Preventative and Personalized Approach to the Treatment of Malignant Melanoma: A Case Report.

This case report is focused on malignant melanoma, a common potentially lethal skin cancer, and its unique management. In our pa­tient’s case, the primary cutaneous melanoma occurred 28 years prior to presenting with axillary lymphadenopathy, which was later determined to be a metastatic focus of melanoma; subsequent nodules were found in his spleen. After completion of his treatment and routine screening, additional nodules were discovered in his chest. Primary and secondary prevention were important in the man­agement of this patient, as well as personalization of his treatment. Cette étude de cas porte sur le mélanome malin, un cancer de la peau potentiellement mortel avec une gestion unique. Dans le cas de notre patient, le mélanome s’est présenté 28 ans avant la présentation d’une lymphadénopathie axillaire, ce qui a été démontré par la suite comme une zone étant métastatique du mélanome. Des nodules ont été découverts dans sa rate. Suite à la fin des traitements et des suivis de routine, des nodules additionnels ont été découverts dans sa poitrine. Des préventions primaires et secondaires sont importantes pour la gestion de ce patient ainsi qu’un traitement personnalisé

624 - Vitiligo biomarker CXCL10 correlates with clinical response in the phase 2 randomized, double-blind, vehicle-controlled TRuE-V mechanism of action study

Abstract: Introduction/Background: Ruxolitinib cream is a topical formulation of the selective Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib and is the first and only repigmentation treatment approved by the US Food and Drug Administration and European Commission for nonsegmental vitiligo in patients ≥12 years old. Objectives: To evaluate treatment-associated changes in biomarkers among patients with vitiligo, correlate changes in key biomarkers with efficacy, and assess the safety and tolerability of ruxolitinib cream. Methods: The phase 2, randomized, double-blind, vehicle-controlled TRuE-V mechanism of action study (NCT04896385) was conducted in adult patients (≥18 years) with vitiligo ≤50% of total body surface area. Patients were randomized 2:1 to twice-daily 1.5% ruxolitinib cream or vehicle cream for 24 weeks, after which all patients could apply 1.5% ruxolitinib cream through Week 52. Changes from baseline in local and systemic immune biomarkers, including C-X-C motif chemokine ligand 10 (CXCL10), were evaluated at Weeks 4, 12, and 24. The relative expression of >3000 serum protein analytes was assessed using the Olink Explore platform, and a validated Meso Scale Discovery (MSD) assay was used to confirm absolute levels of serum CXCL10. Relative CXCL10 expression was determined by quantitative polymerase chain reaction (qPCR) from isolated biopsy samples. Punch biopsies (2.5 mm) were taken from lesional and nonlesional skin at baseline and lesional skin (even if the lesion had cleared) at Weeks 12, 24, and 40. Treatment efficacy was determined by the percentage change from baseline in facial and total Vitiligo Area Scoring Index (F-VASI and T-VASI, respectively). Safety was evaluated by the frequency and severity of adverse events. Results: The study enrolled 60 patients (ruxolitinib cream, n=41; vehicle, n=19). Patients’ mean (SD) age was 44.7 (12.8) years, 56.7% were male, and 53.3% had lighter skin (Fitzpatrick skin types I–III). At baseline, patients had a median (range) disease duration of 12.0 (0.1–52.9) years and mean (SD) F-VASI and T-VASI scores of 1.1 (0.6) and 12.1 (9.4), respectively. Olink Explore identified few differentially expressed proteins in patient sera (adjusted P<0.05 and log2 fold change >1.25), including CXCL10, SH2D1A, and granzyme B. As early as Week 12, serum CXCL10 levels (in MSD assay) were significantly reduced in ruxolitinib cream–treated patients compared with baseline. Skin CXCL10 levels were similar in lesional and nonlesional skin at baseline but were significantly lowered in lesional skin at Week 12 with ruxolitinib cream. In ruxolitinib cream–treated patients, significant mean [SD] percentage reductions from baseline were seen in F-VASI scores at Week 12 (–32.9 [33.6]) and in T-VASI scores at Week 24 (–21.2 [18.5]). Further, T-VASI scores significantly correlated with a change in serum CXCL10 levels between baseline and Week 24. Most systemic proteins did not correlate or only weakly correlated with F-VASI and T-VASI scores. Through Week 24, 46.3% of 41 patients who applied ruxolitinib cream reported treatment-emergent adverse events (none serious), the most common being COVID-19 (9.8%), application site acne (4.9%), and application site rash (4.9%). Conclusions: Taken together, these data are consistent with the role of the interferon-gamma:CXCL10 axis as a central mediator of vitiligo pathogenesis. Serum CXCL10 levels decreased significantly in patients who applied ruxolitinib cream, which correlated with improvement in T-VASI scores. Additionally, skin CXCL10 levels were significantly reduced after 12 weeks of ruxolitinib cream treatment

Digital Dermoscopy Photographs Outperform Handheld Dermoscopy in Melanoma Diagnosis

Background: Pigmented lesion clinics (PLCs) that use technology such as digital dermoscopy and total-body photography are thought to confer a clinical advantage for patients at high risk of developing melanoma over general dermatology clinics (GDCs) with regular dermoscopy. Objective: To examine the difference between depths of melanomas diagnosed in a PLC and a GDC. Methods: Medical records from 257 patients at the PLC at The Ottawa Hospital and 441 patients from a GDC were reviewed. Results: Invasive melanoma was less frequent than in situ melanoma at the PLC (7.14% vs 38.27%; P = .02). The average Breslow depth for melanomas at the PLC was also smaller compared with the GDC (0.0371 vs 0.3450 mm; P = .02). Conclusions: The use of digital dermoscopy and total-body photography together in a PLC appears to be an effective way to monitor patients at high risk of melanoma. </jats:sec

Treatment of Moderate to Severe Psoriasis With High-Dose (450-mg) Secukinumab: Case Reports of Off-Label Use

Treatment of moderate to severe psoriasis often requires systemic therapy, including biologics. Partial response to biologics and relapses are commonly managed with dose escalation. Secukinumab is a relatively new biologic that is currently used to treat moderate to severe psoriasis. There has been no literature published on dose escalation of secukinumab. This article describes the off-label use of a higher dose of secukinumab (450 mg every 4 weeks) instead of the standard dosing (300 mg every 4 weeks) in 2 patients with moderate to severe psoriasis. The first case involves a male patient with a high body mass index (BMI) (≥30 kg/m2) and severe psoriasis who was started on secukinumab at 450 mg following a partial response to treatment with the standard 300-mg dose. His psoriasis significantly improved with the higher dose of secukinumab. The second case discusses a female patient with treatment-resistant psoriasis and a BMI of 31.6 kg/m2 who initially achieved a complete remission with standard dosing of secukinumab. Later, her psoriasis relapsed and she was dose-escalated to secukinumab 450 mg in an attempt to recapture response, but this dose escalation was unsuccessful. In both cases, there were no adverse events observed with a higher dose of secukinumab. These cases demonstrate that dose escalation of secukinumab (450 mg rather than on-label 300 mg every 4 weeks) may be considered in selected patients with incomplete clearance, particularly for those with a high BMI. However, secukinumab dose escalation may not be as beneficial in patients with loss of efficacy. </jats:p

Dyshidrotic eczema in two patients on secukinumab for plaque psoriasis: A case report

Secukinumab was the first fully human anti-interleukin-17a monoclonal antibody and successfully treated moderate-severe psoriasis. These new, targeted, medications are becoming more ubiquitous, but long-term side effects are not fully known. Post-market surveillance is crucial to identify delayed adverse events, analogous to the paradoxical development of pustular psoriasis in a subset of patients treated with the anti-tumor necrosis factor-alpha class drugs. Dyshidrotic eczema and pompholyx are rare variants of dermatitis characterized by vesicles or bullae on the palms, soles and sides of the fingers. The etiology of dyshidrotic eczema is not always known, but medications have been implicated in a minority of patients. Herein, we present two cases of dyshidrotic eczema developing in patients on secukinumab for psoriasis. Extended follow-up and larger numbers of patients are needed to fully understand the potential association between secukinumab and dyshidrotic eczema. </jats:p

Management of Common Side Effects of Apremilast

Apremilast is a relatively new therapy for the treatment of moderate to severe plaque psoriasis in adults. While this medication is considered safe with a very low risk of serious side effects, a few common (≥5% of patients) mild to moderate side effects have been reported, including diarrhea, nausea, headache, and nasopharyngitis. Not addressing these symptoms may lead to medication nonadherence and unnecessary discontinuation of therapy. These side effects are often easily managed with interventions available to the practicing dermatologist, and in only rare instances will these side effects require dose adjustment or discontinuation of therapy. The purpose of this article is to review common side effects of apremilast at its approved dose of 30 mg orally twice daily (BID) and to provide clear, simple recommendations for their management in dermatological practice. </jats:p

Frontal Fibrosing Alopecia: Update and Review of Challenges and Successes

Background: Frontal fibrosing alopecia (FFA) is a variant of lichen planopilaris (LPP) and is characterised as a progressive cicatricial alopecia affecting the frontotemporal hairline. Objectives: To perform a comprehensive, up-to-date review of the etiopathogenesis, clinicopathological features, and therapeutic options for FFA. Methods: A literature search was conducted using PubMed (from 1946) and Cochrane (from 1991) databases on March 7, 2017. We included all retrospective and prospective studies reported in English. Only cases studies with reported treatment regimen and outcome were included. No randomised control trials were found. MeSH terms used included frontal fibrosing alopecia, postmenopausal, histopathologic, cicatricial, and treatment. Results: With an increasing incidence of FFA occurring predominantly in postmenopausal women, progress has been made clinically and histologically in understanding this scarring alopecia. Conflicting results have been reported with various treatments, including intralesional or oral corticosteroids, antiandrogens, antimalarials, antibiotics, and surgery. To date, no randomised control trials for treatment of FFA have been conducted. Conclusion: The aetiology and clinical course of FFA remain to be established. Unfortunately, despite the numerous treatment options available, no one therapeutic regimen has proven effective in stopping recession of the hairline and inducing hair growth. </jats:sec