Low Complement Levels Research Articles

Neonatal thrombotic microangiopathy secondary to factor I variant with Hirschsprung disease.

Neonatal thrombotic microangiopathy (TMA) is a rare and severe disease characterized by a triad of non-immune hemolytic anemia, thrombocytopenia, and organ dysfunction in neonates. We describe herein an early-term infant who underwent hemicolectomy at 4days of age due to intestinal perforation. Following surgery, the patient had recurrent bouts of vomiting and abdominal distention, together with acute kidney injury, non-immune hemolytic anemia, and severe thrombocytopenia. Low complement levels raised the possibility of complement-mediated neonatal TMA. Finally, genetic tests identified a heterozygous mutation in the complement factor I gene. Anti-C5 monoclonal antibody therapy led to complete cessation of the hematological and renal manifestations, but symptoms of intestinal obstruction recurred. Intestinal biopsy demonstrated aganglionosis, compatible with Hirschsprung disease. This presentation is the first known case of neonatal complement-mediated TMA associated with Hirschsprung disease. Moreover, it highlights the importance of considering a diagnosis of TMA in cases of atypical neonatal infectious presentation.

FRI0154 SHOULD BE OLDER PATIENTS TESTED FOR ANTIPHOSPHOLIPID ANTIBODIES? 695 CASES FROM THE RETROSPECTIVE SERIES HIBISCUS

Background:Although guidelines do not recommend antiphospholipid antibodies testing after 60 yo, recent data reported late onset antiphospholipid syndrome (APS).Objectives:To comparatively analyse the clinical, laboratory features and outcomes in 695 cases with primary APS between patients older and younger than 70 yo.Methods:we have performed an international study within the framework of the International Registry of primary APS patients treated with Hydroxychloroquine, HIBISCUS (an ongoing retrospective and prospective register launched in 2016). 28 centres from 17 countries participate. Data about late onset APS were analysed in 695 patients and were obtained from a standardized form registered in the database containing 66 items with respect to demographics, clinical and biological features.Results:Arterial events and especially stroke represented the main initial and recurrent clinical manifestation in 40 primary APS patients older than 70 yo. There were not statistically significant differences with respect to cardiovascular risk factors between the two groups of patients. A significant male predominance, a familial APS history, a higher prevalence of triple positivity, lower complement levels, and anticardiolipin antibodies (aCL) IgA isotype were found in older patients. Low anticoagulation regimens were safe and efficient, with a low relapse rate in older patients.Conclusion:we suggest that the detection of aPL antibodies should be included into the initial screening panel tests in elderly with thrombotic events, especially arterial, in particular those with recurrent stroke and familial APS.Our study further suggests that lower intensity anticoagulation regimens could be a therapeutic option in older APS patients, as no differences in outcomes and relapse rate were found between patients with high and low intensity anticoagulation regimens.

Ciprofloxacin-Induced Reaction Imitating a Lupus Flare: A Case Report

Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect almost any organ in the body. It usually runs a chronic course with systemic inflammation, and age at diagnosis varies from 15 to 44 years. Laboratory reports often show high anti-nuclear antibody (ANA) levels, increased anti-double-stranded deoxyribonucleic acid (anti-dsDNA) levels, and low complement levels. 'Lupus flare' is a term used for an acute exacerbation of previously existing SLE. It usually manifests as an acute worsening of clinical signs and symptoms, along with an abrupt change in typical laboratory values. Triggers for a lupus flare include viral or bacterial infections, acute stress, and various environmental factors such as ultraviolet (UV) light. Ciprofloxacin is a broad-spectrum fluoroquinolone antibiotic used for various bacterial infections. On rare occasions, ciprofloxacin can cause adverse effects in the body, which may resemble an acute flare of SLE symptoms in patients with previously controlled disease. We have presented such a case of ciprofloxacin-induced reactions mimicking a lupus flare in an SLE patient.

Complement Deficiencies Result in Surrogate Pathways of Complement Activation in Novel Polygenic Lupus-like Models of Kidney Injury.

Lupus nephritis (LN) is a major contributor to morbidity and mortality in lupus patients, but the mechanisms of kidney damage remain unclear. In this study, we introduce, to our knowledge, novel models of LN designed to resemble the polygenic nature of human lupus by embodying three key genetic alterations: the Sle1 interval leading to anti-chromatin autoantibodies; Mfge8-/- , leading to defective clearance of apoptotic cells; and either C1q-/- or C3-/- , leading to low complement levels. We report that proliferative glomerulonephritis arose only in the presence of all three abnormalities (i.e., in Sle1.Mfge8 -/- C1q -/- and Sle1.Mfge8 -/- C3 -/- triple-mutant [TM] strains [C1q -/-TM and C3-/- TM, respectively]), with structural kidney changes resembling those in LN patients. Unexpectedly, both TM strains had significant increases in autoantibody titers, Ag spread, and IgG deposition in the kidneys. Despite the early complement component deficiencies, we observed assembly of the pathogenic terminal complement membrane attack complex in both TM strains. In C1q-/- TM mice, colocalization of MASP-2 and C3 in both the glomeruli and tubules indicated that the lectin pathway likely contributed to complement activation and tissue injury in this strain. Interestingly, enhanced thrombin activation in C3-/- TM mice and reduction of kidney injury following attenuation of thrombin generation by argatroban in a serum-transfer nephrotoxic model identified thrombin as a surrogate pathway for complement activation in C3-deficient mice. These novel mouse models of human lupus inform the requirements for nephritis and provide targets for intervention.

P57 IGG4-related disease causing sudden cardiac death

Abstract Background IgG4-related disease (IgG4-RD) is a chronic systemic inflammatory disorder presenting with mass lesions in various organs and showing plasma cell infiltration, storiform fibrosis and obliterative phlebitis on histology. IgG4-RD has previously been identified as a rare cause of sudden cardiac death (SCD) in case reports, but in settings where pathology has been unexpectedly found on post-mortem examination. To our knowledge, there are no published case reports of SCD in patients during treatment for IgG4-RD. Methods A 43-year old chef with a 15 pack-year smoking history presented with portal vein thrombosis, widespread lymphadenopathy, proptosis and inflammatory lung changes. He was found to have IgG4-RD on submandibular lymph node biopsy with storiform fibrosis and abundance of IgG4-positive plasma cells. Test showed a high IgG and low complement levels and a persistent eosinophilia. He was anticoagulated with warfarin for the HPV thrombosis. Treatment with steroids (initially prednisolone 40mg/day) was initially successful and he continued at work and kept fit in the gym. There was also a good biochemical and radiological response to steroids, with normalisation of eosinophil count, IgG level, complements and CRP along with regression of imaging changes. After a period of 12 months steroid weaning (prednisolone 5mg) and having been well at OPD review, he was unexpectedly found dead at home. Post-mortem examination identified IgG4-RD coronary pan-arteritis as the cause of death. The finding of this unanticipated severe complication raises new questions about surveillance and prevention. Results Coronary involvement in IgG4-RD is thought to be rare but may reflect difficulty obtaining coronary artery tissue and clinically silent disease remaining undiagnosed. A systematic review of IgG4-RD outcomes (7 studies comprising 294 patients, follow-up mean of 29 months) identified 26 deaths (8.8%). One was from an aneurysm and four from other cardiovascular disease, while most deaths were from disease progression or cancer. Case reports describe IgG4-RD coronary artery disease pathologies, including inflammatory pseudotumour, periarterial thickening, coronary artery aneurysm and coronary artery stenosis. Conclusion This case raises important questions about identifying and monitoring for asymptomatic cardiovascular involvement in IgG4-RD. Steroid treatment may be less effective for coronary involvement, and in theory, could precipitate rupture or dilatation of the arteries. Recent IgG4-RD management guidelines have not addressed surveillance for cardiovascular disease. ECG and echocardiography are reasonable initial surveillance options, but we suggest clinicians have a low threshold for CT coronary angiography and/or cardiac MR. Invasive coronary angiography and CT-PET can then be used to provide additional information if required. We noted a normal CRP despite active coronary inflammation in our patient and therefore look forward to improved biomarkers for disease activity in IgG4-RD. Disclosures R. Haigh None. L. Smyth None. A. Ludman None.

Association of systemic lupus erythematosus disease activity index score with clinical and laboratory parameters in pediatric onset systemic lupus erythematosus.

Objective:To determine the association of systemic lupus erythematosus disease activity index (SLEDAI) score in pediatric onset SLE (p-SLE) with clinical and laboratory parameters.Methods:This cross sectional observational study was conducted at Division of Rheumatology, Fatima Memorial Hospital, Lahore from November 2018 to January 2019. Total 23 patients diagnosed with p-SLE having onset of symptoms at ≤ 18 years of age, irrespective of their current age at presentation, of either gender, fulfilling criteria of 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria were enrolled. Patients’ clinical symptoms and laboratory parameters were reviewed, SLEDAI scores were calculated. Collected Data were entered in proforma and analyzed on SPSS version 23.Results:There were 91.3% females. Mean age at diagnosis was 11years ± 4years. At presentation patients had hematological involvement 69.6% followed by mucocutaneous symptoms 65.2% and renal involvement 21.6%. ANA by IFA was positive in all, while anti-ds-DNA was positive in 78.3% patients. SLEDAI score was ≥6 in 87% patients, average SLEDAI score was higher in patients with renal involvement (p=0.06). Elevated ESR (r=0.48, p=0.02), Anti-dsDNA (r=0.44, p=0.05) and low complement levels (p=0.03) were significantly positively correlated, while hemoglobin (r= -0.43, p=0.04) was negatively correlated with the SLEDAI score.Conclusion:In this study, patients with Lupus Nephritis had high SLEDAI scores. Elevated Anti-dsDNA titer, ESR, low complement levels and hemoglobin were significantly associated with high SLEDAI scores. We recommend that SLEDAI score should be calculated in p-SLE patients for stringent disease monitoring and treatment.

Diffuse alveolar hemorrhage - An uncommon cause of dyspnea

Diffuse alveolar hemorrhage (DAH) is an uncommon but alarming manifestation of systemic lupus erythematosus (SLE). It can occur anytime during the disease course. Timely and appropriate management can lead to better results improving the patient’s condition. A 21-year-old female presented with fever for 1 month and progressive respiratory distress for 20 days. Laboratory tests revealed raised anti-nuclear antibody and anti-dsDNA along with low complement levels of C3 and C4. Her chest X-ray showed bilateral pleural effusion with diffuse reticulonodular opacities. Computed tomography thorax was done which was suggestive of areas of consolidation and alveolar nodular lesions in bilateral lung fields favoring diffuse alveolar hemorrhage. She was treated with intravenous pulse methylprednisolone, mycophenolate mofetil, and hydroxychloroquine and she improved. Lupus presenting with DAH as its initial manifestation is rare and has got worse prognosis with mortality approaching up to 50%. Therefore, the patient with diffuse alveolar hemorrhage should be evaluated for lupus as delay in initiation of therapy may lead to a rapid worsening of the patient’s condition.

Disordered cutaneous microbiota in systemic lupus erythematosus

The correlation between systemic lupus erythematosus (SLE) and microbiota colonization has been receiving much attention during recent years. Here, we screened the cutaneous bacterial spectrums of 69 SLE patients, 49 healthy controls and 20 dermatomyositis (DM) patients and identified the specific changes of cutaneous microbial composition and abundance in SLE patients. We observed the decreasing diversity in community richness and evenness and the greater heterogeneity in SLE patients compared to healthy controls, which were also different from the cutaneous microbiome of DM patients. The skin microbial community disorders in SLE patients were correlated with several clinical features such as serum low complement level, gender, renal involvement and myositis. According to the Kruskal-Wallis (KW) test, receiver operating characteristic (ROC) curve and LDA Effect Size (LEfSe) analysis, several bacterial taxa such as Staphylococcus, especially Staphylococcus aureus and Staphylococcus epidermidis, were identified to be potential markers for SLE skin lesions. Furthermore, Picrust analysis showed that Staphylococcus aureus infection pathway was significantly enriched and exhibited a strong correlation with genus Staphylococcus in SLE patients. The changes in the composition and abundance of cutaneous microbiota in SLE patients suggest that the microbial dysbiosis is associated with the pathogenesis of SLE, which may be potentially reliable biomarker or therapeutic target for SLE.

Increased levels of anti-dsDNA antibodies in immune complexes before treatment with belimumab associate with clinical response in patients with systemic lupus erythematosus

IntroductionImmune complexes are of importance in systemic lupus erythematosus pathogenesis, and autoantibodies are believed to participate in immune complex formation. Quantification of autoantibody levels in circulating IC might be of prognostic value.MethodsA C1q-binding-eluting technique was applied to purify immune complexes from 55 belimumab-treated systemic lupus erythematosus patients during a 24-month follow-up. Autoantibodies in serum and in solubilized immune complexes were quantified using addressable laser bead immunoassay. We investigated whether levels of autoantibodies in immune complexes associate with disease activity and response to belimumab treatment.ResultsHigh baseline anti-double-stranded DNA and anti-histone levels in immune complexes associated with attainment of zero scores in clinical systemic lupus erythematosus disease activity index 2000 during the 24-month follow-up (p = 0.003 and p = 0.048, respectively). Low complement levels associated with high serum anti-double-stranded DNA and anti-ribosomal P levels (p = 0.003 and p = 0.008, respectively) and high anti-double-stranded DNA (p = 0.002) but not anti-ribosomal P levels in immune complexes. Anti-SSA/SSB serum levels were lower in patients attaining lupus low disease activity state at month 6; these associations were stronger for corresponding immune complex levels. Serum levels of most autoantibodies had declined at month 3, whereas autoantibody levels in immune complexes, except for anti-double-stranded DNA, showed a more gradual decline over 1–2 years. Serum anti-double-stranded DNA levels decreased in all patients irrespective of systemic lupus erythematosus disease activity index 2000=0 attainment, whereas immune complex levels decreased only in achievers.ConclusionImmune complex levels of autoantibodies against double-stranded DNA and the SSA/SSB complex show more specific associations with treatment outcome compared with serum levels in belimumab-treated systemic lupus erythematosus patients. Characterization of autoantibody content in circulating immune complexes could prove useful in treatment evaluation in systemic lupus erythematosus and other immune complex-associated diseases.

Complement Activation in Patients With Probable Systemic Lupus Erythematosus and Ability to Predict Progression to American College of Rheumatology-Classified Systemic Lupus Erythematosus.

ObjectiveTo evaluate the frequency of cell‐bound complement activation products (CB‐CAPs) as a marker of complement activation in patients with suspected systemic lupus erythematosus (SLE) and the usefulness of this biomarker as a predictor of the evolution of probable SLE into SLE as classified by the American College of Rheumatology (ACR) criteria.MethodsPatients in whom SLE was suspected by lupus experts and who fulfilled 3 ACR classification criteria for SLE (probable SLE) were enrolled, along with patients with established SLE as classified by both the ACR and the Systemic Lupus International Collaborating Clinics (SLICC) criteria, patients with primary Sjögren's syndrome (SS), and patients with other rheumatic diseases. Individual CB‐CAPs were measured by flow cytometry, and positivity rates were compared to those of commonly assessed biomarkers, including serum complement proteins (C3 and C4) and autoantibodies. The frequency of a positive multianalyte assay panel (MAP), which includes CB‐CAPs, was also evaluated. Probable SLE cases were followed up prospectively.ResultsThe 92 patients with probable SLE were diagnosed more recently than the 53 patients with established SLE, and their use of antirheumatic medications was lower. At the enrollment visit, more patients with probable SLE were positive for CB‐CAPs (28%) or MAP (40%) than had low complement levels (9%) (P = 0.0001 for each). In probable SLE, MAP scores of >0.8 at enrollment predicted fulfillment of a fourth ACR criterion within 18 months (hazard ratio 3.11, P < 0.01).ConclusionComplement activation occurs in some patients with probable SLE and can be detected with higher frequency by evaluating CB‐CAPs and MAP than by assessing traditional serum complement protein levels. A MAP score above 0.8 predicts transition to classifiable SLE according to ACR criteria.

Serum Complement Levels in Immune Thrombocytopenia: Characterization and Relation to Clinical Features

Background Complement may contribute to platelet destruction in immune thrombocytopenia (ITP), but serum complement levels of ITP patients are not well defined. This study characterized C3, C4, and CH50 levels from 108 ITP patients in comparison with 120 healthy subjects. Methods Results of complement testing performed using commercially available turbidimetric immunoassays were retrospectively analyzed. Mean complement levels in patients with ITP were compared with levels from a sample of 120 healthy subjects, and subgroups of ITP patients were compared. Regression analyses evaluated for relations between low complement levels and disease severity and response to ITP treatments. Results One hundred eight patients with ITP were included. Mean C3, C4, and CH50 were significantly lower in patients with ITP compared with healthy subjects, largely driven by the 32% of patients with ITP with substantial reductions in one or more assays. Patients requiring treatment had lower mean C4 (18.1 vs 23.1 mg/dL; P = .042) and CH50 (50.4 vs 63.0 mg/dL; P = .004). Mean C3 was higher in splenectomized versus nonsplenectomized patients (120.6 vs 101.0 mg/dL; P = .035). In multivariable analyses, reduced complement did not predict treatment response to corticosteroids, intravenous immunoglobulin, or thrombopoietin receptor agonists but low C4 levels did predict more severe ITP (relative to nonsevere disease, odds ratio for severe/refractory disease: 6.28; 95% confidence interval, 0.75-52.54; P = .090). Complement levels in patients with ITP were generally consistent over repeat measurements. Conclusions Complement levels are reduced in one-third of patients with ITP and are associated with more severe disease. Additional study is needed to evaluate if hypocomplementemia is predictive of response to emerging complement-directed therapies.

Clinical characteristics and risk factors of microvascular involvement in primary antiphospholipid syndrome: a longitudinal single-center study in China.

The objective of this study was to investigate risk factors of microvascular involvement and survival in Chinese patients with primary antiphospholipid syndrome. In this single-center, retrospective study, we enrolled 112 patients with a confirmed diagnosis of primary antiphospholipid syndrome who were admitted to Peking Union Medical College Hospital from January 2004 to December 2016. Demographic data, clinical characteristics, laboratory results, and follow-up records were collected. A total of 112 patients with primary antiphospholipid syndrome were studied. Microvascular involvement was identified in 21 patients (18.75%). Patients with microvascular involvement experienced fewer episodes of arterial or venous thrombosis (28.6% vs. 84.6%) and a higher incidence of thrombocytopenia (85.7% vs. 54.9%), respectively. Low complement and elevated high-sensitivity CRP levels were observed more frequently in the microvascular group compared with the non-microvascular group (complement 38.1% vs. 18.7%; high-sensitivity CRP 71.4% vs. 31.9%, respectively). Anti-β2-glycoprotein I antibodies were more prevalent in patients with microvascular involvement than in patients without (66.7% vs. 33.0%, respectively). Multivariate logistic regression analysis revealed that thrombocytopenia (odds ratio = 4.523, 95% confidence interval 1.139-17.962), elevated high-sensitivity CRP levels (odds ratio = 6.385, 95% confidence interval 1.969-20.704), and anti-β2-glycoprotein I antibody positivity (odds ratio = 5.042, 95% confidence interval 1.555-16.352) were independent risk factors for microvascular involvement. A Kaplan-Meier analysis revealed that survival was significantly poorer in patients with microvascular involvement compared with patients without (p = 0.0278). In addition to arterial and venous thrombosis, antiphospholipid syndrome can affect the microvasculature of select organs. It is thus important for clinicians to be aware that antiphospholipid syndrome-associated microvascular involvement has a unique pathogenesis and can be a life-threatening condition.

TTP AS INITIAL PRESENTATION FOR AN 82-YEAR-OLD FEMALE WITH SYSTEMIC LUPUS

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Thrombotic Thrombocytopenic Purpura (TTP) can be idiopathic or acquired. Most common cause for TTP is illegal drugs, other causes are medications like Quinin, Gemcitabine, oxaliplatin, and quetiapine, or in rare cases it can be secondary to other diseases like connective tissue diseases mostly SLE. We are reporting a case of an 82 y/o Caucasian female who presented with TTP which was found to be secondary to underlying undiagnosed Systemic Lupus Erythematous (SLE). CASE PRESENTATION: 82 y/o F newly diagnosed schizophrenia who presented with generalized fatigue, she was found to have hemoglobin of 4.1 and platelet count of 4000 and creatinine level of 1.8. Lab work for hemolysis showed high LDH, low Haptoglobin, and schistocytes where seen on peripheral blood smear. ADAMTS 13 activity was mildly decreased at 38%. TTP diagnosis was made. She received 5 plasmapheresis rounds and she responded very well. Patient renal function was improved after the first round of plasmapheresis. Laboratory work up showed positive ANA and dsDNA with low complement level. Diagnosis of SLE was made. Patient was treated with Prednisone. Patient did very well and she was discharged home on Prednisone in a good condition. DISCUSSION: TTP is a disease of a broader spectrum diseases of Thrombotic Microangiopathy. TTP is defined by hemolysis, renal impairment, Microangiopathy hemolytic anemia, fever, and neurologic symptoms which all exist only in 5% of cases. ADAMTS 13 activity level is a helpful measurement to approach the diagnosis, but mild impairment of ADAMTS 13 level does not` exclude severe TTP. Acquired TTP incidence based on the Oklahoma TTP-HUS registry is three per one million case a year, 1-4% of these cases are related to SLE. SLE usually more common in Asians and African American females between 16-55 years of age and it is extremely rare in older than 65 years. CONCLUSIONS: • Connective tissue diseases should always be considered in the differential diagnosis when a patient presents with TTP • ADAMTS 13 activity is a helpful test for TTP diagnosis, but not always correlate with the severity of the disease Reference #1: 4. Reese JA, Muthurajah DS, Kremer Hovinga JA, et al. Children and adults with thrombotic thrombocytopenic purpura associated with severe, acquired Adamts13 deficiency: comparison of incidence, demographic and clinical features. Pediatr Blood Cancer 2013; 60:1676. Reference #2: 2. Pons-Estel GJ, Alarcón GS, Scofield L, et al. Understanding the epidemiology and progression of systemic lupus erythematosus. Semin Arthritis Rheum 2010; 39:257. Reference #3: 7. Froissart A, Buffet M, Veyradier A, et al. Efficacy and safety of first-line rituximab in severe, acquired thrombotic thrombocytopenic purpura with a suboptimal response to plasma exchange. Experience of the French Thrombotic Microangiopathies Reference Center. Crit Care Med 2012; 40:104. DISCLOSURES: No relevant relationships by Muhammad Farhan Khaliq, source=Web Response no disclosure on file for Hesham Mohamed; No relevant relationships by Dany Tager, source=Web Response

SKIN NECROSIS SECONDARY TO LEVAMISOLE-CONTAMINATED COCAINE USE

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Levamisole has been increasingly detected in street cocaine as an adulterant likely due to its related cocaine effect potentiation. It is also used as a bulking and cutting agent as it is physically similar to cocaine hence enhancing lucrative profit. CASE PRESENTATION: We report the case of a 44 year old male with a prior history of polysubstance abuse ( IV cocaine, IV heroin), right sided endocarditis and MRSA bacteremia, who initially presented to the Emergency Department with a 1 week history of altered mental status and lethargy. The patient had symptoms consistent with sepsis on presentation. Presenting vitals were a blood pressure of 93/57, heart rate of 112 bpm, high grade temperature (40.3 C) and a respiratory rate of 20/min. Clinical examination was remarkable for confusion, dry mucous membranes, regular tachycardia, absence of a murmur, and most notably, a black eschar on both of his ear helices, tip of his nose and multiple needle track marks on both upper limbs. Initial workup showed a Hb of 7.4 g/dl, WBC 4.5 *10 ˆ3 U/L, platelets of 92*10 ˆ3 U/L, creatinine 1.31 mg/dl, BUN 43 mg/dl, and a urine tox screening was positive for cocaine. The patient’s wife reported that he has been using levamisole to cut cocaine and had previous presentations to the hospital with blackish purpuric rash on both dorsal hands that had since resolved after stopping his drug intake. He was admitted to the Intensive care unit (ICU), started on intravenous (IV) fluids and IV broad-spectrum antibiotics pending blood culture data. Blood cultures were positive for MRSA and the patient had septic emboli to the lungs in the setting of tricuspid valve endocarditis. Noted that he was evaluated by plastic surgery who recommended sulfamylon dressing and debridement of the dead tissue. DISCUSSION: Clinically, Levamisole induced skin toxicity manifests typically as large painful bullae and/or necrosis with the face being mostly involved (especially helices and cheeks) as was the case of our patient. The underlying mechanism of skin necrosis may or may not be related to an underlying induced complex-mediated vasculitis. Histopathologic examination may show a small/medium vessel necrotizing and occlusive vasculopathy with fibrin deposition. Interestingly, the workup may show elevated ANA and p-ANCA titers. Low C4 complement levels have also been reported. The diagnosis of our case was mostly clinical with the reported Levamisole use. He was found to have a urine tox positive for cocaine. Levamisole presence in the urine was not tested and is usually not necessary for the diagnosis as the substance has a short half life. CONCLUSIONS: Levamisole related toxicity, though well described in the medical literature, is still under recognized.We present this case to shed light on a clinical presentation that will increasingly face clinicians in the setting of increasing Levamisole-contaminated cocaine use. Reference #1: Lee, K. C., Ladizinski, B., & Federman, D. G. (2012). Complications Associated With Use of Levamisole-Contaminated Cocaine: An Emerging Public Health Challenge. Mayo Clinic Proceedings,87(6), 581-586. https://doi.org/10.1016/j.mayocp.2012.03.010. Reference #2: Chang, A. , Osterloh, J. and Thomas, J. (2010), Levamisole: A Dangerous New Cocaine Adulterant. Clinical Pharmacology & Therapeutics, 88: 408-411. https://doi.org/10.1038/clpt.2010.156. Reference #3: Tallarida, C. S., Egan, E., Alejo, G. D., Raffa, R., Tallarida, R. J., & Rawls, S. M. (2014). Levamisole and cocaine synergism: a prevalent adulterant enhances cocaine's action in vivo. Neuropharmacology, 79, 590 DISCLOSURES: No relevant relationships by Moayad Al Sona, source=Web Response No relevant relationships by Sandrine Hanna, source=Web Response No relevant relationships by Jason Lyons, source=Web Response

Correlation Between Serological Makers and Immunofluorescence Deposits i n Kidney Tissue of Patients with Lupus Nephritis

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease. Few biomarkers for SLE have been validated and widely accepted for the laboratory follow-up of inflammatory activity. In SLE patients, with lupus nephritis (LN), complement activation leads to fluctuation of serum C3 and C4 that are frequently used as clinicalm biomarker of disease activity in SLE. Patients and Methods: In this study the number of patients were 37, seven patients were excluded for incomplete data collection, 28 were females ,2 were males. The duration of the study is two years from 2015 to 2017. Patients were considered to have SLE and LN according to American College of Rheumatology (ACR) criteria, and International Society of Nephrology/ Renal Pathology Society (ISN/RPS). All patients were evaluated withm clinical presentation, laboratory investigations. Our patients underwent kidney biopsy according to standard procedure by Kerstin Amann, and their tissue specimens were studied in the laboratory with light microscope (LM) and immunofluorescence microscope reagents. The relationship between the serological markers and immunofluorescence deposits in kidney biopsy of all patients were studied using the statistical analysis of Pearson correlation and single table student's T test. A P value 0.05 was considered statistically significant. Results: The granular pattern of IF deposits was present in all LN patients, and in more than two third of patients these IF deposits presented in glomerular, tubular, and mesangium sites. While less than one third of patients had IF deposits in the mesangium only. There was no statistically significant correlation between serum ANA, anti-dsDNA, and IF deposits of different types. There was significant correlation between serum C3 and C4 hypocomplementemia and IgG immune deposits in kidney biopsy, and there was significant relationship between serum C3 hypocomplementemia and full house immunofluorescence (FHIF) deposits inm kidney biopsy.Conclusions:Immunofluorescence deposits is mainly granular pattern in LN patients. There was no significant association between serum ANA, anti-dsDNA, and immune deposits in kidney tissue. Immunofluorescence deposits of IgG type correlates significantly with serum C3 and C4 hypocomplemetemia, and these immune deposits in association with low complement levels correlates with LN flare. There was significant correlation between C3 hypocomplementemia and FHIF.

Invasive meningococcal disease in patients with complement deficiencies: a case series (2008\u20132017)

BackgroundTo describe patients with inherited and acquired complement deficiency who developed invasive meningococcal disease (IMD) in England over the last decade.MethodsPublic Health England conducts enhanced surveillance of IMD in England. We retrospectively identified patients with complement deficiency who developed IMD in England during 2008–2017 and retrieved information on their clinical presentation, vaccination status, medication history, recurrence of infection and outcomes, as well as characteristics of the infecting meningococcal strain.ResultsA total of 16 patients with 20 IMD episodes were identified, including four with two episodes. Six patients had inherited complement deficiencies, two had immune-mediated conditions associated with complement deficiency (glomerulonephritis and vasculitis), and eight others were on Eculizumab therapy, five for paroxysmal nocturnal haemoglobinuria and three for atypical haemolytic uraemic syndrome. Cultures were available for 7 of 11 episodes among those with inherited complement deficiencies/immune-mediated conditions and the predominant capsular group was Y (7/11), followed by B (3/11) and non-groupable (1/11) strains. Among patients receiving Eculizumab therapy, 3 of the 9 episodes were due to group B (3/9), three others were NG but genotypically group B, and one case each of groups E, W and Y.ConclusionsIn England, complement deficiency is rare among IMD cases and includes inherited disorders of the late complement pathway, immune-mediated disorders associated with low complement levels and patients on Eculizumab therapy. IMD due to capsular group Y predominates in patient with inherited complement deficiency, whilst those on Eculizumab therapy develop IMD due to more diverse capsular groups including non-encapsulated strains.

Disease presentation of 1312 childhood-onset systemic lupus erythematosus: influence of ethnicity.

To evaluate the influence of ethnicity in presentation of childhood-onset systemic lupus erythematosus (cSLE) patients. This multicenter study included cSLE patients (American College of Rheumatology criteria) followed in 27 Pediatric Rheumatology services of Brazil. Ethnicities were classified in four groups according to the parents' and all four grandparents' self-reported ethnicity. The statistical analysis was performed using the Bonferroni's correction (p < 0.0027). According to ethnic groups, 1537 cSLE patients were classified in Caucasian (n = 786), African-Latin American (n = 526), Asian (n = 8), and others/unknown (n = 217). Comparisons between 1312 African-Latin American and Caucasian revealed similar median age at cSLE diagnosis [12.2(2.6-18) vs. 12.1(0.3-18) years, p = 0.234], time interval to diagnosis [0.25(0-12) vs. 0.3(0-10) years, p = 0.034], and SLEDAI-2K score [14(0-55) vs. 14(0-63), p = 0.781] in both groups. The mean number of diagnostic criteria according to SLICC (6.47 ± 1.911 vs. 5.81 ± 1.631, p < 0.0001) and frequencies of maculopapular lupus rash (8% vs. 3%, p < 0.0001), palate oral ulcers (17% vs. 11%, p = 0.001), tongue oral ulcers (4% vs. 1%, p = 0.001), and nonscarring alopecia (29% vs. 16%, p < 0.0001) were significantly higher in African-Latin American, whereas malar rash (45% vs. 58%, p < 0.0001) was more frequent in Caucasian. The presence of anti-phospholipid antibody (23% vs. 12%, p < 0.0001), low complement levels (58% vs. 41%, p < 0.0001), and isolated direct Coombs test (10% vs. 5%, p = 0.001) was also significantly higher in the former group. Our study demonstrated that disease presentation severity of African-Latin American cSLE patients is comparable with Caucasian. Mucocutaneous manifestations and autoantibodies profile were the only distinctive features of the former group. The unique mixed background of Brazilian patients probably minimized race diversity spectrum of these patients. Key Points • Our study demonstrated that disease presentation severity of African-Latin American cSLE patients is comparable with Caucasian. • Mucocutaneous manifestations and autoantibodies profile were the only distinctive features of African-Latin American cSLE patients. • African-Latin American cSLE patients had more often anti-phospholipid antibodies and hypocomplementemia. • The unique mixed background of Brazilian patients probably minimized race diversity spectrum of these patients.

Changes of Serum IL-6, IL-17, and Complements in Systemic Lupus Erythematosus Patients.

Cytokines activation and low complement levels are common in systemic lupus erythematosus (SLE) patients. This study is aimed to explore the relationship and clinical significance of cytokines and complements with SLE activity. Serum samples of 140 SLE patients and 36 age- and gender-matched healthy controls (HC) were collected. Serum interleukin (IL)-6, IL-17, high-sensitivity C-reactive proteins (hsCRP), and complements (C3, C4) were measured in all samples. These patients were divided into 3 subgroups based on clinical disease activity with SLE Disease Activity Index 2000 (SLEDAI-2K): stationary status subgroup, mild activity subgroup, and moderate/severe activity subgroup. The serum IL-6, IL-17, and hsCRP levels in SLE patients (4.72 ± 0.28 pg/mL, 23.34 ± 1.32 pg/mL, and 4.78 ± 0.34 mg/mL) were significantly higher than those in the HC group (1.51 ± 0.05 pg/mL, 18.28 ± 1.93 pg/mL, and 1.32 ± 0.29 mg/mL), whereas C3 and C4 levels in SLE patients (0.80 ± 0.28 and 0.21 ± 0.08 g/L) were significantly lower than those in the HC group (1.49 ± 0.08 and 0.36 ± 0.02 g/L). A positive correlation was noted between the SLEDAI-2K scores and serum IL-6, IL-17, and hsCRP levels. These results support the proinflammatory cytokines and complements in the pathogenesis of SLE. The serum IL-6, IL-17, and hsCRP levels were correlated with the disease activity.

Unique Characteristics of Prepubertal Onset Systemic Lupus Erythematosus.

Objectives The aim of this study was to investigate the influence of age at disease onset on disease expression and outcomes of pediatric systemic lupus erythematosus SLE (pSLE). Methods A total of 103 patients with pSLE from Sultan Qaboos University Hospital, Oman, were retrospectively studied. Epidemiological, clinical phenotype, disease severity, serology, treatment, and outcome were compared among the three groups using univariate statistical tests. Results The mean disease duration of the cohort was 9.8 ± 4.7 years. The patients were divided into three groups: prepubertal onset (n=39) with mean age at diagnosis of 5.1 ± 2.0 years and pubertal disease onset (n=29) with mean age at diagnosis of 10.8 ± 1.0 years as well as postpubertal disease onset (n=35) group with mean age at diagnosis of 15.3 ± 1.6 years. The prepubertal pSLE cohort demonstrates unique characteristics with increased frequency of familial SLE (61%) of which 49% were from first-degree relatives. Similarly, this group had distinctive clinical features, which included increased renal disease in pubertal and postpubertal groups, respectively (51% vs 23% vs 20%; p=0.039). Prepubertal, similar to pubertal group, had a higher incidence of cutaneous manifestations than in the postpubertal group (74% vs 69% vs 46%; p=0.029). Laboratory features in prepubertal group were distinct with increased frequency of positive anti-cardiolipin antibodies (47%), anti-glycoprotein antibodies (42%), ANCA (62%), and low complement levels (97%) compared to pubertal and postpubertal group. The prepubertal group also has the lowest frequency of positive SSA antibodies (18%) and SSB antibodies (5.1%). The overall mean SLEDAI score in pSLE cohort was 15.6 ± 18.5. The mean SLEDAI scores among the groups showed no significance difference (p=0.110). The overall SLICC DI ≥1 was 36% with a mean damage score of 0.76 ± 1.38. No significant differences in damage index (SLICC DI ≥1) were noted among the groups. Conclusions Distinct clinical features were identified in prepubertal onset pSLE population of Arab ethnicity. Given the high rate of consanguineous marriage and high frequency of familial SLE in this cohort, these manifestations could be explained by higher frequency of genetic factors that influence the disease pathogenesis.

Prevalence of cryoglobulinemia and cryoglobulinemic vasculitis in chronically HCV-infected Brazilian patients

Introduction and ObjectivesCryoglobulinemia is one of the most frequent extrahepatic manifestations of chronic hepatitis C virus (HCV) infection and it may evolve to cryoglobulinemic vasculitis (CryoVas) which is a systemic vasculitis that affects small-sized vessels. The objective of this study was to evaluate the prevalence of cryoglobulinemia and CryoVas in HCV patients in São Paulo, Brazil. Materials and methodsA cross-sectional study was conducted and included sixty-eight viremic HCV patients, without HIV or hepatitis B coinfection. A thorough clinical and laboratory evaluation was performed including the detection of serum cryoglobulins and measurement of serum complement components. The classification criteria for CryoVas were applied. ResultsThe study population comprised mainly women (61.8%) with long term HCV infection (median 11.0 years). Advanced hepatic fibrosis was detected in 20.6% (14/68) of cases. Cryoglobulins were detected in 48.5% (33/68) of HCV-patients with type III cryoglobulinemia being the most frequent. CryoVas was present in 10.3% (7/68) and the main manifestations were peripheral neuropathy (85.7%), palpable purpura (42.8%), arthralgias (42.8%) and renal involvement (42.8%). Life-threatening manifestations were rare. Low hemolytic C2, C4 and total hemolytic complement (CH100) levels were common findings in the cryoglobulinemia group. Low C4 levels were independently associated with the development of CryoVas. ConclusionA high prevalence of cryoglobulinemia and CryoVas was found in Brazilian HCV-patients. CryoVas patients mostly presented non-life-threatening manifestations, especially peripheral neuropathy. Complement abnormalities were common in patients with cryoglobulinemia and low serum C4 levels were associated with CryoVas.