- Leslie C Grammer, MD
Leslie C Grammer, MD
- Professor of Medicine
- Northwestern University Feinberg School of Medicine
Anaphylaxis is often associated with an identifiable trigger, such as a food, medication, or insect sting. Idiopathic anaphylaxis 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 idiopathic anaphylaxis. Other aspects of anaphylaxis are discussed separately. (See "Anaphylaxis: Emergency treatment" and "Differential diagnosis of anaphylaxis in children and adults".)
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 and diagnosis'.)
The diagnosis of anaphylaxis is based upon a detailed description of the acute episode, including antecedent activities and events. The diagnosis of idiopathic anaphylaxis 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.
Idiopathic anaphylaxis is more common in adults, although it also occurs in children [2-4]. In several series, up to 70 percent of patients with idiopathic anaphylaxis were female and approximately 50 percent of patients were atopic [2,5,6]. Patients with idiopathic anaphylaxis may also have episodes of anaphylaxis caused by known triggers, such as food, medications, and exercise . The prevalence of idiopathic anaphylaxis in the United States is estimated at approximately 1 in 10,000 .
- Sampson HA, Muñoz-Furlong A, Campbell RL, et al. Second symposium on the definition and management of anaphylaxis: summary report--Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol 2006; 117:391.
- Ditto AM, Harris KE, Krasnick J, et al. Idiopathic anaphylaxis: a series of 335 cases. Ann Allergy Asthma Immunol 1996; 77:285.
- Ditto AM, Krasnick J, Greenberger PA, et al. Pediatric idiopathic anaphylaxis: experience with 22 patients. J Allergy Clin Immunol 1997; 100:320.
- Greenberger PA. Idiopathic anaphylaxis. Immunol Allergy Clin North Am 2007; 27:273.
- Tejedor Alonso MA, Sastre DJ, Sanchez-Hernandez JJ, et al. Idiopathic anaphylaxis: a descriptive study of 81 patients in Spain. Ann Allergy Asthma Immunol 2002; 88:313.
- Webb LM, Lieberman P. Anaphylaxis: a review of 601 cases. Ann Allergy Asthma Immunol 2006; 97:39.
- Patterson R, Hogan MB, Yarnold PR, Harris KE. Idiopathic anaphylaxis. An attempt to estimate the incidence in the United States. Arch Intern Med 1995; 155:869.
- Shanmugam G, Schwartz LB, Khan DA. Prolonged elevation of serum tryptase in idiopathic anaphylaxis. J Allergy Clin Immunol 2006; 117:950.
- Grammer LC, Shaughnessy MA, Harris KE, Goolsby CL. Lymphocyte subsets and activation markers in patients with acute episodes of idiopathic anaphylaxis. Ann Allergy Asthma Immunol 2000; 85:368.
- Howell DL, Jacobs C, Metz G, et al. Molecular profiling distinguishes patients with active idiopathic anaphylaxis from normal volunteers and reveals novel aspects of disease biology. J Allergy Clin Immunol 2009; 123:S150 (Abstract).
- Moneret-Vautrin DA, Morisset M, Lemerdy P, et al. Food allergy and IgE sensitization caused by spices: CICBAA data (based on 589 cases of food allergy). Allerg Immunol (Paris) 2002; 34:135.
- Greenberger PA, Flais MJ. Bee pollen-induced anaphylactic reaction in an unknowingly sensitized subject. Ann Allergy Asthma Immunol 2001; 86:239.
- Sánchez-Borges M, Suárez-Chacón R, Capriles-Hulett A, Caballero-Fonseca F. An update on oral anaphylaxis from mite ingestion. Ann Allergy Asthma Immunol 2005; 94:216.
- Furlong TJ, DeSimone J, Sicherer SH. Peanut and tree nut allergic reactions in restaurants and other food establishments. J Allergy Clin Immunol 2001; 108:867.
- Heaps A, Carter S, Selwood C, et al. The utility of the ISAC allergen array in the investigation of idiopathic anaphylaxis. Clin Exp Immunol 2014; 177:483.
- Commins SP, Platts-Mills TA. Anaphylaxis syndromes related to a new mammalian cross-reactive carbohydrate determinant. J Allergy Clin Immunol 2009; 124:652.
- DiCello MC, Myc A, Baker JR Jr, Baldwin JL. Anaphylaxis after ingestion of carmine colored foods: two case reports and a review of the literature. Allergy Asthma Proc 1999; 20:377.
- Khalili B, Bardana EJ Jr, Yunginger JW. Psyllium-associated anaphylaxis and death: a case report and review of the literature. Ann Allergy Asthma Immunol 2003; 91:579.
- Becker K, Southwick K, Reardon J, et al. Histamine poisoning associated with eating tuna burgers. JAMA 2001; 285:1327.
- Sondhi D, Lippmann M, Murali G. Airway compromise due to angiotensin-converting enzyme inhibitor-induced angioedema: clinical experience at a large community teaching hospital. Chest 2004; 126:400.
- Castells MC, Horan RF, Sheffer AL. Exercise-induced Anaphylaxis. Curr Allergy Asthma Rep 2003; 3:15.
- Beaudouin E, Renaudin JM, Morisset M, et al. Food-dependent exercise-induced anaphylaxis--update and current data. Eur Ann Allergy Clin Immunol 2006; 38:45.
- Gelincik A, Ozşeker F, Büyüköztürk S, et al. Recurrent anaphylaxis due to non-ruptured hepatic hydatid cysts. Int Arch Allergy Immunol 2007; 143:296.
- Moffitt JE, Venarske D, Goddard J, et al. Allergic reactions to Triatoma bites. Ann Allergy Asthma Immunol 2003; 91:122.
- Stoevesandt J, Grundmeier N, Trautmann A. Gastroesophageal hymenoptera stings add to causes of idiopathic anaphylaxis. Ann Allergy Asthma Immunol 2012; 108:125.
- Müller UR. Elevated baseline serum tryptase, mastocytosis and anaphylaxis. Clin Exp Allergy 2009; 39:620.
- Brockow K, Jofer C, Behrendt H, Ring J. Anaphylaxis in patients with mastocytosis: a study on history, clinical features and risk factors in 120 patients. Allergy 2008; 63:226.
- Akin C, Scott LM, Kocabas CN, et al. Demonstration of an aberrant mast-cell population with clonal markers in a subset of patients with "idiopathic" anaphylaxis. Blood 2007; 110:2331.
- Gülen T, Hägglund H, Sander B, et al. The presence of mast cell clonality in patients with unexplained anaphylaxis. Clin Exp Allergy 2014; 44:1179.
- Sampson HA, Mendelson L, Rosen JP. Fatal and near-fatal anaphylactic reactions to food in children and adolescents. N Engl J Med 1992; 327:380.
- Bock SA, Muñoz-Furlong A, Sampson HA. Further fatalities caused by anaphylactic reactions to food, 2001-2006. J Allergy Clin Immunol 2007; 119:1016.
- Pumphrey RS, Gowland MH. Further fatal allergic reactions to food in the United Kingdom, 1999-2006. J Allergy Clin Immunol 2007; 119:1018.
- Greenberger PA, Rotskoff BD, Lifschultz B. Fatal anaphylaxis: postmortem findings and associated comorbid diseases. Ann Allergy Asthma Immunol 2007; 98:252.
- Boxer MB, Greenberger PA, Patterson R. The impact of prednisone in life-threatening idiopathic anaphylaxis: reduction in acute episodes and medical costs. Ann Allergy 1989; 62:201.
- Khan DA, Yocum MW. Clinical course of idiopathic anaphylaxis. Ann Allergy 1994; 73:370.
- Patterson R, Fitzsimons EJ, Choy AC, Harris KE. Malignant and corticosteroid-dependent idiopathic anaphylaxis: successful responses to ketotifen. Ann Allergy Asthma Immunol 1997; 79:138.
- Warrier P, Casale TB. Omalizumab in idiopathic anaphylaxis. Ann Allergy Asthma Immunol 2009; 102:257.
- Demirtürk M, Gelincik A, Colakoğlu B, et al. Promising option in the prevention of idiopathic anaphylaxis: omalizumab. J Dermatol 2012; 39:552.
- Borzutzky A, Morales PS, Mezzano V, et al. Induction of remission of idiopathic anaphylaxis with rituximab. J Allergy Clin Immunol 2014; 134:981.
- Mast cell activation
- Lymphocyte and basophil activation
- CLINICAL MANIFESTATIONS
- DIAGNOSIS AND REFERRAL
- Evaluate for possible triggers
- Exclude other disorders
- - Exclusion of a monoclonal mast cell population
- DIFFERENTIAL DIAGNOSIS
- Mast cell activation disorders
- Systemic mastocytosis
- Acute management
- Long-term management
- - Combination therapy with glucocorticoids and antihistamines
- - Other treatments
- - Glucocorticoid-dependent idiopathic anaphylaxis
- Management of refractory symptoms
- - Omalizumab
- - Rituximab
- Medications to be avoided
- SUMMARY AND RECOMMENDATIONS