title: Peripheral sympathetic nerve dysfunction in adolescent Japanese girls following immunization with the human papillomavirus vaccine.
abstract: OBJECTIVE
  To investigate the causes of neurological manifestations in girls immunized with the human papillomavirus (HPV) vaccine.
  
  
  METHODS
  During the past nine months, 44 girls visited us complaining of several symptoms after HPV vaccination. Four patients with other proven disorders were excluded, and the remaining forty subjects were enrolled in this study.
  
  
  RESULTS
  The age at initial vaccination ranged from 11 to 17 years, and the average incubation period after the first dose of the vaccine was 5.47±5.00 months. Frequent manifestations included headaches, general fatigue, coldness of the legs, limb pain and weakness. The skin temperature examined in 28 girls with limb symptoms exhibited a slight decrease in the fingers (30.4±2.6 °C) and a moderate decrease in the toes (27.1±3.7 °C). Digital plethysmograms revealed a reduced height of the waves, especially in the toes. The limb symptoms of four girls were compatible with the Japanese clinical diagnostic criteria for complex regional pain syndrome (CRPS), while those in the other 14 girls were consistent with foreign diagnostic criteria for CRPS. The Schellong test identified eight patients with orthostatic hypotension and four patients with postural orthostatic tachycardia syndrome. The girls with orthostatic intolerance and CRPS commonly experienced transient violent tremors and persistent asthenia. Electron-microscopic examinations of the intradermal nerves showed an abnormal pathology in the unmyelinated fibers in two of the three girls examined.
  
  
  CONCLUSIONS
  The symptoms observed in this study can be explained by abnormal peripheral sympathetic responses. The most common previous diagnosis in the studied girls was psychosomatic disease. The social problems of the study participants remained unresolved in that the severely disabled girls stopped going to school.
authors.affiliation: Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Ryu-Ta
authors.initials: RT
authors.lastname: Abe
authors.forename: Akiyo
authors.initials: A
authors.lastname: Hineno
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsunekawa
authors.forename: Shunya
authors.initials: S
authors.lastname: Nakane
authors.forename: Shu-Ichi
authors.initials: S
authors.lastname: Ikeda
mesh_terms: D000293:Adolescent; D001342:Autonomic Nervous System Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D001706:Biopsy; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007024:Hypotension, Orthostatic / Q000139:chemically induced / Q000175:diagnosis / Q000453:epidemiology; D007114:Immunization / Q000009:adverse effects*; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D030361:Papillomavirus Infections / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000009:adverse effects*; D011379:Prognosis; D012189:Retrospective Studies; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*
chemical_list: D053918:Papillomavirus Vaccines