Assuntos
Antineoplásicos Fitogênicos , Neoplasias do Endométrio , Paclitaxel , Penfigoide Bolhoso , Humanos , Feminino , Penfigoide Bolhoso/induzido quimicamente , Penfigoide Bolhoso/tratamento farmacológico , Neoplasias do Endométrio/tratamento farmacológico , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêutico , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/uso terapêutico , Idoso , Pessoa de Meia-IdadeRESUMO
Background: 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. Methods: A systematic search of PubMed and Embase was performed for articles published between 1982 to June 2, 2024. Results: 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. Conclusion: 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.
Assuntos
Falência Renal Crônica , Penfigoide Bolhoso , Humanos , Penfigoide Bolhoso/terapia , Penfigoide Bolhoso/tratamento farmacológico , Penfigoide Bolhoso/etiologia , Penfigoide Bolhoso/imunologia , Falência Renal Crônica/terapia , Falência Renal Crônica/etiologia , Falência Renal Crônica/complicações , Imunossupressores/uso terapêutico , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversosRESUMO
Bullous pemphigoid (BP) is a chronic autoimmune disease affecting the elderly population and characterized by the formation of subepidermal tense bullae. Treatment options include topical steroids, systemic steroids, immunosuppressants, and antimicrobials, and there is emerging evidence of the efficacy of omalizumab. In this study, we aimed to demonstrate omalizumab's efficacy for treating BP, and we also reported treatment-related adverse events. The retrospective cohort study included patients with BP who were followed up in our clinic's bullous diseases department between 2016 and 2023. Patients who received omalizumab were included in the study. Treatment responses of all patients were assessed by BP Disease Area Index activity and damage scores, treatment scale scoring, steroid dose reduction, and the presence/absence of pruritus. Also, total IgE levels of patients before the treatment onset and at the last visit were compared. There were 15 (male/female = 8/7) BP patients receiving omalizumab treatment. Omalizumab therapy allowed steroid dose reduction at a median of 1 month. Omalizumab (25.5 mg, 95% confidence interval 17.2-33.9, Pâ <â .001) provided a significant steroid dose reduction at the last visit compared to the beginning of treatment. Omalizumab resulted in a decrease in BP Disease Area Index activity score of 80.8 (95% confidence interval 71.8-89.8, Pâ <â .001). Also, omalizumab caused significant decline in IgE levels compared to baseline (1102.5â ±â 834.5 vs 834.6â ±â 613.6, Pâ =â .002). In this study, omalizumab treatment was an effective and safe option in BP patients with high baseline IgE levels who are refractory to or cannot tolerate other immunosuppressive therapies.
Assuntos
Omalizumab , Penfigoide Bolhoso , Humanos , Omalizumab/uso terapêutico , Omalizumab/administração & dosagem , Penfigoide Bolhoso/tratamento farmacológico , Masculino , Feminino , Estudos Retrospectivos , Idoso , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Resultado do Tratamento , Imunoglobulina E/sangue , Antialérgicos/uso terapêutico , Antialérgicos/administração & dosagemAssuntos
Anticorpos Monoclonais Humanizados , Penfigoide Bolhoso , Humanos , Penfigoide Bolhoso/tratamento farmacológico , Penfigoide Bolhoso/complicações , Anticorpos Monoclonais Humanizados/uso terapêutico , Masculino , Feminino , Resultado do Tratamento , Tuberculose/tratamento farmacológico , Tuberculose/complicações , IdosoRESUMO
Bullous pemphigoid is often difficult to treat with the limited therapies available. Here, we describe clinical outcomes among 30 adults with bullous pemphigoid patients treated with dupilumab. We performed a multicenter, retrospective case series between March 2020 to August 2022. Patients received a loading dose of dupilumab 600 mg, followed by 300 mg maintenance dose with varying administration frequency tailored to individual patient response. All patients experienced at least some improvement in blister formation and pruritus, with 23 (76.7%) of patients demonstrating either complete clearance of blistering or marked response. Complete clearance of pruritus or marked response was noted in 25 (83.3%) of patients. Eight patients were effectively maintained solely on dupilumab. One (3.3%) patient reported an injection site reaction. Thirty patients represent a small sample, however, to our knowledge, this is the second largest group of BP treated with dupilumab. Furthermore, we provide an understandable framework for clinicians outside of academics to follow and assess treatment responses in their BP patients treated with dupilumab. Dupilumab should be considered as a therapeutic option in patients with bullous pemphigoid given its ability to induce sustained blistering and pruritus response in both typical and refractory cases while maintaining a favorable safety profile. J Drugs Dermatol. 2024;23(6):e144-e148. doi:10.36849/JDD.8258e.
Assuntos
Anticorpos Monoclonais Humanizados , Penfigoide Bolhoso , Prurido , Humanos , Penfigoide Bolhoso/tratamento farmacológico , Penfigoide Bolhoso/diagnóstico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Estudos Retrospectivos , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Resultado do Tratamento , Idoso de 80 Anos ou mais , Prurido/tratamento farmacológico , Prurido/etiologia , Prurido/diagnóstico , Adulto , Reação no Local da Injeção/etiologia , Reação no Local da Injeção/diagnósticoAssuntos
Anticorpos Monoclonais Humanizados , Artrite Psoriásica , Penfigoide Bolhoso , Psoríase , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Penfigoide Bolhoso/tratamento farmacológico , Penfigoide Bolhoso/patologia , Psoríase/tratamento farmacológico , Resultado do Tratamento , Masculino , Feminino , Pessoa de Meia-IdadeRESUMO
Aim: Bullous pemphigoid induced by secukinumab in treatment of psoriasis is rare.Methods: We report a 49-year-old man with psoriasis who developed bullous pemphigoid during treatment with secukinumab.Results: Scattered tense vesicles with itching appeared all over the body after the fourth treatment. Bullous pemphigoid was confirmed by pathological examination and direct immunofluorescence. The patient was treated with topical corticosteroids, oral nicotinamide and minocycline hydrochloride. The lesions of bullous pemphigoid improved significantly after 7 days of treatment.Conclusions: Bullous pemphigoid is a rare adverse event following administration of secukinumab.
Assuntos
Anticorpos Monoclonais Humanizados , Penfigoide Bolhoso , Psoríase , Humanos , Penfigoide Bolhoso/induzido quimicamente , Penfigoide Bolhoso/tratamento farmacológico , Penfigoide Bolhoso/patologia , Penfigoide Bolhoso/diagnóstico , Masculino , Pessoa de Meia-Idade , Anticorpos Monoclonais Humanizados/efeitos adversos , Psoríase/tratamento farmacológico , Psoríase/induzido quimicamente , Minociclina/efeitos adversos , Niacinamida/análogos & derivados , Niacinamida/efeitos adversos , Niacinamida/uso terapêutico , Fármacos Dermatológicos/efeitos adversos , Resultado do TratamentoRESUMO
Background: The manifestations of bullous pemphigoid (BP) and herpes simplex virus (HSV) infection are similar in oral mucosa, and the laboratory detection of HSV has some limitations, making it difficult to identify the HSV infection in oral lesions of BP. In addition, the treatments for BP and HSV infection have contradictory aspects. Thus, it is important to identify the HSV infection in BP patients in time. Objective: To identify the prevalence and clinical markers of HSV infection in oral lesions of BP. Methods: This prospective cross-sectional descriptive analytical study was conducted on 42 BP patients with oral lesions. A total of 32 BP patients without oral lesions and 41 healthy individuals were enrolled as control groups. Polymerase chain reaction was used to detect HSV. Clinical and laboratory characteristics of patients with HSV infection were compared with those without infection. Results: A total of 19 (45.2%) BP patients with oral lesions, none (0.0%) BP patients without oral lesions, and four (9.8%) healthy individuals were positive for HSV on oral mucosa. Among BP patients with oral lesions, the inconsistent activity between oral and skin lesions (p=0.001), absence of blister/blood blister in oral lesions (p=0.020), and pain for oral lesions (p=0.014) were more often seen in HSV-positive than HSV-negative BP patients; the dosage of glucocorticoid (p=0.023) and the accumulated glucocorticoid dosage in the last 2 weeks (2-week AGC dosage) (p=0.018) were higher in HSV-positive BP patients. Combining the above five variables as test variable, the AUC was 0.898 (p<0.001) with HSV infection as state variable in ROC analysis. The absence of blister/blood blister in oral lesions (p=0.030) and pain for oral lesions (p=0.038) were found to be independent predictors of HSV infection in multivariable analysis. A total of 14 (73.7%) HSV-positive BP patients were treated with 2-week famciclovir and the oral mucosa BPDAI scores significantly decreased (p<0.001). Conclusion: HSV infection is common in BP oral lesions. The inconsistent activity between oral and skin lesions, absence of blister in oral lesions, pain for oral lesions, higher currently used glucocorticoid dosage, and higher 2-week AGC dosage in BP patients should alert physicians to HSV infection in oral lesions and treat them with 2-week famciclovir in time.
Assuntos
Herpes Simples , Penfigoide Bolhoso , Simplexvirus , Humanos , Penfigoide Bolhoso/epidemiologia , Penfigoide Bolhoso/tratamento farmacológico , Penfigoide Bolhoso/diagnóstico , Masculino , Feminino , Idoso , Prevalência , Estudos Transversais , Pessoa de Meia-Idade , Estudos Prospectivos , Simplexvirus/isolamento & purificação , Mucosa Bucal/patologia , Mucosa Bucal/virologia , Idoso de 80 Anos ou mais , Biomarcadores , Doenças da Boca/epidemiologia , Doenças da Boca/virologia , AdultoRESUMO
Bullous pemphigoid (BP) is a rare blistering disease often considered a primary sign of a paraneoplastic syndrome. Retrospective studies have established its link with hematological malignancies, particularly lymphoproliferative disorders. Here, we present what we believe to be the inaugural case of successful simultaneous management of BP and de novo acute myeloid leukemia (AML) in a 28-year-old male patient. Given the rarity and severity of both conditions, our treatment strategy aimed to maximize efficacy by combining immunosuppressive therapy (initially plasmapheresis with high-dose corticosteroids, followed by anti-CD20 monoclonal antibody and intravenous immunoglobulins 2 g/m2) with lymphodepleting antileukemic chemotherapy utilizing Fludarabine (FLAG-IDA induction regimen). Following diagnosis, considering the patient's youth and the concurrent presence of two rare and potentially life-threatening diseases, we opted for an aggressive treatment. Upon achieving complete morphological remission of AML with measurable residual disease (MRD) negativity, despite incomplete resolution of BP, we proceeded with high-dose cytarabine consolidation followed by peripheral stem cell harvest and autologous stem cell transplantation (ASCT). Our conditioning regimen for ASCT involved Bu-Cy with the addition of anti-thymocyte globulins. At day + 100 post-ASCT, bone marrow evaluation confirmed morphological remission and MRD negativity. Meanwhile, BP had completely resolved with normalization of BP180 antibody levels.
Assuntos
Leucemia Mieloide Aguda , Síndromes Paraneoplásicas , Humanos , Masculino , Adulto , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/complicações , Síndromes Paraneoplásicas/etiologia , Síndromes Paraneoplásicas/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Penfigoide Bolhoso/terapia , Penfigoide Bolhoso/tratamento farmacológico , Citarabina/administração & dosagem , Citarabina/uso terapêutico , Imunossupressores/uso terapêutico , Pênfigo/terapia , Pênfigo/complicações , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico , Vidarabina/administração & dosagem , Imunoglobulinas Intravenosas/uso terapêutico , Plasmaferese , Medicina de PrecisãoAssuntos
Anticorpos Monoclonais Humanizados , Penfigoide Bolhoso , Psoríase , Humanos , Psoríase/tratamento farmacológico , Psoríase/complicações , Anticorpos Monoclonais Humanizados/uso terapêutico , Penfigoide Bolhoso/tratamento farmacológico , Resultado do Tratamento , Masculino , Feminino , LamininaRESUMO
Background: Lichen planus pemphigoides (LPP), an association between lichen planus and bullous pemphigoid lesions, is a rare subepithelial autoimmune bullous disease. Mucous membrane involvement has been reported previously; however, it has never been specifically studied. Methods: We report on 12 cases of LPP with predominant or exclusive mucous membrane involvement. The diagnosis of LPP was based on the presence of lichenoid infiltrates in histology and immune deposits in the basement membrane zone in direct immunofluorescence and/or immunoelectron microscopy. Our systematic review of the literature, performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, highlights the clinical and immunological characteristics of LPP, with or without mucous membrane involvement. Results: Corticosteroids are the most frequently used treatment, with better outcomes in LPP with skin involvement alone than in that with mucous membrane involvement. Our results suggest that immunomodulators represent an alternative first-line treatment for patients with predominant mucous membrane involvement.
Assuntos
Líquen Plano , Mucosa , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Corticosteroides/uso terapêutico , Líquen Plano/tratamento farmacológico , Líquen Plano/patologia , Líquen Plano/imunologia , Líquen Plano/diagnóstico , Mucosa/patologia , Mucosa/imunologia , Penfigoide Bolhoso/imunologia , Penfigoide Bolhoso/tratamento farmacológico , Penfigoide Bolhoso/patologia , Penfigoide Bolhoso/diagnósticoRESUMO
BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune blistering disease. Most patients are older and have associated multiple comorbidities. Topical and systemic corticosteroids are considered the first-line treatment for BP, and immunosuppressants are used as steroid-sparing treatments. However, both have side-effects and contraindications, which are even more common in this older population. New treatments targeting interleukins and receptors related to BP pathogenesis have been proposed to decrease these side-effects while achieving equal or better effectiveness and response rates. Omalizumab is a monoclonal antibody that targets IgE and has been proposed for the treatment of BP due to the evidence that IgE autoantibodies play an essential role in BP pathogenesis. OBJECTIVES: To assess the efficacy and safety of omalizumab for the treatment of BP. METHODS: We carried out a multicentre, retrospective, observational study including patients diagnosed with BP who received omalizumab for ≥ 3 months from 15 tertiary hospitals in Spain. IgE levels prior to treatment were measured, and we evaluated the possible correlation with clinical response. We excluded patients treated with omalizumab for < 3 months, as we consider this duration to be insufficient for a comprehensive assessment of its efficacy. To evaluate the effectiveness of the treatment, we used the percentage of body surface area improvement. RESULTS: We included 36 patients. The vast majority had associated multiple comorbidities, and all patients had used other systemic therapies apart from corticosteroids before omalizumab. In total, 83% experienced some kind of treatment response and 42% of all patients treated achieved complete response. We did not find any correlation between higher IgE levels and a better response (P = 0.2). All patients tolerated omalizumab without reported side-effects. CONCLUSIONS: Omalizumab is a good therapeutic alternative for BP as it provided clinical response in most patients, and nearly one-half of the cases achieved complete response. It showed no side-effects, which is crucial in older patients with BP.
Assuntos
Omalizumab , Penfigoide Bolhoso , Humanos , Omalizumab/uso terapêutico , Omalizumab/efeitos adversos , Penfigoide Bolhoso/tratamento farmacológico , Feminino , Masculino , Idoso , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Espanha , Resultado do Tratamento , Pessoa de Meia-Idade , Imunoglobulina E/sangueRESUMO
BACKGROUND: Bullous pemphigoid (BP) is a rare, autoimmune, blistering skin disease associated with high disease burden, profoundly decreased quality of life and increased morbidity. Emerging evidence supports an important role for type 2 inflammation in disease pathogenesis. Current management relies on topical and/or systemic corticosteroids, non-selective immunosuppressants and antibiotics with anti-inflammatory properties, which are all limited by side effects and toxicities. Therefore, targeted, efficacious and safe therapies are needed. Dupilumab blocks the shared receptor component for interleukin (IL)-4 and IL-13, key and central drivers of type 2 inflammation. Several reports of patients successfully treated with dupilumab have been published; however, dupilumab has not been formally assessed in a double-blind, placebo-controlled trial. OBJECTIVES: We report the design of LIBERTY-BP ADEPT, a multicenter, randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of dupilumab in adults with BP. METHODS: LIBERTY-BP ADEPT comprises a 35-day screening, 52-week treatment and 12-week follow-up period. Approximately 98 adults aged 18-90 years with moderate-to-severe BP are being enrolled at 51 sites on 4 continents and randomized 1:1 to subcutaneous dupilumab or placebo every 2 weeks. All participants will receive concomitant oral corticosteroids (OCS). PLANNED OUTCOMES: The primary endpoint is the proportion of patients achieving complete remission off steroid therapy at week 36. Key secondary endpoints include total cumulative OCS dose to week 36, percent change and proportion of patients with ≥ 4-point reduction in the weekly average of daily Peak Pruritus Numerical Rating Scale from baseline to week 36 and percent change in Bullous Pemphigoid Area Index score from baseline to week 36. CONCLUSION: The trial results will provide evidence on whether the efficacy and safety of dupilumab support its use as a potential novel treatment approach for BP and will provide new insights into the role of type 2 inflammation in BP pathogenesis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04206553.
Assuntos
Anticorpos Monoclonais Humanizados , Penfigoide Bolhoso , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Penfigoide Bolhoso/tratamento farmacológico , Método Duplo-Cego , Adulto , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Resultado do TratamentoRESUMO
BACKGROUND: Bullous pemphigoid (BP) is an antibody-mediated blistering disease predominantly affecting the elderly. The pathogenesis involves both complement-dependent and complement-independent mechanisms. The therapeutic potential of targeting complement-independent mechanism has not yet been determined. The mainstay of treatment, corticosteroid, has many side effects, indicating the needs of better treatments. OBJECTIVE: We tempted to establish an in vitro model of BP which resembles complement-independent mechanism and to examine the therapeutic potential of a novel anti-inflammatory agent, diacerein. METHODS: Cultured HaCaT cells were treated with purified antibodies from BP patients, with or without diacerein to measure the cell interface presence of BP180, protein kinase C, and the production of proinflammatory cytokines. An open-label, randomized, phase 2 trial was conducted to compare topical diacerein and clobetasol ointments in patients with mild-to-moderate BP (NCT03286582). RESULTS: The reduced presentation of BP180 at cell interface after treating with BP autoantibodies was noticed in immunofluorescence and western blotting studies. The phenomenon was restored by diacerein. Diacerein also reduced the autoantibody-induced increase of pro-inflammatory cytokines. Reciprocal changes of BP180 and protein kinase C at the cell interface were found after treating with BP autoantibodies. This phenomenon was also reversed by diacerein in a dose-dependent manner. The phase 2 trial showed that topical diacerein reduced the clinical symptoms which were comparable to those of topical clobetasol. CONCLUSION: Diacerein inhibited BP autoantibody-induced reduction of BP180 and production of proinflammatory cytokines in vitro and showed therapeutic potential in patients with BP. It is a novel drug worthy of further investigations.
Assuntos
Antraquinonas , Autoanticorpos , Citocinas , Colágenos não Fibrilares , Penfigoide Bolhoso , Idoso , Feminino , Humanos , Masculino , Antraquinonas/farmacologia , Antraquinonas/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Autoanticorpos/imunologia , Autoanticorpos/sangue , Autoantígenos/imunologia , Linhagem Celular , Clobetasol/uso terapêutico , Clobetasol/farmacologia , Colágeno Tipo XVII , Proteínas do Sistema Complemento/imunologia , Citocinas/metabolismo , Citocinas/imunologia , Células HaCaT , Queratinócitos/imunologia , Queratinócitos/efeitos dos fármacos , Colágenos não Fibrilares/imunologia , Penfigoide Bolhoso/imunologia , Penfigoide Bolhoso/tratamento farmacológico , Penfigoide Bolhoso/patologia , Proteína Quinase C/antagonistas & inibidores , Proteína Quinase C/metabolismo , Proteína Quinase C/imunologia , Resultado do TratamentoRESUMO
Mucous membrane pemphigoid (MMP) is a rare, immune-mediated, vesiculobullous disease that predominantly affects the oral cavity and conjunctiva. In MMP, autoantibodies are directed against hemidesmosomal proteins in the basement membrane zone, most commonly BP180. Clinical signs and symptoms include gingival desquamation, erosions, and ulcerations. Differential diagnoses include other immune-mediated blistering diseases, such as bullous pemphigoid. Definitive diagnosis is reached through history taking, physical examination, tissue biopsy and/or serology testing. MMP, although not curable, is typically managed with topical or systemic corticosteroids, in addition to immunosuppressive therapies and biologic agents in recalcitrant cases. Untreated MMP can lead to life-threatening complications, such as blindness. As a condition that affects the oral cavity, it is important that dentists understand how to recognise, diagnose and manage the disease.
Assuntos
Úlceras Orais , Penfigoide Mucomembranoso Benigno , Penfigoide Bolhoso , Humanos , Penfigoide Bolhoso/diagnóstico , Penfigoide Bolhoso/tratamento farmacológico , Penfigoide Mucomembranoso Benigno/diagnóstico , Penfigoide Mucomembranoso Benigno/tratamento farmacológico , Autoanticorpos/uso terapêutico , Mucosa/patologiaRESUMO
Pemphigus disease and mucous membrane pemphigoid are autoimmune blistering diseases (AIBDs) which may involve both oral and extra-oral tissues. The Bristol Joint Oral Medicine and Dermatology Combined Clinic was set up in 2014, with the primary aim of improving the standard of care for patients with AIBDs. This interdisciplinary approach aimed to address the medical management challenges due to the multisite nature of these AIBDs.We present a narrative report of the clinical work undertaken within this clinic, focused on the management of this patient cohort within a five-year span (2017-2022). This report outlines the multisite nature of AIBDs and the range of topical and systemic treatments that were employed to achieve adequate disease control and optimise outcomes for patients. We reflect on the experiential benefits of this multidisciplinary clinic extended beyond immediate patient benefits to areas such as specialist training, both from a dermatologist's and oral physician's perspective.