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1.
Chest ; 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33667492

RESUMO

BACKGROUND: Pleural and pericardial involvements are well recognized in eosinophilic granulomatosis with polyangiitis (EGPA) but considered rare manifestations of the other forms of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). RESEARCH QUESTION: What are the frequency and clinical characteristics of pleuritis and pericarditis in AAV? STUDY DESIGN: and Methods: Using an institutional database of 1,830 patients with AAV, we analyzed clinical notes and diagnosis codes for key words related to pleuritis and pericarditis. Chart review to confirm these findings was performed. RESULTS: Eighty-eight of 1,058 patients (8.3%) with granulomatosis with polyangiitis (GPA), 27 of 267 (10.1%) with microscopic polyangiitis (MPA), and 35 of 201 (17.4%) with EGPA had a manifestation of pleuritis and/or pericarditis attributable to vasculitis. There was a higher frequency of pericarditis in EGPA compared with that in the other AAVs (P < .0001). There was no difference in the frequency of pleuritis in GPA, MPA, or EGPA. In the 156 patients with AAV with pleuritis and/or pericarditis, this was a presenting feature in 127 (81.4%). Overall, it was a presenting feature in 6.9% of all patients with AAV, including 6.5% with GPA, 8.6% with MPA, and 15.9% with EGPA. INTERPRETATION: Pleuritis and pericarditis occur across all the AAVs and, when present, are commonly presenting features of these diseases. Patients with EGPA have a higher proportion of pericardial involvement compared with pleural involvement, whereas this distribution is more equal in patients with GPA and MPA. Pleuritis and pericarditis are underrecognized features of AAV. All forms of AAV should be considered in the differential diagnosis when evaluating a patient with pleuritis or pericarditis.

3.
JAMA Ophthalmol ; 139(4): 406-413, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33599705

RESUMO

Importance: Frozen section temporal artery biopsy (TAB) may prevent a contralateral biopsy from being performed. Objective: To evaluate the sensitivity and specificity of TAB frozen vs permanent section pathology results for giant cell arteritis (GCA) and determine the discordance rate of bilateral TABs. Design, Setting, and Participants: In this retrospective cohort study, medical records were reviewed from 795 patients 40 years or older who underwent TAB from January 1, 2010, to December 1, 2018, treated at a single tertiary care center with the ability to perform both frozen and permanent histologic sections. Data were analyzed from January 2019 to December 2020. Main Outcomes and Measures: Sensitivity and specificity of frozen section TAB for detecting GCA, and discordance rates of bilateral permanent section TAB. Results: Of the 795 included participants, 329 (41.4%) were male, and the mean (SD) age was 72 (10) years. From the 795 patients with 1162 TABs, 119 patients (15.0%) and 138 TABs had positive findings on permanent section. Of these 119 patients, 103 (86.6%) also had positive results on the frozen section, with 4 false-positives (0.6%) and 20 false-negatives (16.8%). Frozen section had a specificity of 99.4% (95% CI, 98.5-99.8), sensitivity of 83.2% (95% CI, 75.2-89.4), positive predictive value of 96.1% (95% CI, 90.4-98.9), negative predictive value of 96.6% (95% CI, 94.9-97.8), positive likelihood ratio of 140.6 (95% CI, 72.7-374.8), and a negative likelihood ratio of 0.17 (95% CI, 0.11-0.25). Simultaneous bilateral TABs were performed in 60 patients (7.5%) with a 5% discordance rate on permanent section. In comparison, bilateral frozen section-guided sequential TABs were performed in 307 patients (38.6%) with 5.5% discordance based on permanent section. In multivariate models, there was a greater odds of positive findings with age (odds ratio [OR], 1.04; 95% CI, 1.01-1.07; P = .008), vision loss (OR, 2.72; 95% CI, 1.25-5.75; P = .01), diplopia (OR, 3.33; 95% CI, 1.00-10.29; P = .04), headache (OR, 2.32; 95% CI, 1.25-4.53; P = .01), weight loss (OR, 2.37; 95% CI, 1.26-4.43; P = .007), and anorexia (OR, 5.65; 95% CI, 2.70-11.89; P < .001). Conclusions and Relevance: These results support the hypothesis that negative findings from frozen sections should not be solely relied on to refute the diagnosis of GCA, whereas positive findings from frozen sections can be reliably used to defer a contralateral biopsy pending the permanent section results.

5.
J Rheumatol ; 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33589549

RESUMO

Takayasu arteritis (TA) is a rare inflammatory condition of the large blood vessels that affects the aorta and its branches. Young females of Asian descent are typically the most affected by this disease; however, in the United States, most patients with TA are White1,2,3.

8.
J Rheumatol ; 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33452164

RESUMO

OBJECTIVE: Cardiac involvement is a poor prognostic marker in systemic sclerosis (SSc). While diastolic dysfunction, myocardial fibrosis, and arrhythmias are traditionally considered features of primary cardiac involvement in SSc, the incidence of valvular heart disease (VHD) is not well reported. Our objective was to examine the prevalence of VHD at the time of SSc diagnosis and incidence of VHD during follow-up compared to non-SSc subjects. METHODS: Medical records of patients with suspicion of SSc were reviewed to identify incident cases. SSc subjects were matched 1:2 by age and sex to non-SSc subjects. RESULTS: The study included 78 incident SSc cases and 156 non-SSc comparators (56 yrs [± 15.7], 91% female). A nearly 4-fold increase in the prevalence of moderate/severe VHD prior to SSc diagnosis compared to non-SSc subjects (6% vs 0%; P = 0.004) was identified. During follow-up, 18 SSc and 12 non-SSc patients developed moderate/severe VHD. The cumulative incidence of VHD at 10 years after SSc incidence/index was 17.9% (95% CI 10.7-29.9) in patients with SSc compared with 2.3% (95% CI 0.7-7.0) in non-SSc subjects (HR 4.23, 95% CI 2.03-8.83). Coronary artery disease was the only significant risk factor for VHD. CONCLUSION: Patients with SSc have a 4-fold increase in the prevalence of moderate/severe VHD at diagnosis compared to non-SSc patients. They also have a 4-fold increased risk of developing moderate/severe VHD after diagnosis of SSc. Aortic stenosis and mitral regurgitation have a much higher prevalence in patients with SSc, besides secondary tricuspid regurgitation. Underlying mechanisms for this association require further elucidation.

9.
BMJ Case Rep ; 14(1)2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436357

RESUMO

The objectives of this article are to present a case of type II cryoglobulinemic vasculitis, explain why mucosa-associated lymphoid tissue (MALT) lymphoma is an unusual cause of type II cryoglobulins and to discuss the aetiology, epidemiology, pathophysiology and treatment of cryoglobulinemic vasculitis. A 67-year-old woman presented with 4 months of weight loss, intermittent epistaxis and a purpuric skin rash. Prior to presentation, she was found to have an elevated rheumatoid factor. Further investigation revealed an acute kidney injury and elevated type II cryoglobulins suspicious for cryoglobulinemic vasculitis, which was confirmed by kidney biopsy. Additional workup for the weight loss included biopsy of newly found splenomegaly. Pathology revealed MALT lymphoma, a rare cause of type II cryoglobulinemic vasculitis. Successful medical therapy required treating the underlying malignancy with rituximab and high-dose steroids. After initial resolution of symptoms with this regimen, the patient's vasculitis worsened, which was thought to be secondary to undertreatment of the lymphoma. Bendamustine was added to further treat the lymphoma, after which the patient recovered and was able to discharge without recurrence of symptoms at 6 months.


Assuntos
Crioglobulinemia/etiologia , Linfoma de Zona Marginal Tipo Células B/complicações , Vasculite/etiologia , Lesão Renal Aguda/etiologia , Corticosteroides/uso terapêutico , Idoso , Antineoplásicos Imunológicos/uso terapêutico , Cloridrato de Bendamustina/uso terapêutico , Feminino , Humanos , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Rituximab/uso terapêutico , Esplenomegalia/etiologia
10.
Am J Hum Genet ; 108(1): 84-99, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33308445

RESUMO

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 × 10-5) 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.


Assuntos
Predisposição Genética para Doença/genética , Arterite de Takayasu/genética , Estudos de Casos e Controles , Feminino , Estudo de Associação Genômica Ampla/métodos , Humanos , Doenças Inflamatórias Intestinais/genética , Masculino , Polimorfismo de Nucleotídeo Único/genética
12.
J Rheumatol ; 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-33191288

RESUMO

OBJECTIVE: Few studies have estimated the healthcare resource usage of patients with systemic sclerosis (SSc). The purpose of this study was to compare hospitalization among incident cases of SSc vs age- and sex-matched comparators. METHODS: A retrospective, population-based cohort of patients with SSc in Olmsted County, MN from Jan 1, 1980 to Dec 31, 2016 was assembled. A 2:1 cohort of age- and sex-matched patients without SSc from the same population was randomly selected for comparison. All hospitalizations in the geographic area from Jan. 1, 1987 to Sept. 30, 2018 were obtained. Rates of hospitalization, lengths of stay, and readmissions were compared between groups. RESULTS: 76 incident SSc cases and 155 non-SSc comparators (mean age of 56 ± 16 years at diagnosis/index, 91% female) were included. Rates of hospitalization among cases and comparators were 31.9 and 17.9 per 100 person-years, respectively (rate ratio [RR]:1.78; 95% confidence interval (CI):1.52-2.08). Hospitalization rates were higher in patients with SSc than comparators during the first 5 years after SSc diagnosis (RR: 2.16; 95%CI: 1.70-2.74). This difference decreased over time and was no longer significant at ≥15 years after SSc incidence/index. Lengths of stay (median (IQR) 4 (2-6) vs 3(2-6); p=0.52) and readmission rates (25% vs 23%; p=0.51) were similar between groups. CONCLUSION: Patients with SSc were hospitalized more frequently than comparators, indicating high inpatient care needs in this population. Hospitalization rates were highest during the first 5 years following SSc diagnosis.

13.
Curr Rheumatol Rep ; 22(12): 88, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33159612

RESUMO

PURPOSE OF REVIEW: To provide an overview of mimickers of large vessel vasculitis (LVV), by the main presenting manifestation, i.e., systemic, vascular, and cranial manifestations. RECENT FINDINGS: The main differential diagnoses in patients with giant cell arteritis (GCA) and Takayasu arteritis (TAK) presenting with systemic manifestations (i.e., fever, anorexia, weight loss, night sweats, arthralgia/myalgia, and/or increased inflammatory indexes) are neoplastic, infectious, or other inflammatory conditions. In patients with vascular manifestations (such as peripheral ischemia, vascular stenoses, or aneurysms), atherosclerosis and non-inflammatory vascular diseases should be excluded. In those presenting with predominant cranial symptoms (i.e., temporal headache, jaw claudication, scalp tenderness, transient or permanent vision loss), other causes of headache, cerebrovascular accidents, optic neuropathy, and neuromuscular syndromes need to be considered. The diagnosis of LVV maybe challenging, especially when patients present with atypical or incomplete clinical forms. In these cases, a multidisciplinary approach is strongly recommended.

14.
Autoimmun Rev ; 19(12): 102688, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33131703

RESUMO

OBJECTIVE: Omega-3 fatty acids may decrease systemic lupus erythematosus (SLE) disease activity, however randomized controlled trials (RCT) have been small with conflicting findings. We conducted a systematic review and meta-analysis to estimate the effect of omega-3 fatty acids on SLE disease activity in adults. METHODS: A literature search was conducted from database inception to January 2020. RCTs of adults with SLE comparing omega-3 fatty acids supplementation to placebo or standard of care that evaluated SLE disease activity were included. Abstracts, full text reviews, data abstraction and statistical analysis were evaluated independently by two investigators. Study-specific standardized mean differences (SMD) were estimated and combined using random-effects model. RESULTS: Five RCTs with 136 patients in the comparison groups and 138 in the treatment groups, were included. All the studies used ≤3 g of omega-3 fatty acids. The trial follow-up time ranged from 12 to 52 weeks. The mean age of the patients was 43 years and 80% or more were female. Omega-3 fatty acids reduced SLE activity [SMD -0.33 (95CI: -0.57, -0.09), low certainty evidence, moderate effect size]. Transforming the SMD to the SLE Disease Activity Index (SLEDAI) scale, omega-3 fatty acids reduced disease activity by 0.9 (95CI: -1.6, -0.3, I2 = 0%) SLEDAI points compared to placebo. CONCLUSION: This meta-analysis suggests that omega-3 fatty acids could provide therapeutic benefit in addition to immunosuppressive regimens used for SLE.

15.
Arthritis Rheumatol ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33021335

RESUMO

OBJECTIVES: Deficiency of adenosine deaminase 2 (DADA2) is a monogenic form of vasculitis that can resemble polyarteritis nodosa (PAN). This study screened for DADA2 in patients with presumed idiopathic PAN, granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA) by DNA sequencing. METHODS: Patients with idiopathic PAN (n=118) and patients with GPA or MPA (n=1107) were screened for rare non-synonymous variants in ADA2 using sequencing methods. ADA2 enzyme activity was determined on selected serum samples. RESULTS: Nine of 118 patients (7.6%) with PAN were identified as having rare non-synonymous variants in ADA2. Four (3.4%) were biallelic for pathogenic or likely pathogenic variants and five (4.2%) were monoallelic carriers for three variants of uncertain significance and two likely pathogenic variants. Serum samples of patients with PAN were available for two individuals with biallelic variants and showed markedly reduced ADA2 enzyme activity. ADA2 enzyme testing of 86 additional patients revealed one individual with strongly reduced ADA2 activity without detectable pathogenic variants. Patients with PAN and biallelic variants in ADA2 were younger at diagnosis than patients with one or no variant in ADA2, with no other clinical differences noted. None of the patients with GPA or MPA carried biallelic variants in ADA2. CONCLUSION: A subset of patients with idiopathic PAN meet genetic criteria for DADA2. Given that TNF-inhibition is efficacious in DADA2 but is not conventional therapy for PAN, these findings suggest that ADA2 testing should strongly be considered in patients with HBV-negative idiopathic PAN.

16.
Curr Rheumatol Rep ; 22(12): 86, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067687

RESUMO

PURPOSE OF REVIEW: Giant cell arteritis (GCA) and Takayasu arteritis (TAK) comprise the primary systemic large-vessel vasculitides. In these conditions, arterial stenosis, occlusion, aneurysm, and dissection can lead to severe disease-related consequences. This review focuses on disease-related manifestations of GCA and TAK, emphasizing the impact of these findings on long-term morbidity and mortality. RECENT FINDINGS: Vision loss remains a main contributor of morbidity in GCA. Non-invasive imaging allows for recognition of aortic disease in GCA but monitoring and intervention guidelines require further development. TAK represents a severe disease of early-onset with high risk of morbidity due to aortic, pulmonary, cardiovascular, and neurologic involvement. Overall, patients with GCA have similar mortality rates to comparators but mortality is notably higher than the general population in TAK. A multidisciplinary approach of expert subspecialists is required to assist with the complex care of patients with GCA and TAK in order to appropriately surveil, identify, and address the multi-faceted co-morbidities of these diseases.

17.
Rheumatol Int ; 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33095281

RESUMO

To describe the clinical characteristics, management, and outcome of a series of patients with giant cell arteritis (GCA) and inflammatory bowel disease (IBD). Patients with both GCA and IBD evaluated between 1/1/1996 and 12/30/2018 were retrospectively identified. Clinical characteristics, laboratory parameters, radiologic features, histopathology, management and outcomes were abstracted. A systematic literature review identifying patients with IBD and GCA was performed via a Medline and EMBASE search from inception through December 31 2019. Six patients were identified with GCA and IBD (66% male). Five (83%) had ulcerative colitis (UC) and one had Crohn's disease (CD). Diagnosis of IBD preceded GCA in four patients with an average interval of 30 years (range 14-42). Average time to IBD diagnosis in those with prior GCA diagnosis was 1.5 years. During mean follow-up of 4.3 years, GCA relapse was infrequent with only one patient with relapse observed. Systematic literature review identified six additional patients with confirmed coexistence of GCA and IBD. Similar to the current series, male sex was more common and ulcerative colitis was the predominant IBD phenotype. The current study reports findings from the largest single-institution case-series of co-existent GCA and IBD. In contrast to Takayasu arteritis with co-existent IBD, which displays a predilection for female sex and Crohn's disease phenotype, both the current study and review of literature demonstrate a stronger association of GCA with male sex and ulcerative colitis. Further studies addressing a potential pathophysiologic connection between GCA and IBD are suggested.

18.
J Am Heart Assoc ; 9(18): e015977, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32893708

RESUMO

Background Recent investigations suggest that inflammation and autoimmunity might have a role in the pathophysiology of atrial fibrillation (AF). Given that abnormal ventriculovascular coupling often coexists with AF, we hypothesize that autoimmune vasculitis plays a significant role in the pathogenetic mechanism of AF. Methods and Results A standardized retrospective population-based case-control study was conducted to evaluate the association between autoimmune vasculitis and AF, and all-cause mortality. The study included 8459 patients with a new diagnosis of AF and 8459 age-, sex-, and registration calendar year-matched controls in Olmsted County, Minnesota, between January 1, 1980 and December 31, 2010. The association of each clinical characteristic, diagnosis, and treatment was assessed using conditional logistic regression to account for the matched case-control study design. Cox proportional hazards regression models and Kaplan-Meier curves were used to detect independent predictors of mortality and examine cumulative survival. Of a total of 16 918 patients (mean age 72.3+14.4 years; 48.7% women), 320 (1.9%) were diagnosed with autoimmune vasculitis before the index date during the 30-year period. Among the cases, the prevalence of any autoimmune vasculitis was 2.3%, whereas the frequency of autoimmune vasculitis in controls was 1.5% (P<0.001). After adjusting for potential confounders, the odds of autoimmune vasculitis in AF cases was 1.5 times higher than in controls (odds ratio, 1.47; 95% CI, 1.04-2.01; P=0.03). Patients with AF and autoimmune vasculitis had worse 5-year survival than those without autoimmune vasculitis or AF (44.7% versus 77.2%; log-rank P<0.001). Conclusions Autoimmune vasculitis is significantly associated with AF and independently confers worse survival. These observations may represent one mechanism linking autoimmunity and inflammation to the pathogenesis and prognosis of AF.

19.
Semin Arthritis Rheum ; 50(5): 923-929, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32906026

RESUMO

OBJECTIVE: To compare temporal artery biopsy (TAB)-positive giant cell arteritis (GCA) to TAB-negative GCA and patients with GCA mimics METHODS: PATIENTS DIAGNOSED WITH TAB-POSITIVE AND TAB-NEGATIVE GCA BETWEEN 1/1/1998 AND 12/31/2013 WERE: retrospectively identified. These two groups were compared to a cohort of patients with TAB performed between 1/1/2009 and 12/31/2010 in which the TAB was negative and alternative diagnosis was provided after a minimum of 6-months of follow-up. Baseline characteristics were compared between groups using chi-square and rank sum tests. RESULTS: 591 study subjects were identified (286 TAB-positive, 110 TAB-negative GCA and 195 TAB-negative GCA mimics) during the respective study periods. Compared to TAB-negative GCA, GCA mimics had similar rates of headache and vision loss but significantly less frequent jaw/limb claudication, arterial bruits and constitutional symptoms, as well as lower platelet levels. Compared to TAB-positive GCA patients, TAB-negative GCA were younger, had shorter time to diagnosis, met fewer 1990 ACR classification criteria and had lower frequencies of polymyalgia rheumatica, jaw claudication and temporal artery abnormalities; but, higher frequency of arm claudication and constitutional symptoms. Among 61 TAB-negative patients with advanced arterial imaging, 43 (69%) had at least one abnormality consistent with GCA. CONCLUSION: Consideration of alternative diagnoses is requisite in evaluating patients with negative TAB. Advanced imaging assists in identifying occult large-vessel vasculitis and should be employed in all TAB-negative patients with suspicion for GCA.

20.
J Clin Invest ; 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32960812

RESUMO

The aorta and the large conductive arteries are immunoprivileged tissues and are protected against inflammatory attack. A breakdown of the immunoprivilege leads to autoimmune vasculitis, such as giant cell arteritis (GCA), in which CD8+ T regulatory (Treg) cells fail to contain CD4+ T cells and macrophages, resulting in the formation of tissue-destructive granulomatous lesions. Here, we report that the molecular defect of malfunctioning CD8+ Treg cells lies in aberrant NOTCH4 signaling that deviates endosomal trafficking and minimizes exosome production. By transcriptionally controlling the profile of RAB GTPases, NOTCH4 signaling restricted membrane translocation and vesicular secretion of the enzyme NADPH oxidase 2 (NOX2). Specifically, NOTCH4hiCD8+ Treg cells increased RAB5A and RAB11A expression and suppressed RAB7A, culminating in the accumulation of early and recycling endosomes and trapping of NOX2 in an intracellular, non-secretory compartment. RAB7AloCD8+ Treg cells failed in the surface translocation and the exosomal release of NOX2. NOTCH4hi RAB5Ahi RAB7Alo RAB11Ahi CD8+ Treg cells left adaptive immunity unopposed, enabling a breakdown in tissue tolerance and aggressive vessel wall inflammation. Inhibiting NOTCH4 signaling corrected the defect and protected arteries from inflammatory insult. The study implicates NOTCH4-dependent transcriptional control of RAB proteins and intracellular vesicle trafficking in autoimmune disease and in vascular inflammation.

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