Antivenom Reactions

Table: Classification of antivenom reactions based on the World Health Organisation (WHO) classification and the NIAID-FAAN consensus criteria.1-4
Reaction Type
Clinical Features
Early: Pyrogenic reactions
1 hour after antivenom
Fever, rigors and chills, headache, tachycardia and rarely hypotension.
Microbial contaminants in the antivenom such as bacterial endotoxins.
Early: Systemic hypersensitivity reactions (SHR)/ Anaphylaxis1
1 to 4 hours after antivenom
  1. Skin only SHR: Generalised itch, erythema, urticaria, or angioedema without other organ involvement
  2. Anaphylaxis: Sentinel features from 2 or more organ systems: skin (as above); cardiovascular (hypotension, SBP<90mmHg); respiratory (stridor, throat tightness, dyspnea, wheeze, hypoxemia (cyanosis or SpO2 <92%); gastrointestinal (abdominal pain, vomiting)2
  3. Severe anaphylaxis: if there is hypotension or hypoxemia.
These reactions are likely triggered by non allergen-specific (non-IgE) activation of mast cells. Mast cell activation may be influenced by antivenom quality and a priming effect from the immune response to the venom. The complement pathway does not appear to play a major role.
Serum Sickness (Late)
5 to 20 days after antivenom administration
Fever, myalgia, arthralgia, urticaria, erythematous rash, headache, lymphadenopathy and gastrointestinal symptoms
Due to the formation of immune-complexes between human IgG and antivenom proteins
1WHO includes IgE mediated reactions as early antivenom reactions but there is little evidence to support this type of reaction; 2 In some cases anaphylaxis may only manifest as hypotension of respiratory compromise alone and meets the definition of anaphylaxis if occurs within hours of antivenom administration4. SBP – systolic blood pressure; SHR – systemic hypersensitivity reaction; SpO2 – oxygen saturation;

1. Leon G, Herrera M, Segura A, Villalta M, Vargas M, Gutierrez JM. Pathogenic mechanisms underlying adverse reactions induced by intravenous administration of snake antivenoms. Toxicon. 2013.
2. Sampson HA, Munoz-Furlong A, Campbell RL, Adkinson NF, Jr., Bock SA, Branum A, Brown SG, Camargo CA, Jr., Cydulka R, Galli SJ, Gidudu J, Gruchalla RS, Harlor AD, Jr., Hepner DL, Lewis LM, Lieberman PL, Metcalfe DD, O'Connor R, Muraro A, Rudman A, Schmitt C, Scherrer D, Simons FE, Thomas S, Wood JP, Decker WW. 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. Journal of Allergy and Clinical Immunology. 2006; 117(2): 391-7.
3. Brown SG. Clinical features and severity grading of anaphylaxis. Journal of Allergy and Clinical Immunology. 2004; 114(2): 371-6.
4. Stone SF, Isbister GK, Shahmy S, Mohamed F, Abeysinghe C, Karunathilake H, Ariaratnam A, Jacoby-Alner TE, Cotterell CL, Brown SG. Immune response to snake envenoming and treatment with antivenom; complement activation, cytokine production and mast cell degranulation. PLoS Negl Trop Dis. 2013; 7(7): e2326.