Lamotrigine-induced hemophagocytic lymphohistiocytosis with Takotsubo cardiomyopathy: a case report

Abstract

BackgroundHemophagocytic lymphohistiocytosis is a rare hematological syndrome characterized by excessive and uncontrolled activation of the immune system. The often nonspecific nature of early symptoms and the potential for progression to multiorgan failure and death if appropriate therapy is not started promptly, highlight the importance of heightened recognition for this uncommon disease. Although there are well-described associations of hemophagocytic lymphohistiocytosis with infectious, malignant, and autoimmune diseases and an established treatment protocol for these cases, the link between medications and hemophagocytic lymphohistiocytosis is less clearly established and the optimal treatment of these cases less well defined.Case presentationHere we describe the case of a 45-year-old caucasian woman presenting with signs and symptoms consistent with hemophagocytic lymphohistiocytosis, induced by recent exposure to lamotrigine. She had a rapidly progressive clinical course, complicated by multiorgan failure including stress-induced Takotsubo cardiomyopathy and cardiac arrest. With dexamethasone and etoposide therapy, she made a full and sustained recovery.ConclusionsThis case highlights that medication-induced hemophagocytic lymphohistiocytosis appears to respond similarly to the same dexamethasone and etoposide treatment regimen developed for other non-drug-induced forms of hemophagocytic lymphohistiocytosis. With the continued cessation of the offending agent there has not been need for maintenance therapy and no relapse to date. In addition, given the risk for cardiomyopathy, a clinical complication not classically associated with hemophagocytic lymphohistiocytosis, echocardiogram and telemetry monitoring should be considered in the initial workup of suspected hemophagocytic lymphohistiocytosis.

Analysis of the clinical characteristics of lamotrigine‐induced haemophagocytic lymphohistiocytosis

“…The triglyceride levels for 2 patients were in the normal range 9,12 12,19 and 3 patients had normal white blood cell counts 10,11,14 . Ferritin levels ranged from 787 ng/ml to 117,000 ng/ml.…”

“…Past medical history appeared in 8 patients, 8,9,15,17–20,22 and concomitant medication use was a factor in 12 patients 8–11,16–22 …”

“…Lamotrigine was immediately discontinued in 16 patients, continued to be used in one patient and switched to lacosamide and zonisamide in 2 patients 8,12 . In addition, 14 patients received steroid therapy, 8–10,13–22 7 patients received etoposide therapy, 8–10,13‐15,19 6 patients received antibiotics, 9,11,14,16,20 5 patients received immunoglobulin therapy, 14,17,18,20,22 2 patients received cyclosporine therapy, 16,22 and 1 patient received lenograstim 16 . One patient underwent intermittent dialysis and extracorporeal membrane oxygenation (ECMO) 10,14 .…”

“…In addition, 14 patients received steroid therapy, 8–10,13–22 7 patients received etoposide therapy, 8–10,13‐15,19 6 patients received antibiotics, 9,11,14,16,20 5 patients received immunoglobulin therapy, 14,17,18,20,22 2 patients received cyclosporine therapy, 16,22 and 1 patient received lenograstim 16 . One patient underwent intermittent dialysis and extracorporeal membrane oxygenation (ECMO) 10,14 . After the above treatment, these symptoms gradually improved within a few days to several months in 15 patients, and 2 patients eventually died 15,21 …”

Lamotrigine-associated haemophagocytic lymphohistiocytosis (HLH) confounded with underlying rheumatoid arthritis

“…Reviewing the literature, it is evident that lamotrigine has been associated with iatrogenic/treatment associated HLH (Rx-HLH), although very rarely. To our knowledge, less than 10 cases were reported worldwide 17–23…”