Alpha-gal Syndrome Research Timeline 

2007

van Nunen et al. [1]

25

Ixodes holocyclus

Australia

Described occurrence in adults

Described association with previous tick bites

Described large local reactions at the site of the tick bites

Described frequency of beef>lamb>pork>game skin prick tests

Used raw organic meats for skin prick tests

Described patients with multiple meat sensitisations

Described skin prick test positivity with kangaroo, goat, venison and rabbit

Described specific immunoglobulin E presence for beef, mutton and pork

2008

Commins et al. [5]

10

–

USA

Described alphagal as the epitope

Documented the typically delayed nature of the response

Confirmed use of raw organic meats suitable for skin prick tests

Documented a lack of immunoglobulin E specific for poultry and fish

Described serum immunoglobulin E specific for cat, dog and cow’s milk (similar levels of cat and dog)

Determined the cat-specific immunoglobulin E was not directed against Fel d1

2008

Mulllins [6]

16

–

Australia

Described gelatine as an allergen in mammalian meat allergy

Documented anaphylaxis due to gelatine-containing colloid in red meat allergy

Documented oral gelatine allergic reactions in mammalian meat-allergic patients

Noted intradermal testing required to detect sensitisation

2009

Commins et al. [7]

24

Amblyomma genus

USA

Confirmed alphagal as the epitope

Noted only a 2- to 3-year history since onset of allergic reactions

Noted symptoms occurred after cow’s milk in almost half

Noted ability of patients to tolerate small amounts of meat

Previous tick bite history noted in great majority

Quantitated amount of alphagal in fresh and skin prick test reagents

Reported exercise as a co-factor within 2 h after beef

Documented fewer or lack of reactions with avoidance

Demonstrated no difference between commercial and conventional prick-prick tests

Demonstrated superior results with fresh meat extracts

2009

van Nunen et al. [2]

25

Ixodes holocyclus

Australia

Additional information: no patient with mammalian meat allergy had tick anaphylaxis

Confirmed delayed reactions most common

2009

Jacquenet et al. [20]

Renaudin et al. [21]

2

6

–

France

Confirmed alphagal as the epitope and occurrence of delayed urticarial and angioedema

Used cetuximab intradermal testing

Showed raw meat (beef, rabbit) skin prick test gave a larger result

Described offal skin prick test positivity

Added horse to list of mammalian meats

Noted allergic reaction did not invariably occur after ingestion

Noted low levels of meat-specific immunoglobulin E may explain above

2011

Nunez et al. [24]

5

Ixodes ricinus

Spain

Documented tick bites in mammalian meat allergy in Europe

Documented alphagal positivity in Europeans with mammalian meat allergy

Documented use of cetuximab as a skin prick test agent

Verified utility of fresh, raw meat extracts for a skin prick test

2012

Sekiya et al. [30]

1

–

Japan

Reported a case of mammalian meat anaphylaxis after tick bite

Recorded a mammalian meat-allergic patient who also had anaphylaxis to cow’s milk (beef had also provoked anaphylaxis)

Cetuximab-specific immunoglobulin E elevated

Confirmed the diagnosis of delayed mammalian meat anaphylaxis by open oral challenge with pork

2012

Morisset et al. [22•]

14

–

France

Documented reactions to offal in mammalian meat allergy

Challenge confirmation obtained in a small number of patients

Confirmed exercise as a co-factor

Documented alcohol as the most common co-factor

Demonstrated offal had a higher concentration of alphagal

Demonstrated co-factors likely to bring forward reactions

2012

Mullins et al. [11]

40

Ixodes holocyclus

Australia

Majority of patients co-sensitised to mammalian meat and gelatine

Recorded clinical reactivity in mammalian meat allergy to both intravenous and oral gelatine

Noted gelatine allergy may be the initial presentation of mammalian meat allergy

Reported a small number of patients with gelatine tests positive and mammalian meat tests negative who reacted to gelatine challenge and who remained free of anaphylaxis avoiding meat and gelatine

Documented alphagal presence in gelatine and bovine products

2013

Caponetto et al. [25•]

21

Ixodes ricinus

Germany

Confirmed persistent reactions may occur at tick bite site

Confirmed foods containing gelatine can provoke anaphylaxis in mammalian meat allergy

Confirmed that intra-cutaneous testing may be required to detect gelatine sensitisation

Reported a reaction to ingested gelatine delayed by 10 h

Demonstrated variability in severity between meats and offal

Confirmed exercise as a co-factor

Noted that repeatedly elevated tryptase levels in the absence of mammalian meat ingestion became normal after meticulous exclusion of dietary gelatine as well as mammalian meat

2012

Lee et al. [31, 32]

1

–

Korea

Confirmation of a case of delayed mammalian meat anaphylaxis (beef and pork) with cetuximab intradermal testing

2013

Hamsten et al. [29••]

5

Ixodes ricinus

Sweden

Confirmed alphagal-specific immunoglobulin E presence in mammalian meat allergy

Confirmed beef-specific immunoglobulin E presence

2013

Morisset et al. [23•]

1

Ixodes ricinus

France

Reported a case of cow’s milk product anaphylaxis (yoghurt and cheese) in mammalian meat allergy

Documented cow’s milk product reactions occurred after mammalian meat avoidance and following a further tick bite

2013

Hamsten et al. [9]

39

Ixodes ricinus

Sweden

Documented moose as another mammalian meat capable of provoking mammalian meat allergy

2014

Michel et al. [27]

3

–

Switzerland

Confirmed utility of cetuximab skin testing

Examined basophil activation test utility

2014

Wickner and Commins [10]

4

Amblyomma cajennense

Central America

Documented delayed mammalian meat allergy and alphagal positivity

Described another tick species

Represents a potential model for the natural history of the condition