Purpose
To evaluate diagnostic delays in biopsy-proven giant cell arteritis (GCA) within the Veterans Health Administration (VHA), with a focus on the impact of presenting symptoms and provider specialty on time to treatment.
Design
Retrospective, multicenter cohort study.
Subjects
Using the VHA Informatics and Computing Infrastructure, we identified 24,857 patients with GCA-related diagnostic codes or temporal artery biopsy procedures.
Methods
A multistep filtering process, including positive diagnostic coding and pathology-confirmed biopsy report review, yielded 300 cases of biopsy-proven GCA for final analysis. Detailed chart review captured presenting symptoms, initial provider specialty, and diagnostic timeline intervals, including symptom onset to clinical visit and visit to corticosteroid initiation. Group comparisons were assessed using the Kruskal–Wallis test, and post-hoc pairwise comparisons used Dunn’s Test with Bonferroni adjustments.
Main Outcome Measures
Time from first symptom to initial clinical visit, and time from initial visit to corticosteroid initiation.
Results
The cohort was predominantly male (94.3%) and White (89.9%), with a mean age of 75.3 years. The average delay from symptom onset to first clinical encounter was 22 days (SD: 31.9), and from encounter to treatment initiation was 11 days (SD: 26.0). Patients initially evaluated by emergency department or eye care providers were treated significantly sooner than those seen by primary care. Presenting symptoms influenced timeliness: patients with ocular symptoms, including transient vision loss and visual disturbances, were treated more promptly (mean: 8.3 days from presentation compared to those with headache (12.9 days) or systemic complaints (20.2 days; P <.001). Classic symptoms such as scalp tenderness and temporal pain led to the shortest delays following examination. Inflammatory markers such as erythrocyte sedimentation rate and C-reactive protein were elevated in the majority of cases, while platelet elevation was less frequent.
Conclusions
This is the first national VHA study to evaluate diagnostic delay in biopsy-proven GCA by provider specialty and symptom type. Our findings demonstrate that visual symptoms prompt more rapid diagnosis and treatment, whereas nonspecific symptoms result in significant delays, particularly in primary care settings. These results highlight a need for improved provider education and systematic approaches to recognize and manage GCA in its varied presentations. Early diagnosis remains critical to prevent irreversible vision loss and other complications.
INTRODUCTION
Giant cell arteritis (GCA), also known as temporal arteritis, is the most common systemic vasculitis in adults over age 50, with peak incidence between ages 70 and 79. It primarily affects medium to large-size arteries, especially the cranial branches of the carotid arteries. The incidence of GCA is highest in Scandinavian countries, or among those of Scandinavian ancestry. GCA is more common in women, with a lifetime risk of 1% in females vs 0.5% in males in the United States.
Diagnosing GCA is often difficult due to its nonspecific and variable presentation. Symptoms frequently overlap with other common conditions in older adults, such as arthritis, dental disorders, or chronic headaches. Clinical manifestations may include new-onset headaches, scalp tenderness, jaw claudication, visual symptoms such as transient vision loss and diplopia, and systemic complaints like malaise, weight loss, and fatigue. The lack of a definitive laboratory test necessitates a high index of suspicion and thorough clinical evaluation. Although temporal artery biopsy (TAB) is considered the diagnostic gold standard, it is limited by its invasive nature and potential for false negatives due to skip lesions. Furthermore, one Veteran Health Administration (referred to henceforth as “VA”) study revealed a lower positivity rate of biopsies for Veterans (13.7%) vs other studies of the general population, making diagnosis of GCA within the veteran population a particular challenge.
The consequences of delayed or missed diagnosis can be severe, including irreversible vision loss, myocardial infarction, and stroke. , Studies report a mean diagnostic delay of approximately 9 weeks, with even longer delays among patients lacking classic cranial symptoms. This underscores the urgent need for improved diagnostic vigilance. Furthermore, it has prompted several hospital systems to start developing expedited “fast track” GCA diagnosis programs, the efficacy of which have not yet been fully validated but appear promising . ,,
The VA, which serves a predominantly elderly population, provides a unique opportunity to study GCA within the original and largest single integrated health care system in the United States. As of 2023, the VA provides medical care to 6.4% of Americans, including 20% of Americans between 65 and 74 yo and 29% of those over 75 yo, making the VA a valuable setting for examining diagnostic patterns in this demographic. Additionally, the VA’s integrated electronic medical records system enables robust, multicenter data analysis of the entire nation’s enrolled veteran population.
In this study, we assessed the time from symptom onset to treatment in patients with biopsy-confirmed GCA across various clinical encounters at the VA. To our knowledge, this is the first national study to examine diagnostic timelines of GCA by provider specialty. Identifying such trends may inform efforts to expedite recognition and management of GCA and reduce associated morbidity.
METHODS
study design and patient selection
This retrospective, multicenter cohort study was approved by the Portland VA Health Care System’s Institutional Review Board.
A three-step process was used to define the final cohort ( Figure 1 ):
Flowchart illustrating the three-step selection process used to identify the final cohort of 300 biopsy-proven GCA patients from an initial pool of 24,857 individuals with a GCA ICD code or CPT code for TAB. CPT = current procedural terminology; GCA = giant cell arteritis; ICD = international classification of diseases; TAB = temporal artery biopsy.
1. Initial selection
Using the Veterans Health Administration Informatics and Computing Infrastructure Comprehensive Data Warehouse, 24,857 patients were identified by searching for GCA-related International Classification of Diseases (ICD-9 or-10) codes or current procedural terminology (CPT) codes for TAB from 01/01/2001 to 12/31/2022. Within this group, approximately 10,000 patients had both a corresponding ICD-10 code and the CPT code, indicating that their biopsies were performed within the VA system, thus allowing accurate measurement of diagnostic timing.
2. Presumed GCA diagnosis
To improve specificity, we included only patients who received a GCA ICD 9 or 10 code between 14 and 60 days after a TAB CPT codedate, reflecting a diagnosis likely made after positive histopathologic confirmation rather than suspicion alone. This step yielded 2285 patients with presumed biopsy-confirmed GCA.
3. Pathology report verification
Of this group, 836 patients underwent comprehensive chart review for TAB pathology report validation through the Veterans Information Systems and Technology Architecture Joint Legacy Viewer. Following the American College of Rheumatology (ACR) criteria, a true positive TAB was defined by at least one of the following findings:
-
a.
A clearly stated diagnosis in the pathology report
-
b.
Classic histopathological findings, including transmural mononuclear cell infiltrate involving all three arterial layers, with or without granulomatous inflammation
-
c.
Healed arteritis, indicated by a mononuclear infiltrate with insufficient classic findings but determined to be GCA by rheumatologic clinical correlation.
Ultimately, this rigorous screening process yielded 300 confirmed, robustly biopsy-positive GCA cases for final analysis ( Figure 1 ). It should be noted that this final data set was designed to eliminate as much diagnostic uncertainty as possible, therefore, our final cohort does not represent the entire nationwide prevalence of GCA-positive individuals.
chart review process
We extracted demographic information, presenting symptoms, initial provider specialty (eg, primary care, emergency department [ED], ophthalmology), and diagnostic timeline intervals (eg, symptom onset to first visit, first clinical encounter to treatment initiation).
When patients reported multiple GCA symptoms, the primary chief complaint at presentation was recorded as the presenting symptom. GCA symptoms were defined according to the 2022 ACR diagnostic criteria, including temporal headache, scalp tenderness, fever, and arthralgia. Ocular symptoms included were transient vision loss, diplopia, and monocular or binocular persistent vision loss. Because rheumatic diseases can present with symptoms that overlap with GCA, exacerbation of chronic conditions such as polymyalgia rheumatica flares were excluded as the presenting symptoms of GCA, to avoid misclassification bias.
Treatment initiation was defined as the chart’s recorded date that either high-dose oral or intravenous corticosteroids were first prescribed. Diagnostic delay was defined as the time from initial clinic encounter with GCA symptoms to treatment initiation. Provider specialties were categorized to evaluate diagnostic timelines across various healthcare settings.
statistical analysis
Descriptive statistics were calculated using means and standard deviations for continuous variables and frequencies for categorical variables ( Table 1 ). Given the absence of a normal distribution and unequal variance, the Kruskal–Wallis test was used for group comparisons. Posthoc examination of the results was completed using Dunn’s Test for Multiple Pairwise Comparison with Bonferroni adjustment. Analyses were conducted in Stata 18 (StataCorp).
TABLE 1
Demographic Characteristics and Inflammatory Markers Among Biopsy-Proven GCA Veterans.
| Demographics | N (%) 300 (100%) | Mean Age (SD) | Elevated ESR (%) | Elevated CRP (%) | Elevated Platelets (%) |
|---|---|---|---|---|---|
| Sex | |||||
| Male | 283 (94.3) | 75.5 (8.9) | 223 (78.8) | 178 (62.9) | 80 (28.3) |
| Female | 17 (5.7) | 71.9 (11.6) | 15 (88.2) | 12 (70.6) | 5 (29.4) |
| Race | |||||
| White | 259 (89.9) | 75.4 (8.9) | 202 (78) | 167 (64.5) | 77 (29.7) |
| Black/African American | 25 (8.3) | 72.8 (10.4) | 23 (92) | 16 (64) | 4 (16.0) |
| Native American | 3 (0.7) | 79.3 (12.5) | 3 (100) | – | – |
| Hawaiian Native/Pacific Islander | 1 (0.3) | 59 | 0 | – | – |
| Missing/not specified | 12 (4.0) | 77.1 (9.8) | 10 (83.3) | 7 (58.3) | 4 (33.3) |
– No results recorded.
Demographic characteristics and the proportion of patients with elevated Inflammatory markers–erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and platelets among the final cohort of 300 biopsy-confirmed GCA cases.
RESULTS
study population
A total of 836 charts were manually reviewed, resulting in 300 biopsy-confirmed GCA cases that met the strict inclusion criteria. The cohort was predominantly male (94.3%) and White (89.9%, n = 259); 8.3% ( n = 25) were Black/African American, and 4.0% ( n = 12) had no specified race. The mean age at diagnosis was 75.3 years (SD: 9.1), ranging from 49 to 96 ( Table 1 ).
timeline of presentation and diagnosis
On average, patients waited 22 days (SD: 31.9; range: 0-216 days) from symptom onset to their first clinical visit. The time from that initial encounter to treatment initiation—that is, diagnostic delay—averaged 11 days (SD: 26.0; range: 0-315 days) ( Table 2 ).
TABLE 2
Time Intervals from Symptom Onset to Care and Treatment Stratified by Demographics, Symptoms, and Initial Provider.
| Days From Symptom Onset to Initial Visit Mean (95% CI) a | Days From Initial Visit to Treatment Mean (95% CI) b | |
|---|---|---|
| All | 22 (18.4-25.6) | 11 (8.1-13.9) |
|
Sex
Male ( n = 283) Female ( n = 17) |
P
=.84
21.0 (17.5-24.5) 30.6 (4.3-56.9) |
P
=.32
10.8 (7.9-13.7) 22 (4.1-39.9) |
|
Race
White ( n = 259) Black/African American ( n = 25) Native American ( n = 3) Hawaiian Native ( n = 1) Missing ( n = 12) |
P
=.07
21.5 (17.6-25.4) 21.6 (17.5-25.7) 3.3 (−2.2 to 8.8) 1 28.8 (9.4-48.2) |
P
=.45
11.3 (8.8-13.8) 5.1 (1.9-8.3) 1.7 (0.0-3.4) 22 28.9 (−28.5 to 86.1) |
|
Presenting symptoms
Headache ( n = 164) Eye/visual symptoms ( n = 113) Vision loss (n = 85) Eye pain (n = 18) Diplopia (n = 6) Amaurosis fugax (n = 7) Malaise ( n = 6) Arthralgia ( n = 30) Jaw claudication ( n = 37) Scalp tenderness ( n = 36) |
P
<
.001
24.2 (18.9-29.4) 16.9 (10.7-23.1) 12.8 (8.1-17.5) 21.3 (1.3-41.3) 37.7 (7.6-67.8) 40.4 (−19.3 to 100.1) 40.2 (−15.2 to 95.5) 29.8 (15.2-44.3) 21.1 (13.6-28.5) 17.1 (11.8-22.5) |
P
<
.001
12.9 (8.1-17.7) 8.3 (4.9-11.7) 6.0 (2.3-9.7) 15.1 (5.6-24.6) 19.5 (9.3-29.7) 10.1 (0.2-19.9) 44.3 (−7.2 to 95.9) 18.9 (8.4-29.5) 14.8 (8.8-20.9) 4.7 (1.5-7.9) |
|
Initial provider
Primary care ( n = 120) Emergency department ( n = 95) Eye clinic ( n = 65) Ophthalmology (n = 55) Optometry (n = 10) Rheumatology ( n = 12) Neurology ( n = 4) |
P
<
.001
27.6 (21.0-34.2) 13.7 (9.6-17.8) 18.5 (12.3-24.7) 15.5 (10.0-21.1) 34.8 (10.2-59.4) 20.1 (10.6-29.6) 89.8 (−7.5 to 187.1) |
P
<
.03
16.3 (10.0-22.6) 7.0 (4.8-9.2) 7.1 (3.1-11.1) 7.5 (2.8-12.2) 4.5 (1.4-7.6) 19.2 (−4.2 to 42.6) 16.0 (−2.4 to 34.4) |
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