Atlantic Salmon

Diagnostic Skin Prick Testing

For the diagnosis of food allergy, the standard adult dose involves the application of one drop of the Atlantic Salmon extract (usually at a concentration of 1:10 or 1:20 w/v in a glycerinated solution) to the skin, typically on the forearm or back. A sterile lancet is then used to prick the skin through the drop. A positive control (histamine) and a negative control (saline) are applied simultaneously for comparison.

Intradermal Testing

If a skin prick test is negative but the clinical history strongly suggests an allergy, a healthcare provider may perform intradermal testing. This involves injecting 0.02 mL to 0.05 mL of a highly diluted extract (e.g., 1:100 or 1:1000) into the dermal layer of the skin.

Estrogenic Modulation

When used for its estrogenic properties, dosages are highly individualized and based on serum hormone levels. Typical investigational doses range from 50 mg to 200 mg of specific salmon-derived bioactive compounds daily, though this must be strictly managed by an endocrinologist.

Children (Ages 2 and older)

Pediatric dosing for skin testing is identical to adult dosing in terms of the concentration used. However, the number of tests performed in a single session may be limited to reduce the risk of systemic reactions and patient discomfort. Atlantic Salmon extract is not generally recommended for skin testing in infants under 6 months of age unless the clinical necessity outweighs the risks.

Renal Impairment

No specific dosage adjustments are required for diagnostic skin testing in patients with kidney disease. For systemic use of estrogenic components, caution is advised as metabolites are renally excreted; however, formal GFR-based guidelines have not been established.

Hepatic Impairment

Patients with significant liver dysfunction (Child-Pugh Class B or C) may experience slower metabolism of the estrogenic components of the extract. In such cases, lower doses and frequent monitoring of liver function tests (LFTs) and hormone levels are recommended.

Elderly Patients

Elderly patients may have thinner skin, which can lead to more frequent false-positive results in skin testing. Additionally, the estrogenic effects must be carefully weighed against the risk of cardiovascular events or hormone-sensitive cancers in this population.

• Preparation: Ensure the skin site is clean and free of topical creams or ointments. Avoid the use of antihistamines for at least 48 to 72 hours prior to testing.
• Administration: For diagnostic use, the extract must be administered by a healthcare professional. For oral forms (if prescribed), it should be taken at the same time each day to maintain steady-state levels, ideally with a small meal to improve absorption of lipid-soluble components.
• Storage: Vials should be stored in a refrigerator between 2°C and 8°C (36°F to 46°F). Do not freeze. Discard the vial if the solution becomes turbid or changes color significantly.

For diagnostic testing, a missed appointment simply requires rescheduling. For therapeutic use, if a dose is missed, take it as soon as remembered. If it is almost time for the next dose, skip the missed dose and resume the regular schedule. Do not double the dose to catch up.

An overdose of Atlantic Salmon extract, particularly during skin testing or immunotherapy, can lead to systemic anaphylaxis. Signs include:

• Generalized hives (urticaria)
• Swelling of the throat or tongue (angioedema)
• Difficulty breathing or wheezing
• Rapid or weak pulse
• Low blood pressure (hypotension)

In the event of an overdose or systemic reaction, emergency administration of epinephrine (0.3 mg for adults) is the first-line treatment, followed by immediate transport to an emergency facility.

> Important: Follow your healthcare provider's dosing instructions exactly. Do not attempt to self-administer allergenic extracts at home.

• Localized Wheal and Flare: This is the expected reaction during a positive skin test. It involves a raised, itchy bump (wheal) surrounded by a red area (flare). This typically peaks at 15-20 minutes and resolves within a few hours.
• Local Pruritus (Itching): Intense itching at the site of application is very common and is caused by the release of histamine in the skin.
• Erythema (Redness): Redness extending beyond the test site is common and generally harmless unless accompanied by systemic symptoms.

• Delayed Local Reaction: Some patients may experience swelling and redness at the test site 6 to 24 hours after the test. This is known as a late-phase reaction.
• Nausea: Mild gastrointestinal upset may occur if the extract is used systemically or if a mild systemic allergic response occurs.
• Headache: Some patients report mild headaches following exposure to allergenic extracts or estrogenic compounds.
• Breast Tenderness: Due to the Estrogen Receptor Agonist [MoA], some individuals may experience sensitivity or tenderness in the breast tissue.

• Syncope (Fainting): Often a vasovagal response to the needle prick rather than a reaction to the extract itself.
• Lymphadenopathy: Swelling of the lymph nodes near the site of administration.
• Uterine Spotting: In post-menopausal women, the estrogenic activity may rarely trigger minor endometrial thickening or spotting.

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

• Respiratory Distress: Shortness of breath, wheezing, or a feeling of tightness in the chest. This indicates airway constriction.
• Angioedema: Significant swelling of the lips, tongue, or throat that may interfere with swallowing or breathing.
• Hypotension: A sudden drop in blood pressure, which may feel like extreme dizziness, lightheadedness, or fainting.
• Generalized Urticaria: Hives that spread across the entire body, away from the site of the skin test.
• Cyanosis: A bluish tint to the lips or fingernails, indicating poor oxygenation.

With repeated exposure, such as in immunotherapy or long-term hormonal use, patients may develop:

• Increased Sensitivity: In rare cases, repeated skin testing could theoretically sensitize a previously non-allergic individual.
• Hormonal Imbalance: Prolonged use of estrogen agonists can lead to changes in the menstrual cycle or increase the risk of gallbladder disease.
• Bone Mineral Density Changes: While often positive (preventing osteoporosis), long-term estrogenic modulation requires careful monitoring of bone health.

WARNING: RISK OF SYSTEMIC ANAPHYLAXIS

Atlantic Salmon allergenic extract can cause severe, life-threatening systemic allergic reactions, including anaphylaxis. Because of this risk, skin testing should only be performed by healthcare professionals who are experienced in the diagnosis and treatment of severe allergic reactions and who have immediate access to emergency medications, including epinephrine injection. Patients should be observed for at least 30 minutes following administration to monitor for signs of a systemic reaction.

Report any unusual symptoms or persistent side effects to your healthcare provider immediately.

Atlantic Salmon extract is a potent biological agent. Its use must be restricted to clinical environments equipped with resuscitation equipment. Patients with a history of severe asthma are at a higher risk for complications during skin testing and must be stabilized before the procedure begins.

No FDA black box warnings for Atlantic Salmon as a food product, but as an Allergenic Extract, it carries the standard class warning for Anaphylaxis Risk. The extract must be administered under medical supervision, and patients must be monitored for 30 minutes post-injection. Epinephrine must be available for immediate use.

• Allergic Reactions / Anaphylaxis Risk: The primary risk is a systemic Type I hypersensitivity reaction. This risk is higher in patients with high levels of specific IgE or those undergoing testing during peak allergy seasons for other substances.
• Asthma Exacerbation: Patients with poorly controlled asthma may experience a severe bronchospasm (tightening of the airways) if a systemic reaction occurs. Testing should be postponed if the patient is experiencing an acute asthma flare.
• Cardiovascular Risk: Due to its Estrogen Receptor Agonist properties, there is a theoretical risk of increased blood clotting (thromboembolism). Caution is advised in patients with a history of Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE).
• Hormone-Sensitive Cancers: Patients with a history of breast, uterine, or ovarian cancer should avoid the systemic use of Atlantic Salmon extract due to its estrogenic activity, which could potentially stimulate the growth of malignant cells.

• Immediate Post-Test Observation: 30-minute mandatory wait time after skin testing.
• Pulmonary Function: For asthmatic patients, a peak flow meter or spirometry may be used before and after testing.
• Hormone Panels: If used for estrogenic effects, regular monitoring of estradiol, FSH, and LH levels is necessary.
• Liver Function Tests (LFTs): Periodic monitoring of ALT, AST, and bilirubin if used systemically over long periods.

Atlantic Salmon extract generally does not interfere with the ability to drive. However, if a systemic reaction occurs or if the patient feels dizzy/lightheaded after testing, they should avoid operating machinery until symptoms have completely resolved and they have been cleared by a physician.

Alcohol consumption should be avoided on the day of skin testing. Alcohol can increase blood flow to the skin (vasodilation), which may lead to exaggerated skin test results or potentially accelerate the absorption of the extract into the systemic circulation.

There are no withdrawal syndromes associated with discontinuing Atlantic Salmon extract after diagnostic use. For those using it for its estrogenic effects, tapering is generally not required, but patients should be monitored for the return of estrogen-deficiency symptoms (e.g., hot flashes).

> Important: Discuss all your medical conditions, especially heart disease, asthma, and cancer history, with your healthcare provider before starting Atlantic Salmon.

• Beta-Blockers (e.g., Propranolol, Atenolol): These medications are contraindicated during skin testing with Atlantic Salmon extract. Beta-blockers can make a systemic allergic reaction more severe and, crucially, can interfere with the effectiveness of epinephrine if it is needed to treat anaphylaxis.
• MAO Inhibitors (e.g., Phenelzine): These can potentiate the effects of sympathomimetic amines used in emergency treatment, complicating the management of a reaction.

• Antihistamines (H1 Blockers): Drugs like cetirizine, loratadine, and diphenhydramine must be stopped 3-7 days before skin testing. They block the histamine receptors in the skin, leading to false-negative results (the test shows no allergy even if one exists).
• Tricyclic Antidepressants (TCAs): Medications such as amitriptyline have potent antihistamine properties and can suppress skin reactivity for up to two weeks.
• Systemic Corticosteroids: Long-term use of oral steroids (like prednisone) can suppress the immune response and dampen skin test results, though short-term use may have less impact.

• H2 Antagonists (e.g., Famotidine): While less potent than H1 blockers, they can still slightly reduce the size of the wheal during skin testing.
• Aromatase Inhibitors (e.g., Anastrozole): Since Atlantic Salmon has estrogenic activity, it may counteract the efficacy of medications used to lower estrogen levels in cancer treatment.
• CYP3A4 Inducers (e.g., Rifampin, St. John's Wort): These may speed up the metabolism of the estrogenic components of the extract, reducing their effectiveness.

• Caffeine: High intake of caffeine may increase heart rate and anxiety during testing, potentially masking or mimicking early signs of a systemic reaction.
• High-Fat Meals: If taking oral forms of salmon-derived compounds, high-fat meals may increase the absorption of fat-soluble estrogenic ligands.

• St. John's Wort: May induce liver enzymes and decrease the levels of estrogenic components.
• Soy Isoflavones: These also have estrogenic activity and may have additive effects with Atlantic Salmon extract, potentially increasing the risk of estrogen-related side effects.

• Skin Testing Results: The presence of other allergens can cause cross-reactivity. For example, a patient allergic to other salmonids (like Trout) may show a positive result for Atlantic Salmon due to shared protein structures (Parvalbumins).
• Thyroid Function Tests: Estrogens can increase the levels of thyroid-binding globulin, which may affect the results of total T4 and T3 tests, though free T4 levels usually remain normal.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, especially those for allergies, depression, or heart rhythm.

• History of Severe Anaphylaxis to Salmon: If a patient has a documented history of near-fatal anaphylaxis to Atlantic Salmon, skin testing is generally contraindicated as even a minute amount of the extract could trigger a life-threatening event. In vitro (blood) testing like RAST or ImmunoCAP is preferred.
• Uncontrolled Asthma: Patients with an FEV1 (Forced Expiratory Volume) of less than 70% of predicted values or those with frequent acute exacerbations should not undergo testing until their asthma is well-controlled.
• Recent Myocardial Infarction: Patients who have had a heart attack within the last 3-6 months should avoid testing, as the physiological stress of a potential reaction or the administration of epinephrine could be fatal.
• Active Skin Disease: Testing cannot be performed on skin with active eczema, psoriasis, or severe dermatitis, as these conditions interfere with the interpretation of results.

• Pregnancy: While not strictly forbidden, skin testing is usually deferred until after delivery to avoid the risk of uterine contractions or fetal distress in the event of a systemic reaction.
• Beta-Blocker Therapy: If a patient cannot safely discontinue beta-blockers, the risk-benefit ratio of skin testing must be carefully evaluated.
• Dermographism: This is a condition where the skin wheals easily from simple pressure. In these patients, the negative control will also be positive, making the test results uninterpretable.

Patients with known allergies to other members of the Salmonidae family (such as Rainbow Trout, Brown Trout, or Arctic Char) are highly likely to exhibit cross-sensitivity to Atlantic Salmon extract. This is due to the highly conserved nature of the Parvalbumin protein across these species. Caution is also advised in patients with allergies to Gadiformes (cod-like fish), though the degree of cross-reactivity is generally lower than within the salmonid family.

> Important: Your healthcare provider will evaluate your complete medical history and current skin condition before prescribing or administering Atlantic Salmon extract.

FDA Pregnancy Category C. There are no adequate and well-controlled studies of Atlantic Salmon extract in pregnant women. Diagnostic skin testing is generally not recommended during pregnancy because of the risk of systemic anaphylaxis, which can cause maternal hypoxia (low oxygen) and subsequent fetal distress or preterm labor. If the extract's estrogenic properties are being utilized, it is important to note that exogenous estrogens can interfere with the normal hormonal milieu of pregnancy and are generally avoided unless specifically indicated for a condition like luteal phase support in IVF, though Atlantic Salmon is not the standard agent for this.

It is not known whether the allergenic proteins or the specific estrogenic components of Atlantic Salmon extract are excreted in human milk. Because many drugs are excreted in milk and because of the potential for the infant to develop a sensitivity, caution should be exercised. For diagnostic skin testing, the systemic absorption is so low that it is unlikely to affect a nursing infant. However, the mother should be monitored closely for any systemic reaction that could interfere with her ability to breastfeed.

Atlantic Salmon extract is commonly used in children for the diagnosis of food allergies. The safety and efficacy of skin testing have been established in children as young as 2 years old. In younger children, the skin may be less reactive, leading to smaller wheal sizes. Healthcare providers must use smaller lancets and ensure the child is properly immobilized to prevent injury. The use of the extract for its estrogenic properties is NOT approved in the pediatric population and could lead to premature epiphyseal closure (stopping of bone growth) and precocious puberty.

Clinical studies of Atlantic Salmon extract did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, elderly patients have a higher prevalence of cardiovascular disease and may be taking medications like beta-blockers or ACE inhibitors, which increase the risk and complexity of treating an allergic reaction. Furthermore, age-related skin atrophy can make the interpretation of skin tests more difficult.

In patients with renal impairment, the clearance of the estrogenic metabolites may be reduced. While this does not affect diagnostic skin testing, it is a critical consideration for any systemic therapeutic application. No specific dosage adjustments are provided in the labeling, but close monitoring of serum levels is advised for patients with a GFR < 30 mL/min.

Since the liver is the primary site for the metabolism of estrogenic compounds, patients with hepatic impairment (e.g., cirrhosis, hepatitis) may experience prolonged effects and increased toxicity. Diagnostic skin testing remains safe, but systemic use requires a reduction in frequency or dose based on Child-Pugh scores.

> Important: Special populations require individualized medical assessment and often a more conservative approach to dosing and monitoring.

Atlantic Salmon extract functions via two distinct molecular pathways:

1. 1IgE-Mediated Degranulation: The allergenic proteins (primarily Sal s 1) bind to bivalent IgE molecules on the surface of mast cells. This triggers the activation of tyrosine kinases (like Lyn and SyK), leading to an influx of calcium ions and the subsequent release of pre-formed mediators (histamine) and newly synthesized mediators (leukotrienes) into the local tissue.
2. 2Estrogen Receptor Modulation: The extract contains ligands that bind to the ligand-binding domain (LBD) of Estrogen Receptors Alpha and Beta. This induces a conformational change that allows the receptor to dimerize and interact with co-activator proteins. This complex then binds to specific DNA sequences (Estrogen Response Elements), initiating the transcription of genes that regulate various physiological processes.

• Onset of Action (Allergy): 5 to 10 minutes for the initial wheal to appear.
• Peak Effect (Allergy): 15 to 20 minutes.
• Duration (Allergy): 2 to 4 hours for the immediate reaction; up to 24 hours for late-phase reactions.
• Hormonal Effect: Requires several days of consistent dosing to reach a steady-state physiological effect on gene expression.

| Parameter | Value |

|---|---|

| Bioavailability | <1% (Skin Prick); ~15-20% (Oral Estrogenic Components) |

| Protein Binding | 95-98% (primarily to SHBG and Albumin) |

| Half-life | 20-30 minutes (Allergenic Proteins); 4-6 hours (Estrogenic Metabolites) |

| Tmax | 15 minutes (Local); 1-2 hours (Systemic) |

| Metabolism | Hepatic (CYP3A4, CYP1A2) |

| Excretion | Renal (80%), Fecal (20%) |

• Molecular Formula: Complex biological mixture (N/A)
• Molecular Weight: Ranges from 12 kDa (Parvalbumin) to >100 kDa (Complex proteins)
• Solubility: Soluble in aqueous solutions and 50% glycerin/water mixtures.
• Structure: The primary allergen, Sal s 1, is a calcium-binding albumin protein with a characteristic EF-hand motif, which is highly stable and resistant to heat and proteolytic digestion.

Atlantic Salmon is classified as a Non-Standardized Food Allergenic Extract and an Estrogen Receptor Agonist. It is related to other fish extracts like Codfish and Tuna extracts, as well as phytoestrogens and selective estrogen receptor modulators (SERMs) in its hormonal activity.