Publications by authors named "Lindsay Lally"

14 Publications

  • Page 1 of 1

Identification of susceptibility loci for Takayasu arteritis through a large multi-ancestral genome-wide association study.

Am J Hum Genet 2021 01 11;108(1):84-99. Epub 2020 Dec 11.

Department of Internal Medicine, Division of Rheumatology, Ankara Numune Training and Research Hospital, Ankara 06100, Turkey; Department of Internal Medicine, Division of Rheumatology, Ankara University, Faculty of Medicine, Ankara 06100, Turkey.

Takayasu arteritis is a rare inflammatory disease of large arteries. We performed a genetic study in Takayasu arteritis comprising 6,670 individuals (1,226 affected individuals) from five different populations. We discovered HLA risk factors and four non-HLA susceptibility loci in VPS8, SVEP1, CFL2, and chr13q21 and reinforced IL12B, PTK2B, and chr21q22 as robust susceptibility loci shared across ancestries. Functional analysis proposed plausible underlying disease mechanisms and pinpointed ETS2 as a potential causal gene for chr21q22 association. We also identified >60 candidate loci with suggestive association (p < 5 × 10) and devised a genetic risk score for Takayasu arteritis. Takayasu arteritis was compared to hundreds of other traits, revealing the closest genetic relatedness to inflammatory bowel disease. Epigenetic patterns within risk loci suggest roles for monocytes and B cells in Takayasu arteritis. This work enhances understanding of the genetic basis and pathophysiology of Takayasu arteritis and provides clues for potential new therapeutic targets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajhg.2020.11.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820633PMC
January 2021

Localized Granulomatous with Polyangiitis (GPA): Varied Clinical Presentations and Update on Treatment.

Curr Allergy Asthma Rep 2020 07 9;20(10):56. Epub 2020 Jul 9.

Division of Rheumatology, Department of Medicine, Weill Cornell Medicine, Scleroderma, Vasculitis and Myositis Center, Hospital for Special Surgery, 525 East 71st Street, 7th Floor, New York, NY, 10021, USA.

Purpose Of Review: Granulomatosis with polyangiitis is a primary systemic vasculitis commonly described with the typical triad of upper airway, lung, and kidney involvement. Upper and lower airway involvement is characteristic in patients with granulomatosis with polyangiitis and can sometimes represent the initial or in some instances the sole manifestation. The objective of this review is to summarize the various clinical manifestations of localized disease in GPA and their treatment.

Recent Findings: Sinonasal disease is seen in up to 90% of patients. Otologic and ocular involvement is also commonly seen. Laryngeal and tracheal disease although less common is associated with significant morbidity and can be therapeutically challenging. Clinicians need to be aware of these localized GPA manifestations as they may be presenting disease features in the absence of other systemic findings. Treatment of localized GPA involves both immunosuppressive and surgical interventions for specific manifestations. Collaboration between specialists including rheumatologists, otolaryngologists, and ophthalmologists is often crucial to ensure optimal outcomes for patients. This is a narrative review that provides a comprehensive overview of localized granulomatosis with polyangiitis and current treatment options.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11882-020-00953-1DOI Listing
July 2020

Management of difficult polymyalgia rheumatica and giant cell arteritis: Updates for clinical practice.

Best Pract Res Clin Rheumatol 2018 12 23;32(6):803-812. Epub 2019 May 23.

Hospital for Special Surgery, United States. Electronic address:

Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) represent a family of systemic inflammatory diseases occurring in adults aged 50 years and above. Clinical presentation of PMR/GCA can be variable, making diagnosis at times challenging. There has been an increased appreciation of the role of various large-vessel imaging modalities to help confirm a diagnosis of GCA. Systemic corticosteroids (CS) remain the mainstay of treatment for both PMR and GCA, yet both relapses and CS-related side effects are common. Recent research has demonstrated efficacy of certain biologic agents in these diseases, with particular emphasis on the role of interleukin-6 (IL-6) blockade in GCA. This chapter discusses the latest updates on the diagnosis and treatment of PMR/GCA, with an emphasis on clinical care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.berh.2019.04.006DOI Listing
December 2018

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

Arthritis Rheumatol 2016 10;68(10):2550-4

Hospital for Special Surgery, New York, New York.

Objective: 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.

Methods: In a single-center open-label study, patients with newly diagnosed PMR who had been treated with glucocorticoids (GCs) for <1 month were treated monthly with intravenous (IV) TCZ 8 mg/kg for 1 year, with a rapid tapering of GCs according to standardized protocol. The primary end point was the proportion of patients in relapse-free remission without GC treatment at 6 months. Secondary outcome measures included duration of GC use and cumulative GC dose. Patients were followed up for 15 months.

Results: Ten patients were enrolled in the study. One patient withdrew after 2 months, leaving 9 patients in whom the primary end point was assessed. The primary end point of relapse-free remission without GC treatment at 6 months was achieved by all 9 of these patients. All patients who received TCZ treatment were able to discontinue GCs within 4 months of study entry. The cumulative mean ± SD prednisone dose was 1,085 ± 301 mg and the total duration of GC exposure was 3.9 ± 0.9 months. Remission persisted without relapse, in all 9 patients, throughout the entire 15-month study.

Conclusion: Our findings suggest that TCZ may be an effective, safe, and well-tolerated treatment for newly diagnosed patients with PMR, with a robust steroid-sparing effect.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/art.39740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837044PMC
October 2016

B-cell-targeted therapy in systemic vasculitis.

Curr Opin Rheumatol 2016 Jan;28(1):15-20

Hospital for Special Surgery, New York, New York, USA.

Purpose Of Review: The 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 Findings: Long-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.

Summary: B-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 Takayasu's arteritis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/BOR.0000000000000235DOI Listing
January 2016

Pregnancy Does Not Adversely Affect Postoperative Pain and Function in Women With Total Hip Arthroplasty.

J Clin Rheumatol 2015 Sep;21(6):323-5

Division of Rheumatology Department of Medicine Hospital for Special Surgery New York, NY

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/RHU.0000000000000286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4552051PMC
September 2015

Pulmonary vasculitis.

Rheum Dis Clin North Am 2015 May 27;41(2):315-31. Epub 2015 Feb 27.

Division of Rheumatology, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA.

Pulmonary vasculitis encompasses inflammation in the pulmonary vasculature with involved vessels varying in caliber from large elastic arteries to capillaries. Small pulmonary capillaries are the vessels most commonly involved in vasculitis affecting the lung. The antineutrophil cytoplasmic antibody-associated vasculitides, which include granulomatosis with polyangiitis (formerly Wegener granulomatosis), microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome), are the small vessel vasculitides in which pulmonary vasculitis is most frequently observed and are the major focus of this review. Vasculitic involvement of the large pulmonary vessels as may occur in Behçet syndrome and Takayasu arteritis is also discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rdc.2015.01.004DOI Listing
May 2015

Vasculitis in antiphospholipid syndrome.

Rheum Dis Clin North Am 2015 ;41(1):109-23, ix

Division of Rheumatology, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rdc.2014.09.009DOI Listing
July 2015

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

Rheum Dis Clin North Am 2015 ;41(1):1-19, vii

Division of Rheumatology, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rdc.2014.09.003DOI Listing
July 2015

Current therapies for ANCA-associated vasculitis.

Annu Rev Med 2015 17;66:227-40. Epub 2014 Oct 17.

Department of Medicine/Division of Rheumatology, Hospital for Special Surgery, New York, NY 10021; email: ,

The ANCA-associated vasculitides, granulomatosis with polyangiitis (GPA, formerly Wegener's), 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-med-011514-023051DOI Listing
September 2015

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

Arthritis Care Res (Hoboken) 2014 Sep;66(9):1403-9

Objective: Ear, nose, and throat (ENT) involvement is the most prevalent manifestation of granulomatosis with polyangiitis (Wegener's) (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.

Methods: We performed a retrospective analysis of 975 visits from 99 GPA patients seen at a tertiary care ENT practice between 2003 and 2013. At each visit, subjects had a complete ENT examination, with ENT activity assessed by a single expert otolaryngologist. ENT disease activity during the observational period in subjects receiving RTX was compared to subjects receiving all other therapy.

Results: In total, 48 subjects had never received RTX and 51 received RTX at least once. There was no active ENT disease during 92.4% of the observational period (days) for subjects receiving RTX, compared with 53.7% of the observational period for subjects not receiving RTX (odds ratio 11.0 [95% confidence interval 5.5–22.0], P < 0.0001). Subjects receiving RTX, compared with those receiving methotrexate, azathioprine, cyclophosphamide, or trimethoprim-sulfamethoxazole, were significantly more likely to have no active ENT disease (P < 0.0001 for each comparison).

Conclusion: RTX is an effective treatment for ENT manifestations of GPA. Subjects treated with RTX were significantly less likely to have active ENT disease compared with those not receiving RTX. Patients being treated with RTX were 11 times less likely to have active ENT disease than patients being treated with other therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acr.22311DOI Listing
September 2014

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

Rheumatology (Oxford) 2015 Mar 10;54(3):554-8. Epub 2014 Sep 10.

Department of Rheumatology, Hospital for Special Surgery, Department of Medicine, Weill-Cornell Medical College, Autoimmunity and Inflammation Program, Hospital for Special Surgery and Department of Clinical Pathology and Laboratory Medicine, Weill-Cornell Medical College, New York, NY, USA. Department of Rheumatology, Hospital for Special Surgery, Department of Medicine, Weill-Cornell Medical College, Autoimmunity and Inflammation Program, Hospital for Special Surgery and Department of Clinical Pathology and Laboratory Medicine, Weill-Cornell Medical College, New York, NY, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rheumatology/keu364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334685PMC
March 2015

Biomarkers in ANCA-associated vasculitis.

Curr Rheumatol Rep 2013 Oct;15(10):363

Division of Rheumatology, Hospital for Special Surgery, 535 E. 70th Street, New York, NY 10021, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11926-013-0363-xDOI Listing
October 2013
-->