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1.
Eur J Cancer ; 209: 114261, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39128185

RESUMO

AIM: Avelumab has been approved worldwide for treatment of metastatic Merkel cell carcinoma (mMCC), a rare and aggressive skin cancer. This study evaluated outcomes in patients with mMCC in France who received avelumab as second-line or later (2L+) treatment in routine clinical practice. METHODS: This retrospective, noninterventional study evaluated all patients diagnosed with mMCC using two databases: CARADERM (French national database of rare dermatological cancers) and SNDS (national healthcare database), identified via probabilistic linkage. Eligible patients initiated avelumab as 2L+ treatment between August 2016 and December 2019 and were followed for 24 months. The primary endpoint was overall survival (OS) at 24 months. RESULTS: Overall, 180 patients who received 2L+ avelumab were identified (112 from CARADERM, 68 after SNDS linkage). Median age at diagnosis was 74.0 years and 177 (98.3 %) had received chemotherapy alone as first-line treatment. Median follow-up was 13.1 months. Median OS from start of avelumab was 14.6 months (95 % CI, 9.9-21.3) in the overall population, 15.9 months (95 % CI, 8.6-28.3) in CARADERM patients, and 13.3 months (95 % CI, 6.7-19.1) in non-CARADERM patients. OS rates at 12 and 24 months were 53.8 % (95 % CI, 46.2 %-60.8 %) and 40.5 % (95 % CI, 33.2 %-47.6 %), respectively. In evaluable patients (CARADERM database), median progression-free survival was 3.6 months (95 % CI, 2.7-7.5) and the objective response rate was 55.3 % (95 % CI, 45.3-65.4), including complete response in 31.9 %. CONCLUSIONS: Real-world outcomes with 2L+ avelumab treatment for mMCC are consistent with clinical trial findings, supporting the recommendation of avelumab as a standard of care.


Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma de Célula de Merkel , Bases de Dados Factuais , Neoplasias Cutâneas , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Masculino , Feminino , Idoso , Carcinoma de Célula de Merkel/tratamento farmacológico , Carcinoma de Célula de Merkel/mortalidade , Carcinoma de Célula de Merkel/patologia , França , Estudos Retrospectivos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Antineoplásicos Imunológicos/uso terapêutico , Resultado do Tratamento , Adulto
2.
EClinicalMedicine ; 73: 102679, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39007062

RESUMO

Background: Sézary syndrome is an extremely rare and fatal cutaneous T-cell lymphoma (CTCL). Mogamulizumab, an anti-CCR4 monoclonal antibody, has recently been associated with increased progression-free survival in a randomized clinical trial in CTCL. We aimed to evaluate OS and prognostic factors in Sézary syndrome, including treatment with mogamulizumab, in a real-life setting. Methods: Data from patients with Sézary (ISCL/EORTC stage IV) and pre-Sézary (stage IIIB) syndrome diagnosed from 2000 to 2020 were obtained from 24 centers in Europe. Age, disease stage, plasma lactate dehydrogenases levels, blood eosinophilia at diagnosis, large-cell transformation and treatment received were analyzed in a multivariable Cox proportional hazard ratio model. This study has been registered in ClinicalTrials (SURPASSe01 study: NCT05206045). Findings: Three hundred and thirty-nine patients were included (58% men, median age at diagnosis of 70 years, Q1-Q3, 61-79): 33 pre-Sézary (9.7% of 339), 296 Sézary syndrome (87.3%), of whom 10 (2.9%) had large-cell transformation. One hundred and ten patients received mogamulizumab. Median follow-up was 58 months (95% confidence interval [CI], 53-68). OS was 46.5% (95% CI, 40.6%-53.3%) at 5 years. Multivariable analysis showed that age ≥ 80 versus <50 (HR: 4.9, 95% CI, 2.1-11.2, p = 0.001), and large-cell transformation (HR: 2.8, 95% CI, 1.6-5.1, p = 0.001) were independent and significant factors associated with reduced OS. Mogamulizumab treatment was significantly associated with decreased mortality (HR: 0.34, 95% CI, 0.15-0.80, p = 0.013). Interpretation: Treatment with mogamulizumab was significantly and independently associated with decreased mortality in Sézary syndrome. Funding: French Society of Dermatology, Swiss National Science Foundation (IZLIZ3_200253/1) and SKINTEGRITY.CH collaborative research program.

4.
Am J Clin Dermatol ; 25(2): 299-314, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38263353

RESUMO

BACKGROUND: The ALLEGRO phase 2a and 2b/3 studies demonstrated that ritlecitinib, an oral JAK3/TEC family kinase inhibitor, is efficacious at doses of ≥ 30 mg in patients aged ≥ 12 years with alopecia areata (AA). OBJECTIVE: The objective of this study was to evaluate the safety of ritlecitinib in an integrated analysis of four studies in AA. METHODS: Two cohorts were analyzed: a placebo-controlled and an all-exposure cohort. Proportions and study size-adjusted incidence rates (IRs) of adverse events (AEs) of interest and laboratory abnormalities are reported. RESULTS: In the placebo-controlled cohort (n = 881; median exposure: 169 days), the proportion of ritlecitinib-treated patients with AEs was 70.2-75.4% across doses versus 69.5% in the placebo group; serious AEs occurred in 0-3.2% versus 1.9% for the placebo. A total of 19 patients permanently discontinued due to AEs (5 while receiving the placebo). In the all-exposure cohort (n = 1294), median ritlecitinib exposure was 624 days [2091.7 total patient-years (PY)]. AEs were reported in 1094 patients (84.5%) and serious AEs in 57 (4.4%); 78 (6.0%) permanently discontinued due to AEs. The most common AEs were headache (17.7%; 11.9/100 PY), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test (15.5%; 9.8/100 PY), and nasopharyngitis (12.4%; 8.2/100 PY). There were two deaths (breast cancer and acute respiratory failure/cardiorespiratory arrest). Proportions (IRs) were < 0.1% (0.05/100 PY) for opportunistic infections, 1.5% (0.9/100 PY) for herpes zoster, 0.5% (0.3/100 PY) for malignancies (excluding nonmelanoma skin cancer), and 0.2% (0.1/100 PY) for major adverse cardiovascular events. CONCLUSIONS: Ritlecitinib is well tolerated with an acceptable safety profile up to 24 months in patients aged ≥ 12 years with AA (video abstract and graphical plain language summary available). TRIAL REGISTRIES: ClinicalTrials.gov: NCT02974868 (date of registration: 11/29/2016), NCT04517864 (08/18/2020), NCT03732807 (11/07/2018), and NCT04006457 (07/05/2019).


Assuntos
Alopecia em Áreas , Antineoplásicos , Triptaminas , Humanos , Alopecia em Áreas/tratamento farmacológico , Alopecia em Áreas/epidemiologia , Carbazóis , Janus Quinase 3 , Inibidores de Proteínas Quinases/efeitos adversos , SARS-CoV-2 , Resultado do Tratamento
5.
JAMA Dermatol ; 160(3): 290-296, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38265821

RESUMO

Importance: The Ritux 3 trial demonstrated the short-term efficacy and safety of first-line treatment with rituximab compared with a standard corticosteroid regimen in pemphigus. No data on the long-term follow-up of patients who received rituximab as first line are available. Objective: To assess the long-term efficacy and safety of the Ritux 3 treatment regimen. Design, Setting, and Participants: This 7-year follow-up study of the Ritux 3 trial included patients with pemphigus from 25 dermatology departments in France from January 1, 2010, to December 31, 2015. Exposure: Patients were initially randomized in the rituximab plus prednisone group or prednisone-alone group. Main outcomes and measures: The primary outcome was the 5- and 7-year disease-free survival (DFS) without corticosteroids, assessed by Kaplan-Meier curves. Secondary outcomes were occurrence of relapse, occurrence of severe adverse events (SAEs), and evolution of antidesmoglein (Dsg) antibody enzyme-linked immunosorbent assay values to predict long-term relapse. Results: Of the 90 patients in the Ritux 3 trial, 83 were evaluated at the end of follow-up study visit (44 in the rituximab plus prednisone group; 39 in the prednisone-alone group) with a median (IQR) follow-up of 87.3 (79.1-97.5) months. Forty-three patients (93%) from the rituximab plus prednisone and 17 patients (39%) from the prednisone-alone group had achieved complete remission without corticosteroids at any time during the follow-up. Patients from the rituximab group had much longer 5- and 7-year DFS without corticosteroids than patients from the prednisone-alone group (76.7% and 72.1% vs 35.3% and 35.3%, respectively; P < .001), and had about half the relapses (42.2% vs 83.7%; P < .001). Patients who received rituximab as second-line treatment had shorter DFS than patients treated as first line (P = .007). Fewer SAEs were reported in the rituximab plus prednisone group compared with the prednisone-alone group, 31 vs 58 respectively, corresponding to 0.67 and 1.32 SAEs per patient, respectively (P = .003). The combination of anti-Dsg1 values of 20 or more IU/mL and/or anti-Dsg3 values of 48 or more IU/mL yielded 0.83 positive predictive value and 0.94 negative predictive value to predict long-term relapse. Conclusions and Relevance: In this secondary analysis of the Ritux 3 trail, first-line treatment of patients with pemphigus with the Ritux 3 regimen was associated with long-term sustained complete remission without corticosteroid therapy without any additional maintenance infusion of rituximab.


Assuntos
Pênfigo , Humanos , Rituximab/efeitos adversos , Pênfigo/tratamento farmacológico , Prednisona/efeitos adversos , Seguimentos , Recidiva Local de Neoplasia , Corticosteroides , Recidiva , Resultado do Tratamento
7.
J Eur Acad Dermatol Venereol ; 37(6): 1118-1134, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36965110

RESUMO

BACKGROUND: Paraneoplastic pemphigus (PNP), also called paraneoplastic autoimmune multiorgan syndrome (PAMS), is a rare autoimmune disease with mucocutaneous and multi-organ involvement. PNP/PAMS is typically associated with lymphoproliferative or haematological malignancies, and less frequently with solid malignancies. The mortality rate of PNP/PAMS is elevated owing to the increased risk of severe infections and disease-associated complications, such as bronchiolitis obliterans. OBJECTIVES: These guidelines summarize evidence-based and expert-based recommendations (S2k level) for the clinical characterization, diagnosis and management of PNP/PAMS. They have been initiated by the Task Force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology with the contribution of physicians from all relevant disciplines. The degree of consent among all task force members was included. RESULTS: Chronic severe mucositis and polymorphic skin lesions are clue clinical characteristics of PNP/PAMS. A complete assessment of the patient with suspected PNP/PAMS, requiring histopathological study and immunopathological investigations, including direct and indirect immunofluorescence, ELISA and, where available, immunoblotting/immunoprecipitation, is recommended to achieve a diagnosis of PNP/PAMS. Detection of anti-envoplakin antibodies and/or circulating antibodies binding to the rat bladder epithelium at indirect immunofluorescence is the most specific tool for the diagnosis of PNP/PAMS in a patient with compatible clinical and anamnestic features. Treatment of PNP/PAMS is highly challenging. Systemic steroids up to 1.5 mg/kg/day are recommended as first-line option. Rituximab is also recommended in patients with PNP/PAMS secondary to lymphoproliferative conditions but might also be considered in cases of PNP/PAMS associated with solid tumours. A multidisciplinary approach involving pneumologists, ophthalmologists and onco-haematologists is recommended for optimal management of the patients. CONCLUSIONS: These are the first European guidelines for the diagnosis and management of PNP/PAMS. Diagnostic criteria and therapeutic recommendations will require further validation by prospective studies.


Assuntos
Síndromes Paraneoplásicas do Sistema Nervoso , Síndromes Paraneoplásicas , Animais , Ratos , Doenças Autoimunes , Neoplasias/complicações , Síndromes Paraneoplásicas/diagnóstico , Síndromes Paraneoplásicas/etiologia , Síndromes Paraneoplásicas/terapia , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico , Síndromes Paraneoplásicas do Sistema Nervoso/etiologia , Síndromes Paraneoplásicas do Sistema Nervoso/terapia , Sociedades Médicas
8.
JAMA Dermatol ; 159(4): 403-410, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36884234

RESUMO

Importance: Poor therapeutic results have been reported in patients with alopecia areata totalis (AT) or universalis (AU), the most severe and disabling types of alopecia areata (AA). Methotrexate, an inexpensive treatment, might be effective in AU and AT. Objective: To evaluate the efficacy and tolerance of methotrexate alone or combined with low-dose prednisone in patients with chronic and recalcitrant AT and AU. Design, Setting, and Participants: This academic, multicenter, double-blind, randomized clinical trial was conducted at 8 dermatology departments at university hospitals between March 2014 and December 2016 and included adult patients with AT or AU evolving for more than 6 months despite previous topical and systemic treatments. Data analysis was performed from October 2018 to June 2019. Interventions: Patients were randomized to receive methotrexate (25 mg/wk) or placebo for 6 months. Patients with greater than 25% hair regrowth (HR) at month 6 continued their treatment until month 12. Patients with less than 25% HR were rerandomized: methotrexate plus prednisone (20 mg/d for 3 months and 15 mg/d for 3 months) or methotrexate plus placebo of prednisone. Main Outcome and Measures: The primary end point assessed on photos by 4 international experts was complete or almost complete HR (Severity of Alopecia Tool [SALT] score <10) at month 12, while receiving methotrexate alone from the start of the study. Main secondary end points were the rate of major (greater than 50%) HR, quality of life, and treatment tolerance. Results: A total of 89 patients (50 female, 39 male; mean [SD] age, 38.6 [14.3] years) with AT (n = 1) or AU (n = 88) were randomized: methotrexate (n = 45) or placebo (n = 44). At month 12, complete or almost complete HR (SALT score <10) was observed in 1 patient and no patient who received methotrexate alone or placebo, respectively, in 7 of 35 (20.0%; 95% CI, 8.4%-37.0%) patients who received methotrexate (for 6 or 12 months) plus prednisone, including 5 of 16 (31.2%; 95% CI, 11.0%-58.7%) who received methotrexate for 12 months and prednisone for 6 months. A greater improvement in quality of life was observed in patients who achieved a complete response compared with nonresponder patients. Two patients in the methotrexate group discontinued the study because of fatigue and nausea, which were observed in 7 (6.9%) and 14 (13.7%) patients receiving methotrexate, respectively. No severe treatment adverse effect was observed. Conclusions and Relevance: In this randomized clinical trial, while methotrexate alone mainly allowed partial HR in patients with chronic AT or AU, its combination with low-dose prednisone allowed complete HR in up to 31% of patients. These results seem to be of the same order of magnitude as those recently reported with JAK inhibitors, with a much lower cost. Trial Registration: ClinicalTrials.gov Identifier: NCT02037191.


Assuntos
Alopecia em Áreas , Metotrexato , Adulto , Humanos , Masculino , Feminino , Metotrexato/efeitos adversos , Prednisona/efeitos adversos , Alopecia em Áreas/tratamento farmacológico , Qualidade de Vida , Recidiva Local de Neoplasia/tratamento farmacológico , Método Duplo-Cego , Resultado do Tratamento
9.
Int J Low Extrem Wounds ; 22(1): 135-138, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33076722

RESUMO

Eccrine syringofibroadenoma (ESFA) is a rare adnexal tumor deriving from the acrosyringeal portion of the eccrine duct. Five subtypes of ESFA were described including a reactive form. Reactive ESFAs are associated with inflammatory and neoplastic dermatoses. In this article, we report the case of a 90-year-old woman presenting with 3 leg ulcers evolving for 2 years surrounded by large verrucous and eczematous lesions. Multiple skin biopsies showed anastomosing epithelial cords connected to the epidermis consistent with ESFA. We identified 8 cases of ESFA associated with chronic leg ulcers in the literature and reviewed their main clinical and histological features.


Assuntos
Adenoma de Glândula Sudorípara , Úlcera da Perna , Neoplasias Cutâneas , Neoplasias das Glândulas Sudoríparas , Úlcera Varicosa , Feminino , Humanos , Idoso de 80 Anos ou mais , Adenoma de Glândula Sudorípara/complicações , Adenoma de Glândula Sudorípara/patologia , Neoplasias das Glândulas Sudoríparas/complicações , Neoplasias das Glândulas Sudoríparas/diagnóstico , Neoplasias das Glândulas Sudoríparas/patologia , Pele/patologia , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Úlcera Varicosa/patologia , Úlcera da Perna/patologia , Glândulas Écrinas/patologia
10.
Melanoma Res ; 32(6): 485-487, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36125885

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease characterized by aberrant immune hyperactivation of T CD8 lymphocytes and macrophages driven by cytokine dysfunction. We report a 64-year-old man, with advanced BRAF-mutant melanoma treated by combined targeted therapies who had a recalcitrant and cortico-dependent Epstein-Barr virus (EBV)-induced HLH. One rituximab cycle led to a rapid and prolonged HLH remission which allowed to switch the targeted therapy for immunotherapy rituximab thus makes it possible to limit the use of corticosteroids, which limits the effectiveness of immunotherapy. The patient finally died of a cerebral tumoral progression 2 years later. Despite secondary hypogammaglobulinemia, we did not observe any severe infections during this period. This case suggests that rituximab can be a valuable option for EBV-induced HLH to avoid the T-suppressive effects of high-dose of corticosteroids in immunotherapy-treated patients.


Assuntos
Infecções por Vírus Epstein-Barr , Linfo-Histiocitose Hemofagocítica , Melanoma , Neoplasias Cutâneas , Masculino , Humanos , Pessoa de Meia-Idade , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Rituximab/farmacologia , Rituximab/uso terapêutico , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Herpesvirus Humano 4 , Melanoma/complicações , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico
11.
JID Innov ; 2(4): 100129, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35860447

RESUMO

Many treatments are currently proposed for treating patients with bullous pemphigoid (BP). We assessed treatment modalities of BP depending on the different countries, BP extent, and patients' comorbidities. We surveyed worldwide experts about how they treat patients with BP. A total of 61 experts from 27 countries completed the survey. Severe and moderate BP were treated with oral prednisone (61.4 and 53.7%, respectively) or superpotent topical corticosteroids (CSs) (38.6 and 46.3%, respectively). Conventional immunosuppressants were more frequently combined with oral prednisone (74.5%) than with superpotent topical CS (37.5%) in severe BP. Topical CSs were mainly used in Europe in mild (81.1%), moderate (55.3%), and severe (54.3%) BP. In the United States of America and Asia, systemic CSs were mainly proposed for treating severe (77.8 and 100%, respectively), moderate (70 and 77.8%, respectively), and also mild (47.1 and 33.3%, respectively) BP. Most experts reduced the initial dose of oral CS in patients with diabetes mellitus (48.1%) or cardiac insufficiency (40.2%) but rarely changed BP treatment in patients with neurological disorders or neoplasia. This survey showed major differences in the way patients with BP are treated between AmeriPac countries (United State of America, Latin America, and Australia) and Asia on the one hand and Europe and the Middle East on the other hand.

13.
Acta Derm Venereol ; 102: adv00733, 2022 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-35506359

RESUMO

Paediatric psoriasis has been associated with school absenteeism, limitation of physical activities, psychiatric disorders and, in the longer term, with sexual dysfunction and addictions. This raises the hypothesis that childhood onset psoriasis may affect patients' educational development, and further social and professional outcomes. This study evaluated the relationship between childhood onset psoriasis and patients' educational and socioeconomic characteristics, and the development of addictions in adulthood. This cross-sectional ancillary study captured patients' characteristics at baseline in the French PSOBIOTEQ registry. Data in adulthood included: educational (baccalaureate) and socioeconomic (working activity) groups, smoking status (self-reporting of being a current smoker vs past smoker or non-smoker), alcohol consumption (defined as at least 1 glass of alcoholic beverage per day), and living conditions (alone/family/social institutions; child at home). A total of 1,960 patients were included, of whom 26.2% had childhood onset psoriasis. In multivariate analyses, childhood onset psoriasis was associated with smoker status (p = 0.02). No association was observed with educational level, working activity, living conditions, or alcohol consumption. This study provides reassuring data overall with regard to the impact of childhood onset psoriasis on major social outcomes. Evidence for some association with addictive behaviours paves the way for larger prospective studies assessing in depth the social and educational impact of this disease.


Assuntos
Comportamento Aditivo , Psoríase , Adulto , Comportamento Aditivo/epidemiologia , Criança , Estudos Transversais , Escolaridade , Humanos , Estudos Prospectivos , Psoríase/diagnóstico , Psoríase/epidemiologia , Fatores Socioeconômicos
14.
Acta Derm Venereol ; 102: adv00717, 2022 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-35470404

RESUMO

An improved understanding of the impact of skin cancer on patients' daily life may optimize disease management. This questionnaire survey of adult patients in real-world settings aimed to assess patient perception of the diagnosis announcement, and the impact of the diagnosis on the patients' professional and personal life. Data from 355 patients with melanoma and 320 patients with basal cell carcinoma (BCC) were analysed. Melanoma significantly impacted the couple, and sexual relationships, as well as family and social life, and reduced the patient's libido more significantly than did BCC (all p < 0.05). Melanoma and BCC significantly impacted the patients' professional and personal lives. The word "cancer" used for a BCC announcement has a high anxiety-producing meaning for the patient. The announcement of each skin cancer should be made during a dedicated consultation, with more time devoted to the patient and with specific empathy, in order to improve reassurance of the patient.


Assuntos
Carcinoma Basocelular , Carcinoma de Células Escamosas , Melanoma , Neoplasias Cutâneas , Adulto , Carcinoma Basocelular/diagnóstico , Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/patologia , Humanos , Melanoma/diagnóstico , Melanoma/patologia , Percepção , Qualidade de Vida , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia
16.
Clin Dermatol ; 39(3): 359-368, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34517993

RESUMO

Since the beginning of the COVID-19 outbreak, attention has gradually moved from the respiratory manifestations of the disease toward its dermatologic aspects. The need for wearing personal protective measures and their cutaneous side effects, detection of related or specific COVID-19 skin eruptions, and the evaluation of certain risk groups of immunosuppressed dermatologic patients have initiated significant discussions about various therapeutic interventions and, in particular, about biologic therapy for psoriasis and for autoinflammatory, orphan, or malignant cutaneous disorders. Autoimmune bullous dermatoses have been of concern due to their chronic course, at times life-threatening prognosis, and the need for prolonged and often aggressive immunomodulatory therapy. We have summarized the current knowledge regarding the impact of COVID-19 infection on autoimmune bullous dermatoses, including recommendations for the main treatment strategies, available patient information, and the registries organized for documentation during the COVID-19 pandemic.


Assuntos
Doenças Autoimunes , COVID-19 , Dermatopatias Vesiculobolhosas , Doenças Autoimunes/complicações , Doenças Autoimunes/epidemiologia , Humanos , Pandemias , SARS-CoV-2 , Dermatopatias Vesiculobolhosas/tratamento farmacológico , Dermatopatias Vesiculobolhosas/epidemiologia
17.
Front Immunol ; 12: 666022, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34054835

RESUMO

The efficacy of the B-cell-depleting agent rituximab has been reported in immune diseases but relapses are frequent, suggesting the need for repeated infusions. The B-cell activating factor (BAFF) is an important factor for B cell survival, class switch recombination and selection of autoreactive B cells, as well as maintaining long-lived plasma cells. It has been hypothesized that relapses after rituximab might be due to the increase of serum BAFF levels. From the Ritux3 trial, we showed that baseline serum BAFF levels were higher in pemphigus patients than in healthy donors (308 ± 13 pg/mL versus 252 ± 28 pg/mL, p=0.037) and in patients with early relapse compared who didn't (368 ± 92 vs 297 ± 118 pg/mL, p=0.036). Rituximab and high doses of CS alone have different effects on the BAFF/BAFF-R axis. Rituximab led to an increase of BAFF levels associated to a decreased mRNA (Day 0: 12.3 ± 7.6 AU vs Month 36: 3.3 ± 4.3 AU, p=0.01) and mean fluorescence intensity of BAFF-R in non-autoreactive (Day 0: 3232 vs Month 36: 1527, mean difference: 1705, 95%CI: 624 to 2786; p=0.002) as well as on reappearing autoreactive DSG-specific B cells (Day 0: 3873 vs Month 36: 2688, mean difference: 1185, 95%CI: -380 to 2750; p=0.20). Starting high doses of corticosteroids allowed a transitory decrease of serum BAFF levels that re-increased after doses tapering whereas it did not modify BAFF-R expression in autoreactive and non-autoreactive B cells. Our results suggest that the activation of autoreactive B cells at the onset of pemphigus is likely to be related to the presence of high BAFF serum levels and that the decreased BAFF-R expression after rituximab might be responsible for the delayed generation of memory B cells, resulting in a rather long period of mild pemphigus activity after rituximab therapy. Conversely, the incomplete B cell depletion and persistent BAFF-R expression associated with high BAFF serum levels might explain the high number of relapses in patients treated with CS alone.


Assuntos
Corticosteroides/uso terapêutico , Fator Ativador de Células B/sangue , Receptor do Fator Ativador de Células B/metabolismo , Pênfigo/tratamento farmacológico , Rituximab/uso terapêutico , Receptor do Fator Ativador de Células B/genética , Linfócitos B/citologia , Linfócitos B/metabolismo , Humanos , Fatores Imunológicos/uso terapêutico , Pênfigo/sangue , Pênfigo/imunologia , RNA Mensageiro/metabolismo
18.
Rheumatology (Oxford) ; 60(12): 5863-5867, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33764396

RESUMO

OBJECTIVE: To deep sequence the TRIM33 gene in tumours from patients with cancer-associated anti-TIF1γ autoantibody-positive dermatomyositis (DM) as TRIM33 somatic mutations in tumours may trigger this auto-immune disease. METHODS: Next generation sequencing of tumour DNA samples from patients with cancer-associated anti-TIF1γ autoantibody-positive DM. Fourteen tumours from 13 anti-TIF1γ autoantibody-positive DM individuals were sequenced along with two control tumours from non-DM individuals. RESULTS: Fourteen probable somatic variants from four tumours were identified in the TRIM33 gene. CONCLUSION: These results are in accordance with the previous report of Pinal-Fernandez et al. and support the hypothesis of a role of TRIM33 gene mutations in the pathophysiology of anti-TIF1γ autoantibody-positive DM.


Assuntos
DNA/genética , Dermatomiosite/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Mutação , Neoplasias/complicações , Fatores de Transcrição/genética , Idoso , Análise Mutacional de DNA , Dermatomiosite/etiologia , Dermatomiosite/metabolismo , Feminino , Humanos , Masculino , Fatores de Transcrição/metabolismo , Dedos de Zinco
19.
J Invest Dermatol ; 141(9): 2132-2140.e1, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33766510

RESUMO

Pemphigus is an autoimmune blistering disease mediated by autoantibodies directed against desmogleins (DSGs). We recently showed that first-line treatment with rituximab (RTX) enables more patients to achieve long-lasting remission off therapy than corticosteroids alone. To understand the immunological mechanisms that mediate long-lasting clinical remission after RTX treatment, we analyzed the phenotype of DSG-specific memory B cells and DSG-specific T follicular helper cells by flow cytometry and measured antibody-secreting cells by enzyme-linked immune absorbent spot in patients treated with corticosteroids alone or RTX. This post hoc analysis of the RITUX3 trial showed that RTX induced a significant decrease of IgG-switched DSG-specific memory B cells. Accordingly, anti-DSG antibody-secreting cells were no longer detected in patients in complete remission after RTX. In contrast, corticosteroids did not modify the frequency or the phenotype of DSG-specific memory B cells, and anti-DSG antibody-secreting cells were still detected after treatment, even in patients in remission. Using peptide-HLADRB1∗0402 tetramer staining, we identified DSG-3-specific T follicular helper cells, which dramatically decreased after RTX, while remaining stable after corticosteroid treatment. Our findings suggest that long-lasting response to RTX in pemphigus relies on the decrease of DSG-specific circulating T follicular helper cells, which correlates with a sustained depletion of IgG-switched memory autoreactive B cells, leading to the disappearance of anti-DSG antibody-secreting cells.


Assuntos
Corticosteroides/uso terapêutico , Subpopulações de Linfócitos B/imunologia , Centro Germinativo/imunologia , Imunossupressores/uso terapêutico , Pênfigo/imunologia , Rituximab/uso terapêutico , Linfócitos T Auxiliares-Indutores/imunologia , Autoimunidade , Células Cultivadas , Desmogleínas/imunologia , Cadeias HLA-DRB1/metabolismo , Humanos , Memória Imunológica , Imunofenotipagem , Interleucinas/sangue , Pênfigo/tratamento farmacológico
20.
Ital J Dermatol Venerol ; 156(2): 174-183, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33070576

RESUMO

Originally described by Anhalt as paraneoplastic pemphigus in 1990, paraneoplastic autoimmune multiorgan syndrome (PAMS) is a potentially lethal blistering disease, characterized by polymorphous clinical features, including mucocutaneous erosions, blisters, lichenoid papules, and erythemas. Several autoantibodies have been detected in serum of PAMS patients, including antiplakins, anti-alpha-2-macroglobulin like 1, and antidesmogleins autoantibodies. The mortality rate of PAMS is up to 90%. This is due on the one hand to the poor response to treatments and on the other hand to the delay in the diagnosis and to the prognosis of the underlying neoplasia.


Assuntos
Doenças Autoimunes , Neoplasias , Síndromes Paraneoplásicas , Pênfigo , Autoanticorpos , Doenças Autoimunes/diagnóstico , Humanos , Síndromes Paraneoplásicas/diagnóstico , Pênfigo/diagnóstico
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