[Social rights claims for malignant melanoma patients : Providing patient information in German dermatological practices]. / Sozialrechtliche Ansprüche beim malignen Melanom : Aufklärung von Patienten in deutschen dermatologischen Praxen.

BACKGROUND: Treatment of patients with malignant melanoma includes informing the patients about their rights regarding social/disability benefits. In particular, every patient has the right to rehabilitation treatment according to SGB V and IX (SGB: Sozialgesetzbuch; Social Security Code) and to an examination regarding the classification of the disability. OBJECTIVES: The present study examines the extent to which patients with invasive malignant melanoma are informed after initial diagnosis about their social rights to medical rehabilitation measures and the classification of disability. MATERIALS AND METHODS: In the course of a survey in 2014, n = 1800 German dermatological practices were contacted and provided a standardized questionnaire on several care-relevant questions, including the aforementioned ones. RESULTS: Evaluable questionnaires were submitted by n = 424 practices. In all, 52% of dermatologists stated that they regularly provided information on the right to rehabilitation, 15% sometimes, 41% rarely or never. Furthermore, 44% of dermatologists regularly, 17% sometimes and 38% rarely or never informed their patients about the classification of disability. Relevant differences were found in regional comparisons. CONCLUSIONS: Practicing dermatologists seem to transfer the information requirement to the clinics involved in the treatment. It would be beneficial if the information were also provided again by the dermatologists in private practice. In view of the known limited capacity to receive new information from patients with newly diagnosed melanoma, repeated counselling appears to be more patient-friendly.

The genetic basis for most patients with pustular skin disease remains elusive.

BACKGROUND: Rare variants in the genes IL36RN, CARD14 and AP1S3 have been identified to cause or contribute to pustular skin diseases, primarily generalized pustular psoriasis (GPP). OBJECTIVES: To better understand the disease relevance of these genes, we screened our cohorts of patients with pustular skin diseases [primarily GPP and palmoplantar pustular psoriasis (PPP)] for coding changes in these three genes. Carriers of single heterozygous IL36RN mutations were screened for a second mutation in IL36RN. METHODS: Coding exons of IL36RN, CARD14 and AP1S3 were sequenced in 67 patients - 61 with GPP, two with acute generalized exanthematous pustulosis and four with acrodermatitis continua of Hallopeau. We screened IL36RN and AP1S3 for intragenic copy-number variants and 258 patients with PPP for coding changes in AP1S3. Eleven heterozygous IL36RN mutations carriers were analysed for a second noncoding IL36RN mutation. Genotype-phenotype correlations in carriers/noncarriers of IL36RN mutations were assessed within the GPP cohort. RESULTS: The majority of patients (GPP, 64%) did not carry rare variants in any of the three genes. Biallelic and monoallelic IL36RN mutations were identified in 15 and five patients with GPP, respectively. Noncoding rare IL36RN variants were not identified in heterozygous carriers. The only significant genotype-phenotype correlation observed for IL36RN mutation carriers was early age at disease onset. Additional rare CARD14 or AP1S3 variants were identified in 15% of IL36RN mutation carriers. CONCLUSIONS: The identification of IL36RN mutation carriers harbouring additional rare variants in CARD14 or AP1S3 indicates a more complex mode of inheritance of pustular psoriasis. Our results suggest that, in heterozygous IL36RN mutation carriers, there are additional disease-causing genetic factors outside IL36RN.

[Depression and anxiety disorders among psoriasis patients: protective and exacerbating factors]. / Depression und Angststörung bei Psoriasispatienten: Schutz- und Risikofaktoren.

BACKGROUND: Psoriasis is associated with higher risk for depression and anxiety disorders. Yet the complex system linking disease symptoms with physical and mental outcomes is poorly understood. OBJECTIVES: The central aim of this study was to identify physical, psychological, and social factors that exacerbate or protect against the perception of symptoms of depression and anxiety among individuals starting in-patient treatment for psoriasis. Another aim was to investigate if improved clinical status of the psoriasis is associated with improved psychological and physical wellbeing one year after treatment. MATERIALS AND METHODS: In this follow-up study a sample of 381 psoriasis in-patients in Germany were questioned before starting treatment and one year after treatment (166 participants) using instruments to measure socioeconomic variables, perceived somatic severity, life quality (DLQI, SF-8), feelings of stigmatization (QES), and depression and anxiety (HADS-D). Coping (Trier Coping Scale) and pathological worry (PSWQ-PW) were also measured at the initial time point. Multiple regression analyses of variance for repeated measurements and of correlation were conducted. RESULTS: Self-reported symptoms of anxiety and depression were higher than in normal populations. Perceived severity of physical symptoms was not correlated with depression or anxiety at the initial time point. The strongest predictors of depression and anxiety in our sample were measures of life quality. Life quality was predicted in a large part by stigmatization. Increased momentary symptom severity and increased perceived discomfort over time was not associated with increased perception of symptoms of depression. CONCLUSIONS: Our findings extend previous research on the importance of stigmatization for quality of life to the specific outcome of depression and anxiety. It confirms the desirability of early screening of psoriasis patients for depression and anxiety and initiating treatment by a qualified therapist.

Perceived relationships between severity of psoriasis symptoms, gender, stigmatization and quality of life.

BACKGROUND: Psoriasis is a skin disease with negative physical, psychological and social repercussions for those affected, but we still lack knowledge of how somatic and non-somatic factors directly and indirectly combine to affect patients' quality of life (QoL). OBJECTIVES: This study seeks a better understanding of the relations between symptom severity, discomfort, stigmatization, gender and QoL among psoriasis patients. METHODS: The sample comprised 381 psoriasis patients in inpatient care. Symptom severity and discomfort were measured subjectively with single items. Stigmatization was measured with the Questionnaire on Experience with Skin Complaints. QoL was measured using the Dermatology Life Quality Index (DLQI) and the Short Form-8 Health Survey (SF-8). RESULTS: Symptom severity was associated with higher discomfort, stigmatization and lower skin-related QoL. Symptom severity correlated weakly with more general aspects of QoL as measured by the SF-8. Men and women reported different experiences with discomfort, stigmatization and mental aspects of QoL (SF-8 mental component summary score). Some stigmatization parameters function as mediating variables between symptom severity and QoL. CONCLUSIONS: Our findings suggest that the effect of stigmatization on skin-related QoL is driven by symptom severity and stigmatization combined, whereas its effect on mental health is driven mostly by stigmatization alone. Further, although women and men experience the social impact of psoriasis differently, the effect of stigmatization on QoL is similar for both genders.

Detection of mRNA for eotaxin-2 and eotaxin-3 in human dermal fibroblasts and their distinct activation profile on human eosinophils.

As many new biologically active chemokines have been cloned exploring the genomic DNA sequence database in the vicinity of already known chemokine sequences without demonstrating their natural origin, it is important to transfer findings from in vitro experiments with chemokines into the in vivo situation. With respect to eosinophils and fibroblasts that play an important part in the pathogenesis of allergic and autoimmune diseases, the role of the recently discovered members of the eotaxin family, eotaxin-2 and eotaxin-3, is not really understood. In order to elucidate the origin and biologic potency of the eotaxin family this study was performed. Conventional reverse transcription-polymerase chain reaction analysis was suitable to detect mRNA for eotaxin and eotaxin-3 but not for eotaxin-2 in dermal fibroblasts. In contrast to conventional reverse transcription-polymerase chain reaction, LightCycler analysis revealed that dermal fibroblasts constitutively expressed mRNA not only for eotaxin and eotaxin-3 but also for eotaxin-2. Moreover, with this technique we investigated mRNA expression levels after stimulation of fibroblasts with interleukin-4 and interleukin-4 plus tumor necrosis factor-alpha: the rank order of expression levels within the eotaxin family was eotaxin > eotaxin-3 > eotaxin-2. To address the question of the efficacy of eotaxin-3, we compared its activity with eotaxin, eotaxin-2, monocyte chemotactic protein-3, monocyte chemotactic protein-4, and RANTES in different test systems for eosinophils. The efficacy of the CC chemokines at equimolar concentrations with respect to the chemotactic response of human eosinophils was eotaxin-3 = eotaxin = eotaxin-2 > RANTES > monocyte chemotactic protein-4. The rank order of activity with respect to actin polymerization and release of toxic reactive oxygen species was eotaxin-3 = eotaxin = eotaxin-2 and eotaxin = eotaxin-2 > eotaxin-3 = monocyte chemotactic protein-3 = monocyte chemotactic protein-4 = RANTES, respectively. This study indicated a distinct profile in expression levels of the members of the eotaxin family in dermal fibroblasts. Indeed, all three eotaxin ligands demonstrated activation of human eosinophils with similar efficacies for chemotaxis, cytoskeletal rearrangements, activation of Gi proteins and transients of [Ca2+]i, but a distinct profile of activity with respect to the binding to CCR3 and the release of toxic reactive oxygen species. These findings may help to understand further the role of CC chemokines in fibroblast/eosinophil activation, which is of interest particularly in allergic and autoimmune diseases.

Characterization of synthetic C3a analog peptides on human eosinophils in comparison to the native complement component C3a.

The C3a anaphylatoxin is a potent proinflammatory mediator derived from the complement system inducing biologic effects of human eosinophils like Ca2+ transients and the activation of the respiratory burst. These findings support an important role for C3a in diseases typically associated with a peripheral blood or tissue eosinophilia. Synthetic human C3a analogue peptides with variations at the C-terminal effector domain have been evaluated with respect to their binding affinity and signaling potency on human eosinophils. Flow cytometrical analysis and RT-PCR revealed that the C3a receptor is constitutively expressed on human eosinophils. Peptides bearing an N-terminal 9-fluorenylmethoxycarbonyl and the 6-aminohexanoyl motif were the most powerful peptides tested. Amino acid replacements in the conserved C-terminal pentapeptide decreased binding affinity and functional potency substantially. In addition, synthetic C3a analogue peptides induced C3aR internalization, led to transient changes of intracellular Ca2+ concentration, and did release reactive oxygen species in human eosinophils indicating the in vivo relevance of C3a-related sequences. The tripeptide LAR was found to be essential for C3a receptor binding on human eosinophils. Moreover, the putative binding motif of C3a anaphylatoxin is also crucial for the induction of biologic effects in the human system such as changes of intracellular Ca2+ concentration and the release of reactive oxygen species. This study demonstrates that the carboxyl terminus is important for the interaction with the C3aR and the biologic potency of C3a anaphylatoxin in the human system and plays a key role in the activation process of human eosinophils.