Anaphylaxis: Unique aspects of clinical diagnosis and management in infants (birth to age 2 years)

Anaphylaxis is reported to occur with increasing frequency in infants. An illustrated Rostrum on the diagnosis, treatment, and long-term management of anaphylaxis in this age group has been published by Simons and Sampson (J Allergy Clin Immunol 2015;135: 1125-31).

Foods such as milk, egg, and peanut are by far the most common triggers of anaphylaxis in infancy, although medications and other triggers can also be implicated. Infants with anaphylaxis typically present with sudden onset of skin signs such as generalized urticaria, respiratory symptoms such as cough, wheeze, stridor, and dyspnea, and/or gastrointestinal symptoms such as persistent vomiting.

Clinical criteria for diagnosis of anaphylaxis are validated for use in children and adults, but have not yet been validated for use in infants. A high index of suspicion is required to diagnose anaphylaxis in babies, as they cannot describe symptoms such as itching, and signs of infant anaphylaxis such as flushing, dysphonia, incontinence, and behavior changes (irritability, somnolence) also occur in healthy infants.

The differential diagnosis of anaphylaxis in infancy includes unique entities such as congenital abnormalities of the respiratory tract or gastrointestinal tract, and food protein-induced enterocolitis syndrome. Epinephrine injection is the treatment of choice in both clinical and community settings.

Co-morbidities that increase the risk of severe anaphylaxis are not well-defined, but probably include croup, bronchiolitis, or asthma; likewise, amplifying co-factors are not well-defined in this age group.

Long-term management focuses on follow-up with a physician, preferably an allergy/immunology specialist who can train caregivers of infants to recognize and treat anaphylaxis in the community and help them to prevent anaphylaxis episodes.

Epinephrine auto-injectors (EAIs) are under-prescribed and under-used for anaphylaxis in infants. In a study in which a minority of infants with severe anaphylaxis were treated with epinephrine, reasons for not using it included failure to recognize anaphylaxis symptoms and being afraid to inject epinephrine.

Strict avoidance of exposure to culprit allergens (as confirmed by skin prick tests and specific IgE measurements) prevents recurrences but requires sustained vigilance from all the infant’s caregivers. Natural desensitization to foods such as milk or egg eventually occurs in many infants and children, especially those with mild initial reactions and low levels of sensitization.

Simons and Sampson have outlined specific goals for research on anaphylaxis in infancy. These include validation of the clinical criteria for diagnosis, studies of infant co-morbidities and amplifying co-factors that increase the risk of severe anaphylaxis, development of EAIs containing a 0.1 mg epinephrine dose suitable for this age group, and inclusion of infants in prospective studies of immune modulation to prevent anaphylaxis.

 Question for the authors: In addition to being alert to the possibility of some infants eventually undergoing natural desensitization to milk or egg and helping to facilitate this desensitization, what other possibilities for prevention of anaphylaxis in infants do you see?

Answer: In an important prospective randomized trial in carefully-selected, high-risk infants age 4-11 months (Du Toit G et al, N Engl J Med 2015;372:803-13), early introduction of peanut significantly decreased the frequency of the development of peanut allergy and modulated immune responses to peanut. Although it remains to be proven whether these findings can be translated to other foods such as milk and egg and additional questions need to be addressed, this research suggests that the increase in prevalence of food-induced anaphylaxis in infants might eventually be halted.