Tocilizumab for massive refractory pleural effusion in an adolescent with systemic lupus erythematosus

Background Pleural effusion in systemic lupus erythematous (SLE) is a common symptom, and recent studies demonstrated that IL-6 has a pivotal role in its pathogenesis. Case presentation We report a case of a 15 years old Caucasian boy with a history of persistent pleural effusion without lung involvement or fever. Microbiological and neoplastic aetiologies were previously excluded. Based on the presence of pleuritis, malar rash, reduction of C3 and C4 levels and positivity of antinuclear antibody (ANA) and anti-double stranded DNA (dsDNA), the diagnosis of juvenile SLE (JSLE) was performed. Treatment with high dose of intravenous glucocorticoids and mycophenolate mofetil was started with partial improvement of pleural effusion. Based on this and on adults SLE cases with serositis previously reported, therapy with intravenous tocilizumab (800 mg every two weeks) was started with prompt recovery of pleural effusion. Conclusion To the best of our knowledge, this is the first case of JSLE pleuritis successfully treated with tocilizumab.

A Self-Limited Facial Rash in a Lupus Patient: The Case of Primary Facial Raynaud’s Phenomenon

Skin is involved in 80% of systemic lupus erythematosus (SLE) and the second most affected after joint disease. Lupus-specific lesions include (a) acute ones viz. malar rash (80%), (b) subacute ones viz. photosensitive maculopapular dermatitis (50%), and (c) chronic ones viz. discoid rash. The lupus nonspecific lesions include; (a) nonscarring alopecia (86.67%), oral ulcers (56.67%), vasculitic lesions (33.34%), bullous lesions (10%), and Raynaud’s phenomenon (6.67%). In this case report, we describe a patient with SLE and antiphospholipid antibodies that had developed a transient facial form of Raynaud’s phenomenon that was not associated with disease activity and digital changes. Its association with SLE is discussed.

Differential diagnosis of a thyroid mass, facial malar rash and ptosis on the flora in the primavera by Sandro Botticelli (1445–1510)

Purpose The Primavera is considered amongst the greatest and controversial artistic masterpieces worldwide painted by renaissance artist Sandro Botticelli. The aim was to identify any underlying medical foundations for the painting. Methods Observational study. Results The painting reveals, a ‘butterfly’ malar rash, bilateral ptosis and a clear neck swelling consistent with a goitre in the figure of Flora. This could be explained by concomitant Graves’ disease and systemic lupus erythematosus, or other presentations of multiple autoimmune syndrome. Conclusion These findings highlight the likely presentation of the earliest pictorial depictions of thyroid disease with systemic lupus erythematosus and emphasize the exactitude of depiction demonstrated by Botticelli in renaissance era.

Lupus Eritematosus Sistemik pada Pria

Introduction: Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by presence of nucleus autoantibody and affected multiple organ. Systemic lupus erythematosus is more common in women than men with ratio 2:1 to 15:1. Men with SLE often have a more aggressive clinical course, lead to a poorer prognosis compared with women with SLE. Case Report: A man, 29 years old came to hospital with main complain joint pain increased since 1 week ago, accompanied with red spot on face, trunk, hands, foot, and back, hair loss, swollen leg, mouth ulcer, and fatique. Malar rash and discoid rash were identified from physical examination. From laboratorium, ANA profile was positive for RNP/Sm, Sm, dsDNA, and histone. Skin biopsy showed a lupus discoid. Conclusion: The patient was treated with pulse-dose methylprednisolone for 3 days and showed a good response clinically.

Clinical Manifestation and Hematologic Interpretation of Pediatric Systematic Lupus Erythematosus at Initial Presentation: 2-Years Observation

Background: Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by a spectrum of clinical manifestations, immunological abnormalities, and varied laboratories results. In children, SLE manifestation is particularly more severe, involving more organs. Hematological manifestation has been known as the most common manifestation. The purpose of this study was to describe the clinical manifestations and hematologic interpretation of pediatric SLE at initial presentation.Methods: This retrospective data collection study was conducted at the Department of Child Health Dr. Hasan Sadikin General Hospital Bandung on medical records from a two-year period of 2017–2018. The clinical manifestations were categorized into malar rash, discoid rash, photosensitivity, oral ulcers, arthritis, renal disorders, and neurological disorders. The hematologic interpretations were categorized into anemia, leukopenia, neutropenia, lymphopenia, and thrombocytopenia. Clinical manifestations and hematological interpretations were presented as occurrence percentages and stratified into three age-group of pre-pubertal, peri-pubertal, and post-pubertal.Results: Among 79 pediatric SLE patients (median age 14 years old; IQR 11–16), female gender was predominant. Abnormalities hematologic interpretation occurs in more than half of the patients (83.5%). Malar rash and anemia were the commonest findings among all age groups. Increased occurrence of neuropsychiatric and renal disorders were observed in all age-groups.Conclusions: Malar rash and anemia are important findings among pediatric SLE patients. Furthermore, the occurrences of the neuropsychiatric and renal disorders are also important.

POS0204 AUTOANTIBODIES AND SYSTEMIC LUPUS ERYTHEMATOSUS INDUCED BY ANTI-TUMOUR NECROSIS FACTOR ALPHA THERAPY IN RHEUMATOID ARTHRITIS

Background:Anti-tumour necrosis factor alpha (anti-TNF-α) therapy is commonly used to treat inflammatory conditions such as rheumatoid arthritis (RA). Autoantibodies namely antinuclear antibodies (ANA) induced by these treatments are well established. However, anti-TNF-α-induced systemic lupus erythematosus (SLE) is rarely described and its incidence is yet unknown.Objectives:This study aimed to determine the prevalence of ANA seroconversion and to characterize the development of SLE induced by anti-TNF-α therapy in patients with RA over time.Methods:An observational retrospective cohort study was conducted with at least one year of follow-up. Patients with diagnosis of RA, according to American College of Rheumatology criteria (ACR), and registered on Rheumatic Diseases Portuguese Register (Reuma.pt) who started their first anti-TNFα between 2003 and 2019 were included. Patients with positive ANA (titer ≥100) and/or positive double-strand DNA (dsDNA) antibodies and/or with a diagnosis of SLE at their first visit were excluded. Demographic, clinical and laboratory data were obtained by consulting Reuma.pt. As there are no recognized criteria for drug-induced SLE, the diagnosis of SLE induced by anti-TNF-α was considered if there is a temporal relationship between clinical manifestations and anti-TNF-α-therapy, the presence of at least 1 serologic ACR criteria (ANA or anti-dsDNA) and at least 1 nonserologic ACR criteria (arthritis, serositis, hematologic disorder or malar rash) [1]. Continuous variables are presented with mean, standard deviation, median, quartile 1 and quartile 3. Categorical variables are presented with absolute and relative frequencies.Results:A total of 211 patients (mean age of 49.9±10.9 years old; 84.4% female) were included with a median follow-up time of 6 [3-14] years. We found a seroconversion rate for ANA of 75.4% (n=159) with median treatment duration of 31 [8.5-70.5] months. The most common titre was 1/100 with diffuse and speckled patterns. ANA seroconversion was higher for etanercept (47.8%, n=76) than with adalimumab (23.9%, n=38), infliximab (13.8%, n=22), golimumab (12.6%, n=20) or certolizumab (1.9%, n=3). SLE induced by anti-TNF-α occurred in two patients (0.9%) with erosive and seropositive (rheumatoid factor and anti-citrullinated protein antibodies) RA previously treated with two conventional synthetic disease-modifying antirheumatic drugs, including methotrexate. The first patient, a female with 66 years old and 17 years of disease duration, developed SLE after 16 months of infliximab, with constitutional symptoms, abrupt worsening of polyarthritis, ANA titer of 1/320 diffuse pattern and positive dsDNA (248 UI/mL) antibodies. The second patient, a woman with 43 years old and 11 years of disease duration, developed SLE after 41 months of adalimumab with malar rash and ANA titer of 1/320 diffuse pattern, positive dsDNA (285 UI/mL), positive anti-histone antibodies and hypocomplementemia. In these two cases, anti-TNF-α therapy was stopped and recovery was spontaneous without treatment. The first patient switched to adalimumab and the second switched to golimumab without recurrence of SLE for more than ten years.Conclusion:We found a high rate of ANA seroconversion induced by anti-TNFα therapy in patients with RA. However, similar to previous literature, only 0.9% of patients developed SLE with mild manifestations without major organ involvement. Although the drug with the highest ANA seroconversion rate was etanercept, those responsible for induced SLE were infliximab and adalimumab. Patients improved after discontinuation of therapy and tolerated an alternative anti-TNF-α drug without recurrence of induced SLE over time. Therefore, ANA and SLE induced by anti-TNF-α should be considered and reported in the follow-up of RA patients. Further research is needed to explore the impact of this adverse event on the outcomes of treatment over time.References:[1]Hochberg MC. Arthritis Rheum. 1997;40(9):1725.Disclosure of Interests:None declared

POS0725 CLINICAL AND IMMUNOLOGICAL CHARACTERISTICS OF PATIENTS WITH JUVENILE-, ADULT- AND LATE-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS

Background:Systemic lupus erythematosus (SLE) predominantly develops in women of child-bearing age. However, nearly 20% of cases present during childhood, generally after puberty (juvenile-onset SLE, JSLE). On the other hand, 10-20% of patients develop SLE after the age of 45-50 years (late-onset SLE, LSLE) [1]. It is known that age at disease onset can influence the clinical presentation and course of SLE, but the findings are not always consistent across the studies [2].Objectives:The aim of this study was to evaluate the spectrum of clinical manifestations and autoantibody profile in patients with SLE in the central region of Ukraine regarding age at onset.Methods:The study included 258 SLE patients before starting an adequate therapy, comprising 225 females (87.2%) and 33 males (12.8%). The median age at SLE onset was 28 (20-39) years. The patients were classified into 3 groups: I – age at SLE onset ≤18 years (JSLE; n=52; 20.2%), II – SLE onset at age 19-44 years (adult-onset SLE, ASLE; n=161; 62.4%), III – age at disease onset ≥45 years (LSLE; n=45; 17.4%). The clinical and demographic data, SLE Disease Activity Index (SLEDAI), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and autoantibody profile were analyzed. Quantitative and categorical data were compared using Kruskal-Wallis test and chi-square test, respectively.Results:There was a difference in prevalence of malar rash between the groups (p=0.022): it was more common in JSLE (40.4%) and ASLE (34.4%) than in LSLE patients (15.6%; p=0.04 and 0.05, respectively). Similar distribution was found for renal involvement: JSLE and ASLE patients presented higher rates of nephritis (55.8% and 49.4%, respectively) than LSLE patients (23.8%; p=0.012 and 0.014, respectively). But the groups did not differ significantly with regard to nephrotic syndrome (p=0.224). ASLE was associated with more frequent alopecia (38.8%) comparing with JSLE (19.2%; p=0.04). Moreover, ASLE patients also had the highest frequency of lymphadenopathy (56.3%) whereas in LSLE it was observed only in 25.0% of patients (p=0.001). Serositis was more common in LSLE (54.5%) and ASLE (43.8%) than in JSLE (23.1%; p=0.011 and 0.034, respectively). Although secondary Sjögren’s syndrome was more frequently observed in ASLE (7.6%) and LSLE (7.3%) than in JSLE (0.0%), the difference did not achieve statistical significance (p=0.157). Also, no differences were observed in the occurence of arthritis, pulmonary and neurological manifestations, constitutional symptoms, SLEDAI score among the groups. Median CRP level in LSLE was significantly higher (14.0 (1.1-46.4) mg/L) than in JSLE (0.7 (0.0-12.0) mg/L) (p<0.05). But all groups did not differ significantly with regard to ESR levels. When differences in antinuclear antibodies were analyzed, we disclosed that the frequency of anti-dsDNA positive results was significantly higher in JSLE (68.6%) and ASLE (70.1%) patients when compared with that found in LSLE patients (31.3%) (p=0.016 and 0.001, respectively). There were no significant differences between groups with regard to positivity for other antibodies (anti-Sm, -Ro, -La, -RNP, antiphospholipid antibodies).Conclusion:JSLE and ASLE patients are more likely to have malar rash, nephritis and anti-dsDNA positivity. Alopecia and lymphadenopathy are most frequent in ASLE patients. JSLE are far less likely to have serositis than any other group. Patients with LSLE demonstrate comparatively low frequency of major organ involvement, but they have higher levels of CRP.References:[1]Ambrose N., et al. Differences in disease phenotype and severity in SLE across age groups. Lupus. 2016;25(14):1542-1550.[2]Livingston B., et al. Differences in autoantibody profiles and disease activity and damage scores between childhood- and adult-onset systemic lupus erythematosus: a meta-analysis. Seminars in Arthritis and Rheumatism. 2012;42(3):271-280.Disclosure of Interests:None declared

Covid-19 in Lupus Nephritis

COVID-19 outbreak is currently being concerned for managing patients withimmunological disorders nowadays, including SLE. Lupus is a complexautoimmune disease characterized by the presence of autoantibodies that againstcell nucleus involved many organs in the body. Patients with SLE will increaserisk of severe infection because the intrinsic respond attack with their immunerespond though immunosuppressive drugs consumption, and will potentiallydamage some organs target associated with their disease. Lupus have multipleclinical manifestations with a fluctuating symptom. Patient who come with thesymptom ofbreathlessness will getworse day by day. The symptom could be felt inthe same time as fatigue, joint pain, hair loss, malar rash, oral ulcer, pleuraleffusion and swollen feet. There's a patient with antinuclear antibody positive foranti-smith and anti-Ro/SS-A. She was diagnosed with COVID-19, SLE withnephritis, haemolytic anemia, vasculitis and pleural effusions. The clinicalmanifestations of this patient indicate a COVID-19 with lupus nephritis that hassevere disease. She was being treated with methylprednisolone andhydroxychloroquine for SLE and azithromycin plus oseltamivir as a therapy forCOVID-19. The effect of hydroxychloroquine on SARS-CoV-2 was better seen inpatients with SLE who gotthe medication regularly. Patients went home after 24days of hospitalization after negative RT-PCR results and clinical improvement ofLES.

Covid-19 in Lupus Nephritis

COVID-19 outbreak is currently being concerned for managing patients withimmunological disorders nowadays, including SLE. Lupus is a complexautoimmune disease characterized by the presence of autoantibodies that againstcell nucleus involved many organs in the body. Patients with SLE will increaserisk of severe infection because the intrinsic respond attack with their immunerespond though immunosuppressive drugs consumption, and will potentiallydamage some organs target associated with their disease. Lupus have multipleclinical manifestations with a fluctuating symptom. Patient who come with thesymptom ofbreathlessness will getworse day by day. The symptom could be felt inthe same time as fatigue, joint pain, hair loss, malar rash, oral ulcer, pleuraleffusion and swollen feet. There's a patient with antinuclear antibody positive foranti-smith and anti-Ro/SS-A. She was diagnosed with COVID-19, SLE withnephritis, haemolytic anemia, vasculitis and pleural effusions. The clinicalmanifestations of this patient indicate a COVID-19 with lupus nephritis that hassevere disease. She was being treated with methylprednisolone andhydroxychloroquine for SLE and azithromycin plus oseltamivir as a therapy forCOVID-19. The effect of hydroxychloroquine on SARS-CoV-2 was better seen inpatients with SLE who gotthe medication regularly. Patients went home after 24days of hospitalization after negative RT-PCR results and clinical improvement ofLES.