Background Hepatitis A is an indolent disease with a varying clinical spectrum and consequences. Little is known about the immune response to hepatitis A virus (HAV) vaccination in children with Periodic Fever, Aphtous Stomatitis, Pharyngitis, Adenitis Syndrome (PFAPA).
Objectives To assess the sero-protective efficacy and safety of immunization against hepatitis A in PFAPA patients, not previously exposed to HAV, and compare these to healthy controls.
Methods Matched case control study including patients with PFAPA and controls. All subjects received two doses of the inactivated anti-HAV vaccine at zero and six months. Seroconversion and seroprotection rates and anti-HAV-IgG antibodies were assessed at enrollment,1 month after the first dose and 1 and 12 months after the last dose. Exclusion criteria were infection or disease flare concomitant or up to ten days prior to immunization, known liver disease or immunodeficiency, and serum testing positive for HAV-infection. Clinical,demographic data and medications used were collected for each patient. Onset of PFAPA symptoms within a week from vaccination was defined as a flare.
Results 28 patients with a mean age of 4.4 years completed the study. Thirteen (46%) patients received NSAIDS, 9 (32%) received NSAIDS+steroids, 3 (10%) patients received steroids and 3 did not receive any treatment at the time of PFAPA flares. The control group consisted of 76 healthy individuals (mean age 4.75 years). A month after primary vaccination 92.9% of patients and 77.6% of the controls attained seroprotection (p=0.07), while rates further increased to 100% and and 96.1% a month after the second dose respectively (p=0.2). In both groups, seroprotection rates remained elevated 12 months following completion of the study (100% vs 95%).Seroconversion rates measured at timely intervals were satisfactory for both groups. No statistically significant difference was detected amongst the two groups.
Mean anti-HAV IgG concentration at 4 weeks was 110mIU/ml in the patient and 96mIU/ml in the control group while it reached 223mIU/ml and 218mIU/ml after the second dose respectively, and at 18 months it was 278 mIU/ml in the patient group and 245 mIU/ml in the control group. Mean IgG concentration was not statistically different between patient and control groups at 1 month after the first dose (p=0.3), 1 month after the second dose (p=0.8) and at 18 months after initial vaccination (p=0.2).
Subgroup analysis of the PFAPA group showed that the use of steroids or NSAIDS did not affect sero-conversion and seroprotection rates or mean antibody titers. Overall four (14.2%) patients in the PFAPA group developed a flare (one after the first dose, three after the second dose). The use of steroids did not seem to affect the development of flare. Mild adverse events were noticed in 6 (17%) patients and 15 (21%) controls.
Conclusions Two doses of HAV vaccine are safe and effective in the vast majority of children with PFAPA. In fact, patients with PFAPA boosted a better immune response at all time points compared to their healthy counterparts. Nevertheless, a proportion of these patients developed a flare. Systemic illness should not preclude from completion of the vaccination schedule in cases where anti-HAV vaccine is mandatory, provided the parents are aware of the possibility of a flare. Larger prospective studies are required to verify the aforementioned results.
Disclosure of Interest None declared