Pediatric Beta Blocker Therapy: A Comprehensive Review of Development and Genetic Variation to Guide Precision-Based Therapy in Children, Adolescents, and Young Adults.

Beta adrenergic receptor antagonists, known as beta blockers, are one of the most prescribed medications in both pediatric and adult cardiology. Unfortunately, most of these agents utilized in the pediatric clinical setting are prescribed off-label. Despite regulatory efforts aimed at increasing pediatric drug labeling, a majority of pediatric cardiovascular drug agents continue to lack pediatric-specific data to inform precision dosing for children, adolescents, and young adults. Adding to this complexity is the contribution of development (ontogeny) and genetic variation towards the variability in drug disposition and response. In the absence of current prospective trials, the purpose of this comprehensive review is to illustrate the current knowledge gaps regarding the key drivers of variability in beta blocker drug disposition and response and the opportunities for investigations that will lead to changes in pediatric drug labeling.

Cardiac Biomarkers Aid in Differentiation of Kawasaki Disease from Multisystem Inflammatory Syndrome in Children Associated with COVID-19.

Kawasaki disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 show clinical overlap and both lack definitive diagnostic testing, making differentiation challenging. We sought to determine how cardiac biomarkers might differentiate KD from MIS-C. The International Kawasaki Disease Registry enrolled contemporaneous KD and MIS-C pediatric patients from 42 sites from January 2020 through June 2022. The study population included 118 KD patients who met American Heart Association KD criteria and compared them to 946 MIS-C patients who met 2020 Centers for Disease Control and Prevention case definition. All included patients had at least one measurement of amino-terminal prohormone brain natriuretic peptide (NTproBNP) or cardiac troponin I (TnI), and echocardiography. Regression analyses were used to determine associations between cardiac biomarker levels, diagnosis, and cardiac involvement. Higher NTproBNP (≥ 1500 ng/L) and TnI (≥ 20 ng/L) at presentation were associated with MIS-C versus KD with specificity of 77 and 89%, respectively. Higher biomarker levels were associated with shock and intensive care unit admission; higher NTproBNP was associated with longer hospital length of stay. Lower left ventricular ejection fraction, more pronounced for MIS-C, was also associated with higher biomarker levels. Coronary artery involvement was not associated with either biomarker. Higher NTproBNP and TnI levels are suggestive of MIS-C versus KD and may be clinically useful in their differentiation. Consideration might be given to their inclusion in the routine evaluation of both conditions.

Disseminated Juvenile Xanthogranuloma with a Novel MYH9-FLT3 Fusion Presenting as a Blueberry Muffin Rash in a Neonate.

Juvenile xanthogranuloma (JXG) is a benign proliferative histiocytic disorder of the dendritic cell phenotype. It mostly presents in the pediatric age group as a solitary skin lesion. We describe a rare case of an infant born with disseminated JXG who presented with a blueberry muffin rash at birth. A term infant was noted to have multiple petechiae, purple nodules, and macules (1 mm-2 cm in diameter) and hepatosplenomegaly, at the time of birth. Further investigations revealed thrombocytopenia and direct hyperbilirubinemia and a magnetic resonance imaging showed scattered tiny foci of restricted diffusion in multiple areas of the brain. Patient received multiple platelet transfusions in the first few weeks with gradual improvement in thrombocytopenia. Ultimately, a biopsy of one of the lesions revealed the diagnosis of disseminated JXG with notable atypical features. Somatic mutation analysis showed a novel MYH9-FLT3 fusion, but a bone marrow biopsy was negative. The lesions faded over time, relative to patient's growth and normal neurodevelopment was noted at 18 months of age. JXG should be considered in the differentials of blueberry muffin rash in an infant. Although, JXG is mostly a self-limited condition, congenital disseminated JXG may be associated with significant morbidity and mortality.

Infected subgaleal hematoma in a 4-month-old girl.

Subgaleal hematoma is an uncommon, but potential sequela of birth trauma and instrument-assisted delivery of neonates, as well as head trauma in young children. A rare complication is an infection of the subgaleal hematoma, which typically happens due to concomitant scalp lacerations. Escherichia coli is the most common causative pathogen in peripartum cases, and Staphylococcus aureus predominates in trauma cases. An even more rare complication is infection of the hematoma with intact overlying skin, the proposed mechanism of action of which is a hematogenous spread of the bacteria. In this case, we report a 4-month-old unimmunized girl who sustained a subgaleal hematoma after a falling incident that did not result in any scalp laceration. She presented 5 days later with fever, irritability, increased scalp swelling, skin erythema, and site tenderness. Her blood culture remained sterile, but the hematoma aspirate culture grew Streptococcus pneumoniae. The patient had a recent upper respiratory tract infection that we suspected to be the primary source of infection. She responded well to antibiotic therapy and required no surgical intervention. Conclusion: Subgaleal hematoma infection should be suspected in a child who presents with increased hematoma swelling, irritability, fever, and local signs of infection. Early recognition and treatment with antibiotics can prevent further complications, such as abscess formation and skull osteomyelitis.

Forgotten but Not Gone! Syphilis Induced Tenosynovitis.

Objective. Tenosynovitis, inflammation of a tendon and its synovial sheath, is a rare manifestation of secondary syphilis and if diagnosed early is reversible. Background. A 52-year-old male with past medical history of untreated syphilis presented with gradual onset of swelling and pain of the right fourth metacarpophalangeal joint (MCP). He reported a history of painless penile lesions after having sexual intercourse with a new partner approximately five months ago which was treated with sulfamethoxazole/trimethoprim. An RPR done at that time came back positive with a high titer; however, patient was lost to follow-up. On examination, patient had an edematous, nonerythematous right fourth proximal interphalangeal (PIP) joint. Urgent irrigation, debridement, and exploration of the right hand into the tendon sheath were performed. With his history of syphillis, an RPR was done, which was reactive with a titer of 1 : 64. A confirmatory FTA-ABS test was completed, rendering a positive result. Based on his history of untreated syphilis, dormancy followed by clinical scenario of swelling of the right fourth finger, and a high RPR titer, he was diagnosed with secondary syphilis manifesting as tenosynovitis.