Abstract

Lichen planus pigmentosus inversus (LIPPI) is a rare variant within the spectrum of lichenoid dermatoses, characterized by sharply demarcated hyperpigmented lesions predominantly affecting intertriginous areas. Its pathogenesis remains incompletely understood, but immune-mediated mechanisms triggered by exogenous factors have been proposed. We report the case of an 80-year-old Caucasian female who developed extensive, reticulated brownish-grey hyperpigmentation involving multiple flexural sites shortly after the fifth intra-articular injection of the homeopathic combination preparation Zeel comp. N for knee pain. Histopathological examination showed a markedly atrophic epidermis with compact orthokeratosis, focal hypergranulosis, basal vacuolar/interface change, pigment incontinence, and a band-like lymphocytic infiltrate; these findings were compatible with LIPPI. The temporal association with repeated intra-articular administration of botanical and sulfur-containing compounds suggests a possible trigger; however, causality remains speculative. Prick and patch testing with the injection solution were negative, no rechallenge was performed, and pharmacovigilance assessment by the Naranjo algorithm supported only a possible adverse drug reaction. Several constituents, including Toxicodendron derivatives, Arnica montana and Solanum dulcamara, are recognized sensitizers capable of inducing delayed-type immune responses. Importantly, allergic contact sensitization and lichenoid interface dermatitis are distinct processes; in the present case, sensitization or systemic immune stimulation is considered only as a potential upstream trigger of a lichenoid reaction pattern. Similar lichenoid eruptions, including LIPPI, have been reported after systemic immune stimulation such as COVID-19 vaccination or targeted therapies. Differential diagnoses, particularly ashy dermatosis, were considered less likely because of the inverse/flexural distribution and clinico-pathological evidence of lichenoid interface dermatitis with epidermal atrophy. Treatment with systemic corticosteroids, acitretin, and topical tacrolimus improved pruritus, whereas hyperpigmentation persisted. This case highlights a possible temporal association between intra-articular administration of biologically active compounds and LIPPI, while emphasizing the need for cautious interpretation, pharmacovigilance data, and further reports.

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