Pemphigoid Diseases Research Articles

Serum interleukin-10 level is increased and correlated positively with disease severity in patients with dipeptidyl peptidase-4 inhibitor-related bullous pemphigoid.

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease with a linear deposit of autoantibodies at the epidermal basement membrane zone. It was reported that diabetes patients who took a dipeptidyl peptidase-4 inhibitor (DPP4i), an oral antidiabetic drug, had an increased incidence of BP. However, data on DPP4i-related BP are limited. In our study, we measured serum levels of various cytokines using LEGENDplex and assessed correlations of these serum levels with clinical severity and laboratory data. Serum samples obtained from BP patients who visited our hospital from June 2016 to February 2023 were collected in this study. Patients' background, characteristics, and clinical data were retrospectively collected from their charts. Serum samples from 27 patients with DPP4i-unrelated BP, 17 patients with DPP4i-related BP, and 13 healthy controls were analyzed. Patients with DPP4i-related BP had lower score of Bullous Pemphigoid Disease Area Index (BPDAI)-erythema/urticaria, lower number of circulating eosinophils, and lower titer of anti-BP180 antibody than patients with DPP4i-unrelated BP. The serum interleukin (IL)-6 level was significantly higher in patients with DPP4i-related BP than in healthy controls (P = 0.0037). The serum IL-10 level was significantly higher in patients with DPP4i-related BP than in patients with DPP4i-unrelated BP and in healthy controls (P = 0.0006, P = 0.0448), and was positively correlated with the BPDAI-blister/erosions score (r = 0.757, P = 0.001), BPDAI-erythema/urticaria score (r = 0.616, P = 0.013), and BPDAI-total score (r = 0.833, P < 0.001) in patients with DPP4i-related BP. In conclusion, patients with DPP4i-related BP had increased serum levels of IL-6 and IL-10 compared with healthy controls and positive correlations between the serum IL-10 level and BPDAI scores reflecting clinical severity, indicating that the serum IL-10 level is a potential objective biomarker of disease severity in patients with DPP4i-related BP.

Clinical Outcomes After Distal Bypass in Patients With Chronic Limb-Threatening Ischemia due to Connective Tissue Disease.

Chronic limb-threatening ischemia (CLTI) is mostly caused by arteriosclerosis, but is sometimes due to connective tissue disease. However, there is a limited knowledge of clinical outcomes of patients with CLTI with connective tissue disease. The objective of the study was to assess outcomes after distal bypass in these patients using global vascular guidelines. Data from distal bypasses performed for CLTI at a single center from 2014 to 2023 were evaluated retrospectively. Clinical outcomes after distal bypass were compared for patients with CLTI with arteriosclerosis (AS group) and those with connective tissue disease (CD group). The primary endpoints were limb salvage and wound healing. Of the 282 distal bypasses performed for 222 patients with CLTI, 22 were conducted for 21 patients with connective tissue disease (CD group). The connective tissue disease was progressive systemic scleroderma (n = 11 patients), pemphigoid diseases (n = 2), polyarteritis nodosa (n = 2), rheumatoid arthritis (n = 2), and others (n = 4). Compared with the AS group, the CD group included more females (P = .007) and had greater oral steroid use (P < .001) and a higher Global Limb Anatomical Staging System (GLASS) inframalleolar (IM) modifier P2 (P < .001). The mean follow-up period of the whole cohort was 27 ± 22 months with no significant difference between the groups (P = .25), and 22 limbs required major amputation during this period. The 2-year limb salvage rate was significantly lower in the CD group compared to the AS group (75% vs 94%, P = .020). Wound healing was achieved in 220 (78%) limbs, and the 12-month wound healing rate was significantly lower in the CD group (52% vs 86%, P = .006). The low 2-year limb salvage and 12-month wound healing rates in patients with CLTI with connective tissue disease indicate that distal bypass may be challenging in these patients.

Polarization of circulating Follicular Helper T cells correlates with the severity of Bullous Pemphigoid.

T-follicular-helper (Tfh) cells form a distinct population of T-helper cells with different polarizations (type 1, type 2 and type 17) that regulates humoral responses and may participate in the pathophysiology of B-cell mediated autoimmune diseases, such as bullous pemphigoid (BP), a dermatosis mediated by auto-antibodies specific for hemidesmosomal proteins. The aim was to evaluate the impact of superpotent topical corticosteroid (TCS) treatment, which is more effective and safer than high doses of oral corticosteroids and recommended first-line treatment of BP, on circulating Tfh cells. We compared by flow cytometry the frequency, polarization and activation of blood Tfh cells from patients with BP at baseline and longitudinally after initiation of TCS treatment to age- and sex-matched healthy subjects. We observed that circulating Tfh cells were more frequent in patients with BP at baseline than in healthy subjects and exhibited an activated phenotype. We further showed a decrease of type 1 and an increase of type 17 Tfh cells in the blood of patients, which resulted in a higher (type 2+type 17) to type 1 Tfh cell ratio. This ratio correlated positively with disease severity as measured by the Bullous Pemphigoid Disease Area Index. Remarkably, along TCS treatment, although the frequency of Tfh cells returned to a level similar to control, the activated phenotype persisted. Interestingly serum IL-21 levels and the Tfh cell subset ratio, similarly to disease activity and serum anti-BP180 and anti-BP230 auto-antibodies, were decreased under the TCS treatment. Overall, our findings suggest an involvement of the polarization of Tfh cells in the pathophysiology of BP and open the door to a modulation of their activity for therapeutic purposes.

Diagnosis of autoimmune bullous dermatoses: Comparative analysis of immunohistochemical staining using C4d, C3d, IgG, and IgG4 in lesional tissues and perilesional frozen skin samples

Immunohistochemical staining with immunoglobulins and complements may aid the diagnosis of patients whose clinical and histological findings are consistent with autoimmune bullous dermatoses (AIBD). We aimed to investigate the diagnostic value of immunohistochemical markers in lesional biopsy and perilesional frozen samples in AIBD. We included 136 cases from whom lesional biopsies and perilesional samples for direct immunofluorescence (DIF) examination were collected with a preliminary diagnosis of AIBD between January 2019 and January 2023. All diagnoses were reconfirmed by evaluating the clinical, histopathological, and serological findings and DIF results (C3, IgG, IgA, or IgM positivity compatible with the clinical diagnosis) altogether, although DIF results were considered a priority. After confirming the diagnoses, the samples were categorized as AIBD or the others. The perilesional tissues obtained for DIF simultaneously with skin biopsy and stored at −80 °C were thawed, and FFPE tissues were prepared. We performed immunohistochemical staining (C4d, C3d, IgG, and IgG4) on FFPE tissues of both lesional and perilesional samples. Strong, linear, or granular staining patterns at the dermoepidermal junction or the intraepidermal blistering space were considered positive in line with the diagnosis of the case. Cases other than AIBD were used as negative control tissues to assess the specificity of immunohistochemical markers. Of the 136 cases, 52 were diagnosed with AIBD. In lesional samples, the sensitivity of C4d, C3d, IgG, and IgG4 was 80.6 %, 69.4 %, 75 %, and 5.7 % with corresponding specificity of 100 %, 98.7 %, 89.6 %, and 97.4 %, respectively in pemphigoid diseases compared to a sensitivity of 18.2 %, 9.1 %, 70 %, and 9.1 % and specificity of 98.7 %, 100 %, 89.6 %, and 97.4 %, respectively in pemphigus diseases. In frozen samples, we detected expression in a limited number of cases. The sensitivity of C4d, C3d, IgG, and IgG4 was 8.7 %, 2.2 %, 19.4 %, and 2.2 %, with corresponding specificity of 100 %, 100 %, 98.5 %, and 98.6, respectively. There was a none to slight concordance rate between the IHC results of lesional tissues and perilesional frozen samples. Kappa coefficients for C4d, C3d, IgG, and IgG4 were 0.120 (P = 0.029), 0.111 (P = 0.050), 0.203 (P = 0.003), and - 0.15 (P = 0.846), respectively. Immunohistochemical staining with C4d, C3d, IgG, and IgG4 on biopsy samples collected from lesions may guide the diagnosis of AIBD, thereby eliminating the need for an additional biopsy and accelerating the diagnostic process.

Scoring Criteria for Autoimmune Bullous Diseases: Utility, Merits, and Demerits.

Scoring systems play a crucial role in dermatology by providing objective measurements of disease severity, treatment efficacy, and outcome comparisons. In autoimmune blistering diseases (AIBDs), standardized scoring systems are essential for accurate evaluations; however, there is currently a lack of consensus on scoring methods. This literature review explores scoring systems in AIBDs by tracing their development, addressing challenges, and highlighting their role in defining endpoints, regulatory considerations, and clinical trials. Existing scoring systems for AIBDs, such as the Pemphigus Disease Area Index, Autoimmune Bullous Skin Disorder Intensity Score, Pemphigus Oral Lesions Intensity Score, Oral Disease Severity Score, and Pemphigus Vulgaris Activity Score, are examined for their validity, reliability, and responsiveness. The Bullous Pemphigoid Disease Area Index for bullous pemphigoid is also discussed. The concept of minimal clinically important differences is explored to determine clinically significant improvements in disease severity. This review provides a comprehensive understanding of the central role of scoring systems in dermatology and their implications for research and clinical practice in AIBDs.

Clinical and immunoserological characteristics of anti-p200 pemphigoid: Comparisons of patients with epitope spreading and non-epitope spreading.

Anti-p200 pemphigoid is a rare autoimmune subepidermal blistering disease. Although the phenomenon of epitope spreading has been reported to be common in anti-p200 pemphigoid, the association between its clinical and immunoserological features has yet to be elucidated. Our aim was to compare the clinical and immunoserological characteristics of anti-p200 pemphigoid patients with and without epitope spreading. We performed a retrospective cohort study encompassing 30 patients with anti-p200 pemphigoid between January 2015 and December 2022. The clinical and immunoserological characteristics of anti-p200 pemphigoid were analyzed using combined immunoserological assays. Epitope spreading was observed in 11 of 30 patients (36.7%) with anti-p200 pemphigoid. Compared with patients in the non-epitope spreading group, patients in the epitope spreading group showed more heterogeneous clinical presentations (P = 0.018), a higher proportion of mucosal involvement (P = 0.003), higher Bullous Pemphigoid Disease Area Index (BPDAI) scores for skin erosions/blisters (P = 0.018), mucosal erosions/blisters (P = 0.001), activity (P = 0.017) and total scores (P = 0.022), and required a higher initial dose of prednisone for disease control (P = 0.040). This study supported the idea that anti-p200 pemphigoid was prone to epitope spreading. Anti-p200 pemphigoid patients with epitope spreading are more likely to present heterogeneous clinical phenotypes, frequent mucosal involvement, and a more severe and recalcitrant disease course.

Frequency and Correlation of Peripheral and Tissue Eosinophilia with Clinical Manifestations in Patients with Bullous Pemphigoid.

Bullous pemphigoid (BP) is an autoimmune disease involving the sub-epidermal layer. Eosinophilia may play a role in the pathogenesis of BP. We aimed to investigate the correlation between dermal or peripheral eosinophilia with clinical presentations in patients with BP. This cross-sectional study was conducted on 108 BP patients from January 2010 to September 2019. Clinical data were recovered. Skin biopsies were re-evaluated, and the Bullous Pemphigoid Disease Area Index (BPDAI) severity score was calculated. Finally, the relationship between clinical features of BP and dermal or peripheral eosinophilia was analyzed. A total number of 108 patients were included in this study. Thirty-five were excluded due to our exclusion criteria. Finally, data from 73 patients were analyzed. Fifty-seven point five percent of the population was female. There was a significant direct correlation (r = 0.33) between BPDAI severity score and tissue eosinophilia (P = 0.03). No significant relationship was found between BPDAI severity score and peripheral eosinophilia (P = 0.52). There were significant positive correlations between tissue eosinophilia with absolute serum eosinophil count (P = 0.002; r = 0.49) and percentage (P < 0.0001; r = 0.89). This study revealed significant relationships between tissue eosinophilia and BP severity. These findings could be useful in clinical practice. The possible role of eosinophils in BP clinical features should be considered as a promising help for better diagnosis and treatment.

Fast itch relief during dupilumab predicts clinical efficacy in bullous pemphigoid, a retrospective cohort study.

Dupilumab has emerged as a promising treatment option for bullous pemphigoid (BP). Rapid identification of responders could avoid the need of additional immunosuppressive treatments that are associated with increased morbidity and mortality. To investigate the course of itch as an early indicator of treatment response, data of 12 BP patients treated with dupilumab at the University Hospital of Zurich were retrospectively evaluated. Disease severity was assessed by bullous pemphigoid disease area index (BPDAI) and pruritus by a numeric rating scale (NRS, 0-10) at baseline, day 1, 3, 14, month 1, 2 and last follow-up. 8/12 patients (67%) had complete, and 4/12 patients (33%) had partial response during dupilumab treatment. Notably, a highly significant reduction of pruritus (p &lt; 0.0001) was observed already on day 1 with further improvement at later time points. Moreover, fast relief of itch could predict treatment response with a significant correlation to clinical response on day 14 (Spearman correlation R 0.70, p-value 0.025), with a positive but non-significant trend on day 3 (R 0.63, p-value 0.091). Additionally, 92% (11/12 patients) were on dupilumab monotherapy at last follow-up without any concomitant systemic or topical treatment for BP. The rapid and significant decline in BP-associated pruritus observed with dupilumab correlated significantly with disease remission. Early evaluation of pruritus response could change how bullous pemphigoid is treated in the future and avoid additional immunosuppressive treatment in BP.

Pemphigoid diseases in patients with end-stage kidney diseases: pathogenesis and treatment.

Pemphigoid diseases constitute a group of autoimmune blistering disorders characterized by subepithelial blistering. The association between pemphigoid diseases and both end-stage kidney disease (ESKD) and its treatment is notable. However, there is limited evidence about the management of pemphigoid diseases in patients with ESKD. This systematic review compiled case reports and relevant studies, summarized the underlying mechanisms of pemphigoid diseases in patients with ESKD, and summarized the efficacy of various therapies. A systematic search of PubMed and Embase was performed for articles published between 1982 to June 2, 2024. Fifty-three case reports and eight relevant studies were included. Triggers for pemphigoids in patients with ESKD included materials used to treat ESKD, immune dysregulation of patients with ESKD, and rejection of renal allograft. Treatment for these patients included removing triggers, as well as administering of corticosteroids, mycophenolate mofetil (MMF), tetracyclines, rituximab, methotrexate, dapsone, azathioprine, cyclosporine, intravenous immunoglobin (IVIG), plasmapheresis, and Janus kinase inhibitors. Removing triggers is the most effective strategy. Despite their suboptimal efficacy, corticosteroids remain the most commonly used agents in this patient population. MMF, tetracyclines, and rituximab are less used but with benefits. There are significant adverse effects associated with methotrexate treatment. Other treatment may also be beneficial and require further investigation. These findings may enable clinicians to optimize the therapeutic approach for these patients.

Reactivity against the BP180 ectodomain in patients with bullous pemphigoid, mucous membrane pemphigoid, multiple sclerosis and Parkinson disease

AbstractThe 16th non‐collagenous domain (NC16A) of BP180 is the main antigenic target of autoantibodies in bullous pemphigoid (BP) and mucous membrane pemphigoid (MMP). Commercially available assays detect serum autoantibodies against NC16A in the majority of BP (80%–90%) and in approximately 50% of MMP patients. However, a standardized test system for detecting antibodies against other regions of BP180 is still lacking. Moreover, anti‐BP180 autoantibodies have been found in neurological conditions such as multiple sclerosis and Parkinson disease. This study aimed at identifying primary epitopes recognized by BP autoantibodies on the BP180 ectodomain. Serum samples of 51 BP and 30 MMP patients both without anti‐NC16A reactivity were included along with 44 multiple sclerosis and 75 Parkinson disease sera. Four overlapping His‐tagged proteins covering the entire BP180 ectodomain (BP180(ec)1–4) were cloned, expressed, purified and tested for reactivity by immunoblot. IgG antibodies to BP180(ec)3 were detected in 98% of BP, 77% of MMP and 2% of normal human sera. Only weak reactivity was detected for neurological diseases against BP180(ec)1, BP180(ec)2 and BP180(ec)4, in 3%, 11% and 7% of tested multiple sclerosis sera, respectively. 8% of Parkinson disease sera reacted with BP180(ec)2 and 9% with BP180(ec)4. In conclusion, this study successfully identified epitopes recognized by BP autoantibodies outside the NC16A domain in pemphigoid diseases. These findings contribute to a better understanding of the immune response in BP and MMP with potential implications for a future diagnostic assay for NC16A‐negative pemphigoid patients.

High serum total IgE levels correlate with urticarial lesions and IgE deposition in perilesional skin of bullous pemphigoid patients: An observational study.

Background In the pathophysiology of bullous pemphigoid, besides IgG, there has been evidence that supports the role of IgE antibodies. However, there have been no studies to evaluate total serum IgE levels or detect IgE deposits in the skin of Vietnamese patients. Aim To analyse the association between IgE levels in the serum and disease severity as well as eosinophils and IgE basement membrane zone (BMZ) deposition in Vietnamese bullous bullous pemphigoid patients. Methods A single-centre observational research on 35 newly diagnosed and untreated bullous bullous pemphigoid patients. Total serum IgE levels were analysed using enzyme-linked immunosorbent assay (ELISA). For controls, we collected sera of 30 pemphigus patients and 30 elderly patients with pruritus. Perilesional skin biopsies underwent direct immunofluorescence (DIF) staining, with biopsies of pemphigus patients as controls. Results Elevated total serum IgE was observed in 60% of bullous pemphigoid patients, the percentage in the pemphigus group and pruritus group was 20% and 40%, respectively. The mean total serum IgE level among the bullous pemphigoid group was higher than that of the pemphigus group (123.3 ± 102.4 IU/mL vs. 64.3 ± 45.1 IU/mL, p = 0.010). Total serum IgE levels of bullous pemphigoid patients correlated with higher eosinophil counts (r = 0.61; p = 0.018) and urticaria/erythema (U/E) Bullous Pemphigoid Disease Area Index (BPDAI) score (r = 0.50; p = 0.035). Among 35 bullous pemphigoid patients, 5 patients showed positive IgE DIF staining, accounting for 14.3%. Higher serum IgE levels correlated with the deposition of IgE in patients' perilesional skin (p = 0.037). Limitations Due to the rarity of bullous pemphigoid, the effect of the COVID-19 pandemic, and self-treatment issues in Vietnam, we could not recruit a larger number of participants. Conclusions Total serum IgE values correlated with urticarial lesions and IgE deposition in perilesional skin of Vietnamese bullous pemphigoid patients. IgE autoantibodies present in the skin of bullous pemphigoid patients support the role of IgE in bullous pemphigoid pathogenesis.

Bullous pemphigoid and lichen planus pemphigoides in monozygotic twins with a long-standing history of psoriasis.

In the medical literature, occurrence of pemphigoid diseases in twins has rarely been reported in the literature. We report identical twins with a long-standing history of psoriasis who developed in their third decades bullous pemphigoid (BP) and lichen planus pemphigoides (LPP), respectively.

Diacron-Reactive Oxygen Metabolites Levels Are Initially Elevated in Patients with Bullous Pemphigoid

Reactive oxygen species (ROS) are involved in the pathogenesis of bullous pemphigoid (BP), but this involvement has not been fully elucidated. In this study, to further elucidate the pathogenic role of ROS in BP, we examined the results of the diacron-reactive oxygen metabolite (d-ROMs) test and the biological antioxidant potential test for 16 BP patients who visited our hospital before being treated with systemic corticosteroids. In the BP patients, the average d-ROMs levels, expressed in Carratelli units (U.CARR), were significantly reduced at 1 month of treatment (from 335.6 ± 40.3 U.CARR to 224.7 ± 61.6 U.CARR, P<0.001). Bullous Pemphigoid Disease Area Index (erosions/blisters) scores correlated with d-ROMs levels (r=0.51), suggesting that those levels reflect the disease severity. We also performed staining of 3,5-dibromotyrosine (DiBrY) in skin tissues. DiBrY is expected to be a marker of tissue damage related to inflammation and allergies. The DiBrY was stained in infiltrated cells around the dermis, throughout the blister fluid, and at the basement membrane within the blister. It is considered that tissue destruction caused by the myeloperoxidase released from neutrophils and by eosinophil peroxidase released from eosinophils is involved in blister formation. The results suggest that ROS play a role in BP.

The pathological function of neutrophils in pemphigoid diseases

Abstract Pemphigoid diseases (PDs) are a group of autoimmune blistering diseases, including bullous pemphigoid, epidermolysis bullosa acquisita, mucous membrane pemphigoid, linear immunoglobulin A disease, and other rare variants. These diseases are characterized by the presence of autoantibodies that target proteins at the dermal-epidermal junction, resulting in the formation of tense blisters and erosions on the skin and/or mucosa. The current therapeutic approaches, such as systemic corticosteroid, are associated with significant adverse effects, highlighting that safer and more effective treatment options are an urgent clinical need. To address this unmet need, a comprehensive understanding of the detailed mechanisms underlying PDs is essential. Based on their histopathological infiltration in pemphigoid lesions, neutrophils have long been implicated as major contributors to the initiation and progression of the diseases. Numerous in vivo and in vitro studies have investigated the role of neutrophils in the pemphigoid pathology, revealing various pathological mechanisms induced by these cells, including the release of neutrophil elastase and matrix metalloproteinase-9, as well as the formation of neutrophil extracellular traps. The present review provides a comprehensive summary and critical evaluation of the current understanding regarding the role of neutrophils in PDs. In addition, it discusses the potential of targeting neutrophil-associated pathways as a novel therapeutic approach for the diseases.

Clinical manifestation variability of bullous pemphigoid.

Bullous pemphigoid (BP) is arare autoimmune blistering disease predominantly affecting the elderly population. The present study aims to identify clinical factors that may influence outcomes of BP, including skin phenotype, serology, mucosal involvement, pruritus, and triggers. Aretrospective analysis was conducted on 70 cases with BP registered from January 2019 to December 2022. The Bullous Pemphigoid Disease Activity Index (BPDAI) score was used to assess disease intensity. The BPDAI-Pruritus score and amodified Brest questionnaire were used to document pruritus. Anti-BP180 and anti-BP230 autoantibodies were regularly recorded. Peripheral blood eosinophil counts were documented during flare-up and remission phases of BP. Of the cases, 81.4% were identified with bullous BP, 12.9% with nonbullous BP and 5.7% with localized BP. Oral involvement was documented in 17.1% of cases. Increased peripheral eosinophilia was prominent in the nonbullous phenotype and returned to normal level during remission in both phenotypes. The outcomes of BP depended on the disease phenotype and trigger types. Bullous BP showed more intense disease activity, while nonbullous BP demonstrated more intense pruritus. BP associated with diabetes mellitus (DM) or psoriasis manifested as amore severe disease, predominantly with the bullous phenotype and pruritus, compared to cases without comorbidities. New triggers, including SARS-CoV-2 infection and vaccination, were documented (Tab. 6, Ref. 43). Text in PDF www.elis.sk Keywords: bullous pemphigoid, nonbullous pemphigoid, pruritus, comorbidity, eosinophilia, new triggers.

A case of bullous pemphigoid and renal disease after dipeptidyl peptidase 4 inhibitor administration

A 62-year-old man with type 2 diabetes was admitted because of a decrease in estimated glomerular filtration rate from 72 to 17.5 mL/min/1.73 m2 in 10 years and development of widespread bullous skin lesions. His hemoglobin A1c level had been maintained at 6.0–7.0% for 10 years with a dipeptidyl peptidase (DPP)-4 inhibitor. Skin biopsy showed typical bullous pemphigoid, and kidney biopsy showed tubulointerstitial nephritis with eosinophilic infiltration and glomerular endothelial cell proliferation. After discontinuing the DPP-4 inhibitor, skin lesions improved, and renal decline slowed. This case indicates that DPP-4 inhibitors can cause not only skin lesions but also renal disease.

Monocyte populations are involved in the pathogenesis of experimental epidermolysis bullosa acquisita.

Monocytes play a significant role in the pathogenesis of most inflammatory diseases, including autoimmune diseases. Herein, different subpopulations of monocytes often play differential, partially antagonistic roles, in the regulation of tissue populations. Pemphigoid diseases constitute a group of autoimmune blistering skin diseases featuring a marked infiltration of the dermis with immune cells, including monocytes. The monocyte subsets infiltrating the skin, however, have largely remained elusive. Monocyte adhesion and recruitment into the inflamed tissues are regulated by chemokine receptors, most prominently by CCR2 and CX3CR1. To delineate the involvement of monocyte populations in autoimmune blistering skin diseases, we spatiotemporally monitored the dynamic spectrum of monocyte populations that infiltrate the inflamed skin using multiphoton intravital imaging and reporter mice for chemokine receptors. Experimental epidermolysis bullosa acquisita (EBA) was induced by injection of anti-murine type VII collagen (amCOLVII) IgG into the Csf1rEGFP-reporter mice, where circulating myeloid cells, such as monocytes and neutrophils, express an EGFP. EGFP+ cells, including neutrophils and monocytes, were present in the skin, immediately after the deposition of the amCOLVII antibody at the dermal-epidermal junction. To investigate the recruitment and involvement of different monocyte-derived cell populations in the disease course further, EBA was induced in CCR2RFP/+-reporter and CX3CR1GFP/+-reporter mice. A comparable distribution of red fluorescent protein (RFP)+ or green fluorescent protein (GFP)+ was found in both diseased mice and their respective controls over time, indicating the similar recruitment of monocytes into the skin following the binding of autoantibodies. Experiments were extended to the CCR2RFP/RFP-deficient and CX3CR1GFP/GFP-deficient mice to determine whether monocyte recruitment and disease severity are compromised in the absence of the receptor. A comparable pattern was seen in the recruitment of monocytes into the skin in both reporter and deficient mice. However, in contrast to similar disease severity between CX3CR1-deficient and reporter mice, CCR2-deficient mice developed significantly less disease than CCR2-reporter mice, as indicated by the percentage of affected area of ears. Collectively, our observations indicate that while CCR2 and CX3CR1 receptors are not involved in the recruitment of monocytes into the skin, CCR2 deficiency is associated with improved disease outcomes in experimental EBA in mice.

IgE anti-BP180 NC16A autoantibody in both serum and blister fluid samples does not correlate with disease activity of bullous pemphigoid.

The correlation between IgE anti-BP180 NC16A autoantibody and disease activity of bullous pemphigoid (BP) remains disputable. To determine the levels of IgE anti-BP180 NC16A autoantibody and its clinical significance in untreated BP patients. IgG and IgE anti-BP180 NC16A autoantibody in serum and blister fluid samples of 34 untreated BP patients was detected by enzyme-linked immunosorbent assay (ELISA), and correlation with clinical and pathological features of BP were statistically analysed. The Bullous Pemphigoid Disease Area Index (BPDAI) was used to measure disease activity of BP. The mean baseline level of IgG anti-BP180 NC16A autoantibody in serum and blister fluid samples of untreated BP patients was 75.3U/mL and 1.54U/mL, respectively (A450, cutoff: 0.126). IgE anti-BP180 NC16A autoantibody was positive in 21.9% serum and 14.7% blister fluid samples of untreated BP patients. IgE anti-BP180 NC16A autoantibody levels in serum samples positively correlated with those from blister fluid samples (r = 0.983, p < 0.05). However, IgE anti-BP180 NC16A autoantibody level in both serum and blister fluid samples of untreated BP patients did not correlate with IgG anti-BP180 NC16A autoantibody, age, extent of elevated peripheral blood eosinophils, BPDAI erosion/blister score, BPDAI urticaria/erythema score, BPDAI pruritus score, BPDAI without damage score, or BPDAI total score (all p > 0.05). No significant correlation was identified between disease activity and positive or negative anti-BP180 NC16A IgE autoantibody. Conclusion: IgE anti-BP180 NC16A autoantibody in both serum and blister fluid samples does not appear to correlate with disease activity of BP.

Long-term efficacy and safety of dupilumab for severe bullous pemphigoid: A prospective cohort study

BackgroundBullous pemphigoid (BP) is a common subepidermal bullous disease. Dupilumab is a novel treatment for BP. However, its long-term efficacy and safety have not been demonstrated in prospective studies. ObjectiveEvaluate the long-term efficacy and safety of dupilumab in treating severe BP. MethodsPatients were divided into two groups: the methylprednisolone monotherapy group (M), and the methylprednisolone and dupilumab combination therapy group (D + M). This study consisted of two stages. The first stage focused on the initial treatment phase, where the early efficacy and safety was evaluated. The study then entered the 12-month maintenance treatment stage, where we assessed recurrence in both groups. Additionally, we evaluated the rate of healing of skin lesions, glucocorticoids burden and length of hospital stay and various laboratory test indicators. ResultsAfter four weeks of treatment, the Bullous Pemphigoid Disease Area Index (BPDAI) and pruritus Numerical Rating Scale scores of the D + M group decreased significantly more than those of the M group. The median BPDAI at week 4 was 0 (range: 0.0–3.0) in the D + M group and 10.0 (5.0–12.0) in the M group (P < 0.001). Patients treated with dupilumab experienced a faster cessation of new blisters, quicker glucocorticoid reduction, shorter healing times, and shorter hospital stays (P < 0.001). Additionally, after two weeks of treatment, the levels of eosinophils and immunoglobulin E also decreased (P < 0.001). Follow-up studies further demonstrated that dupilumab monotherapy was associated with a lower recurrence rate. Notably, no serious adverse effects were observed in the study. ConclusionsOur study provides evidence for the efficacy of dupilumab in the treatment of BP based on prospective studies. Additionally, our findings suggest that dupilumab can be considered a reliable single-agent maintenance treatment due to its good safety profile and lower relapse.

Rare variants of pemphigoid diseases

Pemphigoid diseases comprise aheterogeneous group of subepidermal autoimmune blistering dermatoses characterized by autoantibodies against structural proteins of the dermal-epidermal junction. Recent decades have witnessed asignificant surge in the incidence of these diseases, which, in addition to general aging of the population, can be attributed to the availability of precise diagnostic methods and improved knowledge of the clinical and immunopathological spectrum. While bullous pemphigoid, mucous membrane pemphigoid, and linear IgA disease account for most pemphigoid disorders, less frequent, presumably underdiagnosed variants are increasingly becoming relevant for clinicians. These include epidermolysis bullosa acquisita, anti-p200 pemphigoid, pemphigoid gestationis, lichen planus pemphigoides, and recently defined entities such as IgM pemphigoid and Orf-induced pemphigoid. Accurate characterization and differentiation of these subtypes are not only of diagnostic relevance but may also be associated with therapeutic and prognostic implications for affected individuals. Due to the rarity of these diseases, no controlled prospective clinical trials currently exist, making their diagnosis and therapy challenging.