Drug desensitization is the process by which a patient is densensitized to a drug that they allergic to in the past. This induces a temporary state of tolerance, during which the drug can be administered safely.
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Allergic reactions to drugs account for over 15% of medication adverse effects and can vary from mild symptoms such as hives, rash, flushing, and itching, to severe reactions such as anaphylaxis. Almost any drug can cause an allergic reaction, and the likelihood of another reaction means that most patients will simply avoid that drug in the future.
In certain situations, no alternative drug is available to treat a patient. In these situations, drug desensitization is an option that allows for continued treatment. However, drug desensitization is considered controversial due to the lack of clearly defined protocols, indications and contraindications, and variability in patient tolerance. Patient safety is the top priority, and as such, a number of factors need to be considered before proceeding with desensitization therapy.
Drug desensitization procedure
Drug desensitization has been performed successfully with chemotherapy, antibiotics, monoclonal antibodies and other biologics, antiretrovirals, and anti-mycobacterials, vaccinations, insulin, and hormonal therapy.
Patients are candidates for therapy on the basis of severity of the reaction, and type of reaction (rapid or delayed). Skin tests are usually performed following an initial reaction to confirm hypersensitivity to a particular medication.
For immediate reaction types, rapid desensitization can be performed. Small doses of medication are introduced at regular time intervals, with a larger doses (usually double the previous dose) at each administration. This gradual increase accustoms the immune system to the drug slowly so that no allergic reaction occurs. Rapid desensitization is always performed in an inpatient center where the patient can have immediate access to intubation and resuscitation is needed.
A number of different protocols have been published for rapid desensitization involving chemotherapy, monoclonal antibodies, antibiotics, and iron treatment. Protocols differ in the rate, volume, time and (cumulative) dose of the drug administered.
Drug desensitization safety
To maximize safety, patients must be selected carefully. Considerations include patient’s existing comorbidities and medications, such as steroids or beta-blockers. The main risk associated with drug desensitization is a recurrence of an immediate and severe allergic reaction (including anaphylaxis), the treatment is always performed in a carefully monitored environment where qualified personnel can take precautionary measures. One-to-one nursing is provided and an allergy specialist, as well as rescue medicines must be available in the treatment center.
Because drug desensitization is performed by introducing larger doses of medication at each step, the treatment can be stopped immediately if an adverse reaction occurs. The doses can then be readjusted and treatment continued using a different protocol. In rare cases, a late-onset may occur. This reaction may manifest with serum sickness, anemia, nephritis (inflammation of the kidneys), and thrombocytopenia.
Despite the lack of uniform protocols and safety concerns, drug desensitization has a number of advantages over alternative therapy options. The treatment may provide higher efficacy, lower treatment costs, and avoidance of microbial resistance and toxicities associated with suboptimal alternative antimicrobial use. Drug desensitization has allowed for successful continuation of chemotherapy treatment in patients with cancer where no alternative treatments exist for a particular disease.
Sources
- Desensitization in delayed drug hypersensitivity reactions – an EAACI position paper of the Drug Allergy Interest Group. Allergy 2013; 68: 844–852.
- General considerations on rapid desensitization for drug hypersensitivity – a consensus statement. Allergy 2010; DOI: 10.1111/j.1398-9995.2010.02441.
- American Academy of Allergy Asthma & Immunology – What is Drug Desensitization?
- Merck Manual, Drug Hypersensitivity by Peter J. Delves, PhD, Professor of Immunology, Division of Infection & Immunity, Faculty of Medical Sciences, University College London, London, UK
- Bernard Y.-H. Thong and Miguel Blanca, Drug allergy/hypersensitivity in adults and children, Current Opinion in Allergy and Clinical Immunology, 10.1097/ACI.0000000000000382, 17, 4, (239-240), (2017).
Further Reading