Subcutaneous methotrexate in patients with moderate to severe psoriasis: a critical appraisal

Summary

Aim

Warren et al¹ set out to assess the effect of an intensified dosing schedule of subcutaneous methotrexate in patients with moderate to severe chronic plaque psoriasis.

Setting and design

This is a prospective, double-blind, randomised (3:1), placebo-controlled study, conducted across 16 centres in Germany, France, the Netherlands, and the UK.

Study exposure

Methotrexate-naïve adults with a diagnosis of moderate to severe chronic plaque psoriasis for at least 6 months before baseline were randomly assigned to receive weekly subcutaneous injections of either methotrexate at a starting dose of 17.5 mg, or placebo for 16 weeks (first phase).Dose escalation to 22.5 mg/week was implemented after 8 weeks if patients did not achieve PASI 50. Treatment was combined with folic acid 5 mg/week. The first phase of the study was followed by an open-label period from 16-52 weeks (second phase), in which both groups received weekly methotrexate injections. At week 24, dose escalation to 22.5 mg/week was possible in patients not achieving PASI 50.

Outcomes

Psoriasis severity was measured using the PASI (Psoriasis Area and Severity Index). The authors also used two other psoriasis severity measures and two quality of life measures, looked at safety indices and performed a sub-study analysing paired skin biopsies at baseline and week 16 (histopathology, immunohistochemistry and expression of interleukin (IL)17A, interferon-γ and tumour necrosis factor-α).

Primary outcome measures

The primary outcome was the proportion of patients reaching PASI 75 at week 16.

Results

120 patients were included in this trial, most of whom were middle-aged white men with longstanding psoriasis and a mean BMI of 30.1 kg/m². PASI 75 was achieved in 41% of patients receiving methotrexate vs. 10% of patients receiving placebo (RR 3.93, 95% CI 1.31–11.81; p=0.0026) at week 16. Subcutaneous methotrexate was generally well tolerated, with no serious adverse events related to this treatment over the 52-week study.

Conclusions

Warren et al conclude that the 52-week risk-benefit profile of subcutaneous methotrexate is favourable in patients with psoriasis.

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Oral retinoids and depression

Abstract

We are concerned about the content and possible misinterpretation of a research letter by Le Moigne et al. published on 19 June 2017 in the British Journal of Dermatology online.[1]

We share the concern expressed by the authors about possible psychiatric effects of oral retinoids. However, case reports rank low in the hierarchy of evidence, as a result of their inherent limitations, including publication bias and a lack of control groups.

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A new mobile learning module using smartphone wallpapers in identification of medical fungi for medical students and residents

Abstract

Introduction

Medical students and residents will encounter many cutaneous fungal infections in medical practice. However, the training for identification of medical fungi has been insufficient due to limited lecture-based courses. The objective of this study was to evaluate the impact of using smartphone-based wallpapers in learning the microscopic morphology and colony characteristics of medical fungi for medical students and residents.

Methods

A smartphone-based wallpaper learning module using a wallpaper-changing software application (app) was introduced in this 3-week training course. Twenty-six participants were enrolled and divided into two groups: nondermatology trainees, including medical students and postgraduate year one (PGY-1) doctors who have not yet specialized, and dermatology trainees (dermatology residents). All of the participants completed a 3-week training course, and the effectiveness of the module was evaluated by pre- and post-course multiple-choice examinations.

Results

Both nondermatology and dermatology trainees scored significantly higher in post-course examinations than pre-course examinations (P < 0.001). The dermatology trainees performed better than nondermatology trainees in the pre-course examinations (P < 0.001). In the post-course examinations, no significant difference in scores was noted between dermatology and nondermatology trainees (P = 0.573).

Discussion

The smartphone-based wallpaper learning module was effective in helping medical students and residents learn and memorize morphologic characteristics of fungi. In comparison to conventional lecture-based learning, this new mobile module was more readily accessible and convenient for learners to engage in learning.

Disseminated actinomycetoma due to Nocardia wallacei

Abstract

Background

Actinomycetoma caused by Nocardia usually responds well to antibiotics. Emerging species of Nocardia, such as N. wallacei, can be a therapeutic challenge.

Aims

Confirm the therapeutic effectivity of linezolid in multidrug resistant Nocardia Wallacei actinomycetoma.

Materials and Methods

We evaluated the medical management of an 18-year-old man with multidrug resistant actinomycetoma of the left leg caused by N. transvalensis complex treated 17 years ago with linezolid 1200 mg a day. This bacteria was recently reclassified as Nocardia Wallacei by specific molecular biology technique.

Results

The infection was cured after 3 months of treatment; the patient remained asymptomatic for the past 17 years. No adverse effects were found.

Discussion

Frequently, strains of N. transvalensis complex have aminoglycoside resistance; in this case, we highlight the effectiveness of linezolid for the successful medical management of multidrug resistant actinomycetoma.

Conclusion

Linezolid can be an alternative for the treatment of multidrug resistant Nocardia Wallacei.

Treatment response to omalizumab in patients with refractory chronic spontaneous urticaria

Abstract

Background

Previous clinical trials have demonstrated the efficacy and safety of the anti-IgE monoclonal antibody omalizumab in chronic spontaneous urticaria (CSU) not responding to antihistamine treatment. The primary aim of our study was to describe the response patterns of patients with refractory CSU treated with omalizumab in a real-world clinical setting.

Methods

A retrospective analysis of medical records of 20 patients with refractory CSU was performed. Demographic, clinical, and laboratory features were retrieved and analyzed in correlation with treatment data.

Results

Mean age of our patient population was 54.5 years, while the majority were females (15/20 cases, 75%). Mean disease duration prior to omalizumab administration was 21.8 months. All patients had a history of chronic urticaria, refractory to high antihistamine and corticosteroid treatment, and responded favorably to omalizumab after administration of 1–5 doses of omalizumab; complete response was observed in 17/20 patients (85%) and well-controlled disease in the remaining 3/20 patients (15%). In a subset of cases (6/20, 30%), best response to omalizumab was achieved after interval administration of a 9-day course of methylprednisolone (total dose of 188 mg). Late response to omalizumab (after three-month treatment) was significantly correlated (P = 0.026) with shorter disease duration before initiation of omalizumab.

Conclusion

In the present series, omalizumab, either alone or in combination with a short-term course of corticosteroids, was highly effective in resolution of refractory CSU. Furthermore, disease duration prior to omalizumab had a significant effect on timing of response.

Occupational allergic contact dermatitis caused by antibiotics in healthcare workers – relationship with non-immediate drug eruptions

Summary

Background

Occupational allergic contact dermatitis (ACD) in healthcare workers (HCWs) is common, but systemic antibiotics are rarely reported as the cause.

Objectives

Characterize occupational ACD by handling systemic antibiotics.

Method

A retrospective analysis was performed of ACD caused by systemic antibiotics among HCWs patch tested between 2010 and 2016 with a series of systemic antibiotics.

Results

We studied 4 female nurses aged 28–47 years who developed ACD while working in surgical departments. They had eczema of the hands, and forearms or face, and 1 patient, who previously had exanthema caused by flucloxacillin, also developed a generalized rash following airborne exposure to systemic antibiotics. Patch tests showed positive reactions to ampicillin and cefazolin in 1 patient, to cefotaxime and ceftriaxone in 2 patients, and to several penicillins in another patient. Three patients also reacted to rubber allergens, fragrances, and/or preservatives. All patients admitted having direct and sporadic exposure to systemic antibiotic solutions. Avoidance resulted in a significant improvement of ACD, but 1 patient had to change job.

Conclusions

Occupational ACD caused by β-lactam antibiotics, particularly cephalosporins, is significant in HCWs. Cross-reactions between β-lactams are similar to those described in non-immediate drug eruptions. A relationship between systemic delayed drug hypersensitivity and ACD, as observed in 1 case, suggests that patients should avoid future use of the antibiotic to which they are sensitized.

Textile contact dermatitis caused by octylisothiazolinone in compression stockings

Toying with the Toolbox: How Metaphysics Can Still Make a Contribution

Abstract

Current analytic metaphysics has been claimed to be, at best, out of touch with modern physics, at worst, actually in conflict with the latter (Callender, in: French, Saatsi (eds) The continuum companion to the philosophy of science, Continuum, London, 2011; Ladyman and Ross Every thing must go: metaphysics naturalized, Oxford University Press, Oxford, 2007). While agreeing with some of these claims, it has been suggested that metaphysics may still be of service by providing a kind of 'toolbox' of devices that philosophers of science can access in order to help provide an interpretation of theories in fundamental physics (French and McKenzie in Eur J Anal Philos 8:42–59, 2012; see also French and McKenzie, in: Bigaj, Wuthrich (eds) Metaphysics in contemporary physics, Rodopi, Amsterdam, 2015). In this context it has been argued that 'standard' forms of dispositionalism simply cannot be sustained in the context of modern physics but that certain 'non-standard' views may provide the resources to help explicate the sense in which physics may be regarded as 'modally informed'. Here that suggestion will be further extended in order to consider the implications both with regard to the overall relevance of metaphysics given advances in science and for the prospects of a naturalised metaphysics more generally. In particular, this paper will focus on three concerns: (1) that the particular tools identified are not, in fact, 'scientifically disinterested' and thus that the distinction between 'naturalised' and 'non-naturalised' metaphysics is at best vague or poorly drawn; (2) that the usefulness of such tools depends on their being shaped to fit the relevant physics and thus the latter 'guts' metaphysics; (3) that if metaphysics does prove to be useful in this sense then we have no reason to scorn non-naturalised metaphysics to begin with.

Social Science as a Guide to Social Metaphysics?

Abstract

If we are sympathetic to the project of naturalising metaphysics, how should we approach the metaphysics of the social world? What role can the social sciences play in metaphysical investigation? In the light of these questions, this paper examines three possible approaches to social metaphysics: inference to the best explanation from current social science, conceptual analysis, and Haslanger-inspired ameliorative projects.

Phase 1/2 study assessing the safety and efficacy of dabrafenib and trametinib combination therapy in Japanese patients with BRAF V600 mutation-positive advanced cutaneous melanoma

Abstract

The combination of dabrafenib and trametinib demonstrated encouraging antitumor activity and tolerability, at initial analysis, in Japanese patients with BRAF V600 mutant advanced melanoma warranting further investigation. This study evaluated the safety and tolerability, pharmacokinetics (PK) and preliminary efficacy of dabrafenib 150 mg b.i.d. plus trametinib 2 mg q.d. in Japanese patients with BRAF V600E/K mutant solid tumors (phase 1) and melanoma (phase 2). Phase 1 was primarily intended to assess safety and tolerability as assessed by adverse events (AE), and the primary end-point in phase 2 was to assess confirmed overall response rate (ORR). The secondary end-points in phase 1 included PK, confirmed/unconfirmed ORR and duration of response (DOR). The secondary end-points in phase 2 were PK, unconfirmed ORR, DOR, safety and tolerability. A total of 12 cutaneous melanoma patients were enrolled in the study (six in phase 1 and six in phase 2) and received the combination therapy of dabrafenib and trametinib. Common AE (≥50.0%) included pyrexia (75%), increased aspartate aminotransferase (67%), peripheral edema (50%) and nasopharyngitis (50%). The investigator-assessed ORR was reported in five patients (83%) in phase 1 and was also reported in five patients (83%; 95% confidence interval, 35.9–99.6; P < 0.0001) in phase 2. Plasma concentrations of both dabrafenib and trametinib seemed to a reach steady state by week 3. Overall, efficacy and PK properties for the dabrafenib plus trametinib combination in Japanese patients were comparable with those seen in global studies.

Efficacy of oral cholecalciferol on rhododendrol-induced vitiligo: A blinded randomized clinical trial

Abstract

Rhododendrol (RD), 4-(4-hydroxyphenyl)-2-butanol, inhibits melanin synthesis and has been used for skin-whitening cosmetic products. RD has been very effective in lightening skin pigmentation, but some persons have developed so-called RD vitiligo, in which vitiligo starts on the face, neck and hands where topical RD has been applied and even extended over skin areas where RD has not been applied. RD vitiligo lesions in some patients have lasted for years and have been resistant to conventional vitiligo treatments. We examined the effects of cholecalciferol on RD vitiligo in a blinded randomized clinical trial. Forty-eight female RD vitiligo patients were recruited for the trial and were randomized into two groups: the vitamin D (VD)-intervention group that received daily 5000 IU cholecalciferol for 5 months and the control group. Three blinded investigators scored vitiligo improvement by comparing photographic images of baseline and at 5-month observation. Serum 25(OH)D3 of RD vitiligo patients was not significantly different from age-matched healthy volunteers. Twenty-two in the VD-intervention group and 23 in the control group completed the 5-month observation. Serum 25(OH)D3 levels were significantly increased after the 5-month VD intervention, while the control group did not change. The improvement scores were significantly higher in the VD-intervention group than the control group. The improvement scores were positively correlated with the serum 25(OH)D3 levels after the 5-month intervention period but not before the treatment. This blinded randomized clinical trial showed favor in administrating 5000 IU cholecalciferol daily to RD vitiligo patients.

Case of atopic dermatitis concurrent with idiopathic thrombocytopenic purpura, whose serum thymus and activation-regulated chemokine level remained undetectable

Abstract

We report a 9-year-old Japanese female patient with atopic dermatitis associated with idiopathic thrombocytopenic purpura. She demonstrated high serum immunoglobulin (Ig)E and IgE specific to several environmental allergens, but extremely low serum thymus and activation-regulated chemokine (TARC) levels regardless of the disease progression. This case suggests platelets as the main source of serum TARC.

A novel image processing workflow for the in vivo quantification of skin microvasculature using dynamic optical coherence tomography

Abstract

Background

Currently, imaging technologies that can accurately assess or provide surrogate markers of the human cutaneous microvessel network are limited. Dynamic optical coherence tomography (D-OCT) allows the detection of blood flow in vivo and visualization of the skin microvasculature. However, image processing is necessary to correct images, filter artifacts, and exclude irrelevant signals. The objective of this study was to develop a novel image processing workflow to enhance the technical capabilities of D-OCT.

Materials and methods

Single-center, vehicle-controlled study including healthy volunteers aged 18-50 years. A capsaicin solution was applied topically on the subject's forearm to induce local inflammation. Measurements of capsaicin-induced increase in dermal blood flow, within the region of interest, were performed by laser Doppler imaging (LDI) (reference method) and D-OCT.

Results

Sixteen subjects were enrolled. A good correlation was shown between D-OCT and LDI, using the image processing workflow. Therefore, D-OCT offers an easy-to-use alternative to LDI, with good repeatability, new robust morphological features (dermal-epidermal junction localization), and quantification of the distribution of vessel size and changes in this distribution induced by capsaicin. The visualization of the vessel network was improved through bloc filtering and artifact removal. Moreover, the assessment of vessel size distribution allows a fine analysis of the vascular patterns.

Conclusion

The newly developed image processing workflow enhances the technical capabilities of D-OCT for the accurate detection and characterization of microcirculation in the skin. A direct clinical application of this image processing workflow is the quantification of the effect of topical treatment on skin vascularization.

Editor's Choice

Editorial board

Horizontal and vertical sections of scalp biopsy specimens from dermatomyositis patients with scalp involvement

Scalp involvement in dermatomyositis manifests as a pruritic eruption with erythema and scaling associated with nonscarring alopecia. We characterized the histologic features of scalp dermatomyositis using horizontal and vertical sections. Characteristic findings of scalp dermatomyositis include preserved follicular architecture, hair counts consistent with chronic telogen effluvium, telangiectasia and mucin.

Skin in the Game: Existing and Upcoming Physician Payment Models in Dermatology

Efficacy and Safety of Topical Oxymetazoline Cream 1.0% for Treatment of Persistent Facial Erythema Associated With Rosacea: Findings From the Two Phase 3, 29-Day, Randomized, Controlled REVEAL Trials

Most rosacea treatments targeting inflammatory lesions do not improve persistent facial erythema.Topical oxymetazoline hydrochloride cream 1.0% effectively reduced erythema versus vehicle in patients with moderate to severe persistent facial erythema of rosacea, with favorable tolerability.Topical oxymetazoline represents a new treatment option for patients with persistent erythema of rosacea.

Consultative Teledermatology in the Emergency Department and Inpatient Wards: A Survey of Potential Referring Providers.

Surgical treatment of axillary bromhidrosis by combining suction-curettage with subdermal undermining through a miniature incision

The suction-curettage technique has been widely applied in the treatment of axillary bromhidrosis. However, it can only moderately eradicate the malodor. From 2011 to 2013, we performed the suction-curettage procedure alone in 91 patients with primary axillary bromhidrosis (group A). From 2014 to 2016, we refined the suction-curettage technique by performing wide subdermal scissors undermining through a miniature incision in 80 patients (group B). Through a miniature incision at the inferior pole of the central axillary crease, the entire subcutaneous tissues containing apocrine glands were initially dissected with scissors within the axillary area and then the undermined apocrine glands were removed by suction-curettage.