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.

Efficacy and safety of low-dose interleukin 2 in the treatment of moderate-to-severe bullous pemphigoid: A single center perspective-controlled trial.

BACKGROUND: Regulatory T cells (Tregs) are reduced in the peripheral blood and skin lesions of patients with bullous pemphigoid (BP). Low-dose interleukin 2 (IL-2) therapy can stimulate Tregs specifically, suggesting potential for the treatment of BP. OBJECTIVE: To evaluate the response to low-dose IL-2 therapy in the treatment of moderate-to-severe BP. METHODS: Forty-three patients with moderate-to-severe BP were included. The therapy included systemic corticosteroids with an initial dose of 0.5 mg/kg/d for moderate and 1.0 mg/kg/d for severe disease, respectively, combined with allowed immunosuppressants for the control group, whereas in addition to the same corticosteroid therapy, IL-2 (half million IU) was administered subcutaneously every other day for the treatment group for 8 weeks. The primary outcome was the number of days required to achieve disease control. Secondary outcomes included other clinical responses. RESULTS: The number of days required to achieve disease control with the treatment group was (7.60 ± 3.00), which was shorter than in the control group (10.43 ± 3.06) (P = .008). The total amount of systemic corticosteroids was less, and no serious infections were detected in the treatment group. LIMITATIONS: Single center, open-label study with short duration and small size. CONCLUSION: Our trial supports the potential of low-dose IL-2 therapy for patients with moderate-to-severe BP, which showed earlier treatment responses.

Clinical manifestations of alopecia in autoimmune blistering diseases: A cross-sectional study.

Background: Alopecia is a complication of autoimmune blistering diseases (AIBDs) that affects patients' quality of life; however, it has generally been overlooked in patients with severe disease because it is regarded as a cosmetic issue. Objective: To study the epidemiologic data and clinical presentations of alopecia in our cohort of patients with AIBDs. Methods: Forty-one patients with AIBDs were assessed in this cross-sectional study. An assessment tool to collate patient information, including AIBD scalp involvement, trichoscopic findings, and Severity of Alopecia Tool II scores, was used. Results: More than 70% of patients in our cohort had at least 1 type of alopecia, with 10% presenting with a nonspecific (end-stage) scarring alopecia. Elevated Dsg1 ratios were predictive of hair loss in pemphigus vulgaris (P < .001) and increased alopecia was associated with worse disease severity in bullous pemphigoid (P = .001). Limitations: The small sample size and lack of severe cases. Conclusion: There is a likelihood that 1 in 10 patients with AIBDs have a scarring alopecia related to their disease. To our knowledge, this is the first study including alopecia prevalence in patients with bullous pemphigoid, which was not significantly increased despite providing clues to disease severity.

Clinical Phenotypes and the Clinical Course of Bullous Pemphigoid Receiving Dipeptidyl Pepitidase-4 Inhibitor Treatment: An Analysis of Cases in a Single Japanese Center.

Objective Several studies have shown an increased risk of bullous pemphigoid (BP) when receiving dipeptidyl pepitidase-4 inhibitor (DPP-4i) treatment. The present study explored the associations of DPP-4i treatment with the clinical phenotypes and clinical course of BP. Methods We analyzed data of 146 patients with BP at Tokai University School of Medicine from December 1, 2009, to December 31, 2021. We obtained data by a retrospective medical record review and compared the bullous pemphigoid disease area index (BPDAI) between diabetes patients receiving DPP-4i treatment and those not receiving DPP-4i treatment. We employed multivariable linear regression models to explore the association between the DPP-4i treatment and the BPDAI scores. Results Among 53 BP patients with diabetes, 33 had developed BP during treatment with DPP-4i agents, among which vildagliptin was the most frequently used. The urticaria/erythema scores of the BPDAI were significantly lower in patients who developed BP while receiving DPP-4i treatment than among others. Of note, 69.2% of the patients who stopped DPP-4i treatment experienced complete remission, and the clinical course was more favorable in patients with lower scores for urticaria/erythema than among others. Conclusion These findings suggest that, in patients who developed BP while receiving DPP-4i treatment, a noninflammatory phenotype may indicate a high likelihood that DPP-4i treatment contributes to the development of BP. The discontinuation of DPP-4i should be carefully considered in close consultation with dermatologists.

Assessing Disease Outcome Measures in Bullous Pemphigoid on Standard-Of-Care Therapies.

Bullous pemphigoid (BP) is an autoimmune blistering disease resulting in pruritus and cutaneous blistering. Longitudinal studies characterizing the disease course of patients with BP on conventional therapy are lacking. We sought to characterize the changes in disease activity and pruritus of patients with BP on standard-of-care treatments. We conducted a retrospective cohort study on patients with BP on standard-of-care therapy. Generalized Estimating Equations were used to estimate the mean and standard errors for Bullous Pemphigoid Disease Activity Index (BPDAI) total activity score, BPDAI pruritus component score, and anti-BP180 autoantibody levels (BP180) over time. A total of 80 patients with BP showed consistent reductions in BPDAI total activity score and BPDAI pruritus component score, with a nadir at 4 months. BP180 decreased over time, with the largest reductions at 6 and 9 months. Median partial/complete remission was at 6.7 months, with relapses at a median time of 15.9 months. Receiving operating characteristic analysis determined an optimal BPDAI total activity score cutoff of 3.3 to discriminate partial/complete remission incidence (area under the curve = 0.895, sensitivity = 0.844, specificity = 0.78). In conclusion, in patients with BP on standard-of-care therapy, a natural course of BPDAI total activity score and BPDAI pruritus component score over time was comprehensively projected. BPDAI ≤ 3.3 was associated with partial/complete remission. These results provide reference data to guide future clinical trial design for BP.

Factors associated with the activity and severity of bullous pemphigoid: a review.

Bullous pemphigoid (BP) is the most common subepidermal autoimmune blistering disease. It usually affects people older than 70 years of age. The two main autoantigens are BP180 and BP230, both of which are components of hemidesmosomes. Immunoglobulin (Ig)G and IgE autoantibodies to BP180 detected by the enzyme-linked immunoassay (ELISA) show close associations with the activity and severity of BP. In addition, inflammatory cells (eosinophils, neutrophils and mast cells) and cytokines (e.g. interleukins and CC chemokine ligands) play an important part in the pathogenesis, activity and severity of BP. We summarized the potential contribution of each factor postulated to be associated with the activity and severity of BP, and provide guidance for clinicians to pay timely and close attention to such parameters. This review may also promote the development of novel therapies for BP.Key MessagesBullous Pemphigoid Disease Area Index (BPDAI) is a scoring system which can reflect the extent of clinical involvement of BP patients.The titres of IgE autoantibodies and IgG autoantibodies against the NC16A domain of BP180 are closely correlated with the activity and severity of BP.Many inflammatory cells and molecules, such as eosinophils and interleukins, can also reflect the activity and severity of BP.

Complement-Activating Capacity of Autoantibodies Correlates With Disease Activity in Bullous Pemphigoid Patients.

Background: Bullous pemphigoid is a subepidermal blistering skin disease, associated with autoantibodies to hemidesmosomal proteins, complement activation at the dermal-epidermal junction, and dermal granulocyte infiltration. Clinical and experimental laboratory findings support conflicting hypotheses regarding the role of complement activation for the skin blistering induced by pemphigoid autoantibodies. In-depth studies on the pathogenic relevance of autoimmune complement activation in patients are largely lacking. Therefore, the aim of this study was to investigate the pathogenic relevance of complement activation in patients with bullous pemphigoid. Complement activation by autoantibodies in vivo as measured by the intensity of complement C3 deposits in the patients' skin and ex vivo by the complement-fixation assay in serum was correlated with the clinical disease activity, evaluated by Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and Bullous Pemphigoid Disease Area Index (BPDAI), as well as, with further immunopathological findings in patients with bullous pemphigoid. Results: Complement-activation capacity of autoantibodies ex vivo, but not deposition of complement in the perilesional skin of patients, correlates with the extent of skin disease (measured by ABSIS and BPDAI) and with levels of autoantibodies. Conclusions: Our study provides for the first time evidence in patients for a pathogenic role of complement activation in bullous pemphigoid and should greatly facilitate the development of novel diagnostic tools and of more specific therapies for complement-dependent autoimmune injury.

Pemphigoid gestationis and intravenous immunoglobulin therapy.

Pemphigoid gestationis, which is also known as herpes gestationis, is a rare, pregnancy-associated, autoimmune bullous disease. Treatment depends on the severity of the disease for each patient and the safety and use of these drugs during pregnancy and breastfeeding must be taken into consideration to guide their use. We describe the therapeutic response of two cases of pemphigoid gestationis that did not respond to conventional immunosuppressive therapy or adverse effects limited their use. Both patients eventually received treatment with intravenous immunoglobulin therapy, which resulted in clinical remission. This clinical improvement with disappearance of lesions and a reduction in pruritus was paralleled in a decline in Bullous Pemphigoid Disease Activity Index activity scores, which is a validated scoring system to measure the related condition, bullous pemphigoid.