Sars-Cov-2 Induces a Sjogren's Syndrome-Like Phenotype

Sjogren's syndrome (SS) is a chronic and systemic autoimmune disease characterized by lymphocytic infiltration and the development of dry eyes and dry mouth due to the secretory dysfunction of the lacrimal and salivary glands. In recent years, infectious pathogens have been proved to be associated with SS, including Cytomegalovirus, Coxsackie, EBV, and lymphotropic virus-1 (HTLV-1). Studies suggest that infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may trigger an autoimmune response, as evidenced by increased autoantibodies in patients diagnosed with Coronavirus disease 2019 (COVID-19). To investigate the relationship between SARS-CoV-2 and SS, the study was performed by infecting humanized ACE2 mice with SARS-CoV-2. Mice infected with the virus showed a decreased saliva flow rate, elevated antinuclear antibodies (ANAs) and anti-SSB/La, and lymphocyte infiltration in the lacrimal and salivary glands. We detected the viral nucleocapsid protein in mice exocrine glands with significant apoptotic bodies by the acinar cells. Confirmed with clinical data, we also observed the elevation of SS-specific autoantibodies (ANA, anti-SSB/Ro52, and anti-SSA/La) and specific ANA patterns in sera from COVID-19 patients. One unique aspect of SS is the high degree of sexual dimorphism, with women being affected 10-20 times more than men. To determine whether COVID-19 patients exhibited an element of sexual dimorphism in the autoantibody response, we grouped the sera by sex. We found the male patients showed elevated anti-SSA/Ro52 compared to female patients (p=0.0029), and female patients had more diverse ANA patterns. Lastly, monoclonal antibodies isolated from recovered patients using singlecell antibody nanowells technology were shown to recognize the nuclear antigens. Overall, by observing SS-like phenotypes in mouse models and patients, our study confirms a direct pathogenic role of SARS-CoV-2 in SS.

Immunogenicity and Safety of Chadox1 Ncov- 19 Vaccine in Primary Sjogren's Syndrome

Introduction. There are few studies that evaluated the response to Covid- 19 vaccines, in primary Sjogren's Syndrome (pSS) and none evaluated ChAdOx1 n-Cov19 (AstraZeneca/Fiocruz). The aim of this study was to evaluate the efficacy and safety of the ChAdOx1 n-Cov19, a viral vector vaccine, in pSS compared to healthy control (HC). Methods. Patients with pSS >18 years, classified according to ACR/EULAR 2016 were included. Neutralizing antibodies against the Receptor Binding Domain - RBD portion of the Spike protein of SARS-CoV-2 (IgGS) were measured by chemiluminescence (Abbott), before the first dose (D0) and 28 days after the second dose (D28*). The test is considered reactive if >50 AU/ml. Results. Sixty pSS patients and 62 HC were recruited from a single center (HUCAM-UFES, Vitoria, ES, Brazil). The HC group was homogeneous for sex (92% women) and younger than HC (47+/-11 vs. 39+/-13, p<0.05). In the pSS group, 45.2% were anti-Ro positive, mean ESSDAI was 3.2, 83.3% were using DMARD or immunosuppressant/biological therapy, 31.9% were in high immunosuppression. The frequency of mild adverse events (AE) was similar in both two groups. No serious AE, hospitalizations or death were reported. There was no difference between the PGA ("Patient's Global Assessment") after vaccination (4.5 vs.5, p=0.903). Among seronegative individuals at baseline, the seroconversion rate (100% vs. 89%, p=0.02) was lower, and geometric mean titers (GeoMean IgG-S) was similar in pSS=696.9(CI95%237.6 -2,043) compared to HC=1,986(CI95%1,463-2,697;p=0.316). However, in those with high immunosuppression, the seroconversion (71%, p=0.001) and GeoMean titers were lower 229.4 (CI95%14.64-3,594, p=0.004). Patients in moderate to high disease activity (ESSDAI >=5) showed lower seroconversion (60%, p=0.006) and Geomean titers 31.7 (CI95%0.06-15.4;p=0.004). Conclusions. ChAdOX1 vaccine is safe and induced high GeoMean neutralizing antibodies titers and seroconversion rate in pSS patients similar to HC. Immunossuppression therapy and disease activity decreased the immune response to the vaccine.

A CASE OF ANTISYNTHETASE SYNDROME: THE IMPORTANCE OF HISTORY IN DISTINGUISHING ETIOLOGY OF INTERSTITIAL LUNG DISEASE IN A COVID-19 WORLD

SESSION TITLE: Systemic Diseases Causing Pulmonary Havoc SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: In the coronavirus disease 2019 (COVID-19) era, the etiology of interstitial lung disease (ILD) should remain broad to ensure accurate diagnosis and the proper treatment of patients. Vital to the art of medicine is taking a comprehensive history, and anchoring on a common diagnosis such as COVID-19 can result in early dismissal of alternate etiologies that physicians have an obligation to explore. CASE PRESENTATION: A 58-year-old male with a history of diabetes, hypothyroidism, and hypertension presented to the emergency department (ED) with dyspnea and fever. Initial CT chest imaging was significant for reticular and fibrotic changes with peripheral ground-glass and solid nodular opacities, some with areas of central clearing. Despite negative PCR testing, he was diagnosed with COVID-19 and discharged on oxygen with pulmonary follow-up. He continued to have arthralgias, proximal muscle weakness, low-grade fevers, and weight loss. He re-presented to the ED and was admitted for hypovolemia and further exploration into a potential autoimmune etiology of his symptoms. Labs were significant for a creatine kinase of 3,381 U/L, positive autoimmune antibodies [ANA (1:320), Jo-1 (>8.0 U), and SS-A/Ro (1.4 U)], and elevated ESR and CRP (30 mm/hr and 81 mg/L). Repeat CT revealed persistent parenchymal changes. Bronchoscopy was performed without anatomical abnormalities, and bronchoalveolar lavage (BAL) fluid was normal in appearance and negative for infectious etiologies. Though the patient was a farmer and possessed risk factors for hypersensitivity pneumonitis, lack of lymphocytic predominance on BAL, negative hypersensitivity panel, and uncharacteristic CT findings helped exclude this diagnosis. The patient was diagnosed with antisynthetase syndrome and treated with pulse dose intravenous solumedrol before transitioning to prednisone with resolution of muscle weakness and radiographic improvement in lung infiltrates. Muscle biopsy was deferred given the rapid clinical response and serum markers consistent with the diagnosis. DISCUSSION: Antisynthetase syndrome is a rare cause of ILD and often presents with myositis, arthritis, skin changes, Raynaud's phenomenon, and fever [1]. These symptoms, combined with the aminoacyl-tRNA synthetase antibody—most commonly the Jo-1 antibody—help confirm the diagnosis [2]. Due to a lack of established diagnostic criteria, muscle biopsy is often used to exclude other causes of myositis [3]. The ILD associated with antisynthetase syndrome is a significant cause of morbidity and mortality, and delay in diagnosis can lead to progression of lung injury. CONCLUSIONS: Chest imaging findings in COVID-19 are nonspecific, and post-COVID lung disease often presents similarly to other ILDs [1]. Because of this, history and physical exam remain crucial tools to reflect on alternate diagnoses for ILD and will continue to be necessary as we evolve through this COVID-19 era. Reference #1: Devi HG, Pasha MM, Padmaja MS, Halappa S. Antisynthetase Syndrome: A Rare Cause for ILD. Journal of Clinical and Diagnostic Research : JCDR. 2016;10(3):OD08. doi:10.7860/JCDR/2016/16872.7361 Reference #2: Cavagna L, Trallero-Araguás E, Meloni F, et al. Influence of Antisynthetase Antibodies Specificities on Antisynthetase Syndrome Clinical Spectrum Time Course. Journal of Clinical Medicine. 2019;8(11). doi:10.3390/jcm8112013 Reference #3: Schmidt J. Current Classification and Management of Inflammatory Myopathies. J Neuromuscul Dis. 2018;5(2):109-129. doi: 10.3233/JND-180308. PMID: 29865091;PMCID: PMC6004913. DISCLOSURES: No relevant relationships by Dustin Norton No relevant relationships by Alyssa Simon No relevant relationships by Kang Rui Xiang

ONE YEAR PROGRESSION of INTERSTITIAL LUNG DISEASE in CONNECTIVE TISSUE DISEASES. A DESCRIPTIVE STUDY in A SINGLE TERTIARY CENTER

Background: Interstitial lung disease (ILD) in connective tissue diseases (CTD) is an important cause of morbidity and mortalitiy. Objectives: To evaluate ILD in CTD (systemic sclerosis, myositis, Sjögren syndrome, rheumatoid arthritis, mixed connective tissue disease), sarcoidosis and interstitial pneumonia with autoimmune features and its progression in 12 months evaluated through high resolution computed tomography (HRCT) and pulmonary function test (PFT). Methods: A retrospective single tertiary center cohort study in CTD-ILD outpatients seen between 2012 and 2021. Clinical, serological data, PFT and HRCT results were collected. ILD patterns were classifed into: usual interstitial pneumonia (UIP), inconsistent UIP, nonspecifc interstitial pneumonia (NSIP), fbrosing NSIP, organizing pneumonia, interstitial lymphoid pneumonia and associated to sarcoidosis. Progression of ILD was defned as:->10% decline in FVC in PFT.->15% decline in DLCO in PFT.-Progression of fbrosis in HRCT. IBM SPSS v23 was used for statistical analysis. Results: 51 patients were collected. Baseline characteristics are shown in Table 1. Figure 1 shows ILD progression in 1 year. During follow up, 1 patient with sarcoidosis died of COVID19 bilateral pneumonia. Conclusion: In our series most patients were middle aged women. Anti-Ro antibodies and smoking status (former or current) were common among patients. Common clinical features were Raynaud (45%), skin affection (45%) and arthritis (40%). 47% of the patients expressed dyspnea at ILD diagnosis. 29,4% were treated with MP pulses, 23,5% with rituximab, 31,4% with mycofenolate mophetil. Fibrosing pattern in HRCT (UIP and fb-NSIP) was the most prevalent. 20% of the patients had progressive fbrosis under PFT criteria and 18% under HCRT. More studies of ILD-CTD are necessary to identify factors for progression and response to treatment and throw out more conclusions of prediction and prognosis of disease.

PRIMARY SJÖGREN'S SYNDROME with JUVENILE ONSET: REPORT of 15 CASES

Background: Primary Sjögren's syndrome (pSS) is a chronic and progressive multisystem autoimmune disease which rarely onset in children and adolescents. Diagnostic delay in large part of patients are common due to the non-specifc and variable symptoms and the slow progression of disease. Objectives: To analyse demographic data, specifc extraglandular, salivary and ocular manifestations, laboratory parameters and therapy of pSS with juvenile onset. Methods: Retrospective study of all patients (pts) with pSS in single center. Results: pSS was verifed in 15 pts (6.7% were boys), which amounted to 23.8% of all pts with SS in our pediatric rheumatologic department. The median age of pSS onset was 8.0 y.o. [IQR 7.0;10.2]. The median of disease duration at the time of pSS verifcation was 2.75 years [2.2;5.6]. All patients had systemic manifestations at onset: constitutional abnormalities-33.3%, nonerosive polyarthritis-64.3%, polyarthralgias-26.7%, lymphadenopathy-73.3%, cutaneous involvement-53.3% (2-xerosis, 2-annular erythema, 1-erythema nodo-sum, 2-Raynaud phenomenon, 2-nonspecifc spotty rashes, 1-hemorrhagic rash). At the time of diagnosis 7 pts (46.7%) had isolated involvement of salivary glands, 8 pts (53.3%)-combined with involvement of lacrimal glands. The decrease in salivary gland function was recorded in 80% of cases, hypolacrimia-in 46.7%, 1 patient had isolated hypolacrimia. Recurrent parotitis was present in 6 pts (40.0%). At time of diagnosis pulmonary involvement had 20.0% of pts, 1 patient had renal tubular acidosis. 8 pts (53.3%) had various hematological disorders: anemia-in 3 pts (20.0%), leukopenia-in 6 (40.0%). ANA Hep-2 were detected in 100% pts (in titer 1/640-4, 1/1280-7, 1/2560-3, 1/20480-1, with mixed patterns in all pts: speckled + homogeneous-9 pts, speckled + homogeneous+cytoplasmic-6 pts), anti-Ro-in 12 pts (80.0%), anti-La-in 8 pts (53.3%), RF+-in 9 pts (60.0%). 6 pts (40.0%) had polyclonal hypergammaglob-ulinemia, max 42%. 2 pts (13.3%) had concomitant autoimmune non-rheumatic disease;1-cutaneous psoriasis, 1-autoimmune thyroiditis. The treatment of each patient was justifed by the main individual manifestations: 93.3% received glucocorticoids, 26.7%-methotrexate, 33.3%-hydroxychloroquine, 6.7%-mycophenolate mofetil. Treatment with biologics (B) was received by 13 (93.3%) pts (7-rituximab (RTM), 6-abatacept (ABA)) with a good response in 10 pts, including improvement in the function of the salivary and lacrimal glands in 7 pts. 1 patient received 2B-RTM and ABA sequentially due to the development of MAS 7 days after 1st RTM infusion. B was discontinued in 3 pts: 1 due to development of hemorrhagic vasculitis 2 days after the 1st RTM infusion, 1-COVID-19 with lung involvement (CT 3-4) 2 weeks after the 1st RTM infusion, 1-inefficiency of ABA during 15 months. Conclusion: In our pediatric rheumatologic department pts with pSS made up less than a quarter of all pts with SS. The diagnosis was verifed delayed in all pts, which can be explained by a wide range of nonspecifc manifestations at the onset. However, the manifestations of SS that were present at the time of diagnosis were brought under control on the background of complex therapy, including the prescription of B, with a good efficacy and safety profile of therapy.

SLE ONSET POST COVID-19 VACCINATION: COINCIDENTAL or ASSOCIATION?

Background: Numerous immune-mediated diseases fare or new disease onset after SARS-CoV2-vaccination have been reported. There were case reports showed the immune-mediated disease fare post vaccination but study on new disease occurs post Covid-19 vaccination is still lacking. Objectives: To describe two SLE cases that diagnosed post Covid-19 vaccination. Methods: Case report Results: 14 years old girl, post Covid-19 vaccination 1st dose 3 weeks ago presented with 2 day history of giddiness, breathlessness, vomiting and diarrhea prior to admission. She also complained of frothy urine for the past 1 week associated with lower limbs swelling and facial puffiness. Clinical examination noted she had sparse hair, oral ulcers and discoid lupus at the ear concha. She also noted to have periorbital puffiness with pedal edema. Lung auscultation noted bi-basal crepitations. Blood investigation noted ANA positive (1:640, speckled) with low complement 3 (0.1g/L). Her full blood count showed leucopenia (3100 UL) with low lymphocyte count of 810UL. UFEME noted protein of 3 + and red blood cell of 2+ with normal renal profile. Her serum albumin was 22g/L. Chest x ray showed clear lung field with no cardiomegaly. Her 24-hour urine protein showed proteinuria of 2.345g/dl and her renal biopsy showed mesangial proliferative lupus nephritis class iI. She was given intravenous methyl-prednisolone 500mg OD for 3 days and discharged with tapering dose of prednisolone, hydroxychloroquine, calcium supplements, perindopril and frusemide. Another case was a 17 year-old female, post covid-19 vaccination 10 weeks, presented with 3 weeks history of bilateral lower limbs weakness with difficulty in getting up from chair. She also had fever on and off with cough for 1 week. There was no alopecia, oral ulcer, facial rash or photosensitivity. No joints pain. Clinical examination noted presence of proximal myopathy with stable vital signs. Other systemic examinations were unremarkable. Blood investigation noted ANA positive (1: 640, homogenous and speckled) with low complements level (C3 0.19g/L and C4 0.049 g/L).Her creatine kinase was 2367U/L and EMG showed evidence of irritable myopathic process which is consistent with inflammatory myositis. Her TFT was normal. Myositis panel showed anti-Ku and anti-Ro 52 were positive. She was treated as SLE with myositis and intravenous methylprednisolone was given. She discharge well with tapering dose of prednisolone and azathioprine. Her creatine kinase showed improvement with immunosuppression therapy and she was advised on intensive physiotherapy. Conclusion: The onset of these two SLE cases were occurred within the 2 month of post covid-19 vaccination. Whether Covid-19 vaccination direct contribute to the occurrence of SLE remained inconclusive. More studies are required to show its correlation between onset of SLE and Covid-19 vaccination.

A RARE CASE of ACUTE INFLAMMATORY DEMYELINATING POLYRADICULOPATHY FOLLOWING the SECOND DOSE of PFIZER COVID-19 VACCINE

Background: We present a case of a 36 year-old female who developed Acute Immune-mediated Demyelinating Polyneuropathy (AIDP) after receiving the second dose of Pfzer COVID-19 vaccine. Objectives: To report a rare auto-immune complication of COIVD-19 vaccination. To educate and inform physicians about the approach to diagnosing AIDP and narrowing down its etiology. Methods: Case report and literature review Results: A 36 year-old female with no signifcant past medical history presented to the hospital with progressive bilateral paresthesia. She started to experience numbness and tingling sensation in her extremities 1 week after receiving the second dose of Pfzer COVID-19 vaccine. Following 5 days of symptoms onset, she was no longer able to hold onto objects and experienced difficulty ambulating without assistance. Physical exam was notable for decreased distal sensation to touch and pain in all 4 limbs, otherwise, the rest of her neurological and musculoskeletal evaluation was normal. MRI-head showed small scattered foci of increased FLAIR signal in the white matter, suggesting an underlying infammatory process. Electromyography (EMG) was performed and showed evidence of acute diffuse sensorimotor neuropathy with mixed axonal and demyelinating features. These results along with the clinical features allowed us to diagnose our patient with Acute Immune-mediated Demyelinating Polyneuropathy (AIDP). Extensive autoimmune workup, including anti-GM1, GD1b, Gq1b, ANA, DS-DNA, RF, CCP, and C/P ANCA, were unremarkable. She had positive anti-Ro atb but did not have any clinical or physical features that would suggest Sjogren's Syndrome. Vitamin levels (B12, folate, thiamine) were found to be normal. Infectious workup of serum and CSF which included hepatitis serologies, Campylobacter jejuni serology, Lyme atb, CMV atb, EBV atb were all negative. The possible etiology of her disease was attributed to Pfzer COVID-19 vaccine given the temporal correlation. She was subsequently treated with 6 cycles of IVIG which resulted in moderate symptomatic improvement. Conclusion: AIDP is an autoimmune-guided infammatory neuropathy which result in axonal degeneration of myelinated nerves [1]. In some extremely rare cases, molecular mimicry following vaccination may lead to this disease [1]. There have been reports of AIDP linked to Johnson & Johnson and AstraZeneca COVID-19 vaccines [2]. Recently, a few cases have also been observed with Pfzer COVID-19 vaccine [2-3]. Interestingly, the majority of these cases occurred after the frst dose of the vaccine, making our case even more peculiar [2]. We report this case as physicians should be made aware that AIDP is a potential complication of COVID-19 vaccination. Given the extreme rarity of these cases, it is also important to note that more common infectious and autoimmune etiology of AIDP should be investigated before attributing any potential causal relationship to COVID-19 vaccines.

Subacute cutaneous lupus erythematosus after COVID-19 vaccination

Numerous cutaneous reactions have been reported secondary to COVID-19 vaccinations. The most commonly reported include local site reactions, delayed large local reactions, urticaria and morbilliform eruptions. Here we report a case of de novo subacute cutaneous lupus erythematosus (SCLE) after COVID-19 immunization. A 56-year-old woman presented with a 3-month history of a rash. The onset was 1 week following the first dose of the AstraZeneca COVID-19 vaccine. She reported lesions characterized by erythema, pruritus and a burning sensation. She also described mouth dryness. Examination revealed scaly annular erythematous plaques on the chest, arms, legs and scalp. Blood results were positive for anti-Ro antibodies and strongly positive for anti-nuclear antibodies (1: 2560 titre). Anti-Smith, anti-centromere and double- stranded DNA antibodies were negative. Skin biopsy revealed the histological appearance of an interface of dermatitis. Direct immunofluorescence was negative. These clinical and histopathological findings are consistent with a diagnosis of SCLE. The patient was treated with hydroxychloroquine, a weaning course of prednisolone, topical steroids and topical tacrolimus. Her hydroxychloroquine dose was 200 mg twice daily for the first 3 months and then increased to 400 mg twice daily. This resulted in an improvement of her presentation although she has yet to achieve complete remission. It has been suggested that enhanced interferon responses with COVID-19 vaccination and interactions of the SARS-CoV-2 spike protein with cytoplasmic RNA-binding proteins could contribute to disease flares in lupus. There are two other recent reports of SCLE developing or being exacerbated by COVID-19 vaccination. More research is required to determine how COVID-19 vaccinations affect patients with autoimmune skin diseases.

A Case of Transverse Myelitis After Moderna SARS-CoV-2 Vaccination

Objective: This case report describes a longitudinally-extensive transverse myelitis after Moderna SARS-CoV-2 vaccination. Background: Transverse myelitis (TM) is an inflammatory spinal cord syndrome presenting with acute-to-subacute neurological deficits. A lesion spanning three or more vertebral segments on imaging is considered “longitudinally-extensive.” The TM differential is broad-- among these etiologies, vaccination is a rare but recognized entity. Design/Methods: 60-year-old, right-handed man with chronic right hemisphere stroke with residual left hemiparesis admitted for four days of bilateral lower extremity numbness progressing to weakness and urinary and bowel incontinence 10 days after receiving his second Moderna SARS-CoV-2 vaccination. Examination showed hypotonic lower extremities, proximal greater than distal weakness, a T9 dermatome sensory level, perineal numbness, mildly-reduced rectal tone, and preserved reflexes. MRI spine revealed a longitudinallyextensive, non-enhancing T2-hyperintense lesion spanning T8-T12. CSF analysis demonstrated 5 white blood cells, 1271 red blood cells, 124 glucose, and 55 protein. Aside from mildly elevated ESR and CRP, extensive serum and CSF work-up for other causes of myelopathy, including nutritional/toxic (copper, zinc, heavy metals), infectious (RPR/VDRL, HIV, HTLV, HSV, VZV, West Nile), and rheumatologic (anti-Jo, anti-Mi-2, anti-Ro/La, anti-smith, anti-Scleroderma, anti-dsDNA, anti-ribosomal P, anti-RNP), were unremarkable. Anti-NMO and anti-MOG antibodies were negative. He improved with methylprednisolone 1000 mg daily for five days suggesting an autoimmune etiology. Results: NA Conclusions: Transverse myelitis has a broad presentation and differential, requiring detailed history-taking to determine the cause as management differs between etiologies. SARS-CoV-2 and post-vaccination are known etiologies for TM. Given the timing of our patient's symptom onset after vaccination and thorough exclusion of other causes, we postulate a potentially novel case of TM associated with the Moderna SARS-CoV-2 vaccine. Though post-vaccination myelopathy is potentially debilitating if untreated, it is rare, and the benefits of vaccination appear to outweigh the risks.

NEW-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS FOLLOWING COVID-19 VACCINATION: A REPORT OF TWO CASES

Background/Aims There is a growing number of reports of new-onset autoimmune disease or complications of underlying autoimmune disorders following COVID-19 infection and vaccination. Methods We describe two cases of systemic lupus erythematosus (SLE) that developed De novo in two female patients shortly after receiving their COVID-19 vaccinations. Results The first case is a 29-year-old female with no prior medical history. One week following her COVID-19 Pfizer/BioNTech vaccination, she developed widespread pruritus, fatigue, myalgia, arthralgia, fever and night sweats. Blood tests showed pancytopenia and she was referred for an urgent haematology opinion due to lymphoma. Positron Emission Tomography/computed tomography (PET/CT) demonstrated widespread lymphadenopathy. Bone and lymph node biopsy showed reactive changes only. Her symptoms progressed with polyarticular inflammatory arthritis, oral ulceration, Raynaud's, pleuritic chest pain, palmar purpuric rash, and a widespread tender urticarial rash. Further investigations showed low complement C3/C4, anti-double stranded DNA antibody titre (dsDNA) >200 IU/mL, positive Anti-Ro antibody, positive Anti-La antibody, weakly positive anti-RNP antibody and an Anti-C1q antibody >400 units/ml with a urine protein/creatinine ratio (PCR) of 39 mg/mmol. A diagnosis of SLE with urticarial vasculitis was made and she commenced Hydroxychloroquine in addition to weaning prednisolone (60mg). A skin biopsy confirmed lupus vasculitis. Despite high dose prednisolone, urine PCR increased over 2 weeks from 39 to 84 mg/mmol. Renal biopsy demonstrated class 3 lupus nephritis. She was pulsed with 500mg IV methyl prednisolone over 3 days and commenced mycophenolate 1g BD. Within weeks she was in clinical remission. The second case is a 70-year-old female with a past medical history of diverticulosis, uterine fibroids and small hand joint osteoarthritis. She presented with a sudden onset, 6-week history of bilateral symmetrical small and large joint synovitis that developed 8 days following the first dose of the COVID-19 Oxford-AstraZeneca vaccine. Her investigations showed reduced lymphocyte counts (0.9 109/L), raised CRP 26 mg/L and ESR 32 mm/hr. Antinuclear antibodies were weakly positive with a homogenous pattern. DsDNA titre was raised at 175 IU/mL and C4 reduced at 0.14 g/L. There was no proteinuria or any evidence of major internal organ involvement. She was started on a short reducing course of oral prednisolone given the severity of her presenting clinical features. Her symptoms improved, with no recurrence on stopping steroids but she has continued elevation in DsDNA;a conservative management approach is being adopted. Conclusion Both cases met the EULAR/ACR and SLICC classification criteria for SLE. There was a clear temporal association between the onset of SLE symptoms and COVID-19 vaccination. Our cases raise the possible association/causation of SLE following COVID-19 vaccination. Potential mechanisms include immune responses elicited by the COVID-19 vaccination, triggering autoimmunity in genetically predisposed individuals. Further research and data from registries are required.

DOENÇA AUTO-IMUNE SUGERINDO AO PET RECIDIVA DE LINFOMA HODGKIN - CONFIRMAÇÃO DA NECESSIDADE DE RE-BIOPSIAR SÍTIOS SUSPEITOS

Relato de caso: STP, 49 anos, feminino, diagnóstico Linfoma Hodgkin Clássico, Estadio III agosto/2019. Tratamento: ABVD, 4 ciclos + Radioterapia, resposta completa ao PET CT dezembro/2019. HP: Artrite Reumatóide diagnosticada 2015, em remissão e sem tratamento na ocasião do diagnóstico do Linfoma Hodgkin;Hipertensão Arterial Sistêmica. Após 8 meses do término tratamento do linfoma teve infecção por Covid-19 e percebeu gânglio palpável região axilar direita. VHS 102 mm. Realizou PET CT - aumento do metabolismo glicolítico em linfonodomegalias supra e infradiafragmáticas compatíveis com doença linfoproliferativa em atividade. Maior linfonodo: axilar direita nível II medindo 25,6 × 10 mm e SUV = 4,97. Biópsia de linfonodos axilares e cervicais à direita: Hiperplasia reacional. Imunohistoquímica negativa para malignidade na amostra. Mantinha bom estado geral, sem sintomas B, sorologias virais negativas para hepatites, CMV, EBV, HIV. Evoluiu nos meses seguintes com herpes zoster região inguinal esquerda, artralgia simétrica de mãos, ombros e joelhos, além de relato de olhos e boca secos. No exame físico mantinha linfonodomegalia axilar direita móvel e indolor 4 cm e linfonodomegalia em cadeia cervical anterior direita 2 cm. TC tórax: linfonodomegalia axilar direita e supraclavicular. Fator Anti-Nuclear positivo, Anti-Ro positivo, hipergamaglobulinemia policlonal. Us glândulas salivares com aumento de volume e padrão sugestivo de parotidite inflamatória. Feito diagnóstico de Síndrome de Sjogren e iniciou tratamento com corticóide e metotrexato, com rápida melhora dos sinais e sintomas clínicos. Três meses após repetiu PET- CT - redução das dimensões e intensidade do metabolismo glicolítico nas linfonodomegalias supra e infradiafragmáticas (Deauville 2). VHS 18 mm. Conclui-se agora contexto de doença oncohematológica em remissão, assim como doença reumatológica em controle sob tratamento. Paciente segue em acompanhamento trimestral, sem queixas clínicas.

An unusual case of systemic lupus erythematosus with Sjögren syndrome and recurring episodes of macrophage activation syndrome in a boy - difficulties to diagnose, difficulties to treat

Introduction: systemic lupus erythematosus with juvenile onset (jSLE), especially in boys, can occur with unusual manifestations, including Sjogren's syndrome (SS), accompanied by unexpected complications and difficulties in choosing therapy. Objectives: to present a rare case of successfully application of abatacept in an jSLE+SS in a boy who had two episodes of macrophage activation syndrome (MAS). Methods: Case report. Results: 4-year-old boy admitted to our clinic for the first time in 2010 presenting the 6-month history of disease. There were fever up to 39°C, polyarthritis, anemia, trombocytopenia, hyperIgG-emia, increase TA (2N), CRP (20 mg/l), RF 30 mg/l at the disease onset. Initially JIA, polyarthicular sybtype, RF+ was diagnosed in regional hospital. Treatment with NSAIDs, GC iv 125 mg No3, methotrexati 7,5 mg weekly was started. During the next 3 weeks laboratory results were constantly getting worse (HB 80 τ/π, trombocytes 145000, leucocytes 1000, increase TA 10N) and new clinical symptoms occurred (maculopapular rash with itching;splenomegaly;febrile fever). He received GC iv + per os 1 mg/ kg with a short-term effect. On 1st admission in our clinic in September of 2010, he had general fatigue and tiredness, classic malar rash, severe cutaneous vasculitis (palpable purpura and digital capillaritis), Raynaud's syndrome, enanthema, myopathy, lymphadenopathy, hepatosplenomegaly, polyarthritis. Data of laboratory tests: Hb 96g/l, ESR 27 mm/h, ANA titer 1:640 h+sp+cytopl, anti-SS-A(Ro)>200 U/ml, RF 230 ME/ml, C4 0.07 g/l. The revision of bone marrow biopsy showed changes typical for MAS. So jSLE was diagnosed as with SLICC criteria, 2012 with MAS at onset according the preliminary diagnostic criteria for MAS Complicating SLE. The initial SLEDAI was 29. Patient failed to respond to GC iv repeating courses, GC per os max 0.7 mg/kg, IVIG repeating courses, DMARDs consequentially: cyclophosphamide iv, azathioprine, mycophenolate mofetil (MMF) + hydroxychloroquine. Rituximab (RTX) was introduced in November of 2013 due to inefficiency of prior therapy in dose 375mg/m2 weekly N2 on course. Concomitant therapy: GC per os 0.5 mg/kg, MMF 500 mg/day, hydroxychloroquine 200 mg/day. Treatment with RTX allowed to decrease the dose of GC to 0.2 mg/kg, to reduce the activity of the disease (SLEDAI=4), but relapses of the disease required a repeat of RTX therapy every 6 months (5 courses in total). Patient developed a recurrent episode of MAS on 6th years of disease (the 8th day after RTX - 5th course, 1st infusion). Therapy of RTX was discontinued. In June 2016 Sjogren's syndrome has been verified (according to parotid sialography, unstimulated sialometry in combination with clinical signs of dry mouth, anti-SS-A(Ro)+, RF+). Correction of therapy was carried out at the expense of the change a dose of GC, the dose of MMF was increased to 750 mg per day. Patient received repeat courses of IVIG due to recurrent infections of mouth. Since October 2017 flare due to fever, polyarthritis, skin and mucosal lesions. The dose of GC has been increased to 0.5 mg/kg. In November 2017, abatacept therapy with 10 mg/kg was started with good safety. Inactive status of the disease was achieved after 12 months of therapy. Now boy receives abatacept during 42 months, continues GC 5 mg per day, hydroxychloroquine 100 mg per day, MMF 750 mg per day. In November 2020, he underwent COVID-19 with minimal manifestations (runny nose, fatigue, positive PCR test) without reactivation of rheumatic disease. Conclusion: This clinical case demonstrates efficacy and safety of abatacept in the rare combination of jSLE, SS and recurring episodes of MAS in boy with early onset.

COVID-19 and the biliary tree: Atypicall manifestations of disease during the pandemic

Case report-IntroductionCOVID-19, the infectious disease caused by the novel coronavirus SARS-CoV-2, and first described in Wuhan, China in December 2019, has affected more than 19 million patients worldwide and resulted in more than 700,000 deaths at the time of writing1. Patients with rheumatic diseases and those receiving immunosuppressive treatment are felt to be at greater risk of complications from this illness, though registry and trial data should help refine our understanding of these risks. We hereby describe a case of COVID-19 complicating an unusual rheumatic illness, resulting in severe multi-system disease and premature death.Case report-Case descriptionA 69 year-old male presented to rheumatology and haematology with symmetrical polyarthritis, thrombocytopenia (18 x 109/L), eosinophilia (25.4 x 109/L), raised C-reactive protein (CRP, 43 mg/L), positive rheumatoid factor (>200), antinuclear antibody (ANA) and anti-Ro. Bone marrow biopsy did not demonstrate evidence of haematological malignancy.Seropositive rheumatoid arthritis and connective tissue disease overlap were diagnosed, and treatment with Prednisolone 60mg daily was initiated. Despite rituximab and intravenous immunoglobulins, thrombocytopenia deteriorated on reducing corticosteroids, however the addition of mycophenolate mofetil (MMF) allowed gradual prednisolone tapering to 3mg daily. Hydroxychloroquine was briefly added but discontinued due to headaches. MMF was discontinued after he developed fungal pneumonia followed by jaundice. Liver biopsy was consistent with drug-induced cholestasis, attributed to co-amoxiclav, and his liver function tests (LFTs) improved on ursodeoxycholic acid. Following a further deterioration in thrombocytopenia, hyperferritinaemia and new onset erythema nodosum, he had a repeat bone marrow examination. This demonstrated large areas of fibrosis and granulomatous inflammation with a dense, pleomorphic T-cell infiltrate, but no haemophagocytosis. Haematologists felt this was reactive and prednisolone dose was increased to 10mg daily.Six months later he developed cholangitis. Magnetic resonance cholangiopancreatography (MRCP) demonstrated a tight 4cm stricture of the distal common bile duct (CBD) within the head of pancreas, which was diffusely swollen without any clear focal mass. Serum amylase was mildly elevated (316 units/L). Concurrent CT thorax, abdomen and pelvis demonstrated bilateral ground-glass changes within the lungs, and a SARS-CoV-2 nasopharyngeal PCR test was positive, though he had no respiratory symptoms or oxygen requirement at that stage.Sadly, four days after the CT scan and before a planned endoscopic retrograde cholangiopancreatography (ERCP) could be performed, he became markedly hypoxic with plain chest X-ray features suggestive of COVID-19 pneumonia. Despite medical management, including doubling of his prednisolone dose, he rapidly deteriorated and died.Case report-DiscussionThis case highlights an unusual presentation of COVID-19 in a patient with a complex background of inflammatory arthritis with immune-mediated thrombocytopenia. At the time of his final illness, these conditions were managed with steroid monotherapy. Based on the COVID-19 risk matrix recommended by the British Society for Rheumatology, he was not identified as a patient requiring shielding.Cholangitis was the major problem precipitating his final admission to hospital, and at the time of admission he had no respiratory symptoms. One week prior to this admission, his father-in-law had died of COVID-19 pneumonia, though they had not been in recent direct contact. Interstitial lung changes were incidentally noted on a CT performed to identify the cause of cholangitis, which prompted the nasopharyngeal PCR that detected SARS-CoV-2. This occurred prior to widespread routine testing of hospital inpatients for SARS-CoV-2 by PCR. Unfortunately he then rapidly developed COVID-19 pneumonia and died before the underlying cause of cholangitis could be definitively identified, though an MRCP demonstrated an obstructed CBD within a diffusely swollen pancreas, where a differential diagnosis of pancreatic malignancy or autoimmune pancreatitis was suggested by the reporting radiologist.There are emerging case reports of COVID-19 resulting in significant pancreatic injuryand a further recent laboratory analysis has suggested that ACE2 receptors, which are utilised by SARS-CoV-2 to gain entry to host cells, are highly expressed on cholangiocytes at a comparable level to type II alveolar cells. Whilst the ultimate cause of cholangitis will remain unknown in this patient, this case highlights the potential for atypical presentations and extra-pulmonary manifestations of COVID-19.Case report-Key learning points COVID-19 is a multi-system illness which can cause significant extra-pulmonary as well as pulmonary pathology, with emerging reports that the biliary tract and pancreas are frequently affected.Evidence to inform accurate prediction of which patients with rheumatic diseases are at highest risk of acquiring severe COVID-19 disease remains insufficient, with current shielding guidelines based on expert consensus.This case highlights the importance of widespread testing for COVID-19 in hospital patients, as not all patients carrying the SARS-CoV-2 virus will demonstrate classical respiratory features of the disease at the point of admission.

A case of anca vasculitis presenting with Sjögren's serology

Case report-IntroductionSjögren's is an autoimmune multisystem disorder characterised by xerostomia, keratoconjunctivitis sicca and extra glandular manifestations. The presence of sicca symptoms helps with diagnosis but up to 20% patients do not have these. The prevalence of lung involvement has been reported up to 9-24% and includes changes such as NSIP and organising pneumonia. We present an interesting patient who had no sicca symptoms but positive immunology to suggest Sjögren's. Changes in sequential CT chest scans were in keeping with Connective Tissue Disease-Associated Interstitial Lung disease (CTAILD). However, presentation with an acute renal injury resulted in a diagnosis of ANCA positive vasculitis.Case report-Case descriptionA 64-year-old Indian gentleman with medical background of controlled asthma was referred after 9 months of investigations for gluteal weakness. Initial blood tests included normal CK, ESR, CRP, vitamin B12, HbA1c and TFTs. Rheumatoid factor was low positive (20IU/ml), CCP negative. ANA was 1:80 with positive Ro, negative dsDNA. MRI of thighs was normal-no evidence of myositis. Nerve conduction studies showed no active denervation to suggest inflammatory myopathy and muscle biopsy showed myopathic features only. A CT scan revealed 3 small lung nodules recommending repeat scan.When seen in rheumatology clinic, there was additional bilateral shoulder arthralgia with no reports of sicca symptoms or rashes. A repeat autoimmune screen and CT chest was sent. His ANA was 1:1280 with Ro antibodies;CT showed new ground glass changes (with old nodules). Organising Pneumonia was suggested, and respiratory opinion sought. Extended myositis screen was negative. When seen in respiratory clinic he had new haematuria-ANCA screen showed positive anti-PR3 antibody (23U/ml) with normal U+Es, urine PCR and CRP 8mg/L. Based on these results a renal biopsy was performed-which showed no obvious morphological abnormalities. Thus, a suspected diagnosis of CTAILD with Sjögren's was made.In clinic 2 months later, there was new shortness of breath and haemoptysis. Urine dip showed haematoproteinuria and Chest X-ray showed increase in peri-hilar masses. He was admitted urgently-blood tests showed a decline in renal function-urea 26.8mmol/L, Creatinine 838umol/L, CRP of 435mg/L and Haemoglobin 100g/L. Urgent repeat renal biopsy was done and CT thorax showed deterioration with bilateral consolidation and new lung lesions. Urgent Plasma exchange and dialysis (9 cycles) was given. Initial results from renal biopsy showed presence of crescents and he was started on cyclophosphamide. On this kidney function has improved-urea 18.4mmol/L and Creatinine 302umol/L;he remains on oral cyclophosphamide.Case report-DiscussionWith ongoing symptoms, an underlying autoimmune cause of his symptoms was felt likely. However inflammatory markers remained normal and so did CK. Despite this MRI and muscle biopsies were performed-which again were normal. The only tests that were positive were immunology (Ro antibodies) and a CT chest (showing initial small lung nodules). These findings pointed toward CTAILD with Sjögren's being the likely diagnosis.As new lung nodules were seen, repeat CT scans were done-which showed gradual interstitial changes-the main radiological differential diagnosis was Organising pneumonia. Further investigations were delayed due to patient travel and COVID, but ongoing respiratory advice was sought. Even with changes in CT findings the patient remained stable with normal inflammatory markers. However, the clinical picture changed quite rapidly over a month (despite 2+ years of previous symptoms) with presentation of pulmonary-renal vasculitis. Plasma exchange and dialysis were given. A good response with a positive renal biopsy confirmed the most likely diagnosis was Granulomatosis with Polyangiitis (GPA).This case was interesting-the main complaint was of myopathy with no physical signs. Despite this biopsy were performed (muscle and kidney), which were all normal. The red herring in his case was a no mal renal biopsy-steering us in the direction of CTD-AILD instead of GPA.Case report-Key learning pointsIn patients with clear symptoms matching their investigations the diagnosis is often obvious. When this is not the case and symptomatology does not match results (i.e. no Sicca symptoms but positive immunology to suggest Sjögren's) suspicion should remain high. Multidisciplinary working can provide insight, which this case does highlight-with input required from Neurology, Respiratory and Renal medicine.Negative results should be taken in context with patients and their symptoms. Initial renal biopsy in this case was normal-however after a review, further comments were made on the sparsity of glomeruli in the sample. Therefore, tissue obtained for diagnosis should always be questioned and clinical suspicion should remain high. In addition, repeat investigations (6 monthly CT scans) can help note any interval change.Thorough history and examination in follow up of patients can help look out for evolving changes. With the new symptoms of haemoptysis and haematoproteinuria this pointed us to the eventual diagnosis. The road to diagnosis in this case was prolonged with an acute drop in kidney function and pulmonary haemorrhage needing urgent Plasma exchange and dialysis. Thankfully, the patient continues to make a good recovery.A last point to add is although isolated myalgia has been described as a presentation of systemic vasculitis in the literature, those patients have had elevated CK and positive muscle biopsy. Our patient did not have any positive findings with over 2 years of symptoms. Therefore, we feel this case was unique in presentation and has valid learning points as above.