Bath-PUVA therapy in three patients with scleredema adultorum Carina M. Hager, MD,a Hussein A. Sobhi, MD,a Nicolas Hunzelmann, MD,a Claudia Wickenhauser, MD,b Rüdiger Scharenberg,c Thomas Krieg, MD,a and Karin Scharffetter-Kochanek, MDa Cologne and Lüneburg, Germany Background: Scleredema adultorum (SA) is a rare connective tissue disorder for which no treatment has proven to be effective. Objective: Our purpose was to determine the effect of bath-PUVA therapy on SA. Methods: Three patients were treated. Clinical evaluation of skin induration and thickness as well as ultrasonography were performed at baseline and after treatment. Results: All three patients showed substantial clinical improvement with bath-PUVA therapy (median of 59 treatments and a cumulative UVA dose of 245.7 J/cm2). Ultrasonography showed significant reduction in both skin thickness and density. Conclusion: Bath-PUVA therapy appears to be effective in the treatment of SA. (J Am Acad Dermatol 1998;38:240-2.)
Scleredema adultorum (SA) is a rare disorder of unknown cause.1-3 It is characterized by nonpitting induration of the skin and is associated with infections, paraproteinemia, multiple myeloma and poorly controlled diabetes mellitus.4-11 SA commonly is self-limiting. In 50% of patients it clears within 2 years.12-14 Many therapies have been proposed,6,15-17 but none have proved effective. The significant responses of three patients with SA treated with bath-PUVA therapy are described. CASE REPORTS
Case 1 A 55-year-old white man (skin type IV) had a 10year history of general fatigue and progressive tightness and thickening of the skin of his upper and lower extremities and back. Biopsy specimens showed a thickened dermis with thickened collagen bundles separated by clear spaces with Alcian blue–staining mucin lying between them. The patient had no preceding trauma, infection, or diabetes mellitus. He was treated with intravenous penicillin without improvement. After determination of From the Departments of Dermatologya and Pathology,b University of Cologne, and taberna pro medicum, Lüneburg.c Reprint requests: Karin Scharffetter-Kochanek, MD, Department of Dermatology, University of Cologne, Joseph-Stelzmann-Str. 9, 50924 Cologne, Germany. Copyright © 1998 by the American Academy of Dermatology, Inc. 0190-9622/98/$5.00 + 0 16/1/87653
the patient's minimal phototoxic dose, bath-PUVA therapy18 was started with a dose of 0.5 J/cm2 and the dosage was increased by 0.5 J/cm2 every third day. He received 62 treatments in 3 months with a cumulative UVA dose of 242.7 J/cm2. There was a significant reduction in the degree of skin thickness and the patient's range of motion in his extremities.
Case 2 A 59-year-old white man (skin type II) had a 2-year history of SA of the neck and shoulder region. He had diabetes mellitus type I, necrobiosis lipoidica, hyperlipoproteinemia type IIb and had experienced the onset of mycosis fungoides (T1, N0, M0) 1 year earlier. Treatment with intravenous penicillin produced no change in his skin condition. He received UVB radiation (1810 mJ/cm2) with no significant improvement. He was then given 0.5 J/cm2 bath-PUVA treatment with a total of 62 UVA radiations (304.8 J/cm2 dose). This resulted in marked improvement in his range of motion and softening of the skin. A biopsy specimen before treatment showed marked thickening of the dermis with thickened collagen bundles separated by clear spaces with mucin lying between them. A posttreatment specimen showed a slight reduction in the thickness of collagen bundles, but was still consistent with SA. Comparison of ultrasonographic pictures from before and after therapy showed a significant reduction of both sonographic density and thickness of the involved skin.
Journal of the American Academy of Dermatology Volume 38, Number 2, Part 1
Case 3 A 58-year-old man with adult-onset diabetes had a 6-month history of skin "changes" on his upper back. A biopsy specimen confirmed the diagnosis of SA. He received a total of 54 treatments with a cumulative UVA dose of 189.8 J/cm2. His skin softened significantly. Ultrasonographic images at baseline and after treatment showed a significant reduction in sonographic density and thickness of the affected skin. DISCUSSION
The mechanism responsible for the reduction of skin thickness in SA with bath-PUVA therapy is unknown but it is possible that it may modulate the biosynthetic capacities of dermal fibroblasts, similar to localized scleroderma.19,20 UVA radiation and PUVA treatment of human dermal fibroblast resulted in an induced synthesis of intestinal collagenase in vivo and in vitro.21-23 We used bath-PUVA instead of systemic PUVA therapy for the following reasons: First, bath-PUVA appears to have lower long-term side effects than systemic PUVA. Second, bath-PUVA has already been proven to be effective in the treatment of localized scleredema.19 Third, UV radiation of different spectra and modalities are able to stimulate the synthesis and release of epidermal cytokines such as tumor necrosis factor-α, interleukin-1 and αmelanocyte stimulating hormone which then enhance the synthesis and activation of fibroblastrelated matrix–metalloproteinases, like interstitial collagenase.24-31 REFERENCES 1. Buschke A. Vorstellung eines Falles von Skerödem vor der Berliner Gesellschaft für Dermatologie. Arch Dermatol Syph 1900;53:383-6. 2. Holubar K, Mach KW. Scleredema (Buschke): histological and histochemical investigations. Acta Derma Venereol (Stockh) 1967;47:102-10. 3. Graff R. Discussion of scleredema adultorum. Arch Dermatol 1969;98:319-20. 4. Fleischmajer R, Faludi G, Krol S. Scleredema and diabetes mellitus. Arch Dermatol 1970;101:21-6 5. Cohn BA, Wheeler CE, Briggeman RA. Scleredema adultorum of Buschke and diabetes mellitus. Arch Dermatol 1970;101:27-35. 6. Ohta A, Uitto J, Oikarinen AI, Palatsi R, Mitrane M, Bancila EA, et al. Paraproteinemia in patients with scleredema. J Am Acad Dermatol 1987;16:96-107. 7. Oikarinen A, Ala-Kokko L, Palatsi R, Palatsi R, Peltonene L, Uitto J. Scleredema and paraproteinemia. Arch Dermatol 1987;123:226-9. 8. McFadden N, Ree K, Soyland E, Larsen TE. Scleredema adultorum associated with monoclonal gammopathy and generalized hyperpigmentation. Arch Dermatol 1987; 123:629-32.
Hager et al. 241 9. Salisbury JA, Shallcross H, Leigh IM. Scleredema of Buschke associated with multiple myeloma. Clin Exp Dermatol 1988;13:269-70. 10. Hodak E, Tamir R, David M, et al. Scleredema adultorum associated with IgG-kappa multiple myeloma: a case report and review of the literature. Clin Exp Dermatol 1988;13:271-4. 11. Kövary PM, Vakilzadeh F, Macher E, Zaun H, Merk H, Goerz G. Monoclonal gammopathy in scleredema: observation in three cases. Arch Dermatol 1981;117:5369. 12. Venencie PY, Powell FC, Su WPD, Perry HO. Scleredema: a review of thirty-three cases. J Am Acad Dermatol 1984;11:128-34. 13. Carrington PR, Danusi ID, Winder PR, et al. Scleredema adultorum. Int J Dermatol 1984;23:514-22. 14. Schmidt KT, Gattuso P, Messmore H, et al. Scleredema and smoldering myeloma. J Am Acad Dermatol 1984; 26:319-21. 15. Angeli-Besson C, Koeppel MC, Jaquet P, Andrac L, Sayag J. Electro-beam therapy in scleredema adultorum with associated monoclonal hypergammaglobulinaemia. Br J Dermatol 1994;130:394-7. 16. Krasagakis K, Hettmannsperger U, Trautmann C, Tebbe B, Garbe C. Persistent scleredema of Buschke in a diabetic: improvement with high-dose penicillin (correspondence). Br J Dermatol 1996;134:593-606. 17. Keinig E, Dorner G. Rascher Behandlungserfolg mit Penicillin bei Scleredema adultorum. Hautarzt 1950;1: 231-2. 18. Streit V, Wiedow O, Christophers E. Innovative Balneotherapie mit reduzierten Badevolumina: Folienbäder. Hautarzt 1994;45:140-4. 19. Kerscher M, Volkenandt M, Meurer M, Lehmann P, Plewig G, Roecken M. Treatment of localized scleredema with PUVA bath chemotherapy. Lancet 1994;343: 1233. 20. Scharffetter-Kochanek K, Goldermann R, Lehmann P, Hölzle E, Goerz G. PUVA therapy is disabling pansclerotic morphea of children. Br J Dermatol 1995;132:830. 21. Scharffetter K, Wlaschek M, Hogg A, Bolsen K, Schothorst A, Goerz G, et al. UVA irradiation induces collagenase in human fibroblasts in vitro and in vivo. Arch Dermatol Res 1991;283:506-11. 22. Petersen MJ, Handen C, Craig S. Ultraviolet A irradiation stimulates collagenase production in cultured human fibroblasts. J Invest Dermatol 1992;99:440-4. 23. Herrmann G, Wlaschek M, Lange TS, Prenzel K, Goerz G, Scharffetter-Kochanek K. UVA irradiation stimulates the synthesis of various matrix-metalloproteases (MMPs) in cultured human fibroblasts. Exp Dermatol 1993;2:92-7. 24. Wlaschek M, Bolsen K, Herrmann G, Schwarz A, Wilmroth F, Heinrich PC, et al. UVA-induced autocrine stimulation of fibroblast-derived collagenase by IL-6. A possible mechanism in dermal photodamage? J Invest Dermatol 1993;101:164-8. 25. Stege H, Berneburg M, Humke S, Klammer M, Grewe M, Grether-Beck S, et al. High-dose UVA1 radiation therapy for localized scleroderma. J Am Acad Dermatol 1997;36:938-44. 26. Schwarz T, Luger TA. Effects of UV-irradiation of epidermal cell cytokine production. Photochem Photobiol 1989;4:1-13. 27. Scharffetter K, Heckmann M, Hatamochi A, Mauch C, Stein B, Riethmüller G, et al. Synergistic effect of tumor
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242 Hager et al. necrosis factor alpha and interferon gamma on collagen synthesis of human skin fibroblasts in vitro. Exp Cell Res 1989;181:4009-417. 28. Scharffetter K, Wlaschek M, Hogg A, Bolsen K, Schothorst A, Goerz G, et al. UVA irradiation induces collagenase in human dermal fibroblasts in vitro and in vivo. Arch Dermatol Res 1991;283:506-11. 29. Wlaschek M, Heinen G, Poswig A, Schwarz A, Krieg T, Scharffetter-Kochanek K. UVA-induced autocrine stimulation of fibroblast-derived–collagenase/MMP-1 by interrelated loops of interleukin-1 and interleukin-6. Photochem Photobiol 1994;59:550-6.
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NATIONAL REGISTRY FOR ICHTHYOSIS AND RELATED DISORDERS The National Institutes for Health, through the National Institute for Arthritis, Musculoskeletal and Skin Diseases, has sponsored a National Registry for Ichthyosis and Related Disorders. The goals of the Registry are to promote the search for basic defects, improve methods of diagnosis, and develop effective methods of treatment and/or prevention of these disorders. Diagnosis of affected persons will be made on the basis of specific listed clinical and histologic criteria and will be confirmed by determination of steroid sulfatase activity where indicated. Investigators and practitioners treating patients afflicted with these disorders or desiring access to the Registry database are encouraged to write or call for information and enrollment forms to: The National Registry for Ichthyosis and Related Disorders University of Washington Dermatology Box 356524 Seattle, WA 98195-65524 Telephone: 1-800-595-1265 Fax: 206-616-4302 E-mail: [email protected]