RESUMO
We present the case of a 42-year-old male patient with ST-segment elevation myocardial infarction and pericardial effusion due to rupture of the left anterior descending artery most likely secondary to polyarteritis nodosa. Successful surgery was performed under cardiopulmonary bypass using antegrade and retrograde cardioplegia combined. (Level of Difficulty: Intermediate.).
RESUMO
Systemic mast cell activation syndrome is a mast cell disorder characterized by an unregulated increased activation of mast cells leading to a pathologically enhanced release of mediators. Mutations in tyrosine kinase kit which crucially determines mast cell activity have been suggested as a necessary condition for the development of a clinically symptomatic mast cell disease. At the level of mRNA in mast cell progenitor cells of 20 patients with systemic mast cell activation syndrome and of 20 gender- and age-matched healthy volunteers, the tyrosine kinase kit was investigated for genetic alterations by means of RT-PCR and direct sequencing of the amplificates. In mast cells of 13 out of these 20 patients, multiple predominantly novel potential functionally activating point mutations or complex alterations of the mRNA sequence encoding the tyrosine kinase kit were detected. In contrast, in 19 of the 20 healthy subjects, no functionally relevant alterations of c-kit transcripts were detected. The present findings support the idea that the systemic mast cell activation syndrome is a clonal disease most commonly associated with variable activating mutations in the tyrosine kinase kit.
Assuntos
Mastocitose/genética , Mutação , Proteínas Proto-Oncogênicas c-kit/genética , Adulto , Estudos de Casos e Controles , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND/AIMS: This study was aimed at investigating the form and prevalence of liver involvement in patients with systemic mast cell activation syndrome, a possibly common subvariant of systemic mastocytosis. An attempt was made to shed light on potential mechanisms responsible for mast cell mediator-related liver abnormalities. METHODS: The methods used were clinical investigation, biochemical determination of cholesterol, transaminases and bilirubin in blood, determination of chitotriosidase by enzyme-linked immunosorbent assay technique, and quantitative reverse transcribed-polymerase chain reaction to determine chitotriosidase expression. RESULTS: An elevation of plasma cholesterol was detected in 75% of the patients; elevations of transaminases and bilirubin were determined in 40 and 36% of the patients respectively; hepatomegaly or morphological hepatic alterations were observed in 34%. Chitotriosidase level in blood as a surrogate parameter for Kupffer cell activation in the liver was unchanged. However, chitotriosidase expression in isolated mast cells was downregulated at the mRNA level. CONCLUSIONS: Hypercholesterolaemia and liver abnormalities are frequently found in patients with the mast cell activation syndrome. Hence, the mast cell activation syndrome should be considered at an early stage as a possible cause of hypercholesterolaemia and of hepatic abnormalities of unknown reason. Mast cell activation may be indicated by a reduced expression of the enzyme chitotriosidase in blood-derived mast cells as well as by an increased plasma cholesterol level.
Assuntos
Hexosaminidases/metabolismo , Hipercolesterolemia/metabolismo , Hepatopatias/patologia , Mastocitose Sistêmica/patologia , Adolescente , Adulto , Idoso , Bilirrubina/sangue , Colesterol/sangue , Estudos Transversais , Análise Mutacional de DNA , Ensaio de Imunoadsorção Enzimática , Feminino , Hexosaminidases/genética , Humanos , Hipercolesterolemia/etiologia , Hepatopatias/etiologia , Masculino , Mastocitose Sistêmica/complicações , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-kit/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transaminases/sangueRESUMO
Urolithiasis is expected to cause a considerable complication in patients with systemic mastocytosis. The aim of the present report is to demonstrate that due to pathological activation and irritability of mast cells, special features in the diagnostic investigation and therapy of urolithiasis have to be considered in patients with systemic mastocytosis. The clinical presentation, diagnostic investigation and therapeutic procedure of urolithiasis in a patient with systemic mastocytosis are described. Urolithiasis may be a significant complication of systemic mastocytosis. Non-contrast CT is the main tool for diagnosing urolithiasis after a detailed history and clinical exam. Patients with systemic mastocytosis should receive a premedication composed of a glucocorticoid and H(1)- and H(2)-histamine receptor antagonists. An increased vulnerability of mucosal tissues is expected in patients with systemic mastocytosis that may limit the options of operative and postoperative therapy. Opioids should be used cautiously for analgesia in patients with systemic mastocytosis.
Assuntos
Glucocorticoides/uso terapêutico , Mastocitose Sistêmica/diagnóstico , Mastocitose Sistêmica/tratamento farmacológico , Cálculos Ureterais/diagnóstico , Urolitíase/diagnóstico , Urolitíase/tratamento farmacológico , Diagnóstico Diferencial , Antagonistas não Sedativos dos Receptores H1 da Histamina/uso terapêutico , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Humanos , Histeroscopia , Masculino , Mastócitos/patologia , Mastocitose Sistêmica/patologia , Pessoa de Meia-Idade , Exame Físico , Prednisolona/uso terapêutico , Ranitidina/uso terapêutico , Terfenadina/análogos & derivados , Terfenadina/uso terapêutico , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Cálculos Ureterais/patologia , Urolitíase/patologiaRESUMO
Traditionally, mast cell activation disease (MCAD) has been considered as just one rare (neoplastic) disease, mastocytosis, focused on the mast cell (MC) mediators tryptase and histamine and the suggestive, blatant symptoms of flushing and anaphylaxis. Recently another form of MCAD, the MC activation syndrome, has been recognized featuring inappropriate MC activation with little to no neoplasia and likely much more heterogeneously clonal and far more prevalent than mastocytosis. Increasing expertise and appreciation has been established for the truly very large menagerie of MC mediators and their complex patterns of release, engendering complex, nebulous presentations of chronic and acute illness best characterized as multisystem polymorbidity of generally inflammatory ± allergic theme. We describe the pathogenesis of MCAD with a particular focus on clinical cardiovascular symptoms and the therapeutic options for MC mediator-induced cardiovascular symptoms.
Assuntos
Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/patologia , Mastócitos/patologia , Mastocitose/complicações , Mastocitose/patologia , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/fisiopatologia , Humanos , Mastocitose/diagnóstico por imagem , Mastocitose/fisiopatologiaRESUMO
Systemic mastocytosis comprises disorders characterized by an accumulation of genetically altered mast cells in all organs and tissues due to an increased proliferation rate and reduced apoptosis of those pathologic mast cells. Release of their mediators can effectively influence organ function and can lead to systemic effects without inducing traces in routinely used laboratory parameters or imaging methods. In most cases, little invasive investigations allow diagnosing the disease and, hence, an appropriate therapy consisting of a basic medication with antihistamine and mast cell membrane-stabilizing compounds that should be supplemented, if required, by a medication adapted to individual symptoms, can be initiated. Because of the probably high prevalence of the disorder, systemic mastocytosis should be considered as a differential diagnosis in particular in the case of chronic gastrointestinal complaints such as abdominal pain/discomfort possibly associated with diarrhea, at an early stage.
Assuntos
Mastocitose/diagnóstico , Algoritmos , Apoptose/fisiologia , Ácido Ascórbico/administração & dosagem , Biópsia , Medula Óssea/patologia , Códon/genética , Terapia Combinada , Cromolina Sódica/uso terapêutico , Análise Mutacional de DNA , Preparações de Ação Retardada , Diagnóstico Diferencial , Quimioterapia Combinada , Gastroenteropatias/fisiopatologia , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Humanos , Cetotifeno/uso terapêutico , Mastócitos/fisiologia , Mastocitose/tratamento farmacológico , Mastocitose/genética , Mastocitose/fisiopatologia , Fenótipo , Proteínas Proto-Oncogênicas c-kit/genéticaRESUMO
OBJECTIVE: Sequencing efforts to discover mutations in the tyrosine kinase Kit related to systemic mast cell disorders have so far been focused mainly on only a few of the 21 exons of the encoding gene c-kit, thus considerably limiting the possibility to quantitatively reveal pathogenetic relationships. The purpose of this study was to analyze and compare the total sequence of Kit tyrosine kinase at the level of the mRNAs obtained from patients with clear systemic signs of a pathologically increased mast cell mediator release and those from healthy volunteers. MATERIAL AND METHODS: Kit encoding mRNA isolated from mast cell progenitors in peripheral blood from 17 patients with a mast cell activation disorder and from 5 healthy volunteers as well as from the human mast cell leukemia cell line HMC1 was analyzed for alterations. RESULTS: Multiple novel point mutations and six isoforms of Kit which are due to alternative mRNA splicing were detected. One isoform, the insertion of a glutamine residue at amino acid position 252, was found to be a new splice variant expressed in all patients but in none of the healthy volunteers. CONCLUSIONS: Systemic mast cell activation disorder was pathogenetically characterized by two or more alterations in the Kit tyrosine kinase providing not only a means of confirming the diagnosis, but also of assessing prognosis and of starting adequate therapeutic interventions. The insertion of Q252 appears to be pathognomic for that disease, providing a novel means for the identification of chronic non-specific gastrointestinal symptoms as manifestations of a systemic mast cell activation disorder.