Comparison of Two Diagnostic Assays for Anti-Laminin 332 Mucous Membrane Pemphigoid

Anti-laminin 332 mucous membrane pemphigoid (MMP) is an autoimmune blistering disease characterized by predominant mucosal lesions and autoantibodies against laminin 332. The exact diagnosis of anti-laminin 332 MMP is important since nearly 30% of patients develop solid cancers. This study compared two independently developed diagnostic indirect immunofluorescence (IF) tests based on recombinant laminin 332 expressed in HEK239 cells (biochip mosaic assay) and the migration trails of cultured keratinocytes rich in laminin 332 (footprint assay). The sera of 54 anti-laminin 332 MMP, 35 non-anti-laminin 332 MMP, and 30 pemphigus vulgaris patients as well as 20 healthy blood donors were analyzed blindly and independently. Fifty-two of 54 and 54/54 anti-laminin 332 MMP sera were positive in the biochip mosaic and the footprint assay, respectively. In the 35 non-anti-laminin 332 MMP sera, 3 were positive in both tests and 4 others showed weak reactivity in the footprint assay. In conclusion, both assays are easy to perform, highly sensitive, and specific, which will further facilitate the diagnosis of anti-laminin 332 MMP

Clinical and Serological Characterization of Orf-Induced Immunobullous Disease

Importance: Ecthyma contagiosum, or orf, is a viral zoonotic infection caused by Poxviridae. Although human orf infection is considered to follow a self-limited course, various immunological reactions may be triggered, including immunobullous diseases. In the majority of the latter cases, the antigenic target remained enigmatic. Objective: To characterize the predominant autoantigen in orf-induced immunobullous disease and further describe this clinical entity. Design, Setting, and Participants: This multicenter case series sought to provide detailed clinical, histopathological and immunological characteristics of a patient with orf-induced pemphigoid. Based on this index patient, serological analyses were conducted of 4 additional patients with previously reported orf-induced immunobullous disease. Immunoblotting with extracellular matrix and a recently established indirect immunofluorescence assay for detection of serum anti-laminin 332 IgG were performed. Exposures: The disease course and clinical characteristics of orf-induced immunobullous disease were observed. Main Outcomes and Measures: Orf-induced immunobullous disease is primarily characterized by anti-laminin 332 autoantibodies, predominant skin involvement, and a self-limiting course. The study provides further details on epidemiological, clinical, immunopathological, diagnostic, and therapeutic aspects of orf-induced immunobullous disease. Results: In all 5 patients, IgG1 and/or IgG3 autoantibodies against laminin 332 were identified. The α3, β3, and γ2 chains were recognized in 2, 4, and 1 patient(s), respectively. Conclusions and Relevance: In this case series, laminin 332, a well-known target antigen in mucous membrane pemphigoid, was a major autoantigen in orf-induced immunobullous disease, even though predominant mucosal lesions were lacking in this autoimmune blistering disease. Orf-induced anti-laminin 332 pemphigoid is proposed as distinct clinical entity

Effectiveness of outpatient cognitive-behavioral therapy for adolescents under routine care conditions on behavioral and emotional problems rated by parents and patients: an observational study

Few studies have examined the effectiveness of outpatient cognitive-behavioral therapy (CBT) delivered in routine care settings for children and adolescents with mental disorders. This observational study examined changes in behavioral and emotional problems of adolescents with mental disorders during routine outpatient CBT delivered at a university outpatient clinic and compared them with a historical control group of youths who received academic tutoring of comparable length and intensity. Assessments were made at the start and end of treatment (pre- and post-assessment) using parent ratings of the German versions of the Child Behavior Checklist (CBCL) and self-ratings of the Youth Self-Report (YSR) scale. For the main analysis, 677 adolescents aged 11aEuro'21 years had complete data. Changes from pre- to post-assessment showed significant reductions in mental health problems on both parent- and self-ratings. Pre- to post-effect sizes (Cohen's d) were small-to-medium for the total sample (d = 0.23 to d = 0.62) and medium-to-large for those adolescents rated in the clinical range on each (sub)scale at the start of treatment (d = 0.65 to d = 1.48). We obtained medium net effect sizes (d = 0.69) for the CBCL and YSR total scores when patients in the clinical range were compared to historical controls. However, a substantial part of the sample remained in the clinical range at treatment end. The results suggest that CBT is effective for adolescents with mental disorders when administered under routine care conditions but must be interpreted conservatively due to the lack of a direct control condition

Treatment satisfaction following routine outpatient cognitive-behavioral therapy of adolescents with mental disorders: a triple perspective of patients, parents and therapists

The present study investigates treatment satisfaction (TS) rated by multiple informants (patient, parent, therapist) following routine outpatient cognitive-behavioral therapy (CBT) within a large sample (n=965) of clinically referred adolescents aged 11-20years. Moreover, potential predictors of TS were analyzed (patient-related variables, mental disorder characteristics, socio-demographic factors and treatment variables). Overall, our results show a high treatment satisfaction in patient, parent and therapist ratings, with the therapists being the most critical raters (completely/predominantly satisfied: 87.8% in patient, 92.0% in parent, and 64.0% in therapist ratings). Correlations between the three raters were only small to moderate, but statistically significant. Regression analysis examining differential effects found that mental disorder characteristics (parent- and patient-reported symptoms at post) and treatment variables (especially cooperation of patients and parents as rated by therapists) explained most of the variance in TS, whereas patient-related or socio-demographic variables did not emerge as relevant predictors of TS. The amounts of explained variance were R-adj(2) = 0.594 in therapist rating, R-adj(2) = 0.322 in patient rating and R-adj(2). = 0.203 in parent rating

Parent- and Teacher-Rated Effectiveness of Cognitive-Behavioral Therapy for Children and Adolescents Under Usual Care Conditions in a University Outpatient Clinic

Compared to randomized controlled trials, studies examining the effectiveness of cognitive behavioral therapy (CBT) in children and adolescents with mental disorders are rare, and a teacher perspective is scarce. The present study investigated the effectiveness of routine CBT in 519 patients aged 6-18years with mental disorders. Changes in mental health problems were assessed in teacher (Teacher Report Form, TRF) and parent rating (Child Behavior Checklist, CBCL) and were analyzed within the total sample, yielding statistically significant, small to medium effect sizes (teacher rating: d=.74-2.39; parent rating: d=.65-1.18). Changes in a subgroup of patients with elevated symptom scores at treatment start were compared to a historical control group receiving weekly academic tutoring. Net total score effect sizes lay between d=0.98 and d=1.29 for teacher rating (parent rating: d=0.84 to d=1.01). Nevertheless, a substantial number of patients remained in the clinical range. Symptom changes during family- and patient-based CBT interventions did not differ from treatments including additional school-based interventions, as was also the case for the comparison of treatments with and without additional pharmacotherapy

Parent- and therapist-rated treatment satisfaction following routine child cognitive-behavioral therapy

This observational study examined treatment satisfaction (TS) following routine outpatient cognitive-behavioral therapy (CBT) in a large sample of children (n = 795; aged 6 to 10 years). TS was investigated in parent and therapist rating. Means, standard deviations and inter-rater correlations were calculated to investigate TS. Regression analysis was conducted to examine potential correlates of TS (patient-related variables, mental disorder characteristics, socio-demographic factors and treatment variables). High TS in parent and therapist rating was found, with therapists showing a lower degree of TS than parents (completely or predominantly satisfied: parent rating 94.1%, therapist rating 69.5%). A statistically significant, moderate inter-rater correlation was found. Regression analysis explained 21.8% of the variance in parent rating and 57.2% in therapist rating. Most of the TS variance was explained by mental disorder characteristics (parent-rated symptoms and therapist-rated global impairment at treatment end) and by treatment variables (especially the therapist-rated cooperation of parents and patients), whereas socio-demographic and patient-related variables did not show any relevant associations with TS. Based on these results, to optimize TS, therapists should concentrate on establishing a sustainable cooperation of parents and children during therapy, and work to achieve a low global impairment at treatment end

Multiple modes of action mediate the therapeutic effect of IVIg in experimental epidermolysis bullosa acquisita

Substitution of IgG in antibody deficiency or application of high-dose intravenous IgG (IVIg) in patients with autoimmunity are well-established treatments. Data on the mode of action of IVIg are, however, controversial and may differ for distinct diseases. In this study, we investigated the impact and molecular mechanism of high-dose IgG treatment in murine autoantibody-induced skin inflammation, namely, epidermolysis bullosa acquisita (EBA). EBA is caused by antibodies directed against type VII collagen (COL7) and is mediated by complement activation, release of reactive oxygen species, and proteases by myeloid cells. In murine experimental EBA the disease can be induced by injection of anti-COL7 IgG. Here, we substantiate that treatment with high-dose IgG improves clinical disease manifestation. Mechanistically, high-dose IgG reduced the amount of anti-COL7 in skin and sera, which is indicative for an FcRn-dependent mode-of-action. Furthermore, in a non-receptor-mediated fashion, high-dose IgG showed antioxidative properties by scavenging extracellular reactive oxygen species. High-dose IgG also impaired complement activation and served as substrate for proteases, both key events during EBA pathogenesis. Collectively, the non-receptor-mediated anti-inflammatory properties of high-dose IgG may explain the therapeutic benefit of IVIg treatment in skin autoimmunity

Effectiveness of Cognitive-Behavioral Therapy for Children and Adolescents Under Routine Care Conditions in a University Outpatient Clinic As Rated by Parents

Background: There is a lack of studies examining the effectiveness of cognitive-behavioral therapy under routine care conditions. Objective: Changes in mental health problems of children and adolescents as rated by parents during outpatient therapy within a university clinic were examined. Psychologists or educationalists in advanced psychotherapy training provided all therapies. Therapists were guided by accredited supervisors for cognitive-behavioral therapy (one hour of supervision every fourth therapy session). Method: 976 completed treatments were analyzed with parent rating, using the Child Behavior Checklist's pre-post-comparisons. Effect sizes were computed and the clinical relevance of these changes was analyzed. Examinations were done for the whole sample and separately for youths that were rated within a clinical range by their parents at the beginning of treatment. Additionally, analyses for representativeness were calculated. Results: Within the complete sample, small to medium statistically significant decreases of mental health problems were observed. Youths who had been rated within clinical range by parent rating on the CBCL mainly showed large effect sizes. Neither could be explained by spontaneous changes or regression effects. It has to be noted that one quarter to one third of all patients were rated within a clinical range by their parents. Conclusions: These results show first hints of the effectiveness of cognitive-behavioral therapy of youths with mental health problems under routine care conditions. The results must be interpreted conservatively because of the lack of a control group