The association between pathogen infections and the onset of Henoch-Sch&;ouml;nlein purpura

• Main Authors: Chun-Jung Tsai, 蔡君蓉
• Other Authors: Bor-Luen Chiang
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/24777740680123766129

碩士 === 國立臺灣大學 === 臨床醫學研究所 === 102 === Background and objective: Henoch-Sch&;ouml;nlein purpura (HSP) is the most common systemic small vessel vasculitis of children. HSP is characterized by seasonal variation, with most cases occurring in the winter or spring. Although the etiology of HSP remains unclear, the seasonal nature suggests that antecedent infections at least partially contribute to disease pathogenesis. We choose an indirect method to evaluate at a national population level whether the outbreaks of certain pathogens are significantly correlated with the onset of HSP. Methods: We conduct a retrospective cohort study using the administrative database of Bureau of the NHI (BNHI), from 1 January 1999 to 31 December 2009, which contains comprehensive inpatient and outpatient data from all ranks of medical institutions in Taiwan. All patients below the age of 20 years (according to the ACR criteria) with the diagnosis of HSP and without other rheumatoid diseases were included into this study. Data for each patient including sex, age, date of onset, length of hospitalization, systemic organ involvement and discharge outcome were analyzed. The statistical analyses were conducted using SAS 9.1.3 for Windows. We also utilized the data of Notifiable Infectious Diseases Statistics System (NIDSS) from the Center for Disease Control (CDC) and used Poisson-autoregressive-Fourier (PARF) modeling with identity link on the time series data to study the association between the onset of HSP and certain pathogen infections, including influenza/parainfluenza viruses, enteroviruses, respiratory syncytial virus (RSV), adenovirus, invasive pneumococcal diseases, invasive Haemophilus influenzae type B (Hib) diseases, enterovirus infection with severe complications and severe complicated influenza on a monthly basis. Results and Discussion: During the 11-year study period, a total of 8271 patients below the age of 20 year had ever visited outpatient department (OPD) for HSP, and a total of 4317 HSP patients had ever hospitalized. The mean age at onset is 8.2 years. Among the overall population below the age of 20 year in Taiwan, the annual incidence was 10.8 to 14.7 cases per 100,000 people. Among the OPD cases, a male to female ratio is 1.01. OPD visits were most frequent in October through March. Among the hospitalized cases, a male to female ratio is 1.21. The hospitalization rate is decreasing since 2006. Compare to previous retrospective studies of HSP, our study duration is the longest, the age selection of HSP patients is according to the ACR criteria, the data source is NHI database and NIDSS from CDC, and the population of our study is national population. The comparison of this study and the previous HSP study using NHI database in Taiwan from 1999 to 2002 by Yang et al. shows our OPD patients are of no gender difference, the mean age at onset and the hospitalization rates are higher, and the mean duration of hospitalization is shorter. These differences may be due to the change of demographics of HSP patients in recent 10 years in Taiwan. In addition, the universal and quality healthcare provided by the NHI system to the people of Taiwan at affordable cost, the decreasing birth rates and our attention to child care may result in the increasing children hospitalization rates and the decreasing severity of hospitalized children. The confirmed cases of adenovirus, enteroviruses, influenza, parainfluenza and RSV infections, as well as invasive Hib diseases, invasive pneumococcal diseases, enterovirus infection with severe complications and severe complicated influenza are more males (55%). Ninety-five percent of the cases of adenovirus, enteroviruses, parainfluenza and RSV infections occurred before 10 years of age; more than 90% of cases of RSV infections are before the age of 5; about 80% of cases of invasive Hib and pneumococcal diseases are before the age of 5; about 60% cases of influenza virus infections are before 10 years of age. The increasing rates of influenza and parainfluenza infections since March 1993 are probably due to our national epidemic prevention policy and the alertness of clinical physicians to influenza syndrome. The reason for the decreasing of confirmed case numbers of invasive Hib diseases since 1999 may be due to the increasing vaccination rates of Hib vaccine. The pneumococcal vaccination rates were also increasing in recent years in Taiwan, but there is no obvious change of case numbers of invasive pneumococcal diseases because the time of invasive pneumococcal diseases being listed in the notifiable infectious diseases began in October 2007, and the duration between October 2007 and December 2009 is short. From January 2001 to December 2009, the onset of HSP was significantly related to the infectious of adenovirus and parainfluenza viruses (p = 0.0205 and p=0.0446, respectively). Form each infectious disease being listed in the notifiable infectious diseases in Taiwan to December 2009, the onset of HSP was significantly correlated with the occurrence of enterovirus infection with severe complications and severe complicated influenza (p = 0.0001 and p = 0.0067, respectively). To our knowledge, there is only one case report of Henoch-Sch&;ouml;nlein nephritis after adenovirus infection by Meadow et al. Lee et al. reported a case of systemic small vessel vasculitis after influenza A and the histopathology of skin biopsy showing leukocytoclastic vasculitis. Costa et al reported one case of leukocytoclastic vasculitis occurred after coxsackievirus B1 infection, and Chia et al reported a case of leukocytoclastic vasculitis occurred after echovirus 7 infection. We already know that the early phase of immune responses in severe H1N1 influenza cases is to activate Th1 and Th17 cells to produce pro-inflammatory cytokines, which may induce vasculitis. Besides, it is supposed that the virus or virus-antibody complex can bind to the CD55 on vascular endothelial cells during the enteroviruses viremia and lead to CD55 decreasing, which in turn over-activates the induced complement system and produces the clinical manifestation of leukocytoclastic vasculitis. Conclusions: Our study is the first large clinical trial to evaluate the association between certain pathogen infections and the onset of HSP. The study results reveal that the onset of HSP was significantly correlated with the infectious of adenovirus and parainfluenza viruses as well as the occurrence of enterovirus infection with severe complications and severe complicated influenza. Although our study is not prospective and cannot demonstrate the direct association between the onset of HSP and these infectious diseases, the study duration is currently the longest and the population size is large. Therefore, our study results could provide some reference for future clinical studies designed to assess the etiology of HSP.