Annals of the Rheumatic Diseases | 2019
SAT0517\u2005MANAGEMENT OF RISK OF VARICELLA INFECTION IN IMMUNOCOMPROMISED CHILDREN: WHAT IS THE EVIDENCE?
Abstract
Background Varicella-naive children on methotrexate are at risk of severe infection if they encounter varicella. Current guidance advises that children on low-dose methotrexate can safely receive live vaccines1, but management of children on higher doses or combination immunosuppression is challenging as there is no consensus about their management. Acyclovir and varicella-zoster immune globulin (VZIG) are commonly used as post-exposure prophylaxis (PEP). Objectives Assess the evidence for use of acyclovir and/or VZIG as PEP in the management of varicella exposure in susceptible children taking methotrexate. Methods A literature search using PubMed, the Cochrane Library and EMBASE was conducted from November to December 2017, using the terms methotrexate, immunocompromised, varicella, child, prophylaxis, acyclovir, VZIG and their variations. Only full papers, in English language, studying children were analysed (63 abstracts read for relevance, 28 papers obtained, 11 papers included). Results There have been no randomised controlled trials (RCTs) analysing the effectiveness of acyclovir and/or VZIG as PEP in immunocompromised children. The studies that do exist (see table for key publications) are small and uncontrolled and have largely been carried out in oncology rather than rheumatology patients. While they suggest that acyclovir and VZIG are effective at reducing historical infection rates of >70%1, a significant proportion of recipients still get varicella. Authors No. of Patients & VZV Status Cause of Immunosuppression Treatment Outcomes Evans et al (1980)2 102 immunosuppressed children, 80 of whom were known to be seronegative for VZ IgG antibodies Variable Zoster immune globulin (ZIG) as a single dose - up to 1 year, 100 mg; 1-5 years, 250 mg; 6-10 years, 500 mg; 11-14 years, 750 mg; 15-16 years, 1000 mg 24/80 became infected; 17 with symptoms Zaia et al (1983)3 164 immunocompromised children Variable131: malignancy30: other immunosuppressive treatment3: primary immunodeficiency 81 given VZIG83 given ZIG Dose: 1.25 ml/10 kg (max dose, 6.25 ml), given within 96 hours of exposure VZIG: 49/81 became infectedZIG: 57/83 became infectedVaricella pneumonia occurred in 3 cases in each group Shinjoh et al (2009)4 65 immunocompromised children (some with a history of varicella); 76 immunocompetent children; 11 immunocompetent controls Variable Oral acyclovir (10 mg/kg/dose; 400 mg max dose; 4 times daily). Minimum of 7 days treatment, starting from 7 days after exposure 2/65 immunocompromised children developed varicella. 1/76 immunocompetent children developed varicella. 2/11 controls developed varicella Conclusion There is only level 3 evidence for the use of acyclovir and/or VZIG as PEP in susceptible children on methotrexate. The literature indicates acyclovir is more effective, but this is a grade 3 recommendation only. A RCT to compare the effectiveness and acceptability of VZIG and acyclovir is needed, however the difficulty of randomising a cohort of similarly immunocompromised patients should not be underestimated. References [1] Public Health England (2017). Contraindications and special considerations: the green book, chapter 6. Immunisation against infectious disease. [2] Evans, et al. (1980). HUMAN ANTI-CHICKENPOX IMMUNOGLOBULIN IN THE PREVENTION OF CHICKENPOX. The Lancet 315(8164):354-356. [3] Zaia, et al. (1983). Evaluation of Varicella-Zoster Immune Globulin: Protection of Immunosuppressed Children after Household Exposure to Varicella. The Journal of Infectious Diseases147(4):737-743. [4] Shinjoh, et al. (2009). Varicella zoster exposure on paediatric wards between 2000 and 2007: safe and effective post-exposure prophylaxis with oral aciclovir. Journal of Hospital Infection72(2):163-168. Disclosure of Interests Maria Seago: None declared, Kate Armon Speakers bureau: Abbvie, but the fee was paid into Addenbrookes charitable account