The treatment of severe autoimmune skin diseases and of toxic epidermal necrolysis (ICD: L51.2) with high-dose intravenous immunoglobulins (IVIg) is an established therapeutic procedure in dermatology. As IVIg are usually only administered in rare autoimmune diseases or in particularly severe disease courses, use of immunoglobulins in dermatology is commonly not based on experience from controlled and randomized studies typically demanded by evidence-based medicine. In face of the rarity of indications for IVIg it is improbable that such studies will be performed in the foreseeable future. Further, as the high costs of IVIg treatment limits its use as first-line therapy, no clear guidelines exist yet on IVIg use in skin diseases. The present recommendation is based on a consensus of the Working Group on European Guidelines of the EDF (European Dermatology Forum) and the EADV (European Association of Dermato-Venereology) and should provide aid in decision making for the use of IVIg in treating dermatologic diseases
Type VII collagen (COL7) is a major constituent of the cutaneous basement membrane. Loss of tolerance to COL7 leads to the blistering skin disease epidermolysis bullosa acquisita (EBA). Antibodies to COL7 have also been detected in patients with inflammatory bowel disease (IBD), yet reports on the expression of COL7 in the gut are controversial and a pathogenic relevance of anti-COL7 autoantibodies in IBD has not been demonstrated. We therefore characterized the expression patterns of COL7 in murine gastrointestinal organs and investigated if anti-COL7 antibodies induce an inflammatory response in the gut. COL7 expression was analysed on the mRNA and protein levels. Mice were injected with rabbit anti-murine COL7 IgG (passive EBA) or immunized with a fragment of murine COL7 (active EBA). COL7 was found to be expressed in buccal mucosa, oesophagus, stomach, small intestine, and colon. In addition to skin blistering, in both passive and active EBA, autoantibodies bound to the gastrointestinal basement membrane, fixed complement, and led to recruitment of leukocytes. Furthermore, blister formation was observed in the oesophagus (40%/38% of mice in passive/active model), stomach (40%/63%), small intestine (20%/13%), and colon (20%/13%). Compared to control animals, we found a significantly reduced body weight in diseased mice, suggesting that autoantibody-induced gastrointestinal inflammation is clinically relevant. Those observations may help us to understand the co-incidence of IBD with EBA, and vice versa: The inflammatory response in IBD might expose novel antigens (COL7), which leads to the formation of anti-COL7 antibodies. On the contrary, anti-COL7 antibody-induced gastrointestinal inflammation might pave the way for IBD pathogenesis. In summary, our results provide strong evidence that COL7 is expressed in different portions of the gut and that anti-COL7 antibodies induce distinct gastrointestinal tissue damage.
Subepidermal autoimmune bullous diseases are a diverse group of diseases with overlapping clinical and immunopathological features. Indirect immunofluorescence microscopy on artificially split skin helps to classify these conditions into those with staining on the epidermal side of the split ("roof-binding") and those with staining on the dermal side ("floor-binding"). Epidermolysis bullosa acquisita is the prototype of "floor-binding" subepidermal autoimmune bullous diseases. However, not all floor-binding sera are associated with epidermolysis bullosa acquisita.The aim of this study was to evaluate the clinical and immunological profile of patients with floor-binding subepidermal autoimmune bullous disease by indirect immunofluorescence microscopy and to identify the target antigens in them.Ten patients who showed a floor-binding pattern were studied with regard to their clinical and immunopathological characteristics. Target antigens were identified by modified indirect immunofluorescence microscopy using recessive dystrophic epidermolysis bullosa skin, enzyme linked immunosorbent assay, and immunoblotting.Diagnosis of epidermolysis bullosa acquisita was confirmed in six patients. Three patients with an inflammatory subepidermal autoimmune bullous disease mimicking bullous pemphigoid reacted with a 200 kDa protein on immunoblotting with dermal extract, as is characteristic of anti-p200 pemphigoid. One serum showed both roof and floor binding, and reacted with the BP180 antigen.We could not perform serration pattern analysis in our patients.In this study, we report three cases of anti-p200 pemphigoid from India. These cases, though indistinguishable clinically from bullous pemphigoid, revealed a floor-binding pattern on indirect immunofluorescence using salt-split skin.
Abstract Anti‐laminin γ1 pemphigoid is an autoimmune subepidermal bullous disease first described in 1996, and has been distinct from previously known subepidermal blistering diseases, such as bullous pemphigoid and epidermolysis bullosa acquisita. Circulating autoantibodies of the patients do not react to any known autoantigen of the skin, but react to a 200‐kDa molecule (p200) from dermal extracts. The identity of p200 was unmasked as laminin γ1, an extracellular matrix glycoprotein composing several forms of laminin heterotrimers. We renamed this disease from the previously used anti‐p200 pemphigoid to anti‐laminin γ1 pemphigoid, a new entity of an autoimmune bullous disease. In this decade, we have experienced over 70 cases of this disease. Although the number of the cases of anti‐laminin γ1 pemphigoid is half as many as the number of definitely diagnosed cases of epidermolysis bullosa acquisita in the same duration, a considerable number of the cases could be clinically misdiagnosed as epidermolysis bullosa acquisita. Unveiling the pathogenicity and development of a useful diagnostic method is necessary for appropriate management of this new disease.
Journal Article Long‐standing remission of recalcitrant juvenile pemphigus vulgaris after adjuvant therapy with rituximab Get access E. Schmidt, E. Schmidt Department of Dermatology, University of Würzburg, 97080 Würzburg, Germany Search for other works by this author on: Oxford Academic Google Scholar S. Herzog, S. Herzog Department of Dermatology, University of Würzburg, 97080 Würzburg, Germany Search for other works by this author on: Oxford Academic Google Scholar E‐B. Bröcker, E‐B. Bröcker Department of Dermatology, University of Würzburg, 97080 Würzburg, Germany Search for other works by this author on: Oxford Academic Google Scholar D. Zillikens, D. Zillikens Department of Dermatology, University Hospital of Schleswig‐Holstein, Campus Lübeck, 23538 Lübeck, Germany Search for other works by this author on: Oxford Academic Google Scholar M. Goebeler M. Goebeler Department of Dermatology, University of Würzburg, 97080 Würzburg, GermanyDepartment of Dermatology, University Medical Center Mannheim, University of Heidelberg, Theodor‐Kutzer‐Ufer, 68135 Mannheim, Germany Matthias Goebeler E‐mail: matthias.goebeler@haut.ma.uni‐heidelberg.de Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 153, Issue 2, 1 August 2005, Pages 449–451, https://doi.org/10.1111/j.1365-2133.2005.06740.x Published: 01 August 2005
Mucous membrane pemphigoid (MMP) is a rare, heterogeneous subepithelial autoimmune bullous disease. The association between its clinical and immunological features is yet to be fully evaluated.To characterize the clinical, immunoserological, and immunopathological characteristics of patients with MMP and to identify site- and autoantigen-specific characteristics.A retrospective cohort study encompassing all consecutive patients diagnosed with MMP from January 2007 through February 2020 in 2 tertiary referral centers in Germany.The clinical, immunoserological, and immunopathological features of eligible patients were evaluated. Associations of different anatomical sites and autoantigens were assessed using a multivariable logistic regression model.The study encompassed 154 patients (96 [62.3%] women and 58 [37.7%] men; mean [SD] age at diagnosis, 66.2 [13.8] years) with MMP, of whom 125 (81.2%), 61 (39.6%), 34 (22.1%), and 16 (10.4%) presented with lesions involving the oral, ocular, nasal, and genital mucosae, respectively, and 35 (22.7%) presented with cutaneous involvement. Among the 154 patients, the most frequently targeted antigen was BP180 (90 patients [58.4%]), followed by laminin 332 (13 patients [8.4%]) and BP230 (3 patients [1.9%]). Ocular disease was inversely associated with oral (adjusted odds ratio [aOR], 0.02; 95% CI, 0.01-0.13) and nasal (aOR, 0.20; 95% CI, 0.04-0.91) involvement and was associated with a 13-fold increased risk of malignant neoplasm (aOR, 13.07; 95% CI, 1.56-109.36). Anti-laminin 332 reactivity was associated with malignant neoplasm (aOR, 23.27; 95% CI, 1.83-296.68), whereas anti-BP180 NC16A immunoglobulin G seropositivity was associated with absence of ocular lesions (aOR, 0.09; 95% CI, 0.01-0.99).In this cohort study of patients with MMP, malignant neoplasms were associated with ocular disease and anti-laminin 332 reactivity, suggesting potential benefit of malignant neoplasm screening in these patients.
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