Intravenous immunoglobulin in the treatment of drug rash eosinophilia and systemic symptoms caused by phenytoin
A 32 year old Asian lady underwent excision surgery of a left frontal meningioma under Neurosurgery and was started on phenytoin at a dose of dose of 300 mg / day along with dexamethasone in the perioperative period. Dexamethasone was discontinued after 2 days and she was discharged from hospital with normal blood parameters including liver function tests 6 days after the surgery. While at home she developed fever and skin rash 12 days from the date of surgery. Phenytoin was promptly discontinued and it was replaced with Leviteracetam by the neurosurgeon but this was also discontinued 2 days later because of the rash becoming more widespread. She was then referred to the Neurology department 3 weeks after the onset of rash for further management.\nOn examination she had extensive maculopapular rash all over the body involving the face, trunk, upper and lower limbs. She had cervical and posterior auricular lymphadenopathy, jaundice, and splenomegaly. She denied any history of exposure to any other drug, recreational drug abuse, alcohol or blood transfusion.\nLab investigation including complete blood count showed absolute eosinophilia 14.9% (Normal-0 to 7%), marked impairment of liver function []. Investigations for other causes of hepatic disease including Serum copper, serum ceruloplasmin, screening for collagen disease, viral markers for hepatitis were all negative (HAV, HBV, HCV).\nEpstein Barr virus IgM and IgG antibodies were both positive. Cytomegalovirus Ab-IgG positive and IgM- negative\nSerum ammonia, serum amylase, D Dimers were negative.\nUrine R/M –no cells, Protein -1. Urine, throat, blood cultures were negative.\nDrug hypersensitivity due to phenytoin was diagnosed and she was started on oral prednisolone 1 mg /Kg. However there was no improvement and the rashes were becoming more florid and liver function tests deteriorated further. Investigations 7 days after admission showed persistent increase of liver enzymes. Despite stopping phenytoin and treatment with prednisolone (1 mg /Kg) the rash was becoming more diffuse and serial LFT revealed increasing enzyme levels. Dermatology consultation confirmed the case as DRESS syndrome (Drug rash, Eosinophilia, Systemic symptoms) syndrome based on fever (39 to 40°c) drug rash, facial edema, eosinophilia, systemic manifestations of lymphadenopathy, splenomegaly, liver and renal impairment.\nIVIG (0.4 Gm/ Kg) was added to prednisolone as there was no improvement even after 7 days of steroid treatment. After 5 days of I.V. Immunoglobulin (0.4 Gram/Kg) clinical improvement was evident, the rash subsided and a rapid decline of liver enzymes was observed [ and ]. Blood parameters returned to normal 3 weeks after starting IVIG and 6 weeks after the onset of the rash. In the meantime she was started on Topiramate which she tolerated well and was discharged from the hospital with tapering dose of prednisolone. On follow up till 2 months she was asymptomatic and well.