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Multiple Drug Intolerance Syndrome

Multiple Drug Intolerance SyndromeOverview
Multiple drug intolerance syndrome is defined as having greater than 3 or more unrelated drug intolerances or allergies. Based on medical record data, about 2 to 5% of the population that uses health care may have multiple drug intolerance syndrome in North America and Europe, with higher rates seen in hospitalized patients.

Multiple drug intolerance syndrome is more likely to occur with increasing age as the number of life-time drug exposures increases. It is more common in females and in individuals being treated for higher numbers of different specific health conditions. Multiple drug intolerance syndrome can appear in patients with true allergies as have been reported in patients allergic to penicillin and quinolones antibiotics.

Multiple drug intolerance syndrome can be managed by medication avoidance and careful rechallenge when needed.

Symptoms & Diagnosis
Adverse drug reactions can occur with all medications. Common medication–associated reactions include rashes, gastrointestinal problems, headaches, coughing, muscle aches, and fevers. The more medications one is exposed to over time, the more likely an adverse drug reaction will occur. However, only a small minority of medication-associated reactions are true allergies or caused by the body’s own immune system over reacting to the drug, and these are the ones that need special care.

Most adverse drug reactions have other explanations and do not always re-occur with repeat exposures. It may also be possible to use lower doses of the same medication or other related medications if needed.

The diagnosis of multiple drug intolerance syndrome is made by taking a careful history of what medications have not been tolerated and what medications have been tolerated. The interaction between medications used and underlying conditions is also important in determining the risks of recurrent reactions with repeat medication exposures.

All individuals with multiple drug intolerance syndrome should be evaluated by an allergist / immunologist. An allergist can figure out the risks associated with re-exposure to specific medications or classes of medications and develop a comprehensive plan for future medication use. Certain specific diagnostic tests, such as penicillin allergy testing, may also be done if indicated. Allergists are also experts in performing challenge tests and managing adverse reactions associated with these tests.

Treatment & Management
Most individuals with multiple drug intolerance syndrome can tolerate needed medications after an appropriate evaluation.

Schiavino D, Nucera E, Roncallo C, Pollastrini E, DePasquale T, Lombardo C, Altomonte G, Buonomo A, Patriarcia G. Multiple-drug intolerance syndrome: clinical findings and usefulness of challenge tests. Ann Allergy Asthma Immunol, 2007;99:136-42.

Macy E, Ho NJ.  Multiple drug intolerance syndrome: prevalence, clinical characteristics and management. Ann Allergy Asthma Immunol, 2012;108:88-93.

Chiriac AM, Demoly P. Multiple drug hypersensitivity syndrome. Curr Opin Allergy Clin Immunol 2013;13:323-9.

Omer HMRB, Hodson J, Thomas SK, Coleman JJ. Multiple drug intolerance syndrome: A large-scale retrospective study. Drug Saf, 2014;37:1037-45.

Find out more about drug allergies.

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Podcast Episode: Ask the Researcher: Delabeling Penicillin Allergy Through Oral Challenges


Elina Jerschow, MD, FAAAAI, joins the podcast to discuss her latest research study. By giving amoxicillin to patients with a history of reported mild reactions to penicillin, Dr. Jerschow demonstrated that 97% of patients could safely receive penicillin again. This is a useful episode for allergists, primary care providers and anyone with their own suspected penicillin allergy. (March 24, 2019)

Click here to listen to the podcast.
Read the transcript of the conversation.

Podcast Episode: Penicillin Allergies: Over-diagnosed and Under-addressed

Are you among the 10% of the population who report having a penicillin allergy? This patient centered episode discusses why 90% of those who report a penicillin allergy are not truly allergic. Listen to expert Kimberly G. Blumenthal, MD, MSc, FAAAAI, discuss the complicated reasons why penicillin allergies are over-reported and the many ways in which this can be addressed. This information packed episode is useful for patients, the general public and medical professionals. (February 10, 2019)

Click here to listen to the podcast.
Read the transcript of the conversation.