Systemic Lupus Erythematosus Vasculitis Research Articles

#760 Monogenic lupus with ANCA associated vasculitis-phenotype and ANCA positivity due to DNASE1L3 mutations: case report and review of the literature

Abstract Background and Aims Monogenic systemic lupus erythematosus (SLE) accounts for 7-10% of cases of early-onset SLE. DNASE1L3 is an extracellular nuclease that digests chromatin released from apoptotic cells and its deficiency, enhance autoantibody production and type I interferon responses and cause different autosomal recessive phenotypes including SLE and hypocomplementemic urticarial vasculitis syndrome (HUVS) [1]. In some cases patients can have a mixed SLE-AAV phenotype. Kidney involvement in patients with DNASE1L3 mutations is poorly characterised. Method We present the case report of a 7-years-old boy with monogenic SLE due to DNASE1L3 mutations who developed severe glomerulonephritis leading to kidney failure. Results The patient had a history of urticaria and arthralgia and presented with fever, haemolytic anaemia, lymphadenopathy, hepato-splenomegaly, erythematous- macular and necrotic skin lesions, and interstitial lung disease. He also had acute kidney injury (serum creatinine 5.4 mg/dL), nephrotic- range proteinuria (3.9 g/24 h) and microhaematuria. Immunological tests revealed low C3 and C4, positive anti-nuclear antibody (ANA) and myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA), with negativity of anti-extractable nuclear antigen antibodies (anti-ENA) and anti-double stranded DNA (anti-dsDNA). Kidney biopsy showed pauci-immune (mesangial C3+ and IgG+) necrotising crescentic glomerulonephritis. The patient proved refractory to standard immunosuppression with cyclophosphamide and steroids. Two years later, due to renal function decline, a new kidney biopsy was performed and showed diffuse necrotising glomerulonephritis with endo- and extra-capillary proliferation; intense mesangial and subendothelial full-house deposits were evident on immunofluorescence. The patient did not respond to other lines of immunosuppression (mycophenolate mofetil, tacrolimus, azathioprine, rituximab), including the JAK inhibitor ruxolitinib. Kidney failure progressed to end stage at the age of 15 years, when the patient began haemodialysis. The kidney presentation, immunological profile and the first kidney biopsy led to diagnosis of AAV. However, the diagnosis was questioned due to the refractory course, the systemic clinical presentation and the second kidney histology (consistent with lupus nephritis). High interferon signature was detected and in the suspicion of a monogenic lupus nephritis Whole Exome Sequencing was performed and revealed homozygous DNASE1L3 variants (c.290_291delCA p.T97Ifs*2); thus, a final diagnosis of DNASE1L3 monogenic SLE was made. DNASE1L3 serum levels were normal but the DNAse enzymatic activity was low. Conclusion Renal involvement is one of the most frequent manifestations of DNASE1L3-related lupus; in the literature 32 cases of DNASE1L3-associated lupus nephritis are described. ANCA are positive in about 55% of these cases and are associated with a mixed lupus-AAV phenotype. All cases are characterized by resistance to common immunosuppressors and poor renal prognosis [2]. DNASE1L3 regulates neutrophil extracellular trap (NET) clearance and when this function is reduced the permanence of NETs induces endothelial damage and autoantibody formation. This pathogenic pathway is shared both by SLE and by AAV. There is no association between specific mutations and antibody positivity or clinical manifestations.

P158 Cutaneous vasculitis in systemic lupus erythematosus: trends of incidence and risk factors

Abstract Background/Aims Cutaneous vasculitis (CV) is the most common form of vasculitis observed in patients with SLE; however, the precise epidemiological trends and underlying risk factors remain uncertain. The aim of this study was to define the incidence, prevalence, and risk factors of CV in systemic lupus erythematosus (SLE) patients over a period of 20 years. Methods The Birmingham Lupus Cohort is a longitudinal observational cohort of patients with SLE. All patients fulfilled the 1997 ACR Updated Classification Criteria for SLE. Inception patients were recruited within three years of their fourth ACR criterion. Disease activity was assessed using the classic BILAG index and laboratory results recorded. The BILAG vascular domain was used to determine the incidence rate, which refers to the rate at which new cases of minor and major CV attributed to active SLE occur. Cox proportional hazards frailty models were developed to identify clinical and laboratory variables associated with development of CV. Results We analysed 392 patients, of whom 375 (92.5%) were females. There were 213 (55.0%) White, 72 (18.6%) African-Caribbean, 82 (21.1%) South Asian, 9 (2.3%) East Asian, and 11 (2.8%) other ethnicities. The median (IQR) age at enrolment was 33 (26 - 44) years and the median duration of follow up was 9.2 (5.1 - 14.7) years. The incidence rates of minor and major CV were reported in Table 1. In Cox proportional hazards models, there was a positive association between CV and discoid rash (hazard ratio [HR] 2.16 [95% CI: 1.01, 4.61]), Raynaud’s phenomenon (HR 5.67 [95% CI: 4.11, 7.81]), livedo reticularis (HR = 4.69 [95% CI: 1.83, 12.0]), arthritis (HR 3.02 [95% CI: 2.20, 4.15]), renal involvement (OR 2.40 [95% CI: 1.55, 3.71]), haematological involvement (HR = 2.46 [95% CI: 1.80, 3.36]), and Afro-Caribbean descent (HR 1.96 [95% CI: 1.03, 3.74]). In addition, CV was positively associated with anti-dsDNA (HR = 2.33 [95% CI: 1.67, 3.27]), low C3 or C4 (HR 2.29 [95% CI: 2.18, 4.10]), and history of anti-Ro or anti-La (HR = 1.92 [95% CI: 1.15, 3.21]). Conclusion The incidence rates of CV decrease over the duration of follow-up and are associated with defined clinical and serological features. Disclosure A. Saleh: Grants/research support; A.S. is a sponsored PhD student by the Egyptian ministry of higher education represented by The Egyptian Bureau for Cultural & Educational Affairs in London. C. Gordon: None. J. Reynolds: None.

A 15-year report of indications, adverse events, and effectiveness of therapeutic plasma exchange in patients with rheumatic diseases

Therapeutic plasma exchange (TPE) is a type of treatment, which eliminates harmful antibodies, immune complexes, cytokines, and inflammatory products. Due to the lack of sufficient data on indications, effectiveness, and side effects of TPE in patients with rheumatic disease, we evaluated TPE in our center. All consecutive patients registered in university hospitals with definite rheumatologic indications for TPE during 15 years were evaluated. 680 sessions of TPE were performed on 166 patients, aged between 19 and 83 years. The most common underlying causes were collagen vascular diseases (60%) including systemic lupus erythematosus (SLE) (98%), and antiphospholipid antibody syndrome (APS) (1%); and then, primary small vessel vasculitis (SVV) (39.8%). The main indications for TPE in all patients were rapidly progressive glomerulonephritis (RPGN) (69.8%) and pulmonary hemorrhage (39.1%). During 12 months follow-up, in SLE and SVV patients 17 (17.3%) and 20 (30.3%) entered complete remission; 37 (37.3%) and 12 (18.1%) entered partial remission; 44 (44.8%) and 34 (51.5%) had no recovery; and 37(37%) and 19 (28.7%) died, respectively. A total of 18 (10.8%) patients experienced TPE-related adverse events during TPE [hypotension 15 (9%), allergic reaction 1 (0.6%), fever 1 (0.6%), and hypocalcemia 1 (0.6%)]. The most common indication for TPE is SLE and primary vasculitis. The RPGN and pulmonary hemorrhage were the main indications. Although the rate of response to treatment was acceptable according to the fatal nature of these complications, further case-control studies are suggested to assess the effectiveness of TPE.

Cutaneous Leukocytoclastic Vasculitis as the Presenting Sign of Systemic Lupus Erythematosus

Cutaneous involvement occurs in 72-85% of cases of systemic lupus erythematosus and may be the first clinical sign in up to 25% of cases. 1. Chottawornsak N Rodsaward P Suwannachote S et al. Skin signs in juvenile- and adult-onset systemic lupus erythematosus: clues to different systemic involvement. Lupus. 2018; 27: 2069-2075https://doi.org/10.1177/0961203318805851 Crossref Scopus (8) Google Scholar Recognizing these cutaneous manifestations is essential to early diagnosis and management. 1. Chottawornsak N Rodsaward P Suwannachote S et al. Skin signs in juvenile- and adult-onset systemic lupus erythematosus: clues to different systemic involvement. Lupus. 2018; 27: 2069-2075https://doi.org/10.1177/0961203318805851 Crossref Scopus (8) Google Scholar Here, we present a case of systemic lupus erythematosus with cutaneous leukocytoclastic vasculitis—rare presenting sign of systemic lupus erythematosus 2 Kallas R Goldman D Petri MA. Cutaneous vasculitis in SLE. Lupus Sci Med. 2020; 7e000411https://doi.org/10.1136/lupus-2020-000411 Crossref Google Scholar —as the initial manifestation to highlight the opportunity for prompt diagnosis and management of systemic lupus erythematosus. 3 Barile-Fabris L Hernández-Cabrera MF Barragan-Garfias JA. Vasculitis in systemic lupus erythematosus. Curr Rheumatol Rep. 2014; 16: 440https://doi.org/10.1007/s11926-014-0440-9 Crossref PubMed Scopus (99) Google Scholar

Cryoglobulinemia in systemic lupus erythematosus: a retrospective study of 213 patients

ObjectivesThe clinical value of cryoglobulinemia (CG) in systemic lupus erythematosus (SLE) is largely unknown. The aim of this retrospective study was to describe the characteristics of CG in SLE, its impact on SLE phenotype, and the features associated with cryoglobulinemic vasculitis (CryoVas) in SLE patients.MethodsThis retrospective study conducted in a French university hospital reviewed the data from 213 SLE patients having been screened for CG between January 2013 and December 2017. SLE patients positive for CG were compared to SLE patients without CG. Patients were classified as CryoVas using the criteria of De Vita et al.ResultsOf the 213 SLE patients included (mean age 29.2 years, female sex 85%), 142 (66%) had at least one positive CG in their history, 67% of them having a persistent CG at follow-up. CG was type III in 114 (80%) cases and type II in 27 (19%) cases. The mean concentration of the cryoprecipitate was 40mg/L (range 0-228). Patients with CG had significantly more C4 consumption. Among patients with CG, 21 (15%) developed a CryoVas. The clinical manifestations of patients with CryoVas were mainly cutaneous (purpura, ulcers, digital ischemia) and articular, without any death at follow-up. Severe manifestations of CG included glomerulonephritis in 1/21 (5%) patients and central nervous system involvement in 4/21 (19%) patients. A response to first-line treatments was observed in 12/13 (92%) patients, but relapses were observed for 3 of them.ConclusionCG is frequent in SLE, but mostly asymptomatic. CryoVas features involve mostly joints, skin, and general symptoms. CryoVas in SLE appears to be a specific condition, with a low prevalence of neuropathy, membranoproliferative glomerulonephritis, and severe manifestations.

The role of neutrophils in rheumatic disease-associated vascular inflammation.

Vascular pathologies underpin and intertwine autoimmune rheumatic diseases and cardiovascular conditions, and atherosclerosis is increasingly recognized as the leading cause of morbidity in conditions such as systemic lupus erythematosus (SLE), rheumatoid arthritis and antineutrophil cytoplasmic antibody-associated vasculitis. Neutrophils, important cells in the innate immune system, exert their functional effects in tissues via a variety of mechanisms, including the generation of neutrophil extracellular traps and the production of reactive oxygen species. Neutrophils have been implicated in the pathogenesis of several rheumatic diseases, and can also intimately interact with the vascular system, either through modulating endothelial barriers at the blood-vessel interface, or through associations with platelets. Emerging data suggest that neutrophils also have an important role maintaining homeostasis in individual organs and can protect the vascular system. Furthermore, studies using high-dimensional omics technologies have advanced our understanding of neutrophil diversity, and immature neutrophils are receiving new attention in rheumatic diseases including SLE and systemic vasculitis. Developments in genomic, imaging and organoid technologies are beginning to enable more in-depth investigations into the pathophysiology of vascular inflammation in rheumatic diseases, making now a good time to re-examine the full scope of roles of neutrophils in these processes.

Lupus-related vasculitis in a cohort of systemic lupus erythematosus patients.

Objectives This study aims to examine the frequency and clinical association of lupus-related vasculitis in patients with systemic lupus erythematosus (SLE).Patients and methods We retrospectively analyzed medical records of a total of 565 SLE patients (42 males, 523 females; mean age: 32.7±9.5 years; range, 13 to 63 years) between January 2017 and February 2020. Demographic, clinical data, and laboratory data and treatment modalities applied were recorded. Lupus-related vasculitis and its different types were documented, and the patients with vasculitis were compared with those without vasculitis.Results The mean disease duration was 8.9±6.3 years. Vasculitis associated with lupus was found in 191 (33.45%) patients. Cutaneous vasculitis was found in 59.2%, visceral vasculitis in 34.0%, and both in 6.8% of total vasculitis patients. The patients with vasculitis had a longer disease duration (p=0.01), were more likely to have juvenile onset (p=0.002), livedo reticularis (p<0.001), Raynaud's phenomenon (RP) (p<0.001), digital gangrene (p<0.001), thrombosis (p=0.003), and cranial neuropathy (p=0.004). The patients with vasculitis showed a higher prevalence of hypercholesterolemia (p=0.045), diabetes mellitus (p=0.026), higher Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) at disease onset (p<0.001), and Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (p=0.003) scores. They had more prevalent hematological manifestations (p<0.001), hypocomplementemia (p=0.007), received a higher cumulative dose of intravenous methylprednisolone (p<0.001), and had also more frequent cyclophosphamide (p=0.016) and azathioprine intake (p<0.001). In the logistic regression analysis, SLE vasculitis was independently associated with juvenile disease onset, livedo reticularis, RP, hematological manifestations, and higher scores of SLEDAI at disease onset (p<0.05).Conclusion Juvenile disease onset, livedo reticularis, RP, hematological manifestations, and higher SLEDAI scores at disease onset may be associated with the development of vasculitis in SLE patients.

A case of C-ANCA-positive systematic lupus erythematous and ANCA-associated vasculitis overlap syndrome superimposed by COVID-19: a fatal trio.

Coronavirus disease 2019 (COVID-19) possesses a substantial challenge for rheumatologists and rheumatologic patients. They are concerned about the reciprocal interaction between connective tissue diseases, such as systemic lupus erythematosus (SLE), and the virus. Here, we report a 21-year-old female SLE patient presented to the emergency department with gastrointestinal symptoms and kidney involvement evidence. Based on the pathology and laboratory assessments, she was suspected of C-anti-neutrophil cytoplasmic antibody (ANCA) positive SLE and ANCA-associated vasculitis overlap syndrome (SLE/AAV OS), and plasmapheresis every other day was performed due to this diagnosis alongside the high titer of C-ANCA. We also administered methylprednisolone (1 g/day, IV) for three days, followed by dexamethasone with the maintenance dosage (1mg/kg/day, IV). Although the patient’s general condition improved the next days, her condition deteriorated suddenly on the 7th day of hospitalization. She got intubated and went to the intensive care unit. Despite taking possible measures to manage the patient’s condition, she eventually passed away due to severe acute respiratory distress syndrome (ARDS), triggered by COVID-19. The distinct role of C-ANCA in SLE/AAV vascular damage and activating neutrophil cytokine release accompanied by the impaired immune system while facing COVID-19 seems to lead to increased morbidity and mortality in such patients. This report was presented to bring into consideration the possible role of C-ANCA in the burden and prognosis of COVID-19 in SLE/AAV OS patients.

Proteomic Data Analysis for Differential Profiling of the Autoimmune Diseases SLE, RA, SS, and ANCA-Associated Vasculitis.

Early and correct diagnosis of inflammatory rheumatic diseases (IRD) poses a clinical challenge due to the multifaceted nature of symptoms, which also may change over time. The aim of this study was to perform protein expression profiling of four systemic IRDs, systemic lupus erythematosus (SLE), ANCA-associated systemic vasculitis (SV), rheumatoid arthritis (RA), and Sjögren’s syndrome (SS), and healthy controls to identify candidate biomarker signatures for differential classification. A total of 316 serum samples collected from patients with SLE, RA, SS, or SV and from healthy controls were analyzed using 394-plex recombinant antibody microarrays. Differential protein expression profiling was examined using Wilcoxon signed rank test, and condensed biomarker panels were identified using advanced bioinformatics and state-of-the art classification algorithms to pinpoint signatures reflecting each disease (raw data set available at https://figshare.com/s/3bd3848a28ef6e7ae9a9.). In this study, we were able to classify the included individual IRDs with high accuracy, as demonstrated by the ROC area under the curve (ROC AUC) values ranging between 0.96 and 0.80. In addition, the groups of IRDs could be separated from healthy controls at an ROC AUC value of 0.94. Disease-specific candidate biomarker signatures and general autoimmune signature were identified, including several deregulated analytes. This study supports the rationale of using multiplexed affinity-based technologies to reflect the biological complexity of autoimmune diseases. A multiplexed approach for decoding multifactorial complex diseases, such as autoimmune diseases, will play a significant role for future diagnostic purposes, essential to prevent severe organ- and tissue-related damage.

Combined Brain/Heart Magnetic Resonance Imaging in Systemic Lupus Erythematosus.

Cardiovascular Disease (CVD) in Systemic Lupus Erythematosus (SLE) and Neuropsychiatric SLE (NPSLE) has an estimated prevalence of 50% and 40%, respectively and both constitute major causes of death among SLE patients. In this review, a combined brain/heart Magnetic Resonance Imaging (MRI) for SLE risk stratification has been proposed.The pathophysiologic background of NPSLE includes microangiopathy, macroscopic infarcts and accelerated atherosclerosis. Classic brain MRI findings demonstrate lesions suggestive of NPSLE in 50% of the NPSLE cases, while advanced MRI indices can detect pre-clinical lesions in the majority of them, but their clinical impact still remains unknown. Cardiac involvement in SLE includes myo-pericarditis, valvular disease/endocarditis, Heart Failure (HF), coronary macro-micro-vascular disease, vasculitis and pulmonary hypertension. Classic and advanced Cardiovascular Magnetic Resonance (CMR) indices allow function and tissue characterization for early diagnosis and treatment follow-up of CVD in SLE.Although currently, there are no clinical data supporting the combined use of brain/heart MRI in asymptomatic SLE, it may have a place in cases with clinical suspicion of brain/heart involvement, especially in patients at high risk for CVD/stroke such as SLE with antiphospholipid syndrome (SLE/APS), in whom concurrent cardiac and brain lesions have been identified. Furthermore, it may be of value in SLE with multi-organ involvement, NPSLE with concurrent cardiac involvement, and recent onset of arrhythmia and/or heart failure.

Risk of incident autoimmune diseases in patients with thymectomy.

ObjectivesThe data concerning the association between Tx and ADs remain unclear and are scarce. This study was undertaken to investigate whether people with Tx are more likely to develop ADs, compared to those without Tx.MethodsIndividuals who received Tx between 2002 and 2015 were identified and matched on age and sex with individuals without Tx. We performed multivariate and stratified analysis using the Kaplan–Meier method and Cox proportional hazards models in order to estimate the association between Tx and the risk of developing ADs.ResultsA total of 2550 thymectomized (Txd) patients and 24,664.941 non‐Txd comparison subjects were selected from NHIRD. Tx‐MG (myasthenia gravis) as compared with general population (nonTx‐nonMG), adjusted hazard ratio (aHR) were higher for incident Addison disease (aHR = 10.40, 95% CI 1.01–107), autoimmune hemolytic anemia (aHR = 21.54, 95% CI 2.06–14.8), Hashmoto thyroiditis (aHR = 5.52, 95% CI 1.34–34.7), ankylosing spondylitis (aHR = 2.73, 95% CI 1.09–6.84), rheumatoid arthritis (aHR = 5.25, 95% CI 1.79–15.47), primary Sjogren syndrome (pSS) (aHR = 3.77, 95% CI 1.30–11.0), and systemic lupus erythemtoasus (aHR = 10.40). Tx‐nonMG as compared with general population, aHR were higher for incident autoimmune hemolytic anemia (aHR = 25.50), Hashmoto thyroiditis (aHR = 6.75) and systemic lupus erythematosus (SLE) (aHR = 13.38). NonTx‐MG as compared with general population, aHR were higher for incident Hashmoto thyroiditis (aHR = 6.57), pSS (aHR = 4.50), SLE (aHR = 17.29), and systemic vasculitis (aHR = 25.86).InterpretationIn conclusion, based on a retrospective cohort study throughout Taiwan, patients with Tx have a higher risk of new onset ADs than patients without Tx.

Intravascular Mechanical Thrombectomy for a Patient with Systemic Lupus Erythematosus and Acute Cerebral Infarction with Antiphospholipid Syndrome

Systemic lupus erythematosus (SLE) is a diffuse connective tissue disease that is characterized by autoimmune-mediated inflammation. Antiphospholipid syndrome (APS) is a non-inflammatory autoimmune disease. A 55-year-old female patient was admitted to the hospital due to ‘sudden speech insufficiency and aggravation of 5 h’. The patient developed sudden dizziness, facial numbness, and slurred speech and was transported to the emergency department in a local hospital, and was diagnosed ‘cerebral infarction’ after a CT examination. According to the medical records, the patient developed SLE at the age of 25. CT showed low density lesions of the left pons and occipital lobe; emergent MRI showed bilateral infarction in the cerebellum and brainstem, and magnetic resonance angiography (MRA) showed upper basilar artery occlusion. Ischemic stroke was diagnosed and NIHSS scored 30. The occluded artery was successfully recanalized with endovascular mechanical thrombectomy. Modified thrombolysis in cerebral infarction (mTICI) blood flow perfusion grade was grade 3. The case is the first one in the literature that acute ischemic stroke related to SLE vasculitis and antiphospholipid syndrome was treated successfully with endovascular mechanical thrombectomy.

3053 A Non-biopsied Mystery: Vasculitis or HSV Colitis?

INTRODUCTION: Ischemic Colitis is uncommon in patients with systemic lupus erythematosus (SLE). Herpes Simplex Virus colitis is also very uncommon and tends to occur in immunocompromised patients. Here we report a case of a patient with a lupus flare with ulcers in the colon and HSV esophagitis. CASE DESCRIPTION/METHODS: A 21-year-old female with a PMH of SLE complicated by lupus nephritis, thrombotic thrombocytopenic purpura, and factor XI deficiency admitted for nausea and low urine output. The patient was found to have an active SLE flare, complicated by Guillain-Barre syndrome. Ten days after admission, she was found to have BRBPR, loose stools and mild epigastric abdominal pain. She denied hematemesis. Clinical exam showed bright red blood and evidence of melena on digital rectal exam. Initial workup showed 1 g/dl hemoglobin drop. The patient's EGD revealed a non-bleeding distal esophageal ulcer which was biopsy proven to be herpetic HSV-1 esophagitis (Figure 1), and a single bleeding gastric angioectasia which was treated with argon plasma coagulation. Colonoscopy revealed multiple scattered small circumferential ulceration in the right colon suggestive of ischemic colitis which were not biopsied (Figures 2 and 3). The patient's GI bleed resolved, she was started on Acyclovir. She had complete resolution in her abdominal pain in a week. DISCUSSION: Vasculitis is one of the most commonly recognized complications of SLE. Ischemic colitis due to Intestinal vasculitis can often go unrecognized. The pathophysiology behind gastrointestinal ischemic colitis is the deposition of immune complexes in active disease which leads to tissue damage. Herpes simplex virus enteritis is a very rarely reported entity and tends to complicate the course of inflammatory bowel disease patients and immunocompromised patients. The case we are presenting is likely to be ischemic colitis secondary to SLE vasculitis. The segmental findings of ulcers on the right side of the colon suggest ischemia involving branches of the SMA and point towards SLE vasculitis as the vasculopathy leading to direct tissue damage and eventually ischemia. HSV colitis causes terminal diarrhea, and unlikely to be evident macroscopically. Nonetheless, the patient had active esophageal HSV and is on an aggressive immunosuppressive regimen, so high risk for disseminated HSV. Ultimately, colonic biopsies of the colonic ulceration would have confirmed a diagnosis, but given the overall clinical picture, SLE colitis is more likely.

Cutaneous alterations in vasculitides : Part2: Special aspects of diseases of large, medium and small vessels

Cutaneous vasculitides present with typical clinical signs depending on the size and distribution of the affected vessels. Since there are no large vessels in the skin, giant cell arteritis and Takayasu's arteritis only rarely lead to cutaneous symptoms. The classical systemic polyarteritis nodosa (PAN) is very rare. More frequent is cutaneous PAN presenting with atypical localized livedo racemosa and palpable subcutaneous nodules. The ANCA-associated vasculitides, which belong to the small vessel vasculitides, usually show systemic involvement and manifest on the skin with adiverse picture. Immune complex vasculitides are characterized by deposition of immunoglobulins on the walls of small vessels. The most common form is IgA vasculitis with the cardinal symptoms of palpable, round or oval and partially branched (retiform) purpura and a clear predilection for the legs. Serum disease is apríme example of systemic immune complex diseases due to large circulating immune complexes. Cryoglobulinemic vasculitis primarily involves small as well as medium sized vessels. Simultaneous involvement of vessels of different sizes is characteristic for vasculitis in systemic lupus erythematosus (SLE), Sjögren's syndrome, rheumatoid arthritis and sarcoidosis. Recurrent macular vasculitis in hypergammaglobulinemia is an episodic macular vasculitis of the small blood vessels. Bacteremic vasculitis of the small vessels (without direct microbial infection of the vessel wall) can typically also affect capillaries of dermal papillae and is usually accompanied by adisseminated intravascular coagulation (DIC). In some cases more than one distinct cutaneous vasculitis can occur in the same patient.

032 Il-1b is essential for anti-galectin3 antibody induced cutaneous vasculitis in systemic lupus erythematosus

032 Il-1b is essential for anti-galectin3 antibody induced cutaneous vasculitis in systemic lupus erythematosus

Annals for Educators - 19 February 2019.

Annals for Educators - 19 February 2019.

Utility of neutrophil CD64 and serum TREM-1 in distinguishing bacterial infection from disease flare in SLE and ANCA-associated vasculitis.

Bacterial and opportunistic infections are a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE) and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis owing to treatment with immunosuppressants. Commonly used laboratory tests are unreliable in differentiating infection from active disease patients. Fc receptor (FcγR1 or CD64) expression on neutrophils and soluble TREM-1 (triggering receptor expressed on monocytes) are potential biomarkers of bacterial infections. Our aim was to measure the clinical usefulness of quantitative CD64 measurement on neutrophils and soluble TREM-1 measurements in differentiating bacterial infection from active disease in patients with SLE and ANCA vasculitis. Patients with bacterial infection (n = 25), active disease (n = 51), and healthy controls (n = 20) were included. Neutrophil CD64 expression using flow cytometry and sTREM-1 and procalcitonin levels by ELISA were studied. The percentage of neutrophils with CD64 expression and their mean fluorescence intensity in patients with infection (68.8 (56.9-86.5)%, 1037 (229-1828)) were significantly (p < 0.05) higher as compared to those without infection (7.7 (2.6-13.1)%, 456 (20-968)) and controls (7.05 (1.4-9.5)%, 99.5 (54.7-140.7)). The sensitivity and specificity of CD64 expression on neutrophils to diagnose bacterial infection (using a cutoff value of 30%) was 85% and 84%, respectively, whereas the sensitivity and specificity of procalcitonin was 75% and 85%, respectively. There was no significant difference in soluble TREM-1 levels between the two groups. Quantitative measurement of CD64 on neutrophils can distinguish between systemic infection and the flare of autoimmune diseases.

Zoster after Cyclophosphamide for Systemic Lupus Erythematosus or Vasculitis: Incidence, Risk Factors, and Effect of Antiviral Prophylaxis.

To assess the incidence and the risk factors for zoster in patients exposed to intravenous cyclophosphamide (CYC) for systemic vasculitis or systemic lupus erythematosus (SLE), as well as the protective effect of prophylaxis by valacyclovir (VCV). This retrospective study included all adults treated by intravenous CYC for SLE or systemic vasculitis between 2011 and 2015 at Toulouse University Hospital, France. Zoster occurrence was recorded using medical chart review, laboratory data, and patient interviews. Univariate Cox models were computed to assess the risk factors for zoster and the protective effect of prophylaxis by VCV. The cohort consisted of 110 patients (81 systemic vasculitis and 29 SLE). During a mean followup of 3.4 years after CYC initiation, 10 cases of zoster occurred, leading to an overall incidence of 27.9/1000 patient-years (95% CI 15.2-50.6); it was 59.4/1000 patients (95% CI 27.5-123.6) during the year after CYC initiation. Four patients experienced persistent postherpetic neuralgia. Probable risk factors were lymphopenia < 500/µl at CYC initiation (HR 5.11, 95% CI 0.94-27.93) and female sex (HR 4.36, 95% CI 0.51-37.31). The incidence was higher in patients with SLE (HR as compared with systemic vasculitis patients = 2.68, 95% CI 0.54-13.26). None of the 19 patients exposed to VCV during the followup developed zoster. The incidence of zoster is high in systemic vasculitis and in patients with SLE exposed to intravenous CYC. CYC may favor postherpetic neuralgia. Prophylaxis by VCV should be considered, particularly in cases of lymphopenia < 500/µl at CYC initiation and during the year after.

Anti-tubulin-α-1C autoantibody in systemic lupus erythematosus: a novel indicator of disease activity and vasculitis manifestations.

A variety of autoantibodies has been involved in the pathogenesis of systemic lupus erythematosus (SLE), some of which are well known and applied as disease biomarkers. This study aimed to determine the prevalence of a novel autoantibody, anti-tubulin-α-1C, in patients with SLE and investigate its clinical significance. Anti-tubulin-α-1C autoantibody levels were determined by enzyme-linked immunosorbent assay (ELISA) in 128 SLE patients, 38 primary Sjögren's syndrome (pSS) patients, and 106 healthy controls (HCs).White blood cell (WBC) count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), IgM, IgG, C3, C4, RF, ANA, dsDNA, Sm, AnuA, aCL, anti-SSA, and anti-SSB were measured by standard laboratory techniques. SLE Disease Activity Index (SLEDAI) was evaluated accordingly. Anti-tubulin-α-1C antibody levels were significantly increased in SLE patients. Elevated anti-tubulin-α-1C were correlated with higher levels of SLEDAI, increased titers of anti-Sm antibody, and decreased titers of anti-dsDNA antibody and significantly associated with cutaneous and mucosal vasculitis and milder renal involvement. Anti-tubulin-α-1C may become a novel biomarker indicative of active vasculitis in SLE and could be applied in future clinical practice.

Abstract WMP70: Yield of Screening Tests for Systemic Vasculitis in Ischemic Stroke in Young Adults

Background and Purpose: The causes of ischemic stroke in young adults are more heterogeneous than in the elderly. Sometimes ischemic stroke in young adults is complicated by a systemic vasculitis, which can involve the brain. Therefore, a panel for systemic vasculitis could be considered as one of the etiological work-up of ischemic stroke in young adults. However, little is known about the yield of screening tests for systemic vasculitis in young ischemic stroke patients. Methods: Consecutive patients aged 18 to 45 years with ischemic stroke between January 2011 and June 2017 were included. They all underwent screening tests for systemic vasculitis including rheumatoid factor (RF), antinuclear antibody (ANA), antineutrophil cytoplasmic antibodies (ANCAs), anticardiolipin antibody, lupus anticoagulant, antiphospholipid antibody, anti-DNA antibody, and anti-Ro/SSA and La/SSB antibodies. Results: Among consecutive 2,938 acute ischemic stroke patients during study period, 177 patients (6.0%) were aged 18-45 years. The mean age was 39.0 years. Vasculitis panel screening results were positive in three patients (1.7%). They all had other symptoms or signs of systemic vasculitis. Two female patients with positive ANA and anti-DNA antibody were finally diagnosed as systemic lupus erythematosus (SLE). One patient was compatible with the diagnosis of anti-phospholipid antibody syndrome, and the other patient’s stroke was thought to be related to SLE vasculitis. They all had clinical symptoms of SLE including malar rash and Raynaud phenomenon. One male patient showed positive pANCA. A year previously, he was diagnosed with asthma. Inflammation markers in peripheral blood exams were elevated (CRP 8.21 mg/dl, leukocyte count 17.7/nl), the rate of eosinophilic cells increased (42%). He fulfilled the criteria for the diagnosis of Churg-Strauss syndrome. Conclusions: In the absence of systemic symptoms or signs of vasculitis, vasculitis panel screening in young ischemic stroke patients has a low yield. It’s better to consider individual clinical features and cost effectiveness before screening tests for systemic vasculitis in ischemic stroke in young adults.