Using standardized patients for undergraduate clinical skills training in an introductory course to psychiatry

Background The goal of this study was to assess the value and acceptance of Standardized or Simulated Patients (SPs) for training clinically inexperienced undergraduate medical students in psychiatric history taking, psychopathological assessment, and communication with psychiatric patients. Methods As part of a newly developed introductory course to psychiatry, pairs of 3rd year medical students conducted psychiatric assessments of SPs, including history and psychopathological state, under the supervision of a clinical lecturer. Prior to the assessment, students attended introductory lectures to communication in psychiatry and psychopathology but were clinically inexperienced. After the interview, the students’ summary of their findings was discussed with other students and the lecturer. Students, lecturers, and actors were invited to a survey after the course. Questions for the students included self-reports about perceived learning success and authenticity of the interviews. Results 41 students, 6 actors and 8 lecturers completed the survey (response rates of 48%, 50%, and 100%, respectively). The survey results indicated that, despite their lack of clinical experience, students learned how to conduct a psychiatric interview, communicate in a non-judgmental and empathetic manner, take a psychiatric history and perform a psychopathological examination. SPs were perceived as authentic. The survey results suggested that this setting allowed for an enjoyable, non-distressful and motivating learning experience within a restricted time frame of just two afternoons. Conclusion The results indicated that the SP approach presented is useful for teaching clinical skills in psychiatry to students with limited previous clinical experience and knowledge of psychiatry. We argue that SPs can be used to teach practical psychiatric skills already during an early phase of the curriculum. Limitations of our study include a limited sample size, a temporal gap between the course and the survey, reliance on self-reports, and lack of comparison to alternative interventions

Bullous pemphigoid in infants: characteristics, diagnosis and treatment

BACKGROUND: Bullous pemphigoid (BP) in infants is a rare but increasingly reported autoimmune blistering skin disease. Autoantibody reactivity is usually poorly characterized. Current guidelines do not address specific aspects of the infantile form of BP. The objectives of this study are to define clinical and diagnostic characteristics of infantile BP and develop a treatment algorithm. METHODS: Detailed characterization of a current case series of five infants with BP from our departments. Comprehensive analysis of all reported cases (1-12 months) with respect to clinical and laboratory characteristics, treatment and outcome. RESULTS: In total 81 cases were identified (including our own). The mean age was 4.5 months. Moderately severe and severe disease was seen in 84% of cases. Involvement of hands and feet was present in all cases. Immunofluorescence microscopy was comparable with BP in adults. Where analyzed, the NC16A domain of bullous pemphigoid 180 kDa antigen/collagen XVII (BP180) was identified as the major target antigen. BP180 NC16A ELISA values in our cohort were significantly higher than in a control cohort of 28 newly diagnosed adult patients. 50% of patients were treated with systemic corticosteroids, 20% with a combination of systemic corticosteroids and dapsone or sulfapyridine and 10% with topical corticosteroids alone. 14% of patients needed a combination of multiple immunosuppressants. All but one patient reached remission. Relapses were rare. CONCLUSIONS: Presentation of infantile BP is often severe with blistering of hands and feet present in all cases. Pathogenesis and diagnostic criteria are comparable to adult BP, yet BP180 NC16A ELISA levels seem to be significantly higher in infants. The overall disease outcome is favorable. Based on the results of this study we propose a treatment algorithm for infantile BP

Protective Endogenous Cyclic Adenosine 5'-Monophosphate Signaling Triggered by Pemphigus Autoantibodies

Pemphigus vulgaris (PV) is an autoimmune skin disease mediated by autoantibodies directed against the cadherin-type cell adhesion molecules desmoglein (Dsg) 3 and Dsg1 and is characterized by loss of keratinocyte cohesion and epidermal blistering. Several intracellular signaling pathways, such as p38MAPK activation and RhoA inhibition, have been demonstrated to be altered following autoantibody binding and to be causally involved in loss of keratinocyte cohesion. In this paper, we demonstrate that cAMP-mediated signaling completely prevented blister formation in a neonatal pemphigus mouse model. Furthermore, elevation of cellular cAMP levels by forskolin/rolipram or β receptor agonist isoproterenol blocked loss of intercellular adhesion, depletion of cellular Dsg3, and morphologic changes induced by Ab fractions of PV patients (PV-IgG) in cultured keratinocytes. Incubation with PV-IgG alone increased cAMP levels, indicating that cAMP elevation may be a cellular response pathway to strengthen intercellular adhesion. Our data furthermore demonstrate that this protective pathway may involve protein kinase A signaling because protein kinase A inhibition attenuated recovery from PV-IgG–induced cell dissociation. Finally, cAMP increase interfered with PV-IgG–induced signaling by preventing p38MAPK activation both in vitro and in vivo. Taken together, our data provide insights into the cellular response mechanisms following pemphigus autoantibody binding and point to a possible novel and more specific therapeutic approach in pemphigus

Diagnostic Value of Linear Fluorescence Along the Basement Membrane of Sweat Gland Ducts in Bullous Pemphigoid

Linear IgG deposits along the basement membrane of adnexa has been proposed to be useful in the diagnosis of bullous pemphigoid (BP), but no controlled studies have been performed. This study evaluated linear IgG fluorescence of the basement membrane of sweat gland ducts (SGD) and other adnexa in perilesional biopsies from patients with BP (n = 64) and controls (n = 82), using direct immunofluorescence microscopy. Fluorescence intensity was graded semi-quantitatively. Positive SGDs were found in 58 (90.6%) patients with BP and 44 (53.7%) controls, a statistically significant difference (p < 0.0001). The sensitivity of positive SGDs for BP was high (90.6%), but the specificity was low (46.3%). Only strong fluorescence intensity was associated with high specificity. In conclusion, positive SGDs in direct immunofluorescence microscopy are highly sensitive for BP;however, only strong fluorescence has acceptable specificity. Weak positivity of SGDs without linear fluorescence of the epidermal basement membrane may not be sufficiently specific for BP

Serration pattern analysis for differentiating epidermolysis bullosa acquisita from other pemphigoid diseases

Background: Direct immunofluorescence (DIF) microscopy of a skin biopsy specimen is the reference standard for the diagnosis of pemphigoid diseases (PDs). Serration pattern analysis enables the differentiation of epidermolysis bullosa acquisita (EBA) from other PDs using DIF microscopy alone. However, practice gaps need to be addressed in order to implement this technique in the routine diagnostic procedure. Objective: We sought to determine and optimize the technical requirements for serration pattern analysis of DIF microscopy and determine interrater conformity of serration pattern analysis. Methods: We compared serration pattern analysis of routine DIF microscopy from laboratories in Groningen, The Netherlands and Lubeck, Germany with 4 blinded observers. Skin biopsy specimens from 20 patients with EBA and other PDs were exchanged and analyzed. Various factors were evaluated, including section thickness, transport medium, and biopsy specimen processing. Results: The interrater conformity of our 4 observers was 95.7%. Recognition of serration patterns was comparable in samples transported in saline and in Michel's medium and with section thicknesses of 4, 6, and 8 mu m. Limitations: Limitations include our small sample size and the availability of 20 samples that were compared retrospectively. Conclusion: DIF serration pattern analysis is not restricted by variation in laboratory procedures, transport medium, or experience of observers. This learnable technique can be implemented as a routine diagnostic method as an extension of DIF microscopy for subtyping PD. (J Am Acad Dermatol 2018;78:754-9.

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

The relevance of complement in pemphigoid diseases: A critical appraisal

Pemphigoid diseases are autoimmune chronic inflammatory skin diseases, which are characterized by blistering of the skin and/or mucous membranes, and circulating and tissue-bound autoantibodies. The well-established pathomechanisms comprise autoantibodies targeting various structural proteins located at the dermal-epidermal junction, leading to complement factor binding and activation. Several effector cells are thus attracted and activated, which in turn inflict characteristic tissue damage and subepidermal blistering. Moreover, the detection of linear complement deposits in the skin is a diagnostic hallmark of all pemphigoid diseases. However, recent studies showed that blistering might also occur independently of complement. This review reassesses the importance of complement in pemphigoid diseases based on current research by contrasting and contextualizing data from in vitro, murine and human studies

Autoantibodies in a Subgroup of Patients with Linear IgA Disease React with the NC16A Domain of BP1801

Linear IgA disease is an autoimmune subepidermal blistering disease characterized by IgA deposits at the cutaneous basement membrane zone. IgA antibodies from linear IgA disease sera react with antigens of 97 kDa (LABD97) and 120 kDa (LAD-1), both of which appear to be fragments of the extracellular domain of bullous pemphigoid 180 (type XVII collagen). The aim of this study was to determine whether linear IgA disease sera react with the immunodominant region of BP180 (NC16A domain), which is a major target of IgG autoanti-bodies produced by patients with bullous pemphigoid. Indeed, 11 of 50 linear IgA disease sera were found to contain IgA autoantibodies that recognized a recombinant form of NC16A by immunoblotting. The same sera also reacted with NC16A by enzyme-linked immunosorbent assay. An epitope mapping analysis uncovered four linear IgA disease-associated epitopes located within the 45 amino acid N-terminal stretch of NC16A, all of which were previously identified as antigenic sites targeted by bullous pemphigoid autoantibodies. Eight of the linear IgA disease sera that were reactive with NC16A also recognized LAD-1 secreted by the SCC-25 cell line, and five sera recognized BP180 extracted from keratinocytes. Linear IgA disease sera depleted of reactivity to NC16A by immunoadsorption continued to react with both the LAD-1 antigen and BP180 by immunoblotting and with the basement membrane zone by indirect immunofluorescence microscopy. Our results demonstrate that IgA autoantibodies from a subset of linear IgA disease patients react with the same sites on BP180 that are targeted by IgG autoantibodies in bullous pemphigoid