The BRCA1-associated protein-1 (BAP1) tumor predisposition syndrome (BAP1-TPDS) is a hereditary tumor syndrome caused by germline pathogenic variants in BAP1 encoding a tumor suppressor associated with uveal melanoma, mesothelioma, cutaneous melanoma, renal cell carcinoma, and cutaneous BAP1-inactivated melanocytic tumors. However, the full spectrum of tumors associated with the syndrome is yet to be determined. Improved understanding of the BAP1-TPDS is crucial for appropriate clinical management of BAP1 germline variant carriers and their families, including genetic counseling and surveillance for new tumors. We collated germline variant status, tumor diagnoses, and information on BAP1 immunohistochemistry or loss of somatic heterozygosity on 106 published and 75 unpublished BAP1 germline variant-positive families worldwide to better characterize the genotypes and phenotypes associated with the BAP1-TPDS. Tumor spectrum and ages of onset were compared between missense and null variants. All statistical tests were two-sided. The 181 families carried 140 unique BAP1 germline variants. The collated data confirmed the core tumor spectrum associated with the BAP1-TPDS and showed that some families carrying missense variants can exhibit this phenotype. A variety of noncore BAP1-TPDS -associated tumors were found in families of variant carriers. Median ages of onset of core tumor types were lower in null than missense variant carriers for all tumors combined (P < .001), mesothelioma (P < .001), cutaneous melanoma (P < .001), and nonmelanoma skin cancer (P < .001). This analysis substantially increases the number of pathogenic BAP1 germline variants and refines the phenotype. It highlights the need for a curated registry of germline variant carriers for proper assessment of the clinical phenotype of the BAP1-TPDS and pathogenicity of new variants, thus guiding management of patients and informing areas requiring further research.

Pityriasis rosea (PR) is an acute, self-limiting exanthematous disease associated with the endogenous systemic reactivation of human herpesvirus (HHV)-6 and/or HHV-7. The disease typically begins with a single, erythematous plaque followed by a secondary eruption with lesions on the cleavage lines of the trunk (configuration of a ‘Christmas tree'). The duration may vary from 2 weeks to a few months. Besides the typical presentation of PR, atypical forms have been described. The previous classifications of PR are mainly based on its atypical morphological features rather than on the pathogenetic mechanisms that underlie the different presentations of the disease. Notably, most of the morphologically atypical forms follow a course amenable to the classic form. The classification that we propose, taking into account the pathogenesis, clinical features, and course of the disease, is easy and intuitive and may be helpful in identifying the atypical forms of PR in order to avoid misdiagnosis and establish the best treatment options. Finally, this classification provides indications for managing potentially harmful forms of PR (such as PR in pregnancy) and PR-like eruptions.

In spite of its immutable susceptibility to penicillin,Treponema pallidum(T.pallidum) subsp.pallidumcontinues to cause millions of cases of syphilis each year worldwide, resulting in significant morbidity and mortality and underscoring the urgency of developing an effective vaccine to curtail the spread of the infection. Several technical challenges, including absence of anin vitroculture system until very recently, have hampered efforts to catalog the diversity of strains collected worldwide. Here, we provide near-complete genomes from 196T.pallidumstrains–including 191T.pallidumsubsp.pallidum–sequenced directly from patient samples collected from 8 countries and 6 continents. Maximum likelihood phylogeny revealed that samples from most sites were predominantly SS14 clade. However, 99% (84/85) of the samples from Madagascar formed two of the five distinct Nichols subclades. Although recombination was uncommon in the evolution of modern circulating strains, we found multiple putative recombination events betweenT.pallidumsubsp.pallidumand subsp.endemicum, shaping the genomes of several subclades. Temporal analysis dated the most recent common ancestor of Nichols and SS14 clades to 1717 (95% HPD: 1543–1869), in agreement with other recent studies. Rates of SNP accumulation varied significantly among subclades, particularly among different Nichols subclades, and was associated in the Nichols A subclade with a C394F substitution in TP0380, a ERCC3-like DNA repair helicase. Our data highlight the role played by variation in genes encoding putative surface-exposed outer membrane proteins in defining separate lineages, and provide a critical resource for the design of broadly protective syphilis vaccines targeting surface antigens.

Nicotinamide is the precursor of nicotinamide adenine dinucleotide (NAD+), an essential cofactor for adenosine triphosphate (ATP) production. It has recently been reported to be effective in reducing the rates of new non-melanoma skin cancers (NMSCs) and actinic keratosis (AKs). We studied the efficacy of oral nicotinamide as treatment for AKs in transplant recipients. We recruited 38 transplant (eight liver and 30 kidney) patients with single or multiple AKs. Nineteen patients were randomly assigned to Group 1 and took nicotinamide 500 mg/daily (cases); the other 19 patients were randomly assigned to Group 2 without nicotinamide (controls). At baseline, AKs were identified, measured, and photographed for follow-up. Five patients underwent an AK biopsy for histopathology. Statistical analyses were performed using the Student t test. At baseline, no statistically significant differences were observed regarding AK size between the two groups. After six months, among the cases, AKs had significantly decreased in size in 18/19 patients (88%). Among these 18 patients, seven patients (42%) had shown complete clinical regression and no patient developed new AKs. Conversely, among the controls, 91% showed an increase in AK size and/or developed new AKs. Seven pre-existing AKs progressed to squamous-cell carcinoma. Nicotinamide appears to be effective in preventing and treating AKs, although the mechanisms are still unclear. Further studies with a larger sample of organ transplant recipients and a longer follow-up period are needed to further support our conclusions.

An exanthem is a skin rash that may be associated with mucous membrane eruption, fever or other symptoms. It may develop as manifestation of an infectious disease or as adverse reaction to drugs. Beside the ‘classical exanthems’ commonly occurring in childhood, other exanthems, defined as ‘atypical’ for the different morphology and causal agents, may occur. Among the atypical exanthems with infectious etiology, viral, bacterial, parasitic and helminth infections are implicated. We describe herein etiology and epidemiology of the atypical exanthems caused by infectious agents. In case of exanthem, to make a correct etiological diagnosis is crucial for both the patient and community concerning issues such as time off school, immunizations and risk in pregnancy and immunocompromised individuals.