Human Papillomavirus Vaccine in Patients with Systemic Lupus Erythematosus (2013)

To the Editor: Human papillomavirus (HPV) infection is one of the most common sexually transmitted infections worldwide.1 Although usually transient and asymptomatic, HPV infection can result in cervical cancer in some predisposed women,1 and thus, many programs have been developed to foster HPV immunization. People who are at a particularly high risk for cervical cancer include those affected by systemic lupus erythematosus because of intrinsic immunological defiance and immunosuppressive treatments.2 In view of the higher risk of cervical cancer, guidelines urge HPV vaccination of these patients during adolescence.3 One concern about HPV vaccination in patients with systemic lupus erythematosus is the possible reactivation of the disease triggered by viral antigens or adjuvants contained in the vaccine.4 Although a recent case-control study did not find any increased risk of flares in a group of 50 patients,4 factors such as the variability in immunological response5 and the possible presence of genetic predisposing factors may limit the ability of studies to detect rare adverse events.5 Several case reports have described a possible correlation in predisposed patients,6,7 and 100 cases have been reported in pharmacovigilance databases in Europe, United States, and Australia.8–10 In the view of this limited knowledge, we assessed whether the number of hospitalizations for lupus in the United States increased after introduction of the HPV vaccination in 2006, using data from the National Hospital Discharge Survey, the National Inpatient Sample, and the Kids’ Inpatient Sample. We examined data on patients (all ages and ≤17 years of age) with first-line diagnosis of systemic lupus erythematosus at hospitalization or emergency department admission, in accordance with the codes in the International Classification of Disease, 9th revision Clinical Modification. We considered the years before and after 2006 as “before” or “after” vaccine introduction. Data on HPV vaccine coverage, estimated by the National Institutes of Health based on the vaccination in the age group 13–17 years, were retrieved from the Centers for Disease Control Web site.11 We included both sexes because, from the beginning of 2011, the Advisory Committee on Immunization Practices has recommended the routine use of the quadrivalent (HPV) vaccine in young men and young women. We analyzed data on the rates of disease and vaccination considering the variation between calendar years in women of all ages and patients of both sexes 17 years of age and younger because these groups were most likely to be exposed to the HPV vaccine. As shown in Figure A, there was no increase in hospitalizations after the introduction of the HPV vaccine, considering women of all ages. Similarly, there was no increase when we considered only patients 17 years of age and younger from the National Inpatient Sample and the Kids’ Inpatient Sample (Figure B).FIGURE: Hospitalizations (National Inpatient Sample [NIS], National Hospital Discharge Survey [NHDS] and Kids’ Inpatient Sample [KID]) and emergency department visits (Nationwide Emergency Department Sample [NEDS]) in the United States (years 2003–2013). A, Women of all ages and (B) patients 1–17 years of age. Vaccine coverage was estimated by the National Institutes of Health for the age group 13–17 years. ED indicates emergency department.We carried out a further analysis of data from the Nationwide Emergency Department Sample for people admitted to the emergency department with systemic lupus erythematosus as their first diagnosis. There was an increase in the number of emergency department admissions for women (Figure A). However, this appeared to apply only to older patients because it was not reproduced among those younger than 17 years (Figure B). We could not obtain a reliable estimate of lupus hospitalization from the National Hospital Discharge Survey database because of the small number of patients who possibly had received the HPV vaccine. We found no evidence of an increase in the number of hospitalizations or emergency department admissions because of lupus in patient groups exposed to HPV vaccine. This is consistent with results from studies of patients receiving the HPV vaccine4 and with recently published guidelines from the European League Against Rheumatism.3 ACKNOWLEDGMENT The financial support by Regione Lombardia (Monitoraggio degli Eventi Avversi in Pediatria project) is gratefully acknowledged. Paolo Pellegrino * Carla Carnovale* Valentina Perrone Dionigi Salvati Marta Gentili Unit of Clinical Pharmacology, University Hospital “Luigi Sacco”, Università di Milano, Milan, Italy Stefania Antoniazzi IRCCS Foundation, Ca’ Granda Ospedale, Maggiore Policlinico, Milan, Italy Emilio Clementi Scientific Institute, IRCCS E. Medea, Bosisio Parini, Lecco, Italy Sonia Radice Unit of Clinical Pharmacology, University Hospital “Luigi Sacco”, Università di Milano, Milan, Italy, sonia.ra[email protected]