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Thalidomide Effects in Behçet's Syndrome and Pustular Vasculitis

Thalidomide Effects in Behçet's Syndrome and Pustular Vasculitis Abstract • Pustular vasculitis is a new disease concept that links cutaneous, and possibly systemic, aspects of Behçet's, bowel bypass, bowel-associated dermatosis-arthritis, and disseminated gonorrhea syndromes. The pathomechanism of pustular vasculitic lesion generation may relate to circulating immune complex (CIC)-mediated vessel damage and serum enhancement of neutrophil migration. Thalidomide, an oral pharmaceutical available on strict protocol, has therapeutic effects based on proposed modulation of CIC- and neutrophil-mediated cytotoxicity. Thalidomide therapy was started for four patients with significant morbidity from Behçet's syndrome and for one patient with bowel-associated dermatosis-arthritis syndrome. Clinical benefit was dramatic in all patients who completed sequential four-week "on" and "off" thalidomide therapeutic cycles. In three of four patients, in vivo testing for CIC after histamine injection immunopathology converted from positive (immunoreactant deposition in dermal vasculature [four hours after histamine] and CIC-mediated vasculitis [24 hours after histamine]) to negative during therapy. No effects were noted on neutrophil migration or on the LFA-1/Mac-1/p150,95 family of glycoproteins associated with neutrophil adherence as assessed qualitatively by tritium labeling of neutrophil cell surfaces. In this small patient group, thalidomide was a clinically effective, safe (with rigid monitoring) therapy whose mechanism of action may relate more to inhibitory effects on CIC-induced vasculitis than to effects on neutrophil-mediated cytotoxicity. (Arch Intern Med 1986;146:878-881) References 1. Jorizzo JL: Pustular vasculitis: An emerging disease concept. J Am Acad Dermatol 1983;9:160-162.Crossref 2. Jorizzo JL, Apisarnthanarax P, Subrt P, et al: Bowel-bypass syndrome without bowel bypass: Bowel-associated dermatosis-arthritis syndrome. Arch Intern Med 1983;143:457-461.Crossref 3. Williams BD, Lehner T: Immune complexes in Behçet's syndrome and recurrent oral ulceration. Br Med J 1977;1:1387-1389.Crossref 4. Takeuchi A, Kobayashi K, Mori M, et al: The mechanism of hyperchemotaxis in Behçet's disease. J Rheumatol 1981;8:40-44. 5. Jorizzo JL, Hudson RD, Schmalstieg FC, et al: Behçet's syndrome: Immune regulation, circulating immune complexes, neutrophil migration, and colchicine therapy. J Am Acad Dermatol 1984;10:205-214.Crossref 6. Stein HB, Schlappner OLA, Boyko W, et al: The intestinal bypass arthritis-dermatitis syndrome. Arthritis Rheum 1982;24:684-690.Crossref 7. Jorizzo JL, Schmalstieg FC, Dinehart SM, et al: Bowel-associated dermatosis-arthritis syndrome: Immune complex-mediated vessel damage and increased neutrophil migration. Arch Intern Med 1984;144:738-740.Crossref 8. Moran CJ, Ryden G, Turk JL, et al: Evidence for circulating immune complexes in lepromatous leprosy. Lancet 1972;2:572-573.Crossref 9. Barnhill RL, McDougall AC: Thalidomide: Use and possible mode of action in reactional lepromatous leprosy and in various other conditions. J Am Acad Dermatol 1982;7:317-323.Crossref 10. Faure M, Thivolet J, Gaucherand M: Inhibition of polymorphonuclear leukocyte chemotaxis by thalidomide. Arch Dermatol Res 1980;269:275-280.Crossref 11. Hendler SS, McCarty MF: Thalidomide for autoimmune disease. Med Hypotheses 1983;10:437-443.Crossref 12. Clemmensen OJ, Olsen PZ, Anderson KE: Thalidomide neurotoxicity. Arch Dermatol 1984;120:338-341.Crossref 13. Braverman IM, Yen A: Demonstration of immune complexes in spontaneous and histamine-induced lesions and in normal skin of patients with leukocytoclastic angiitis. J Invest Dermatol 1975;64:105-112.Crossref 14. Anderson DC, Schmalstieg FC, Kohl S, et al: Abnormalities of polymorphonuclear leukocyte function associated with a heritable deficiency of high molecular weight surface glycoproteins (GP138): Common relationship to diminished cell adherence. J Clin Invest 1984;74:536-551.Crossref 15. Gahmberg CG, Hakomori SI: External labeling of cell-surface galactose and galactosamine in glycolipid and glycoprotein of human erythrocytes. J Biol Chem 1973;248:4311-4317. 16. Todd RF III, Nadler LM, Schlossman SF: Antigens on human monocytes identified by monoclonal antibodies. J Immunol 1981;126:1435-1442. 17. Fearon DT, Collins LA: Increased expression of C3b receptors on polymorphonuclear leukocytes induced by chemotactic factors and by purification procedures. J Immunol 1983;130:370-375. 18. Jorizzo JL, Solomon AR, Cavallo T: Behçet's syndrome: Immunopathologic and histopathologic assessment of pathergy lesions is useful in diagnosis and follow-up. Arch Pathol Lab Med 1985;109:747-751. 19. Knop J, Bonsmann G, Happle R, et al: Thalidomide in the treatment of 60 cases of chronic discoid lupus erythematosus. Br J Dermatol 1983;108: 461-466.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

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Publisher
American Medical Association
Copyright
Copyright © 1986 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinte.1986.00360170074012
Publisher site
See Article on Publisher Site

Abstract

Abstract • Pustular vasculitis is a new disease concept that links cutaneous, and possibly systemic, aspects of Behçet's, bowel bypass, bowel-associated dermatosis-arthritis, and disseminated gonorrhea syndromes. The pathomechanism of pustular vasculitic lesion generation may relate to circulating immune complex (CIC)-mediated vessel damage and serum enhancement of neutrophil migration. Thalidomide, an oral pharmaceutical available on strict protocol, has therapeutic effects based on proposed modulation of CIC- and neutrophil-mediated cytotoxicity. Thalidomide therapy was started for four patients with significant morbidity from Behçet's syndrome and for one patient with bowel-associated dermatosis-arthritis syndrome. Clinical benefit was dramatic in all patients who completed sequential four-week "on" and "off" thalidomide therapeutic cycles. In three of four patients, in vivo testing for CIC after histamine injection immunopathology converted from positive (immunoreactant deposition in dermal vasculature [four hours after histamine] and CIC-mediated vasculitis [24 hours after histamine]) to negative during therapy. No effects were noted on neutrophil migration or on the LFA-1/Mac-1/p150,95 family of glycoproteins associated with neutrophil adherence as assessed qualitatively by tritium labeling of neutrophil cell surfaces. In this small patient group, thalidomide was a clinically effective, safe (with rigid monitoring) therapy whose mechanism of action may relate more to inhibitory effects on CIC-induced vasculitis than to effects on neutrophil-mediated cytotoxicity. (Arch Intern Med 1986;146:878-881) References 1. Jorizzo JL: Pustular vasculitis: An emerging disease concept. J Am Acad Dermatol 1983;9:160-162.Crossref 2. Jorizzo JL, Apisarnthanarax P, Subrt P, et al: Bowel-bypass syndrome without bowel bypass: Bowel-associated dermatosis-arthritis syndrome. Arch Intern Med 1983;143:457-461.Crossref 3. Williams BD, Lehner T: Immune complexes in Behçet's syndrome and recurrent oral ulceration. Br Med J 1977;1:1387-1389.Crossref 4. Takeuchi A, Kobayashi K, Mori M, et al: The mechanism of hyperchemotaxis in Behçet's disease. J Rheumatol 1981;8:40-44. 5. Jorizzo JL, Hudson RD, Schmalstieg FC, et al: Behçet's syndrome: Immune regulation, circulating immune complexes, neutrophil migration, and colchicine therapy. J Am Acad Dermatol 1984;10:205-214.Crossref 6. Stein HB, Schlappner OLA, Boyko W, et al: The intestinal bypass arthritis-dermatitis syndrome. Arthritis Rheum 1982;24:684-690.Crossref 7. Jorizzo JL, Schmalstieg FC, Dinehart SM, et al: Bowel-associated dermatosis-arthritis syndrome: Immune complex-mediated vessel damage and increased neutrophil migration. Arch Intern Med 1984;144:738-740.Crossref 8. Moran CJ, Ryden G, Turk JL, et al: Evidence for circulating immune complexes in lepromatous leprosy. Lancet 1972;2:572-573.Crossref 9. Barnhill RL, McDougall AC: Thalidomide: Use and possible mode of action in reactional lepromatous leprosy and in various other conditions. J Am Acad Dermatol 1982;7:317-323.Crossref 10. Faure M, Thivolet J, Gaucherand M: Inhibition of polymorphonuclear leukocyte chemotaxis by thalidomide. Arch Dermatol Res 1980;269:275-280.Crossref 11. Hendler SS, McCarty MF: Thalidomide for autoimmune disease. Med Hypotheses 1983;10:437-443.Crossref 12. Clemmensen OJ, Olsen PZ, Anderson KE: Thalidomide neurotoxicity. Arch Dermatol 1984;120:338-341.Crossref 13. Braverman IM, Yen A: Demonstration of immune complexes in spontaneous and histamine-induced lesions and in normal skin of patients with leukocytoclastic angiitis. J Invest Dermatol 1975;64:105-112.Crossref 14. Anderson DC, Schmalstieg FC, Kohl S, et al: Abnormalities of polymorphonuclear leukocyte function associated with a heritable deficiency of high molecular weight surface glycoproteins (GP138): Common relationship to diminished cell adherence. J Clin Invest 1984;74:536-551.Crossref 15. Gahmberg CG, Hakomori SI: External labeling of cell-surface galactose and galactosamine in glycolipid and glycoprotein of human erythrocytes. J Biol Chem 1973;248:4311-4317. 16. Todd RF III, Nadler LM, Schlossman SF: Antigens on human monocytes identified by monoclonal antibodies. J Immunol 1981;126:1435-1442. 17. Fearon DT, Collins LA: Increased expression of C3b receptors on polymorphonuclear leukocytes induced by chemotactic factors and by purification procedures. J Immunol 1983;130:370-375. 18. Jorizzo JL, Solomon AR, Cavallo T: Behçet's syndrome: Immunopathologic and histopathologic assessment of pathergy lesions is useful in diagnosis and follow-up. Arch Pathol Lab Med 1985;109:747-751. 19. Knop J, Bonsmann G, Happle R, et al: Thalidomide in the treatment of 60 cases of chronic discoid lupus erythematosus. Br J Dermatol 1983;108: 461-466.Crossref

Journal

Archives of Internal MedicineAmerican Medical Association

Published: May 1, 1986

References