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Hematology Reports Mar 2024Factor VII (FVII) deficiency is a rare bleeding disorder that can be classified as congenital or acquired, and the majority of acquired cases are due to vitamin K...
Factor VII (FVII) deficiency is a rare bleeding disorder that can be classified as congenital or acquired, and the majority of acquired cases are due to vitamin K deficiency or liver disease. Isolated acquired FVII deficiency is a rare occurrence and has been associated with inhibitors or auto-antibodies. Here, we describe a patient with polycythemia vera who developed systemic mastocytosis and FVII deficiency simultaneously. FVII deficiency was not caused by inhibitors and improved with antineoplastic treatment. Acquired FVII deficiency has been reported in cases of sepsis, possibly due to proteolytic degradation induced by the activation of monocytes or endothelial cells. Malignancies have been shown to cause a depletion in circulating FVII through the direct binding of cancer cells. This case report suggests a potential association between SM associated with a hematological neoplasm (SM-AHN) and acquired FVII deficiency. Further evaluations are recommended in patients with systemic mastocytosis to gain a better understanding of the relationship between pathological mast cells and clotting factor concentrations.
PubMed: 38534884
DOI: 10.3390/hematolrep16010014 -
Frontiers in Allergy 2024Empty mast cell syndrome, also named post anaphylaxis mast cell anergy (PAMA), is a temporary state of loss of mast cell responsiveness after a severe immediate...
Empty mast cell syndrome, also named post anaphylaxis mast cell anergy (PAMA), is a temporary state of loss of mast cell responsiveness after a severe immediate hypersensitivity reaction. In this study, we describe a case of PAMA after accidental re-exposure to amoxicillin in a patient who developed severe anaphylaxis to this drug three days earlier in the operating room. To our knowledge, this report is the second to document this phenomenon.
PubMed: 38529125
DOI: 10.3389/falgy.2024.1366922 -
Arerugi = [Allergy] 2024A 2-year-old, male patient presented with an 18-month history of scattered, brown macules and nodules up to 2 cm in size on his trunk and extremities. These macules were...
A 2-year-old, male patient presented with an 18-month history of scattered, brown macules and nodules up to 2 cm in size on his trunk and extremities. These macules were accompanied by pruritus and were positive for Darier's sign. A skin biopsy of a brown macule on the left thigh revealed a dense accumulation of CD117-positive, round or oval cells with amphophilic cytoplasm within the upper to middle dermis. The patient was otherwise healthy and had normal laboratory and imaging test results. Sequence analysis of genomic DNA from a skin biopsy demonstrated the presence of an Asp419del mutation in exon 8 of the KIT gene. Based on these findings, maculopapular cutaneous mastocytosis (MPCM) was diagnosed. The patient received H 1-antihistamine. Although the pruritus resolved, the brown macules remained for one year after the initial treatment. To the best of our knowledge, only three cases of cutaneous mastocytosis (CM) with an Asp419del mutation, including the present case, have been reported in the Japanese literature to date; moreover, while the previous two cases were of DCM, the present case was the first instance of MPCM. Normally, the symptoms of childhood-onset MPCM are dormant until puberty. However, a recent study reported that many MPCM patients may experience persistent or exacerbated symptoms. The present study therefore evaluated 53 Japanese cases of childhood onset MPCM with a KIT gene mutation and discussed the patients' clinical outcomes.
Topics: Humans; Male; Child, Preschool; Urticaria Pigmentosa; Mastocytosis, Cutaneous; Skin; Mutation; Pruritus
PubMed: 38522933
DOI: 10.15036/arerugi.73.189 -
Blood Mar 2024
Topics: Humans; Mastocytosis, Systemic; Tumor Necrosis Factor-alpha; Survivin; Mastocytosis; Prognosis
PubMed: 38483409
DOI: 10.1182/blood.2023023532 -
Dermatology Online Journal Dec 2023Diffuse cutaneous mastocytosis with bullous formation is a rare childhood disease. We report a 5-month-old male who presented with a 3-week history of cutaneous bullae...
Diffuse cutaneous mastocytosis with bullous formation is a rare childhood disease. We report a 5-month-old male who presented with a 3-week history of cutaneous bullae and pruritus. On examination, he had erythema of the cheeks bilaterally and diffuse slightly hyperpigmented, indurated skin on his trunk and abdomen. There were tense vesicles, bullae, and erosions linearly arranged on his trunk and extremities. Both the laboratory and imaging workup were normal. Subsequently, a punch biopsy of a vesicle on the abdomen was obtained and findings confirmed a diagnosis of diffuse cutaneous mastocytosis. An EpiPen(r) was prescribed due to the slightly increased anaphylaxis risk compared to other forms of mastocytosis. There are many purported triggers of diffuse cutaneous mastocytosis and there is currently no known cure which makes management of this disease challenging. This case highlights a rare condition for which official treatment guidelines do not exist. A prompt dermatologic diagnosis is necessary to ensure proper workup and regulation is in place.
Topics: Humans; Male; Child; Infant; Blister; Mastocytosis, Cutaneous; Skin; Pruritus; Erythema
PubMed: 38478675
DOI: 10.5070/D329663004 -
Allergy Mar 2024In patients who require venom immunotherapy (VIT), there is a need to identify underlying mast cell (MC) disorders since these may affect the risk and severity of future...
BACKGROUND
In patients who require venom immunotherapy (VIT), there is a need to identify underlying mast cell (MC) disorders since these may affect the risk and severity of future sting reactions and the long-term effectiveness of VIT.
METHODS
1319 individuals with Hymenoptera venom allergy (HVA) who needed VIT from referral centers in Slovenia, Austria, Croatia, and Poland underwent examination for KIT p.D816V in peripheral blood leukocytes (PBL) using a highly sensitive PCR test and tryptase genotyping by digital droplet PCR. We also included 183 control individuals with large local reactions (LLRs) to Hymenoptera stings and with asymptomatic sensitization to Hymenoptera venoms.
RESULTS
285 of 1319 individuals recommended for VIT (21.6%) were positive for KIT p.D816V in PBL, preferably those who present with severe reaction (33.9% [n = 207 of 610] with Ring-Messmer grade 3-4 vs. 11% [n = 78 of 709] with Grade 1-2; p < .0001), whereas only 1.3% (n = 2 of 152) of controls with LLR and none with asymptomatic sensitization (n = 31) had KIT p.D816V. KIT p.D816V allelic burden was higher in those with severe reaction (median 0.018% [n = 207] in Grade 3-4 vs. 0.001% [n = 78] in Grade 1-2; p < .0001), and the majority had normal baseline serum tryptase levels (69% [n = 196 of 285]). All KIT p.D816V-positive individuals (n = 41) who underwent bone marrow (BM) biopsy were found to have underlying clonal diseases, principally BM mastocytosis. HαT was also associated with severe HVA and symptoms (p < .01), and remarkably, 31.0% (n = 31 of 100) were found to have concomitant KIT p.D816V. Concomitant HαT and KIT p.D816V showed an additive effect, and having both was associated with the highest risk for severe HVA, even higher than having either HαT or KIT p.D816V alone (OR = 3.8; p < .01).
CONCLUSIONS
By employing prospective universal tryptase genotyping and examination for KIT p.D816V in PBL in large HVA populations, we have demonstrated a high burden of clonal MC disorders and HαT in patients who require VIT.
PubMed: 38477502
DOI: 10.1111/all.16084 -
Leukemia Apr 2024Systemic Mastocytosis (SM) is a multifaceted clinically heterogeneous disease. Advanced SM (AdvSM) comprises three entities: aggressive SM (ASM), mast cell leukaemia... (Review)
Review
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.
Topics: Humans; Mastocytosis, Systemic; Antineoplastic Agents; Mastocytosis; Leukemia, Mast-Cell; Hematopoietic Stem Cell Transplantation; Proto-Oncogene Proteins c-kit; Mast Cells
PubMed: 38472477
DOI: 10.1038/s41375-024-02182-1 -
British Journal of Haematology Jun 2024
Topics: Humans; Mastocytosis, Systemic; Hemorrhage; Male; Hypereosinophilic Syndrome; Female; Middle Aged
PubMed: 38471752
DOI: 10.1111/bjh.19349 -
Cancer Genetics Jun 2024Systemic mastocytosis (SM) is a myeloproliferative neoplasm displaying abnormal mast cell proliferation. It is subdivided into different forms, including aggressive...
Systemic mastocytosis (SM) is a myeloproliferative neoplasm displaying abnormal mast cell proliferation. It is subdivided into different forms, including aggressive systemic mastocytosis (ASM) and systemic mastocytosis with an associated hematologic neoplasm (SM-AHN). Oncogenic genetic alterations include point mutations, mainly the KIT D816V, conferring poor prognosis and therapy resistance, and fusion genes, with those involving PDGFRA/PDGFRB as the most recurrent events. We here describe an ASM case negative to the KIT D816V and JAK2 V617F alterations but showing a RUNX1 frameshift heterozygous mutation and the co-occurrence of three fusion transcripts. The first one, PRKG2::PDGFRB, was generated by a balanced t(4;5)(q24;q32) translocation as the sole abnormality. Other two novel chimeras, KAT6A::NCOA2 and RXRA::NOTCH1, originated from cryptic intra-chromosomal abnormalities. The patient rapidly evolved towards SM-AHN, characterized by the persistence of the PRKG2::PDGFRB chimera, due to the presence of an extra copy of the der(5)t(4;5)(q24;q34) chromosome and an increase in the RUNX1 mutation allelic frequency. The results indicated that the transcriptional landscape and the mutational profile of SM deserve attention to predict the evolution and prognosis of this complex disease, whose classification criteria are still a matter of debate.
Topics: Humans; Frameshift Mutation; Core Binding Factor Alpha 2 Subunit; Mastocytosis, Systemic; Oncogene Proteins, Fusion; Receptor, Notch1; Nuclear Receptor Coactivator 2; Male; Heterozygote; Female; Middle Aged; Histone Acetyltransferases
PubMed: 38471404
DOI: 10.1016/j.cancergen.2024.03.002 -
European Journal of Dermatology : EJD Dec 2023
Topics: Humans; Panniculitis; Lymphoma, T-Cell; Skin Neoplasms; Diagnosis, Differential; Lymphoma, T-Cell, Cutaneous
PubMed: 38465570
DOI: 10.1684/ejd.2023.4626