RESUMO
BACKGROUND: Mastocytosis and monoclonal mast cell (MC) activation syndrome (MMAS) are heterogeneous conditions characterized by the accumulation of atypical MCs. Despite the recurrent involvement of KIT mutations, the pathophysiologic origin of mastocytosis and MMAS is unclear. Although hereditary α-tryptasemia (HαT, related to TPSAB1 gene duplication) is abnormally frequent in these diseases, it is not known whether the association is coincidental or causal. OBJECTIVE: We evaluated the prevalence of HαT in all mastocytosis subtypes and MMAS and assessed the pathophysiologic association with HαT. METHODS: Clinical data, laboratory data, KIT mutations, TPSAB1 duplication (assessed by droplet digital PCR), and HαT prevalence were retrospectively recorded for all patients with mastocytosis and MMAS registered in the French national referral center database and compared to a control cohort. To increase the power of our analysis for advanced systemic mastocytosis (advSM), we pooled our cohort with literature cases. RESULTS: We included 583 patients (27 with MMAS and 556 with mastocytosis). The prevalence of HαT in mastocytosis was 12.6%, significantly higher than in the general population (5.7%, P = .002) and lower than in MMAS (33.3%, P = .02). HαT+ patients were more likely to have anaphylactic reactions and less likely to have cutaneous lesions than HαT- patients (43.0% vs 24.4%, P = .006; 57.7% vs 75.6%, respectively, P = .006). In the pooled analysis, the prevalence of HαT was higher in advSM (11.5%) than in control cohorts (5.2%, P = .01). CONCLUSION: Here we confirm the increase incidence of anaphylaxis in HαT+ mastocytosis patients. The increased prevalence of HαT in all subtypes of systemic mastocytosis (including advSM) is suggestive of pathophysiologic involvement.
Assuntos
Anafilaxia , Mastocitose Sistêmica , Mastocitose , Humanos , Mastocitose Sistêmica/epidemiologia , Mastocitose Sistêmica/genética , Mastocitose Sistêmica/patologia , Estudos Retrospectivos , Prevalência , Mastocitose/epidemiologia , Mastocitose/genética , Mastocitose/patologia , Anafilaxia/patologia , Mastócitos/patologia , Triptases/genéticaRESUMO
BACKGROUND AND AIMS: Systemic mastocytosis (SM) is characterized by the accumulation of atypical mast cells (MCs) in organs. Liver histology of SM has been marginally described and accurate histological classification is critical, given the consequences of aggressive SM diagnosis. We aimed to describe the histological features associated with liver SM using updated tools. METHODS: Using the database of the French Reference Centre for Mastocytosis, we retrospectively identified patients with a liver biopsy (LB) and a diagnosis of SM. All LB procedures were performed according to the local physician in charge and centrally reviewed by an expert pathologist. RESULTS: A total of 28 patients were included: 6 had indolent SM, 9 had aggressive SM, and 13 had SM with an associated hematologic neoplasm. Twenty-five (89%) patients presented hepatomegaly, and 19 (68%) had portal hypertension. The LB frequently showed slight sinusoid dilatation (82%). Fibrosis was observed in 3/6 indolent SM and in almost all advanced SM cases (21/22), but none of them showed cirrhosis. A high MC burden (>50 MCs/high-power field) was correlated with elevated blood alkaline phosphatase levels (p = .030). The presence of portal hypertension was associated with a higher mean fibrosis grade (1.6 vs. 0.8 in its absence; p = .026). In advanced SM, the presence of nodular regenerative hyperplasia (NRH) was associated with decreased overall survival (9.5 vs. 46.3 months, p = .002). CONCLUSIONS: MC infiltration induced polymorphic hepatic lesions and the degree of fibrosis is associated with portal hypertension. NRH identifies a poor prognosis subgroup of patients with advanced SM. Assessing liver histology can aid in SM prognostic evaluation.
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Hepatomegalia , Fígado , Mastocitose Sistêmica , Humanos , Mastocitose Sistêmica/patologia , Mastocitose Sistêmica/complicações , Estudos Retrospectivos , Feminino , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Adulto , Biópsia , Hepatomegalia/patologia , Hepatomegalia/etiologia , Idoso , Hipertensão Portal/patologia , Hipertensão Portal/etiologia , França , Cirrose Hepática/patologia , Mastócitos/patologia , Fosfatase Alcalina/sangue , PrognósticoRESUMO
Background: Hereditary angioedema (HAE) is characterized by unpredictable and potentially life-threatening attacks of cutaneous and submucosal swelling. Over the past decade, new agents, based on a better understanding of the underlying biologic mechanisms of HAE, have changed the face of long-term prophylaxis (LTP). Objective: The objective was to describe current practices and unmet needs with regard to LTP for HAE in expert centers in France. Methods: The study was conducted in France in 2020. Based on their experience with patients with HAE who had visited their center at least once in the past 3 years, physicians from 25 centers who are expert in the management of HAE were requested to fill in a questionnaire that encapsulated their active patient list, criteria for prescribing LTP, and medications used. They were asked about potential unmet needs with currently available therapies. They were asked to express their expectations with regard to the future of HAE management. Results: Analysis was restricted to 20 centers that had an active patient file and agreed to participate. There were 714 patients with C1 inhibitor (C1-INH) deficiency, of whom 423 (59.2%) were treated with LTP. Altered quality of life triggered the decision to start LTP, as did the frequency and severity of attacks. Ongoing LTP included androgens (28.4%), progestins (25.8%), lanadelumab (25.3%), tranexamic acid (14.2%), intravenous C1-INHs (5.6%), and recombinant C1-INH (0.7%). Twenty-nine percent of the patents with LTP were considered to still have unmet needs. Physicians' concerns varied among therapies: poor tolerability for androgens and progestins, a lack of efficacy for tranexamic acid and progestins, dosage form, and high costs for C1-INHs and lanadelumab. Physicians' expectations encompassed more-efficacious and better-tolerated medications, easier treatment administration for the sake of improved quality of life of patients, and less-expensive therapies. Conclusion: Despite the recent enrichment of the therapeutic armamentarium for LTP, physicians still expressed unmet needs with currently available therapies.
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Angioedemas Hereditários , Ácido Tranexâmico , Androgênios/uso terapêutico , Angioedemas Hereditários/tratamento farmacológico , Angioedemas Hereditários/prevenção & controle , Proteína Inibidora do Complemento C1/uso terapêutico , Humanos , Progestinas/uso terapêutico , Qualidade de Vida , Ácido Tranexâmico/uso terapêuticoRESUMO
Acute attacks could occur during the convalescent phase of COVID-19 illness, more commonly in patients with a history of frequent attacks. However it is unclear whether the acute attacks during the convalescent phase are specifically triggered by COVID-19 or not.
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Angioedemas Hereditários , COVID-19/metabolismo , Sistema de Registros , Adulto , Idoso , Idoso de 80 Anos ou mais , Angioedemas Hereditários/sangue , Angioedemas Hereditários/epidemiologia , Angioedemas Hereditários/terapia , COVID-19/sangue , COVID-19/epidemiologia , COVID-19/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2Assuntos
Toxinas Botulínicas Tipo A , Dermatite Alérgica de Contato , Humanos , Dermatite Alérgica de Contato/etiologia , Dermatite Alérgica de Contato/diagnóstico , Feminino , Toxinas Botulínicas Tipo A/efeitos adversos , Albumina Sérica Humana/efeitos adversos , Testes do Emplastro , Fármacos Neuromusculares/efeitos adversos , Pessoa de Meia-IdadeRESUMO
We investigated the plasma levels of PMPs in patients with 45 stage III and 45 stage IV melanoma. PMPs were characterised by flow cytometry and their thrombogenic activity. We also investigated the link between PMPs circulating levels and tumor burden. The circulating levels of PMPs were significantly higher in stage IV (8500 µL-1 ) than in patients with stage III (2041 µL-1 ) melanoma (P=.0001). We calculated a highly specific (93.3%) and predictive (91.7%) cut-off value (5311 µL-1 ) allowing the distinction between high-risk stage III and metastatic stage IV melanoma. The thrombogenic activity of PMPs was significantly higher in patients with stage IV melanoma (clotting time: 40.7 second vs 65 second, P=.0001). There was no significant association between the radiological tumoral syndrome and the plasma level of PMPs. Our data suggest the role of PMPs in metastatic progression of melanoma.
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Plaquetas , Micropartículas Derivadas de Células , Melanoma/sangue , Neoplasias Cutâneas/sangue , Biomarcadores Tumorais/sangue , Coagulação Sanguínea , Humanos , Melanoma/secundário , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Neoplasias Cutâneas/patologia , Carga TumoralAssuntos
Corantes/efeitos adversos , Corantes de Rosanilina/efeitos adversos , Urticária/induzido quimicamente , Acetaminofen/efeitos adversos , Administração Oral , Analgésicos não Narcóticos/efeitos adversos , Antibacterianos/efeitos adversos , Neoplasias da Mama/cirurgia , Corantes/administração & dosagem , Excipientes , Feminino , Humanos , Hipersensibilidade Imediata/induzido quimicamente , Testes Intradérmicos , Metaciclina/efeitos adversos , Pessoa de Meia-Idade , Corantes de Rosanilina/administração & dosagem , Biópsia de Linfonodo Sentinela , Testes CutâneosRESUMO
Psoriasis involves TNF-α secretion leading to release of microparticles into the bloodstream. We investigated the effect of TNF blockers on microparticles levels before and after treatment in patients (twenty treated by anti-TNF-α agents and 6 by methotrexate) with severe psoriasis. Plasmatic microparticles were labelled using fluorescent monoclonal antibodies and were analysed using cytometry. Three months later, 70% of patients treated with anti-TNF-α agents achieved a reduction in PASI score of at least 75%. The clinical improvement in patients treated with anti-TNF-α agents was associated with a significant reduction of the mean number of platelet microparticles (2837/µl vs 1849/µl, P = 0.02) and of endothelial microparticles (64/µl vs 22/µl, P = 0.001). Microparticles are significantly decreased in psoriatic patients successfully treated by anti-TNF-α. Microparticles levels as circulating endothelial cells represent signs of endothelial dysfunction and are elevated in psoriasis. Then, TNF blockade may be effective to reduce cardiovascular risk through the reduction of circulating microparticles.
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Micropartículas Derivadas de Células/patologia , Psoríase/sangue , Psoríase/terapia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Anticorpos Monoclonais/uso terapêutico , Plaquetas/patologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/prevenção & controle , Fármacos Dermatológicos/uso terapêutico , Células Endoteliais/patologia , Humanos , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Psoríase/complicaçõesAssuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Melanoma/tratamento farmacológico , Melanoma/secundário , Pigmentação da Pele/efeitos dos fármacos , Neoplasias Uveais/patologia , Vitiligo/induzido quimicamente , Progressão da Doença , Feminino , Humanos , Melanoma/diagnóstico por imagem , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Vitiligo/diagnóstico , Vitiligo/fisiopatologiaRESUMO
Introduction: Various clinical decision-making tools for penicillin allergy have been developed to guide delabeling strategies. Objective: To evaluate the penicillin allergy PEN-FAST decision score in a retrospective cohort of patients, adults and children, with penicillin-reported allergy. Methods: This monocentric retrospective cohort included patients with penicillin-reported allergy. All patients underwent penicillin allergy testing using skin tests and/or drug challenge. The PEN-FAST score sensitivity, specificity, negative (NPV) and positive (PPV) predictive values, and the area under the receiver operating characteristics curve (AUC) were calculated. Results: Two hundred and fourteen patients were included (64 children and 150 adults). Allergy was confirmed in 52 cases (24%). A PEN-FAST score <3 points showed a poor discrimination capacity for the whole population (AUC = 0.66; 95% CI: 0.58-0.75), while it demonstrated a better discrimination capacity in the adults group (AUC = 0.71; 95% CI: 0.63-0.80). The sensitivity to identify penicillin allergy using this cutoff of less than 3 points was 0.67 (95% CI: 0.52-0.80); specificity, 0.58 (95% CI: 0.48-0.68); PPV, 0.43 (95% CI: 0.32-0.55); and NPV, 0.78 (95% CI: 0.68-0.87). Conclusions: Although our data confirm a rather good discrimination value of a PEN-FAST score <3 points, its low negative predictive value (78%) did not advocate for its use as an accurate, simple and cost-effective clinical decision-making tool to effectively reduce the number of penicillin skin tests required before direct oral challenge. Further studies are required to improve the predictive capacity of the PEN-FAST score.
RESUMO
BACKGROUND: Few studies have evaluated allergy workup in fixed drug eruption (FDE) in a large population. OBJECTIVE: To evaluate the sensitivity of a standardized allergy workup for diagnosing the cause of FDE, with a focus on in situ repeated open application tests (ROATs). METHODS: In a retrospective multicenter study, we analyzed the practice of conducting a complete allergy workup for the etiological diagnosis of FDE. It consisted of 3 steps: in situ patch tests (PTs) for all cases except pure mucosal involvement, followed by in situ ROAT if in situ PT results were negative, and finally a drug challenge (DC). The in situ ROAT involved daily application of the suspected drug on a previously affected FDE site for 7 days. RESULTS: Of 98 suspected FDE cases, 61 patients (median age 61 y; male-to-female ratio 1.8) with a complete allergy workup were included. In 4 cases, even the DC yielded negative results. Among the remaining 57 patients with a positive workup, implicated drugs included paracetamol (12 cases), ß-lactams (11 cases), imidazoles (9 cases, including 5 with metronidazole), nonsteroidal anti-inflammatory drugs (8 cases), iodinated contrast media (4 cases), cotrimoxazole (3 cases), and various other drugs in 10 patients. The diagnosis was confirmed by in situ PT in 17 of 54 cases (31.5%), in situ ROAT in 14 of 40 cases (35%) (with 4 cases showing remote reactivation of FDE sites), and DC in 26 cases. CONCLUSIONS: The sequential allergy workup involving successively in situ PT, in situ ROAT, and DC is a reliable and safe method for diagnosing the cause of FDE. In situ tests exhibited a sensitivity of over 50%.
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Toxidermias , Hipersensibilidade , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Testes do Emplastro , Toxidermias/etiologia , Anti-Inflamatórios não Esteroides/efeitos adversos , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Hipersensibilidade/complicaçõesRESUMO
BACKGROUND: Angioedema (AE) due to acquired C1-inhibitor (C1-INH) deficiency (AAE-C1-INH) is related to excessive consumption of C1-INH or to anti-C1-INH antibodies, and is frequently associated with lymphoproliferative syndromes or monoclonal gammopathies. Standard of care for prophylactic treatment in this condition is not established. Rituximab may be effective to prevent attacks, especially if the lymphoid hemopathy is controlled, but data are scarce. OBJECTIVE: To evaluate efficacy of rituximab in AAE-C1-INH. METHODS: A retrospective multicenter study was carried out in France, including patients with AAE-C1-INH treated with rituximab between April 2005 and July 2019. RESULTS: Fifty-five patients with AAE-C1-INH were included in the study, and 23 of them had an anti-C1-INH antibody. A lymphoid malignancy was identified in 39 patients, and a monoclonal gammopathy in 9. There was no associated condition in 7 cases. Thirty patients received rituximab alone or in association with chemotherapy (n = 25). Among 51 patients with available follow-up, 34 patients were in clinical remission and 17 patients had active AE after a median follow-up of 3.9 years (interquartile range, 1.5-7.7). Three patients died. The presence of anti-C1-INH antibodies was associated with a lower probability of AE remission (hazard ratio, 0.29 [95% CI, 0.12-0.67]; P = .004). Relapse was less frequent in patients with lymphoma (risk ratio, 0.27 [95% CI, 0.09-0.80]; P = .019) and in patients treated with rituximab and chemotherapy (risk ratio, 0.31 [95% CI, 0.12-0.79]; P = .014). CONCLUSIONS: Rituximab is an efficient and well-tolerated therapeutic option in AE, especially in lymphoid malignancies and in the absence of detectable anti-C1-INH antibodies.
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Angioedema , Angioedemas Hereditários , Humanos , Angioedema/tratamento farmacológico , Angioedemas Hereditários/tratamento farmacológico , Proteína Inibidora do Complemento C1/genética , França , Estudos Retrospectivos , Rituximab/uso terapêuticoAssuntos
Compostos de Anilina/efeitos adversos , Automóveis , Dermatite Alérgica de Contato/etiologia , Dermatite Ocupacional/etiologia , Poliuretanos/efeitos adversos , Adulto , Compostos de Anilina/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Poliuretanos/química , Estudos RetrospectivosRESUMO
BACKGROUND: Since the introduction of sentinel lymph node biopsy (SLNB), its use as a standard of care for patients with clinically node-negative cutaneous melanoma remains controversial. We wished to evaluate our experience of SLNB for melanoma. METHODS: A single center observational cohort of 203 melanoma patients with a primary cutaneous melanoma (tumour thickness > 1 mm) and without clinical evidence of metastasis was investigated from 2002 to 2009. Head and neck melanoma were excluded. SLN was identified following preoperative lymphoscintigraphy and intraoperative gamma probe interrogation. RESULTS: The SLN identification rate was 97%. The SLN was tumor positive in 44 patients (22%). Positive SLN was significantly associated with primary tumor thickness and microscopic ulceration. The median follow-up was 39.5 (5-97) months. Disease progression was significantly more frequent in SLN positive patients (32% vs 13%, p = 0.002). Five-year DFS and OS of the entire cohort were 79.6% and 84.6%, respectively, with a statistical significant difference between SLN positive (58.7% and 69.7%) and SLN negative (85% and 90.3%) patients (p = 0.0006 and p = 0.0096 respectively). Postoperative complications after SLNB were observed in 12% of patients. CONCLUSION: Our data confirm previous studies and support the clinical usefulness of SLNB as a reliable and accurate staging method in patients with cutaneous melanoma. However, the benefit of additional CLND in patients with positive SLN remains to be demonstrated.