Chief of the Rickettsial Zoonoses Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Atlanta, GA
Disclosure: Gilbert Kersh, PhD, has disclosed no relevant financial relationships.
| December 18, 2024
Editorial Collaboration
&
Alpha-gal syndrome (AGS), a tickborne disease commonly called “red meat allergy,” is a serious, potentially life-threatening allergy to the carbohydrate alpha-gal. The alpha-gal carbohydrate is found in most mammals, though it is not in humans, apes, or old-world monkeys. People with AGS can have allergic reactions when they consume mammalian meat, dairy products, or other products derived from mammals. People often live with this disease for years before receiving a correct diagnosis, greatly impacting their quality of life. The number of suspected cases is also rising.
More than 110,000 suspected AGS cases were identified between 2010 and 2022, according to a Centers for Disease Control and Prevention (CDC) report. However, because the diagnosis requires a positive test and a clinical exam and some people may not get tested, as many as 450,000 people might be affected by AGS in the United States. Additionally, a CDC survey found that nearly half (42%) of US healthcare providers had never heard of AGS. Among those who had, less than one third (29%) knew how to diagnose the condition.
Here are 5 things clinicians need to know about AGS.
1. People can develop AGS after being bitten by a tick, primarily the lone star tick (Amblyomma americanum), in the United States.
In the United States, AGS is primarily associated with the bite of a lone star tick, but other kinds of ticks have not been ruled out. The majority of suspected AGS cases in the United States were reported in parts of Arkansas, Delaware, Illinois, Indiana, Kansas, Kentucky, Maryland, Mississippi, Missouri, North Carolina, Oklahoma, Tennessee, and Virginia. The lone star tick is widely distributed with established populations in Alabama, Arkansas, Connecticut, Delaware, Florida, Georgia, Illinois, Indiana, Iowa, Kansas, Kentucky, Louisiana, Michigan, Minnesota, Mississippi, Missouri, Nebraska, New Hampshire, New Jersey, New York, North Carolina, Ohio, Oklahoma, Pennsylvania, South Carolina, Tennessee, Texas, Virginia, and West Virginia.
While AGS is associated with tick bites, more research is needed to understand the role ticks play in starting this condition, and why certain people develop AGS. Anyone can develop AGS, but most cases have been reported in adults.
Know how to recognize the symptoms of AGS and be prepared to test, diagnose, and manage AGS, particularly in states where lone star ticks are found.
Distribution of suspected AGS cases in the United States per 1 million population per year, 2017–2022. Source: Thomson et al 2023
2. Tick bites are only one risk factor for developing AGS.
Many people are bitten by lone star ticks and will never develop AGS. Scientists are exploring the connection between other risk factors and developing AGS. A recent study has shown that people diagnosed with AGS may be more likely to have a family member who was also diagnosed with AGS, have another food allergy, have an allergy to stinging or biting insects, or have A or O blood types.
Research has also shown that environmental risk factors could contribute to developing AGS, like living in an area with lone star ticks, remembering finding a tick on themselves, recalling multiple tick bites, living near a wooded forest, spending more time outside, or living in areas with deer, such as larger properties, wooded forests, and properties with shrubs and brush.
Ask your patient questions about other allergies and history of recent tick bites or outdoor exposure to help determine if testing for AGS is appropriate.
3. Symptoms of AGS are consistently inconsistent.
There is a spectrum of how sensitive AGS patients are to alpha-gal, and reactions are often different from person to person, which can make it difficult to diagnose. The first allergic reaction to AGS typically occurs between 1-6 months after a tick bite. Symptoms commonly appear 2-6 hours after being in contact with products containing alpha-gal, like red meat (beef, pork, lamb, venison, rabbit, or other meat from mammals), dairy, and some medications. Symptoms can range from mild to severe and include hives or itchy rash; swelling of the lips, throat, tongue, or eyelids; gastrointestinal symptoms such as nausea, vomiting, or diarrhea; heartburn or indigestion; cough, shortness of breath, or difficulty breathing; dizziness or a drop in blood pressure; or anaphylaxis.
Consider AGS if a patient reports waking up in the middle of the night with allergic symptoms after eating alpha-gal containing products for dinner, if allergic reactions are delayed, or if a patient has anaphylaxis of unknown cause, adult-onset allergy, or allergic symptoms and reports a recent tick bite.
4. Diagnosing AGS requires a combination of a blood test and a physical exam.
Diagnosing AGS requires a detailed patient history, physical exam, and a blood test to detect specific immunoglobulin-E (IgE) antibodies specific to alpha-gal (alpha-gal sIgE). Tests for alpha-gal sIgE antibodies are available at several large commercial laboratories and some academic institutions. Skin tests to identify reactions to allergens like pork or beef may also be used to inform AGS diagnosis. However, a positive alpha-gal sIgE test or skin test does not mean a person has AGS. Many people, particularly those who live in regions with lone star ticks, have positive alpha-gal specific IgE tests without having AGS.
Consider the test results along with your patient’s symptoms and risk factors.
5. There is no treatment for AGS, but people can take prevention steps and AGS can be managed.
People can protect themselves and their family from AGS by preventing tick bites. Encourage your patients to use an Environmental Protection Agency-registered insect repellent outdoors, wear permethrin-treated clothing, and conduct thorough tick checks after outdoor activities.
Once a person is no longer exposed to alpha-gal containing products, they should no longer experience symptoms. People with AGS should also proactively prevent tick bites. Tick bites can trigger or reactivate AGS.
Thompson JM, Carpenter A, Kersh GJ, Wachs T, Commins SP, Salzer JS. Geographic distribution of suspected alpha-gal syndrome cases — United States, January 2017–December 2022. MMWR Morb Mortal Wkly Rep. 2023;72:815-820. Source https://dx.doi.org/10.15585/mmwr.mm7230a2.
Carpenter A, Drexler NA, McCormick DW, et al. Health care provider knowledge regarding alpha-gal syndrome — United States, March–May 2022. MMWR Morb Mortal Wkly Rep. 2023;72:809-814. Source
Taylor ML, Kersh GJ, Salzer JS, et al. Intrinsic risk factors for alpha-gal syndrome in a case-control study, 2019 to 2020. Ann Allergy, Asthma & Immunol. 2024 Jun;132(6):759-764.e2. Source
Kersh GJ, Salzer J, Jones ES, et al. Tick bite as a risk factor for alpha-gal-specific immunoglobulin E antibodies and development of alpha-gal syndrome. Ann Allergy, Asthma & Immunol. 2023 Apr;130(4):472-478. Source
COMMENTARY
Alpha-Gal Syndrome: 5 Things to Know
Gilbert Kersh, PhD
DISCLOSURES
| December 18, 2024Editorial Collaboration
&
Alpha-gal syndrome (AGS), a tickborne disease commonly called “red meat allergy,” is a serious, potentially life-threatening allergy to the carbohydrate alpha-gal. The alpha-gal carbohydrate is found in most mammals, though it is not in humans, apes, or old-world monkeys. People with AGS can have allergic reactions when they consume mammalian meat, dairy products, or other products derived from mammals. People often live with this disease for years before receiving a correct diagnosis, greatly impacting their quality of life. The number of suspected cases is also rising.
More than 110,000 suspected AGS cases were identified between 2010 and 2022, according to a Centers for Disease Control and Prevention (CDC) report. However, because the diagnosis requires a positive test and a clinical exam and some people may not get tested, as many as 450,000 people might be affected by AGS in the United States. Additionally, a CDC survey found that nearly half (42%) of US healthcare providers had never heard of AGS. Among those who had, less than one third (29%) knew how to diagnose the condition.
Here are 5 things clinicians need to know about AGS.
1. People can develop AGS after being bitten by a tick, primarily the lone star tick (Amblyomma americanum), in the United States.
In the United States, AGS is primarily associated with the bite of a lone star tick, but other kinds of ticks have not been ruled out. The majority of suspected AGS cases in the United States were reported in parts of Arkansas, Delaware, Illinois, Indiana, Kansas, Kentucky, Maryland, Mississippi, Missouri, North Carolina, Oklahoma, Tennessee, and Virginia. The lone star tick is widely distributed with established populations in Alabama, Arkansas, Connecticut, Delaware, Florida, Georgia, Illinois, Indiana, Iowa, Kansas, Kentucky, Louisiana, Michigan, Minnesota, Mississippi, Missouri, Nebraska, New Hampshire, New Jersey, New York, North Carolina, Ohio, Oklahoma, Pennsylvania, South Carolina, Tennessee, Texas, Virginia, and West Virginia.
While AGS is associated with tick bites, more research is needed to understand the role ticks play in starting this condition, and why certain people develop AGS. Anyone can develop AGS, but most cases have been reported in adults.
Know how to recognize the symptoms of AGS and be prepared to test, diagnose, and manage AGS, particularly in states where lone star ticks are found.
2. Tick bites are only one risk factor for developing AGS.
Many people are bitten by lone star ticks and will never develop AGS. Scientists are exploring the connection between other risk factors and developing AGS. A recent study has shown that people diagnosed with AGS may be more likely to have a family member who was also diagnosed with AGS, have another food allergy, have an allergy to stinging or biting insects, or have A or O blood types.
Research has also shown that environmental risk factors could contribute to developing AGS, like living in an area with lone star ticks, remembering finding a tick on themselves, recalling multiple tick bites, living near a wooded forest, spending more time outside, or living in areas with deer, such as larger properties, wooded forests, and properties with shrubs and brush.
Ask your patient questions about other allergies and history of recent tick bites or outdoor exposure to help determine if testing for AGS is appropriate.
3. Symptoms of AGS are consistently inconsistent.
There is a spectrum of how sensitive AGS patients are to alpha-gal, and reactions are often different from person to person, which can make it difficult to diagnose. The first allergic reaction to AGS typically occurs between 1-6 months after a tick bite. Symptoms commonly appear 2-6 hours after being in contact with products containing alpha-gal, like red meat (beef, pork, lamb, venison, rabbit, or other meat from mammals), dairy, and some medications. Symptoms can range from mild to severe and include hives or itchy rash; swelling of the lips, throat, tongue, or eyelids; gastrointestinal symptoms such as nausea, vomiting, or diarrhea; heartburn or indigestion; cough, shortness of breath, or difficulty breathing; dizziness or a drop in blood pressure; or anaphylaxis.
Consider AGS if a patient reports waking up in the middle of the night with allergic symptoms after eating alpha-gal containing products for dinner, if allergic reactions are delayed, or if a patient has anaphylaxis of unknown cause, adult-onset allergy, or allergic symptoms and reports a recent tick bite.
4. Diagnosing AGS requires a combination of a blood test and a physical exam.
Diagnosing AGS requires a detailed patient history, physical exam, and a blood test to detect specific immunoglobulin-E (IgE) antibodies specific to alpha-gal (alpha-gal sIgE). Tests for alpha-gal sIgE antibodies are available at several large commercial laboratories and some academic institutions. Skin tests to identify reactions to allergens like pork or beef may also be used to inform AGS diagnosis. However, a positive alpha-gal sIgE test or skin test does not mean a person has AGS. Many people, particularly those who live in regions with lone star ticks, have positive alpha-gal specific IgE tests without having AGS.
Consider the test results along with your patient’s symptoms and risk factors.
5. There is no treatment for AGS, but people can take prevention steps and AGS can be managed.
People can protect themselves and their family from AGS by preventing tick bites. Encourage your patients to use an Environmental Protection Agency-registered insect repellent outdoors, wear permethrin-treated clothing, and conduct thorough tick checks after outdoor activities.
Once a person is no longer exposed to alpha-gal containing products, they should no longer experience symptoms. People with AGS should also proactively prevent tick bites. Tick bites can trigger or reactivate AGS.
For patients who have AGS, help manage their symptoms and identify alpha-gal containing products to avoid.
CDC resources:
About Alpha-gal Syndrome | Alpha-gal Syndrome | CDC
Clinical Testing and Diagnosis for Alpha-gal Syndrome | Alpha-gal Syndrome | CDC
Clinical Resources | Alpha-gal Syndrome | CDC
References
Public Information from the CDC and Medscape
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