Immunization stress-related reactions (ISRR) are AEFI arising from stress about the immunization. Individuals can react in anticipation to and as a result of an injection of any kind. These reactions are not related to the vaccine, but to fear of the injection. Formerly, this spectrum was described as an Adverse Event Following Immunization arising from anxiety about immunization. The term ISRR was introduced, as the word “anxiety” does not adequately capture all the elements of the presentation of these AEFI. Unlike other AEFI, ISRR may also occur immediately before immunization. In addition, an ISRR may affect an individual or groups of individuals, resulting in a cluster, often referred to as “mass psychogenic illness”.
The types of reactions caused by ISRR include but are not limited to:
- Vasovagal mediated reactions
- Hyperventilation mediated reactions
- Stress-related psychiatric disorders
- Dissociative neurological symptom reaction (DNSR)
Unfortunately, no diagnostic test can assure that anxiety associated to immunization is the cause of a reaction. These type of reactions affected immunization programmes in several countries and drawn the attention of media and the public globally.
Most symptoms and signs of an ISRR are transient and resolve spontaneously, whether they manifest just before, during or immediately after immunization. An initial acute stress response (consistent with a “fight or flight” response) may be followed by an overcompensatory parasympathetic reaction, in which the heart rate and blood pressure fall precipitously. Thus, in some individuals, an acute stress response may lead to physiological overcompensation and a vasovagal reaction.
An acute stress response may range from mild feelings of worry and “butterflies” in the stomach to symptoms of sympathetic nervous system stimulation – increased heart rate, palpitations and difficulty in breathing.
The symptoms of vasovagal reactions (“fainting” in lay terms) range from mild dizziness to a brief loss of consciousness (syncope) because of insufficient blood flow to the brain resulting from low blood pressure due to a decreased heart rate, vasodilatation of blood vessels or both. It can be associated with prodromal symptoms such as nausea, sweating or pallor. Rarely, it is associated with a syncopal seizure or can result in injury from falling.
Hyperventilation syndrome (rapid breathing) may be part of an acute stress response and include features of a DNSR. The presenting features are dyspnoea (shortness of breath), chest pain, paraesthesia (tingling sensation) in the fingers, light-headedness, dizziness and headache. In some individuals, this maybe a recurrent symptom and not necessarily associated with recent provocative stress. Syncope and non-epileptic seizures characterized by pseudo-absence spells may occur. Episodes may often recur, and the diagnosis may be missed and ascribed to cardiac or other life-threatening disorders.
Importantly, ISRR can sometimes manifest with dissociative neurological symptoms such as weakness or paralysis, abnormal movements or limb posturing, gait irregularities, speech difficulties or non-epileptic seizures with no apparent neurological basis. The symptoms and signs may be delayed, especially when such symptoms occur in clusters involving many vaccine recipients. DNSRs appear to be more common in females; they are not typically diagnosed in infants. In children, DNSRs typically manifest with a single symptom. DNSRs are considered to be the result of numerous factors that interact at different levels, which can be understood within the biopsychosocial framework
One form of DNSR presents as non-epileptic seizures, which are less common in early childhood (the youngest patient reported was 5 years old) and appear to become more common in adolescence. This is typically a diagnosis of “exclusion”. Non-epileptic seizures are also often referred to as pseudo-seizures or psychogenic seizures. They are events that resemble an epileptic seizure but without the characteristic neural discharges (detected on an electroencephalogram) associated with epilepsy. Non-epileptic seizures are considered involuntary, and affected individuals may or may not report feeling fearful or anxious.
ISRR reporting requirements:
In general, individual acute stress responses need not be notified or reported as part of AEFI surveillance, with the exception of a vasovagal reaction with syncope, especially if an injury results. DNSRs, including non-epileptic seizures that develop later, may be reported if the patient seeks the intervention of a health care provider and attributes the symptoms to immunization.
Clusters of such events should be reported immediately to higher authorities by the fastest means possible (e.g. telephone). Depending on the seriousness of the event or the presence of a cluster, the responsible authorities should initiate a detailed investigation. During the investigation, it is important to ask relevant stakeholders probing questions and collect evidence on the biopsychosocial aspects to determine whether the event is a stress response to immunization.
The causality of all ISRR should be assessed with the WHO classification of causality for AEFI. The first step is to determine whether the reported symptoms and signs fulfil the definition of an acute stress response, vasovagal reaction or DNSR. If so, causality assessment should be continued. The next step is to formulate the question. Unlike other adverse events, the symptoms of an acute stress response may precede administration of a vaccine. After exclusion of coincidental events, such cases may be classified as “consistent with a causal association to immunization” in the category of ISRR.
Case Study:
Psychogenic non-epileptic seizures (PNES) in a suspected outbreak of an ISRR cluster following human papillomavirus vaccination in Rio Branco, Brazil.
Twelve patients with convulsive seizures were submitted to prolonged intensive video-electroencephalography monitoring, brain magnetic resonance imaging, cerebrospinal fluid diagnostic testing, laboratory subsidiary examinations, and complete neurological and psychiatric evaluations. Ten patients received the positive diagnosis of PNES, and two patients received the diagnosis of idiopathic generalized epilepsy. No biological association was found between the HPV vaccine and the clinical problems presented by the patients.
Reference:
- https://www.sciencedirect.com/science/article/pii/S0264410X20310859?via%3Dihub
- WHO’s IMMUNIZATION STRESS-RELATED RESPONSES – A Synopsis
- CIOMS-WHO – definition and application of terms for vaccine pharmacovigilance: report of cioms/who working group on vaccine pharmacovigilance
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