A randomized, multinational, noninferiority, phase III trial to evaluate the safety and efficacy of BF-200 aminolaevulinic acid gel vs. methyl aminolaevulinate cream in the treatment of nonaggressive basal cell carcinoma with photodynamic therapy.

BACKGROUND: Basal cell carcinoma (BCC) represents the most common nonmelanoma skin cancer worldwide, affecting mainly adult, fair-skinned individuals. The World Health Organization distinguishes aggressive and nonaggressive forms, of which prototypical variants of the latter are primary nodular and superficial BCC. OBJECTIVES: To demonstrate noninferiority of BF-200 ALA (a nanoemulsion gel containing 5-aminolaevulinic acid) compared with MAL (a cream containing methyl aminolaevulinate) in the treatment of nonaggressive BCC with photodynamic therapy (PDT). Noninferiority of the primary efficacy variable (overall patient complete response 12 weeks after last PDT) would be declared if the mean response for BF-200 ALA was no worse than that for MAL, within a statistical margin of Δ = -15%. METHODS: The study was a randomized, phase III trial performed in Germany and the U.K. with ongoing 5-year follow-up. Of 281 randomized patients, 138 were treated with BF-200 ALA and 143 with MAL. Patients received two PDT sessions 1 week apart. Remaining lesions 12 weeks after the second PDT were retreated. Illumination was performed with a red light source (635 nm, 37 J cm-2 ). The results shown include clinical end points and patients' reassessment 12 months after the last PDT. The study was registered with EudraCT (number 2013-003241-42). RESULTS: Of the BF-200 ALA-treated patients, 93·4% were complete responders compared with 91·8% in the MAL group. The difference of means was 1·6, with a one-sided 97·5% confidence interval of -6·5, establishing noninferiority (P < 0·0001). The results for secondary efficacy parameters were in line with the primary outcome. Recurrence rates 12 months after the last treatment were ≤ 10%. CONCLUSIONS: Treatment of nonaggressive BCC with BF-200 ALA-PDT is highly effective and well tolerated with proven noninferiority to MAL-PDT. It demonstrates low recurrence rates after 1 year of follow-up.

German S3-guidelines on the treatment of psoriasis vulgaris (short version).

Psoriasis vulgaris is a common and often chronic inflammatory skin disease. The incidence of psoriasis in Western industrialized countries ranges from 1.5 to 2%. Patients afflicted with severe psoriasis vulgaris may experience a significant reduction in quality of life. Despite the large variety of treatment options available, patient surveys have revealed insufficient satisfaction with the efficacy of available treatments and a high rate of medication non-compliance (Richards et al. in J Am Acad Dermatol 41(4):581-583, 1999). To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologische Gesellschaft (DDG) and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence-based guidelines for the management of psoriasis first published in 2006 and now updated in 2011. The Guidelines focus on induction therapy in cases of mild, moderate, and severe plaque-type psoriasis in adults. This short version of the guidelines presents the resulting series of therapeutic recommendations, which were based on a systematic literature search and discussed and approved by a team of dermatology experts. In addition to the therapeutic recommendations provided in this short version, the full version of the guidelines includes information on contraindications, adverse events, drug interactions, practicality, and costs, as well as detailed information on how best to apply the treatments described (for full version please see Nast et al. in JDDG Suppl 2:S1-S104, 2011 or http://www.psoriasis-leitlinie.de ).

UVB 308-nm excimer light and bath PUVA: combination therapy is very effective in the treatment of prurigo nodularis.

BACKGROUND: Prurigo nodularis (PN) is a chronic inflammatory skin disease with nodular itching lesions. UV therapy--both PUVA and NUVB--are known to clear up PN temporarily due to the antipruritic effect of UV light. However, relapse after treatment is common in PN, which means that either long-term therapy is necessary or the treatment protocols have to be optimized to minimize side-effects. OBJECTIVE: The aim of this study was to evaluate the effect that combining bath PUVA and targeted UVB 308 nm excimer radiation has on recalcitrant nodular prurigo. METHODS: In a prospective trial, 22 patients with PN were treated with either PUVA alone or with a combination of PUVA and excimer UVB. The end point was complete or almost complete remission of PN. RESULTS: Adding a 308-nm excimer UVB to the treatment of the pruritic nodules sped up the healing process; 30% less PUVA radiation was needed. CONCLUSION: The combination of PUVA and excimer UVB in PN appears to be very efficacious. Reducing psoralen UVA doses by 30% offered long-term benefits in phototherapy of chronic recalcitrant diseases like PN.

[New approach to photoepilation. Diode laser with SHR (Super Hair Removal) compared to alexandrite laser]. / Ein neuer Ansatz in der Laser-Haarreduktion. Diodenlaser mit SHR ("Super Hair Removal") im Vergleich mit dem Alexandritlaser.

BACKGROUND: Photoepilation has been an essential field of application of dermatologic laser therapy for many years. The present article evaluates whether the use of a new operation mode of a long-pulsed diode laser can be effective, nearly painless, with few side effects and independent of the skin type. To this aim, its use has been compared to an established method of photoepilation. MATERIAL AND METHODS: In a controlled prospective study with 18 (♀=12, ♂=6) patients aged between 22 and 58 years, the effects of photoepilation with the long-pulsed alexandrite laser and the long-pulsed diode laser, operated in the Super Hair Removal mode (SHR), were compared. RESULTS: The alexandrite laser is slightly more effective with fair skin types; the SHR mode is clearly more effective with dark skin types. Regarding painfulness, the SHR mode is clearly superior. In terms of speed, the two systems are comparable. The alexandrite laser is more user-friendly because of its light and small handpiece. CONCLUSION: The major advantages of the SHR mode are its effectiveness in dark skin types and its lack of pain. The alexandrite laser is slightly more effective with fair skin types, slightly faster and its handling is considerably more comfortable. None of the two systems has yet brought about a breakthrough with fair hair.

[Psoriasis. Natural versus artificial balneophototherapy]. / Psoriasistherapie. Künstliche versus natürliche Photosole.

Artificial balneophototherapy is an imitation of the natural balneophototherapy (Dead Sea climatotherapy; DSC) using highly concentrated salt solutions (25%) and UVB radiation. In 2008 the artificial balneophototherapy was included in the German healthcare system as an effective, evidence-based therapy for patients with moderate-severe psoriasis. In contrast, natural DSC is still considered a "non-standard and off-label therapy". Therefore we analyzed all studies published in the past two decades on both artificial and natural balneophototherapy comparing them in effectiveness, length of remission and practicability. Evidence-based studies on DSC showed good clinical results and long remission periods in psoriatic patients; the two methods seem comparable in effectiveness. Patients with chronic, therapy-resistant psoriasis should have access to DSC if they fail routine measures.

[Targeted UVB-308 nm (NUVB) therapy with excimer laser in the treatment of atopic dermatitis and other inflammatory dermatoses]. / UVB-308-nm- (NUVB-)Therapie mittels Excimer-Laser bei atopischer Dermatitis und weiteren inflammatorischen Dermatosen.

UVB 311 nm phototherapy (NUVB) is used successfully in the treatment of psoriasis or atopic dermatitis and is often chosen as "first-line" therapy. In a prospective study we investigated the efficacy of the targeted UVB 308 phototherapy by excimer laser in the treatment of 57 patients with localized, mild therapy-resistant atopic dermatitis. We achieved a complete remission (CR) in nearly 85% and a partial remission (PR) in 15% after 10 treatments during 6-8 weeks in all patients. A mean reduction in patient-reported pruritus was one hallmark after 3-4 treatments. 48 other patients with lichen simplex chronicus Vidal, nodular prurigo, granuloma anulare, alopezia areata (AA) and lichen ruber planus were also treated by targeted NUVB. We found higher rates of CR and PR only in patients with AA and in patients with oral Lichen ruber mucosae. These results and the systematically reviewing of the current medical literature shows that targeted NUVB by excimer laser cannot be successfully transferred for all inflammatory skin diseases. In particular, Excimer UVB treatment expands the therapeutic options in patients with localized and therapy-resistant atopic dermatitis enormously.

[Laser treatment of warts]. / Laser in der Therapie der Warzen.

Human papilloma viruses (HPV) lead to common warts in 5% of the population and genital warts in 1% of sexually-active individuals. Although about 50% of HPV infections regress spontaneously, the course is uncertain. Expectant waiting often leads to progression and dissemination. Plantar warts may cause pain on walking, while palmar and genital warts may impair social contacts. There are many treatments for warts, including a variety of laser systems. The CO(2) laser is the best ablative approach, producing cure rates of up to 75% for therapy-resistant common warts in cohort and case-control studies. Side effects such as bleeding, pain and reduced function over weeks must be weighed against the likelihood of success. Considering non-ablative approaches, pulsed dye lasers can be used for a selective, non-bloody destruction of extragenital and genital warts and may become the treatment of choice. In prospective randomized studies, they produced cure rates of up to 82% for therapy-resistant warts with few side effects.

[Treating papillomatous intradermal nevi: lasers - yes or no? A prospective study]. / Management papillomatöser intradermaler Nävi: Laser ja oder nein? Eine Prospektivstudie.

BACKGROUND: Papillomatous intradermal nevi are common acquired melanocytic nevi. Although harmless, they can be - especially on the face - cosmetically disturbing. At selected sites on the trunk, they may be traumatized by clothing, so that patients often wish to have them removed with a low likelihood of recurrence. MATERIAL AND METHODS: In a prospective study with 90 (female symbol=77, male symbol=13) patients aged between 13 and 67 years, 130 intradermal nevi (female symbol=114, male symbol=16) were removed using a combined therapy with CO(2), erbium: YAG and ruby lasers. RESULTS: After therapy, 2.3% of intradermal nevi recurred as a pigmented macule, while 6.9% reappeared as a papule or nodule (volume recurrence). 88% of the patients were very satisfied with the result; 11%, satisfied; and 1%, not satisfied. 99% would undergo the therapy again. CONCLUSION: The combined laser method (CO(2), erbium: YAG and ruby lasers) for the treatment of intradermal nevi produces excellent cosmetic results, is easily performed, leads to high patient satisfaction and is safe if correctly applied.

Does dye laser treatment with higher fluences in combination with cold air cooling improve the results of port-wine stains?

BACKGROUND AND OBJECTIVE: The use of cold air cooling (CAC) and cryogen spray cooling during dye laser treatment of port-wine stains (PWS) has become a standard in recent years. Still unsolved is the question of which fluences are necessary in combination with CAC in order to achieve an optimum clearance and the lowest possible rate of side-effects. STUDY DESIGN: In a prospective study, we treated 11 patients with PWS with pulsed dye laser (Photogenica V, Cynosure, lambda = 585 nm, iota(p) = 0.5 ms, spot size = 7 mm). Each PWS was partitioned into three areas: (area 1) 6 J/cm(2) without CAC, (area 2) 6 J/cm(2) with CAC (level 4), (area 3) 9 J/cm(2) with CAC (level 4). RESULTS: Area 3 (mean, 59%) showed a slightly better clearance than area 1 (mean, 57%); in area 2, we observed a reduced clearance (mean, 45%). Compared with area 1, we achieved a reduction of pain through CAC in areas 2 and 3. The healing periods as well as the rate of side-effects were comparable in all areas. CONCLUSION: We observed a slight but not statistically relevant increase in clearance with the use of higher fluences and CAC compared with lower fluences without CAC. Because pain is lowered significantly when using CAC, and because this makes the treatment more comfortable for the patients, we tend to recommend the use of higher fluences (9 J/cm(2)) with simultaneous CAC for treating PWS.

[Venous lakes. Treatment with a combination of diode laser (910 nm) and radio frequency]. / Lippenrandangiome. Behandlung mit einer Kombination aus Diodenlaser (910 nm) und Radiofrequenzenergie.

BACKGROUND: Venous lakes of the lip are a cosmetic problem for many patients due to their exposed location, nodularity, fragility and blue color. We sought an effective and well tolerated therapy method. PATIENTS AND METHODS: Over one year, we treated 20 patients with a combination of diode laser (910 nm) and radiofrequency. RESULTS: In all cases, there was complete regression of the venous lake (average: 1.4 treatment sessions). Side effects were transient pain that was assessed as mild by the patients, and transient swelling. Scarring or hypo-/hyperpigmentation did not occur. CONCLUSION: This combined approach is a recommended option at least equivalent to other therapy methods (argon laser, CO(2) laser, pulsed-dye-laser, and others), or even superior to them due to the low rates of side effects and low number of treatment sessions.

German evidence-based guidelines for the treatment of Psoriasis vulgaris (short version).

Psoriasis vulgaris is a common and chronic inflammatory skin disease which has the potential to significantly reduce the quality of life in severely affected patients. The incidence of psoriasis in Western industrialized countries ranges from 1.5 to 2%. Despite the large variety of treatment options available, patient surveys have revealed insufficient satisfaction with the efficacy of available treatments and a high rate of medication non-compliance. To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologische Gesellschaft and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence-based guidelines for the management of psoriasis. The guidelines focus on induction therapy in cases of mild, moderate, and severe plaque-type psoriasis in adults. The short version of the guidelines reported here consist of a series of therapeutic recommendations that are based on a systematic literature search and subsequent discussion with experts in the field; they have been approved by a team of dermatology experts. In addition to the therapeutic recommendations provided in this short version, the full version of the guidelines includes information on contraindications, adverse events, drug interactions, practicality, and costs as well as detailed information on how best to apply the treatments described (for full version, please see Nast et al., JDDG, Suppl 2:S1-S126, 2006; or http://www.psoriasis-leitlinie.de ).

[Unilateral acral necrosis as a minor form of hand-foot syndrome. Patient with unilateral acral necrosis secondary to capecitabine therapy for metastatic breast cancer]. / Unilaterale akrale Nekrosen als Abortivform einer palmoplantaren Erythrodysästhesie. Patientin mit unilateralen akralen Nekrosen unter Capecitabine-Therapie bei metastasiertem Mammakarzinom.

Hand-foot syndrome is a common toxic side-effect, particularly during chemotherapy, with an incidence of 6-64% overall and 10-24% for capecitabine (Xeloda) monotherapy. Consequently, differential diagnostic considerations should include hand-foot syndrome when acral skin lesions appear, particularly during capecitabine monotherapy. The dosage should be reduced or therapeutic regimen changed. We present a unique patient who while on capecitabine developed unilateral acral necrosis which should be classified as a minor form of hand-foot syndrome.

Ultraviolet B 308-nm excimer laser treatment of psoriasis: a new phototherapeutic approach.

BACKGROUND: Excimer laser-derived 308-nm ultraviolet (UV) B therapy is a new alternative for treating psoriasis by phototherapy. Some studies have been made showing the effectiveness of intralesional phototherapy technology in treating psoriasis. However, there has been no information available so far with regard to the cumulative dosage on a larger group of patients and on therapy optimized treatment strategies. OBJECTIVES: One hundred and twenty psoriatic patients were treated according to standard protocol to define the effectiveness. Our aim was to develop new parameters and determine whether effectiveness could be improved and whether treatment exposure, the cumulative UVB dose and adverse effects could be minimized. METHODS: Initially, the excimer laser's effectiveness in treating psoriasis was evaluated in an open prospective study according to standard protocol. This included 120 adult patients (67 female/53 male) with chronic plaque psoriasis and < 20% involved body surface. The initial dose was based on three multiples of a predetermined minimal erythema dose (MED). Patients were treated twice a week for the first 3 weeks, then once a week until clearance was achieved. The main parameters were the initial starting dose, psoriasis area and severity index (PASI), the number of treatments needed, the time in treatment and the cumulative dose needed to clear psoriatic plaques. Thereafter, 43 patients were treated as a second comparable group. Therapy began with a starter dose, defined as MED-I. MED-I was defined as a UVB 308-nm dose which provoked a visible increase in erythema after 24 h. In addition, the epidermal thickness of the plaques was measured on an individual basis by 20-MHz ultrasound and correlated to the MED-I. RESULTS: Of the patients who met the standard protocol, 65.7% were at least 90% clear after a maximum of 10 treatments; an even greater number (85.3%) showed a > or = 90% improvement in PASI after 13 sessions, while 14.7% of patients had only a < or = 50% PASI improvement. The cumulative UVB dose was 11.25 +/- 4.21 J cm-2 and the average treatment time was 7.2 weeks. Patients treated individually with the MED-I starter dose showed nearly identical rates of clearance (83.7%), but were clear in 7.07 +/- 2.15 sessions with a cumulative dose of 6.25 +/- 4.02 J cm-2. CONCLUSIONS: The majority of our patients benefited greatly from laser-derived 308-nm UVB therapy, which cleared skin lesions faster than conventional phototherapy. As this therapy targets only the involved skin, the thickness of the plaques and individual MED-I should determine the initial dose, thus increasing the effectiveness of the therapy. We propose that light therapy sparing uninvolved skin will become predominant in the future.

[Trigger factors for psoriasis]. / Triggermechanismen der Psoriasis.

Psoriasis is often defined as a disease in which there is a genetic predisposition but environmental stimuli ("trigger factors") are also necessary for clinical expression. Various endogenous and exogenous factors can either induce or exacerbate the clinical features. Knowledge of these factors is of primary importance in clinical practice. This review focuses on the most common environmental trigger factors (infection/superantigens, injury/Köbner phenomenon, stress/neuropeptides, smoking and alcohol) and evaluates the clinical and experimental concepts to explain "environmentally" triggered psoriasis.

The antipsoriatic agent dimethylfumarate immunomodulates T-cell cytokine secretion and inhibits cytokines of the psoriatic cytokine network.

Interactions between infiltrating T cells and keratinocytes via the secretion of the TH1 cytokines interleukin (IL) 2 and interferon gamma (INF-gamma), the keratinocyte growth factor transforming growth factor alpha (TGF-alpha) and the cytokines IL-6 and IL-8 are thought to be the predominant mechanisms inducing skin lesions in psoriatic patients. Systemic treatment of psoriasis with fumaric acid derivatives (FAEs) has been reported to be effective in the treatment of psoriasis, but the mode of action is still unknown. To clarify this phenomenon, keratinocytes from psoriatic patients as well as from healthy volunteers were mono- and cocultured with HUT 78 T cells with/without the addition of FAEs; the cytokine concentrations were then measured in the culture supernatants. Furthermore, mRNA expression was determined in epidermal growth factor (EGF) -activated keratinocytes as well as in phytohaemagglutinin (PHA)-activated HUT 78 T cells. Only dimethylfumarate (DMF) diminished IL-6 and TGF-alpha secretion in the psoriatic cocultures. However, it did not have this effect on cocultures from control subjects or on monocultures. DMF suppresses EGF-induced TGF-alpha mRNA induction in psoriatic keratinocytes. DMF inhibited INF-gamma secretion in all cultures but stimulated the IL-10 secretion. This immunomodulation away from the TH1 cytokine IFN-gamma to the TH2 cytokine IL-10 was confirmed in HUT 78 T cells by Northern blot analysis. An increased number of eosinophils is a known side-effect in patients treated with this drug, suggesting a clinical relevance of this immunomodulation in vivo. This immunomodulation and the suppression of cytokines from the psoriatic cytokine network could be responsible for the beneficial effect of DMF in the treatment of a hyperproliferative and TH1 cytokine-mediated skin disease.

[Contact eczema in housewives. Update from 1986 with reference to results of epicutaneous tests in 2,633 patients]. / Kontaktekzeme bei Hausfrauen. Update nach 1986 unter Berücksichtigung der Epikutantestergebnisse von 2633 Patienten.

The development of hand eczema is a relatively commonly seem dermatosis in housewives. In 1986 we presented a first survey of potential contact dermatitis sources for a housewife. Now, we present an update in which we analyse the different contact sources in the household and grade them in comparison to the data of 1986. The results are based on the analysis of a large population of 2633 patients with the occupation "housewife" and the diagnosis "eczema" who have been seen in departments of dermatology belonging to the Information Network of Departments of Dermatology (IVDK).

Contact allergy in patients with periorbital eczema: an analysis of allergens. Data recorded by the Information Network of the Departments of Dermatology.

BACKGROUND: Periorbital eczema may be an expression of a constitutional disease or an irritant or allergic dermatitis. An allergic contract dermatitis is believed to be the most common cause. OBJECTIVE: We tried to determine which allergens may cause an allergic contact dermatitis and if there exists a leading allergen. METHODS: 609 patients with periorbital eczema were assessed with patch testing in 22 hospitals to evaluate the relevance of an allergic contact dermatitis in the pathogenesis of periorbital eczema. Additionally, 116 patients were tested with their own products. RESULTS: 81% of the cases involving the eyelids were women. A relevant allergic contact dermatitis was found in 52% of the patients with periorbital eczema. Furthermore, a positive patch test was present in every third patient with the clinical diagnosis of an atopic dermatitis. Antibiotics, phenylephrine and thimerosal could be determined to be the leading allergens responsible for allergic periorbital eczema. Positive reactions for potassium dichromate and fragrance mix occurred less frequently in patients with periorbital eczema. 132 positive reactions were found in patients tested with their own products, including 33% with a positive reaction to eye ointments, 15% to face creams, 10% to eye shadows, 10% to makeup, 10% to shampoos and 4% to nail varnish. Only 6% reacted to perfume. CONCLUSION: The data underline the importance of performing patch tests in the case of periorbital eczema, especially in atopic patients.

Ethanol enhances the IFN-gamma, TGF-alpha and IL-6 secretion in psoriatic co-cultures.

Evidence suggests an association between alcohol consumption and psoriasis. This relationship is still undefined, although long-term alcohol intake influences the immune system. Interactions between T cells and keratinocytes are important for the pathogenesis of psoriasis, by secretion of pro-inflammatory cytokines and growth factors in psoriatic skin. IL-2, IL-6, IL-8, IFN-gamma and TGF-alpha are hallmark cytokines in a psoriatic cytokine network. We investigated whether ethanol influences the secretion of these cytokines using a co-culture model with keratinocytes from psoriatic patients (n = 9) or from healthy controls (n = 9), with HUT 78 lymphocytes, and determined the cytokine levels with or without ethanol treatment in the culture supernatants. TGF-alpha and IFN-gamma levels were elevated in the ethanol-treated psoriatic co-cultures, to 150% and 175% respectively, but neither in co-cultures with keratinocytes derived from healthy control individuals nor in monocultures. Treatment with ethanol elevated slightly the IL-6 levels in the monocultures from psoriatic and control keratinocytes to 125% but not in HUT 78 monocultures. In the psoriatic co-cultures, IL-6 levels were elevated in the culture supernatants to almost 160%, but they were not influenced by ethanol in co-cultures with control keratinocytes. The cytokine levels of IL-8 or IL-2 were not significantly influenced in the psoriatic mono- and co-cultures or in HUT 78 cultures. If ethanol influences the cytokine secretion of psoriatic keratinocytes and HUT 78 lymphocytes in co-culture conditions, these data suggest that ethanol could also influence the psoriatic cytokine network in vivo, which may explain the explain the aggravation of this disease in alcohol-consuming psoriatic patients.

Ethanol enhances the mitogen-driven lymphocyte proliferation in patients with psoriasis.

Ethanol has been reported to exacerbate psoriasis. Since immunological mechanisms are considered to be important for the pathogenesis of psoriasis, we compared the effects of ethanol on lymphocyte proliferation in 15 healthy control individuals and 15 patients with psoriasis. We employed the spontaneous and phytohemagglutin in (PHA)-induced uptake of 3H-TdR to measure lymphocyte proliferation. Ethanol was added to cultures at concentrations ranging from 0.5 to 0.0005% (vol./vol.). We found that both spontaneous and PHA-driven lymphocyte proliferations were significantly lower in patients with psoriasis (P < 0.002). Spontaneous blastogenesis in both controls and patients remained stable under ethanol. In controls, ethanol suppressed the PHA-driven lymphocyte proliferation in a dose-dependent fashion. By contrast, in patients with psoriasis ethanol significantly increased lymphocyte proliferation by 2-3 times (p < 0.002). Our data indicate that in psoriasis the lower lymphocyte transformation is abnormally enhanced by minimal doses of ethanol.