0.03) and the severity of inflammatory infiltrate (moderate/severe versus mild) (hazard ratio 5.41; 95% confidence interval, 1.64-17.87, P = 0.006) were significantly associated with an increased risk of flares. In conclusion, a flaring course is common in GCA and it is associated with prolonged GC requirements. Fever at diagnosis and severity of inflammation at TAB appear to predict the development of disease flares.

Conflict of interest statement

The authors report no conflicts of interest.

Figures

FIGURE 1

Different intensity of transmural inflammation in temporal artery biopsy specimens: mild (A), moderate (B) and severe (C). (A) Hematoxylin-Eosin, 40×; (B,C) Hematoxylin-Eosin, 20×.

FIGURE 2

Kaplan-Meier estimate of the probability of flare (relapse or recurrence) over time.

FIGURE 3

(A) Survival curve showing the time required to reach a maintenance prednisone dose P = 0.19). (B) Survival curve showing the time required to reach a maintenance prednisone dose <5 mg/day in patients with (broken line) and without (solid line) flares. The median time in patients with flares was 48 weeks (95% CI: 40.6–56.8 weeks), whereas in patients without flares was 38.9 weeks (95% CI: 33.7–44.0 weeks) (P = 0.014). (C) Survival curve showing the time required to reach a stable dose of prednisone 0 mg/day in patients with (broken line) and without (solid line) flares. The median time in patients with flares was 151.9 weeks (95% CI: 109.9–193.8 weeks), whereas in patients without flares was 73.3 weeks (95% CI: 64.2–82.3 weeks) (P = 0.002).