Diagnosis of Autoimmune Blistering Diseases

Abstract

Autoimmune skin blistering diseases (AIBD) are characterized by autoantibodies that are directed against structural proteins in the skin and adjacent mucous membranes. Some clinical signs are typical for a specific AIBD, however, correct diagnosis requires the detection of tissue-bound or circulating autoantibodies. The gold standard for diagnosis of AIBD is the detection of autoantibodies or complement component 3 by direct immunofluorescence (DIF) microscopy of a perilesional biopsy. Circulating antibodies can be detected via indirect immunofluorescence (IIF) microscopy of different tissue substrates including human skin, monkey esophagus, and more recently, recombinant forms of the different target antigens. Latter are also employed in various commercial ELISA systems and by immunoblotting in in-house assays available in specialized laboratories. ELISA systems are also particularly valuable for monitoring of the disease activity during the disease course which can be helpful for treatment decisions. Exact diagnosis is essential for both treatment and prognosis, since some AIBD are associated with malign tumors such as paraneoplastic pemphigus and anti-laminin 332 mucous membrane pemphigoid. This review presents clinical and immunopathological features of AIBD for the state-of the art diagnosis of these disorders.

Paraneoplastic pemphigus: a clinical, laboratorial, and therapeutic overview

“…23 The most common antibodies against proteins of the plakin family in PNP are anti-envoplakin and anti-periplakin antibodies. 24 IgG autoantibodies against cytosolic proteins of the plakin family do not attack directly in vivo, an with unclear role in the pathogenesis of PNP. 21 The possible antibody-mediated mechanisms in PNP related to neoplasias are as follows: 16,[25][26][27][28] 1.…”

“…18 PNP lesions may clinically resemble pemphigus vulgaris, bullous pemphigoid, erythema multiforme, lichen planus, and graft-versus-host disease. 1,10,24 The variable clinical presentations of PNP may be related to the predominant pathogenic mechanisms involved: antibody--mediated immunity -PNP lesions resembling pemphigus vulgaris and bullous pemphigoid; cell-mediated cytotoxicity -PNP lesions resembling erythema multiforme, graft-versus-host disease, and lichen planus. Mucosal lesions occur as erosions and crusting in the mouth, nose, pharynx, larynx, esophagus, eyes, and anogenital area.…”

Treatment with anti‐neonatal Fc receptor (FcRn) antibody ameliorates experimental epidermolysis bullosa acquisita in mice

“…Immunoadsorption material was obtained from two patients with bullous pemphigoid (BP). BP was diagnosed based on clinical presentation, IgG, and/or C3 deposition along the dermal–epidermal junction in direct immunofluorescent microscopy from a peri‐lesional skin biopsy, detection of anti‐BP180‐NC16A antibodies by ELISA, and binding of patient IgG to the blister roof in indirect immunofluorescent microscopy using human salt split skin as a substrate (Witte, Zillikens, & Schmidt, ).…”

Pemphigus Foliaceus and Pemphigus Erythematosus are the Most Common Subtypes of Pemphigus in Northern Finland

“…P emphigus comprises a group of rare autoimmune bullous diseases, characterized by the production of autoantibodies against desmogleins, a family of epidermal adhesion proteins. Autoantibodies against desmogleins (Dsg) 1 and 3 cause loss of intraepidermal adhesion, resulting in epidermal acantholysis, blistering and erosions of the skin and mucous membranes (1)(2)(3)(4). Due to the rarity of pemphigus and the diversity of its variants, it is challenging to distinguish the different types of pemphigus using clinical findings alone.…”