More on cutaneous reactions to recombinant cytokine therapy

650

Journal of the American Academy of Dermatology October 1996

Correspondence

represents a faulty neologism. A perfectly acceptable formarion, in addition to photoaging, would be heliodermatosis, a term I have used for several years, in a reasonably successful local effort to ward off the use of dermatoheliosis. It requires only the assemblage of two old standbys: helio- and dermatosis and follows the precedent of standard terms like radiodermatitis. I suppose a creation corresponding to dermatoheliosis would be dermatoradi-

osis. Robert S. Bart, MD 562 First Avenue New York, NY 10016

tients with vitiligo in a series of 623 patients with melanoma. Our four patients are from a series of 12 patients with stage llI or IV melanomas (staged according to nomenclature from the American Joint Committee on Cancer) that had been treated with interferon. Interferon alfa augments expression of major histocompatibility complex class I molecules and rumor-associated antigens on melanoma cells and subsequently increases their susceptibility to cytolytic T lymphocytes.3 Numerous observations suggest that vitiligo results from an immune response to antigens common to both malignant and nonmalignant melanocytes.4

Frdddrique-Anne Le Gal, MD Carle Paul, MD Philippe Chemaly, MD Louis Dubertret, MD Department of Dermatology H@ital Saint Louis 1, avenue Claude Vellefaux 75010, Paris, France

M o r e on cutaneous reactions to r e c o m b i n a n t cytokine therapy To the Editor." We read with great interest the CME article by Asnis and Gaspari, which reviewed cutaneous reactions to recombinant cytokine therapy (J A m Acad Dermatol 1995;33:393-410). The authors mentioned induction of vitiligo in patients treated with interleukin-2 for metastatic melanoma but did not report a similar phenomenon with interferons alfa or gamma. We have also failed to find a previous report of interferon-induced vitifigo in the literature. We have seen vitiligo associated with interferon alfa (three cases) and interferon gamma (one case) in patients with stage HI metastatic melanoma (three patients) and stage IV disease (one). They had no history of previous depigmentation or autoimmune disease. In each patient vitiligo occurred at a distance from the site of the primary lesion and correlated with a good response to treatment; three patients are in complete remission 2 to 4 years after treatment. The fourth patient first received chemotherapy (dacarbazine with fotemustine). Because of its inefficacy, this treatment was replaced with interferon alfa associated with monthly infusions of carboplatin. Rapid improvement was observed, and vitiligo appeared on the face 2 months after the beginning of treatment. Only the interferon therapy was discontinued because of hematologic intolerance; the extent of vitifigo subsequently decreased while the malignant process reactivated. The association of vitiligo and interferon therapy appears to be significant for several reasons; first, vitiligo was associated with a good response to treatment. Second, in the fourth patient vitiligo did not occur with the initial treatment and disappeared on interruption of interferon therapy. Third, a spontaneous association between vifiligo and malignant melanoma has been described but is infrequent. Several studies estimate its frequency as less than 5%; in a series of 1130 melanomas, Bystryn et al.1 reported 4.1% associated hypopigmentation and only 1.3% with distant hypopigmentation. More recently, Schallreuter, Levenig, and Berger a reported 3.7% of pa-

REFERENCES 1. Bystryn JC, Rigel D, Friedman RJ, et al. Prognostic significance of hypopigmentation in malignant melanoma. Arch Dermatol 1987;123:1053-5. 2. Schallreuter KU, Levenig C, Berger J. Vitiligo and cutaneous melanoma. Dermatologica 1991;183:239-45. 3. Barth A, Morton DL. The role of adjuvant therapy in melanoma management. Cancer 1995;75:726-34. 4. Cui J, Bystryn JC. Melanoma and vifiligo are associated with antibody responses to similar antigens on pigment cells. Arch D ermatol 1995; 131:314-8. Reply To the Editor." We appreciate the comments of Le Gal et al. regarding the role of interferon in the pathogenesis of immunotherapy-induced vitiligo in patients with metastatic melanoma. The clinical histories summarized by this group are compatible with this phenomenon. Three of their patients had received interferon alfa and one had received interferon gamma as immunotherapy for stage HI or'IV melanoma. In their series of 12 patients who had been treated with interferon there was a remarkably high incidence of vitiligo (25% [3 of 12 patients]), which is higher than has been reported for spontaneously occurring vitifigo in patients with metastatic melanoma (estimated frequency of approximately 4%).1, 2 The interesting fact about these patients described by Le Gal et al. is that only one of four patients received chemoimmunotherapy (a term used to describe traditional chemotherapy sequentially followed by interferon immunotherapy). Thek findings suggest that interferon immunotherapy alone can induce vitiligo and that previous chemotherapy is not necessary to prime the patient for this phenomenon. In the studies that we summarized in our review, all patients who had vifiligo had received