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We present the case of a 63 years old male patient known for type 2 diabetes and sleep apnoea. He was admitted as inpatient for a nontraumatic severe and disabling left hip pain. The pain started progressively one month ago. The medical history was otherwise irrelevant, with no general symptoms nor other symptoms suggestive of an inflammatory disease. To mention a history of an asymptomatic SARS-COV2 infection, diagnosed by a naso-pharyngial PCR, approximately 10 days before the onset of the pain. On physical examination, the patient was afebrile. The palpation of the inguinal region was tender on palpation with marked limitation of the hip range of motion. The spine and other peripheral joints were painless without inflammatory sign. Moreover, there was no skin lesion nor inguinal lymph nods enlargement. Due to the importance of pain with marked functional limitation, the patient is hospitalized for investigations and pain-management. On blood sample there was a mild increase of inflammatory markers (CRP 25mg/l, VS 20mm/h) with normal cell count. Standard X-rays of the pelvis and hip were normal. The MRI of the hip showed a mild coxo-femoral arthritis with marked inflammation of the surrounding musculature. An arthrocentesis was performed and 2ml of serous fluid was aspirated. There were no crystals. The cellularity could not be tested due to small amounts of fluid. The synovial culture showed a polymicrobious growth compatible with contamination. In summary, we were facing a patient with an acute and very painful hip monoarthritis. There was no history of gastrointestinal or urinary tract infection, the search for C. trachomatis and N. gonorrhoea in urines was negative. An extensive serologic testing (HIV, HBV, HCV, HBV, HCV, HIV, Lyme, Syphilis, Coxiella, Bartonella, Brucella & Quantiferon) and the search for T. whipplei were negative as well. There was no HLA-B27 and rheumatoid factor, ACPA, ANA, ANCA and specific antibodies related to polymyositis were negative. The chest-abdomen-pelvis scan showed no sign of neoplasia. To rule out a vasculitis we proceeded to a PET-CT, which showed no sign of vasculitis or myositis. Considering the timing of the onset of the symptoms and the absence of any other diagnosis, the patient was diagnosed with reactive arthritis caused by SARS-COV2. The patient was treated with Diclofenac 150 mg/day and opioids. The clinical evaluation one month after discharge showed a spontaneous significant improvement.
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Background: Upadacitinib (UPA) was shown to be safe and effective through 2 years in patients (pts) with active ankylosing spondylitis (AS) naïve to biologic disease-modifying antirheumatic drugs (bDMARDs) in the pivotal phase 2/3 SELECT-AXIS 1 trial.1,2 Objectives: To assess the efficacy and safety of UPA in pts with active AS with an inadequate response (IR) to bDMARDs. Methods: SELECT-AXIS 2 (NCT04169373) was conducted under a master protocol and includes two separate studies (one for AS bDMARD-IR and one for non-radiographic axial spondyloarthritis [nr-axSpA]). The AS bDMARD-IR study is a randomized, double-blind, placebo (PBO)-controlled, phase 3 trial that enrolled adults ≥18 years with AS who met modifed New York criteria, had BAS-DAI and pt's assessment of total back pain scores ≥4 (numeric rating scale 0-10) at study entry, and had an IR to one or two bDMARDs (TNF inhibitor or IL-17 inhibitor). Pts were randomized 1:1 to receive oral UPA 15 mg once daily (QD) or PBO during the 14-week (wk) double-blind treatment period. The primary endpoint was ASAS40 response at wk 14. Multiplicity-controlled secondary endpoints evaluated at wk 14 were improvements from baseline in disease activity (ASDAS [CRP], ASDAS ID [<1.3], ASDAS LDA [<2.1], BASDAI50, ASAS20, and ASAS PR), pain (total and nocturnal back pain), function (BASFI), objective measure of infammation (SPARCC MRI score of the spine), spinal mobility (BASMI), enthesitis (MASES), and quality of life (ASQoL and ASAS HI). Non-responder imputation incorporating multiple imputation (NRI-MI) was used to handle intercurrent events and missing data for binary endpoints. Cochran-Mantel-Haenszel (CMH) test and mixed-effect model for repeated measures (MMRM) were used for analyzing binary and continuous endpoints, respectively. Treatment-emergent adverse events (TEAEs) assessed through wk 14 are reported for pts who had ≥1 dose of study drug. Results: All 420 randomized pts with active AS received assigned treatment (UPA 15 mg, n=211;PBO, n=209);409 (97%) received study drug through wk 14. Baseline demographic and disease characteristics were generally similar between treatment groups and refective of an active AS bDMARD-IR population (74% male;mean age 42.4 years;mean disease duration 7. 7 years;83% HLA-B27 positive;mean BASDAI 6.8). Signifcantly more pts achieved the primary endpoint of ASAS40 response at wk 14 with UPA vs PBO (45% vs 18%;P<0.0001;Figure 1);UPA showed onset of effect in ASAS40 as early as wk 4 (nominal P≤0.05). All multiplicity-controlled secondary endpoints met statistical signifcance for UPA vs PBO at wk 14 across multiple clinical domains of AS (P<0.0001;Figure 1). The rate of TEAEs was similar between treatment groups through wk 14 (UPA, 41%;PBO, 37%). TEAEs led to discontinuation in 3 (1.4%) pts treated with PBO and none with UPA. Serious infections occurred with UPA (2.4%) but not with PBO and included 4 events of COVID-19 and 1 event of uveitis. Additional events of uveitis were reported in 3 (1.4%) pts treated with PBO. Infammatory bowel disease (IBD) occurred in 1 (0.5%) pt on UPA and none on PBO. No malignancy, major adverse cardiovascular events, venous thromboembolic events, or death were reported with UPA;1 event of malignancy was observed with PBO. Conclusion: UPA 15 mg QD was signifcantly more effective than PBO over 14 wks of treatment in pts with active AS and IR to bDMARDs. No new safety risks were identifed with UPA compared with its known safety profile.3,4 These fndings are consistent with and complementary to those of SELECT-AXIS 1 (bDMARD-naïve AS population),1,2 and support the use of UPA in pts with active AS, including those who had a previous IR to bDMARD therapy.
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Background: SARS-Cov-2 infection had a major impact on patients with infam-matory rheumatic diseases. Spondyloarthritis (SpA) patients were one of the most affected groups of these patients. Objectives: To assess the impact of Covid19 in spondyloarthritis patients under biological disease modifying anti-rheumatic drugs (bDMARDs). Methods: A retrospective observational study was conducted using registry data of patients with SpA under bDMARD therapy, followed at a tertiary level hospital, that have been diagnosed with COVID19 from March 2019 to December 2021. At least one evaluation previous (t0) and two evaluations after SARS-CoV-2 infection (t1, t2) were included in our analysis. Sociodemographic, clinical, disease activity, therapeutic response, function and general health status data were collected. Statistical analysis (signifcance at p < 0.05) was performed using paired T-test, Wilcoxon test and McNemar tests for paired samples. Linear and logistic regression models were performed to assess direction and strength of association Results: Thirty-two patients with SpA under bDMARD had COVID19, mostly women (20, 62.5%), with a disease course time averaged 18.65 (± 9.69) years, mainly with axial involvement (19, 59.4%) and positive for HLA-B27 antigen (11, 64.7%). The majority were under TNF inhibitors (30, 93.75%), with golimumab being the most common (9, 28.1%), and with a median bDMARD persistence of 2.63 (5.09) years. Seven (21.9%) were under a cDMARD, 3 (9.4%) under NSAID and 18 (56.3%) under corticosteroids. Three (9.4%) were already vaccinated against SARS-CoV-2, 2 (66.6%) with the mRNA-1273 vaccine, presenting a medium time since inoculation of 240 (± 234.01) days. Arterial hypertension was the most common comorbidity (5, 15.6%) and one patient (3.1%) had a previous diagnosis of type 2 diabetes. Most were never-smokers (17, 53.1%) and never-drinkers (29, 90.6%). The average age at infection was 40.97 (± 6.15) years and the most common symptom was cough (22, 68.8%), followed by headache (20, 62.5%) and myalgia (19, 59.4%). Event tree analysis didn't show association with SpA subtype, education level, work status, tobacco or alcohol consumption. Only one patient needed hospital admission but without needing of oxygen, therapy, ventilator or ECMO. Only one patient had an overlaid bacterial infection and no thromboembolic complications were observed. Two patients needed specific SARS CoV-2 infection treatment, one with hydroxychloroquine and another with azithromycin. Twelve (37.5%) patients suspended bDMARD at the time of infection, with only 2 (6.3%) maintaining suspension at the time of the first post-infection visit. When comparing clinical variables, higher disease activity was seen at t1 only for BASDAI mean values, without statistical signifcance. Higher all domains VAS scores were also observed at t1, but not at t2, also without statistical signifcance;moreover, physical function didn't change signifcantly. No differences were observed according to gender or SpA subtype, nor with the use of cDMARDs, NSAIDs or corticosteroids. The only statistically signifcant difference concerned MASES score between t0 and t1 (1 ± 4 vs. 2 ± 6, p=0.04), but not between t0 and t2. Higher baseline tender joint score (p < 0.01) and higher baseline LEI (p=0.03) negatively correlated with MASES score variation. Several baseline variables correlated positively with MASES at t1, including female gender (p < 0.01), corticosteroid use (p = 0.04), BASDAI (p < 0.01), ASDAS-ESR (p < 0.01), ASDAS-CRP (p < 0.01), DAS28 (p < 0.01), SPARCC (p = 0.04), physician VAS (p = 0.03) and total spine VAS (p = 0.01). Working status varied signifcantly after SARS-Cov-2 infection (at least part-time-29, 90.6% vs. 22, 68.8%, p= 0.016). Conclusion: SpA patients on bDMARD had a mild course of SARS-CoV-2 infection, with slight changes in enthesitis score in the short term, the latter particularly in those with higher disease activity in the pre-infection period. Long-term effects on work status could represent confounding factors related to the e onomic constraints of the pandemic.
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introduction. hla alleles play a fundamental role in the development of the immune response against viral infections. objective. Gather the information available on the association of different hla alleles with increased protection or susceptibility;furthermore, the impact on complications associated with sars-cov-2 infection. methodology. An information search was carried out in the Scopus, PubMed/Medline, lilacs and Academic Google databases that answered the research question: What is the association between hla and sars-cov-2 infection and the severity of the illness? Records of clinical trials from the databases of the who International Clinical Trials Platform were included. results. It was found that the hla-a* 25: 01, hla-b* 46: 01 and hla-c* 01: 02 alleles were associated with greater susceptibility to infection, while the hla-a* 02: 01 alleles, hla-a* 24: 02 and hla-b*27: 07 were associated with greater severity of the disease and the alleles hla-a* 02: 02, hla-b* 15: 03 and hla-c* 12: 03 as protective factor in covid-19. conclusions. The association between susceptibility, protection and severity with the different types of hla are mainly reported in silico analysis, and its precision is limited, requiring support based on in vitro and in vivo experimental studies and clinical trials in different populations. A greater focus is needed on the affinity of the various hla alleles by the sars-cov-2 proteome to elucidate the immunopathogenesis of the disease.
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Objective: COVID-19 pandemic was associated with increased risk of hypovitaminosis D due to lockdown regulations and limited outdoor activities, while young adult patients with autoimmune conditions may associated decreased values of 25-hydroxyvitamin D due to copresence of celiac disease, glucocorticoid exposure, malabsorption, overtreatment of autoimmune hypothyroidism, etc. (1-5).We aim to introduce a female case known with autoimmune conditions who was admitted for vitaminD deficiency related symptoms during pandemic. Case report: A 41-year-old, nonsmoker female is admitted for nonspecific muscle cramps, and joints pain, asthenia which is persistent for the last several months in addition to chronic low back pain (which required chronic use of nonsteroid anti-inflammatory medication). Her personal medical background reveals a diagnosis of HLA-B27-positive ankylosing spondylitis that was established seven years before current admission. She is also known with autoimmune thyroiditis with negative antibodies, a diagnostic that was based on suggestive ultrasound features with highly hypoechoic pattern of relative small thyroid gland (and normal thyroid function). She is also confirmed with thrombophilia. She has a negative personal history of confirmed COVID-19 infection and she followed the lockdown restrictions for several weeks. The family medical history is irrelevant. On admission, clinical examination of the thyroid is within normal limits on amenstruated normal weighted female. Biochemistry data points out normal total calcium of 9.45 mg/dL (normal: 8.4-10.3 mg/dL). Endocrine panel shows TSH=1.28 μUI/mL (normal: 0.5-4.5 μUI/mL), free levothyroxine=11.65 pmol/L (normal: 9-19 pmol/L), anti-thyroperoxidase antibodies=10.88 UI/mL (normal: 0-35), anti-thyroglobulin antibodies=10 UI/mL (normal: 0-115 UI/mL). 25-hydroxyvitamin D=10 ng/mL (normal >30 ng/mL) with increased PTH levels and negative antibodies for celiac disease. Supplementation with daily 2000 UI of vitamin D for 12 weeks followed by daily 1000 UI was recommended. Conclusion: The association thrombophilia-hypovitaminosis D has been reported in some patients, but it is rather incidental. Chronic use of antiinflammatory medication may cause malabsorption, and also the potential of a second autoimmune disease at intestinal level may cause this deficiency, but the current pandemic reality has become a new cause of it.
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Case report-IntroductionSince the emergence of Coronavirus disease 2019 (COVID-19) there has been increasing recognition of the potential associated cardio-vascular manifestations. There have been reports of Kawasaki like disease in children. However, in adults there are very few reports of non-cutaneous vasculitis. Here we report the case of an adult male presenting with an inflammatory aortitis associated with COVID-19 infection.Case report-Case descriptionA 71-year-old Caucasian male with a background of cholecystectomy and rotator cuff repair presented to hospital in May 2020 with a 3-month history of feeling generally unwell, weight loss and worsening thoraco-lumbar back pain. Prior to the onset of these symptoms he had had a 2-week illness in March 2020 clinically consistent with COVID-19 infection comprising fevers, hot sweats, dry cough, and chest tightness for which he had not sought medical attention. He had no recent travel history. Physical examination was unremarkable.On admission, COVID-19 tests revealed evidence of prior infection with negative SARS-CoV-2 polymerase chain reaction test but positive SARS-CoV-2 antibodies. Blood tests revealed a marked inflammatory state with a C-reactive protein of 122mg/L, plasmas viscosity of 2.76, Ferritin 777ug/L, Interleukin-6 of 25 ng/L and normocytic anaemia with a Haemoglobin of 77g/L. Immunology tests were negative for anti-neutrophil cytoplasmic antibody, anti-glomerular basement antibodies, HLA-B27, anti-citrullinated protein antibody, rheumatoid factor, and nuclear antibodies, with normal IgG 4 subclasses. Microbiology workup showed negative blood cultures, syphilis screen and Hepatitis B and C serology. Temporal artery ultrasound was unremarkable. Troponin-T, pro-B-type natriuretic peptide, electrocardiogram and echocardiogram were normal. CT thorax abdomen pelvis revealed inflammatory change surrounding the aortic arch extending all the way down the aorta in keeping with a florid inflammatory aortitis with no aneurysms seen.Rapid resolution of symptoms was seen with commencement of Prednisolone 40mg once daily, with normalisation of CRP one week later and subsequent normalisation of haemoglobin and plasma viscosity. A repeat CT aorta 2 weeks after commencement of prednisolone demonstrated a reduction in the thickness of the inflammatory rind over the aorta from 6mm to 2mm. The patient now continues a reducing regime of prednisolone and remains in clinical remission.Case report-DiscussionIn children, Kawasaki like disease associated with COVID-19 is well described and can result in coronary artery inflammation and aneurysm. In adults, COVID-19 associated cutaneous vasculitis is well recognised however there are only a small number of case reports of organ specific vasculitis including the central nervous system, retina, and small bowel. To our knowledge this is the first reported case of aortitis associated with COVID-19 infection in an adult patient.The mechanisms underlying the development of COVID-19 associated vasculitis are not established but may be secondary to endothelial inflammation. Findings from a histological case series suggest that SARS-CoV-2 can infect endothelial cells directly, possibly via endothelial ACE2 receptors, leading to inflammation in the endothelium. Another postulated mechanism is that endothelial cell dysfunction and inflammation is caused by the cytokine storm that can be seen in some patients with COVID-19 infection.Our patient responded very well to corticosteroid treatment. However, in case of a relapse his cytokine profile could be helpful in directing further therapeutic options. IL-6 levels were elevated in our patient. Studies show that IL-6 appears to play a dominant role in the cytokine storm. In a report of 150 patients IL-6 was found to be significantly higher in the group with severe disease and possibly predictive of mortality. The IL-6 antagonist, Tocilizumab, has also been used with promising results. The first report of its use was in China in 21 critically ill COVID-19 patients with significant improvements Since this first report, further clinical trials are underway investigating the efficacy and tolerability of IL-6 antagonists in patients with COVID-19 disease. Expanding our understanding of the pathogenesis of COVID-19 associated vasculitis is a critical area for future research to identify other immune targets for novel/existing therapeutic agents.Case report-Key learning points Vasculitis including aortitis can be a complication of COVID-19 infection.Endothelial cell inflammation is likely to play key role in the pathogenesis of COVID-19 associated vasculitis.In addition to corticosteroids, other immune-modulating drugs presently used in rheumatology may be effective therapeutic agents.