Histopathologic findings did not help rule out giant cell arteritis (GCA) in patients whose temporal artery biopsy findings were negative, a retrospective study found.
Among patients who ultimately were diagnosed with GCA but whose temporal artery biopsies showed no evidence of an inflammatory giant cell infiltrate, 89.5% showed histologic evidence of fragmentation of the inner elastic lamina, as did a similar 83.9% of those who eventually were given an alternate diagnosis (P=0.721), according to , of Arcispedale Santa Maria Nuova in Reggio Emilia, Italy, and colleagues.
Action Points
- The gold standard for diagnosis of giant cell arteritis (GCA) is temporal artery biopsy documenting transmural inflammation, but a negative biopsy result does not rule out the disease.
- Histopathologic changes other than mural inflammation in the wall of temporal arteries are not specific or useful for the diagnosis of giant cell arteritis (GCA).
Another common histologic findings, intimal hyperplasia, also did not differ in prevalence between the GCA and non-GCA patients (71.1% versus 54.8%, P=0.163), the researchers reported online in
The gold standard for diagnosis of GCA is temporal artery biopsy documenting transmural inflammation, but a negative biopsy result does not rule out the disease, because there can be unaffected arterial segments and previous steroid treatment could influence the results. In fact, up to 40% of temporal artery biopsies have been reported as negative in patients who have clinical findings consistent with GCA.
Nonetheless, it's important to make the diagnosis and initiate glucocorticoids as soon as possible.
"The risks of not treating GCA are substantial, since around 19% of patients with GCA develop permanent visual loss, mostly before starting glucocorticoid treatment. On the other hand, glucocorticoid treatment should only be given when clearly indicated because of the high frequency of glucocorticoid-related adverse events," Salvarani and colleagues wrote.
In addition, structural changes frequently are visible in the temporal artery wall, and it's not known if these changes result from the GCA, atherosclerosis, or normal aging.
Therefore, to evaluate the histopathologic findings among patients lacking an inflammatory infiltrate on biopsy and to determine if these findings can differentiate GCA from non-GCA, Salvarani and colleagues reviewed the records of 112 patients who had temporal artery biopsies for possible GCA at their center during 2009 to 2012.
Clinical history and examinations had been performed for all patients, and color duplex sonography was used to examine the temporal artery and epiaortic vessels.
In 69 of the biopsy samples, no evidence of an inflammatory infiltrate was found.
For the retrospective analysis of these 69, patients were classified as GCA and non-GCA according to the final diagnosis in the medical record. Biopsy-negative GCA was diagnosed in 55% after a median of 19 months' follow-up and ruled out in the other 45% after a median of 26.3 months.
Three-quarters of the patients were women, and mean age at disease onset was 74. The median time from the onset of symptoms until temporal artery biopsy was done was 14 weeks.
Among those who were diagnosed with GCA, 94.7% had any cranial symptoms compared with 61.3% of patients eventually diagnosed with other conditions such as polymyalgia rheumatica and rheumatoid arthritis (P=0.001).
The GCA patients also more often reported headache (84.2% versus 45.2%, P=0.001) and had abnormalities of temporal arteries identified on physical examination (50% versus 6.7%, P<0.0001).
In addition, the GCA group more often were found to have a positive "halo sign" on ultrasound, had higher erythrocyte sedimentation rates and C-reactive protein levels, and more often met the American College of Rheumatology
Prednisone use prior to the temporal artery biopsy was similar in the GCA and non-GCA groups, with 62.2% and 67.7% reporting steroid use, respectively, and in mean daily doses of 16.6 and 14.8 mg and for 33 and 60 days.
After the biopsy, 97.4% of the GCA and 58.1% of the non-GCA group received steroid treatment, in daily doses of 37.3 mg and 16.8 mg, respectively (P<0.0001).
At the final follow-up visit, 70.3% of the biopsy-negative GCA group continued to take prednisone in daily doses of 12.2 mg, compared with 51.7% of non-GCA patients, whose daily dose was 6.7 mg.
Additional histologic findings that were less common than fragmentation of the inner elastic lamina and intimal hyperplasia also could not differentiate the GCA from the non-GCA patients. For instance, medial attenuation was present in 10.5% of the GCA patients and 12.9% of the non-GCA group (P=1), and adventitial fibrosis was found in 7.9% and 3.2% (P=0.622).
"Our main finding is that there are no significant differences in the frequencies of the histologic features evaluated in the two study groups," the study authors wrote.
Rather, "the diagnosis is generally driven by the appropriate combination of clinical features -- typically headache, scalp tenderness, vision loss or diplopia, and/or jaw claudication -- and laboratory findings, usually confirmed by a temporal artery biopsy which shows inflammation featuring giant cells," explained , of the Mayo Clinic in Rochester, Minn.
If the biopsy is negative, according to Ytterberg, who was not involved in the study, "It comes down to an assessment of the clinical and laboratory features and a decision about how convincing they are to support a diagnosis of GCA."
"If I see a patient who has a negative biopsy but strong clinical and laboratory features, I would treat them as I would a patient with a positive biopsy, although I may be inclined to taper the prednisone a bit more quickly," Ytterberg told 51˶.
For patients whose clinical and laboratory features do not support the GCA diagnosis, like the 45% of patients in this study for whom the diagnosis was ultimately ruled out, "quick tapering of prednisone, or not initiating it in the first place, would be appropriate," he said.
Disclosures
The authors reported no conflicts of interest.
Primary Source
Arthritis Care & Research
Muratore F, et al "Histopathologic findings of patients with biopsy-negative giant cell arteritis compared to those without arteritis: a population based study" Arthritis Care Res 2015; DOI:10.1002/acr.22736.