Original Article
Low Frequency of IgE-Mediated Food Hypersensitivity in Mastocytosis

https://doi.org/10.1016/j.jaip.2020.05.044Get rights and content

Background

Patients with mastocytosis have an increased risk for severe anaphylaxis, particularly to Hymenoptera venoms. These patients may also develop more often systemic hypersensitivity reactions to certain foods. However, this issue has not been systematically investigated.

Objective

To determine prevalence and severity of food hypersensitivity (FH) reactions among patients with clonal mast cell disorders (CMDs).

Methods

A retrospective study was conducted among 204 (age ≥18 years) consecutive patients who presented with confirmed CMD (170 with mastocytosis and 34 with monoclonal mast cell activation syndrome). All patients underwent thorough allergy workup where self-reported FH reactions were evaluated.

Results

The prevalence of self-reported FH was 20.6%. The frequency of immunologically mediated reactions was uncommon, because only 3.4% were confirmed by relevant history and IgE sensitization. Among patients with FH, 5 had severe anaphylaxis corresponding to an overall prevalence of 2.5%. Most symptoms were restricted to skin (86%), followed by gastrointestinal tract symptoms (45%)—similar to symptoms that occur in patients with mastocytosis also without food intake. Nuts, spicy foods, seafood, and alcohol were the most common incriminated elicitors. There was no significant difference between the groups regarding age, sex, atopic status, or IgE levels.

Conclusions

Anaphylaxis from foods in mastocytosis does exist and is severe, although foods are less frequent elicitors than insect venoms. Furthermore, the frequency of overall FH reactions is comparable with that in the general population and most reactions are mild, nonallergic, and unconfirmed. Consequently, our results do not support the elimination of any diet in patients with CMD without a history of FH.

Introduction

Food hypersensitivity (FH) is commonly suspected in adults. Although food allergy (FA) involves a specific, mostly IgE-mediated, immune response to a given food, exceptionally non–IgE-mediated FH also exists.1 Diagnostic procedures include clinical history, allergy tests such as skin prick test (SPT), specific IgE measurement, and oral food challenges.1 Furthermore, severe reactions many hours after ingestion of mammalian food is a novel type of FA, in which IgE antibodies are directed against the carbohydrate galactose-α-1,3-galactose (α-Gal).2 In addition, oral allergy syndrome (OAS) occurs when IgE antibodies against aeroallergens cross-react with certain food proteins, such as birch-fruit, mugwort-celery-spice, and ragweed-melon-banana.3

The general population frequently overestimates the prevalence of “true” FH in self-reports, because FH can be confirmed by clinically relevant sensitization or by challenge only in a fraction of patients.1,4,5 The estimated FH prevalence in Europe is approximately 17%,4 and it is suggested to have increased during the last 2 decades.6 In adults, foods as elicitors of anaphylaxis have not been as excessively studied as in children, in whom more than 80% of all anaphylaxis cases are attributed to foods.7 In Europe, foods have been reported to cause 8% to 17% of all anaphylaxis cases in adults,8, 9, 10 whereas food-induced anaphylaxis (FIA) was estimated to be the trigger in 32% of adults in an American survey,11 emphasizing the influence of geographical locations. Risk factors for FIA include an existing FA, age, sex, presence of atopic diseases, and possibly low levels of vitamin D.7,12

Anaphylaxis is a well-known feature in patients with clonal mast cell disorders (CMDs), which comprise mastocytosis and monoclonal mast cell activation syndrome (MMAS).13, 14, 15 Mast cells (MCs) of these patients carry an activating gain-of-function mutation (D816V) in the tyrosine kinase receptor KIT and/or immunophenotypically aberrant MCs expressing CD25.16 Mastocytosis can be systemic (SM) or cutaneous. In patients with MMAS, the World Health Organization criteria for SM are not fully met.16 Because of underlying intrinsic MC defects and MC dysfunction, MC mediator release may be increased.17 Anaphylaxis in these patients often presents with severe cardiovascular symptoms including syncope.15,18, 19, 20 Anecdotal cases of FIA in patients with mastocytosis exist14,21, 22, 23; however, without doubt, Hymenoptera venoms constitute the most common cause of anaphylaxis.15,24

Widespread beliefs in the lay press and within patient support groups encourage patients with mastocytosis to avoid certain foods. Particularly, it has been suggested that biogenic amines and histamine-releasing foods may cause severe, allergy-like symptoms. Because no study has yet systematically explored FH reactions in patients with mastocytosis, it is largely unknown as to what extent these patients are affected by food elicitors.25 Consequently, there is an apparent need for more data on FH reactions. Here, we sought to evaluate the prevalence and clinical features of FH reactions in a large cohort of patients with CMD. Also, we analyzed the food elicitors and explored whether the occurrence and severity of reactions were influenced by certain risk factors, such as serum baseline tryptase (sBT) levels, total IgE levels, atopic status/disease, sex, or type of CMD.

Section snippets

Patients and clinical procedures

The Mastocytosis Center Karolinska was established in 2006 at Karolinska University Hospital and Karolinska Institute in Stockholm, Sweden, and receives referrals from the entire country. As of March 31, 2019, 416 consecutive adult patients had been referred to the center because of suspected MC disorders. In accordance with the World Health Organization criteria,16,26 the diagnostic workup included histopathologic evaluation of bone marrow, flow cytometry, KIT D816V mutation analysis, and

Patient characteristics

In the cohort, 53% were women (n = 109) and the median age at diagnosis was 52 years (range, 18-84 years) (Table I). Median sBT levels were 24 ng/mL (range, 2.8-650 ng/mL), and total IgE levels were 16 kU/L (range, 1-1600 kU/L). Almost one-third of the patients showed the presence of atopy and atopic diseases, such as asthma or rhinoconjunctivitis (29% and 28%, respectively). Although 50% of the included patients (n = 102) had suffered at least 1 episode of anaphylaxis of any type, the overall

Discussion

This is the first systematic study on FH in patients with CMD showing that 1 in 5 adults with CMD reported FH reactions. This is comparable with the prevalence in the general population. Although true FA does exist (3.4%), most reactions were nonallergic, mild, limited to skin or the GI tract, and similar to symptoms that were commonly reported by patients with mastocytosis unrelated to food ingestion. Furthermore, FIA occurs more severely in patients with mastocytosis and is not always easy to

Conclusions

The lack of well-designed studies investigating the role of FH reactions in adult patients with CMD made it difficult to adequately advise patients. However, the present study, for the first time, systematically shows that although rare, severe FIA exists in patients with mastocytosis and may become dangerous because of the inherent MC dysfunction. Nevertheless, the prevalence of FH in patients with CMD is comparable with that in the general adult population. The frequency of immunologically

Acknowledgments

We thank all the patients for their participation.

Authors contributed as follows: J. Jarkvist took active part in the acquisition, analysis and interpretation of the data, and drafting and revising of the manuscript. K. Brockow analyzed and interpreted the data and revised the manuscript critically. T. Gülen conceptualized and designed the study; collected, analyzed and interpreted the data; and wrote and revised the manuscript.

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    This study was supported by grants from the Konsul TH C Bergh Foundation, Sweden, and through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet.

    Conflicts of interest: T. Gülen has received lecture fees from Thermo Fisher Scientific and Shire. The rest of the authors declare that they have no relevant conflicts of interest.

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