Improving the Diagnosis, Treatment and Understanding of Adverse Drug Reactions
The Risma Lab investigates adverse drug reactions, which refer to either an immune-mediated, medication hypersensitivity reaction that recurs predictably (usually referred to as classical allergy), or an immune reaction to a medication that recurs unpredictably (referred to as idiosyncratic). The Risma Lab conducts clinical and translational research to improve diagnosis, treatment and understanding of adverse drug reactions, including classical and idiosyncratic reactions to medications, such as antibiotics, biologics, chemotherapy agents, vaccines and numerous others.
Types of Immune-mediated Reactions to Medications
Immune-mediated, classical drug allergies are historically categorized by their timing of both the initial reaction and the timing of predictable recurrence. Test-proven, classical drug allergies are quite rare in the pediatric population and, instead, most allergic reactions are better classified as idiosyncratic.
Immediate Reactions (Symptoms Occur Within 60 Minutes)
Immediate allergic drug reactions to medications typically include hives or flushing, swelling or, if serious (rare), change in blood pressure and/or difficulty breathing. The symptoms resolve in hours to a day with treatments such as antihistamines and epinephrine. After repeat exposure to the medication during testing (or accidental administration), the symptoms recur within an hour of the dose and symptoms typically do not last longer than a day. This is like an immediate allergic reaction to a food such as peanut or shrimp.
Delayed Reactions (Symptoms Occur Within Hours to Weeks)
Delayed-onset allergic drug reactions most often include rash, fever, vomiting, swelling, eye redness/pain, malaise or (rarely) other organ involvement if serious. With the first ever reaction, the symptoms may occur several days to weeks after starting the medication (after more than one dose). If the medication is taken again during testing (or accidentally), symptoms recur faster (within hours to days of a single dose). The allergic symptoms resolve after several days, typically requiring treatments such as steroids or other immune-suppressing treatments. As such, a delayed-onset drug allergy is like an allergy to poison ivy rather than an immediate allergy to a food.
Idiosyncratic Reactions (Unpredictable Recurrence)
In children, allergy testing to medications by giving a repeat dose in the office rarely shows confirmation of the two types of classical allergy (with immediate or delayed allergic reactions during testing). We have observed that it is more common for children to experience allergic symptoms after multiple doses/days of medication exposure (particularly antibiotics) either during an extended home challenge or during treatment for illness. This suggests a medication side effect rather than classical allergy. Alternatively, allergic symptoms may be related to illness rather than medication. Due to unpredictable occurrence and recurrence, we refer to these as idiosyncratic reactions. As the symptoms are identical to classical allergic reactions, management options are similar. However, we do not understand the necessary triggers for either the initial or subsequent sporadic occurrences.
