Claus Zachariae

Anti–Interleukin-17 Monoclonal Antibody Ixekizumab in Chronic Plaque Psoriasis

BACKGROUND Type 17 helper T cells have been suggested to play a pathological role in psoriasis. They secrete several proinflammatory cytokines, including interleukin-17A (also known as interleukin-17). We evaluated the safety and efficacy of ixekizumab (LY2439821), a humanized anti-interleukin-17 monoclonal antibody, for psoriasis treatment. METHODS In our phase 2, double-blind, placebo-controlled trial, we randomly assigned 142 patients with chronic moderate-to-severe plaque psoriasis to receive subcutaneous injections of 10, 25, 75, or 150 mg of ixekizumab or placebo at 0, 2, 4, 8, 12, and 16 weeks. The primary end point was the proportion of patients with reduction in the psoriasis area-and-severity index (PASI) score by at least 75% at 12 weeks. Secondary end points included the proportion of patients with reduction in the PASI score by at least 90% or by 100%. RESULTS At 12 weeks, the percentage of patients with a reduction in the PASI score by at least 75% was significantly greater with ixekizumab (except with the lowest, 10-mg dose)--150 mg (82.1%), 75 mg (82.8%), and 25 mg (76.7%)--than with placebo (7.7%, P<0.001 for each comparison), as was the percentage of patients with a reduction in the PASI score by at least 90%: 150 mg (71.4%), 75 mg (58.6%), and 25 mg (50.0%) versus placebo (0%, P<0.001 for each comparison). Similarly, a 100% reduction in the PASI score was achieved in significantly more patients in the 150-mg group (39.3%) and the 75-mg group (37.9%) than in the placebo group (0%) (P<0.001 for both comparisons). Significant differences occurred at as early as 1 week and were sustained through 20 weeks. Adverse events occurred in 63% of patients in both the combined ixekizumab groups and in the placebo group. No serious adverse events or major cardiovascular events were observed. CONCLUSIONS Use of a humanized anti-interleukin-17 monoclonal antibody, ixekizumab, improved the clinical symptoms of psoriasis. Further studies are needed to establish its long-term safety and efficacy in patients with psoriasis. (Funded by Eli Lilly; ClinicalTrials.gov number, NCT01107457.).

Psychological symptoms and quality of life of dermatology outpatients and hospitalized dermatology patients

The aim of the investigation was to compare psychological symptoms and health-related quality of life of dermatology patients and healthy controls. The sample consisted of 333 consecutively recruited patients from four dermatology outpatient clinics, 172 hospitalized dermatological patients from two university hospitals and 293 matched healthy controls. All patients and controls completed Becks Depression Inventory, the Brief Symptom Inventory and the Dermatology Life Quality Index. Hospitalized patients were more distressed than outpatients and healthy controls and reported greater impairment of disease-related quality of life than outpatients. More hospitalized patients had suicidal thoughts and were characterized as having severe to moderate depression compared with outpatients and controls. Female patients and younger patients were generally more distressed than male patients and older patients, and patients with atopic dermatitis and psoriasis were more distressed than patients with urticaria and eczemas. Disease-related impairment of quality of life was the main predictor of psychological symptoms, when controlling for diagnosis, age, gender, disease duration and disease severity. Although older age was associated with fewer psychological symptoms, our data suggest that skin disease affects quality of life equally in young and older patients. The findings highlight the importance of recognizing disease-related psychological problems and possible psychiatric comorbidity of dermatology patients, especially among patients with atopic dermatitis and psoriasis.

Contamination versus preservation of cosmetics: a review on legislation, usage, infections, and contact allergy

Cosmetics with high water content are at a risk of being contaminated by micro‐organisms that can alter the composition of the product or pose a health risk to the consumer. Pathogenic micro‐organisms such as Staphylococcus aureus and Pseudomonas aeruginosa are frequently found in contaminated cosmetics. In order to avoid contamination of cosmetics, the manufacturers add preservatives to their products. In the EU and the USA, cosmetics are under legislation and all preservatives must be safety evaluated by committees. There are several different preservatives available but the cosmetic market is dominated by a few preservatives: parabens, formaldehyde, formaldehyde releasers, and methylchloroisothiazolinone/methylisothiazolinone.

Dermatology Life Quality Index: Data from Danish Inpatients and Outpatients

The aim of the present study was to provide data on the reliability and validity of a Danish translation of the Dermatology Life Quality Index (DLQI), a short measure of the impact of dermatological diseases on quality of life. The DLQI was administered to 200 outpatients and 100 hospitalized patients suffering from a range of dermatological diseases and to 100 sex- and age-matched healthy controls. Mean scores, internal consistency and test-retest reliability were comparable to the results reported for the original English version. Hospitalized patients reported greater impairment of disease-related quality of life than outpatients, and patients with atopic dermatitis and psoriasis exhibited greater scores than patients suffering from other dermatological diseases. Discriminant, construct and predictive validities of the Danish translation of the DLQI were satisfactory, as indicated by significant associations between DLQI scores and physician-rated disease severity, disease duration and the time patients were willing to spend each day on a hypothetical effective treatment. The results also suggest that the emphasis Danish patients place on various aspects of disability covered by the questionnaire is similar to that of English patients. In conclusion, the Danish translation of the DLQI showed satisfactory reliability and the preliminary results indicate that this version is a valid measure, which can be used in both research and clinical settings.

Effect of Weight Loss on the Severity of Psoriasis: A Randomized Clinical Study

IMPORTANCE Psoriasis is associated with adiposity and weight gain increases the severity of psoriasis and the risk of incident psoriasis. Therefore, we aimed to measure the effect of weight reduction on the severity of psoriasis in obese patients with psoriasis. OBJECTIVE To assess the effect of weight reduction on the severity of psoriasis in overweight patients. DESIGN Sixty obese patients with psoriasis from our dermatology outpatient clinic were enrolled in a prospective randomized clinical trial in which they were allocated to a control group or an intervention group. SETTING University hospital outpatient dermatology clinic. PARTICIPANTS We included 60 of 69 eligible overweight patients with psoriasis (body mass index [calculated as weight in kilograms divided by height in meters squared], 27-40; aged 25-71 years). INTERVENTIONS The intervention group received a low-energy diet (LED) (800-1000 kcal/d) for 8 weeks to induce weight loss, followed by 8 weeks of reintroduction of normal food intake, reaching 1200 kcal/d. The control group was instructed to continue eating ordinary healthy foods. MAIN OUTCOMES AND MEASURES Psoriasis Area and Severity Index (PASI) after 16 weeks, with Dermatology Life Quality Index (DLQI) as a secondary end point. RESULTS The median PASI for all patients was 5.4 (interquartile range, 3.8-7.6) at baseline. At week 16, the mean body weight loss was 15.4 kg (95% CI, 12.3-18.5 kg; P < .001) greater in the intervention group than in the control group. The corresponding mean differences in PASI and DLQI, also in favor of the LED group, were -2.0 (95% CI, 4.1 to -0.1; P = .06) and -2.0 (95% CI, -3.6 to -0.3; P = .02), respectively. CONCLUSIONS AND RELEVANCE Treatment with an LED showed a trend in favor of clinically important PASI improvement and a significant reduction in DLQI in overweight patients with psoriasis. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01137188.

Production of monocyte chemotactic and activating factor (MCAF) by human dermal fibroblasts in response to interleukin 1 or tumor necrosis factor

Normal human dermal fibroblasts rapidly expressed (less than 30 min.) considerable mRNA for monocyte chemotactic and activating factor (MCAF) and released high levels of biological activity in response to interleukin 1 (IL 1) or tumor necrosis factor (TNF). In contrast, cultured normal human keratinocytes did not express MCAF mRNA when stimulated with IL 1 or TNF. These results suggest the important role of dermal fibroblasts, the predominant cells in dermal connective tissue, in the recruitment of monocytes during inflammation. This is the first report of the induction of MCAF by IL 1 or TNF in any cell type.

Chromium allergy in consecutive patients in a country where ferrous sulfate has been added to cement since 1981

Cement eczema used to be a common occupational disease in Denmark. Since 1981, ferrous sulfate has been added to all cement produced in Denmark to reduce the amount of soluble hexavalent chromate to below 2 mg/kg (2 ppm). The aim of the study was to analyse a material of consecutive chromate‐sensitive patients in an urban tertiary referral centre with respect to primary cause of sensitization, in a geographical area where the risk of chromate exposure from cement had been reduced. In the 6‐year period January 1989 to December 1994, a total of 4511 patients were patch tested with the European standard series, including chromate. 79 patients, 31 male and 48 female, were diagnosed as chromate sensitive. Relevant chromate exposure was established in 34 of these 79 patients. Leather was the most frequent source of chromate sensitization (19 out of 34) (47%). Chromate sensitization from cement was considered likely in 10 out of 34 subjects. Of these, 7 had been sensitized before 1981, 2 had been sensitized by non‐occupational exposure to cement, and only 1 had been sensitized from occupational cement exposure in the 6‐year period.

IL-8 as antibody therapeutic target in inflammatory diseases: Reduction of clinical activity in palmoplantar pustulosis

IL-8 is a chemokine that has been implicated in a number of inflammatory diseases involving neutrophil activation. HuMab 10F8 is a novel fully human mAb against IL-8, which binds a discontinuous epitope on IL-8 overlapping the receptor binding site, and which effectively neutralizes IL-8-dependent human neutrophil activation and migration. We investigated whether interference in the cytokine network by HuMab 10F8 might benefit patients suffering from palmoplantar pustulosis, a chronic inflammatory skin disease. Treatment of patients with HuMab 10F8 was well tolerated and significantly reduced clinical disease activity at all five endpoints, which included a ≥50% reduction in the formation of fresh pustules. IL-8 neutralization was monitored at the site of inflammation by assessing exudates of palmoplantar pustulosis lesions. HuMab 10F8 sequestered IL-8 in situ, as observed by rapid dose-dependent decreases of IL-8 concentrations immediately following Ab infusion. These data demonstrate a critical role for IL-8 in the pathophysiology of palmoplantar pustulosis. HuMab 10F8 is capable of interrupting IL-8 activity in vivo and represents a candidate for treatment of inflammatory diseases and other pathological conditions associated with IL-8 overproduction.

Prevalence and cause of methylisothiazolinone contact allergy.

Background: Methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) has been one of the most frequent sensitizers since the 1980s. In 2005, the use of MI alone was approved for the preservation of cosmetic and household products in the EU. Before that, MI was used in industrial products, and the first cases of isolated MI contact allergy were published.

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.