Atlantic Cod

Dosage for Atlantic Cod is not standardized across all manufacturers, meaning the potency can vary between 'Protein Nitrogen Units' (PNU) and 'Weight/Volume' (w/v) ratios.

• Skin Prick Testing: A single drop of the 1:10 or 1:20 w/v extract is applied to the skin, followed by a light puncture.
• Intradermal Testing: If the prick test is negative, a dose of 0.02 mL to 0.05 mL of a 1:1000 w/v dilution may be injected into the dermis.
• Immunotherapy: Dosing begins at an extremely low concentration (e.g., 0.1 mL of a 1:100,000 dilution) and is gradually increased over several months (the 'build-up phase') to a maintenance dose determined by the allergist.

Atlantic Cod extracts are approved for use in children, provided the procedure is performed by a qualified specialist.

• Infants and Children: The dosage for skin prick testing is identical to adults (one drop). However, the number of simultaneous tests may be limited to prevent excessive discomfort or systemic absorption in very small children.
• Safety: Pediatric patients must be monitored more closely for systemic signs of anaphylaxis, as they may not be able to verbalize early symptoms like throat tightness.

Renal Impairment

No specific dosage adjustments are required for renal impairment when used for diagnostic skin testing, as systemic absorption is negligible. However, in immunotherapy, patients with severe renal disease may have a reduced capacity to clear inflammatory mediators released during a reaction.

Hepatic Impairment

No dosage adjustments are formally established for patients with liver disease. The metabolic breakdown of the proteins occurs via ubiquitous proteases rather than specific hepatic CYP450 pathways.

Elderly Patients

Elderly patients may have reduced skin reactivity (atopy) due to the natural thinning of the dermis and a decrease in mast cell density. Healthcare providers may need to interpret 'borderline' wheal sizes with caution in patients over 65.

Atlantic Cod extracts are never for self-administration or oral consumption. They must be administered by a healthcare professional in a clinical setting equipped to handle emergencies.

• Preparation: The skin (usually the forearm or back) is cleaned with alcohol and allowed to dry.
• Application: The extract is applied using a sterile lancet or multi-test device.
• Observation: The patient must remain in the office for at least 30 minutes after application to monitor for systemic reactions.
• Storage: Vials must be stored in a refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze, as freezing can denature the parvalbumin proteins and render the extract ineffective.

In the context of diagnostic testing, a missed appointment simply requires rescheduling. For patients on an immunotherapy schedule, a missed dose may require 'backing up' to a lower concentration to ensure safety, depending on how much time has passed since the last injection.

An 'overdose' of Atlantic Cod extract typically occurs if too much extract is injected intradermally or if the concentration is too high for the patient's sensitivity level.

• Signs: Rapid development of a large wheal (>20mm), generalized hives (urticaria), swelling of the face or throat (angioedema), wheezing, and drop in blood pressure.
• Emergency Measures: Immediate administration of Epinephrine (0.3mg IM for adults), oxygen, and intravenous fluids. The site of the injection may be tied off with a tourniquet to slow further absorption.

> Important: Follow your healthcare provider's dosing instructions. Do not adjust your dose without medical guidance.

The most frequent side effects of Atlantic Cod extract are localized to the site of administration. These are often expected results of a diagnostic test:

• Pruritus (Itching): Intense itching at the site of the skin prick, usually beginning within 5 minutes and lasting up to an hour.
• Wheal Formation: A raised, pale bump resembling a mosquito bite. This is the primary indicator of a positive test.
• Erythema (Redness): A 'flare' of redness surrounding the wheal, caused by localized vasodilation.
• Local Tenderness: The area may feel warm or slightly sore for several hours following the procedure.

• Late-Phase Reactions: Swelling and redness that reappear 4 to 8 hours after the initial test. These are typically not dangerous but can be uncomfortable.
• Lymphadenopathy: Mild swelling of the lymph nodes near the testing site (e.g., in the axilla/armpit if the test was on the arm).
• Fatigue: Some patients report feeling unusually tired for the remainder of the day after extensive allergy testing.

• Systemic Urticaria: Hives appearing on parts of the body far away from the test site.
• Vasovagal Response: Fainting or lightheadedness due to the stress of the needle prick, rather than the extract itself.
• Estrogenic Fluctuations: In highly sensitive individuals, the estrogen receptor agonist properties might theoretically cause minor breast tenderness or mood shifts, though this is rarely reported in diagnostic contexts.

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

• Respiratory Distress: Difficulty breathing, wheezing, or a high-pitched sound when breathing (stridor).
• Upper Airway Edema: Feeling of a 'lump in the throat,' hoarseness, or difficulty swallowing.
• Cardiovascular Collapse: Rapid or weak pulse, dizziness, or loss of consciousness.
• Gastrointestinal Distress: Severe abdominal cramping, vomiting, or diarrhea occurring immediately after the test.

When used as a diagnostic agent, there are no known long-term side effects. In the context of long-term immunotherapy, patients may develop 'granulomas' (small firm bumps) at the injection site over several years. Additionally, because of its classification as an estrogen receptor agonist, long-term exposure in a research or off-label setting would require monitoring for estrogen-dependent tissues (e.g., endometrial thickness), though this is not a concern for standard allergy patients.

WARNING: RISK OF SEVERE ALLERGIC REACTIONS

Atlantic Cod allergenic extract can cause severe, life-threatening systemic reactions, including anaphylaxis.

1. 1This product should only be administered by healthcare professionals experienced in the diagnosis and treatment of type I hypersensitivity.
2. 2Patients must be observed for at least 30 minutes following administration.
3. 3Emergency equipment, including epinephrine, oxygen, and airway management tools, must be immediately available.
4. 4Patients with unstable asthma are at a significantly higher risk for fatal reactions and should be evaluated carefully before testing.

Report any unusual symptoms to your healthcare provider.

Atlantic Cod extract is a potent biological agent. It is designed to provoke an immune response, which inherently carries the risk of that response becoming systemic and life-threatening. Patients must provide a full medical history, specifically highlighting any history of severe asthma or previous reactions to fish.

No FDA black box warnings are currently issued for Atlantic Cod as a food item, but as an Allergenic Extract, it carries the standard class warning for anaphylaxis. The full text mandates that the extract be used only in settings where emergency resuscitation is possible and that patients be monitored for a minimum of 30 minutes post-exposure.

• Anaphylaxis Risk: This is the primary concern. Reactions can occur within seconds or minutes. Risk is increased in patients who are currently symptomatic from their allergies or who have high levels of baseline IgE.
• Asthma Status: Patients with poorly controlled or severe asthma are at the highest risk for a fatal outcome if a systemic reaction occurs. Testing should be postponed if the patient is experiencing an asthma flare.
• Cardiovascular Disease: Patients with pre-existing heart conditions may not tolerate the physiological stress of a systemic reaction or the effects of the epinephrine used to treat it.
• Estrogenic Sensitivity: Due to its MoA as an Estrogen Receptor Agonist, individuals with estrogen-sensitive cancers (e.g., certain types of breast or uterine cancer) should discuss the theoretical risks with their oncologist if they are undergoing intensive immunotherapy.

• Immediate Observation: Vital signs (blood pressure, heart rate) should be checked if the patient feels unwell during testing.
• Peak Flow: For asthmatic patients, a peak flow meter may be used before and after testing to ensure no bronchospasm has occurred.
• Skin Site Inspection: The test site must be measured precisely (in millimeters) to ensure accurate diagnosis and to monitor for excessive local swelling.

Atlantic Cod extract does not typically cause sedation. However, if a patient experiences a vasovagal response (fainting) or a systemic reaction requiring medication (like antihistamines or epinephrine), they should not drive or operate machinery for at least 24 hours.

Alcohol consumption should be avoided for 24 hours before and after testing. Alcohol can increase blood flow to the skin (vasodilation), which may lead to false-positive results or accelerate the absorption of the allergen into the bloodstream.

There is no 'withdrawal' from Atlantic Cod extracts. However, if a patient is undergoing immunotherapy and stops treatment, their sensitivity to fish will likely return to its baseline level over time.

> Important: Discuss all your medical conditions with your healthcare provider before starting Atlantic Cod.

• Beta-Blockers (e.g., Propranolol, Atenolol): These medications are contraindicated in patients undergoing allergy testing or immunotherapy. If a patient has a severe reaction, beta-blockers prevent epinephrine from working effectively, making the reaction much harder to treat and potentially fatal.
• MAO Inhibitors (e.g., Phenelzine): These can potentiate the effects of epinephrine used in emergencies, leading to dangerous spikes in blood pressure.

• ACE Inhibitors (e.g., Lisinopril): Some studies suggest ACE inhibitors may increase the risk of severe systemic reactions or interfere with the body's natural compensatory mechanisms during anaphylaxis.
• Tricyclic Antidepressants (e.g., Amitriptyline): Similar to MAOIs, these can interfere with the metabolism of emergency medications.

• Antihistamines (e.g., Loratadine, Cetirizine): These must be stopped 3 to 7 days before testing. They do not cause a dangerous interaction, but they will suppress the skin's reaction to the Atlantic Cod extract, leading to a false-negative result.
• H2 Blockers (e.g., Famotidine): These should also be discontinued as they can partially suppress the wheal and flare response.
• Systemic Corticosteroids: Long-term use of oral steroids (like Prednisone) can thin the skin and reduce the inflammatory response, potentially masking a positive allergy test.

• Cross-Reactive Foods: Patients allergic to Atlantic Cod often react to other white fish (Haddock, Pollock) due to similar parvalbumin structures. Consuming these foods shortly before a test can prime the immune system for a more severe reaction.
• High-Fat Meals: Theoretically, high-fat meals can alter the absorption of lipid-soluble components of the extract, though the clinical significance in diagnostic testing is low.

• St. John's Wort: May interact with the estrogenic pathways of the extract, potentially altering the cellular response in research settings.
• Phytoestrogens (e.g., Soy Isoflavones): May compete for the same estrogen receptors (ER-alpha/beta), potentially blunting the estrogenic MoA of the Atlantic Cod extract.

• Skin Testing: The extract itself is the tool for the test. However, recent use of the extract can temporarily deplete local mast cell mediators, potentially affecting the results of subsequent skin tests performed at the same site within 48 hours.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking.

• Unstable Asthma: Patients with an FEV1 (Forced Expiratory Volume) less than 70% of predicted or those with recent exacerbations must not undergo testing, as a systemic reaction could lead to fatal airway closure.
• Recent Myocardial Infarction (Heart Attack): Within the last 3-6 months. The heart cannot tolerate the stress of a potential anaphylactic reaction or the high-dose epinephrine required to treat it.
• History of Severe Anaphylaxis to Fish: If a patient has previously stopped breathing or lost consciousness after eating cod, a skin prick test may be too dangerous; a blood test (sIgE) is preferred.
• Hypersensitivity to Phenol: Most extracts use phenol as a preservative. Patients with a known allergy to phenol must not be exposed to these extracts.

• Pregnancy: While not strictly forbidden, diagnostic testing is usually postponed until after delivery to avoid the risk of anaphylaxis-induced fetal hypoxia (lack of oxygen).
• Beta-Blocker Therapy: If the medication cannot be safely paused, the risk of testing must be weighed against the diagnostic necessity.
• Severe Atopic Dermatitis: If the skin is extensively inflamed or damaged, there may be no 'clear' skin available for an accurate test.

Patients sensitive to Atlantic Cod extract are highly likely to show cross-sensitivity to:

• Other Gadiformes: Haddock, Whiting, and Hake.
• Other Fish Classes: Salmon, Trout, and Tilapia (due to the highly conserved nature of parvalbumin proteins).
• Fish Gelatin: Used in some pharmaceutical capsules and food products.

> Important: Your healthcare provider will evaluate your complete medical history before prescribing Atlantic Cod.

Atlantic Cod extract is classified as FDA Pregnancy Category C. This means that animal reproduction studies have not been conducted, and it is unknown if the extract can cause fetal harm. The primary risk is not the extract itself, but the potential for maternal anaphylaxis. A severe allergic reaction can cause a sudden drop in maternal blood pressure, leading to placental hypoperfusion and fetal distress. Consequently, healthcare providers typically avoid initiating allergy testing or 'up-dosing' immunotherapy during pregnancy.

It is not known whether the protein components of Atlantic Cod extract pass into human breast milk. However, since the proteins are largely degraded at the site of injection or by systemic proteases, the risk to a nursing infant is considered extremely low. The decision to continue immunotherapy during breastfeeding should be a shared decision between the patient and their allergist.

Atlantic Cod extracts are widely used in pediatric allergy clinics. Children as young as infants can be tested, though the immune system's reactivity matures with age.

• Efficacy: Skin testing is highly accurate in children for diagnosing IgE-mediated fish allergy.
• Safety: The risk of systemic reactions in children is similar to adults, but monitoring is more difficult. Pediatricians must watch for behavioral changes (irritability, lethargy) as signs of an early reaction.

In patients over 65, several factors must be considered:

• Skin Reactivity: Reduced histamine response in the skin may lead to smaller wheal sizes, potentially causing false-negative results.
• Comorbidities: Higher prevalence of cardiovascular disease and use of beta-blockers increases the risk profile for diagnostic procedures.
• Pharmacokinetics: Slower lymphatic clearance may slightly prolong the duration of local reactions.

In patients with chronic kidney disease (CKD), the clearance of inflammatory markers released during an allergic reaction may be delayed. While no dose adjustment is needed for a single skin test, caution is advised during repeated exposures in immunotherapy.

Liver disease does not significantly impact the safety or efficacy of Atlantic Cod extract, as the liver is not the primary site of protein allergen metabolism. However, patients with severe hepatic encephalopathy may be unable to report early symptoms of a reaction.

> Important: Special populations require individualized medical assessment.

Atlantic Cod extract functions through two distinct pathways:

1. 1Immunological: The parvalbumin protein (Gad m 1) contains specific epitopes (binding sites) that are recognized by IgE antibodies. Upon binding, it triggers the high-affinity IgE receptor (FcεRI) on mast cells, leading to a calcium-dependent release of pre-formed mediators (histamine) and newly synthesized mediators (leukotrienes).
2. 2Endocrinological: As an Estrogen Receptor Agonist, specific lipid-soluble components or peptide sequences within the extract exhibit affinity for the Estrogen Receptor (ER). This MoA involves the classical genomic pathway where the ligand-receptor complex acts as a transcription factor in the nucleus.

• Onset of Action: For skin testing, the immunological response begins within 1-2 minutes, peaking at 15-20 minutes.
• Duration: The wheal typically subsides within 1-2 hours, though the underlying immunological priming remains.
• Dose-Response: There is a linear correlation between the concentration of parvalbumin and the diameter of the wheal, up to a 'saturation' point.

| Parameter | Value |

|---|---|

| Bioavailability | High (Local); Low (Systemic) |

| Protein Binding | Primarily to IgE and Albumin |

| Half-life | ~30-60 minutes (local tissue) |

| Tmax | 15-20 minutes (for skin reaction) |

| Metabolism | Proteolytic cleavage by Trypsin/Chymotrypsin-like enzymes |

| Excretion | Renal (as small peptides) |

• Molecular Weight: Major allergen Gad m 1 is approximately 12,388 Daltons.
• Solubility: Highly soluble in aqueous solutions and 50% glycerin.
• Structure: Parvalbumins are calcium-binding proteins with a characteristic 'EF-hand' motif, which is highly resistant to heat and acid digestion.

Atlantic Cod belongs to the therapeutic class of Allergenic Extracts and the functional class of Estrogen Receptor Agonists. It is grouped with other fish extracts like Salmon and Tuna in the 'Non-Standardized Food Allergenic Extract' category.