Baseline Tryptase Levels Research Articles

Diagnostic Accuracy of Tryptase Levels for Pediatric Anaphylaxis: A Case-Control Study

Introduction: Anaphylaxis is a severe allergic reaction which can be difficult to diagnose. Two strategies evaluating changes in tryptase levels were proposed for diagnosing anaphylaxis. Strategy 1 established a threshold of tryptase levels during reaction exceeding 2 ng/mL + 1.2* (baseline tryptase levels) as a rule for detecting anaphylaxis, while strategy 2 established the ratio of tryptase levels during reaction versus baseline tryptase exceeding a threshold of 1.685. We aimed to compare the diagnostic test accuracy of the two strategies in pediatric anaphylaxis. Methods: We conducted a case-control study. Cases consisted of 89 patients with anaphylaxis who had reaction tryptase and subsequent baseline tryptase measured. Controls consisted of 25 patients with chronic urticaria who had two tryptase measurements. Sensitivity and specificity for each of the strategies were computed and compared using McNemar test. The area under the curve (AUC) between the two strategies was compared using the DeLong test. Results: The sensitivity and specificity for strategy 1 was 53.3% and 95.0%, respectively. For strategy 2, the sensitivity and specificity was 54.4% and 85.0%, respectively. There was no significant difference between both strategies’ sensitivity and specificity. The Delong test determined that the AUC was significantly (p < 0.05) higher for strategy 1 (0.69) than strategy 2 (0.64). Conclusion: The Delong test determined that strategy 1 was slightly better in validating anaphylaxis diagnosis than strategy 2. However, both strategies demonstrated a low sensitivity <55%.

Retesting Intervals for Tryptase

What Is the Issue? Tryptase is a serine protease primarily produced and released by mast cells. Tryptase measures are most used to diagnose and manage anaphylaxis and mastocytosis, and the timing of tryptase measurement is crucial for its utility. The clinical utility of tryptase remains unclear, and available evidence showed that more than 30% of patients with acute anaphylaxis did not exhibit an elevated tryptase level, which suggests that repeated tryptase testing may be overused in this population. Appropriate retesting intervals or frequency for tryptase retesting in patients with anaphylaxis or mastocytosis remain unclear. What Did We Do? To inform decisions about the use and timing of repeat tryptase testing for patients with confirmed or suspected anaphylaxis and patients with cutaneous or systemic mastocytosis, we identified and summarized related recommendations and publications on the potential biological or physiological factors that may impact retesting intervals in these populations. We searched key resources, including journal citation databases, and conducted a focused internet search for relevant evidence published since 2014. One reviewer screened articles for inclusion based on predefined criteria, critically appraised the included evidence-based guidelines, and narratively summarized the findings. What Did We Find? For patients with suspected anaphylaxis, identified guidelines suggest measuring tryptase levels 1 to 2 times during the event onset (e.g., immediately or within 4 hours) and 1 to 2 times after resolution of symptoms (e.g., after 24 hours) to establish baseline tryptase levels. These recommendations were based on very low certainty of evidence. For patients with systemic mastocytosis, 1 evidence-based guideline in Brazil recommends testing tryptase once a year, which is based on very low certainty of evidence. Baseline tryptase level varies very little over time within the same individual and is determined by their genetic background. For patients with anaphylaxis, the timing of the peak tryptase level is from 1 minute to 6 hours (median 30 minutes), and the half-life of serum tryptase is about 1.5 hours to 2.5 hours and needs up to 24 hours to return to baseline level. We did not find any recommendations that met our inclusion criteria regarding the minimum retesting interval for tryptase testing or the use of repeat or serial tryptase testing in patients with confirmed or suspected anaphylaxis or with cutaneous or systemic mastocytosis. What Does It Mean? The available recommendations suggest testing blood tryptase at the acute (1 or 2 times) and baseline phases (1 or 2 times) for patients with suspected anaphylaxis. There is little rationale for the ongoing monitoring of tryptase levels beyond the recommended 4 time points for patients with anaphylaxis. For patients with mastocytosis, the guidelines recommend retesting tryptase only once a year and do not support frequent repeat tryptase testing within a year. Decision-makers and clinicians should consider the cost of tryptase testing, potential burden on health care resources, local lab capacity, or accessibility of testing facilities when making decisions regarding tryptase retesting. Given the very low-quality evidence regarding measuring tryptase and the unclear utility of tryptase testing for patients with anaphylaxis, future research that focuses on the clinical utility of tryptase relative to clinical assessment for anaphylaxis is needed.

Successful desensitization to etoposide in a patient after cardiac arrest.

Etoposide phosphate is a chemotherapeutic agent used to treat various malignant neoplasms. Hypersensitivity reactions may occur with its use, and in rare cases, an anaphylactic reaction can manifest. Available options for patients experiencing hypersensitivity reactions include premedication, changing treatment, or undergoing desensitization. Various pediatric desensitization protocols have been described, ranging from six to fifteen steps, while published adult cases are rare. We report the case of a 61-year-old woman with small-cell lung cancer and brain metastases. In November 2019, she underwent the second cycle of cisplatin and etoposide phosphate treatment. While receiving etoposide phosphate, she experienced dyspnea and suffered a cardiorespiratory arrest, leading to cardiopulmonary resuscitation and subsequent admission to the Intensive Care Unit. Her acute tryptase levels were notably elevated at 18 µg/L (compared to a baseline tryptase level of 6,6 µg/L) during the reaction. We implemented a 16-step desensitization protocol (without premedication) under close monitoring in an intermediate care unit. The protocol was successfully executed over three cycles until tumor progression mandated a modification in systemic treatment. To our knowledge, this is the first documented case of successful desensitization to etoposide phosphate in a patient who experienced cardiac arrest during a hypersensitivity reaction. Although protocols of varying lengths have been published, we emphasize the importance of individualizing each protocol to fit the severity of the reaction and the resources and experience of each unit.

Agaricus bisporus mushroom anaphylaxis: A case report and review of the literature

Anaphylaxis in response to edible mushrooms is uncommon, and sensitization may be independent of occupational exposure. Globally, A garicus bisporus is one the most cultivated mushroom species, comprising the button, portobello, and Swiss brown varietals. Our aim was to describe a case of anaphylaxis in an older nonatopic patient following ingestion of A bisporus and undertake a review of the literature. A 77-year-old female was referred to the allergy clinic with a history of grade 3 hypotensive anaphylaxis following ingestion of a mushroom omelette. Her tryptase level 4 hours following acute symptoms was elevated. She continued to consume all other omelette ingredients with the exception of mushroom. Additional investigations included specific IgE testing as well as comprehensive skin prick testing (SPT) to raw and boiled mushrooms. One month after her index reaction, the result of SPT to boiled button mushroom was positive. The patient's baseline tryptase level was normal. The results of further SPT with other commonly available boiled mushrooms (the A bisporus mushrooms portobello and Swiss brown, as well as enoki, oyster, and shiitake mushrooms) were also positive.A review of the literature revealed 27 other cases, with an average patient age of 28.8 years (range 8-68 years) and no gender predisposition. Cases from Europe (n= 14, 51.8%) and Asia (n= 12, 44.4%) comprised the majority of the reports. A bisporus was reported in more than one-third of the cases (n= 10, 37.1%) from Australia, India, Portugal, Spain, and the United Kingdom. Cross-sensitization among the edible mushroom species was evident for those individuals who were tested, but no clear and consistent pattern was identified. In some cases, further diagnostics identified α-mannosidase, α-trehalose, mannitol, and ribosomal protein as specific mushroom allergens. Clinicians should be aware of mushroom as a cause for anaphylaxis, especially in nonatopic and de novo presentations.

Tryptase in drug-induced anaphylaxis: the need for acute and baseline values.

The purpose of this narrative review was to summarize data and official recommendations purporting to paired tryptase determination in patients experiencing drug-induced anaphylaxis, published between January 1, 2023 and June 1, 2024. Three main lines of evidence obtained through paired acute and baseline tryptase determination were identified: diagnostic criterion for hypersensitivity reactions involving systemic mast cell activation; differential diagnostic criterion for hypersensitivity reactions involving other mechanisms of immediate reactions; and added value of acute and baseline tryptase levels for personalized management following drug-induced anaphylaxis: cause, risk of recurrence, underlying mast cell conditions including hereditary α-tryptasemia, familial clusters. The implementation of existing guidelines which consensually recommend paired tryptase measurement is a persistent unmet need hampering optimal diagnosis of drug-induced anaphylaxis and patient management. Another major unmet need is the lack of standardized recommendations for hereditary α-tryptasemia testing and counselling. Progress in this field is seen at a rapid pace, requiring significant efforts of continued medical education for practicing clinicians and laboratory specialists worldwide.

Test Panel of Hidden Allergens for “Idiopathic Anaphylaxis” Reveals Wheat Allergy Dependent on Augmentation Factors as Common Final Diagnosis

Idiopathic anaphylaxis (IA) is an unresolved concern. Hidden allergens may be relevant in IA and in nonsteroidal anti-inflammatory drug hypersensitivity (NSAID-HS). To identify hidden elicitors for IA and NSAID-HS by a skin prick test (SPT) (13 allergens) and allergen-specific IgE (sIgE) panel (12 allergens) and to determine the value of each tested allergen. We retrospectively included all patients from 2018 to 2021 referred with a suspicion of IA or NSAID-HS by history in whom SPT and/or sIgE to allergens of the IA panel were performed. Patient characteristics from patients' records included comorbidities, history and symptoms of anaphylaxis, serum baseline tryptase level, total IgE level, SPT, sIgE, challenge results, and final diagnoses. A total of 134 patients (77 female, mean age 39.7 ± 14.6 years) were included. Median serum baseline tryptase and total IgE levels were 4.23 μg/L and 133.5 kU/L, respectively. Allergologic workup with the IA panel resulted in positive SPT and sIgE in 61 (47%) and 66 (60%) patients, respectively. In those, confirmation or exclusion of allergy, mostly by challenge, led to a definitive diagnosis in 61 of 134 patients (46%). Skin prick test was most frequently positive to gluten (22.4%) and sIgE to ω5-gliadin (21.6%), which correlated with the history (r= 0.310, P < .001; and r= 0.407, P < .001, respectively). In 28 of 134 patients (21%) with initially suspected IA or NSAID-HS, challenges confirmed occult food allergy in which wheat allergy dependent on augmentation factors was the most frequent cause of anaphylaxis (19%). Wheat allergy dependent on augmentation factors should be considered in all patients with anaphylaxis of unknown cause or after NSAID intake.

Elevated tryptase level in a child with idiopathic anaphylaxis: a case of hereditary alpha-tryptasemia

Hereditary alpha-tryptasemia (HαT) is an autosomal dominant disorder estimated to affect 5% of the population. High baseline tryptase level is a consistent finding, but there is a great variability of clinic manifestations, including no symptoms at all. We describe a case of HαT in a 5 years 8 months old girl manifesting with idiopathic anaphylaxis and elevated baseline tryptase level. As more cases of HαT are described, a better understanding of the clinical phenotype will be acquired.

Low Prevalence of Idiopathic Mast Cell Activation Syndrome Among 703 Patients With Suspected Mast Cell Disorders

BackgroundIdiopathic mast cell activation syndrome (iMCAS) is characterised by severe, episodic systemic mast cell (MC) activation and mediator-related symptoms, event-related increase in serum tryptase levels and response to MC-targeted therapies, in the absence of underlying IgE-mediated allergy or clonal MC disorder. Studies indicating its prevalence using evidence-based diagnostic criteria are currently lacking. ObjectiveThe present study aimed to assess prevalence, as well as clinical and laboratory features of patients with iMCAS. MethodsWe conducted a retrospective evaluation of the data from 703 consecutive patients (≥18 years old) who were referred to our centre based on suspected MC disorders. Patients underwent a thorough clinical work-up including patient history, allergy tests, KIT D816V mutation analysis and/or bone marrow investigation. Disease activity was prospectively assessed during follow-up visits. ResultsThirty-one cases with confirmed iMCAS were identified. Furthermore, hereditary alpha-tryptasemia was detected in three of the cases with baseline tryptase levels >8 ng/ml. The most common clinical presentation during the MCAS episodes was mucocutaneous symptoms in patients with iMCAS, especially urticaria/angioedema. However, these symptoms were less prevalent in clonal MCAS patients (p=0.015). The duration of diagnostic delay was significantly longer in iMCAS compared to cMCAS patients (p=0.02). ConclusionOverall prevalence of iMCAS was 4.4% in the entire cohort, which indicates that iMCAS is an uncommon condition. Screening suspected patients for the three diagnostic criteria and performing a comprehensive allergy work-up including laboratory tests and ultrasensitive mutation analysis of KIT D816V followed by applying recommended diagnostic algorithms is crucial for the diagnosis of iMCAS.

Defining hereditary alpha-tryptasemia as a risk/modifying factor for anaphylaxis: are we there yet?

Hereditary α-tryptasemia (HαT) is a common autosomal dominant genetic trait with variable penetrance associated with increased serum baseline tryptase (SBT) levels. Clinical manifestations may range from an absence of symptoms to overtly severe and recurrent anaphylaxis. Symptoms have been claimed to result from excessive activation of EGF-like module-containing mucin-like hormone receptor-like 2 (EMR2) and protease-activated receptor 2 (PAR-2) receptors by α/β-tryptase heterotetramers. Herein, we aimed to review the evidence on whether HαT can be considered a hereditary risk factor or a modifying factor for anaphylaxis.Increased SBT levels have been linked to an increased risk of anaphylaxis. Likewise, recent studies have shown that HαT might be associated with a higher risk of developing anaphylaxis and more severe anaphylaxis. The same has also been shown for patients with clonal mast cell disorders, in whom the co-existence of HαT might lead to a greater propensity for severe, potentially life-threatening anaphylaxis. However, studies leading to such conclusions are generally limited in sample size, while other studies have shown opposing results. As such, further studies investigating the potential association of HαT with anaphylaxis caused by different triggers, and different severity grades, in both patients with clonal mast cell activation syndromes and the general population are still needed.

Bone and Cytokine Markers Associated With Bone Disease in Systemic Mastocytosis

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. 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. 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. 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. 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.

Non-steroidal anti-inflammatory drug-induced anaphylaxis infrequent in 388 patients with mastocytosis: A two-center retrospective cohort study.

Anaphylaxis is a well-known feature of mastocytosis, particularly in relation to hymenoptera venom stings. It is therefore hypothesized that mastocytosis patients may also be predisposed to severe hypersensitivity reactions to certain medications including non-steroidal anti-inflammatory drugs (NSAIDs). For this reason, these patients are usually discouraged from using these drugs. The current study aimed to determine the prevalence and evaluate the severity of NSAID-related hypersensitivity reactions among patients with mastocytosis. A retrospective study was conducted among a total of 388 (≥18 years old) consecutive patients from two independent European mastocytosis centers, in Sweden and Italy. Patients underwent a thorough allergy work-up where self-reported NSAID-hypersensitivity reactions were re-evaluated by an allergist in the first cohort (202 patients) and results were validated in the second cohort (186 patients). Overall frequency of NSAID-hypersensitivity was 11.3% in the total study cohort. Most patients reacted with cutaneous symptoms (89%), whereas severe hypersensitivity reactions were infrequent with only 11 patients (2.8%) experiencing anaphylaxis. All NSAID-related hypersensitivity reactions had occurred before mastocytosis was diagnosed. There was no difference between the groups regarding gender, baseline tryptase levels or presence of atopy, asthma/rhinitis. Our study indicates an approximate 4-fold increased prevalence of NSAID hypersensitivity among mastocytosis patients compared to the general population. However, most NSAID reactions were limited to the skin as the prevalence of overall anaphylaxis was infrequent. Our results support that mastocytosis patients with a known tolerance to NSAIDs can continue using these medications without special precautions, whereas those with a prior reaction to NSAIDs should undergo thorough allergy work-up, including drug challenges.

A DISCUSSION OF THE REFRACTORY PERIOD IN VENOM IMMUNOTHERAPY

<h3>Introduction</h3> Refractory periods are inconsistently observed phenomena that follow hypersensitivity reactions wherein a reaction is followed by a period of time during which additional reactions cannot be triggered. We discuss a case that challenges this theory. <h3>Case Description</h3> A 56-year-old male with Diabetes Mellitus II, Hypertension, and HIV presented with history of two prior episodes of fire ant stings leading to anaphylaxis. His baseline tryptase level was 6.1 ug/mL and sIgE to fire ant (Solenopsis invicta) was 42.3 kU/L. The patient completed the immunotherapy ultrarush induction protocol using 1:100wt/v Solenopsis invicta whole body extract (WBE) as the maintenance (1:1v/v) concentration. One hundred minutes after completion of the protocol, he developed throat tightness, nasal congestion, diffuse pruritus, and urticaria. Symptoms resolved after two injections of 0.5mL intramuscular epinephrine. One week later, he received 0.2 mL of 1:1 v/v and developed stridor, productive cough, and injected sclera 30 minutes after injection. Symptoms resolved with intramuscular epinephrine. The following week, he received another injection (decreased to 0.5 mL of 1:10 v/v) without incident. He continued weekly buildup to maintenance dose and subsequent monthly injections without additional reactions. <h3>Discussion</h3> In this case, completion of an ultrarush induction protocol and anaphylaxis failed to result in a refractory period of unresponsiveness, allowing for a second anaphylactic reaction to S. invicta WBE one week after desensitization should have been achieved. Additional research is needed to reliably identify patients experiencing a refractory period following an anaphylactic event. This would improve the accuracy of allergy testing and has the potential to make desensitization safer.

EFFICACY OF CONCURRENT TREATMENT WITH OMALIZUMAB IN A PATIENT WITH ANAPHYLAXIS TO VENOM IMMUNOTHERAPY

<h3>Introduction</h3> Anaphylaxis is a life-threatening IgE mediated systemic reaction. Hymenoptera stings induced reactions are estimated 3.3% in the United States. Venom immunotherapy (VIT) is a well-established treatment modality with ≥ 98% protection rate. We describe a case of anaphylaxis with profound hypotension on standard maintenance dosing of VIT, successfully treated with a higher dosing of VIT concurrently with omalizumab. <h3>Case Description</h3> 55-year-old male with history of asthma who presented due to hymenoptera sting anaphylaxis, which resulted in severe hypotension. Venom skin testing revealed positive yellow Jacket, honeybee and wasp. Baseline tryptase level was normal. Patient was started on VIT to mixed vespid, honeybee, and wasp with standard maintenance dose (100 microgram). Several weeks after achieving maintenance VIT dose, he developed anaphylactic reaction with facial flushing, severe hypotension & tachycardia. Standardized treatment for anaphylaxis was administered with improvement. Later, screening for occult mastocytosis with c-KIT mutation was negative. VIT build was restarted concurrently with omalizumab, and higher recommended maintenance dose of 200 microgram was achieved. On six months follow-up, he continued to tolerate the VIT. <h3>Discussion</h3> This case illustrates a promising treatment for patients at risk for hymenoptera VIT anaphylaxis. Our patient did not confer protection at recommended maintenance VIT dose of 100 microgram. Concurrent treatment with omalizumab and VIT was effective in preventing further anaphylaxis and achieving higher recommended maintenance VIT dosage in our patient. This treatment strategy may mitigate the risk of recurrent anaphylaxis during VIT, however long-term effectiveness and duration is yet to be determined.

A CASE OF HEREDITARY ALPHA TRYPTASEMIA MASQUERADING AS CHEMOTHERAPY HYPERSENSITIVITY REACTION

<h3>Introduction</h3> Hereditary alpha-tryptasemia (HaT) is an established modifier of anaphylaxis and mast cell mediator-associated symptoms. We present a case of HaT diagnosed after hypersensitivity reactions to chemotherapeutic agents treated with a prolonged desensitization protocol. <h3>Case Description</h3> A 56-year-old female with high-grade serous ovarian cancer presented after a hypersensitivity reaction to paclitaxel with an event tryptase of 87.2 ng/mL. She subsequently tolerated nab-paclitaxel and was transitioned to liposomal doxorubicin therapy. During the first infusion of liposomal doxorubicin, she developed gastrointestinal pain, flushing, and hypotension. Despite re-administration via 3-bag, 13-step desensitization, the patient again experienced similar symptoms. A baseline tryptase level was elevated at >30 ng/mL. She had no symptoms in between anaphylactic events, and had previously experienced multiple insect stings without adverse reaction. A bone marrow biopsy was negative for mastocytosis. Genetic testing showed extra-allelic copies of TPSAB1 consistent with HaT. She subsequently tolerated liposomal doxorubicin via slowed 4-bag, 17-step desensitization protocol and seven days of premedication with cetirizine, cromolyn, montelukast, and famotidine. After multiple cycles, her imaging showed improvement in peritoneal carcinomatosis. However, she also developed a new reaction to iodinated contrast media which she had previously tolerated. Despite a similar premedication regimen and use of non-ionic, iso-osmolar contrast media, she experienced recurrent contrast-induced anaphylaxis. Omalizumab is being pursued as a potential treatment for preventing anaphylaxis. <h3>Discussion</h3> This patient with hypersensitivity reactions to chemotherapy agents and iodinated contrast was found to have underlying HaT. The use of a slowed desensitization protocol and multi-day premedication regimen allowed for treatment of her malignancy.

AN UNUSUAL TRANSITION FROM CUTANEOUS TO SYSTEMIC MASTOCYTOSIS IN A PEDIATRIC PATIENT

<h3>Introduction</h3> Cutaneous mastocytosis (CM) occurs when abnormal mast cells accumulate in the skin whereas in systemic mastocytosis (SM), accumulation also occurs in organs such as the gastrointestinal tract, liver, spleen, or bone marrow. A transition from CM to SM has not been previously described in the pediatric population. <h3>Case Description</h3> An eight-month-old female presented with a three-month history of diffuse hyperpigmented macules over her entire body and was found to have a normal tryptase level of 7 ug/L, consistent with a diagnosis of CM. At 2.5 years of age, cutaneous lesions significantly increased prompting repeat tryptase level, which was elevated at 34 ug/L. Subsequent testing for serum KIT D816V mutation was negative. Over the next six months, tryptase levels continued to increase (43 and 46 ug/L), raising concern for systemic involvement. At 3 years of age, repeat serum KIT D816V mutation testing resulted positive, prompting performance of a bone marrow biopsy. Bone marrow analysis revealed mildly hypocellular marrow, trilineage hematopoiesis, and aberrant mast cell clusters (>15 cells per aggregate expressing KIT, CD2, and CD25 on flow cytometry) without evidence of malignancy. These findings diagnosed SM. The patient has been treated with an antihistamine regimen, carries an epinephrine autoinjector, and has been advised on avoidance of potential triggers of mast cell degranulation. <h3>Discussion</h3> A diagnosis of CM in a pediatric patient does not rule out the possibility of transformation to SM. Despite normal baseline tryptase levels, minimal mediator symptoms, and lack of organomegaly, frequent and watchful monitoring may be warranted in some patients.

Nontryptase Urinary and Hematologic Biomarkers of Mast Cell Expansion and Mast Cell Activation: Status 2022

Quantitation of urinary metabolites of histamine, prostaglandin D2, and leukotriene E4 can fill the gap in our current efforts to improve diagnosis and management of symptomatic patients with systemic mastocytosis, and/or mast cell activation syndrome, In addition, patients symptomatic due to mast cell activation but who do not meetall the criteria for mast cell activation syndrome can have elevated baseline mediator metabolites. Serum tryptase levels have been the workhorse in diagnosing these disorders, but it has several drawbacks including the need to obtain acute and baseline samples, which require 2 visits to health care facilities and 2 venipunctures. Recently, increased baseline tryptase level has been reported in hereditary alpha tryptasemia, complicating diagnostic possibilities of an increased baseline tryptase level. Furthermore, no treatment can specifically be targeted at tryptase itself. In contrast, the finding of 1 or more elevated urinary levels of histamine, prostaglandin D2, and/or leukotriene E4 metabolites (1) greatly narrows diagnostic possibilities for causes of symptoms; (2) informs the practitioner what specific metabolic pathways are involved; and (3) targets the treatment in a specific, direct fashion. As a bonus, baseline spot/random urine samples can be obtained by the patients themselves and repeated at exactly the correct time when symptoms occur.

Biomarqueurs et tests fonctionnels dans l’hypersensibilité immédiate aux vaccins ARNm dirigés contre le SARS-CoV-2

Hypersensitivity to mRNA vaccines directed against SARS-CoV-2 are rare. They may be related to an IgE-dependent mechanism involving PEG contained in vaccines in the form of liposomes. Direct activation of the classical complement pathway (CARPA) has also been strongly suspected. In addition to skin tests, biomarkers have been proposed: anti-PEG antibodies, determination of anaphylatoxins C5a and C3a, or soluble complex C5b-9. Anti-PEG antibodies can be measured by non-standardized in house methods; their presence in post-vaccination reactions against SARS-CoV2 has not been confirmed by all the studies as well as for complement proteins. Mast cell mediators (histamine and tryptase) could rarely be assayed at the time of reaction and their increase is inconstant depending on studies. A slightly elevated baseline tryptase level in some patients suggests that hyper-alphatryptasemia might be involved. A basophil activation test (BAT) can be performed but the results are still preliminary depending on the allergens used: PEG, PEG in the form of liposomes or vaccine itself. The lack of positivity of skin tests in some patients even though basophils are able to be activated in the presence of the same allergen confirms the hypothesis in this case of a possible non-IgE-dependent phenomenon. In conclusion, concerning the exploration of immediate reactions to mRNA vaccines directed against SARS-CoV-2, the place of biological markers requires additional studies in order to better identify the actors and mechanisms involved.

COVID-19 vaccination in the setting of mastocytosis—Pfizer-BioNTech mRNA vaccine is safe and well tolerated

COVID-19 vaccination in the setting of mastocytosis—Pfizer-BioNTech mRNA vaccine is safe and well tolerated

Impact of mental health on disease activity in mastocytosis during COVID-19 pandemic

BackgroundMast cell-related symptoms might be influenced by mental health status in mastocytosis. In this study, we aimed to investigate the influence of mental health problems developed during the COVID-19 pandemic on the course of mastocytosis. MethodsMental health status in 60 adult patients with mastocytosis was prospectively evaluated with the total Depression-Anxiety-Stress Scale (tDASS-21) and Fear of COVID-19 Scale (FCV–19S) in the lockdown period (LP) and the return to normal period (RTNP) during the pandemic. The disease course was assessed from emergency and outpatient medical reports, including Scoring Mastocytosis (SCORMA) index and serum baseline tryptase levels, by telephone interviews and clinical visits. ResultsThe mean FCV-19S and median tDASS-21 scores were significantly higher in LP than RTNP (p < 0.001) and there was a positive correlation between FCV-19S and tDASS-21 in LP (r = 0.820, p < 0.001) and in RTNP (r = 0.572 p= <0.001). Disease-related symptoms including skin lesions, flushing and anaphylaxis attacks increased in 22 patients in LP, and in this group, mean FCV-19S and median tDASS-21 were higher than those without symptom exacerbation (p < 0.001). During the study period, four (6.7%) patients who experienced COVID-19 recovered without any requirement for hospitalization and had not experienced symptom exacerbation. ConclusionsFear of COVID-19 can be a reason for mental health changes, including depression, anxiety and stress which may further increase mast cell-related symptoms. Therefore, psychological support is important to control the severity of mast cell-related symptoms in mastocytosis during a pandemic.

Routine KIT p.D816V screening identifies clonal mast cell disease in patients with Hymenoptera allergy regularly missed using baseline tryptase levels alone

Clonal mast cell disorders and elevated basalserum tryptase (BST) levels with unknown cause(s)are associated with severe Hymenoptera venom-triggered anaphylaxis (HVA). However, some individuals with clonal disease have a normal BST level (<11.4 ng/mL). Our aim was to evaluate whether screening for KIT p.D816V in the blood is a useful clinical tool to risk-stratify patients with venom allergy. We prospectively recruited 374 patients with Hymenoptera allergy and no overt signs of mastocytosis who were referred to our center during the years 2018 and 2019. KIT p.D816V was determined in their peripheral blood by quantitative PCR, and tryptase genotyping was performed by droplet digital PCR. In all, 351 patients (93.9%) had normal levels of BST, and KIT p.D816V was detected in 8% of patients (28 of 351), predominantly in patients with the most severe Mueller grade IV anaphylaxis (18.2% [24 of 132] vs 1.8% in patients with lower grades [4 of 88 with grade III and 0 of 131 with other grades]; P< .001). In grade IV patients with a normal BST level, KIT p.D816V was associated with more severe symptoms, including a significantly higher frequency of loss of consciousness (58.3% [14 of 24] vs 34.3% [37 of 108]; P= .03) and absence of skin symptoms (41.7% [10 of 24] vs 15.7% [17 of 108]; P= .004). Among patients with a normal BST level, KIT p.D816V (OR= 10.25 [95% CI= 3.75-36.14]; P< .0001) was the major risk factor associated with severe HVA. Hereditary α-tryptasemia (HαT) due to increased germline copies of TPSAB1 encoding α-tryptase was the most common cause (65.2% [15 of 23]) of elevated BST level in patients with HVA, and together with KIT p.D816V, it accounted for 90% of BST level elevations (20 of 23) in patients with HVA. These results indicate that routine KIT p.D816V screening identifies clonal disease in high-risk patients withHVA who are regularly missed when BST level is used alone.