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Cyclosporin for palmoplantar pustulosis
Journal of Autoimmunity (1992) 5 (Supplement A), 285-287
Cyclosporin for Palmoplantar Pustulosis
Sakari Reitamo,
Pekka Erkko and Anita Remitz
Department of Dermatology, Helsinki University Central Hospital, HeIsinki, Finland
Palmoplantar pustulosis (PPP) is a chronic skin disease characterized by persistent erythematous, scaly plaques incorporating sterile pustules on palms and soles, which is resistant to most treatments. Recently, two published uncontrolled studies suggested that cyclosporin (CsA) could be an effective treatment for PPP. Similarly, an unpublished, randomized, placebo-controlled study showed that CsA is effective in preventing new pustule formation in PPP. In the present paper we review the treatment of P P P with special emphasis on CsA treatment.
Introduction
Palmoplantar pustulosis (PPP) is a chronic skin disease characterized by persistent erythematous, scaly plaques incorporating sterile pustules on palms and soles. Some authors regard P P P as a form of psoriasis, whereas others regard it as a separate disease entity because of the following: higher age of onset, a clear female predominance, no observed seasonal variation, different histopathology and lack of increased frequency of psoriasis-linked alloantigens (for review see ref 1). PPP is frequently associated with joint symptoms [2, 3] and thyroid disease [4, 5]. In addition, PPP is strongly associated with cigarette smoking [6, 7]. Treatments of PPP
PPP is often resistant to both topical and systemic treatments. T h e most frequently used treatments include potent topical corticosteroids, oral tetracyclines [8] and topical P U V A [9]. These treatments show only limited efficacy in PPP. Better results have been obtained with oral retinoids or PUVA, and combinations of these two treatments [10-13]. Preliminary studies of cyclosporin treatment of PPP
Since Mueller and H e r r m a n n published in 1979 a short paper on cyclosporin (CsA) treatment of psoriasis [ 14], many reports have shown its efficacy psoriasis. Since PPP 285 0896-8411/92/0A0285+03 $03.00/0
© 1992AcademicPress Limited
286
S. R e i t a m o e t a l .
is resistant to most treatments, we decided to try CsA treatment of PPP in a preliminary uncontrolled study of six patients [15]. CsA was taken twice daily at a dosage of 2.5 mg/kg/day for 1-3 months. T h e skin eruptions of both palms and soles clearly improved in all six patients. N o serious side effects were seen. Recently another uncontrolled study suggested that CsA could be effective in the treatment of PPP. Meinardi et al. [16] treated patients with psoriasis who had additional clinical signs of PPP. CsA treatment was p e r f o r m e d at various dosages of CsA which ranged from 1.1 and 6.1 mg/kg/day. All seven patients treated with CsA responded to treatment.
A c o n t r o l l e d s t u d y o f c y c l o s p o r i n in the t r e a t m e n t o f P P P In a double-blind, placebo-controlled study of 40 patients, published in abstract form [17], CsA treatment at 2.5 mg/kg/day for 4 weeks significantly reduced new pustule formation. In a second open label phase of 3 months a daily CsA dose of 1.25 mg/kg proved to be of similar efficacy to 2.5 mg/kg. After termination of CsA treatment, formation of new pustules returned to pretreatment levels after 1 week. T h e major side effect was headache in the 2.5 mg/kg/day group; no significant side effects were seen in the 1.25 mg/kg/day group. W h e n followed up for 1 year after CsA treatment, the majority of the patients were without need for any specific treatment. T h i s study suggests that CsA treatment of 3 to 4 months may cause, after initial flare-up of the disease, a prolonged downregulation of disease activity in PPP.
Conclusion T h e present studies suggest that CsA at 2.5 mg/kg/day is an effective treatment for PPP. Moreover, it seems that m a n y patients with P P P can be treated at lower CsA dosages of approximately 1 mg/kg/day. T h i s is in contrast to psoriasis, which usually does not respond to a CsA dose of 1 mg/kg/day. M o r e importantly, long-term remissions were observed, a p h e n o m e n o n which has not been described in psoriasis patients after CsA treatment. Although CsA is very effective in the treatment of skin lesions in PPP, it remains to be established, whether this drug has an effect on other clinical manifestations frequently accompanying PPP, i.e. thyroid abnormalities and arthropathies.
Acknowledgements T h e original studies reported here were supported by the Paulo Foundation and Sandoz Ltd.
References 1. Ashurst, P.J.C. 1964. Relapsing pustular eruptions of the hands and feet. Br. J. Dermatol. 76:169-180 2. Hradil, E., C. F. Gentz, T. Matilainen, H. M611er, L. Sauz6n, and A. Ud6n. 1988. Skeletal involvement in pustulosis plamo-plantaris with special reference to sterno-costoclavicular joints. Acta Derm. Venereol. ( Stockh. ) 68:65-73
Cyclosporin forpalmoplantar pustulosis 287 3. Jurik, A. G. and T. Ternowitz. 1988. Frequency of skeletal disease, artro-osteitis, in patients with pustulosis palmoplantaris. J. Am. Acad. Dermatol. 18:666-671 4. Ros~n, K., G. Lindstedt, H. Mobacken, and E. Nystr6m. 1988. Thyroid function in patients with pustulosis palmoplantaris. J. Am. Acad. Dermatol. 19:1009-1016 5. Agner, T., J. H. Sindrup, M. Hoier-Madsen, and L. Hegedfis. 1989. Thyroid disease in pustulosis palmoplantaris. Br. J. Dermatol. 121:487--491 6. O'Doherty, C.J. andC. Macintyre. 1985. Palmoplantarpustulosisandsmoking. Br. Med. J. 291:861-864 7. Cox, N. H. and S. Ray. 1987. Neutrophil leucocyte morphology, cigarette smoking and palmoplantar pustulosis. Int. J. Dermatol. 26:445--447 8. Ward, J. M., M. F. Corbett, and M. J. Hanna. 1976. A double-blind trial of clomocycline in the treatment of resistant palmoplantar pustulosis. Br. J. Dermatol. 95:317-322 9. Layton, A. M., R. Sheehan-Dare, and W. J. Cunliffe. 1991. A double-blind, placebocontrolled trial of topical PUVA in persistent palmoplantar pustulosis. Br. J. Dermatol. 124:581-584 10. Fredriksson, T. 1978. Oral treatment of psoriasis and pustulosis palmoplantaris with RO 10-9359. Dermatologica 157 (Suppl 1): 13-18 11. Lassus, A., J. Lauharanta, and A. Eskelinen. 1985. The effect ofetretinate compared with different regimens of PUVA in the treatment of persistent palmoplantar pustulosis. Br. J. Dermatol. 112:455-459 12. Ros6n, K., H. Mobacken, and G. Swanbeck. 1987. PUVA, etretinate and PUVAetretinate therapy for pustulosis palmoplantaris. Arch. Dermatol. 123:885-889 13. Lassus, A. and J. M. Geiger. 1988. Acitretin and etretinate in the treatment of palmoplantar pustulosis: a double-blind comparative trial. Br. J. Dermatol. 119:755-759 14. Mueller, W. and B. Herrmann. 1979. Cyclosporin A for psoriasis. N. EngL J. Med. 301: 555 15. Reitamo, S., P. Puska, and A. Lassus. 1989. Cyclosporin in the treatment of palmoplantar pustulosis. Br. J. DermatoL 120:857 16. Meinardi, M. M. H. M., M. A. de Rie, and J. D. Bos. 1990. Oral cyclosporin A is effective in clearing persistent pustulosis palmaris et plantaris. Acta Derm. Venereol. (Stockh.) 70: 77-81 17. Reitamo, S., P. Erkko, A. Remitz, A. I. Lauerma, H. S. I. Anttila, O. Montonen, and K. Harjula. 1992. Cyclosporin for palmo-plantar pustulosis. J. Autoimmunity 5 (Suppl. A): Abstr. 104
Cyclosporin for Palmoplantar Pustulosis
Sakari Reitamo,
Pekka Erkko and Anita Remitz
Department of Dermatology, Helsinki University Central Hospital, HeIsinki, Finland
Palmoplantar pustulosis (PPP) is a chronic skin disease characterized by persistent erythematous, scaly plaques incorporating sterile pustules on palms and soles, which is resistant to most treatments. Recently, two published uncontrolled studies suggested that cyclosporin (CsA) could be an effective treatment for PPP. Similarly, an unpublished, randomized, placebo-controlled study showed that CsA is effective in preventing new pustule formation in PPP. In the present paper we review the treatment of P P P with special emphasis on CsA treatment.
Introduction
Palmoplantar pustulosis (PPP) is a chronic skin disease characterized by persistent erythematous, scaly plaques incorporating sterile pustules on palms and soles. Some authors regard P P P as a form of psoriasis, whereas others regard it as a separate disease entity because of the following: higher age of onset, a clear female predominance, no observed seasonal variation, different histopathology and lack of increased frequency of psoriasis-linked alloantigens (for review see ref 1). PPP is frequently associated with joint symptoms [2, 3] and thyroid disease [4, 5]. In addition, PPP is strongly associated with cigarette smoking [6, 7]. Treatments of PPP
PPP is often resistant to both topical and systemic treatments. T h e most frequently used treatments include potent topical corticosteroids, oral tetracyclines [8] and topical P U V A [9]. These treatments show only limited efficacy in PPP. Better results have been obtained with oral retinoids or PUVA, and combinations of these two treatments [10-13]. Preliminary studies of cyclosporin treatment of PPP
Since Mueller and H e r r m a n n published in 1979 a short paper on cyclosporin (CsA) treatment of psoriasis [ 14], many reports have shown its efficacy psoriasis. Since PPP 285 0896-8411/92/0A0285+03 $03.00/0
© 1992AcademicPress Limited
286
S. R e i t a m o e t a l .
is resistant to most treatments, we decided to try CsA treatment of PPP in a preliminary uncontrolled study of six patients [15]. CsA was taken twice daily at a dosage of 2.5 mg/kg/day for 1-3 months. T h e skin eruptions of both palms and soles clearly improved in all six patients. N o serious side effects were seen. Recently another uncontrolled study suggested that CsA could be effective in the treatment of PPP. Meinardi et al. [16] treated patients with psoriasis who had additional clinical signs of PPP. CsA treatment was p e r f o r m e d at various dosages of CsA which ranged from 1.1 and 6.1 mg/kg/day. All seven patients treated with CsA responded to treatment.
A c o n t r o l l e d s t u d y o f c y c l o s p o r i n in the t r e a t m e n t o f P P P In a double-blind, placebo-controlled study of 40 patients, published in abstract form [17], CsA treatment at 2.5 mg/kg/day for 4 weeks significantly reduced new pustule formation. In a second open label phase of 3 months a daily CsA dose of 1.25 mg/kg proved to be of similar efficacy to 2.5 mg/kg. After termination of CsA treatment, formation of new pustules returned to pretreatment levels after 1 week. T h e major side effect was headache in the 2.5 mg/kg/day group; no significant side effects were seen in the 1.25 mg/kg/day group. W h e n followed up for 1 year after CsA treatment, the majority of the patients were without need for any specific treatment. T h i s study suggests that CsA treatment of 3 to 4 months may cause, after initial flare-up of the disease, a prolonged downregulation of disease activity in PPP.
Conclusion T h e present studies suggest that CsA at 2.5 mg/kg/day is an effective treatment for PPP. Moreover, it seems that m a n y patients with P P P can be treated at lower CsA dosages of approximately 1 mg/kg/day. T h i s is in contrast to psoriasis, which usually does not respond to a CsA dose of 1 mg/kg/day. M o r e importantly, long-term remissions were observed, a p h e n o m e n o n which has not been described in psoriasis patients after CsA treatment. Although CsA is very effective in the treatment of skin lesions in PPP, it remains to be established, whether this drug has an effect on other clinical manifestations frequently accompanying PPP, i.e. thyroid abnormalities and arthropathies.
Acknowledgements T h e original studies reported here were supported by the Paulo Foundation and Sandoz Ltd.
References 1. Ashurst, P.J.C. 1964. Relapsing pustular eruptions of the hands and feet. Br. J. Dermatol. 76:169-180 2. Hradil, E., C. F. Gentz, T. Matilainen, H. M611er, L. Sauz6n, and A. Ud6n. 1988. Skeletal involvement in pustulosis plamo-plantaris with special reference to sterno-costoclavicular joints. Acta Derm. Venereol. ( Stockh. ) 68:65-73
Cyclosporin forpalmoplantar pustulosis 287 3. Jurik, A. G. and T. Ternowitz. 1988. Frequency of skeletal disease, artro-osteitis, in patients with pustulosis palmoplantaris. J. Am. Acad. Dermatol. 18:666-671 4. Ros~n, K., G. Lindstedt, H. Mobacken, and E. Nystr6m. 1988. Thyroid function in patients with pustulosis palmoplantaris. J. Am. Acad. Dermatol. 19:1009-1016 5. Agner, T., J. H. Sindrup, M. Hoier-Madsen, and L. Hegedfis. 1989. Thyroid disease in pustulosis palmoplantaris. Br. J. Dermatol. 121:487--491 6. O'Doherty, C.J. andC. Macintyre. 1985. Palmoplantarpustulosisandsmoking. Br. Med. J. 291:861-864 7. Cox, N. H. and S. Ray. 1987. Neutrophil leucocyte morphology, cigarette smoking and palmoplantar pustulosis. Int. J. Dermatol. 26:445--447 8. Ward, J. M., M. F. Corbett, and M. J. Hanna. 1976. A double-blind trial of clomocycline in the treatment of resistant palmoplantar pustulosis. Br. J. Dermatol. 95:317-322 9. Layton, A. M., R. Sheehan-Dare, and W. J. Cunliffe. 1991. A double-blind, placebocontrolled trial of topical PUVA in persistent palmoplantar pustulosis. Br. J. Dermatol. 124:581-584 10. Fredriksson, T. 1978. Oral treatment of psoriasis and pustulosis palmoplantaris with RO 10-9359. Dermatologica 157 (Suppl 1): 13-18 11. Lassus, A., J. Lauharanta, and A. Eskelinen. 1985. The effect ofetretinate compared with different regimens of PUVA in the treatment of persistent palmoplantar pustulosis. Br. J. Dermatol. 112:455-459 12. Ros6n, K., H. Mobacken, and G. Swanbeck. 1987. PUVA, etretinate and PUVAetretinate therapy for pustulosis palmoplantaris. Arch. Dermatol. 123:885-889 13. Lassus, A. and J. M. Geiger. 1988. Acitretin and etretinate in the treatment of palmoplantar pustulosis: a double-blind comparative trial. Br. J. Dermatol. 119:755-759 14. Mueller, W. and B. Herrmann. 1979. Cyclosporin A for psoriasis. N. EngL J. Med. 301: 555 15. Reitamo, S., P. Puska, and A. Lassus. 1989. Cyclosporin in the treatment of palmoplantar pustulosis. Br. J. DermatoL 120:857 16. Meinardi, M. M. H. M., M. A. de Rie, and J. D. Bos. 1990. Oral cyclosporin A is effective in clearing persistent pustulosis palmaris et plantaris. Acta Derm. Venereol. (Stockh.) 70: 77-81 17. Reitamo, S., P. Erkko, A. Remitz, A. I. Lauerma, H. S. I. Anttila, O. Montonen, and K. Harjula. 1992. Cyclosporin for palmo-plantar pustulosis. J. Autoimmunity 5 (Suppl. A): Abstr. 104