Atlantic Provinces Pediatric Hematology Oncology Network Réseau d oncologie et d hématologie pédiatrique des provinces de l Atlantique Reviewed and approved by specialists at the IWK Health Centre, Halifax, NS and the Janeway Children s Health and Rehabilitation Centre, St. John s, NL. 5850/5980University Avenue, PO Box 9700, Halifax, NS, B3K 6R8 APPHON/ROHPPA supportive care guidelines are developed by Atlantic Provinces health professional specialists using evidence-based or best practice references. Format and content of the guidelines will change as they are reviewed and revised on a periodic basis. Care has been taken to ensure accuracy of the information. However, any physician or health professional using these guidelines will be responsible for verifying doses and administering medications and care according to their own institutional formularies and policies and acceptable standards of care. Unofficial document if printed. To ensure that this printed is the latest version, please check website http://www.apphon-rohppa.com. Guidelines for Varicella Zoster/Herpes Zoster Varicella zoster is a highly contagious, DNA virus which is considered relatively benign in normal children but can cause disseminated and potentially fatal disease in immunocompromised children. The illness is spread primarily by respiratory secretions and direct contact. The disease can be more severe in adolescents and adults. It is possible, although uncommon, to get chicken pox more than once, especially if the first episode was before two years of age. Risk: Who is at risk? Children at high risk for severe or disseminated chickenpox or shingles are those in any of the following patient groups: receiving chemotherapy or radiotherapy known immunodeficiency, or immunosuppressed state (i.e., post solid organ transplant) receiving high doses of systemic corticosteroids ( 2 mg/kg per day of prednisone or its equivalent or 20 mg/day of prednisone or its equivalent if weight >10 kg) completed chemotherapy in last six months, without a previous history of chicken pox illness bone marrow transplantation up to one (1) year post transplant or longer if still on immunosuppression - Bone marrow transplant patients should still be considered at risk, even with normal levels of IgG, until one year post transplant or off all immunosuppression with good T cell function. Guidelines for Varicella Zoster/Herpes Zoster January 2005 Page 1 of 6
Who is not at risk? Children who have previously received the varicella vaccine or had a previous history of chickenpox, and have a documented immune varicella titre, are not at risk for severe chickenpox. Diagnosis: Clinical picture is usually diagnostic. vesicular rash (raised red spots filled with clear fluid) often associated with elevated temperature and pruritus can occur anywhere on the body including in the mouth, scalp is often the first area involved herpes zoster ( shingles or zoster ) appears as grouped vesicular lesions in the distribution of 1 to 3 dermatomes, sometimes accompanied by localized pain or parasthesias Labs: culture in viral media (aggressively swab BASE OF LESION) vesicular scrapings: DFA (Direct Fluorescent Antibody test) - distinguishes VZV from HSV (more rapid than culture) PCR (Polymerase Chain Reaction) on CSF for suspected VZV encephalitis; can distinguish wild type strains from vaccine virus (very sensitive). Requires consult with Infectious Disease Incubation period: usually 14-16 days (10-21 days) if child received zoster immune globulin (VZIG), incubation period may be as long as 28 days isolate child in contact with varicella from other immune compromised children during the incubation period Chemotherapy - The decision to hold chemotherapy during the incubation period is based on the intensity of exposure, the general condition of the patient, and the intensity, phase and type of the chemotherapy. High risk patients may be asked to temporarily hold chemotherapy during incubation period (e.g., delay in planned Bone Marrow Transplant). Chemotherapy and other therapy during the incubation period must be discussed with the pediatric hematologist/oncologist. Contact: Varicella is highly contagious and transmitted by air or droplet and direct contact with lesions. It is infectious for 24-48 hours prior to onset of rash and until the last vesicle is scabbed over. The most contagious phase is during the development of the vesicles. Significant contact: 5 minutes of face to face contact or an hour in a room with an individual in the infectious phase of varicella presence in the same household within 48 hours of a person developing chickenpox Guidelines for Varicella Zoster/Herpes Zoster January 2005 Page 2 of 6
simultaneous play with the same objects as a person with shingles on any part of the body presence in the room for more than one hour with a person with shingles on an exposed area of skin or direct contact with a lesion Guidelines for Varicella Zoster/Herpes Zoster January 2005 Page 3 of 6
Prevention of Chicken Pox: Avoiding contact Avoid visiting anyone with known chicken pox. Avoid contact with anyone who has had contact with an individual with chicken pox during the isolation period (8-21 days, and 8-28 days for those who received VZIG). Isolation period differs from incubation period in that an individual can be contagious for 2 days prior to the onset of rash. Avoid school if an outbreak of chickenpox occurs within the school. Notify school to increase school awareness of chickenpox illness in classmates of the child. Notify caregivers and friends of the risk to these children and the necessity of informing the family and the appropriate health care professional of contacts. Siblings should be immune by previous disease or vaccine. If they are not immune, they should be vaccinated at child s diagnosis. If siblings have a significant contact with chickenpox and are not immune, allow them to stay at home, but get them vaccinated if they don t develop the disease. Respiratory isolation for all identified cases. Zoster immunoglobulin (VZIG) All new oncology patients will have baseline serological testing for varicella immunity (preferably prior to any blood transfusions). Time: Should be given within 72 hours of contact. May be given up to 96 hours No indication for VZIG more than 96 hours after contact. Who: 1. All patients at risk who have had a significant shingles or chickenpox contact (as defined above) History of chickenpox, shingles, or Baseline Serology Action vaccine administration Negative Negative Give VZIG Positive Negative Give VZIG Negative Positive Give VZIG* Positive Positive No VZIG *Expert opinion is divided on this. Usually, VZIG is given regardless of serological results with a negative history. However, if the patient has not received a blood product that could have provided the passive antibody, some experts do not recommend VZIG administration. 2. All bone marrow transplant recipients at risk who have had a significant contact, regardless of their immune status at diagnosis Dosing Guidelines: Patient Weight Dose (maximum dose 625 units) Route 10 kg or less 125 units (1 vial) Intramuscular (IM) 10.1 20 kg 250 units (2 vials) IM 20.1 30 kg 375 units (3 vials) IM Guidelines for Varicella Zoster/Herpes Zoster January 2005 Page 4 of 6
Patient Weight Dose (maximum dose 625 units) Route 30.1 40 kg 500 units (4 vials) IM More than 40 kg 625 units (5 vials) IM Effective for approximately 3-4 weeks. Repeat dose for further exposure more than 21 days after the last dose, if varicella did not develop. Isolate from other susceptible children, such as clinic patients, day 8 to day 28. Chickenpox may still occur as an attenuated illness. If this occurs, immediately contact a pediatric hematologist/oncologist. It must be treated with IV acyclovir. Acyclovir is only rarely indicated for chicken pox or shingles exposure and must be discussed with a pediatric hematologist/oncologist. If VZIG is unavailable, or for patients with a bleeding diathesis, IV gamma globulin 400 mg/kg over 3-4 hours attains an antibody titre approximately equivalent to VZIG. Varicella vaccination (Varivax, Varivax II, Varilrix ) Efficacy of the varicella vaccine is approximately 95% in normal hosts. This requires two doses in those over age 12 years, at least 28 days apart. Who: 1. All household contacts (see contraindications below) without a previous history of varicella disease or vaccination should receive the varicella vaccine at the time of an oncology diagnosis in a child. Consideration should be given to checking the titre of those who have a history of varicella disease or vaccination to confirm immunity. 2. Household contacts who are not immune to chickenpox (no previous disease or vaccination), and experience a chickenpox exposure, should receive the varicella vaccine immediately. Consider vaccination of siblings if child with cancer comes in contact with varicella and the sibling was not vaccinated at diagnosis or is not immune already. 3. Vaccination of children receiving maintenance treatment for acute lymphoblastic leukemia (who do not have documented immunity either by previous disease or vaccination), should be considered after one year of continuous remission when the child has a lymphocyte count >700/µL (0.7 x 10 9 /L) and a platelet count >100 x 10 9 /L. This must be discussed with the pediatric hematologist/oncologist. 4. All patients (except bone marrow transplant), without a previous history of varicella disease or vaccination, and titre is non-immune, should receive varicella vaccine 6 months after completing chemotherapy. 5. In consultation with pediatric hematology/oncology and immunology, all bone marrow transplant patients should receive the varicella vaccine 24 months after transplant. Consideration should be given to administering this vaccine based on a risk benefit assessment and level of immune suppression and assessment of immune competence and T cell number and function. Consideration may be given to administering the vaccine 18 months post transplantation in selected patients with documented adequate T cell number and function. Varicella vaccine should not be administered if evidence of GVHD or continued immunosuppression is present and until 3 months after stopping all chronic GVHD therapy, if >18 months post transplant. The varicella vaccine should be administered only after seroconversion to MMR and Hepatitis B is demonstrated. Guidelines for Varicella Zoster/Herpes Zoster January 2005 Page 5 of 6
6. Varicella vaccine may be given concurrently with MMR vaccine in a different site. If not given concurrently, a one month interval is needed between vaccines. Varicella vaccine can be given during the same visit with killed vaccines (e.g., DTaP, IPV, and HiB) in a different site. 7. Avoid pregnancy for 12 weeks and salicylates for 6 weeks after vaccination. Contraindications to vaccine: pregnancy age < one year old receiving chronic systemic steroids ( 2 mg/kg per day of prednisone or its equivalent, or 20 mg/day of prednisone or its equivalent if weight > 10 kg) immunodeficiency state sensitivity to vaccine components Dosage: Varivax II - 0.5 ml subcutaneously (subq) x 1 dose for ages 1-12 years Varivax II - 0.5 ml subcutaneously (subq) x 2 doses 4-8 weeks apart for ages 13 years or see package insert for the specific product currently available. Note: A local rash at the site (or the portion of the limb) of vaccination is expected in 4% of children and 8% of adults. If this occurs, the site should be kept covered. VZIG is not indicated if the oncology patient has not been directly exposed to the lesions. A disseminated rash (widespread or spread beyond the local area of the injection site) is rarer. If this occurs, the oncology patient should receive VZIG Treatment of Chickenpox/Shingles: All immunosuppressed patients should inform their physician immediately at first signs of chickenpox infection. Confirmation is often clinically obvious but in some cases direct viral smear or culture will be required. All children who develop chickenpox or shingles must be admitted to hospital for observation and intravenous acyclovir. Some lower risk patients may be considered for oral therapy to complete a course of IV acyclovir, but only after consultation with a pediatric hematologist/oncologist. They must continue to have frequent reassessment. Management: 1. Stop chemotherapy and consult with oncologist concerning any administration. 2. Start acyclovir immediately. For children 1 year of age, use acyclovir 1500 mg/m 2 /day IV in 3 divided doses for 7-10 days. For children < 1 year of age, use acyclovir 30 mg/kg/day IV in 3 divided doses for 7-10 days. If completing a course orally, use acyclovir 80 mg/kg/day in 4 divided doses (maximum 4000 mg/day) Guidelines for Varicella Zoster/Herpes Zoster January 2005 Page 6 of 6
3. Ensure adequate hydration at a minimum of 1500 ml/m²/day. 4. Monitor for systemic involvement - liver function tests, respiratory and neurological status. 5. Monitor renal function. 6. General management: Local control measures: cut finger nails short, keep nails clean, treat secondary infection, Calamine and/or Benadryl for itchiness, cool baths soothe and Aveeno baths may lessen itchiness. Avoid Aspirin or any product containing acetylsalicylic acid (risk of Reye s syndrome). Discourage breakage of blisters. Encourage oral intake with clear fluids. Monitor fever, appetite, fluid intake and appearance of lesions. Isolate child in hospital with airborne precautions. Notify infection control. 7. After discharge, instruct the family to contact the physician to be seen, or return immediately if child develops: secondary fever cough zoster (shingles) dissemination jaundice signs of bleeding into the lesions and the platelets are low (risk of hemorrhagic varicella is low but the child must return if occurs.) References: 1. Altman AJ, Wolff LT. The prevention of infections. In: Altman AJ, editor. Supportive care of children with cancer. 3 rd ed. Baltimore: John Hopkins University Press; 2004, p. 1-12. 2. American Academy of Pediatrics. Varicella-zoster infections. In: Pickering LK, editor. Red Book 2003 Report of the Committee on Infectious Diseases. 26 th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2003, p. 672-732. 3. American Academy of Pediatrics. Antiviral drugs for no-human immunodeficiency virus infections. In: Pickering LK, editor. Red Book 2003 Report of the Committee on Infectious Diseases. 26 th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2003, p. 729-732. 4. Hastings C. Immunization. In: Altman AJ, editor. Supportive care of children with cancer. 3 rd ed. Baltimore: John Hopkins University Press; 2003, p. 13-34. 5. IWK Health Centre. Children with cancer: A handbook for families. Halifax, Nova Scotia: IWK Health Centre; 2003, p. 86-87. 6. IWK Health Centre. Formulary of Drugs and Dosing Manual, 7 th edition. Halifax, Nova Scotia: IWK Health Centre; 2004/2005. 7. IWK Health Centre. Infection Control Manual. Transmission summary tables for acute care centers. Halifax, Nova Scotia: IWK Health Centre; 2004, p. 52. Date: 25 January 2005 Guidelines for Varicella Zoster/Herpes Zoster January 2005 Page 7 of 6