A case report described a temporal association between tirzepatide use and the onset of lichen planus pigmentosus inversus, adding to limited reports of rare cutaneous reactions associated with glucagon-like peptide-1 receptor agonist–based therapies.
The report involved a 46-year-old female patient with Fitzpatrick skin type II who developed pruritic brown macules in the bilateral axillae and groin 6 to 7 months following initiation of tirzepatide for weight loss. The patient reported a 1-year history of lesions that began 6 to 7 months following tirzepatide initiation and had remained stable for approximately 10 months.
Lichen planus pigmentosus inversus refers to involvement of intertriginous areas rather than the more typical photodistributed presentation. The researchers noted that lichen planus pigmentosus is most commonly reported in patients with Fitzpatrick skin types III–IV, making this presentation in a patient with type II skin notable.
The patient reported no new oral, injectable, or topical medications — prescribed, over-the-counter, or naturopathic — within the preceding 2 years. She also reported no hair, nail, oral, ocular, genital, or systemic symptoms. On examination, clinicians observed well-demarcated, nonerythematous, uniformly brown macules with scant scale in the bilateral axillae; groin lesions were reported historically but were not present at the visit.
A shave biopsy demonstrated lichenoid interface dermatitis with dyskeratotic keratinocytes, abundant pigment incontinence, scattered melanophages, and scattered eosinophils, supporting a diagnosis of lichen planus pigmentosus. The eosinophilic component was considered supportive of a drug-induced lichenoid eruption pattern.
The patient received topical tacrolimus ointment, which resolved the associated pruritus, although the hyperpigmentation persisted. Additional treatment options for residual hyperpigmentation were discussed but declined.
The researchers noted that drug-induced lichen planus pigmentosus has previously been reported with infliximab, gefitinib, hydroxyurea, and gold. To their knowledge, however, no prior reports have described lichen planus pigmentosus or hyperpigmentation associated with glucagon-like peptide-1 or glucose-dependent insulinotropic polypeptide receptor agonists.
The timing was considered compatible with drug-induced lichenoid eruptions, which have been reported to occur from 1 to 208 weeks following exposure, with an average latency of 15.7 weeks and most cases occurring within the first 12 months. The patient’s onset at 6 to 7 months fell within that expected timeframe, which the researchers cited as supporting the plausibility of the association.
The researchers discussed tirzepatide discontinuation with the patient, but she elected to continue therapy. The absence of drug discontinuation or rechallenge limits causal interpretation, and the report cannot establish incidence, recurrence risk, or whether the finding reflects a broader class effect.
“The mechanism by which tirzepatide induces lichen planus pigmentosus remains unclear,” wrote lead study author Craig M. Fisher, MD, of Wilford Hall Ambulatory Surgical Center, and colleagues. The researchers noted that glucagon-like peptide-1 receptor agonists may influence innate immune regulation, raising the possibility that immune-mediated interface injury contributed to pigment incontinence and subsequent hyperpigmentation, although this hypothesis remains speculative.
The researchers reported no conflicts of interest.
Source: JAAD Case Reports
