Abstract
Leukocytoclastic vasculitis (LV) is a systemic inflammatory disorder involving mostly the small vessels. It is characterised by segmental angiocentric neutrophilic inflammation, endothelial cell damage and fibrinoid necrosis. LV is related to a variety of clinical disorders including cryoglobulinemia and, very rarely, multiple myeloma (MM), among many others. The development of LV in patients with MM has been linked to cryoglobulinemia, infections, drugs and paraneoplasia. It has been speculated that myeloma patients with a poorer prognosis and progressive disease are more prone to develop LV. Thalidomide is a rediscovered old drug with anti-angiogenic, immunomodulatory and anti-inflammatory properties. It is highly effective in the treatment of MM and other clinical disorders such as leprosy, various cancers, graft-versus-host disease and autoimmune diseases. We report here a female patient with Durie–Salmon stage IIA MM who initially presented with cryoglobulinemia and LV. LV in this patient was primarily considered to be the result of progressive cryoglobulinemia, which was closely associated with MM. She was successfully managed with thalidomide and dexamethasone.
References
Anagnostopoulos A, Weber D, Rankin K et al (2003) Thalidomide and dexamethasone for resistant multiple myeloma. Br J Haematol 121:768–769
Barnhill RL, Doll NJ, Millikan LE et al (1984) Studies on the anti-inflammatory properties of thalidomide: effects on polymorphonuclear leukocytes and monocytes. J Am Acad Dermatol 11:814–819
Bayer-Garner IB, Smoller BR (2003) Leukocytoclastic (small vessel) vasculitis in multiple myeloma. Clin Exp Dermatol 28:521–524
Bayer-Garner IB, Smoller BR (2003) The spectrum of cutaneous disease in multiple myeloma. J Am Acad Dermatol 48:497–507
D’Amato RJ, Loughnan MS, Flynn E et al (1994) Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci U S A 91:4082–4085
Damiano JS, Cress AE, Hazlehurst LA et al (1999) Cell adhesion mediated drug resistance (CAM-DR): role of integrins and resistance to apoptosis in human myeloma cell lines. Blood 93:1658–1667
Dammacco F, Sansonno D, Piccoli C et al (2001) The cryoglobulins: an overview. Eur J Clin Investig 31:628–638
Davies FE, Raje N, Hideshima T et al (2001) Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood 98:210–216
Faure M, Thivolet J, Gaucherand M (1980) Inhibition of polymorphonuclear leukocytes chemotaxis by thalidomide. Arch Dermatol Res 269:275–280
Garcia-Porrua C, Gonzales-Gay MA (1998) Cutaneous vasculitis as paraneoplastic syndrome in adults. Arthritis Rheum 41:1133–1136
Geitz H, Handt S, Zwingerberger K (1996) Thalidomide selectively modulates the density of cell surface molecules involved in the adhesion cascade. Immunopharmacology 31:213–221
Hamuryudan V, Mat C, Saip S et al (1998) Thalidomide in the treatment of the mucocutaneous lesions of Behçet’s syndrome: a randomized, double-blind, placebo controlled trial. Ann Intern Med 128:443–459
Haslett PA, Corral LG, Albert M et al (1998) Thalidomide co-stimulates primary human T lymphocytes, preferentially inducing proliferation, cytokine production, and cytotoxic responses in the CD8+ subset. J Exp Med 187:1885–1892
Hideshima T, Chauhan D, Shima Y et al (2000) Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy. Blood 96:2943–2950
Highet AS (1980) Urticarial vasculitis and IgA myeloma. Br J Dermatol 102:355–357
Kois JM, Sexton FM, Lookingbill DP et al (1991) Cutaneous manifestations of multiple myeloma. Arch Dermatol 127:69–74
Li X, Liu X, Wang J et al (2003) Thalidomide down-regulates the expression of VEGF and b-FGF in cisplatin-resistant human lung carcinoma cells. Anticancer Res 23:2481–2487
Lotti T, Ghersetich I, Comacchi C et al (1998) Cutaneous small-vessel vasculitis. J Am Acad Dermatol 39:667–687
Lucas E, Martinez A, Guerao MR et al (1997) Hypersensitivity vasculitis as the first manifestation of a multiple myeloma. An Med Interna 14:374–375
McMillen JJ, Krueger SK, Dyer GA (1986) Leukocytoclastic vasculitis in association with immunoglobulin A myeloma. Ann Intern Med 105:709–710
Means RT, Greer JP, Sergent JS et al (1987) Leukocytoclastic vasculitis and multiple myeloma. Ann Intern Med 106:329–331
Mileshkin L, Biagi JJ, Mitchell P et al (2003) A multi-center phase II trial of thalidomide in relapsed/refractory multiple myeloma: adverse prognostic impact of advanced age. Blood 102:69–77
Mitsiades N, Mitsiades CS, Poulaki V et al (2002) Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood 99:4525–4530
Moehler TM, Neben K, Benner A et al (2001) Salvage therapy for multiple myeloma with thalidomide and CED chemotherapy. Blood 98:3846–3848
Moriera AL, Sampaio EP, Zmuidzinas A et al (1993) Thalidomide exerts its inhibitory action on tumor necrosis factor alpha by enhancing mRNA degradation. J Exp Med 177:1675–1680
Neben K, Moehler T, Kraemer A et al (2001) Response to thalidomide in progressive multiple myeloma is not mediated by inhibition of angiogenic cytokine secretion. Br J Haematol 115:605–608
Neben K, Moehler T, Benner A et al (2002) Dose-dependent effect of thalidomide on overall survival in relapsed multiple myeloma. Clin Cancer Res 8:3377–3382
Sanchez NB, Canedo IF, Garcia-Patos PE et al (2004) Paraneoplastic vasculitis associated with multiple myeloma. J Eur Acad Dermatol Venereol 18:731–735
Singhal S, Mehta J, Desikan R et al (1999) Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 341:1565–1571
Turk BE, Jiang H, Liu JO (1996) Binding of thalidomide to alpha 1-acid glycoprotein may be involved in its inhibition of tumor necrosis factor alpha production. Proc Natl Acad Sci U S A 93:7552–7556
Weber D, Rankin K, Gavino M et al (2003) Thalidomide alone or with dexamethasone for previously untreated multiple myeloma. J Clin Oncol 21:16–19
Witzens M, Moehler T, Neben K et al (2004) Development of leukocytoclastic vasculitis in a patient with multiple myeloma during treatment with thalidomide. Ann Hematol 83:467–470
Yabu T, Tomimoto H, Taguchi Y et al (2005) Thalidomide-induced anti-angiogenic action is mediated by ceramide through depletion of VEGF receptors, and antagonized by sphingosine-1-phosphate. Blood (prepublished online March 1, 2005; DOI 10.1182/blood-2004-09-3679)
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We thank Prof. H.M. Moutsopoulos (Athens, Greece) for his help in the management of this patient.
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Cem Ar, M., Soysal, T., Hatemi, G. et al. Successful management of cryoglobulinemia-induced leukocytoclastic vasculitis with thalidomide in a patient with multiple myeloma. Ann Hematol 84, 609–613 (2005). https://doi.org/10.1007/s00277-005-1053-1
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DOI: https://doi.org/10.1007/s00277-005-1053-1