Case Presentation: A 57 year old male with HIV/AIDS was transferred to our hospital for acute onset of lethargy and incoherent speech. He intially presented with a few weeks of headaches, slurred speech, and intermittent confusion, and was diagnosed with toxoplasmosis. He was started on atovaquone and sulfadiazine for taxoplasmosis and levetiracetam for seizure prophylaxis, with gradual improvement in mental status and speech. However, 13 days into therapy he was noted to have acutely decreased responsiveness associated with incoherent speech. Computed tomography (CT) of the head initially showed hyperdensities concerning for hemorrhage (ICH) in the right frontal region, however repeat CT head was negative for ICH. On Day 14, atovaquone was switched to leucovorin and pyrimethamine. Lumbar puncture revealed cerebrospinal fluid (CSF) studies with WBC 20, lymphocytes 88%. Acyclovir was started. CSF bacterial, fungal and viral cultures were negative, and CSF meningitis and enecephalitis panel were negative. On Day 17, he began to spike high grade fevers, and a worsening exfoliative rash was noted. Ethambutol and azithromycin were started. Work up including blood cultures, urinalysis, and chest radiography were negative. Mental status remained unimproved. On Day 27, antiretroviral therapy (ART) was started. On Day 29, he was noted to have worsening transaminitis with direct hyperbilirubinemia. Viral hepatitis serology was negative, abdominal ultrasound showed no pathology. Liver biopsy showed no steatosis, with mixed portal inflammation including lymphocytes, plasma cells, few histiocytes and eosinophils, mild bile duct damage and endothelitis. Fevers persisted and ART was stopped. Chest CT revealed ground-glass and nodular opacities in the lower lobes, with bilateral axillary lymphadenopathy. Procalcitonin was negative. He underwent bronchoscopy; bronchoalveolar lavage cultures, Pneumocystis jiroveci studies, and cytology were negative. Though patient was neutropenic on admission, he developed worsening leukocytosis with WBC of 12.2 with eosinophilia 24% and atypical lymphocytes 1.0%. His over-all presentation became concerning for Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), and his computed RegiSCAR score was 6, which gave him a definite diagnosis of DRESS. Levetiracetam was stopped, and he was started on methylprednisolone, with gradual and sustained improvement in mentation, respiratory status, and transaminitis.
Discussion: Diagnosis of DRESS remains challenging because it affects multiple organs and presents variably. While liver and hematologic abnormalities have been well documented, central nervous system involvement has been infrequently noted. Recognition of the syndrome is also made difficult in a patient with multiple co-morbidities. To prevent delays in treatment and associated morbidity, keeping a high index of suspicion for DRESS in a patient presenting with a rash and non-specific symptoms is imperative.
Conclusions: DRESS is a rare and potentially life threatening condition. It is frequently associated with antiepileptic drugs, but only a few reports of DRESS in relation to levetiracetam have been published, and none have reported altered mental status as a presenting symptom. Recognition of this syndrome remains challenging because of its variable presentation.