Polyarteritis Research Articles

New-onset autoimmune disease after COVID-19.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may trigger autoimmune disease (AD) through initial innate immune activation with subsequent aberrations in adaptive immune cells leading to AD. While there are multiple reports of incident AD diagnosed after COVID-19, the risk in the context of key circulating strains is unknown. TriNetX, a global, federated, health research network providing access to electronic medical records across 74 healthcare organizations, was utilized to define an adult cohort between January 1, 2020, and March 3, 2023. Exposure was defined as COVID-19 diagnosis (ICD-10 code or positive laboratory test). Age- and sex-propensity score-matched controls never had COVID-19 diagnosed. Outcomes were assessed 1 month to 1 year after the index date. Patients with AD prior to or within 1 month after the index date were excluded from the primary analysis. Incidence and risk ratios of each AD were assessed. A total of 3,908,592 patients were included. Of 24 AD patients assessed, adjusted risk ratios for eight AD patients who had COVID-19 were higher compared to those who had no COVID-19. Cutaneous vasculitis (adjusted hazard ratio (aHR): 1.82; 95% CI 1.55-2.13), polyarteritis nodosa (aHR: 1.76; 95% CI 1.15-2.70), and hypersensitivity angiitis (aHR: 1.64; 95% CI 1.12-2.38) had the highest risk ratios. Overall, psoriasis (0.15%), rheumatoid arthritis (0.14%), and type 1 diabetes (0.13%) had the highest incidence during the study period, and of these, psoriasis and diabetes were more likely after COVID-19. The risk of any AD was lower if COVID-19 was diagnosed when Omicron variants were the predominant circulating strains. A positive antinuclear antibody was more likely and predictive of AD after COVID-19. SARS-CoV-2 may be a potential trigger for some AD, but the risk for AD may decrease with time given the apparent lower risk after infection with Omicron variants.

Nationwide epidemiological survey of polyarteritis nodosa in Japan in 2020.

Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis that predominantly affects medium-sized arteries. With advances in our understanding of the pathogenesis and classification of vasculitis, PAN and microscopic polyangiitis (MPA), a disease of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), were separated from the group of diseases previously diagnosed as periarteritis nodosa (PN) at the Chapel Hill Consensus Conference (CHCC) in 1994 (1).

Ruptured Saccular Aneurysm Caused by Necrotizing Arteritis of the Polyarteritis Nodosa Type in Primary Angiitis of Central Nervous System.

Primary angiitis of central nervous system (PACNS) is a rare idiopathic vasculitis that typically involves small arteries. An 18-year-old woman was operated on for resection of a ruptured aneurysm in a cerebral artery. Multiple aneurysms of cerebral arteries had been detected by neuroimaging examinations since the age of 12, and she had been administered drugs following a diagnosis of PACNS since the age of 15. The resected aneurysm was a ruptured saccular aneurysm occurring in a medium-sized artery. Histologically, necrotizing arteritis of the polyarteritis nodosa (PAN) type was noted in the aneurysmal wall. It consisted of an admixture of acute and healing stages. In the acute stage, fibrinoid necrosis in the intima and media and intense inflammatory cell infiltrate in the entire wall were present. The inflammatory cells mainly consisted of lymphocytes, including plasma cells, neutrophils, and macrophages. In the healing stage, disappearance of fibrinoid necrosis, fibrosis in the intima and media, and scarce inflammatory cells were noted. The acute stage was mainly present near the ruptured site. From these findings, the aneurysm was considered to have been caused by necrotizing arteritis of the PAN type. Although saccular aneurysmal formation in a medium-sized artery is rare in PACNS, an understanding of aneurysms produced by necrotizing arteritis of the PAN type offers useful information for the diagnosis and treatment of PACNS.

Von Willebrand factor: a possible biomarker for disease activity in vasculitis

Objective Inflammation markers, e.g. C- reactive protein (CRP) and sedimentation rate, can be normal despite active vasculitis. Von Willebrand factor (vWF) is secreted from endothelial cells in response to vascular damage. Some reports suggest increased vWF levels in vasculitis. This study aimed to evaluate vWF serum concentration in vasculitis patients as a possible biomarker of disease activity and to review the current literature. Method Adult patients with systemic vasculitis were prospectively enrolled. Disease activity was recorded using the Birmingham Vasculitis Activity Score (BVAS) version 3. Blood group-adjusted vWF antigen serum level was evaluated at diagnosis and, when available, after treatment. Results Twenty-five vasculitis patients were compared to 15 healthy controls. The mean age of patients was 56 ± 17 years and 56% were women. Forty percent had anti-neutrophil cytoplasmic autoantibody-associated vasculitis, 20% giant cell arteritis, 16% polyarteritis nodosa, 8% Takayasu arteritis, and the rest had other vasculitides. The mean disease duration was 3.4 ± 4.8 years. Mean vWF was higher in patients with active vasculitis than in healthy controls (212 ± 81% vs 106 ± 26%, p < 0.001). vWF levels directly correlated with BVAS. In 13 patients with active vasculitis who reached remission or low disease activity after treatment, vWF level at follow-up decreased significantly. In three out of five patients who were treated with interleukin-6 inhibitors, vWF was elevated despite normal CRP levels, while vasculitis was clinically active. Conclusion vWF antigen serum level is increased in active vasculitis and could potentially serve as a biomarker for active disease.

Clinical features of the course of polyarteritis nodosa in combination with familial Mediterranean fever

There are certain difficulties with diagnosing of poliarteritis nodoza, that is explained by the folllowung factors: non-specificity of the initial symptoms, polymorphism of clinical manifestations, the abcence of specific laboratory markers. Тhe diagnosis is made primarily on the basis of the clinical picture, that becomes apparent during the first three months of illness. The abcence of a detailed clinical picture does not exclude the presense of poliarteritis nodoza. It may be explained by the concomitant pathology, in this case periodic illness (familian mediterranean fever). Due to medical literature data, poliarteritis nodoza is surely associated with periodic illness. The prevalence of poliarteritis nodoza in general population is about 6 on 100 000 people.The prevalence of poliarteritis nodoza among the patients suffering from periodic illness is 1%. The patients when they are diagnosed polyarteritis nodosa in association with periodic illness are younger than the patients when they are diagnosed only polyarteritis nodosa. It turned out to be interesting that the treatment of patients with polyarteritis nodosa in association with periodic illness through glucocorticoid drugs in the combination with colchicines proved to be successful and resulted in remission.

Left main and three vessels spontaneous coronary artery dissection as an incidental finding in young man with history of Hodgkin’s lymphoma-a case report

BackgroundSpontaneous coronary artery dissection is a rare and important cause of myocardial infarction, especially in young women without other coronary artery disease. This arterial dissection can occur within or between any of the 3 layers.Its predisposing factors include connective tissue diseases (Marfone syndrome, Ehlers-Danlos syndrome), vasculitis (polyarteritis nodosa, systemic lupus erythematosus, and Kawasaki disease), atherosclerosis and fibromuscular dysplasia.Clinical presentations of spontaneous coronary artery dissection are wide spectrum from asymptomatic to acute coronary disease, sustained ventricular arrhythmia and sudden cardiac death.Case presentationWe describe A 33-year-old man with history of Hodgkin’s lymphoma five years earlier that became a candidate for Patent foramen ovale closure due to recurrent embolic cerebrovascular accident. Before the intervention, coronary angiography incidentally showed dissection in the left main and all major coronary arteries.ConclusionsBased on our hypothesis, chemoradiotherapy-induced arteriopathies could be consider as a predisposing factor for spontaneous coronary artery dissection.

Polyarteritis nodosa and Kawasaki syndrome : Vasculitis predominantly of medium size and small vessels

Polyarteritis nodosa (PAN) and Kawasaki syndrome (KS) are rare forms of primary vasculitis with heterogeneous manifestations and courses of the disease. According to the Chapel Hill Consensus Conference 2012 they belong to the vasculitis of medium size vessels. In contrast to microscopic polyangiitis (MPA), PAN and KS do not affect microscopic vessels such as arterioles, venules or capillaries and are not associated with antineutrophil cytoplasmic antibodies (ANCA). The diagnostics are based on the typical constellation of clinical symptoms, on angiographic findings, the exclusion of other differential diagnoses and, in the case of PAN, in the histopathological confirmation. The therapeutic options of KS in childhood and PAN in adults and children, which are dependent on the severity and the prognosis, are presented.

From macular lymphocytic arteritis to cutaneous polyarteritis nodosa: A spectrum of the same disease? Two cases of the same clinical presentation yet different histopathological findings

Macular lymphocytic arteritis (MLA) is a type of indolent cutaneous vasculitis that affects small to medium-sized blood vessels. Histopathologically, it is characterized by a predominantly lymphocytic leukocytic infiltrate (unlike polyarteritis nodosa, in which neutrophils predominate) in the blood vessels of the deep dermis and superficial hypodermis. The disease mainly affects females (17:3), with a mean age of forty years. In general, this entity is considered benign with a variable clinical presentation. The importance of knowing this entity lies in the fact that the pathological findings are discordant with the clinic and an erroneous diagnosis may lead to unnecessary treatments. This vasculitis usually has a benign course and no progression to systemic disease. Herein, we present two cases of this rare vasculitis. Key words: Macular lymphocytic arteritis, Cutaneous polyarteritis nodosa, Vasculitis, Systemic lupus erythematosus

Unravelling a Case of Coronary Vasculitis

Background Coronary vasculitis is a rare cause of myocardial infarction through varied mechanisms. We report the case of a 32-year-old female found to have diffuse coronary microaneurysms during treatment for an Inferior ST Elevation Myocardial Infarction (STEMI), with challenges in pinpointing the underlying aetiology. Results Our patient has been diagnosed with a seronegative arthritis and had been initiated on regular Golimumab 4 months prior. She presented with prolonged fever for 4 weeks and inflammatory oligoarthritis with left sacroiliac joint pain. During this admission, Antinuclear antibody was 1:2560 and anti ds DNA was 1:80. She had highly positive Rickettsia conorii IgG titres of 1:128, suggestive of acute infection with Orientia tsustsugamushi. Meropenem and doxycyclin for presumed typhus had no impact on her fever spikes. In the 10th week of the illness, she developed ischaemic chest pain with electrocardiographic changes of inferior STEMI and was thrombolysed. Invasive coronary angiography revealed numerous coronary microaneurysms affecting all major myocardial vessels, with minimal coronary artery disease. Following multidisciplinary discussion, she was treated with intravenous methylprednisolone, antiplatelets, a statin and warfarin for a diagnosis of coronary vasculitis. Repeat angiography showed complete resolution of the microaneurysms. She continues on anticoagulation and has since had no coronary events. Conclusion Typhus and medium vessel vasculitis such as Kawasaki and Polyarteritis Nodosa were potential diagnoses for this presentation. A diagnosis of SLE was established due to the highly specific immunological profile. As there are reports of high Rickettsial titres in autoimmune disease, which alongside the lack of response to doxycyclin makes Typhus unlikely. The possibility of golimumab induced SLE was briefly entertained due to similar reports, but the positivity of ds DNA and major organ involvement made this possibility unlikely. We highlight the cardiac involvement in this case due to its high morbidity on young patients, and the current paucity of knowledge on SLE-related endothelial dysfunction and immune-mediated vascular damage. The role of anticoagulation in this inflammatory milieu too, is controversial. This case highlights a rare presentation of SLE, with an emphasis on coronary vasculitis. It adds to the current knowledge on the complex cardiovascular risk in SLE and highlights ambiguous areas in current management strategies to prompt further research.

Critical Limb Threatening Ischemia Due to Severe Polyarteritis Nodosa-A Case Report.

A delayed diagnosis of polyarteritis nodosa may lead to critical limb-threatening ischemia (CLTI). A 74-year-old woman presented with left-foot pain and was treated with oral vasodilators and antiplatelet agents. However, the distal ischemia progressed to CLTI, including gangrene of the fingers and toes, and bilateral foot dropping appeared because of peroneal nerve paralysis. Angiography of the extremities revealed obstruction and stenosis of medium-sized arteries. Based on the progressive distal gangrene, mononeuropathy multiplex, and pathological findings of necrotic vasculitis, polyarteritis nodosa was diagnosed, and the patient's condition improved. A biopsy and neurological examination are essential for the appropriate diagnosis of PAN and immediate treatment.

VEXAS syndrome: Clinical manifestations, diagnosis, and treatment.

VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is an adult-onset autoinflammatory syndrome characterized by somatic mutations in the UBA1 gene and is considered the prototype of hematoinflammatory diseases. Patients with VEXAS syndrome exhibit inflammatory and hematological manifestations that can lead to clinical diagnoses such as relapsing polychondritis, polyarteritis nodosa, Sweet syndrome, and myelodysplastic syndrome. Diagnosis requires bone marrow evaluation to identify cytoplasmic vacuoles in myeloid and erythroid precursors. However, genetic confirmation of mutations in UBA1 is necessary. Treatment is challenging and often involves glucocorticoids and immunosuppressants with variable responses. Hypomethylating agents and allogenic haemopoietic stem cell transplant are considered promising therapies. Prognosis is influenced by genetic and clinical factors. The aim of this review is to provide an overview of the pathogenesis, clinical presentation, treatment, and prognosis of VEXAS syndrome for the Latin American medical community.

Vasculitis-panniculitis mimicking unresolved diabetic foot ulcer.

Diabetes foot ulcer (DFU) is a common long-term complication of diabetes. Intractable chronic wounds to standard care of diabetic foot raise the question of whether other factors intervene in disease development. We report a case of a 54-year-old male patient who came to Sardjito General Hospital with leg pain and previous history of multiple debridement and amputation for DFU referred from a remote hospital yet no improvement was evident in the surrounding lesion following treatment. Consequently, a histopathological examination was carried out proving the presence of other aetiologic factors, vasculitis and panniculitis existing in the lesion. In this case, we report a rare type of causative factor of foot ulcers among diabetic patients. Vasculitis suspected for polyarteritis nodosa accompanied by panniculitis is considered in this patient. The treatment of choice is corticosteroids or immunosuppressants based on the clinical condition, contrary to usual wound care in DFU. Based on the evidence, clinicians need to consider other causes than only macrovascular complications in a diabetic patient with DFU that is intractable to standard wound care. In this patient, vasculitis may be considered in forming diabetic foot ulcers alongside macrovascular complications. A thorough examination is essential to rule out other processes in intractable DFU patients. Prompt management based on proper diagnosis is crucial to prevent peripheral arterial disease complications. Vasculitis and macrovascular complication are inseparable processes forming DFU in this patient.

Comparison of EULAR/PRINTO/PReS Ankara 2008 and 2022 ACR/EULAR classification criteria for granulomatosis with polyangiitis in children.

Granulomatosis with polyangiitis (GPA) is an ANCA-associated vasculitis. The 2022 ACR/EULAR-endorsed classification criteria for GPA was derived using data only from adult patients. We aimed to assess the performance of the ACR/EULAR classification criteria for GPA in paediatric patients and compare it with the EULAR/Pediatric Rheumatology International Trials Organization (PRINTO)/Pediatric Rheumatology European Society (PReS)-endorsed Ankara 2008 criteria for GPA. Retrospective data of paediatric patients with GPA in 20 centres from 9 countries were evaluated. The diagnosis of GPA was made according to the expert opinion. The sensitivity, specificity, positive predictive value, and negative predictive value of the criteria sets were evaluated. The study included 77 patients with GPA and 108 controls [IgA vasculitis (n = 44), Takayasu's arteritis (n = 20), microscopic polyangiitis (n = 16), polyarteritis nodosa (n = 14), Behçet's disease (n = 12), eosinophilic granulomatosis with polyangiitis (n = 1) and Cogan's syndrome (n = 1)] with a median age of 17.8 and 15.2 years, respectively. Among patients with GPA, constitutional symptoms (85.7%) and ENT involvement (79.2%) were the most common presentations. In the GPA group, 73 patients fulfilled the Ankara 2008 criteria and 69 the ACR/EULAR classification criteria. Sensitivities of the Ankara 2008 criteria and the ACR/EULAR classification criteria were 94.8% and 89.6%, while specificities were 95.3% and 96.3%, respectively. No significant difference was found between sensitivities and specificities of both classification criteria (P = 0.229 and P = 0.733, respectively). In children, both the ACR/EULAR and EULAR/PRINTO/PReS Ankara 2008 classification criteria for GPA perform well and similarly.

Clinical characteristics, disease trajectories and management of vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome: a systematic review.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly discovered autoinflammatory condition characterised by somatic mutation of the UBA1 gene. The syndrome leads to multi-system inflammation affecting predominantly the skin, lungs and bone marrow. We undertook a systematic review of the multisystem features and genotypes observed in VEXAS syndrome. Articles discussing VEXAS syndrome were included. Medline, Embase and Cochrane databases were searched. Information was extracted on: demographics, type and prevalence of clinical manifestations, genetic mutations and treatment. Meta-analysis using a random effects model was used to determine pooled estimates of serum markers. From 303 articles, 90 were included, comprising 394 patients with VEXAS. 99.2% were male, with a mean age of 67.1 years (SD 8.5) at disease onset. The most frequent diagnoses made prior to VEXAS were: relapsing polychondritis (n = 59); Sweet's syndrome (n = 24); polyarteritis nodosa (n = 11); and myelodysplastic syndrome (n = 10). Fever was reported in 270 cases (68.5%) and weight loss in 79 (20.1%). Most patients had haematological (n = 342; 86.8%), dermatological (n = 321; 81.5%), pulmonary (n = 297; 75.4%%) and musculoskeletal (n = 172; 43.7%) involvement, although other organ manifestations of varying prevalence were also recorded. The most commonly reported mutations were "c.122T > C pMET41Thr" (n = 124), "c.121A > G pMET41Val" (n = 62) and "c.121A > C pMet41Leu" (n = 52). Most patients received glucocorticoids (n = 240; 60.9%) followed by methotrexate (n = 82; 20.8%) and IL-6 inhibitors (n = 61, 15.4%). One patient underwent splenectomy; 24 received bone marrow transplants. VEXAS syndrome is a rare disorder affecting predominantly middle-aged men. This is the first systematic review to capture clinical manifestations, genetics and treatment of reported cases. Further studies are needed to optimise treatment and subsequently reduce morbidity and mortality.

A Case of Polyarteritis Nodosa and Antiphospholipid Antibody Positivity Presenting with Intramuscular Haematoma

Polyarteritis nodosa (PAN) is a medium-sized vessel vasculitis often presenting report as both stenotic and aneurysmal lesions. Association with antiphospholipid antibody (aPL) has also been described. Here, we reported a case of PAN with history of cutaneous vasculitis presenting as multiple territory ischemic stroke, mesenteric panniculitis, coronary artery stenosis on imaging; lupus anticoagulant (LA) was also identified, patient was treated with immunosuppressants and anticoagulation. Disease course was, however, complicated by development of thigh haematoma. Clinical manifestation of PAN and its association with aPL will be discussed.

Polyarteritis Nodosa: Old Disease, New Etiologies

Polyarteritis nodosa (PAN), also known as panarteritis nodosa, represents a form of necrotizing vasculitis that predominantly affects medium-sized vessels, although it is not restricted to them and can also involve smaller vessels. The clinical presentation is heterogeneous and characterized by a significant number of patients exhibiting general symptoms, including asthenia, fever, and unintended weight loss. Although PAN can involve virtually any organ, it preferentially affects the skin, nervous system, and the gastrointestinal tract. Orchitis is a rare but specific manifestation of PAN. The absence of granulomas, glomerulonephritis, and anti-neutrophil cytoplasmic antibodies serves to distinguish PAN from other types of vasculitis. Major complications consist of hemorrhagic and thrombotic events occurring in mesenteric, cardiac, cerebral, and renal systems. Historically, PAN was frequently linked to hepatitis B virus (HBV) infection, but this association has dramatically changed in recent years due to declining HBV prevalence. Current epidemiological research often identifies a connection between PAN and genetic syndromes as well as neoplasia. This article provides a comprehensive review of PAN, specifically focusing on the progression of its clinical manifestations over time.

Wünderlich Syndrome Associated with Obstructive Uropathy due to Coralliform Renal Lithiasis: Case Report and Literature Review.

Wünderlich syndrome or non-traumatic spontaneous renal hemorrhage is a rare entity, with less than 500 cases reported to date. It has multiple associated risk factors, the tumoral etiology is the principal one and the angiomyolipoma is the most frequently associated benign tumor. Other causes that are less frequent are systemic diseases such as polyarteritis nodosa, ruptured renal cysts, coralliform renal lithiasis, among others. It´s most common clinical presentation only occurs in 20% of cases and consists of Lenk's triad. Even in cases where the triad is present, the initial diagnosis is by computed tomography (CT) where the retroperitoneal hematoma is observed and sometimes evidencing the underlying etiology as in cases of renal lithiasis. Treatment depends on its severity and extension, ranging from conservative treatment in mild cases to urgent surgery in cases with hemodynamic instability. We present the case of a 58-year-old male patient with previous inpatient history of acute urinary retention and the finding of right coralliform renal lithiasis, without accepting surgical treatment and was readmitted a few weeks later presenting the characteristic clinical Lenk´s triad he undergoing to simple abdominopelvic computed tomography TC, as initial study and reporting a right perirenal hematoma secondary to obstructive uropathy due to renal lithiasis.

Cutaneous vasculitis in autoinflammatory diseases.

Autoinflammatory diseases (AIDs) characterized by recurrent episodes of localized or systemic inflammation are disorders of the innate immune system. Skin lesions are commonly found in AIDs and cutaneous vasculitis can coexist with AIDs and even present as the most striking feature. This review aims to focus on the frequent cutaneous vasculitis association in three monogenic AIDs including familial Mediterranean fever (FMF), deficiency of adenosine deaminase type 2 (DADA2), and the recently identified adult-onset VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Cutaneous vasculitis in FMF is characterized by: (1) small-vessel vasculitis similar to IgA vasculitis with palpable purpura but increased intussusception complication and less vascular IgA deposit, and (2) cutaneous arteritis-like vasculitis presenting as subcutaneous nodules most often with higher glomerular involvement. DADA2 has a wide spectrum of clinical presentations ranging from fatal systemic vasculitis with multiple strokes, especially in pediatric patients, to limited cutaneous disease in middle-aged patients. DADA2 shares similar clinical and histopathological features with polyarteritis nodosa (PAN). As a result, DADA2 is commonly initially misdiagnosed as childhood PAN. Livedo racemosa reveals the most common cutaneous manifestation of cutaneous vasculitis in patients with DADA2. VEXAS syndrome is a life-threatening disease. A diagnosis of VEXAS syndrome should be strongly considered or could be made in patients with skin lesions characterized by Sweet syndrome-like eruption, livedo racemosa, concomitant relapsing polychondritis, deep venous thrombosis, pulmonary involvement, and progressive hematologic abnormalities such as myelodysplastic syndrome with a unique finding of cytoplasmic vacuoles in myeloid and erythroid precursor cells from bone marrow aspirate smear. As skin involvement is common in AIDs and may present as the most frequent manifestation, especially in DADA2 (70% to 90%) and VEXAS syndrome (83% to 91%), dermatologists play a crucial role in contributing to the early diagnosis of these AIDs with early initiation of the appropriate therapy to avoid progressing fatal outcomes.

Tuberculosis among children and adolescents with rheumatic diseases - case series

Background: Rheumatic patients have a higher frequency of tuberculosis(TB) than the general population. This study aimed to describe children and adolescents with TB and rheumatic diseases(RD) who were being treated in a reference center. Methods: A series of TB cases were investigated in a reference center for childhood TB in Rio de Janeiro, Brazil, from 1995 to 2022. Results: Fifteen patients with underlying RD and TB were included with 8(53%) being female. The mean age at RD diagnosis was 7.10years (SD ± 0,57 years), and the mean age at TB diagnosis was 9.81 years(SD ± 0.88 years). A total of 9 cases of pulmonary TB(PTB) and 6 cases of extrapulmonary TB—pleural(2), joint/osteoarticular(1), cutaneous(1), ocular(1), and peritoneal(1)- were described. The RD observed in the 15 patients included juvenile idiopathic arthritis(9), juvenile systemic lupus erythematosus(3), juvenile dermatomyositis(1), polyarteritis nodosa(1), and pyoderma gangrenosum(1). Among the immunosuppressants/immunobiologics, methotrexate(8) was the most commonly used, followed by corticosteroids(6), etanercept(2), mycophenolate mofetil(1), cyclosporine A(1), adalimumab(1), and tocilizumab(1). The most common symptoms were fever and weight loss, and a predominance of PTB cases was noted. GeneXpert MTB/RIF® was performed in six patients and was detectable in two without rifampicin resistance; Xpert Ultra® was performed in five patients, and traces with indeterminate rifampicin resistance were detected in three. One female patient discontinued treatment, and another passed away. Conclusions: The case series demonstrated the importance of suspecting and investigating TB in RD affected patients who are using immunosuppressants/ immunobiologics, particularly in countries with high rates of TB such as Brazil.

Abstract 12881: Lnc(RNA)-ing COX-2 and Cardioprotection: A PACERR Story

NSAIDs are amongst the most commonly used drugs by adults, but their use is complicated by an increased risk of adverse cardiovascular events that are consequent to suppression of cyclooxygenase-2 (COX-2) dependent prostaglandin (PG) formation, particularly prostacyclin (PGI 2 ). Amongst the mechanisms HDL may help to mediate cardiovascular risk is via its regulated expression of COX-2 and production of PGI 2 by vascular cells. This affords restraint on thrombogenesis, atherogenesis and hypertension. Another might be to accelerate cholesterol efflux by macrophages in the atherosclerotic plaque. Depletion of COX-2 has been reported to reduce efflux coincident with an altered HDL phenotype that fosters atherogenesis. Long non-coding RNAs (lncRNAs) contribute to the regulation of essential cellular processes, such as the progression of cardiovascular disease. Through the investigation of lncRNAs involved in the cellular response to HDL we have uncovered a regulatory role for a lncRNA encoded on the opposite strand of COX-2, called PACERR. Examining the human GTEx database, we found PACERR is most highly expressed in vascular tissues including aorta with several cis -eQTLs modulating aortic PACERR expression. Patients in the Penn Medicine Biobank with these SNPs exhibit an increase in odds ratio towards vascular inflammatory traits including polyarteritis nodosa (PAN). HDL induces the expression of PACERR in vascular cells, signifying its potential role in mitigating risk towards cardiovascular disease phenotypes. Using gain-and-loss of function approaches we have found that PACERR modulates HDL induced COX-2 and prostaglandin formation by smooth muscle and endothelial cells under flow as well as HDL mediated cholesterol efflux by macrophages via the regulation of the cholesterol transporter ABCG1. By modulating the expression of PACERR in vitro and in vivo, we have elucidated a mechanism by which both HDL and COX-2 have a linked cardio-protective effect contributing to our understanding of the heterogeneous effects of current drugs used to raise HDL cholesterol levels and the cardiotoxicity of NSAIDs observed in clinical trials.