Continuing Education Activity

Varicella-zoster immune globulin (VZIG) is a medication used for postexposure prophylaxis and treatment of varicella. It is in the "Opportunistic Infections and Co-infections" treatment class of drugs. Varicella-zoster immune globulin is indicated for post-exposure prophylaxis in high-risk individuals. This activity reviews the indications, contraindications, mechanism of action, adverse effects, and other vital elements of varicella-zoster immune globulin therapy in the clinical setting. It relates to the essential points needed by members of an interprofessional team managing high-risk individuals and prevents them against varicella and its related conditions.

Objectives:

• Identify the indications for varicella-zoster immune globulin.
• Describe the contraindications of varicella-zoster immune globulin.
• Review appropriate monitoring of varicella-zoster immune globulin.
• Summarize interprofessional team strategies for improving care coordination and communication about varicella-zoster immune globulin to advance and improve outcomes in susceptible patient populations.

Indications

Varicella-zoster virus (HHV-3) is a highly contagious virus that can cause either chickenpox or herpes zoster. It is transmitted mainly through inhalation of the virus-infected aerosolized droplets. It initially presents as an upper airway infection, which enters the circulation after 2 to 3 days. It subsequently causes another bout of viremia (after 10 to 12 days) when it presents with a characteristic, pruritic, vesicular rash over the skin and mucous membranes. Additional features include fever and a loss of appetite. This rash typically begins on the face and the trunk and then spreads to the extremities, usually resolving in 4 to 7 days. Individul=als produce immunoglobulins like IgA, IgM, IgG as a response to the infection, and IgG antibodies provide lifelong immunity against the virus. Varicella-Zoster Virus (VZV) can remain dormant in the sensory nerves after a primary varicella infection. Its reactivation can cause herpes zoster, a painful vesicular rash along a dermatome that does not cross the midline.[1]

VZV vaccinations, approved by the FDA, have significantly decreased the number of patients admitted with varicella each year in the United States. The vaccines are available for ages 12 months and older, making chickenpox a preventable disease. However, immunocompromised and pregnant patients are ineligible for these vaccinations.[2] 

Varicella-zoster immune globulin (VZIG) was first researched in the 1960s and prepared from patients recovering from varicella-zoster. It reduces the severity and attack rates of primary varicella. Following modification in the late 70s, the varicella immune globulin came onto the market for high-risk individuals with varicella exposure. It underwent further revision to the current immune globulin sold in the United States.

Varicella-zoster immune globulin should be a consideration for post-exposure prophylaxis in individuals who have a high risk of developing severe disease, lack evidence of immunity, or are ineligible for the vaccination.[3] The CDC recommends varicella-zoster immune globulin either immediately or up to 10 days following exposure for maximal efficacy for the following patient groups:

• Immunocompromised patients with no evidence of immunity (including those who have primary or secondary immunodeficiencies), patients with an underlying neoplastic disease, and persons receiving immunosuppressive therapies are also indicated for patients undergoing hematopoietic cell transplantation who have not yet been re-immunized against varicella infection.
• Mothers of newborn infants who have signs and symptoms of varicella around the time of delivery (i.e., five days before delivery and up to two days after); VZV transmission can be transplacental (in utero) or can happen during a contact perinatally or postnatally.
• Premature infants hospitalized or born at ≥28 weeks of gestation whose mothers lack evidence of immunity to varicella.
• Premature infants hospitalized or born at <28 weeks of gestation or weighing <1000g at birth, even if their mothers have evidence of immunity to varicella.
• Pregnant women lacking evidence of immunity

Immunocompromised patients who were receiving a monthly high dose of intravenous immune globulin (IVIG) and received the dose <3 weeks before exposure, were likely to be protected from varicella.[3][4][5]

Mechanism of Action

B lymphocytes (plasma cells) produce immunoglobulins, which function as antibodies and can recognize a vast spectrum of antigenic epitopes. Adequate functioning of these immunoglobulins is essential for a healthy humoral immune response. Each immunoglobulin structure is unique, and an extensive collection of immunoglobulins allows the body to respond to a wide variety of antigens, termed passive protection. This passive protection should have a duration to protect the patient until they can produce their own antibodies to protect against VZV.[6]

Human immunoglobulin products are produced from an amalgamation of plasma from several donors; this ensures that the final product contains a wide variety of antibody repertoires with a collection of variable domains of antibodies within the regular serum. The IgG molecules must have suitable functional activities such as complement-mediated bactericidal activity, virus-neutralizing activity, opsonization (i.e., marking a pathogen for destruction), and the ability to inactivate toxins to create an effective immune response against a range of microorganisms.

The herpes zoster immune globulin contains antibodies (IgG) from pooled human plasma of individuals with high titers of varicella-zoster and therefore provides passive immunity.[7][8]

Administration

Human immunoglobulin products are available as intravenous immune globulin (IVIG), Subcutaneous immune globulin (SCIG), and intramuscular immune globulin (IMIG). Varicella-zoster immune globulin is available only as Intramuscular immune globulin (IMIG) in the United States. The FDA approved it in December 2012.

Varicella-zoster immune globulin comes in 125-IU vials, and administration should only be intramuscular and as directed by the manufacturer. No dose adjustments are recommended for renal or hepatic impairment. Individuals who later become eligible for vaccination should receive varicella vaccine ≥five months after varicella-zoster immune globulin administration.[3]

Adverse Effects

Local pain at the injection site is the most typical adverse reaction from medication administration. Statistically, a few (1 to 10%) patients have developed headaches, fatigue, and chills. Other less common reactions include skin rash and nausea. Very rarely, patients also develop DVT, serum sickness, hypersensitivity reaction, and thrombosis.[9]

Contraindications

Varicella-zoster immune globulin administration is contraindicated in patients with a history of IgA deficiency. Contraindications also include patients with a history of anaphylaxis to human immune globulin. Clinicians should not administer the drug once the clinical illness has developed as it is ineffective.[10][4]

Monitoring

For patients receiving varicella-zoster immune globulin, observation for 28 days after exposure for any signs and symptoms of the varicella infection is the recommended approach. The administration of immune globulin might increase the incubation period of the disease by ≥ one week. If a patient develops signs and symptoms of varicella, antiviral therapy should start immediately.[3]  

Enhancing Healthcare Team Outcomes

While the demand for varicella-zoster immune globulin has reduced significantly, it is essential to remember that exposure to varicella and herpes zoster might still occur. Early recognition of exposure is especially important in pregnant females as there is a high risk of maternal complications due to varicella infection. The use of varicella-zoster immune globulin helps to modify disease and reduces maternal morbidity.

Similar principles also apply to immunocompromised patients and premature neonates.[4] Varicella-zoster immune globulin must not be confused with the varicella virus vaccine, which clinicians can erroneously give to pregnant women who have been exposed to the varicella virus and is contraindicated during pregnancy. Additionally, it is important to remember that clinicians should administer varicella-zoster immune globulin as soon as possible after exposure and within ten days.[11][12][5][3]

An interprofessional team approach is the optimal means for administering therapy with varicella-zoster immune globulin. This interprofessional team will include all clinicians (MDs, DOs, PAs, NPs)

Outcomes

Varicella-zoster immune globulin has minimal adverse reactions and toxicity. Studies have shown that early administration, especially in pregnant women, decreases maternal morbidity; and that exposed patients have good clinical outcomes. Additionally, varicella-zoster immune globulin prophylaxis reduced the incidence and the morbidity of varicella-zoster in preterm and in-utero exposed infants.[13]