Diagnostic delay for giant cell arteritis – a systematic review and meta-analysis

Background Giant cell arteritis (GCA), if untreated, can lead to blindness and stroke. The study’s objectives were to (1) determine a new evidence-based benchmark of the extent of diagnostic delay for GCA and (2) examine the role of GCA-specific characteristics on diagnostic delay. Methods Medical literature databases were searched from inception to November 2015. Articles were included if reporting a time-period of diagnostic delay between onset of GCA symptoms and diagnosis. Two reviewers assessed the quality of the final articles and extracted data from these. Random-effects meta-analysis was used to pool the mean time-period (95% confidence interval (CI)) between GCA symptom onset and diagnosis, and the delay observed for GCA-specific characteristics. Heterogeneity was assessed by I 2 and by 95% prediction interval (PI). Results Of 4128 articles initially identified, 16 provided data for meta-analysis. Mean diagnostic delay was 9.0 weeks (95% CI, 6.5 to 11.4) between symptom onset and GCA diagnosis (I 2 = 96.0%; P < 0.001; 95% PI, 0 to 19.2 weeks). Patients with a cranial presentation of GCA received a diagnosis after 7.7 (95% CI, 2.7 to 12.8) weeks (I 2 = 98.4%; P < 0.001; 95% PI, 0 to 27.6 weeks) and those with non-cranial GCA after 17.6 (95% CI, 9.7 to 25.5) weeks (I 2 = 96.6%; P < 0.001; 95% PI, 0 to 46.1 weeks). Conclusions The mean delay from symptom onset to GCA diagnosis was 9 weeks, or longer when cranial symptoms were absent. Our research provides an evidence-based benchmark for diagnostic delay of GCA and supports the need for improved public awareness and fast-track diagnostic pathways

Characteristics of patients with giant cell arteritis who experience visual symptoms

Permanent vision loss is one of the most serious complications of giant cell arteritis (GCA) and therefore prompt diagnosis is paramount. However, diagnosis of GCA remains challenging due to its frequently non-specific presentation. Our aim was to identify differences in the characteristics of GCA patients with, and without, current visual symptoms. A cross-sectional survey was mailed to patients with a GCA Read code entered in their GP electronic medical record. Responders were categorised as those currently reporting a visual symptom or not. We compared general and GCA-specific characteristics in these two groups. The association of diagnostic delay with subsequent experience of visual symptoms was examined using unadjusted and adjusted linear regression analysis. 318 GCA patients responded to the survey (59.6%). Responders were predominantly female (69.8%), with a mean age of 73.7 years (SD 8.2). 28% reported current visual symptoms. There was no statistically significant difference in the general characteristics between those with and without visual symptoms. Of GCA-specific characteristics, pre-GCA diagnosis of diplopia (p = 0.018), temporary (p ≤ 0.001) or permanent visual problems (p = 0.001) and hoarseness (p = 0.004) were more common among those reporting current visual symptoms. There was no association between the extent of diagnostic delay and reporting of current visual symptoms. Though we found few characteristics to distinguish between GCA patients with or without current visual symptoms, diagnostic delay was not associated with current visual symptoms. Our findings highlighted the continued difficulty for clinicians to identify GCA patients at the highest risk of visual complications

Systematic review of the literature and a case report informing biopsy-proven giant cell arteritis (GCA) with normal C-reactive protein

Giant cell arteritis (GCA) is a vasculitis of large- vessels. A markedly elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels are characteristics of GCA, although temporal artery biopsy remains the gold standard for the diagnosis. We describe a case of biopsy-proven GCA showing a heavy infiltration of CD68 macrophages and CD3 T cells and with normal ESR and CRP levels at diagnosis. Key points (1) GCA may occur with normal ESR in a percentage of about 4 to 15 % (although the American College of Rheumatology classification criteria for giant cell arteritis include an ESR of 50 mm/h or more), while it can occur with normal ESR and normal CRP in a percentage of about 0.8 %. So, the clinical suspicion must be confirmed with a positive biopsy. (2) GCA patients with ESR >40 mm/h are characterized by higher incidence of headache and jaw claudication compared to patients with normal ESR. In our case, it occurred with normal ESR. (3) Color duplex ultrasonography is a noninvasive, easy, and inexpensive method for supporting a diagnosis of TA, with a high sensitivity and specificity. It can predict which patient will need TAB

Rituximab in systemic lupus erythematosus: an updated systematic review and meta-analysis

The wide spectrum of clinical manifestations and high relapse rate represent a therapeutic challenge in systemic lupus erythematosus (SLE). Observational studies suggested efficacy of rituximab (RTX), a B-cell-targeting antibody, to control the activity of SLE. Two randomized trials controlled by placebo did not prove the superiority of RTX when used in addition to conventional treatment in nonrenal (EXPLORER) and renal (LUNAR) lupus. A systematic review of studies exploring the efficacy of RTX in SLE patients was conducted. The pooled percentages of response were assessed. Thirty studies with 1243 patients were analyzed. In studies using the British Isles Lupus Assessment Group (BILAG), the complete response (CR) rate was 46.7% (95% CI 36.8%-56.8%) and the partial response (PR) was 37.9% (95% CI 30.6%-45.8%). With the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), the CR was 56.6% (95% CI 32.4%-78.1%) and the PR was 30.9% (95% CI 8.9%-46%). In renal lupus the CR was 36.1% (95% CI 25.2%-48.6%); PR was 37.4% (95% CI 28.5%-47.3%). In EXPLORER, CR was 12.4% and PR was 17.2%; in LUNAR CR was 26.4% and PR was 30.6%, in both cases not different from controls. Assessment and standardization of SLE response to treatment remain a challenge. The discrepancy in the perceived efficacy of RTX between controlled and observational studies reflects the heterogeneity of lupus and stringency in criteria of response. Further randomized trials focusing on selected SLE manifestations and using composite response indices are warranted

Parameters related to a positive test result for FDG PET(/CT) for large vessel vasculitis: a multicenter retrospective study

The purpose of this study was to identify clinical and laboratory parameters that may improve the effectiveness of the use of fluorodeoxyglucose positron emission tomography ((18) F-FDG PET)(/CT) for diagnosing large vessel vasculitis (LVV), and secondarily to assess the contribution of (18) F-FDG PET/CT in finding other diagnoses for patients without signs of LVV on the scan. A multicenter retrospective study of (18) F-FDG PET(/CT) scans performed between January 2000 and December 2009 for clinical suspicion of LVV was conducted. A total of 304 (18) F-FDG PET(/CT) scans were included, of which 62 (20%) were positive and 242 (80%) were negative for LVV. Univariate analysis showed that patients with a positive scan were older (65.9 +/- 13.4 versus 58.6 +/- 16.5 years, p = 0.002), were more frequently female (76% versus 55%, p = 0.002), more often had a history of temporal arteritis (10% versus 3%, p = 0.044), less frequently had artralgia (31% versus 67%, p = 0.000), and had higher thrombocyte counts (434 +/- 161 versus 373 +/- 168 x 10(9)/l, p = 0.049) and a higher erythrocyte sedimentation rate (ESR) (72.6 +/- 31.0 versus 51.4 +/- 30.5 mm/h, p = 0.001) than patients with a negative scan. In the multivariate analysis, only artralgia (OR 0.091; 95% CI 0.023-0.366) and ESR (OR 1.024; 95% CI 1.002-1.046) remained statistically significant predictors. The presence of artralgia is a statistically significant negative predictor and an elevated ESR a statistically significant positive predictor of LVV showing up on (18) F-FDG PET(/CT). A reliable prediction of the outcome of the scan, based on these two parameters, is not possible however. (18) F-FDG PET(/CT) allows early diagnosis of LVV and may discover occult inflammatory or neoplastic disorders