7.3 Immunology, Allergy, & Vaccine-Preventable Diseases

Immunology, Allergy, & Vaccine-Preventable Diseases

Pharmacists play a critical role in promoting public health through vaccination administration, evaluating complex allergy profiles, and managing severe immunological emergencies. Understanding the precise interplay between a patient's baseline immune status and immunotherapeutic interventions is a core competency required for the BCPS exam.

Vaccine Schedules and Guidelines (CDC Recommendations)

Adult immunization recommendations are continuously evaluated and updated by the CDC's Advisory Committee on Immunization Practices (ACIP). The clinical pharmacist must memorize the age, risk, and timeline parameters for primary adult vaccines.

Pneumococcal Vaccination

Pneumococcal disease is a leading cause of vaccine-preventable mortality. The current guidelines simplify previous complex algorithms:

• Routine Age-Based: All adults ≥ 65 years who have not previously received a pneumococcal conjugate vaccine (or whose history is unknown) should receive either:
  • PCV20 (Prevnar 20) as a single dose.
  • PCV15 (Vaxneuvance) followed by PPSV23 (Pneumovax 23) one year later.
• Risk-Based (Aged 19–64 years): Patients with underlying medical conditions (e.g., diabetes mellitus, chronic heart/lung/liver disease, alcoholism) or immunocompromising conditions (e.g., HIV, chronic renal failure, solid organ transplant) should also follow the same regimen (PCV20 alone OR PCV15 followed by PPSV23).
  • Note: In severely immunocompromised patients, the interval between PCV15 and PPSV23 may be shortened to 8 weeks to provide rapid, broad serotype coverage.

General Adult Vaccines

• Influenza: Recommended annually for all persons ≥ 6 months. Adults ≥ 65 years should preferentially receive a high-dose inactivated vaccine (Fluzone High-Dose) or an adjuvanted inactivated vaccine (Fluad) to boost the senescent immune response.
• Tetanus, Diphtheria, Pertussis: All adults require one dose of Tdap, followed by a Td or Tdap booster every 10 years. Crucially, pregnant individuals must receive Tdap during every pregnancy (optimally between 27 and 36 weeks gestation) to maximize the passive transfer of protective maternal antibodies to the infant.
• RSV: A single dose is recommended for adults ≥ 60 years using shared clinical decision-making. It is also recommended for pregnant individuals at 32-36 weeks gestation to protect the infant from severe lower respiratory tract disease.
• Zoster: The recombinant zoster vaccine (Shingrix/RZV) is an inactive vaccine and is routinely recommended for immunocompetent adults ≥ 50 years, and for immunocompromised adults ≥ 19 years old (administered as 2 doses, 2-6 months apart).

Immunocompromised Patients and Vaccination Rules

Severely immunocompromised patients are at a massive risk of developing systemic, unchecked infections from the attenuated viral or bacterial strains utilized in live vaccines. Live vaccines are strictly contraindicated in this population. Examples of live vaccines include:

• Measles, Mumps, Rubella (MMR)
• Varicella (Chickenpox)
• Live Attenuated Influenza Vaccine (LAIV - Flumist)
• Yellow Fever

Clinical Definition of Severe Immunosuppression includes:

• HIV infection with a CD4 count < 200 cells/mm³.
• Primary immunodeficiency syndromes.
• Malignant neoplasms involving the bone marrow or lymphatic system (e.g., leukemia, lymphoma).
• Patients receiving high-dose systemic corticosteroids (defined as ≥ 20 mg/day of prednisone equivalent, or ≥ 2 mg/kg/day, for ≥ 14 consecutive days).
• Patients on biologic immunosuppressants (e.g., TNF-alpha inhibitors like adalimumab, B-cell depleting therapies like rituximab).

Timing Considerations

• Inactive Vaccines: Should ideally be administered at least 2 weeks before initiating immunosuppressive therapy to ensure an adequate humoral immune response.
• Live Vaccines: Must be administered at least 4 weeks prior to the start of immunosuppression.
• Post-Chemotherapy: If a patient is already receiving systemic chemotherapy, vaccination is usually delayed until at least 3 months after chemotherapy discontinuation to allow for immune system recovery.

Drug Allergies vs. Intolerances

Accurate documentation and differentiation of drug reactions prevents the unnecessary avoidance of first-line optimal therapies, particularly beta-lactam antibiotics.

• Intolerance: An expected, predictable, non-immune mediated pharmacological side effect (e.g., nausea with erythromycin, diarrhea with amoxicillin-clavulanate, headache with nitrates).
• Type I Hypersensitivity (IgE-Mediated): True allergic reactions occurring rapidly (within minutes to a few hours) after exposure to an antigen. The antigen cross-links IgE on the surface of mast cells, causing massive degranulation of histamine, tryptase, and leukotrienes. Manifestations include urticaria (hives), angioedema, intense bronchospasm, and anaphylaxis.
• Type IV Hypersensitivity (T-cell Mediated): Delayed reactions occurring days to weeks after exposure. These include benign maculopapular rashes, or severe cutaneous adverse reactions (SCARs) like Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), and DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms).

Drug Desensitization Protocols

When a patient has a documented IgE-mediated Type I allergy to a medication that is considered the absolute therapy of choice with no viable alternatives (e.g., treating neurosyphilis with intravenous penicillin in a severe penicillin-allergic patient), desensitization may be pursued.

Procedure and Restrictions

• Mechanism: Desensitization induces a state of temporary clinical tolerance by slowly and safely depleting IgE cross-linking on mast cells, thereby preventing sudden, massive, life-threatening degranulation.
• Procedure: The drug is administered starting at an extremely low micro-dose (e.g., a 1:10,000 dilution). The dose is systematically doubled every 15 to 30 minutes until the full therapeutic target dose is successfully reached. This is strictly performed in an ICU setting with crash carts and airway management tools immediately available.
• Duration of Tolerance: The state of tolerance is entirely dependent on the continuous presence of the drug in the body. If the medication is discontinued and cleared from the body (e.g., missing several half-lives), the patient's mast cells will reset, they will revert to being fully allergic, and the entire desensitization protocol must be repeated from the beginning.
• Absolute Contraindications: Desensitization can NEVER be used for patients with a history of Type IV delayed hypersensitivity reactions, specifically SJS, TEN, DRESS, or hemolytic anemia. Re-exposing a patient to a drug that caused SJS, even via desensitization, is universally fatal.

Anaphylaxis Management

Anaphylaxis is an acute, life-threatening, multi-systemic syndrome resulting from the sudden systemic release of mast cell and basophil mediators, triggering profound vasodilation and smooth muscle contraction.

Acute Medical Management

1. Epinephrine (Adrenalin): The absolute definitive first-line and immediate treatment.
   • Dose: 0.3 to 0.5 mg in adults (0.01 mg/kg in pediatrics, max 0.3 mg).
   • Route/Location: Intramuscular (IM) injection into the vastus lateralis (anterolateral aspect of the thigh). Subcutaneous administration has highly variable and delayed absorption during shock.
   • Mechanism: Alpha-1 agonism causes potent vasoconstriction (rapidly reversing profound hypotension and mucosal airway edema), Beta-1 agonism increases cardiac output, and Beta-2 agonism causes intense bronchodilation and actively stabilizes mast cells to halt further histamine release.
   • Repeat: Can be repeated every 5 to 15 minutes if symptoms do not rapidly improve.
2. Adjunctive Therapies: (These are secondary, have a delayed onset, and absolutely do not replace Epinephrine)
   • H1-antihistamines (e.g., Diphenhydramine IV/PO) for the relief of cutaneous pruritus and urticaria.
   • H2-antihistamines (e.g., Famotidine IV) may provide additional histamine receptor blockade.
   • Corticosteroids (e.g., Methylprednisolone IV) are given to prevent the biphasic (delayed) anaphylactic response that can occur 8-12 hours later; their onset of action takes several hours.
   • Albuterol nebulizers for residual bronchospasm resistant to initial epinephrine.
   • Aggressive IV fluid resuscitation (Normal Saline or Lactated Ringer's) for persistent, refractory hypotension.

Confounding Medications in Anaphylaxis

• Beta-Blockers: Patients taking non-selective beta-blockers (e.g., propranolol) may present with anaphylaxis that is highly refractory to standard doses of epinephrine. In these cases, Glucagon is administered intravenously. Glucagon bypasses the blocked beta-receptors, activating adenylate cyclase directly to provide positive inotropic and chronotropic effects on the failing heart.
• ACE Inhibitors: Can severely worsen anaphylaxis presentations by inhibiting the breakdown of bradykinin, significantly increasing the severity and duration of angioedema and hypotension.