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Pediatric Dermatology 2024Mast cells (MCs) can release a variety of biologically active mediators under different circumstances, such as fever or vaccination. Our aim was to evaluate the...
Mast cells (MCs) can release a variety of biologically active mediators under different circumstances, such as fever or vaccination. Our aim was to evaluate the incidence and severity of MC activation symptoms induced by SARS-CoV-2 virus (COVID-19) infection and vaccination in a cohort of 92 pediatric patients with cutaneous mastocytosis. Our findings support previous evidence on the safety of COVID-19 infection and vaccination in patients with MC disorders.
Topics: Adolescent; Child; Child, Preschool; Female; Humans; Infant; Male; COVID-19; COVID-19 Vaccines; Cross-Sectional Studies; Mastocytosis, Cutaneous; Retrospective Studies; SARS-CoV-2; Vaccination
PubMed: 38305078
DOI: 10.1111/pde.15551 -
Current Allergy and Asthma Reports Feb 2024Symptoms of depression and cognitive dysfunction are commonly reported in mastocytosis. The aims of this review paper are to summarize the current literature on... (Review)
Review
PURPOSE OF REVIEW
Symptoms of depression and cognitive dysfunction are commonly reported in mastocytosis. The aims of this review paper are to summarize the current literature on cognitive dysfunction and depressive symptoms, elucidate some of the mechanistic pathways underlying depressive symptoms in mastocytosis, identify gaps in the literature, and offer guidance for future research in this area.
RECENT FINDINGS
The study of cognition and depression in mastocytosis is in its infancy and the methodological flaws of the current literature limit interpretability. There is preliminary evidence that some individuals with mastocytosis might experience mild deficits in memory. On average, depression symptom scores fell within the mild to moderate or sub-syndromal range. Regrettably, only one study utilized a standardized diagnostic instrument to assess major depressive disorder. The authors' tendency to inaccurately equate depressive symptoms with a diagnosis of major depressive disorder presents a notable issue. The prevalence of cognitive deficits and depression appears to be similar to other chronic illnesses. Future work needs to better characterize cognition and characterize "depression" in this population.
Topics: Humans; Depression; Depressive Disorder, Major; Cognitive Dysfunction; Cognition Disorders; Mastocytosis
PubMed: 38294589
DOI: 10.1007/s11882-024-01127-z -
Pediatric Blood & Cancer Apr 2024
Topics: Humans; Child; Mastocytosis, Systemic; Decitabine; Leukemia, Myeloid, Acute; Core Binding Factors; Proto-Oncogene Proteins c-kit; Mutation; Pyrazoles; Pyrroles; Triazines
PubMed: 38291730
DOI: 10.1002/pbc.30898 -
Scientific Reports Jan 2024Hereditary α tryptasemia (HαT) is an autosomal dominant trait characterized by increased TPSAB1 copy number (CN) encoding α-tryptase. The determination of HαT is...
Hereditary α tryptasemia (HαT) is an autosomal dominant trait characterized by increased TPSAB1 copy number (CN) encoding α-tryptase. The determination of HαT is being discussed as an important biomarker to be included in risk assessment models and future diagnostic algorithms for patients with mastocytosis and anaphylaxis. Due to the complex genetic structure at the human tryptase locus, genetic testing for tryptase gene composition is presently notably limited and infrequently pursued. This study aimed to develop, optimise and validate a multiplex droplet digital PCR (ddPCR) assay that can reliably quantify α- and β-tryptase encoding sequences in a single reaction. To optimise the ddPCR conditions and establish an amplitude-based multiplex ddPCR assay, additional primers and probes, a thermal gradient with varying annealing temperatures, different primers/probe concentrations, and various initial DNA quantities were tested. Results obtained from all 114 samples analysed using multiplex ddPCR were identical to those obtained through the use of original duplex assays. Utilizing this multiplex ddPCR assay, in contrast to conducting distinct duplex ddPCRs, presents noteworthy benefits for tryptase genotyping. These advantages encompass a substantial threefold decrease in material costs and considerable time savings. Consequently, this approach exhibits high suitability and particularly captures interest for routine clinical implementation.
Topics: Humans; Tryptases; Genotype; Multiplex Polymerase Chain Reaction; Genetic Testing; Mastocytosis
PubMed: 38287122
DOI: 10.1038/s41598-024-52983-8 -
Genes Jan 2024Mast 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... (Review)
Review
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. gene mutations are very often seen in abnormal mast cells. In SM, high KIT/CD117 expression is observed; however, there are usually no 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 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 gene, promote metastasis. In contrast, the gene blocks the expression of metastasis genes. The panel of , , and 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.
Topics: Humans; Animals; Dogs; Mice; Mast Cells; Proto-Oncogene Proteins c-kit; Mastocytosis; Prognosis; Myeloproliferative Disorders; MicroRNAs
PubMed: 38275618
DOI: 10.3390/genes15010137 -
Journal of Investigational Allergology... Jun 2024
Topics: Humans; Multiple Myeloma; Desensitization, Immunologic; Mastocytosis, Systemic; Antibodies, Monoclonal, Humanized
PubMed: 38275249
DOI: 10.18176/jiaci.0992 -
Leukemia Research Reports 2024Systemic mastocytosis is a rare hematologic malignancy that leads to the accumulation of neoplastic mast cells in the bone marrow, visceral organs, and skin. Mutations...
BACKGROUND
Systemic mastocytosis is a rare hematologic malignancy that leads to the accumulation of neoplastic mast cells in the bone marrow, visceral organs, and skin. Mutations in the receptor tyrosine kinase, KIT are seen in most patients with systemic mastocytosis. The most common mutation is a gain of function mutation in KIT D816V. Avapritinib is a highly selective KIT D816V inhibitor approved for the treatment of advanced systemic mastocytosis. Recent studies have also suggested that avapritinib is active across other KIT mutations located in exon 11 and exon 17.
CASE PRESENTATION
A 68 year old woman was referred for a history of lymphadenopathy and diarrhea and was ultimately found to have systemic mastocytosis with involvement in her bone marrow, gastrointestinal tract, liver, and spleen. The bone marrow biopsy reveled a novel KIT p.D816-N822delinsMIDSI mutation in exon 17. The patient was started on avapritinib leading to significant decrease in the frequency of her diarrhea and a significant reduction in her tryptase levels. Her course was complicated by arthralgias leading to a decrease in her avapritinib dose and ultimately a degranulation episode requiring hospitalization. Following dose re-escalation, patient has remained clinically stable without any further adverse events.
CONCLUSION
We report a case of aggressive systemic mastocytosis with a novel KIT mutation on exon 17 treated with avapritinib leading to a sustained response. While avapritinib is known as a potent inhibitor against the D816V mutation, our case suggests that it may also be effective against other rare KIT mutations in systemic mastocytosis offering more potential treatment options in patients with rare mutations.
PubMed: 38273969
DOI: 10.1016/j.lrr.2023.100409 -
Current Allergy and Asthma Reports Feb 2024Mast cell (MC) activation can present with a wide range of symptoms. The mechanisms that cause such activation are varied. One of them is the presence of clonal MCs... (Review)
Review
PURPOSE OF REVIEW
Mast cell (MC) activation can present with a wide range of symptoms. The mechanisms that cause such activation are varied. One of them is the presence of clonal MCs which is defined, within other possible changes, by the presence of a somatic, activating mutation in the KIT gene. The clinical course and prognosis of patients with this underlying disease may be different from other causes of MC activation (MCA). For this reason, it is important to early diagnose, or at least suspect, which patients with MCA are due to clonal MCs.
RECENT FINDINGS
The diagnosis of clonality must be made in a comprehensive manner. However, this paper reviews chronologically each of the stages from the patient's first visit to the doctor's office which can be indicative of clonality: clinical presentation of MCA, physical examination, analytical determinations of tryptase, and/or KIT mutational analysis and bone involvement, among others. The different clonality predictive scores proposed are also reviewed and compared. Although the gold standard for the diagnosis of certainty of MC clonality is the performance of a bone marrow (BM) biopsy, there are clinical symptoms, signs, and biological parameters suggestive of clonality, as well as predictive scores, which can guide (or rule out) an early diagnosis and avoid unnecessary BM biopsies.
Topics: Humans; Mast Cells; Mast Cell Activation Syndrome; Mastocytosis; Mutation; Prognosis; Tryptases; Proto-Oncogene Proteins c-kit
PubMed: 38270805
DOI: 10.1007/s11882-023-01122-w -
American Journal of Hematology May 2024Mastocytoma in a colon polyp positive for tryptase, CD117/KIT, S100, weakly positive for CD25.
Mastocytoma in a colon polyp positive for tryptase, CD117/KIT, S100, weakly positive for CD25.
Topics: Humans; Incidental Findings; Mastocytoma; Myeloproliferative Disorders; Proto-Oncogene Proteins c-kit; Colon
PubMed: 38270251
DOI: 10.1002/ajh.27209 -
Deutsches Arzteblatt International Apr 2024Hereditary alpha-tryptasemia (HAT) is a genetic predisposition of autosomal dominant inheritance that leads to a high normal (≥ 8-11.4 μg/L) or pathologically... (Review)
Review
BACKGROUND
Hereditary alpha-tryptasemia (HAT) is a genetic predisposition of autosomal dominant inheritance that leads to a high normal (≥ 8-11.4 μg/L) or pathologically elevated (>11.4 μg/L) basal serum tryptase (BST) concentration. Its prevalence in the United Kingdom and France is reportedly 5%-6%; its prevalence in Germany is unknown. Symptomatic persons with HAT suffer from a complex constellation of symptoms. As described in this review, HAT is an important differential diagnosis in interdisciplinary practice.
METHODS
This review is based on publications about HAT retrieved by a selective search in PubMed, on relevant presentations at scientific meetings, and on our clinical experience. We also collected our own data on the prevalence and clinical manifestations of HAT.
RESULTS
According to the literature, HAT is very common among patients in medical centers with BST values of 8 μg/L or above (64-74%). HAT is most commonly associated with neuropsychiatric symptoms such as exhaustion (85%), depressive episodes (59%), sleep disturbances (69%), and memory impairment (59%-68%), followed by gastrointestinal symptoms such as irritable bowel (30%-60%), nausea (51%), and reflux (49%-77%). Typical mast cell-mediated symptoms, such as flushing (47%), itch (69%), urticaria (37%), and anaphylaxis (14%-28%), are reported as well. Less commonly reported are cardio vascular manifestations, such as hypotonia, dizziness, and tachycardia (34%), and joint hyper - mobility (28%). HAT is more common among patients with systemic mastocytosis (SM; 12%-21%). It is often associated with severe anaphylaxis induced by insect toxins or unknown triggers. The therapeutic options include treatment with antihistamines, mastcell stabilizers, or IgE antibodies.
CONCLUSION
A diagnosis of hereditary alphatryptasemia can be strongly suspected on the basis of thorough history-taking and BST measurement and then confirmed by molecular genetic testing.
Topics: Humans; Tryptases; Diagnosis, Differential; Prevalence; Genetic Predisposition to Disease; Mastocytosis; Germany
PubMed: 38260947
DOI: 10.3238/arztebl.m2023.0287