Long-read assembly of a Great Dane genome highlights the contribution of GC-rich sequence and mobile elements to canine genomes.

Technological advances have allowed improvements in genome reference sequence assemblies. Here, we combined long- and short-read sequence resources to assemble the genome of a female Great Dane dog. This assembly has improved continuity compared to the existing Boxer-derived (CanFam3.1) reference genome. Annotation of the Great Dane assembly identified 22,182 protein-coding gene models and 7,049 long noncoding RNAs, including 49 protein-coding genes not present in the CanFam3.1 reference. The Great Dane assembly spans the majority of sequence gaps in the CanFam3.1 reference and illustrates that 2,151 gaps overlap the transcription start site of a predicted protein-coding gene. Moreover, a subset of the resolved gaps, which have an 80.95% median GC content, localize to transcription start sites and recombination hotspots more often than expected by chance, suggesting the stable canine recombinational landscape has shaped genome architecture. Alignment of the Great Dane and CanFam3.1 assemblies identified 16,834 deletions and 15,621 insertions, as well as 2,665 deletions and 3,493 insertions located on secondary contigs. These structural variants are dominated by retrotransposon insertion/deletion polymorphisms and include 16,221 dimorphic canine short interspersed elements (SINECs) and 1,121 dimorphic long interspersed element-1 sequences (LINE-1_Cfs). Analysis of sequences flanking the 3' end of LINE-1_Cfs (i.e., LINE-1_Cf 3'-transductions) suggests multiple retrotransposition-competent LINE-1_Cfs segregate among dog populations. Consistent with this conclusion, we demonstrate that a canine LINE-1_Cf element with intact open reading frames can retrotranspose its own RNA and that of a SINEC_Cf consensus sequence in cultured human cells, implicating ongoing retrotransposon activity as a driver of canine genetic variation.

Infliximab-induced amicrobial pustulosis of the folds in a patient with Crohn disease.

Tumor necrosis factor (TNF) inhibitors may paradoxically induce pustular eruptions, most of which are classified as pustular psoriasis. Amicrobial pustulosis of the folds (APF) is a much rarer entity that was recently recognized to occur in the setting of chronic anti-TNF therapy and inflammatory bowel disease, with 12 existing cases in the literature. Amicrobial pustulosis of the folds is a neutrophilic dermatosis characterized by aseptic pustules involving the major and minor skin folds, genital regions, and scalp. Herein, we report an additional case of paradoxical APF induced by chronic infliximab therapy in a patient with Crohn disease.

Prescribing Isotretinoin for Transgender Patients: A Call to Action and Recommendations.

Case Scenerio: A 26-year-old patient presents to the dermatology clinic with severe nodulocystic scarring acne. The patient identifies as a transgender male and notes that he has been receiving hormone replacement therapy for the past 4 years with weekly intramuscular testosterone injections.

The use of Goeckerman therapy in managing erythrodermic psoriasis resistant to multiple medications.

Erythrodermic psoriasis is a relatively rare, more dangerous inflammatory variant of psoriasis associated with high morbidity and mortality. It can be exceptionally challenging to manage, defeating even the most experienced dermatologist's arsenal of treatment strategies. Goeckerman therapy, a regimen of ultraviolet B phototherapy and crude coal tar, has demonstrable efficacy in severe and recalcitrant plaque-type psoriasis. However, its utility in erythrodermic psoriasis has not been explored within the dermatology literature. Herein, we present a patient with a long-standing history of erythrodermic psoriasis refractory to eleven treatment modalities including four biologic agents, who had his erythroderma 'turned around' following Goeckerman therapy. 'Turned around' is used to describe dramatically reducing a patient's cutaneous inflammation so that previously recalcitrant disease can now respond to maintenance therapy. The importance of a one to three week 'cool down' period of topical corticosteroid therapy prior to phototherapy or crude coal tar use is highlighted in this case as well. Although Goeckerman therapy is no longer regularly used, it remains one of the most efficacious treatments available for intractable psoriasis, attracting patients from all over the country desperate for symptom relief. This case suggests it may be useful in 'turning around' extremely difficult-to-treat erythrodermic psoriasis as well.

Management strategies for borderline and narcissistic personality disorders in dermatology practice: a review.

Dermatologists are often ill-equipped to promptly identify and manage patients with personality disorders. Patients with borderline personality disorder (BPD) and narcissistic personality disorder (NPD) frequently present to dermatology clinics, particularly those that provide esthetic services. Although dermatologists should ideally utilize specific management strategies when working with these patients, there is a lack of awareness and availability of resources on how to do so. Here, we review the psychiatry, plastic and reconstructive surgery, and dermatology literature to provide recommendations on tangible management strategies for dermatologists to avoid common mistakes that are made while managing patients with BPD and NPD. Additionally, we also discuss common dermatologic manifestations of BPD and NPD to improve providers' ability to identify patients with these conditions in their practices.

Optimizing doxepin therapy in dermatology: introducing blood level monitoring and genotype testing.

Doxepin, a tricyclic antidepressant, is the most efficacious antipruritic available to dermatologists; however its use is often suboptimal because of significant interindividual variability in doxepin plasma levels and clinical response between patients taking the same dose. As result, the Food and Drug Administration approves a maximum dose of 300 mg of doxepin per day and a 10 mg per cc liquid doxepin concentrate. These allow patients to significantly increase or decrease their dose, due to either a lack of clinical efficacy or side effects at typical dermatologic doses (often 10-25 mg per day). This review initially discusses the unique advantages of doxepin in dermatology. Then, it explores internal and external reasons why doxepin plasma levels and clinical response vary so significantly between patients, including genetic polymorphisms, drug interactions, comorbidities, sex, and ethnicity. Blood level monitoring is introduced, a tool dermatologists can use to optimize doxepin dosing in patients responding subtherapeutically to typical dermatologic doses. Without blood level monitoring, patients initially unresponsive to treatment could be labeled treatment failures when in fact they may be cases of inadequate dosing. Blood level monitoring allows for safe dose adjustments in these individuals to maximize patients' chances of achieving therapeutic success with this agent.

Evaluation of a Case Series of Patients With Generalized Pustular Psoriasis in the United States.

IMPORTANCE: Generalized pustular psoriasis (GPP) is a chronic, orphan disease with limited epidemiological data. OBJECTIVE: To describe the clinical characteristics, treatments, longitudinal disease course, and disease-specific health care utilization among patients with GPP across the United States. DESIGN, SETTING, AND PARTICIPANTS: A retrospective longitudinal case series involving 95 adults who met the European Rare and Severe Psoriasis Expert Network consensus definition for GPP and were treated at 20 US academic dermatology practices between January 1, 2007, and December 31, 2018. MAIN OUTCOMES AND MEASURES: The primary outcome is to describe the patient characteristics, associated medical comorbidities, treatment patterns complications, and GPP-specific health care utilization. RESULTS: Sixty-seven of 95 patients (70.5%) were women (mean age, 50.3 years [SD, 16.1 years]). In the initial encounter, 35 patients (36.8%) were hospitalized and 64 (67.4%) were treated with systemic therapies. In total, more than 20 different systemic therapies were tried. During the follow-up period, 19 patients (35.8%) reported hospitalizations at a median rate of 0.5 hospitalizations per year (IQR, 0.4-1.6). Women had a decreased risk of an emergency department or hospital encounter (odds ratio, 0.19; 95% CI, 0.04-0.83). CONCLUSIONS AND RELEVANCE: Generalized pustular psoriasis is a rare, chronic disease without standard treatment and is associated with continued health care utilization over time.

Evaluation of a Case Series of Patients With Palmoplantar Pustulosis in the United States.

IMPORTANCE: Palmoplantar pustulosis (PPP) is a is a chronic, orphan disease with limited epidemiological data. OBJECTIVE: To describe the clinical characteristics, treatments, longitudinal disease course, and health care utilization in adults with PPP across the US. DESIGN, SETTING, AND PARTICIPANTS: This retrospective, longitudinal case series from 20 academic dermatology practices in the US included a consecutive sample of 197 adults who met the European Rare and Severe Psoriasis Expert Network consensus definition for PPP between January 1, 2007, and December 31, 2018. Data analysis was performed June 2020 to December 2020. MAIN OUTCOMES AND MEASURES: The primary outcome was to describe the patient characteristics, associated medical comorbidities, treatment patterns, complications, and PPP-specific health care utilization. RESULTS: Of 197 patients, 145 (73.6%) were female, and the mean (SD) age at presentation was 53.0 (12.6) years, with a mean (SD) follow-up time of 22.1 (28.0) months. On initial presentation, 95 (48.2%) patients reported skin pain, and 39 (19.8%) reported difficulty using hands and/or feet. Seventy patients (35.5%) were treated with systemic treatments, and use of more than 20 different systemic therapies was reported. In patients with at least 6 months of follow-up (n = 128), a median (IQR) of 3.7 (4-10) dermatology visits per year were reported; 24 (18.8%) patients had 5 or more visits during the study period. CONCLUSIONS AND RELEVANCE: In this case series, PPP was associated with persistent symptoms, continued health care utilization, and a lack of consensus regarding effective treatments, emphasizing the unmet medical need in this population. Additional research is necessary to understand treatment response in these patients.

Biologic Treatment of 4 HIV-Positive Patients: A Case Series and Literature Review.

The management of psoriatic disease in human immunodeficiency virus (HIV)-positive patients is challenging. Psoriasis in HIV-positive patients is often severe, progressive, and resistant to first- and second-line therapies, including topical treatments, phototherapy, highly active antiretroviral therapy (HAART), and oral retinoids. Other systemic agents used to treat psoriasis, such as methotrexate and cyclosporine, are immunosuppressants and thus many dermatologists may not feel comfortable prescribing them to HIV-positive patients who are already immunocompromised. Biologic agents, which target specific aspects of overactive immune pathways in psoriasis, have revolutionized the management of moderate-to-severe psoriasis. However, data is limited regarding their safety and efficacy in HIV-positive patients. OBJECTIVE: Report four cases of HIV-positive patients managed on biologic therapy and summarize the cases of psoriasis in HIV-positive patients managed on biologic therapy that have been published in dermatologic literature to date. METHODS: We searched PubMed and Embase databases using the terms HIV and psoriasis or HIV and psoriatic arthritis combined with one of the eleven biologics currently approved for treating psoriasis. RESULTS: We identified 48 cases of anti-psoriasis biologic therapy (including adalimumab, infliximab, etanercept, ustekinumab, and guselkumab) in HIV-positive patients and added four. While data is limited, the evidence available suggests biologic agents are safe and efficacious in moderate-to-severe psoriasis and may even have a favorable effect on CD4 and HIV viral counts when used with concomitant HAART. CONCLUSION: Further research would be helpful to establish practical guidelines for the use of anti-psoriasis biologic therapy in the HIV population, including that of newer agents.

Dupilumab-Induced Facial Flushing After Alcohol Consumption.

Dupilumab is a biologic agent approved by the US Food and Drug Administration for the treatment of atopic dermatitis (AD). Here, we report 2 patients with AD who were treated with dupilumab and subsequently developed facial flushing after consuming alcohol. A possible mechanism of action for this side effect is discussed along with a potential role of dupilumab.

Sleep and the gut microbiome in psoriasis: clinical implications for disease progression and the development of cardiometabolic comorbidities.

Background: Sleep dysfunction and sleep disorders are important comorbidities of psoriasis. Not only do these sleep comorbidities contribute to reduced quality of life, but they may also lead to worsening psoriasis and increased susceptibility to cardiometabolic diseases. While psoriasis and sleep dysfunction are thought to be linked by itch, depression, and immune system dysregulation, the relationship between psoriasis and sleep dysfunction is not yet fully understood. Objective: We sought to compare previous studies characterizing the gut microbiome in psoriasis and sleep dysfunction and examine the potential relevance of shared findings on cardiometabolic and overall health. Methods: We performed literature searches of PubMed and Embase databases to find studies evaluating the gut microbiome in psoriasis, sleep dysfunction, and cardiometabolic diseases. Results: Studies characterizing the gut microbiome in psoriasis and sleep dysfunction reveal shared findings, specifically an increased Firmicutes to Bacteroidetes ratio and reduced abundance of short chain fatty acid-producing bacteria. These dysbiotic features have also been shown to promote systemic inflammation and cardiometabolic disease. Conclusion: In favoring an increased Firmicutes to Bacteroidetes ratio and reduced abundance of short chain fatty acid-producing bacteria, sleep dysfunction could be contributing to worsening psoriasis and cardiometabolic comorbidities through intestinal dysbiosis. Future studies are needed to determine whether gut- and sleep-targeting interventions could be therapeutic in psoriasis patients with poor sleep.

New Frontiers in Psoriatic Disease Research, Part II: Comorbidities and Targeted Therapies.

Although psoriasis and psoriatic arthritis (PsA) have been classically considered to be diseases of the skin and joints, respectively, emerging evidence suggests that a combination of innate and environmental factors creates widespread immune dysfunction, affecting multiple organ systems. A greater understanding of the pathogenesis of psoriasis and the systemic effects of psoriatic inflammation has allowed for the development of new, more effective treatments. The second portion of this two-part review series examines the comorbidities associated with psoriasis and PsA as well as the most recent advances in targeted systemic therapies for these conditions.

Impact of Halobetasol Propionate and Tazarotene Lotion 0.01%/0.045% in the Management of Plaque Psoriasis in Adults.

Halobetasol propionate and tazarotene lotion 0.01%/0.045% (HP/TAZ) is a topical medication approved for the treatment of plaque psoriasis in adults. As a treatment modality, HP/TAZ has a combinatory therapeutic effect because it contains both a corticosteroid (HP) and a retinoid (TAZ) component. Here, we review the important clinical efficacy and safety data derived from pivotal clinical trials for HP/TAZ in the treatment of plaque psoriasis. We also discuss the mechanism of action, dosage guidelines, pharmacokinetics/pharmacodynamics, and clinical considerations for HP/TAZ, including why HP/TAZ should be avoided in pregnant patients.

Clinical Evaluation of Risankizumab-rzaa in the Treatment of Plaque Psoriasis.

Risankizumab-rzaa (Skyrizi®; AbbVie) is a humanized IgG monoclonal antibody directed against interleukin-23p19 (IL-23p19) indicated for the treatment of moderate-to-severe psoriasis in adults who are candidates for systemic therapy or phototherapy. Four pivotal Phase III trials: UltIMMa-1, UltIMMa-2, IMMhance, and IMMvent have demonstrated efficacy and safety in patients with moderate-to-severe plaque psoriasis. This review highlights important findings from these and other clinical trials that have evaluated risankizumab. In addition, we discuss the mechanism of action, pharmacokinetics/pharmacodynamics, dosing recommendations, drug interactions, other potential indications, and ongoing clinical trials.

Machine Learning in Dermatology: Current Applications, Opportunities, and Limitations.

Machine learning (ML) has the potential to improve the dermatologist's practice from diagnosis to personalized treatment. Recent advancements in access to large datasets (e.g., electronic medical records, image databases, omics), faster computing, and cheaper data storage have encouraged the development of ML algorithms with human-like intelligence in dermatology. This article is an overview of the basics of ML, current applications of ML, and potential limitations and considerations for further development of ML. We have identified five current areas of applications for ML in dermatology: (1) disease classification using clinical images; (2) disease classification using dermatopathology images; (3) assessment of skin diseases using mobile applications and personal monitoring devices; (4) facilitating large-scale epidemiology research; and (5) precision medicine. The purpose of this review is to provide a guide for dermatologists to help demystify the fundamentals of ML and its wide range of applications in order to better evaluate its potential opportunities and challenges.

Psoriasis Vulgaris Successfully Treated with Goeckerman Treatment at Home: A Patient and Physician's Experience.

Goeckerman therapy is a highly effective treatment regimen for moderate-to-severe psoriasis. It involves regular exposure to ultraviolet B radiation and the application of crude coal tar. To our knowledge, only three centers in the USA currently offer a formal Goeckerman therapy treatment program; thus, access to this therapy is geographically limited. In this article, a motivated patient discusses his experience with generalized plaque psoriasis. This patient, while living in a Goeckerman-inaccessible area, deferred treatment with biologics and outpatient phototherapy to develop a modified Goeckerman regimen for at-home use. This home regimen, which did not involve the use of prescription-strength medications, resulted in full clearance of his psoriasis. We also discuss the patient's case from the perspective of a dermatology treatment team that has reviewed his experience.

Novel Coronavirus Disease (COVID-19) and Biologic Therapy for Psoriasis: Successful Recovery in Two Patients After Infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

The outbreak of the novel coronavirus known as SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) causing COVID-19 was first reported in late December 2019. Many patients with psoriasis on biologic therapy have asked their medical providers about the effect of biologics on COVID-19. However, it is currently unknown how biologic therapy for psoriasis might impact patients with psoriasis and COVID-19. In this article, we report on the clinical course of two patients on biologic medication for psoriasis who developed COVID-19 and successfully recovered from SARS-CoV-2 infection. Both patients presented with fever and respiratory symptoms, but neither patient required hospitalization. While more research is needed, it is reassuring to know that successful recovery is possible after COVID-19 infection in patients on biologic therapy for psoriasis.

Novel Coronavirus Disease (COVID-19) and Biologic Therapy in Psoriasis: Infection Risk and Patient Counseling in Uncertain Times.

With the emergence of the novel coronavirus disease (COVID-19) viral pandemic, there is uncertainty whether biologic agents for psoriasis may place patients at a higher risk for infection or more severe disease course. This commentary offers patient counseling recommendations based on the current available evidence. While there are currently no specific data for psoriasis biologics and COVID-19, data are presented here from phase III clinical trials of psoriasis biologics on rates of upper respiratory infection, influenza, and serious infection. Overall these data reveal that on the whole, psoriasis biologics do not show major increases in infection risk compared to placebo during the course of these trials. However, as the COVID-19 virus is a novel pathogen that is associated with mortality in a subset of patients, a cautious approach is warranted. We discuss factors that may alter the benefit-risk ratio of biologic use during this time of COVID-19 outbreak. Ultimately, treatment decisions should be made on the basis of dialogue between patient and provider, considering each patient's individualized situation. Once this pandemic has passed, it is only a matter of time before a new viral disease reignites the same issues discussed here.