Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a life-threatening, drug-induced hypersensitivity syndrome, characterized by rash, fever, lymphadenopathy, eosinophilia, and internal organ involvement. Most cases of DRESS involve the liver with transaminitis less than 10 times the upper limit of normal, however, severe disease can also rarely be seen - as presented in this case. A 39-year-old woman with psoriatic arthritis (PsA) presents with progressive whole body pruritic rash for one week. Ten months prior to admission, she started apremilast and then one month prior to presentation also started sulfasalazine for her PsA. One week prior to presentation, she noticed an erythematous, pruritic maculopapular rash on her face, chest, arms, legs, and with associated fever. At that time, her rheumatologist discontinued all PsA medications, and she was treated with penicillin for suspected scarlet fever. Her rash worsened, developing facial edema and confluent blistering of her arms and legs. She also developed painful cervical lymphadenopathy. Upon admission, she had a new transaminitis (AST and ALT > 1000 IU/L), elevated INR (1. 4), leukocytosis (30 x103/uL) with eosinophilia (3300 cells/uL), positive HHV-6, and negative viral and autoimmune hepatitis serologies. She had no infectious or neurologic evidence of symptomatic HHV-6 infection. Dermatology, gastroenterology and infectious disease were consulted. A skin biopsy showed a robust lymphomatoid cellular immune reaction with dermal infiltration of eosinophils, consistent with DRESS syndrome. She was started on intravenous and topical steroids and transitioned to a long oral steroid taper, with subsequent resolution of her rash, leukocytosis, and acute liver injury. DRESS syndrome is associated with a range of drugs, including anticonvulsants (phenytoin), sulphonamides, and rarely sulfasalazine. As seen in our case, the onset of the disease is delayed, and ranges from 2 to 6 weeks after the initiation of the therapy. While most cases of DRESS involve only a mild hepatoxicity, severe disease can rarely induce severe transaminitis (AST and ALT >1000 IU/L), hepatomegaly and fulminant liver failure. Treatment involves withdrawal of the causative drug, systemic high dose corticosteroids, and in rare cases with fulminant liver failure even liver transplantation. DRESS syndrome has a mortality rate of 10%, most commonly due to liver failure, making liver involvement a poor prognostic marker.Figure: Trend of Laboratory Values During Hospital Course.Figure: All samples were stained with Hematoxylin-eosin. The biopsy revealed a striking interface dermatitis with marked papillary edema leading to focal areas of epidermaldermal separation (A, B). The supervening epidermis showed spongiosis and eczematous changes (C, D). Many dermal vessels were surrounded by a dense lymphocytic infiltrate containing scattered transformed immunoblastic elements as well as eosinophils (E). There was vascular mural fibrin deposition with mural edema and concomitant endothelial cell swelling, consistent with a lymphomatoid vasculitis (F). ((A) 4x; (B) 10x; (C) 20x; (D) 40x; (E) 100x; (F) 100x).