低渗-低反应发作 (HHE)

背景

A hypotonic-hyporesponsive episode (HHE) is defined as the sudden onset of hypotonia (muscle limpness), reduced responsiveness or unresponsiveness, and skin colour changes (pallor or cyanosis) occurring after vaccination in early childhood (< 2 years of age). 

HHEs can occur in the period immediately following vaccination, or up to 48 hours after vaccine administration (delayed HHE). The average episode lasts 6 to 30 minutes. 

HHEs resolve spontaneously, with most children returning to their pre-vaccination state within 6 hours. There are no long-term sequelae (conditions caused by a previous disease or injury) from having an HHE.

诊断

HHEs are diagnosed based on clinical presentation (e.g. symptoms, timing, resolution of symptoms). Investigations are not helpful for confirming a diagnosis of HHE; this is because HHEs present with transient, self-limiting (resolve on their own) symptoms, and have no long-term sequelae. 

Investigations may, however, be useful to exclude other diagnoses such as seizure activity or an allergic reaction (e.g. wheezing, rash or hives). 

Immediate HHEs can appear like an immediate vasovagal phenomenon (a fainting episode) but there are some key differences. Fainting episodes present with similar signs and symptoms (e.g. muscle limpness, unresponsiveness, pallor) but with drops in blood pressure and heart rate, usually presenting in an older age group (≥ 2 years of age). HHEs are often preceded by crying and breath holding, with vital signs remaining stable. 

协会和发病率

HHEs can occur after any immunisation regardless of the type of vaccine; historically, HHEs were most associated with whole-cell

vaccines in early infancy. There has been a decrease in HHE incidence since the change from using whole-cell to acellular pertussis vaccines. 

HHE has been observed most often after the first doses of vaccines at 6 to 8 weeks of age. In 2012, 2.2 cases of HHE were reported per 100,000 doses of pertussis-containing vaccine given to children under 1 year of age. 

The cause of HHEs is yet to be determined.

治疗

HHEs self-resolve and do not need any active treatment. 

Assessment of airway, breathing and circulation is advised as a basic precaution. This can exclude other diagnoses. Careful clinical observation and documentation of the event are vital for a differential diagnosis.  

Suspected HHE should be assessed by a medical professional. 

对未来剂量的影响

HHE is not a contraindication to further doses of vaccines, including pertussis-containing vaccines. Recurrence rates of a further HHE following subsequent immunisations are low (3.5%). 

Your local 疫苗安全服务 can provide advice on whether subsequent vaccines needs to be administered under a period of observation. 

Any adverse event following immunisation (AEFI), including HHEs, in Victoria should be reported to 赛维克. 

资源

• 澳大利亚免疫手册：接种疫苗后
• 低渗-低反应发作——SAEFVIC 案例研究，2017 年 7 月
• Buettcher M, Heininger U, Braun M, et al. Hypotonic-hyporesponsive episode (HHE) as an adverse event following immunization in early childhood: Case definition and guidelines for data collection, analysis, and presentation. 疫苗. 2007;25(31):5875-5881. doi:10.1016/j.vaccine.2007.04.061
• Hansen J, Decker MD, Lewis E, et al. Hypotonic-hyporesponsive episodes after diphtheria, tetanus and acellular pertussis vaccination. Pediatr Infect Dis J. 2021;40(12):1122-1126. doi:10.1097/INF.0000000000003308
• Crawford NW, McMinn A, Royle J, et al. Recurrence risk of a hypotonic hyporesponsive episode in two Australian specialist immunisation clinics. 疫苗. 2018:36(41):6152-6157. doi:10.1016/j.vaccine.2018.08.062
• ScienceDirect: Hypotonic hyporesponsive episode