Long-term safety and effectiveness of roflumilast cream 0.3% in adults with chronic plaque psoriasis: A 52-week, phase 2, open-label trial.

BACKGROUND: Efficacy and/or safety profiles limit topical psoriasis treatments. OBJECTIVE: Evaluate long-term effects of once-daily roflumilast cream 0.3% in patients with psoriasis. METHODS: In this open-label phase 2 trial, adult patients (N = 332) with psoriasis who completed the phase 2b parent trial or were newly enrolled applied roflumilast once-daily for 52 weeks. Safety and effectiveness were assessed. RESULTS: Overall, 244 patients (73.5%) completed the trial; 13 patients (3.9%) discontinued due to adverse events (AEs) and 3 (0.9%) due to lack of efficacy. Twelve patients (3.6%) reported treatment-related AEs; none were serious. ≥97% of patients had no irritation. No tachyphylaxis was observed with 44.8% of the patients achieving Investigator Global Assessment (IGA) Clear or Almost Clear at Week 52. LIMITATIONS: Intertriginous-IGA and Psoriasis Area and Severity Index (PASI) were not evaluated in all patients. CONCLUSIONS: In this long-term trial, once-daily roflumilast cream was well-tolerated and efficacious up to 64 weeks in patients in the earlier trial, suggesting it is suitable for chronic treatment, including the face and intertriginous areas.

Transition of Topical Therapy Formulation in Psoriasis: Insights from a Canadian Practice Reflective.

Patient preferences for psoriasis treatment may affect treatment adherence and disease control; changing topical formulation may improve adherence and patient acceptance of treatment. This study explored dermatologists' reasons for transitioning psoriasis patients from an ointment or gel (Dovobet®) formulation to an aerosol foam (Enstilar®) formulation of calcipotriol and betamethasone dipropionate (Cal/BD), and to assess the success of this transition. Medical records of 81 Canadian patients from 9 dermatologists were retrospectively reviewed for symptoms affecting quality of life, reasons for transitioning treatment, and whether transition was successful. Reasons for transition included efficacy, quality of life, and patient adherence. At follow-up, median psoriasis severity and body surface area affected had decreased from baseline, and patients experienced improved quality of life. Itch and itch-related sleep loss, which were identified as burdensome in 63% of patients at baseline, had resolved in 33% and improved in 54% of patients at follow-up. Dermatologists deemed the transition successful in 85% of patients, with the most common reasons being patient-reported success, clearance of signs/symptoms, and continued prescription refills. Transition from Cal/BD ointment or gel to aerosol foam was generally deemed successful by patients and dermatologists, and was associated with improved quality of life and improved itch control.

Pretibial Lymphoplasmacytic Plaque in Children: Case Report and Review of the Literature.

An 8-year-old girl presented with a persistent 5 × 2-cm violaceous doughy plaque on the left lower leg. Histologic examination revealed hyperkeratosis, variable but mild epidermal hyperplasia, and vacuolar interface changes with melanin pigment incontinence confined to the papillary dermis. A diagnosis of pretibial lymphoplasmacytic plaque in children was made. This report outlines the clinical characteristics of this entity and a review of other cases reported in the literature.

Matching-Adjusted Indirect Comparison of Long-Term Efficacy and Safety Outcomes for Calcipotriol Plus Betamethasone Dipropionate Foam Versus Halobetasol Proprionate Plus Tazarotene Lotion in the Treatment of Plaque Psoriasis.

INTRODUCTION: To date, there have been no head-to-head clinical studies comparing calcipotriol 0.005% plus betamethasone dipropionate 0.064% (Cal/BD) aerosol foam and halobetasol propionate 0.01% plus tazarotene 0.045% (HP/Taz) lotion for the treatment of plaque psoriasis. However, the efficacy of 4 weeks of Cal/BD foam and 8 weeks of HP/Taz lotion has been compared using a matching-adjusted indirect comparison (MAIC) approach. Here, we compare the efficacy and safety of Cal/BD foam and HP/Taz lotion for up to 52 weeks. METHODS: An unanchored MAIC was conducted using individual patient data from the PSO-LONG Cal/BD foam trial and a 52-week, open-label phase 3 study of HP/Taz lotion (NCT02462083). Key outcomes of interest were Physician's Global Assessment (PGA) success (PGA 0/1 with ≥ 2-point improvement) after 4 or 8 weeks of open-label therapy; the proportion of patients who had body surface area affected (BSA) ≤ 3 after open-label therapy who maintained BSA ≤ 3 to week 52; and adverse events (AEs). RESULTS: After matching, patients were statistically significantly more likely to have PGA success after 4 weeks of Cal/BD foam than after 8 weeks of HP/Taz lotion (84.5% versus 54.4%; p < 0.01). At week 52, 92.5% and 92.4% of patients receiving proactive and reactive Cal/BD foam, respectively, maintained BSA ≤ 3, compared with 49.3% of those treated with HP/Taz lotion (both p < 0.01). Treatment-related AEs, AEs leading to withdrawal, and AEs associated with drug application (dermatitis, application site pain, and pruritus) were significantly rarer with Cal/BD foam than with HP/Taz lotion (all p < 0.01). CONCLUSIONS: Cal/BD aerosol foam demonstrated significantly greater efficacy than HP/Taz lotion, and had a more favorable safety profile, compared with HP/Taz lotion, for up to 52 weeks. Proactive Cal/BD foam maintenance therapy and reactive use of Cal/BD foam following relapse both had significant advantages over HP/Taz lotion.

Tralokinumab Plus Topical Corticosteroids as Needed Provides Progressive and Sustained Efficacy in Adults with Moderate-to-Severe Atopic Dermatitis Over a 32-Week Period: An ECZTRA 3 Post Hoc Analysis.

BACKGROUND: The efficacy and safety of tralokinumab, a fully human monoclonal antibody that specifically neutralizes interleukin-13, plus topical corticosteroids (TCS) as needed were evaluated over 32 weeks in the phase III ECZTRA 3 trial. Significantly more tralokinumab- versus placebo-treated patients achieved the primary endpoints of Investigator's Global Assessment (IGA) score of 0/1 and 75% improvement in Eczema Area and Severity Index (EASI-75) and all confirmatory endpoints at Week 16. OBJECTIVE: This post hoc analysis investigated the impact of tralokinumab plus TCS on atopic dermatitis (AD) severity, symptoms, and health-related quality of life (QoL) over the entire 32-week treatment period of ECZTRA 3, including all patients initiated on tralokinumab irrespective of the response achieved at Week 16. METHODS: Patients were randomized 2:1 to receive subcutaneous tralokinumab 300 mg or placebo every 2 weeks (q2w) with TCS as needed for an initial 16 weeks. At Week 16, patients who achieved the clinical response criteria (IGA 0/1 and/or EASI-75) with tralokinumab were re-randomized 1:1 to tralokinumab q2w or every 4 weeks (q4w), with TCS as needed, for another 16 weeks. Patients not achieving the clinical response criteria with tralokinumab received tralokinumab q2w plus TCS from Week 16. All patients randomized to tralokinumab in the initial treatment period were pooled for this analysis, irrespective of response at Week 16 or dosing regimen beyond Week 16. RESULTS: Continued tralokinumab (q2w, N = 164; q4w, N = 69) plus TCS treatment provided progressive improvements from Week 16 onwards in AD signs, with 70.2% (177/252) of patients achieving EASI-75 and 50.4% (127/252) achieving EASI-90 at Week 32. Improvements in patient-reported outcomes were observed within the first few weeks of tralokinumab q2w plus TCS treatment and were sustained throughout the 32-week period. At Week 32, patients initiated on tralokinumab q2w plus TCS achieved a relative improvement versus baseline of 70.8% (standard error (SE), 2.4) in eczema-related sleep interference numeric rating scale (NRS) and 66.8% (SE, 3.1) in Dermatology Life Quality Index (DLQI). Mean TCS use during Weeks 16-32 ranged from 9.2 to 13.6 g (SE, 1.2-2.0) q2w. Most patients (89.9% (222/247)) initiated on tralokinumab q2w plus TCS achieved a meaningful improvement in at least one of the three disease domains, including AD signs (EASI-50), symptoms (pruritus NRS improvement ≥ 3), and QoL (DLQI improvement ≥ 4) at Week 16. Of patients initiated on tralokinumab q2w plus TCS, 53.4% (132/247) achieved a clinically meaningful improvement in all three domains at Week 16 (vs. placebo, 28.5% (35/123); p < 0.001). CONCLUSIONS: Continued tralokinumab treatment plus TCS as needed provides progressive and sustained improvements in AD signs, symptoms, and health-related QoL over 32 weeks. CLINICAL TRIAL REGISTRATION: NCT03363854; study start date: 22 February 2018; primary completion date: 8 March 2019; study completion date: 26 September 2019.

Atopic dermatitis (AD) is a chronic inflammatory disease that causes excessively dry and itchy skin that can negatively impact sleep and overall quality of life for patients. Topical corticosteroids (TCS) are the most common medication used for AD, but they are not able to control the most severe cases. Tralokinumab is a treatment injected under the skin that targets an immune messenger protein called interleukin 13, which plays a key role in driving the signs and symptoms of AD. The ECZTRA 3 clinical trial, funded by LEO Pharma, compared the use of TCS as needed with either tralokinumab or placebo in over 350 adult patients with moderate-to-severe AD over a 32-week period. After 16 weeks, more patients taking tralokinumab plus TCS had clear or almost clear skin compared with patients taking placebo plus TCS. Patients taking tralokinumab also used less TCS than patients taking placebo. In new analyses presented here, we found that the proportion of patients with clear or almost clear skin continued to increase with on-going treatment from Week 16 to Week 32. Tralokinumab plus TCS treatment also led to clinically meaningful improvements in outcomes important to patients, including itch, sleep, and quality of life. Improvements occurred early, within the first few weeks of therapy, and lasted through Week 32. Our assessment of multiple outcomes over time clearly demonstrates the positive impact of tralokinumab on different aspects of AD.

Practical Management of Patients with Atopic Dermatitis on Dupilumab.

INTRODUCTION: Dupilumab is approved to treat moderate-to-severe atopic dermatitis (AD) in several countries in patients as young as 6 years of age. Since its approval, practical issues related to the use of dupilumab for AD have arisen, with particular interest in transitioning from current therapies and managing medication overlap, considerations for special populations of patients with AD, and management of potential adverse events. METHODS: This article aims to review the literature addressing several practical management issues related to dupilumab use for AD and to provide a framework for clinical decision-making in these circumstances and sub-populations. Each statement was reviewed, revised and voted on by authors to provide their level of agreement and degree of uncertainty for each statement. RESULTS: An agreement level > 80% was achieved for all of the statements. CONCLUSION: The expert panel provides statements considering the practical management of patients with AD taking dupilumab to inform clinical decision-making in specific but frequently encountered clinical situations.

Review of intravascular lymphoma with a report of treatment with allogenic peripheral blood stem cell transplant.

Intravascular lymphoma (IVL) is a non-Hodgkin lymphoma in which atypical lymphocytes accumulate within small blood vessels. Patients most commonly present with neurologic and cutaneous findings; however, any organ system may be affected, which leads to difficulties in diagnosis. The objectives of this article are to review the current IVL literature and stress the importance of multiple skin biopsies in diagnosis. We also describe, to our knowledge, the first case of IVL treated with allogenic peripheral blood stem cell transplant (PBSCT). Intravascular lymphoma should be considered in the differential diagnosis of unexplained erythematous tender indurated plaques, nodules, and telangiectases. Single biopsy is not sufficient to rule out this entity. Intravascular lymphoma is a recalcitrant malignancy, and we describe a case that quickly recurred after treatment with cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (CHOP-R), and necessitated allogenic bone marrow transplantation (BMT).

Localized topical steroid use and central serous retinopathy.

OBJECTIVES: The link between topical steroid use and central serous retinopathy (CSR) is poorly understood as there are a limited number of reported cases, with most cases typically occurring in patients using oral or inhaled steroids. CSR is a common retinal disease that can cause loss of vision as a result of accumulated subretinal fluid leading to localized serous retinal detachments. CSR is associated with systemic steroid use. The objective of this case series and the review was to further understand the relationship between localized topical steroid use and CSR. METHODS: The medical charts of two patients who developed CSR after using topical steroids were reviewed. RESULTS: These cases demonstrate that CSR is associated with consistent topical steroid use to even limited areas of the body. These cases are unique, as other published cases describe patients who used topical steroids either on multiple or larger areas of the body. CONCLUSION: It is critical that dermatologists are aware of this association, and refer patients who develop ocular symptoms after using topical steroids to ophthalmology.

Spotlight on pembrolizumab in the treatment of advanced melanoma.

Metastatic melanoma is an aggressive cancer with a poor prognosis. Many approved therapies often do not achieve durable responses in patients. This underscores the need for novel therapeutic strategies. Recruiting a robust immune response is an important antineoplastic treatment strategy. Immune checkpoints offer a molecular target for modulating the immune response and a promising therapeutic target in metastatic melanoma. Here we discuss the recent approval of pembrolizumab by the US Food and Drug Administration for the treatment of metastatic melanoma and its impact on future management of the disease.

Tinea pedis presenting as asymmetric purpuric papules on the sole of the foot: a case report.

In this report we describe a unique case of tinea pedis. A 29-year-old man presented with a 3-day history of asymptomatic purpuric papules predominantly on his left foot. Potassium hydroxide preparation demonstrated fungal hyphae and culture yielded Trichophyton mentagrophytes. This patient presented unusually with purpuric papules, unlike the three commonly described types of tinea pedis. Given the morphology, positive potassium hydroxide slide preparation, T. mentagrophytes on fungal culture and clinical response to ketoconazole cream, we conclude that this represents a unique variant of tinea pedis. We recognize that even common dermatological diagnoses can have unique presentations, and it is important for clinicians to maintain a broad differential for new dermatologic cases.

Bench to bedside: mechanistic principles of targeting the RAF kinase in melanoma.

Melanoma, in its advanced form, is an aggressive cancer with a poor prognosis. To date, no therapeutic modality has afforded a high likelihood of curative outcome, with the exception of early surgical resection in patients diagnosed with local disease. However, recent advances in our understanding of the molecular mechanisms and pathophysiology of melanoma have paved the way towards the development of targeted therapeutics. A central player in melanomagenesis is the RAF family of kinases. Key mechanistic details regarding the regulation of RAF kinases have now begun to emerge. Already, vemurafenib, a tailored kinase inhibitor of aberrant RAF function in melanoma, has led to clinical benefit. Despite vemurafenib's success, acquired resistance to the drug warrants the need for further drug development. In this review, we discuss the critical role of RAF dimerization in both melanomagenesis and resistance to RAF inhibitors such as vemurafenib. We also highlight the potential for inhibitors of RAF dimerization to lead to improved outcomes in patients with advanced melanoma.

Plasmapheresis and steroid treatment of levamisole-induced vasculopathy and associated skin necrosis in crack/cocaine users.

BACKGROUND: Levamisole was removed from the market due to complications of agranulocytosis and skin necrosis. Levamisole has been reported in a high proportion of seized cocaine in North America and has been associated with multiple cases of skin necrosis. OBJECTIVE: We report three cases of levamisole/cocaine-induced skin necrosis who responded to treatment with plasmapheresis and immunosuppression. RESULTS: Three patients presented with painful necrotic skin lesions on the ears, cheeks, breasts, and buttocks. The extremities were involved in two patients and the upper respiratory tract mucosa in one patient. All had markers of immune activation, with elevated C-reactive protein, antinuclear antibody, and perinuclear antineutrophil cytoplasmic antibody. Skin biopsy in all cases revealed a mixed pattern of thrombosis and vasculitis within dermal vessels, with overlying ischemic ulceration of skin and soft tissues. One patient required extensive débridement of the skin and soft tissue of the calves and also had respiratory involvement. All patients were treated with plasmapheresis and immunosuppression with rapid stabilization and/or improvement of the lesions. CONCLUSION: Levamisole is frequently added to crack/cocaine; we report three patients who developed vascular lesions and skin necrosis after using cocaine/levamisole. These improved with plasmapheresis and immunosuppression as well as abstention from the drugs; one patient with severe disease required débridement and skin grafting.

Transdermal rivastigmine: management of cutaneous adverse events and review of the literature.

Alzheimer's disease is a chronic neurodegenerative disorder resulting in part from the degeneration of cholinergic neurons in the brain. Rivastigmine, a cholinesterase inhibitor, is commonly used as a treatment for dementia due to its ability to moderate cholinergic neurotransmission; however, treatment with oral rivastigmine can lead to gastrointestinal adverse effects such as nausea and vomiting. Transdermal administration of rivastigmine can minimize these adverse effects by providing continuous delivery of the medication, while maintaining the effectiveness of the oral treatment. While the transdermal form of rivastigmine has been found to have fewer systemic adverse effects compared with the oral form, cutaneous reactions, such as contact dermatitis, can lead to discontinuation of the drug in its transdermal form. Lack of patient compliance with regard to applying the patch to the designated site, applying the patch for the correct length of time or rotating patch application sites increases the risk of cutaneous adverse reactions. This article outlines the diagnosis and management of irritant contact dermatitis and allergic contact dermatitis secondary to transdermal rivastigmine. The large majority of reactions to transdermal patches are of an irritant type, which can be diagnosed clinically by the presence of a pruritic, erythematous, eczematous plaque strictly confined to the borders of the patch. In contrast, an allergic reaction can be differentiated by the presence of vesicles and/or oedema, erythema beyond the boundaries of the transdermal patch and lack of improvement of the lesion 48 hours after removal of the offending treatment. By encouraging the patient to follow a regular rotation schedule for the patch, and using lipid-based emollients for irritant dermatitis and pre- and post-treatment topical corticosteroids for allergic dermatitis, cutaneous reactions can often be alleviated and patients can continue with their medication regimen. Other simple changes to a patient's treatment routine, including minimizing the use of harsh soaps, avoiding recently shaven or damaged areas of skin and carefully removing the patch after use, can help to further decrease the risk of dermatitis development.

Pyogenic granuloma of the foot with satellitosis: a role for conservative management.

BACKGROUND: Pyogenic granuloma (PG) with satellitosis is a rare phenomenon that typically occurs in children and teenagers. It can be seen after excision or trauma to the original lesion. OBJECTIVE: The aim is to review an atypical case of PG with satellitosis and to highlight a conservative approach to management. METHODS: This article includes a case report of a 48-year-old woman developing PG with satellitosis in her right foot and includes a review of the literature. RESULTS: There are few cases of PG with satellitosis in the literature. Our patient differs from most given her age and the location of the lesions. She was managed differently with a conservative observational approach, and, over time, her symptoms abated. CONCLUSION: PG with satellitosis can occur in varying patient populations with varying presentations. Although several treatment options exist, managing patients conservatively should be considered an approach to management. Early investigations should be conducted to rule out more sinister items in the differential diagnosis.

Efficacy of a day-care program in the treatment of psoriasis.

BACKGROUND: Few data exist documenting the effectiveness of psoriasis day-care treatment programs (PDTPs) using standardized efficacy measurements. OBJECTIVES: We sought to analyze the efficacy of a PDTP using the Psoriasis Area and Severity Index (PASI). METHODS: A retrospective review was performed on 132 patients treated at our PDTP. Sufficient data existed to permit PASI analysis using a simplified method for a representative subgroup of 64 patients, who formed the study population. Patients received phototherapy and topical treatments over 2 weeks. The outcome measures included a baseline and day 11 PASI, a physician global assessment (PGA), and adverse events reported by the patients. RESULTS: Mean baseline PASI was 13.6 (N = 64), with a 59.6% reduction by day 11. A PASI reduction of > or = 50% was seen in 75% of patients, with 30% of patients achieving > or = 75% reduction of PASI. Day 11 PGA demonstrated a 69.9% improvement. CONCLUSION: With a reduction in PASI of 59.6% at 11 days, our PDTP, with phototherapy and topical agents, seems to be a rapid and effective therapy for psoriasis.