Autoimmune Bullous Diseases: Clinical Appearance, Diagnostic Evaluation and new therapeutic approaches

This paper presents an overview of the group of blistering autoimmune dermatoses, focusing on their most important forms: bullous pemphigoid, pemphigus vulgaris and pemphigus foliaceus. The most common form of blistering autoimmune dermatosis - a rare disease overall - is bullous pemphigoid (BP), which mainly affects patients over the age of 60. Its characteristic symptom is the appearance of tense blisters accompanied by severe itching. A longer stage without blistering, also known as premonitory stage, is not uncommon. There are also variants with a different appearance, such as localised BP. The gold standard in diagnosis is direct immunofluorescencemicroscopy of a perilesional skin biopsy, which shows linear deposits of IgG and C3 along the basement membrane. Indirect immunofluorescencemicroscopy and further ELISA examinations, which help to detect circulating autoantibodies in the patient's serum, complete the diagnosis. The most important target antigen is BP180, a hemidesmosomal protein expressed by keratinocytes. In addition, a histopathological examination can be performed. However, this only provides information on the cleavage plane and the infiltrate pattern (mostly dominated by eosinophils) and is not sufficient on its own for establishing the diagnosis. The pathogenesis of BP is the subject of scientific debate. Drugs such as dipeptidyl peptidase-4 inhibitors may be triggers; associations with neurological diseases are common. According to current guidelines, BP is treated with topical or systemic glucocorticoids, possibly in combination with doxycycline, dapsone or an immunosuppressant. In case of therapy resistance, intravenous immunoglobulins or the anti-CD-20 antibody Rituximab are used. As mortality is relatively high due to patient age and iatrogenic immunosuppression, new therapeutic approaches are being sought. Case series, cohort analyses and phase 1/2 studies with anti-IgE antibodies and inhibitors of eosinophil granulocytes as well as the complement system show promising effects in some cases. The most important forms of the pemphigus diseases are pemphigus vulgaris (PV), pemphigus foliaceus (PF) and the very rare paraneoplastic pemphigus (PNP). Clinically, PV presents with mucosal erosions, mostly enoral, and sometimes additional erosions on the free skin. PF manifests only on free skin. As in BP, the diagnosis is made by direct immunofluorescencemicroscopy, which in PV and PF shows reticular deposits of IgG and C3 within the epidermis. The most common target antigens are desmogleins 1 and 3. It is known that there are genetic predispositions for PV and PF, and these are the reason why the frequency varies globally. PNP is always associated with malignant disease and is characterised by a progressive course with high mortality. Therapeutically, pemphigus often requires more aggressive approaches than BP. In addition to systemic glucocorticoids and immunosuppressants, the anti-CD-20 antibody rituximab is recommended for PV and PF. New therapeutic approaches include the inhibition of Bruton's tyrosine kinase as well as the neonatal Fc receptor (FcRN). In a phase 2 trial, efgartigimod, an antagonist of FcRN, has shown high treatment efficacy for patients with PV and PF.