Revisiting childhood herpes zoster.

Herpes zoster is rare in otherwise healthy children, but it is more common in association with immunosuppression. Maternal varicella infection during pregnancy and varicella occurring in the newborn represent risk factors for childhood herpes zoster. However, some controversies persist about risk factors, diagnosis, and the natural history of childhood disease. In a 2-year prospective study, 18 children with herpes zoster were clinically diagnosed in outpatient consultations in a hospital dermatology unit. Data about age, dermatome involvement, underlying disease, and history of previous varicella were recorded. Tzanck smears, biopsy specimens, and sera were obtained from 18, 4, and 10 children, respectively. The varicella zoster virus major envelope glycoprotein gE was detected in 16 of 18 smears and all four biopsies. Herpes simplex virus I was demonstrated in one of the smears. The established risk factors for childhood herpes zoster were only found in one child. Evidence for previous full-blown varicella and varicella with few lesions was recorded in 7 and 4 of the 17 immunocompetent children, respectively. No history of varicella was recalled in 6 of 17 cases, although a serologic clue of past varicella infection (IgM negative, IgG positive) was disclosed. Recurrent herpes zoster was diagnosed in one immunocompromised child. Zoster-associated pain was localized and the disease severity remained mild in all children. Established risk factors for childhood herpes zoster were only rarely found in our series of patients. In contrast, unrecognized varicella and varicella with few lesions were frequently recorded and may represent additional risk factors for shingles in childhood. Zosteriform herpes simplex virus infections should be differentiated from childhood herpes zoster, emphasizing the importance of precise viral identification

The Multiple Sclerosis Genomic Map: Role of peripheral immune cells and resident microglia in susceptibility

We assembled and analyzed genetic data of 47,351 multiple sclerosis (MS) subjects and 68,284 control subjects and establish a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 independent associations within the extended MHC. We used an ensemble of methods to prioritize up to 551 potentially associated MS susceptibility genes, that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we do find enrichment for MS genes in these brain - resident immune cells. Thus, while MS is most likely initially triggered by perturbation of peripheral immune responses the functional responses of microglia and other brain cells are also altered and may have a role in targeting an autoimmune process to the central nervous system. One Sentence Summary: We report a detailed genetic and genomic map of multiple sclerosis, and describe the role of putatively affected genes in the peripheral immune system and brain resident microglia