In this study, fucoidan/chitosan nanoparticles were developed for the topical delivery of methotrexate towards the treatment of skin-related inflammatory diseases. Based on the fucoidan/chitosan (F/C) weight ratio, three different nanoparticles (1F/1C; 3F/1C; 5F/1C) were produced and characterized. Methotrexate was loaded in these polymeric nanoparticles achieving a drug loading of ca. 14% and an entrapment efficiency of 96, 87 and 80% for 1F/1C; 3F/1C and 5F/1C nanoparticles, respectively. Methotrexate-loaded fucoidan/chitosan nanoparticles exhibited size within the 300-500 nm range, positive zeta potential for 1F/1C nanoparticles (+60 mV) and negative surface charge for the 3F/1C and 5F/1C nanoparticles (-40 and -45 mV, respectively). Methotrexate loaded in 3F/1C and 5F/1C nanoparticles did not affect cells viability and presented lower cytotoxicity than free methotrexate, in fibroblasts and human keratinocytes. MTX-loaded fucoidan/chitosan nanoparticles lead to a significant reduction of pro-inflammatory cytokines produced by activated human monocytes. Skin permeation studies showed that methotrexate-loaded nanoparticles permeated the pig ear skin barrier reaching after 6 h, a 2.7- and 3.3-fold increase for 3F/1C and 5F/1C nanoparticles, relative to free methotrexate. In conclusion, fucoidan/chitosan nanoparticles, in particular the ratio 5F/1C, is safe, exerts an anti-inflammatory effect and increase skin permeation thus can potentially be used for methotrexate topical delivery.

Is conservative surgery (laparoscopic salpingotomy) cost-effective, using fertility as the endpoint compared with medical management (Methotrexate) in women with an early tubal pregnancy?

Pityriasis rubra pilaris (PRP) is a rare papulosquamous disorder. Treatment is challenging; the armamentarium consists of topical corticosteroids, phototherapy, classic systemic treatments such as retinoids or immunosuppressive drugs, and most recently biologicals. However, the relative effectiveness of therapies is unclear. Our objective was to review the published literature on systemic treatment of PRP. A systematic review was conducted on PubMed and the Cochrane Library up to 5 September 2017. Studies evaluating any systemic treatments of PRP (except for historical treatments) were included. Overall, 182 studies met the predefined inclusion criteria, and reported on 475 patients and 652 courses of treatment. 42.0 % (225/514) of all patients treated with retinoids achieved an excellent response (isotretinoin: 61.1 % [102/167], etretinate: 47 % [54/115], and acitretin: 24.7 % [43/174]) compared to an excellent response rate of 33.1 % (53/160) with methotrexate. Therapy with biologicals was successful in 51.0 % of patients (71/133) (ustekinumab: 62.5 % [10/16], infliximab: 57.1 % [28/49], etanercept: 53.3 % [16/30], and adalimumab: 46.4 % [13/28]). This review balances effectiveness, side effects, experience, and drug costs in order to suggest a treatment regimen starting with isotretinoin as first-line, methotrexate as second-line and biologicals as third-line treatment for this difficult-to-treat dermatosis.

Caesarean scar ectopic pregnancy (CSEP) is one of the rarest forms of ectopic pregnancies. With rising caesarean delivery (CD) rates worldwide, there is an increase in the incidence of CSEP. Patients usually present with painless vaginal bleeding and often misdiagnosed as spontaneous miscarriage. The use of ultrasonography with colour flow Doppler helps in the differential diagnosis. Different treatment options are described in the literature, although there is insufficient evidence regarding the best approach. We report the diagnosis and management of a case of CSEP in a woman with four previous CD who presented with vaginal bleeding and lower abdominal cramps at six weeks of gestation. She was treated with laparoscopic and ultrasound guided aspiration of the gestational sac and local injection of methotrexate supplemented by intramuscular methotrexate injection.

Goujon et al. submit a letter-type manuscript to JEADV (1), as a comment to the recently published European consensus-based S2k guidelines or treatment of atopic eczema (2,3). The assigned writing subgroups for each topic were encouraged to include the 'best available evidence' for all chapters of the guideline (2). Data were included only if a reference had been published as a full paper in a peer-reviewed journal by March 2017 (see page 661 of the guideline), but not based on an abstract or a conference presentation only (2). This article is protected by copyright. All rights reserved.

The recent European guidelines for the treatment of atopic eczema (AE) are a thorough overview of therapeutic opportunities for AE.1 Among the systemic treatments, we propose to bring further insights on methotrexate (MTX) use in adult AE patients. This article is protected by copyright. All rights reserved.

Several case reports and retrospective studies have demonstrated that intralesional methotrexate (MTX) could be a very effective and safe alternative treatment of keratoacanthoma (KA). Here, we report a rapid clinical efficacy of two intralesional MTX injections (total dose 40 mg) that were performed 1 week apart in the treatment of a large KA lesion of the dorsal hand in a 99-year-old woman. The lesion, with a 3-cm major axis diameter and a thickness of 2 cm with a central ulceration had rapidly appeared on the right dorsal hand. A 3-mm punch biopsy confirmed the diagnosis of a well-differentiated KA-type spinous cellular carcinoma. Due to the presence of comorbidities (arterial hypertension and atrial fibrillation) and chronic treatment with antihypertensive and oral anticoagulant drugs, treatment with intralesional MTX was proposed to the patient. Two intralesional MTX injections of 20 mg each were performed 1 week apart. A very fast resolution of the lesion was observed after the first injection. A week after the second injection a full resolution of the skin lesion was observed, with a nearly complete resolution of the central ulceration. The treatment was very well tolerated. No local or systemic side effects were observed. This case report confirms that intralesional MTX could be considered an effective and safe treatment of KA also in very old subjects.