Anaphylaxis

Case 1:

A 47-year-old patient originally from Greece presented with an episode of throat swelling, dyspnea, pruritus, urticaria and loss of consciousness while operating a jackhammer. He presented to the emergency room (ER) where he was noted to be hypotensive and received epinephrine and antihistamines. Two weeks later, he presented with left upper quadrant pain. His history was significant for chronic hepatitis B infection but no history of atopy or prior anaphylaxis. Chemistries, transaminases, and CBC with differential were normal. An IgE was elevated at 386 IU/ml. Imaging was notable for a large multiseptated cyst in his liver (Supplemental; slide 6) and he was taken to surgery.

Case 2:

A 55-year-old Puerto Rican patient with a history of hypereosinophilia, a transient ischemic attack, as well as shellfish, environmental, and venom sting allergies presented for annual follow-up reporting the new onset of episodes of anaphylaxis. The first episode started with itching of the hands and feet followed by tongue swelling requiring 2 doses of epinephrine in the ER. No previously known triggers were implicated. Over the next 10 months, she had 5 additional episodes of anaphylaxis (pruritus, tongue swelling, abdominal pain, diarrhea, urticaria, and hypotension) without an identifiable trigger, and required administration of epinephrine in the ER. All laboratory tests were within normal limits except for an absolute eosinophil count of 3230 cells/μL and a baseline serum tryptase level of 13.3 ng/mL. She had an extensive evaluation for disorders associated with increased serum tryptase, including bone marrow biopsy and imaging. No abnormalities in KIT D816V or PDGFRA were demonstrated. Hereditary α-tryptasemia and α-gal syndrome were excluded. A log of foods and exposures that preceded the anaphylaxis episodes was unrevealing.

Diagnoses:

• Case 1: Echinococcal infection. The patient had surgical resection of the cyst (histopathologically identified as Echinococcus granulosis [Eg] and experienced hypotension with associated urticaria operatively. The post-surgical course was complicated by release of cyst contents into the thorax and peritoneal cavity leading to disseminated echinococcosis. IgG anti-Eg antibodies were positive in serum obtained after surgery. The patient was subsequently referred to the NIH and was treated with multiple courses of albendazole.

• Case 2: Idiopathic anaphylaxis. The patient was advised to carry 2 or more epinephrine autoinjectors and an emergency action plan was discussed.

Discussion:

Anaphylaxis is defined as a severe systemic allergic reaction with rapid onset often involving more than one organ symptom. Clinical criteria include acute symptom onset with involvement of the skin or mucosal tissue and at least one of the following: 1) respiratory compromise, 2) hypotension, or 3) persistent GI symptoms. In the case of a known allergen, reduced blood pressure after exposure is sufficient for diagnosis.^1–3. The initial development of anaphylaxis results from cross-linking of IgE by antigens on the surface of mast cells, leading to the release of preformed mediators (e.g., histamine and proteases) and the production of inflammatory mediators (e.g., leukotrienes and prostaglandins).⁴

Parasitic infection is not often included in the differential diagnosis of anaphylaxis, but can be seen in patients infected with Echinococcus granulosis or Anisakis simplex.⁵ Echinococcosis (also known as hydatid disease) is caused by infection with cestodes of the genus Echinococcus. Eg, the cause of cystic echinococcosis, is most commonly associated with anaphylaxis. The cystic structure of Eg consists of a parasite-derived inner (germinative) membrane and a host-derived outer membrane that shields the cestode from the host inflammatory response. Although leakage of small amounts of Eg antigens likely causes sensitization, the development of severe anaphylaxis occurs when the cysts rupture either spontaneously or due to trauma⁶. Anaphylaxis is one of the most common initial presentations of hydatid disease secondary to abdominal trauma.^{5 7}

In patients presenting with anaphylaxis, the initial approach is to determine exposure to commonly described triggers such as food, medications, insect stings, and vaccines (see table 1). If no clear cause is determined, parasites should be considered particularly if there is an appropriate exposure history (both patients grew in rural areas with livestock exposure). For cystic echinococcosis, imaging (e.g. CT and/or ultrasound) should be performed and serology, if available, may be useful⁷. For Anasakis, almost all cases have been from the Iberian Peninsula and have been associated with exposure to or consumption of raw or undercooked seafood.⁵ Eosinophilia is not often associated with echinococcus or anisakis infection but may be seen in some cases of complicated echinococcal disease (e.g presence of pre-surgical fistula) or following cyst leakage.⁸

Table 1.

Differential Diagnosis of Anaphylaxis

Non-Infectious	Parasitic infections	Anaphylaxis mimics
Foods IgE mediated reactions (foods, drugs, latex, venom)	Echinococcus spp. (E. granulosis most common)	Somatoform symptom disorder
non-IgE mediated reactions (e.g. MRGXPR2) to drugs, anesthetics or other exposures	Anisakis simplex	Acute asthma exacerbation
Food-dependent exercise-induced anaphylaxis		Hereditary, acquired or drug-induced angioedema
Mastocystosis/ Clonal mast cell disorders
Idiopathic anaphylaxis

Idiopathic anaphylaxis is a diagnosis of exclusion, and parasitic causes should be included among the potential triggers typically considered by allergists-immunologists. There is no clear association between eosinophilia and anaphylaxis, but eosinophilia can co-exist with both parasitic infection and mast cell disorders, which should be considered in patients with a history of eosinophilia and new onset episodes of anaphylaxis.