Cezary Kowalewski

Direct immunofluorescence studies of sodium chloride—separated skin in the differential diagnosis of bullous pemphigoid and epidermolysis bullosa acquisita

Bullous pemphigoid and epidermolysis bullosa acquisita may have indistinguishable clinical, histologic, and routine immunohistologic features. In those cases these two diseases can be reliably distinguished in routine diagnostic studies only in seropositive cases by tests on lamina lucida-split skin and in research studies by direct immunoelectron microscopy or, in patients with circulating autoantibodies, by immunoblotting studies. The use of these methods is limited by the expense and unavailability of the methods, the requirement for circulating autoantibodies, or both. We describe a method to distinguish between the two diseases on the basis of findings of direct immunofluorescence of a biopsy specimen after separation through the lamina lucida with 1.0 mol/L sodium chloride. The IgG appeared in the dermal side of the split specimens in epidermolysis bullosa acquisita and predominantly or exclusively in the epidermal side in pemphigoid. The method was found to be relatively simple, inexpensive, applicable to specimens preserved in transport media, and 100% reliable in our group of 22 patients.

Management of bullous pemphigoid: the European Dermatology Forum consensus in collaboration with the European Academy of Dermatology and Venereology

Bullous pemphigoid is the most common autoimmune subepidermal blistering disease of the skin and mucous membranes. This disease typically affects the elderly and presents with itch and localized or generalized bullous lesions. In up to 20% of affected patients, bullae may be completely absent, and only excoriations, prurigo‐like lesions, eczematous lesions, urticated lesions and/or infiltrated plaques are observed. The disease is significantly associated with neurological disorders. The morbidity of bullous pemphigoid and its impact on quality of life are significant. So far, a limited number of national treatment guidelines have been proposed, but no common European consensus has emerged. Our consensus for the treatment of bullous pemphigoid has been developed under the guidance of the European Dermatology Forum in collaboration with the European Academy of Dermatology and Venereology. It summarizes evidence‐based and expert‐based recommendations.

Pemphigus. S2 Guideline for diagnosis and treatment – guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV)

Pemphigus encompasses a group of life‐threatening autoimmune bullous diseases characterized by blisters and erosions of the mucous membranes and skin. Before the era of immunosuppressive treatment, the prognosis of pemphigus was almost fatal. Due to its rarity, only few prospective controlled therapeutic trials are available.

Definitions and outcome measures for mucous membrane pemphigoid: Recommendations of an international panel of experts

Mucous membrane pemphigoid encompasses a group of autoimmune bullous diseases with a similar phenotype characterized by subepithelial blisters, erosions, and scarring of mucous membranes, skin, or both. Although knowledge about autoimmune bullous disease is increasing, there is often a lack of clear definitions of disease, outcome measures, and therapeutic end points. With clearer definitions and outcome measures, it is possible to directly compare the results and data from various studies using meta-analyses. This consensus statement provides accurate and reproducible definitions for disease extent, activity, outcome measures, end points, and therapeutic response for mucous membrane pemphigoid and proposes a disease extent score, the Mucous Membrane Pemphigoid Disease Area Index.

The COL7A1 mutation database

Dystrophic Epidermolysis Bullosa (DEB) is a genetic disease caused by mutations in the COL7A1 gene that is inherited in the autosomal dominant or recessive mode. We have developed a curated, freely accessible COL7A1 specific database (http://www.col7a1‐database.info), which contains more than 730 reported and unpublished sequence variants of the gene. Molecular defects are reported according to HGVS recommendation. The clinical description module is provided with an advanced search tool together with a CSV (comm. separated values) data format download option. This compilation of COL7A1 data and nomenclature is aimed at assisting molecular and clinical geneticists to enhance the collaboration between researchers worldwide. Hum Mutat 33:327–331, 2012.

Pemphigus herpetiformis: from first description until now.

Pemphigus herpetiformis is one of the less common forms of pemphigus, first introduced by Jabłońska and colleagues in 1975. This autoimmune bullous disease combines the clinical features of dermatitis herpetiformis and the immunologic characteristics of pemphigus. The target autoantigen is usually desmoglein 1 (or less frequently desmoglein 3), although recently it has become increasingly obvious that patients with pemphigus herpetiformis also demonstrate autoantibodies against desmocollin. Here, we summarize reported cases of pemphigus herpetiformis and describe current knowledge considering epidemiology, clinical manifestations, histologic findings, immunopathology, pathophysiologic concepts, associated diseases, and treatment of this rare disorder.

IGA PEMPHIGUS FOLIACEUS WITH A CLINICAL PRESENTATION OF PEMPHIGUS HERPETIFORMIS

A patient with clinical features of herpetiform pemphigus of the foliaceus type had histologic findings consistent with pemphigus. Intercellular IgA deposits in a pattern like that of IgG in pemphigus were present. Circulating pemphigus-type IgA-class antibodies reacted first only with guinea pig and later in the disease also with monkey esophagus sections. IgG-class pemphigus antibodies were blocked by the IgA-class antibodies of this patient. In addition, the IgA-class pemphigus antibodies in this patient were blocked by the IgG-class pemphigus antibodies in tests on guinea pig and monkey esophagus. This indicates that the IgA-class antibodies in this patient were directed either to the same antigen as the IgG-class pemphigus foliaceus antibodies or to one that is close enough to it to give steric hindrance. The skin lesions responded poorly to systemic corticosteroid therapy. Dapsone therapy initially produced dramatic improvement, but the condition flared to the point that plasmapheresis, in addition to high doses of corticosteroids and cyclophosphamide, had to be used to control it.

Alterations of basement membrane zone and cutaneous microvasculature in morphea and extragenital lichen sclerosus.

The aim of this study was to compare alterations of the basement membrane zone (BMZ) and to visualize changes within the skin vascular network in morphea and extragenital lichen sclerosus with the use of laser scanning confocal microscopy. This work was performed in eight plaques of morphea (three active and five inactive) and eight of lichen sclerosus (three of short duration and five long-lasting). Biopsy specimens from six healthy individuals served as controls. The biopsies were cut into 40-μm-thick sections, labeled with antibodies against β4-intergin (a lamina lucida marker), collagen IV, and the N-terminal end of collagen VII (lamina densa markers) and C-terminal end of collagen VII (a sublamina densa marker) and studied using laser scanning confocal microscopy. Three-dimensional reconstruction of various regions of the BMZ showed a decreased number and size of the dermal papillae both in morphea and lichen sclerosus compared with normal skin. In morphea, the continuity of the BMZ at the level of lamina lucida, lamina densa, and sublamina densa was preserved whereas in LS numerous invaginations and holes were present in the BMZ at the level of the lamina lucida and lamina densa. Thus the alterations of the BMZ in morphea differ from those in lichen sclerosus. Three-dimensional reconstruction of the skin vascular network showed increased angiogenesis only in the early inflammatory stage of morphea, whereas in inactive morphea and lichen sclerosus various numbers of enlarged vessels were visible. The changes in the vascular network in morphea appear to be related to the activity of the disease.

Detection of anti-basement membrane zone antibodies in bullous systemic lupus erythematosus

We describe a 42-year-old black woman with long-standing systemic lupus erythematosus in whom vesiculobullous lesions developed. Routine histologic and immunologic studies fulfilled the criteria for the diagnosis of bullous systemic lupus erythematosus. Indirect immunofluorescence showed antinuclear antibodies without basement membrane zone fluorescence. We destroyed the nuclear antigens of the indirect immunofluorescence substrate with 2 mol/L sodium chloride, which unmasked basement membrane zone linear IgG staining. We also confirmed anti-basement membrane zone antibodies by employing a new technique of direct immunofluorescence on sodium chloride-split skin. Our finding prove that a thorough search for anti-basement membrane zone antibodies can be revealing. Our results support the idea that a subset of bullous systemic lupus erythematosus has the staining characteristics of epidermolysis acquisita, with the dermal side of the split skin showing linear immunoglobulin deposition.

Penicillin-induced anti-p200 pemphigoid: an unusual morphology.

We report here a case of a 52-year-old woman with erythema gyratum repens-like lesions appearing during anti-p200 pemphigoid, probably induced by oral penicillin. The diagnosis of anti-p200 pemphigoid was made by the presence of in vivo bound and circulating IgG anti-basement membrane zone auto-antibody reactive with the dermal side of salt-split skin and with 200 kDa protein in dermal extract on Western immunoblot. Laser scanning confocal microscopic study disclosed the localization of IgG at the lamina lucida-lamina densa border. Skin lesions responded poorly to high dose of prednisone and the combination of prednisone and dapsone. When methotrexate was added, skin lesions healed within 3 weeks. To our knowledge, erythema gyratum repens-like lesions have not been described previously in this disorder. Thus, we have expanded the clinical morphological spectrum of patients with anti-p200 pemphigoid and first described a patient whose disorder was probably drug-induced.