Proliferating cells depend on glucose uptake more than quiescent cells for their growth. While glucose transport in keratinocytes is mediated largely by the Glut1 facilitative transporter, the keratinocyte-specific ablation of Glut1 did not compromise mouse skin development and homeostasis. Ex vivo metabolic profiling revealed altered sphingolipid, hexose, amino acid, and nucleotide metabolism in Glut1-deficient keratinocytes, suggesting metabolic adaptation. On the other hand, Glut1-deficient keratinocytes in culture displayed metabolic and oxidative stress and impaired proliferation. Similarly, Glut1 deficiency impaired in vivo keratinocyte proliferation and migration within wounded or UV-damaged mouse skin. Notably, both genetic and pharmacological Glut1 inactivation reduced hyperplasia in mouse models of psoriasis-like disease. Topical application of a Glut1 inhibitor also reduced inflammation in these models. Glut1 inhibition decreased expression of pathology-associated genes in human psoriatic skin organoids. Thus, Glut1 is selectively required for injury- and inflammation-associated keratinocyte proliferation, and its inhibition offers a novel treatment strategy for psoriasis.

Background Human Polyomavirus 6 (HPyV6) and Human Polyomavirus 7 (HPyV7) are shed chronically from human skin. HPyV7, but not HPyV6, has been linked to a pruritic skin eruption of immunosuppression. Objective We determined whether biopsies showing a characteristic pattern of dyskeratosis and parakeratosis might be associated with polyomavirus infection. Methods We screened biopsies showing “peacock plumage” histology by PCR for human polyomaviruses. Cases positive for HPyV 6 or 7 were then analyzed by immunohistochemistry, electron microscopy (EM), immunofluorescence, quantitative PCR, and complete sequencing, including unbiased, next generation sequencing (NGS). Results We identified three additional cases of HPyV6 or 7 skin infections. Expression of T antigen and viral capsid was abundant in lesional skin. Dual immunofluorescence staining experiments confirmed that HPyV7 primarily infects keratinocytes. High viral loads in lesional skin compared to normal skin and the identification of intact virions by both EM and NGS support a role for active viral infections in these skin diseases. Limitation This was a small case-series of archived materials. Conclusion We have found that HPyV6 and HPyV7 are associated with rare, pruritic skin eruptions with a unique histologic pattern and describe this entity as “HPyV6- and HPyV7-associated pruritic and dyskeratotic dermatosis (H6PD and H7PD).”

IMPORTANCE Leishmaniasis is recognized as an endemic human disease in Africa, the Middle East, Asia, and South America. Yet despite case reports of endemic human leishmaniasis in the United States, and well-documented occurrences of disease in various animal vectors and reservoirs, the endemicity of leishmaniasis in North America has not yet been established. Moreover, leishmaniasis is not a federally reportable disease in the United States. Clinical awareness of endemic disease therefore remains low, with North American physicians considering leishmaniasis a tropical disease. OBJECTIVE To assess the endemicity of human leishmaniasis in the United States. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional multicenter observational study reviewed cases of human leishmaniasis occurring in the United States from 2007 through 2017. Previously diagnosed, deidentified cases of leishmaniasis were reported by the institutions of the authors and acknowledged contributors, as well as the Texas Department of State Health Services. Cases of leishmaniasis were identified by searching by disease name (leishmaniasis) or International Classification of Diseases, 9th and 10th Revisions diagnosis codes in the respective laboratory information systems. EXPOSURES Via examination of deidentified demographics, cases of leishmaniasis were classified as one of the following: (1) documentation of no history of travel outside of the United States within 10 years; (2) positive history of travel outside of the United States within 10 years; or (3) unknown or no documentation of travel history. MAIN OUTCOMES AND MEASURES Cases of leishmaniasis were considered endemic if identified in patients with documentation of no travel history outside of the United States within 10 years. RESULTS Of the 69 novel cases of human cutaneous leishmaniasis identified in this study, 41 (59%) were endemic; the median age at diagnosis was 61 years (range, 3-89 years), and 28 (68%) of the endemic cases occurred in female patients. Twenty-two (32%) cases had documentation of Leishmania speciation performed by polymerase chain reaction, and in 100% of these cases the infectious organism was identified as Leishmania mexicana. CONCLUSIONS AND RELEVANCE Human cutaneous leishmaniasis is endemic in the United States, and, at least regionally, is acquired endemically more frequently than it is via travel. Our data argue in favor of making leishmaniasis a federally reportable disease and may have substantial implications on North American public health initiatives, with climate models predicting the number of citizens exposed to leishmaniasis will double by 2080.