SummaryExposure to titanium (Ti) from implants and from personal care products as nanoparticles (NPs) is common. This article reviews exposure sources, ion release, skin penetration, allergenic effects, and diagnostic possibilities. We conclude that human exposure to Ti mainly derives from dental and medical implants, personal care products, and foods. Despite being considered to be highly biocompatible relative to other metals, Ti is released in the presence of biological fluids and tissue, especially under certain circumstances, which seem to be more likely with regard to dental implants. Although most of the studies reviewed have important limitations, Ti seems not to penetrate a competent skin barrier, either as pure Ti, alloy, or as Ti oxide NPs. However, there are some indications of Ti penetration through the oral mucosa. We conclude that patch testing with the available Ti preparations for detection of type IV hypersensitivity is currently inadequate for Ti. Although several other methods for contact allergy detection have been suggested, including lymphocyte stimulation tests, none has yet been generally accepted, and the diagnosis of Ti allergy is therefore still based primarily on clinical evaluation. Reports on clinical allergy and adverse events have rarely been published. Whether this is because of unawareness of possible adverse reactions to this specific metal, difficulties in detection methods, or the metal actually being relatively safe to use, is still unresolved.Key words: contact allergy; corrosion; dermatitis; hypersensitivity; lymphocyte transformation test; patch test; penetration; release; titanium; toxicity. Titanium (Ti) is a non-essential metallic element with the atomic number 22 and a silvery colour. It is the ninth most abundant element in the earth's crust and the seventh most abundant metal overall (1). Major deposits of Ti minerals are found in Australia, Canada, India, Norway, South Africa, Ukraine, and the United States. The +4 oxidation state dominates Ti chemistry, but compounds in the +3 oxidation state are also common. TheCorrespondence: Jacob P. Thyssen, National Allergy Research Centre, Department of Dermato-Allergology, Copenhagen University Hospital HerlevGentofte, University of Copenhagen, Kildegaardsvej, DK-2900 Hellerup, Denmark. Tel: +45 3977 7307; Fax: +45 3977 7118. E-mail: jacob.p. thyssen@regionh.dk Accepted for publication 8 February 2016most important oxide is Ti dioxide (TiO 2 ), which exists in three different crystalline forms -anatase, brookite, and rutile -in addition to an amorphous phase (2, 3). Both the anatase, rutile and brookite mineral forms of TiO 2 occur naturally.TiO 2 is widely applied as microparticles and nanoparticles (NPs) in consumer goods, including cosmetics and foods, to obtain a white colour and ultraviolet light protection (4). Moreover, Ti is combined with a variety of other elements to produce strong lightweight alloys that provide resistance against corrosion and show a very high strength/density ratio (5). Because of this and the...

SummaryThe world production of copper is steadily increasing. Although humans are widely exposed to copper-containing items on the skin and mucosa, allergic reactions to copper are only infrequently reported. To review the chemistry, biology and accessible data to clarify the implications of copper hypersensitivity, a database search of PubMed was performed with the following terms: copper, dermatitis, allergic contact dermatitis, contact hypersensitivity, contact sensitization, contact allergy, patch test, dental, IUD, epidemiology, clinical, and experimental. Human exposure to copper is relatively common. As a metal, it possesses many of the same qualities as nickel, which is a known strong sensitizer. Cumulative data on subjects with presumed related symptoms and/or suspected exposure showed that a weighted average of 3.8% had a positive patch test reaction to copper. We conclude that copper is a very weak sensitizer as compared with other metal compounds. However, in a few and selected cases, copper can result in clinically relevant allergic reactions.

Studies on switch between interleukin (IL)-17 inhibitors are scarce. We assessed the effectiveness of brodalumab in patients with previous treatment failure of . Patients with psoriasis and previous treatment failure of an IL-17A inhibitor were treated with brodalumab at standard dose. Effectiveness was assessed after 12, 26, and 52 weeks of treatment. The primary outcome was the proportion of patients that had achieved an absolute psoriasis area and severity index (PASI) ≤2 and/or a relative reduction of PASI of 75% (PASI75) at week 12. Plasma cytokine levels were measured at baseline and after 12 weeks of treatment. In total, 20 patients were included, seven (35%) were female, the median age was 50 years, and the median baseline PASI was 13.5. Analyzing the data using nonresponder imputation, 14 (70%) patients had achieved either PASI75 and/or PASI ≤2, 8 (40%) had achieved PASI90, and three (15%) had achieved PASI100 at week 12. In total, nine patients (45%) completed the 52-weeks trial and seven patients (35%) still had PASI75 throughout 52 weeks. Seventeen out of 20 patients experienced any adverse events (AEs) during 52 weeks with no serious AEs or deaths. Patients responding to treatment had lower levels of tumor necrosis factor (TNF)-α and IL-6 at baseline compared with those who did not respond to treatment (TNF-α, p = 0.041, IL-6, p = 0.0054). In conclusion, treatment with brodalumab despite previous treatment failure with an IL-17A inhibitor can be effective and well-tolerated.

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To describe our three year experience with intralesional injection of sodium thiosulfate (STS) as treatment for dystrophic calcification (DC) in patients suffering from systemic sclerosis (SSc), overlap syndrome, or dermatomyositis. Methods: Between September 2016 and October 2019, selected SSc, overlap syndrome, and dermatomyositis patients with problematic DC were systematically and prospectively recruited to treatment once a week for four weeks and follow up after 12-16 weeks. During each visit, data concerning DC size, ulceration, inflammation, and both patient and physician global score (1-10) (PtGA and PhGA) were collected on customized data sheets. The DC lesions were injected with STS 150mg/ml on top or in the upper part of the lesion by the same clinician. After treatment, the lesion was covered up with a pressure distributing plaster for at least 24 hours. Results: Among 43 patients offered treatment, 38 patients, 33 women and 5 men, had one or more problematic DC treated with intralesional STS. The total number of treatments was 463. The patients had between 1 and >200 DC lesions and at each session between 1 and 22 lesions were treated. A total of 36 series consisting of 4 treatments were performed in 29 patients, 26 women and 3 men. Among these patients, 18 had systemic sclerosis of limited cutaneous type (lcSSc), 8, 2, and 1 patient had systemic sclerosis of diffuse cutaneous type (dcSSc), overlap syndrome, and dermatomyositis respectively. The average PtGA and PhGA before treatment was 6.4 and 6.1 respectively. A significantly decrease of the average PtGA and PhGA score was observed week by week and after the third treatment the average decrease in PtGA and PhGA was 2.7 and 2.5 respectively (p<<0.001). Almost all patients experienced intense pain during and after injection (up to several minutes), but otherwise side effects were few and not serious. Conclusions: We find that intralesional STS injections have positive effect with limited side effects on selected SSc patients with problematic DC. We recognize the limitations of the study design leaving plenty of questions to be addressed. It is our clinical impression that patient, lesion, and clinician related factors may influence the outcome of the treatment. We hope that our treatment regimen may inspire physicians to consider STS injections as a possible treatment for troublesome DC before referring to surgical interventions.