Resolution of unilateral sensorineural hearing loss in a pediatric patient with a severe phenotype of Muckle-Wells syndrome treated with Anakinra: a case report and review of the literature.

BACKGROUND: Muckle-Wells syndrome (MWS) is a rare auto-inflammatory disease characterized by the presence of recurrent urticaria, deafness and amyloidosis. Progressive sensorineural hearing loss (SNHL) is reported to occur in up to 85% of patients occurring in the second and third decades and as early as the first decade in patients with a more severe phenotype, thus potentially having a significant impact on a child's development. IL-1 inhibitors, such as Anakinra, have been described to improve systemic inflammation, and stabilize or improve hearing status as well. However, complete resolution of hearing loss has been rarely reported. The objective of this article is to highlight the clinical presentation of a pediatric patient with a severe form of MWS and report on the complete resolution of SNHL with the use of Anakinra. CASE PRESENTATION: A 3-year-old boy was referred to our hospital to assess for the possibility of MWS given a history of hives and recurrent episodes of fever with a family history of MWS in his mother. Of note, the patient's history was significant for conductive hearing loss, speech delay, as well as recurrent acute otitis media episodes. Genetic analysis was performed and diagnosis of MWS was confirmed due to the presence of a NLRP3 gene mutation. Further work-up demonstrated the presence of papilledema and elevation of systemic inflammatory markers for which Canakinumab was initiated. Despite initiation of this treatment, audiogram evaluation demonstrated a new right-sided SNHL. Lumbar puncture also revealed aseptic meningitis. Canakinumab was eventually discontinued and Anakinra initiated. Within 7 months of treatment with Anakinra at 5 mg/kg sc daily, resolution of the SNHL was observed. With further escalation of the Anakinra dose, there was also complete resolution of the aseptic meningitis. CONCLUSIONS: Progressive hearing loss is a significant finding in patients with MWS. Early screening as well as initiation of Anakinra can lead to complete resolution of SNHL even in a patient with a severe spectrum of MWS. However, as this case demonstrates, longer treatment duration and higher doses of Anakinra may be required to achieve this.

Aspirin Dose and Prevention of Coronary Abnormalities in Kawasaki Disease.

BACKGROUND: Acetylsalicylic acid (ASA) is part of the recommended treatment of Kawasaki disease (KD). Controversies remain regarding the optimal dose of ASA to be used. We aimed to evaluate the noninferiority of ASA at an antiplatelet dose in acute KD in preventing coronary artery (CA) abnormalities. METHODS: This is a multicenter, retrospective, nonrandomized cohort study including children 0 to 10 years of age with acute KD between 2004 and 2015 from 5 institutions, of which 2 routinely use low-dose ASA (3-5 mg/kg per day) and 3 use high-dose ASA (80 mg/kg per day). Outcomes were CA abnormalities defined as a CA diameter with a z score ≥2.5. We assessed the risk difference of CA abnormalities according to ASA dose. All subjects received ASA and intravenous immunoglobulin within 10 days of fever onset. RESULTS: There were 1213 subjects included, 848 in the high-dose and 365 in the low-dose ASA group. There was no difference in the risk of CA abnormalities in the low-dose compared with the high-dose ASA group (22.2% vs 20.5%). The risk difference adjusted for potential confounders was 0.3% (95% confidence interval [CI]: -4.5% to 5.0%). The adjusted risk difference for CA abnormalities persisting at the 6-week follow-up was -1.9% (95% CI: -5.3% to 1.5%). The 95% CI of the risk difference of CA abnormalities adjusted for confounders was within the prespecified 5% margin considered to be noninferior. CONCLUSIONS: In conjunction with intravenous immunoglobulin, low-dose ASA in acute KD is not inferior to high-dose ASA for reducing the risk of CA abnormalities.