Page 1807 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

1276 PART 11: Special Problems in Critical Care

The onset of symptoms in scombroidosis occurs within a few anaphylaxis secondary to an injected medication or an insect sting and
minutes to several hours after the ingestion of fish. Several members anaphylaxis associated with hypotension or shock but it is less likely to
eating at the same table may be affected. The episodes usually last a be increased in those with anaphylaxis secondary to food and anaphy-
few hours, but can persist for days. Symptoms include urticaria, flush, laxis not associated with hypotension. 84,85
angioedema, nausea, vomiting, diarrhea, and a fall in blood pressure. Serum tryptase levels peak one to one and one-half hours after the
Neurological findings and wheezing may also occur. The most com- onset of anaphylaxis and can persist for as long as 5 hours after the onset
mon manifestation is face and neck flush accompanied by a sensation of symptoms. The best time to measure serum tryptase is between 1 and
of heat and discomfort. The rash can resemble sunburn. Serum trypt- 2 hours but no longer than 6 hours after the onset of symptoms. 120
ase levels are not elevated in histamine poisoning, whereas plasma Postmortem elevation of serum tryptase concentrations is not a
histamine and 24-hour urinary histamine metabolites are present in specific finding and therefore cannot be considered diagnostic of an
increased amounts. anaphylactic death. There are reports of nonanaphylactic deaths with
■ LABORATORY IN THE DIAGNOSIS OF ANAPHYLAXIS elevated postmortem serum tryptase levels. 121-123 Thus, the presence of
an elevated postmortem tryptase level cannot be considered pathogno-
The diagnosis of an anaphylactic event is based on a clinical interpretation monic for a death due to anaphylaxis. At the same time, the absence of
of the manifestations. However, laboratory tests may be useful for confir- an elevated serum tryptase postmortem cannot be considered sufficient
mation. Table 128-7 is a list of those tests that may confirm the diagnosis to rule out anaphylaxis as the cause of death. 121
of anaphylaxis in an event with suggestive clinical manifestations. Plasma histamine rises much more rapidly than does serum trypt-
Presently, commercially available tests to confirm the diagnosis of ase. Plasma histamine levels can be elevated 5 to 10 minutes after
anaphylaxis are the serum tryptase, plasma histamine, and 24-hour the onset of symptoms. However, such levels are evanescent, usually
urinary histamine metabolites. Tests that hold promise and are being returning to normal within 60 minutes after the onset of the event.
investigated for potential use in diagnosing anaphylactic events include The best time to measure plasma histamine is between 10 minutes and
120
carboxypeptidase A-3, platelet-activating factor, and platelet-activating 1 hour after the onset of symptoms. For this reason, plasma hista-
factor hydrolase. mine levels are of little help if the patient is seen as long as an hour
Human mast cells contain tryptase, and small amounts are also found after the event. In this case, however, a 24-hour urinary collection for
in human basophils. Serum tryptase is specific to these cells. Tryptase histamine metabolites may be useful. Such metabolites can be elevated
is secreted constitutively in small amounts. The constitutively secreted for as long as a day.
tryptase is a mixture of α- and β-protryptase (mostly β). Marked Unfortunately, there are disparities between histamine and tryptase
increases in tryptase levels seen during an anaphylactic event are com- levels. If the patient is seen soon enough, plasma histamine levels may be
prised of mature β-tryptase. 84,119 more sensitive and may also correlate better with clinical manifestations.
124
By far, the most commonly employed biomarker used to confirm In a study of episodes of allergic reactions presenting to the emergency
a diagnosis of anaphylaxis is the measurement of total serum trypt- room, elevated concentrations of plasma histamine were observed in
ase. Unfortunately, this test lacks sensitivity, but is highly specific. 42 of 97 adult patients, whereas only 20 such patients had elevations
Nonetheless, because of the lack of sensitivity, a normal total tryptase of serum tryptase. In this study, histamine levels correlated better
value obtained during an event does not rule out the diagnosis of ana- with clinical signs than did tryptase. Patients with elevated histamine
phylaxis. The total tryptase level is typically increased in patients with were more likely to have urticaria, more extensive erythema, abnormal
abdominal findings, and wheezing.
There are other potential markers for anaphylactic events which
have not been as well studied and confirmed for their sensitivity and
TABLE 128-7 Tests Used to Confirm the Diagnosis of Anaphylaxis and Exclude specificity. These include increased expression of CD63 detected by
Other Causes flow cytometry, indicating activation and degranulation of basophils;
Test Comment urinary prostaglandin D2 determinations and serum carboxypeptidase
A levels. Flow cytometry-assisted anaphylaxis diagnosis has been shown
Serum tryptase Levels usually peak 60 to 90 minutes after the to be reliable for reactions caused by food, hymenoptera venom, latex,
onset of symptoms and persist for 6 hours. Ideally, and drugs. 125,126 Prostaglandin D2 levels have been found elevated in
measurement should be obtained between one anaphylactic events secondary to mastocytosis. Perhaps, however, the
10
and 2 hours after onset of symptoms.
most promising mediator is carboxypeptidase A. Mast cell carboxypep-
Plasma histamine Levels rise within 5 to 10 minutes after the onset of tidase A levels in serum or plasma collected within 8 hours of the onset
symptoms and returns to normal after 60 minutes. of allergic reactions in mastocytosis patients were significantly greater
24-Hour urinary histamine metabolites Urinary histamine metabolites can be elevated than those found in control groups. In 83% of cases that had an elevated
(N-methylhistamine) for up to 24 hours after the onset of the event. tryptase, concentrations of carboxypeptidase levels were elevated. Out of
110 cases of suspected anaphylaxis that were tryptase negative, elevated
Serum serotonin and urinary Used to rule out carcinoid syndrome 127
5-hydroxyindoleacetic acid concentrations of carboxypeptidase were found in 77 (70%) cases.
Other mediators that have been reported to be useful in confirming the
Gastrointestinal vasopeptides including Useful to rule out the presence of a vasoactive diagnosis of anaphylaxis include platelet-activating factor (PAF), cyto-
pancreastatin, vasointestinal polypep- polypeptide secreting pancreatic or small bowel kines such as IL-2, IL-6, IL-10, IL-33, TNF-receptor I, urinary cysteinyl
tide, substance P, neurokinin, and others tumors and medullary carcinoma of the thyroid leukotrienes E4, and 9-α-11-β prostaglandin F2. 87-90 It is of note that
Plasma-free metanephrine and urinary Useful in ruling out a paradoxical response to a platelet-activating factor and its hydrolase are both measureable and
vanillylmandelic acid pheochromocytoma that the severity of anaphylaxis is directly correlated with serum levels
Other potential tests that would be Carboxypeptidase A, CD63 basophil marker, prosta- of platelet-activating factor and inversely correlated with serum levels of
90
available in future glandin derivatives in the urine, platelet-activating platelet-activating factor hydrolase. Given that different mediators are
factor, platelet-activating factor hydrolase. These released from mast cells at different time courses and patients arrive in the
84
markers would be used for diagnosis of anaphylaxis. emergency room at different times after the onset of event, Simons et al
suggested measuring a panel of different biomarkers would be help-
Bone marrow biopsy Most definitive test to establish the diagnosis of ful in confirming the diagnosis. When other conditions are consid-
systemic mastocytosis. Analysis for c-kit mutations, ered to be the cause of the event in question, laboratory testing may
mast cell markers, and histology can be done. also be highly useful (Table 128-5). Serum serotonin and urinary-5

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