A Rare Case of DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) Syndrome with Cholecystitis in a Patient on Levetiracetam

Abstract

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare idiosyncratic drug reaction with a mortality of up to 10%. As the name suggests, it is characterized by skin rash, eosinophilia, and systemic symptoms resulting from the involvement of visceral organs. We present a case of DRESS in a patient who was on both lamotrigine and levetiracetam, where levetiracetam turned out to be the inciting agent. The interesting features of the case include the onset of symptoms about 70 days after the initiation of levetiracetam, the lack of prominent eosinophilia and the involvement of the gall bladder, which was previously unknown with Levetiracetam. It also reinforces the importance of using the RegiSCAR score in the diagnosis of DRESS. The symptoms resolved over the next few months after drug withdrawal.

Levetiracetam and cutaneous adverse reactions: A systematic review of descriptive studies

“…Even though a majority of CADRs are hypersensitivity reactions, there are various mechanisms implicated in it. In case of DRESS, there is slow acetylation (detoxification defects) of the drug and accumulation of drug metabolite leading to immunological reactions, reactivation of herpes virus (HHV-6 and 7) by interacting with drugs, genetic predisposition and previous immunosuppression [8,12,13]. Drug-induced hyperpigmentation involves the formation of a drug-melanin complex that stimulates overproduction of epidermal melanocytes and prevents melanin clearance in dermal macrophages [1].…”

“…The treatment duration of LEV varied from 1week to 1 year except in 1 case reported by Koklu et al, [11] where CADRs progressed spontaneously on the intravenous administration of LEV in a 40-week infant. CADRs such as DRESS, SJS, TEN and Acute generalized exanthematous pustulosis were induced by LEV monotherapy and only 2 studies, Singh et al, [8] and Hall and Fromm [13], reported DRESS induced by LEV with concomitant administration of another AED such as LTG and PHY, respectively. The complete treatment characteristics are presented in Table 4.…”

“…Singh et al, [8] A reticulated macular erythematous rash on the upper extremities and trunk that later spread to the patient's face and lower extremities. Pharynx was noted to be erythematous, and the patient's tonsils were enlarged and covered with exudates.…”

“…Treatment provided for CADR Outcomes Singh et al, [8] Allergies to nuts and pollen LTG was stopped immediately; LEV was stopped after 10 days NR Resolved gradually after a few weeks Algahtani et al, [1] Unremarkable A gradual decrease in LEV dose until complete discontinuation NR Skin hyperpigmentation improved significantly and continued to be seizure free after 6-month follow-up Gupta [21] Unremarkable LEV was stopped immediately and replaced with clonazepam while phenytoin was continued Prednisolone (30 mg/day), mometasone furoate 0.1%, emollients, levocetirizine 5 mg…”

“…Commonly known adverse effects of LEV include somnolence, headache, dizziness, asthenia, infection, pharyngitis, anorexia, cough and rash [5]. Toxic epidermal necrolysis (TEN), Steven-Johnson syndrome (SJS) and drug reaction with eosinophilia and systemic T symptoms syndrome (DRESS) are the serious fatal cutaneous reactions associated with AEDs such as lamotrigine (LTG), carbamazepine (CBZ), phenytoin (PHY), valproic acid (VPA) and rarely associated with second-line drugs such as LEV as per the post-marketing surveillance reports and these cutaneous adverse drug reactions (CADRs) are most commonly seen with aromatic AEDs [6][7][8].…”