Histological characterization of liver involvement in systemic mastocytosis.

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.

Epidemiology of mastocytosis: a population-based study (Sweden).

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.

A clinical, morphological and molecular study of 70 patients with gastrointestinal involvement in systemic mastocytosis.

In 70 patients with KIT D816V positive systemic mastocytosis (SM) including 36 patients with advanced SM (AdvSM), we correlated the extent of reported mucosal mast cell ([m]MC) infiltration of the upper and/or lower gastrointestinal tract (UGIT, n = 63; LGIT, n = 64; both, n = 57) with symptoms and markers of MC burden/subtype. GI symptoms were reported by all patients (mean 2.1 number of symptoms). A strong mMC infiltration was identified in 24 patients (UGIT, 17/63, 27%; LGIT, 19/64, 30%). Concurrent involvement of UGIT and LGIT (n = 12) correlated with female gender (75%) and a higher symptom burden (mean 2.7) but not with MC burden or subtype. Significant differences between non-AdvSM and AdvSM were reported regarding food intolerance (54% vs. 17%), cramping (54% vs. 22%) and weight loss (0% vs. 64%). KIT D816V was identified in 54/56 (96%) available biopsies. In 46 patients, digital PCR revealed a correlation with low albumin levels (r = - 0.270, P = 0.069) and the KIT D816V VAF in peripheral blood (r = 0.317, P = 0.036) but not with the extent of mMC infiltration or markers of MC burden/subtype. Although MC mediator triggered GI symptoms have a substantial impact on the quality of life, correlation to objective disease parameters is lacking thus making its systematic assessment challenging.

Underlying systemic mastocytosis in patients with unexplained osteoporosis: score proposal.

BACKGROUND: A score to predict the association between unexplained osteoporosis and an underlying systemic Mastocytosis (SM) is lacking. OBJECTIVE: This study aimed at identifying criteria able to predict the diagnosis of SM without skin involvement and provide an indication for bone marrow (BM) assessment. METHODS: We included 139 adult patients with unexplained osteoporosis and suspected SM. After BM evaluation, 63 patients (45.3 %) were diagnosed with SM, while the remaining 76 patients (54.7 %) negative for clonal mast cell (MC) disorders, constituted our control group. Univariate and multivariate analysis identified three independent predictive factors: age (<54 years: +1 point, >64 years: -1 point), serum basal tryptase (sBT) levels >19 ng/mL (+2 points) and vertebral fractures (+2 points). RESULTS: These variables were used to build the OSTEO-score, able to predict the diagnosis of SM before BM assessment with a sensitivity of 73.5 % and a specificity of 67.1 %. Patients with a score < 3 had a lower probability of having SM compared to patients with a score ≥ 3 (28.5 % and 71.4 %, respectively, p < 0.0001). When sBT levels were corrected for the presence of hereditary alpha-tryptasemia (HαT) using the BST calculater (https://bst-calculater.niaid.nih.gov/) recently published [1,2], the sensitivity of ΗαT-adjusted OSTEO-score increased to 87.8 %, and the specificity reached 76.1 %. Also, the positive predictive value of a score ≥ 3 increased to 85.2 %. CONCLUSIONS: Further studies are needed to validate these results and characterize the role of tryptase genotyping in patients with unexplained osteoporosis in reducing the risk of misdiagnosing patients with SM. Our proposed scoring model allows the identification of patients with the highest probability of having SM, avoiding unnecessary BM studies.

An Unusual Transition from Cutaneous to Systemic Mastocytosis in a Pediatric Patient.

Background: Cutaneous mastocytosis (CM) occurs when abnormal mast cells accumulate in the skin, whereas in systemic mastocytosis (SM), accumulation also occurs in other tissues. A transition from CM to SM is an atypical occurrence in pediatric patients. Case Presentation: An 8-month-old female presented with a 3-month history of whole body hyperpigmented macules with a normal serum tryptase level, consistent with a diagnosis of CM. At age 2.5 years, cutaneous lesions increased and repeat serum tryptase levels were elevated. Subsequent positive peripheral blood KIT D816V mutation testing furthered concern for a monoclonal mast cell disorder; therefore, prompting a bone marrow biopsy which was consistent with a diagnosis of SM. Conclusion: Our case depicts the possible transition from CM to SM in a pediatric patient. Despite an initial presentation consistent with a diagnosis of CM, watchful monitoring for signs and symptoms indicative of systemic involvement may be warranted in some pediatric patients.

Consideraciones anestésicas en una parturienta con mastocitosis sistémica / Anesthetic considerations in a laboring woman with systemic mastocytosis

La mastocitosis se caracteriza por la expansión clónica de mastocitos, con acumulación anormal en diferentes órganos. Perioperatoriamente, numerosos estímulos pueden originar la liberación de sustancias vasoactivas por parte de los mastocitos. Las parturientas con mastocitosis sistémica plantean una dificultad al anestesiólogo: por un lado, el dolor y el estrés del parto pueden causar una mayor activación de los mastocitos y, por otro, la administración de fármacos puede desencadenar posiblemente la liberación de mediadores de los mastocitos. Los autores describen un caso de una embarazada de 34 años de edad con mastocitosis sistémica que solicita analgesia para el parto. Se realizó analgesia epidural tras la inducción del parto, una vez consideradas las particularidades anestésicas. El procedimiento epidural, el parto y la expulsión transcurrieron sin incidentes. Se aporta una revisión de la mastocitosis sistémica y se abordan sus consideraciones anestésicas.(AU)

Mastocytosis is characterized by clonal expansion of mast cells, with abnormal accumulation in different organs. Perioperatively, numerous stimuli may lead to the release of vasoactive substances by mast cells. Parturients with systemic mastocytosis pose a challenge to the anesthesiologist: on one hand, the pain and stress of labor may lead to greater mast cell activation and, on the other, the administration of drugs that may possibly trigger the release of mast cell mediators. The authors describe a case of a 34-year-old pregnant woman with systemic mastocytosis who requests labor analgesia. An epidural analgesia was performed after induction of labor, after considering anesthetic particularities. The epidural procedure, labor and delivery were uneventful. A review of systemic mastocytosis is provided and its anesthetic considerations are discussed.(AU)

Fracturas vertebrales múltiples en varón joven como primera manifestación de una mastocitosis sistémica / Multiple vertebral fractures in young man as first manifestation of systemic mastocytosis

La mastocitosis sistémica (MS) es una enfermedad clonal de los progenitores mastocíticos de la médula ósea. El cuadro clínico varía desde una forma asintomática (indolente) hasta una forma altamente agresiva con una supervivencia muy corta (leucemia de mastocitos). Un 28-34% de los pacientes con MS tiene síntomas relacionados con la afección ósea en el momento del diagnóstico y el 16% fracturas. La presentación de MS como fracturas vertebrales clínicas en varones jóvenes no es frecuente. A continuación describimos un caso de osteoporosis establecida como única manifestación de MS (AU)

Systemic mastocytosis (SM) is a clonal disease of mast cell progenitors from the bone marrow. The clinical picture varies from asymptomatic forms (indolent) to a highly aggressive form with a very short (mast cell leukemia) survival. Between 28-34% of patients with SM are related to bone condition at the time of diagnosis and 16% have symptomatic fractures. The presentation of SM as clinical vertebral fractures in young men is rare. Here, we describe a case of established osteoporosis as the only manifestation of SM (AU)

Compromiso óseo en mastocitosis sistémica: una asociación frecuente, pero muchas veces inadvertida / Bone involvement in systemic mastocytosis: report of two cases

Systemic mastocytosis (SM) is characterized by pathologic expansion and activation of mast cells. The main clinical manifestations of SM include skin involvement, gastrointestinal symptoms and anaphylaxis due to the release of its mediators. Thirty percent of pat ients with SM have a low bone mass and 20% fractures. At the same time, SM affects 10% of male patients with idiopathic osteoporosis. Measuring serum tryptase is essential for the screening of MS. We report two cases of SM with bone involvement. A 25-year- old woman with prior diagnosis of SM, based on skin involvement, flushing, high serum tryptase and compatible bone marrow (BM) biopsy and genetic study. Low bone mass was diagnosed and treatment was started with calcium and vitamin D plus oral bisphosphona tes with adequate response. A 47 years old man who presented with multiple osteoporotic vertebral fractures and low bone mass. Treatment with vitamin D and alendronate was started, but the patient developed new vertebral fractures. The study was extended w ith measurement of serum tryptase that was elevated. Diagnosis of SM was confirmed with BM biopsy and the patient was referred to hematology for specific care. These cases emphasize the importance of bone assessment in SM, as well as the need to rule out S M in patients with osteoporosis and no evident cause.

Cirugía oral en pacientes con mastocitosis: a propósito de un caso / Oral surgery in mastocytosis patients: a case report

Las mastocitosis son un grupo heterogéneo de enfermedades que se caracterizan por la proliferación de mastocitos en uno o más órganos o tejidos. Se denomina mastocitosis sistémica (MS) cuando hay afectación de un tejido distinto a la piel. La MS es una enfermedad poco frecuente. Los pacientes con mastocitosis tienen más susceptibilidad de padecer shocks anafilácticos. Éstos podrían ser causados por procedimientos de cirugía odontológicos y de cirugía oral. En ello influye el estrés que suponen para el paciente así cómo el material, medicación y productos de higiene oral. Se presenta el caso de una chica de 18 años con MS programada para la extracción de cordales 18, 18, 38 y 48 incluidos y enucleación quística, bajo anestesia general (AU)

Mastocytoses are a heterogeneous group of entities characterized by mast cell proliferation in one or more organs or tissues. When tissues other than the skin are involved, the disease is called systemic mastocytosis (SM). SM is a highly infrequent disease. Patients with mastocytosis are prone to suffer from anaphylaxis. These and other severe reactions may be caused by oral surgeries, dental procedures, through the exposure to stress, dental materials and oral higiene products. A case of a 18 years old female with SM is presented. She was programmed for the extraction of 4 wisdom teeth and posterior cyst enucleation, under general anesthesia (AU)

Psychosocial factors and mental work load: a reality perceived by nurses in intensive care units / Fatores psicossociais e carga mental de trabalho: uma realidade percebida pelos enfermeiros em Unidades de Terapia Intensiva / Factores psicosociales y Carga mental de trabajo: una realidad percibida por enfermeras/os en Unidades Críticas

OBJECTIVE: To analyse the perception of psychosocial factors and mental workload of nurses who work in intensive care units. It is hypothesised that nurses in these units could perceive psychosocial risks, manifesting in a high mental work load. The psychosocial dimension related to the position's cognitive demands is hypothesised to mostly explain mental work load. METHOD: Quantitative study, with a descriptive, cross-sectional, and comparative design. A total of 91% of the intensive care unit populations of three Chilean hospitals was surveyed, corresponding to 111 nurses. The instruments utilised included (A) a biosociodemographic history questionnaire; (b) the SUSESO-ISTAS 21 questionnaire; and (c) the Mental Work Load Subjective Scale (ESCAM, in Spanish). RESULTS: In total, 64% and 57% of participants perceived high levels of exposure to the psychosocial risks Psychosocial demands and Double shift, respectively. In addition, a medium-high level of overall mental load was observed. Positive and significant correlations between some of the SUSESO-ISTAS 21 and ESCAM dimensions were obtained. Using a regression analysis, it was determined that three dimensions of the psychosocial risk questionnaire helped to explain 38% of the overall mental load. CONCLUSION: Intensive care unit nurses felt that inadequate psychosocial factors and mental work overload existed in several of the tested dimensions. .

OBJETIVO: analisar a percepção de fatores psicossociais e a carga mental de trabalho de enfermeiros que trabalham em unidades de terapia intensiva. A hipótese é que os enfermeiros dessas unidades podem perceber os riscos psicossociais e manifestar uma alta carga mental de trabalho. Além disso, a dimensão psicossocial relacionada às demandas cognitivas do cargo explicaria a maior parte da carga mental de trabalho. MÉTODO: estudo quantitativo, com delineamento descritivo, transversal e comparativo. Foi examinada 91% da população das Unidades de Terapia Intensiva de três hospitais chilenos, correspondente a 111 enfermeiros. Os instrumentos utilizados incluíram (a) um questionário do histórico biossociodemográfico; (b) o questionário SUSESO-ISTAS 21; e (c) a Escala Subjetiva de Carga Mental de Trabalho (ESCAM). RESULTADOS: no total, 64% e 57% dos participantes perceberam um alto nível de exposição aos riscos psicossociais Demanda psicológica e Jornada dupla, respectivamente. Além disso, foi observado um nível de médio para alto de carga mental global. Foram obtidas correlações positivas e significativas entre algumas das dimensões do SUSESO-ISTAS 21 e do ESCAM. Utilizando uma análise de regressão, determinou-se que três dimensões do questionário de risco psicossocial ajudaram a explicar 38% da carga mental total. CONCLUSÃO: os enfermeiros das unidades de terapia intensiva percebem os fatores psicossociais e a sobrecarga mental de trabalho em várias de suas dimensões. .

OBJETIVO: analizar la percepción de Factores psicosociales y Carga mental de trabajo de enfermeras/os que laboran en Unidades Críticas. Se hipotetiza que los/as enfermeros/as de estas unidades pudieran percibir riesgos psicosociales; Mostrarán una Carga mental de trabajo alta; y la dimensión psicosocial relacionada con exigencias cognitivas del puesto explicará en mayor medida la Carga Mental. MÉTODO: estudio cuantitativo, de diseño descriptivo, transversal y comparativo. Se censó el 91% de la población de Unidades Críticas de tres hospitales chilenos, correspondiente a 111 enfermeras/os. Los instrumentos utilizados fueron: (a) Cuestionario de antecedentes biosociodemográficos; (b) Cuestionario SUSESO-ISTAS 21; y (c) Escala Subjetiva de Carga Mental de Trabajo (ESCAM). RESULTADOS: el 64% y el 57% de los/as participantes perciben un alto nivel de exposición a los riesgos psicosociales Demandas psicológicas y Doble presencia, respectivamente. Además, se obtiene un nivel de Carga mental global media-alta. Se obtuvo correlaciones positivas y significativas entre algunas dimensiones de SUSESO-ISTAS 21 y ESCAM, y mediante un análisis de regresión se obtuvo que tres dimensiones del cuestionario de riesgos psicosociales contribuyen a explicar un 38% de la Carga mental global. CONCLUSIÓN: las/os enfermeras/os de unidades críticas, perciben factores psicosociales inadecuados y sobrecarga mental de trabajo, en varias de sus dimensiones. .