[Bullous pemphigoid: diagnosis and therapy]. / Bullöses Pemphigoid--Diagnostik und Therapie.

Bullous pemphigoid is the most common autoimmune bullous skin disease which occurs more often at higher age. Clinically it presents with tense blisters and eczematous lesions combined with severe pruritus. The pemphigoid-like diseases include mucous membrane pemphigoid, pemphigoid gestationis and linear IgA disease. Diagnosis is based on immunofluorescence microscopy and confirmatory tests (ELISA, immunoblotting). Classical bullous pemphigoid presents with IgG autoantibodies against BP180 and BP230. Treatment includes topical and systemic corticosteroids and adjuvant immunosuppressants.

Autoimmune bullous skin diseases. Part 2: diagnosis and therapy.

Autoimmune bullous skin diseases represent a heterogenous group of disorders of skin and mucosa which are commonly associated with IgG or IgA autoantibodies against distinct adhesion molecules of the skin. The antibodyinduced loss of adhesion between epidermis and dermis results in blister formation and extensive erosions. There is a great need for rapidly establishing the diagnosis of these disorders since they may run a severe and potentially life-threatening course. In addition, because of their rarity and heterogeneous symptoms, autoimmune bullous skin diseases often pose a major diagnostic challenge. While histopathological examinations provide evidence for the level of blister formation, immunofluorescence microscopy has been established to identify tissue-bound and circulating autoantibodies. Direct immunofluorescence microscopy represents the gold standard for detecting tissue-bound autoantibodies. Indirect immunofluorescence microscopy with defined tissue substrates is considered the first step in detecting circulating autoantibodies. Confirmatory tests such as ELISA, immunoblot or immunoprecipitation analyses are performed utilizing recombinant proteins or keratinocyte extracts. The later assays can be used for primary diagnosis as well as for immunoserological follow-up. Systemic immunosuppressive drugs usually represent the main therapeutic regimen. Initially, systemic corticosteroids are commonly administered in combination with steroid-sparing, immunosuppressive agents. Novel targeted treatments such as immunoadsorption, rituximab or high-dose intravenous immunoglobulins have proven to be highly effective in severe and refractory pemphigus. This review presents a state-of-the-art algorithm for making the diagnosis of autoimmune bullous disorders and provides an overview on currently available therapeutic options.

Autoimmune bullous skin diseases. Part 1: Clinical manifestations.

Autoimmune bullous skin diseases are characterized by autoantibodies against adhesion molecules of the skin. Pemphigus is a disorder with an intraepidermal loss of adhesion and is characterized by fragile blisters and erosions. Pemphigus vulgaris often shows extensive lesions of the oral mucosa, while pemphigus foliaceus is commonly restricted to cutaneous involvement with puff pastry-like scale formation. Paraneoplastic pemphigus is obligatorily associated with malignancies and often presents as hemorrhagic stomatitis with multiforme-like exanthems. IgA pemphigus typically presents with pustules and annular plaques but not with mucosal involvement. The clinical spectrum of the pemphigoids includes tense blisters, urticarial plaques, and prurigo- like eczematous lesions. Pemphigoid gestationis mostly occurs during the last trimester of pregnancy and mucous membrane pemphigoid primarily involves the oral mucosa and conjunctivae and leads to scarring. Linear IgA bullous dermatosis manifests with tense blisters in a "cluster of jewels"-like pattern in childhood and is more heterogeneous in adulthood. Classical epidermolysis bullosa acquisita shows extensive skin fragility. Dermatitis herpetiformis is associated with gluten-sensitive enteropathy and manifests clinically with severe itching and papulovesicles on the extensor surfaces of the extremities and the lumbosacral area. The intention of the review is to demonstrate the heterogeneous clinical spectrum of autoimmune bullous disorders.

Clinical and immunological follow-up of pemphigus patients on adjuvant treatment with immunoadsorption or rituximab.

BACKGROUND: Pemphigus vulgaris (PV) is a life-threatening autoimmune blistering skin disease which is associated with pathogenic IgG autoantibodies against desmogleins (Dsg) 1 and 3. Novel therapeutic strategies such as immunoadsorption (IA) or the anti-CD20 antibody rituximab (Rtx) hold promise to be effective in severe or recalcitrant PV. PATIENTS AND METHODS: In the present retrospective study, 6 patients with extensive cutaneous PV were subjected to adjuvant IA treatment while 5 patients with severe mucosal PV received adjuvant Rtx treatment. RESULTS: Within 6 months, IA and Rtx induced excellent clinical responses which were associated with a significant reduction of prednisolone doses and a decrease in anti-Dsg-specific IgG. Over a 12-month period, 3 IA-treated patients required additional adjuvant drugs while all of the PV patients on Rtx had no or only minimal residual symptoms. CONCLUSION: The relative therapeutic (long-term) efficacy of IA and Rtx in cutaneous versus mucosal PV needs to be evaluated in a prospective study.

Herpes simplex virus infection in pemphigus vulgaris: clinical and immunological considerations.

Different environmental factors have been implicated in the pathogenesis of pemphigus vulgaris (PV), including drugs, diet, burns, X-rays, ultraviolet radiation, neoplasms, and infections. Several reports described the manifestation or aggravation of PV due to herpes simplex virus (HSV), varicella-zoster virus, Epstein-Barr virus, cytomegalovirus and human herpesvirus-8 infections. In the present study, we correlated secondary HSV1 infection in 3 PV patients on immunosuppressive treatment with the titers of IgG autoantibodies against desmoglein 1 (DSG1) and 3 (DSG3) over a follow-up period of at least 18 months. In these patients, the detection of HSV1 and clinical flare-up of PV did not correlate with a significant increase of DSG-specific IgG. Thus, secondary cutaneous HSV infections should be considered in patients with chronic PV with atypical sudden relapses or resistance to sufficient immunosuppressive treatment who do not show an increase of DSG-specific IgG autoantibodies.

Targeted gene correction of hprt mutations by 45 base single-stranded oligonucleotides.

Targeted correction of a single base in a gene of an eucaryotic cell by specific oligonucleotides is a yet controversial technique. Here, we introduce the correction of point mutations in the hypoxanthine-guanine-phosphoribosyl-transferase (HPRT) gene as an additional model system to test targeted gene correction. In human, Hprt mutations cause Lesch-Nyhan syndrome. Using hamster V79 cells, we generated three cell lines with one hprt point mutation each. These cell lines were treated with specific single-stranded 45 base phosphothioate modified oligonucleotides and selected by HAT medium. The surviving clones were investigated for the correction of the respective hprt mutation. Treatment with the oligonucleotides was successful in repairing all three hprt mutations (hprt cDNA position 74, C --> T; position 151, C --> T; and position 400, G --> A). The correction efficiency was very low but reproducible. We suggest that this system allows one to investigate targeted gene correction in dependence on the target sequence and the oligonucleotides used.