Allergy to meats

INTRODUCTION — Meat allergy is uncommon in resource-abundant countries, despite relatively high levels of meat consumption [1]. Childhood meat allergy is usually associated with atopic dermatitis and outgrown during the first years of life. Meat allergy can also develop in adulthood.

The epidemiology, clinical manifestations, diagnosis, and natural history of allergy to meats will be discussed in this topic review. Fish and seafood allergies are mentioned briefly here and discussed in greater detail elsewhere. General issues related to food allergies are presented separately:

●(See "Seafood allergies: Fish and shellfish".)

●(See "Clinical manifestations of food allergy: An overview".)

●(See "History and physical examination in the patient with possible food allergy".)

●(See "Diagnostic evaluation of IgE-mediated food allergy".)

EPIDEMIOLOGY — Meat allergy is relatively uncommon, although the overall incidence and prevalence of allergies to meat in the general population are not known. Among patients with food allergies, meat allergy has been reported in approximately 3 to 15 percent of pediatric cases [2,3] and 3 percent of adult cases [4]. The low prevalence of meat allergy may be in part attributable to the fact that most meats are eaten in cooked forms, and cooking usually (not always) reduces the immunogenicity of allergens. (See 'Allergens' below.)

CAUSATIVE MEATS — The type of meats that cause allergy appear to be related to their prominence in the diet, and geographic variations are evident [5,6]. Overall, allergy to mammalian meats is more prevalent than allergy to poultry.

Beef is the most commonly reported allergy, with a prevalence of beef allergy ranging from 1.5 to 6.5 percent among children with atopic dermatitis or food allergies/intolerances [1,7,8]. However, the prevalence of beef allergy can be as high as 20 percent in children allergic to cow's milk [1]. (See 'Patterns of cross-reactivity' below.)

Allergic reactions to pork, lamb, rabbit, chicken, and turkey are also reported [9-11]. Case reports describe allergies to kangaroo meat in Australia, as well as seal and whale meats in Alaskan Native populations [12,13].

Risk factors — Risk factors for the development of allergy to meats have not been fully defined and may be different depending on the allergen to which the patient is sensitized:

●Growing evidence suggests that multiple tick bites may be a risk factor for allergy to nonprimate mammalian meats. (See 'The role of ticks in red meat allergy' below.)

●An association between blood groups A and O and sensitization to galactose-alpha-1,3-galactose (alpha-gal) has been noted [14,15].

●Children with atopic dermatitis or cow's milk allergy may be at increased risk, based on earlier epidemiologic studies [1,7].

●Patients with gelatin allergy may also be sensitized or clinically reactive to meats [16].

The allergens involved in meat allergy are discussed in more detail below. (See 'Allergens' below.)

The role of ticks in red meat allergy — In susceptible individuals, multiple tick bites appear to result in sensitization to the carbohydrate allergen alpha-gal, which is present in many mammalian meats [17]. (See 'Alpha-gal' below.)

Meat allergy caused by alpha-gal sensitization has been reported in several parts of the world, including the United States, Australia, Spain, Germany, Japan, and Sweden [18-21]. Alpha-gal is present in the gastrointestinal tract of at least one species of tick [22] and the saliva of others [23,24]. Many of the patients described have reported that allergic symptoms to meat ingestion began after a series of tick bites [25]. Thus, it is possible that some patients become sensitized as a result of tick bites. The tick species most often implicated in meat allergy have been Amblyomma americanum (ie, the lone star tick) (picture 1) in the Southeastern United States and other species (Ixodes ricinus, Ixodes holocyclus, Amblyomma cajennense, Amblyomma sculptum, and Haemaphysalis longicornis) in other parts of the world [22,26,27].

CLINICAL REACTIONS — Both immunoglobulin E (IgE) mediated and non-IgE-mediated forms of meat allergy have been described.

IgE-mediated reactions — IgE-mediated allergic reactions present with signs and symptoms caused by widespread activation of mast cells (table 1).

Variable presentations — IgE-mediated reactions can present in several different ways:

●Children with meat allergy often have atopic dermatitis and present with exacerbations of skin inflammation following ingestion of certain meats [28], although they can also develop classic IgE-mediated allergic symptoms, such as pruritus, urticaria, or even asthma [7]. (See "Role of allergy in atopic dermatitis (eczema)", section on 'Food allergies'.)

●In adults, skin symptoms are also common during allergic reactions to meat. One series of 10 patients with symptoms beginning in adulthood reported that the most common symptoms after meat and milk ingestion were cutaneous pruritus and/or urticaria (70 percent), followed by gastrointestinal symptoms (40 percent) [29]. Other responses included contact urticaria of the oral mucosa (oral allergy syndrome) and anaphylaxis. These 10 patients developed symptoms after ingestion, but not in response to contact or inhalational exposures. All 10 patients had specific IgE to one or more meats or milk upon serologic testing.

●IgE-mediated allergic reactions to meat caused by galactose-alpha-1,3-galactose (alpha-gal) present in a distinct manner, in that symptoms are relatively delayed in onset. In patients with convincing evidence of IgE-mediated allergy, reactions began as quickly as several minutes or as delayed as three to six hours after ingestion [18,19,30]. Patients may develop symptoms in the middle of the night after eating meat for dinner. This disparity in time to symptoms may be explained by the nature of the allergen (ie, protein versus carbohydrate). Whether a reaction occurs is highly variable from exposure to exposure, and cofactors such as alcohol and exercise appear to be important. (See 'Alpha-gal' below.)

Allergy to alpha-gal can also cause unusual reactions that are isolated to gastrointestinal distress and emesis, without other symptoms of anaphylaxis [31-34]. For unclear reasons, gastrointestinal reactions tend to begin sooner after meat ingestion (eg, 1.5 to 2 hours) and are more common in children [32].

Allergens — Limited information is available about the allergens responsible for IgE-mediated meat-allergic reactions [35]. Both protein and carbohydrate allergens have been identified.

Serum proteins — Serum albumins and immunoglobulins appear to be the primary allergenic proteins in beef and other mammalian meats [11,36]. Albumins have been implicated in allergies to beef, pork, lamb, and rabbit, as well as chicken [9-11,36,37]. The International Union of Immunological Societies lists just three meat proteins in its official listing of important food allergens. Two of bovine origin (a serum albumin, Bos d 6, and an immunoglobulin, Bos d 7) and one from chicken (serum albumin) [38]. (See "Food allergens: Clinical aspects of cross-reactivity" and "Molecular features of food allergens".)

Sequence homology between bovine serum albumin (BSA) and pig, sheep, and chicken serum albumins were 80, 92, and 44, respectively, supporting the clinical observation that individuals tend to react to mammalian meats or poultry but rarely both [39-41]. Cross-reactivity between beef and whey proteins from milk has been attributed to serum albumins and gamma-immunoglobulin [35]. (See 'Meats and other foods' below.)

The low prevalence of meat allergy may be in part attributable to the heat-labile properties of serum albumins and the fact that most meats are eaten in cooked forms.

Additional proteins in meat that may act as major and minor allergens have been identified [11-13,36,41-43]. As an example, denatured type I bovine collagen has been identified as the major allergenic component of bovine gelatin [44]. The clinical significance of some meat allergens is not known. These proteins are diverse and likely represent light chain immunoglobulins, heavy chain immunoglobulins, and muscle proteins, such as actin.

Alpha-gal — Although most known food allergens are proteins, carbohydrate epitopes, bound to either protein or lipid molecules, can also act as allergens. The carbohydrate moiety galactose-alpha-1,3-galactose (alpha-gal) is abundantly expressed on cells and tissues of all mammalian species except primate mammals (ie, humans, chimpanzees, and Old World monkeys). Patients sensitized to alpha-gal report delayed symptoms to a wide range of mammalian meats, especially beef, pork, and lamb [18]. They can also react to organ meats (ie, kidney), gelatins in foods and candies, and milk [16,45,46]. Patients with allergies to gelatins and milk can be sensitized to allergens other than alpha-gal and require further evaluation if mammalian meat is clearly tolerated.

The IgE response to alpha-gal has been found in both adults and children but most commonly presents in adults [47-50]. Patients may have urticaria, angioedema, or anaphylaxis, although some have isolated gastrointestinal symptoms (diarrhea, vomiting, cramping) accompanied by presyncope or syncope without urticaria or angioedema, a presentation that is more difficult to recognize as an allergic reaction [51]. The onset of symptoms caused by alpha-gal reactions is significantly later compared with typical IgE-mediated reactions, beginning two to eight hours after ingestion. Data from a United States national testing center documented increasing prevalence over the past two decades [52,53]. Similar patients have been reported in Europe, Asia, Scandinavia, South Africa, and Australia [15,19-21,25,54-58].

The delayed onset of symptoms may be related to binding of the alpha-gal allergen to lipids, which are absorbed more slowly and by different mechanisms compared with proteins. An in vitro model found that only alpha-gal bound to lipids was able to cross a monolayer of intestinal epithelial cells and activate basophils from a patient with alpha-gal allergy [59].

In addition to reacting to foods, patients sensitized to alpha-gal may also have reactions to the monoclonal antibody cetuximab, gelatin administered in vaccines [47,60], vaginal capsules [61], intravenous colloids [62], heparin [63], bovine or porcine heart valves [63], pancreatic enzymes [64], and possibly other hemostatic agents derived from animal products. Meat byproducts can also be added to foods as "natural flavorings."

●Cross-reactivity with the medication cetuximab is discussed below. (See 'Meats and monoclonal antibodies (cetuximab)' below.)

●Alpha-gal-related reactions to vaccines, heart valves, hemostatic agents, and colloids are discussed in more detail separately. (See "Allergic reactions to vaccines", section on 'Gelatin' and "Perioperative anaphylaxis: Clinical manifestations, etiology, and management", section on 'Role of alpha-gal allergy'.)

Role of cooking — Domestic or industrial processing can alter the allergenicity of foods by modifying or inactivating the epitopes for IgE binding. In most cases (not all), this results in no change [65] or decreased reactivity [1,30,36,39], and this is probably true for meat allergens as well. (See "Pathogenesis of food allergy" and "Molecular features of food allergens", section on 'Protein stability'.)

Other forms of processing, such as homogenization or freeze drying, can also alter allergenicity. A study of 12 children with clinically documented beef allergy found that all of the children reacted to home-cooked beef during oral challenges, and some of them reacted to heated BSA [66]. However, none reacted to either homogenized or freeze-dried beef (the industrial processes that are usually used in the production of baby foods). Homogenization and/or freeze drying have been shown to decrease the content of blood albumins and immunoglobulins (eg, the primary allergenic proteins) in meat. Digestion with pepsin was also shown to nearly eliminate allergenicity for most patients.

Eosinophilic esophagitis — Eosinophilic esophagitis (EoE) typically presents with symptoms of gastroesophageal reflux unresponsive to acid suppression and dysphagia for solids, especially in young men or boys. The majority of patients (90 percent) are sensitized to both food and aeroallergens, yet only 10 to 30 percent have a history of food anaphylaxis [67]. The diagnosis is based on the presence of characteristic clinical features, a large number of eosinophils on esophageal biopsy, and the exclusion of other causes. The pathogenesis of EoE is believed to involve both IgE-mediated and non-IgE-mediated hypersensitivity. (See "Clinical manifestations and diagnosis of eosinophilic esophagitis (EoE)" and "Treatment of eosinophilic esophagitis (EoE)".)

Beef, chicken, and cow's milk have been implicated as causing esophageal inflammation in patients with EoE. Patients typically develop symptoms in response to more than one food. In one study, an average of three to six problematic foods per patient were identified [67]. The foods most often implicated were milk, egg, soy, chicken, wheat, beef, corn, and peanuts [68].

Food protein-induced enterocolitis syndrome — Food protein-induced enterocolitis syndrome (FPIES) represents a non-IgE-mediated form of food allergy that usually presents in infants [8,66]. Symptoms of typical FPIES are delayed by a median of two hours and include vomiting, diarrhea, and lethargy/dehydration [69]. Bloody diarrhea may be present, and infants are generally ill appearing. (See "Food protein-induced allergic proctocolitis of infancy".)

Although cow's milk and soy protein are the most common triggers, FPIES can be triggered by other proteins, including beef, chicken, and turkey [70]. The author is not aware of published reports of enterocolitis caused by meats beginning in adulthood.

PATTERNS OF CROSS-REACTIVITY — Several clinical syndromes have been described that involve cross-reactivity or cross-sensitization between meat allergens and other types of allergens.

Meats from different animal species — The probability of cross-reactivity is increased the more closely related the animals are evolutionarily [41]. Patients allergic to beef may react to mutton or pork but rarely to poultry or fish. Similarly, patients may react to chicken and turkey but not to mammalian meats [11]. Cross-reactivity among goose, duck, turkey, and chicken meat has been demonstrated [71]. In many cases, cross-reactivity has been shown to be due to IgE specific for common determinants on serum albumins [43]. (See 'Allergens' above.)

Fish/chicken allergy — Patients have been described who are allergic to chicken meat (but not hen's egg) and to fish due to sensitization to cross-reactive parvalbumins, enolases, and aldolases [72].

Meats and other foods — The following observations have been made about cross-reactivity between meats and other animal-derived foods:

●Beef and cow's milk – Allergy to cow's milk is present in 73 to 93 percent of beef-allergic patients, most of whom are children [38,71]. Sensitization to bovine serum albumin (BSA) is the main predictive marker of this cross-reactivity [71]. Milk allergy is reviewed in more detail separately. (See "Milk allergy: Clinical features and diagnosis" and "Milk allergy: Management".)

●Beef and beef gelatin – Allergy to beef gelatin is seen in some patients with allergy to beef. The responsible allergen may be galactose-alpha-1,3-galactose (alpha-gal) [16]. Patients with gelatin allergy may report reactions to vaccines or foods that do not contain obvious meats. (See "Allergic reactions to vaccines", section on 'Gelatin'.)

On the other hand, patients with a meat allergy may not react to other foods/inhalants derived from the same animal source. As examples:

●Anaphylaxis due to ingestion of porcine gut and kidney, with tolerance of pork meat, has been described [42]. This patient also reacted to lamb gut. This case illustrates that allergens can be tissue specific.

●Adults have been described who are allergic to poultry meat but tolerant of eggs and not allergic to poultry feathers or dander [11,73]. The responsible allergen(s) have not been identified, although they are likely different from the allergens that cause bird-egg syndrome. (See 'Meats and animal dander/epithelium' below.)

Meats and animal dander/epithelium — Patients allergic to meats may show cross-reactivity with animal epithelia or dander. The following have been reported:

Bird-egg allergy — "Bird-egg syndrome" is a term used to describe adults with allergic respiratory disease provoked by the inhalation of bird feathers or dander who also develop allergic symptoms with hen's egg ingestion [74]. Alpha livetin (also known as chicken serum albumin, Gal d 5) found in the dander and yolk proteins of chicken egg is the major allergen responsible for these reactions [75-77]. This allergen is also present in chicken meat, but only a minority of patients with bird feather allergy report chicken meat allergy, most likely because the allergen is altered by cooking [78].

Pork-cat allergy — There is cross-reactivity between cat epithelia and pork meat due to sensitization to homologous serum albumins [79-81]. A case of fatal anaphylaxis was described in a patient who had known allergy to pork and ingested wild boar meat [82]. This patient was also sensitized to cat albumin (Fel d 2), which is now a commercially orderable IgE test. The term "pork-cat syndrome" was coined by the group who reported this case. Sensitization to cat serum albumin was also demonstrated in a series of eight patients from the United States [81]. The reactions to pork began soon (within two hours) after ingestion, distinguishing this syndrome from that of alpha-gal. Of note, patients with pork-cat syndrome may not have allergic rhinitis symptoms to cat dander. Most patients with allergic symptoms to cat dander are sensitized to a different allergen (Fel d 1).

A similar cross-reactivity syndrome has been noted with dog exposure where dog serum albumin (Can f 3) is the primary sensitizer, and reactions occur with pork meat. Due to high homology between cat and dog serum albumins, testing is frequently positive to both allergens in these patients and can complicate a clear understanding of the primary sensitizing exposure in some cases.

Pork meat causes allergic symptoms more consistently than beef or lamb due to greater homology between pork and pet albumins. Some patients with pork-cat allergy tolerate beef and lamb, while others do not. We do not advise avoidance of beef and lamb unless the patient reports symptoms with these meats.

Horse meat-horse dander allergy — Cross-reactivity between horse meat and horse epithelium was demonstrated in a young female who was sensitized to horse epithelium and experienced anaphylaxis after unknowingly eating a meal with horse meat [30].

Meats and monoclonal antibodies (cetuximab) — The cross-reactive carbohydrate determinant, alpha-gal, which is present on a range of mammalian meats, has been shown to be a potent allergen [18]. Patients who have IgE to alpha-gal can develop severe hypersensitivity reactions to the monoclonal antibody cetuximab, which also contains alpha-gal [83]. This association was made after a group of patients experienced anaphylaxis upon their initial exposure to cetuximab, indicating that they had been previously sensitized to some component of the drug. A subset of these patients living in the Southeastern United States described delayed anaphylaxis to beef, pork, or lamb, despite having tolerated these meats previously. These reactions are atypical for IgE-mediated allergy in that they do not start until several hours after meat ingestion and are associated with negative or very weak wheal responses to prick tests with meat extracts [18]. (See 'Alpha-gal' above and 'Diagnosis' below.)

DIAGNOSIS

Elements of the diagnosis — A definitive diagnosis of an IgE-mediated meat allergy requires consistent symptoms (table 1), in combination with the demonstration of IgE specific to the culprit meat, or an oral challenge with the culprit meat that reproduces the symptoms in question. The diagnosis of non-IgE-mediated reactions are discussed separately. (See 'For other types of reactions' below.)

In whom to suspect the diagnosis — Meat allergy can have varying presentations, depending on the allergen and the mechanism:

●IgE-mediated immediate reactions typically occur within minutes to an hour after ingestion. Pruritus, urticaria, pruritus of the oral mucosa, as well as gastrointestinal symptoms are common, but a range of symptoms is possible, and severity also varies (table 1).

Although it is also IgE mediated, alpha-gal syndrome is an important exception to the classic presentation of symptoms that begin shortly after meat ingestion. Children and adults with this disorder have reactions that are typically delayed two to eight hours, sometimes waking them in the middle of the night (after ingesting meat with dinner) (see 'Alpha-gal' above). Alpha-gal syndrome was described in 2009 but still is unfamiliar to many clinicians [18]. In a 2023 web-based survey of 1500 health care professionals in the United States, 42 percent were unaware that the disorder exists [84]. As a result, alpha-gal syndrome often evades diagnosis for years [85].

●Children with meat allergy often have significant atopic dermatitis. The allergic reaction can manifest as an exacerbation of skin inflammation minutes to hours following ingestion of the culprit meat or as a flare of atopic dermatitis 24 to 48 hours later. Patients may also develop noncutaneous symptoms, such as pruritus, urticaria, or (less commonly) asthma. (See 'IgE-mediated reactions' above.)

●Meat allergy in patients with eosinophilic esophagitis (EoE) can present with chronic symptoms of gastroesophageal reflux unresponsive to acid suppression and dysphagia for solids. (See 'Eosinophilic esophagitis' above.)

●Infants have been reported with food protein-induced enterocolitis syndrome (FPIES) caused by non-IgE-mediated allergy to meat, although this is uncommon. Symptoms are delayed by several hours and include vomiting, diarrhea (sometimes bloody), and lethargy/dehydration. (See 'Food protein-induced enterocolitis syndrome' above.)

Limitations of standard testing methods — Several studies have described poor correlation between the clinical history, skin test results, immunoassays to food-specific IgE, and outcomes of food challenges in patients with meat allergy [1,35,86-88]:

●Conventional diagnostic techniques for food allergy have low sensitivity and specificity in the diagnosis of allergy to meats, as illustrated in a series of 13 patients with convincing clinical histories of chicken, beef, or pork allergy [86]. Three had life-threatening reactions and positive skin tests to the suspect meat and so were not challenged, but the remaining 10 underwent a double-blind placebo-controlled food challenge (DBPCFC) with up to 50 grams of well-cooked meat. Only 3 of the 10 challenged patients reacted to challenge. However, other beef challenge protocols had identified positive reactions at higher doses, such as 75 grams (ie, 2.6 ounces). Thus, meat allergy was confirmed in 6 of 13 patients. Just one of the challenge-positive individuals had positive skin tests to a commercial extract of the suspect meat. Two patients had demonstrable meat-specific IgE (by ImmunoCAP testing). Five of the seven patients with a negative challenge test showed evidence of specific IgE to the suspect meat, either by skin testing or immunoassay, reflecting a state of "silent sensitization."

●In another report of 12 patients with suspected beef allergy, all 12 patients had positive immunoassays to beef, and 7 of the 12 reacted to either a labial or open-food challenge [87]. Two of the patients with positive challenges ingested 75 grams of beef before symptoms appeared, despite each having a relatively high level of specific IgE (at least class III) in the serum.

●In a third study of 10 adults with a history of recurrent food allergy symptoms on exposure to milk and meat, skin prick testing (SPT) with standard extracts for beef, pork, chicken, and milk produced negative results in all patients [29]. In contrast, immunoassays to meats and milk were positive in nine patients.

●Some published data indicate that wheal reactions are consistently larger with fresh meat, suggesting the usefulness of the native allergen in meat allergy skin testing [18,89].

In summary, the utility of IgE determinations, either by skin testing or immunoassay, is less certain for the diagnosis of meat allergy than for many other food allergies.

Available tests — The following forms of testing may be required to demonstrate meat-specific IgE:

●Epicutaneous or skin prick testing (SPT) with commercial extracts of meat.

●SPT with fresh meats (also called "prick-by-prick testing"). Details of the patient's history should guide preparation of the meat for testing. The meat should be cooked in a manner similar to the way the meat was prepared when it allegedly caused symptoms. As an example, if rare steak seemed to cause the reaction, then raw beef should be purchased and cooked rare just prior to the testing. We advise the patient to have a family member or friend cook the meat to avoid having the patient handle raw meat to which they could be allergic.

●IgE immunoassays to individual meats.

●IgE immunoassays to galactose-alpha-1,3-galactose (alpha-gal), which are commercially available [90,91].

●IgE immunoassays to cat and dog serum albumin, which are commercially available [92].

●Food challenge or, if feasible, DBPCFC. The total amount ingested during a challenge should mimic the amount ingested by the patient prior to developing symptoms. One study found that 75 grams of beef was necessary to identify allergy in some patients [87]. Factors to consider prior to performing an oral food challenge are listed in the table (table 2). Techniques are described elsewhere. (See "Oral food challenges for diagnosis and management of food allergies".)

Approach to allergy testing — The diagnostic approach to meat allergy is not standardized, and the author's approach is described here.

For suspected IgE-mediated reactions — For patients with signs and symptoms that are consistent with an IgE-mediated allergy (table 1), the diagnosis could be made by the combination of a positive (ie, elevated to any degree) immunoassay for IgE to alpha-gal or another meat allergen and resolution of symptoms with meat avoidance. These immunoassays are commercially available, and the diagnosis can be made by the generalist. If more in-depth testing is required by an allergy specialist, our approach to testing differs depending on how rapidly the reaction begins after meat ingestion.

●Immediate reactions – In a patient who reports the relatively immediate onset of allergic symptoms following ingestion of meat (ie, minutes to an hour), the author performs SPT to the meat(s) in question using commercial extracts initially or obtains IgE immunoassays, whichever is more feasible. If the results are consistent with the patient's clinical history, a diagnosis of meat allergy is made for the specific meat(s). In the author's experience, commercial extracts produce small wheals (ie, usually ≤4 mm in diameter) in sensitized patients [18].

If SPT using commercial extracts is negative, SPT using fresh meat (so-called "prick-by-prick testing"), cooked in a manner similar to that which caused symptoms, is then performed. If this testing is positive to clinically suspected meat(s), then the diagnosis of meat allergy is confirmed. As mentioned previously, skin testing with fresh meat may be more sensitive than testing with commercial extracts [18,89].

If prick-by-prick testing with fresh meats is negative, immunoassays are sent for the clinically suspected meats, if not already performed.

If all testing is negative, then food challenge is indicated if the patient wishes to pursue a more certain diagnosis. When feasible, this should be performed in a single- or double-blinded manner. (See "Oral food challenges for diagnosis and management of food allergies".)

•Modifications for suspected pork allergy – In patients with suspected pork reactions who have not had reactions to beef or lamb, we also test for sensitization to cat, either with cat extract (hair or pelt) or with an immunoassay to cat serum albumin [92], to identify those patients with pork-cat syndrome. These patients usually report symptoms that begin within two hours of eating pork products rather than the delayed reactions seen in patients sensitized to alpha-gal. (See 'Meats and animal dander/epithelium' above.)

●Delayed reactions – For patients who report symptoms that occur three to six hours after eating mammalian meat (or consistently occur at night, even if the association with meat ingestion is not clear), the author obtains an immunoassay to detect IgE to alpha-gal as an initial diagnostic test. This preference is based on the observation that skin testing with commercial meat extracts is often negative in patients who have IgE to alpha-gal. Immunoassays to detect alpha-gal are commercially available in the United States and some other countries [91,93,94]. When ordering IgE to alpha-gal, clinicians should confirm that the test they are requesting is not a test of the enzymatic activity of alpha-galactosidase A, which is a diagnostic test for Fabry disease [95].

If IgE immunoassay to alpha-gal is negative, SPT can be performed to commercial extracts of beef, pork, lamb, chicken, turkey, milk, and cat and dog dander. The author includes poultry in the testing to determine if the patient is sensitized to mammalian meats only or to an allergen found on nonmammalian meats also. Sensitization to alpha-gal can yield positive results to all mammalian meat extracts, as well as to cat and dog extracts, but not to poultry. Milk is included because it contains alpha-gal, and many patients with IgE to alpha-gal report difficulty tolerating milk.

If SPT using commercial extracts is negative, then prick-by-prick testing with fresh meat is performed next. If this testing is positive to clinically suspected meat(s), then the diagnosis of meat allergy is confirmed.

If all testing is negative, then food challenge is indicated if the patient wishes to pursue a more certain diagnosis and there is a setting available in which challenges can be safely performed. When feasible, this should be performed in a single- or double-blinded manner. In the author's center, challenges to patients with negative tests as a single "dose" followed by three to six hours of observation have been administered. Food challenges are discussed in more detail separately. (See "Oral food challenges for diagnosis and management of food allergies".)

For other types of reactions — The evaluation of patients with EoE or FPIES who are suspected to have sensitivity to foods is discussed elsewhere. (See "Food protein-induced enterocolitis syndrome (FPIES)", section on 'Diagnosis' and "Future diagnostic tools for food allergy", section on 'Gastrointestinal food allergy'.)

DIFFERENTIAL DIAGNOSIS — The following disorders can mimic meat allergy:

●Chronic spontaneous urticaria, especially when it first develops, can mimic an allergic reaction, especially if there is accompanying angioedema. Patients often question the foods most recently ingested. However, the persistence of chronic urticaria eventually distinguishes it from an allergic reaction.

●Severe irritable bowel symptoms can mimic the gastrointestinal symptoms of an allergic reaction, but symptoms outside of the gastrointestinal tract (eg, pruritus, urticaria or angioedema, wheezing) would be absent. Still, in patients presenting with repeated episodes of isolated abdominal cramping several hours after consuming mammalian meat, galactose-alpha-1,3-galactose (alpha-gal) allergy should be considered.

●Allergic reactions to antibiotics in meat, particularly penicillin and possibly streptomycin, can mimic meat allergy [96-98]. Patients allergic to penicillin will generally be aware of this, and penicillin skin testing can confirm the allergy. In contrast, allergy to streptomycin is rare and may not be apparent from the clinical history. Skin testing can be performed but has been associated with anaphylaxis and should be undertaken with caution [99].

●Adverse reactions to additives, such as natural colorings (carmine red or annatto), can also mimic food allergies. Allergic and asthmatic reactions to food additives are reviewed separately. (See "Allergic and asthmatic reactions to food additives".)

MANAGEMENT — Management of food allergy most commonly involves avoidance of the culprit meat(s). If the patient reacted to raw or rare meat, then it may be helpful to determine if the meat is tolerated in a well-cooked form, as the patient may be able to keep the food in their diet in cooked forms. Patients with IgE-mediated meat allergy should be equipped with an epinephrine autoinjector and taught how and when to use it. General issues in food-induced anaphylaxis and food allergen avoidance are reviewed elsewhere. (See "Food-induced anaphylaxis" and "Management of food allergy: Avoidance".)

A small number of reports of successful desensitization protocols have been published in both adults and children with alpha-gal allergy [100,101]. Since alpha-gal allergy appears to resolve over time without additional tick bites, it is unclear whether risks associated with immunologic desensitization offer benefit beyond the natural history of the syndrome [102].

PROGNOSIS — Children with cow's milk allergy who are also allergic to beef (representing the largest group of meat-allergic children) tend to outgrow both the beef and cow's milk sensitivities [103]. In one study, tolerance of beef was reached after a median duration of three years and has been reported to occur prior to tolerance to cow's milk in those allergic to both foods [103].

There is a paucity of published data regarding the natural history of meat allergy in adults. Case reports suggest that some individuals who acquired the allergy as adults lose the sensitivity over time [104]. One case report described a middle-aged patient with IgE-mediated allergy to several mammalian meats who subsequently developed an allergy to bovine serum albumin (BSA). Three years later, he began to tolerate ingestion of cooked lamb and pork [105]. A review of 12 cases of beef allergy also reported that some patients became tolerant [87].

The natural history of reactions caused by sensitization to galactose-alpha-1,3-galactose (alpha-gal) is not well studied. While there are no data from long-term series or controlled studies, initial evidence suggests that IgE antibodies to alpha-gal decrease in some patients over time [102]. However, additional tick bites appear to increase the antibody level (figure 1).

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Food allergy".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Alpha-gal syndrome (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Epidemiology – Meat allergy is uncommon. Exceptions are noted among certain patient groups: Children with atopic dermatitis and patients with delayed anaphylaxis in the Southeastern United States. The prevalence of allergies to specific meats appears to be related to the prominence of a given meat in the diet. Allergy to beef is reported most commonly. (See 'Epidemiology' above.)

●Types of clinical reactions – Both immunoglobulin E (IgE) mediated and non-IgE-mediated forms of meat allergy have been described. IgE-mediated reactions may be immediate or delayed up to three to six hours after ingestion. Non-IgE-mediated disorders in which meats have been implicated include eosinophilic esophagitis (EoE) and pediatric food protein-induced enterocolitis syndrome (FPIES). (See 'Clinical reactions' above.)

●Allergens – The main allergens in meats are serum albumins and immunoglobulins, both of which are significantly altered by cooking. This may partly explain why meat allergy is uncommon. A carbohydrate allergen has also been identified, galactose-alpha-1,3-galactose (alpha-gal), which seems to be particularly prevalent in patients in the Southeastern United States. (See 'Allergens' above.)

●Cross-reactivity patterns – The similarity of various serum albumins leads to cross-sensitization among meats and/or allergy to milk and animal dander. Sensitization to alpha-gal can cause cross-sensitization to gelatins and the monoclonal antibody cetuximab. (See 'Patterns of cross-reactivity' above.)

●Diagnostic approach – The diagnosis of meat allergy involves history, objective testing, and possibly food challenge. However, the sensitivity and specificity of tests for meat-specific IgE are relatively poor. The use of fresh meat for skin testing may improve sensitivity. (See 'Diagnosis' above.)

●Management – Management largely consists of avoidance of the causative meat and patient education about how to self-inject epinephrine if needed for accidental exposures. (See "Food-induced anaphylaxis" and "Management of food allergy: Avoidance".)

●Prognosis – Many children and some adults become tolerant to meat over time. (See 'Management' above and 'Prognosis' above.)