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The Journal of Molecular Diagnostics :... Jun 2024Mastocytosis is a heterogeneous disorder characterized by abnormal mast cell accumulation, in which the clinical severity may be explained by distinct molecular...
Mastocytosis is a heterogeneous disorder characterized by abnormal mast cell accumulation, in which the clinical severity may be explained by distinct molecular mechanisms. This study aimed to explore plasma protein biomarkers associated with systemic mastocytosis subtypes, as well as the cellular origin of the identified proteins. Plasma samples from patients with mastocytosis, including cutaneous mastocytosis (CM), indolent systemic mastocytosis (ISM), advanced SM (AdvSM), and a reference group of patients with polycythemia vera (PCV), were analyzed by Proximity Extension Assay (OLINK technology) targeting 275 proteins. Furthermore, potential cellular origin was explored using an available scRNA sequencing data set generated from ISM patients. The study cohort included 16 patients with CM, 92 patients with SM (ISM, n=80; AdvSM, n=12), and 60 PCV patients. A Principal Component Analysis based on 275 plasma proteins revealed one cluster of CM and ISM patients that was separated from AdvSM patients. Up to 29 proteins were associated to distinct severe activity in SM patients (ISM vs AdvSM), including IL-1RT1, and TNFSF13B (q<0.01). Furthermore, scRNA seq analysis from ISM-derived bone marrow cells revealed that the mRNA for the identified proteins was not exclusive of mast cells. Distinct plasma protein profiles show potential to refine ISM and AdvSM diagnoses, possibly reflecting differences in pathogenic mechanisms and diverse clinical manifestations.
PubMed: 38925457
DOI: 10.1016/j.jmoldx.2024.05.010 -
European Annals of Allergy and Clinical... Jun 2024Pediatric cutaneous mastocytosis patients diagnosed and followed up by our specialist were enrolled in this study, and clinical and laboratory evaluations were...
Pediatric cutaneous mastocytosis patients diagnosed and followed up by our specialist were enrolled in this study, and clinical and laboratory evaluations were retrospectively analyzed from patients' archived files. Patients, who applied to the Division of Pediatric Allergy And Immunology Unit of a University Training and Research Hospital between 01.01.2010 and 28.04.2021, were enrolled in this study. Of the 33 patients included in the study, 11 (33.3%) were female and 22 (67.7%) were male. The median age of onset of the patient's complaints was 7 (0-60) months. The median age at diagnosis was 11 (2-64) months. Their complaints' median regression age was 54 (6-192) months. Resistant clinical findings were followed in 13 (39.4%) patients. Itching, redness, gastrointestinal symptoms, and maculopapular eruption were the most common complaints. The rashes were mostly polymorphic and larger than 1 cm. Heat was the most common trigger. Darier's sign was positive in 97% of the patients. Antihistamines were the most commonly used drug for prophylaxis and treatment. The autoinjector prescription rate was 24.2%. Quality of life was mildly affected in 48,5% of the patients based on the CDLQI scores. Thus, patients should be followed up through adolescence for the development of systemic signs and symptoms.
PubMed: 38913387
DOI: 10.23822/EurAnnACI.1764-1489.348 -
Journal of Investigational Allergology... Jun 2024
Successful Desensitization to Isatuximab in a Patient With Refractory Multiple Myeloma and Indolent Systemic Mastocytosis. Reply to: Anaphylactic Shock due to Isatuximab and Successful Desensitization.
Topics: Humans; Multiple Myeloma; Anaphylaxis; Mastocytosis, Systemic; Desensitization, Immunologic; Antibodies, Monoclonal, Humanized; Drug Hypersensitivity
PubMed: 38888584
DOI: 10.18176/jiaci.0990 -
Cureus May 2024We report an atypical case of systemic mastocytosis in a 66-year-old asymptomatic female, diagnosed incidentally during a routine colonoscopy. This case highlights the...
We report an atypical case of systemic mastocytosis in a 66-year-old asymptomatic female, diagnosed incidentally during a routine colonoscopy. This case highlights the diversity of clinical presentations and emphasizes the role of colonoscopy and the need for thorough histopathological examinations in routine endoscopic procedures with subtle abnormalities.
PubMed: 38872692
DOI: 10.7759/cureus.60286 -
Cureus May 2024We present a case of an adult male who presented with pancytopenia accompanied by symptomatic anemia, necessitating chronic transfusions. He was diagnosed with systemic...
We present a case of an adult male who presented with pancytopenia accompanied by symptomatic anemia, necessitating chronic transfusions. He was diagnosed with systemic mastocytosis with an associated hematologic neoplasm. Following an inadequate response to midostaurin therapy, the patient was initiated on the newly approved avapritinib. The patient showed significant improvements in all three blood cell lines; however, he developed leg edema, blepharedema, and gum bleeding on this medication. This case underscores the intricacies of managing a patient with advanced systemic mastocytosis, the emerging role of highly selective KIT inhibition in its treatment, and the practical management of adverse medication effects.
PubMed: 38868249
DOI: 10.7759/cureus.60161 -
Clinical and Experimental Allergy :... Jun 2024In this review, we compare different refractory anaphylaxis (RA) management guidelines focusing on cardiovascular involvement and best practice recommendations, discuss... (Review)
Review
In this review, we compare different refractory anaphylaxis (RA) management guidelines focusing on cardiovascular involvement and best practice recommendations, discuss postulated pathogenic mechanisms underlining RA and highlight knowledge gaps and research priorities. There is a paucity of data supporting existing management guidelines. Therapeutic recommendations include the need for the timely administration of appropriate doses of aggressive fluid resuscitation and intravenous (IV) adrenaline in RA. The preferred second-line vasopressor (noradrenaline, vasopressin, metaraminol and dopamine) is unknown. Most guidelines recommend IV glucagon for patients on beta-blockers, despite a lack of evidence. The use of methylene blue or extracorporeal life support (ECLS) is also suggested as rescue therapy. Despite recent advances in understanding the pathogenesis of anaphylaxis, the factors that lead to a lack of response to the initial adrenaline and thus RA are unclear. Genetic factors, such as deficiency in platelet activating factor-acetyl hydrolase or hereditary alpha-tryptasaemia, mastocytosis may modulate reaction severity or response to treatment. Further research into the underlying pathophysiology of RA may help define potential new therapeutic approaches and reduce the morbidity and mortality of anaphylaxis.
PubMed: 38866583
DOI: 10.1111/cea.14514 -
Journal of the National Comprehensive... Jun 2024Mastocytosis is a heterogeneous group of disorders comprising cutaneous mastocytosis, systemic mastocytosis, and mast cell sarcoma. It is associated with a variety of...
Mastocytosis is a heterogeneous group of disorders comprising cutaneous mastocytosis, systemic mastocytosis, and mast cell sarcoma. It is associated with a variety of symptoms related to the release of mast cell mediators and mast cell tissue infiltration. Referral to specialized centers with expertise in the management of mastocytosis and multidisciplinary collaboration with subspecialists (eg, allergists for the management of anaphylaxis and drug hypersensitivities, anesthesiologists for invasive procedures or surgery, high-risk obstetrician for pregnancy) is recommended. The NCCN Guidelines for Systemic Mastocytosis provide evidence- and consensus-based recommendations for the diagnosis and comprehensive care of patients with systemic mastocytosis. The multidisciplinary panel of experts convenes at least once a year to review requested changes to the guidelines from both internal and external entities as well as to discuss data on existing and new therapies. These NCCN Guidelines Insights focus on some of the recent updates to the guidelines.
Topics: Humans; Mastocytosis, Systemic; Disease Management; Medical Oncology
PubMed: 38862005
DOI: 10.6004/jnccn.2024.0030 -
The Journal of Allergy and Clinical... Jun 2024Mast cell activation syndrome (MCAS) is a term applied to several clinical entities which have gained increased attention from patients and medical providers. While...
Mast cell activation syndrome (MCAS) is a term applied to several clinical entities which have gained increased attention from patients and medical providers. While several descriptive publications about MCAS exist, there are many gaps in knowledge resulting in confusion about this clinical syndrome. Whether MCAS is a primary syndrome or exists as a constellation of symptoms in the context of known inflammatory, allergic, or clonal disorders associated with systemic mast cell (MC) activation is not well understood. More importantly, the underlying mechanisms and pathways that lead to MC activation in MCAS patients remain to be elucidated. The purpose of this manuscript is to summarize the known literature, identify gaps in knowledge, and highlight research needs. Several topics are covered: 1) Contextualization of MCAS and MCAS-like endotypes and related diagnostic evaluations; 2) Mechanistic research; 3) Management of typical and refractory symptoms, and 4) MCAS-specific education for patients and healthcare providers.
PubMed: 38851398
DOI: 10.1016/j.jaci.2024.05.025 -
Allergy Jun 2024
PubMed: 38850228
DOI: 10.1111/all.16185 -
Bone May 2024A score to predict the association between unexplained osteoporosis and an underlying systemic Mastocytosis (SM) is lacking.
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.
PubMed: 38823568
DOI: 10.1016/j.bone.2024.117141