NEW YORK CITY—There is much we still do not know about anaphylaxis. For example, its incidence remains uncertain, and the available information about its causes and risk factors is inadequate. And, idiopathic anaphylaxis can be a diagnostic quagmire because it is easily confused with many other conditions. Two top experts on anaphylaxis attempted to unravel these mysteries at the recent annual meeting of the American Academy of Allergy, Asthma, & Immunology in New York City.[1]

The incidence of anaphylaxis is unclear because of a lack of data and underreporting of cases. However, two groups have published some of the best available estimates, said Phillip L. Lieberman, MD, a Clinical Professor of Medicine and Pediatrics at the University of Tennessee College of Medicine in Knoxville.

In a study by Yocum et al[2] of 1,255 residents of Olmsted County, Minnesota, the annual incidence of anaphylaxis averaged 21 cases per 100,000 persons. During the five-year study, 133 residents suffered 154 anaphylaxis episodes; only one episode resulted in death. “The hospitalization rate was 7%, which is quite high,” Dr. Lieberman remarked.

Using prevalence data on four causes of anaphylaxis (food, medications, latex, and Hymenoptera stings), Neugut et al[3] estimated that 1.24% to 16.8% of the US population—3.3 to 43 million persons—are at risk for anaphylaxis. A far smaller proportion, 0.002%, is at risk for a fatal reaction, the researchers also estimated.

Another, albeit indirect, method of gauging anaphylaxis incidence is to analyze computerized pharmacy records for anaphylaxis medication prescriptions among the general population. Such an analysis has shown a 0.8% prescription rate for the epinephrine auto-injectors often used to treat anaphylaxis.[4] However, these analyses may not allow firm conclusions about anaphylaxis rates, Dr. Lieberman acknowledged, because the auto-injectors may have been prescribed for other purposes (eg, they are sometimes given to patients receiving immunotherapy).

The best data on the causes of anaphylaxis come from surveys of allergists’ practices; these surveys suggest that about half of all cases are idiopathic. Virtually all of the surveys have found the next most common types of anaphylaxis are induced by foods (peanuts in children, shellfish in adults) and drugs, particularly antibiotics and nonsteroidal anti-inflammatory medications.

Atopy is the most interesting anaphylaxis risk factor because atopy predisposes to anaphylaxis not just through immunoglobulin E–mediated mechanisms (as one would expect) but through a variety of pathways, said Dr. Lieberman. The reason for this is unknown, he admitted, but one suggested explanation is that the mast cells of atopic individuals have a greater propensity to degranulate and release histamine.

Age appears to be another important risk factor for anaphylaxis; in most studies, incidence peaks between ages 20 and 30 years. In most types of anaphylaxis, incidence is higher in women than in men; the exception is cases due to Hymenoptera stings. In children, however, the sex/incidence ratio may be reversed; auto-injectors are prescribed more often for boys than for girls.

Some investigators have reported a higher incidence in rural areas than in urban areas, suggesting that geographic location may also influence the risk. And, income may play a role, said Dr. Lieberman. Studies have shown that epinephrine auto-injectors are more likely to be prescribed to patients in higher-income groups than to those in lower-income groups; this difference could not be explained simply by the wealthier groups’ greater access to health care.

Anaphylaxis is considered idiopathic when specific causes have been excluded with reasonable certainty, related Paul A. Greenberger, MD.[1] In addition to food, drug, latex, and insect-sting reactions, specific problems that must be ruled out include hereditary angioedema, systemic mastocytosis, factitious anaphylaxis, and undifferentiated somatoform idiopathic anaphylaxis, said Dr. Greenberger, a Professor of Medicine in the Division of Allergy and Immunology at Northwestern University Medical School in Chicago.

Acute severe asthma and vocal cord dysfunction are two less likely conditions that should also be considered in the differential diagnosis of idiopathic anaphylaxis.[5] Rarely, patients may suffer from Munchausen stridor or anaphylaxis, psychologic disorders in which patients imitate stridor or intentionally induce anaphylaxis by consuming anaphylactogenic foods or medications.

Episodes of idiopathic anaphylaxis may occur in all age-groups, but they are most likely to affect persons between the ages of 20 and 40 years. The manifestations almost always include urticaria or angioedema and often include upper airway obstruction and bronchospasm. Gastrointestinal symptoms, syncope, and hypotension are sometimes present.

Many conditions can coexist with idiopathic anaphylaxis, including atopy; allergic rhinitis; asthma; food- or medication-induced anaphylaxis; and atopic dermatitis. Episodes of idiopathic anaphylaxis may occur every couple of months or about only once a year. Patients with daily attacks do not have idiopathic anaphylaxis, Dr. Greenberger stressed.

Northwestern University has established a prevention program that has been shown to decrease the number of anaphylactic episodes by about 50% in adults with idiopathic anaphylaxis. The program also markedly reduces the rates of emergency room visits, hospitalizations, and intensive care unit admissions for the disorder, Dr. Greenberger said.

The program includes prednisone treatment, usually for a maximum of two to three months. Patients start at 50 to 60 mg/d for one to two weeks; this is followed by a conversion to alternate-day prednisone administration and then gradual tapering (a reduction of 5 to 10 mg/d every two weeks). Patients receive cetirizine or hydroxyzine as well, and they are given an emergency plan that specifies what measures they should take for an anaphylactic attack before going to the emergency room.

Such a program may be best suited to patients with more frequent episodes of idiopathic anaphylaxis (eg, six or more per year), Dr. Greenberger noted. For those who have an attack only once a year or so, it may be preferable to teach them to use epinephrine and other appropriate treatments at the time of the attack. Comparative data suggest that epinephrine is absorbed more rapidly when administered intramuscularly than subcutaneously, he added.

Prednisone-dependent idiopathic anaphylaxis is more likely to go into remission or, at least, to decrease in frequency and severity than is an ongoing, relentless condition such as prednisone-dependent asthma, Dr. Greenberger pointed out. “That is an optimistic piece of information we can give our patients,” he concluded.

—Timothy Begany

References
1. Lieberman PL, Greenberger PA, Conboy-Ellis KA. Anaphylaxis: clinical patterns and management. Presented at: Annual Meeting of the American Academy of Allergy, Asthma, & Immunology; March 2, 2002; New York, NY.
2. Yocum MW, Butterfield JH, Klein JS, et al. Epidemiology of anaphylaxis in Olmsted County: a population-based study. J Allergy Clin Immunol. 1999;104(2 pt 1):452-456.
3. Neugut AI, Ghatak AT, Miller RL. Anaphylaxis in the United States: an investigation into its epidemiology. Arch Intern Med. 2001;161:15-21.
4. Simons FE, Peterson S, Black CD. Epinephrine dispensing for the out-of-hospital treatment of anaphylaxis in infants and children: a population-based study. Ann Allergy Asthma Immunol. 2001;86:622-626.
5. Greenberger PA. Differential diagnosis of idiopathic anaphylaxis. In: Patterson R, ed. Idiopathic Anaphylaxis. Providence, RI: Oceanside Publications; 1997:7-17.

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