Tanaz A. Kermani

Large-vessel involvement in giant cell arteritis: a population-based cohort study of the incidence-trends and prognosis

Objectives To evaluate incidence-trends and timing of large-vessel (LV) manifestations in patients with giant cell arteritis (GCA), and to examine the influence of LV manifestations on survival. Methods A population-based incident cohort of patients diagnosed with GCA between 1950 and 2004 was used. LV involvement was defined as large-artery stenosis or aortic aneurysm/dissection that developed in the 1 year before GCA diagnosis or at any time thereafter. Patients were followed up until death or 31 December 2009. Results The study included 204 patients, 80% women, mean age at diagnosis of GCA 76.0 years (±8.2 years). Median length of follow-up was 8.8 years. The cumulative incidence of any LV manifestation at 10 years was 24.9% for patients diagnosed with GCA between 1980 and 2004 compared with 8.3% for patients diagnosed with GCA between 1950 and 1979. The incidence of any LV event was high within the first year of GCA diagnosis. The incidence of aortic aneurysm/dissection increased 5 years after GCA diagnosis. Compared with the general population, survival was decreased in patients with an aortic aneurysm/dissection (standardized mortality ratio (SMR) 2.63; 95% CI 1.78 to 3.73) but not in patients with large-artery stenosis (SMR 1.44; 95% CI 0.87 to 2.25). Patients with GCA and aortic manifestations had a higher than expected number of deaths from cardiovascular and pulmonary causes than the general population. Among patients with GCA, aortic manifestations were associated with increased mortality (HR=3.4; 95% CI 2.2 to 5.4). Conclusions Vigilance and screening for aortic aneurysms should be considered in all patients 5 years after the incidence of GCA. Aortic aneurysm/dissection is associated with increased mortality in GCA.

Utility of Erythrocyte Sedimentation Rate and C-Reactive Protein for the Diagnosis of Giant Cell Arteritis

OBJECTIVES To evaluate the utility of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) for the diagnosis of giant cell arteritis (GCA) and to determine the frequency of normal ESR and CRP at diagnosis of GCA. METHODS All patients undergoing temporal artery biopsy (TAB) between 2000 and 2008 were identified. Only subjects with both ESR and CRP at the time of TAB were included. The medical records of all patients were reviewed. RESULTS We included 764 patients (65% women), mean age 72.7 (±9.27) years, who underwent TAB. Biopsy was consistent with GCA in 177 patients (23%). Elevated CRP and elevated ESR provided a sensitivity of 86.9% and 84.1%, respectively, for a positive TAB. The odds ratio of a concordantly elevated ESR and CRP for positive TAB was 3.06 (95% CI 2.03, 4.62), whereas the odds ratio for concordantly normal ESR and CRP was 0.49 (95% CI 0.29, 0.83). Seven patients (4%) with a positive TAB for GCA had a normal ESR and CRP at diagnosis. Compared with GCA patients with elevated markers of inflammation, a greater proportion of these patients had polymyalgia rheumatica symptoms (P = 0.008), whereas constitutional symptoms, anemia and thrombocytosis, were observed less often (P < 0.05). CONCLUSIONS CRP is a more sensitive marker than ESR for a positive TAB that is diagnostic of GCA. There may be clinical utility in obtaining both tests in the evaluation of patients with suspected GCA. A small proportion of patients with GCA may have normal inflammatory markers at diagnosis.

Large-vessel giant cell arteritis: a cohort study

OBJECTIVE The aim of this study was to compare baseline variables, treatment and outcomes in patients with large-vessel GCA (LV-GCA), primarily of the upper extremities, with those with cranial disease (C-GCA). METHODS All patients >50 years of age with radiographic evidence of subclavian LV-GCA diagnosed between 1 January 1999 and 31 December 2008 were identified and compared with those with biopsy-positive C-GCA diagnosed in the same period. RESULTS The study included 120 LV-GCA patients and 212 C-GCA patients. Compared with C-GCA, patients with LV-GCA were younger [68.2 years (s.d. 7.5) vs 75.7 (7.4), P < 0.001] and had longer duration of symptoms at GCA diagnosis (median 3.5 vs 2.2 months, P < 0.001). A history of PMR was more common in LV-GCA patients (26% vs 15%, P = 0.012), but a smaller proportion had cranial symptoms (41% vs 83%, P < 0.001) and vision loss (4% vs 11%, P = 0.035). ACR classification criteria for GCA were satisfied in 39% of LV-GCA patients and 95% of C-GCA patients (P < 0.001). Compared with C-GCA, patients with LV-GCA had more relapses (4.9 vs 3.0/10 person-years, P < 0.001), higher cumulative corticosteroid (CS) doses at 1 year [11.4 g (s.d. 5.9) vs 9.1 (s.d. 3.7), P < 0.001] and required longer treatment (median 4.5 vs 2.2 years, P < 0.001). CONCLUSION Although patients with LV-GCA had a lower rate of vision loss, they had a higher relapse rate and greater CS requirements. The ACR criteria for GCA are inadequate for the classification of patients with LV-GCA.

A Randomized, Double-Blind Trial of Abatacept (CTLA-4Ig) for the Treatment of Takayasu Arteritis

To compare the efficacy of abatacept to that of placebo for the treatment of giant cell arteritis (GCA).

Idiopathic Retroperitoneal Fibrosis: A Retrospective Review of Clinical Presentation, Treatment, and Outcomes

OBJECTIVE To describe the clinical manifestations, laboratory results, imaging findings, and treatments in patients with idiopathic retroperitoneal fibrosis (IRF) seen at Mayo Clinic in Rochester, MN. PATIENTS AND METHODS In this retrospective study, we used International Classification of Diseases, Ninth Revision codes to identify all patients evaluated for IRF between January 1, 1996, and December 31, 2006, at Mayo Clinic in Rochester, MN. Medical records were reviewed, and clinical information was abstracted. Idiopathic retroperitoneal fibrosis was diagnosed on the basis of compatible imaging findings. Patients were followed up until their last visit at Mayo Clinic, death, or December 31, 2008, whichever came first. RESULTS Of the 185 patients identified as having IRF, 113 (61%) were men and 72 (39%) were women. Mean ± SD age at diagnosis was 57.6 ± 11.8 years. Biopsy specimens were obtained in 142 cases (77%). The most common presenting symptoms were back pain (38%) and abdominal pain (40%). Baseline erythrocyte sedimentation rate and/or C-reactive protein levels were elevated in 88 (58%) of the 151 patients tested. The median creatinine level at diagnosis was 1.3 mg/dL (interquartile range, 1.1-2.1 mg/dL). Fifteen patients (8%) were treated with ureteral procedures only, 58 patients (31%) with medications only, and 105 patients (57%) with a combination of medical and surgical therapies. Seven patients (4%) were not treated. Corticosteroids were initiated in 116 patients (63%), and tamoxifen was used in 120 patients (65%). Follow-up was available for 151 patients (82%). Creatinine levels were normal at last visit in 102 (68%) of the 151 patients with follow-up. No patient developed end-stage renal disease. Relapses occurred in 18 (12%) of the 151 patients. Eleven patients died. CONCLUSION In this cohort, outcomes such as end-stage renal disease or death from renal failure were not observed. Relapses may occur, and patients with IRF warrant long-term follow-up.

Tumor necrosis factor inhibitors in patients with Takayasu arteritis: experience from a referral center with long-term followup.

To report a single‐center experience with the use of tumor necrosis factor (TNF) inhibitors in patients with Takayasu arteritis (TA).

Development of Outcome Measures for Large-vessel Vasculitis for Use in Clinical Trials: Opportunities, Challenges, and Research Agenda

Giant cell (GCA) and Takayasu’s arteritis (TAK) are 2 forms of large-vessel vasculitis (LVV) that involve the aorta and its major branches. GCA has a predilection for the cranial branches, while TAK tends to affect the extracranial branches. Both disorders may also cause nonspecific constitutional symptoms. Although some clinical features are more common in one or the other disorder and the ages of initial presentation differ substantially, there is enough clinical and histopathologic overlap between these disorders that some investigators suggest GCA and TAK may be 2 processes within the spectrum of a single disease. There have been few randomized therapeutic trials completed in GCA, and none in TAK. The lack of therapeutic trials in LVV is only partially explained by the rarity of these diseases. It is likely that the lack of well validated outcome measures for LVV and uncertainties regarding trial design contribute to the paucity of trials for these diseases. An initiative to develop a core set of outcome measures for use in clinical trials of LVV was launched by the international OMERACT Vasculitis Working Group in 2009 and subsequently endorsed by the OMERACT community at the OMERACT 10 meeting. Aims of this initiative include: (1) to review the literature and existing data related to outcome assessments in LVV; (2) to obtain the opinion of experts and patients on disease content; and (3) to formulate a research agenda to facilitate a more data-based approach to outcomes development.

Symptomatic Lower Extremity Vasculitis in Giant Cell Arteritis: A Case Series

Objective. To describe the clinical features and outcomes of 19 patients with giant cell arteritis (GCA) and symptomatic lower extremity (LE) vasculitis. Methods. We reviewed medical records of all patients diagnosed with GCA and symptomatic LE involvement between January 1, 1983, and June 30, 2007, for clinical features, laboratory and radiographic findings, and outcomes. Results. From 6212 people evaluated for GCA at our institution between 1983 and 2007, we identified 19 cases of GCA with LE vasculitis, all women. Mean age at GCA diagnosis was 70 years (± standard deviation 7.99). Sixteen patients (84.2%) had LE symptoms preceding the diagnosis of GCA, median interval 3 months (range 1–48). Three patients (15.8%) had GCA prior to developing LE claudication, median interval 16 months (range 9–34). Cranial symptoms were absent in 42.1%. No patient had permanent visual loss. Erythrocyte sedimentation rate (ESR) was elevated in 16 patients (84.2%), with median ESR 42.5 mm/h (range 8–103). Imaging studies revealed stenotic, occlusive, or aneurysmal disease that was frequently bilateral and consistent with vasculitis. The superficial femoral arteries were most commonly affected. Five patients (26.3%) had upper extremity involvement. Hypertension was the most common cardiovascular risk factor. All patients received glucocorticoid therapy, with clinical improvement in 15 patients (79%). Median length of followup was 41 months (range 11–180 mo). Five patients (26.3%) underwent LE revascularization surgery. Two patients required LE amputation and 1 patient underwent toe amputation. Five patients received additional immunosuppressive therapy. Conclusion. Symptomatic LE vasculitis from GCA is rare. Patients typically present with rapidly progressive LE claudication and elevated inflammatory markers, while cranial symptoms may be absent. GCA with LE involvement is associated with significant morbidity; prompt diagnosis and treatment is essential.

Increase in Age at Onset of Giant Cell Arteritis: A Population-based Study

Giant cell arteritis (GCA) is a granulomatous vasculitis of large and medium-sized arteries that occurs in individuals aged ≥50 years.1 A recent study suggested that the age at incidence of GCA may be increasing.2 To address this issue, we studied the trends in mean age at onset of GCA over a 55-year period. A population-based incident cohort of 173 patients with GCA diagnosed between 1 January 1950 and 31 December 1999 has been established using the resources of the Rochester Epidemiology Project.3 4 We extended the cohort to include 34 new cases of GCA diagnosed between 1 January 2000 and 31 December 2004. Patients were included in the study if they fulfilled the 1990 American College of Rheumatology criteria.5 Age- and sex-specific incidence rates were calculated based …

Disease Relapses among Patients with Giant Cell Arteritis: A Prospective, Longitudinal Cohort Study

Objective. To evaluate the frequency, timing, and clinical features of relapses in giant cell arteritis (GCA). Methods. Patients with GCA enrolled in a prospective, multicenter, longitudinal study were included in the analysis. Relapse was defined as either new disease activity after a period of remission or worsening disease activity. Results. The study included 128 subjects: 102 women (80%) and 26 men (20%). Mean ± SD age at diagnosis of GCA was 69.9 ± 8.6 years. Mean followup for the cohort was 21.4 ± 13.9 months. Median (interquartile range) duration of disease at study enrollment was 4.6 months (1.2, 16.8). During followup, 59 relapses were observed in 44 patients (34%). Ten patients (8%) experienced 2 or more relapses. The most common symptoms at relapse were headache (42%) and polymyalgia rheumatica (51%), but ischemic (some transient) manifestations (visual symptoms, tongue or jaw claudication, and/or limb claudication) occurred in 29% of relapses (12% cohort). Forty-three relapses (73%) occurred while patients were taking glucocorticoid therapy at a median (range) prednisone dose of 7.5 (0–35) mg. In 21% of relapses, both erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were normal. Among 69 patients enrolled in the cohort with newly diagnosed disease, 24% experienced a first relapse within 12 months after diagnosis. Conclusion. Among patients with GCA, relapses are common, often occurring during treatment. ESR and CRP are frequently normal at times of clinical relapse, highlighting the need for better biomarkers to assess disease activity in GCA. There remains a need for effective therapeutic alternatives to glucocorticoids in GCA.