Systematic review and network meta-analysis of the risk of malignancy with biologic therapies and selective Janus kinase-1 inhibitors in atopic dermatitis.

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease with multifactorial pathophysiology. Biologic therapies, including dupilumab (IL-4/IL-13 inhibitor) and tralokinumab (IL-13 inhibitor), as well as selective Janus kinase-1 (JAK-1) inhibitors such as upadacitinib and abrocitinib, have been approved for the treatment of moderate to severe AD. However, their association with the incidence of malignancy in AD patients remains uncertain. Aim: We conducted a systematic review and network meta-analysis (NMA) to investigate and compare the indidence and risk of malignancy in individuals with moderate-to-severe AD treated with abrocitinib, upadacitinib, tralokinumab, or dupilumab. Material and methods: Systematic searches were conducted in Ovid MEDLINE and EMBASE that included AD, malignancy, biologic and advanced therapies. The primary outcome was incidence of malignancy in AD patients receiving placebo or at least one of the following advanced therapies: dupilumab, tralokinumab, abrocitinib or upadacitinib. A random-effects NMA was conducted with odds ratios and a frequentist model. Results: Our search identified 11 trials comprising 10097 patients. The NMA did not show any statistically significant association between dupilumab or selective JAK-1 inhibitors and the incidence of malignancy up to an average of 41 weeks of treatment. Conclusions: Our analysis revealed no statistically significant increased risk of malignancy and no significant difference in the incidence of malignancy between selective JAK-1 inhibitors and dupilumab for the treatment of AD up to an average follow-up of 41 weeks. Nevertheless, further prospective studies with longer follow-up periods are warranted to confirm the safety of these therapies and their impact on the risk of malignancy.

Comparison of the Efficacy of Clascoterone, Trifarotene, and Tazarotene for the Treatment of Acne: A Systematic Literature Review and Meta-Analysis.

INTRODUCTION: Acne vulgaris, a chronic inflammatory condition, is associated with significant physical and psychosocial burden. Since 2019, three new topical agents for acne vulgaris have been approved in the USA and Canada. We performed a systematic review and meta-analysis to compare the efficacy between twice-daily clascoterone cream 1%, once-daily trifarotene 0.005% cream, and once-daily tazarotene 0.045% lotion for acne treatment. METHODS: Randomized controlled trials (RCTs) comparing clascoterone, trifarotene, or tazarotene with vehicle in patients with moderate-to-severe acne were identified from a systematic literature review and included in a meta-analysis. Primary outcomes were percentage reduction in inflammatory and noninflammatory lesion count (ILC and NILC, respectively) and treatment success rate (≥ 2-grade improvement in Investigator's Global Assessment or Evaluator's Global Severity Score and a rating of clear or almost clear) at week 12. DerSimonian and Laird random-effects models with the inverse variance method were used to calculate the mean difference (MD) for percentage reduction in ILC and NILC, and odds ratios (ORs) for the rate of treatment success. RESULTS: Six Phase 3 RCTs were included in the meta-analysis. The analyses showed robust differences favoring the interventions for ILC (MD: - 11.5; 95% confidence interval [CI]: - 14.39, - 8.62), NILC (MD: - 12.25; 95% CI: - 15.21, - 9.29), and treatment success rate (OR: 2.14; 95% CI: 1.81, 2.53). No differences were observed between clascoterone, trifarotene, and tazarotene for ILC (MD: - 12.8, - 11.2, and - 10.1, respectively), NILC (MD: - 11.6, - 13.9, and - 12.8, respectively), or treatment success rate (OR: 2.9, 1.9, and 2.1, respectively (all P > 0.05). CONCLUSION: No significant differences in efficacy were observed between clascoterone, trifarotene, and tazarotene after 12 weeks of treatment in patients with moderate-to-severe acne. Differences in application frequency and safety profile should also be taken into consideration when making treatment decisions.

A systematic review of the risk of cutaneous malignancy associated with ultraviolet nail lamps: what is the price of beauty?

Gel manicures have become part of a popular personal care service in the last two decades due to increased longevity of the polish and the added strength to the nail plate. Prolonged exposure to nail ultraviolet (UV) lamps is required to cure the gel polish. Despite the increased use of UV nail lamps, there is limited consensus in the literature on the risk of skin malignancy associated with UV nail lamps. The objective of this article was to provide a systematic review of the risk of skin malignancy associated with the use of UV nail lamps and to synthesize evidence-based recommendations on their safe usage. A systematic review of the literature was conducted on the databases, Medline and Embase, in accordance with PRISMA guidelines. The search yielded 2,331 non-duplicate articles. Nine were ultimately included, of which three were case reports, one was a cross-sectional study, and five were experimental studies. The risk of bias per the Joanna Briggs Institute guidelines was high or unclear, likely due to the number of case reports included. Prolonged and repeated exposure to UV nail lamps may pose a low risk of skin cancer. It is important to note that the available evidence is weak, and patients should be informed about the limited data to make their own decisions. Dermatologists and other healthcare providers should be updated with the latest evidence to address patients' concerns about gel manicures and suggest practices which can effectively reduce the risk of cutaneous malignancy associated with gel manicures, such as the use of UV-blocking gloves or properly applied sunscreens.

Systematic review and network meta-analysis of the risk of Herpes zoster with biological therapies and selective Janus kinase-1 inhibitors in atopic dermatitis.

Introduction: Atopic dermatitis (AD) patients have an increased risk of herpes zoster (HZ). The relationship of dupilumab, tralokinumab, upadacitinib, and abrocitinib to HZ incidence in AD patients remains unclear. Aim: To evaluate and compare the incidence and risk of HZ among patients with moderate to severe atopic dermatitis treated with advanced systemic therapies. Material and methods: Systematic searches were conducted in Ovid Medline and Embase. The primary outcome was incidence of HZ in patients with moderate to severe AD receiving placebo or the aforementioned treatments. A frequentist random-effects NMA was conducted with odds ratio. Results: Our search identified 16 trials comprising 10,689 patients. Upadacitinib was associated with a dose-dependent increase in the incidence of HZ compared to placebo (OR = 2.55 [1.09, 5.95] and (OR = 4.29 [1.89, 9.74], respectively) and compared to various dupilumab doses (OR = 4.48 [1.29, 15.57], 3.61 [1.28, 10.18] and 7.54 [2.21, 25.68], 6.09 [2.24, 16.52], respectively). Upadacitinib 30 mg was associated with a higher incidence of HZ when compared to upadacitinib 15 mg (OR = 1.68 [1.19, 2.38]). Abrocitinib 200 mg was associated with a higher increase in HZ compared to placebo (OR = 3.34 [1.34, 8.31]). According to SUCRA ranks, both JAK-1 inhibitors had a higher cumulative incidence of HZ compared to dupilumab. Conclusions: JAK-1 inhibitors are associated with a significantly higher incidence of HZ compared to dupilumab and placebo. Our results suggest that recombinant HZ vaccination should be highly considered for all adult patients prior to starting oral JAK-1 inhibitors.

A real-world study of dupilumab in patients with atopic dermatitis including patients with malignancy and other medical comorbidities.

Background: Dupilumab is a monoclonal antibody approved for the treatment of moderate-to-severe atopic dermatitis (MtS-AD). Various clinical trials have established the effectiveness and safety of dupilumab for the treatment MtS-AD; however, the real-world experiences of patients treated with dupilumab with malignancy and other comorbidities are lacking. Objective: To assess the real-life effectiveness and safety of dupilumab in the treatment of MtS-AD within Canadian adult patient population, including those with other significant comorbidities such as malignancy. Methods: In this retrospective study, records of adult patients diagnosed with MtS-AD, with a Physician Global Assessment (PGA) score of 3 or 4, and treated with dupilumab for 52 weeks were reviewed and collected. Results: A total of 155 adult patients with atopic dermatitis (AD) treated with dupilumab were included in the study. Asthma was the most common comorbidity. One hundred twenty-three (80%) patients received either phototherapy and/or at least 1 systemic agent (methotrexate and cyclosporine) before initiation of dupilumab. PGA score of 0 or 1 was achieved by 64% of patients at week 52. Adverse effects including injection site reactions, ocular surface disease, facial and neck redness, and arthropathy occurred in 6%, 10%, 8%, and 6% of patients, respectively. Three patients continued receiving dupilumab throughout pregnancy, all maintaining PGA score of 0 or 1 with no impact on pregnancy, delivery, or the newborn. Twelve patients with prior or active malignancy were included, with no reported negative impact on malignancy. Conclusion: Dupilumab is an effective and safe option for patients with AD in real life, including patients with malignancy and other medical comorbidities.

Updates on Pityriasis Rubra Pilaris: A Scoping Review.

Pityriasis rubra pilaris (PRP) is a rare, inflammatory papulosquamous skin disease with unknown exact etiology. Historically, PRP has been challenging to diagnose, especially during the acute phase, and to treat, due to its unclear pathogenesis. To better inform clinical practice, a literature review was conducted employing a broad search strategy to capture PRP-related published studies between January 1, 2012 to October 31, 2022. Two hundred twenty-one studies were identified, which were categorized into 9 themes: (1) potential causes and triggering factors, (2) comorbidities, (3) diagnostic difficulties, (4) genetics, (5) clinical manifestations and laboratory values, (6) treatment, (7) treatment-related adverse events, (8) quality of life, and (9) other. COVID-19 infection, COVID-19 vaccination, and malignancy were the most commonly reported potential triggering factors. Misdiagnosis is very common during the early acute stages. Pathogenesis and genetic studies have further implicated caspase recruitment domain family member 14 (CARD14) mutations in the development of familial PRP (Type V) and have underlined the overlap between psoriasis and PRP. To date, there are currently no specific and validated scoring systems or tools to assess the severity of PRP. While large, randomized trials are still lacking, biologic agents remain the most effective therapy.

Clinical Characteristics and Treatment Outcomes of Prurigo Nodularis: A Retrospective Study.

BACKGROUND: Prurigo nodularis (PN) is a complex chronic skin disease characterized by severe pruritic nodules. PN is often associated with mental health disorders and chronic medical comorbidities. Until recently, PN treatment has been challenging and difficult. OBJECTIVES: This study aims to describe the demographic, clinical characteristics, and comorbidities associated with PN. Also, we aim to describe the effectiveness of systemic therapies, including methotrexate, cyclosporine, and narrow band ultraviolet (NB-UVB) in adult patients with PN. METHODS: This is a retrospective chart review of adult patients diagnosed with PN at Hamilton Health Science Center and/or McMaster University in Hamilton, Ontario, between 2015 and 2023. RESULTS: The study included 81 patients (57% female). The mean age was 52.8 years, and the mean age of PN diagnosis was 50 years. Reported symptoms included: itching (100%), dry skin (53%), pain (17%), and burning sensation (5%). Lower and upper extremities were the most common areas involved in 93% and 69%, respectively. Mental health disorders were present in 79% of patients, with depression (58%) and anxiety (52%) being the most common. Atopic dermatitis was the most common skin comorbidity noted. Treatments used included cyclosporine, and NB-UVB, and MTX, which resulted in significant improvement of pruritus in 38%, 35%, and 31% of patients, respectively, at week 16. CONCLUSIONS: PN is associated with increased risk of mental health disorders and other medical comorbidities. Cyclosporine, methotrexate, and NB-UVB therapy may be effective treatment options, however clinicians must consider the potential short- and long-term adverse effects of these treatments.

Incidence of melanoma and non-melanoma skin cancer in patients with celiac disease: a systematic review and meta-analysis.

There is conflicting observational evidence regarding the association between skin cancer and celiac disease (CD). The purpose of this review was to investigate the incidence rate ratio (IRR) of skin cancer incidence between patients with and without CD. MEDLINE and EMBASE databases were searched on October 27th, 2021 and eight articles were identified for review. Quality assessment was conducted using the Newcastle Ottawa Scale. Seven articles were included in meta-analysis for a pooled estimate of IRR across all skin cancers, malignant melanoma (MM), and non-melanoma skin cancers (NMSC). In total, 74,860 CD patients were followed for 710,214 person-years in the meta-analysis. Overall combined incidence was 99.8 cases per 100,000 person-years. Meta-analysis of all skin cancer incidence showed no significant difference in CD patients compared to controls (IRR: 1.06; 95% CI: 0.95, 1.17; p=0.29; I2: 0%). Five studies reported on MM incidence; there was no significant difference in incidence compared to controls (IRR: 0.87, 95% CI: 0.72, 1.06; p=0.22; I2: 9%). Five studies reported on NMSC incidence, revealing a significantly increased risk of NMSC in CD patients (IRR: 1.14; 95% CI: 1.01, 1.28; p=0.04; I2: 0%). Our findings suggest a significantly increased incidence of NMSC in CD patients compared to control data and no significant association between CD and MM incidence. The findings are limited by the quantity and quality of the evidence. Nonetheless, clinicians should emphasize the importance of sun protection, such as sunscreen usage and self-examination for patients with CD.

Low Dose Oral Alitretinoin With Narrowband Ultraviolet B Therapy for Chronic Hand Dermatitis.

BACKGROUND: Chronic hand dermatitis (CHD) is difficult to treat and has high individual and societal burdens. Phototherapy and oral alitretinoin are safe monotherapies for CHD, but their combination has not been assessed. OBJECTIVE: To assess the effectiveness and safety of low dose oral alitretinoin combined with phototherapy versus high dose oral alitretinoin for CHD refractory to topical corticosteroids. METHODS: This retrospective study of adult patients with CHD refractory to topical corticosteroid therapy compared low dose oral alitretinoin (10 mg three times weekly) combined with narrowband ultraviolet B therapy (three times weekly; LDA-UVB) to high dose oral alitretinoin (30 mg daily; HDA) for 16 weeks. Outcomes were improvement in disease severity measured by the Physician's Global Assessment and quality of life measured with the Dermatology Life Quality Index. RESULTS: The mean age of the study population (n = 64) was 41.25 years and 57.8% were male. Both cohorts experienced improvements in disease severity and quality of life after 16 weeks, however, significantly more participants who received LDA-UVB (n = 21/33, 63.6%) achieved "clear" or "almost clear" assessments compared to those who received HDA (n = 12/31, 38.7%; P < .05). Adverse effects were significantly more prevalent in the HDA group (P < .0001) and included headache, elevated cholesterol, and dry lips. CONCLUSIONS: The combination of low dose oral alitretinoin with narrowband-UVB therapy was more effective and had fewer adverse effects compared to high dose oral alitretinoin for participants with CHD refractory to topical corticosteroid therapy.

Morbidity and Mortality of Melanoma on the Trunk and Extremities Treated With Mohs Surgery Versus Wide Excision: A Systematic Review.

BACKGROUND: Recommendations for the approved use of Mohs surgery for cutaneous melanoma on the trunk and extremities remain uncertain. OBJECTIVE: To compare survival and recurrence between patients treated with Mohs surgery versus wide excision for melanoma on the trunk and extremities. METHODS: The databases Medline, Embase, Web of Science, CENTRAL, and EMCare were searched from inception on January 11, 2021. Contemporary comparisons were included exclusively. Meta-analysis was conducted using generic inverse variance and a fixed effects model. RESULTS: Four studies were eligible for inclusion. The study population (n = 279,556) was 52.1% men and 97.2% White. There were no observed differences in 5-year overall survival (hazard ratio 0.98, 95% confidence interval 0.90-1.07, I2 = 0%), disease-free survival (HR 0.89, 95% CI 0.12-6.47, I2 = 0), or local recurrence among patients treated with Mohs surgery relative to wide excision. Quality of the evidence was very low. CONCLUSION: This systematic review found survival and local recurrence were comparable among patients treated with Mohs surgery or wide excision for melanoma on the trunk and extremities. Future prospective contemporary studies with more diverse representation that report surgical complications and costs may facilitate more definitive recommendations.

Super giant basal cell carcinoma in an autistic patient: A case report.

Basal cell carcinoma is the most common skin cancer in the world and is generally treated when small in size with an excellent prognosis. Rarely, basal cell carcinoma will grow to be larger than 5 cm, at which point they are termed giant basal cell carcinoma. Giant basal cell carcinoma comprises only 0.5% of all basal cell carcinoma, but is associated with impaired quality of life and increased risk of metastasis. When a basal cell carcinoma grows to over 20 cm in size, it is termed super giant basal cell carcinoma. Here, we report a case of both a super-giant basal cell carcinoma and a giant basal cell carcinoma developing over 10-12 years on the upper back and anterior chest wall of an autistic male. Generally, this presentation is associated with neglect on the part of the patient. This case report demonstrates a super-giant basal cell carcinoma developing secondary to patient neglect in the context of comorbid mental illness.