Are polymyalgia rheumatica and giant cell arteritis the same disease?

OBJECTIVE: To summarize the evidence about the relationship between polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). METHODS: Review of relevant articles from the English-language literature. RESULTS: Epidemiologic studies suggest that PMR and GCA are closely related conditions affecting people over 50 years and frequently occurring in the same patient. PMR symptoms have been observed in 40 to 60 percent of GCA clinical series. Also, temporal artery biopsy may yield positive results for GCA in patients with isolated PMR. Conflicting HLA-DRB1 genotype results have been reported, and recent studies have shown that PMR and GCA have different expression of RANTES, TNFalpha microsatellite, and IL-6 promoter genetic polymorphisms. Search for a possible common infectious agent have yielded disappointing results. Although parvovirus B19 DNA is present in the artery wall of patients with GCA, this virus may be only an innocent bystander. Cytokine studies on a limited number of temporal artery biopsy specimens have shown that interferon-gamma is produced in GCA and not in PMR, suggesting that this cytokine may be crucial to the development of overt vasculitis. CONCLUSIONS: PMR and GCA frequently occur together but no definitive conclusions can be drawn about the nature of this association.     

Are steroids alone sufficient for the treatment of giant cell arteritis?

Glucocorticosteroids are the cornerstone of treatment of giant cell arteritis. An initial dose of prednisone or its equivalent of at least 40-60mg per day as single or divided dose is usually adequate. Glucocorticosteroids may prevent, but usually do not reverse, visual loss. A treatment course of 1-2 years is often required. Some patients, however, have a more chronic-relapsing course and may require low doses of glucocorticosteroids for several years. Glucocorticosteroid-related adverse events are common. In studies on immunosuppressant agents, methotrexate has been used as a glucocorticosteroid-sparing drug with conflicting results. This drug may, however, be given to patients who need high doses of glucocorticosteroids to control active disease and who have serious side effects. A recent pilot study found that infliximab was efficacious in patients with glucocorticosteroid-resistant giant cell arteritis. However, randomized controlled trials are required to define the role of anti-tumor necrosis factor-alpha agents in the treatment of giant cell arteritis. Finally, low-dose aspirin has been shown in a recent retrospective study to decrease the rate of cranial ischemic complications secondary to giant cell arteritis. It is conceivable that the definition of different patterns of inflammation in giant cell arteritis in the future might facilitate the design of differentiated therapeutic approaches.     

Fulminant alveolar hemorrhage: evolution of giant cell arteritis to ANCA-positive vasculitis?

INTRODUCTION: Giant cell arteritis (GCA) is a granulomatous vasculitis of the large and medium size vessels with a remarkable sensitivity to corticosteroids, although it may be dependent to therapy. In rare cases, a vasculitis of the medium or small-size vessels may mimic, be associated to, or follow GCA. We report a case of GCA dependent to corticosteroids that was followed five years after diagnosis by an alveolar hemorrhage leading to the diagnosis of a possible Wegener's granulomatosis. EXEGESIS: A 70-year-old man had a diagnosis of GCA fulfilling the ACR criteria in 1999. Temporal artery biopsy revealed a typical histological pattern. The initial response to corticosteroids was excellent, but the patient became dependent to corticosteroids, so he was given methotrexate from 2002. Severe alveolar haemorrhage occurred in December 2004, leading to the diagnosis of possible ANCA positive, anti-proteinase 3 positive Wegener's granulomatosis. CONCLUSION: ANCA-positive vasculitis may complicate the course of GCA. This evolution should be rapidly recognized, because its treatment differs to that of GCA.     

What have we learned about giant cell arteritis during the last decade?

INTRODUCTION: We propose a review on the current state of knowledge in giant cell arteritis (GCA), with particular emphasis on advances produced during the past 10 years. CURRENT KNOWLEDGE AND KEY POINTS: The physiopathology of GCA is better understood. GCA is considered as a T-cell mediated, antigen driven disease. The expression of interferon-gamma greatly influences the clinical expression of the vasculitis. The disease occurs preferentially in women. HLADR4 group and an atheromatous background have been shown to be risk factors for the disease. Infections (parainfluenzae virus, parvovirus B19) may act as triggers at the onset of GCA. In Europe, GCA incidence seems to be increasing in most countries in which it has been studied, especially in women. The diagnostic usefulness of the halo sign detected by high resolution Doppler ultrasonography seems limited. An excess of cardiovascular mortality is described in some countries. There is no consensus regarding the risk factors for thrombotic events. Randomized studies have not proved that methotrexate is a significantly efficient corticosteroid sparing agent. The value of high doses of methylprednisolone for severe thrombotic events has not been established. Benefits and risks of antiaggregation and anticoagulation are unknown. PERSPECTIVES: Numerous important questions regarding the management of GCA remain unresolved. Well designed prospective studies are rare, and necessary in the future.     

Is intimal hyperplasia a marker of neuro-ophthalmic complications of giant cell arteritis?

Objective. The ischaemic complications of giant cell arteritis(GCA) such as blindness and stroke may result from luminal narrowingof the affected arteries. This study focuses on the associationbetween the severity of intimal proliferation on temporal arterybiopsy (TAB) histology and neuro-ophthalmic complications (NOCs)of GCA. Method. We identified 30 cases of biopsy-proven temporal arteritis.One histopathologist (blinded to the clinical details) evaluatedthe TAB specimens and categorized the degree of maximum stenosisdue to intimal hyperplasia into four grades: grade 1 is <50%luminal occlusion due to intimal hyperplasia, grade 2 is 50–75%,grade 3 is >75% and grade 4 is complete luminal occlusion.A second histopathologist (also blinded to the clinical details)independently evaluated the TAB specimens using the same gradingsystem. The NOCs in these patients were noted after a case recordreview. Results. Of the 30 patients, 12 had NOC-10 with eye complications(complete visual loss, anterior ischaemic neuropathy, visualfield defects), one patient had cerebral infarcts and one hadboth cerebral infarcts and vision loss. There was evidence fora statistically significant trend of NOC associated with higherintimal hyperplasia scores (P = 0.001). The scores of the histopathologistsagreed for 23 (77%) patients and differed by 1 category forthe remaining 7 (-statistic 0.88). Conclusions. Our study suggests that the degree of intimal hyperplasiaon TAB histology (routinely available to all hospital units)seems to be closely associated with NOCs of GCA. The study highlightsthe possible prognostic as well as diagnostic role of the biopsy.We feel that intimal hyperplasia noted in biopsy specimens mayhelp us in the risk stratification of GCA patients and targetingof appropriate and novel therapies. KEY WORDS: Intimal hyperplasia, Giant cell arteritis, Neuro-ophthalmic complications Submitted 1 June 2007; revised version accepted 7 January 2008.     

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.     

Alport’s syndrome: case of a giant esophageal tumor

Alport’s syndrome–diffuse leiomyomatosis (AS–DL) is a rare clinical entity. The syndrome consists of hematuric nephropathy, ocular lesions, and sensorineural deafness associated with leiomyomas of the gastrointestinal, respiratory and female reproductive tracts. Esophageal leiomyomatosis is characterized by diffuse proliferation of the esophageal wall smooth muscle layer, causing obstruction. The usual presenting symptom is dysphagia. We describe a patient with Alport’s syndrome associated with a large esophageal leiomyoma with dyspnoea as the first presenting symptom. Imaging such as computed tomography (CT) is useful in aiding diagnosis. A high index of suspicion is needed for diagnosis of Alport’s syndrome in a patient presenting with esophageal leiomyomatosis. Surgical resection is currently the treatment of choice in symptomatic individuals.     

Prevalence and prognostic factors for aortic dilatation in giant cell arteritis – a longitudinal study

ObjectivesPredictive data for the development of aortic dilatation (AD) in giant-cell arteritis (GCA) are controversial. The aim was to investigate by computed tomography (CT) the prevalence of AD in a consecutive cohort of GCA patients and controls, and to identify possible predictors for AD.MethodsGCA patients and controls were identified by electronic search and underwent aortic contrast enhanced CT defining AD by aortic diameter adjusted to age, gender and body surface area. Pulse-wave velocity, intima-media thickness (IMT) and laboratory studies including lymphocyte subsets were conducted identifying potential factors associated with AD. Clinical and laboratory parameters at disease onset, occurrence of aortic rupture/dissection before and up to five years after study visit were retrieved by chart review.Results144 GCA patients and 115 controls were included. GCA patients developed more frequently AD of the ascending and thoracic descending aorta compared to controls (OR 2.60, p = 0.016; OR 3.65, p = 0.005, respectively). Factors associated with AD development of thoracic descending aorta, but not of the ascending aorta, were higher percentages of circulating CD3+CD4+ cells, higher CD4/CD8 ratio, presence of polymyalgia rheumatica and increased carotid IMT at disease onset (OR range 1.10-3.11, all with p < 0.05). During follow-up, no GCA patient required surgical aortic repair or suffered aortic rupture/dissection.ConclusionsThoracic but not abdominal ADs occur more commonly in GCA patients, however, the subsequent risk for aortic repair, rupture or dissection is low. Changes of T-cell subsets, presence of polymyalgia rheumatica and increased carotid IMT at disease onset are associated with AD development.     

Temporal artery biopsy for diagnosing giant cell arteritis: the longer, the better?

OBJECTIVE: To investigate the relation between temporal artery biopsy (TAB) length and diagnostic sensitivity for giant cell arteritis. METHODS: Histological TAB reports generated from four hospital pathology departments were reviewed for demographics, histological findings, and formalin fixed TAB lengths. A biopsy was considered positive for giant cell arteritis if there was a mononuclear cell infiltrate predominating at the media-intima junction or in the media. RESULTS: Among 1821 TAB reports reviewed, 287 (15.8%) were excluded because of missing data, sampling errors, or age < 50 years. Mean TAB length of the 1520 datasets finally analysed (67.2% women; mean (SD) age, 73.1 (10.0) years) was 1.33 (0.73) cm. Histological evidence of giant cell arteritis was found in 223 specimens (14.7%), among which 164 (73.5%) contained giant cells. Statistical analyses, including piecewise logistic regression, identified 0.5 cm as the TAB length change point for diagnostic sensitivity. Compared with TAB length of < 0.5 cm, the respective odds ratios for positive TAB without and with multinucleated giant cells in samples > or = 0.5 cm long were 5.7 (95% confidence interval, 1.4 to 23.6) and 4.0 (0.97 to 16.5). CONCLUSIONS: A fixed TAB length of at least 0.5 cm could be sufficient to make a histological diagnosis of giant cell arteritis.