Response durability after cessation of immune checkpoint inhibitors in patients with metastatic Merkel cell carcinoma: a retrospective multicenter DeCOG study.

BACKGROUND: Immune checkpoint inhibitors (ICI) have led to a prolongation of progression-free and overall survival in patients with metastatic Merkel cell carcinoma (MCC). However, immune-mediated adverse events due to ICI therapy are common and often lead to treatment discontinuation. The response duration after cessation of ICI treatment is unknown. Hence, this study aimed to investigate the time to relapse after discontinuation of ICI in MCC patients. METHODS: We analyzed 20 patients with metastatic MCC who have been retrospectively enrolled at eleven skin cancer centers in Germany. These patients have received ICI therapy and showed as best overall response (BOR) at least a stable disease (SD) upon ICI therapy. All patients have discontinued ICI therapy for other reasons than disease progression. Data on treatment duration, tumor response, treatment cessation, response durability, and tumor relapse were recorded. RESULTS: Overall, 12 of 20 patients (60%) with MCC relapsed after discontinuation of ICI. The median response durability was 10.0 months. Complete response (CR) as BOR to ICI-treatment was observed in six patients, partial response (PR) in eleven, and SD in three patients. Disease progression was less frequent in patients with CR (2/6 patients relapsed) as compared to patients with PR (7/11) and SD (3/3), albeit the effect of initial BOR on the response durability was below statistical significance. The median duration of ICI therapy was 10.0 months. Our results did not show a correlation between treatment duration and the risk of relapse after treatment withdrawal. Major reasons for discontinuation of ICI therapy were CR (20%), adverse events (35%), fatigue (20%), or patient decision (25%). Discontinuation of ICI due to adverse events resulted in progressive disease (PD) in 71% of patients regardless of the initial response. A re-induction of ICI was initiated in 8 patients upon tumor progression. We observed a renewed tumor response in 4 of these 8 patients. Notably, all 4 patients showed an initial BOR of at least PR. CONCLUSION: Our results from this contemporary cohort of patients with metastatic MCC indicate that MCC patients are at higher risk of relapse after discontinuation of ICI as compared to melanoma patients. Notably, the risk of disease progression after discontinuation of ICI treatment is lower in patients with initial CR (33%) as compared to patients with initial PR (66%) or SD (100%). Upon tumor progression, re-induction of ICI is a feasible option. Our data suggest that the BOR to initial ICI therapy might be a potential predictive clinical marker for a successful re-induction.

Elevated baseline serum PD-1 or PD-L1 predicts poor outcome of PD-1 inhibition therapy in metastatic melanoma.

BACKGROUND: Programmed cell death protein 1 (PD-1) checkpoint inhibition has recently advanced to one of the most effective treatment strategies in melanoma. Nevertheless, a considerable proportion of patients show upfront therapy resistance and baseline predictive biomarkers of treatment outcome are scarce. In this study we quantified PD-1 and programmed death-ligand 1 (PD-L1) in baseline sera from melanoma patients in relation to therapy response and survival. PATIENTS AND METHODS: Sera taken at therapy baseline from a total of 222 metastatic melanoma patients (two retrospectively selected monocentric discovery cohorts, n = 130; one prospectively collected multicentric validation cohort, n = 92) and from 38 healthy controls were analyzed for PD-1 and PD-L1 concentration by sandwich enzyme-linked immunosorbent assay. RESULTS: Melanoma patients showed higher serum concentrations of PD-1 (P = 0.0054) and PD-L1 (P < 0.0001) than healthy controls. Elevated serum PD-1 and PD-L1 levels at treatment baseline were associated with an impaired best overall response (BOR) to anti-PD-1 (P = 0.014, P = 0.041), but not to BRAF inhibition therapy. Baseline PD-1 and PD-L1 serum levels correlated with progression-free (PFS; P = 0.0081, P = 0.053) and overall survival (OS; P = 0.055, P = 0.0062) in patients who received anti-PD-1 therapy, but not in patients treated with BRAF inhibitors. By combining both markers, we obtained a strong discrimination between favorable and poor outcome of anti-PD-1 therapy, with elevated baseline serum levels of PD-1 and/or PD-L1 associated with an impaired BOR (P = 0.037), PFS (P = 0.048), and OS (P = 0.0098). This PD-1/PD-L1 combination serum biomarker was confirmed in an independent multicenter validation set of serum samples prospectively collected at baseline of PD-1 inhibition (BOR, P = 0.019; PFS, P = 0.038; OS, P = 0.022). Multivariable Cox regression demonstrated serum PD-1/PD-L1 as an independent predictor of PFS (P = 0.010) and OS (P = 0.003) in patients treated with PD-1 inhibitors. CONCLUSION: Our findings indicate PD-1 and PD-L1 as useful serum biomarkers to predict the outcome of PD-1 inhibition therapy in melanoma patients and to select patients for PD-1-based versus BRAF-based therapy strategies.

Atopy patch testing with aeroallergens in a large clinical population of dermatitis patients in Germany and Switzerland, 2000-2015: a retrospective multicentre study.

BACKGROUND: The diagnostic significance of the atopy patch test for the management of dermatitis possibly triggered by aeroallergens is still controversial. However, sufficiently large studies with routinely tested standardized aeroallergen patch test preparations in dermatitis patients are lacking. OBJECTIVE: To evaluate the reaction frequency and the reaction profiles of 10 until mid-2015 commercially available, standardized aeroallergen patch test preparations of the 'Stallerpatch' test series (Stallergenes, Antony Cedex, France) in a large multicentre patient cohort. METHODS: A retrospective data analysis of patients with suspected aeroallergen-dependent eczematous skin lesions was performed, who were patch tested in 15 Information Network of Departments of Dermatology-associated clinics between 2000 and 2015. Patients were stratified according to their atopic dermatitis (AD) status. RESULTS: The study group included 3676 patients (median age 41 years, 34.8% males, 54.5% AD). The most common aeroallergens causing positive patch test reactions were Dermatophagoides pteronyssinus (19.6%), Dermatophagoides farinae (16.9%), birch (6.2%), timothy grass (6.0%), cat dander (5.4%), mugwort (4.9%) and dog dander (4.6%). Reactions to other pollen allergen preparations, that is 5 grasses (3.2%), cocksfoot (2.1%) and plantain (1.6%), were less common. Positive patch test reactions to aeroallergens were consistently more frequent in patients with AD. These patients showed proportionally less dubious, follicular, irritant and weak positive reactions. Independent of AD status, a patient history of past or present allergic rhinitis was associated with an increased chance of a positive aeroallergen patch test reaction to pollen allergens. CONCLUSION: The aeroallergen patch test is a useful add-on tool in clinical routine, especially in patients with AD and/or respiratory allergy. A patch test series comprising Dermatophagoides pteronyssinus, Dermatophagoides farinae, birch, timothy grass, cat dander and mugwort seems to be suitable. Controlled studies with specific provocation and elimination procedures are required to further evaluate the diagnostic significance of the proposed screening series.

Factors increasing the risk for a severe reaction in anaphylaxis: An analysis of data from The European Anaphylaxis Registry.

BACKGROUND: Preventive measures to decrease the frequency and intensity of anaphylactic events are essential to provide optimal care for allergic patients. Aggravating factors may trigger or increase the severity of anaphylaxis and therefore need to be recognized and avoided. OBJECTIVE: To identify and prioritize factors associated with an increased risk of developing severe anaphylaxis. METHODS: Data from the Anaphylaxis Registry (122 centers in 11 European countries) were used in logistic regression models considering existing severity grading systems, elicitors, and symptoms to identify the relative risk of factors on the severity of anaphylaxis. RESULTS: We identified higher age and concomitant mastocytosis (OR: 3.1, CI: 2.6-3.7) as the most important predictors for an increased risk of severe anaphylaxis. Vigorous physical exercise (OR: 1.5, CI: 1.3-1.7), male sex (OR: 1.2, CI: 1.1-1.3), and psychological burden (OR: 1.4, CI: 1.2-1.6) were more often associated with severe reactions. Additionally, intake of beta-blockers (OR: 1.9, CI: 1.5-2.2) and ACE-I (OR: 1.28, CI: 1.05, 1.51) in temporal proximity to allergen exposition was identified as an important factor in logistic regression analysis. CONCLUSION: Our data suggest it may be possible to identify patients who require intensified preventive measures due to their relatively higher risk for severe anaphylaxis by considering endogenous and exogenous factors.

Adjuvant treatment with pegylated interferon α-2a versus low-dose interferon α-2a in patients with high-risk melanoma: a randomized phase III DeCOG trial.

BACKGROUND: Adjuvant treatment with interferon (IFN)-α-2a improved disease-free survival (DFS) and showed a trend for improving overall survival (OS) in melanoma. This trial was designed to examine whether PEG-IFN is superior to IFN with regard to distant metastasis-free survival (DMFS), DFS and OS. PATIENTS AND METHODS: In this multicenter, open-label, prospective randomized phase III trial, patients with resected cutaneous melanoma stage IIA(T3a)-IIIB (AJCC 2002) were randomized to receive PEG-IFN (180 µg subcutaneously 1×/week; 24 months) or IFN α-2a (3MIU subcutaneously 3×/week; 24 months). Randomization was stratified for stage, number of metastatic nodes, age and previous IFN treatment. The primary end point was DMFS; secondary end points were OS, DFS, quality of life (QoL) and tolerability. RESULTS: A total of 909 patients were enrolled (451 PEG-IFN versus 458 IFN). Neither 5-year DMFS [PEG-IFN 61.0% versus IFN 67.3%; hazard ratio (HR) 1.16, P = 0.21] nor 5-year OS (PEG-IFN 73.2% versus IFN 75.2%; HR 1.05, P = 0.70) nor 5-year DFS (PEG-IFN 57.3% versus IFN 60.9%; HR 1.09, P = 0.40) showed significant differences. Subgroup analyses in patients ± ulcerated primaries and of different tumor stages did not find differences in DMFS, OS or DFS between the treatment groups. One hundred and eighteen patients (26.2%) in the PEG-IFN and 61 patients (13.3%) in the IFN population did not receive the full dosage and length of treatment due to adverse events (P < 0.001). Leukopenia and elevation of liver enzymes were more common in the PEG-IFN arm (56% versus 23.5% LCP; 19.1% versus 9.4% AST; 33.0% versus 16.5% ALT). QoL was identical for nearly all domains. CONCLUSION: PEG-IFN did not improve the outcome over IFN. A higher percentage of patients under PEG-IFN discontinued treatment due to toxicity. CLINICAL TRIALSGOV IDENTIFIER: NCT00204529.

[Contact allergic gastritis : Rare manifestation of a metal allergy]. / Kontaktallergische Gastritis : Seltene Manifestation einer Metallallergie.

Only a few cases of contact allergic gastritis in patients with nickel allergy have been reported in the literature. We report a case of probable contact-allergic gastritis in a 46-year-old woman. Clinical examination revealed lichenoid mucosal lesions of the gums adjacent to a bridge and crowns that had been implanted several weeks previously. Since implantation, the patient suffered from gastrointestinal complaints including stomach pain. Gastroscopy and histological investigation of stomach biopsies showed eosinophilic gastritis. Patch testing done under the diagnosis of contact allergic stomatitis showed positive reactions to gold sodium thiosulphate, manganese (II) chloride, nickel (II) sulphate, palladium chloride, vanadium (III) chloride, zirconium (IV) chloride, and fragrances. The crowns and the bridge contained gold, palladium, and zirconium, hence they were replaced by titan-based dentition. Shortly after replacing the artificial dentition, all gastrointestinal symptoms resolved spontaneously without further treatment. Delayed-type allergy to components in the artificial dentition seem to have caused the gastritis.

A multicenter DeCOG study on predictors of vemurafenib therapy outcome in melanoma: pretreatment impacts survival.

BACKGROUND: Kinase inhibitors targeting the BRAF V600 mutation have become standard in the treatment of metastatic melanoma. Albeit in wide clinical use, the patterns associated with therapy outcome are not fully elucidated. The present study was aimed to identify predictive factors of therapy response and survival under the BRAF inhibitor vemurafenib. PATIENTS AND METHODS: This multicenter retrospective study analyzed patient, tumor, and pretreatment characteristics collected in BRAF V600-mutated stage IV melanoma patients before single-agent therapy with the BRAF inhibitor vemurafenib. RESULTS: A total of 300 patients from 14 centers were included into this study with a median follow-up time of 13.0 months. Median progression-free survival (PFS) was 5.1 months; median overall survival (OS) was 7.6 months. Best response under vemurafenib was associated with serum lactate dehydrogenase (LDH; ≤ versus >upper normal limit; P = 0.0000001), Eastern Cooperative Oncology Group (ECOG) overall performance status (OPS) (0 versus ≥ 1; P = 0.00089), and BRAF mutation subtype (V600E versus V600K; P = 0.016). Multivariate analysis identified ECOG OPS ≥ 1 [hazard ratio (HR) = 1.88; P = 0.00005], immunotherapy pretreatment (HR = 0.53; P = 0.0067), elevated serum LDH (HR = 1.45; P = 0.012), age >55 years (HR = 0.72; P = 0.019), and chemotherapy pretreatment (HR = 1.39; P = 0.036) as independent predictors of PFS. For OS, elevated serum LDH (HR = 1.99; P = 0.00012), ECOG OPS ≥ 1 (HR = 1.90; P = 0.00063), age >55 years (HR = 0.65; P = 0.011), kinase inhibitor pretreatment (HR = 1.86; P = 0.014), immunotherapy pretreatment (HR = 0.57; P = 0.025), chemotherapy pretreatment (HR = 2.17; P = 0.039), and male gender (HR = 0.70; 95% confidence interval 0.50-0.98; P = 0.039) were found as predictors. CONCLUSION: Our data demonstrate that the type of pretreatment strongly influences the outcome of vemurafenib therapy, with a precedent immunotherapy showing a positive, and a prior chemotherapy and kinase inhibitors showing a negative impact on survival, respectively. Moreover, we show that the patient's OPS, serum LDH, age, and gender independently impact vemurafenib therapy outcome. These findings should be taken into account for the future design of therapy sequencing in BRAF V600 mutation-positive melanoma patients.

Contact allergy induced by bisphenol A diglycidyl ether leachables from aluminium tubes for pharmaceutical use.

BACKGROUND: Aluminium tubes for pharmaceutical use are internally lacquered with epoxy resins (ER) based on bisphenol A diglycidyl ether (BADGE). Recently, it was shown that remnants of ER polymerization like BADGE are extractable from epoxy-based coatings of commercially available tubes and may leach into semi-solid drug preparations. We aimed to evaluate the safety of BADGE-contaminated macrogol ointments in individuals sensitized to ER based on BADGE by use tests. METHODS: Repeated open application testing (ROAT) in 11 patients sensitized to ER based on BADGE with BADGE in macrogol ointments (3 mg/kg; 30 mg/kg, equivalent to BADGE concentration determined in macrogol ointment after storage in a commercially available tube; 300 mg/kg). RESULTS: The 30 mg/kg BADGE ointment elicited reactions in three patients, and another three patients reacted to 300 mg/kg BADGE ointment. No reactions to the vehicle control and 3 mg/kg BADGE were observed. CONCLUSIONS: Elevated BADGE concentrations in ER-coated aluminium tubes pose a risk of developing contact dermatitis to patients sensitized to ER based on BADGE. Quality standards are deemed necessary for the production of ER-coated aluminium tubes intended for pharmaceutical use and should consider the results of the present ROAT study.

[Malignant head and neck melanoma: Part 2: Therapy]. / Maligne Melanome im Kopf-Hals-Bereich: Teil 2: Therapie.

Resection margins of melanomas in the head and neck region often have to be adapted according anatomical circumstances. In the case of thicker primary tumors or after complete resection of locoregional lymph node metastases, adjuvant therapy with interferon-α can be performed; in some cases, adjuvant radiotherapy may also be indicated. In the case of inoperable lymph node or distant metastases, systemic treatment is required. Beside well-established mono- or polychemotherapy regimens, newer targeted therapies with BRAF inhibitors (vemurafenib, dabrafenib), mitogenic-activated protein kinase (MEK) inhibitors (trametinib, binimetinib, and cobimetinib), and kinase inhibitors (imatinib, sunitinib, nilotinib, dasatinib) are also available.

[Malignant head and neck melanoma : Part 1: Diagnosis and histological particularities]. / Maligne Melanome im Kopf-Hals-Bereich : Teil 1: Diagnostik und histologische Besonderheiten.

About 15% of all cutaneous melanomas develop in the head and neck region. Mucosal melanomas are rare and represent only 1% of all melanomas, however, most frequently, these are located in the nose, the paranasal sinuses and the oral cavity. Visual diagnosis and reflected-light microscopy are relevant for the evaluation of melanoma-suspect lesions. Histological investigation of resected tumors need special skills of the histopathologist and includes in case of high-risk tumors investigations of mutations in the tumor tissue concerning NRAS, BRAF and KIT. The risk of lymphatic or hematogeneous spread rises with increasing tumor thickness and the presence of further prognostic risk factors such as ulceration of the primary tumor or the presence of mitoses within the tumor.

Symptom profile and risk factors of anaphylaxis in Central Europe.

BACKGROUND: Anaphylaxis is the most severe manifestation of an IgE-dependent allergy. Standardized acquired clinical data from large cohorts of well-defined cases are not available. The aim of this study was to analyse the symptom profile and risk factors of anaphylaxis in a large Central European cohort. METHODS: We acquired data from patients in Germany, Austria and Switzerland who experienced a severe allergic reaction defined by the onset of severe pulmonary and/or severe cardiovascular symptoms. The data were gained via an online questionnaire from 83 medical centres specialized in allergy. Data were collected from 2006 to 2010 and analysed by using a multinomial regression model. RESULTS: A total of 2012 paediatric and adult patients were included into the present analysis. The skin (84%) was the most frequently affected organ followed by the cardiovascular (72%) and the respiratory (68%) system. The regression model analysing the onset of cardiovascular versus respiratory symptoms revealed a strong impact of age (adjusted OR = 6.08; 95% CI, 3.35-11.01; P < 0.001). Furthermore, the elicitor food (adjusted OR = 0.29; 95% CI, 0.21-0.41, P < 0.001) and the presence of atopic diseases (adjusted OR = 0.54; 95% CI, 0.40-0.73, P < 0.001) were significantly associated with the onset of respiratory symptoms. CONCLUSION: Data from individuals who experienced anaphylaxis can support the identification of risk factors. The present study indicates that age, the elicitor itself and the presence of atopic diseases have an impact on the symptom profile of anaphylaxis. Identifying further risk factors of anaphylaxis is of significant importance for clinical practice in the future.

[Disseminated infiltrated cutaneous pruritis]. / Disseminierte infiltrierte juckende Läsionen am Körper.

The diagnosis of scabies is clinically not always simple without the detection of mites. Histology can be difficult, particularly without clinico-pathologic correlation. [corrected] Even after adequate antiscabies treatment the dermatological symptoms and complaints can persist and necessitate an [corrected] intensive follow-up treatment. The case example described here underlines that in consideration of the multifaceted clinical appearance and the sometimes difficult detection of mites, scabies should always be considered as a differential diagnosis in cases of persistent pruritis.

Lichen striatus and blaschkitis: reappraisal of the concept of blaschkolinear dermatoses.

BACKGROUND: Blaschkitis (BL) and lichen striatus (LS) are rare dermatoses occurring along the Blaschko lines of the skin with preferential occurrence in distinct age categories. Controversy exists regarding the pathogenesis and classification of BL and LS within the spectrum of blaschkolinear dermatoses. OBJECTIVES: To describe the clinicopathological characteristics of six cases of BL/LS with special emphasis on immunophenotyping the inflammatory infiltrate. Additionally, we review and critically discuss current concepts of the blaschkolinear dermatoses. METHODS: Skin biopsies from six patients with BL and LS were analysed retrospectively. The immunophenotypes of the inflammatory cells were determined and related to clinical features. RESULTS: The clinical characteristics of the diseases occurred equally in both genders and all ages. BL and LS had similar histopathological findings with respect to epidermal changes and composition of the inflammatory infiltrates. Characteristically, a lichenoid lymphocytic infiltrate with exocytosis of inflammatory cells and obvious alterations of the interface zone was observed. CONCLUSIONS: We characterize the two main blaschkolinear dermatoses BL and LS sensu stricto morphologically and open new insights into the pathogenesis of these diseases. We propose the concept of a wide spectrum of blaschkolinear dermatoses with BL and LS located somewhere within the spectrum. We do not think that it is helpful for clinicians to enlarge the spectrum of blaschkolinear diseases and to create numerous 'new' entities. Rather, our aim was to unify diseases with similar clinical and histopathological features and common genetic pathomechanisms underlying phenotypic variations.

Expression of CD30 antigen in superficial mycotic infections of the skin: a possible non-specific finding without clinical relevance.

Expression of CD30 is a distinct marker of lymphocytic activation, originally described in Reed-Sternberg cells of Hodgkin's disease. Recently, the first two cases in which CD30 was expressed in tissue samples derived from superficial cutaneous fungal infections have been reported. The objective of this study was to investigate the expression of CD30 in tinea corporis and to discuss the clinical relevance of CD30. Twenty-three skin biopsies from 23 patients with mycotic infections of the skin were analysed retrospectively. The immunophenotypic expression of CD30 was investigated. In the series investigated, some large CD30-positive cells located in the upper dermal infiltrate were noted in two of 23 biopsy specimens (8.7%). The existence of CD30-positive cells was independent of the density and composition of the accompanying inflammatory infiltrate. We showed that the expression of CD30 in dermatophytoses is not a consistent finding. Instead, as a sign of lymphocytic activation, CD30 expression is observed coincidentally in cutaneous fungal infections. Our data confirm the observation that CD30 antigen is expressed in a variety of benign and malignant skin disorders, including cutaneous fungal infections, probably as an epiphenomenon without clinical relevance.

[Reticulated teleangiectatic erythema after implantation of medical devices. An increasingly occurring phenomenon?]. / Retikuläre teleangiektatische Erytheme nach Implantation von elektrischen medizinischen Geräten. Ein an Häufigkeit zunehmendes Phänomen?

Reticulated telangiectatic erythema (RTE) is a rare skin reaction to extraneous materials. We present three cases in which asymptomatic persistent erythemas developed in the area of implantation after medical devices were inserted. Topical and systemic treatment did not improve the skin changes. Patch testing including applied materials showed negative results in all cases. Histological investigation of punch biopsy specimens showed moderate dilatated vessels and a slight lymphocytic infiltrate. Due to our findings and in synopsis with the clinical impression we diagnosed RTE. As RTE is asymptomatic in most cases, the devices need not be removed.

[Adder bite. A rare dermatologic emergency]. / Kreuzotterbiss. Ein seltener dermatologischer Notfall.

Bites by poisonous snakes are rare dermatologic emergencies. A 43-year-old woman was bitten on her right forefinger by an adder during a hiking vacation in Austria. Her right arm and chest wall became swollen and then hemorrhagic, but she responded well to analgesics and immobilization. Administration of a specific antiserum was not necessary because of the lack of a systemic reaction.

Temozolomide plus pegylated interferon alfa-2b as first-line treatment for stage IV melanoma: a multicenter phase II trial of the Dermatologic Cooperative Oncology Group (DeCOG).

BACKGROUND: Combination of temozolomide (TMZ) with nonpegylated interferon alfa is associated with increased efficacy in terms of response rates compared with monotherapy. A multicenter phase II study was carried out to assess the activity and toxicity of TMZ plus pegylated interferon alfa-2b (peg-IFNalpha-2b), hypothesizing improved efficacy due to modified pharmacokinetic properties of the novel interferon (IFN) formulation. PATIENTS AND METHODS: In all, 124 patients with stage IV melanoma without prior chemotherapy and no cerebral metastases were treated with 100 mug peg-IFNalpha-2b s.c. per week and oral TMZ 200 mg/m(2) (days 1-5, every 28 days). Primary study end point was objective response, and secondary end points were overall and progression-free survival (PFS) and safety. RESULTS: In all, 116 patients were assessable for response: 2 (1.7%) had a complete response and 19 (16.4%) a partial response (overall response rate 18.1%). Of total, 25.0% achieved disease stabilization and 56.9% progressed. Overall survival was 9.4 months; PFS was 2.8 months. Grade 3/4 thrombocytopenia occurred in 20.7% and grade 3/4 leukopenia in 23.3%. CONCLUSIONS: The efficacy of TMZ plus peg-IFNalpha-2b in this large phase II study is moderate and comparable to published results of the combination of TMZ with non-peg-IFN. Likewise, the safety profile of peg-IFNalpha-2b seems to be similar to non-peg-IFN when combined with TMZ.

[Cutaneous reactions to molecular targeted therapies]. / Kutane Nebenwirkungen molekular zielgerichteter Therapien.

The use of molecular targeted therapies currently is on the rise in the treatment of severe diseases, particularly for malignant tumors. The targeted agents show a high specificity against one or more molecular target structures, hereby inhibiting or modifying signal transduction pathways connected to these targets, and thus strongly altering proliferation, activation and interaction of the targeted cells. These manipulations of highly specific signaling pathways are associated with again highly specific side effects, which often affect the skin. These cutaneous reactions present a new spectrum of adverse drug events to the dermatologist. We reviews the cutaneous reactions of molecular targeted agents used in the treatment of psoriasis (alefacept, efalizumab, etanercept, infliximab and adalimumab), as well as agents used in cancer therapy (imatinib, sorafenib, sunitinib, EGFR antagonists and CTLA-4-antagonists).

[Gastric signet ring cell carcinoma presenting. An erysipelas-like cutaneous metastasis of the abdominal skin]. / Erysipelas carcinomatosum der Abdominalhaut. "Erstmanifestation" eines Siegelringzellkarzinoms des Magens.

A 71-year-old patient presented with diffuse and poorly circumscribed erythematous plaques of the abdominal skin, present for 5 months. Histology revealed a diffuse infiltration of the entire dermis with cytokeratin-positive signet-ring-cells. Subsequently, an extensive search for a primary adenocarcinoma uncovered a locally advanced signet-ring-cell gastric carcinoma. There were no metastases to other organs. This case shows the unusual clinical-diagnostic sequence of a patient with a signet-ring-cell-carcinoma of the stomach presenting with an erysipelas-like cutaneous metastasis of the abdominal skin.

Contact dermatitis of the lips due to late-type sensitization against dalbergiones in a wooden recorder.

BACKGROUND: Late-type sensitizations against wood are rare and are mostly seen in patients with occupational contact with saw dust. Generally, commercial wooden products only lead to sensitization or dermatitis in cases when contact to the unprotected skin is direct, intensive and of longer duration, i.e. by wearing wooden jewelry or by playing wooden instruments. Causative for the sensitization process are ingredients of the wood core such as alkaloids, glycosides, anthrachinones, saponines, phenols, catechols, flavonoids, cumarins, and benzo-, naphtho-, furano-, and phenanthrenquinones and their precursors. CASE REPORT: We report the case of a 70-year-old patient who developed cheilitis after playing different wooden recorders made of African blackwood, rosewood, cedar, olive, and pear. METHODS: Patch testing with baseline series of contact allergens and saw dust of the recorders were performed as well as skin prick tests with common inhalant allergens and saw dust of the recorders. RESULTS: Patch testing showed sensitizations against African blackwood, rosewood, fragrance mix 2 and hydroxyisohexyl-3-cyclohexene carboxaldehyde. Skin prick testing was without pathological results. CONCLUSION: African blackwood and rosewood contain (S)-4'-hydroxy-4-methoxydalbergione and (S)-4-methoxydalbergione. As a result of the chemical affinity between the dalbergiones, cross-reactions between different woods are observed. The case presented shall show the diagnostic procedure in cases in which sensitizations against wood components are suspected.