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Allergie multiple aux antibiotiques
Multiple Drug Allergy Syndrome (MDAS) to Multidrug Resistant Tuberculosis Medications
Eric M Chen
Harold S Novey
Dennis C Jerome
University of California - Irvine,
Irvine, CA

Multiple drug allergy syndrome (MDAS) is defined as a condition of having reactions to several
immunochemically distinct antimicrobial drugs. The premise is that certain individuals with reactions to two or
more drugs will have an increased incidence of adverse reactions to the addition of newer drugs. We describe
a case of a 49 year old Vietnamese female with multidrug resistant tuberculosis whom suffered MDAS with
second-line anti-tuberculosis medications. The patient initially presented to the health department with fatigue,
weight loss, hemoptysis, back pain and a 1cm right upper lobe lung lesion on chest x-ray with negative sputum
AFB. She was started on INH, rifampin, and B 6 for 2 months until she developed elevated liver enzymes. She
was lost to follow up and presented with similar symptoms 1 year later. She was then started on INH, rifampin,
ethambutol, pyrazinamide, and B 6 with improvement of symptoms. Her sputum AFB however, showed
resistance to: INH, rifampin, ethambutol, streptomycin, and pyrazinamide. The sputum AFB was sensitive to:
amikacin, cycloserine, clofazimine, levofloxacin, capreomycin, rifabutin, PAS, and ethionamide. The health
department started her on rifabutin, capreomycin, levofloxacin, and PAS without incident. Cycloserine was then started, but caused a fever. The regimen was modified to capreomycin, levofloxacin, and PAS. A rash
developed and the medications were stopped. When the three medications were restarted seven days later,
she developed syncope, hypotension, incontinence, fever, and a rash. She was then admitted to the hospital.
During her hospitalization she was rechallenged to each medication at one quarter the therapeutic dose. This
dose was repeated in quarter increments at 4 hour intervals until the full dose was given. Due to the lack of
standard protocols for testing these second-line tuberculosis medications for adverse reactions, we elected to
perform provocative dose challenges to each drug in the same manner. She developed the following reactions
during the challenges: capreomycin (rash), PAS (hypotension, fever, rash, myalgia, leukophilia), rifabutin (no
reaction), clofazamine (no reaction), levofloxacin (hypotension, wheeze, rash, myalgia), cycloserine
(lightheaded, pruritis, myalgia, arthralgia), and ethionamide (?pruritis, and arthralgia). She was discharged 19
days later on capreomycin, rifabutin, clofazamine, cycloserine, ethionamide, and B 6 with mild pruritis as her
only symptom. This case illustrates the complexity of MDAS, when a combination of drugs are necessary for
treating a particular condition and the methods for identifying the suspected drugs