Hala J. M. Redwan
Secretary-General - Palestinian Pharmaceutical Students' Federation (PPSF - Palestine).
Training Committee - International Pharmaceutical Students' Federation (IPSF).
University PR - International Medical Research Association (IMedRA).
Faculty of Pharmacy - Al-Azhar University - Gaza, Palestine
What is drug desensitization and what is graded challenge dosing? When is each indicated?
Desensitization (DS) a procedure in which administered as therapeutic tool to induce
temporary drug tolerance by modifying patient immune response to drug, performed to allow the patient to take drug temporarily in a safe fashion, it works by different mechanisms including: IgE immune mechanism, non IgE immune mechanism, pharmacological mechanism and undefined mechanism so we can concluded them
into two methods: Immunological or non-immunological mechanism. DS was developed due to the pressing need to reintroduce drugs in a safe fashion in patients who had developed IgE/non IgE type I Hypersensitivity reactions (HSRs) to critical antibiotics and/or other drugs. Also DS is achieved by incrementally escalating the sub-optimal doses of the culprit drug until the required dose is reached, and DS induces a temporary tolerance which protects the patient from anaphylaxis.
In contrast, a graded challenge, or test dosing, is a procedure that used to determine if
the patient will have an adverse reaction to specific drug by administering doses lower
than therapeutic doses over a period of time with reactions detection and to assess if the patient is actually allergic to specific medications in which is intended as diagnostic tool. It does not alter immunological or non-immunological response to
specific drugs. Reliable for and drug and useful as long as reactions is not serious, so
a graded challenge is more appropriate for a patient who is unlikely to be allergic to
the implicated drug, whereas desensitization should be considered in a patient who is
likely to be allergic to the implicated drug.
The starting dose for graded challenge is generally higher than for DS procedures due
to the number of steps, in which test dosing describes administration of progressively
increasing doses of drug until a full doses is reached where is the typical starting dose
for a graded challenge is 1/100th of the final treatment dose, this is through 3 doses:
- Time 0 minutes: administer 1/100th therapeutic dose
- Time 30 minutes: administer 1/10th therapeutic dose
- Time 60 minutes: administer full therapeutic dose
While a typical starting dose for an IgE immune induction of drug tolerance (DS), is
often 1/10,000th of the final dose followed by doubling of the previous dose. The length of the procedure depends on the drug and route of administration.
The choice about when to use a clinically indicated drug through a graded challenge
doses or through DS generally depends on the likelihood that the patient is allergic at the time of the procedure. Patients who, based on their history, diagnostic test results, or both, are unlikely to be allergic to a drug can undergo graded challenge. In which the DS is indicated when no alternative drug is available; when the suggested drug is more effective than other possible alternatives; if there are no co-morbidities leading the patient to increased risk during the procedure; and when the reported drug reaction was not a severe, life-threatening immune-toxic reaction.
DS indicated for patient with High likehood or confirmed drug allergy like antibiotic allergy (e.g. positive skin test) and in need of culprit drug where no therapeutic alternative exist. Whereas graded challenge doses indicated for patient with low likehood or with negative skin test, For example, if penicillin skin testing is unavailable and a patient with a history of a mild pruritic rash during penicillin treatment 20 years ago requires penicillin therapy, it would be reasonable to
administer penicillin through a graded oral challenge doses while Patients who have a
relatively higher likelihood of being allergic to a drug should undergo an induction of
drug tolerance procedure. For example, if penicillin skin testing is unavailable and a
patient with a recent history of penicillin-induced anaphylaxis requires penicillin, it
should be administered through induction of drug desensitization.
Both graded challenge and DS are contraindicated in patients with a history of
Stevens-Johnson syndrome, toxic epidermal necrolysis, or exfoliated dermatitis, as a
small doses of the drug can induce potentially lethal recurrent desquamative reactions
because the interaction between the antigen and the antibody may possibly lead to the
activation and consumption of the complement system. Also, neither procedure
should be attempted in patients with a history of serious non-IgE-mediated, immunologic reactions, such as serum sickness reactions, nephritis, hepatitis, or hemolytic anemia..
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