Annesofie Faurschou

Metal allergen of the 21st century—a review on exposure, epidemiology and clinical manifestations of palladium allergy

Consumers are mainly exposed to palladium from jewellery and dental restorations. Palladium contact allergy is nearly always seen together with nickel allergy, as palladium and nickel tend to cross‐react. We aimed to analyse the available palladium patch test data and case reports to determine whether the prevalence of palladium mono‐sensitization has increased. Based on available patch test data from the period 1986–2008, a total of 10 778 patients were patch tested with palladium chloride. The median prevalence of palladium allergy was 7.8% (range <1.0–19.0%) in dermatitis patients and 7.4% (range 1.3–13.9%) in dental patients. The median prevalence of palladium mono‐sensitization (defined as the presence of palladium allergy and the absence of nickel allergy) was 0.2% (range 0–1.6%) in dermatitis patients and 0.5% (range 0–7.2%) in dental patients. A slight increase in the prevalence of palladium mono‐sensitization was observed over the study period. We conclude that clinically relevant palladium allergy should mainly be suspected in patients who present with allergic contact granulomas at sites of piercing, but also in patients who have clinical disease and palladium patch test reactivity without concomitant nickel reactivity. Palladium salts should be included in dental screening patch test series. Palladium use in jewellery should be limited until we know more about the risk of sensitization.

Pulsed dye laser vs. intense pulsed light for port‐wine stains: a randomized side‐by‐side trial with blinded response evaluation

Background  Pulsed dye lasers (PDLs) are considered the treatment of choice for port‐wine stains (PWS). Studies have suggested broadband intense pulsed light (IPL) to be efficient as well. So far, no studies have directly compared the PDL with IPL in a randomized clinical trial.

Two courses of rituximab (anti-CD20 monoclonal antibody) for recalcitrant pemphigus vulgaris.

Background  Pemphigus vulgaris (PV) is a severe autoimmune blistering disease involving the skin and mucous membranes. The response to therapy varies greatly amongst patients and treatment may be challenging. Rituximab is a chimeric monoclonal antibody that selectively targets cell surface antigen CD20, thus depleting mature B cells in vivo.

TNF‐α stimulates Akt by a distinct aPKC‐dependent pathway in premalignant keratinocytes

Abstract:  Tumor necrosis factor‐α (TNF‐α) is an important proinflammatory cytokine involved in the pathogenesis of inflammatory skin diseases and cutaneous squamous cell carcinoma. Some of these effects are mediated by the stimulatory effect of this cytokine on the Akt signalling pathway, which renders keratinocytes less susceptible to proapoptotic stimuli and enhances cell growth. We have recently shown that TNF‐α‐induced Akt activation may promote the early stages of skin cancer. In this work, we demonstrate that in the premalignant keratinocyte cell line HaCaT, TNF‐α activates Akt, ERK1/2 and p38. The specific peptide blocking the activity of the atypical protein kinase C (aPKC) species ζ and ι/λ abrogated the effects of TNF‐α on Akt and ERK1/2 but increased the activation of p38. The TNF‐α‐dependent phosphorylation of Akt–ERK1/2 was slightly decreased by NFκB inhibition and in the presence of p38 blockers. Akt/ERK signalling but not p38 activation was abolished in the presence of the iron chelator desferroxamine that blocks formation of hydroxyl (˙OH) radicals. Thus, the TNF‐α signalling in keratinocytes seems to bifurcate into an aPKC‐, NFkB‐ and ˙OH‐dependent pathway resulting in the activation of survival and mitogenic pathways mediated by Akt and ERK1/2, and a signalling pathway conveyed by p38 that contributes to Akt activation but is suppressed by aPKC. Our data may be utilized in the development of more selective anti‐TNF‐α therapeutic strategies.

Durability of the sun protection factor provided by dihydroxyacetone

Background/Purpose: The sunless tanning agent dihydroxyacetone (DHA) is known to protect against longwave ultraviolet radiation (UVA) and visible light. Recently, our laboratory has shown that DHA in addition offers a modest sun protection factor (SPF) in humans. We conducted this study in order to investigate the durability of the SPF provided by DHA.

Gastric bypass surgery: Improving psoriasis through a GLP-1-dependent mechanism?

Psoriasis is a common inflammatory skin disease and obesity constitutes a risk factor for the disease. Obese patients with psoriasis are often more difficult to treat and are at increased risk for dyslipidemia, diabetes, hypertension and cardiovascular disease. Case reports suggest that gastric bypass surgery in patients with psoriasis may result in complete remission of the disease. A substantial weight loss is achieved in the months following surgery, which is likely to reduce psoriasis symptoms and risk of comorbidities. Interestingly, however, it has been described that improvement of psoriasis is initiated immediately following surgery before any weight loss could have happened. We hypothesize that the glucose-lowering gut incretin hormone glucagon-like peptide-1 (GLP-1) is responsible for this effect. The levels of GLP-1 have been shown to increase up to 20 times after gastric bypass surgery. This most likely contributes importantly to the acute remission of type 2 diabetes, which is often induced by gastric bypass operations. The hormone is not hypersecreted after the purely restrictive bariatric procedure gastric banding and no case reports exist on improvement in psoriasis following gastric banding. Intriguingly, recent studies describe that GLP-1 may convey anti-inflammatory effects in addition to its effects on glucose homeostasis. Also, GLP-1 reduces appetite and gastrointestinal motility including gastric emptying, which reduces food intake and leads to weight loss. Thus, both a direct anti-inflammatory effect of GLP-1 as well as an indirect effect through weight loss could contribute to improvement in psoriasis. A potential involvement of GLP-1 in the remission of psoriasis observed after bariatric surgery offers exciting possibilities for research and eventually perhaps new ways of anti-psoriatic treatment.

TNF-α Impairs the S-G2/M Cell Cycle Checkpoint and Cyclobutane Pyrimidine Dimer Repair in Premalignant Skin Cells: Role of the PI3K–Akt Pathway

Tumor necrosis factor-alpha (TNF-alpha) is induced by UVB radiation and has been implicated in the early stages of skin carcinogenesis. Here, we show that in normal keratinocytes and the transformed keratinocyte cell lines, HaCaT and A431, TNF-alpha stimulates protein kinase B/Akt, which results in activation of the survival complex mTORC1 (mammalian target of rapamycin complex 1) and inhibition of the proapoptotic proteins Bad and FoxO3a. In UVB-irradiated HaCaT cells (10-20 mJ cm(-2)), TNF-alpha increased the proportion of cycling cells and enhanced the rate of apoptosis. A significantly higher proportion of UVB-treated HaCaT cells containing unrepaired cyclobutane pyrimidine dimers (CPDs) escaped the G2/M cell cycle checkpoint in the presence of TNF-alpha (9.5+/-3.3 vs 4.8+/-2.2%). After treatment with the PI3K inhibitor LY294002, only 1.2+/-0.7% of CPD-containing HaCaT cells were actively cycling. TNF-alpha enhanced apoptosis less potently and did not increase the level of CPD or stimulate cell cycle progression in normal keratinocytes. Our data suggest that TNF-alpha overrides the G2/M checkpoint in premalignant skin cells and allows for some cells containing unrepaired CPD to enter the cell cycle. The effect of TNF-alpha seems to be dependent on Akt activation and may constitute a relevant mechanism enhancing mutagenesis and tumor development.

Topical corticosteroids in the treatment of acute sunburn: a randomized, double-blind clinical trial.

OBJECTIVE To examine the effect of topical corticosteroid treatment on acute sunburn. DESIGN Randomized, double-blind clinical trial. SETTING University dermatology department. PATIENTS Twenty healthy volunteers with Fitzpatrick skin types I (highly sensitive, always burns easily, tans minimally) through III (sun-sensitive skin, sometimes burns, slowly tans to light brown). INTERVENTION Seven 34-cm(2) areas were marked on the upper aspect of the back of each participant. An untreated area was tested to determine UV sensitivity. Two areas were treated with excess amounts (2 mg/cm(2)) of either a moderate-potency corticosteroid or a high-potency corticosteroid 30 minutes before UV-B exposure as controls. Six or 23 hours after exposure to radiation, the remaining areas were treated with the 2 corticosteroid preparations. MAIN OUTCOME MEASURES The sunburn improvement factor (SIF) was determined by the following equation: SIF = MED (minimal erythema dose) on treated skin/MED on nontreated skin. An SIF greater than 1 indicated an effect of topical corticosteroids in sunburn relief. RESULTS The SIFs in the areas treated with either topical corticosteroid 30 minutes before UV-B exposure or high-potency corticosteroid 6 hours after UV-B exposure were significantly different from SIFs in areas that received no treatment (SIF 1.1-1.7; P < .05). Only the median SIF of 1.7 in the areas treated with high-potency corticosteroid 30 minutes before UV-B exposure was clinically relevant. The areas treated 23 hours after UV-B exposure and the areas treated with a moderate-potency corticosteroid 6 hours after UV-B exposure showed no significant reduction in redness. CONCLUSION Treatment with topical moderate-potency or high-potency corticosteroids does not provide a clinically useful decrease in the acute sunburn reaction when applied 6 or 23 hours after UV exposure.

Sun protection factor persistence on human skin during a day without physical activity or ultraviolet exposure

Background/purpose: Recently, we showed that the sun protection factor (SPF) decreases by a constant factor to reach 55% during a day with activities. Organic sunscreens but not inorganic ones are absorbed through the skin. We wished to determine the SPF decrease caused by absorption by investigating the difference in SPF decreases between an organic and an inorganic sunscreen, assuming that the sunscreens are stable, and that the SPF decrease is time dependent if caused by absorption.

Increased expression of glucagon-like peptide-1 receptors in psoriasis plaques.

Recent case reports suggest that treatment with glucagon‐like peptide‐1 (GLP‐1) agonists results in clinical improvement of psoriasis. The purpose of this study was to determine whether GLP‐1 receptors (GLP‐1Rs) are found in the skin of healthy volunteers and psoriasis patients and if so, whether GLP‐1Rs are located on keratinocytes or immune cells.