Clonal mast cell disorders in patients with severe Hymenoptera venom allergy and normal serum tryptase levels

Zanotti, Roberta; Lombardo, Carla; Passalacqua, Giovanni; Caimmi, Cristian; Bonifacio, Massimiliano; Matteis, Giovanna De; Perbellini, Omar; Rossini, Maurizio; Schena, Donatella; Busa, Moira; Marcotulli, M.; Bilò, Maria Beatrice; Franchini, Maurizio; Marchi, G.; Simioni, Livio; Bonadonna, Patrizia

doi:10.1016/j.jaci.2014.11.035

Cited by 107 publications

(66 citation statements)

References 17 publications

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“…However, it must be stressed that in light of the recent reports, mastocyte disorders may also be suspected in patients presenting with a SAR with hypotension and showing no skin symptoms (urticaria, angioedema) irrespective of tryptase levels. 31,32 In contrast, in patients with extremely high tryptase levels (above 191 ng/ml) and patients with an aggressive form of SM, severe systemic HVA symptoms are rare.…”

Section: Tablementioning

confidence: 99%

Insect sting allergy in adults: key messages for clinicians

Nittner-Marszalska¹,

Cichocka‐Jarosz²

2015

Polish Archives of Internal Medicine

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In most affected persons, a Hymenoptera sting results in local itching and mild induration. There are some individuals, however, who additionally respond to a sting by developing sensitization manifested by the presence of venom-specific immunoglobulin E (IgE) antibodies (vsIgE) to various components of insect venoms (in honeybee venom, 12 allergens have been identified so far: Api m1 -Api m 12; in wasp venom, 5 allergens have been identified: Vesp v 1, V v 2, Vesp v 3, Vesp v5, and Ves v 6). 2 Venom sensitization is the key factor for but is not synonymous with venom allergy. Sensitization to Hymenoptera venoms may be asymptomatic (hypersensitivity not clinically relevant) or symptomatic defined as Hymenoptera--venom allergy (HVA). The asymptomatic sensitization is common and found in 9.3% to 40.7% of the general population and in 30% to 60% of beekeepers (which reflects the effect of exposition toThe occurrence of Hymenoptera-venom allergy Allergic reactions to insect bites result most frequently from stings of flying insects of the Hymenoptera order. From among over 100 000 species of Hymenoptera, the ones mainly responsible for sting reactions are usually honeybee (Apis mellifera) as well as wasps and hornets (eg, Vespula germanica, V. vulgaris, V. rufa, Vespae sp.). However, potential perpetrators of Hymenoptera allegry are diverse and vary with geography. In southern Europe, there are paper wasps (Polistinae subfamilies); in the United States, there are fire ants (Solenopsis invicta); and in Australia, there are Jack jumper ants (Myrmecia pilosula) that seem to cause more problems. A large number of Hymenoptera species, their ways of feeding, and their aggressive defense behavior result in as many as 56.6% to 94.5% of people experiencing at least 1 sting in their lives. ABSTRACTDuring their lifetime, 94.5% of people are stung by wasps, honeybees, hornets, or bumble-bees (order Hymenoptera). After a sting, most people show typical local symptoms, 5% to 15% develop local allergic reactions, and 3% to 8.9%-systemic allergic reactions (SARs), which may be potentially life-threatening in about 10% of them. In mild forms of Hymenoptera-venom allergy (HVA), the leading symptoms are urticaria and edema (grades I and II, respectively, according to the Mueller classification). Severe SARs are classified as grade III (respiratory symptoms) and IV (cardiovascular symptoms). Rare manifestations of HVA are Kounis syndrome and takotsubo cardiomyopathy. All patients after an SAR require standard (skin test, IgE, tryptase) or comprehensive (component diagnosis, basophil activation test) allergy testing. All patients with severe systemic symptoms (hypertension, disturbances in consciousness) should be tested for mastocytosis. Additionally, a relationship was found between the severity of HVA symptoms and intake of angiotensin-converting enzyme inhibitors (ACEIs). There is a similar concern, although less well-documented, about the use of β-blockers. Patients with HVA who have experienced a SAR are potential candidates for ...

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Section: Tablementioning

confidence: 99%

Insect sting allergy in adults: key messages for clinicians

Nittner-Marszalska¹,

Cichocka‐Jarosz²

2015

Polish Archives of Internal Medicine

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“…The frequent absence of urticaria/angioedema during severe, venom‐induced anaphylaxis has been attributed to either counter‐regulatory release of endogenous epinephrine or preferential activation of cardiac mast cells . The complete lack of cutaneous symptoms, or flushing rather than urticaria/angioedema, is associated with increased tryptase levels and was recently suggested to be an even stronger predictor of mast cell clonality than tryptase elevation itself in venom‐allergic patients with severe, hypotensive sting reactions . The REMA score as proposed by the Red Española de Mastocitosis (Spanish Network on Mastocytosis) for screening patients for the necessity of bone marrow biopsy accordingly includes the absence of urticaria/angioedema during anaphylaxis as a predictor of bone marrow mast cell clonality along with male sex, hypotensive shock, and tryptase elevation >25 ng/mL …”

Section: Observations From Previous Sting Reactionsmentioning

confidence: 99%

Risk factors and indicators of severe systemic insect sting reactions

Stoevesandt

Sturm

Bonadonna

et al. 2019

Allergy

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Hymenoptera venom allergy ranks among the top three causes of anaphylaxis worldwide, and approximately one‐quarter of sting‐induced reactions are classified as severe. Fatal sting reactions are exceedingly rare, but certain factors may entail a considerably higher risk. Delayed administration of epinephrine and upright posture are situational risk factors which may determine an unfavorable outcome of the acute anaphylactic episode and should be addressed during individual patient education. Systemic mastocytosis and senior age are major, unmodifiable long‐term risk factors and thus reinforce the indication for venom immunotherapy. Vespid venom allergy and male sex likewise augment the risk of severe or even fatal reactions. Further studies are required to assess the impact of specific cardiovascular comorbidities. Available data regarding potential effects of beta‐blockers and/or ACE inhibitors in coexisting venom allergy are inconclusive and do not justify recommendations to discontinue guideline‐directed antihypertensive treatment. The absence of urticaria/angioedema during sting‐induced anaphylaxis is indicative of a severe reaction, serum tryptase elevation, and mast cell clonality. Determination of basal serum tryptase levels is an established diagnostic tool for risk assessment in Hymenoptera venom‐allergic patients. Measurement of platelet‐activating factor acetylhydrolase activity represents a complementary approach but is not available for routine diagnostic use.

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“…Clonal mast cell activation syndrome is considered a risk factor both for experiencing SR in VIT and for severe and fatal reactions with a subsequent sting after interrupting treatment [49,68,69]. However, in the absence of mastocytosis, the association between BST and lack of efficacy of VIT is controversial.…”

Section: Clonal Mast Cell Activation Syndromementioning

confidence: 99%

Key Issues in Hymenoptera Venom Allergy: An Update

Alfaya

Soriano-Gomis

Mera

et al. 2017

J Investig Allergol Clin Immunol

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In this review, the Hymenoptera Allergy Committee of the SEAIC analyzes the most recent scientific literature addressing problems related to the diagnosis of hymenoptera allergy and to management of venom immunotherapy. Molecular diagnosis and molecular risk profiles are the key areas addressed. The appearance of new species of hymenoptera that are potentially allergenic in Spain and the associated diagnostic and therapeutic problems are also described. Finally, we analyze the issue of mast cell activation syndrome closely related to hymenoptera allergy, which has become a new diagnostic challenge for allergists given its high prevalence in patients with venom anaphylaxis.

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Clonal mast cell disorders in patients with severe Hymenoptera venom allergy and normal serum tryptase levels

Abstract: The absence of urticaria or angioedema in severe reactions to Hymenoptera stings with hypotension might represent the most relevant factor in identifying patients with mastocytosis, regardless of their serum tryptase levels.

Cited by 107 publications

References 17 publications

Insect sting allergy in adults: key messages for clinicians

Insect sting allergy in adults: key messages for clinicians

Risk factors and indicators of severe systemic insect sting reactions

Key Issues in Hymenoptera Venom Allergy: An Update

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