Objective:

To report a case of drug reaction with eosinophilia and systemic symptoms (DRESS) with presumed autoimmune encephalitis mimicking HHV (human herpesvirus)-6 encephalitis, complicated by refractory status epilepticus. 

Background:

HHV-6 reactivates in DRESS, raising the question of whether DRESS-associated encephalitis is driven by HHV-6 or represents a secondary autoimmune encephalitis with unrelated HHV-6 reactivation. To our knowledge, refractory status epilepticus has not been reported in DRESS-associated encephalitis.

Design/Methods:

Case report. 

Results:

Six weeks after unintentional phenobarbital ingestion, a 38-year-old woman presented with a generalized tonic-clonic seizure. Skin biopsy two weeks prior, prompted by fever, maculopapular rash, and eosinophilia, was consistent with DRESS. Electroencephalogram (EEG) showed status epilepticus with right temporal and midline onset, requiring six anti-seizure medications.  Brain MRI revealed T2/FLAIR hyperintensities, restricted diffusion, and cortical thickening of bilateral hippocampi. Serum showed HHV-6 viral load of 288,500 copies/mL and a negative autoimmune encephalopathy panel (Mayo clinical labs). Cerebrospinal fluid (CSF) revealed lymphocytic pleocytosis (7 cells/mm3), elevated protein (51 mg/dL), 2 red blood cells/mm3, normal glucose, negative autoimmune encephalopathy panel, and low HHV-6 viral load of 14,000 copies/mL. The CSF/serum replication ratio of <0.05 suggested against HHV-6 as the primary driver of encephalitis in our host with altered immunity. The patient met diagnostic criteria for definite autoimmune limbic encephalitis based on clinical onset, MRI, EEG, and low probability of HHV-6 encephalitis given the low CSF viral load (Graus et al., 2016). Brain MRI after 11 days showed marginal improvement. Acute treatments included IVIg, high-dose methylprednisolone, ganciclovir, and fluid restriction for SIADH. She was maintained on a prolonged prednisone taper with rituximab due to persistent cognitive dysfunction.  

Conclusions:

In the context of DRESS, HHV-6 viral load requires cautious interpretation, and autoimmune encephalitis should be considered even with HHV-6 viremia or CSF viral load. We present a unique case of status epilepticus attributable to autoimmune encephalitis in DRESS.