84 yo M with a history of CAD with HFrEF presented for a routine BiV AICD upgrade whose course was complicated by VT storm requiring amiodarone and lidocaine before conversion back to his outpatient medication mexiletine. Postoperatively, the patient developed a morbilliform rash, which was attributed to an antibiotic allergy as the patient was given perioperative cefazolin. However, acute kidney injury, acute liver injury, and eosinophilia were noted prompting further investigation with a skin biopsy. The biopsy showed an eosinophilic and lymphocytic infiltrate in the superficial dermis, findings suggestive of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome. Medication review, with the understanding that DRESS presents a few weeks after medication initiation, showed the only medication started within the past three months was mexiletine and it was discontinued. Although initially hesitant to use corticosteroids in the setting of heart failure and recent ICD placement, prednisone was dosed due to progressively worsening liver and kidney injury. Following this, there was improvement in his skin rash and multi-organ injury.
Discussion:
DRESS syndrome is well known in textbooks, but often masquerades as a number of other clinical entities. The incidence of DRESS ranges from 1/1000 to 1/10,000 drug exposures. DRESS is unique compared to other drug reactions in that it can have a latent period up to 3 months and for its multi-organ involvement, most commonly the skin, liver, and kidneys. Commonly implicated drugs are anticonvulsants, such as carbamazepine and phenytoin. In one literature review of 172 case reports, between 1997-2009, only 5 cases involved mexiletine. Attention to detail is vital to proper diagnosis, as a thorough physical exam and lab values point to DRESS. There are no definitive criteria for DRESS, although a morbilliform rash, liver abnormalities, and eosinophilia can point to the diagnosis as in this case. Fever and lymphadenopathy can also be seen. Mortality can range from 10-20% from multi-organ failure and thus discontinuation of the drug and possible steroids are important steps in treatment. Treatment decisions were complicated as the risks/benefits of stopping mexiletine along with the risks/benefits of starting prednisone had to be balanced against the effects of DRESS syndrome.
Conclusions:
This case highlights the importance of having a high clinical suspicion of complicated drug rashes. It shows how, in the right clinical setting, a thorough medication review along with knowledge of the timeline of the DRESS syndrome will help establish the diagnosis. A rash should always be investigated with appropriate blood work and a thorough physical exam and not just be attributed to a drug reaction. Identifying DRESS is vital, since if left unrecognized, the disease can progress causing organ failure and ultimately death.