Diagnosis and management of anaphylaxis in precision medicine

Abstract

Anaphylaxis is the most severe and frightening of the allergic reactions, placing patients at high risk and demanding prompt recognition and immediate management by health care providers. Yet because its symptoms imitate those of other diseases, such as asthma and urticaria, current data suggest that its diagnosis is often missed, with underuse of tryptase measurement; its treatment is delayed, with little use of epinephrine; and its underlying cause or causes are poorly investigated. Deaths from anaphylaxis are difficult to investigate because of miscoding. Surprisingly, patients treated with new and powerful chemotherapy agents and humanized mAbs present with nonclassical symptoms of anaphylaxis, and patients may present with unrecognized clonal mast cell disorders with KIT mutations may present as Hymenoptera-induced or idiopathic anaphylaxis. The goal of this review is to recognize the presentations of anaphylaxis with the description of its current phenotypes, to provide new insight and understanding of its mechanisms and causes through its endotypes, and to address its biomarkers for broad clinical use. Ultimately, the aim is to empower allergists and heath care providers with new tools that can help alleviate patients' symptoms, preventing and protecting them against anaphylaxis.

Serum Baseline Tryptase Level as a Marker for the Severity of Anaphylaxis

“…IgE-mediated reactions frequently underlie the development of anaphylaxis; however, other pathways have also been described [1]. Due to the lack of universally accepted clinical ­criteria for the diagnosis of anaphylaxis, this condition is often underrecognized, underdiagnosed, and, consequently, undertreated [2-5].…”

“…Currently, anaphylaxis phenotypes have been defined as type-I-like reactions, when classical allergic symptoms due to the release of inflammatory mediators from mast cells and basophils are present, including flushing, pruritus, urticaria, angioedema, dyspnea, wheezing, nausea, vomiting, diarrhea, hypotension, and cardiovascular collapse; cytokine storm-like reactions and mixed reactions, which are frequently provoked by chemotherapy or monoclonal antibodies and induce atypical symptoms such as chills, fever, or pain, in addition to classical symptoms, and reactions mediated by complement, which can be caused by contrast dyes or dialysis membranes, and often induce hypotension and oxygen desaturation [1, 7, 8]. Endotypes underlying these clinical presentations include IgE and non-IgE-mediated mechanisms, cytokine release, direct mast cell and basophil activation, complement activation with generation of anaphylatoxins C3a and C5a, contact system activation with bradykinin release, IgG-mediated cell activation which is still debat able in humans, and mixed reactions [1, 7, 8].…”

“…Endotypes underlying these clinical presentations include IgE and non-IgE-mediated mechanisms, cytokine release, direct mast cell and basophil activation, complement activation with generation of anaphylatoxins C3a and C5a, contact system activation with bradykinin release, IgG-mediated cell activation which is still debat able in humans, and mixed reactions [1, 7, 8]. …”

“…Serum tryptase concentrations > 11.4 ng/mL indicate mast cell/basophil activation, and during anaphylaxis, levels correlate with severity. In patients with low baseline tryptase levels, levels may increase during anaphylaxis but still remain in the normal range; therefore, levels of 2 ng/mL plus 1.2 times baseline have been considered significantly increased [1]. Measurements of the histamine metabolite methylhistamine; prostaglandin D 2 and its metabolite 9α-11β prostaglandin F 2 ; and leukotrienes E 4 and C 4 have also been investigated; however, difficulties in obtaining 24-h urine samples in the scenario of anaphylaxis may hamper their practical use [7, 8].…”

“…Measurements of the histamine metabolite methylhistamine; prostaglandin D 2 and its metabolite 9α-11β prostaglandin F 2 ; and leukotrienes E 4 and C 4 have also been investigated; however, difficulties in obtaining 24-h urine samples in the scenario of anaphylaxis may hamper their practical use [7, 8]. Elevated IL-6 levels have been proposed as a marker of cytokine storm-type anaphylaxis [1]. …”