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Bupropion for Blau syndrome
Medical Hypotheses (2004) 62, 297–298
http://intl.elsevierhealth.com/journals/mehy
Bupropion for Blau syndrome Eric Lewin Altschulera,b,*, Richard E. Kastc a
Mount Sinai School of Medicine, 1425 Madison Avenue, P.O. Box 1240, New York, NY 10029, USA Brain and Perception Laboratory, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0109, USA c Department of Psychiatry, University of Vermont, 2 Church Street, Burlington, VT 05401, USA b
Received 20 March 2003; accepted 15 October 2003
Summary Blau syndrome (BS) is an autosomal dominantly inherited disease characterized by granulomas and arthritis. The gene mutated in BS was recently found to be CARD15. Mutations in this gene also occur in about 20% of patients with Crohn’s disease (CD), though with different mutations than in the Crohn’s patients. We are not aware of any cure or specific treatment for BS. We have found that bupropion is effective for CD, and we now suggest that bupropion be considered for treatment of BS. c 2003 Elsevier Ltd. All rights reserved.
Blau syndrome (BS) is an autosomal dominantly inherited disease characterized by granulomas and arthritis [1]. The gene for the disease was mapped to chromosome 16 [2]. The gene mutated in BS was recently found to be CARD15 (also formerly known as NOD2) [3,4] a gene which is involved in activating NF-kB. Mutations in this gene also occur in about 20% of patients with Crohn’s disease (CD) [5,6], though with different mutations than in the Crohn’s patients [7]. We are not aware of any cure or specific treatment for BS. We have found that bupropion is effective for CD [8,9], and we now suggest that bupropion be considered for treatment of BS. While bupropion is typically thought of as an antidepressant, or a medication to aid in smoking cessation we had found that a number of patients taking bupropion [8,9] or a monoamine oxidase * Corresponding author. Tel.: +1-212-659-9351; fax: +1-212348-5901. E-mail addresses: [email protected], ealtschuler@ ucsd.edu (E.L. Altschuler).
inhibitor [10] have experienced profound (to near normal bowel) and long lasting (>2 years) remissions of their CD. By increasing monoamineric and dopaminergic tone, these medicines may be able to lower, via increased intracellular cAMP (see e.g., [11,12]) levels of the pathologically significant proinflammatory cytokine TNF [13]. In one CD patient in whom we measured TNF, the value dropped from 29 pg/ml before treatment (Specialty Labs, Santa Monica, CA; normal <20 pg/ml) to 3 on bupropion. We have seen seven other patients in whom TNF dropped dramatically on bupropion, six of these into the normal range [14]. Another group has found bupropion effective for a majority of patients with psoriasis, another TNF associated disease [15]. We have not yet tested the our CD patients treated with bupropion for CARD15 mutations. Also, we have not seen any studies on TNF in BS. Nevertheless, we think that bupropion should be considered for treatment of BS, especially if it is found that macrophages and monocytes in BS elaborate high levels of TNF.
0306-9877/$ - see front matter c 2003 Elsevier Ltd. All rights reserved. doi:10.1016/S0306-9877(03)00334-7
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References [1] Blau EB. Familial granulomatous arthritis, iritis, and rash. J Pediat 1985;107:689–93. [2] Tromp G, Kuivaniemi H, Raphael S, et al. Genetic linkage of familial granulatous inflammatory arthritis, skin rash, and uveitis to chromosome 16. Am J Hum Genet 1996;59:1097–107. [3] Miceli-Richard C, Lesage S, Rybojad M, et al. CARD 15 mutations in Blau syndrome. Nat Genet 2001;29:19–20. [4] Wang X, Kuivaniemi H, Bonavita G, et al. CARD 15 mutations in familial granulomatosis syndromes: a study of the original Blau syndrome kindred and other families with large-vessel arteritis and cranial neuropathy. Arthritis Rheum 2002;46:3041–5. [5] Hugot JP, Chamailard M, Zouali H, et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature 2001;411:599–603. [6] Ogura Y, Bonen DK, Inohara N, et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature 2001;411:603–6. [7] Chamaillard M, Philpott D, Girardin SE, et al. Geneenvironment interaction modulated by allelic heterogeneity in inflammatory diseases. Proc Natl Acad Sci USA 2003; 100:3455–60.
Altschuler, Kast
[8] Kast RE, Altschuler EL. Remission of Crohn’s disease on bupropion. Gastroenterology 2001;121:1260–1. [9] Kane SV, Altschuler EL, Kast RE. Crohn’s disease remission on bupropion. Gastroenterology 2003;125:1290. [10] Kast RE. Crohn’s disease remission with phenelzine treatment. Gastroenterology 1998;115:1034–5. [11] Talmadge J, Scott R, Castelli P, Newman-Tarr T, Lee J. Molecular pharmacology of the beta-adrenergic receptor on THP-1 cells. Int J Immunopharmacol 1993;15:219–28. [12] Guirao X, Kumar A, Katz J, et al. Catecholamines increase monocyte TNF receptors and inhibit TNF through b-2 adrenoreceptor activation. Am J Physiol 1997;273: E1203–8. [13] Scallon B, Cai A, Solowski N, et al. Binding and functional comparisons of two types of tumor necrosis factor antagonists. J Pharmacol Exp Therap 2002;301:418–26. [14] Altschuler EL, Kast RE. Bupropion in psoriasis and atopic dermatitis: decreased tumor necrosis factor-alpha? Psychosom Med 2003;65:719. [15] Modell JG, Boyce S, Taylor E, Katholi C. Treatment of atopic dermatitis and psoriasis vulgaris with bupropion-SR: a pilot study. Psychosom Med 2002;64:835–40.
http://intl.elsevierhealth.com/journals/mehy
Bupropion for Blau syndrome Eric Lewin Altschulera,b,*, Richard E. Kastc a
Mount Sinai School of Medicine, 1425 Madison Avenue, P.O. Box 1240, New York, NY 10029, USA Brain and Perception Laboratory, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0109, USA c Department of Psychiatry, University of Vermont, 2 Church Street, Burlington, VT 05401, USA b
Received 20 March 2003; accepted 15 October 2003
Summary Blau syndrome (BS) is an autosomal dominantly inherited disease characterized by granulomas and arthritis. The gene mutated in BS was recently found to be CARD15. Mutations in this gene also occur in about 20% of patients with Crohn’s disease (CD), though with different mutations than in the Crohn’s patients. We are not aware of any cure or specific treatment for BS. We have found that bupropion is effective for CD, and we now suggest that bupropion be considered for treatment of BS. c 2003 Elsevier Ltd. All rights reserved.
Blau syndrome (BS) is an autosomal dominantly inherited disease characterized by granulomas and arthritis [1]. The gene for the disease was mapped to chromosome 16 [2]. The gene mutated in BS was recently found to be CARD15 (also formerly known as NOD2) [3,4] a gene which is involved in activating NF-kB. Mutations in this gene also occur in about 20% of patients with Crohn’s disease (CD) [5,6], though with different mutations than in the Crohn’s patients [7]. We are not aware of any cure or specific treatment for BS. We have found that bupropion is effective for CD [8,9], and we now suggest that bupropion be considered for treatment of BS. While bupropion is typically thought of as an antidepressant, or a medication to aid in smoking cessation we had found that a number of patients taking bupropion [8,9] or a monoamine oxidase * Corresponding author. Tel.: +1-212-659-9351; fax: +1-212348-5901. E-mail addresses: [email protected], ealtschuler@ ucsd.edu (E.L. Altschuler).
inhibitor [10] have experienced profound (to near normal bowel) and long lasting (>2 years) remissions of their CD. By increasing monoamineric and dopaminergic tone, these medicines may be able to lower, via increased intracellular cAMP (see e.g., [11,12]) levels of the pathologically significant proinflammatory cytokine TNF [13]. In one CD patient in whom we measured TNF, the value dropped from 29 pg/ml before treatment (Specialty Labs, Santa Monica, CA; normal <20 pg/ml) to 3 on bupropion. We have seen seven other patients in whom TNF dropped dramatically on bupropion, six of these into the normal range [14]. Another group has found bupropion effective for a majority of patients with psoriasis, another TNF associated disease [15]. We have not yet tested the our CD patients treated with bupropion for CARD15 mutations. Also, we have not seen any studies on TNF in BS. Nevertheless, we think that bupropion should be considered for treatment of BS, especially if it is found that macrophages and monocytes in BS elaborate high levels of TNF.
0306-9877/$ - see front matter c 2003 Elsevier Ltd. All rights reserved. doi:10.1016/S0306-9877(03)00334-7
298
References [1] Blau EB. Familial granulomatous arthritis, iritis, and rash. J Pediat 1985;107:689–93. [2] Tromp G, Kuivaniemi H, Raphael S, et al. Genetic linkage of familial granulatous inflammatory arthritis, skin rash, and uveitis to chromosome 16. Am J Hum Genet 1996;59:1097–107. [3] Miceli-Richard C, Lesage S, Rybojad M, et al. CARD 15 mutations in Blau syndrome. Nat Genet 2001;29:19–20. [4] Wang X, Kuivaniemi H, Bonavita G, et al. CARD 15 mutations in familial granulomatosis syndromes: a study of the original Blau syndrome kindred and other families with large-vessel arteritis and cranial neuropathy. Arthritis Rheum 2002;46:3041–5. [5] Hugot JP, Chamailard M, Zouali H, et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature 2001;411:599–603. [6] Ogura Y, Bonen DK, Inohara N, et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature 2001;411:603–6. [7] Chamaillard M, Philpott D, Girardin SE, et al. Geneenvironment interaction modulated by allelic heterogeneity in inflammatory diseases. Proc Natl Acad Sci USA 2003; 100:3455–60.
Altschuler, Kast
[8] Kast RE, Altschuler EL. Remission of Crohn’s disease on bupropion. Gastroenterology 2001;121:1260–1. [9] Kane SV, Altschuler EL, Kast RE. Crohn’s disease remission on bupropion. Gastroenterology 2003;125:1290. [10] Kast RE. Crohn’s disease remission with phenelzine treatment. Gastroenterology 1998;115:1034–5. [11] Talmadge J, Scott R, Castelli P, Newman-Tarr T, Lee J. Molecular pharmacology of the beta-adrenergic receptor on THP-1 cells. Int J Immunopharmacol 1993;15:219–28. [12] Guirao X, Kumar A, Katz J, et al. Catecholamines increase monocyte TNF receptors and inhibit TNF through b-2 adrenoreceptor activation. Am J Physiol 1997;273: E1203–8. [13] Scallon B, Cai A, Solowski N, et al. Binding and functional comparisons of two types of tumor necrosis factor antagonists. J Pharmacol Exp Therap 2002;301:418–26. [14] Altschuler EL, Kast RE. Bupropion in psoriasis and atopic dermatitis: decreased tumor necrosis factor-alpha? Psychosom Med 2003;65:719. [15] Modell JG, Boyce S, Taylor E, Katholi C. Treatment of atopic dermatitis and psoriasis vulgaris with bupropion-SR: a pilot study. Psychosom Med 2002;64:835–40.