Artery Biopsy Specimens Research Articles

A3.33 Increased rho-kinase activity in temporal artery biopsies from patients with giant cell arteritis

Background/PurposeROCKs are implicated in the pathogenesis of many vascular diseases. ROCK activation is associated with Th17 differentiation and production of Th17-associated cytokines, IL-17 and IL-21. Th17 cells and related cytokines...

FRI0037 IL-33 is over-expressed in the inflamed arteries of patients with giant cell arteritis

BackgroundGiant-cell arteritis (GCA) is an inflammatorydisease of blood vessels most commonly involving large and medium arteriesof the head. Interleukin-33 (IL-33), a member of the IL-1 cytokine family [6], is a...

Th1 and Th17 lymphocytes expressing CD161 are implicated in giant cell arteritis and polymyalgia rheumatica pathogenesis

Giant cell arteritis (GCA) is the most frequently occurring vasculitis in elderly individuals, and its pathogenesis is not fully understood. The objective of this study was to decipher the role of the major CD4+ T cell subsets in GCA and its rheumatologic form, polymyalgia rheumatica (PMR). A prospective study of the phenotype and the function of major CD4+ T cell subsets (Th1, Th17, and Treg cells) was performed in 34 untreated patients with GCA or PMR, in comparison with 31 healthy control subjects and with the 27 treated patients who remained after the 7 others withdrew. Compared with control subjects, patients with GCA and patients with PMR had a decreased frequency of Treg cells and Th1 cells, whereas the percentage of Th17 cells was significantly increased. Furthermore, an analysis of temporal artery biopsy specimens obtained from patients affected by GCA for whom biopsy results were positive demonstrated massive infiltration by Th17 and Th1 lymphocytes without any Treg cells. After glucocorticoid treatment, the percentages of circulating Th1 and Th17 cells decreased, whereas no change in the Treg cell frequency was observed. The frequency of CD161+CD4+ T cells, which are considered to be Th17 cell precursors, was similar in patients and control subjects. However, these cells highly infiltrated GCA temporal artery biopsy specimens, and their ability to produce interleukin-17 in vitro was significantly enhanced in patients with GCA and patients with PMR and was correlated with a decrease in the phosphorylated form of STAT-1. This study is the first to demonstrate that the frequency of Treg cells is decreased in patients with GCA and patients with PMR, and that CD161+CD4+ T lymphocytes, differentiated into Th1 cells and Th17 cells, are involved in the pathogenesis of GCA and PMR.

IL-33 is overexpressed in the inflamed arteries of patients with giant cell arteritis

ObjectiveTo study the expression of interleukin (IL)-33 and to evaluate its relationship with macrophage polarisation in artery biopsy specimens from patients with giant cell arteritis (GCA).MethodsIL-33, ST2, p-STAT-6 and perivascular...

Small‐vessel vasculitis surrounding an uninflamed temporal artery and isolated vasa vasorum vasculitis of the temporal artery: Two subsets of giant cell arteritis

To evaluate the frequency and clinical characteristics of periadventitial small-vessel vasculitis (SVV) and isolated vasa vasorum vasculitis (VVV). We identified 455 temporal artery biopsies performed in residents of Reggio Emilia, Italy between 1986 and 2003. Slides of temporal artery biopsy specimens were reviewed by a pathologist who was blinded with regard to clinical data. SVV was defined as inflammation of the small vessels external to the temporal artery adventitia, and VVV was defined as isolated inflammation of temporal artery vasa vasorum. Medical records of patients with SVV and/or VVV were reviewed, and demographic, clinical, laboratory, and followup data were collected. For comparison purposes, we collected the same data from an equal number of randomly selected patients with evidence of classic giant cell arteritis (GCA). Sixteen patients had SVV, 18 had isolated VVV, and 5 had both SVV and VVV. Compared with patients with classic GCA, the frequencies of headache, scalp tenderness, abnormalities of temporal arteries, jaw claudication, anorexia, and weight loss, the levels of acute-phase reactant at diagnosis, and the initial and cumulative doses prednisone were significantly lower and the frequency of peripheral synovitis was higher in the patients with SVV, and the frequency of cranial ischemic events was similar in the 2 groups. In contrast, the clinical characteristics and erythrocyte sedimentation rate at diagnosis of patients with isolated VVV were similar to those of patients with classic GCA. Our findings indicate that isolated VVV and SVV should be considered part of the histopathologic spectrum of GCA.

Abstract 17956: Serpin Treatment Reduces Inflammation in Transplanted Temporal Artery Biopsy Specimens from Patients with Suspected Giant Cell Arteritis in Immunodeficient Mice

Background - Giant cell / temporal arteritis (GCTA) is a severe inflammatory vasculitic syndrome (IVS), which causes arterial occlusion and sudden loss of vision. Treatment for IVS remains limited. Intra-aortic full thickness implants of human TA biopsy and left internal mammary artery (LIMA) specimens were surgically engrafted into the abdominal aorta of immunodeficient SCID mice as a new model for analyzing development of vascular inflammation, as well as response to new treatments. Serp-1 is a myxomaviral-derived serine protease inhibitor (serpin) that blocks thrombotic and thrombolytic protease pathways, arterial inflammation, and plaque growth. Serp-1 was recently tested in acute coronary syndromes (ACS), where reduced markers of myocardial damage were detected after stent implant. Objective - We assessed the effects of Serp-1 or saline treatment on inflammatory cell invasion and plaque growth after TA and LIMA engraftment in NOD-SCID mice. Results - Normal arterial (LIMA) specimens were harvested during bypass surgery and implanted into 24 SCID mice. Half the mice had saline (N=12) and half had Serp-1 treatment (N=12). In each group 6 mice had 5x106 peripheral blood mononuclear cells (PBMCs) infusions from the same patient as the donor LIMA graft, given immediately postop by tail vein and 6 had no cell infusion. TA grafts from patients with suspected GCA were implanted into a separate group of 24 SCID mice - 12 mice had saline (100µl) and 12 Serp-1 (100ng/g/100µl) treatment (one i.v. injection followed by daily i.p. injection for 10 days). in each treatment group 4 mice had infusion of non-matched PBMCs. At 4 weeks LIMA (P < 0.034) or TA (P < 0.0001) grafts, had significantly reduced plaque growth with Serp-1 treatment when human PBMC were also infused (p<0.05). In the absence of PBMC, Serp-1 had minimal effect. Mononuclear cell invasion was reduced in Serp-1 treated mice with PBMCs. Flow cytometry did not detect significant changes in splenocytes. Conclusions - Aortic implant of human LIMA or TA xenografts in SCID mice provides a physiological model for investigating inflammatory vasculitis. With PBMC infusion, treatment with the myxomaviral Serp-1, reduced inflammatory cell invasion and plaque growth in arterial xenografts.

Expression of interleukin-32 in the inflamed arteries of patients with giant cell arteritis

Giant cell (temporal) arteritis (GCA) is a vasculitis that mainly affects the large and medium arteries, especially the branches of the proximal aorta. Interleukin-32 (IL-32) is a recently described Th1 proinflammatory cytokine, and is mainly induced by interferon-γ (IFNγ), IL-1β, and tumor necrosis factor α (TNFα). This study was undertaken to investigate the expression and tissue distribution of IL-32 in artery biopsy specimens from patients with GCA. Quantitative gene expression analysis of IL-32, IL-1β, TNFα, IFNγ, IL-6, and IL-27 was performed in artery biopsy specimens obtained from 18 patients with GCA and 15 controls. Immunohistochemistry analysis was performed to evaluate IL-32 tissue distribution and identify IL-32-producing cells. Circulating Th1 lymphocytes were evaluated by flow cytometry. We demonstrated a strong and significant up-regulation of IL-32 at both the messenger RNA and protein levels in the artery biopsy samples from patients with GCA. IL-32 was abundantly expressed by vascular smooth muscle cells of inflamed arteries and neovessels within inflammatory infiltrates. IL-32 expression strongly correlated with the intensity of the systemic inflammatory response. IL-32 overexpression was accompanied by strong overexpression of Th1 cytokines, such as IFNγ and IL-27p28, in inflamed arteries from GCA patients. The Th1 lymphocyte population was also expanded among peripheral blood mononuclear cells from GCA patients and produced higher amounts of IL-32 compared to controls. Our findings indicate that overexpression of IL-32 together with a clear Th1 response immunologically characterizes the inflammatory response in GCA. In particular, IL-32 seems to be an important mediator of artery inflammation in GCA.

Evaluation for Clinical Predictors of Positive Temporal Artery Biopsy in Giant Cell Arteritis

Conclusions: A positive temporal artery biopsy specimen is more likely if patients present with weight loss or pain with mastication. Corticosteroid therapy before temporal artery biopsy does not affect positivity of a temporal artery biopsy specimen. Summary: In patients aged >50 years, temporal arteritis (TA) is the most common systemic vasculitis. Tenderness of the scalp or new onset of headache are common complaints. Ocular manifestations of TA include decreased vision, diplopia, and amaurosis fugax, and up to 20% of patients may develop irreversible visual loss from optic nerve ischemia. Pain with mastication is present in 50% of patients (Salbarani C, et al; Lancet 2008;372:234). However, many patients present with predominately constitutional symptoms such as weight loss, fatigue, or fever. Inflammatory markers, such as erythrocyte sedimentation rate and C-reactive protein, are frequently elevated in patients with TA, but they are not specific. Diagnosis of TA can therefore be difficult. An abnormal finding on a temporal artery biopsy specimen is a part of the American College of Rheumatology criteria for diagnosis of TA (Hunder GG, et al; Arthritis Rheum 1990;33:112); however, up to two-thirds of temporal artery biopsy specimens are negative. It would therefore be useful to determine if there are clinical parameters that most likely correlate with TA to identify patients who will most likely benefit from treatment while waiting to undergo a temporal artery biopsy (Youngee BR; Mayo Clin Proc 2004;79:483). In this study, the authors examined clinical parameters associated with a positive temporal artery biopsy specimen in patients with symptoms suggestive of TA. This was a retrospective study of 82 consecutive patients who underwent temporal artery biopsies by a single surgeon at a single institution. Medical records were reviewed for clinical symptoms, laboratory findings, final diagnosis, and biopsy results. The microscopic examination suggested evidence of arteritis in 22 patients (26.8%). In two patients, TA was clinically diagnosed with a negative temporal artery biopsy specimen. Patients presenting with weight loss or pain with mastication were most likely to have a positive temporal artery biopsy specimen (odds ratio, 4.5 [95% CI, 1.45-13.93] and odds ratio, 3.71 [95% CI, 1.28-10.76]). Laboratory findings did not predict a positive temporal artery biopsy specimen. Use of steroids before the temporal artery biopsy was not associated with a decreased likelihood of a positive specimen. Comment: High doses of corticosteroids are the initial treatment of TA. These drugs are clearly not benign in the elderly patient. For logistical and referral reasons, a temporal artery biopsy specimen may not be available as rapidly as desirable. If one does not wish to treat all patients suspected of TA before biopsy results, the study provides some guidance for determining patients who are at the highest risk of actually having a positive biopsy specimen. Pain with mastication and weight loss appear to be more important parameters in predicting a positive temporal artery biopsy specimen than laboratory markers of inflammation. It is also useful to know that prednisone therapy will not decrease the likelihood of a positive temporal artery biopsy specimen, at least if the biopsy occurs relatively soon after the beginning of steroid therapy.

Temporal Small-Vessel Inflammation in Patients with Giant Cell Arteritis: Clinical Course and Preliminary Immunohistopathologic Characterization

To investigate the occurrence, clinical correlates, and immunohistochemical phenotype of temporal small-vessel inflammation (TSVI) in temporal artery biopsies from patients presenting with clinical features of giant cell arteritis (GCA). We retrospectively reviewed 41 temporal artery biopsy specimens for the presence of inflammatory infiltrates in small vessels external to the temporal artery adventitia (TSVI); 33 had sufficient clinical and pathological data for detailed analysis. Clinical and laboratory features at presentation and corticosteroid treatment patterns of patients with isolated TSVI were compared to those of patients with positive and negative biopsies. The cellular composition of the infiltrates was further characterized by immunohistochemistry. Twenty-three (70%) specimens had evidence of TSVI including 10 with concurrent GCA and 13 (39%) with isolated TSVI. TSVI was found in all positive temporal artery biopsies. The proportion of macrophages and of lymphocyte subpopulations differed between infiltrates observed in TSVI and those of the main temporal artery wall. Initial erythrocyte sedimentation rate (ESR) was similar in the TSVI and positive biopsy groups and was significantly higher than in the negative biopsy group. Patients with isolated TSVI more often had symptoms of polymyalgia rheumatica compared to the positive biopsy group. Patients with TSVI received corticosteroid doses that were intermediate between patients with positive and those with negative biopsies. A significant number of patients with clinical features of GCA demonstrated isolated TSVI. Differences in the clinical presentation and cellular composition suggest that TSVI may represent a subset of GCA and should be considered in the interpretation of temporal artery biopsies and treatment decisions.

Angiotensin-converting Enzyme Inhibition Down-regulates the Pro-atherogenic Chemokine Receptor 9 (CCR9)-Chemokine Ligand 25 (CCL25) Axis

Many experimental and clinical studies suggest a relationship between enhanced angiotensin II release by the angiotensin-converting enzyme (ACE) and the pathophysiology of atherosclerosis. The atherosclerosis-enhancing effects of angiotensin II are complex and incompletely understood. To identify anti-atherogenic target genes, we performed microarray gene expression profiling of the aorta during atherosclerosis prevention with the ACE inhibitor, captopril. Atherosclerosis-prone apolipoprotein E (apoE)-deficient mice were used as a model to decipher susceptible genes regulated during atherosclerosis prevention with captopril. Microarray gene expression profiling and immunohistology revealed that captopril treatment for 7 months strongly decreased the recruitment of pro-atherogenic immune cells into the aorta. Captopril-mediated inhibition of plaque-infiltrating immune cells involved down-regulation of the C-C chemokine receptor 9 (CCR9). Reduced cell migration correlated with decreased numbers of aorta-resident cells expressing the CCR9-specific chemoattractant factor, chemokine ligand 25 (CCL25). The CCL25-CCR9 axis was pro-atherogenic, because inhibition of CCR9 by RNA interference in hematopoietic progenitors of apoE-deficient mice significantly retarded the development of atherosclerosis. Analysis of coronary artery biopsy specimens of patients with coronary artery atherosclerosis undergoing bypass surgery also showed strong infiltrates of CCR9-positive cells in atherosclerotic lesions. Thus, the C-C chemokine receptor, CCR9, exerts a significant role in atherosclerosis.

Giant cell arteritis in Alaska Natives

Objective: To investigate the incidence of biopsy-proven giant cell arteritis in the Native population of Alaska. Design: Retrospective review of medical diagnostic and Current Procedural Terminology (CPT) codes. Participants: 110 000 Alaska Native patients. Methods: We conducted a retrospective review of medical diagnostic codes for temporal arteritis, giant cell arteritis, and anterior ischemic optic neuropathy in the medical records of 110 000 Alaska Native patients seen between 1983 and 2003. We examined this same database in search of the CPT code for the temporal artery biopsy procedure. We also re-examined all temporal artery biopsy specimens that had been reported as positive. Results: We identified 122 patients whose diagnostic codes matched those of giant cell arteritis, temporal arteritis, or anterior ischemic optic neuropathy. We found that of 20 temporal artery biopsies that had been performed on this group, only 4 were reported to have had positive results. On re-examination of pathologic specimens, 1 of the 4 was found not to meet the latest pathologic criteria for this disease, leaving only 3 cases of biopsy-proven giant cell arteritis. The calculated incidence of giant cell arteritis in the Alaska Native population is approximately 1/100 000 in those over 50 years old. Conclusions: Compared with previous epidemiologic studies performed worldwide, our review suggests a very low incidence of biopsy-proven giant cell arteritis among Alaska Natives.

A case of systemic polyarteritis nodosa with spermatic cord involvement

A 50-year-old man with a history of hyperlipidemia and hypertension presented to an emergency department after 10 days of fevers (temperature 40 degrees C), headache, malaise, myalgia, poor appetite, diarrhea, and weight loss of 6.35 kg. He would subsequently develop bilateral scrotal swelling and pain during his evaluation. Physical examination, CBC, blood chemistry panel, measurement of erythrocyte sedimentation rate and C-reactive protein level, liver function profile, urinalysis, lumbar puncture, blood cultures, urine cultures, cerebrospinal fluid culture, stool analysis and cultures, multiple viral studies including hepatitis serologies, measurement of antineutrophil cytoplasmic autoantibody levels, urine protein electrophoresis, serum protein electrophoresis, CT of the head, chest, abdomen and pelvis, MRI of the brain, temporal artery biopsy and pathologic analysis, scrotal ultrasonography, right spermatic cord biopsy and pathologic analysis. Polyarteritis nodosa with involvement of both spermatic cords. Prednisone 60 mg daily was started for presumed temporal arteritis, but was discontinued when no evidence of arteritis was found in the temporal artery biopsy specimen. When pathologic analysis of the spermatic cord biopsy tissue confirmed polyarteritis nodosa, prednisone 40 mg twice daily was administered and the patient's scrotal pain and swelling resolved quickly. Steroids were slowly tapered and discontinued over the next 18 months. He remained free of systemic symptoms, with normal results on physical examination and laboratory evaluation, including urinalysis, CBC, erythrocyte sedimentation rate and C-reactive protein level, 5.5 months after discontinuation of glucocorticoid therapy.

Pathological features of temporal arteries in patients with giant cell arteritis presenting with permanent visual loss

Background:Permanent visual loss (PVL) is the most feared complication of giant cell arteritis (GCA), and its risk factors are still unclear.Objectives:The aim of our study was to assess the pathological...

Infection and temporal arteritis: A PCR‐based study to detect pathogens in temporal artery biopsy specimens

The possibility of infectious triggers stimulating the development of inflammatory vascular diseases has generated much recent interest. This study uses PCR to detect the presence of Chlamydia pneumoniae, parvovirus B19 and all the human herpes viruses except HHV8 in temporal artery biopsy specimens. Samples from 37 temporal artery biopsies with histological evidence of arteritis and 66 samples from histologically negative temporal artery biopsies, all from different patients, were negative for C. pneumoniae, HSV, VZV, EBV, and HHV7 DNA. Two of the 37 histologically positive specimens were positive for HHV6, another two for CMV and a further two for parvovirus B19 DNA. Parvovirus B19 DNA was also detected in five histologically negative biopsies, one positive for HCMV DNA and a further one was positive for HHV6 DNA. There is no statistically significant difference to the presence of virus DNA in the two types of specimens (P = 0.538). This study does not support a role for C. pneumoniae, parvovirus B19 or human herpes viruses in the pathogenesis of temporal arteritis.

Simultaneous Ischemic Optic Neuropathy and Third Cranial Nerve Palsy in Giant Cell Arteritis

We report for the first time the concurrence of ischemic optic neuropathy and third cranial nerve palsy in a case of histologically proven giant cell arteritis (GCA). An 87-year-old woman was admitted to the hospital with a 4-week history of pain on her scalp, under her chin, and in the occipital area and neck. In addition, she had jaw claudication, which gradually increased in intensity. One day earlier, the patient simultaneously developed sudden profound vision loss and ptosis of the right eye. She had lost the vision in the left eye many years earlier from direct trauma. Our examination revealed a best-corrected visual acuity of 20/200 in the right eye and no light perception in the left eye. The right pupil measured 5 mm in dim illumination and did not constrict to direct light. The left pupil was irregular, measured about 2.5 mm, and did not constrict to direct light. The right upper lid had 3 mm of ptosis. In the right eye, abduction was normal, but adduction, supraduction, and infraduction were absent. Ophthalmoscopy of the right eye revealed mild optic disc swelling. Evaluation of the left eye could not be done because of the history of trauma. Pulsations of the right temporal artery were not palpable, and those of the left temporal artery were feeble. There was scalp tenderness. The erythrocyte sedimentation rate was 55 mm/h (normal value <15 mm/h), C-reactive protein (CRP) was 8.3 mg/L (normal value <6 mg/L), and platelet count was 625,000/μL (normal value 142,000-424,000/μL). Brain MRI was normal. On color duplex ultrasonography, no fluximetric alterations of carotid and vertebral arteries were seen. The following day, biopsy of the right temporal artery showed marked inflammation and intimal fibrosis (Fig. 1). The media contained lymphocytes and giant cells. Fragmentation of the internal elastic lamina of the artery was evident. A diagnosis of giant cell arteritis was made and treatment with 50 mg oral prednisolone was started. Within a few days, the headache disappeared. The medication was continued at the same dose for 20 days, after which the dose was tapered. Three months after the corticosteroid treatment was started, the features of third cranial nerve palsy had disappeared except for a dilated unreactive pupil. The vision loss persisted.FIG. 1: Histopathologic analysis of a temporal artery biopsy specimen shows an inflammatory infiltrate in the media and intimal fibrosis (hematoxylin-eosin).Impairment of the third, fourth, or sixth cranial nerves has been reported in only 2% of patients with GCA (1-8). This case illustrates the fact that ischemic optic neuropathy and third cranial nerve palsy may be coincident manifestations of GCA. Çağatay Öncel, MD Neurology Department Pamukkale University Denizli, Turkey Ferda Bir, MD Pathology Department Pamukkale University Denizli, Turkey L. Sinan Bir, MD Neurology Department Pamukkale University Denizli, Turkey [email protected]

Biopsy-negative giant cell arteritis: Does anti-CD83 immunohistochemistry advance the diagnosis?

Background In situ maturation of adventitial dendritic cells (DC) with expression of CD83 has been proposed as an early event in the pathogenesis of giant cell arteritis (GCA), preceding the appearance of an inflammatory infiltrate. The aim of this study was to evaluate the added value of anti-CD83 staining of temporal artery biopsy (TAB) specimens in patients with biopsy-negative temporal arteritis. Methods Fourteen patients with TAB performed in our medical center since 2001 and considered negative for GCA due to the absence of any inflammatory infiltrate were identified by a computerized search of patient records. Their paraffin-embedded TAB specimens were retrieved, reprocessed, and stained with anti-CD83 monoclonal antibody (Serotec, 1:40). Three TAB specimens of patients with biopsy-proven GCA served as positive controls and three specimens of popliteal and/or tibial arteries of patients with atherosclerotic peripheral vascular disease were used as negative controls. Follow-up of the patients was confirmed by personal contact with their rheumatologists and analysis of their hospital charts. Results Follow-up was available for 12 of 14 patients. Five of these patients were considered to have biopsy-negative GCA: they satisfied the ACR classification criteria, were successfully treated with glucocorticosteroids, and had a follow-up of at least 10 months with no alternative diagnosis established. Anti-CD83 staining was negative in all but one patient who demonstrated a single CD83-positive cell adjacent to the internal elastic membrane. Positive anti-CD83 staining of the inflammatory infiltrate throughout the arterial wall was observed in all patients with biopsy-proven GCA (positive controls). Negative controls did not show any CD83-positive cells. Conclusions In this pilot study, anti-CD83 immunohistochemical staining of paraffin-embedded specimens did not improve the yield of TAB in patients with suspected GCA.

THE LENGTH OF SUPERFICIAL TEMPORAL ARTERY BIOPSIES

To compare temporal artery biopsy specimen lengths from a tertiary care and a community hospital in New South Wales to recommended clinical guidelines in suspected giant cell arteritis. A retrospective observational study of all patients who underwent temporal artery biopsy at Bathurst Base Hospital (BBH) and Royal Prince Alfred Hospital (RPAH) over a 5-year period. Patients who underwent temporal artery biopsy during the 5-year period were identified using computerized hospital databases. A retrospective chart review was carried out on all cases. Data were collected regarding patient age, patient sex, length of biopsy specimen, histopathological results and surgical team carrying out the biopsy. During the 5-year period, 157 temporal artery biopsies were carried out at both hospitals, with 38/157(24%) at BBH and 119/157 (76%) at RPAH. There was no significant difference in biopsy length at the two hospitals. The mean specimen length at BBH was 12.1 mm compared with 11.7 mm at RPAH (t=0.35; P=0.73). At RPAH, there was no significant difference in specimen length between the surgical specialties carrying out the biopsy (ANOVA F=1.37; P=0.26). Specimens of length 20 mm or greater were 2.8 times more likely to show features of giant cell arteritis than those less than 20 mm. The mean length of temporal artery biopsy specimens at both hospitals was substantially shorter than recommended guidelines of a minimum 20 mm. We recommend all surgeons carrying out temporal artery biopsies ensure a specimen of sufficient length is obtained.

Histologic parameters helpful to recognize steroid-treated temporal arteritis: An analysis of thirty-five cases

This study was performed in order to establish the important histologic and immunohistochemical parameters that are helpful in recognizing temporal arteritis in patients who have been treated with steroids prior to the biopsy, and to analyze the clinical features and correlate them with the histologic findings. A retrospective review of charts of 35 patients treated with steroids prior to obtaining temporal artery biopsy specimens, spanning an 11 year period from1995 to 2005. The study was conducted at the Ophthalmic Pathology Laboratory at the Cullen Eye Institute. The clinical features were evaluated and correlated with the histopathologic findings. Each case was evaluated with respect to age, gender, race, clinical findings, erythrocyte sedimentation rate, corticosteroid dosage (oral vs intravenous), and the duration of the treatment. The time interval between obtaining the biopsy specimen and the onset of steroid therapy was carefully recorded from each patient. In selected cases, histiocytic markers (CD68 and HAM-56) were performed to identify the presence of epithelioid histiocytes, which characterizes a granulomatous inflammation. Other immunohistochemical studies (CD3, CD20, CD4, CD8, CD45RO, CD45RA, and S-100 protein) were performed in selected cases to characterize the inflammatory cells. The authors believe that the three most reliable histopathologic parameters of corticosteroid-treated temporal arteritis are the following: 1) Complete or incomplete mantle of lymphocytes and epithelioid histiocytes located between the outer muscular layer and the adventitia, 2) large circumferential defects in the elastic lamina (best seen with the Movat pentachrome), and 3) absent or few small multinucleated giant cells. In some cases the main artery appears normal while the primary branches show evidence of a healing arteritis. The histologic findings vary according to the route of steroid administration (oral vs intravenous) and the duration of treatment prior to obtaining the biopsy specimen. Striking histologic differences can be recognized objectively between patients with active (untreated) giant cell arteritis (GCA) and patients who have been treated with corticosteroids. The earliest histopathologic changes were detected by the end of the first week following steroid therapy (usually after day 4 to the end of the first week). The histologic findings were more difficult to recognize after two to three months following steroid treatment. We believe ophthalmic and general pathologists should be able to recognize this entity on the basis of the histologic findings including the special stains and results of immunohistochemical markers (CD68 and HAM-56).—Hans E. Grossniklaus

Quantitative analysis of temporal artery contraction after biopsy for evaluation of giant cell arteritis

Background: Although the degree of contraction of temporal artery biopsy specimens after formalin fixation has been previously reported to range from 6% to 13%, the degree of contraction before fixation has not been previously studied.The aim of this study was to quantify the postexcision (prefixation) contraction of temporal artery biopsy specimens and to determine the relationship between contraction and the result of the biopsy. Methods: All patients undergoing temporal artery biopsies from February 2003 through May 2004 were retrospectively reviewed. Contraction was determined by subtracting the in vivo and ex vivo lengths, then dividing the difference by the in vivo length to obtain a percentage of contraction. Statistical analysis was performed with the unpaired t test and Fisher exact test. Results: We reviewed 37 negative and 7 positive biopsies for giant cell arteritis (GCA). For specimens positive for GCA, the mean contraction was 12%, whereas for negative specimens, mean contraction was 22%. There was a significant difference in the contraction between the specimens positive and negative for GCA ( p = 0.009).The Fisher exact test revealed that GCA was positively associated with arterial contraction of less than 15% ( p = 0.002). Interpretation:The temporal artery can contract substantially after excision and before tissue fixation. GCA-positive specimens exhibit statistically less contractility than negative specimens.

Giant cell arteritis manifesting as mesenteric ischemia

We report a case of giant cell arteritis in an 80-year-old woman who presented with chronic mesenteric ischemia to our vascular surgery service. Computed tomography, arteriography, and magnetic resonance angiography revealed long, smooth stenosis of the superior mesenteric artery and focal stenosis of the celiac artery. After the patient was found to have an elevated erythrocyte sedimentation rate and a positive temporal artery biopsy specimen, glucocorticoid therapy was initiated. Giant cell arteritis is a rare and easily overlooked cause of vascular insufficiency that can result in a devastating clinical outcome if not recognized before surgical therapy or other interventions are attempted.