Distribution of arterial lesions in Takayasu's arteritis and giant cell arteritis.

OBJECTIVES: To compare patterns of arteriographic lesions of the aorta and primary branches in patients with Takayasu's arteritis (TAK) and giant cell arteritis (GCA). METHODS: Patients were selected from two North American cohorts of TAK and GCA. The frequency of arteriographic lesions was calculated for 15 large arteries. Cluster analysis was used to derive patterns of arterial disease in TAK versus GCA and in patients categorised by age at disease onset. Using latent class analysis, computer derived classification models based upon patterns of arterial disease were compared with traditional classification. RESULTS: Arteriographic lesions were identified in 145 patients with TAK and 62 patients with GCA. Cluster analysis demonstrated that arterial involvement was contiguous in the aorta and usually symmetric in paired branch vessels for TAK and GCA. There was significantly more left carotid (p=0.03) and mesenteric (p=0.02) artery disease in TAK and more left and right axillary (p<0.01) artery disease in GCA. Subclavian disease clustered asymmetrically in TAK and in patients ≤55 years at disease onset and clustered symmetrically in GCA and patients >55 years at disease onset. Computer derived classification models distinguished TAK from GCA in two subgroups, defining 26% and 18% of the study sample; however, 56% of patients were classified into a subgroup that did not strongly differentiate between TAK and GCA. CONCLUSIONS: Strong similarities and subtle differences in the distribution of arterial disease were observed between TAK and GCA. These findings suggest that TAK and GCA may exist on a spectrum within the same disease.

Takayasu arteritis and giant cell arteritis: a spectrum within the same disease?

Giant cell arteritis (GCA) and Takayasu arteritis (TAK) have been considered distinct disorders based on their clinical features, age of onset, and ethnic distribution. However, on closer examination, these disorders appear more similar than different. The histopathology of arterial lesions in these diseases may be indistinguishable. Imaging studies have revealed large vessel inflammation in at least 60% of patients with GCA. We questioned whether the distinctions between these diseases might in part be an artifact due to bias in gathering historical and physical data. We postulated that signs and symptoms of GCA and polymyalgia rheumatica occur in patients with TAK but have been under-reported as a result of this bias.We performed a retrospective review of 75 patients with TAK and 69 patients with GCA (per American College of Rheumatology criteria). Signs and symptoms attributable to disease within the year before and following diagnosis, treatment and interventional outcomes, and mortality were recorded using a standardized database. All cases were evaluated by a single physician, using identical history and physical examination forms for patients with both diseases.Patients were predominantly female (TAK 91%, GCA 82%) and white (TAK 88%, GCA 95%). New headache was a presenting symptom in 52% of TAK and in 70% of GCA patients. All TAK patients underwent vascular imaging studies and were demonstrated to have large vessel abnormalities. However, only a subset of patients with GCA (43/69, 62%) was similarly studied. Among this group, 73% of GCA patients had at least 1 arterial lesion identified. In both TAK and GCA, the most common sites of involvement were the aorta (TAK 77%, GCA 65%) and subclavian (TAK 65%, GCA 37%) arteries. Compared to patients with TAK, patients with GCA had a greater prevalence of jaw claudication (GCA 33%, TAK 5%), blurred vision (GCA 29%, TAK 8%), diplopia (GCA 9%, TAK 0%), and blindness (GCA 14%, TAK 0%).Symptoms, signs, and imaging abnormalities that are characteristic of GCA or TAK are often present, albeit in differing frequencies, in both disorders. These findings lend support to the hypothesis that these diseases may not be distinct entities, but represent skewed phenotypes within the spectrum of a single disorder. Differences in frequencies of manifestations may reflect a significant bias in how data are gathered for patients with each disease, as well as the influence of vascular and immunologic senescence.

Limited utility of rapamycin in severe, refractory Wegener's granulomatosis.

OBJECTIVE: We report our experience using rapamycin in patients with Wegener's granulomatosis (WG) who failed to achieve remission with conventional treatment. METHODS: Eight patients received rapamycin for severe, refractory WG. Clinical outcomes were reviewed retrospectively. RESULTS: Four patients treated with rapamycin sustained remissions of at least 6 months' duration while receiving prednisone

Substitution of methotrexate for cyclophosphamide in Wegener granulomatosis: a 12-year single-practice experience.

We conducted a retrospective review to assess outcomes of therapy in patients with newly diagnosed Wegener granulomatosis (WG) using methotrexate (MTX) for mild to moderate disease and short-term treatment with cyclophosphamide (CYC) followed by MTX for severe disease. Patients with WG were included if their initial plan of therapy and subsequent care were directly supervised by the Cleveland Clinic Center for Vasculitis Care and Research. Severe disease (immediately life-threatening or involving critical organs) was initially treated with CYC and glucocorticoids. Mild to moderate disease was initially treated with MTX and glucocorticoids if serum creatinine was less than 2 mg/dL. Following initial improvement of severe disease, treatment was changed to MTX if serum creatinine was originally less than 2 mg/dL or had diminished to less than 2 mg/dL. Disease activity was determined at each visit and later converted to a Birmingham Vasculitis Activity Score, as modified for Wegener granulomatosis (BVAS/WG). Laboratory monitoring of disease and treatment toxicity was initially weekly and never less than monthly.Eighty-two (32%) of 253 patients with WG referred to the Center for Vasculitis Care and Research met eligibility criteria. Ineligible patients did not have new-onset disease or were not able to be followed principally in our center. Seventy percent of patients (57/82) initially had severe disease and received a short course of CYC for remission induction. In over half of these patients, illness was judged to be severe because of pulmonary hemorrhage; rapidly progressive glomerulonephritis, including need for dialysis; or neurologic abnormalities. All patients improved: remission was achieved in 50% (41/82) of patients within 6 months and in 72% (59/82) within 12 months. Sustained remission (BVAS/WG = 0 for at least 6 consecutive months) was ultimately achieved in 78% (64/82) of patients. Among the 75 (91%) patients who achieved remission of any duration, 45% relapsed within 1 year and 66% relapsed within 2 years following remission. Eighty-two percent of relapsed patients achieved subsequent remissions after additional treatment. About three-quarters of relapses were mild and promptly responded to treatment. Seventeen percent of patients developed serious infections. CYC-associated cystitis or bladder cancer did not occur in any patients. At least 1 form of permanent morbidity from WG alone was noted in 74.0% of patients. Three patients (3.7%) died over a median follow-up period of 4.5 years; no deaths were due to active disease. Although treatment was primarily directed toward achieving clinical improvement and not calculated to achieve marked lymphopenia, patients in whom treatment produced lymphocyte counts of 1000/mm was associated with a hazard ratio for relapse of 3.0, although the latter difference was not statistically significant. In patients with WG, a strategy that limits or avoids CYC therapy produced a frequency of remission comparable to that achieved with conventional CYC protocols, excellent survival, and avoidance of long-term CYC toxicity. However, relapses were common and incremental permanent morbidity occurred in most patients. While not a goal of therapy, when treatment produced marked lymphopenia, prolonged remissions were more likely.

Limitations of therapy and a guarded prognosis in an American cohort of Takayasu arteritis patients.

OBJECTIVE: To describe the clinical, laboratory, and radiographic manifestations of Takayasu arteritis (TA) in a cohort from the US, evaluate the response to interventions, remission and relapse rates, and disease progression, and compare these observations with those from other cohorts in the US, Japan, India, Italy, and Mexico. METHODS: Seventy-five patients were retrospectively studied using a uniform database that included clinical, laboratory, and imaging data. Vascular imaging studies were performed at least yearly to monitor disease progression. RESULTS: Common manifestations at disease onset included loss or asymmetry of pulses (57%), limb blood pressure discrepancy (53%), and bruits (53%). Eleven percent of patients were asymptomatic prior to disease diagnosis. Initial angiographic studies showed aortic abnormalities in 79% of patients and frequent involvement of the subclavian (65%) and carotid (43%) arteries.Ninety-three percent of longitudinally followed patients attained disease remission of any duration, but only 28% sustained remission of at least 6 months' duration after prednisone was tapered to <10 mg daily. Both angioplasty and vascular surgery were initially successful, but recurrent stenosis occurred in 78% of angioplasty and 36% of bypass/reconstruction procedures. More than two-thirds of patients had difficulty performing routine daily activities and approximately one-fourth of all patients were unable to work. Our cohort was similar to the National Institutes of Health, Italian, Japanese, and Mexican cohorts in terms of the predominance of female subjects and disease manifestations, but differed from the Indian cohort in that the latter group had a higher frequency of male subjects, abdominal aorta and renal artery involvement, and hypertension. CONCLUSION: Although improvement of symptoms in TA usually follows glucocorticoid therapy, relapses usually occur with dosage reduction. Attempts to restore vascular patency are often initially successful, but restenosis occurs frequently. Chronic morbidity and disability occur in most patients with TA in the US.