Differentials
Somatoform disorders
SIGNS / SYMPTOMS
Patient describes subjective symptoms that are consistent with unprovoked anaphylaxis but no objective signs and symptoms can be observed or documented on physical exam.[60] Such patients can have panic attacks, vocal cord dysfunction, or even Munchausen syndrome, and may attend the emergency department repeatedly, for instance reporting a sensation of throat tightness (globus sensation).
INVESTIGATIONS
Serum tryptase levels are not elevated during the episode.
Vasovagal reaction
SIGNS / SYMPTOMS
Bradycardia is typical in vasovagal reactions whereas tachycardia is usually present during an acute MCAS episode. Physical examination of patients with vasovagal reaction generally shows pallor (pale skin) and sometimes diaphoresis whereas flushing is more typical during acute MCAS.
INVESTIGATIONS
Auscultation of the heart and/or ECG will show bradycardia (usually <50 bpm).
Serum tryptase levels are not elevated during the event.
Carcinoid syndrome
SIGNS / SYMPTOMS
Typical symptoms are similar to those that can occur in MCAS, including flushing, diarrhea, palpitations, tachycardia, abdominal pain and severe hypotension.[61]
INVESTIGATIONS
Elevated levels of 24-hour urinary 5-hydroxyindoleacetic acid (5-HIAA) and serum chromogranin A/B (where available)
Serum tryptase levels remain normal during an episode of carcinoid syndrome.[2]
Pheochromocytoma
SIGNS / SYMPTOMS
Paroxysmal hypertension and pale face are features of pheochromocytoma (as opposed to hypotension and flushing during acute episodes of MCAS).
Other symptoms that are typical in pheochromocytoma (but not in MCAS) include headaches, heavy sweating, tremor, and irritability in the setting of paroxysmal hypertension.[62]
INVESTIGATIONS
Elevated levels of 24-hour urinary catecholamines, metanephrines, normetanephrines, and creatinine.
Elevated serum free metanephrines and normetanephrines.
Serum tryptase levels remain normal.
Septic shock
SIGNS / SYMPTOMS
Fever, lack of allergen exposure, slower onset and other signs of localized infection often differentiate septic shock from anaphylaxis/MCAS.
INVESTIGATIONS
Increased WBC count and increased temperature.
Blood cultures may be positive for infection-causing pathogen.
Lactate elevated in severe cases.
Serum tryptase levels are not elevated.
Hereditary angioedema
SIGNS / SYMPTOMS
Recurrent episodes are slowly progressive rather than acute-onset, with angio-edema of the skin, mucosa, or submucosal tissue and in some cases gastrointestinal edema; patients may present with isolated throat discomfort.
Patients have no history of allergen exposure and there is no urticaria or hypotension during the episodes. Family history is positive.
INVESTIGATIONS
Deficiency or underactivity of the C1 esterase inhibitor enzyme.
Serum complement C4 and CH50 and C1 inhibitor functions are low.
Serum tryptase levels are not elevated during the episodes.
Hereditary alpha tryptasemia
SIGNS / SYMPTOMS
Most cases are believed to be asymptomatic but hereditary alpha tryptasemia may increase the risk for severe anaphylactic reactions in patients with venom allergies or with idiopathic anaphylaxis.[25][26]
INVESTIGATIONS
Baseline serum tryptase levels generally >8 ng/ml.[18] Copy number analysis of TPSAB1 gene confirms the diagnosis.
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