What is idiopathic anaphylaxis?
The word “idiopathic” means of unknown cause. It is used to designate a disease or condition that originated "without an apparent extrinsic cause." Reference [Banay GL. An introduction to medical terminology: I. Greek and Latin derivations. Bull Med Libr Assoc. January 1948; 36(1):1–27].
Usually when a person has anaphylaxis, a readily identifiable trigger can be found. Whether it’s the sting of a bee, the injection of an antibiotic, anesthesia used during surgery, or a specific food the person has eaten, the most likely cause of the anaphylaxis is apparent. If the trigger cannot be immediately discerned, a workup by an allergist will be sufficient, in most cases, to track it down.
However, if a cause for multiple episodes of anaphylaxis cannot be found and if a complete and thorough workup rules out all of the conditions that are known to cause the problem, then the problem is diagnosed as idiopathic anaphylaxis (IA). While a diagnosis of IA could be viewed as the allergist shrugging his or her shoulders and saying, “I’m sorry, but I don’t know why you have anaphylaxis,” it is important to realize that the phenomenon of IA has been carefully described and documented in a substantial number of patients — and that the currently available treatments for the condition can usually control it fairly well.
What we do know
There are some things we do know about IA. For example, it affects more women than men. The most recent article describing IA, written by Karen Hsu Blatman and Leslie C. Grammer [Blatman KH, Grammer LC. Idiopathic anaphylaxis. In: Castells MC, ed. Anaphylaxis and Hypersensitivity Reactions. New York, NY: Humana Pr (Springer); 2011, 223–334], notes that “…Several studies [report] more than 60% of affected patients were women….”
The same authors report that about half of IA patients also have allergies or asthma. At this point you may wonder, “Wait a minute, I thought you said that no cause could be found for the anaphylaxis? If someone has allergies or asthma, aren't they what’s causing the anaphylaxis?” Not necessarily. If someone has a well-documented allergy to, say, bee stings, but also has recurrent anaphylaxis in which no bee stings are implicated, the cause of the attacks is still unknown.
Age of onset
Blatman and Grammer [Blatman KH, Grammer LC. Idiopathic anaphylaxis. In: Castells MC, ed. Anaphylaxis and Hypersensitivity Reactions. New York, NY: Humana Pr (Springer); 2011, 223–334] tell us that, “Idiopathic anaphylaxis has been reported across the entire age spectrum.” Two-thirds of people have onset before age 40, but there is no age at which one is “too young” or “too old” to develop this mysterious condition.
Estelle Simons [Simons FE. Anaphylaxis: Recent advances in assessment and treatment. J Allergy Clin Immunol 2009; 124:625-36; quiz 37–8.] notes that “In children, adolescents, and young adults, foods are the most common trigger. In middle-aged and older adults, medications and stinging insect venoms are important considerations, as is idiopathic anaphylaxis.”
Idiopathic anaphylaxis is not only a problem for Western children. In a four-year span, 63 children were brought to an Asthma and Allergy Research Institute in Iran because of episodes of anaphylaxis. Altogether the 63 children had 193 nonfatal anaphylactic attacks, and among the 63 children, two were found to have IA. Reference [Barzegar S, Rosita A, Pourpak Z, Bemanian MH, Shokouhi R, Mansouri M, et al. Common causes of anaphylaxis in children: The first report of anaphylaxis registry in Iran. WAO Journal. 2010; 3:9–13].
The youngest person so far diagnosed with idiopathic anaphylaxis would be a 2-and-a-half-month-old female infant who demonstrated severe swelling of lips, face, tongue, and hands, diffuse redness, respiratory distress and wheezing. Reference [Cooper SM, Schuller DE, Fausnight TB. Idiopathic anaphylaxis in infancy. J Allergy Clin Immunol 2011; 127:AB249Cooper SM, Schuller DE, Fausnight TB. Idiopathic anaphylaxis in infancy. J Allergy Clin Immunol. 2011; 127:AB249]. By the age of 5 months, she had had two more, similar episodes. An extensive workup revealed no cause for the attacks. Switching the child from breast milk to formula was not helpful. As the authors point out: “Idiopathic anaphylaxis may occur at any age, even in early infancy.”
At the other end of the age spectrum, Blatman and Grammer [Blatman KH, Grammer LC. Idiopathic anaphylaxis. In: Castells MC, ed. Anaphylaxis and Hypersensitivity Reactions. New York, NY: Humana Pr (Springer); 2011, 223–334] report that in a large sample of 335 people diagnosed with idiopathic anaphylaxis, 11 (3.3%) were older than 70.
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A “wastebasket diagnosis”?
Because IA is a diagnosis of exclusion, it can also be regarded as a kind of “wastebasket diagnosis.”
Imagine that diagnosis works like a conveyor belt. Each patient sits on the conveyor belt, and at various stations along the way, he or she is tested for various conditions, like carcinoid tumors or mastocytosis. If the patient is found to have one of these conditions, he or she is pulled off the conveyor belt at that point. If the patient rides the conveyor belt all the way to the end, they fall into a basket labelled, “IA.”
It is altogether possible that everyone diagnosed with IA does not actually have the exact same disease, and recent medical research supports this idea. See What causes IA? for more on this topic.
It is also not unusual to encounter medical personnel who assert that they “don’t believe in” idiopathic anaphylaxis. What some doctors mean is that they do not accept the idea that anyone can have anaphylaxis that is not in response to some kind of external factor. Reference [Sheffer AL. Unraveling the mystery of idiopathic anaphylaxis. NEJM. 1984; 311(19):1248—1249.]. These doctors believe that if the allergist/immunologist cannot find an allergen responsible for the attacks of anaphylaxis, then he or she has either been unlucky or hasn’t looked hard enough!
And there have been unlikely allergens discovered that could explain at least some of the cases that may have been diagnosed as IA. For example, Commins, James, et al [Commins SP, James H, Tran N, et al. Testing for IgE antibody to the carbohydrate galactose-α-1,3-galactose (alpha-gal) in patients with recurrent, idiopathic anaphylaxis: How many cases are we missing? J Allergy Clin Immunol 2010; 125:AB119–AB.]., published the abstract last year of a study in which 20 patients diagnosed with recurrent, idiopathic anaphylaxis were tested for the presence of antibodies (IgE) to alpha-gal [galactose-α-1,3-galactose, a carbohydrate that can act as an allergen in meat]. One quarter of the patients studied were found to test positive for IgE to alpha-gal. (Note: These patients also had elevated total IgE levels in comparison to the IA patients who tested negative to alpha-gal IgE.)
In other cases, it is not clear just why the diagnosis of IA is rejected out of hand — it is not an opinion I have heard from anyone who has spent much time working with people who have this condition.
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Frequency of anaphylaxis
Not everyone who has idiopathic anaphylaxis (IA) experiences it in exactly the same way. There are differences in terms of how often the person may have anaphylaxis (frequency), as well as in the constellation of symptoms that occur either in conjunction with, or separately from, the anaphylaxis itself.
The first group to study IA arbitrarily divided their patients into two groups, based on how frequently they had anaphylaxis. They defined the IA as infrequent (I) if the person, prior to treatment, had anaphylaxis less than six times per year, and frequent (F) if the person had attacks six or more times per year. Reference [Patterson R, Harris, KE. Classification of idiopathic anaphylaxis (IA) and an algorithm for the management of IA. In: Patterson R, ed. Idiopathic anaphylaxis. Providence, RI: OceanSide Publications; 1997; 19–23].
Today that definition has been modified slightly: Having six or more attacks in one year or two or more attacks within two months is considered “frequent.” Reference [Blatman KH, Grammer LC. Idiopathic anaphylaxis. In: Castells MC, ed. Anaphylaxis and Hypersensitivity Reactions. New York, NY: Humana Pr (Springer); 2011, 223–334]. Once treatment of the condition has begun, the goal, of course, is to achieve complete control, that is zero episodes of anaphylaxis per week, month, or year.
Spectrum of symptoms
Some researchers further classify IA patients into two groups: idiopathic anaphylaxis-generalized (IA-G) versus idiopathic anaphylaxis-angioedema (IA-A).
The most recent article describing IA, written by Karen Hsu Blatman and Leslie C. Grammer [Blatman KH, Grammer LC. Idiopathic anaphylaxis. In: Castells MC, ed. Anaphylaxis and Hypersensitivity Reactions. New York, NY: Humana Pr (Springer); 2011, 223–334], explains the distinction this way:
Patients with IA-A experience urticaria [hives] or angioedema [swelling of areas of skin, mucous membranes and/or internal organs] with upper airway compromise such as laryngeal edema [swelling near the voice box], severe pharyngeal edema [swelling of the soft palate] or massive tongue swelling without other signs of systemic anaphylaxis. Patients with IA-G suffer from urticaria or angioedema with bronchospasm [narrowing of lung passageways], hypotension [decrease in blood pressure], syncope [fainting], or gastrointestinal symptoms [vomiting, diarrhea, cramping] with or without upper airway compromise. Reference [Blatman KH, Grammer LC. Idiopathic anaphylaxis. In: Castells MC, ed. Anaphylaxis and Hypersensitivity Reactions. New York, NY: Humana Pr (Springer); 2011, 229].
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IA as patients experience it
While some distinctions — like how much angioedema is involved in a particular person’s attacks or whether or not a patient’s symptoms can be controlled without daily prednisone — may be meaningful to some researchers, those are not the characteristics that are most meaningful to the average patient with idiopathic anaphylaxis (IA).
We find that not every instance of anaphylaxis begins the same way or follows the same course. Some of us have had both attacks that emphasized angioedema and attacks that were generalized. In fact, thinking that every instance of anaphylaxis will be similar to those that have preceded it is a good way to lull oneself into a dangerous feeling of complacency.
A much more salient distinction for IA patients is that which researcher Ann Dvorak [Dvorak AM. Piecemeal degranulation of basophils and mast cells is effected by vesicular transport of store secretory granule contents. In: Dvorak AM. Ultrastructure of Mast Cells and Basophils. Chem Immunol Allergy. 2005;85: 135–184.] has so painstakingly delineated: The difference between the anaphylactic degranulation (AND) and piecemeal degranulation (PMD) of mast cells and/or basophils.
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Page last updated: September 10, 2014