Inflammatory bowel disease (IBD), consisting of Crohn disease, ulcerative colitis, and indeterminate colitis, is an inflammation of the gastrointestinal tract that likely results from an inappropriate and ongoing inflammatory response to intestinal microbes in genetically susceptible people (1,2). The fundamental pathophysiologic process that causes these diseases is unknown and no cure exists. The disease is managed by decreasing or controlling the inflammation using immunosuppressants including corticosteroids, 6-mercaptopurine, and anti-tumor necrosis factor antibodies, alone or in combination, in addition to nutritional support and 5-aminosalicylates.
Before varicella zoster vaccine became available in 1995, varicella in the United States (chickenpox) was a universal childhood disease with a peak incidence in spring and fall, and an annual incidence of 15 to 16 cases per 1000 population (3). Before the introduction of the vaccine, there were approximately 4 million varicella cases each year, about 11,000 hospitalizations, and 100 deaths (4). Varicella vaccine is safe and about 85% effective (3). After the introduction of the single-dose vaccine available during the time of the study, the number of cases decreased dramatically and the peak age of the disease changed from 3 to 6 years to 9 to 12 years (3). Subsequently, in 2007, the American Academy of Pediatrics (AAP) recommended a second vaccine because outbreaks of varicella occurred, even among highly immunized populations (5).
Primary varicella infection is a more severe disease in adolescents and adults, and the frequency of moderate-to-severe disease increases with increasing age regardless of the vaccination status (6). Varicella can be a devastating disease for immunosuppressed children (7–9). Severe and fatal varicella infection can occur in otherwise healthy children receiving intermittent courses of high-dose corticosteroids, >2 mg/kg prednisone or equivalent. Overwhelming pneumonia is described in a teenager with IBD on 6-mercaptopurine (10). Hemorrhagic varicella is more common in immunocompromised patients (11).
In pediatric gastroenterology practices, IBD is most commonly diagnosed during the adolescent years, when varicella disease is a more severe illness than during childhood. Immunosuppressants often are used to control IBD, and at the time of the data collection for the present study, varicella vaccination was not mandated. Because of the possible severe complications of varicella infection in immunocompromised patients, we routinely obtain a varicella titer at the time of diagnosis of IBD and suggest vaccination if the titer is not measurable. For this study, we wanted to know how many patients diagnosed as having IBD had the benefit of immunity to varicella either from natural infection or by vaccination. We hypothesized that at least 90% of patients newly diagnosed as having IBD had antibodies against varicella and were protected by vaccination or natural disease.
MATERIALS AND METHODS
The charts of all of the patients diagnosed as having IBD from January 1, 2005 to December 31, 2009 were reviewed. Information on the following categories was included in the data collection: demographics, date of diagnosis, age at diagnosis, IBD disease type, history of varicella disease, history of varicella vaccination, and varicella titers, and was obtained both from the patient chart and the checklist kept by the nurse practitioners on each newly diagnosed patient. In addition, pediatricians were contacted to provide their immunization records, parents were contacted for immunization records, and the New York State Immunization Information System was accessed. A patient was considered to have had disease or to have been vaccinated if there was written, dated documentation of such. Data was entered into an Excel spreadsheet and then imported from the Microsoft Excel database into the SAS (SAS Institute, Cary, NC) software package. Descriptive statistics were generated using frequency tables.
Varicella zoster immunoglobulin G (IgG) titers were qualitatively detected using the Wampole Laboratory's (Princeton, NJ) Varicella-Zoster IgG ELISA II kit. The sensitivity of this kit is 96.3% and the specificity is 94.4% for individuals who have had varicella disease. Performance characteristics with individuals vaccinated with varicella have not been established (package insert). Vaccination and remeasure of antibody titers were recommended for those who had negative titers.
Comparisons were performed by SAS statistical software. For comparison of continuous variables, analysis of variance was used, and for categorical variables, the Fisher exact test was performed.
This study was approved by the children and youth institutional review board at the Women and Children's Hospital at Buffalo with a waiver for consent (DB#2377).
One hundred sixty-three children and adolescents, average age 12 years (range 1 to 19 years), were diagnosed as having IBD; 57% were boys. One hundred one (62%) had Crohn disease, 54 (33%) had ulcerative colitis, and 8 (5%) had indeterminate colitis. Sixty-two percent of those diagnosed as having Crohn disease were boys, 48% of those with ulcerative colitis were boys, and 50% of those with indeterminate colitis were boys. There was no significant difference in age at the time of IBD diagnosis among those who had Crohn disease, ulcerative colitis, or indeterminate colitis.
Table 1 provides information on the varicella status at the time of diagnosis of IBD, whether varicella disease was documented or evidence of vaccination had been provided. A total of 66% of all of the patients either had a history of disease or had received at least 1 vaccination. There was no statistical difference among those diagnosed as having Crohn disease, ulcerative colitis, or indeterminate colitis with respect to age at the time of disease or vaccination or sex, except that statistically more patients in the indeterminate colitis group were immunized. However, this group is small in number, however, and it is likely this finding has no clinical significance.
Table 2 shows that 77% of patients had measurable titers at the time of diagnosis. No information was available for 20 (12%) patients. Vaccination was recommended for all of the patients who had a negative titer or whose titer was unknown. Of that group, 10 patients were vaccinated and 8 patients had follow-up titers. All 8 patients had positive titers.
Varicella can be a devastating disease in immunocompromised individuals. Fortunately, a vaccine is now available and is required in some states. This study shows that even though varicella disease was considered a universal childhood disease during the time of the study, <80% of newly diagnosed patients with IBD had measurable titers for varicella. The kit that was clinically available for this retrospective study is a qualitative enzyme-linked immunosorbent assay that either detects or does not detect varicella zoster IgG, and the effectiveness of the kit has not been established for vaccinated individuals (12). Thus, our estimate of the individuals who were protected against varicella could have been higher or lower than the 77% we found. Sixty-seven percent of the patients included in this study were born before the availability of the vaccine, and the commercial assay would have identified them to be immune if they had the disease itself. Nevertheless, we did not meet our hypothesized target of 90%.
The results suggested that children and adolescents cannot be presumed to have immunity to varicella at the time of diagnosis of IBD; thus, their immune status should be assessed and ensured if possible.
The children whose charts were reviewed had the varicella titer drawn at the time of diagnosis and were not yet receiving immunosuppressive medication. The AAP recommends against the routine vaccination of children receiving long-term immunosuppressive therapy. Furthermore, the AAP recommends against vaccinating children who are receiving ≥2 mg · kg−1 · day−1 of prednisone or its equivalent, or 20 mg/day of prednisone or its equivalent for ≥14 days (5). Corticosteroid therapy should cease at least 1 month before varicella vaccine is administered.
With the recommendations of the AAP for a 2-dose varicella immunization schedule and the requirement of some states for varicella vaccination to attend school, it is likely that our hypothesized targeted of 90% of newly diagnosed patients with IBD will provide measurable protection against varicella in the near future. In the meantime, some advocate for the immunization of patients who are receiving immunosuppression (13). At this time, it is not clear whether it is a safe practice to vaccinate all patients with IBD receiving immunosuppression with varicella vaccine. In the coming years, it is likely that this will become a moot point as 2-dose vaccination is implemented beginning at 12 to 15 months of age (3,5) and will likely be a requirement for school enrollment/attendance in many states.
Lack of varicella immunity is common in children and adolescents at the time of diagnosis of IBD. Routine screening for varicella immune status may be warranted. Offering immunization to susceptible patients should confer protection, but it may be difficult to achieve once immunosuppression has begun.
Faaiza Ansari was a fourth-year medical student who worked on the study concept and design, acquisition of data, analysis, and interpretation of data. She died tragically in a fire and was awarded her MD posthumously. We dedicate this article to her in recognition of her intellect, her conscientious perseverance, and her love of science, pediatrics, and children who have inflammatory bowel disease. Statistical analysis was performed by a professional statistician, Chang-Xang Ma, PhD, at the University at Buffalo, Buffalo, NY.
1. Podolsky DK. Inflammatory bowel disease. N Engl J Med
2. Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med
3. Marin M, Guris D, Chaves SS, et al. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep
4. Meyer PA, Seward JF, Jumaan AO, et al. Varicella mortality: trends before vaccine licensure in the United States, 1970-1994. J Infect Dis
5. Prevention of varicella: recommendations for use of varicella vaccines in children, including a recommendation for a routine 2-dose varicella immunization schedule. Pediatrics
6. Chaves SS, Gargiullo P, Zhang JX, et al. Loss of vaccine-induced immunity to varicella over time. N Engl J Med
7. Feldman S, Hughes WT, Daniel CB. Varicella in children with cancer: seventy-seven cases. Pediatrics
8. Gershon AA, Mervish N, LaRussa P, et al. Varicella-zoster virus infection in children with underlying human immunodeficiency virus infection. J Infect Dis
9. Derryck A, LaRussa P, Steinberg S, et al. Varicella and zoster in children with human immunodeficiency virus infection. Pediatr Infect Dis J
10. Deutsch DE, Olson AD, Kraker S, et al. Overwhelming varicella pneumonia in a patient with Crohn's disease treated with 6-mercaptopurine. J Pediatr Gastroenterol Nutr
11. Pickering L. Red Book, 2006 Report of the Committee on Infectious Diseases
. Elk Grove Village, IL: American Academy of Pediatrics; 2006.
12. Wampole Laboratories I. Varicella-Zoster Virus IgG (VZV)
ELISA II. Princeton, NJ: Wampole Laboratories; 2005.
13. Lu Y, Bousvaros A. Varicella vaccination in children with inflammatory bowel disease receiving immunosuppressive therapy. J Pediatr Gastroenterol Nutr