Increased levels of lipocalin 2 in palmoplantar pustular psoriasis.

BACKGROUND: Palmoplantar pustular psoriasis (PPP) is a recalcitrant chronic skin disease affecting the palms and soles. OBJECTIVE: To identify and characterize pathogenetic players in PPP. METHODS: Clinical and anamnestic data as well as skin and blood samples of 60 PPP patients were collected. Healthy participants served as controls. Analysis of patient samples and cultured primary skin cells was performed by ELISA, qRT-PCR, and immunohistochemistry. RESULTS: Upon screening of blood mediators in PPP patients, lipocalin 2 (LCN2) emerged as being significantly upregulated compared to healthy participants. LCN2 blood levels were independent of age, sex, or concomitant psoriasis vulgaris. Keratinocytes in PPP skin lesions were important LCN2 producers. In vitro, LCN2 production of these cells was upregulated by IL-1ß and further enhanced by IL-17 and TNF-α, while IL-22 had no effect. Accordingly, a positive relationship between blood IL-1ß and LCN2 levels was evident in PPP. LCN2 blood levels also showed a positive correlation with PPP pustule score, Dermatology Quality of Life Index and blood levels of the pro-atherogenic molecule resistin. CONCLUSIONS: In PPP, increased blood levels of LCN2 indicate an important activity of IL-1ß in the epidermis, may contribute to skin neutrophil infiltration, and may point to an increased pro- atherosclerosis risk.

Palmoplantar pustulosis - a cross-sectional analysis in Germany.

BACKGROUND: Palmoplantar pustulosis (PPP) is a recalcitrant chronic inflammatory skin disease. Data relevant for the medical care of patients with PPP are scarce. Thus, the aim of this work was to investigate the disease burden, clinical characteristics, and comorbidity of PPP patients in Germany. PATIENTS AND METHODS: PPP patients were examined in a crosssectional study at seven specialized psoriasis centers in Germany. RESULTS: Of the 172 included patients with PPP, 79.1% were female and 69.8% were smokers.In addition, 25.0% suffered from psoriasis vulgaris, 28.2% had documented psoriatic arthritis, and 30.2% had a family history of psoriasis. In 77 patients the mean Dermatology Life Quality Index (DLQI) was 12.2 ± 7.7 (mean ± SD). The mean Psoriasis Palmoplantar Pustulosis Area and Severity Index (PPPASI) was 12.6 ± 8.6. Mean body mass index was above average at 27.1 ± 5.5. The PPP patients had previously received an average of 2.6 ± 2.1 different anti-psoriatic systemic drugs or UV-therapies. The systemic drugs that had been used most frequently were corticosteroids in 40.1% of patients, followed by acitretin (37.8%), and methotrexate (27.9%). The PPPASI was 13.4 ± 8.9 in patients without current systemic therapy and 10.4 ± 7.9 in patients with systemic therapy. CONCLUSION: Many PPP patients had a concomitant diagnosis of psoriasis vulgaris and/or psoriatic arthritis or had a family history of psoriasis. Despite the fact that many of the patients were using anti-psoriatic therapies, there was still a high burden of disease within this PPP cohort. This insufficient control of symptoms demonstrates the urgent need for new PPP treatments.

Systemic antipsoriatic combination therapy with fumaric acid esters for plaque-type psoriasis: report on 17 cases.

BACKGROUND: In the literature as well as in existing psoriasis guidelines, only little evidence is available on combination regimens with systemic antipsoriatic agents. However, if systemic monotherapy is not efficacious enough to control the disease, a combination therapy might be necessary. OBJECTIVE: To evaluate the use of fumaric acid esters (FAEs) in combination with other antipsoriatic agents in 6 specialized dermatological departments in Germany. METHODS: A systematic retrospective chart review of patients receiving FAEs was performed. RESULTS: A total of 17 cases of patients receiving FAEs combined with at least one other systemic therapy (methotrexate, acitretin, etanercept, cyclosporine, leflunomide and infliximab) to treat psoriasis or psoriatic arthritis were identified. CONCLUSION: FAEs can be combined in an off-label setting with conventional as well as biological agents to treat recalcitrant psoriasis or psoriatic arthritis. Safety monitoring should be taken seriously as no controlled data for these combination regimens exist.

Combination of adalimumab with traditional systemic antipsoriatic drugs - a report of 39 cases.

BACKGROUND: Monotherapy with TNF-α inhibitors does not always produce a sufficient response in psoriasis patients. Combinations of TNF-α antagonists such as adalimumab with systemic antipsoriatic therapies such as methotrexate are not approved for use in psoriasis, and the published data are scarce. PATIENTS AND METHODS: The charts of 39 psoriasis patients from 6 dermatology departments were reviewed retrospectively. All patients were given adalimumbab with another systemic antipsoriatic drug. RESULTS: Combination therapy with methotrexate was most common (n = 32), followed by acitretin (n = 4) and cyclosporine (n = 3). Combination therapy with methotrexate lasted 10.8 ± 11.2 months (mean), with cyclosporine for 6.8 ± 3.3 months, and with acitretin 12.9 ± 12.4 months. Combinations were effective in the majority of patients: 30/39 (76.9 %) had a good (n = 9) or excellent (n = 21) response. Two patients had a moderate response and 7 patients had a poor response and were switched to another treatment. Overall, safety was very good. Eighteen patients experienced 24 adverse events; none was severe and/or required hospitalization. Of these, 10/24 adverse events were infections, most often infections of the upper respiratory tract (n = 5), bronchitis (n = 2), and influenza (n = 1). CONCLUSIONS: Combinations of adalimumab with traditional systemic antipsoriatic treatments offer a promising method for managing severe or recalcitrant psoriasis. More data are needed to determine the long-term safety and efficacy of these combinations.

Quantitative repeated open application testing with a rinse-off product in methyldibromo glutaronitrile-sensitive patients: results of the IVDK.

BACKGROUND: While the use of methyldibromo glutaronitrile (MDBGN) in leave-on products is clearly associated with high sensitization or elicitation risk, such a clear-cut relation could be questioned with regard to rinse-off products. OBJECTIVE: The objective of this study was to find a maximum non-eliciting concentration for rinse-off products in MDBGN patch test-positive patients. PATIENTS AND METHODS: We performed a use-related test [repeated open application test (ROAT)] in patients sensitized to MDBGN with a liquid soap containing three concentrations of MDBGN (50, 200, and 400 p.p.m. MDBGN, respectively). The soap at 50 p.p.m. was used twice daily for 4 weeks. If no reaction of the skin was observed, the product with the next higher concentration was used for another 4 weeks, etc. RESULTS: In total, 32/37 evaluated cases [86.5%; lower exact one-sided 95% confidence limit (CL): 73.7%] did not react to any of the preparations. The remaining reacted as follows: 1/37 reacted to 50 p.p.m., 3/37 to 200 p.p.m., and 1/37 to 400 p.p.m. The cumulative non-response to 50 p.p.m. was 97.3% (lower CL: 87.8%). CONCLUSIONS: The majority of subjects sensitized to MDBGN-tolerated rinse-off products containing a maximum concentration of 400 p.p.m. A concentration in rinse-off products in the range of 50 p.p.m. could be regarded as safe for most individuals already sensitized. These concentrations will presumably prevent induction (sensitization) also.

Quantitative patch and repeated open application testing in hydroxyisohexyl 3-cyclohexene carboxaldehyde sensitive-patients.

OBJECTIVE: To identify the concentration of the fragrance compound hydroxyisohexyl 3-cyclohexene carboxaldehyde (INCI) (HICC) that is sufficiently low not to cause an allergic reaction in patients with proven sensitization. METHODS: Repeated open application testing (ROAT) in 64 subjects with 2 preparations (perfume and cream) in different concentration (0.005-2.5%). Confirmatory patch testing with four preparations in two different concentrations (2.5% and 5%). RESULTS: The concentrations of HICC being tolerated by 90% of those sensitized to HICC are estimated as <88.2 ppm (cream) and <270 ppm (perfume) equivalent to 1.2 microg/cm(2) (perfume) and 4.9 microg/cm(2) (cream). Patch test preparations differed with regard to sensitivity (88.5-98.1%) and specificity (37.5-87.5%) against the ROAT result as external criterion. ROAT concentrations and the reaction strength in patch testing were inversely correlated (Kendall's tau-b: 0.69), both indicating the existence of different degrees of susceptibility. CONCLUSION: To protect 90% (50%) of people sensitized, the use concentration should be in the range of 0.009-0.027% (0.18-0.34%), depending on the product type. Taking into account these results, excessive concentrations should be avoided, as this would continue to sensitize people. Close monitoring is indispensable to prove the efficacy of any recommendations aiming to prevent induction.

Topical methyl aminolevulinate photodynamic therapy using red light-emitting diode light for multiple actinic keratoses: a randomized study.

BACKGROUND: Photodynamic therapy (PDT) is an effective treatment for actinic keratoses (AKs). Light-emitting diodes (LEDs) offer practical advantages when treating multiple lesions. OBJECTIVE: To evaluate the efficacy and tolerability of PDT using a LED and topical methyl aminolevulinate (MAL) for treatment of multiple AKs. METHODS AND MATERIALS: One hundred thirty-one patients with four to 10 non-pigmented, previously untreated thin or moderately thick AKs on the face or scalp were enrolled in this multicenter, double-blind, randomized, placebo-controlled study. MAL or matching placebo cream was applied to the débrided lesion surface for 3 hours before illumination with noncoherent red light (630 nm, light dose 37 J/cm(2)). Treatment was repeated 1 week later. RESULTS: Efficacy was evaluated in 57 patients with 418 lesions treated with MAL PDT and 58 with 414 lesions treated with placebo PDT. Sixteen patients were excluded as protocol violators (not randomized). MAL PDT was superior (p< .001) to placebo PDT in lesion complete response rates (83.3%, 95% confidence interval (CI)=79.3-86.7%, vs 28.7%, 95% CI=24.4-33.4%) and patient complete response rates (all lesions showing complete response; 68.4%, 95% CI=54.8-80.1% vs 6.9%, 95% CI=1.9-16.7%). CONCLUSIONS: Topical MAL PDT using a LED is an effective treatment for multiple AKs.

Effective photodynamic therapy of actinic keratoses on the head and face with a novel, self-adhesive 5-aminolaevulinic acid patch.

BACKGROUND: Photodynamic therapy (PDT) is increasingly used for the treatment of actinic keratosis (AK). OBJECTIVES: To investigate both the efficacy of different application times and the safety of a novel patch (PD P 506 A) containing aminolaevulinic acid in the PDT of mild to moderate AK. METHODS: Applications of PD P 506 A for 0.5, 1, 2 and 4 h were compared in a multicentre, randomized, blinded-observer, parallel-group study. After patch removal, study lesions were illuminated with red light (lambda(em) approximately 630 nm; 37 J/cm(2)). Study lesions were not pretreated (e.g. by curettage) prior to PDT. Efficacy was evaluated 4 and 8 weeks after treatment. Safety and tolerability were determined through laboratory analyses and documentation of both local reactions and adverse events. RESULTS: A total of 149 patients were initially enrolled. Of these, 140 patients (520 lesions) completed the study according to protocol. Eight weeks after treatment, 86% of the AK lesions (74% of the patients) treated with 4-h patch application showed complete clearance. The complete clearance rates of lesions (patients) for the 2-, 1- and 0.5-h treatment arms were 73% (47%), 72% (50%) and 51% (24%), respectively. Statistically, the 4-h application was identified as the 'best treatment'. Patients with clearance seemed to experience local reactions to a greater extent than patients without clearance. Local reactions to study treatments did not exceed the expected range. CONCLUSIONS: The results of this first clinical efficacy study suggest excellent therapeutic outcomes with a single PD P 506 A PDT with a 4-h application.