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Systemic therapy with cyclosporine
Journal of the American Academy of Dermatology
278 Correspondence fusion between what is inborn and what is culturally acquired is understandably one of the hallmarks of racism andas such should not be permitted in scientific literature. Stephen E. Silver, MD 301 Montauk Ave. New London, CT 06320
treatment with cyclosporine [Letter reply]. J AM ACAD DERMATOL 1991;24:152. 3. Boixeda JP, Soria C, Medina S, et al. Bullous pemphigoid and psoriasis: treatment with cyclosporine. J AM ACAD DERMATOL 1991;24:152. 4. Koerber WA, Price NM, Watson W. Coexistence of psoriasis and bullous pemphigoid. Arch Dermatol 1978;114:
1643-6. . 5. Albergo R, Gilgor R. Delayed onset of bullous pemphigoid
after PUVA and sunlight treatment of psoriasis. Cutis
Bullous pemphigoid and severe erythrodermic psoriasis: Combined low-dose treatment with cyclosporine and systemic steroids To the Editor: We read with interest the debate regarding the use of dapsone, 1,2 100 mg/day, versus cyclosporine,3 5 mg/kg/day, as alternative treatments of coexisting bullous pemphigoid and psoriasis. We have seen a 57-year-old man, with mild dilatative cardiomyopathy and a 7-year history of psoriasis, who received different antipsoriatic treatments (sunlight, tar, anthralin).4.5 Recently, after long-term sunlight exposure, he had a generalized flare of psoriasis that evolved into an exfoliative erythroderma complicated by the onset of severe bullous pemphigoid with large and widely distributed bullae. The exfoliative erythroderma and the blistering eruption cleared in 2 to 3 weeks after administration of cyclosporine at a dose of 3 mg/kg/day instead of 5 mg/kg/day3 or 6 to 8 mg/kg/day6 as reported by others. The lower dose was used because of his cardiovascular impairment and to keep his whole-blood cyclosporine levels below 200 to 300 ng/ml(monoclonal antibody radioimmunoassay). The cyclosporine was combined with oral Deflazacort, 12 mg/day. After the initial clearing, we could reduce the dosage of the two drugs to 1.5 mg/kg/day and 6 mg/day, respectively, to complete healing. After 11 months, clinical remission has been maintained and there have been no side effects. We emphasize the effectiveness of this combined low-dose treatment for severe cases such as ours, especially when complicated by renal, cardiovascular, or metabolic disorders. The considerable reduction in dosage of both cyclosporine and steroids compared with those usually suggested allows for the avoidance of significant side effects and minimizes the occurrence of rebound phenomena. Luca Bianchi, MD, Stefano Gatti, MD, and Gabriele Nini, MD Department of Dermatology Tor Vergata University, Rome. Italy
REFERENCES 1. Hisler B, Blumenthal NC, Aronson Pl, et al. Bullous pemphigoid in psoriatic lesions. JAM ACAD DERMATOL 1989; 20:683-4.
2. Hashimoto K, Hisler B. Bullous pemphigoid and psoriasis:
1982;30:621-4.
6. Barthelemy H, Thivolet J, Cambazard F, et aL La ciclosporine dans Ie traitment de la pemphigoide bulleuse: etude preliminaire. Ann Dermatol Venereal 1986;113:309-13. Reply To the Editor: The case discussed by Drs. Bianchi, Gatti, and Nini uses low-dose cyclosporine and steroids in the treatment of coexisting bullous pemphigoid and erythrodermic psoriasis. Treatment remains an interesting challenge. Certainly cyclosporine in low doses still has considerable risk in a patient already with impaired cardiac function. Unfortunately, studies show that moderate nonprogressive nephrotoxicity can be expected even at a low dosage of cyclosporine. Therefore its long-term use is limited. We wonder whether this patient could have been maintained with alternative therapy such as ours once the erythroderma and bullous lesions subsided. Barbara M. Hisler, MD,a and Ken Hashimoto, MJY Dermatology Division Long Island Jewish Medical Center Long Island Campus for the Albert Einstein College ofMedicine New Hyde Park, NY 11 042 a and the Department ofDermatology and Syphilology Wayne State University School of Medicinei' 540 E. Canfield Ave. Detroit, MI48201
Systemic therapy with cydosporine To the Editor: In the article by Fradin et al. (J AM ACAD DERMATOL 1991;25:1065-7), the authors describe the complete resolution ofsymptoms during systemic therapy with cyclosporine in three cases of severe chronic idiopathic urticaria and angioedema. We would like to comment on the possible mechanisms of these observations. To clarify the mechanism of action of cyclosporine in mast cell-mediated skin diseases such as urticaria and eczema, we recently investigated its effects on isolated skin mast cells. The results demonstrate that pharmacologicallyrelevantconcentrations (l nmol/Lto 10J1.mol/L) of cyclosporine inhibit FcERI-mediated and calcium ionophore A23187-induced releaseofhistamine and tryptase
Volume 27 Number 2, Part 1 August 1992
Correspondence 279
in a dose-dependent fashion (unpublished observations, manuscript submitted). The biologically inactive analog cyclosporine H did not exert any inhibitory functions, suggesting that the cyclosporine-induced effects in basephils and mast cells are mediated by the cyclosporinebinding protein cyclophilin. 1 Thus these antiallergic properties of cyclosporine and the findings from other laboratories2,3 may contribute to some of its excellent therapeutic effects in chronic urticaria and severe inflammatory skin diseases. Ulrich Amon, MD Helmut H. Wolff, MD Department ofDermatology, Medical University ofLubeck Ratzeburger Allee 160 D-2400 Lubeck, Germany REFERENCES 1. Quesniaux VFJ, Schreier MH, Wenger RM, et al. Cyclophilin binds to the region of cyclosporine involved in its immunosuppressive activity. Eur J Immunol1987;17:1359. 2. Hultsch T, Rodriguez JL, Kaliner MA, et al. Cyclosporin A inhibits degranulation of rat basophilic leukemia cells and human basophils: inhibition of mediator release without affecting PI hydrolysis and Ca2+ fluxes. J Immunol 1990; 144:2659. 3. Cirillo R, Triggiani M, Siri L, et al. Cyclosporin A rapidly inhibits mediator release from human basophils presumably by interacting with cyclophilin. J Immunol 1990; 144:3891.
Sebaceous carcinomas of the ocular adnexa and the Muir-Torre syndrome To the Editor: Lober and Fenske are to be commended on their excellent review of basal cell, squamous cell, and sebaceous gland carcinomas of the periorbital region (J AM ACAD DERMATOL 1991;25:685-90). An important issue that was not addressed in their manuscript concerns the evaluation for the Muir-Torre syndrome in a patient in whom a sebaceous gland carcinoma of the periorbital region is diagnosed. The Muir-Torre syndrome is an autosomal dominant genodermatosis characterized by the concurrent or sequential documentation of at least a single sebaceous gland tumor (adenoma, epithelioma, or carcinoma), with or without keratoacanthomas, and a minimum of one internal malignancy.l To date, approximately 130 patients with the syndrome have been reported. I- 13 A minimum of 29 patients with the MuirTorre syndrome had an associated sebaceous gland carcinoma; in 15 of these persons, the sebaceous carcinoma was ocular in origin. l -4 Muir-Torre syndrome-associated sebaceous gland tumors are rare. The incidence of Muir-Torre syndrome in patients diagnosed with one of these sebaceous lesions has
only been addressed in one retrospective study: a review of the histopathologic specimens stored within the Department of Dermatology at the Mayo Clinic during a 60-year period (1923 through 1983) revealed that 25 of the 59 patients (42%) with at least one sebaceous gland tumor had one or more associated visceral cancers. 5 Two retrospective studies on persons having sebaceous gland carcinomas of the eyelid commented on the development of a second primary malignancy in these patients (who thereby fulfilled the currently accepted diagnostic criteria for the Muir-Torre syndrome). Doxanas and Green 2 reported that two of the 40 patients with sebaceous gland carcinomas that they reviewed died of other malignant neoplasms. Of the 43 patients with sebaceous carcinoma of the eyelid reviewed by Wolfe et al.,3 a maximum of seven persons (who had not been exposed to irradiation) had a second malignant tumor. A long-term prospective study to determine the incidenceof Muir-Torresyndrome in patients diagnosed with an ocular or a nonocular sebaceous gland carcinoma, a sebaceous epithelioma, and/or a sebaceous adenoma is warranted. Until such a study is performed, the current medical! and dermatologic6 literature suggests that the detection of even a single MuirTorre syndrome-associated sebaceous gland neoplasm should prompt the consideration of and appropriate evaluation for this syndrome. Philip R. Cohen, MD Departments ofDermatology and Pathology The University of Texas Medical School at Houston Houston, TX 77030 REFERENCES 1. Cohen PR, Kohn SR, Kurzrock R. Association of sebaceous gland tumors and internal malignancy: the MuirTorre syndrome. Am J Moo 1991;90:606-13. 2. Doxanas MT, Green WR. Sebaceous gland carcinoma: review of 40 cases. Arch Ophthahnol 1984;102:245-9. 3. Wolfe JT III, Yeatts RP, Wick MR, et al. Sebaceous carcinoma of the eyelid: errors in clinical and pathologic diagnosis. Am J Surg PathoI1984;8:597-606. 4. Cohen PRo The Muir-Torre syndrome in patients with hematologic malignancies. Am J Hematol (In press.) 5. Finan MC, Connolly SM. Sebaceous gland tumors and systemic disease: a clinicopathologic analysis. Medicine (Baltimore) 1984;63:232-42. 6. Rothenberg J, Lambert WC, Vail JT Jr, et aI. The MuirTorre (Torre's) syndrome: the significance of a solitary sebaceous tum01:' JAM ACAD DERMATOL 1990;23:638-40. 7. Vignon-Pennanmen MD, Houitte 0, Foldes C, et al. Syndrome de Torre-Muir. Ann Dermatol Venereal 1986;113:1030-2. 8. Bonetti M, Facchetti F, Gavazzoni R, et al. Muir-Torre's syndrome: report of a case with a long follow-up. Pathologica 1987;79:647-53. 9. Wyman A, Brown IN, Zeiderman MR, et al. Multiple sebaceous neoplasms and visceral carcinomas: Torre's syndrome. Eur J Surg OncoI1990;16:74-6. 10. Wagner RF Jr, Sanchez RL. Presentation of sebaceous
278 Correspondence fusion between what is inborn and what is culturally acquired is understandably one of the hallmarks of racism andas such should not be permitted in scientific literature. Stephen E. Silver, MD 301 Montauk Ave. New London, CT 06320
treatment with cyclosporine [Letter reply]. J AM ACAD DERMATOL 1991;24:152. 3. Boixeda JP, Soria C, Medina S, et al. Bullous pemphigoid and psoriasis: treatment with cyclosporine. J AM ACAD DERMATOL 1991;24:152. 4. Koerber WA, Price NM, Watson W. Coexistence of psoriasis and bullous pemphigoid. Arch Dermatol 1978;114:
1643-6. . 5. Albergo R, Gilgor R. Delayed onset of bullous pemphigoid
after PUVA and sunlight treatment of psoriasis. Cutis
Bullous pemphigoid and severe erythrodermic psoriasis: Combined low-dose treatment with cyclosporine and systemic steroids To the Editor: We read with interest the debate regarding the use of dapsone, 1,2 100 mg/day, versus cyclosporine,3 5 mg/kg/day, as alternative treatments of coexisting bullous pemphigoid and psoriasis. We have seen a 57-year-old man, with mild dilatative cardiomyopathy and a 7-year history of psoriasis, who received different antipsoriatic treatments (sunlight, tar, anthralin).4.5 Recently, after long-term sunlight exposure, he had a generalized flare of psoriasis that evolved into an exfoliative erythroderma complicated by the onset of severe bullous pemphigoid with large and widely distributed bullae. The exfoliative erythroderma and the blistering eruption cleared in 2 to 3 weeks after administration of cyclosporine at a dose of 3 mg/kg/day instead of 5 mg/kg/day3 or 6 to 8 mg/kg/day6 as reported by others. The lower dose was used because of his cardiovascular impairment and to keep his whole-blood cyclosporine levels below 200 to 300 ng/ml(monoclonal antibody radioimmunoassay). The cyclosporine was combined with oral Deflazacort, 12 mg/day. After the initial clearing, we could reduce the dosage of the two drugs to 1.5 mg/kg/day and 6 mg/day, respectively, to complete healing. After 11 months, clinical remission has been maintained and there have been no side effects. We emphasize the effectiveness of this combined low-dose treatment for severe cases such as ours, especially when complicated by renal, cardiovascular, or metabolic disorders. The considerable reduction in dosage of both cyclosporine and steroids compared with those usually suggested allows for the avoidance of significant side effects and minimizes the occurrence of rebound phenomena. Luca Bianchi, MD, Stefano Gatti, MD, and Gabriele Nini, MD Department of Dermatology Tor Vergata University, Rome. Italy
REFERENCES 1. Hisler B, Blumenthal NC, Aronson Pl, et al. Bullous pemphigoid in psoriatic lesions. JAM ACAD DERMATOL 1989; 20:683-4.
2. Hashimoto K, Hisler B. Bullous pemphigoid and psoriasis:
1982;30:621-4.
6. Barthelemy H, Thivolet J, Cambazard F, et aL La ciclosporine dans Ie traitment de la pemphigoide bulleuse: etude preliminaire. Ann Dermatol Venereal 1986;113:309-13. Reply To the Editor: The case discussed by Drs. Bianchi, Gatti, and Nini uses low-dose cyclosporine and steroids in the treatment of coexisting bullous pemphigoid and erythrodermic psoriasis. Treatment remains an interesting challenge. Certainly cyclosporine in low doses still has considerable risk in a patient already with impaired cardiac function. Unfortunately, studies show that moderate nonprogressive nephrotoxicity can be expected even at a low dosage of cyclosporine. Therefore its long-term use is limited. We wonder whether this patient could have been maintained with alternative therapy such as ours once the erythroderma and bullous lesions subsided. Barbara M. Hisler, MD,a and Ken Hashimoto, MJY Dermatology Division Long Island Jewish Medical Center Long Island Campus for the Albert Einstein College ofMedicine New Hyde Park, NY 11 042 a and the Department ofDermatology and Syphilology Wayne State University School of Medicinei' 540 E. Canfield Ave. Detroit, MI48201
Systemic therapy with cydosporine To the Editor: In the article by Fradin et al. (J AM ACAD DERMATOL 1991;25:1065-7), the authors describe the complete resolution ofsymptoms during systemic therapy with cyclosporine in three cases of severe chronic idiopathic urticaria and angioedema. We would like to comment on the possible mechanisms of these observations. To clarify the mechanism of action of cyclosporine in mast cell-mediated skin diseases such as urticaria and eczema, we recently investigated its effects on isolated skin mast cells. The results demonstrate that pharmacologicallyrelevantconcentrations (l nmol/Lto 10J1.mol/L) of cyclosporine inhibit FcERI-mediated and calcium ionophore A23187-induced releaseofhistamine and tryptase
Volume 27 Number 2, Part 1 August 1992
Correspondence 279
in a dose-dependent fashion (unpublished observations, manuscript submitted). The biologically inactive analog cyclosporine H did not exert any inhibitory functions, suggesting that the cyclosporine-induced effects in basephils and mast cells are mediated by the cyclosporinebinding protein cyclophilin. 1 Thus these antiallergic properties of cyclosporine and the findings from other laboratories2,3 may contribute to some of its excellent therapeutic effects in chronic urticaria and severe inflammatory skin diseases. Ulrich Amon, MD Helmut H. Wolff, MD Department ofDermatology, Medical University ofLubeck Ratzeburger Allee 160 D-2400 Lubeck, Germany REFERENCES 1. Quesniaux VFJ, Schreier MH, Wenger RM, et al. Cyclophilin binds to the region of cyclosporine involved in its immunosuppressive activity. Eur J Immunol1987;17:1359. 2. Hultsch T, Rodriguez JL, Kaliner MA, et al. Cyclosporin A inhibits degranulation of rat basophilic leukemia cells and human basophils: inhibition of mediator release without affecting PI hydrolysis and Ca2+ fluxes. J Immunol 1990; 144:2659. 3. Cirillo R, Triggiani M, Siri L, et al. Cyclosporin A rapidly inhibits mediator release from human basophils presumably by interacting with cyclophilin. J Immunol 1990; 144:3891.
Sebaceous carcinomas of the ocular adnexa and the Muir-Torre syndrome To the Editor: Lober and Fenske are to be commended on their excellent review of basal cell, squamous cell, and sebaceous gland carcinomas of the periorbital region (J AM ACAD DERMATOL 1991;25:685-90). An important issue that was not addressed in their manuscript concerns the evaluation for the Muir-Torre syndrome in a patient in whom a sebaceous gland carcinoma of the periorbital region is diagnosed. The Muir-Torre syndrome is an autosomal dominant genodermatosis characterized by the concurrent or sequential documentation of at least a single sebaceous gland tumor (adenoma, epithelioma, or carcinoma), with or without keratoacanthomas, and a minimum of one internal malignancy.l To date, approximately 130 patients with the syndrome have been reported. I- 13 A minimum of 29 patients with the MuirTorre syndrome had an associated sebaceous gland carcinoma; in 15 of these persons, the sebaceous carcinoma was ocular in origin. l -4 Muir-Torre syndrome-associated sebaceous gland tumors are rare. The incidence of Muir-Torre syndrome in patients diagnosed with one of these sebaceous lesions has
only been addressed in one retrospective study: a review of the histopathologic specimens stored within the Department of Dermatology at the Mayo Clinic during a 60-year period (1923 through 1983) revealed that 25 of the 59 patients (42%) with at least one sebaceous gland tumor had one or more associated visceral cancers. 5 Two retrospective studies on persons having sebaceous gland carcinomas of the eyelid commented on the development of a second primary malignancy in these patients (who thereby fulfilled the currently accepted diagnostic criteria for the Muir-Torre syndrome). Doxanas and Green 2 reported that two of the 40 patients with sebaceous gland carcinomas that they reviewed died of other malignant neoplasms. Of the 43 patients with sebaceous carcinoma of the eyelid reviewed by Wolfe et al.,3 a maximum of seven persons (who had not been exposed to irradiation) had a second malignant tumor. A long-term prospective study to determine the incidenceof Muir-Torresyndrome in patients diagnosed with an ocular or a nonocular sebaceous gland carcinoma, a sebaceous epithelioma, and/or a sebaceous adenoma is warranted. Until such a study is performed, the current medical! and dermatologic6 literature suggests that the detection of even a single MuirTorre syndrome-associated sebaceous gland neoplasm should prompt the consideration of and appropriate evaluation for this syndrome. Philip R. Cohen, MD Departments ofDermatology and Pathology The University of Texas Medical School at Houston Houston, TX 77030 REFERENCES 1. Cohen PR, Kohn SR, Kurzrock R. Association of sebaceous gland tumors and internal malignancy: the MuirTorre syndrome. Am J Moo 1991;90:606-13. 2. Doxanas MT, Green WR. Sebaceous gland carcinoma: review of 40 cases. Arch Ophthahnol 1984;102:245-9. 3. Wolfe JT III, Yeatts RP, Wick MR, et al. Sebaceous carcinoma of the eyelid: errors in clinical and pathologic diagnosis. Am J Surg PathoI1984;8:597-606. 4. Cohen PRo The Muir-Torre syndrome in patients with hematologic malignancies. Am J Hematol (In press.) 5. Finan MC, Connolly SM. Sebaceous gland tumors and systemic disease: a clinicopathologic analysis. Medicine (Baltimore) 1984;63:232-42. 6. Rothenberg J, Lambert WC, Vail JT Jr, et aI. The MuirTorre (Torre's) syndrome: the significance of a solitary sebaceous tum01:' JAM ACAD DERMATOL 1990;23:638-40. 7. Vignon-Pennanmen MD, Houitte 0, Foldes C, et al. Syndrome de Torre-Muir. Ann Dermatol Venereal 1986;113:1030-2. 8. Bonetti M, Facchetti F, Gavazzoni R, et al. Muir-Torre's syndrome: report of a case with a long follow-up. Pathologica 1987;79:647-53. 9. Wyman A, Brown IN, Zeiderman MR, et al. Multiple sebaceous neoplasms and visceral carcinomas: Torre's syndrome. Eur J Surg OncoI1990;16:74-6. 10. Wagner RF Jr, Sanchez RL. Presentation of sebaceous