18 F-Fluorodeoxyglucose-Positron Emission Tomography As an Imaging Biomarker in a Prospective, Longitudinal Cohort of Patients With Large Vessel Vasculitis.

OBJECTIVE: To assess the clinical value of 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in a prospective cohort of patients with large vessel vasculitis (LVV) and comparator subjects. METHODS: Patients with Takayasu arteritis and giant cell arteritis were studied, along with a comparator group consisting of patients with hyperlipidemia, patients with diseases that mimic LVV, and healthy controls. Participants underwent clinical evaluation and FDG-PET imaging, and patients with LVV underwent serial imaging at 6-month intervals. We calculated sensitivity and specificity of FDG-PET interpretation for distinguishing patients with clinically active LVV from comparator subjects and from patients with disease in clinical remission. A qualitative summary score based on global arterial FDG uptake, the PET Vascular Activity Score (PETVAS), was used to study associations between activity on PET scan and clinical characteristics and to predict relapse. RESULTS: A total of 170 FDG-PET scans were performed in 115 participants (56 patients with LVV and 59 comparator subjects). FDG-PET distinguished patients with clinically active LVV from comparator subjects with a sensitivity of 85% (95% confidence interval [95% CI] 69, 94) and a specificity of 83% (95% CI 71, 91). FDG-PET scans were interpreted as active vasculitis in most patients with LVV in clinical remission (41 of 71 [58%]). Clinical disease activity status, disease duration, body mass index, and glucocorticoid use were independently associated with activity on PET scan. Among patients who underwent PET during clinical remission, future clinical relapse was more common in patients with a high PETVAS than in those with a low PETVAS (55% versus 11%; P = 0.03) over a median follow-up period of 15 months. CONCLUSION: FDG-PET provides information about vascular inflammation that is complementary to, and distinct from, clinical assessment in LVV. FDG-PET scan activity during clinical remission was associated with future clinical relapse.

Muslin-induced intracranial vasculopathic stenosis: a report of two cases.

Muslin wrapping is a commonly utilized alternative technique in the treatment of aneurysms that are not amenable to direct clipping. In this case report, we describe two patients from different institutions who both required aneurysm wrapping with gauze/muslin for aneurysm reinforcement. Both patients developed an inflammatory foreign body response to muslin visible on MRI that resulted in a vasculitic stenosis. The onset of TIAs was at 6 months and 1 month postoperatively, respectively. The stenoses rapidly progressed to near occlusion despite antiplatelet therapy, and in one case, an aggressive corticosteroid regimen. One patient eventually developed leptomeningeal collateral flow that allowed tolerance of the stenosis, while the other patient required microsurgical bypass. These cases reports are the first to our knowledge that describe the adverse effects of muslin wrapping without adhesive reinforcement, as well as one of few reports to include follow-up angiographic imaging.

HIV-associated intracranial aneurysmal vasculopathy in adults.

Diffuse fusiform intracranial aneurysms have been reported in children with human immunodeficiency virus (HIV) for over 2 decades, but have only recently been reported in adults with HIV. Although these aneurysms have important clinical implications, their etiology and optimal therapy are unknown. We present a systematic review of diffuse intracranial fusiform aneurysmal vasculopathy in patients who are HIV-positive. We conducted a comprehensive literature search for relevant case reports and reviews published before February 2009. Patients were included if they had HIV infection and radiographic imaging consistent with fusiform aneurysmal vasculopathy. We identify 11 published adult cases of intracranial fusiform aneurysmal vasculopathy and describe 1 unpublished case from our own institution. Available data regarding clinical presentation, characteristic imaging findings, and treatment of this complex syndrome are reviewed. Adults with HIV-associated intracranial aneurysmal vasculopathy typically are significantly immunosuppressed and present with gross neurologic dysfunction. Characteristic radiographic findings include diffuse cerebral fusiform aneurysms with hemorrhage or infarct. Treatment of any active infection followed by the initiation of antiretroviral therapy and corticosteroids may be a reasonable approach in this complex syndrome.

Lower extremity ulcers in connective tissue disease.

Lower extremity ulcers are a late complication of connective tissue diseases and occur more commonly in patients with these diseases than in the general population. Although these lesions have historically been attributed to vasculitis, it is now recognized that inflammatory vessel injury accounts for fewer than 20% of ulcers in connective tissue disease. The pathogenesis of these lesions is complex, and often several processes act synergistically to initiate and perpetuate tissue injury. We review the evidence for antiphospholipid antibodies and prothrombotic states contributing to a vasculopathy in patients with connective tissue disease, precipitating ulceration and impairing healing.

The rheumatic causes of elbow instability.

Rheumatoid arthritis is the most common cause of elbow instability, but other causes include other erosive arthritides and noninflammatory diseases. Surgical consultation should be obtained for refractory pain or disability, or when physical examination or imaging reveals instability, erosions, or impending pathologic fracture. Medical management for rheumatoid arthritis includes early treatment and combination therapy, including biologic response modifiers. Current recommendations for rheumatic medicines, including perioperative use, are discussed.

Treatment of fibromyalgia with formula acupuncture: investigation of needle placement, needle stimulation, and treatment frequency.

OBJECTIVES: The objective of this study was to investigate whether typical acupuncture methods such as needle placement, needle stimulation, and treatment frequency were important factors in fibromyalgia symptom improvement. DESIGN/SETTINGS/SUBJECTS: A single-site, single-blind, randomized trial of 114 participants diagnosed with fibromyalgia for at least 1 year was performed. INTERVENTION: Participants were randomized to one of four treatment groups: (1) T/S needles placed in traditional sites with manual needle stimulation (n = 29): (2) T/0 traditional needle location without stimulation (n = 30); (3) N/S needles inserted in nontraditional locations that were not thought to be acupuncture sites, with stimulation (n = 28); and (4) N/0 nontraditional needle location without stimulation (n = 2 7). All groups received treatment once weekly, followed by twice weekly, and finally three times weekly, for a total of 18 treatments. Each increase in frequency was separated by a 2-week washout period. OUTCOME MEASURES: Pain was assessed by a numerical rating scale, fatigue by the Multi-dimensional Fatigue Inventory, and physical function by the Short Form-36. RESULTS: Overall pain improvement was noted with 25%-35% of subjects having a clinically significant decrease in pain; however this was not dependent upon "correct" needle stimulation (t = 1.03; p = 0.307) or location (t = 0.76; p = 0.450). An overall dose effect of treatment was observed, with three sessions weekly providing more analgesia than sessions once weekly (t = 2.10; p = 0.039). Among treatment responders, improvements in pain, fatigue, and physical function were highly codependent (all p < or = 0.002). CONCLUSIONS: Although needle insertion led to analgesia and improvement in other somatic symptoms, correct needle location and stimulation were not crucial.

Leukocytoclastic vasculitis associated with tumor necrosis factor-alpha blocking agents.

OBJECTIVE: To describe the clinical features of leukocytoclastic vasculitis (LCV) associated with the use of tumor necrosis factor-alpha (TNF-alpha) blockers. METHODS: The Adverse Events Reporting System (AERS) of the US Food and Drug Administration (FDA) was queried for reports of patients who developed LCV during or after starting etanercept or infliximab from date of approval of each agent through September 6, 2002. RESULTS: Thirty-five cases of LCV were identified, 20 following etanercept administration and 15 following infliximab administration. Seventeen of the 35 (48.5%) were biopsy-proven cases and the others had skin lesions that were clinically typical for LCV. Twenty-two of 35 (62.8%) patients had complete or marked improvement of skin lesions upon stopping the TNF-alpha blocker. Three patients who had received etanercept had continuing lesions despite discontinuation of the drug; one of these patients improved when switched to infliximab. One patient who received infliximab was reported to have continuing lesions despite discontinuation of the drug and treatment with prednisone and antihistamines. Six patients experienced a positive rechallenge (recurrence of LCV on restarting therapy with a TNF-alpha blocker) and 3 patients a negative rechallenge phenomenon. LCV lesions improved in patients despite continuing use of concomitant medications reportedly associated with LCV. CONCLUSION: Therapy with TNF-alpha blocking agents may be associated with the development of LCV. Skin lesions improved on discontinuation of anti-TNF-alpha therapy in most patients. Other causes of LCV should be excluded, and evaluation for systemic involvement with appropriate investigations is recommended.

Knee pain and radiographic osteoarthritis interact in the prediction of levels of self-reported disability.

OBJECTIVE: To determine predictors of disability depending on whether joint deformity and pain reporting exist independently or concurrently. METHODS: Subjects were 154 volunteers for an osteoarthritis screening examination. Eligible subjects completed questionnaires for physical function, pain, and depressive symptoms; underwent evoked pain testing for tenderness assessment; and had anteroposterior and lateral radiographs taken of both knees. Two blinded rheumatologists scored the images using Kellgren-Lawrence criteria to determine presence of deformity. RESULTS: Subjects were divided into 3 subgroups based on radiographic evidence of deformity and self-reported pain. Disability was greatest when pain and deformity occurred together (F[2,151] = 18.8, P < 0.0001). Self-reported disability in the absence of deformity was predicted by body mass index, pain threshold, and anxiety symptoms; disability was predicted by the number of osteophytes and depressive symptoms when pain and deformity occurred together. CONCLUSION: Self-reported disability in osteoarthritis of the knee is greatest with concurrent pain and joint deformity. When pain and deformity do not cooccur, disability appears to be related to separate factors, including anxiety and pain threshold (e.g., tenderness).

Subgrouping of fibromyalgia patients on the basis of pressure-pain thresholds and psychological factors.

OBJECTIVE: Although the American College of Rheumatology (ACR) criteria for fibromyalgia are used to identify individuals with both widespread pain and tenderness, individuals who meet these criteria are not a homogeneous group. Patients differ in their accompanying clinical symptoms, as well as in the relative contributions of biologic, psychological, and cognitive factors to their symptom expression. Therefore, it seems useful to identify subsets of fibromyalgia patients on the basis of which of these factors are present. Previous attempts at identifying subsets have been based solely on psychological and cognitive features. In this study, we attempt to identify patient subsets by incorporating these features as well as the degree of hyperalgesia/tenderness, which is a key neurobiologic feature of this illness. METHODS: Ninety-seven individuals meeting the ACR criteria for fibromyalgia finished the same battery of self-report and evoked-pain testing. Analyzed variables were obtained from several domains, consisting of 1) mood (evaluated by the Center for Epidemiologic Studies Depression Scale [for depression] and the State-Trait Personality Inventory [for symptoms of trait-related anxiety]), 2) cognition (by the catastrophizing and control of pain subscales of the Coping Strategies Questionnaire), and 3) hyperalgesia/tenderness (by dolorimetry and random pressure-pain applied at suprathreshold values). Cluster analytic procedures were used to distinguish subgroups of fibromyalgia patients based on these domains. RESULTS: Three clusters best fit the data. Multivariate analysis of variance (ANOVA) confirmed that each variable was differentiated by the cluster solution (Wilks' lambda [degrees of freedom 6,89] = 0.123, P < 0.0001), with univariate ANOVAs also indicating significant differences (all P < 0.05). One subgroup of patients (n = 50) was characterized by moderate mood ratings, moderate levels of catastrophizing and perceived control over pain, and low levels of tenderness. A second subgroup (n = 31) displayed significantly elevated values on the mood assessments, the highest values on the catastrophizing subscale, the lowest values for perceived control over pain, and high levels of tenderness. The third group (n = 16) had normal mood ratings, very low levels of catastrophizing, and the highest level of perceived control over pain, but these subjects showed extreme tenderness on evoked-pain testing. CONCLUSION: These data help support the clinical impression that there are distinct subgroups of patients with fibromyalgia. There appears to be a group of fibromyalgia patients who exhibit extreme tenderness but lack any associated psychological/cognitive factors, an intermediate group who display moderate tenderness and have normal mood, and a group in whom mood and cognitive factors may be significantly influencing the symptom report.

Isolated superior mesenteric artery vasculitis with response to glucocorticoids.

This report describes a patient with abdominal pain at presentation, which on angiography was found to be caused by vasculitis limited to the superior mesenteric artery. He was treated with oral glucocorticoids after an initial 5-day course of pulse therapy and obtained excellent relief of symptoms. Steroids were tapered over 8 months. Repeat angiography revealed complete resolution of the vasculitis with a residual aneurysm of a branch of the left gastric artery, which was resected to avoid the risk of rupture. Histologic analysis revealed thickened intima with myxoid degeneration and no evidence of active vasculitis. Extensive laboratory and clinical investigations did not reveal an underlying connective tissue disorder to account for the gastrointestinal vasculitis. This report of an angiographically defined regional vasculitis involving the superior mesenteric artery with complete clinical as well as radiologic resolution on treatment with glucocorticoids alone emphasizes the need to differentiate between an isolated or regional vasculitis, which has an excellent prognosis, to avoid subjecting the patient to cytotoxic therapy with significant toxicities.

A General Synthesis of 4-Substituted 6-(2-Imidazolinylamino)-5,8-dimethylquinolines.

A general synthesis of 4-substituted 6-(2-imidazolinylamino)-5,8-dimethylquinolines 1 has been developed. All new compounds were synthesized from a common intermediate, 5,8-dimethyl-6-nitro-4-quinolone 3, the structure of which was confirmed by X-ray crystallography. This methodology involved the conversion of 3 into either a 4-chloro- or 4-bromoquinoline followed by the introduction of various 4-substituents late in the synthetic sequence. Substituents introduced in this way include alkyl (18a), alkoxy (12a, 12b), halo (9, 12c, 16), cyano (18b), thioalkyl (12d), acetamido (14), carboxamido (19), and hydroxy (10). This work illustrates the utility of 4-haloquinoline intermediates in the general synthesis of 4-substituted quinolines.