RESUMO
Activating mutations in KIT, particularly D816V, have been associated with mastocytosis. Additionally, expression of heterozygous KIT M541L has been primarily reported in patients with pediatric mastocytosis. We thus examined the prevalence of this variant in pediatric and adult patients with mastocytosis (n = 100) compared to ancestry-matched 1000 genomes controls (n = 500) and patients with idiopathic anaphylaxis (n = 23). We then compared clinical symptoms and laboratory data on patients with systemic and cutaneous mastocytosis and bone marrow histopathology on a matched cohort with and without the KIT M541L variant. Overall, the KIT M541L variant was identified in 19 individuals; the majority were diagnosed with systemic mastocytosis (89.4%) with an associated KIT D816V mutation. There were no significant differences in peripheral blood parameters between groups. Patients with mastocytosis carrying the KIT M541L variant did not demonstrate significant differences in symptomatology compared to a matched reference cohort (n = 13/81) without KIT M541L. In patients with idiopathic anaphylaxis, no significant associations were observed. This study uniquely examines the prevalence and impact of the KIT M541L variant in both adult and pediatric patients with mastocytosis further stratified by disease variant. To our knowledge, this is the first case/control study to show a significant genetic association with mastocytosis at the KIT M541L locus.
Assuntos
Proteínas Proto-Oncogênicas c-kit , Humanos , Proteínas Proto-Oncogênicas c-kit/genética , Masculino , Feminino , Adulto , Criança , Pessoa de Meia-Idade , Prevalência , Estudos de Casos e Controles , Adolescente , Mutação , Mastocitose/genética , Mastocitose/epidemiologia , Idoso , Adulto Jovem , Pré-Escolar , Anafilaxia/genética , Anafilaxia/epidemiologia , Predisposição Genética para Doença , Mastocitose Sistêmica/genética , Mastocitose Sistêmica/epidemiologiaRESUMO
BACKGROUND: Systemic mastocytosis (SM) is a clonal disorder of mast cells (MCs) frequently associated with vertebral osteoporosis (OP) and subsequent vertebral fractures (VFs). The natural history of this OP remains unclear. Importantly, we do not know whether OP represents an early event triggered alongside MC abnormalities, and whether MC clonality is sufficient to trigger osteoporosis. OBJECTIVE: To describe OP in patients with medullar clonality in cutaneous mastocytosis (CM) and monoclonal mast cell activation syndrome (MMAS) and to compare their osteoporosis characteristics with those of nonadvanced SM patients (bone marrow mastocytosis and indolent systemic mastocytosis). METHODS: We retrospectively analyzed clinical, biological, and densitometric data of 27 CM, 13 MMAS, and 135 SM patients from the Mastocytosis Expert Center (CEREMAST) in Toulouse, France. RESULTS: The OP (respectively 3.7, 30.8, and 34.1%) and VFs (0.0%, 15.4%, and 20%) were less frequent in CM than in MMAS and SM, despite the presence of clonal MCs in the bone marrow. Most patients with OP and VFs in the non-SM groups had the usual risk factors for OP. Interestingly, the only non-SM patient with a typical SM-like OP had high bone marrow tryptase, developed bone marrow KIT mutation during follow-up, and had a family history of SM. Our data show that OP is not a common clinical finding in CM but is frequent in MMAS. When OP and VFs occur in CM and MMAS patients, they differ from the usual phenotype of SM bone fragility. CONCLUSIONS: Our findings suggest that, in most CM patients, the meaning and management of OP differs from that of OP in MMAS and nonadvanced SM. Prospective longitudinal studies and the validation of predictors are needed to identify CM and MMAS patients developing SM-related OP.
Assuntos
Mastocitose Cutânea , Mastocitose Sistêmica , Osteoporose , Humanos , Osteoporose/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Prevalência , Estudos Retrospectivos , Idoso , Mastocitose Cutânea/epidemiologia , Mastocitose Sistêmica/epidemiologia , Mastócitos/imunologia , França/epidemiologia , Medula Óssea/patologia , Proteínas Proto-Oncogênicas c-kit/genética , Fraturas da Coluna Vertebral/epidemiologiaRESUMO
BACKGROUND: Mastocytosis is a disease characterized by accumulation of aberrant mast cells and mediator-related symptoms and is divided into systemic mastocytosis (SM) and cutaneous mastocytosis (CM). The epidemiology of mastocytosis remains incompletely understood. OBJECTIVE: To estimate the incidence, prevalence, overall survival (OS) and burden of comorbidities in adult mastocytosis patients identified in Swedish population-based registries. METHODS: Individuals (≥ 20 years of age) with a mastocytosis diagnosis in the National Patient Register (NPR) and/or the Swedish Cancer Register (SCR) between 2001 and 2018, were identified. In a matched cohort design, for each case five randomly selected mastocytosis-free comparators matched on age, sex, and county of residence were chosen from the Population Register. The Kaplan-Meier method was used to compare OS between individuals with mastocytosis and comparators. Information on concomitant disease at baseline was assessed by use of the Charlson Comorbidity Index (CCI). RESULTS: We identified 2,040 adults with a mastocytosis diagnosis yielding an annual incidence of 1.56 per 100,000 (95% CI 1.29-1.87) and a prevalence of 23.9 per 100,000 (95% CI 22.8-25.0). The comorbidity burden was higher, and the OS lower, in patients with mastocytosis compared to comparators. INTERPRETATION: We found a higher incidence and prevalence of mastocytosis compared to assessments in other settings and confirmed that the prognosis generally is favorable. Of special note was evidence of a higher comorbidity burden in mastocytosis patients compared to the background population. LIMITATIONS: Underreporting and inconsistencies in the use of diagnostic codes.
Assuntos
Mastocitose Sistêmica , Mastocitose , Adulto , Humanos , Mastócitos , Mastocitose/epidemiologia , Mastocitose/complicações , Mastocitose/diagnóstico , Mastocitose Sistêmica/epidemiologia , Mastocitose Sistêmica/complicações , Mastocitose Sistêmica/diagnóstico , Prognóstico , Suécia/epidemiologia , Adulto Jovem , Masculino , FemininoRESUMO
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
This article reviews the effects of gender on anaphylaxis in general and focuses on mastocytosis-specific issues. Incidence of anaphylaxis is increased in female compared with male patients during the pubertal years through the fifth decade of life, in which these disparities decrease. Estrogen is thought to increase the severity of anaphylaxis through increased endothelial nitric oxide synthase release. Despite this, all-cause fatal anaphylaxis does not appear to show a gender predilection. Systemic mastocytosis incidence is higher in women; however, mortality is increased in men owing to increased molecular and cytogenetic abnormalities.
Assuntos
Anafilaxia , Mastocitose Sistêmica , Mastocitose , Humanos , Masculino , Feminino , Anafilaxia/epidemiologia , Anafilaxia/etiologia , Mastocitose/diagnóstico , Mastocitose/epidemiologia , Mastocitose Sistêmica/diagnóstico , Mastocitose Sistêmica/epidemiologia , Incidência , TriptasesRESUMO
BACKGROUND: Organomegaly, including splenomegaly, hepatomegaly, and/or lymphadenopathy, are important diagnostic and prognostic features in patients with cutaneous mastocytosis (CM) or systemic mastocytosis (SM). OBJECTIVES: To investigate the prevalence and prognostic impact of 1 or more organomegalies on clinical course and survival in patients with CM/SM. METHODS: Therefore, 3155 patients with CM (n = 1002 [32%]) or SM (n = 2153 [68%]) enrolled within the registry of the European Competence Network on Mastocytosis were analyzed. RESULTS: Overall survival (OS) was adversely affected by the number of organomegalies (OS: #0 vs #1 hazard ratio [HR], 4.9; 95% CI, 3.4-7.1, P < .001; #1 vs #2 HR, 2.1, 95% CI, 1.4-3.1, P < .001; #2 vs #3 HR, 1.7, 95% CI, 1.2-2.5, P = .004). Lymphadenopathy was frequently detected in patients with smoldering SM (SSM, 18 of 60 [30%]) or advanced SM (AdvSM, 137 of 344 [40%]). Its presence confered an inferior outcome in patients with AdvSM compared with patients with AdvSM without lymphadenopathy (median OS, 3.8 vs 2.6 years; HR, 1.6; 95% CI, 1.2-2.2; P = .003). OS was not different between patients having organomegaly with either ISM or SSM (median, 25.5 years vs not reached; P = .435). At time of disease progression, a new occurrence of any organomegaly was observed in 17 of 40 (43%) patients with ISM, 4 of 10 (40%) patients with SSM, and 33 of 86 (38%) patients with AdvSM, respectively. CONCLUSIONS: Organomegalies including lymphadenopathy are often found in SSM and AdvSM. ISM with organomegaly has a similar course and prognosis compared with SSM. The number of organomegalies is adversely associated with OS. A new occurrence of organomegaly in all variants of SM may indicate disease progression.
Assuntos
Linfadenopatia , Mastocitose Cutânea , Mastocitose Sistêmica , Mastocitose , Humanos , Prognóstico , Mastocitose/diagnóstico , Mastocitose Sistêmica/diagnóstico , Mastocitose Sistêmica/epidemiologia , Progressão da DoençaRESUMO
BACKGROUND: Systemic mastocytosis (SM) is a rare clonal neoplasm driven by KIT D816V and other mutations. Data were collected from the patient perspective on disease burden and included an SM-specific symptom assessment tool. METHODS: US adults aged 18 years and older with a self-reported SM diagnosis completed an online TouchStone SM Patient Survey of 100 items, including the 12-item Short-Form Health Survey, the Indolent Systemic Mastocytosis Symptom Assessment Form, and the Work Productivity and Activity Impairment Questionnaire, as well as questions about SM diagnosis, the impact of SM on daily activities, work impairment, and health care use. The results were analyzed using descriptive statistics. RESULTS: Fifty-six individuals completed the survey (89% women; median age, 48 years; mean time since diagnosis, 6.7 years), reporting indolent SM (66%), aggressive SM (9%), smoldering SM (5%), and unknown SM subtype (18%). Over a 1-year recall, respondents reported seeking emergency care for anaphylaxis (30%) and taking three or more prescription medications (52%) for SM. Over one half of patients (54%) reduced their work hours because of SM, and 64% avoided leaving home because of symptoms. A majority of respondents (93%) had experienced ≥10 SM-related symptoms, noting that the most bothersome were anaphylactic episodes (18%), abdominal/stomach pain (16%), diarrhea/loose stools (13%), and fatigue (11%). Whereas an Indolent Systemic Mastocytosis Symptom Assessment Form-derived total symptom score of 28 is used to indicate moderate-to-severe symptoms, the mean total symptom score was 52.7. Mental and physical component summary scores from the 12-item Short-Form Health Survey were below population norms. CONCLUSIONS: Patients who were surveyed reported substantial symptom burden and unmet needs because of SM, as evidenced by seeking emergency care and reporting bothersome symptoms, poor quality of life, and reduced work hours and productivity. LAY SUMMARY: The objective of this research was to understand the burden and unmet needs in the rare disease of systemic mastocytosis (SM) to guide future care. Fifty-six patients completed an online survey containing questions about their diagnosis, medications, health care use, quality of life, and SM symptoms. The results demonstrated that SM is associated with severe and burdensome symptoms, anaphylactic events, emergency department visits, use of multiple medications, reduced ability to work, and poor physical and psychological quality of life. These findings suggest the need for future advances to address unmet needs in patients affected by SM.
Assuntos
Anafilaxia , Mastocitose Sistêmica , Adulto , Anafilaxia/diagnóstico , Diarreia , Feminino , Humanos , Masculino , Mastocitose Sistêmica/diagnóstico , Mastocitose Sistêmica/epidemiologia , Mastocitose Sistêmica/terapia , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Proteínas Proto-Oncogênicas c-kit/genética , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
The systemic mast cell disease (MCAD; prevalence 17%) may occur frequently in urological patients. MCAD-induced changes include cysts in all organs, also in the urogenital system. In the presence of MCAD, the surgical removal of such cysts must consider specific features of the MCAD in order to reduce surgical and complication risks. Vice versa, if in urological examinations multiple cysts are found, this could be an indication of a possibly existing, in some circumstances, unrecognized MCAD.
Assuntos
Cistos , Transtornos da Ativação de Mastócitos , Mastocitose Sistêmica , Urologia , Cistos/cirurgia , Humanos , Mastocitose Sistêmica/epidemiologia , PrevalênciaRESUMO
In the current classification of the World Health Organization (WHO), bone marrow mastocytosis (BMM) is a provisional variant of indolent systemic mastocytosis (ISM) defined by bone marrow involvement and absence of skin lesions. However, no additional diagnostic criteria for BMM have been proposed. Within the registry dataset of the European Competence Network on Mastocytosis, we compared characteristics and outcomes of 390 patients with BMM and 1175 patients with typical ISM. BMM patients were significantly older, predominantly male, had lower tryptase and lower burden of neoplastic mast cells, and displayed a higher frequency of allergic reactions, mainly triggered by Hymenoptera, than patients with typical ISM. The estimated 10-year progression-free survival of BMM and typical ISM was 95.9% and 92.6%, respectively. In BMM patients defined by WHO-based criteria, the presence of one B-Finding and tryptase level ≥125 ng/mL were identified as risk factors for progression in multivariate analyses. BMM patients without any of these risk factors were found to have better progression-free survival (p < 0.05) and better overall survival (p < 0.05) than other ISM patients. These data support the proposal to define BMM as a separate SM variant characterized by SM criteria, absence of skin lesions, absence of B-Findings, and tryptase levels <125 ng/mL.
Assuntos
Medula Óssea/patologia , Mastócitos/patologia , Mastocitose Sistêmica/diagnóstico , Mastocitose/diagnóstico , Dermatopatias/fisiopatologia , Triptases/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/metabolismo , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Mastócitos/metabolismo , Mastocitose/epidemiologia , Mastocitose/metabolismo , Mastocitose Sistêmica/epidemiologia , Mastocitose Sistêmica/metabolismo , Pessoa de Meia-Idade , Prognóstico , Taxa de SobrevidaRESUMO
Indolent systemic mastocytosis (ISM) is a group of heterogenous diseases characterized by abnormal accumulation of mast cells in at least one organ. ISM can be a cause of osteoporosis. The aim of this study is to determine the prevalence, and the prognosis of ISM in a cohort of patients with osteoporosis. In this monocentric and retrospective study, patients with osteoporosis who did not receive a bone biopsy (cohort 1) and patients that subsequently received a diagnostic bone biopsy for differential diagnosis (cohort 2) are compared with patients who are diagnosed with ISM (cohort 3). A total of 8392 patients are diagnosed with osteoporosis. Out of these patients 1374 underwent a diagnostic bone biopsy resulting in 43 patients with ISM. These figures indicate that ISM is diagnosed in 0.5% of patients with osteoporosis and in 3.1% (men 5.8%) of patients who underwent bone biopsies. Patients with ISM sustained significantly more vertebral fractures in comparison to patients in cohort 2 (4.4 ± 3.6 versus 2.4 ± 2.5 vertebral fractures, p < 0.001) and women were significantly younger compared to cohort 2 (57.3 ± 12 versus 63.6 ± 12 years, p < 0.05). Only 33% showed an involvement of the skin (urticaria pigmentosa). ISM is a rare cause of osteoporosis (0.5%). However, in a subgroup of rather young male patients with osteoporosis the prevalence is more than 5%. Thus, ISM should be considered in premenopausal women and men presenting with vertebral fractures even if urticaria pigmentosa is not present.
Assuntos
Mastocitose Sistêmica , Osteoporose , Estudos de Coortes , Feminino , Humanos , Masculino , Mastocitose Sistêmica/complicações , Mastocitose Sistêmica/epidemiologia , Osteoporose/epidemiologia , Prevalência , Estudos RetrospectivosRESUMO
BACKGROUND: The Advanced Systemic Mastocytosis Symptom Assessment Form (AdvSM-SAF) was developed to evaluate symptoms of advanced systemic mastocytosis (AdvSM). This study aimed to psychometrically evaluate AdvSM-SAF scores and provide score interpretation guidelines. METHODS: The 10-item AdvSM-SAF was administered daily (scored as a seven-day average) in EXPLORER, an open-label Phase 1 study in AdvSM. Score distribution, reliability, construct-related validity, sensitivity to change, and interpretation guidelines were evaluated for AdvSM-SAF items, gastrointestinal symptom score (GSS), skin symptom score (SSS), and total symptom score (TSS). RESULTS: Thirty-one patients contributed to the analyses. At Baseline, the GSS, SSS, and TSS had adequate internal consistency (α > 0.7) and test-retest reliability (intraclass correlation coefficients >0.7). AdvSM-SAF scores were moderately to strongly correlated with variables as expected, and distinguished among clinically distinct groups. Observed relationships between change scores in the AdvSM-SAF and other assessments reflect evidence that AdvSM-SAF scores change in concert with other assessments designed to measure similar constructs. The magnitude of AdvSM-SAF weekly TSS mean change scores based on different anchor groupings was as expected (improvement > stable > worsening). Candidate clinically meaningful between-group difference estimates (GSS = 2-4, SSS = 2-3, and TSS = 4-7 points) and within-person change estimates (GSS = 6-9, SSS = 1-4, TSS = 9-14) for AdvSM-SAF weekly scores were generated. CONCLUSION: The AdvSM-SAF produced reliable, construct-valid, and sensitive scores when administered in the target patient population. These results, along with its strong development history and evidence of content validity, indicate that the AdvSM-SAF is fit for the purpose of measuring treatment benefit in individuals with AdvSM.
Assuntos
Mastocitose Sistêmica/diagnóstico , Mastocitose Sistêmica/psicologia , Psicometria/métodos , Qualidade de Vida , Índice de Gravidade de Doença , Avaliação de Sintomas/métodos , Feminino , Seguimentos , Humanos , Masculino , Mastocitose Sistêmica/epidemiologia , Pessoa de Meia-Idade , Prognóstico , Reprodutibilidade dos Testes , Inquéritos e Questionários , Reino Unido/epidemiologia , Estados Unidos/epidemiologiaRESUMO
PROBLEM: Associations between immune dysfunction conditions (eg, systemic lupus erythematous, rheumatoid arthritis) and endometriosis have been observed in adult women, but not assessed among a younger population. We investigated the association between immune-mediated conditions and endometriosis among young women. METHOD OF STUDY: This cross-sectional analysis in the Women's Health Study: From Adolescence to Adulthood included 551 participants with surgically diagnosed endometriosis (median age=19) and 652 controls without endometriosis (median age=24). Participants completed an expanded Endometriosis Phenome and Biobanking Harmonization Project questionnaire. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) to investigate the associations between autoimmune/inflammatory, atopic, chronic pain/fatigue, and endocrine disorders with endometriosis, adjusting for confounders. RESULTS: Participants with any autoimmune and/or inflammatory condition had an increased odds of co-occurring endometriosis (OR: 1.87; CI: 0.92-3.80), as did participants with allergies (OR: 1.76; CI: 1.32-2.36), asthma (OR: 1.35; CI: 0.97-1.88), chronic fatigue syndrome and/or fibromyalgia (OR: 5.81; CI: 1.89-17.9), or previous mononucleosis (OR: 1.75; CI: 1.14-2.68). Odds of endometriosis were lower among participants with eczema (OR: 0.68; CI: 0.44-1.04). We observed a positive trend between the number of immune-mediated conditions and the odds of endometriosis (p-trend=0.0002). Endocrine disorders were not associated with endometriosis. CONCLUSIONS: Among this population of adolescents and adult women, endometriosis was more likely among participants with autoimmune and/or inflammatory diseases, allergies, asthma, previous mononucleosis infection, and chronic fatigue and/or fibromyalgia. We observed that an increasing number of immune-mediated conditions were positively associated with endometriosis risk. It is important for clinicians who care for adolescents and women with these conditions to consider endometriosis as a comorbidity.
Assuntos
Fatores Etários , Artrite Reumatoide/epidemiologia , Endometriose/epidemiologia , Mastocitose Sistêmica/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Comorbidade , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Adulto JovemRESUMO
OVERVIEW: Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MC) in extra-cutaneous organs. DIAGNOSIS: The major criterion is presence of multifocal clusters of spindled MC in the bone marrow. Minor diagnostic criteria include elevated serum tryptase level, abnormal MC CD25 expression, and presence of KITD816V mutation. RISK STRATIFICATION: Establishing SM subtype as per the World Health Organization classification system is an important first step. Broadly, patients either have indolent/smoldering SM (ISM/SSM) or advanced SM, the latter includes aggressive SM (ASM), SM with associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL). Identification of poor-risk mutations (ie, ASXL1, RUNX1, SRSF2, NRAS) further refines the risk stratification. Recently, clinical and hybrid clinical-molecular risk models have been developed to more accurately assign prognosis in SM patients. MANAGEMENT: Treatment goals for ISM patients are primarily directed towards anaphylaxis prevention/symptom control/osteoporosis treatment. Patients with advanced SM frequently need MC cytoreductive therapy to ameliorate disease-related organ dysfunction. High response rates have been seen with small-molecule inhibitors that target mutant-KIT, including midostaurin (Food and Drug Administration approved) or avapritinib (investigational). Other options for MC cytoreduction include cladribine or interferon-α, although head-to-head comparisons are lacking. Treatment of SM-AHN primarily targets the AHN component, particularly if an aggressive disease such as acute myeloid leukemia is present. Allogeneic stem cell transplant can be considered in such patients, or in those with relapsed/refractory advanced SM. Imatinib has a limited therapeutic role in SM; effective cytoreduction is limited to those with imatinib-sensitive KIT mutations.
Assuntos
Mastocitose Sistêmica , Adulto , Algoritmos , Animais , Medula Óssea/patologia , Gerenciamento Clínico , Modelos Animais de Doenças , Drogas em Investigação/uso terapêutico , Mutação com Ganho de Função , Neoplasias Hematológicas/epidemiologia , Humanos , Hidroxiureia/uso terapêutico , Subunidade alfa de Receptor de Interleucina-2/análise , Estimativa de Kaplan-Meier , Leucemia de Mastócitos/epidemiologia , Leucemia de Mastócitos/etiologia , Mastócitos/química , Mastócitos/patologia , Mastocitose Sistêmica/diagnóstico , Mastocitose Sistêmica/tratamento farmacológico , Mastocitose Sistêmica/epidemiologia , Mastocitose Sistêmica/genética , Camundongos , Camundongos Transgênicos , Mutação de Sentido Incorreto , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-kit/genética , Medição de Risco , Triptases/sangueRESUMO
BACKGROUND: Mastocytosis in adults often presents with skin lesions. A bone marrow biopsy is necessary to confirm or exclude the presence of systemic mastocytosis (SM) in these cases. When a bone marrow biopsy is not performed, the provisional diagnosis is mastocytosis in the skin (MIS). No generally accepted scoring system has been established to estimate the risk of SM in these patients. OBJECTIVE: To develop a risk score to predict SM in adults with MIS. METHODS: We examined 1145 patients with MIS from the European Competence Network on Mastocytosis Registry who underwent a bone marrow biopsy. A total of 944 patients had SM and 201 patients had cutaneous mastocytosis; 63.7% were female, and 36.3% were male. Median age was 44 ± 13.3 years. The median serum tryptase level amounted to 29.3 ± 81.9 ng/mL. We established a multivariate regression model using the whole population of patients as a training and validation set (bootstrapping). A risk score was developed and validated with receiver-operating curves. RESULTS: In the multivariate model, the tryptase level (P < .001), constitutional/cardiovascular symptoms (P = .014), and bone symptoms/osteoporosis (P < .001) were independent predictors of SM (P < .001; sensitivity, 90.7%; specificity, 69.1%). A 6-point risk score was established (risk, 10.7%-98.0%) and validated. CONCLUSIONS: Using a large data set of the European Competence Network on Mastocytosis Registry, we created a risk score to predict the presence of SM in patients with MIS. Although the score will need further validation in independent cohorts, our score seems to discriminate safely between patients with SM and with pure cutaneous mastocytosis.
Assuntos
Mastocitose Cutânea , Mastocitose Sistêmica , Mastocitose , Adulto , Medula Óssea , Feminino , Humanos , Masculino , Mastócitos , Mastocitose Cutânea/diagnóstico , Mastocitose Cutânea/epidemiologia , Mastocitose Sistêmica/diagnóstico , Mastocitose Sistêmica/epidemiologia , Pessoa de Meia-Idade , TriptasesRESUMO
The coronavirus disease 2019 (COVID-19) (caused by severe acute respiratory syndrome coronavirus 2) pandemic has massively distorted our health care systems and caused catastrophic consequences in our affected communities. The number of victims continues to increase, and patients at risk can only be protected to a degree, because the virulent state may be asymptomatic. Risk factors concerning COVID-19-induced morbidity and mortality include advanced age, an impaired immune system, cardiovascular or pulmonary diseases, obesity, diabetes mellitus, and cancer treated with chemotherapy. Here, we discuss the risk and impact of COVID-19 in patients with mastocytosis and mast cell activation syndromes. Because no published data are yet available, expert opinions are, by necessity, based on case experience and reports from patients. Although the overall risk to acquire the severe acute respiratory syndrome coronavirus 2 may not be elevated in mast cell disease, certain conditions may increase the risk of infected patients to develop severe COVID-19. These factors include certain comorbidities, mast cell activation-related events affecting the cardiovascular or bronchopulmonary system, and chemotherapy or immunosuppressive drugs. Therefore, such treatments should be carefully evaluated on a case-by-case basis during a COVID-19 infection. In contrast, other therapies, such as anti-mediator-type drugs, venom immunotherapy, or vitamin D, should be continued. Overall, patients with mast cell disorders should follow the general and local guidelines in the COVID-19 pandemic and advice from their medical provider.
Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Gerenciamento Clínico , Mastocitose Cutânea/tratamento farmacológico , Mastocitose Sistêmica/tratamento farmacológico , Pandemias , Pneumonia Viral/epidemiologia , Betacoronavirus/imunologia , COVID-19 , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/patologia , Difosfonatos/uso terapêutico , Prova Pericial , Glucocorticoides/efeitos adversos , Antagonistas dos Receptores Histamínicos/uso terapêutico , Humanos , Imunossupressores/efeitos adversos , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Mastócitos/patologia , Mastocitose Cutânea/diagnóstico , Mastocitose Cutânea/epidemiologia , Mastocitose Cutânea/patologia , Mastocitose Sistêmica/diagnóstico , Mastocitose Sistêmica/epidemiologia , Mastocitose Sistêmica/patologia , Agonistas Mieloablativos/efeitos adversos , Pneumonia Viral/diagnóstico , Pneumonia Viral/patologia , Medicina de Precisão/métodos , Fatores de Risco , SARS-CoV-2 , Vitamina D/uso terapêuticoRESUMO
BACKGROUND: Little is known about the epidemiology of advanced systemic mastocytosis (advSM). OBJECTIVES: To investigate epidemiologic features and diagnostic pitfalls of advSM in Germany. METHODS: Therefore, 140 patients from a single German reference center of the European Competence Network on Mastocytosis between 2003 and 2018 were analyzed. RESULTS: The patients' median age was 68 years (range, 26-86 years), and male versus female ratio was 2:1. An elevated serum tryptase, a KIT D816 mutation, and additional somatic mutations, for example, in SRSF2, ASXL1, or RUNX1, were identified in 95%, 91%, and 74% of patients, respectively. Median overall survival was 3.5 years (range, 0.03-14.3 years; male vs female 2.6 vs 4.2 years; P = .02). Two categories of misdiagnoses were identified in 51 of 140 (36%) patients: First, systemic mastocytosis (SM) was overlooked in 28 of 140 (20%) patients primarily diagnosed with various subtypes of myeloid neoplasms. Second, 23 of 140 (16%) patients were diagnosed with supposed progression from indolent SM to advSM; however, combination of an elevated KIT D816V variant allele frequency in peripheral blood (n = 22), monocytosis (n = 9), eosinophilia (n = 6), and/or mutations in SRSF2, ASXL1, or RUNX1 (n = 10) suggest that distinct signs of potential advSM were overlooked in virtually all patients. Based on locally diagnosed patients in an area of 2.5 million inhabitants, but obviously without considering more, yet unrecognized cases, the incidence and prevalence of advSM is at least 0.8 and 5.2, respectively, per 1 million inhabitants. CONCLUSIONS: Adequate analyses of tryptase levels, bone marrow morphology, and genetics in patients with myeloid neoplasms or SM would help to prevent the significant underdiagnosis of advSM.
Assuntos
Mastocitose Sistêmica , Mastocitose , Idoso , Medula Óssea , Feminino , Alemanha , Humanos , Masculino , Mastocitose Sistêmica/diagnóstico , Mastocitose Sistêmica/epidemiologia , Mastocitose Sistêmica/genética , Mutação , Proteínas Proto-Oncogênicas c-kit/genéticaRESUMO
BACKGROUND: In indolent systemic mastocytosis (ISM), several risk factors of disease progression have been identified. Previous studies, performed with limited patient numbers, have also shown that the clinical course in ISM is stable and comparable to that of cutaneous mastocytosis (CM). The aim of this project was to compare the prognosis of patients with ISM with that of patients with CM. METHODS: We employed a dataset of 1993 patients from the registry of the European Competence Network on Mastocytosis (ECNM) to compare outcomes of ISM and CM. RESULTS: We found that overall survival (OS) is worse in ISM compared to CM. Moreover, in patients with typical ISM, bone marrow mastocytosis (BMM), and smoldering SM (SSM), 4.1% of disease progressions have been observed (4.9% of progressions in typical ISM group, 1.7% in BMM, and 9.4% in SSM). Progressions to advanced SM were observed in 2.9% of these patients. In contrast, six patients with CM (1.7%) converted to ISM and no definitive progression to advanced SM was found. No significant differences in OS and event-free survival (EFS) were found when comparing ISM, BMM, and SSM. Higher risk of both progression and death was significantly associated with male gender, worse performance status, and organomegaly. CONCLUSION: Our data confirm the clinical impact of the WHO classification that separates ISM from CM and from other SM variants.
Assuntos
Mastocitose Sistêmica , Mastocitose , Medula Óssea , Humanos , Masculino , Mastócitos , Mastocitose Sistêmica/diagnóstico , Mastocitose Sistêmica/epidemiologia , Prognóstico , Organização Mundial da SaúdeRESUMO
Little is known about osteoporosis in mast cell disorders (MCDs) not related to systemic mastocytosis. We described osteoporosis and fractures in MCDs and showed that systemic mastocytosis was the only studied MCDs associated with osteoporotic vertebral fractures. INTRODUCTION: To describe osteoporosis (OP) and fragility fractures in mast cell disorders (MCDs). METHODS: We retrospectively analyzed data concerning all successive patients with systemic mastocytosis (SM), cutaneous mastocytosis (CM), and mast cell activation syndromes (MCAS) diagnosed in our mastocytosis expert center between 2004 and 2015. We collected data concerning demographic profiles, clinical signs of MCD, osteoporosis, fractures, densitometry, and biological assessment of MCD. We compared CM and MCAS patients with SM patients with regard to the characteristics of OP and fragility fractures. RESULTS: We assessed 89 SM patients, 20 CM patients, and 20 MCAS patients. Osteoporosis was less frequent in CM (15.0%) and MCAS (10.0%) than in SM (44.9%). Similarly, fractures were less frequent in non-SM MCDs, respectively 5.0%, 5.0%, and 28.1%. SM patients displayed high prevalence of vertebral fractures (22.5%), mostly multiple. Conversely, in non-SM patients, vertebral fractures appeared to be uncommon (5%) and more frequently associated with risk factors for osteoporosis. CONCLUSIONS: SM is associated with multiple vertebral osteoporotic fractures, whereas CM and MCAS do not appear to be associated with this phenotype.
Assuntos
Mastocitose/complicações , Fraturas por Osteoporose/etiologia , Fraturas da Coluna Vertebral/etiologia , Adulto , Densidade Óssea/fisiologia , Feminino , França/epidemiologia , Articulação do Quadril/fisiopatologia , Humanos , Vértebras Lombares/fisiopatologia , Masculino , Mastocitose/epidemiologia , Mastocitose/fisiopatologia , Mastocitose Cutânea/complicações , Mastocitose Cutânea/epidemiologia , Mastocitose Cutânea/fisiopatologia , Mastocitose Sistêmica/complicações , Mastocitose Sistêmica/epidemiologia , Mastocitose Sistêmica/fisiopatologia , Pessoa de Meia-Idade , Osteoporose/epidemiologia , Osteoporose/etiologia , Osteoporose/fisiopatologia , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/fisiopatologia , Prevalência , Estudos Retrospectivos , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/fisiopatologiaRESUMO
BACKGROUND: Mast cell diseases such as mastocytosis and mast cell activation syndrome involve abnormal proliferation and/or activation of these cells, leading to many clinically relevant symptoms. OBJECTIVE: To determine the characteristics and experiences of people known or suspected to have a mast cell disorder, The Mastocytosis Society, a US-based patient advocacy, research, and education organization, conducted a survey of patients. METHODS: This Web-based survey was publicized through specialty clinics and the society's newsletter, Web site, and online blogs. Both online and paper copies of the questionnaire were provided together with required statements of consent. RESULTS: The first set of results from this survey of 420 respondents has been previously published; the second set is presented in this article. These results include source(s) of diagnosis, clinical and laboratory tests reported, comorbidities, dietary practices, possible familial occurrence of mast cell disorders, and perceptions concerning mast cell disorder-related medical care needs in the United States. CONCLUSIONS: These patient survey results are provided to assist medical professionals in learning patients' perceptions of their experiences and to give patients with mast cell disorders and caregivers the opportunity to compare experiences with those of other affected individuals.
Assuntos
Dieta , Família , Mastocitose Cutânea/diagnóstico , Mastocitose Sistêmica/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alergistas , Anafilaxia/diagnóstico , Anafilaxia/terapia , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico , Doenças Ósseas Metabólicas/tratamento farmacológico , Doenças Ósseas Metabólicas/epidemiologia , Cálcio/uso terapêutico , Criança , Pré-Escolar , Técnicas de Laboratório Clínico , Dermatologistas , Dietoterapia , Feminino , Testes Genéticos , Comportamentos Relacionados com a Saúde , Humanos , Lactente , Masculino , Mastocitose/diagnóstico , Mastocitose/epidemiologia , Mastocitose/terapia , Mastocitose Cutânea/epidemiologia , Mastocitose Cutânea/terapia , Mastocitose Sistêmica/epidemiologia , Mastocitose Sistêmica/terapia , Pessoa de Meia-Idade , Avaliação das Necessidades , Oncologistas , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Médicos de Atenção Primária , Inquéritos e Questionários , Estados Unidos , Vitamina D/uso terapêutico , Adulto JovemRESUMO
AIM: We collected 'real-life' data on the management of patients with mastocytosis in the Italian Mastocytosis Registry. METHODS: Six hundred patients diagnosed with mastocytosis between 1974 and 2014 were included from 19 centers. RESULTS: Among adults (n = 401); 156 (38.9%) patients were diagnosed with systemic mastocytosis. In 212 adults, no bone marrow studies were performed resulting in a provisional diagnosis of mastocytosis of the skin. This diagnosis was most frequently established in nonhematologic centers. In total, 182/184 pediatric patients had cutaneous mastocytosis. We confirmed that in the most patients with systemic mastocytosis, serum tryptase levels were >20 ng/ml and KIT D816V was detectable. CONCLUSION: The Italian Mastocytosis Registry revealed some center-specific approaches for diagnosis and therapy. Epidemiological evidence on this condition is provided.