ABSTRACT
Drug development in lupus has improved over the past 10 years but still lags behind that of other rheumatic disease areas. Assessment of prospective lupus therapies in clinical trials has proved challenging for reasons that are multifactorial including the heterogeneity of the disease, study design limitations and a lack of validated biomarkers which greatly impacts regulatory decision-making. Moreover, most composite outcome measures currently used in trials do not include patient-reported outcomes. Given these factors, the Addressing Lupus Pillars for Health Advancement Global Advisory Committee members who serve on the drug development team identified an opportunity to convene a meeting to facilitate information sharing on completed and existing outcome measure development efforts. This meeting report highlights information presented during the meeting as well as a discussion on how the lupus community may work together with regulatory agencies to simplify and standardise outcome measures to accelerate development of lupus therapeutics.
Subject(s)
Lupus Erythematosus, Systemic , Humans , Prospective Studies , Lupus Erythematosus, Systemic/drug therapy , Outcome Assessment, Health Care , Research Design , Patient Reported Outcome MeasuresABSTRACT
BACKGROUND: Coronary artery (CA) aneurysms in children are a rare but potentially life-threatening finding and are highly associated with Kawasaki disease (KD). CASE PRESENTATION: We describe a four-year-old female with a vasculitis and CA aneurysms. She had a prolonged course with recurrent fever and systemic inflammation several times upon discontinuation of steroid treatment. Due in part to the CA aneurysms, she initially was diagnosed with KD but due to the unusual clinical course, further evaluation was performed. Abdominal and chest MRI/A revealed diffuse aortitis suggestive of a large vessel vasculitis, specifically Takayasu arteritis. With treatment targeted for Takayasu arteritis, there was resolution of fever and inflammation and the CA aneurysms improved. CONCLUSIONS: This case demonstrates the utility in broadening the differential diagnosis in cases of presumed KD with CA involvement in which the clinical course is atypical for KD.
ABSTRACT
Clinical features of Kawasaki disease (KD) display overlap with common pediatric viral illnesses, leading some to hypothesize that a viral infection is the inciting event for KD. To investigate viral infection history in KD patients, we performed comprehensive serological profiling using a high-throughput phage immunoprecipitation sequencing assay covering the complete reference protein sequences of known viruses with human tropism. KD and matched febrile control sera did not demonstrate differences in antiviral antibody profiles. We conclude that in the acute and subacute phases of disease, KD patients do not exhibit serologic evidence of exposure to known viruses that differs from controls.
Subject(s)
Antibodies, Viral/blood , High-Throughput Screening Assays/methods , Mucocutaneous Lymph Node Syndrome/blood , Mucocutaneous Lymph Node Syndrome/immunology , Antiviral Agents , Bacteriophages , Child, Preschool , Female , Humans , Immunoglobulin G/blood , Infant , Male , Mucocutaneous Lymph Node Syndrome/diagnosisABSTRACT
Febrile infection-related epilepsy syndrome (FIRES) is characterized by new onset refractory status epilepticus in a previously healthy child that is associated with poor cognitive outcomes and chronic epilepsy. Innate immune system dysfunction is hypothesized to be a key etiologic contributor, with a potential role for immunotherapy blocking pro-inflammatory cytokines, such as interleukin-1ß and interleukin-6. We present a case of FIRES refractory to anakinra, an interleukin-1 receptor antagonist, subsequently treated with the ketogenic diet and tocilizumab, an interleukin-6 receptor antagonist, temporally associated with seizure cessation and a favorable 1-year outcome.
