Dupilumab-associated ocular surface disease : an interdisciplinary decision framework for prescribers in the Australian setting

Background/Objectives: Dupilumab-associated ocular surface disease (DAOSD) is of particular relevance in patients with atopic dermatitis (AD). Guidance on DAOSD assessment and management in the Australian setting is needed to reduce its impact and minimise disruption to treatment. Methods: A systematic review of the literature was undertaken to identify data pertaining to the incidence, pathophysiology, risk factors and management of DAOSD. A critical review of this literature was used to inform a decision framework for dupilumab-prescribers and develop a graded severity scoring tool to guide appropriate management options. Results: DAOSD typically emerges within 4 months of commencing dupilumab and the occurrence of new events diminishes over time. The reported incidence varies widely depending on the nature and source of the data: 8.6–22.1% (clinical trials programme), 0.5–70% (real-world data; differences in study size, duration of follow-up, ophthalmologist intervention, use of prophylaxis). Occurrence increases with AD severity and in patients with prior history of ocular disease; pathophysiology is still to be fully characterised. Management options have evolved over time and include lubricants/artificial tears, corticosteroids, calcineurin inhibitors, antihistamines, anti-inflammatory agents and antimicrobial agents. Current therapies aim to resolve symptoms or reduce severity to levels sufficiently tolerable to enable continuation of dupilumab therapy. Conclusions: Recommendations for DAOSD assessment and management include identification of high-risk patients, vigilance for red flags (keratoconus, herpetic and bacterial keratitis), regular assessment of symptom severity (before and during dupilumab therapy), conservative management of mild DAOSD by the prescribing physician and ophthalmologist referral for collaborative care of moderate–severe DAOSD and high-risk patients

Clinical similarity of biosimilar ABP 501 to adalimumab in the treatment of patients with moderate to severe plaque psoriasis: A randomized, double-blind, multicenter, phase III study

Background ABP 501 is a biosimilar of adalimumab. Objective We sought to compare the efficacy and safety of ABP 501 with adalimumab. Methods This 52-week, double-blind study randomized patients with moderate to severe psoriasis to ABP 501 or adalimumab. At week 16, those with 50% or more improvement in Psoriasis Area and Severity Index score from baseline on ABP 501 continued the same treatment, whereas adalimumab-treated patients were rerandomized to adalimumab or ABP 501. Clinical similarity in Psoriasis Area and Severity Index percent improvement from baseline to week 16 (primary end point) was established if the point estimate of treatment difference and its 2-sided 95% confidence interval between groups was within equivalence margin of ±15. Patients, including those undergoing a single transition at week 16, were evaluated for safety and immunogenicity. Results Psoriasis Area and Severity Index percent improvement at week 16 was 80.9 for ABP 501 and 83.1 for adalimumab (least-square mean difference −2.18 [95% confidence interval −7.39 to 3.02]). Adverse events (67.2% [117/174] vs 63.6% [110/173]) and antidrug antibody incidence (55.2% [96/174] vs 63.6% [110/173]) for ABP 501 vs adalimumab were similar. Safety, including immunogenicity, was similar among groups after single transition (week 20). Limitations The 52-week data are not reported here. Conclusions ABP 501 was shown to be clinically similar to adalimumab. Safety and immunogenicity were not impacted immediately after single transition (adalimumab to ABP 501)

Effect of three wound dressings on infection, healing comfort, and cost in patients with sternotomy wounds - a randomized trial

Study objective: To compare three dressing types in terms of their ability to protect against infection and promote healing, patient comfort, and cost-effectiveness.Design: Prospective, randomized controlled trial.Setting: Major metropolitan, academically affiliated, tertiary referral center.Patients: Seven hundred thirty-seven patients were randomized to receive a dry absorbent dressing (n = 243) [Primapore; Smith &amp; Nephew; Sydney, NSW, Australia], a hydrocolloid dressing (n = 267) [Duoderm Thin ConvaTec; Mulgrave, VIC, Australia], or a hydroactive dressing (n = 227) [Opsite; Smith &amp; Nephew] in the operating theater on skin closure.Results: There was no difference in the rate of wound infection or wound healing between treatment groups. The Primapore dressing was the most comfortable and cost-effective dressing option for the sternotomy wound. Duoderm Thin dressings were associated with increased wound exudate (p &lt; 0.001), poor dressing integrity (p &lt; 0.001), more frequent dressing changes (p &lt; 0.001), more discomfort with removal (p &lt; 0.05), and increased cost (p &lt; 0.001).Conclusions: In the context of no additional benefit for the prevention of wound infection or the rate of wound healing for any of the three dressing products examined, dry absorbent dressings are the most comfortable and cost-effective products for sternotomy wounds following cardiac surgery.<br /

Seborrhoeic keratosis and malignancy: Collision tumour or malignant transformation?

A retrospective study of 813 histological specimens reported as seborrhoeic keratoses included 43 (5.3%) associated with non-melanoma skin cancer. Intraepidermal carcinoma (squamous cell carcinoma in situ) was the most common of these (36). There were five basal cell carcinomas (one with intraepidermal carcinoma also) and two invasive squamous cell carcinomas. No melanomas were reported. Twenty-seven of the intraepidermal carcinomas appeared to arise within the seborrhoeic keratosis as did one of the invasive squamous cell carcinomas. Of these 28 lesions, the head was the most common site. Fourteen were clinically diagnosed as a non-melanoma skin cancer with only nine clinically felt to be a seborrhoeic keratosis. These lesions may represent malignant transformation within the seborrhoeic keratosis. Twelve specimens reported adjacent dual pathologies, with the trunk and limbs the most common sites. Seven were diagnosed clinically as a skin malignancy, whereas three were thought to be solar keratoses. Clinically, the remaining two were seborrhoeic keratoses. The origin of the malignancy in these cases is less obvious and may represent collision tumours. Three curette specimens could not be assessed for architecture

Germline Fumarate Hydratase Mutations in Families with Multiple Cutaneous and Uterine Leiomyomata

9 páginas, 2 figuras, 2 tablas.Germline mutations in the fumarate hydratase gene (FH) predispose to multiple cutaneous and uterine leiomyoma syndrome (MCL) and MCL associated with renal cell cancer. MCL is inherited in an autosomal dominant pattern, manifesting as skin leiomyoma and uterine fibroids in affected individuals. Fumarate hydratase, a component of the tricarboxylic acid cycle, acts as a tumor suppressor gene in the development of cutaneous and uterine leiomyoma and renal cell cancer in this syndrome. Here we report the clinical and mutational analysis of five families with MCL, with the identification of five new mutations affecting highly conserved residues of the FH protein. These results provide further evidence for the role of the FH gene in the pathogenesis of MCL.This work was supported in part by the Skin Disease Research Center, Department of Dermatology, Columbia University (P30 AR44535); a research grant K01-HG0005501 (to D.G.); and a research grant from the Women's Health Program, supported by HWZOA (to A.Z. and B.G.). G.S.C. is a Medical Student Research Training Fellow of Howard Hughes Medical Institute.Peer reviewe