DRESS and PRES in a Patient with Epilepsy: Unexpect- ed Consequences of Adding Lamotrigine

Drug reaction with eosinophilia and systemic symptoms [DRESS] syndrome is a rare but potentially life-threatening syndrome characterized by skin rash, fever, lymph node enlargement, and involvement of internal organs. It is most commonly induced by aromatic anticonvulsants and antibiotics. Lamotrigine has been implicated as a cause. Posterior reversible encephalopathy syndrome (PRES)presents with rapid onset of symptoms including headache, seizures, altered consciousness, and visual disturbance. It is often associated with acute hypertension. If promptly recognized and treated, the clinical syndrome usually resolves. We report a case of a patient with absence epilepsy, who developed these two conditions within a few days of initiating the anti-seizure medication lamotrigine. The case exemplifies how the addition of anti-seizure medications is not always benign and can have severe unpredictable consequences. Volume 1 Issue 1 1006 Page: 2 of 8 Citation: Anita Datta and Peter K.H. Wong DRESS and PRES in a Patient with Epilepsy: Unexpected Consequences of Adding Lamotrigine STJ Paediatrics.2016 Nov;1(1):1006. Volume 1 Issue 1 1006 Case History The patient is a healthy 16 year old female with a diagnosis of childhood absence epilepsy since 4 years of age. She has an unremarkable past medical history and normal development. Her mother was diagnosed with multiple sclerosis, but there are no other pertinent findings in the family history. Her typical seizures consisted of brief episodes of staring and eye fluttering. Her EEG’s showed 3 Hz spike wave discharges consistent with absence epilepsy. Her seizures were initially difficult to control. Antiepileptic medications tried include valproic acid, ethosuximide. clobazam, keppra, lamotrigine and sulthiame. She developed a rash with lamotrigine initially, but tolerated a repeat trial when she was younger. Her seizures were finally controlled with a combination of valproic acid and sulthiame. She finally became seizure free at 13 years of age and had normal EEG two and three years after becoming seizure free. Her primary neurologist recommended weaning off medications at that time. However, she did not agree as she wanted to obtain her driver’s license first. In Canada, a patient must be seizure free for 1 year after weaning medications before they can drive. Therefore, her neurologist recommended to replace valproic acid with lamotrigine, as this medication has less teratogenic effects and is often preferred in a young adolescent female. She was started on lamotrigine 12.5 mg daily and was provided with a slow titration schedule. She continued on valproic acid at 750mg twice daily and sulthiame 150mg/100mg. Five days after initiation of lamotrigine, she developed nausea, vomiting and diarrhea. She had multiple non-bilious, non-bloody emesis per day. She also developed progressive generalized fatigue, diffuse maculopapular rash and fever. Her mother also noted that she was confused. She went to her local hospital and was treated empirically for sepsis with broad-spectrum antibiotics and fluids. Her initial blood pressure was 105/64 and she was febrile. The remainder of her vitals were stable. She was subsequently transferred to the pediatric tertiary center. Lamotrigine.valproic acid and sulthiame were discontinued. On arrival, her blood pressure was 92/52, pulse was 97 and respiratory rate was 16. Her oxygen saturation was 99% on room air. She was having intermittent fever up to 39 degrees. She had fluctuating confusion and was intermittently disoriented to time and place. She could not do serial sevens or spell “world” backwards. At times, she was answering questions inappropriately. On physical exam, it was noted that she had small sub-centimeter lymph nodes in the anterior cervical chain, with no other lymphadenopathy. Erythematous non-blanching maculopapular rash was noted on her face, chest and back. She appeared dehydrated. Cardiac exam was normal. Chest was clear. On abdominal exam, she had no hepatomegaly, but had splenomegaly. Her initial lab results showed thrombocyotopenia, with a platelet count of 26. There was also neutropenia and mildly abnormal coagulation factors. No eosinophilia was evident. Her peripheral blood film demonstrated giant platelets with hypolobulated neutrophils. She also had acute kidney failure with a creatinine of 380. Her AST was minimally elevated at 44, with normal ALT and ALP. LDH was 1262 and CRP 45. Vasculitic work up, including anti-nuclear antibody and rheumatoid factor were negative. Valproic acid level was within normal limits. Infectious workup including blood culture, urine culture, lumbar puncture and stool studies, was all negative. CMV IgM was positive and IgG and PCR were both negative. She was empirically treated for sepsis with cefotaxime and acyclovir, which were discontinued when the studies were normal. Abdominal ultrasound showed no hepatomegaly, but splenomegaly of 12.8cm. Cardiac echo was normal. Due to her thrombocytopenia, she required a platelet transfusion and was followed by Hematology, no other causes for her abnormal blood work was found. She received vitamin K for 3 days. Her platelets normalized to 197 within a few days. She was investigated by numerous specialists. Rheumatology did not feel she had vasculitis. Nephrology confirmed her kidney injury could be secondary to severe dehydration in addition to a hypersensitivity reaction. With IV fluid replacement, her creatinine gradually normalized. Infectious Disease did not think her symptoms were secondary Page: 3 of 8 Citation: Anita Datta and Peter K.H. Wong DRESS and PRES in a Patient with Epilepsy: Unexpected Consequences of Adding Lamotrigine STJ Paediatrics.2016 Nov;1(1):1006. Volume 1 Issue 1 1006 to infection, even though she was empirically treated with antiobiotics. Dermatology felt the rash was consistent with a hypersensitivity reaction, but no biopsy was performed. The rash resolved within 3 days. She continued to have mild encephalopathy that was fluctuating, but improving. Her brain MRI was normal. Initial EEG showed diffuse slowing consistent with a mild encephalopathy of non-specific etiology. No epileptiform discharges were noted. By day seven of admission, her encephalopathy improved and her mother thought she was returning to baseline. Overall, her diagnosis was most consistent with probable DRESS syndrome. She was not treated with steroid, as she was clinically improving. 10 days after admission to hospital, the plan was to discharge her home, as she had recovered from her symptoms. However, the night before discharge, she was noted to have elevated blood pressure of 130140/80. The next day, she developed blurred vision and headaches. She then had a new type of seizure, where she was seeing coloured lines lasting for a few minutes. 24 hour continuous EEG monitoring showed bilateral occipital periodic lateralized epileptiform discharges (PLEDS). An urgent MRI showed evidence of vasogenic edema within the occipital and parietal regions that was most consistent with PRES. Leviteracetam was started to treat her seizures. Her elevated blood pressure was treated with amlodipine. Nephrology could not find any underlying cause for her elevated blood pressure, except for the aggressive fluid replacement she received initially. Her renal function had normalized and she was no longer on any medications at the time of her elevated blood pressure. She did not have any further seizures and returned to baseline in a few days. She was discharged from hospital 3 days later in improved stable condition.