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Hypersensitivity Reactions

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Background

All biological agents, particularly monoclonal antibodies, or chemotherapies derived from plant- or metal-based materials can cause hypersensitivity reactions (HSRs) or allergic-type reactions. HSRs occur when the immune system identifies an infused or oral agent as an antigen and initiates a complex reaction involving production of antibodies, release of histamine, and sensitization of T lymphocytes and macrophages.

  • Anaphylactic reactions are caused by the sudden release of mast cell and basophil mediators. The fixation of immunoglobulin E (IgE) to human mast cells and basophils, a process termed sensitization, prepares these cells for antigen-specific activation with subsequent exposure to the antigen. When mediated by IgE, anaphylaxis occurs.1
  • If the reaction is not IgE mediated, it is termed anaphylactoid, occurs because of partial hypersensitivity, and is less life threatening.1
  • The clinical features of HSR can be categorized as immediate (occurring during or just after administration of the drug) or delayed (driven by a secondary cellular response that can occur up to 72 hours after antigen exposure).1,2
  • HSR may be manifested by a macular, erythematous skin rash, hives, nausea, fever or chills, or dizziness, or it may present emergently with full anaphylaxis.2

Three of the newer agents used in the treatment of colorectal cancer (CRC) are notable for causing HSR: oxaliplatin (Eloxatin), bevacizumab (Avastin), and cetuximab (Erbitux). HSRs occur in 10% to 15% of patients who receive oxaliplatin, an organoplatinum compound.3,4 The humanized monoclonal antibodies bevacizumab and cetuximab rarely cause severe HSRs (incidence < 3%).5,6 The appearance of a pustulopapular, acneiform rash in patients receiving cetuximab is not an indication of HSR.7

Anaphylactic reactions require a swift response to prevent escalation to life-threatening conditions such as airway obstruction or vascular collapse. Patients who express feelings of impending doom or begin to develop respiratory distress, urticaria, or erythema should receive emergent management of their symptoms. Per general guidelines, first-line treatment is epinephrine given intramuscularly (0.2 to maximum 0.5 mL aqueous epinephrine 1:1000).1,2 Subsequent management of HSRs should follow your institution’s protocol. A suggested algorithm can be found in Figure 1. An anaphylaxis kit should be kept in the infusion room at all times and should have the following components:1,2

  • 2 automated delivery devices with epinephrine 1:1,000 (EpiPen®, TwinJect®)
  • 1 L normal saline solution for infusion
  • 1 intravenous (IV) tubing set
  • 1 IV start kit
  • 1 20-mg vial dexamethasone
  • 1 50-mg vial diphenhyrdramine
  • 1 50-mg vial ranitidine

A patient experiencing an anaphylactic reaction should be transferred to an emergency department for continued management of the reaction.1

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Assessment Tools

Table 1. Common Toxicity Criteria (ver 3.0) of the National Cancer Institute

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Adverse Event Grade 1 Grade 2 Grade 3 Grade 4 Grade 5
Allergic reaction/
hypersensitivity		 Transient flushing or rash
Drug fever <100.4°F		 Rash; urticaria; dyspnea
Drug fever >100.4°F and/or asymptomatic bronchospasm		 Symptomatic bronchospasm with or without urticaria; parenteral medication(s) indicated; allergy-related edema/anigiodema Anaphylaxis Death

Data from National Cancer Institute Cancer Therapy Evaluation Program.8

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References

  1. Lieberman P, Kemp SF, Oppenheimer J, et al. The diagnosis and management of anaphylaxis: an updated practice parameter. J Allergy Clin Immunol. 2005;115:S483-S523.
  2. Zanotti KM, Markman M. Prevention and management of antineoplastic-induced hypersensitivity reactions. Drug Saf. 2001;24:767-779.
  3. Meyer L, Zuberbier T, Worm M, et al. Hypersensitivity reactions to oxaliplatin: cross-reactivity to carboplatin and the introduction of a desensitization schedule. J Clin Oncol. 2002;20:1146-1147.
  4. Bonosky K, Miller R. Hypersensitivity reactions to oxaliplatin: what nurses need to know. Clin J Oncol Nurs. 2005;9:325-330.
  5. Avastin (bevacizumab), full prescribing information. Available at: http://www.gene.com/gene/products/information/oncology/avastin/insert.jsp. Accessed August 15, 2006.
  6. Erbitux (cetuximab), full prescribing information. Available at: http://www.bms.com/cgi-bin/anybin.pl?sql=select%20PPI%20from%20TB_PRODUCT_PPI%20where%20PPI_SEQ=106&key=PPI. Accessed August 15, 2006.
  7. Thomas M. Cetuximab: adverse event profile and recommendations for toxicity management. Clin J Oncol Nurs. 2005;9:332-338.
  8. National Cancer Institute Cancer Therapy Evaluation Program. Common terminology criteria for adverse events v3.0. Available at: http://ctep.cancer.gov/reporting/ctc.html.

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Patient Care Management Protocols or Algorithms

Figure 1. Management of hypersensitivity reaction (HSR) Note: Individual institutions may have HSR protocols in place. Pharmacologic interventions should be based on individual institutional protocols.

Management of hypersensitivity reaction

Data from Leibermann et al1 and Zanotti and Markman.2

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This page was last modified on 9/18/2006, at 1:41:44 pm ET.