Disseminated cutaneous gout: a rare manifestation of a common disease

Disseminated cutaneous gout is a rare atypical cutaneous manifestation of gout in which widespread dermal and subcutaneous tophi develop at extra-articular body sites. Given the lack of joint involvement that is typically a feature in tophaceous gout, the diagnosis may not be initially suspected. We present the case of a 50-year-old Hispanic man with poorly controlled gout who was evaluated for several years of firm papulonodules over the trunk and upper and lower extremities, sparing the joints; histopathology confirmed, the diagnosis of disseminated cutaneous gout. Per our literature review, disseminated cutaneous gout presents with polymorphous papules and nodules that can mimic other, more common cutaneous diseases. There is a preponderance of cases in males, Asians, and patients with longstanding gout. The lower extremities are involved in nearly all reports. Uric acid-lowering therapy with allopurinol has been reported to decrease the size and number of lesions in a minority of treated patients

Deletions in the MAL gene result in loss of Mal protein, defining the rare inherited AnWj-negative blood group phenotype

The genetic background of the high prevalence red blood cell antigen AnWj has remained unresolved since its identification in 1972, despite reported associations with both CD44 and Smyd1 histone methyltransferase. Development of anti-AnWj, which may be clinically significant, is usually due to transient suppression of antigen expression, but a small number of individuals with persistent, autosomally-recessive inherited AnWj-negative phenotype have been reported. Whole exome sequencing of individuals with the rare inherited AnWj-negative phenotype revealed no shared mutations in CD44H or SMYD1, but instead we discovered homozygosity for the same large exonic deletion in MAL, which was confirmed in additional unrelated AnWj-negative individuals. MAL encodes an integral multi-pass membrane proteolipid, Myelin and Lymphocyte protein (Mal), which has been reported to have essential roles in cell transport and membrane stability. AnWj-positive individuals were shown to express full-length Mal on their red cell membranes, which was not present on the membranes of AnWj-negative individuals, whether of an inherited or suppression background. Furthermore, binding of anti-AnWj was able to inhibit binding of anti-Mal to AnWj-positive red cells, demonstrating the antibodies bind to the same molecule. Over-expression of Mal in an erythroid cell-line resulted in expression of AnWj antigen, regardless of the presence or absence of CD44, demonstrating that Mal is both necessary and sufficient for AnWj expression. Our data resolve the genetic background of the inherited AnWj-negative phenotype, forming the basis of a new blood group system, further reducing the number of remaining unsolved blood group antigens

Missense mutations in PIEZO1, which encodes the Piezo1 mechanosensor protein, define Er red blood cell antigens

Despite the identification of the high-incidence red cell antigen Era nearly 40 years ago, the molecular background of this antigen, together with the other 2 members of the Er blood group collection, has yet to be elucidated. Whole exome and Sanger sequencing of individuals with serologically defined Er alloantibodies identified several missense mutations within the PIEZO1 gene, encoding amino acid substitutions within the extracellular domain of the Piezo1 mechanosensor ion channel. Confirmation of Piezo1 as the carrier molecule for the Er blood group antigens was demonstrated using immunoprecipitation, CRISPR/Cas9-mediated gene knockout, and expression studies in an erythroblast cell line. We report the molecular bases of 5 Er blood group antigens: the recognized Era, Erb, and Er3 antigens and 2 novel high-incidence Er antigens, described here as Er4 and Er5, establishing a new blood group system. Anti-Er4 and anti-Er5 are implicated in severe hemolytic disease of the fetus and newborn. Demonstration of Piezo1, present at just a few hundred copies on the surface of the red blood cell, as the site of a new blood group system highlights the potential antigenicity of even low-abundance membrane proteins and contributes to our understanding of the in vivo characteristics of this important and widely studied protein in transfusion biology and beyond

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Disseminated cutaneous gout: a rare manifestation of a common disease

Disseminated cutaneous gout is a rare atypical cutaneous manifestation of gout in which widespread dermal and subcutaneous tophi develop at extra-articular body sites. Given the lack of joint involvement that is typically a feature in tophaceous gout, the diagnosis may not be initially suspected. We present the case of a 50-year-old Hispanic man with poorly controlled gout who was evaluated for several years of firm papulonodules over the trunk and upper and lower extremities, sparing the joints; histopathology confirmed, the diagnosis of disseminated cutaneous gout. Per our literature review, disseminated cutaneous gout presents with polymorphous papules and nodules that can mimic other, more common cutaneous diseases. There is a preponderance of cases in males, Asians, and patients with longstanding gout. The lower extremities are involved in nearly all reports. Uric acid-lowering therapy with allopurinol has been reported to decrease the size and number of lesions in a minority of treated patients

Psychiatric comorbidities on an inpatient dermatology consultation service: A cross‐sectional analysis

Abstract Despite the high prevalence of psychiatric illness in hospitalised dermatology patients, characterisation of psychiatric comorbidities on an inpatient dermatology consultation service in the United States has yet to be performed. To fill this gap in knowledge, we investigated the prevalence of and factors associated with psychiatric illness on the inpatient dermatology consultation service at the University of Southern California. Of the 429 patients seen by the dermatology consultation service between June 2021 to July 2022, 147 (34%) had psychiatric illness (defined as having at least 1 psychiatric diagnosis). Increasing age was associated with a decreased likelihood of psychiatric illness, while housing instability, chronic dermatologic disease, drug reaction, and pruritus without rash were associated with an increased likelihood of psychiatric illness. The high prevalence of psychiatric illness observed in hospitalised dermatology patients emphasises the importance of collaboration between consultant dermatologists and mental health specialists, particularly when specific sociodemographic or disease factors are present

The genome organization of <i>Neurospora crassa</i> at high resolution uncovers principles of fungal chromosome topology

AbstractThe eukaryotic genome must be precisely organized for its proper function, as genome topology impacts transcriptional regulation, cell division, replication, and repair, among other essential processes. Disruptions to human genome topology can lead to diseases, including cancer. The advent of chromosome conformation capture with high-throughput sequencing (Hi-C) to assess genome organization has revolutionized the study of nuclear genome topology; Hi-C has elucidated numerous genomic structures, including chromosomal territories, active/silent chromatin compartments, Topologically Associated Domains, and chromatin loops. While low-resolution heatmaps can provide important insights into chromosomal level contacts, high-resolution Hi-C datasets are required to reveal folding principles of individual genes. Of particular interest are high-resolution chromosome conformation datasets of organisms modeling the human genome. Here, we report the genome topology of the fungal model organism Neurospora crassaDpnMseDpnMs

Interobserver reliability of teledermatology across all Fitzpatrick skin types

Introduction Demand for dermatologic services in safety net hospitals, which disproportionately serve patients with darker coloured skin, is growing. Teledermatology has the potential to increase access and improve outcomes, but studies have yet to demonstrate the reliability of teledermatology for all Fitzpatrick skin types. Methods We assessed the reliability of teledermatologists' diagnoses and management recommendations for store-and-forward teledermatology in patients with lightly pigmented (Fitzpatrick skin types I-III) versus darkly pigmented (Fitzpatrick skin types IV-VI) skin, when compared to in-person diagnosis and management decisions. This prospective study enrolled 232 adult patients, presenting with new, visible skin complaints in a Los Angeles county dermatology clinic. Forty-seven percent of patients were Fitzpatrick skin types I-III, and 53% were Fitzpatrick skin types IV-VI. Results Percent concordance for the identical primary diagnosis was 53.2% in lighter (Fitzpatrick I-III) skin types and 56.0% in darker (Fitzpatrick IV-VI) skin types. There was no statistically significant difference in concordance rates between lighter and darker skin types for primary diagnosis. Concordance rates for diagnostic testing, clinic-based therapy, and treatments were similar in both groups of Fitzpatrick skin types. Discussion These results suggest that teledermatology is reliable for the diagnosis and management of patients with all Fitzpatrick skin types

Treatments for Dissecting Cellulitis of the Scalp: A Systematic Review and Treatment Algorithm

Abstract Background Dissecting cellulitis of the scalp (DCS) is a chronic inflammatory skin condition characterized by abscesses, nodules, fistulas, and scarring alopecia. Management of this oftentimes debilitating dermatosis can be challenging due to its recalcitrant nature. There is limited data regarding the efficacy of treatment options for DCS. Objective The aim of this study was to conduct a systematic review of the literature to explore the efficacy and safety of reported DCS treatments. Methods In October 2022, MEDLINE and EMBASE databases were searched for articles on treatments for DCS. Studies that contained outcome efficacy data for DCS treatments were included. Reviews, conference abstracts, meta-analyses, commentaries, non-relevant articles, and articles with no full-text available were excluded. Data extraction was performed by two independent reviewers. Results A total of 110 relevant articles with 417 patients were identified. A majority of studies (86.4%) were case reports or series. Treatment options included systemic antibiotics, oral retinoids, biologics, procedural treatments, combination agents, and topical treatments. Oral retinoids and photodynamic therapy were the most extensively studied medical and procedural interventions, respectively. Conclusion Overall, randomized controlled trials are needed to evaluate various treatment regimens for DCS and provide patients with a robust, evidence-based approach to therapy