Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease of severe hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and macrophages secreting high amounts of inflammatory cytokines. It is a frequent manifestation in patients with predisposing genetic defects, but can occur secondary to various infectious, malignant, and autoimmune triggers in patients without a known genetic predisposition. Clinical hallmarks are prolonged fever, cytopenias, hepatosplenomegaly, and neurological symptoms, but atypical variants presenting with signs of chronic immunodeficiency are increasingly recognized. Impaired secretion of perforin is a key feature in several genetic forms of the disease, but not required for disease pathogenesis. Despite progress in diagnostics and therapy, mortality of patients with severe HLH is still above 40%. Reference treatment is an etoposide-based protocol, but new approaches are currently explored. Key for a favorable prognosis is the rapid identification of an underlying genetic cause, which has been facilitated by recent immunological and genetic advances. In patients with predisposing genetic disease, hematopoietic stem cell transplantation is performed increasingly with reduced intensity conditioning regimes. Current research aims at a better understanding of disease pathogenesis and evaluation of more targeted approaches to therapy, including anti-cytokine antibodies and gene therapy.

Purpose.: Early detection of glaucoma remains a challenging problem and needs long-term, prospective studies. The pattern electroretinogram (PERG) directly reflects retinal ganglion cell function. The PERG was evaluated by extending a prospective study of patients with ocular hypertension and evaluated amplitude, PERG ratio, peak time, and trends thereof. Methods.: One hundred twenty eyes of 64 patients with intraocular pressure greater than 25 mm Hg (or ≥23 mm Hg with additional risk factors), normal visual fields, normal optic disc appearance, and visual acuity ≥0.8 were included in the study. Mean follow-up time was 10.3 years. The per-visit measures of amplitude at 15 reversals/s to 0.8° check size, PERG ratio (0.8°/16°), peak time, visual field, and their trends were analyzed. Results.: Over the course of the study 13 eyes converted to glaucoma according to a visual field definition. Amplitude to 0.8° check size, PERG ratio, and peak time were significantly lower in converters. Amplitude and PERG ratio predicted conversion 4 years ahead with a sensitivity/specificity of 67%/64% and 75%/76%, respectively. At this time, the ROC area was already significantly above chance for the PERG ratio. Comparison of the trends of converters and nonconverters revealed significant differences in the PERG ratio; however, trends did not predict conversion as successfully as single-visit measures. Conclusions.: The PERG, especially the PERG ratio, detected glaucoma patients 4 years before visual field changes occurred, with a sensitivity/specificity of 75%/76%. Slope analysis required multiple visits, but provided little additional information in detecting converters.

The quality and persistence of children’s humoral immune response following SARS-CoV-2 infection remains largely unknown but will be crucial to guide pediatric SARS-CoV-2 vaccination programs. Here, we examine 548 children and 717 adults within 328 households with at least one member with a previous laboratory-confirmed SARS-CoV-2 infection. We assess serological response at 3–4 months and 11–12 months after infection using a bead-based multiplex immunoassay for 23 human coronavirus antigens including SARS-CoV-2 and its Variants of Concern (VOC) and endemic human coronaviruses (HCoVs), and additionally by three commercial SARS-CoV-2 antibody assays. Neutralization against wild type SARS-CoV-2 and the Delta VOC are analysed in a pseudotyped virus assay. Children, compared to adults, are five times more likely to be asymptomatic, and have higher specific antibody levels which persist longer (96.2% versus 82.9% still seropositive 11–12 months post infection). Of note, symptomatic and asymptomatic infections induce similar humoral responses in all age groups. SARS-CoV-2 infection occurs independent of HCoV serostatus. Neutralization responses of children and adults are similar, although neutralization is reduced for both against the Delta VOC. Overall, the long-term humoral immune response to SARS-CoV-2 infection in children is of longer duration than in adults even after asymptomatic infection.

Key Points: Hermansky-Pudlak syndrome type 2 confers a moderate risk for hemophagocytic lymphohistiocytosis.