Clinical Utility of Deucravacitinib for the Management of Moderate to Severe Plaque Psoriasis.

Introduction: Psoriasis is a chronic, immune-mediated skin condition with significant detriments to physical/mental health. While systemic therapies are available for the treatment of moderate-to-severe psoriasis, patients can experience therapeutic failure, loss of efficacy, or medical contraindications that require other therapeutic options. Objective: With the recent approval of deucravacitinib, a first-in-class TYK2 small molecule inhibitor administered orally for psoriasis patients, we reviewed data from randomized controlled trials (RCTs) to synthesize its clinical utility. To our knowledge, this is the first systematic review and meta-analysis of deucravacitinib comparing its clinical efficacy to placebo in psoriasis. Methods: A literature search was conducted in PubMed (MEDLINE), Embase, and the Cochrane Central Register of Controlled Trials to identify RCTs studying deucravacitinib in human patients with moderate-to-severe psoriasis. Results: One placebo-controlled Phase II RCT and two placebo-controlled/active-comparator Phase III RCTs were included for review. Patients (N=1953) treated with deucravacitinib 6 mg daily showed marked improvement in disease severity (Psoriasis Area and Severity Index (PASI), static Physician Global Assessment (sPGA) and quality-of-life outcomes compared to patients administered comparator (apremilast) and placebo. Clinical improvement given deucravacitinib was noted for scalp psoriasis but not fingernail psoriasis. Meta-analysis (deucravacitinib, n=888; placebo, n=466) comparing rates of clearance (sPGA 0/1) demonstrated superior efficacy of deucravacitinib compared to placebo (odds ratio, 12.87; 95% confidence interval, 8.97-18.48; χ2=4.08, I2=51%). Deucravacitinib was well-tolerated, with similar rate of occurrence and type of adverse events reported among patients treated with placebo or apremilast at Week 12-16. No cardiovascular events, serious infections, or lab abnormalities were noted. Conclusion: Deucravacitinib possesses good efficacy, with no report of safety concerns associated with prior JAK inhibitors used for psoriasis. Meta-analysis demonstrated deucravacitinib's superiority compared to placebo, indicating its promising clinical utility. Further studies are needed to observe long-term safety and efficacy, and to compare deucravacitinib to existing treatments.

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.

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.

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.

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.

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.

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.

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.