INTRODUCTION — Anaphylaxis is often associated with an identifiable trigger, such as a food, medication, or insect sting. Idiopathic anaphylaxis (IA) is diagnosed when no specific trigger can be identified after an appropriate evaluation and when conditions, such as systemic mastocytosis, have been ruled out. (See "Anaphylaxis: Confirming the diagnosis and determining the cause(s)".)
This topic will review the pathogenesis, diagnosis, treatment, and prognosis of IA. Other aspects of anaphylaxis are discussed separately. (See "Anaphylaxis: Emergency treatment" and "Differential diagnosis of anaphylaxis in adults and children".)
DEFINITION — Anaphylaxis is defined as a serious allergic reaction that is rapid in onset and may cause death . Symptoms of anaphylaxis involve multiple body organ systems (table 1). (See "Anaphylaxis: Acute diagnosis", section on 'Definition'.)
The diagnosis of IA is made when a patient has signs and symptoms consistent with anaphylaxis, but no specific trigger can be identified, and other diseases have been ruled out .
EPIDEMIOLOGY — IA is more common in adults, although it also occurs in children [3-5]. In several series, up to 70 percent of patients with IA were female, and approximately 50 percent of patients were atopic (defined in the study as having a history of rhinitis or asthma and positive aeroallergen skin test results) [3,6,7]. Patients with IA may also have episodes of anaphylaxis caused by known triggers, such as food, medications, and exercise, but these do not account for all of the anaphylaxis episodes . The prevalence of IA in the United States was estimated at approximately 1 in 10,000 in the mid-1990s .
PATHOGENESIS — IA is associated with widespread mast cell activation, as is anaphylaxis from a known trigger. Mast cells do not appear to be hyperresponsive, although data are limited. Patients with IA also have increased activation of lymphocytes, although the significance of this is not clear . A more detailed discussion of the pathogenesis of anaphylaxis is found separately. (See "Anaphylaxis: Acute diagnosis", section on 'Causes and mechanisms'.)
Mast cell activation — Patients with IA may have transient elevations in levels of mast cell mediators, including plasma and urinary histamine  and serum or plasma total tryptase [5,10], immediately following an episode of anaphylaxis. Between episodes, mediator levels should return to within the normal range. Other disorders with similar elevations in mast cell mediators are discussed below. (See 'Differential diagnosis' below.)
There are no data to support the hypothesis that mast cells in patients with IA are hyperresponsive. In a study of 56 patients with IA, mast cell precursors were collected from peripheral blood, cultured in vitro, and tested for immunoglobulin E (IgE) mediated release of beta-hexosaminidase . Mast cells from patients with IA and healthy controls responded similarly, indicating that the patients' mast cells were not hyperresponsive through the classic IgE-mediated mechanism. However, mast cells have multiple other mechanisms for activation, and other mechanisms have not been specifically studied. The investigators did note that peripheral blood from patients with IA yielded higher mast cell numbers in culture compared with healthy controls for unknown reasons.
Lymphocyte and basophil activation — Patients with IA have an increased percentage of activated T cells in their peripheral blood during acute episodes compared with during remission. In addition, they have more activated B cells, both during acute episodes and in remission, than in the general population or in patients with chronic idiopathic urticaria . In microarray analyses, cells from patients with IA differentially express genes that strongly correlate with the level of CD203c, a marker of basophil activation .
Increased gastrointestinal permeability — Episodes of IA are often accompanied by gastrointestinal manifestations. Surrogate markers of gastrointestinal permeability, soluble CD14 (sCD14) and intestinal fatty acid binding protein (I-FABP), were reported to be elevated in patients with IA as compared with health controls .
CLINICAL MANIFESTATIONS — The signs and symptoms of IA are the same as in anaphylaxis resulting from known triggers (table 1). The severity spectrum is also similar. Fatal and near-fatal cases of IA have been reported . (See "Anaphylaxis: Acute diagnosis", section on 'Definition'.)
EVALUATION AND REFERRAL — All patients suspected of having IA should be referred to an allergy specialist because all possible triggers of anaphylaxis and disorders that mimic anaphylaxis should be considered and ruled out before making the diagnosis. IA is established only after performing a comprehensive history, physical examination, review of medical records, and appropriate laboratory tests. Depending on the allergen that is under consideration, testing may involve skin testing, measurement of allergen-specific serum IgE, component-resolved diagnostics, or challenge procedures. (See "Differential diagnosis of anaphylaxis in adults and children".)
Patients with possible IA should be supplied with at least two epinephrine autoinjectors and instructed on how and when to use them if symptoms recur, even before they are evaluated by an allergy specialist. (See "Prescribing epinephrine for anaphylaxis self-treatment", section on 'Dosing' and "Prescribing epinephrine for anaphylaxis self-treatment", section on 'Available devices'.)
Evaluate for possible triggers — On occasion, patients who were thought to have IA are found to have unusual triggers of anaphylaxis that were initially overlooked. We review all ingestions (foods, medications, beverages), activities, and changes to baseline health in the hours before each episode that the patient can recall.
Symptoms in association with eating — Food-associated triggers should be considered in patients whose reactions occur in close association with eating. Considerations include:
●Undeclared or mislabeled food allergens, or "hidden" food allergens, such as peanut in egg rolls, tree nuts in salad dressing, or soy in canned tuna [14,15]. Patients with food allergy occasionally react to non-food items as well. (See "Management of food allergy: Avoidance", section on 'Food allergens in nonfood items' and "Seafood allergies: Fish and shellfish", section on 'Allergy to additives in canned fish'.)
●Spices, especially members of the Apiaceae (Umbelliferae) family, which include caraway, coriander, and fennel . Other spices that have been implicated in systemic reactions include garlic, onion, mustard, saffron, parsley, and cumin . (See "Pathogenesis of oral allergy syndrome (pollen-food allergy syndrome)", section on 'Celery-mugwort-birch-spice syndrome'.)
●Allergens that can cause reactions in some patients with other food allergies, such as pectin or pink peppercorns in some patients with cashew or pistachio allergies, or lupine flour in some patients with peanut allergies (more common in European populations) .
●Food causing anaphylaxis in the setting of exercise or when taken in temporal proximity to nonsteroidal antiinflammatory drugs (NSAIDs) or alcohol but not with ingestion of the food alone. The best-described example of anaphylaxis that only occurs when other cofactors are present is wheat-dependent exercise-induced anaphylaxis, which is usually caused by sensitization to the allergen omega-5 gliadin [17,18]. Some experts have suggested that sensitization to omega-5 gliadin be assessed in all cases of apparent IA . (See "Exercise-induced anaphylaxis: Clinical manifestations, epidemiology, pathogenesis, and diagnosis".)
●Foods contaminated with aeroallergens (eg, "bee pollen"), which often contains ragweed pollen [22,23], flour contaminated with mite allergens (variably called "pancake" syndrome or oral mite anaphylaxis) [24,25], or grain products contaminated with insects .
●Food additives, such as carmine powder  and psyllium . (See "Allergic and asthmatic reactions to food additives", section on 'Anaphylaxis'.)
●Allergic reactions to Anasakis simplex, a fish nematode, can mimic fish allergy, but symptoms are delayed 2 to 24 hours after the ingestion of fish and testing for specific IgE to fish is negative. This is almost exclusively reported in Spain. (See "Seafood allergies: Fish and shellfish", section on 'Anisakis'.)
Medications — Medication triggers that should be considered before labeling a patient with IA include:
●Ingestion of over-the-counter medications containing NSAIDs that the consumer did not recognize (eg, Alka-Seltzer contains aspirin).
●Ingestion of angiotensin-converting enzyme (ACE) inhibitors or combination angiotensin receptor blocker and a neprilysin inhibitor (ARNI) that can cause angioedema [29,30]. (See "ACE inhibitor-induced angioedema", section on 'Future use of related drugs'.)
Other — Other potential triggers include:
●Exercise (alone and/or in combination with prior ingestion of food or medication) [31,32] (see "Exercise-induced anaphylaxis: Clinical manifestations, epidemiology, pathogenesis, and diagnosis")
●Latex exposure  (see "Latex allergy: Epidemiology, clinical manifestations, and diagnosis")
●Undetected insect bites and stings from Hymenoptera, pigeon ticks, or Triatoma [33-35] (see "Reactions to bites from kissing bugs (primarily genus Triatoma)", section on 'Allergic reactions')
Serum tryptase — An anaphylaxis episode can be confirmed, in some cases, by acute measurement of serum tryptase or other mast cell mediators in the hours after an episode of symptoms (table 2). The minimal elevation in serum total tryptase level that is considered to be indicative of clinically significant mast cell activation is ≥(2 + 1.2 x baseline tryptase levels) . However, a normal serum tryptase does not exclude the diagnosis of anaphylaxis. (See "Laboratory tests to support the clinical diagnosis of anaphylaxis", section on 'Elevations in anaphylaxis'.)
A total tryptase level that is persistently elevated at baseline, rather than only following symptoms, strongly suggests either hereditary alpha tryptasemia or systemic mastocytosis, and further evaluation should be pursued. (See "Laboratory tests to support the clinical diagnosis of anaphylaxis", section on 'Hereditary alpha tryptasemia' and "Systemic mastocytosis: Determining the subtype of disease".)
There are also disorders that can cause persistently elevated tryptase levels in the absence of allergic or anaphylactic symptoms, such as chronic kidney disease and certain myelodysplastic syndromes. These disorders are discussed in more detail separately. (See "Laboratory tests to support the clinical diagnosis of anaphylaxis", section on 'Other conditions'.)
Further testing should focus on ruling out specific triggers of anaphylaxis or conditions with similar symptoms. Testing should be limited to the evaluation of specific triggers or disorders that are suspected based on the patient's history and examination and measurement of a baseline serum total tryptase level [37,38]. (See "Anaphylaxis: Emergency treatment" and "Differential diagnosis of anaphylaxis in adults and children" and "Mastocytosis (cutaneous and systemic) in adults: Epidemiology, pathogenesis, clinical manifestations, and diagnosis" and "An overview of angioedema: Clinical features, diagnosis, and management" and "Overview of shellfish, pufferfish, and other marine toxin poisoning" and "Approach to flushing in adults".)
Exclusion of a monoclonal mast cell population — For patients with difficult-to-control disease or symptoms that change over time or are especially severe, we test for monoclonal mast cell disorders .
●In one study of 30 adults with unexplained anaphylaxis, 47 percent had a clonal mast cell disorder .
●In a subsequent study of 56 patients initially diagnosed with IA, 14 percent were found to have a clonal mast cell disorder .
To exclude a clonal mast cell disorder, serum tryptase should be measured at baseline and after an episode of symptoms, if not already performed. The issue of how aggressively to search for a clonal mast cell disorder with additional testing in patients with IA is influenced by the patient's degree of disability, and practice differs among experts. The diagnosis of monoclonal mast cell disorders, as well as a discussion of the use of peripheral blood allele-specific quantitative polymerase chain reaction (ASqPCR) for KIT D816V mutations compared with bone marrow biopsy is found separately. (See "Mastocytosis (cutaneous and systemic) in adults: Epidemiology, pathogenesis, clinical manifestations, and diagnosis", section on 'KIT mutational analysis'.)
DIAGNOSIS — IA is a diagnosis of exclusion, by definition. Patients must meet clinical criteria for the diagnosis of anaphylaxis (table 3) and have no identifiable cause. These are the minimum requirements for diagnosis.
Classification — IA is classified into subgroups based on frequency of episodes and clinical manifestations .
Frequent versus infrequent — Frequent IA has been defined as at least two episodes in the preceding two months or at least six episodes in the preceding year . Patients with IA who do not meet one of these criteria are categorized as having infrequent IA.
Generalized versus angioedema — IA-generalized is characterized by prominent urticaria with or without angioedema plus other severe systemic symptoms (cardiovascular, respiratory symptoms, and/or gastrointestinal).
IA-angioedema is the term given to occasional patients whose episodes are characterized by marked upper airway obstruction due to severe angioedema of the tongue, pharynx, and/or larynx. In the author's experience, this type of IA may involve upper airway angioedema plus gastrointestinal pain and hypotension (possibly due to bowel angioedema and third-spacing of fluid).
If the patient's angioedema cannot be readily visualized, particularly if the throat is involved, it is important that it be objectively confirmed at some point as several other disorders can cause a subjective sensation of throat tightness or swelling. Common etiologies of subjective throat tightness include vocal cord dysfunction and laryngopharyngeal reflux. An endoscopic exam (by an otolaryngologist or other appropriately trained clinician) during an episode of symptoms is critical to distinguishing these disorders from actual angioedema and should be pursued whenever feasible.
DIFFERENTIAL DIAGNOSIS — The differential diagnosis of IA includes disorders of angioedema, nonanaphylactic disorders, mast cell disorders, and somatoform symptom disorder.
Testing for angioedema disorders — In patients whose symptoms are predominantly angioedema without urticaria, disorders causing bradykinin-induced angioedema, such as hereditary angioedema (due to C1 inhibitor deficiency or other defects) and angiotensin-converting enzyme (ACE) inhibitor-induced angioedema, should be considered in the differential diagnosis. A serum level of C4 is a reasonable screen for C1 inhibitor deficiency (inherited or acquired), although there are several forms of episodic angioedema in which complement studies are normal. (See "Hereditary angioedema (due to C1 inhibitor deficiency): Pathogenesis and diagnosis" and "Hereditary angioedema with normal C1 inhibitor".)
Nonanaphylactic disorders — Other disorders should be considered in the differential diagnosis include disorders that cause flushing, severe acute asthma exacerbations, and somatoform and Munchausen disorders. The differential diagnosis of anaphylaxis is discussed extensively in another topic. (See "Differential diagnosis of anaphylaxis in adults and children".)
Mast cell activation disorders — Idiopathic mast cell activation syndrome (IMCAS) is similar to IA, but signs and symptoms do not meet criteria for anaphylaxis, usually because patients do not become frankly hypotensive. To make the diagnosis of IMCAS, there must be transient elevations in mast cell mediators, which return to normal in between episodes. The definition of IMCAS and IA are evolving, and some experts suggest that IA is better classified as a subset of IMCAS . Another subset of patients has a monoclonal population of mast cells and can be classified as monoclonal mast cell activation syndrome (MMAS) (table 4). Bone marrow biopsy is sometimes required to conclusively exclude a mast cell disorder . (See "Mast cell disorders: An overview".)
Systemic mastocytosis — In contrast to IA and mast cell activation disorders, patients with systemic mastocytosis have elevations of serum total tryptase levels that are persistent and are detectable even after resolution of an acute episode [37-39]. Systemic mastocytosis is characterized by a pathologic increase in mast cell numbers in the tissues. (See "Mastocytosis (cutaneous and systemic) in adults: Epidemiology, pathogenesis, clinical manifestations, and diagnosis".)
Somatoform symptom disorder — Some patients describe subjective symptoms that are consistent with IA but have not had objective signs or symptoms documented, do not have organic disease that can be verified, and do not respond to treatment for IA. For example, patients may report a sensation of throat tightness (ie, globus sensation) and be concerned that their throat may close or that they cannot breathe. It is essential that these patients be evaluated by an otolaryngologist or other provider in the urgent care setting while the symptom is present if episodes become recurrent. Such patients can be very challenging to manage, utilize the emergency department repeatedly, and may meet criteria for somatoform symptom disorder or panic disorder. (See "Somatic symptom disorder: Assessment and diagnosis" and "Panic disorder in adults: Epidemiology, clinical manifestations, and diagnosis".)
TREATMENT OF ACUTE EPISODES — Once the diagnosis of IA is entertained, the patient needs to be equipped to self-administer initial treatment for any future episodes.
Initial management — Epinephrine is the drug of choice for acute treatment of anaphylaxis, and patients should be counseled that it is the only treatment that prevents or reverses laryngeal edema, severe bronchospasm, and cardiovascular collapse. Failure to administer epinephrine early in the course of treatment has been repeatedly implicated in anaphylaxis fatalities [43-46]. The acute treatment of anaphylaxis is discussed separately. (See "Anaphylaxis: Emergency treatment", section on 'Immediate management'.)
Epinephrine should be administered as soon as possible when an episode of significant symptoms begins, and the patient should proceed to the nearest emergency department in the safest manner possible (ie, by ambulance if necessary). Patients may also be instructed to take additional medications for specific residual symptoms, although these usually respond to epinephrine as well:
●An H1 antihistamine (either first or second generation, such as cetirizine, 10 mg) for pruritus or urticaria
●Albuterol by metered-dose inhaler, 2 puffs inhaled, for bronchospasm
●Prednisone 40 or 60 mg (adult dose), for those patients who already have the diagnosis of IA but are not taking prednisone at the time, or are taking a lower dose
Patients with IA should have access to at least two epinephrine autoinjectors and be educated about how and when to self-administer the drug. The different autoinjectors and prefilled syringes available and weight-based dosing are discussed separately. (See "Prescribing epinephrine for anaphylaxis self-treatment".)
Anaphylaxis action plan — Patients and caregivers should be given individualized instructions about how to proceed if symptoms recur. One approach is to provide the patient with a written anaphylaxis action plan. An action plan that can be personalized is available online through the American Academy of Allergy, Asthma, and Immunology :
●English – Anaphylaxis Emergency Action Plan
●Spanish – Anaphylaxis Emergency Action Plan
Ongoing review of clinical details — After each episode of anaphylaxis, it is important to review the details of the episode and events leading up to it. A new clue about a possible etiology may be uncovered, and the clinician can assess whether epinephrine was administered appropriately and, if not, explore the reasons for any aspects of care that were not optimal. Teaching points for patients at risk for anaphylaxis are reviewed separately. (See "Long-term management of patients with anaphylaxis", section on 'Ongoing education for patients'.)
LONG-TERM MANAGEMENT — Long-term pharmacologic management depends on the frequency of episodes [5,48]. Recommendations for the management of patients with IA are based on data from observational studies, case reports/series, and clinical experience.
Algorithmic approach — Our approach to the long-term management of idiopathic anaphylaxis is depicted in an algorithm (algorithm 1).
Patients with infrequent recurrences — Patients with infrequent IA (ie, fewer than two episodes in the preceding two months or six episodes in the preceding year) do not usually require preventative therapy. However, it is important to follow up with the patient after each episode and monitor the frequency of attacks. (See 'Ongoing review of clinical details' above.)
Patients with frequent recurrences — Prophylactic therapy is indicated for patients with frequent IA (ie, at least two episodes in the preceding two months or at least six episodes in the preceding year). It can be started at the time of an acute episode or as soon as the diagnosis has been reached.
With each significant episode of symptoms, it is important to continue to try to find a common exposure or other explanation for the symptoms. If a possible culprit occurs to the patient or clinician, targeted testing can be performed.
Prednisone plus H1 antihistamines — The most common approach is a combination of an oral glucocorticoid and an H1 antihistamine, usually for a minimum of two months.
•For adults, 40 to 60 mg orally per day (depending on the patient's size and the severity of symptoms)
•For children, 1 mg/kg orally (up to a maximum of 60 mg) per day
Once symptoms have stopped, the same dose of 40 to 60 mg is then given on alternate days for one to two more weeks. In the author's experience, the dose can often be tapered quickly at first (eg, from 60 mg every other day to 40 mg every other day) and then more slowly once the dose has been reduced to 20 or 15 mg every other day. The dose is then further reduced by 5 mg (still on alternate days) every one to two weeks, assuming there are no breakthrough symptoms . Alternate-day therapy is sufficient in most cases to avoid patients becoming Cushingoid.
Breakthrough symptoms during the steroid taper are generally milder than the initial episode and may consist of some urticaria with angioedema or other limited symptoms. In response to these, the glucocorticoid dose is increased to the previous dose that appeared to control symptoms, and that dose is continued until the symptoms resolve. The tapering process is then resumed.
If this subsequent taper is not tolerated, adjunctive medications (ie, ketotifen, cromolyn, or leukotriene-modifying drugs) can be added, or the patient can be treated with omalizumab if symptoms are significant and omalizumab is available. (See 'Patients with persistent episodes' below.)
●H1 antihistamines – H1 antihistamines are usually administered concomitantly with prednisone. Although only first-generation antihistamines have been studied for the treatment of IA, second-generation antihistamines, such as cetirizine given at twice standard dosing (ie, 10 mg orally twice daily), are preferred as first-line treatment due to their more favorable benefit-to-risk ratio. In the author's experience, even higher doses of antihistamines, like those used in chronic urticaria, do not provide additional benefit. The H1 antihistamine is often continued after completion of the course of prednisone, especially in patients who are older, have a history of more severe episodes, and have comorbidities. (See "Pharmacotherapy of allergic rhinitis", section on 'Adverse effects and safety'.)
Efficacy — The efficacy of the combination of glucocorticoids and H1 antihistamines can be estimated from case reports and observational series [3,4,48]. All available studies included both glucocorticoids and antihistamines.
●In the largest published series, 132 of 335 patients were available at the time of data collection . Eighty-seven were in remission, and the duration of remission ranged from 1 to 14 years. Prednisone for frequent episodes had been administered to 56 patients, and approximately 20 percent had recurrent symptoms as the prednisone was tapered. Among those who eventually weaned off it, the duration of alternate-day therapy was 3 months to 13 years.
●In a series of 22 pediatric patients, all were treated with prednisone, hydroxyzine, and some also received an oral sympathomimetic (oral albuterol) . Nineteen of 22 patients had fewer attacks after the initiation of treatment. After completing this therapy, approximately 50 percent of patients went into remission (ie, no episodes and no prednisone treatment in the past year). Some of these patients remained on an H1 antihistamine.
Patients with persistent episodes — The term "malignant IA" is used to identify those patients with the most severe form of IA that is resistant to standard therapy. One investigator has classified patients as having malignant IA if the prednisone dose required to control symptoms is ≥20 mg daily or 60 mg on alternate days . Published data on this subset of patients are scant. Case reports describe the use of several other medications that may allow patients to eventually wean off prednisone. One or more of these adjunctive medications can be added when patients appear to be responding to the combination of prednisone and an H1 antihistamine but are having trouble reducing the dose of prednisone without experiencing recurrent symptoms (algorithm 1).
Omalizumab — Omalizumab, a monoclonal antibody directed against IgE, has been reported to be effective in several case reports [50-55]. Variable doses have been used. The dosing and adverse effects of omalizumab are reviewed separately. (See "Anti-IgE therapy".)
●Ketotifen is an H1 antihistamine/mast cell stabilizer that can cause significant sedation. The oral formulation of ketotifen is not approved for use in the United States or many other countries. The usual initial dose is 2 mg orally two or three times per day [3,56].
●Oral cromolyn (dose of 200 mg up to four times daily in patients 13 years or older or 100 mg up to four times daily in patients ages 2 to 12 years) can be helpful for patients with prominent gastrointestinal symptoms. It is generally mixed into a glass of water and taken one hour before meals and then before bed. We typically begin with one or two doses daily and increase gradually to three to four times daily . Some patients do not tolerate this medication because of bloating, cramping, and diarrhea.
●Rituximab was reported to be helpful in a single case report of a patient with severe IA and weekly episodes, refractory to antihistamines, leukotriene antagonists, systemic glucocorticoids, a three-food restricted diet (to exclude occult food allergy), and an eight-month trial of omalizumab . Rituximab (dose of 1000 mg intravenously) was administered, and, after a second dose (two weeks after the first), the episodes stopped and did not recur until her B cell counts recovered nine months later. She was then retreated at six-month intervals.
Medications to be avoided — Beta blockers should be avoided, if possible, in patients with IA since they may interfere with the response to epinephrine . Other general measures in the long-term management of patients with anaphylaxis are reviewed separately. (See "Long-term management of patients with anaphylaxis".)
PROGNOSIS — Most patients experience their most severe symptoms during the first attack, after which they recognize early symptoms and are better able to initiate treatment promptly . The long-term natural history of IA is favorable, even without preventative therapy. Patients who initially present with infrequent episodes rarely progress to frequent episodes [3,58].
With long-term follow-up, over 90 percent of patients with frequent IA and 65 percent with infrequent IA are considered to be in remission (ie, no episodes and no requirement for prednisone therapy in the past year) after a few years . Recurrence after remission is rare .
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Anaphylaxis".)
SUMMARY AND RECOMMENDATIONS
●Definition – The diagnosis of idiopathic anaphylaxis (IA) is made when a patient has signs and symptoms consistent with anaphylaxis (table 1), but no specific trigger can be identified after a thorough evaluation, and other diseases have been ruled out. (See 'Definition' above.)
●Epidemiology – IA is more common in females than males. It is uncommon in children. (See 'Epidemiology' above.)
●Clinical manifestations – The signs and symptoms of IA are the same as those in anaphylaxis resulting from known triggers, and the diagnostic criteria are identical (table 3). Fatal and near-fatal cases of IA have been reported. (See 'Clinical manifestations' above.)
●Treatment of acute episodes – Acute treatment of IA is identical to acute treatment of anaphylaxis of any etiology. All patients with IA, including those with infrequent episodes, should be equipped with an epinephrine autoinjector and an anaphylaxis emergency action plan to manage initial treatment of acute anaphylaxis. (See 'Treatment of acute episodes' above.)
●Classification based on frequency of episodes – IA is categorized as frequent (at least two episodes in the past two months or six or more episodes in the past year) or infrequent (one or no episodes in the past two months or less than six episodes in the past year). (See 'Classification' above.)
●Preventative therapies – For patients with frequent IA, we suggest prophylactic treatment with the combination of an oral glucocorticoid, such as prednisone, and a low-sedating H1 antihistamine, such as cetirizine (Grade 2C). We start with an initial dose of prednisone (in adults) of 40 to 60 mg daily until symptoms have resolved, then change to alternate-day therapy and gradually begin to lower the dose over approximately six to eight weeks. Our approach is summarized in an algorithm (algorithm 1). (See 'Long-term management' above.)
●Options for persistent attacks – For patients who are unable to discontinue oral glucocorticoids without recurrence of symptoms, several other medications can be tried, including omalizumab, ketotifen, oral cromolyn, leukotriene modifiers, and rituximab. (See 'Patients with persistent episodes' above.)
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟