Cutaneous adverse reaction during lithium treatment: a case report and updated systematic review with meta-analysis

Martina Pinna,Giampaolo Minnai,Leonardo Tondo,Piergiorgio Salis,Sergio Puddu,Mirko Manchia

doi:10.1186/s40345-017-0091-7

Abstract

ObjectivesTo present a new case of adverse cutaneous reaction during lithium treatment and to update the systematic review and meta-analysis of the incidence of this adverse reaction.MethodsWe conducted a systematic search (performed in September 2016) for peer-reviewed articles in English indexed in Medline (2011-present). Meta-analytical estimates were obtained using the “Metafor” package.Case presentationMs. H., a 31-year-old Caucasian woman with BD1, was admitted to the inpatient unit for a full-blown psychotic episode and treated with carbamazepine 400 mg q.d., lithium carbonate 450 mg q.d., and risperidone 4 mg q.d. with clinical improvement. After 12 days from the start of psychopharmacological treatment, she manifested a cutaneous reaction that motivated the stop of carbamazepine treatment, as well as the increase in lithium carbonate dose (750 mg q.d.). Risperidone dose remained unvaried. Since the skin lesion persisted after 8 days from withdrawal of carbamazepine, the private practitioner stopped also lithium carbonate treatment (de-challenge), maintaining risperidone treatment. The cutaneous reaction resolved spontaneously after six days from withdrawal of lithium carbonate. Subsequently, the worsening of psychopathological conditions motivated a new admission during which lithium carbonate was reintroduced (16 days after its suspension) (re-challenge). On the following day, we observed an itching erythematous maculopapular rash involving the trunk, the four limbs, and the oral mucosa.ConclusionsOur case of an erythematous maculopapular rash during lithium treatment was the first to present a challenge–de-challenge–re-challenge sequence that suggests causality. Although meta-analysis does not point to an increased rate of adverse skin reaction during lithium treatment, clinicians should not neglect to monitor cutaneous symptoms during lithium treatment.

Highlights

Lithium remains the mainstay for the treatment and prevention of mood episodes in bipolar disorder (BD) (Yatham et al 2013)
Meta-analysis does not point to an increased rate of adverse skin reaction during lithium treatment, clinicians should not neglect to monitor cutaneous symptoms during lithium treatment
Quantitative meta-analytical estimates did not show an increased rate of skin disorders in lithium-treated patients compared to those given placebo (McKnight et al 2012), there is substantial anecdotic evidence supporting this association

Summary

Introduction

Lithium remains the mainstay for the treatment and prevention of mood episodes in bipolar disorder (BD) (Yatham et al 2013). A degree of uncertainty remains, on whether lithium, during short- and long-term treatment, is associated with the manifestation of cutaneous adverse reactions. Quantitative meta-analytical estimates did not show an increased rate of skin disorders in lithium-treated patients compared to those given placebo (McKnight et al 2012), there is substantial anecdotic evidence supporting this association. Some authors indicated that the rate of cutaneous adverse reactions during lithium maintenance therapy might be as high as 45% (Jafferany 2008). Firstly we presented a new case of adverse cutaneous reaction during lithium treatment, confirmed by a re-challenge of the drug after its discontinuation. We updated the study of McKnight et al (2012) which systematically reviewed and performed data synthesis of pertinent literature published until 2010 (McKnight et al 2012)

Objectives

Methods

Findings

Conclusion