Idiopathic Anaphylaxis (IA) is a well-described syndrome of anaphylaxis without
any recognised external trigger. These patients present with the same symptoms as
patients with other types of anaphylactic reaction. The attacks occur with variable
frequency. Fatalities have been reported in patients who have been diagnosed with
Bacal et al first reported IA in 1978 , when they published data on 11
patients whose episode of anaphylaxis could not be explained. The series has been
expanded to include over 335 patients. Atopy was noted in 48% of the patients (the
same percentage implicated in the Spanish series of 81 patients).
The disease exists in all age groups and proves expensive if not diagnosed and treated
early. It is reported to be more common in women, with 65% of 335 idiopathic anaphylaxis
patients being women in the largest published series in the literature.
Prevalence of IA
Idiopathic anaphylaxis is one of the most common causes of anaphylaxis, accounting
for approximately one third of cases in one retrospective study 
IA is estimated to affect 30,000 patients in the USA alone.
Symptoms & signs do not differ from other forms of anaphylaxis and include:
- Hypotension & increased pulse rate
- Wheezing & stridor
- Hives, angioedema, flushing, & itching
- Nausea, vomiting, diarrhea, difficulty swallowing
- Light-headedness and loss of consciousness
In the series of Ditto et al  all of them experienced hives and angioedema,
whereas 60% experienced symptoms of upper airway obstruction. Individual patients
usually tend to have the same manifestations on repeated episodes. Progression from
hives and itching to life-threatening symptoms of wheeze, loss of consciousness,
and laryngeal edema may occur in 10 min to hours after onset.
Classification of Idiopathic Anaphylaxis (IA)
(Adopted from Roy Patterson, M.D. textbook on Idiopathic Anaphylaxis)
Urticaria or angioedema with bronchospasm (asthma)
Hypotension (reduce blood pressure), syncope
Angioedema with upper airway compromise
(Laryngeal, pharyngeal, tongue)
Frequency of episodes
More than 6 episodes per year: Frequent (F)
Less than 6 episodes per year: Infrequent (I)
Summary of Diagnoses
IA-G-F, IA-A-F, IA-G-I, IA-A-I
Variations of IA Diagnoses
Applied when patient is controlled by prednisone but has recurrent episodes of IA
below a threshold of prednisone.
Malignant IA (M-IA);
Applied when patient requires high doses of prednisone to control IA. The dose is
arbitrarily set at 30mg daily
Or 60mg on alternate days but much higher doses may be required.
Applied for a patient with possible IA where Documentation of objective findings
is unsuccessful and diagnosis is uncertain.
Applied when symptoms of IA vary from classical IA.
IA-V may subsequently be classified as IA-I, IA-G, IA-Q or USIA
Undifferentiated Somatoform IA (USIA)
Symptoms mimic IA but no objective findings are documented and the symptoms are
not responsive to the regimen of IA.
Idiopathic anaphylaxis is a diagnosis of exclusion. Only after a thorough history
and physical examination should the diagnosis be entertained. Skin prick testing,
RAST and other lab tests are usually required to rule out culprit allergens and
the numerous disease mentioned below that may masquerade as IA. A proper history
(like in all diagnosis in Allergies) is probably the most important tool in the
work-up, because it will guide subsequent testing.
Serum (mast cell) Tryptase can be very useful in differentiating anaaphylaxis from
the many conditions that can masquerade as anaphylaxis 
Differential Diagnosis of Idiopathic Anaphylaxis
I. Known causes of immediate generalized reactions
Foods is the commonest cause of anaphylaxis and occurs in
1-2% of the population. Symptoms usually start 5 30 min after ingestion,
occasionally after 1-2h, but rarely any longer. Consider an alternative diagnosis
if symptoms began many hours after ingestion or if the patient has since eaten the
suspected food without any reaction. The most common food allergens are milk, eggs,
peanuts, tree nuts, fish, shellfish, soy & wheat, which account for over 90%
of all food allergies. Foods commonly mistaken for IA include mustard and other
Drugs are another common cause of anaphylaxis.
It is important to focus on drugs / supplements / herbal preparation (bee pollen,
Echinacea) and other over-the counter formulations (especially aspirin & NSAIDs)
in the history taking.
B. Exercise Induced Anaphylaxis
C. Food-dependent, Exercise-induced Anaphylaxis
D. Non-IgE Medication-induced reactions
- Aspirin & NSAIDs
- Angiotensin-converting enzyme inhibitors (ACE-inhibitors)
- Radiographic contrast media
- Asthma masquerading as asthma
- Systemic Mastocytosis
- Hereditary Angioedema
- Munchausen's stridor / Anaphylaxis
- Undifferentiated Somatoform idiopathic anaphylaxis
- Miscellaneous Diagnosis
- Panic Attacks
- Globus Hystericus
- Histamine-rich food flushing
Exercise Induced Anaphylaxis (EIA)
This is probably one of the commonest diagnosis mistaken for idiopathic anaphylaxis.
It is due to mast cell activation, triggered by exercise. This results in generalised
itching, urticaria, angioedema, gastrointestinal pain, or diarrhea and hypotensive
collapse. This diagnosis can be difficult to make, as these patients do not always
get the reaction every time they exercise. It often occurs in accomplished athletes.
In one series of 266 patients with anaphylaxis 19 (7.1%) had EIA.
Some patients must ingest a specific food (commonly wheat) within two hours of exercise
to have their reaction. This is known as food-related, exercise-induced anaphylaxis.
Hereditary angioedema resembles idiopathic anaphylaxis, but hives
or other anaphylactic symptoms are not usually present, and the angioedema in this
disorder tends to progress slowly, often painfully, and without itching. A positive
family history is helpful in the diagnosis, but lack of it is not exclusionary.
Episodes may be provoked by dental procedures or other causes of local trauma. It
is important to make the diagnosis as life-threatening reactions may not respond
to adrenaline, but may be prevented by daily doses of androgens such as danazol
Finding decreased level of complement and C1 esterase inhibitor concentration or
function makes diagnosis of IA.
This is a rare condition in which the patients experience episodes of sudden generalized
flushing, itchy skin, hives, abdominal pain, and sometimes hypotension. Over half
of these patients will have "freckles" that urticate on stroking. Internal
involvement includes mast cells infiltrating bone marrow, causing osteoporosis or
live fibrosis. Patients may have peptic ulcer, enlarged liver, diarrhea, lethargy,
and weight loss.
Blood tests for mast cell tryptase is usually high in between attacks and increases
further after attacks. Bone scans can also help in the diagnosis of these patients.
The first Asthma attack in an adult may be difficult to differentiate
from the bronchoconstriction that may accompany an episone of IA. Lack of other
systemic anaphylactic symptoms should help to eliminate IA.
Munchausen's stridor / Anaphylaxis
Munchausens stridor presents as acute shortness of breath with stridorous
sounds over the neck. This is not organic but produced by the patient. Patients
with munchausens anaphylaxis provoke attacks of true anaphylaxis by deliberately
eating foods that they know will cause anaphylaxis. An example is a patient with
known peanut anaphylaxis who deliberately eats peanut and then rings the emergency
Undifferentiated somatoform idiopathic anaphylaxis (US-IA)
US-IA describes a variant form of IA in which there is a lack of documentation of
objective physical findings of anaphylaxis. Patients report dizziness, passing
out, throat closure, hives, and shortness of breath. Nevertheless, there is
no objective evidence during the acute episode to confirm the diagnosis of any form
Treatment of Idiopathic Anaphylaxis
Treatment depends on the severity and frequency of the attacks. Steroids seem to
be universally effective in IA. If symptoms are not controlled on 60 mg daily by
the end of 6 weeks, the diagnosis of IA should be questioned.
- Prednisone 60 mg
- Hydroxyzine 25 mg
- Go to the nearest emergency room
Programme for IA-F
- Arrange acute treatment
Prednisone 40 60 mg daily for at least 1 week or until symptoms controlled,
then decrease to alternate day and the wean by 5 10 mg each month.
If it is proving difficult to wean off steroids ketotifen should be added 
- Cetirizine 10 mg daily or Hydroxyzine 25 mg tds
- Follow-up based on response to treatment
Programme for IA-I
- Arrange acute treatment
- No chronic medication
- Follow to assess response & compliance
 Bacal E, Patterson R et al, Evaluation of severe anaphylactic reactions.
Clin Allergy 1978; 8: 295 309
 Kemp et al, Anaphylaxis, a review of 266 cases
Arch Intern Med 1995; 155: 1749 -1754
 Ditto et al, Idiopathic Anaphylaxis, a series of 335 cases
Ann Allergy Asthma Immunol 1996; 77: 285 291
 Tanus T et al, Serum Tryptase in idiopathic anaphylaxis a case report
and review of the literature. Ann Emergency Med 1994; 24: 104 – 107
 Wong S, Patterson R, et al, Efficacy of ketotifen in corticosteroid-dependent
idiopathic anaphylaxis. Ann Allergy 1991; 67: 359 – 364