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

New Approach to the Treatment of Anaphylaxis: Desensitization

Specific interventions and measures to reduce and prevent the risk of anaphylaxis, such as desensitization, are critical for long-term treatment in the allergic patient (Figure 3).

Drug desensitization is a safe and effective treatment modality in patients with anaphylaxis to chemotherapeutic agents, mAbs,[46–51] antibiotics[52] and other drugs, such as aspirin[53] and iron.[54,55] The goal of desensitization is to maintain patients on their first-line therapy to improve their disease management. Desensitization works by initiating inhibitory mechanisms at low antigen doses, which later dominate over the activation pathways and prevent anaphylaxis.[2,56,57] In a 2016 analysis of 2177 rapid drug desensitization (RDD) procedures to chemotherapy and mAbs, 370 patients with cancer, vasculitis and hematological and connective tissue diseases were desensitized and only 402 reactions were recorded. Of the 2177 desensitizations, 93% had no or mild reactions, whereas 7% had moderate-to-severe reactions, which did not preclude the completion of treatment. No deaths were reported. All patients safely received their target dose regardless of their original reaction.[49] Efficacy and costs were also analyzed, and it was concluded that patients undergoing desensitized had fewer hospital encounters and lower overall costs than nondesensitized patients. Critically, carboplatin-desensitized patients had a nonstatistically significant lifespan advantage over nonallergic controls, indicating that the efficacy of carboplatin was not reduced in allergic patients and that RDD protocols are as effective as regular infusions.[49]

Seminal plasma hypersensitivity is also described to cause anaphylaxis in women, typically at the beginning, during or shortly after sexual intercourse. Desensitization to human seminal fluid has been published as a successful treatment.[58,59]

Venom desensitization, also called ultrarush venom immunotherapy, should be considered in patients who present life-threatening anaphylaxis after Hymenoptera sting with evidence of IgE-mediated mechanism.[60]Hymenoptera anaphylaxis might be the presentation of a mast-cell disorder. Venom immunotherapy in patients with mastocytosis has been demonstrated to reduce the risk of anaphylaxis after resting. In those patients, venom immunotherapy is recommended indefinitely due to the chronic nature of mastocytosis and fatalities have been reported after discontinuation of venom immunotherapy and resting. Omalizumab decreases the severity of reactions in patients under venom immunotherapy and should be considered for patients with severe reactions or underlying mastocytosis.[61]

Food-triggered exercised-induced anaphylaxis was initially described as a syndrome induced during or shortly after exercise in patients sensitized to specific foods. Recently, food ingestion associated with other cofactors such as alcohol, menses, NSAIDs, has also been shown to trigger anaphylaxis.[62–67]

A study showed how long-term treatment with egg OIT enhances sustained unresponsiveness that persists after cessation of therapy. Of 40 OIT-treated patients, 20 (50.0%) demonstrated sustained unresponsiveness by year 4.[68]

Another study has evaluated the clinical and immunological effects of Pru p 3 sublingual immunotherapy (SLIT) on peach and peanut allergy in patients with systemic reactions. The peach nonspecific lipid transfer protein, Pru p 3, is the primary sensitizer in fruits and is responsible for severe reactions in the Mediterranean population. Peach allergy is frequently associated with other allergies such as peanut. After 1 year, Pru p 3 SLIT induced both desensitization and immunological changes not only for peach but also for other food allergens relevant in the induction of severe reactions such as peanut.[69]

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