Atypical Kawasaki Disease after COVID-19 Vaccination: A New Form of Adverse Event Following Immunization

Kawasaki disease (KD) is a medium-vessel vasculitis that is typically presented during childhood; fewer than 100 cases of KD have been reported worldwide in adult patients who met the criteria according to the American College of Rheumatology. This study presents the case of an 18-year-old patient with no previous history of any disease, who presented atypical KD with liver and kidney dysfunction, with a good response to intravenous immunoglobulin therapy. The symptoms began 22 days after the application of the COVID-19 vaccine (nonreplicating viral vector Vaxzevria), and other conditions were ruled out. The term Adverse Events Following Immunization (AEFI)encompasses all the reactions that follow the application of any vaccine with no necessary causal relationship and can be due to the vaccine product, quality of the vaccine, immunization errors, or anxiety or just happen to be coincident events. These reactions should be reported so that clinicians can identify compatible cases and consider that the presentation of this disease, despite being atypical, can be manifested in adult patients. Likewise, case reports are an important basis for the pharmacovigilance of vaccines.

Childhood Systemic Lupus Erythematosus: Presentation, management and long-term outcomes in an Australian cohort

Objectives Systemic Lupus Erythematosus (SLE) is a serious autoimmune disease often resulting in major end-organ damage and increased mortality. Currently, no data exists focussing on the presentation, long-term management and progression of SLE in the Australian paediatric population. We conducted the first Australian longitudinal review of childhood SLE, focussing on response to treatment and outcomes. Methods Detailed clinical and laboratory data of 42 children diagnosed with SLE before 16 years from 1998 to 2018 resident in Western Australia was collected. Data was collected at diagnosis and key clinical review time points and compared using the Systemic Lupus Collaborating Clinics (SLICC) and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) criteria. End organ damage was assessed against Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Incidence rates of disease complications and end organ damage were determined. Results Of the 42 children, 88% were female with average age at diagnosis of 12.5 years. Indigenous Australians were over represented with an incidence rate 18-fold higher than non-Indigenous, although most children were Caucasian, reflecting the demographics of the Australian population. Median duration of follow-up was 4.25 years. On final review, 28.6% had developed cumulative organ damage as described by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (incidence rate: 0.08/PY (95% CI 0.04–0.14)), and one child died. Twenty-nine children had renal involvement (incidence rate: 0.38/PY (95% CI 0.26–0.56)). Of the 27 patients with biopsy proven lupus nephritis, 70% had Class III or IV disease. Average length of prednisolone use from diagnosis was 32.5 months. Hydroxychloroquine ( n = 36) and mycophenolate mofetil ( n =21) were the most widely used steroid sparing agents. 61.9% received rituximab and/or cyclophosphamide. Conclusion This is the first longitudinal retrospective review of Australian children with SLE, with a markedly higher incidence in Indigenous children. Although improving, rates of end organ complications remain high, similar to international cohort outcomes. Longitudinal multi-centre research is crucial to elucidate risk factors for poor outcomes, and identifying those warranting early more aggressive therapy.

Lyme disease: modern approaches to treatment and prevention (based on international recommendations of 2020)

Lyme disease (LD) or tick-borne borreliosis affects thousands of people every year in different regions of the world, primarily in the United States and Europe. Given the great social and medical importance of this problem, an updated version of the clinical guidelines for the prevention, diagnosis and treatment of PD was published in November 2020 by a committee of experts of the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN) and the American College of Rheumatology (ACR). This article discusses the main issues of the use of antibacterial drugs in LD. The most commonly used medications are doxycycline, amoxicillin, cefuroxime axetil, and ceftriaxone. Patients with erythema migrans receive appropriate antibiotics for 7–14 days, depending on the medication used. In case of other clinical manifestations of LD, the duration of treatment is extended to 14–28 days. Antibiotic prophylaxis is carried out using a single oral dose of 200 mg doxycycline for adults and 4.4 mg/kg (with a maximum of 200 mg) for children. This treatment scheme is highly efficient, easy to administer, and has a relatively low risk of adverse events.

Use of protocol-driven medication refills by pharmacists decreases rheumatologist in-basket work and improves rheumatologist satisfaction

Burn-out among US physicians has been on the rise in the past few decades. Similarly, rheumatologists in the Geisinger Health System have experienced professional dissatisfaction through significant administrative burden and in-basket work. We embedded pharmacists into our rheumatology team in 2019 with the aim of reallocating medication refills to pharmacists, trained professionals in this domain, to help reduce physician workload and burn-out and increase satisfaction. Protocol-driven medication refill parameters per the American College of Rheumatology guidelines and new refill workflows for disease-modifying antirheumatic drugs (DMARDs) and non-DMARDs were created for use by our rheumatology pharmacists. Monthly data on medication refill volume and time saved for rheumatologists were collected from 1 January 2019 to 31 March 2021. Statistical analysis was completed via Shewhart p-charts. The volume of refills by rheumatologists decreased by 73% and the time saved per month for all the rheumatologists increased to 41.5 hours within 6 months. Physicians’ feedback was obtained via anonymous electronic surveys preintervention and postintervention. The statistical difference between the presurveys and postsurveys was calculated via two-tailed unpaired t-testing. It demonstrated reduced burn-out and improved workplace satisfaction. This study showed that the integration of rheumatology pharmacists into our practice can help improve the work life of the rheumatologists. It is important for physicians’ well-being to practice at the top of their scope and achieve work–life balance.

Variable presentations of systemic lupus erythematosus based on presence or absence of antidouble stranded DNA antibodies: A case series

Systemic lupus erythematosus (SLE) presents with diverse clinical features causing diagnostic challenges. Apart from the clinical features, autoantibodies are important for diagnosis along with certain laboratory parameters. Diagnosis is made with the European League against Rheumatism/American College of Rheumatology 2019 Criteria. The case series presented here signifies the correlation between anti ds DNA positivity and its association with poor prognosis and renal disease, whereas antidouble stranded DNA (anti-dsDNA) negativity may lead to lack of renal involvement and may be associated with polyserositis. The importance lies in the fact that these patients with anti-dsDNA negativity should be followed up for assessing conversion to positivity of anti-dsDNA, thus altering the prognosis and leading to renal involvement. Moreover, anti-SSA positive SLE patients must be followed up for possible development of sicca symptoms.

Review of guideline for the management of ANCA-associated vasculitis, presented in 2021 by the American College of Rheumatology/Vasculitis Foundation

The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are a group of severe life-threatening autoimmune diseases, and one of the most important problems in practical rheumatology. This article discusses 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of AAVs, including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). The guideline features 26 recommendations and 5 upgraded position statements for GPA/ MPA, as well as 15 recommendations and 5 upgraded position statements for EGPA, which became the basis for the proposed algorithms for the treatment of patients with GPA/MPA and EGPA. Particular attention has been paid to the use of biologics.

Worse cardiovascular and renal outcome in male SLE patients: First sex study from the Swiss SLE Cohort Study

Background: Systemic lupus erythematosus (SLE) in males is rare and poorly understood. Thus, still little is known about sex differences in SLE. We set out to identify sex differences regarding clinical manifestations as well as renal and cardiovascular outcomes of SLE. Methods: We analyzed patient data from the Swiss SLE Cohort Study. Cumulative clinical manifestations according to the updated American College of Rheumatology criteria were recorded at inclusion. Cardiovascular events were recorded within Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC-SDI). Renal failure was defined as eGFR<15 ml/min/1.73m2, initiation of renal replacement therapy or doubling of serum creatinine which were all assessed yearly or documented as end stage renal disease in SLICC-SDI. Risk differences were calculated using logistic regression and cox regression models. Results: We analyzed 93 men and 529 women with a median follow up time of 2 years. Males were significantly older at diagnosis (44.4 versus 33.1 years, p<0.001) and had less often arthritis (57% versus 74%, p=0.001) and dermatological disorders (61% versus 76%, p<0.01). In multivariate analysis female sex remained a significantly associated with arthritis and dermatological disorders. After adjusting for age, disease duration, ethnicity, time to diagnosis, medication and eGFR and SELENA SLEDAI at inclusion men had a significantly higher hazard ratio of 2.5 for renal failure (95% confidence interval (95%-CI) 1.1-6.0, p<0.04). Total SLICC-SDI Score was comparable. Men had significantly more coronary artery disease (CAD) (17% versus 4%, p<0.001) and myocardial infarction (10% versus 2%, p<0.01). In multivariate analysis, male sex remained a significant risk factor for CAD (odds ratio (OR) 5.6, 95%-CI 2.3-13.7, p<0.001) and myocardial infarction (OR 8.3, 95%-CI 2.1-32.6, p=0.002).Conclusion: This first sex study in a western European population demonstrates significant sex differences in SLE. Male sex is an independent risk factor for cardiovascular events and renal failure in SLE. Potential etiological pathomechanisms such as hormonal or X-chromosomal factors remain to be further investigated.

Efficacy And Safety of Canakinumab As A Second-Line Biologic After Tocilizumab Treatment Failure in Children With Systemic Juvenile Idiopathic Arthritis: A Single-Center Cohort Study Using Routinely Collected Health Data

Background: A significant number of systemic juvenile idiopathic arthritis (sJIA) patients discontinue biologic disease-modifying antirheumatic drugs (DMARDs) due to lack of efficacy or safety concerns. Studies of biologic therapy switch regimens in sJIA are required.Methods: Patients with sJIA who switched from tocilizumab (due to lack of efficacy or safety) to canakinumab (4 mg/kg every 4 weeks) and were hospitalized at the rheumatology department from August 2012 to July 2020 were included. Primary efficacy outcomes were 30% or greater improvement based on the pediatric criteria of the American College of Rheumatology (ACR30), achievement of inactive disease (JADAS‑71 =0) and clinical remission (ACR sJIA clinical inactive disease criteria). Follow-up was 12 months or the closest time point (not less than 6 and not more than 18 months). Data were extracted from outpatient medical records.Results: During the study period, 46 patients with sJIA switched from tocilizumab to canakinumab. Median age at canakinumab initiation was 8.2 (interquartile range 4.0; 12.9) years, and median sJIA duration was 1.8 (0.8; 5.8) years; 37 (80%) patients received at least one non-biologic DMARD (oral corticosteroids, methotrexate and/or cyclosporine A). Study outcomes were followed up in 45 patients (one patient did not attend the follow-up for an unknown reason); median follow-up was 359 (282; 404) days. During the follow-up, canakinumab was discontinued in one patient (due to tuberculosis detection) and the dose was reduced or the injection interval increased in four (9%) patients. In total, 27 (60%) patients continued to receive at least one non-biologic DMARD. Improvement according to the ACR30 criteria was achieved in 43 patients (96%; 95% confidence interval, 85–99), inactive disease in 42 (93%; 82–98), and clinical remission in 37 (82%; 69‑91); after adjustment for actual time-at-risk, the rates were 83, 85 and 73 events per 100 person-years, respectively. During follow-up, 23 adverse events (most frequently infections) were reported in 19/45 (42%) patients; 5/45 (11%) patients developed macrophage activation syndrome, with a favorable outcome in all cases.Conclusions: Short-term (about 12 months) canakinumab therapy was found to be potentially effective as second-line biologic therapy after discontinuation of tocilizumab in patients with sJIA. Trial registration: CACZ885G2301E1 (G2301; NCT00891046 registered on April 29, 2009) and CACZ885G2306 (G2306; NCT02296424 registered on November 20, 2014).

Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 1 trial

ObjectiveTo evaluate risankizumab, a biological therapy that inhibits interleukin 23, in patients with active psoriatic arthritis (PsA) who have responded inadequately or are intolerant to ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD).MethodsIn the randomised, placebo-controlled, double-blind KEEPsAKE 1 trial, 964 patients with active PsA were randomised (1:1) to receive risankizumab 150 mg or placebo at weeks 0, 4 and 16. The primary endpoint was the proportion of patients achieving ≥20% improvement in American College of Rheumatology criteria (ACR20) at week 24. Here, we report the results from the 24-week double-blind period; the open-label period with all patients receiving risankizumab is ongoing.ResultsAt week 24, a significantly greater proportion of patients receiving risankizumab achieved the primary endpoint of ACR20 (57.3% vs placebo, 33.5%; p<0.001). Significant differences were also observed for risankizumab versus placebo for the first eight ranked secondary endpoints, including skin and nail psoriasis endpoints, minimal disease activity and resolution of enthesitis and dactylitis (p<0.001). Adverse events and serious adverse events were reported at similar rates in the risankizumab and placebo groups. Serious infections were reported for 1.0% and 1.2% of patients receiving risankizumab and placebo, respectively. There was one death in the risankizumab group (urosepsis deemed unrelated to the study drug).ConclusionsRisankizumab treatment results in significantly greater improvement of signs and symptoms of PsA compared with placebo and is well tolerated in patients with active PsA who have responded inadequately or are intolerant to ≥1 csDMARD.Trial registration numberNCT03675308.