Case Presentation: A 31-year old woman with a history of bipolar disorder presented to the hospital with generalized coarse tremors of the extremities for 2 weeks duration following initiation of lithium for hypomanic episode. Initial vital signs were T 39 °C, HR 103 bpm, BP 98/59 mmHg, RR 16, and O2 saturation 100% on room air. Physical exam was remarkable for facial edema and coarse extremity tremors. Admission labs showed elevated lithium (Li) level 2.56 mEq/L, serum creatinine 2.88 mg/dl, and CPK 5316 u/L, suggestive of lithium toxicity. EKG revealed sinus tachycardia. Renal ultrasound and CT scan of the head were normal. The patient was admitted to telemetry for monitoring and aggressively resuscitated with IV crystalloids for AKI and rhabdomyolysis. 

On day 2 of admission, the patient had a fever to 40 oC associated with new diffuse morbilliform rash over the chest and lower extremity swelling. Further studies showed elevated eosinophils, transaminitis, and worsening AKI. The patient became progressively oliguric with persistently elevated Li levels requiring transfer to the MICU for urgent hemodialysis. Her CPK and LFT’s continued to rise despite normalization of Li levels with hemodialysis. The patient’s clinical findings were consistent with drug reaction with eosinophilia and systemic symptoms (DRESS) due to lithium. Systemic corticosteroids were started immediately with resolution of her symptoms and normalization of CPK and LFT levels soon thereafter. 

Discussion: DRESS is a rare type of drug hypersensitivity which occurs 2-8 weeks after drug initiation most commonly with use of antiepileptics, antibiotics and HAART. Diagnosis of DRESS requires three of the following criteria: acute rash, fever above 38 °C, lymphadenopathy at two sites, involvement of at least one internal organ, thrombocytopenia, or elevated lymphocyte or eosinophil counts. Li-induced DRESS is a rare occurrence with only a few case reports in the literature. The diagnosis can be challenging due to overlapping signs of Li toxicity including AKI and rhabdomyolysis. Our patient’s presentation of morbilliform rash and facial edema were initially concerning for an allergic reaction or even angioedema due to an unknown trigger. However, development of fever, eosinophilia, transaminitis, and worsening renal function led to a diagnosis of Li-induced DRESS. Treatment includes immediate discontinuation of the insulting drug, systemic corticosteroid therapy, and occasionally IVIG. 

Conclusions: Diagnosis of DRESS is challenging due to its rarity, evolving diagnostic criteria, and lack of specific laboratory testing. Thorough medication review both on admission and hospitalization is essential for diagnosis. Lithium-induced toxicity is known to cause renal dysfunction and less commonly dermatoses, but the presence of fever, hematologic disturbance, or underlying organ involvement should raise suspicion for Li-induced DRESS.