Incidence rates of Guillain Barré (GBS), chronic fatigue/systemic exertion intolerance disease (CFS/SEID) and postural orthostatic tachycardia syndrome (POTS) prior to introduction of human papilloma virus (HPV) vaccination among adolescent girls in Finland, 2002–2012

摘要

Background In Finland a vaccination programme against human papillomavirus (HPV) was introduced in November 2013 for girls aged 11–12 years with a catchup for girls 13–15 years. Allegations that HPV vaccine is causing Guillain Barré syndrome (GBS) and non-specific diagnostic entities, such as chronic fatigue syndrome/systemic exertion intolerance disease (CFS/SEID) and postural orthostatic tachycardia syndrome (POTS), continue to surface. We examined population register-based incidence rates of CFS/SEID, GBS and POTS to provide baseline data for future HPV vaccine safety evaluations. Methods First diagnosis of CFS/SEID, GBS and POTS in girls aged 11–15 years were obtained from the National Hospital Discharge Register during 2002–2012. We considered the following ICD-10 codes: G93.3 for CFS; G61.0 for GBS and G90.9, G90.8, G93.3, I49.8 for POTS. We calculated incidence rates per 100,000 person-years with 95% confidence intervals (CI). Results In total, 9 CFS/SEID, 19 GBS and 72 POTS cases were identified. The overall incidence rate was 0.53/100,000 (95% CI; 0.27–1.01) for CFS/SEID, 1.11 (95% CI; 0.71–1.74) for GBS and 4.21 (95%CI; 3.34–5.30) for POTS. Significant relative increase in annual incidence rate with a peak in 2012 was observed in CFS/SEID (33% (95% CI; 3.0–70.3: p=0.029) and POTS (16.5% (95% CI; 7.8–25.9: p0.05), but not in GBS (5.4% (95% CI; ?8.4–21.3: p=0.460). Conclusions Our findings provide baseline estimates of CFS/SEID, GBS and POTS incidences in Finland. However, rates based on register data should be interpreted with caution, especially for non-specific diagnostic entities for which internationally and even nationally agreed criteria are still being discussed. To assess the associations with HPV vaccine, methods using register linkage for cohort and self-controlled case series should be explored in addition to factors contributing to patients seeking care, treating physicians setting the diagnoses, and their preference of using of codes for these clinical entities. Highlights ? CFS/SEID, GBS and POTS can be found in all distinct age- and sex-related diagnostic entities. ? Significant increase in CFS/SEID and POTS but not in GBS rates in years before HPV immunization. ? Rates based on register data should be interpreted with caution, especially for non-specific diagnostic entities. ? Factors contributing to clinicians setting the diagnoses and using different ICD-10 codes should be explored.