Application of Precision Medicine to the Treatment of Anaphylaxis

Marina Labella; Marlene Garcia-Neuer; Mariana Castells

Disclosures

Curr Opin Allergy Clin Immunol. 2018;18(3):190-197. 

In This Article

Acute and Long-term Treatment of Anaphylaxis: 'Walking in a Patient's Shoes'

Acute treatment must focus on prompt recognition of symptoms and prompt use of life-saving epinephrine. Long-term treatment is based on identification of the cause of agent implicated in anaphylaxis and can be treated via desensitization, immunotherapy, TKI (tyrosine kinase inhibitors) and anti-IgE therapy.

Acute Treatment

The first step to successfully manage the acute treatment of HSR and anaphylaxis is its identification. HSR and anaphylactic reactions are classified into three grades based on their severity (Figure 2). Grade I or mild reactions are generally characterized by their cutaneous symptoms (80%), or the involvement of only one organ. Grade II or moderate reactions involve two or more organ systems but without vital sign changes. Grade III or severe reactions are characterized by the involvement of two or more organs with vital sign changes or an acute onset of hypotension, laryngeal edema, hypoxia or seizures.[1]

Figure 2.

Hypersensitivity reactions and anaphylaxis treatment. Acute treatment must focus on prompt recognition of symptoms and prompt use of epinephrine of life-saving. Long-term treatment is based on identification of the cause(s) and desensitization, immunotherapy, tyrosine kinase inhibitors and anti-IgE. Source: Based on [2].

Epinephrine is the first-line treatment in Grade III reactions and should be considered for Grade II reactions. Delayed administration of epinephrine has been associated with fatalities.[18] Intramuscular epinephrine may be repeated at 5–15-min intervals if there is no response or an inadequate response, or even sooner if clinically indicated.[19–26]

Patients at risk for anaphylaxis, who lack cardiovascular disease, are recommended to avoid beta-blockers and ACE (angiotensin converting enzyme) inhibitors due to the increased severity of anaphylaxis, masking of cardiac signs of anaphylaxis and reduced response to epinephrine. However, for those patients with cardiovascular disease, beta-blockers and ACE inhibitors have been shown to decrease mortality and increase life expectancy overall and should not discontinue their use.[27,28]

Adverse effects of epinephrine include anxiety, headache, palpitations, ventricular arrhytmias, myocardial infarction and intracranial hemorrhage; however, the most serious symptoms have been associated with intravenous epinephrine. The use of intravenous and prolonged epinephrine could have a detrimental role in patients with allergic angina (Kounis syndrome) and stress miocardiopathy (Takotsubo syndrome).[29–31]

Corticosteroids and antihistamines are not life-saving, they have not been demonstrated to prevent biphasic anaphylaxis and their use should never delay epinephrine administration.[20–28]

Psychological sequelae are often undervalued. Anaphylaxis can also affect the quality of life of patients and the people around them leading to alteration in their social interactions.[32–34]

Long-term Treatment

Long-term management and treatment for acute episodes include education, early recognition of future episodes, avoidance of specific allergens, optimal management of relevant comorbidities and interventions to reduce or prevent anaphylaxis.[35]

Subcutaneous immunotherapy to environmental allergens such as pollen, dust mites, animal dander and molds constitutes an effective treatment for respiratory allergies reducing and preventing symptoms.[36] Immunotherapy has the ability to modify the underlying immunologic mechanisms of allergic rhinitis and asthma with the potential for long-term benefits even after treatment is discontinued. Immunotherapy may also prevent progression of rhinitis to asthma. Sublingual and oral immunotherapy (OIT) are a self-administered alternative to subcutaneous immunotherapy that also provide benefits without the inconvenience of frequent office visits or the discomfort of injections but require an almost daily administration. The most common adverse events are local reactions such as pruritus and erythema.[37,38]

Omalizumab, anti-IgE mAb, has been shown to be a successful treatment for reducing the number and severity of anaphylactic reactions and improving the quality of life in patients with IgE-mediated diseases.[39]

TKI have been used in patients with systemic mastocytosis.[40,41] Imatinib has demonstrated positive results in patients with negative KIT D816V mutation. Recently, Midostaurin, a KIT inhibitor, has been approved for advanced systemic mastocytosis, neutralizing the release of mast cells and basophil mediators.[42,43] Indications for desensitization as a long-term treatment for anaphylaxis, including Hymenoptera venom, food allergies, drugs and human proteins are discussed in Figure 3.

Figure 3.

Rapid desensitization as a treatment for anaphylaxis. Desensitization as a treatment of anaphylaxis for foods, drugs, Hymenoptera venom and human proteins. Source: Based on [2].

New insights are being investigated to predict early IgE sensitization and provide increased protection and prevention of anaphylaxis. A recent study introduced nanoparticles as a versatile platform for studying allergic sensitization to peanut nanoallergens. This new technique provides information regarding specific allergenic epitopes with the purpose of improving diagnosis, enabling targeted designs for future therapeutics and allowing for personalized treatment options for patients.[44,45]

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