Prevalence of hypersensitivity reactions in various forms of mastocytosis: A pilot study of 2485 adult patients with mastocytosis collected in the ECNM registry.

BACKGROUND: Hypersensitivity reactions (HR) are common in mastocytosis. However, little is known about triggers and risk factors. The registry of the European Competence Network on Mastocytosis (ECNM) enables reliable studies in a larger cohort of mastocytosis patients. We assessed prevalence, triggers and risk factors of HR in adults with mastocytosis in the ECNM registry. METHODS: Data were collected in 27 ECNM centers. We analyzed potential triggers (Hymenoptera venoms, food, drug, inhalant and others) and risk factors at diagnosis and during follow-up. The study group consisted of 2485 adults with mastocytosis, 1379 women (55.5%) and 1106 men (44.5%). Median age was 48.2 years (range 18-91 years). RESULTS: Nine hundred and forty eight patients (38.1%) reported one or more HR`. Most common triggers were Hymenoptera venoms in cutaneous mastocytosis (CM) and indolent systemic mastocytosis (ISM), whereas in advanced SM (advSM), most common elicitors were drugs, including nonsteroidal anti-inflammatory agents and penicillin. In multivariate analyses, tryptase level < 90 ng/mL, <15% infiltration by mast cells in bone marrow biopsy-sections, and diagnosis of ISM were identified as independent risk factors for HR. For drug-induced HR, prominent risk factors were advSM and high tryptase levels. New reactions were observed in 4.8% of all patients during 4 years follow-up. CONCLUSIONS: HR are mainly triggered by Hymenoptera venoms in patients with CM and ISM and by drugs in patients with advSM. Tryptase levels <90 ng/mL, mast cell bone marrow infiltration <15%, and WHO category ISM are predictors of HR. New HR occur in 4.8% of all patients within 4 years.

Factor VII Deficiency in Systemic Mastocytosis with an Associated Myeloid Neoplasm.

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.

Histological characterization of liver involvement in systemic mastocytosis.

BACKGROUND AND AIMS: Systemic mastocytosis (SM) is characterized by the accumulation of atypical mast cells (MCs) in organs. Liver histology of SM has been marginally described and accurate histological classification is critical, given the consequences of aggressive SM diagnosis. We aimed to describe the histological features associated with liver SM using updated tools. METHODS: Using the database of the French Reference Centre for Mastocytosis, we retrospectively identified patients with a liver biopsy (LB) and a diagnosis of SM. All LB procedures were performed according to the local physician in charge and centrally reviewed by an expert pathologist. RESULTS: A total of 28 patients were included: 6 had indolent SM, 9 had aggressive SM, and 13 had SM with an associated hematologic neoplasm. Twenty-five (89%) patients presented hepatomegaly, and 19 (68%) had portal hypertension. The LB frequently showed slight sinusoid dilatation (82%). Fibrosis was observed in 3/6 indolent SM and in almost all advanced SM cases (21/22), but none of them showed cirrhosis. A high MC burden (>50 MCs/high-power field) was correlated with elevated blood alkaline phosphatase levels (p = .030). The presence of portal hypertension was associated with a higher mean fibrosis grade (1.6 vs. 0.8 in its absence; p = .026). In advanced SM, the presence of nodular regenerative hyperplasia (NRH) was associated with decreased overall survival (9.5 vs. 46.3 months, p = .002). CONCLUSIONS: MC infiltration induced polymorphic hepatic lesions and the degree of fibrosis is associated with portal hypertension. NRH identifies a poor prognosis subgroup of patients with advanced SM. Assessing liver histology can aid in SM prognostic evaluation.

Alpha-Tryptase as a Risk-Modifying Factor for Mast Cell-Mediated Reactions.

PURPOSE OF REVIEW: To provide an overview on the current understanding of genetic variability in human tryptases and summarize the literature demonstrating the differential impact of mature tryptases on mast cell-mediated reactions and associated clinical phenotypes. RECENT FINDINGS: It is becoming increasingly recognized that tryptase gene composition, and in particular the common genetic trait hereditary alpha-tryptasemia (HαT), impacts clinical allergy. HαT has consistently been associated with clonal mast cell disorders (MCD) and has also been associated with more frequent anaphylaxis among these patients, and patients in whom no allergic trigger can be found, specifically idiopathic anaphylaxis. Additionally, more severe anaphylaxis among Hymenoptera venom allergy patients has been linked to HαT in both retrospective and prospective studies. An increased relative number of α-tryptase-encoding gene copies, even in the absence of HαT, has also been associated with systemic mastocytosis and has been shown to positively correlate with the severity of mast cell-mediated reactions to vibration and food. These findings may be due to increased generation of α/ß-tryptase heterotetramers and differences in their enzymatic activity relative to ß-tryptase homotetramers. HαT is a naturally occurring overexpression model of α-tryptase in humans. Increased relative α-tryptase expression modifies immediate hypersensitivity symptoms and is associated with more frequent and severe mast cell-mediated reactions, ostensibly due to increased α/ß-tryptase heterotetramer production.

DRUG-INDUCED ANAPHYLAXIS UNCOMMON IN MASTOCYTOSIS: FINDINGS FROM TWO LARGE COHORTS.

BACKGROUND: Anaphylaxis is a common feature of mastocytosis patients, particularly with Hymenoptera venoms. Hence, it is hypothesized that mastocytosis patients may have an increased susceptibility to developing drug-induced anaphylaxis (DIA). Patients and medical practitioners are therefore concerned when there is a need to use various drugs. However, this issue has not been systematically investigated. OBJECTIVE: Our study aimed to investigate the prevalence and clinical characteristics of anaphylaxis to various types of drugs among mastocytosis patients. METHODS: A retrospective study was conducted among 470 consecutive patients (≥ 18 years) with confirmed clonal mast cell diseases recruited from two independent mastocytosis reference centers. All patients underwent a comprehensive, individualized allergy workup with evaluation of the (self)reported drug hypersensitivity. RESULTS: Overall prevalence of DIA was 6.3% accounting for 1/3 of the confirmed drug hypersensitivity reactions. Non-steroidal anti-inflammatory drugs (NSAIDs) were the most common elicitors of DIA (56%), followed by perioperative agents (23%) and antibiotics (13%). Anaphylactic reactions were severe in most cases with 43% of patients experiencing hypotensive syncope. All drug-related hypersensitivity reactions occurred before mastocytosis was diagnosed. CONCLUSIONS: The prevalence of DIA in mastocytosis tends to be higher than in general population, but is overall low. However, its severity is more pronounced. Our results suggest that mastocytosis patients with a prior reaction to drugs should undergo a thorough allergy workup. Well-tolerated drugs can be further used without specific precautions.

High burden of clonal mast cell disorders and hereditary α-tryptasemia in patients who need Hymenoptera venom immunotherapy.

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.

The Prevalence Of Osteoporosis Is Low In Adult Cutaneous Mastocytosis Patients.

BACKGROUND: Systemic mastocytosis (SM) is a clonal disorder of mast cells (MCs) frequently associated with vertebral osteoporosis (OP) and subsequent vertebral fractures (VFs). The natural history of this OP remains unclear. Importantly, we do not know whether OP represents an early event triggered alongside MC abnormalities, and whether MC clonality is sufficient to trigger osteoporosis. OBJECTIVE: To describe OP in patients with medullar clonality in cutaneous mastocytosis (CM) and monoclonal mast cell activation syndrome (MMAS) and to compare their osteoporosis characteristics with those of nonadvanced SM patients (bone marrow mastocytosis and indolent systemic mastocytosis). METHODS: We retrospectively analyzed clinical, biological, and densitometric data of 27 CM, 13 MMAS, and 135 SM patients from the Mastocytosis Expert Center (CEREMAST) in Toulouse, France. RESULTS: The OP (respectively 3.7, 30.8, and 34.1%) and VFs (0.0%, 15.4%, and 20%) were less frequent in CM than in MMAS and SM, despite the presence of clonal MCs in the bone marrow. Most patients with OP and VFs in the non-SM groups had the usual risk factors for OP. Interestingly, the only non-SM patient with a typical SM-like OP had high bone marrow tryptase, developed bone marrow KIT mutation during follow-up, and had a family history of SM. Our data show that OP is not a common clinical finding in CM but is frequent in MMAS. When OP and VFs occur in CM and MMAS patients, they differ from the usual phenotype of SM bone fragility. CONCLUSIONS: Our findings suggest that, in most CM patients, the meaning and management of OP differs from that of OP in MMAS and nonadvanced SM. Prospective longitudinal studies and the validation of predictors are needed to identify CM and MMAS patients developing SM-related OP.

A case of indolent systemic mastocytosis responding to treatment with Avapritinib.

Low dose Avapritinib is a new medication that is a potential treatment option not just for advanced systemic mastocytosis, but also for the indolent form.

Reversible Elevation of Tryptase Over the Individual's Baseline: Why is It the Best Biomarker for Severe Systemic Mast Cell Activation and MCAS?

PURPOSE OF REVIEW: Mast cell (MC) activation syndromes (MCAS) are conditions defined by recurrent episodes of severe systemic anaphylaxis or similar systemic events triggered by MC-derived mediators that can be measured in biological fluids. Since some symptoms of MC activation may occur due to other, non-MC etiologies and lead to confusion over diagnosis, it is of crucial importance to document the involvement of MC and their products in the patients´ symptomatology. RECENT FINDINGS: The most specific and generally accepted marker of severe systemic MC activation is an event-related, transient increase in the serum tryptase level over the individual baseline of the affected individual. However, baseline concentrations of serum tryptase vary among donors, depending on the genetic background, age, kidney function, and underlying disease. As a result, it is of critical importance to provide a flexible equation that defines the diagnostic increase in tryptase qualifying as MCAS criterion in all patients, all situations, and all ranges of baseline serum tryptase. In 2012, the consensus group proposed the 120% + 2 ng/ml formula, which covers the great majority of groups, including cases with low, normal, or elevated basal serum tryptase level. This formula has been validated in subsequent studies and has proven to be a robust and consistent diagnostic criterion of MCAS. The present article is discussing the impact of this formula and possible limitations as well as alternative markers and mediators that may be indicative of MCAS.

Safety and Tolerability of COVID-19 Vaccine in Mast Cell Disorders Real-Life Data from a Single Centre in Italy.

Background In the past three years, COVID-19 has had a significant impact on the healthcare systems and people's safety worldwide. Mass vaccinations dramatically improved the health and economic damage caused by SARS-CoV-2. However, the safety of COVID-19 vaccines in patients at high risk of allergic reactions still has many unmet needs that should be clarified. Material and methods A retrospective, single-centre study was performed by collecting demographic and clinical data of patients with Mast Cell Disorders (MCDs) to evaluate the safety and tolerability of COVID-19 vaccinations. Moreover, any changes in the natural history of the underlying disease following the vaccine have been evaluated. Results This study included 66 patients affected with MCDs. Out of them, 52 (78.8%) received a COVID-19 vaccination and 41 (78.8%) completed the vaccination course. Premedication came first in 86.6% of our patients. A total of seven (4.5%) patients complained about an immediate reaction and two (1.3%) had a late reaction. Worsening of MCD history was observed in a single patient. Conclusions Despite the overall high risk of allergic reactions, our study did not reveal any increased risk for SARS-CoV-2 allergic reactions in MCD patients, thus supporting the recommendation in favour of the SARS-CoV-2 vaccination. However, due to the potentially increased rate of anaphylactic reactions, MCD patients should receive vaccine premedication and should be treated in a hospital setting after an allergological specialistic evaluation.

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.

Poor Applicability of Currently Available Prognostic Scoring Systems for Prediction of Outcome in KIT D816V-Negative Advanced Systemic Mastocytosis.

Within our nationwide registry, we identified a KIT D816V mutation (KIT D816Vpos.) in 280/299 (94%) patients with advanced systemic mastocytosis (AdvSM). Age, cytopenias and the presence of additional somatic mutations confer inferior overall survival (OS). However, little is known about the characteristics of KIT D816V-negative (D816Vneg.) AdvSM. In 19 D816Vneg. patients, a combination of clinical, morphological and genetic features revealed three subgroups: (a) KIT D816H- or Y-positive SM (KIT D816H/Ypos., n = 7), predominantly presenting as mast cell leukemia (MCL; 6/7 patients), (b) MCL with negative KIT sequencing (KITneg. MCL, n = 7) and (c) KITneg. SM with associated hematologic neoplasm (KITneg. SM-AHN, n = 5). Although >70% of patients in the two MCL cohorts (KIT D816H/Ypos. and KITneg.) were classified as low/intermediate risk according to prognostic scoring systems (PSS), treatment response was poor and median OS was shorter than in a KIT D816Vpos. MCL control cohort (n = 29; 1.7 vs. 0.9 vs. 2.6 years; p < 0.04). The KITneg. SM-AHN phenotype was dominated by the heterogeneous AHN (low mast cell burden, presence of additional mutations) with a better median OS of 4.5 years. We conclude that (i) in MCL, negativity for D816V is a relevant prognostic factor and (ii) PSS fail to correctly classify D816Vneg. patients.

Bullous Mastocytosis: A Rare Variant of Diffuse Cutaneous Mastocytosis.

Mastocytosis is a disease of the mast cells caused by an increase in the number of mast cells due to abnormal proliferation. The disease is associated with a mutation in the c-kit gene, which is a key factor in the development of mast cells. Mastocytosis is classified into two main groups, namely, cutaneous and systemic mastocytosis, based on the site of mast cell accumulation. In cutaneous mastocytosis, the cells purely gather in the skin. In contrast, systemic mastocytosis must affect an internal organ, including the bone marrow, lymph nodes, liver, spleen, and/or the gastrointestinal tract with or without skin involvement. Cutaneous mastocytosis has four distinct presentations, including urticaria pigmentosa, cutaneous mastocytoma, diffuse cutaneous mastocytosis, and telangiectasia macularis eruptive perstans listed from most to least common. This case report presents a rare bullous variant of diffuse cutaneous mastocytosis.

Multicolor flow cytometric immunophenotyping is highly sensitive and specific in identifying aberrant mast cells in the diagnostic workup of systemic mastocytosis.

OBJECTIVES: Flow cytometric immunophenotyping (FCI) is a fast and sensitive method for characterizing hematolymphoid neoplasms. It is not widely used in the workup of systemic mastocytosis (SM), in part because of the technical challenges and in part because the utility of FCI in assessing mast cells is not well understood. The objectives of this study were to assess the diagnostic utility of FCI in establishing a diagnosis of SM and distinguishing SM from nonneoplastic mast cells and to examine the immunophenotypic findings among SM subtypes. METHODS: We performed FCI on bone marrow samples suspicious for SM using a panel consisting of CD2, CD25, CD30, CD45, CD117, and HLA-DR. RESULTS: The cohort included 88 SM cases: 67 without an associated hematologic neoplasm (AHN) (PureSM) and 21 with an AHN (SM-AHN). We also assessed 40 normal/reactive controls. Overall, FCI was adequate for interpretation in 87 of 88 (99%) cases and detected at least 1 immunophenotypic aberrancy in 100% of SM cases. CD2, CD25, and CD30 were positive in 78%, 98%, and 90% of SM cases vs 0%, 13%, and 13% of cases with normal/reactive mast cells (P < .0001 for all). Two or 3 abnormalities were observed in 92% of SM cases but not in normal/reactive mast cells. Among SM cases, SM-AHN showed statistically significant less CD2 (38% vs 91%, P < .0001) and less co-expression of all 3 aberrant markers (CD2, CD25, and CD30 positive in 38% vs 86% of cases; P < .0001) than PureSM. Immunohistochemical analysis showed consistently weaker or focal expression of CD2, CD25, and CD30 than FCI, with CD2 and CD30 being falsely negative in 40% and 50% cases, respectively. A KIT D816V mutation was detected in 67% of PureSM cases and 76% of SM-AHN cases. CONCLUSIONS: Flow cytometric immunophenotyping is a quick, sensitive, high-yield tool for evaluating the immunophenotype of mast cells. An abnormal FCI finding should prompt careful histologic evaluation and sensitive KIT D816V mutation testing to address the possibility of SM. CD2, CD25, and CD30 are important markers for the detection of immunophenotypic aberrancy of mast cells, and their frequencies of aberrancy differ across SM subtypes.

Involvement of peripheral mast cells in a fibromyalgia model in mice.

Fibromyalgia is a painful disorder of unknown aetiology that presents activation and recruitment of innate immune cells, including mast cells. Efforts have been made to understand its pathogenesis to manage it better. Thus, we explored the involvement of peripheral mast cells in an experimental model of fibromyalgia induced by reserpine. Reserpine (1 mg/kg) was subcutaneously (s.c.) injected once daily in the back of male Swiss mice for three consecutive days. We analysed mechanical and cold allodynia, muscle fatigue and number of mast cell in plantar tissue. The fibromyalgia induction produced mast cell infiltration (i.e., mastocytosis) in the mice's plantar tissue. The depletion of mast cell mediators with the compound 48/80 (0.5-4 mg/kg, intraperitoneal (i.p.)) or the mast cell membrane stabilizer ketotifen fumarate (10 mg/kg, oral route (p.o.) widely (80-90 %) and extensively (from 1 up to 10 days) prevented reserpine-induced mechanical and cold allodynia and muscle fatigue. Compound 48/80 also prevented the reserpine-induced mastocytosis. Finally, we demonstrated that PAR-2, 5-HT2A, 5-HT3, H1, NK1 and MrgprB2 receptors, expressed in neuronal or mast cells, seem crucial to mediate fibromyalgia-related cardinal symptoms since antagonists or inhibitors of these receptors (gabexate (10 mg/kg, s.c.), ENMD-1068 (10 mg/kg, i.p.), ketanserin (1 mg/kg, i.p.), ondansetron (1 mg/kg, p.o.), promethazine (1 mg/kg, i.p.), and L733,060 (5 mg/kg, s.c.), respectively) transiently reversed the reserpine-induced allodynia and fatigue. The results indicate that mast cells mediate painful and fatigue behaviours in this fibromyalgia model, representing potential therapy targets to treat fibromyalgia syndrome.

T-cell immune profile in blood of systemic mastocytosis: Association with disease features.

BACKGROUND: Systemic mastocytosis (SM) is a heterogeneous disease characterized by an expansion of KIT-mutated mast cells (MC). KIT-mutated MC display activated features and release MC mediators that might act on the tumour microenvironment and other immune cells. Here, we investigated the distribution of lymphocyte subsets in blood of patients with distinct subtypes of SM and determined its association with other disease features. METHODS: We studied the distribution of TCD4+ and TCD4- cytotoxic cells and their subsets, as well as total NK- and B cells, in blood of 115 SM patients-38 bone marrow mastocytosis (BMM), 67 indolent SM (ISM), 10 aggressive SM (ASM)- and 83 age-matched healthy donors (HD), using spectral flow cytometry and the EuroFlow Immunomonitoring panel, and correlated it with multilineage KITD816V , the alpha-tryptasemia genotype (HαT) and the clinical manifestations of the disease. RESULTS: SM patients showed decreased counts (vs. HD) of TCD4- cytotoxic cells, NK cells and several functional subsets of TCD4+ cells (total Th1, Th2-effector memory, Th22-terminal effector and Th1-like Tregs), together with increased T-follicular-helper and Th1/Th17-like Treg counts, associated with different immune profiles per diagnostic subtype of SM, in multilineal versus MC-restricted KITD816V and in cases with a HαT+ versus HαT- genotype. Unique immune profiles were found among BMM and ISM patients with MC-restricted KITD816V who displayed HαT, anaphylaxis, hymenoptera venom allergy, bone disease, pruritus, flushing and GI symptoms. CONCLUSION: Our results reveal altered T- and NK-cell immune profiles in blood of SM, which vary per disease subtype, the pattern of involvement of haematopoiesis by KITD816V , the HαT genotype and specific clinical manifestations of the disease.

A 48-Year-Old Man With a Hip Fracture and Skin Rash: A Case Report.

Background/Objective: Patients with systemic mastocytosis are at high risk of developing osteoporosis and fractures. Herein, we report a case of hip fragility fracture in a patient with indolent systemic mastocytosis and normal bone density. Case Report: A 48-year-old man experienced a left femoral neck fracture after a fall. After a dose of oxycodone/hydromorphone postoperatively, he developed an anaphylactic reaction. Previously, he experienced a few other episodes of flushing, dizziness, and syncope precipitated by stress and alcohol. His examination was notable for pink and brown macules on his chest, back, arms, and legs. His laboratory test revealed a markedly elevated tryptase level of 171 ng/mL (<11 ng/mL). Treatment including cetirizine, montelukast, and ranitidine controlled his symptoms. His bone density test result was normal. Ten months after hip surgery, his c-terminal telopeptide of collagen type 1 and bone-specific alkaline phosphatase levels significantly increased. The bone scan demonstrated diffusely increased radiotracer uptake throughout the osseous structures. Given high bone turnover and the prior hip fracture, he received zoledronic acid yearly for 3 years, and no further fractures have occurred. Discussion: The case is unusual as the fracture occurred despite normal bone density and significant osteosclerosis, which was previously considered protective against fractures. Additionally, rather than the spine, the fracture occurred in the hip, which is an uncommon site for mastocytosis-induced fractures. Conclusion: Mastocytosis is a rare cause of osteoporosis, and it is important to keep this condition in the differential diagnosis of osteoporosis, particularly when the fracture presentation is atypical.

COVID-19 infection and vaccination in 92 pediatric patients with cutaneous mastocytosis: A retrospective, cross-sectional study.

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.