Nut Antigens

Diagnostic Skin Prick Testing (SPT)

For adults, the standard procedure involves applying one drop of the Almond Non-Standardized Food Allergenic Extract (usually at a 1:10 or 1:20 w/v concentration) to the volar surface of the forearm or the back. A sterile lancet is used to prick the skin through the drop.

• Positive Control: Histamine dihydrochloride (10 mg/mL) is used to ensure skin reactivity.
• Negative Control: 50% Glycerin-saline is used to rule out dermatographism (skin sensitivity to the physical prick).
• Interpretation: The test is read 15 to 20 minutes after application. A wheal diameter 3mm larger than the negative control is generally considered a positive result.

Intradermal Testing

If the SPT is negative but clinical suspicion remains high, a healthcare provider may perform intradermal testing. This involves injecting 0.02 mL to 0.05 mL of a much more dilute extract (e.g., 1:1000 or 1:100 w/v) into the dermis. This carries a higher risk of systemic reactions and is often avoided for food allergens like almond due to the risk of anaphylaxis.

Infants and Children

Almond allergenic extracts are used in pediatric populations to diagnose nut allergies. The dosage (one drop for SPT) is the same as in adults; however, the spacing between different tests on the skin must be sufficient (at least 2 cm) to prevent overlapping reactions.

• Age Consideration: Infants under 6 months of age may have reduced skin reactivity, leading to potential false negatives.
• Safety: Testing should be conducted with extreme caution in children with a history of severe asthma.

Renal Impairment

No specific dosage adjustments are required for skin testing in patients with renal impairment, as systemic absorption is minimal. However, patients with end-stage renal disease may exhibit altered skin reactivity (uremic pruritus or reduced inflammatory response).

Hepatic Impairment

No dosage adjustments are necessary for diagnostic extracts. For lipid emulsions containing almond oil, monitoring of serum triglycerides is essential in patients with hepatic dysfunction to prevent fat overload syndrome.

Elderly Patients

Older adults may have thinner skin and reduced subcutaneous fat, which can affect the mechanics of skin testing. Additionally, the 'flare' response (redness) may be less pronounced in geriatric patients, though the 'wheal' (bump) remains a reliable indicator.

Administration for Testing

1. 1The skin site (usually the forearm) is cleaned with an alcohol swab and allowed to dry.
2. 2The skin is marked with a pen to identify the location of each allergen.
3. 3The extract is applied. Do not rub the site.
4. 4The skin is pricked at a 45-degree angle or 90-degree angle depending on the device.
5. 5The patient must remain in the office for at least 30 minutes following the test to monitor for systemic reactions.

Storage Conditions

• Temperature: Allergenic extracts must be stored in a refrigerator at 2°C to 8°C (36°F to 46°F).
• Stability: Do not freeze. Discard if the solution becomes turbid or shows precipitation.

In the context of diagnostic testing, a 'missed dose' is not applicable. If a patient misses a scheduled allergy testing appointment, the procedure is simply rescheduled. For immunotherapy (if almond extract is used off-label for desensitization), a missed dose requires a specific 'step-back' in concentration to avoid reactions; consult your allergist immediately.

An 'overdose' in skin testing occurs if too much extract is injected intradermally or if an excessively high concentration is used for SPT in a highly sensitive individual.

• Symptoms: Rapid onset of a very large wheal, hives (urticaria) spreading beyond the test site, swelling of the throat (angioedema), wheezing, or a drop in blood pressure.
• Emergency Measures: Immediate administration of epinephrine (0.3 mg IM for adults) and activation of emergency medical services. The use of a tourniquet above the test site (if on a limb) was previously recommended but is now secondary to epinephrine administration.

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

When undergoing diagnostic testing with Almond extracts, local reactions are expected and indicate the test is working. These include:

• Pruritus (Itching): Intense itching at the site of the skin prick is the most common side effect. This typically subsides within 30 to 60 minutes.
• Wheal and Flare: A raised white or pale bump (wheal) surrounded by a red area (flare). This is the intended diagnostic response but can be uncomfortable.
• Local Tenderness: The skin may feel slightly sore or sensitive to the touch for a few hours after the test.

• Delayed Local Reaction: Some patients may experience a 'late-phase' reaction where the test site becomes swollen and red 4 to 8 hours after the initial test. This is usually not dangerous but should be reported to the doctor.
• Fatigue: A mild sense of tiredness or 'brain fog' following multiple allergy tests is occasionally reported, likely due to the systemic release of low levels of histamine.
• Contact Dermatitis: In patients with sensitive skin, the glycerin or phenol preservatives in the extract may cause localized irritation or a rash.

• Systemic Urticaria: Hives appearing on parts of the body far away from the testing site (e.g., hives on the legs after testing on the arms).
• Syncope (Fainting): Often a vasovagal response to the needle prick rather than a reaction to the Almond extract itself.
• Lymphangitis: Very rare inflammation of the lymph vessels extending from the test site.

> Warning: Stop the procedure and call for emergency help if you experience any of the following symptoms of anaphylaxis:

1. 1Respiratory Distress: Difficulty breathing, shortness of breath, wheezing, or a persistent cough. This may indicate bronchospasm.
2. 2Angioedema: Swelling of the lips, tongue, or throat that may make swallowing or speaking difficult.
3. 3Cardiovascular Collapse: A sudden drop in blood pressure (hypotension), feeling faint, dizzy, or losing consciousness.
4. 4Gastrointestinal Symptoms: Severe abdominal cramping, vomiting, or diarrhea occurring shortly after the test.
5. 5Generalized Flushing: A sudden feeling of intense heat and redness spreading over the entire body.

Because Almond extracts are used primarily for one-time diagnostic events, long-term side effects are extremely rare. However, repeated exposure to allergenic extracts in an immunotherapy context (off-label) could theoretically lead to:

• Increased Sensitivity: In rare cases, skin testing can 'prime' the immune system, though this is clinically controversial.
• Injection Site Granuloma: A small, hard bump at the site of repeated injections if used for desensitization.

While Almond extracts do not always carry a specific 'Black Box' on the outer carton, the class of Allergenic Extracts carries a general FDA-mandated warning regarding the risk of Severe Anaphylaxis.

Summary of Warning: This product can cause severe life-threatening systemic reactions, including anaphylaxis. Patients must be observed for at least 30 minutes in a facility equipped with emergency supplies, including epinephrine, oxygen, and airway management tools. Patients with unstable asthma are at a significantly higher risk for fatal reactions.

Report any unusual symptoms to your healthcare provider immediately. If you have a history of severe reactions to almonds, ensure your doctor is aware before the test begins.

Almond extracts are intended only for diagnostic use by healthcare professionals. They are not for self-administration. The most critical safety consideration is the potential for a systemic allergic reaction. Patients should be in their baseline state of health; testing during an acute illness or an asthma flare-up is contraindicated.

No specific FDA black box warning exists for Almond extract specifically, but the class-wide warning for Non-Standardized Allergenic Extracts is strictly enforced. This warning emphasizes that these products should only be administered by physicians experienced in allergy skin testing and the treatment of systemic reactions. Epinephrine 1:1000 must be immediately available.

• Anaphylaxis Risk: The risk is highest during intradermal testing. Patients with a known history of near-fatal reactions to almonds should be tested with extreme caution, starting with highly diluted prick tests.
• Asthma: Patients with poorly controlled or severe asthma (FEV1 < 70% of predicted) are at increased risk for a fatal systemic reaction if an extract triggers an allergic response. Asthma must be stable before testing.
• Cardiovascular Disease: Patients with significant heart disease may not tolerate the stress of a systemic reaction or the effects of epinephrine if it becomes necessary to treat a reaction.
• Preservative Sensitivity: Most extracts contain phenol (0.4%) as a preservative. Patients with a known sensitivity to phenol should not be tested.

• Post-Test Observation: A minimum 30-minute wait time in the clinic is mandatory after the last test is applied.
• Baseline Vitals: In high-risk patients, baseline blood pressure and pulse should be recorded.
• Lung Function: For asthmatic patients, a peak flow or spirometry measurement may be taken before testing to ensure stability.

Typically, Almond skin testing does not affect the ability to drive. However, if a systemic reaction occurs or if the patient receives antihistamines or epinephrine, they should not drive until the effects of the medications and the reaction have completely resolved.

Alcohol does not directly interact with Almond extract, but it can cause vasodilation and may theoretically increase the rate of absorption of the allergen from the skin site. It is advisable to avoid alcohol for 24 hours before and after testing to ensure clear results and patient safety.

In a diagnostic setting, 'discontinuation' refers to stopping the test if a systemic reaction begins. If the patient is on a course of almond-based lipid emulsions, they must be tapered according to nutritional guidelines to avoid metabolic disturbances like hyperglycemia.

> Important: Discuss all your medical conditions, especially asthma and heart problems, with your healthcare provider before starting Almond testing.

• Beta-Blockers (e.g., Propranolol, Metoprolol): These medications are contraindicated during allergy testing. In the event of an anaphylactic reaction to the Almond extract, beta-blockers can block the effects of epinephrine, making the reaction much harder to treat and potentially fatal.
• ACE Inhibitors (e.g., Lisinopril): These may increase the risk of severe systemic reactions and interfere with the body's compensatory mechanisms during anaphylaxis.

• Tricyclic Antidepressants (e.g., Amitriptyline): These can potentiate the effect of epinephrine if it is needed to treat a reaction, leading to dangerous increases in blood pressure or heart rhythm issues.
• MAO Inhibitors (e.g., Phenelzine): Similar to TCAs, these medications can interfere with the metabolism of epinephrine, leading to a prolonged and intensified pressor effect.

• Antihistamines (e.g., Loratadine, Cetirizine, Diphenhydramine): These medications must be discontinued prior to testing (usually 3 to 7 days before). They suppress the histamine response, leading to a false-negative test result where the patient appears not to be allergic when they actually are.
• H2 Blockers (e.g., Famotidine): These can also mildly suppress the skin's response to the extract and should be discontinued 24-48 hours before testing.
• Topical Corticosteroids: Applying steroid creams to the test site can suppress the local inflammatory response. These should be avoided on the testing area for at least 2-3 weeks.

• Cross-Reactive Foods: Patients allergic to Almond may also react to other members of the Rosaceae family (peaches, cherries, plums) or other tree nuts (hazelnuts, walnuts). Testing for multiple allergens simultaneously requires careful interpretation due to these cross-reactivities.
• Caffeine: High doses of caffeine can cause tremors or tachycardia, which might be confused with the early signs of a systemic reaction.

• St. John's Wort: May affect the metabolism of medications used to treat allergic reactions.
• Licorice Root: Can have mineralocorticoid effects that may complicate blood pressure management during an emergency.

• Skin Testing: The Almond extract itself is used to 'interact' with the skin. There are no known interactions where Almond extract interferes with standard blood chemistry or hematology labs, other than potentially causing a transient increase in peripheral eosinophil counts if a significant reaction occurs.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, especially any 'heart' or 'blood pressure' pills.

1. 1History of Severe Anaphylaxis to Skin Testing: If a patient has previously had a life-threatening reaction to the testing procedure itself, further testing with Almond extract is absolutely contraindicated.
2. 2Unstable Asthma: Patients with an FEV1 (Forced Expiratory Volume) of less than 70% of their predicted value or those experiencing an acute asthma exacerbation must not undergo testing. The risk of a fatal bronchospasm is too high.
3. 3Acute Infection or Fever: Testing should be delayed until the patient is well to avoid confusing symptoms of illness with an allergic reaction.
4. 4Dermatographism: Patients whose skin welts up in response to any physical touch or pressure cannot be accurately tested, as they will produce a 'positive' result for every substance applied.

1. 1Pregnancy: While not an absolute contraindication, allergy testing is generally avoided during pregnancy unless the information is vital for immediate management. The risk of anaphylaxis-induced fetal hypoxia is a major concern.
2. 2Severe Atopic Dermatitis: If the skin is extensively involved with eczema, there may not be enough 'clear' skin to perform an accurate test.
3. 3Beta-Blocker Therapy: If a patient cannot safely discontinue beta-blockers, the risk-benefit ratio of testing must be carefully evaluated by the physician.

Patients with known allergies to Peanuts or other Tree Nuts (Walnut, Cashew, Pecan) frequently show cross-sensitivity to Almond. Furthermore, because Almond is in the Rosaceae family, cross-reactivity with Birch Pollen (Oral Allergy Syndrome) is common. In these cases, the skin test may be positive due to 'pollen-food syndrome' rather than a primary, potentially life-threatening food allergy.

> Important: Your healthcare provider will evaluate your complete medical history and current skin condition before prescribing or performing an Almond extract test.

Pregnancy Category C. There are no adequate and well-controlled studies of Almond allergenic extract in pregnant women. It is not known whether the extract can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.

• Clinical Consideration: The primary danger to the fetus is maternal anaphylaxis, which can lead to uterine contractions and fetal hypoxia (lack of oxygen).
• Recommendation: Most allergists recommend deferring skin testing until after delivery unless the diagnosis is critical for preventing a life-threatening reaction during the pregnancy.

It is not known whether almond proteins from a skin test are excreted in human milk. Because systemic absorption from a skin prick test is minimal, the risk to a nursing infant is considered extremely low. However, if the mother experiences a systemic reaction requiring medication, the effects of those medications (like epinephrine or antihistamines) on the infant must be considered.

Almond extract is safe and effective for use in children as young as infants for the diagnosis of food allergy.

• Special Considerations: Children are more prone to vasovagal reactions (fainting) and may be more distressed by the procedure.
• Dosing: No dosage adjustment is needed, but the number of tests performed at one time may be limited to reduce the total allergen load.

Clinical studies of Almond extracts did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

• Pharmacokinetics: Reduced skin turgor and capillary fragility in the elderly may lead to larger 'flare' reactions or bruising at the test site.
• Safety: Older patients are more likely to have underlying cardiovascular disease, making them more vulnerable to the effects of a systemic reaction or the epinephrine used to treat it.

No specific studies have been conducted in patients with renal impairment. Systemic clearance of the tiny amounts of protein absorbed is not expected to be a limiting factor. However, uremia (high urea in the blood) can suppress skin test reactivity, potentially leading to false-negative results.

For diagnostic testing, hepatic impairment does not require dose adjustment. For those receiving almond-based lipid emulsions, liver function must be monitored closely, as the liver is the primary site for the metabolism of infused lipids. Impaired clearance can lead to hepatomegaly or 'fat overload syndrome.'

> Important: Special populations, particularly pregnant women and the elderly, require individualized medical assessment before undergoing allergy testing.

Almond extract acts as an antigenic challenge. The specific proteins in the extract, primarily Amandin (Pru du 6) and other allergens like Pru du 4 (a profilin) and Pru du 5 (a ribosomal protein), are recognized by the immune system. In an allergic individual, these proteins bind to the Fab portion of IgE antibodies. These IgE antibodies are 'sensitized' and attached via their Fc portion to high-affinity receptors (FcεRI) on mast cells.

When the almond protein bridges two adjacent IgE molecules, it triggers a signal transduction cascade involving tyrosine kinases (like Syk), leading to an influx of calcium ions. This results in the rapid exocytosis of pre-formed mediators (histamine, tryptase) and the de novo synthesis of lipid mediators. This localized 'allergic explosion' creates the measurable wheal and flare.

• Onset of Action: The wheal and flare response typically begins within 5 minutes of the prick.
• Peak Effect: The maximum reaction size is usually reached between 15 and 20 minutes.
• Duration: The visible reaction generally fades within 1 to 2 hours, though late-phase cellular infiltration can occur 6-12 hours later.

| Parameter | Value |

|---|---|

| Bioavailability | Negligible (Skin Prick); 100% (IV Lipid) |

| Protein Binding | N/A (Local action) |

| Half-life | Proteins: Minutes to Hours (Systemic) |

| Tmax | 15-20 minutes (Skin response) |

| Metabolism | Cellular proteases |

| Excretion | Renal (Metabolites) |

• Molecular Components: A complex mixture of proteins, glycoproteins, and polysaccharides. Amandin is a hexameric protein with a molecular weight of approximately 360 kDa.
• Solubility: The extract is a water-soluble fraction of the almond seed, typically prepared in a buffered saline or glycerin solution.
• Stability: Highly sensitive to temperature; heat denaturation of the proteins will render the extract diagnostically useless.

Almond belongs to the Non-Standardized Food Allergenic Extract [EPC] class. It is grouped with other tree nut extracts (e.g., Walnut, Cashew) and is distinct from 'standardized' extracts like Grass Pollens or Cat Hair, which have federally mandated potency standards.