Diffuse cutaneous mastocytosis masquerading as epidermolysis bullosa.

A 10-month-old boy presented with a history of a generalized cutaneous bullous eruption since 3 months of age. Emesis, flush, pruritus, and fatigue had accompanied relapsing episodes of sometimes extensive blistering. Histopathology showed dense dermal infiltrates of mast cells on hematoxylin and eosin and corroborating immunohistochemical staining. Laboratory examination revealed a markedly high level of serum tryptase. Based on these results and after consecutive staging, the patient was diagnosed with diffuse cutaneous bullous mastocytosis (BM). Mutation analysis detected a deletion mutation (del419) in C-Kit by direct exon sequencing. This rare entity must be considered in the differential diagnosis whenever a child presents with bullae and erosions. A crucial diagnostic hint is that rubbing of affected skin areas results in whealing (Darier's sign). A comprehensive diagnostic approach, advanced therapeutic strategies, regular follow-ups, and instruction of patients and relatives on prevention and prophylaxis are highly indicated.

Epidermolysis bullosa House Austria and Epidermolysis bullosa clinical network : Example of a centre of expertise implemented in a European reference network to face the burden of a rare disease.

Accurately addressing the diverse and complex issues of rare diseases (RD) in terms of prevention, recognition, diagnosis, treatment, care and research along key RD specificities, such as great heterogeneity, a limited number of patients, scarcity of relevant knowledge and expertise as well as enormous costs for patient care is a challenging task for healthcare providers and authorities that makes a supranational approach particularly feasible. The European Union has acknowledged RD matters by several initiatives, including efforts to implement national centres of expertise and European reference networks as well as a cross-border referral mechanism to foster access to expert services and to boost dissemination of clinical expertise and research activities. Exemplified by the EB House Austria, a centre of expertise for epidermolysis bullosa cross-linked with international reference partner institutions, this strategy proves its potential to be translated into optimized patient care and to meet the major medical, scientific, social and health-economic impact of RD.

Direct and indirect immunofluorescence for the diagnosis of bullous autoimmune diseases.

DIF and IIF evaluates in vivo bound and circulating autoantibodies and are the preferred methods for diagnosing AIBDs. In pemphigus diseases and dermatitis herpetiformis, the titer of circulating autoantibodies reflects the disease activity. In patients with a classical clinical picture, the DIF confirms the diagnosis. Furthermore, this technique is essential in subtypes of AIBDs with atypical clinical manifestations (eg, no blisters or erosions) or clinically similar presenting manifestations, such as bullous pemphigoid, MMP, or EBA. A direct or indirect SSST is often crucial for the differential diagnosis between subtypes of these diseases, leading to proper treatment for severely affected patients.

Autoimmune bullous diseases in Austria.

Autoimmune bullous diseases (AIBD) are chronic disorders associated with significant morbidity and even mortality, for which the 19 dermatologic departments in Austria apply standard modalities to provide state-of-the-art diagnosis and treatment. Most of the affected individuals are initially treated on an inpatient basis, with follow-up done in specialized outpatient clinics or in private practices. A well-established system of care for AIBD patients is thus available nationwide. Considering the significant morbidity and mortality but also rareness of AIBD, national and international standardization of AIBD administration in registries is a major requirement of further improvement in patient care.

Epidermolysis bullosa care in Austria and the Epidermolysis Bullosa House Austria.

The Epidermolysis Bullosa (EB) House Austria is a special unit for the multidisciplinary management of children and adults with EB. Major advances in EB care have been made possible by a multidisciplinary approach including most of the medical specialties offered at the General Hospital in Salzburg. The EB House Austria is independently funded by the support group DEBRA Austria. As the EB House Austria fulfills all criteria for a European Union reference center, as stated by the Rare Disease Task Force in 2005, the authors hope that in the near future the EB House Austria will be accepted as such on a European Union level and that they can soon get financial support from this side. This support would be of even more importance in the moment when a causative cure, which is of course supposed to be a cost-intensive gene therapy, is available.

Immunofluorescence mapping for the diagnosis of epidermolysis bullosa.

Immunofluorescence mapping is based on the detection of structural proteins of keratinocytes or of the dermo-epidermal junction using specific poly- or monoclonal antibodies. Through this method, the level of split formation can be determined by investigating the location of a given antigen in a natural or induced blister. This method also allows testing for the normal expression, reduction or absence of various structural proteins depending on the antibodies used. It has widely replaced transmission electron microscopy and is used as the initial laboratory test to prove the clinical diagnosis of epidermolysis bullosa.

Autoantibodies in systemic sclerosis (scleroderma): clues for clinical evaluation, prognosis and pathogenesis.

Systemic sclerosis is a generalized autoimmune connective tissue disease of unknown aetiology. Profound vascular and immunological dysregulations result in tissue fibrosis affecting the skin and internal organs. Currently, two main clinical subtypes are distinguished, i.e. limited and diffuse cutaneous systemic sclerosis, which differ significantly in the clinical course and prognosis. Autoantibodies against topoisomerase (Scl-70), centromere-associated proteins, and nucleolar antigens are important for the diagnosis of the disease and give clues for its clinical manifestations and prognosis (prognostic autoantibodies). For most of these antibodies, however, the role in pathogenesis is not established. Anti-centromere antibodies are associated with limited cutaneous involvement and risk for pulmonary hypertension, whereas anti-topoisomerase I is associated with diffuse progressive disease and severe interstitial lung disease. Anti-Th/To positivity is associated with limited skin involvement but a high risk for severe internal organ involvement (Kidneys, PAH, Lung fibrosis). Anti-RNA polymerase I/III antibodies are associated with a high risk for renal involvement. Autoantibodies against the PDGF receptor and fibrillin-1 seem to play important roles in the pathogenetic process of systemic sclerosis.