Discussion and overview of literature
Eosinophilia, bullae, hypereosinophilia, inflammation, asthma, AD, MP
RECURRENCE, EOSINOPHILIA, BULLOUS PEMPHIGOID, PROLIFERATION, HYPEREOSINOPHILIA, DISEASE, DISEASE, INFLAMMATION, ADVERSE EVENT, BULLOUS PEMPHIGOID, ASTHMA, CHRONIC EOSINOPHILIC PNEUMONIA, REMISSION, SEPARATION, PATHOLOGY, PATHOGENESIS, COMPLICATIONS
BP, the most prevalent autoantibody-mediated cutaneous blistering disorder, is characterized by pruritic vesicles or bullae and primarily affects older people. Pathogenic B and T cells, autoantibodies, and inflammatory cytokines/chemokines are significant in the characteristic pathology of BP (The pathogenesis and emerging therapeutic strategies in bullous pemphigoid. The existence of IgG antibodies and the complement element C3, which attacks the BMZ, characterizes BP. Immune complex production triggers the activation of complement, which results in the migration of eosinophils, mast cells, and neutrophils, as well as the secretion of proteases and inflammatory markers, thereby inducing dermal-epidermal split. The pattern of distribution of the subsets of T cells is atypical. The Th2, Tfh, and Th17 groupings are elevated, whereas the Treg cell count is diminished. By means of the release of IL-17, aberrant Th17 cell types enhance the pro-inflammatory immune reaction, stimulate neutrophils, magnify the inflammatory process, and promote tissue injury. Th2 cells and Th2 cell-released IL-4 stimulates B cell growth, antibody synthesis, and class-switching of immunoglobulins. The improper functioning of Treg cells promotes the activation of autoreactive CD4+ T lymphocytes and the creation of autoantibodies. Enhanced Tfh proliferation facilitates the production of autoantibodies in BP by B cells. Possible targets range from CD20+ lymphocytes with rituximab to the Th2 axis with dupilumab, and omalizumab or the IL-17/IL-23 axis, as well as the inhibition of particular complement or inflammatory mediators.A potent inhibitor of Th2-related chemokines (such as CCL17, CCL18, CCL22, and CCL26) in AD patients, dupilumab, an IL-4 receptor antagonist blocking both IL-4 and IL-13 signaling pathways, significantly improves the molecular signature of AD and exhibits a satisfactory efficacy and safety profile (Our current case series indicates that anti-IL-4 receptor α therapy in combination with immunosuppressive medications is well tolerated even in older BP patients with severe cardiovascular, metabolic, endocrine, infectious, and renal complications or other poor general conditions. Moreover, all mild and moderate patients in our case series achieved CR, and no disease flare-up was noted during the 1-year follow-up period, pointing to excellent efficacy profiles and a low recurrence rate in mild-to-moderate patients receiving dupilumab combined with methylprednisolone and/or TwHF. In these patients, dupilumab therapy also greatly aided the tapering of immunosuppressive medication. In comparison with rituximab (average of 148 days to CR), seven patients in this case series experienced CR 58 days earlier on average, which suggests early effectiveness in dupilumab-treated individuals (When conventional treatments had not yet been prescribed, we discovered a substantial rise of eosinophil counts in two patients with severe BP receiving dupilumab monotherapy. Eosinophilia was documented as an adverse event in 52 patients (4.1%) who received dupilumab for asthma treatment, and 59 patients (9.0%) for AD and mainly were laboratory results without clinical symptoms (only 0.2% of patients receiving asthma treatment were associated with eosinophil-related severe clinical adverse results [aggravation of hypereosinophilia and chronic eosinophilic pneumonia]) (BP is currently a therapeutic challenge, as the validated treatments are corticosteroids and corticosteroid-sparing immunosuppressants, the efficacy of which is counterbalanced by their low safety profile with long-term use. The most recent findings on the pathogenesis of BP have provided an impetus for additional research aimed at identifying novel target treatments for refractory cases, with the intent of ensuring long-term effective and safe treatments for BP patients. Possible targets range from CD20+ lymphocytes with rituximab to the Th2 axis with dupilumab, and omalizumab or the IL-17/IL-23 axis, as well as the inhibition of particular complement or inflammatory mediators. The evidence of these new therapeutic targets and specific investigational compounds is shown in Novel Biologics in the treatment of BP.BP, bullous pemphigoid; IL, interleukin, Pred, prednisone; IVIG, intravenous immunoglobulin; TCS, topical corticosteroid; NA, not available; TwHF, Tripterygium wilfordii Hook F; MP, methylprednisolone; BPDAI, The Bullous Pemphigoid Disease Area Index; MMF, mycophenolate mofetil; AZA, azathioprine; MTX, methotrexine.Eosinophil accumulation and eosinophilic spongiosis are prevalent features of BP, and numerous published data support the essential pathogenic function of eosinophils in BP. In the presence of eosinophil-related cytokines and chemokines, IL-5-activated eosinophils migrate to the BMZ, resulting in derma-epidermal separation (Several lines of research point to an essential role of the IL-17/IL-23 pathway in the pathogenesis of BP. Increased concentrations of IL-17A+ lymphocytes with CD4 expression have been identified in the peripheral blood of patients with BP, and genes encoding the IL-17/23 pathways have been found to be amplified among individuals with BP (Preliminary evidence has demonstrated a prolonged period of remission, steroid-sparing activity, and a satisfactory safety record in patients with severe BP treated with rituximab. Moreover, the evidence supporting the use of omalizumab as an additional agent in the treatment of BP is accumulating. Omalizumab and rituximab are currently administered as additional therapeutic modalities in BP treatment (Limitations exist in this study. We cannot conclude the appropriate dosage and the interval of dupilumab for BP treatment because of the small sample size, short follow-up period, lack of a control group, single-center research, and a retrospective study design. Instead of dupilumab monotherapy, the majority of BP patients received immunosuppressive treatments concurrently. Further clinical trials are needed to deal with these unresolved issues.Our current case series on anti-IL-4 receptor α therapy in treating BP combined with immunosuppressants provides further credentials to a prospective randomized study. A deep understanding of Th2 inflammation and anti-Th2 therapy may yield the clinical development of better-targeted therapies in BP patients.