Rubella viruses (RV) have been found in an association with granulomas in children with primary immune deficiencies (PID). Here, we report the recovery and characterization of infectious immunodeficiency-related vaccine-derived rubella viruses (iVDRV) from diagnostic skin biopsies of four patients. Sequence evolution within PID hosts was studied by comparison of the complete genomic sequences of the iVDRVs with the genome of the vaccine virus RA27/3. The degree of divergence of each iVDRV correlated with the duration of persistence indicating continuous intrahost evolution. The evolution rates for synonymous and nonsynonymous substitutions were estimated to be 5.7 x 10−3 subs/site/year and 8.9 x 10−4 subs/site/year, respectively. Mutational spectra and signatures indicated a major role for APOBEC cytidine deaminases and a secondary role for ADAR adenosine deaminases in generating diversity of iVDRVs. The distributions of mutations across the genes and 3D hotspots for amino acid substitutions in the E1 glycoprotein identified regions that may be under positive selective pressure. Quasispecies diversity was higher in granulomas than in recovered infectious iVDRVs. Growth properties of iVDRVs were assessed in WI-38 fibroblast cultures. None of the iVDRV isolates showed complete reversion to wild type phenotype but the replicative and persistence characteristics of iVDRVs were different from those of the RA27/3 vaccine strain, making predictions of iVDRV transmissibility and teratogenicity difficult. However, detection of iVDRV RNA in nasopharyngeal specimen and poor neutralization of some iVDRV strains by sera from vaccinated persons suggests possible public health risks associated with iVDRV carriers. Detection of IgM antibody to RV in sera of two out of three patients may be a marker of virus persistence, potentially useful for identifying patients with iVDRV before development of lesions. Studies of the evolutionary dynamics of iVDRV during persistence will contribute to development of infection control strategies and antiviral therapies.

Rubella virus (RuV) has recently been found in association with granulomatous inflammation of the skin and several internal organs in patients with inborn errors of immunity (IEI). The cellular tropism and molecular mechanisms of RuV persistence and pathogenesis in select immunocompromised hosts are not clear. We provide clinical, immunological, virological, and histological data on a cohort of 28 patients with a broad spectrum of IEI and RuV-associated granulomas in skin and nine extracutaneous tissues to further delineate this relationship. Combined immunodeficiency was the most frequent diagnosis (67.8%) among patients. Patients with previously undocumented conditions, i.e., humoral immunodeficiencies, a secondary immunodeficiency, and a defect of innate immunity were identified as being susceptible to RuV-associated granulomas. Hematopoietic cell transplantation was the most successful treatment in this case series resulting in granuloma resolution; steroids, and TNF-α and IL-1R inhibitors were moderately effective. In addition to M2 macrophages, neutrophils were identified by immunohistochemical analysis as a novel cell type infected with RuV. Four patterns of RuV-associated granulomatous inflammation were classified based on the structural organization of granulomas and identity and location of cell types harboring RuV antigen. Identification of conditions that increase susceptibility to RuV-associated granulomas combined with structural characterization of the granulomas may lead to a better understanding of the pathogenesis of RuV-associated granulomas and discover new targets for therapeutic interventions.

No abstract

No abstract

No abstract

Background: Atopic dermatitis (AD) patients frequently use both conventional and complementary medicines for treatment. Allopathic and naturopathic providers may be unaware of each other's approach to AD diagnosis, skin care, and treatment, affecting patient and provider communication, patient safety, and potential for collaborative studies.Objective: To identify core commonalities and differences in allopathic and naturopathic approach to AD. Methods: Thirty allopathic and 21 naturopathic providers completed an 11-questionfree-text comment survey, covering patient education and evaluation, skin care, and treatment of AD. Qualitative content analysis detected key ideas and concepts, and word cloud analysis provided a quantitative visual representation of recurrent words in each group's responses.Results: All respondents indicated using similar physical features to diagnose AD.In both allopathic and naturopathic fields, the majority of providers did not perform routine testing for AD diagnosis. Skin care with moisturization and "soak-and-seal" bathing practices were routine in both fields. Naturopathic providers heavily emphasized the role of food and diet in AD pathogenesis, education, and management, while allopathic providers indicated little to no role for food and diet in AD. For treatment, allopathic providers favored topical steroids, phototherapy, and immunomodulators, whereas naturopathic providers recommended botanicals, supplements, and other complementary and alternative methods. Conclusions:Providers should be aware of the differences between allopathic and naturopathic providers and their approach to AD management, particularly concerning the role of food and diet. There may be opportunities to harmonize skin care regimens for patients given similar approach in both fields, and to collaborate further on studies of diet in AD and treatments not yet effectively tested. K E Y W O R D Sallopathy, atopic dermatitis, complementary and alternative medicine, mixed methods, naturopathy, survey Pediatric Dermatology DHOSSCHE Et al.

No abstract

No abstract