Neurally mediated syncope, including vasovagal syncope, postural tachycardia syndrome, orthostatic hypertension, orthostatic hypotension, situational syncope, and carotid sinus syndrome, is the most common underlying disease of paediatric syncope. VVS and POTS are the most common types of paediatric NMS. In recent years, great attention has been paid to the comorbidities of paediatric NMS, such as migraine, mental illness, and chronic fatigue syndrome. Allergic diseases involving multiple systems, such as asthma and allergic rhinitis in the respiratory system and atopic dermatitis in skin, are prevalent in childhood. It is reported that 64.3% of adult AS patients also exhibited orthostatic dysregulation in Japan. A study in China showed that approximately 1/3 of the hospitalized children with VVS and/or POTS had a history of allergic diseases, and the percentage is as high as 42% for children with POTS alone. The study also indicated that allergic status might exacerbate the symptoms of paediatric NMS. Additionally, a review showed that 90% of paediatric cough syncope, which is a type of situational syncope, is related to AS.


Pediatric VVS and/or POTS Comorbid with Allergic Diseases

Clinical Manifestations

VVS and POTS usually occur in older children and adolescents. Recurrent syncope is the major manifestation of VVS with predisposing factors, such as prolonged standing, quick changes from a supine or a squat to an upright position, emotional stress or fear, and a humid environment


Vasoactive Factors Associated with Allergy

Inflammatory Mediators

AS and AR are generally IgE-mediated type I allergic diseases (Figure 1). When individuals are exposed to allergens, activated B cells differentiate into plasma cells and subsequently synthesize and secrete specific IgE (sIgE), which binds to high-affinity receptors on the surface of inflammatory cells, such as mast cells and basophils, resulting in a state of sensitization. When exposed to the same allergens again, sIgE antibodies can recognize the allergens and cause a cross-linking reaction, leading to the activation and degranulation of inflammatory cells to release a variety of inflammatory mediators, such as the classic histamine, LT, bradykinin, and prostaglandin, eventually leading to both acute and chronic inflammation, airway smooth muscle contraction, and increased secretion of mucus, etc.


Situational Syncope Comorbid with Allergic Diseases in Children

Clinical Manifestations

Cough syncope is a form of situational syncope characterized by paroxysmal coughing, facial congestion or cyanosis, and loss of consciousness, and the episode of cough syncope usually occurs within seconds and is followed by recovery within seconds to minutes. Cough syncope in children is thought to be associated with AS. A recent review showed that 90.3% of children with cough syncope had a history of AS. As early as 1876, Charcot first described the loss of consciousness after coughing in children. Nearly a century later, Robert described twelve children with cough syncope companies with AS, of whom eleven were allergic to inhalant allergens and six developed allergic symptoms to certain foods; pulmonary function was measured in eight children, who all showed reversible airflow limitation.



Increasing evidence suggests that allergic diseases are common comorbidities of paediatric NMS, but the data are limited, and the pathogenesis is unclear. It can be speculated that the disturbance of allergy-related vasoactive mediators, autonomic nervous dysfunction, autoimmunity, changes in thoracic compliance, and autonomic nervous reflex may be potential mechanisms for the comorbidity. Further studies are needed to confirm the exact mechanisms.

In addition, there are several other entities of NMS, such as OH, OHT, and other forms of situational syncope, that may share some common pathophysiological mechanisms with VVS, POTS, and cough syncope as mentioned above. However, no studies have been published on the comorbidity of these types of NMS and allergic diseases in children. We believe that great attention should be paid to this topic in the future because comprehensive studies on the clinical characteristics and pathogenesis will help to improve the understanding and therapeutic efficacy of paediatric NMS comorbid with allergic diseases.