A head-to-head comparison of ixekizumab vs. guselkumab in patients with moderate-to-severe plaque psoriasis: 24-week efficacy and safety results from a randomized, double-blinded trial.

BACKGROUND: Significantly more patients with moderate-to-severe plaque psoriasis treated with the interleukin (IL)-17A inhibitor ixekizumab vs. the IL-23p19 inhibitor guselkumab in the IXORA-R head-to-head trial achieved 100% improvement in Psoriasis Area and Severity Index (PASI 100) at week 12. OBJECTIVES: To compare skin and nail clearance and patient-reported outcomes for ixekizumab vs. guselkumab, up to week 24. METHODS: IXORA-R enrolled adults with moderate-to-severe plaque psoriasis, defined as static Physician's Global Assessment ≥ 3, PASI ≥ 12 and involved body surface area ≥ 10%. Statistical comparisons were performed using the Cochran-Mantel-Haenszel test stratified by pooled site. Time-to-first-event comparisons were performed using Kaplan-Meier analysis, and P-values were generated using adjusted log-rank tests stratified by treatment group. Cumulative days at clinical and patient-reported responses were compared by ancova. The trial was registered with ClinicalTrials.gov (NCT03573323). RESULTS: Of the 1027 patients randomly assigned, 90% completed the trial (465 of 520 ixekizumab and 459 of 507 guselkumab). As early as week 2 and through week 16, more patients on ixekizumab achieved PASI 100 (P < 0·01). At week 24, ixekizumab was noninferior to guselkumab (50% vs. 52%, difference -2·3%), with no statistically significant difference in PASI 100 (P = 0·41). More patients receiving ixekizumab showed completely clear nails at week 24 (52% vs. 31%, P = 0·007). The median time to first PASI 50/75/90 and PASI 100 were 2 and 7·5 weeks shorter, respectively, for patients on ixekizumab vs. guselkumab (P < 0·001). Patients on ixekizumab also had a greater cumulative benefit, with more days at PASI 90 and 100, with Dermatology Life Quality Index of 0 or 1, and itch free (P < 0·05). The frequency of serious adverse events was 3% for each group, with no new safety signals. CONCLUSIONS: Ixekizumab was noninferior to guselkumab in complete skin clearance and superior in clearing nails at week 24. Ixekizumab cleared skin more rapidly in patients with moderate-to-severe plaque psoriasis, with a greater cumulative benefit, than guselkumab. Overall, the safety findings were consistent with the known safety profile for ixekizumab.

Non-melanoma skin cancer in Canada chapter 1: introduction to the guidelines

BACKGROUND: Non-melanoma skin cancer (NMSC), including basal and squamous cell carcinoma, represents the most common malignancy. OBJECTIVE: The aim of this document is to provide guidance to Canadian health care practitioners on NMSC management. METHODS: After conducting a literature review, the group developed recommendations for prevention, management, and treatment of basal cell carcinomas, squamous cell carcinomas, and actinic keratoses. These tumour types are considered separately in the accompanying articles. The Grading of Recommendations Assessment, Development and Evaluation system was used to assign strength to each recommendation. RESULTS: This introduction describes the scope and structure of the guidelines and the methods used to develop them. The epidemiology of NMSC is reviewed, as are the pathophysiologic changes occurring with damage to the skin, which lead to the formation of actinic keratoses and invasive squamous or basal cell carcinomas. CONCLUSIONS: This introduction describes the need for primary prevention and offers an overview of treatment options that are discussed in later chapters of the guidelines.(AU)

Treatments for scalp psoriasis with emphasis on calcipotriol plus betamethasone dipropionate gel (Xamiol).

Scalp psoriasis occurs in 50%-75% of patients with plaque psoriasis. It may be the only area of the body affected, or it may be associated with disease elsewhere, including psoriatic arthritis. Most cases are treated topically, usually with steroids and/or calcipotriol. In 2008, Health Canada and the US FDA approved a stable, once-daily 2-compound gel containing calcipotriol and betamethasone dipropionate (Xamiol, LEO Pharma; Taclonex Scalp, Warner Chilcott). This once-daily therapy improves patient quality of life with a quick onset of action and greater efficacy than monotherapy with either ingredient or twice daily treatment with calcipotriol 0.005% (Dovonex, LEO Pharma) scalp solution. The gel vehicle was developed for ease of use, improved cosmetic acceptability and absorption on the scalp. By 2 weeks, approximately 60%, and by 8 weeks, approximately 70% of patients have controlled disease (i.e., absent or very mild disease). At 8 weeks, the calcipotriol and betamethasone dipropionate gel formulation has a safety profile comparable with betamethasone dipropionate and is associated with significantly fewer adverse events than calcipotriol. Xamiol may be safely used for up to 52 weeks. No cases of atrophy, striae, or steroid purpura were noted in two 52-week studies.

Topical tazarotene therapy for psoriasis, acne vulgaris, and photoaging.

Psoriasis, acne vulgaris and photoaging are common conditions. Tazarotene is a pro-drug of tazarotenic acid, a receptor-selective retinoid, which has shown efficacy in the treatment of these disorders. In the treatment of acne vulgaris, it has greater comedolytic activity than the currently available topical retinoids. In psoriasis, tazarotene normalizes keratinocyte differentiation, reverses keratinocyte hyperproliferation and has better anti-inflammatory effects than any of the currently available topical retinoids. It is most commonly used as combination therapy with a topical corticosteroid or phototherapy in psoriasis, or with an antibiotic in acne.

One-year followup on the impact of a sun awareness curriculum on medical students' knowledge, attitudes, and behavior.

BACKGROUND: A one-week sun awareness curriculum was developed at the University of Western Ontario to educate first-year medical students on skin cancer risks and prevention. OBJECTIVE: To assess the retention of knowledge, attitudes, and behavioral practices one year after receiving education in sun awareness. METHOD: Three surveys were administered: before, immediately after the sun awareness teaching, and one year later. Actual practiced behavior in the past year was compared with the intended behavior. RESULTS: Half as many sunburns were reported in the year following the sun awareness curriculum compared with the previous year. Medical students demonstrated a good retention of the knowledge learned a year earlier. However, many students still believed that a tanned appearance looks healthy. While there was intent to adopt more healthy behavior after the curriculum, the actual behavior practiced varied. CONCLUSIONS: An undergraduate medical curriculum on sun awareness can be effective in improving the knowledge, attitudes, and behaviors of future physicians.

A comparison of tazarotene 0.1% gel once daily plus mometasone furoate 0.1% cream once daily versus calcipotriene 0.005% ointment twice daily in the treatment of plaque psoriasis.

BACKGROUND: Both tazarotene (a retinoid prodrug) and calcipotriene (a synthetic analog of vitamin D3) are effective in the treatment of plaque psoriasis, but no reports in the literature directly compare the efficacy and tolerability of these 2 drugs. Tazarotene is commonly used in conjunction with a topical corticosteroid. In this study, tazarotene was used with mometasone furoate (a synthetic corticosteroid), and the 2-drug regimen was compared with calcipotriene monotherapy. OBJECTIVE: This study was conducted to compare the efficacy and tolerability of tazarotene 0.1% gel once daily plus mometasone furoate 0.1% cream once daily with those of calcipotriene 0.005% ointment twice daily in the treatment of plaque psoriasis. METHODS: In this multicenter, investigator-blinded, parallel-group study, adult patients with chronic, stable plaque psoriasis affecting 5% to 20% of their body surface area were randomly allocated to receive up to 8 weeks of treatment with either tazarotene 0.1% gel once daily (in the evening) plus mometasone furoate 0.1% cream once daily (in the morning) or calcipotriene 0.005% ointment twice daily. Patients were assessed at baseline and at weeks 2, 4, and 8 of treatment. Patients who demonstrated complete clearance of plaque psoriasis after 2 or 4 weeks of treatment and those whose psoriasis had improved > or = 50% after 8 weeks of treatment entered a 12-week posttreatment follow-up phase during which they applied only moisturizer. Patients were reassessed after 4, 8, and 12 weeks of posttreatment follow-up. Physician-rated measures of efficacy included global improvement, plaque elevation, scaling, erythema, and percentage of body surface area involvement. Patient-rated assessments included efficacy of study treatment compared with previous therapies, comfort of treated skin, outlook for long-term control of psoriasis, and overall impression of treatment. RESULTS: Of 120 patients with moderate to severe psoriasis enrolled from 3 centers, 106 (88%) completed the study. No significant differences in baseline clinical variables were observed between the 2 groups. Twenty-seven patients (45%) in the tazarotene plus cortico-steroid group achieved marked improvement (> or = 75% global improvement) after 2 weeks of treatment compared with 15 patients (26%) in the calcipotriene group (P < or = 0.05). Between-group comparisons of the percentage of patients achieving complete or almost complete clearance (> or = 90% global improvement) did not reach statistical significance at any time point. When compared with the calcipotriene regimen, the tazarotene plus corticosteroid regimen resulted in significantly greater efficacy on trunk lesions in reducing plaque elevation (at the end of treatment and at week 4 of the posttreatment phase, P < or = 0.05), scaling (week 4 of treatment and week 4 of the posttreatment phase, P < or = 0.05), erythema (week 4 of treatment and at the end of treatment, P < or = 0.05), and percentage of body surface area involvement (weeks 2 and 4 of treatment, P < or = 0.01). In addition, the tazarotene plus corticosteroid regimen was significantly more effective in reducing the percentage of body surface area involvement in upper limb lesions (weeks 2 [P < or = 0.05] and 4 [P < or = 0.01] of treatment). Forty-two of 55 patients (76%) in the tazarotene plus corticosteroid group rated their medication as more or much more effective than previous therapies compared with 30 of 52 patients (58%) in the calcipotriene group (P < or = 0.05). Although adverse events (burning, pruritus, irritation, and erythema) occurred in a significantly greater proportion of patients who received tazarotene plus corticosteroid than in those who received calcipotriene (P < or = 0.05), 47 of 55 patients (85%) in both groups rated the comfort of their treated skin as "somewhat comfortable" or better and both groups had similar discontinuation rates due to treatment-related adverse events (3% and 5%, respectively). CONCL

Proliferating cell nuclear antigen (PCNA); prognostic value in the clinical recurrence of primary basal cell carcinoma.

Proliferating cell nuclear antigen (PCNA) is a nuclear protein which is correlated with the S-phase of the cell cycle and has been utilized by many investigators as a marker of cell proliferation. A previous immunohistochemical study revealed increased PCNA staining in clinically and histologically aggressive basal cell carcinoma and the present study evaluated the prognostic value of PCNA in clinical recurrence of primary basal cell carcinoma. Thirty patients with primary basal cell carcinoma (BCC) treated with shave biopsy followed by electrodesiccation in 1989 and have been regularly followed up for local recurrence were selected for this study. The histology of their primary BCC's was reviewed and the presence of PCNA in the tumor cells was studied immunohistochemically. Ninety-six percent of the non-recurrent BCC's had < 10% of tumor cells showing a positive staining for PCNA whereas 100% of the BCC's that recurred showed more than 30% of tumor cells staining positive for PCNA. In comparison, 88.9% of the non-recurring group showed non-aggressive histological features and only 66.7% of the recurring group was aggressive by microscopic appearance. In summary, the PCNA staining appeared to be superior to traditional histologic features in predicting clinical recurrence in primary BCC's and further prospective studies in a larger patient group are warranted.

Usefulness of the dissecting microscope in the surgical management of skin cancers.

Dermatopathological examination of excised skin cancers serves the dual purposes of defining the nature of the malignancies and evaluating the resection margins for evidence of tumor involvement. Conventional histological techniques, including horizontal frozen sections as prescribed in Mohs micrographic surgery to evaluate resection margins, can often be tedious and not without many pitfalls. In this study, the use of a stereoscopic dissecting microscope is compared with routine microscopy in the examination of 54 skin specimens resected with the clinical diagnosis of cancer. Our results show that the dissecting microscope is more efficient and as accurate in diagnosing basal and squamous cell carcinomas, and in detecting tumor involvement of resection margins. The ability to visualize marginal surfaces in three dimensions allows for a thorough examination and quick localization and mapping of the involved sites. Tissue artifacts due to fixation, freezing, or sectioning are nonexistent. With the lower cost and ease of operation, we suggest that the dissecting microscope is a more superior instrument. Its usefulness in the surgical management of skin cancers should be emphasized and further validated.

Localized childhood vulvar pemphigoid.

Bullous pemphigoid is a disease primarily of the elderly and is uncommon in children. A distinct localized variant of this condition appears to occur in children and is limited to the vulva. Two children with localized disease are discussed.

Cyclosporin A.

Cyclosporin A is a new immunosuppressive agent that selectively affects T helper cells without suppressing the bone marrow. Cyclosporin A has been used primarily to prevent rejection in organ transplantation and acute graft-versus-host disease. Studies suggest that it may be of benefit in psoriasis, pemphigus vulgaris, bullous pemphigoid, Behçet's disease, and collagen vascular disorders. Since cyclosporin A has a potentially important use in dermatology, and since a number of dermatologic side effects are seen as a consequence of its use, it is important that dermatologists be familiar with this drug.

Multicentric reticulohistiocytosis: a report of a case and a review of the pathology.

A case of multicentric reticulohistiocytosis (MR) in a 24-yr-old woman is presented. MR is a rare disorder characterized by progressive polyarthropathy and a papulo-nodular skin rash. The diagnosis was established by histological examination of biopsies of erythematous nodules on the fingers which showed circumscribed collections of large mononuclear cells and multinucleate giant cells in the reticular dermis. These were embedded in a fine network of mature fibrous tissue with a scanty lymphocytic infiltrate. Histochemical, immunopathological and ultrastructural investigations confirmed that the large mononuclear cells had the properties of macrophages. The histopathological features of MR are reviewed in the light of current knowledge of macrophage physiology, and evidence for lymphocyte-histiocyte interactions in the pathogenesis of this bizarre granulomatous disorder is presented.

An evaluation of a 2% erythromycin ointment in the topical therapy of acne vulgaris.

Two hundred eight patients completed a 12-week, multicenter, double-blind, controlled study comparing a 2% erythromycin ointment to its vehicle. Patients were evaluated by inflammatory lesion counts and Cook acne severity grade at the initial visit and at weeks 2, 4, 8, 10, and 12. The 2% erythromycin ointment proved to be statistically more effective than the vehicle in reducing lesion counts and acne severity grade at weeks 4, 8, 10, and 12. The ointment caused few side effects and was well tolerated by most patients.

Inherited disorders of complement.

Isolated complement component deficiencies are uncommon. Deficiencies of all eleven components and two inhibitors of the classical pathway have been described. Complete absence of the components of the alternative pathway has not been described. The consequences of a single defect in complement are often predictable from an understanding of the biologic activities associated with activation of the complement system. Deficiency of C1 esterase inhibitor gives rise to the disease, hereditary angioedema; deficiency of the early components of the classical pathway are associated with lupus erythematosus; C3 and C3 inactivator deficiencies with pyogenic infections; C5 dysfunction with Leiner's disease; deficiencies of the terminal components with recurrent Neisseria bacteremia; and C9 deficiency with normal health. The complement system and its associated biologic activities are reviewed. The present knowledge of the inherited complement deficiencies and associated diseases, with particular emphasis on the dermatologic manifestations, genetics, and diagnosis, is summarized.