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International Journal of Molecular... Oct 2023Advanced systemic mastocytosis (SM) is a heterogeneous group of myeloid neoplasms characterized by an uncontrolled expansion of mast cells (MC) in one or more internal... (Review)
Review
Advanced systemic mastocytosis (SM) is a heterogeneous group of myeloid neoplasms characterized by an uncontrolled expansion of mast cells (MC) in one or more internal organs, SM-induced tissue damage, and poor prognosis. Advanced SM can be categorized into aggressive SM (ASM), MC leukemia (MCL), and SM with an associated hematologic neoplasm (SM-AHN). In a vast majority of all patients, neoplastic cells display a mutation, mostly D816V and rarely other variants. Additional mutations in other target genes, such as , , or , may also be identified, especially when an AHN is present. During the past 10 years, improved treatment approaches have led to a better quality of life and survival in patients with advanced SM. However, despite the availability of novel potent inhibitors of KIT D816V, not all patients enter remission and others relapse, often with a multi-mutated and sometimes D816V-negative disease exhibiting multi-drug resistance. For these patients, (poly)chemotherapy, antibody-based therapies, and allogeneic hematopoietic stem cell transplantation may be viable treatment alternatives. In this article, we discuss treatment options for patients with drug-resistant advanced SM, including novel KIT-targeting drugs, antibody-based drugs, and stem cell-eradicating therapies.
Topics: Humans; Quality of Life; Mastocytosis; Mastocytosis, Systemic; Mast Cells; Mutation; Proto-Oncogene Proteins c-kit
PubMed: 37894806
DOI: 10.3390/ijms242015125 -
Acta Medica Portuguesa Apr 2020Mastocytosis is characterized by the clonal expansion of morphological and immunophenotypically abnormal mast cells in different organs. The skin is the most frequently... (Review)
Review
INTRODUCTION
Mastocytosis is characterized by the clonal expansion of morphological and immunophenotypically abnormal mast cells in different organs. The skin is the most frequently affected tissue. Virtually all children and more than 80% of adult patients with mastocytosis show cutaneous lesions.
MATERIAL AND METHODS
The present article describes the symptoms and signs in cutaneous mastocytosis, based on the review of recently published international consensus guidelines.
DISCUSSION
According to the 2016 World Health Organization classification, mastocytosis can be divided in cutaneous mastocytosis, systemic mastocytosis and mast cell sarcoma. Cutaneous mastocytosis is subclassified in three subtypes: maculopapular cutaneous mastocytosis, diffuse cutaneous mastocytosis and cutaneous astocytoma. Telangiectasia macularis eruptiva perstans is no longer considered a distinct entity.
CONCLUSION
Based on the age of onset, cutaneous manifestations of mastocytosis can be variable. The classification of cutaneous mastocytosis has recently been updated. Typically, in patients with childhood-onset mastocytosis, the disease occurs as cutaneous mastocytosis and shows spontaneous resolution around puberty. In contrast, adult patients, despite having also cutaneous lesions, often show systemic involvement and the course of the disease is usually chronic.
Topics: Adolescent; Adult; Age of Onset; Child; Humans; Mastocytosis; Mastocytosis, Cutaneous; Symptom Assessment
PubMed: 32238242
DOI: 10.20344/amp.12189 -
Current Opinion in Allergy and Clinical... Apr 2023Paediatric mastocytosis is a rare clonal disorder characterized by the overproduction and organ infiltration of mast cells. Symptoms are due to mast cell mediator... (Review)
Review
PURPOSE OF REVIEW
Paediatric mastocytosis is a rare clonal disorder characterized by the overproduction and organ infiltration of mast cells. Symptoms are due to mast cell mediator release. Cutaneous mastocytosis is the most common presentation in children with systemic disease being rare. Our aim is to provide a practical guideline in differentiating subtypes of paediatric mastocytosis while providing actionable recommendations on diagnosis, clinical management, follow-up and prognosis.
RECENT FINDINGS
Longitudinal cohort studies of paediatric cutaneous mastocytosis have shown spontaneous remission with favourable prognosis. Hereditary alpha-tryptasemia may coexist with mastocytosis; thus, screening for this disorder is recommended. There is an emerging role for serum tryptase in asthma endotyping and potential for using therapeutic tryptase inhibitors.
SUMMARY
Morbidity in paediatric mastocytosis typically arises from symptoms secondary to mast cell mediator release. Prognosis for nonaggressive disease is typically favourable; however, risks for anaphylaxis and psychosocial morbidity may be underestimated. Symptomatic management and anticipatory guidance may help support patients and families throughout the disease course.
Topics: Humans; Child; Tryptases; Longitudinal Studies; Mastocytosis; Mast Cells; Mastocytosis, Cutaneous; Anaphylaxis; Rare Diseases
PubMed: 36730855
DOI: 10.1097/ACI.0000000000000869 -
The Journal of Allergy and Clinical... Jun 2023In 2002, the European Competence Network on Mastocytosis (ECNM) was launched as a multidisciplinary collaborative initiative to increase the awareness and to improve... (Review)
Review
In 2002, the European Competence Network on Mastocytosis (ECNM) was launched as a multidisciplinary collaborative initiative to increase the awareness and to improve diagnosis and management of patients with mast cell (MC) disorders. The ECNM consists of a net of specialized centers, expert physicians, and scientists who dedicate their work to MC diseases. One essential aim of the ECNM is to timely distribute all available information about the disease to patients, doctors, and scientists. In the past 20 years, the ECNM has expanded substantially and contributed successfully to the development of new diagnostic concepts, and to the classification, prognostication, and treatments of patients with mastocytosis and MC activation disorders. The ECNM also organized annual meetings and several working conferences, thereby supporting the development of the World Health Organization classification between 2002 and 2022. In addition, the ECNM established a robust and rapidly expanding patient registry and supported the development of new prognostic scoring systems and new treatment approaches. In all projects, ECNM representatives collaborated closely with their U.S. colleagues, various patient organizations, and other scientific networks. Finally, ECNM members have started several collaborations with industrial partners, leading to the preclinical development and clinical testing of KIT-targeting drugs in systemic mastocytosis, and some of these drugs received licensing approval in recent years. All these networking activities and collaborations have strengthened the ECNM and supported our efforts to increase awareness of MC disorders and to improve diagnosis, prognostication, and therapy in patients.
Topics: Humans; Mastocytosis; Mastocytosis, Systemic; Forecasting; Mast Cells
PubMed: 36868470
DOI: 10.1016/j.jaip.2023.02.021 -
Expert Review of Clinical Immunology Jun 2023Mast cells are found in all tissues and express numerous surface receptors allowing them to sense and respond to allergic, autoimmune, environmental, neurohormonal,...
INTRODUCTION
Mast cells are found in all tissues and express numerous surface receptors allowing them to sense and respond to allergic, autoimmune, environmental, neurohormonal, pathogenic and stress triggers. Stimulated mast cells are typically called 'activated' but the mechanisms involved and the mediators released can vary considerably. Mast cell activation diseases (MCADs) include primary, secondary and idiopathic conditions, especially mast cell activation syndrome (MCAS), but mast cells are activated in many other disorders making the diagnosis and treatment challenging.
AREAS COVERED
Mast cells can release numerous biologically active mediators, some of which are prestored in secretory granules while others are newly synthesized and released without degranulation. Most of the emphasis has so far been on secretion of histamine and tryptase, which do not explain all the multisystemic symptoms experienced by patients with MCADs. As a result, drug development has focused on antiproliferative therapy or blocking the action of individual mediators and not on inhibitors of mast cell activation.
EXPERT OPINION
Activated mast cells are involved in the pathogenesis of MCADs, but also in other disorders making appropriate diagnosis and treatment challenging. The definition of mast cell activation should be expanded beyond histamine and tryptase, with an emphasis on better detection and treatments.
Topics: Humans; Mast Cells; Histamine; Tryptases; Mastocytosis; Antigen Presentation
PubMed: 37029958
DOI: 10.1080/1744666X.2023.2200936 -
Skinmed 2022
Topics: Humans; Mastocytosis, Cutaneous; Diagnosis, Differential
PubMed: 36314699
DOI: No ID Found -
Applied Immunohistochemistry &... Apr 2022Mastocytosis is a rare disease with a low incidence in Asia-Pacific populations. CD30 and CD123 may have potential prognostic and therapeutic value, but the results are...
Mastocytosis is a rare disease with a low incidence in Asia-Pacific populations. CD30 and CD123 may have potential prognostic and therapeutic value, but the results are inconsistent. Because racial disparities may exist, we aim to evaluate the expressions of CD30 and CD123 in a series of mastocytosis cases in Taiwan. Twelve patients with systemic and 7 with cutaneous forms of mastocytosis were studied. The expressions of CD30 and CD123 were correlated with the clinical features of the patients. Eighty-three percent (10/12) of patients with systemic mastocytosis (SM) had an associated hematological neoplasm. Four of the SM patients had both "B" and "C" findings, and they had a median survival time of 0.9 months. CD30 expression was positive in 50% (6/12) of SM cases and 100% (6/6) of cutaneous mastocytosis cases. CD123 was expressed focally or weakly in only 2 SM-associated hematological neoplasm cases. The distribution of mastocytosis subtypes and the expression of CD30 and CD123 in Taiwan differed from those reported in North America and Europe. However, mastocytosis, especially indolent forms, is easily overlooked as its heterogeneous and nonspecific clinical manifestations. A high index of suspicion and improved diagnostic methods can be helpful.
Topics: Hematologic Neoplasms; Humans; Interleukin-3 Receptor alpha Subunit; Ki-1 Antigen; Mastocytosis; Mastocytosis, Systemic; Taiwan
PubMed: 35384878
DOI: 10.1097/PAI.0000000000001000 -
Immunology and Allergy Clinics of North... Nov 2023
Topics: Humans; Mastocytosis; Mastocytosis, Systemic
PubMed: 37758415
DOI: 10.1016/j.iac.2023.06.001 -
Haematologica Jan 2020
Topics: Humans; Interleukin-6; Mast Cells; Mastocytosis; Mastocytosis, Systemic; Oncogenes
PubMed: 31894094
DOI: 10.3324/haematol.2019.234864 -
The Journal of Allergy and Clinical... May 2023Mastocytosis encompasses a heterogeneous group of diseases characterized by tissue accumulation of clonal mast cells, which frequently includes bone involvement. Several...
BACKGROUND
Mastocytosis encompasses a heterogeneous group of diseases characterized by tissue accumulation of clonal mast cells, which frequently includes bone involvement. Several cytokines have been shown to play a role in the pathogenesis of bone mass loss in systemic mastocytosis (SM), but their role in SM-associated osteosclerosis remains unknown.
OBJECTIVE
To investigate the potential association between cytokine and bone remodeling markers with bone disease in SM, aiming at identifying biomarker profiles associated with bone loss and/or osteosclerosis.
METHODS
A total of 120 adult patients with SM, divided into 3 age and sex-matched groups according to their bone status were studied: (1) healthy bone (n = 46), (2) significant bone loss (n = 47), and (3) diffuse bone sclerosis (n = 27). Plasma levels of cytokines and serum baseline tryptase and bone turnover marker levels were measured at diagnosis.
RESULTS
Bone loss was associated with significantly higher levels of serum baseline tryptase (P = .01), IFN-γ (P = .05), IL-1β (P = .05), and IL-6 (P = .05) versus those found in patients with healthy bone. In contrast, patients with diffuse bone sclerosis showed significantly higher levels of serum baseline tryptase (P < .001), C-terminal telopeptide (P < .001), amino-terminal propeptide of type I procollagen (P < .001), osteocalcin (P < .001), bone alkaline phosphatase (P < .001), osteopontin (P < .01), and the C-C Motif Chemokine Ligand 5/RANTES chemokine (P = .01), together with lower IFN-γ (P = .03) and RANK-ligand (P = .04) plasma levels versus healthy bone cases.
CONCLUSIONS
SM with bone mass loss is associated with a proinflammatory cytokine profile in plasma, whereas diffuse bone sclerosis shows increased serum/plasma levels of biomarkers related to bone formation and turnover, in association with an immunosuppressive cytokine secretion profile.
Topics: Cytokines; Mastocytosis, Systemic; Bone Remodeling; Bone Resorption; Osteosclerosis; Biomarkers; Humans; Male; Female; Adolescent; Young Adult; Adult; Middle Aged; Aged
PubMed: 36801493
DOI: 10.1016/j.jaip.2023.02.007