Mast Cell Activation Syndrome and Gut Dysfunction: Diagnosis and Management.

PURPOSE OF REVIEW: Mast cell activation syndrome (MCAS) is a clinical disorder that may explain irritable bowel syndrome (IBS) type symptoms as well as other allergic symptoms experienced by an individual. The diagnosis and treatment of MCAS with specific focus on gastrointestinal (GI) manifestations is reviewed. RECENT FINDINGS: Although biomarkers for MCAS remain elusive, testing for baseline serum tryptase will distinguish the type of mast cell disorder and urine tests for mast cell mediator metabolites may support the diagnosis. Endoscopy and Colonoscopy with biopsies is not used to diagnose MCAS but is important to rule out other conditions that may cause symptoms. There is increased awareness of the association between MCAS and autonomic dysfunction, small fiber neuropathy, and connective tissue disorders which all impact GI symptoms. MCAS is a disorder often of unknown etiology (idiopathic) and characterized by intermittent allergy type symptoms that affect multiple organ systems after exposure to a trigger. GI symptoms including abdominal cramping and loose stool are prominent and mimic those of IBS. Diagnostic testing is performed to assess for elevations in mast cell mediators during symptoms and to rule out other conditions. A comprehensive treatment plan includes medications that target mast cells, treatments for associated conditions including autonomic dysfunction, and management of comorbid psychiatric illness and nutritional deficits.

Diffuse Cutaneous Mastocytosis: A Current Understanding of a Rare Disease.

Mastocytosis is a heterogeneous disease characterized by the expansion and accumulation of neoplastic mast cells in various tissues. Diffuse cutaneous mastocytosis (DCM) is a rare and most severe form of cutaneous mastocytosis, which typically occurs in childhood. There have been reports of a familial DCM with specific gene mutations, indicating both sporadic and hereditary factors involved in its pathogenesis. DCM is associated with severe MC mediator-related symptoms and an increased risk of anaphylaxis. The diagnosis is based on the appearance of skin lesions, which typically show generalized thickening, erythroderma, blistering dermographism, and a positive Darier's sign. Recognition, particularly in infants, is challenging due to DCMs resemblance to other bullous skin disorders. Therefore, in unclear cases, a skin biopsy is crucial. Treatment focuses on symptom management, mainly including antihistamines and mast cell stabilizers. In extremely severe cases, systemic steroids, tyrosine kinase inhibitors, phototherapy, or omalizumab may be considered. Patients should be equipped with an adrenaline autoinjector. Herein, we conducted a comprehensive review of literature data on DCM since 1962, which could help to better understand both the management and prognosis of DCM, which depends on the severity of skin lesions, intensity of mediator-related symptoms, presence of anaphylaxis, and treatment response.

Genetic Changes in Mastocytes and Their Significance in Mast Cell Tumor Prognosis and Treatment.

Mast cell tumors are a large group of diseases occurring in dogs, cats, mice, as well as in humans. Systemic mastocytosis (SM) is a disease involving the accumulation of mast cells in organs. KIT gene mutations are very often seen in abnormal mast cells. In SM, high KIT/CD117 expression is observed; however, there are usually no KIT gene mutations present. Mastocytoma (MCT)-a form of cutaneous neoplasm-is common in animals but quite rare in humans. KIT/CD117 receptor mutations were studied as the typical changes for human mastocytosis. In 80% of human cases, the KIT gene substitution p.D816H was present. In about 25% of MCTs, metastasis was observed. Changes in the gene expression of certain genes, such as overexpression of the DNAJ3A3 gene, promote metastasis. In contrast, the SNORD93 gene blocks the expression of metastasis genes. The panel of miR-21-5p, miR-379, and miR-885 has a good efficiency in discriminating healthy and MCT-affected dogs, as well as MCT-affected dogs with and without nodal metastasis. Further studies on the pathobiology of mast cells can lead to clinical improvements, such as better MCT diagnosis and treatment. Our paper reviews studies on the topic of mast cells, which have been carried out over the past few years.

Allogeneic haematopoietic cell transplantation for advanced systemic mastocytosis: Best practice recommendations on behalf of the EBMT Practice Harmonisation and Guidelines Committee.

Systemic Mastocytosis (SM) is a multifaceted clinically heterogeneous disease. Advanced SM (AdvSM) comprises three entities: aggressive SM (ASM), mast cell leukaemia (MCL) and SM with an associated hematologic neoplasm (SM-AHN), the latter accounting for 60-70% of all AdvSM cases. Detection of a disease-triggering mutation in the KIT gene (esp. KIT D816V) in >90% of the patients with ASM or SM-AHN has led to a significant improvement in therapeutic options by the implementation of two KIT-targeting kinase inhibitors: midostaurin and avapritinib. Although complete remissions have been reported, neither of these targeted agents is 'curative' in all patients and the duration of responses varies. The median overall survival, depending on the WHO subtype and scoring result, is approximately 1 to 4 years. Although the European Competence Network on Mastocytosis (ECNM) and American Initiative in Mast Cell Diseases (AIM) consensus groups recommend allogeneic haematopoietic cell transplantation (allo-HCT) in drug-resistant and other high-risk patients, there is a relative lack of information to guide clinicians on which patients with AdvSM should be considered for transplant, and how KIT inhibitors may fit into the transplant algorithm, including their use pre- and post-transplant to optimise outcomes. Following the generation of an expert panel with a specialist interest in allo-HCT and mastocytosis, these best practice recommendations were generated according to the European Society for Blood and Marrow Transplantation (EBMT) Practice Harmonisation and guidelines and ECNM methodology. We aim to provide a practical, clinically relevant and up-to-date framework to guide allo-HCT in AdvsM in 2024 and beyond.

Diagnosis and treatment of mast cell disorders: practical recommendations / Diagnostico e tratamento de doencas mastocitarias: recomendacoes praticas

CONTEXT AND OBJECTIVE The term mastocytosis covers a group of rare disorders characterized by neoplastic proliferation and accumulation of clonal mast cells in one or more organs. The aim of this study was to assess the principal elements for diagnosing and treating these disorders. DESIGN AND SETTING Narrative review of the literature conducted at Grupo Fleury, São Paulo, Brazil. METHODS This study reviewed the scientific papers published in the PubMed, Embase (Excerpta Medica Database), Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde) and Cochrane Library databases that were identified using the search term “mastocytosis.” RESULTS The clinical presentation of mastocytosis is remarkably heterogeneous and ranges from skin lesions that may regress spontaneously to aggressive forms associated with organ failure and short survival. Currently, seven subtypes of mastocytosis are recognized through the World Health Organization classification system for hematopoietic tumors. These disorders are diagnosed based on clinical manifestations and on identification of neoplastic mast cells using morphological, immunophenotypic, genetic and molecular methods. Abnormal mast cells display atypical and frequently spindle-shaped morphology, and aberrant expression of the CD25 and CD2 antigens. Elevation of serum tryptase is a common finding in some subtypes, and more than 90% of the patients present the D816V KIT mutation in mast cells. CONCLUSION Here, we described the most common signs and symptoms among patients with mastocytosis and suggested a practical approach for the diagnosis, classification and initial clinical treatment of mastocytosis. .

CONTEXTO E OBJETIVO O termo mastocitose abrange um grupo de raras doenças caracterizado por proliferação neoplásica e acúmulo de mastócitos clonais em um ou mais órgãos. O objetivo do presente estudo foi avaliar os principais elementos para o diagnóstico e tratamento dessas desordens. TIPO DE ESTUDO E LOCAL Revisão narrativa da literatura realizada no Grupo Fleury, São Paulo, Brasil. MÉTODOS O presente estudo revisou artigos científicos publicados nas bases de dados PubMed, Embase (Excerpta Medica Database), Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde) e Cochrane Library, que foram identificados com o termo de busca “mastocitose”. RESULTADOS A apresentação clínica da mastocitose é marcadamente heterogênea, variando de lesões cutâneas que podem regredir espontaneamente, até formas agressivas associadas a falência de órgãos e curta sobrevida. Atualmente, sete subtipos de mastocitose são reconhecidos pela classificação de tumores hematopoéticos da Organização Mundial de Saúde; o diagnóstico é realizado com base nas manifestações clínicas e na identificação de mastócitos neoplásicos por métodos morfológicos, imunofenotípicos, genéticos e moleculares. Mastócitos anômalos apresentam morfologia atípica, frequentemente fusiforme, e expressão aberrante dos antígenos CD25 e CD2. Aumento de triptase sérica é um achado comum em alguns subtipos; e mais que 90% dos pacientes apresentam mastócitos com a mutação KIT D816V. CONCLUSÃO No presente artigo, descrevemos os sintomas e sinais mais comuns em pacientes com mastocitose e sugerimos uma prática abordagem para o diagnóstico, classificação e tratamento clínico ...

Actualización en mastocitosis. Parte 2: categorías, pronóstico y tratamiento / Update on Mastocytosis (Part 2): Categories, Prognosis, and Treatment

Las mastocitosis constituyen un grupo heterogéneo de enfermedades caracterizadas por la proliferación clonal de mastocitos en distintos órganos, siendo la localización cutánea la más frecuente. La Organización Mundial de la Salud (OMS) clasifica las mastocitosis cutáneas en mastocitomas, mastocitosis máculo-papulosas y mastocitosis cutánea difusa, mientras que las formas sistémicas incluyen las mastocitosis indolentes, las agresivas, las asociadas a otra hematopatía monoclonal y la leucemia mastocitaria; el sarcoma mastocitario y el mastocitoma extracutáneo son variantes muy poco frecuentes. Aunque la evolución de la enfermedad en los niños es impredecible, con frecuencia las lesiones desaparecen durante la infancia; en los adultos la enfermedad tiende a persistir. El tratamiento se dirige a controlar las manifestaciones clínicas debidas a la acción de los mediadores mastocitarios, mientras que las formas agresivas requerirán de tratamientos dirigidos a reducir la masa mastocitaria

Mastocytosis is a term used to describe a heterogeneous group of disorders characterized by clonal proliferation of mast cells in different organs. The organ most often affected is the skin. The World Health Organization classifies cutaneous mastocytosis into mastocytoma, maculopapular cutaneous mastocytosis, and diffuse mastocytosis. The systemic variants in this classification are as follows: indolent systemic mastocytosis (SM), aggressive SM, SM with an associated clonal hematological non-mast cell lineage disease, mast cell leukemia, mast cell sarcoma, and extracutaneous mastocytoma. The two latest systemic variants are rare. Although the course of disease is unpredictable in children, lesions generally resolve by early adulthood. In adults, however, the disease tends to persist. The goal of treatment should be to control clinical manifestations caused by the release of mast cell mediators and, in more aggressive forms of the disease, to reduce mast cell burd

Guías clínicas para el diagnóstico, tratamiento y seguimiento de las mastocitosis / Guidelines for the diagnosis, treatment and management of mastocytosis

Las mastocitosis pertenecen al grupo de las llamadas 'Enfermedades Raras'; es decir, enfermedades poco frecuentes; por ello, es difícil que los médicos, en general, posean la experiencia suficiente para enfocar de forma adecuada su diagnóstico y su tratamiento. El diagnóstico de las mastocitosis se establece por la clínica y los hallazgos histopatológicos en biopsias de los órganos afectados como piel y médula ósea. El signo clínico más frecuente de las mastocitosis es la presencia de lesiones de urticaria pigmentosa. La mayoría de los pacientes presentan síntomas relacionados con la liberación de mediadores del mastocito y la prevención del efecto de estos mediadores sobre los tejidos constituye la clave del tratamiento y manejo clínico de las mastocitosis. En la actualidad no existe un tratamiento curativo, por lo que se trata de unas enfermedades crónicas que tienen un impacto negativo sobre la calidad de vida. El manejo de las mastocitosis para cualquiera de sus categorías incluye: 1. Un cuidadoso entrenamiento en los cuidados de la enfermedad a los pacientes y padres en caso de las formas pediátricas. 2. Evitación de la liberación de mediadores.3. Tratamiento de los episodios agudos de liberación de mediadores. 4. Tratamiento de los síntomas crónicos de liberación de mediadores. 5. Tratamiento de la infiltración de mastocitos en diversos órganos. El objetivo de esta revisión es la elaboración de guías completas y a la vez prácticas de manejar sobre el diagnóstico, tratamiento y manejo clínico de las mastocitosis (AU)

Mastocytosis consists of a group of disorders characterized by a pathologici ncrease in mast cells in tissues including skin, bone marrow, liver, spleen, and lymphnodes. Mastocytosis is a rare disease and general practitioner shave limited exposure to its clinical manifestations, diagnosis, classification, and management. Moreover a complete and clear review in this field is not easy founded. Diagnosis of mastocytosis is suspected on clinical grounds and is established by histopathologic examination of involved tissues such as skin and bone marrow. The most common clinical sign of mastocytosis is the presence of typical skin lesions of urticaria pigmentosa. Most patients experience symptoms related to mast cell mediator release, and prevention of the effects of these mediators on tissues constitutes the major therapeutic goal in the management of mastocytosis. Despite recent advances in knowledge about the pathophysiology, diagnosis, and classification of mastocytosis, a curative treatment for mastocytosis does not now exist; furthermore mastocytosis is a chronic diseases with different severity grades but in all of them with an important negative impact on quality of live of patients. Management of patients within all categories of mastocytosis includes: 1. A careful counselling of patients (parents in paediatric cases) and care providers. 2. Avoidance of factors triggering acute mediator release. 3. Treatment of acute mast cell mediator release. 4. Treatment of chronic mast cell mediator release, and if indicated. 5. An attempt to treat organ infiltration by mast cells. The goal of this review is to provide a practical guide focus on diagnostic criteria for the different treatment options currently available and their management (AU)

Mastocitosis sistémica asociada con leucemia mieloide aguda / Systemic mastocytosis associated with acute mieloid leukemia

Presentación de un caso clínico en el que la terapia con dasatinib y la quimioterapia se asociaron con supervivencia a largo plazo en un paciente de 51 años, diagnosticado con mastocitosis sistémica y un mal pronóstico inicial.

Eritrodermia que respeta los grandes pliegues de flexión / Erythroderma that spares the major flexion creases

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Mastocitosis del adulto. Descripción de 9 casos clínicopatológicos / Mastocytosis in adults

Introducción. La mastocitosis es un proceso hiperplásico caracterizado por la infiltración de diversos órganos y tejidos por mastocitos maduros. Se trata de una enfermedad que es más frecuente en la infancia, aunque también se dan casos en los adultos. Existen notables diferencias entre las formas de presentación de la mastocitosis del adulto y de la infancia, así como en su evolución y pronóstico. Material y métodos. En este trabajo describimos los hallazgos clinicopatológicos de 9 pacientes adultos con mastocitosis. Se comparan las características clínicas, evolutivas y genéticas de la mastocitosis del adulto con la mastocitosis infantil. Resultados. En contraste con la mastocitosis infantil, las lesiones cutáneas de la mastocitosis en adultos son muy monomorfas, y consisten en máculas y pápulas de menos de 1 cm de diámetro y coloración pardo-rojiza. La sintomatología es escasa y lo más habitual suele ser un discreto prurito. El signo de Darier es con gran frecuencia negativo. Además, las lesiones cutáneas no tienden a la regresión espontánea, que es lo habitual en el niño. Por último, la afectación sistémica en el adulto es prácticamente constante, con infiltración mastocitaria de la médula ósea en más del 90 % de los casos y afectación ósea en más del 50 % de los casos, mientras que en los niños la afectación sistémica es más rara. De todas formas, a pesar de que exista infiltración de órganos sistémicos en la mastocitosis de adultos, no suele existir sintomatología acompañante. La mutación del protooncogén c-kit consistente en la sustitución de Asp por Val en el codón 816, se encuentra casi constantemente en las mastocitosis del adulto y es menos frecuente en la mastocitosis infantil. Conclusiones. Todos estos hallazgos permiten separar la mastocitosis del adulto como una entidad clinicopatológica diferente de las mastocitosis infantiles

Introduction. Mastocytosis is a hyperplastic process characterized by the infiltration of different organs and tissues by mature mastocytes. It is more frequent in childhood, although cases also occur in adults. There are significant differences between the ways mastocytosis presents in adults and children, as well as in its development and prognosis. Material and methods. In this work, we describe the clinicopathological findings for 9 adult patients with mastocytosis. The clinical, evolutional and genetic characteristics of mastocytosis in adults are also compared to those of childhood mastocytosis. Results. In contrast with childhood mastocytosis, the skin lesions of adult mastocytosis are very monomorphous, and consist of macules and papules of less than 1 cm in diameter, brownish-red in color. There are few symptoms, and there is usually discrete pruritus. Darier’s sign is very often negative. Furthermore, the skin lesions do not tend to spontaneously regress, which is what usually occurs in children. Finally, systemic involvement in adults is practically a constant, with mastocyte infiltration of the bone marrow in over 90 % of cases, and bone involvement in over 50 % of cases, while systemic involvement is rarer in children. In any case, even if there is infiltration of systemic organs in adult mastocytosis, there are usually no accompanying clinical symptoms. The mutation of the c-kit proto-oncogene consists of the replacement of Asp with Val at codon 816, and this is nearly always found in adult mastocytosis. It is less frequent in childhood mastocytosis. Conclusions. All of these findings make it possible to classify adult mastocytosis as a separate clinicopathological entity from mastocytoses in children

Telangiectasia macularis eruptiva perstans: presentación de ocho casos y estudios ultraestructural / Telangiectasia macularis eruptiva perstans: report of 8 cases and an ultrastructural study

Las mastocitosis son desórdenes caracterizados por la infiltración de mastocitos en los tejidos. Dentro de éstas se encuentra la telangiectasia macularis eruptiva perstans (TMEP), una forma rara de presentación, más frecuente en adulto y de aparición ocasional en niños. El objetivo de este trabajo es realizar una recopilación de ocho pacientes con este cuadro vistos en el Servicio de Dermatología del Hospital Nacional "Prof. Alejandro Posadas", puntualizando sus caracteristicas clínicas e histopatológicas, y a travéz de un estudio con microscopía electrónica, aportar información a fin de aclarar su patogenia

Mastocitosis en un lactante / Mastocytosis in an infant

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Telangiectasia macularis eruptiva perstans: presentación de cuatro casos / Telangiectasia macularis eruptiva perstans: 4 cases report

La telangiectasia macularis eruptiva perstans (TMEP) es una forma de mastocitosis cutánea poco frecuente, que se manifiesta casi exclusivamente en adultos. Su diagnóstico es básicamente clínico y no se dispone hasta la actualidad de una terapéutica específica eficaz. Se presentan cuatro pacientes de sexo masculino, edad promedio de 54 años, con manifestaciones clínicas e histológicas de TMEP, en diferentes períoddos de evolución. Todos presentaron patología úlcero éptica, asociación frecuente de las mastocitosis cutáneas. Objetivo: Presentación clínica de una forma poco frecuente de mastocitosis cutánea y revisión de la bibliografía

Urticária pigmentosa em lactentes: relato de um caso e revisão da literatura / Urticaria pigmentosa in infants: a case report and revision of literature

Paciente pediátrico, 6 meses, masculino, internado no Hospital Geral em Caxias do Sul. Apresentou lesões hipercrômicas maculopapulares descamativas, vermelho-acastanhadas, intensamente pruriginosas, atingindo grande parte do corpo. Recebeu anti-histamínicos e banhos de água e aveia, enquanto internado. Foi realizada biópsia de pele, que constatou quadro compatível com urticária pigmentosa (UP). A UP é a mais freqüente manifestação de mastocitose, ocorrendo na pele e caracterizando-se por lesões cutâneas com pigmentação persistente e pruriginosa. A mastocitose é caracterizada por um acúmulo local ou sistêmico de mastócitos, sendo que os sintomas, dentre os quais o principal é o prurido, resultam da liberação maciça de histamina e outros mediadores pelos mastócitos. O diagnóstico é baseado basicamente na história e apresentação clínica, com confirmação de envolvimento cutâneo por biópsia. Ainda não há tratamento definitivo e eficaz, e somente alívio sintomático pode ser atingido (AU)

Pediatric patient, 6 months old, male, admitted to General Hospital in Caxias do Sul. The patient displays hyperchromic maculopapular peeling lesions, reddish-brown, with intense itching extending over the majority of the body. The patient received anti-histamines and oat water baths while at the hospital. The results of a skin biopsy were indicative of urticaria pigmentosa (UP). UP is the most common manifestation of mastocytosis, occurring in the skin and characterized by cutaneous lesions with persistent and itching spots. Mastocytosis is characterized by a local or systemic accumulation of mast cells, accompanied by symptoms, among which the primary one is itching, resulting from the massive release of histamine and other mediators by the mast cells. Diagnosis is based basically on clinical history and examination, confirmed by cutaneous biopsy. There is still no satisfactory and efficient treatment, and only the symptoms can be alleviated (AU)

Telangiectasia macularis eruptiva perstans: una forma clínica de mastocitosis / Telangiectasia macularis eruptiva perstans: a clinical form of mastocytosis

Comunicamos 6 casos de telangiectasia macularis eruptiva perstans, forma de mastocitosis cutánea de rara observación en la casuística nacional e internacional. Exponemos el hallazgo inusual de compromiso facial, con la presencia de lesiones maculosas y telangiectásicas en dos de los pacientes, así como la ausencia de dermografismo y signo de Darier en todos los casos, hechos que motivaron la presentación de este trabajo. Se efectúa una revisión de las características de la mastocitosis y de distintas clasificaciones de la misma. Se destaca el valor relativo del aumento del número de mastocitos en el estudio histológico de esta entidad

Mastocitosis ampollar / Ampollar mastocytosis

Se presenta un caso clínico de mastocitosis cutánea en un niño de 9 meses de edad. Se revisa el tratamiento y los factores que desencadenan la degranulación de mastocitos.

Mastocitoma solitario / Solitary mastocytoma

Introducción. Se presentan 2 casos de mastocitoma solitario, entidad que es rara de ver aún dentro del contexto de las mastocitosis en general y al final se realiza una breve revisión del material que en general es escaso. Casos clínicos. Se describen 2 pacientes en edad pediátrica diagnosticados clínica e histológicamente como mastocitoma solitario en el Departamento de Dermatología Pediátrica del Hospital General Centro Médico La Raza. Conclusiones. El mastocitoma solitario es una enfermedad rara que tiene una larga permanencia en el paciente y generalmente como en los casos de este reporte cursan con evolución benigna