Anaphylactoid reaction

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vidit Bhargava, M.B.B.S [2]

Synonyms and keywords: Pseudoallergic reaction


Anaphylactoid reaction or pseudoallergic reaction is defined as a condition presenting with symptoms similar to an allergic reaction but without detectable immunological sensitization, as found in classical allergic reactions. It is characterized by elevated IgE levels in the blood.


The pathophysiological mechanism behind anaphylactoid reactions is not clear. One of them is direct release of histamine and other mediators caused by some drugs such as opioids, intravenous narcotics, colloid volume substitutes on gelatin basis, radiographic contrast media, and others.[1][2][3][4][5] Direct activation of complement system and kinin-kallikrein system may also play a role in the development of these reactions.[6] Local anesthetics or stress can induce neuropsychogenic reflexes in the body leading to release of mediators. Involvement of mast cells and basophils has also been found to be involved in the pathogenesis of anaphylactoid reaction.[7]


Several factors/substances have been shown to be associated with anaphylactoid reactions. Listed below is a list of common precipitators of anaphylactoid reactions:[8][9]

  • Drugs (almost any drug can cause anaphylactoid reaction)
  • Foods (foodstuffs such as peanuts, fish, gelatin, etc.)
  • Additives in drugs and foods
  • Occupational substances (e.g., latex)
  • Animal venoms (scorpion, snake, etc.)
  • Aeroallergens
  • Contrast-induced
  • Contact urticariogens
  • Physical agents (cold, heat, UV irradiation)
  • Exercise
  • Idiopathic

Differentiating Anaphylactoid Reaction From Other Diseases

The presentation may mimic a number of conditions, although in most cases the signs and symptoms are sufficient to make the diagnosis of anaphylactoid reaction.

These mimickers include:

  • Drug reactions
  • Foreign body/aspiration
  • Psychogenic



The clinical features are quite similar to anaphylaxis, however the presentation is almost always milder. Most commonly the syndrome begins with involvement of the skin, usually as pruritus, flush, urticaria, or angioedema. Paresthesia, itching of pharynx and genital area, and feeling of anxiety are common symptoms. Almost all organ systems may be involved as explained below:


  • Cough and wheezing
  • Change of voice (dysphonia)
  • Dyspnea due to laryngeal obstruction
  • Cyanosis or even respiratory arrest may occur


  • Nausea and cramping
  • vomiting and diarrhea
  • Micturition and defecation


  • Tachycardia
  • Hypotension
  • Arrythmia
  • Shock
  • Cardiac arrest

The following system of grading is sometimes used to grade the severity of reactions:



Abdomen Respiratory


Grade I Pruritus, flush, urticaria, angioedema - - -
Grade II Pruritus, flush, urticaria, angioedema Nausea, cramping Rhinorrhea, hoarseness, dyspnea Tachycardia, arrhythmia
Grade III Pruritus, flush, urticaria, angioedema Vomiting, defecation, diarrhea Laryngeal edema, bronchospasm, cyanosis Shock
Grade IV Pruritus, flush, urticaria, angioedema Vomiting, defecation, diarrhea Respiratoy arrest Cardiac arrest

Adapted from Ring and Mesmer

Physical Examination

Medical Therapy

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The best way of preventing a reaction is by avoiding the allergen, but this is possible only when allergy diagnosis has been done and patient is informed about the condition and also specific agents involved. It has been found by repeated experiences that drugs are more anaphylactoid when injected as compared to oral administration, so when administering a new drug it's better to do prophetic testing (testing for allergy in the absence of a prior history). Trying first with oral administration or small injectable test doses are other strategies. In some cases, desensitizing a patient to a particular drug is also helpful (Case of Penicillin use for treating syphilis).[10] The induction of immuno-logical tolerance against the xenogeneic protein has been shown to reduce the frequency of side reactions of antilymphocyte globulin therapy.[11] Pseudo allergic reactions can be prevented by H1 and H2 anti histaminics, and includes but is not limited to pseudo allergic reactions caused by IV contrast media, analgesics etc. [1] [2] [3]


  1. 1.0 1.1 Doenicke, A.; Ennis, M.; Lorenz, W. (1985). "Histamine release in anesthesia and surgery: a systematic approach to risk in the perioperative period". Int Anesthesiol Clin. 23 (3): 41–66. PMID 2411666.
  2. 2.0 2.1 Levi, R. (1972). "Effects of exogenous and immunologically released histamine on the isolated heart: a quantitative comparison". J Pharmacol Exp Ther. 182 (2): 227–38. PMID 4114900. Unknown parameter |month= ignored (help)
  3. 3.0 3.1 Lorenz, W.; Doenicke, A.; Dittmann, I.; Hug, P.; Schwarz, B. (1977). "[Anaphylactoid reactions following administration of plasma substitutes in man. Prevention of this side-effect of haemaccel by premedication with H1- and H2-receptor antagonists (author's transl)]". Anaesthesist. 26 (12): 644–8. PMID 23706. Unknown parameter |month= ignored (help)
  4. Gehrhardt, B. (1991). "[Dental assistant. Situation of dental assistant in France]". Quintessenz J. 21 (9): 807–9. PMID 1819105. Unknown parameter |month= ignored (help)
  5. "Management of anaphylactic and anaphylactoid reactions during anesthesia - Springer". Retrieved 14 January 2014.
  6. Caine, M. (1986). "Clinical experience with alpha-adrenoceptor antagonists in benign prostatic hypertrophy". Fed Proc. 45 (11): 2604–8. PMID 2428670. Unknown parameter |month= ignored (help)
  7. Hu, J.; Hou, Y.; Zhang, Q.; Lei, H.; Wang, Y.; Wang, D. (2011). "[Real-time detection of mast cell degranulation in anaphylactoid reaction]". Zhongguo Zhong Yao Za Zhi. 36 (14): 1860–4. PMID 22016948. Unknown parameter |month= ignored (help)
  8. Davila, D. "[Therapeutic systems and drug delivery. 4. The osmotic minipump]". Lijec Vjesn. 114 (1–4): 62–7. PMID 1343031.
  9. Sheffer, AL.; Austen, KF. (1980). "Exercise-induced anaphylaxis". J Allergy Clin Immunol. 66 (2): 106–11. PMID 7400473. Unknown parameter |month= ignored (help)
  10. Sullivan, TJ. (1982). "Antigen-specific desensitization of patients allergic to penicillin". J Allergy Clin Immunol. 69 (6): 500–8. PMID 6176609. Unknown parameter |month= ignored (help)
  11. Ring, J.; Seifert, J.; Lob, G.; Coulin, K.; Angstwurm, H.; Frick, E.; Brass, B.; Mertin, J.; Backmund, H. (1974). "Intensive immunosuppression in the treatment of multiple sclerosis". Lancet. 2 (7889): 1093–6. PMID 4139403. Unknown parameter |month= ignored (help)