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Multiple eruptive benign keratoses associated with cyclosporine therapy for psoriasis
Multiple eruptive benign keratoses associated with cyclosporine therapy for psoriasis Marla Ross, MD,a Matthew M. Goodman, MD,a Ronald J. Barr, MD,a, band Shu Y. Liao, MD b Orange, California Cyclosporine has been shown to be effective in the treatment of several cutaneous disorders. I, 2 A variety of cutaneous side effects of cyc1osporine have been reported. This is the first report of the development of multiple nonpilar benign keratoses in a patient receiving cyclosporine for psoriasis.
CASE REPORT A 55-year~0Id Hispanic woman had a I5-year history of psoriasis. She had previously been treated with topical steroids and had never used tars, psoralens, UV light, or systemic medications. Physical examination showed that her psoriatic plaques involved her extensor extremities, scalp, and trunk. The patient was started with a study protocol with cyclosporine, 2.5 mg/kg every 12 hours for three doses weekly. The dose was increased to 7 mg/kg/ From the Departments of Dermatology" and Pathology,b University of California, Irvine Medical Center. Reprint requests: Marla Ross, MD, Department of Dermatology, University of California, Irvine Medical Center, 101 City Drive South, Orange, CA 92668.
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dose at week 11 because of a limited response. At week 12, she was noted to have 14 verrucous papules, 3 to 5 mm each, that clinically resembled verruca vulgaris. These lesions developed both within or next to psoriatic plaques as well as on uninvolved skin on her extremities and trunk (Fig. 1). Cyclosporine was discontinued. Skin biopsies were performed on three of the verrucous papules. Histologic examination revealed hyperkeratosis, mild hypergranulosis, and acanthosis, consistent with benign keratoses (Fig. 2). Koilocytosis was absent, and pilar structures were not involved. Analysis for human papillomavirus DNA was negative. DISCUSSION In a review of 67 renal transplant patients who were receiving cyclosporine, Bencini et a1. 3 reported skin lesions in more than 80%. Most originated in the pilosebaceous unit and included hypertrichosis, epidermal inclusion cysts, pilar keratoses, acne, folliculitis, and sebaceous hyperplasia. Skin infections, especially herpesvirus infections, were also common, but verrucae were seen in only 4%. There was no correlation between cyc1osporine blood levels and
Fig. 1. Verrucous papules on the arm near psoriatic plaque.
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Fig. 2. Histologic examination of papule reveals hyperkeratosis, mild acanthosis, and papillomatosis. (X40.)
the development ofskin lesions. There have also been several reports of the development of multiple dysplastic (premalignant) keratoses and squamous cell carcinomas in patients treated with cydosporine4, 5 but multiple benign keratoses have not previously been reported. However, Seibel et al. 6 did report the development of multiple cutaneous papillomas in beagles treated with cydosporine. As in our patient, these lesions clinically resembled viral verrucae but did not show histologic evidence of papillomavirus infection nor was papillomavirus DNA detected in the tissue. Benign keratoses have been reported in patients with psoriasis who were not taking cydasporine. However, keratoses in these patients developed after long-term intensive UVB therapy, 7 which our patient did not receive. Cylosporine appears to have contributed to the induction of these benign keratoses in our patient, but the mechanism is unknown. Possible mechanisms include immunomodulation of regulatory controls that suppress development of benign papil-
lomas or even a direct effect on keratinocyte proliferation. REFERENCES
1. Wentzell JM, Baughman RD, O'Connor GJ, et al. Cyclosporine in the treatment of psoriasis. Arch Dermatoll987; 123:163-5. 2. Biren CA, Barr RJ. Dermatologic applications of cyclosporine. Arch Dermatol1986;122:1028-32. 3. Bencini PL, Montagnino G, Sala F, et al. Cutaneous lesions in 67 cyclosporine-treated renal transplant recipients. Dermatologica 1986;172:24-30. 4. Bos JD, Meinardi MMHM. Two distinct squamous cell carcinomas in a psoriasis patient receiving low-dose cyclosporine maintenance treatment. J AM ACAD DERMATOL 1989;21:1305-6. 5. Thompson JF, Allen R, Morris PJ. Skin cancers in renin transplant patients treated with cyclosporine. Lancet 1985; 1:158-9. 6. Seibel W, Sundberg JP, Lesko LJ, et al. Cutaneous papillomatous hyperplasia in cyclosporine-treated beagles. J Invest Dermatol 1989;93:224-30. 7. Gupta AK, Siegel MT, Noble SC, et al. Keratoses in patients with psoriasis: a prospective study in 52 inpatients. J AM ACAD DERMATOL 1990;23:52-5.
CASE REPORT A 55-year~0Id Hispanic woman had a I5-year history of psoriasis. She had previously been treated with topical steroids and had never used tars, psoralens, UV light, or systemic medications. Physical examination showed that her psoriatic plaques involved her extensor extremities, scalp, and trunk. The patient was started with a study protocol with cyclosporine, 2.5 mg/kg every 12 hours for three doses weekly. The dose was increased to 7 mg/kg/ From the Departments of Dermatology" and Pathology,b University of California, Irvine Medical Center. Reprint requests: Marla Ross, MD, Department of Dermatology, University of California, Irvine Medical Center, 101 City Drive South, Orange, CA 92668.
16/4/32371
dose at week 11 because of a limited response. At week 12, she was noted to have 14 verrucous papules, 3 to 5 mm each, that clinically resembled verruca vulgaris. These lesions developed both within or next to psoriatic plaques as well as on uninvolved skin on her extremities and trunk (Fig. 1). Cyclosporine was discontinued. Skin biopsies were performed on three of the verrucous papules. Histologic examination revealed hyperkeratosis, mild hypergranulosis, and acanthosis, consistent with benign keratoses (Fig. 2). Koilocytosis was absent, and pilar structures were not involved. Analysis for human papillomavirus DNA was negative. DISCUSSION In a review of 67 renal transplant patients who were receiving cyclosporine, Bencini et a1. 3 reported skin lesions in more than 80%. Most originated in the pilosebaceous unit and included hypertrichosis, epidermal inclusion cysts, pilar keratoses, acne, folliculitis, and sebaceous hyperplasia. Skin infections, especially herpesvirus infections, were also common, but verrucae were seen in only 4%. There was no correlation between cyc1osporine blood levels and
Fig. 1. Verrucous papules on the arm near psoriatic plaque.
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Fig. 2. Histologic examination of papule reveals hyperkeratosis, mild acanthosis, and papillomatosis. (X40.)
the development ofskin lesions. There have also been several reports of the development of multiple dysplastic (premalignant) keratoses and squamous cell carcinomas in patients treated with cydosporine4, 5 but multiple benign keratoses have not previously been reported. However, Seibel et al. 6 did report the development of multiple cutaneous papillomas in beagles treated with cydosporine. As in our patient, these lesions clinically resembled viral verrucae but did not show histologic evidence of papillomavirus infection nor was papillomavirus DNA detected in the tissue. Benign keratoses have been reported in patients with psoriasis who were not taking cydasporine. However, keratoses in these patients developed after long-term intensive UVB therapy, 7 which our patient did not receive. Cylosporine appears to have contributed to the induction of these benign keratoses in our patient, but the mechanism is unknown. Possible mechanisms include immunomodulation of regulatory controls that suppress development of benign papil-
lomas or even a direct effect on keratinocyte proliferation. REFERENCES
1. Wentzell JM, Baughman RD, O'Connor GJ, et al. Cyclosporine in the treatment of psoriasis. Arch Dermatoll987; 123:163-5. 2. Biren CA, Barr RJ. Dermatologic applications of cyclosporine. Arch Dermatol1986;122:1028-32. 3. Bencini PL, Montagnino G, Sala F, et al. Cutaneous lesions in 67 cyclosporine-treated renal transplant recipients. Dermatologica 1986;172:24-30. 4. Bos JD, Meinardi MMHM. Two distinct squamous cell carcinomas in a psoriasis patient receiving low-dose cyclosporine maintenance treatment. J AM ACAD DERMATOL 1989;21:1305-6. 5. Thompson JF, Allen R, Morris PJ. Skin cancers in renin transplant patients treated with cyclosporine. Lancet 1985; 1:158-9. 6. Seibel W, Sundberg JP, Lesko LJ, et al. Cutaneous papillomatous hyperplasia in cyclosporine-treated beagles. J Invest Dermatol 1989;93:224-30. 7. Gupta AK, Siegel MT, Noble SC, et al. Keratoses in patients with psoriasis: a prospective study in 52 inpatients. J AM ACAD DERMATOL 1990;23:52-5.