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Background: Recently, we published an article retrospectively summarizing the results in 55 anti-laminin 332 (LM332)-type mucous membrane pemphigoid (MMP) cases examined at Kurume University, which were diagnosed by strict inclusion criteria, including positive reactivity in direct immunofluorescence and absence of antibodies to non-LM332 autoantigens. However, indirect immunofluorescence using 1M-NaCl-split normal human skin (ssIIF) is also valuable for diagnosis of anti-LM332-type MMP. Methods: In this second study, we selected 133 anti-LM332-type MMP cases, which were diagnosed by our different inclusion criteria: (i) immunoglobulin G (IgG) deposition to basement membrane zone (BMZ) by direct immunofluorescence or IgG reactivity with dermal side of split skin by ssIIF, (ii) positivity for at least one of the three subunits of LM332 by immunoblotting of purified human LM332, and (iii) the presence of mucosal lesions. Clinical, histopathological, and immunological findings were summarized and analyzed statistically. Although these cases included the 55 previous cases, the more detailed study for larger scale of patients was conducted for further characterization. Results: Clinically, among the 133 patients, 89% and 43% patients had oral and ocular mucosal lesions, respectively, 71% had cutaneous lesions, and 17% had associated malignancies. Histopathologically, 93% patients showed subepidermal blisters. The sensitivities of ssIIF and direct immunofluorescence are similar but are significantly higher than indirect immunofluorescence using non-split human skin (both p < 0.001). In immunoblotting of purified LM332, patient IgG antibodies most frequently reacted with LMγ2 subunit (58%), followed by LMα3 (49%) and LMβ3 (36%). Thirty-four percent patients recognized additional non-LM332 autoantigens. Statistical analysis revealed that autoantibodies against non-LM332 autoantigens might stimulate the production of anti-LMγ2 antibodies. Conclusions: This retrospective study further characterized in more detail the clinical and immunological features of 133 cases of anti-LM332-type MMP, in which the new diagnostic criteria without positive direct immunofluorescence reactivity were useful for the diagnosis. Higher frequency with anti-LMγ2 antibodies suggested more significant pathogenic role of this subunit. Additional autoantibodies to non-LM332 autoantigens detected in one-third of the patients may contribute to complexity in anti-LM332-type MMP, including the induction of anti-LMγ2 antibodies. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors including programmed cell death protein 1 (PD‐1) antibody are used in major breakthrough therapies in cancer, however they cause unique adverse events, termed immune‐related adverse events (irAEs). Among the various dermatological irAEs, an autoimmune bullous disease, bullous pemphigoid (BP), the hallmarks of which are circulating autoantibodies to epidermal basement membrane zone (BMZ) including BP180, have been noted. However, the mechanism and timing of autoantibody production in PD‐1 inhibition remains unclear. Herein we report the case of a lichen planus (LP)‐like lesion in presence of anti‐BMZ antibodies, preceding BP in a patient treated with pembrolizumab, a PD‐1 antibody. A 72‐year‐old Japanese woman with a 3‐month history (6 cycles) of pembrolizumab was referred to our department for pruritic purple‐red papules or plaques. Histological finding revealed LP‐like dermatitis. Although pembrolizumab was stopped because of disease progression, she developed edematous erythematous lesions and tense blisters seven weeks later. Based on histopathological findings, direct immunofluorescence (DIF) assay and positive findings on chemiluminescent enzyme immunoassay (CLEIA) for BP180, she was diagnosed with BP and administered oral prednisolone. The blisters and erythemas improved, whereas her respiratory condition worsened and she died 29 days after the development of BP. We performed DIF of formalin‐fixed, paraffin‐embedded specimens biopsied from the LP‐like lesion and revealed IgG deposition at the epidermal BMZ. This finding showed anti‐BMZ antibodies had already existed at LP‐like lesion preceding development of BP; this suggests that the preceding LP‐like lesion induced anti‐BMZ antibody production, resulting in the development of BP. [ABSTRACT FROM AUTHOR]

Dear Editor, It has been widely known that dipeptidyl peptidase-IV inhibitors (DPP4i) are causative factors of bullous pemphigoid (BP). Anti-laminin-332 antibody usually causes mucous membrane pemphigoid, whereas there have been some conventional pemphigoid cases with anti-laminin-332 antibody showing only skin lesions like our case.5 Although our single case experience cannot make a conclusion, anti-laminin-332 antibody in DPP4i-associated BP might also be associated with an inflammatory phenotype. Anti-BP230 antibody was detected in some DPP4i-associated BP patients in coexistence with the antibody to full-length BP180,4 while only one case of DPP4i-associated BP solely positive for anti-BP230 antibody has been reported.2 That case showed blisters with surrounding erythema similar to our case, suggesting that anti-BP230 antibody might be associated with an inflammatory phenotype in DPP4i-associated BP. [Extracted from the article]

We described a case of BP that developed 2.5 years after the administration of nivolumab for metastatic non‐small cell lung cancer. Our report highlights the fact that dermatologists should be aware of anti PD‐1‐related BP, which can appear very late during treatment. [ABSTRACT FROM AUTHOR]

Pemphigoid diseases ( PD) are a subgroup of rare acute or chronic autoimmune skin disorders characterized and caused by autoantibodies directed against distinct structural components of the dermal-epidermal junction. Binding of autoantibodies to their targets leads to the formation of blisters and erosions in patients. PDs comprise eight disorders for which the molecular target antigens have been identified. First, we review the available in vitro and ex vivo models for analysis of distinct aspects of the pathogenesis of PDs. This includes the binding of autoantibodies to skin sections, the analysis of blister formation capability and skin complement activation as well as investigation of neutrophil and keratinocyte activation. In addition to this, several animal models of PD have been developed during the last decades. These animal models have greatly contributed to our current understanding of the pathogenesis of PDs. We summarize spontaneously arising PD in animals and the induction of PD by transfer of (auto)antibodies, transfer of (auto)-antigen-specific lymphocytes and by immunization. In combined use, these models allow dissecting all aspects of PD pathogenesis, for example loss of tolerance, autoantibody production and inflammatory skin processes that lead to blister formation. Overall, we aimed to foster translational biomedical research, to deepen our understanding of PD pathogenesis and to develop novel treatments for patients suffering from these life-threatening and difficult-to-treat autoimmune diseases. [ABSTRACT FROM AUTHOR]

Case of mucous membrane pemphigoid with immunoglobulin G antibodies to the beta 3 subunit of laminin-332 showing clinically Stevens-Johnson syndrome-like generalized blistering mucocutaneous lesions. Dear Editor, A 72-year-old Japanese woman taking cefcapene pivoxil hydrochloride hydrate (CFPN-PI), tranexamic acid, and acetaminophen for 2 days for fever and flu-like symptoms presented with photophobia, conjunctival hyperemia, and oral mucous erosions; she then discontinued all medications. A case of mucous membrane pemphigoid with anti-laminin alpha 3 and beta 3 antibodies initially mimicking Stevens-Johnson syndrome. [Extracted from the article]

Background Many case reports have described the coexistence of autoimmune bullous diseases (AIBDs) and psoriasis. Among them, anti-laminin γ1 (p200) pemphigoid is the best known. Objectives We sought to characterize patients with AIBDs and psoriasis and to investigate common AIBDs occurring in these patients. Methods This retrospective study included 145 patients with coexisting AIBD and psoriasis given a diagnosis from January 1, 1996, to July 31, 2013, at an academic dermatology department. Of these, 134 were consultation cases regarding AIBD diagnosis. Results Ratio of male to female patients was 5.7:1. Psoriasis onset preceded AIBD onset in most patients. Mean age at AIBD onset was 65.4 years, and mean duration between psoriasis and AIBD onset was 14.6 years. Most cases had single AIBD, whereas 16 cases had combined AIBDs. Bullous pemphigoid was the most prevalent (63.4%) followed by anti-laminin γ1 pemphigoid (37.2%). Limitations Consultation cases may not have included mild AIBD cases. Conclusion This study confirmed the association of psoriasis and anti-laminin γ1 pemphigoid. However, because bullous pemphigoid is a much more common disease, it is seen more frequently in patients with psoriasis than anti-laminin γ1 pemphigoid. [ABSTRACT FROM AUTHOR]

Recovery with milia may occur in bullous pemphigoid (BP), mucous membrane pemphigoid (MMP) and epidermolysis bullosa acquisita (EBA). Scarring commonly occurs in MMP and EBA. Here, we report a 62-year-old man patient with BP, who was left with numerous milia during recovery. The patient had immunoglobulin (Ig)G autoantibodies to the recombinant protein of the BP180-NC16a domain and the soluble 120- kDa ectodomain of BP180 (linear IgA bullous dermatosis [LAD]-1). There are cases of BP with IgG autoantibodies to LAD-1 and/or the recombinant protein of BP180 C-terminal domain. Extensive milia formation during recovery may be associated with immunological predisposition and/or improper interaction between hemidesmosomes and the extracellular matrix components. [ABSTRACT FROM AUTHOR]

B-cell activating factor ( BAFF), an important immune regulatory cytokine, is involved in development of autoimmune diseases. Although BAFF is expressed in various cells, including dendritic cells ( DCs) and monocytes, BAFF expression on B cells has not been well documented. In the present study, BAFF molecules on DCs and naïve and memory B cells in autoimmune bullous diseases, including pemphigus vulgaris, pemphigus foliaceus and bullous pemphigoid ( BP), were analysed by flow cytometry. Compared with healthy controls ( HC), BAFF expression on naïve and memory B cells increased significantly in BP. No difference in BAFF receptor expression in naïve and memory B cells was shown among all study groups. Furthermore, BAFF expression in both naïve and memory B cells of BP, but not HC, was detected by confocal microscopic analysis. These results implied that BAFF expressed by B cells may play a pathogenic role in autoimmune bullous diseases, particularly BP. [ABSTRACT FROM AUTHOR]