Toxicity signals associated with secukinumab: A pharmacovigilance study based on the United States Food and Drug Administration Adverse Event Reporting System database.

AIMS: Secukinumab, the first interleukin 17A inhibitor, is widely used to treat immune diseases, including plaque psoriasis, psoriatic arthritis and ankylosing spondylitis. Recently, many studies have reported adverse events associated with secukinumab, including gastrointestinal disorders, infections and infestations, and hypersensitive and nervous system disorders. OBJECTIVE: Here, we aimed to explore the clinical characteristics, outcomes and time to onset of the four main toxicities of secukinumab using post-marketing data. METHODS: Our study utilized data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database from 2015 to 2021, using disproportionality analysis. Toxicities were defined based on the standardized Medical Dictionary for Regulatory Activities queries. Two disproportionality methods were used to detect potential signals: information component (IC) and reporting odds ratio (ROR). The signals were defined as ROR025 > 1 and IC025 > 0. RESULTS: A total of 73 945 398 records were included in this study, of which 300 665 records were related to secukinumab. Diarrhoea (N = 3538), nasopharyngitis (N = 3458), pruritus (N = 4277) and rash (N = 3270) were the most common adverse events. Inflammatory bowel disease (IC025 /ROR025 = 3.25/9.69), genital candidiasis (IC025 /ROR025 = 3.46/11.54), dermatitis psoriasiform (IC025 /ROR025 = 1.94/4.04) and anosmia (IC025 /ROR025 = 1.62/3.17) had the highest IC025 values of all toxicities. The time to onset of the four toxicities was mainly concentrated in the first month. Some patients simultaneously presented with two or more toxicities. CONCLUSION: This pharmacovigilance study systematically explored the four main toxicities of secukinumab and provided new safety signals based on past safety information. Some high-risk signals need to be given attention.

Tixagevimab/ Cilgavimab Outcomes Among Patients with Immunodeficiency

Rationale: The FDA granted an emergency use authorization for tixagevimab/ cilgavimab in December 2021 for COVID-19 pre-exposure prophylaxis for individuals that are moderate to severely immunocompromised and has since recommended repeat dosing every 6 months. Given its novelty and resultant hesitation for use among some physicians and patients, our study aimed to observe safety and efficacy of tixagevimab/ cilgavimab, including against one of the newest variants, Omicron BA.5, among our patient population with immunodeficiencies 6 months post-administration via a telephone survey. We hypothesized that adverse outcomes would be minimal and COVID-19 incidence and severity would lessen following tixagevimab/cilgavimab administration. Methods: The Atrium Health Wake Forest Baptist Allergy, Asthma, and Immunology department recruited 15 patients with immunodeficiencies receiving immunoglobulin replacement and tixagevimab/ cilgavimab in March 2022 for a prospective cohort study. A telephone survey was conducted 6 months later regarding tixagevimab/ cilgavimab adverse effects and incidence/severity of COVID infection before and after administration. Results: Two patients experienced minor adverse effects (fatigue, bruising) following tixagevimab/ cilgavimab administration. No severe reactions were reported. Two patients required hospitalization for severe COVID-19 infection prior to tixagevimab/cilgavimab administration, whereas 0 patients required hospitalization for COVID-19 in the 6 months following administration. Four of 5 patients that had COVID-19 following administration had not yet received the bivalent Omicron booster vaccine and 2 had received no COVID-19 vaccines. Conclusions: Tixagevimab/ cilgavimab is associated with minor adverse effects and reduction of COVID-19 severity, albeit perhaps not associated with diminished incidence of newest COVID-19 strains, in a prospective, population-based cohort.

Experience of Using Remdesivir in Patients with Novel Coronavirus Infection

Timely, effective, and safe antiviral therapy in COVID-19 patients reduces complications, disability and mortality rates. The greatest concern with remdesivir is the risk of drug-induced liver injury, including in patients whose liver function is compromised by COVID-19. The aim of the study was to investigate the efficacy and safety of remdesivir in patients with confirmed SARSCoV-2 infection who had been admitted to an infectious diseases hospital in the Volgograd region in March 2022. Materials and methods: the authors carried out an open, non-randomised, single-arm study using medical records of 234 patients who had been diagnosed with "U07.1 COVID-19, virus identified” and prescribed remdesivir upon admission. The effectiveness of therapy was evaluated using two criteria: the need for oxygen supplementation or ventilatory support, or mortality. The authors conducted the evaluation on days 7, 14, and 28 using the six-point ordinal severity scale by Y. Wang et al. The safety of therapy was assessed on the basis of complaints and changes in laboratory findings. Results: for the patients prescribed remdesivir at admission, the 7-day mortality rate was 3.0%, the 14-day mortality rate was 5.6%, and the 28-day mortality rate was 7.3%. With the exception of a patient with myocardial infarction, all the patients who had been hospitalised with mild COVID-19 and prescribed remdesivir did not require oxygen therapy and/or transfer to intensive care and were discharged following recovery. The patients with moderate to severe COVID-19 had the 14-day mortality rate of 6.4% and the 28-day mortality rate of 8.6%. 17 patients (7.2%) discontinued remdesivir prematurely for various reasons, including adverse drug reactions. Remdesivir therapy of 5-10 days was associated with an increase in ALT activity by 2.7 ± 0.8 times in 15.9% of patients with mild COVID-19, by 3.8 ± 1.8 times in 20.4% of patients with moderately severe COVID-19, and by 4.8 ± 2.7 times in 24% (12/50) of patients with severe COVID-19. In two patients (0.9%), the increase exceeded 10-fold the upper limit of normal. Conclusions: the obtained results support recommending remdesivir to patients with mild, moderate and severe COVID-19, including those with moderately elevated baseline activity of hepatic transaminases.

Hyper-eosinophilic syndrome with myocarditis after inactivated SARS-CoV-2 vaccination - a case study.

INTRODUCTION: COVID-19 vaccine induced serious adverse reactions are rare. Hyper-eosinophilia syndrome with myocarditis has not been reported earlier following BBV152 vaccine administration. CASE PRESENTATION: A young man without any co- morbidities presented with persistent periorbital swelling along with itchy swelling over fingers, resting tachycardia and exertional breathlessness following first dose of an inactivated SARS-CoV-2 vaccination (BBV152, COVAXIN). On investigation, patient had elevated blood eosinophils (maximum 21.5% with absolute eosinophil count of 2767/mm3) and myocarditis (Lake Louise Criteria). He was successfully treated with steroid and supportive treatment. CONCLUSION: This is the first reported case of hyper-eosinophilia syndrome after COVAXIN administration. Prior history of allergic disease may be a predisposing factor in this case. Hyper-eosinophilia can present with variable symptoms. In the current case, myocarditis was present with presentation as persistent resting tachycardia and dyspnea. Steroid and antiallergic drugs may be successfully used for the treatment of vaccine induced hyper-eosinophilia with myocarditis. Increased vigilance is needed for such adverse events.

Corticosteroids Induced Avascular Necrosis of Hip, a "Long Covid-19" Complication: Case Report

Since it first surfaced, the new Coronavirus has multiplied and mutated into different forms, leading to a significant impact on people's lives. COVID-19's long-term impact is not completely known: It can only be hypothesized based on the prior outbreak of severe acute respiratory syndrome (SARS). Avascular necrosis (AVN) is one of these consequences, which if left untreated can lead to catastrophic events and bone collapse. It's important to remember that individuals who have recovered from COVID-19 infection are still at risk of developing AVN. The pathological findings in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are very similar to those seen in severe acute respiratory syndrome coronavirus (SARS-CoV) infection. We present cases of 27- and 69-years old men with no comorbidities admitted with complaints of bilateral hip pain post Covid treatment with corticosteroids and antivirals. The diagnosis was established based on history, physical examination, and magnetic resonance imaging (MRI). The use of corticosteroids in the treatment of SARS-CoV-2 infection has saved many lives, and it is still advised for moderate to severe cases on a short-term basis. The long-term use of corticosteroids is associated with numerous side effects. One of the most prevalent side effects of steroids is avascular necrosis of the femoral head, which is aggravated by the disease process. Early detection of avascular necrosis is very crucial in its management due to its high progression rate. Low therapeutic doses of corticosteroids with minimal effective duration remain the key to halting its occurrence.

Covid-19 vaccination status and adverse events following sars-cov- 2 vaccine in autoimmune inflammatory rheumatic disease (AIRD) patients: A single center experience

Background: Autoimmune inflammatory rheumatic diseases (AIRD) were associated with an increased risk for COVID-19 infection, worse clinical outcomes, and COVID-19- related deaths. Vaccines carry the potential benefit of reducing disease transmission and disease severity. Issues on vaccine safety, trigger of an autoimmune reaction or disease flares has been a long issue. Thus this study describes the COVID-19 vaccination status and adverse events following SARS-COV 2 vaccine in a tertiary hospital in Manila, Philippines. Method(s): This retrospective cross-sectional study included patients diagnosed with AIRD and seen in the clinics over 12 months (March 2021-March 2022).We collected data from patients' clinic records and analyzed the clinicodemographic profile, vaccination status, adverse events and development of new onset autoimmune reaction and disease flares post vaccination and those who developed COVID-19 infection even after vaccination. Result(s): There were 204 respondents included in this study: 174 (85%) were female and 30 (14%) were male;63.2 % with SLE, 10.8% rheumatoid arthritis, 8.3% psoriatic arthritis, 6.4% ankylosing spondylitis and other systemic autoimmune disease. Others included were scleroderma and inflammatory arthritis and myopathies. The median age is 38.4 years. 100% of the respondents were fully vaccinated;87 (42.6%) received inactivated vaccine, 63 (30.8%) viral vector vaccine and 54 (26.4%) mRNA vaccine. 133 (65.2%) reported no adverse events while 71 (34.8%) experienced constitutional symptoms, musculoskeletal, cutaneous, respiratory, gastrointestinal and cardiovascular symptoms after vaccination. There were 9 (4.4%) of the respondents who developed new onset autoimmune reaction and disease flares 7-28 days post vaccination;1 patient had new onset amyopathic dermatomyositis;3 SLE patients developed severe hematologic, cutaneous and renal flare;2 rheumatoid arthritis, 1 spondyloarthritis, and 1 inflammatory arthritis patients in long remission had disease flares and 1 patient with henoch schonlein purpura developed flare. Twenty two (10.8%)of the respondents developed COVID-19 infection after 30-120 days post vaccination;19 (86.4%) had mild symptoms, 2 (9.1%) moderate infection and 1 (4.5%) had severe infection and all of the patients recovered. Conclusion(s): This study showed that patients with AIRD experienced varied organ system adverse events following vaccination ranging from mild side effects, disease flares and new onset autoimmune reactions. The development of an autoimmune reaction following SARS-COV 2 vaccination is of scientific and public importance and still needs to be investigated. Even after a complete vaccination, some patients still had COVID-19 infection, however preventing them from worse complications, hospitalization and mortality.

Humoral and cellular immunogenicity against SARS-CoV- 2 mRNA vaccine in patients with inflammatory rheumatic disease, Comparison of mRNA-1273 vaccine and BNT162b2

Objectives: To assess humoral and cellular immune responses and safety profiles after two doses of different mRNA vaccine against SARS-CoV- 2;BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) in patients with rheumatic musculoskeletal disease (RMD). Method(s): We enrolled consecutive, previously uninfected RMD patients with inflammatory rheumatic diseases receiving mRNA vaccine including BNT162b2 and mRNA-1273. Healthy participants all receiving BNT162b2 were recruited as control. Blood samples were obtained 3weeks after second dose of vaccines. We measured titres of neutralizing antibodies against SARS-CoV- 2 with chemiluminescent enzyme immunoassay to evaluate humoral responses and assessed T-cell immunity responses with interferon releasing assay against SARS-CoV- 2 in a part of the patients. Adverse reaction symptoms were obtained from participants through questionnaire. Result(s): A total of 1040 RMD patients and healthy 621 control participants were enrolled. Among RMD patients with immunosuppressants, 704 were received BNT162b2 and 156 were received mRNA-1273. Neutralizing antibody titres 3 weeks after vaccination and positive seroconversion rates were significantly higher in healthy participants with BNT162b2 and RMD patients with mRNA-1273 compared with RMD patients with BNT162b2;neutralizing antibody titre, 23.9 +/- 14.2 IU/mL vs 29.4 +/- 33.9 IU/mL vs 10.8 +/- 16.5 IU/mL, p < 0.001;seroconversion rates, 99.5% vs 99.4% vs 80.2%, p < 0.001, respectively, We identified that age, glucocorticoid (prednisolone dose > 7.5mg/day), and use of immunosuppressants including methotrexate, mycophenolate and rituximab, are associated with attenuation of humoral responses in patients with BNT162b2. T cell reaction against SARS-CoV- 2 were also higher in patients with RMD vaccinated with mRNA-1273 than those with BNT162b2 (Interferon gamma levels for antigen 1, 3.2 +/- 6.5 IU/mL vs 0.6 +/- 1.3 IU/mL, p = 0.002;for antigen 2, 3.2 +/- 6.3 IU/mL vs 1.0 +/- 2.1 IU/mL, p = 0.021, respectively). Regarding adverse reaction of mRNA vaccine, the proportion of systemic adverse reactions including fever and general fatigue are significantly higher in healthy controls and RMD patients with mRNA-1273 than those with BNT162b2;fever, 46.2% vs 56.7% vs 14.3%, p < 0.001;general fatigue, 62.6% vs 73.0% vs 38.5%, p < 0.001, respectively, while the frequency of background RMD flare after vaccination were not significantly different between mRNA-1273 and BNT162b2 (5.2% [n = 8] vs. 3.7% [n = 26], p = 0.41) Conclusion(s): We demonstrated higher humoral, cellular immunogenicity of the SARS-CoV- 2 mRNA-1273 (Moderna) compared with the BNT162b2 (Pfizer-BioNTech) in RMD patients. Although reactogenicity including systemic adverse reaction including fever and fatigue were observed mRNA1273 vaccinated patients, proportion of RMD relapse were similar between the patients with mRNA-1273 and BNT162b2.

COVID-19 vaccine-associated autoimmune inflammatory rheumatic diseases

Background/Purpose: Vaccination against the most recently COVID-19 is one of the critical tools to provide herd immunity, reduce mortality, and control the pandemic worldwide. Despite the immense benefits of vaccination, an occasional association between vaccination and autoimmunity induction has been detected in human subjects. The current study presented fourteen cases of autoimmune rheumatic diseases (ARDs) following various COVID-19 vaccines. Method(s): This observational two-center study was conducted in the rheumatology clinics of the Connective Tissue Diseases Research Center at Tabriz University of Medical Sciences and Kashan University of Medical Sciences. All patients were referred to clinics with ARDs symptoms after implementing the COVID-19 vaccination program in Iran from April 2021 and were considered for enrollment in the study. Inclusion criteria were the onset of ARDs symptoms at four weeks post-vaccination, age >=16, no previous history of ARDs, meeting the classification criteria of one of the ARDs, and staying in the follow-up. Result(s): Between April 2021 and January 2022, 22 adult patients with symptoms of ARDs after COVID-19 vaccination were considered for eligibility. Eventually, 14 patients were diagnosed with ARDs based on classification criteria, and whose symptoms had started within four weeks after vaccination were included in the study. The duration of follow-up was 2-10 months. The vaccines used in these patients were Sinopharm [7 cases (50%)], AstraZeneca [6 cases (42.9%)], and COVIran Barakat [1 case (7.1%)]. It should be noted that vaccines that have been used for public vaccination in Iran until January 2022 were Sinopharm (78.9%), AstraZeneca (11.7%), and COVIran Barekat (8.1%), and Sputnik (1.3%). Crosstabulaton analysis showed that ARD was significantly more common in subjects who received AstraZenca vaccine than in subjects who received other vaccines (P < 0.001). Based on the results, the involved patients were diagnosed with RA or one of its subtypes (five cases), vasculitis (four cases), SLE (three cases), and peripheral SpA (pSpA) (two cases). In eleven cases, symptoms started two weeks after vaccination. However, diagnosis in eight patients was delayed for more than four weeks. Except for one patient with self-limitation of ARD, others required treatment with anti-inflammatory drugs and disease-modifying antirheumatic drugs, which even one of them developed irreversible neurological complications. Conclusion(s): Indeed, our data can warn physicians about the possibility of ARDs post-vaccination, lead to faster diagnosis, prevent loss of window of opportunity for treatment, and prevent irreversible organ damages.

Polycythemia in a Pediatric Patient with Chronic Kidney Disease: Overuse of Erythropoetin During COVID-19 Isolation

We describe a case of a patient with Chronic Kidney Disease who developed polycythemia due to Erythropoiesis Stimulating Agents overuse during COVID-19 isolation. A 12-year-old male had not been able to attend routine controls since had been in isolation for 4 months after the COVID-19 outbreak. He had continued to take Erythropoiesis-Stimulating Agents during that period at the starting dose of 150 U/kg/week. He had been on peritoneal dialysis in the last year because of end-stage renal failure. Laboratory investigation revealed a hemoglobin (Hb) level of 20.8 g/dl, hematocrit level of 66%, creatinine level of 6.5 mgr/dl. He underwent daily phlebotomy sessions (10cc/kg/session). During this period aspirin was also started (5mg/kg). After 5 sessions his Hb level decreased to 14 gr/dl and hematocrit to 40%. Pediatric nephrologist should be aware that there is a potential risk of polycythemia with Erythropoiesis Stimulating Agents when Hb level is not appropriately followed on a routine basis. Copyright © 2021 Ankara Pediatric Hematology Oncology Training and Research Hospital. All rights reserved.

COVID-19 associated Mucormycosis (CAM): Implications for perioperative physicians - A narrative review

Mucormycosis once considered a rare disease with an incidence of 0.005 to 1.7 per million, has become one of the greatest menaces during the coronavirus disease (COVID-19) pandemic. India alone has contributed to nearly 70% of the global caseload of COVID-associated mucormycosis (CAM) and it had even been declared as a notifiable disease. Second wave of COVID-19 pandemic saw a steep rise in the incidence of mucormycosis and these patients have been presenting to anesthesiologists for various surgical procedures due to its primary or secondary sequelae. Rhino-orbito-cerebral mucormycosis (ROCM) is the commonest manifestation and is caused by Rhizopus arrhizus. Injudicious use of corticosteroids in vulnerable patients could have been a major contributing factor to the sudden rise in ROCM during the pandemic. Concerns related to anesthetic management include COVID-19 infection and post COVID sequalae, common presence of uncontrolled diabetes mellitus, possibility of difficult mask-ventilation and/or intubation, various drug therapy-associated adverse effects, and interaction of these drugs with anesthetic agents. Thorough preoperative optimization, multidisciplinary involvement, perioperative care, and vigilance go a long way in improving overall outcomes in these patients. Copyright © 2022 Saudi Journal of Anesthesia Published by Wolters Kluwer - Medknow.

New onset clinically amyopathic dermatomyositis following SARS-CoV- 2 vaccine: A case report

Background: Amyopathic dermatomyositis is a rare autoimmune skin disease with similar cutaneous manifestations as classic dermatomyositis (CDM), but with absent or subclinical muscle involvement i.e. Clinically Amyopathic Dermatomyositis (CADM). Inciting agents including vaccines have been linked to CADM. We describe a case of new-onset CADM associated with COVID-19 vaccine. Objective(s): To illustrate the occurrence of new-onset CADM in a 27-year- old male following COVID-19 immunization. Case Summary: A previously well 27-year- old male developed joint and muscle aches accompanied by scattered erythematous patches on the face and both upper and lower extremities, a week after receiving first dose of viral vector SARS-CoV- 2 vaccine. He took an anti-histamine and paracetamol with some relief of pains and slight clearing of the rashes. He proceeded to receive a second dose of the same vaccine 2 months later. A few days following the second dose, there was exacerbation of the skin lesions and was referred to Rheumatology clinics. Physical exam disclosed an ambulatory well-built male with normal vital signs and no objective muscle weakness. Skin involvement included facial rash, and the characteristic Heliotrope rash, Gottron's papules, and Holster sign. Complete blood counts, chemistries and muscle enzymes were within normal. Antinuclear antibody (ANA), erythrocyte sedimentation rate (ESR) and Smith/ribonucleoprotein (Sm/RNP) antibody were positive. He was managed with tapering prednisone and maintained on methotrexate and folic acid with significant improvement at time of this report. Conclusion(s): This is the first reported case of adverse reaction to COVID-19 vaccine that had studied in detail the skin and systemic autoimmune reaction. Development of autoimmune reaction following SARS-CoV- 2 vaccine has been described extensively;however, evidence of autoimmunity following vaccination is still relatively scant. Our case suggests that in predisposed subjects' vaccination could trigger an autoimmune reaction similar to the natural infection.

Systemic lupus erythematosus in a 36-year old Filipino male after SARS-COV- 2 vaccination

Background: Systemic lupus erythematosus (SLE), a multisystem autoimmune disease more common in females, is associated with autoantibodies against different autoantigens forming immune complexes. Inadequate removal of these complexes from the host triggers inflammatory response which causes tissue damage. Some antiviral vaccines have been associated with the onset of SLE. Few cases of SLE occurring after SARS-CoV- 2 vaccines have been reported. Herein, we describe a case of new-onset SLE associated with COVID-19 vaccine. Case Summary: A previously well 36-year- old male with unremarkable family history of autoimmune disease started to develop muscle and joint pains, hair thinning, and ecchymoses 2 months after receiving second dose of inactivated SARS-CoV- 2 vaccine. He was subsequently admitted after consultation due to thrombocytopenia (platelet count of 58). He was given high dose steroid with tapering dose during the entire 14 days admission with significant increase of platelet count after 72 hours of repeat complete blood count. He went consult at rheumatology clinic a month after due to persistent joint and muscle pains, and progression of hair fall with associated facial rash, oral ulcers, easy fatigability and weight loss. Physical exam disclosed an ambulatory well-built male with normal vital signs, alopecia, malar rash, oral ulcers, joint tenderness and no objective muscle weakness. Complete blood counts and Anti-smith were within normal. Urinalysis, Antinuclear antibody (ANA), Anti-SSA, Anti-SSB, complement factor 3 (C3), and Anti-dsDNA were positive. He was managed with tapering prednisone and hydroxychloroquine with significant improvement at time of this report. Conclusion(s): Development of autoimmune reaction following COVID-19 vaccine has been described extensively;however, evidence of autoimmunity following vaccination seems to be lacking at present. Pathomechanisms include defective elimination and/or control of self-reactive lymphocytes resulting in over-stimulation of the immune system leading to clinical manifestations strikingly similar to the infection itself. Management approach to these autoimmune reactions address the immune hyper-stimulation with immunosuppressive or immuno-modulating agents including steroids and hydroxychloroquine.

Characteristics of elderly patients with rheumatoid arthritis who have not responded to methotrexate therapy within 24 weeks

Objective: To describe the clinical, laboratory and pharmacokinetic features of elderly patients with rheumatoid arthritis (RA), with insufficient response to methotrexate (MTX) therapy for 24 weeks compared with patients with a good response. Material(s) and Method(s): The study included 32 patients with RA, according to the older age category according to WHO criteria, 65 (82%) women and 14 (18%) men, BMI was 27 +/- 4 kg/m2, DAS28 was 5.9 +/- 1. In each case, MTX was administered parenterally, at the rate of 10-15 mg/m2 of body surface. therapeutic drug monitoring was carried out, it was the determination of the concentrations of MTX monoglutamate (initial form) and MTX compounds: polyglutamates and 7-hydroxymethotrexate (7-OH- MT) in erythrocytes (ER) and mononuclear cells (MO) after 4, 12 and 24 weeks. We used high performance liquid chromatography with mass spectrometric detection. The MTX metabolite index was calculated (the ratio of the metabolite concentration to the initial concentration of unchanged MT). Achievement of therapy targets (good response to therapy) was established in accordance with the EULAR criteria. The lack of achievement of therapy goals corresponded to an insufficient response to therapy. Result(s): By week 24, 12 patients (36%, group 1) achieved therapy targets, 17 patients (53%, group 2) did not reach treatment targets, and in 3 more, MTX was discontinued due to Adverse reactions (ARs) and/or the development of COVID-19. A comparison was made of clinical and laboratory parameters before the start of MTX treatment and during MTX therapy. At all stages of the study the groups did not differ in terms of: sex, age, BMI, disease duration, VAS (pain), DAS28 index, creatinine, taking glucocorticoids, statins, the presence and frequency of comorbid pathology (arterial hypertension, diabetes mellitus, chronic autoimmune thyroiditis). The 7-OH- MTX( ER) metabolic index after 12 weeks of treatment was higher in group 1 (1.35 [0.8;2.1] versus 0.35 [0.19;0.73] in group 2). Metabolic indices of other MTX metabolites did not differ. ARs were less common in group 1 (in 1 (18%) versus 6 (35%) in group 2), P = 0.09. Conclusion(s): Clinical and laboratory characteristics of patients of the older age group did not differ in groups with different responses to methotrexate therapy. The 7-OH- MT( ER) metabolism index after 12 weeks of treatment was higher in the group of patients with a good response to therapy, which most likely indicates a more rapid catabolism of MTX in this group of patients.

A case of morphea following the inactivated COVID-19 vaccine

Background: The emergence of the coronavirus disease (COVID-19) prompted pharmaceutical companies to develop effective vaccines to address the problem. While studies prove the vaccines are safe, rare systemic side effects remain possible. All types can cause various vaccine-related adverse reactions which are continuously being monitored. This paper aims to highlight new data on immunologic reactions to COVID-19 vaccines. Morphea demonstrated after COVID-19 vaccination is rare. Herein, we report a case of morphea that was most likely triggered by the immune response against inactivated COVID-19 vaccine. Method(s): A case of morphea was reviewed at the clinic in a tertiary hospital in the Philippines. Result(s): A 48 year old Japanese male had no underlying co-morbidities and no previous COVID-19 infection. He had his first dose of inactivated COVID-19 vaccine, coronaVac (sinovac) with no untoward reactions. After a month, he had his second dose. One week later, the patient started to have a red plaque on his upper back, palpable, tender on palpation and pruritic. Review of systems was unremarkable. The patient denied any insect bites or skin trauma. No medications applied or taken. No known allergies to food, medications or vaccines. He is a 32 pack years smoker. No family history of any autoimmune diseases. In five months, the skin lesion insidiously progressed, thickened and now spreading to the left side of the back. The patient sought consult with a dermatologist and rheumatologist. Physical examination revealed thickened skin and subcutaneous tissue on the upper back with post-inflammatory hyperpigmentation. Work-up showed normal complete blood count, normal chest x-ray, non-reactive Hepatitis B antigen. Antinuclear antibody (ANA) was positive with 1:80 titer and nuclear speckled pattern. Anti-double stranded DNA (anti-dsDNA), anti-smith, antinuclear ribonucleoprotein (anti-RNP), anti-SSA, anti-SSB and anti-Jo- 1 were all negative. The patient's skin biopsy to the reticular dermis showed findings that are consistent with Morphea. The patient was then started on Methotrexate. Conclusion(s): People should be educated about the possible outcomes of COVID-19 vaccines. One of these are immune-related diseases, such as morphea. The underlying mechanism of morphea is multifactorial but one hypothesis highlighted that the spike glycoprotein from vaccination drives these skin reactions. Other studies demonstrated molecular mimicry to viral epitopes. Discussing this cutaneous manifestation secondary to COVID-19 vaccine stressed the importance of this clinical condition, in order to provide a proper diagnosis and therapeutic management. Although there are novel case reports of morphea induced by COVID-19 mRNA vaccine, inactivated COVID-19 vaccine-related morphea has not been reported yet.

Pain in COVID-19: Quis est culpa?

Background: At present, during the coronavirus disease (COVID-19) pandemic, chronic pain is becoming more prominent, and it is also associated with the post-COVID-19 syndrome. Thanks to quick decisions on the therapy and as part of COVID-19 prevention, we have succeeded in stabilising the situation all over the world. On the other hand, ‘quick decisions' have contributed to other significant issues which we are beginning to deal with now: in the effort to defeat the virus, many experts regarded the adverse effects of the medications used to be of secondary importance. Purpose: The article aims to demonstrate the side effects of treatment with various drugs (and their combinations) that are used to treat COVID-19 disease. Method: From the beginning of January until mid-May, the COVID-19 department of the 2nd Surgical Clinic of the Faculty of Medicine of the Comenius University in Bratislava (University Hospital Bratislava, Hospital of Saints Cyril and Methodius) treated 221 patients with moderate and severe course of COVID-19 (2nd wave of the pandemic). We saw some adverse effects and lack of effect of certain drugs for COVID-19. Results: The benefits of preventive measures compared to treatment are enormous. For example, corticoids can impair metabolism, cause diabetes, or suppress immunity. Antibiotics may cause colitis and blood pressure medications may negatively impact blood circulation. Conclusion: Preventive measures such as vaccination and activation of intrinsic antiviral immune systems are based on an incomparable benefit. Important in the process of the activation of antiviral immunity (linked to interferon synthesis) in the prevention of COVID-19 is the improvement of vitamin D deficit and the use of other micronutrients. Practical value: The results of the study will be valuable in the field of medicine, for virologists, pharmacologists, pharmacists, and medical professionals.

Evaluation of Side Effects After Heterologous Vaccination with BNT162b2 Vaccine in Healthcare Workers Vaccinated with Two Doses of Inactive COVID-19 Vaccine.

Objective: Vaccination is the most effective way to control the COVID-19 pandemic all over the world. We aimed to evaluate the relationship between antibody titers and vaccine side effects after the BNT162b2 vaccine was administered as a reminder dose in healthcare workers (HCW) who received two doses of inactivated SARS-CoV-2 vaccine name CoronaVac (Sinovac Life Sciences, Beijing, China). Method(s): A total of 428 HCWs participated in the study. Participants who received the mRNA vaccine as a reminder dose were evaluated with a questionnaire regarding antibody values and vaccine side effects. Three weeks after the first BNT162b2 vaccine, the same questionnaire was applied face-to-face to HCW, and the same questionnaire was applied to those who received a second reminder dose via telephone. Result(s): Out of 428, 373 (87.1%) HCWs preferred one and 55 (12.9%) two doses of the BNT162b2 vaccine as reminder doses after being vaccinated with an inactivated vaccine. It was observed that side effects were more frequent in women aged 18-40 after a single dose of the BNT162b2 vaccine (p<0.001). The most common side effects are redness, swelling, and pain at the injection site, with a rate of 59.6%. Fatigue-weakness was the most common systemic reaction, with a rate of 58.6%. Axillary lymphadenopathy was observed seen in 3 (1.1%) HCWs. The median value of IgG titers in the third week after the reminder dose was found to be higher in HCW with side effects than those without side effects (p<0.001). When the cumulative incidence rate of vaccinated people was evaluated over 389 people, no cases were observed on the 14th and 30th days after the first reminder dose of BNT162b2. However, the first case was observed on the 60th day, and after the second reminder dose, cases were seen on the 14th, 30th, and 60th days. Conclusion(s): Since the side effects detected after the BNT162b2 reminder dose were mild to moderate and progressed with local symptoms, it was concluded that highly protective mRNA vaccines could be safely preferred for protection from COVID-19. Copyright © 2022, DOC Design and Informatics Co. Ltd.. All rights reserved.

Anti-phospholipid antibodies were associated with clinical symptoms, disease severity and mortality among hospitalized COVID-19 patient

Background: This study was aimed to find the correlation of anti-phospholipid antibodies in the risk of coagulopathy and disease severity in coronavirus disease-19 (COVID-19). Method(s): Clinical and laboratory findings were obtained from 50 confirmed COVID-19 patients hospitalized in Saiful Anwar General Hospital, Malang, Indonesia from September to November 2020. Anti-phospholipid antibodies were measured by finding of IgM anti-beta2 glycoprotein, lupus anticoagulant and IgM anti-cardiolipin. Clinical Symptoms, thrombotic events, and mortality during hospitalization were recorded. Disease severity was defined by COVID-19 Treatment by multi-departement guidelines, Ministry of Health, Year 2020, Indonesia. Result(s): Among 50 patients, 5 patient (10%) were positive of IgM anti-beta2 glycoprotein (2%), IgG anti-cardiolipin (2%) and IgM anti-cardiolipin (8%). Anti-phospholipid antibodies were associated with anosmia OR 8.1 (1.1-57.9) (P = 0.018), nausea and vomiting OR 12.4 (1.2-122.6) (P = 0.010), diarrhea OR 9.8 (1.3-70.9) (P = 0.010), cardiovascular disease OR 1.4 (1.0-1.9), (P = 0.001), chronic kidney disease OR 12.0 (1.6-90.1) (P = 0.05), acute coronary syndrome (P = 0.001), moderate OR 0.11 (0.01-1.1) (P = 0.031) and severe OR 18.5 (1.8-188.4) (P = 0.002) disease severity, and in-hospital mortality OR 8.1 (1.1-57.9) (P = 0.018). Conclusion(s): In conclusion, anti-phospholipid antibodies show a low prevalence in COVID-19 patients and are associated with increased risk of acute coronary syndrome, clinical manifestations, disease severity, and mortality. Anti-phospholipid antibodies in COVID-19 patients are mainly directed against anti-cardiolipin.

Paediatric Aps - Children Are Not Just Small Adults

Introduction/Background: Antiphospholipid syndrome (APS) is a rare autoimmune multisystem disease characterised by thrombosis and pregnancy morbidity in the presence of persistently elevated titres of: lupus anticoagulant, anticardiolipin and/or anti-glycoprotein 1. It may be primary (occurring alone) or secondary (in combination with another disease, most commonly systemic lupus erythematosus (SLE)). Recent publications highlighted clinical criteria limitations for children and raised awareness of the burden and prevalence of non-criteria manifestations in this population. This case report adds further weight to the need to raise multi-specialty awareness of non-criteria manifestations to aid recognition and treatment of this rare condition with potentially severe sequelae. Description/Method: 13-year-old female with SLE diagnosed aged 8 in India with bilateral optic neuritis occurring two months later. ANA positive at diagnosis with low complement and thrombocytopenia. Treated with prednisolone and hydroxychloroquine. Patient moved to the UK aged 9;initial abnormal bloods: mildly positive ANA (ENA negative), thrombocytopenia, strong lupus anticoagulant. As serology not strongly suggestive and optic neuritis rare in lupus diagnosis questioned. Ophthalmology review confirmed bilateral optic atrophy without evidence of previous vasculitis. There was debate whether the postretinal demyelination was due to antiphospholipid syndrome or a primary demyelinating condition. Hydroxychloroquine stopped and azathioprine started. Following normal neurology investigations (brain, spine MRI/MRV/MRA) concluded if patient developed new APSrelated symptoms or worsening visual evoked potentials anticoagulation would be discussed. Patient remained stable over four years with chronic thrombocytopenia and ESR persistently elevated. Azathioprine changed to Mycophenolate mofetil (MMF) due to side effects. Routine medication monitoring bloods in 2022 showed ESR 97, CRP 78, Platelets 61. Review identified vasculitic rash on soles of both feet with palpable nodules and normal pulses. Further investigation confirmed antiphospholipid antibody triple positivity. Aspirin commenced, hydroxychloroquine restarted, MMF dose increased and rituximab administered. Left foot rash settled but right progressed with toe discolouration and numbness. Skin biopsy considered but not performed due to skin integrity concerns. Foot pulses remained present and normal. Bilateral lower limb doppler reported as normal;increased symptoms resulted in CT angiogram which revealed bilateral non-occlusive popliteal thrombus and left pulmonary embolus. Subsequent echocardiogram was normal. Patient was anticoagulated with low molecular weight heparin followed by warfarin. Vascular surgical team advocated medical management and patient received seven infusions of Iloprost followed by Sildenafil. She achieved near total resolution of skin changes to toes with only minimal loss of skin over tip of right great toe. Patient will now require long-termanticoagulation. Discussion/Results: APS was considered in initial differential diagnosis but patient did not meet current clinical criteria as no past evidence of thrombosis. Lupus anticoagulant was consistently strongly positive and anticardiolipin repeatedly negative. As anti-B2 glycoprotein 1 antibody is not routinely tested and must be verbally requested, it was only checked once (negative) prior to discovery of triple positivity. ANA reported as strongly positive at time of SLE diagnosis but reviewing original notes from India titre was 1:100 and therefore not highly convincing. ENA negative and complement and white cell count normal on repeat testing since. Therefore, it is probable that this patient has primary APS as opposed to secondary APS in association with SLE. However, it is possible that this patient may develop more symptoms of SLE over time. When this patient presented with foot rash there were high numbers of children presenting with varying severity of painful, itchy toes coined 'covid toes' due to suspected lin to SARS-CoV-2 infection. Patient had exposure history, and COVID antibody serology was difficult to interpret due to recent vaccination. Dermatology found appearance to be consistent with 'covid toes' and advised supportive treatment. The triple APS antibody positivity result provided probable aetiology. Providing evidence of thrombus was problematic with false reassurance from apparently normal lower limb arterial doppler when actually popliteal arteries were not checked in view of the presence of normal flow proximally at the groin and distally in the feet. This case highlights the need to continue to search for thrombus in presence of high titres antiphospholipid antibodies and particularly in the case of triple positivity as although patient presented with colour change to toes, she was entirely asymptomatic from her PE and her left foot improved spontaneously despite a left popliteal thrombus also being present. Key learning points/Conclusion: Non-criteria manifestation of thrombocytopenia (occurs in 25% paediatric APS patients) was present throughout and patient had past history of haematuria (a recognised renal non-criteria manifestation). A paediatric specific APS criteria including these may have resulted in earlier detection of triple antiphospholipid antibody positivity and thus earlier treatment escalation and possible avoidance of thrombus. It has been reported that a high proportion of children with positive antiphospholipid antibodies don't develop a thrombus. However, it is interesting that our patient was entirely asymptomatic from her pulmonary embolus which was an incidental finding on her CT angiogram. This prompts a discussion about how much imaging should be performed in those with high levels of persistent positive antiphospholipid antibodies. Rituximab resulted in normalisation of platelet count and ESR for the first time since initial presentation. Anticardiolipin antibodies normalised, lupus anticoagulant decreased from strong to moderate and anti- B2 glycoprotein levels decreased but remained positive. Rituximab is a recognised treatment for catastrophic antiphospholipid syndrome (CAPS) but not routinely used in APS. The consistently raised ESR in an apparently clinically well patient is a reminder to continue to search for causes of inflammation. As the CRP was largely in normal range, this demonstrates the unique value of the ESR. In view of anti-B2 glycoprotein 1 antibody requiring to be verbally requested, discussions are ongoing with the laboratory department regarding the possibility of electronic request and a comment with recommendation to check other two antiphospholipid antibodies following one positive antibody result. As a result of this case, a plan will be put in place to ensure annual screening of antiphospholipid antibodies in all juvenile SLE patients in our care. It is hoped that this case report promotes discussion amongst the paediatric rheumatology community regarding further research required for development of paediatric specific APS criteria and management.

Risk of exacerbation of rheumatic disease after COVID-19 vaccination

Objectives: To investigate the risk of flare-ups after COVID-19 vaccination in patients with rheumatic disease. Method(s): A total of 1617 patients with rheumatic diseases were identified from three rheumatology clinics. Patients were interviewed for demographic data, disease activity, and vaccination status. Clinical disease flare up was determined independently by expert opinion by managing rheumatologists. Change of serum markers and medications were retrieved from medical records. The risk of exacerbation of rheumatic disease, change in serum markers, and escalation of rheumatic medications between vaccinated and non-vaccinated patients were determined using cox, linear and logistic regression models respectively. Possible confounding factors were also taken into consideration. Result(s): There were 562 (34.76%) patients received COVID-19 vaccine. After vaccination, rheumatic disease (HR = 2.10, P < 0.001), inflammatory arthritis (HR = 2.71, P < 0.001), rheumatoid arthritis (RA) (HR = 2.03, P = 0.002), spondyloarthritis (SpA) (HR = 4.78, P < 0.001), autoimmune disease (HR = 1.77, P = 0.01), and systemic lupus erythematosus (SLE) (HR = 1.99, P = 0.02) were associated with clinical flare up. Adult still's disease (B = 12.76, P = 0.03) was associated with an increase in CRP level. Escalation of rheumatic medications were not associated with COVID-19 vaccination in all diseases. Subgroup analyses showed only mRNA vaccine was associated with disease flare ups. Conclusion(s): COVID-19 vaccine was associated with minor disease flare up but not escalation of rheumatic medications. In the absence of absolute contraindications, full COVID-19 vaccination in patients with rheumatic disease should be encouraged by managing rheumatologists.

Incidence and outcome of covid-19 in AIRD patients on concomitant treatment with tofacitinib-results from KRA covid cohort (KRACC) subset

Background: We assessed the risk factors and outcome of COVID-19 in patients with autoimmune rheumatic diseases (AIRD) who contracted infection while on background treatment with tofacitinib. Method(s): This is a non-interventional, cross-sectional, questionnaire based telephonic study which included consecutive AIRD patients on tofacitinib co-treatment. Data related to the AIRD subset, disease modifying anti rheumatic drugs (DMARDs) including glucocorticoids and comorbidities, was collected from 7 rheumatology centers across Karnataka during the second wave of COVID-19 pandemic. The information about COVID-19 occurrence and COVID-19 vaccination was recorded. Result(s): During the study period (June-July 2021), 335 AIRD patients (80.6% female) on treatment with tofacitinib were included. The mean duration of tofacitinib use was 3.4 +/- 3.1 months. Thirty-six (10.75%) patients developed COVID-19. Diabetes mellitus P = 0.04 (OR 2.60 [1.13-5.99]) was identified as a risk factors for COVID-19 in our cohort. Almost half of our cohort was COVID-19 vaccinated with at least one dose, with resultant decline in incidence of COVID-19 (OR 0.15 [0.06-0.39]) among the vaccinated. Recovery among COVID-19 infection group was 91.2%. Conclusion(s): The AIRD patients on co-treatment with tofacitinib had a higher incidence of COVID-19 than the general population during the same time period. Diabetes mellitus was identified as an independent risk factor in our cohort. COVID-19 vaccinated patients contracted COVID-19 at a significantly lesser rate than the non-vaccinated patients.