Description and Validation of Histological Patterns and Proposal of a Dynamic Model of Inflammatory Infiltration in Giant-cell Arteritis

Abstract

The extent of inflammatory infiltrates in arteries from patients with giant-cell arteritis (GCA) have been described using different terms and definitions. Studies investigating the relationship between GCA histological features and clinical manifestations have produced controversial results. The aims of this study were to characterize and validate histological patterns in temporal artery biopsies (TABs) from GCA patients, to explore additional histological features, including the coexistence of different patterns, and also to investigate the relationship of the inflammatory patterns with clinical and laboratory features.We performed histological examination of TAB from patients with GCA consecutively diagnosed between 1992 and 2012. Patterns of inflammation were defined according to the extent and distribution of inflammatory infiltrates within the artery. Clinical and laboratory variables were recorded. Two external investigators underwent a focused, one-day training session and then independently scored 77 cases. Quadratic-weighted kappa was calculated.TAB from 285 patients (200 female/85 male) were evaluated. Four histological inflammatory patterns were distinguished: 1 - adventitial (n = 16); 2 - adventitial invasive: adventitial involvement with some extension to the muscular layer (n = 21); 3 - concentric bilayer: adventitial and intimal involvement with media layer preservation (n = 52); and 4 - panarteritic (n = 196). Skip lesions were observed in 10% and coexistence of various patterns in 43%. Raw agreement of each external scorer with the gold-standard was 82% and 77% (55% and 46% agreement expected from chance); kappa = 0.82 (95% confidence interval [CI] 0.70-0.95) and 0.79 (95% CI 0.68-0.91). Although abnormalities on temporal artery palpation and the presence of jaw claudication and scalp tenderness tended to occur more frequently in patients with arteries depicting more extensive inflammation, no statistically significant correlations were found between histological patterns and clinical features or laboratory findings.In conclusion, we have described and validated 4 histological patterns. The presence of different coexisting patterns likely reflects sequential steps in the progression of inflammation and injury. No clear relationship was found between these patterns and clinical or laboratory findings. However, several cranial manifestations tended to occur more often in patients with temporal arteries exhibiting panarteritic inflammation. This validated score system may be useful to standardize stratification of histological severity for immunopathology biomarker studies or correlation with imaging.

FIGURE 1

Active histological inflammatory patterns involving temporal arteries in giant cell arteritis (GCA). (A) Adventitial pattern, (B) Adventitial extended pattern, and (C) Concentric bilayer pattern. (D) Panarteritic pattern.

FIGURE 2

(A–C) Additional histological patterns observed in temporal artery biopsies from patients with giant cell arteritis (GCA). Normal temporal artery section (A). Vasculitis of small vessels surrounding a spared temporal artery (B). Healing or obsolescent pattern (C). (D–L) Coexistence of different histological patterns in consecutive sections of the same temporal artery biopsy in different patients with GCA: Patient 1 (D–F): (D) normal section; (E) focal adventitial inflammation; and (F) panarteritic involvement; Patient 2 (G–I): (G) adventitial inflammatory infiltrates; (H) concentric bilayer pattern; and (I) panarteritic inflammation; Patient 3 (J–L): (J) adventitial inflammation; (K) inflammatory cells crossing from the adventitia to the intima, leaving a preserved muscular layer (concentric bilayer pattern); and (L) cells crossing from de adventitia to the intima along the media in a subsequent section (focal panarteritic infiltration).

FIGURE 3

Hypothetical model of the sequential invasion of the artery by Inflammatory cells according to our histological findings.