Idiopathic Anaphylaxis: a Perplexing Diagnostic Challenge for Allergists

Abstract

Purpose of Review The aim of this systematic review is to present the proposed theories of pathogenesis for idiopathic anaphylaxis (IA), to discuss its classification, its diagnostic approach, and management. Recent Findings IA represents a major diagnostic challenge and is diagnosed when excluding the possible identifiable triggers of anaphylaxis. The current research, however, revealed that certain conditions including mastocytosis, mast cell activation syndromes, and hereditary alpha tryptasemia can masquerade and overlap with its symptomatology. Also, newly identified galactose-alpha-1,3-galactose mammalian red meat allergy has recently been recognized as underlying cause of anaphylaxis in some cases that were previously considered as IA. Summary IA comprises a heterogenous group of conditions where, in some cases, inherently dysfunctional mast cells play a role in pathogenesis. The standard trigger avoidance strategies are ineffective, and episodes are unpredictable. Therefore, prompt recognition and treatment as well as prophylaxis are critical. The patients should always carry an epinephrine autoinjector.

Mastocytosis and Mast Cell Activation Disorders: Clearing the Air

“…Idiopathic anaphylaxis (IA) is a condition characterized by repeated episodes of anaphylaxis with no demonstrable external trigger [ 86 ]. Human MCs as well as basophils may be responsible for the manifestation of anaphylaxis that accompanies the condition.…”

“…IA was described about four decades ago and since then the classification and management of the disease have been defined. Typically, there is involvement of two or more systems (such as cardiovascular, respiratory, or gastrointestinal) and patients often present to the emergency room or urgent care with urticaria, angioedema of the lips or tongue, wheezing, vomiting, diarrhea, and confusion or syncope [ 86 ]. Fatality due to IA is rare but has been recorded.…”

“…Grammar and coworkers showed that, compared to patients with mast cell disorders, IA patients have evidence of activated T cells and B cells in the peripheral blood, although it is unclear whether this is primary or an epiphenomenon, as some of the patients with activated CD19+ CD23+ B cells were also receiving concomitant glucocorticoids [ 88 ]. One unpublished study that used gene expression profiling showed that patients with IA had activated genes regulating mast cell and basophil degranulation [ 86 ]. In many situations, IA may be difficult to differentiate from idiopathic mast cell activation syndrome.…”

Acute Urticaria and Anaphylaxis: Differences and Similarities in Clinical Management

“…Immunoassays allow detection of both total (baseline release) and mature (released only at the time of activation) tryptase. Another blood sample to measure the basal level of tryptase is needed 24 to 48 h after anaphylaxis ( 69 , 78 ). In general, baseline tryptase levels >8 ng/ml are considered elevated, but this is not always a sign of mast cell activation.…”

Update on idiopathic anaphylaxis

“…Diagnostic work-up of IA usually includes an accurate clinical history, aimed to exclude (A) the most common causes of anaphylaxis (food, drugs, latex, and insects allergy) (B) the less frequent causes, such as summation anaphylaxis, cholinergic or cold urticaria with anaphylaxis, α-gal anaphylaxis, allergy to hidden allergens (sulfite, spices, dust mites, mislabeled or undeclared food allergens, food additive, carmine powder, and psyllium), aeroallergens inducedanaphylaxis, catamenial anaphylaxis, undifferentiated somatoform anaphylaxis; (C) all pathologies that may appear with similar symptoms of anaphylaxis (pheochromocytoma, carcinoid syndrome, medullary thyroid cancer, pancreatic tumors). 3 Several pathogenic mechanisms have been proposed to explain IA. A self-reactive mechanism has been hypothesized, as suggested by the increased number of activated lymphocytes and activation of B lymphocytes (CD18+ CD23+) or by a positive autologous serum test.…”