Lindsay Lally

Brief Report: A Prospective Open-Label Phase IIa Trial of Tocilizumab in the Treatment of Polymyalgia Rheumatica.

Interleukin‐6 (IL‐6) is a pivotal cytokine in the pathogenesis of polymyalgia rheumatica (PMR), yet the efficacy of IL‐6 blockade with tocilizumab (TCZ) for the treatment of PMR is unknown. The aim of this study was to assess the efficacy and safety of TCZ in newly diagnosed PMR.

A Prospective Open Label Phase IIa Trial of Tocilizumab In the Treatment of Polymyalgia Rheumatica

Interleukin‐6 (IL‐6) is a pivotal cytokine in the pathogenesis of polymyalgia rheumatica (PMR), yet the efficacy of IL‐6 blockade with tocilizumab (TCZ) for the treatment of PMR is unknown. The aim of this study was to assess the efficacy and safety of TCZ in newly diagnosed PMR.

Vasculitis in Antiphospholipid Syndrome

The major manifestations of antiphospholipid syndrome (APS) are caused by thrombosis within the venous or arterial vasculature, whereas the vascular lesions in systemic vasculitis result from an inflammatory infiltrate in the vessel wall. There is an association between vascular thrombosis and inflammation, however, as vasculitis can occur in APS and thromboembolic complications are seen in systemic vasculitis. Although differentiating between vasculitis and antiphospholipid-associated thrombosis can be difficult, it may be crucial to do so given the different therapeutic implications for immunosuppression or anticoagulation. This article explores the relationship between thrombosis and inflammation as it relates to APS and systemic vasculitis.

Current Therapies for ANCA-Associated Vasculitis

The ANCA-associated vasculitides, granulomatosis with polyangiitis (GPA, formerly Wegeners), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss), are a group of multisystem autoimmune diseases characterized by necrotizing small- to medium-vessel vasculitis and the presence of anti-neutrophil cytoplasmic antibodies. Current therapeutic strategies consist of glucocorticoids in conjunction with either conventional or biologic agents for both induction of remission and remission maintenance. Treatment goals include reducing toxicity of induction therapy, preventing disease relapse, and limiting overall accrual of both disease-related damage and treatment-related morbidity. Future research directions include investigation of the optimal duration and frequency of maintenance therapy as well as development of targeted therapeutic agents, which is enhanced by emerging insights into disease pathogenesis.

Increased rho kinase activity in temporal artery biopsies from patients with giant cell arteritis

OBJECTIVE Aberrant rho kinase (ROCK) activity is implicated in the pathogenesis of several vascular diseases and is associated with Th17 differentiation. Th17 immune response is recognized in the pathogenesis of GCA. The aim of this study was to assess ROCK activity in GCA. METHODS All patients who underwent temporal artery biopsy (TAB) at a tertiary care centre over 5 years were identified and charts reviewed. Subjects were categorized into three groups: TAB-positive GCA, TAB-negative GCA and age- and sex-matched controls. TABs were stained for phosphorylated ezrin/radixin/moesin (pERM), a surrogate of ROCK activity, and reviewed by a pathologist blinded to clinical status. Three areas were scored for staining intensity on a scale of 0-2, with a maximum possible score of 6. RESULTS Nineteen subjects with TAB-positive GCA, 17 with TAB-negative GCA and 18 controls were analysed. Compared with controls, GCA subjects with either positive or negative TABs had significantly higher pERM intensity scores (P = 0.0109). Adjusting for diabetes, hypertension, prednisone and statin use, GCA subjects still had higher pERM scores [odds ratio 7.3 (95% CI 1.9, 25.9), P = 0.0046]. The high pERM score had a sensitivity of 90% and a negative predictive value of 91% for the diagnosis of GCA in those with a negative TAB, compared with 51% sensitivity for histopathology alone. CONCLUSION Subjects with GCA had more intense pERM staining in TAB specimens compared with age- and sex-matched controls, regardless of whether TAB was positive or negative by routine histopathology, suggesting increased ROCK activity in GCA. The ROCK pathway warrants further investigation in GCA, as it may have diagnostic significance in enhancing the sensitivity of TAB.

B-cell-targeted therapy in systemic vasculitis.

Purpose of reviewThe present review discusses the evidence supporting the use of B-cell-targeted therapy in the treatment of various forms of systemic vasculitis with a focus on the use of rituximab (RTX), in the antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV). Recent findingsLong-term follow-up of the two studies establishing the efficacy of a RTX-based induction regimen for severe AAV have demonstrated noninferiority of a single course of RTX compared with conventional therapy for remission maintenance. In addition, these observations highlight an association between relapse and B-cell reconstitution in patients treated with RTX. The maintenance of remission using rituximab in systemic ANCA-associated vasculitis trial compared a regimen of RTX infusions every 6 months to azathioprine for remission maintenance and concluded that serial RTX lead to higher rates of sustained remission.RTX is also an established therapy for cryoglobulinemic vasculitis associated with hepatitis C viral (HCV) infection. Recently published data support the long-term efficacy and safety of RTX for cryoglobulinemic vasculitis. SummaryB-cell depletion with RTX is an established therapy for both remission induction and maintenance in severe AAV and in HCV-related cryoglobulinemic vasculitis. There are limited data to support use of B-cell-targeted therapy in refractory cases of other forms of systemic vasculitis such as eosinophilic granulomatosis with polyangiitis and Takayasus arteritis.

Current landscape of antineutrophil cytoplasmic antibody-associated vasculitis: classification, diagnosis, and treatment.

This article provides an update on the diagnosis and management of the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides, granulomatosis with polyangiitis (formerly Wegener), microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss). Focus is on new schemes of classification and the importance of ANCAs in the diagnosis and prognosis of these systemic vasculitides. Current therapeutic strategies consisting of glucocorticoids in conjunction with conventional or biologic agents for both induction of remission and remission maintenance are outlined. Future research directions include investigation of the optimal duration and frequency of maintenance therapy and development of targeted therapeutic agents.

Effectiveness of rituximab for the otolaryngologic manifestations of granulomatosis with polyangiitis (Wegener's).

Ear, nose, and throat (ENT) involvement is the most prevalent manifestation of granulomatosis with polyangiitis (Wegeners) (GPA) and correlates with permanent damage and decreased quality of life. Although prior studies have evaluated the efficacy of rituximab (RTX) for granulomatous features of GPA, none have evaluated its efficacy solely for ENT manifestations. We compared the effectiveness of RTX to other therapies for the ENT manifestations of GPA in a large, well‐characterized cohort.

Biomarkers in ANCA-Associated Vasculitis

Despite recent advances in the treatment of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV), relapse remains common and patients often experience a variable clinical course after initial treatment. New biomarkers are needed to aid the management of these complex diseases. Discoveries regarding the pathogenesis of AAV, from the importance both of activated B and T cells and the alternative complement pathway to genomic data, may lay the groundwork for identification of novel biomarkers.

Lepromatous Leprosy Mimicking Systemic Lupus Erythematosus

Keywords leprosy.anthiphospholipidantibodyCase PresentationA 29-year-old Brazilian woman was referred for manage-ment of systemic lupus erythematosus (SLE) withantiphospholipid antibodies (aPL). Her symptoms were1 year of intermittent fever and diffuse, tender, erythe-matosus, and nodular rash that began during her firstpregnancy. She was treated with short course of low-dose corticosteroids, with resolution; however, she suf-fered an embryonic loss at 7 weeks. Six months prior toadmission, she had recurrence of the nodular rash withnew onset arthralgia; a skin biopsy showed panniculitis.Tests done at that time showed lupus anticoagulant(LA), anticardiolipin antibody (aCL) IgM >150 U (nor-mal 0–7 U), anti-β