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Voriconazole is a fluoride-containing anti-fungal. Prolonged exposure can result in fluoride deposition within the bone extracellular matrix, resulting in periostitis and arthritis. We report a patient who developed widespread bony pain and polyarthralgia while on voriconazole therapy for COVID-19-associated pulmonary aspergillosis. No associated autoimmune rheumatic disease or alternative cause was noted. Blood investigations showed elevated total serum alkaline phosphatase, bone-specific ALP and fluoride levels, with normal serum voriconazole levels. A whole body nuclear bone scan showed multifocal periostitis. A diagnosis of voriconazole-induced periostitis and arthritis was made. Complete resolution of clinical symptoms with normalisation of the serum ALP occurred within four weeks of voriconazole cessation. While voriconazole-induced periostitis/arthritis is a recognised phenomenon in solid organ and haematopoietic stem cell transplant patients on long-term voriconazole, this case highlights the importance of having a high index of suspicion in other settings including CAPA. Clinical presentation can be mistaken for bony metastatic disease or other inflammatory arthritis.
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BackgroundEnthesitis and dactylitis are associated with greater disease activity and reduced quality of life. Results from the phase 3 randomized, placebo-controlled KEEPsAKE 1 and 2 studies (NCT03675308;NCT03671148) of risankizumab in active PsA showed greater resolution of enthesitis and dactylitis with risankizumab 150 mg vs placebo at week 24.ObjectivesThis post hoc analysis evaluated improvements in patient-reported outcomes (PROs) among patients who had enthesitis (n=444), dactylitis (n=188), or both (n=128) at baseline and achieved resolution of enthesitis, dactylitis, or both with blinded risankizumab at weeks 0, 4, 16, and open-label risankizumab every 12 weeks thereafter.MethodsAssessments included achievement of minimal clinically important differences (MCID) in pain (≥10-mm decrease on visual analog scale), Health Assessment Questionnaire-Disability Index (HAQ-DI;≥0.35-unit decrease), and Functional Assessment of Chronic Illness Therapy (FACIT-Fatigue;≥4-point increase). Nonresponder imputation (with multiple imputation for COVID-19–related missing data at week 24) was used.ResultsMany patients who achieved resolution of enthesitis at week 24;week 52 also achieved MCID in pain (66.4%;71.4%), HAQ-DI (58.2%;63.4%), and FACIT-Fatigue (59.0%;72.1%). Many patients who achieved resolution of dactylitis at week 24;week 52 also achieved MCID in pain, (72.2%;81.7%), HAQ-DI (56.3%;66.2%), and FACIT-Fatigue (67.7%;69.9%). Many patients who achieved resolution of both enthesitis and dactylitis at week 24;week 52 also achieved MCID in pain (82.1%;86.4%) HAQ-DI (66.7%;69.2%), and FACIT-Fatigue (71.4%;74.6%). PRO results for patients for who did not achieve resolution of enthesitis and/or dactylitis will be presented.ConclusionMajority of patients who achieved resolution of enthesitis and/or dactylitis with risankizumab also reported improvements in pain, disability, and fatigue.AcknowledgementsAbbVie and the authors thank the patients who participated in the study and all study investigators for their contributions. Medical writing assistance, funded by AbbVie, was provided by Lisa M Pitchford, PhD, of JB Ashtin.Disclosure of InterestsShawn Kwatra Consultant of: AbbVie, Aslan Pharmaceuticals, Arcutis, Celldex, Galderma, Genzada Pharmaceuticals, Incyte, Johnson & Johnson, Novartis, Pfizer, Regeneron, and Sanofi., Grant/research support from: Galderma, Incyte, Pfizer, and Sanofi., Saakshi Khattri Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, and UCB, Grant/research support from: Bristol Myers Squibb, LEO Pharma, Novartis, and Pfizer, Ahmad Amin Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, LEO Pharma, Regeneron, Sanofi/Genzyme, Pfizer, and UCB, Ran Liu Shareholder of: AbbVie, Employee of: AbbVie, Byron Padilla Shareholder of: AbbVie, Employee of: AbbVie, Ahmed M. Soliman Shareholder of: AbbVie, Employee of: AbbVie, Blair Kaplan Shareholder of: AbbVie, Employee of: AbbVie, Dennis McGonagle Speakers bureau: AbbVie, Janssen, Novartis, and Pfizer., Grant/research support from: AbbVie, Janssen, Novartis, and Pfizer, UCB, BMS, Celgene.
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Background/Aims Upadacitinib (UPA), an oral Janus kinase (JAK) inhibitor, demonstrated efficacy and safety in patients (pts) with psoriatic arthritis (PsA) and prior inadequate response or intolerance to >=1 biologic disease modifying antirheumatic drug (bDMARD) at week (wk) 56 in the phase 3 SELECT-PsA 2 study. We aimed to evaluate the efficacy and safety of UPA at wk 104 from the ongoing long-term extension of SELECTPsA 2. Methods Pts were randomized to UPA 15mg (UPA15), UPA 30mg (UPA30), or placebo (PBO) for 24 wks;PBO pts were then switched to UPA15 or UPA30. For continuous UPA treatment groups, efficacy endpoints at wk 104 were analyzed using non-responder imputation (NRI) and as observed (AO) (binary endpoints) or mixed-effect model repeated measures (MMRM) and AO (continuous endpoints). Treatmentemergent adverse events (TEAEs) were summarized for pts who received >=1 dose of study drug using visit-based cut-off at wk 104. Results A total of 641 pts received >=1 dose of study drug. At wk 104, 38.4% of all patients had discontinued study drug, with the highest discontinuation observed in patients randomized to PBO at baseline (all PBO: 46.7%). The most common reasons for discontinuation were lack of efficacy (UPA15: 12.3%, UPA30: 8.7%, all PBO: 21.7%) and adverse event (UPA15: 10.9%, UPA30: 13.3%, all PBO: 12.7%). The proportion of UPA pts that achieved ACR20/50/70, MDA, PASI75/90/100, and resolution of dactylitis and enthesitis were generally similar, or further improved, with 104 wks of treatment vs 56 wks. Similarly, mean change from baseline in HAQ-DI, patient's assessment of pain, BASDAI, and ASDAS was improved with UPA treatment. At 104 wks of therapy, clinical responses were largely similar with UPA15 and UPA30. Generally, safety data at wk 104 were consistent with that reported at wk 56. Rates of serious infection, herpes zoster, hepatic disorder, anemia, neutropenia, lymphopenia, and CPK elevation remained numerically higher with UPA30 vs UPA15, while rates of malignancies, MACE, and VTE were similar for both UPA groups. One death was reported with UPA15 (unexplained due to lack of information;however, the patient had recently been diagnosed with ovarian cancer) and two with UPA30 (pancytopenia and COVID-19 pneumonia). Conclusion In PsA pts with prior inadequate response or intolerance to>=1 bDMARD, clinical responses were maintained with UPA15 and UPA30 up to two years of treatment. No new safety signals were identified in this long-term extension.
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Introduction/Background: Primary bone marrow oedema syndrome is an elusive and less well-defined entity. Whether Rheumatologists should consider it as a stand alone diagnosis, is debatable. It possibly would be best described as an MRI feature which could be a finding in a number of diseases which would include the initial phases of Osteonecrosis of the bone, Rheumatoid Arthritis, Spondyloarthritis, Enthesitis related, Post traumatic, OA, Infections and Cancers. The treatment options become constricted due to the paucity of evidence. Rheumatologists need to consider this as an area of unmet need with development of consensus classification criteria and treatment approaches. Description/Method: 27-year-old male, Height 174 cms Weight 90 Kgs BMI 29 Kg/m2, became symptomatic in Jan 2022 with complains of pain in the both hip joints & groin regions, pain became excruciating and he became bed-bound, with early morning stiffness lasting approximately 45 mins. Had received steroids for COVID infection in August 2020. Investigations Hb 13.5gm/dl TLC 7000/mm3 Platelet 400 x 103/mm3 Sr Bil 0.8mg/dl AST 16 IU/L. ALT 24 IU/L Sr Creatininine 1.1mg/dl Blood Sugar Levels, Fasting 89 mg/dl Post Prandial 102 mg/dl ESR 10mm in 1st hour by Wintrobes method CRP Quantitative 29.38mg/L HLA B27 by PCR Negative, RF Negative, ACCP Negative Serum, IgG, Beta2 Glycoprotein 1.44 SGU Serum, IgM, Beta2 Glycoprotein 3.44 SGU Serum, IgG, Cardiolipin antibody 8.4 GPL Serum, IgG, Cardiolipin antibody 17.45 GPL Lupus anticoagulant by DRVVT Negative Sr Cholesterol 211mg/dl HDL 29 mg/dl LDL 156mg/dl TGs 130 mg/dl MRI Hips & SI joints Transient bone marrow oedema/osteopenia of bilateral hip. PET CT Increased metabolic activity in both hip joints Bone Scan (99mTcMDP) Increased vascularity in perfusion phase, increased accumulation in soft tissue in blood pool phase and increased uptake in bilateral Hip joints in skeletal phase scan, suggestive of CRPS Type-I. Management Was initially managed with Tab Etoricoxib 90mg BD, also started on Tab Sulphaslazine and Tab Methotrexate. However, when he had no symptomatic relief he was administered Inj Infliximab on 12 May 2022 and a second dose on 9 June 2022. He had excellent pain relief after the 1st dose, however after 10 days of the administration, he again began experiencing pain especially after walking. He also had pain in the knees on this occasion. He was also administered Inj Zoledronic 4mg on 23 May 2022. He is at present not requiring any NSAIDs over the last 1 month. Discussion/Results: The patient having presented with excruciating and debilitating pain was worked up and evaluation revealed features of bone marrow oedema on MRI which was corroborated with bone scan and PET CT imaging. The acute phase reactant CRP was also significantly elevated. The patient also gave history of early morning stiffness lasting approximately 45 mins. Hence an underlying Inflammatory process such as Spondyloarthritis(Peripheral) with enthesitis was considered. The confounding factors were the pain which worsened on mobilization, HLA B27 negative status, Rheumatoid Factor and ACCP negative status and past history of having received IV Corticosteroids for COVID infection in August 2020. In view of the debilitating pain and aworking diagnosis of Spondyloarthritis, hewas started onNSAIDs alongwith rest, initially, followed by conventional synthetic disease modifying agents in Rheumatic disease followed by biologic synthetic diseasemodifying agent - Inj Infliximab. The thought process was to avoid prolonged NSAID use to prevent the associated side effects. However, since Avascular Necrosis of the Femoral head is a very likely possibility, the patient is planned to be kept under close follow up. Key learning points/Conclusion: Collaborative efforts between the Departments of Nuclear Medicine, Radiology, Orthopaedics and Rheumatology are crucial in the early detection and approach to cases of Bone Marrow oedema. Avascular necrosis of head of Femur is a far more common entity and must be kept in ind even when a diagnosis of Bone Marrow oedema syndrome is being entertained. Diagnosis of Bone Marrow oedema syndrome must be entertained only as a diagnosis of exclusion. Continued follow up and regular imaging must be pursued rigorously in patients diagnosed with Bone Marrow oedema syndromes. There is a requirement to document acute phase reactants such as CRP and ESR in patients diagnosed with Avascular necrosis of bone as this data could help us differentiate AVN from Primary Bone marrow oedema in the early stages.
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Background: According to the recent medical literature, COVID-19 disease can lead to a constellation of clinical syndromes lasting well beyond the frst 30 days of infection. The most common post COVID sequalae includes pulmonary, nervous system and neurocognitive, mental, metabolic, cardiovascular, gastrointestinal and several other clinical manifestations. Regarding joint involvement and particularly reactive arthritis (ReA), literature data is limited and describes case reports or series of cases of patients diagnosed with this condition following COVID-19 disease. Objectives: To describe the pattern and the management of post-COVID reactive arthritis. Methods: We have conducted a descriptive study of consecutive adult patients who presented to rheumatology outpatient clinic for joint or peri-articular pain/swelling/stiffness and received a diagnosis of post-COVID 19 reactive arthritis, by excluding other types of rheumatological conditions. The assessed clinical variables were: visual analogue scale (VAS) pain, swollen joint count (SJC), tender joint count (TJC), duration of morning stiffness, presence of enthesitis/tendinitis and axial involvement. Biochemistry and serology was performed: rheumatoid factor, ACPA, ANA, HLA B27, antiChlamydia Trachomatis, Ureaplasma Urealyticum and Mycoplasma Hominis Ab, anti HBs and HBc Ab, and anti HCV. COVID-19 disease prior to diagnosis of ReA was confrmed by PCR test. Results: In the study were included 16 patients with confrmed post COVID-19 ReA. The mean age of the study group was 43.5±10.8 (range 21-60), the female: male ratio was 4:1 and the duration of joint symptoms was 10.4±11.8 (range 1-42) weeks. The severity of COVID-19 disease was mild in 68.7% cases, moderate in 18.7% and severe in only 6.2% of the cases. The duration between COVID-19 diagnosis and ReA varied between cases, with a mean value of 4.3±4.2 (range 1-12) weeks. In 43.7% of the cases patients had peripheral joint involvement (synovitis), in 37.5%-periarticular involvement (enthesitis), 6.25%-isolate axial involvement (sacroiliac joints), 6.25% enthesitis and axial involvement (cervical spine) and 6.25% synovitis and enthesitis. In patients with peripheral joint pattern, the distribution of pain was symmetric (71.4%). The pattern of synovitis was determined by a TJC of 6.25±5.2 (range 1-16) joints and SJC 1.6±2.4 (range 0-7) joints. Both TJC and SJC correlated positively with the duration of morning stiffness (r=0.9 and r=0.6), but did not correlate with the VAS pain scale. In most of the cases synovitis affected the hand (wrist, MCP and PIP) 62.5% and the knee, feet and ankles-50%. Two patients presented with monoarthritis, 1 with oligoarthritis and 5 with polyarthritis, in the majority of cases, involvement being symmetric (75%). Periarticular pattern was determined by enthesi-tis, affecting the elbow and shoulder (50%), costo-sternal enthesitis (25%) and trochanteritis (25%). From the entire study group, 31.2% had elevated serum infammatory markers (ESR and/or CRP). Patients responded well to NSAIDs alone in 68.7% cases, local (intra-articular or peri-articular infltrations) or and systemic corticoids (5 mg Prednisolone equivalent) were administered in 5.3% and 12.5% cases respectively, in 12.5% cases (two patients) Methotrexate was administered. Conclusion: Reactive arthritis represents a post COVID-19 sequelae. The time of onset of ReA varied between 1 and 12 weeks after COVID-19 diagnosis. The clinical pattern of the disease was expressed by joint or periarticular involvement, mainly affecting the hand, feet and knee symmetrically. Cases of axial manifestations were less common. Most of the patients responded well to NSAIDs, only in a few particular cases, low doses of corticoids and/or Methotrexate were recommended.
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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: Upadacitinib (UPA), an oral Janus kinase (JAK) inhibitor, demonstrated efficacy and safety in patients (pts) with psoriatic arthritis (PsA) and prior inadequate response or intolerance to ≥1 biologic disease-modifying antirheu-matic drug (bDMARD) at week (wk) 56 in the phase 3 SELECT-PsA 2 study.1 Objectives: To evaluate the efficacy and safety of UPA at wk 104 from the ongoing long-term extension of SELECT-PsA 2. Methods: Pts were randomized to UPA 15 mg (UPA15), UPA 30 mg (UPA30), or placebo (PBO) for 24 wks;PBO pts were then switched to UPA15 or UPA30. For continuous UPA treatment groups, efficacy endpoints at wk 104 were analyzed using non-responder imputation (NRI) and as observed (AO) (binary endpoints) or mixed-effect model repeated measures (MMRM) and AO (continuous endpoints). Treatment-emergent adverse events (TEAEs) were summarized for pts who received ≥1 dose of study drug using visit-based cut-off at wk 104. Results: A total of 641 pts received ≥1 dose of study drug. At wk 104, 38.4% of all patients had discontinued study drug, with the highest discontinuation observed in patients randomized to PBO at baseline (all PBO: 46.7%). The most common reasons for discontinuation were lack of efficacy (UPA15: 12.3%, UPA30: 8.7%, all PBO: 21.7%) and adverse event (UPA15: 10.9%, UPA30: 13.3%, all PBO: 12.7%). The proportion of UPA pts that achieved ACR20/50/70, MDA, PASI75/90/100, and resolution of dactylitis and enthesitis were generally similar, or further improved, with 104 wks of treatment vs 56 wks1 (Table 1). Similarly, mean change from baseline in HAQ-DI, patient's assessment of pain, BASDAI, and ASDAS was improved with UPA treatment. At 104 wks of therapy, clinical responses were largely similar with UPA15 and UPA30. Generally, safety data at wk 104 (Figure 1) were consistent with that reported at wk 56.1 Rates of serious infection, herpes zoster, hepatic disorder, anemia, neutropenia, lymphopenia, and CPK elevation remained numerically higher with UPA30 vs UPA15, while rates of malignancies, MACE, and VTE were similar for both UPA groups. One death was reported with UPA15 (unexplained due to lack of information;however, the patient had recently been diagnosed with ovarian cancer) and 2 with UPA30 (pancytopenia and COVID-19 pneumonia). Conclusion: In PsA pts with prior inadequate response or intolerance to ≥1 bDMARD, clinical responses were maintained with UPA15 and UPA30 up to 2 years of treatment. No new safety signals were identifed in this long-term extension.
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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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Among the pathophysiological mechanisms of immune-mediated inflammatory diseases (IMIDs), specific attention has been paid to the abnormal activation of Th17 type immune response related to the dysregulated synthesis of cytokines forming the interleukin (IL)-23 and IL-17 axis. IL-23 blockade is an innovative approach to the treatment of psoriasis and psoriatic arthritis (PsA). Much of the interest has focused on guselkumab (GUS) (TREMFYA, Janssen, Johnson & Johnson, USA), a fully human IgG λ monoclonal antibody (mAb) targeting the p19 IL-23 subunit and the first-in-class treatment approved for patients with psoriasis and PsA. In patients with psoriasis, GUS is at least as effective as other biologic therapies for PsA and is superior to ustekinumab, an anti-IL-12/IL-23 mAb, and secukinumab, an anti-IL-17 mAb. Compared with TNF-α inhibitors, GUS therapy is less likely to cause infections and does not increase the risk of the reactivation of latent TB infection. The new GRAPPA guidelines (2021) recommend GUS (and other IL-23 inhibitors) for patients with PsA resistant to conventional disease-modifying antirheumatic drugs (DMARDs), who have peripheral arthritis, enthesitis, dactylitis, psoriatic skin and nail lesions. The paper discusses new data on the efficacy of GUS in patients resistant to TNF-α inhibitors, its benefits in patients with axial PsA, and safety during the COVID-19 pandemic.
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Background: The coronavirus disease or COVID-19 pandemic is the major global health crisis of the present time. Various rheumatological manifestations have been reported during or after COVID-19 infection, but data are scarce. In this observational study, we have tried to analyze the clinical characteristics of COVID-19 associated arthralgia/arthritis. Methods: We have collected the clinical data of 14 patients over the past 6 months who have developed arthralgia or arthritis during or after symptomatic COVID-19 infection, proven by a positive reverse transcription-polymerase chain reaction test from nasopharyngeal swab. Results: The most common symptoms during COVID-19 infection in the 14 patients were fever and myalgia, being present in 92.8% and 64.3% patients, respectively. Arthralgia/arthritis occurred at a mean interval of 20 days (range: 0-60 days). Knee was the most commonly involved joint (78.6%), followed by the wrist and metacarpophalangeal joints (each in 57.1%). Enthesitis was documented in 21.4% patients. The mean duration of COVID-19 associated arthralgia or arthritis was 53.9 days (range: 7-210 days). In 85.7% patients, joint pains improved within 2 months;in only a small proportion of patients (14.3%), joint pains persisted after 6 months. Nonsteroidal anti-inflammatory drugs (NSAIDs) (given in 64.3% patients) and corticosteroids (in 50%) were the most commonly prescribed and effective treatment options. Conclusion: COVID-19 infections mostly caused reactive arthritis, though acute and chronic arthritis is also seen. In the majority of cases, arthritis started about 3 weeks after COVID-19 infection and subsided within 2 months. NSAIDs and corticosteroids are the most effective treatment options.
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Background/Aims Vaccination of children and young people (CYP) with rheumatic and auto-inflammatory diseases is reported to be lower than amongst healthy peers. Whilst vaccination to confer protection against COVID- 19 is now underway amongst adults and adolescents, vaccination of CYP under 16 years was not available at the time of this study. This study sought to understand the views of parents/carers regarding vaccination against COVID-19 for CYP with rheumatic and autoinflammatory diseases. Methods An online survey was developed and shared via social media and direct contacts, targeted at parents of children with rheumatic and autoinflammatory conditions in Canada. Fieldwork took place during May 2021. Consent was provided during enrolment. Results A total of 157 responses were received (78% female, median age 12). The primary diagnosis for the majority was juvenile idiopathic arthritis (JIA;39% polyarticular, 15% oligoarticular, 8% enthesitis-related JIA, 6% psoriatic, and 9% systemic). At the time of completing the survey, the majority of CYP had received no vaccination against COVID-19 (83%), although 17% had received one dose;none had received both doses. The majority of parents/carers (55%) would agree for their child to be vaccinated to prevent COVID-19 if the vaccine was approved and available at no cost, with only 10% saying they would not agree, and 18% unsure. Overall, 40% would allow their child to have the vaccine as soon as it was available, with a further 22% who would prefer to wait, and 10% who will allow their child to have the vaccine only when required to. Reasons given by parents choosing not to vaccinate their child against COVID-19 focussed on perceived safety, apparent lack of testing, and alleged potential damage caused by vaccines. In addition, some respondents advised that they had seen anti-vaccine videos on social media targeted at young people, but would still have their child vaccinated when it was available. The majority (92%) cited their doctor or health professionals would be a key source of information when deciding whether to vaccinate their child;however, this varied significantly (p=.0017, chisquare) based on whether they currently would agree to have their child vaccinated, with only 69% of parents who would not vaccinate their child saying their healthcare professional would influence their decision. Around 38% of parents would be influenced by information from their patient organisation. Parents who indicated they would not be vaccinated themselves were less likely to agree for their child to be vaccinated (p<.001, chi-square). Conclusion Healthcare professionals play a vital role in supporting, advising and influencing parental decision-making with regards to COVID-19 vaccination amongst CYP with rheumatic and autoinflammatory conditions, particularly amongst parents/carers who are currently undecided. Working collaboratively with patient organisations to deliver simple, clear advice may help reduce vaccine hesitancy.
ABSTRACT
Introduction: Vaccination of children and young people (CYP) with rheumatic and auto-inflammatory diseases is reported to be lower than amongst healthy peers. Whilst vaccination to confer protection against COVID-19 is now underway amongst adults, vaccination of children under 16 years is not yet available. Objectives: To understand the views of parents/carers regarding vaccination against COVID-19 for CYP with rheumatic and autoinflammatory diseases. Methods: An online survey was developed, translated into multiple languages and shared via social media and patient organisations, targeted at parents of children and young people (CYP) with rheumatic, autoimmune and autoinflammatory conditions. Fieldwork took place between 2 and 22 April 2021. Consent was provided during enrolment. Results: A total of 133 CYP were included (66% female, median age 12). The majority were from the UK, Ireland and Greece (53%, 26%, and 9% respectively). The primary diagnosis for the majority was Juvenile Idiopathic Arthritis (JIA;46% polyarticular, 16% oligoarticular, 13% enthesitis-related JIA, 7% psoriatic, and 7% systemic), although no significant differences in outcomes between any diagnoses were identified. At the time of completing the survey, the majority of CYP had received no vaccination against COVID-19 (93%), although 5% had received one dose and 2% had received both doses;those receiving any vaccination were all aged 16 and over. The majority of parents/ carers (65%) would agree for their child to be vaccinated to prevent COVID-19 if the vaccine was approved and available at no cost, with only 8% saying they would not agree, and 21% unsure. Overall, 45% would allow their child to have the vaccine as soon as it was available, with a further 20% who would prefer to wait, and 11% who will allow their child to have the vaccine only when required to. Reasons given by parents choosing not to vaccinate their child against COVID-19 focussed on perceived safety, apparent lack of testing, and alleged potential damage caused by vaccines. When asked about the sources of information most likely to influence their decision about vaccination against COVID-19 for their child, the majority (90%) cited their doctor or health professionals;however this varied significantly (p=.015, chi-square) based on whether they currently would agree to have their child vaccinated, with only 64% of parents who would not vaccinate their child saying their healthcare professional would influence their decision. Around one-third of parents would be influenced by information from their patient organisation. Unsurprisingly, parents who indicated they would not be vaccinated themselves were less likely to agree for their child to be vaccinated (p<.001, chi-square). Conclusion: Healthcare professionals and patient organisations play a key role in supporting, advising and influencing parental decisionmaking with regards to COVID-19 vaccination amongst CYP with rheumatic and autoinflammatory conditions, particularly amongst parents/carers who are currently undecided whether to vaccinate or not. As vaccines become available for CYP there is a need for accurate, reliable and clear information for parents and carers to make informed decisions.
ABSTRACT
Case report-IntroductionIn December 2019, the first cluster of Coronavirus disease 2019 (COVID-19) cases caused by the novel coronavirus SARS-CoV-2 was identified in Wuhan, China. The disease was declared a global pandemic on 11th March 2020. COVID-19 was initially thought to cause respiratory complications only, however several extra pulmonary manifestations of the infection have since emerged.We report a rare case of reactive arthritis (ReA), urticarial rash and angioedema in a young female secondary to COVID-19 infection. Rashes were recently added to the World Health Organisation (WHO) criteria for diagnosis of COVID-19 demonstrating their significance.Case report-Case descriptionA 31-year-old female doctor was admitted with acute swelling of her lips, dysphagia, and a widespread urticarial rash. Preceding this she had a one-week history of fever, cough, and constitutional symptoms of malaise and weight loss. Her symptoms had started at the end of April 2020 during the peak of the COVID-19 pandemic in the United Kingdom. Three days later she developed painful swelling of her wrists, elbows, knees, and hands. She reported no back or sacroiliac joint pain, enthesitis or any previous history of inflammatory joint pains. She had a history of platelet dysfunction and was treated with Desmopressin.Clinical examination revealed a widespread urticarial rash over her face, limbs, and trunk, with no nail abnormalities. She had active synovitis in her right wrist, elbow, and mild bilateral knee effusions. All other joints including spine and sacroiliac joints were normal. She had no dactylitis or enthesitis. Systemic examination was normal. Investigations revealed Hb 113 g/L, MCV 88.2 fL, Platelets 282 x 109/L, WCC 6.6 x 109/L and Lymphocytes of 0.63 x 109/L with normal neutrophil and eosinophil count. CRP was raised at 107mg/L. She had a negative autoimmune screen including ANA, ANCA, IgM-RF, anti-CCP antibodies and HLA B27. Plain radiographs of knees were normal. SARS CoV-2 PCR was positive following a nasal swab. Urine and blood cultures were negative. Treatment was commenced with intravenous hydrocortisone and antihistamines with resolution of her angioedema symptoms;however, her rash and arthritis persisted.The patient was diagnosed with Reactive Arthritis (ReA), urticarial rash and angioedema secondary to COVID-19 infection. Prednisolone 30mg daily was started, and within a week her arthritis and rash markedly improved. Prednisolone was tapered over six weeks. By her two-month clinic follow up, she reported no further joint swelling and was functioning normally.Case report-DiscussionThe most common complication of COVID-19 is Acute Respiratory Distress Syndrome (ARDS) however several other serious complications have been identified including cardiac injury, thromboembolic events, neurological abnormalities, and an aggravated inflammatory response causing a cytokine storm.ReA is a post infectious arthritis commonly seen following gastrointestinal or genitourinary infections and is yet to be recognised as a complication of this disease. ReA most commonly presents as an asymmetrical peripheral or axial spondyloarthropathy. The affected joints do not contain pathogen. More than half of ReA cases resolve spontaneously within six months without requiring long-term treatments.Up to 20% of patients with COVID-19 infection have been shown to develop cutaneous manifestations including erythematous rash, vesicular rash, acral ischaemia, rash with petechiae, and widespread urticaria. This has led to the recent addition of rashes to the World Health Organisation (WHO) Criteria for diagnosis of COVID-19 infection. Additionally, as COVID-19 has an incubation period of 14 days where patients can be asymptomatic, cutaneous manifestations may serve as an early indicator of infection, aiding in a more rapid diagnosis.Case report-Key learning pointsWe present a rare case of ReA secondary to COVID-19 infection, with complete resolution of symptoms following administration of oral glucocorticoids. A detailed history and examination of t e musculoskeletal system should be undertaken in all patients presenting with COVID-19. Urticarial rashes should be considered as an early symptom of COVID-19 infection as per the WHO criteria for diagnosis. Glucocorticoids can be considered in treating patients with this presentation, where traditional anti-inflammatory agents have been refractory or contraindicated.
ABSTRACT
Case report-IntroductionWe describe an acute onset self-limiting seronegative non-destructive symmetrical polyarthritis five weeks after laboratory confirmed COVID-19 infection.Case report-Case descriptionA 37-year-old male hospital doctor of presented to the Early Inflammatory Arthritis clinic with a four-week history of acute onset joint pain, swelling and early morning stiffness in excess of two hours. The symptoms began at the left ankle with Achilles' tendonitis but progressed over the following 72 hours to a symmetrical polyarthritis affecting the wrists, proximal interphalangeal joints, shoulders, elbows, and knees.Approximately five weeks prior to the onset of his joint symptoms he had laboratory confirmed SARS-CoV-2 infection with six days of fever, non-productive cough, and fatigue. He did not require hospitalisation.His past medical history was significant for biopsy proven non-alcoholic fatty liver disease. There was no prior history of inflammatory arthritis and no personal or family history of skin psoriasis, inflammatory bowel disease or uveitis. There was no preceding genitourinary or gastrointestinal upset. His family history was significant for a sister with seronegative rheumatoid arthritis for which she was taking sulfasalazine.Examination revealed a normal BMI, synovitis at the wrists and proximal interphalangeal joints without evidence of joint effusion in the large joints. Blood tests revealed elevations in the ESR (83 mm/hour, reference range 0-10 mm/hour) and CRP (25mg/dL, reference range <5mg/dL). Serology was negative for the rheumatoid factor, anti-CCP antibodies, antinuclear antibodies, and an extractable nuclear antigen panel. Radiographs of the affected joints were unremarkable. Serological testing was positive for anti-SARS-CoV-2 IgG antibodies.He was started on oral Prednisolone 20mg daily and an NSAID with good symptomatic response and normalisation of his ESR (5mm/hour) and CRP (<1mg/dL). The course of prednisolone was tapered over a 6-week period and he is still in steroid free remission with normal inflammatory markers at follow up. The patient was given a diagnosis of a post-viral reactive arthritis which was attributed to the preceding COVID-19 illness.Case report-DiscussionPost infectious inflammatory arthritis has been described with many viral infections including: hepatitis virus, parvovirus B19, enterovirus, rubella, alphavirus (including Chikungunya), flavivirus (including Zika), herpes viruses (including Epstein-Barr virus), varicella, cytomegalovirus and human immunodeficiency virus (HIV). Interestingly, viral arthritis has not been reported in influenza and human coronaviruses (including SARS and MERS). Arthralgia was reported in 14.9% of laboratory confirmed COVID-19 cases in China during the early phases of the pandemic but inflammatory arthritis was not well described.The clinical course of the inflammatory arthritis in this case was self-limiting with enthesitis and synovitis resolving within six weeks of onset with the mainstay of treatment being symptomatic relief in the form of non-steroidal anti-inflammatory drugs and corticosteroids.Patient perspective: When I woke up that Tuesday morning with severe joint pains and stiffness, I knew something was not right. It was not like anything I have felt before in terms of my joints, having had sports injuries in the past. It was to the point where I was even struggling to go from sitting to standing. Without Prednisolone, I feel as if I would not have been able to work and may even have been house bound. I was relieved that this inflammatory arthritis did respond to Prednisolone. After six weeks of taking Prednisolone, the condition seemed to settle.Case report-Key learning pointsA self-limiting episode of inflammatory arthritis may occur following COVID-19 infection.