Franziska Schauer

Targeting epidermal lipids for treatment of Mendelian disorders of cornification

BackgroundInherited ichthyoses or Mendelian disorders of cornification (MeDOC) are clinically heterogeneous disorders with high unmet therapeutic needs, which are characterized by skin hyperkeratosis and scaling. Some MeDOC types are associated with defects of the epidermal lipid metabolism, resulting in perturbed barrier permeability and subsequent epidermal hyperplasia, hyperkeratosis and inflammation. An example is the CHILD (congenital hemidysplasia with ichthyosiform nevus and limb defects) syndrome, an X-linked dominant multisystem MeDOC caused by mutations in the NSDHL (NAD(P)H steroid dehydrogenase-like protein) gene, which is involved in the distal cholesterol biosynthetic pathway. The skin manifestations of the CHILD syndrome have been attributed to two major mechanisms: deficiency of cholesterol, probably influencing the proper corneocyte membrane formation, and toxic accumulation of aberrant steroid precursors.MethodsHere we addressed the efficacy of an ointment containing cholesterol and simvastatin, an agent inhibiting endogenous cholesterol synthesis in a compassionate-use treatment of three patients with CHILD syndrome. To test the specificity of this therapeutic approach, we applied the same topical treatment to two patients with other types of MeDOC with disturbed skin lipid metabolism.ResultsThe therapy with simvastatin and cholesterol was highly effective and well-tolerated by the CHILD syndrome patients; only lesions in the body folds represented a therapeutic challenge. No improvement was noted in the patients with other types of MeDOC.ConclusionsThis therapy is inexpensive and accessible to every patient with CHILD syndrome, because both simvastatin and cholesterol are available worldwide. Our data provide initial evidence of the specificity of the therapeutic effect of the simvastatin-cholesterol ointment in CHILD syndrome in comparison to other types of MeDOC.

Adopting Quality Criteria for Websites Providing Medical Information About Rare Diseases

Background The European Union considers diseases to be rare when they affect less than 5 in 10,000 people. It is estimated that there are between 5000 and 8000 different rare diseases. Consistent with this diversity, the quality of information available on the Web varies considerably. Thus, quality criteria for websites about rare diseases are needed. Objective The objective of this study was to generate a catalog of quality criteria suitable for rare diseases. Methods First, relevant certificates and quality recommendations for health information websites were identified through a comprehensive Web search. Second, all considered quality criteria of each certification program and catalog were examined, extracted into an overview table, and analyzed by thematic content. Finally, an interdisciplinary expert group verified the relevant quality criteria. Results We identified 9 quality certificates and criteria catalogs for health information websites with 304 single criteria items. Through this, we aggregated 163 various quality criteria, each assigned to one of the following categories: thematic, technical, service, content, and legal. Finally, a consensus about 13 quality criteria for websites offering medical information on rare diseases was determined. Of these categories, 4 (data protection concept, imprint, creation and updating date, and possibility to contact the website provider) were identified as being the most important for publishing medical information about rare diseases. Conclusions The large number of different quality criteria appearing within a relatively small number of criteria catalogs shows that the opinion of what is important in the quality of health information differs. In addition, to define useful quality criteria for websites about rare diseases, which are an essential source of information for many patients, a trade-off is necessary between the high standard of quality criteria for health information websites in general and the limited provision of information about some rare diseases. Finally, transparently presented quality assessments can help people to find reliable information and to assess its quality.

Systemic retinoids for treatment of recalcitrant IgA pemphigus

IgA pemphigus is an exceedingly rare autoimmune blistering disorder, caused by IgA autoantibodies against desmosomal proteins. No treatment option has been found to be universally effective. The disease is often recalcitrant to oral steroids and immunosuppressants. Here, we describe the use of systemic retinoids for the treatment of recalcitrant IgA pemphigus in 3 cases. Although the use of acitretin has been reported before, we present for the first time the positive effects of alitretinoin in treatment of 2 patients with IgA pemphigus. Besides hyperlipoproteinaemia requiring use of hypolipidemic agents in one case, alitretinoin was well-tolerated and has generally a more favorable side effect spectrum than immunosuppressants.

Conceptualization and Implementation of the Central Information Portal on Rare Diseases: Protocol for a Qualitative Study

Background Recently, public and political interest has focused on people living with rare diseases and their health concerns. Due to the large number of different types of rare diseases and the sizable number of patients, taking action to improve the life of those affected is gaining importance. In 2013, the federal government of Germany adopted a national action plan for rare diseases, including the call to establish a central information portal on rare diseases (Zentrales Informationsportal über seltene Erkrankungen, ZIPSE). Objective The objective of this study, therefore, was to conduct scientific research on how such a portal must be designed to meet the needs of patients, their families, and medical professionals, and to provide high-quality information for information seekers. Methods We chose a 3-step procedure to develop a needs-based prototype of a central information portal. In the first step, we determined the information needs of patients with rare diseases, their relatives, and health care professionals by means of qualitative interviews and their content-analytical evaluation. On the basis of this, we developed the basic structure of the portal. In the second step, we identified quality criteria for websites on rare diseases to ensure that the information linked with ZIPSE meets the quality demands. Therefore, we gathered existing criteria catalogs and discussed them in an expert workshop. In the third step, we implemented and tested the developed prototypical information portal. Results A portal page was configured and made accessible on the Web. The structure of ZIPSE was based on the findings from 108 qualitative interviews with patients, their relatives, and health care professionals, through which numerous information needs were identified. We placed particularly important areas of information, such as symptoms, therapy, research, and advisory services, on the start page. Moreover, we defined 13 quality criteria, referring to factors such as author information, creation date, and privacy, enabling links with high-quality information. Moreover, 19 users tested all the developed routines based on usability and comprehensibility. Subsequently, we improved the visual presentation of search results and other important search functions. Conclusions The implemented information portal, ZIPSE, provides high-quality information on rare diseases from a central point of access. By integrating the targeted groups as well as different experts on medical information during the construction, the website can assure an improved search for information for users. ZIPSE can also serve as a model for other Web-based information systems in the field of rare diseases. Registered Report Identifier RR1-10.2196/7425

Natural history and clinical outcome of junctional epidermolysis bullosa generalized intermediate due to a LAMA3 mutation

Junctional epidermolysis bullosa (JEB) comprises rare autosomal recessive disorders with a broad spectrum of clinical features and severity. The genetic basis involves mutations in genes encoding proteins of the dermal-epidermal junction, primarily laminin 332. This heterotrimeric glycoprotein consists of laminin α3, β3 and γ2 chains, and the majority of mutations in the respective genes (LAMA3, LAMB3, and LAMC2) lead to premature termination codons resulting in severe generalized JEB (previously Herlitz)1. This article is protected by copyright. All rights reserved.

A new clinical variant of acquired reactive perforating dermatosis-like bullous pemphigoid

Bullous pemphigoid (BP) is a blistering disorder associated with circulating autoantibodies against BP180/ collagen XVII. As part of a prodromal stage patients might present with eczematous lesions or erythematous papules and prurigo- or urticaria-like erythema without any blistering. Recent studies described four patients with clinical features resembling acquired reactive perforating dermatosis (ARPD) co-existing with BP. They initially presented with papules and nodules with a central keratotic plaque; diabetes mellitus (DM) and hemodialysis thought of being causative. This article is protected by copyright. All rights reserved.

Telephone health services in the field of rare diseases: A qualitative interview study examining the needs of patients, relatives, and health care professionals in Germany

BackgroundRare diseases are, by definition, very serious and chronic diseases with a high negative impact on quality of life. Approximately 350 million people worldwide live with rare diseases. The resulting high disease burden triggers health information search, but helpful, high-quality, and up-to-date information is often hard to find. Therefore, the improvement of health information provision has been integrated in many national plans for rare diseases, discussing the telephone as one access option. In this context, this study examines the need for a telephone service offering information for people affected by rare diseases, their relatives, and physicians.MethodsIn total, 107 individuals participated in a qualitative interview study conducted in Germany. Sixty-eight individuals suffering from a rare disease or related to somebody with rare diseases and 39 health care professionals took part. Individual interviews were conducted using a standardized semi-structured questionnaire. Interviews were analysed using the qualitative content analysis, triangulating patients, relatives, and health care professionals. The fulfilment of qualitative data processing standards has been controlled for.ResultsOut of 68 patients and relatives and 39 physicians, 52 and 18, respectively, advocated for the establishment of a rare diseases telephone service. Interviewees expected a helpline to include expert staffing, personal contact, good availability, low technical barriers, medical and psychosocial topics of counselling, guidance in reducing information chaos, and referrals. Health care professionals highlighted the importance of medical topics of counselling—in particular, differential diagnostics—and referrals.ConclusionsTherefore, the need for a national rare diseases helpline was confirmed in this study. Due to limited financial resources, existing offers should be adapted in a stepwise procedure in accordance with the identified attributes.

Papulopustular lesions of the face and scalp

A 43-year-old Central European man presented with painful erythema and widespread pustules that had fi rst appeared on the nose and cheeks in March 2015, and had subsequently spread to the scalp and neck. The patient suspected an association with the rubber breathing mask he had to wear several hours a day during his job as a car painter. He denied any increased photosensitivity. His medical history showed no evidence of preexisting atopic dermatitis, allergic rhinoconjunctivitis, or asthma.

Pruritic intertriginous vesiculopustular eruption

A 64-year-old Turkish woman presented with progressive pr -uritic vesicles and erosions in the intertriginous areas, which she first detected during the summer months of the previous year. She reported developing more than 5 new vesicles each week that ruptured promptly after scratching and resolved le -aving hyperpigmentation but no scarring. Her general health was good and she was on no medications.