Assessment for varicella zoster virus in patients newly suspected of having giant cell arteritis

Abstract

Objectives There is uncertainty if varicella zoster virus (VZV) triggers GCA. This is based on discordant reports of VZV detection in GCA temporal artery biopsies. We conducted a multimodal evaluation for VZV in the inception Giant Cell Arteritis and PET Scan (GAPS) cohort. Methods Consecutive patients who underwent temporal artery biopsy for suspected GCA were clinically reviewed for active and past VZV infection and followed for 6 months. Serum was tested for VZV IgM and IgG. Temporal artery biopsy (TAB) sections were stained for VZV antigen using the VZV Mouse Cocktail Antibody (Cell Marque, Rocklin, CA, USA). A selection of GCA and control tissues were stained with the VZV gE antibody (Santa Cruz Biotechnology, Dallas, TX, USA), which was used in previous studies. Results A total of 58 patients met inclusion criteria, 12 (21%) had biopsy-positive GCA and 20 had clinically positive GCA. None had herpes zoster at enrolment and only one patient developed a VZV clinical syndrome (zoster ophthalmicus) on follow-up. There was no difference in VZV exposure between GCA and non-GCA patients. None of the 53 patients who had VZV serology collected had positive VZV IgM antibodies. VZV antigen was not convincingly demonstrated in any of the TAB specimens; 57 TABs stained negative and 1 stained equivocally positive. The Santa Cruz Biotechnology VZV antibody exhibited positive staining in a range of negative control tissues, questioning its specificity for VZV antigen. Conclusion The absence of active infection markers argues against VZV reactivation being the trigger for GCA. Non-specific immunohistochemistry staining may account for positive findings in previous studies.

Diagnostic Accuracy of Symptoms, Physical Signs, and Laboratory Tests for Giant Cell Arteritis

“…Although the sensitivity of TAB may be 77% for fulfilment of the American College of Rheumatology 1990 criteria for GCA, 91 it is likely lower for the clinical diagnosis in daily clinical practice. 6 Some studies in our meta-analysis 46,68,71,[75][76][77]82 reported a subgroup of patients with TAB findings that were negative for GCA. Patients with GCA may have had TAB findings negative for GCA in other studies, but these patients were simply classified as not having GCA.…”

“…Of the 1436 reports screened, 68 studies 14-17,24-87 fulfilled the selection criteria and were used for the systematic review and metaanalysis (eFigure 1 in the Supplement). These studies included 14 037 patients, of whom 4277 (30.5%) were classified as having GCA ( 16,17,[24][25][26][27][28][29][30][31][32][33][34][35]37,38,[40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][59][60][61][62][66][67][68][69]72,73,[75][76][77][78][79][80][81][82][83][84]…”

“…The clinical diagnosis was typically based on clinical and laboratory findings, imaging and/or TAB results, and a good initial response to glucocorticoid treatment (eTable 5 in the Supplement). In 16 of c Seven studies with the clinical diagnosis as the reference standard 46,68,71,[75][76][77]82 also allowed evaluation of TAB as the reference standard (558 patients). One study with the clinical diagnosis as the reference standard 68 also allowed evaluation of ultrasonography as the reference standard (23 patients).…”

“…the studies using clinic al diagnosis as reference standard, 17,29,31,33,34,36,47,51,53,54,57,61,68,69,76,82 patients were all followed up to verify that the clinical diagnosis was not later revised. Only 1 study 68 allowed us to evaluate imaging as the reference standard in addition to the clinical diagnosis and TAB.…”

“…16,35,36,43,47,52,55,57,58,61,69,73,75,80,84 s From 23 of the analyzed studies. 17,24,25,32-34,37,39,41, 46,48,49,53,58,60,[64][65][66]71,75,76,82,86 t From 4 of the analyzed studies. 16,32,54,79 u From 6 of the analyzed studies.…”