A-20

Dosage for Beef allergenic extracts is highly individualized and must be determined by an allergist or immunologist based on the patient's clinical history and sensitivity levels.

• Skin Prick Testing (SPT): Typically, a single drop of a 1:10 or 1:20 w/v (weight/volume) concentration is applied to the skin (usually the forearm or back), followed by a superficial puncture. A positive control (histamine) and negative control (saline) are used simultaneously.
• Intradermal Testing: If SPT is negative but suspicion remains high, a 1:100 to 1:1000 w/v dilution may be injected intradermally (0.02 mL) to create a small bleb.
• Hormonal Applications: Dosing for estrogenic effects is not standardized and depends entirely on the specific therapeutic protocol being followed by the endocrinologist.

Beef extracts are used in children for allergy diagnosis using similar techniques to adults, though the number of tests performed at one time may be limited to reduce discomfort.

• Infants and Children: SPT is the preferred method. Intradermal testing is generally avoided in very young children unless absolutely necessary, as it carries a higher risk of systemic reactions.
• Estrogen Use: Use in the pediatric population for hormonal purposes is strictly limited to specific endocrine disorders (e.g., Turner syndrome) and must be managed by a pediatric endocrinologist.

Renal Impairment

No specific dosage adjustments are required for localized diagnostic testing in patients with renal impairment. However, if systemic absorption occurs, the clearance of metabolites may be delayed. Monitoring for prolonged estrogenic effects may be necessary in severe renal disease.

Hepatic Impairment

Patients with significant hepatic impairment (e.g., Child-Pugh Class C) may have a reduced capacity to metabolize the estrogenic components of Beef. While not affecting skin test results, it may increase the risk of systemic hormonal side effects if large quantities are utilized or ingested.

Elderly Patients

In elderly patients, skin reactivity may be diminished due to age-related changes in skin physiology (reduced mast cell density). Healthcare providers may need to interpret 'weak' positive results with caution and rely more heavily on clinical history.

Beef allergenic extract is exclusively administered by healthcare professionals in a clinical setting.

• Preparation: The skin site must be cleaned with alcohol and allowed to dry.
• Timing: Testing should be performed at least 48-72 hours after the discontinuation of antihistamines, as these medications will suppress the wheal and flare response.
• Storage: Extracts must be stored under refrigeration (2°C to 8°C or 36°F to 46°F). Do not freeze. If the solution becomes cloudy or changes color, it should be discarded.
• Observation: Patients must remain in the clinic for at least 30 minutes following administration to be monitored for signs of anaphylaxis.

In the context of diagnostic testing, a 'missed dose' simply refers to a cancelled or postponed appointment. If a patient is undergoing a desensitization protocol (immunotherapy) and misses a dose, the next dose may need to be reduced to prevent an allergic reaction. Patients should contact their allergist immediately to reschedule.

An 'overdose' of Beef extract typically manifests as an exaggerated allergic response.

• Signs: Massive localized swelling, generalized hives (urticaria), angioedema (swelling of the face or throat), wheezing, hypotension (low blood pressure), and tachycardia (rapid heart rate).
• Emergency Measures: Administration of epinephrine (0.3 mg IM for adults) is the first-line treatment for systemic reactions. Supportive care includes oxygen, intravenous fluids, and antihistamines/corticosteroids.

> Important: Follow your healthcare provider's dosing instructions. Do not adjust your dose or attempt to perform self-testing without medical guidance.

Most patients undergoing testing with Beef extract will experience localized reactions at the site of administration. These are generally expected and indicate the test is working.

• Local Wheal and Flare: A raised, itchy bump (wheal) surrounded by a red area (flare). This typically appears within 15-20 minutes and resolves within a few hours.
• Pruritus (Itching): Intense itching at the injection site is very common.
• Erythema: Redness of the skin that may spread slightly beyond the immediate test site.

• Delayed Local Swelling: Some patients may experience a 'late-phase' reaction where the test site swells again 4 to 8 hours after the initial test.
• Systemic Pruritus: Itching that occurs in areas away from the test site, such as the palms, soles of the feet, or scalp.
• Mild Urticaria: A few hives appearing on the trunk or limbs.
• Nausea: Some patients may feel slightly queasy, often due to a vasovagal response (fainting reflex) rather than the drug itself.

• Lymphadenopathy: Swelling of the lymph nodes near the injection site (e.g., in the armpit if the test was on the arm).
• Estrogenic Effects: In cases of high systemic exposure, patients may experience breast tenderness, mood swings, or changes in menstrual patterns.
• Syncope: Fainting or lightheadedness immediately following the procedure.

> Warning: Stop taking Beef and call your doctor immediately if you experience any of these symptoms of a systemic allergic reaction (anaphylaxis).

• Anaphylaxis: This is a life-threatening emergency characterized by a rapid onset of multi-organ symptoms.
• Angioedema: Swelling of the lips, tongue, or throat that can obstruct the airway.
• Dyspnea and Wheezing: Difficulty breathing or a whistling sound when breathing, indicating bronchial constriction.
• Hypotension: A sudden drop in blood pressure leading to dizziness, confusion, or loss of consciousness.
• Chest Tightness: A feeling of pressure in the chest, which may indicate cardiac involvement in a severe allergic reaction.

• Sensitization: There is a theoretical risk that repeated exposure to allergenic extracts could cause a person to become allergic to beef when they were not previously. This is why testing is only performed when clinically indicated.
• Hormonal Imbalance: Prolonged, high-level exposure to the estrogenic components of beef could potentially interfere with the body's natural hormone production, though this is rarely seen with diagnostic levels of extract.

WARNING: RISK OF SEVERE ALLERGIC REACTION

Beef allergenic extracts can cause severe, life-threatening systemic allergic reactions, including anaphylaxis. These reactions may occur even in patients who have previously tolerated the extract. Beef extract should only be administered by healthcare providers experienced in the diagnosis and treatment of allergic diseases and in a facility equipped to manage life-threatening emergencies. Patients must be observed for at least 30 minutes following administration. Patients with unstable asthma or those taking beta-blockers may be at increased risk for severe outcomes.

Report any unusual symptoms to your healthcare provider immediately. Even mild symptoms like a scratchy throat or itchy palms can be early signs of a serious reaction.

Beef allergenic extract is a potent biological substance. It must be used with extreme caution in patients with a history of severe food allergies or those who have had previous systemic reactions to skin testing. Because it acts as an estrogen receptor agonist, its use must also be monitored in patients with hormone-sensitive conditions.

No FDA black box warnings are currently mandated for Beef as a general food product; however, as an Allergenic Extract, it carries a standard class warning regarding the risk of Anaphylaxis. This warning emphasizes that Beef extract should only be used by clinicians trained in emergency airway management and that epinephrine must be immediately available.

• Anaphylaxis Risk: The most significant risk is a systemic allergic reaction. This is more common with intradermal testing than skin prick testing. Risk factors include a history of high-grade sensitivity and the use of high-concentration extracts.
• Asthma: Patients with poorly controlled or unstable asthma are at a significantly higher risk for severe respiratory distress if a systemic reaction occurs. Asthma should be stable before testing is initiated.
• Beta-Blocker Use: Patients taking beta-blockers (e.g., metoprolol, propranolol) may be resistant to the effects of epinephrine, making an allergic reaction much harder to treat. This must be discussed with a doctor before testing.
• Hormone-Sensitive Cancers: Due to its Estrogen Receptor Agonist properties, Beef extract should be used with caution in patients with a history of breast, uterine, or ovarian cancer. While diagnostic doses are small, the potential for receptor stimulation exists.
• Cardiovascular Disease: The stress of a systemic reaction or the administration of epinephrine can be dangerous for patients with severe heart disease or recent myocardial infarction (heart attack).

• Post-Administration Observation: Mandatory 30-minute wait time in the clinic.
• Vital Signs: Baseline blood pressure and heart rate should be recorded, especially in high-risk patients.
• Lung Function: In asthmatic patients, a peak flow or spirometry test may be performed before and after administration to ensure no bronchospasm has occurred.
• Hormonal Levels: If used for endocrine purposes, regular monitoring of serum estradiol, FSH, and LH may be required.

Beef extract generally does not affect the ability to drive. However, if a patient experiences a vasovagal reaction (fainting) or a systemic allergic reaction, they should not drive until they have fully recovered and been cleared by a physician.

Alcohol should be avoided for 24 hours before and after testing. Alcohol can increase peripheral blood flow (vasodilation), which may exacerbate the wheal and flare reaction or increase the rate of systemic absorption of the allergen.

There are no tapering requirements for Beef diagnostic extracts. However, if a patient is on an immunotherapy (desensitization) schedule, stopping the injections suddenly will result in a loss of clinical tolerance to beef proteins.

> Important: Discuss all your medical conditions, especially heart disease, asthma, and hormone-sensitive conditions, with your healthcare provider before starting Beef.

• Beta-Blockers (Non-selective and Selective): While not an absolute contraindication for a single test, using Beef extract while on beta-blockers is highly dangerous. Beta-blockers antagonize the effects of epinephrine, which is the only effective treatment for anaphylaxis. A reaction that would normally be treatable can become fatal.
• MAO Inhibitors (MAOIs): Drugs like phenelzine or tranylcypromine can potentiate the effects of sympathomimetics (like epinephrine) used to treat reactions, leading to hypertensive crises.

• Tricyclic Antidepressants (TCAs): Similar to MAOIs, TCAs (e.g., amitriptyline) can increase the body's sensitivity to epinephrine, complicating the management of a side effect.
• Antihistamines (H1 Blockers): Medications like loratadine, cetirizine, and diphenhydramine will block the skin's response to the Beef extract. This results in a false-negative test. These must be stopped 3-7 days before testing.
• H2 Blockers: Drugs like famotidine may also weakly suppress skin reactions and should be discontinued 48 hours prior to the procedure.

• Systemic Corticosteroids: Long-term use of prednisone may thin the skin and suppress the inflammatory response, potentially leading to smaller wheal sizes during testing.
• Topical Corticosteroids: Applying steroid creams to the test site will significantly inhibit the reaction. Do not use these creams on the arms or back for 2 weeks before testing.

• Red Meat and Dairy: In patients with Alpha-gal syndrome, the ingestion of beef or dairy can cause a delayed allergic reaction (3-6 hours later). This can complicate the interpretation of diagnostic tests if the patient ate these foods recently.
• Alcohol: As mentioned, alcohol can increase the severity of an allergic reaction by increasing intestinal permeability and causing vasodilation.

• St. John's Wort: This herb induces CYP3A4, which may speed up the metabolism of the estrogenic components of Beef, potentially reducing their effect.
• Phytoestrogens (Soy, Red Clover): These may have additive effects with the Estrogen Receptor Agonist properties of Beef, potentially leading to increased estrogenic activity in the body.

• Serum IgE Testing: Beef extract administration does not usually interfere with blood tests for IgE (like ImmunoCAP), but the skin test is often more sensitive.
• Estrogen Assays: Large systemic doses of bovine-derived products could theoretically interfere with the accuracy of total estrogen lab results.

For each major interaction, the primary concern is either the safety of the patient during a potential reaction or the accuracy of the diagnostic result. Always provide a full list of medications to your allergist.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, including over-the-counter allergy meds.

Conditions where Beef extract must NEVER be used include:

• Recent Anaphylaxis: If a patient has had a systemic allergic reaction to any substance within the last 24-48 hours, their mast cells may be 'depleted' or hypersensitive, making testing dangerous or inaccurate.
• Severe, Uncontrolled Asthma: Patients with a Forced Expiratory Volume in 1 second (FEV1) of less than 70% of predicted are at extreme risk of death if a systemic reaction occurs.
• Acute Infection or Fever: Testing during an active illness can lead to unpredictable immune responses.
• Known Hypersensitivity to Constituents: If a patient is known to be allergic to phenol (often used as a preservative in extracts), the test should not be performed.

Conditions requiring a careful risk-benefit analysis by the physician:

• Pregnancy: While not directly toxic to the fetus, the risk of maternal anaphylaxis and the subsequent drop in blood pressure (hypotension) can cause fetal hypoxia (lack of oxygen).
• Beta-Blocker Therapy: If the patient cannot safely stop their beta-blocker, the allergist must weigh the need for the test against the increased risk of treatment-resistant anaphylaxis.
• Dermatographism: A condition where any pressure on the skin causes a hive. This makes skin testing impossible to interpret, as every 'prick' will look positive.
• Active Eczema/Atopic Dermatitis: If the skin at the test site is inflamed, the results will be unreliable.

Patients sensitive to Beef extract may also react to:

• Other Mammalian Meats: Lamb, pork, and venison often share the Alpha-gal carbohydrate or similar proteins (serum albumin cross-reactivity).
• Gelatin: Many vaccines and medications contain bovine gelatin, which can trigger reactions in beef-allergic individuals.
• Cow's Milk: There is a significant overlap between beef allergy and cow's milk allergy, particularly in children.

> Important: Your healthcare provider will evaluate your complete medical history, including your current asthma control and medication list, before prescribing or administering Beef extract.

Beef allergenic extract is classified as Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. The primary concern is not the extract itself, but the potential for a systemic allergic reaction (anaphylaxis). Anaphylaxis during pregnancy is a medical emergency that can lead to uterine contractions, placental abruption, and fetal distress due to maternal hypotension. Diagnostic testing should generally be postponed until after delivery unless the information is critical for the immediate management of the patient.

It is not known whether the proteins or estrogenic components of Beef extract are excreted in human milk. Because most allergenic extracts are administered in minute quantities for diagnostic purposes, the risk to a nursing infant is considered very low. However, if used for therapeutic hormonal purposes, the potential for affecting the infant's endocrine development must be considered. Consult a healthcare provider before use while breastfeeding.

Beef extract is approved for use in children for the diagnosis of food allergies. Pediatric patients often have higher skin reactivity than adults.

• Safety: The risk of systemic reactions is present but can be minimized by using skin prick testing rather than intradermal testing.
• Growth Effects: While the extract has estrogenic properties, the amounts used in diagnostic testing are insufficient to affect growth or pubertal development.
• Conditions: It is not approved for use in children with severe, unstable asthma or those with certain autoimmune conditions.

In patients over 65, the immune system undergoes 'immunosenescence,' which can lead to reduced skin test reactivity.

• Pharmacokinetics: Reduced renal and hepatic clearance in the elderly may prolong the presence of systemically absorbed components.
• Polypharmacy: Elderly patients are more likely to be on beta-blockers or ACE inhibitors, which can complicate the management of allergic reactions.
• Fall Risk: If a vasovagal reaction occurs during testing, the risk of injury from a fall is higher in this population.

No specific dose adjustments are provided for Beef allergenic extract in renal impairment. However, clinicians should be aware that in patients with end-stage renal disease (ESRD), the skin may be less reactive (uremic pruritus and altered immune response), potentially leading to false-negative results.

In patients with severe liver disease, the metabolism of the estrogenic components of Beef may be impaired. While this does not impact the safety of a skin test, it should be considered if the patient is consuming large amounts of bovine-derived products as part of a therapeutic or dietary regimen.

> Important: Special populations require individualized medical assessment. Always inform your specialist if you are pregnant, planning to become pregnant, or have underlying kidney or liver issues.

Beef functions through two distinct pharmacological pathways:

1. 1IgE-Mediated Response: The primary allergens in beef, such as Bos d 6 (Bovine Serum Albumin) and the carbohydrate alpha-gal, act as antigens. In a sensitized individual, these antigens cross-link IgE antibodies on the surface of mast cells. This triggers a signal transduction pathway involving tyrosine kinases (like Syk), leading to an influx of calcium ions and the exocytosis of pre-formed mediators (histamine) and the synthesis of new mediators (leukotrienes).
2. 2Estrogen Receptor Agonism: Beef contains bioactive lipids and sterols that act as ligands for Estrogen Receptors (ER). These molecules bind to the ER, causing a conformational change that allows the receptor to dimerize and bind to EREs in the promoter regions of target genes. This modulates the expression of genes involved in the cell cycle (e.g., Cyclin D1) and various metabolic processes.

• Onset of Effect: For skin testing, the onset is rapid (15-20 minutes for the wheal and flare). For estrogenic effects, the onset is delayed, requiring hours to days for gene transcription changes to manifest.
• Duration: The skin reaction typically lasts 2-6 hours. The late-phase allergic response can last up to 24 hours.
• Tolerance: Repeated exposure in a controlled immunotherapy setting can lead to 'desensitization,' where the threshold for mast cell degranulation is increased.

| Parameter | Value |

|---|---|

| Bioavailability | <1% (Skin Prick); ~20-40% (Oral Estrogenic Components) |

| Protein Binding | >90% (Estrogenic components to SHBG/Albumin) |

| Half-life | 2-4 hours (Allergenic proteins); 12-24 hours (Steroidal components) |

| Tmax | 15-20 minutes (Local); 2-4 hours (Systemic) |

| Metabolism | Hepatic (CYP3A4, CYP1A2) for hormones; Proteolysis for proteins |

| Excretion | Renal (>80% as metabolites); Fecal (<20%) |

• Composition: A complex mixture of proteins (Albumins, Globulins, Actin, Myosin), carbohydrates (Alpha-gal), and lipids (Cholesterol, Estrogens).
• Molecular Weight: Varies (Bos d 6 is ~66 kDa).
• Solubility: Proteins are water-soluble; estrogenic components are lipophilic (fat-soluble).

Beef is classified as a Non-Standardized Food Allergenic Extract and an Estrogen Receptor Agonist. It is related to other mammalian extracts like Pork (Sus scrofa) and Horse (Equus caballus).