Case Report: Erythema Multiforme Induced by Lithium Contact

Erythema multiforme (EM) is an acute, self-limited mucocutaneous disorder commonly triggered by infections (especially herpes simplex virus) and drugs. The authors encountered a case of EM triggered by occupational lithium exposure, with disease course influenced by subsequent re-exposures. While lithium is known to cause cutaneous adverse effects when administered orally for bipolar disorder, EM following lithium contact had not been reported. This report presents a rare case of EM induced by occupational lithium contact after a chemical burn.

Most EM cases (approximately 90%) are associated with infections, particularly herpes simplex virus (HSV) and Mycoplasma pneumoniae; drug-induced EM constitutes less than 10% and is linked to NSAIDs, antiepileptics, and antibiotics. Recurrences are common, and identifying triggers is important for prevention. HSV-associated EM involves delayed-type hypersensitivity with CD34+ cells transporting viral DNA to the epidermis, leading to IFN-γ–mediated inflammation. Drug-induced EM is mechanistically distinct, with TNF-α implicated rather than IFN-γ. Contact erythema multiforme (CEM) has been proposed for EM triggered by skin contact with antigens; immunologic profiles (e.g., keratinocyte ICAM-1 and HLA-DR expression; CD8+ T-cell-mediated keratinocyte apoptosis and TNF-α production) resemble those of EM. Lithium has been reported to potentiate TNF-α secretion and mRNA expression in monocytes, suggesting a plausible pathway for EM induction. Prior reports describe EM after systemic lithium therapy, but not after occupational contact exposure.

Case report of a single patient. A 24-year-old male working in a lithium battery factory sustained a lithium chemical burn. Timeline: two weeks post-burn, and one week before presentation, a solitary erythematous papule appeared at the right wrist at the burn site, spreading within a day to both arms and thighs. Examination: multiple erythematous to purple-red papules and plaques with central dark zones on wrists, arms, and thighs; oral and genital mucosa spared. History negative for herpes simplex; laboratory evaluation notable only for WBC count 11,750/µl. Diagnostic procedure: punch biopsy of right wrist lesion showing scattered lymphocytic infiltration, vacuolar degeneration of basal cells, and necrotic keratinocytes, supporting EM. Treatment: oral methylprednisolone 30 mg/day, tapered over three weeks, resulting in full remission. Outcome and provocation: recurrences occurred upon returning to the lithium battery workplace, appearing on prior lesion sites within approximately 12 hours and resolving after workplace avoidance. Informed consent was obtained for publication.

• EM developed after occupational lithium contact following a chemical burn, with initial lesions at the injury site and rapid centrifugal spread.
• Histopathology showed scattered lymphocytic infiltration, vacuolar degeneration, and necrotic keratinocytes, consistent with EM; mucosal surfaces were spared.
• Laboratory testing showed leukocytosis (WBC 11,750/µl) without other abnormalities; no history of HSV infection.
• Treatment with methylprednisolone 30 mg/day tapered over three weeks led to remission.
• Recurrences occurred rapidly (within ~12 hours) upon re-exposure to the lithium work environment and resolved with avoidance, supporting a causal link.
• To the authors’ knowledge, this is the first reported case of EM following chemical burn and occupational lithium exposure, suggesting lithium contact can trigger EM via immunologic mechanisms, potentially TNF-α–mediated.

The clinical course—onset at the site of lithium chemical burn, rapid dissemination, histology consistent with EM, and prompt recurrences after re-exposure with resolution upon avoidance—implicates lithium contact as the trigger. This aligns with the concept of contact erythema multiforme, where antigen exposure through skin initiates a T-cell–mediated response. Lithium’s known enhancement of TNF-α expression provides a mechanistic rationale for a drug/contact-induced EM pathway distinct from HSV-associated EM, which is IFN-γ–driven. The absence of spongiosis and eosinophil-rich infiltrates argues against allergic contact dermatitis. Lithium’s pharmacokinetic properties (no protein binding, no hepatic metabolism) suggest that metabolic idiosyncrasy is unlikely, further supporting a direct immunomodulatory effect. Identifying lithium exposure as the precipitant informs management: avoidance of the trigger is critical to prevent recurrence.

This case documents EM induced by occupational lithium contact following a chemical burn, with reproducible recurrences upon re-exposure and remission after avoidance. The findings support a contact-induced, TNF-α–linked immunologic mechanism for EM triggered by lithium, distinct from HSV-associated EM. Clinicians should consider occupational and contact exposures, including lithium, in recurrent EM. Future research should clarify the immunopathogenesis of lithium-induced EM and evaluate diagnostic tools (e.g., standardized patch testing protocols) and preventive strategies in occupational settings.

Single-patient case report; no close-up clinical photographs were obtained; no patch testing (including lithium) was performed; precise exposure levels and routes (contact vs inhalation) were not quantified; mechanistic inferences are indirect without cytokine profiling or immunohistochemistry beyond routine histology.