A Probable Case of Chlorpromazine-induced Lichenoid Eruptions Initially Involved Palmoplantar Areas.

Sir,

A 30-year-old woman visited our hospital complaining of itchy eruptions of 1 month duration. She had schizophrenia for over 10 years, and had been treated with a number of drugs, such as risperidone, milnacipran hydrochloride, levomepromazine maleate, clonazepam, bromperidol, ethyl loflazepate, diazepam, chlorpromazine, bromazepam, and rilmazafone. Physical examination revealed a number of keratotic erythematous papules on the inner aspects of the feet, soles and palms [Figure 1a–c]. She had neither mucosal nor nail lesions. Treatment with topical corticosteroids was started. However, the skin eruptions were further increased in number and spread to the trunk and umbilicus. Laboratory data of liver and renal function, and anti-nuclear antibody were normal. A biopsy specimen revealed mild acanthosis with mild parakeratosis in the thickened corneum and hypergranulosis, with liquefaction degeneration of the basal cell layers of the epidermis, infiltration of a number of mononuclear cells, colloid bodies, and melanophages in the upper dermis [Figure 1d]. Eosinophil infiltration was not seen. Direct immunofluorescence was not carried out. Because as far as we searched, the only drug that was previously reported to induce lichenoid eruption was chlorpromazine, only chlorpromazine was discontinued. The eruptions soon showed improvement with the aid of topical corticosteroid ointment and completely disappeared within 6 months [Figure 1e]. Neither drug induced lymphocyte stimulation test nor patch test was carried out, and, unfortunately, the patient refused a drug challenge test.

Figure 1

(a) Palmoplantar keratotic papules and plaques. (b and c) In particular, keratotic plaques are prominent on the bilateral soles. (d) Histological features showing lichenoid changes (H and E, original magnification ×100). (e) Marked improvement on the plantar lesion after discontinuance of chlorpromazine

Our patient had been treated with chlorpromazine for schizophrenia for 5 years. At the initial visit, she presented with slightly keratotic erythematous papules on the palmoplantar areas, which were worsened and developed into keratotic plaques, gradually spreading to the trunk during the course. Histological examination revealed lichenoid changes. Although she had been taking various kinds of drugs for schizophrenia, the discontinuance of chlorpromazine only resulted in complete clearance of skin lesions within 6 months.

Chlorpromazine-induced photosensitivity has been previously reported,[123] as well as a case of photosensitive lichenoid reaction due to chlorpromazine.[4] However, to our knowledge, this is the first report of chlorpromazine-induced lichenoid eruption unassociated with photosensitivity. Our case is the first case of lichenoid drug eruption probably due to chlorpromazine, especially with plantar hyperkeratosis. The trunk was later involved, whereas neither the face nor forearms were involved. Although the mechanism predominantly involving the palms and soles is unclear, association with the Koebner phenomenon may exist in our case. Lichenoid tissue reaction is characterized by epidermal basal layers injury by T-cells. Effector T-cells activated by several stimulants or cross-reaction with drugs, viruses, chemicals, or self-antigens induce lichenoid tissue reactions, and in our case, drug-specific T-cells, especially CD8-positive T-cells, may be recruited to the mechanically stimulated sites.

In cases of lichen planus-like drug eruption, neither drug induced lymphocyte stimulation test nor patch test is useful for the identification of the causative drugs. Also, we could not carry out a challenge test of chlorpromazine because the patient did not agree to it. Nevertheless, we concluded that chlorpromazine was probably the causative drug because the cutaneous lesions were completely improved by the discontinuance of chlorpromazine only. Alternatively, another possibility that a combination of chlorpromazine and other drugs precipitated skin rash may still remain. As there are a number of drugs used in the treatment of patients with psychiatric disorders, it is difficult to identify the causative drug. It is currently unknown why cutaneous eruptions appeared after a long period from the start of chlorpromazine in this case. One possibility is that longer time course was needed to gain sensitivity. In conclusion, it is necessary to be aware that chlorpromazine may induce lichenoid drug eruption.

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