Acetaminophen‐induced lichenoid keratosis: a new way to look at an old lesion

Editor Acetaminophen (paracetamol) is a widely used analgesicantipyretic drug, easily obtained over the counter and generally well tolerated. Its potential for drug interactions is often underestimated. Adverse skin reactions, some life threatening, involve almost all arms of the innate and acquired immune systems, and include urticarial anaphylactoid reactions, fixed drug eruptions, pigmented purpuras, acute generalized exanthematous pustulosis, toxic epidermal necrolysis, and even a case of IgA bullous dermatosis. The association of acetaminophen with lichenoid eruption is rare. We encountered a case of what appeared to be acetaminophen-induced lichenoid keratosis (LK) in a 63year-old, otherwise healthy Ashkenazi Jewish woman who presented with a 2-week history of an asymptomatic, solitary, flat-topped, small ovoid plaque on the ventral side of the right arm. The plaque was erythematous, with a brownish hue. She had ingested acetaminophen for a headache 1 day prior to appearance of the lesion. She reported a previous episode of clinically diagnosed lichenoid eruption in the same area following ingestion of acetominophen, which disappeared and reoccurred after challenge, leaving no pigmentary changes. The lag time between ingestion of the drug and appearance of the lesions at that time was much longer than in the current incident. Histological examination of a completely excised lesion revealed a lichenoid inflammatory infiltrate obscuring the dermo-epidermal junction, with vacuolar changes, occasional Civatte bodies and pigment incontinence. The inflammatory infiltrate consisted mainly of T cell lymphocytes, with mixed CD4 and CD8 populations (fig. 1), but no eosinophils or plasma cells. The epidermis showed focal acanthosis without hypergranulosis or parakeratosis. Hyperpigmentation features of solar lentigo were encountered. In vitro interferon gamma release test performed on the patient’s lymphocytes, described previously, showed a rise in interferon release, with acetaminophen over the predrug test level (480 pg/mL vs. 350 pg/mL, respectively). This test is recognized as a safe, informative tool for identifying drugs associated with various forms of adverse cutaneous drug reactions. Table 1 summarizes the major clinical and histological features of LP-associated lesions, showing the overlap between entities. Our case exhibited LK clinically, with mixed histological evidence of LK and lichenoid drug eruption, suggesting that the two are in fact reactive immunological processes, probably to the same insult. This observation was supported by the positive rechallenge to acetaminophen, accompanied by the in vitro rise in the release of interferon gamma, a key orchestrating cytokine in T-lymphocyte processes. In view of the usual slow growth of lichenoid lesions, their appearance the third time only 1 day after ingestion of acetominophen is intriguing. This might be explained by the fact that in reactive recurrent cases like ours, local T cells are already activated, rendering a shortened lag time. fig. 1 Lichenoid inflammatory infiltrate obscuring the dermal epidermal junction with occasional Civatte bodies. Immunohistochemical stains of the lymphocyte infiltrate show pronounced CD4 (× 20).