Comment Dermatology 1992; 185:173-174
Men“ ns
Department of Dermatology
(Director: .ref / Ring).
University of Hamburg. FRG
Key Words L-Tryptophan Progressive systemic sclerosis Eosinophilia-myalgia syndrome Eosinophilic fasciitis
¿-Tryptophan Ingestion Does Not Induce Progressive Systemic Sclerosis (Scleroderma)
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Abstract A retrospective analysis of 153 patients suffering from progressive systemic scle rosis failed to show any correlation between either onset or worsening of the dis ease and E-tryptophan ingestion. Only one woman developed typical acrosclerosis without signs of the eosinophilia-myalgia syndrome during exposure to the drug.
E-tryptophan is an amino acid which has been used by many people as a ‘natural’ cure for sleeplessness and depression. The occurrence of the eosinophilia-myalgia syndrome [1] alarmed the public in 1989 and 1990. because several thousand people suffered from this generalized dis ease, and in a few cases died [2-4]. The cause for this sud den epidemic-like spread of a new entity was uncovered by Bclongia ct al. [5], who found a contaminant in the E-tryp tophan preparations, the so-called ‘peak E \ which was detected in the compound after the main manufacturer of E-tryptophan, the Japanese company Showa-Dcnko K.K., had changed the production process of the drug. Mean while, this ‘peak E’ was characterized as a new amino acid, called l.T-ethylidcnebis(tryptophan) [6], which is able to induce a fibrotic disease when injected into Lewis rats [7], and modulates interleukin-5 production by T cells [8]. The question, whether pure E-tryptophan itself is also able to induce fibrotic diseases, remains of interest: there are reports of a scleroderma-like disorder after therapy with carbidopa and E-5-hydroxytryptophan in patients suf fering from myoclonia [9-11]. Recently, Blauvelt and Falanga 112] reported on patients suffering from eosinophilic fasciitis, who had taken E-tryptophan before the onset of their disease, prior to the era of contamined products in the autumn of 1988. None of their patients with progressive
systemic sclerosis (PSS) had a history of E-tryptophan ingestion. Comparable results were found by Freundlich ct al. [13], In cooperation with the German self-aid group ‘Sclero derma’. 137 PSS patients were questioned concerning their E-tryptophan use before the onset of their disease. 98 patients answered the letter. 55 patients could also be recruited from the connective-tissue clinic of the Depart ment of Dermatology of the University of Hamburg. Alto gether 153 patients fulfilled the ARA criteria (proximal sclerosis of the wrist, or two of the three minor criteria: scle rodactylia, acral fingertip necrosis or bibasilar lung fibro sis). 128 denied any use of E-tryptophan-containing prod ucts in the past. 24 had taken E-tryptophan after the onset of their disease for sleeplessness or depression. 11 of these during the crucial period of 1989 and 1990, but none per ceived any worsening of the PSS. especially in these two years. Only one 47-year-old woman confirmed E-trypto phan ingestion up to one year before the onset of her dis ease. However, she developed typical signs of acrosclerosis with sclerodactylia, acral fingertip necrosis and positive anticcntromcrc antibodies. She never had fasciitis, cosinophilia, myalgia, arthralgia or other signs of fibrotic dis eases possibly linked to E-tryptophan, therefore this associ ation seems to be coincidental (table 1).
Hartwig Mcnsing Universitäts-Hautklinik Hamburg Martinistrassc 52. D-W-2000 Hamburg (FRG)
© 1992 Karger AG. Basel 1018-8665/92/1853-0173 $ 2.75A)
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 4:44:23 AM
H
Table 1. T ryptophan use by patients in the study
Exposure to L-tryptophan Contaminated Non-contaminatcd
PSS n = 153
EF n= 8
24 II 1.3
5 4 1
E F = Eosinophilie fasciitis.
We also analyzed the files of 8 patients formerly diag nosed with eosinophilic fasciitis: 4 had to be reclassified as having the cosinophilia-myalgia syndrome [14], because of the close connection between clinical symptoms and the ingestion of contaminated /.-tryptophan. However, one
further patient, a 57-year-old woman, had taken non-contaminated /.-tryptophan in 1986 at an overall dosage of > 1000 g and developed a rheumatic disease with general ized oedema, severe arthralgias and subsequently the typ ical clinical signs of eosinophilic fasciitis. The ingestion of contaminated /.-tryptophan after the autumn of 1988 is obviously responsible for the eosinophilia-myalgia syndrome, which reached nearly epidemic lev els not only in the USA. but also in central Europe. Noncontaminatcd ¿.-tryptophan may also induce fibrotic dis eases like eosinophilic fasciitis and localized scleroderma [ 12]. In contrast, the pathogenesis of PSS does not seem to be related to this compound, because in several retro spective investigations (including this one) >200 PSS patients [12, 13] have now been analyzed, and no evidence of exposure to /.-tryptophan, produced cither before or after the autumn of 1988, has been identified.
References
174
6 Mayeno AN. Lin F. Foote CS. Loegering DA. Antes MM. Hedberg CW. Glcich GJ: Char acterization of "peak E'. a novel amino acid associated with eosinophilia-myalgia syn drome. Science 1990:250:1707-1708. 7 Crofford LJ. Rader JL Dalakas MC. Hill RH. Page SW. Needham LL. Brady I S. I levés MP. Wilder RL. Gold PW. Ilia I. Smith C. Stern berg EM: /.-Tryptophan implicated in human eosinophilia-myalgia syndrome causes fasciitis and perimyositis in the Lewis rat. J Clin Invest 1990:86:1757-1763. 8 Yamaoka KA. Miyasaka N. Kashiwasaki S: /.Tryptophan contaminant 'peak E' and interleukin-5 production from T cells. Lancet 1991: 338:1468. 9 Sternberg EM. Van Woert MH. Young SN. Magnussen I. Baker II. Gauthier S. Osterland C'K: Development of a scleroderma-like illness during therapy with Z.-5-hydroxytryptophan and carbidopa. N Engl .1 Med 1990:303: 782-787.
Mousing
10 Auffranc JC. Bcrbis P. Fabre JF. Garnier JP. Privat Y : Syndrome sclérodermiforme et poïkilodcrmique observé au cours d‘un traitement par carbidopa et 5-hydroxy-tryptophane. Ann Dermatol Vénéréol 1985;112:691-692. 11 Joly P. Lampert A. Thomine E. Lauret P: Development of pseudobullous morphea and scleroderma-like illness during therapy with /.5-hydroxytryptophan and carbidopa. J Am Acad Dermatol 1991:25:332-333. 12 Blauvelt A. Falanga V: Idiopathic and /.-tryp tophan-associated eosinophilic fasciitis before and after /.-tryptophan contamination. Arch Dermatol 1991:127:1159-1166. 13 Freundlich B. Werth VP. Rook AH. O'Conner CR. Schumacher HR. Levdenn SS. Stolley PD: /.-Tryptophan ingestion associated with eosinophilic fasciitis but not progressive sys temic sclerosis. Ann Intern Med 1990:112: 758-762. 14 Mensing II. Schallreutcr K, Scuff II. Stcinkraus V: Das Eosinophil¡e-Myalgic-Syndrom. Klin k und Verlauf bei 10 Patienten. Hautarzt, in press.
/.-Tryptophan and Scleroderma
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 4:44:23 AM
1 Centers for disease control: Eosinophilia-myalgia syndrome: New Mexico. MMWR 1989:38: 765-767. 2 Silver RM. Heyes MP. Maize JC. Quearry B. Bionnct-Fuassct M. Sternberg EM: Sclero derma. fasciitis and cosinophilia associated with the ingestion of tryptophan. N Engl .1 Med 1990:322:874-881. 3 Swygert LA. Maes EF. Sewell LE. Miller L. Falk H. Kilbourne EM: Eosinophilia-myalgia syndrome. Result of a national surveillance. JAMA 1990:264:1698-1703. 4 Kaufman LD. Scidman RJ. Phillips ME. G ru ber BL: Cutaneous manifestations of the /.tryptophan-associated eosinophilia-myalgia syndrome: A spectrum of sclerodermatous skin disease. .1 Am Acad Dermatol 1990:23: 1063-1068. 5 Belongia EA. HedbergCW . Gleich GJ. White KE. Mayeno AN. LögcringDA. Dunnette SL. Pirie PL. MacDonald KL. Osterholm MT: An investigation of the cause of the eosinophiliamyalgia syndrome associated with tryptophan use. N Engl J Med 1990:323:357-365.
Men“ ns
Department of Dermatology
(Director: .ref / Ring).
University of Hamburg. FRG
Key Words L-Tryptophan Progressive systemic sclerosis Eosinophilia-myalgia syndrome Eosinophilic fasciitis
¿-Tryptophan Ingestion Does Not Induce Progressive Systemic Sclerosis (Scleroderma)
■
■
_
.
^
.
*
Abstract A retrospective analysis of 153 patients suffering from progressive systemic scle rosis failed to show any correlation between either onset or worsening of the dis ease and E-tryptophan ingestion. Only one woman developed typical acrosclerosis without signs of the eosinophilia-myalgia syndrome during exposure to the drug.
E-tryptophan is an amino acid which has been used by many people as a ‘natural’ cure for sleeplessness and depression. The occurrence of the eosinophilia-myalgia syndrome [1] alarmed the public in 1989 and 1990. because several thousand people suffered from this generalized dis ease, and in a few cases died [2-4]. The cause for this sud den epidemic-like spread of a new entity was uncovered by Bclongia ct al. [5], who found a contaminant in the E-tryp tophan preparations, the so-called ‘peak E \ which was detected in the compound after the main manufacturer of E-tryptophan, the Japanese company Showa-Dcnko K.K., had changed the production process of the drug. Mean while, this ‘peak E’ was characterized as a new amino acid, called l.T-ethylidcnebis(tryptophan) [6], which is able to induce a fibrotic disease when injected into Lewis rats [7], and modulates interleukin-5 production by T cells [8]. The question, whether pure E-tryptophan itself is also able to induce fibrotic diseases, remains of interest: there are reports of a scleroderma-like disorder after therapy with carbidopa and E-5-hydroxytryptophan in patients suf fering from myoclonia [9-11]. Recently, Blauvelt and Falanga 112] reported on patients suffering from eosinophilic fasciitis, who had taken E-tryptophan before the onset of their disease, prior to the era of contamined products in the autumn of 1988. None of their patients with progressive
systemic sclerosis (PSS) had a history of E-tryptophan ingestion. Comparable results were found by Freundlich ct al. [13], In cooperation with the German self-aid group ‘Sclero derma’. 137 PSS patients were questioned concerning their E-tryptophan use before the onset of their disease. 98 patients answered the letter. 55 patients could also be recruited from the connective-tissue clinic of the Depart ment of Dermatology of the University of Hamburg. Alto gether 153 patients fulfilled the ARA criteria (proximal sclerosis of the wrist, or two of the three minor criteria: scle rodactylia, acral fingertip necrosis or bibasilar lung fibro sis). 128 denied any use of E-tryptophan-containing prod ucts in the past. 24 had taken E-tryptophan after the onset of their disease for sleeplessness or depression. 11 of these during the crucial period of 1989 and 1990, but none per ceived any worsening of the PSS. especially in these two years. Only one 47-year-old woman confirmed E-trypto phan ingestion up to one year before the onset of her dis ease. However, she developed typical signs of acrosclerosis with sclerodactylia, acral fingertip necrosis and positive anticcntromcrc antibodies. She never had fasciitis, cosinophilia, myalgia, arthralgia or other signs of fibrotic dis eases possibly linked to E-tryptophan, therefore this associ ation seems to be coincidental (table 1).
Hartwig Mcnsing Universitäts-Hautklinik Hamburg Martinistrassc 52. D-W-2000 Hamburg (FRG)
© 1992 Karger AG. Basel 1018-8665/92/1853-0173 $ 2.75A)
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 4:44:23 AM
H
Table 1. T ryptophan use by patients in the study
Exposure to L-tryptophan Contaminated Non-contaminatcd
PSS n = 153
EF n= 8
24 II 1.3
5 4 1
E F = Eosinophilie fasciitis.
We also analyzed the files of 8 patients formerly diag nosed with eosinophilic fasciitis: 4 had to be reclassified as having the cosinophilia-myalgia syndrome [14], because of the close connection between clinical symptoms and the ingestion of contaminated /.-tryptophan. However, one
further patient, a 57-year-old woman, had taken non-contaminated /.-tryptophan in 1986 at an overall dosage of > 1000 g and developed a rheumatic disease with general ized oedema, severe arthralgias and subsequently the typ ical clinical signs of eosinophilic fasciitis. The ingestion of contaminated /.-tryptophan after the autumn of 1988 is obviously responsible for the eosinophilia-myalgia syndrome, which reached nearly epidemic lev els not only in the USA. but also in central Europe. Noncontaminatcd ¿.-tryptophan may also induce fibrotic dis eases like eosinophilic fasciitis and localized scleroderma [ 12]. In contrast, the pathogenesis of PSS does not seem to be related to this compound, because in several retro spective investigations (including this one) >200 PSS patients [12, 13] have now been analyzed, and no evidence of exposure to /.-tryptophan, produced cither before or after the autumn of 1988, has been identified.
References
174
6 Mayeno AN. Lin F. Foote CS. Loegering DA. Antes MM. Hedberg CW. Glcich GJ: Char acterization of "peak E'. a novel amino acid associated with eosinophilia-myalgia syn drome. Science 1990:250:1707-1708. 7 Crofford LJ. Rader JL Dalakas MC. Hill RH. Page SW. Needham LL. Brady I S. I levés MP. Wilder RL. Gold PW. Ilia I. Smith C. Stern berg EM: /.-Tryptophan implicated in human eosinophilia-myalgia syndrome causes fasciitis and perimyositis in the Lewis rat. J Clin Invest 1990:86:1757-1763. 8 Yamaoka KA. Miyasaka N. Kashiwasaki S: /.Tryptophan contaminant 'peak E' and interleukin-5 production from T cells. Lancet 1991: 338:1468. 9 Sternberg EM. Van Woert MH. Young SN. Magnussen I. Baker II. Gauthier S. Osterland C'K: Development of a scleroderma-like illness during therapy with Z.-5-hydroxytryptophan and carbidopa. N Engl .1 Med 1990:303: 782-787.
Mousing
10 Auffranc JC. Bcrbis P. Fabre JF. Garnier JP. Privat Y : Syndrome sclérodermiforme et poïkilodcrmique observé au cours d‘un traitement par carbidopa et 5-hydroxy-tryptophane. Ann Dermatol Vénéréol 1985;112:691-692. 11 Joly P. Lampert A. Thomine E. Lauret P: Development of pseudobullous morphea and scleroderma-like illness during therapy with /.5-hydroxytryptophan and carbidopa. J Am Acad Dermatol 1991:25:332-333. 12 Blauvelt A. Falanga V: Idiopathic and /.-tryp tophan-associated eosinophilic fasciitis before and after /.-tryptophan contamination. Arch Dermatol 1991:127:1159-1166. 13 Freundlich B. Werth VP. Rook AH. O'Conner CR. Schumacher HR. Levdenn SS. Stolley PD: /.-Tryptophan ingestion associated with eosinophilic fasciitis but not progressive sys temic sclerosis. Ann Intern Med 1990:112: 758-762. 14 Mensing II. Schallreutcr K, Scuff II. Stcinkraus V: Das Eosinophil¡e-Myalgic-Syndrom. Klin k und Verlauf bei 10 Patienten. Hautarzt, in press.
/.-Tryptophan and Scleroderma
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 4:44:23 AM
1 Centers for disease control: Eosinophilia-myalgia syndrome: New Mexico. MMWR 1989:38: 765-767. 2 Silver RM. Heyes MP. Maize JC. Quearry B. Bionnct-Fuassct M. Sternberg EM: Sclero derma. fasciitis and cosinophilia associated with the ingestion of tryptophan. N Engl .1 Med 1990:322:874-881. 3 Swygert LA. Maes EF. Sewell LE. Miller L. Falk H. Kilbourne EM: Eosinophilia-myalgia syndrome. Result of a national surveillance. JAMA 1990:264:1698-1703. 4 Kaufman LD. Scidman RJ. Phillips ME. G ru ber BL: Cutaneous manifestations of the /.tryptophan-associated eosinophilia-myalgia syndrome: A spectrum of sclerodermatous skin disease. .1 Am Acad Dermatol 1990:23: 1063-1068. 5 Belongia EA. HedbergCW . Gleich GJ. White KE. Mayeno AN. LögcringDA. Dunnette SL. Pirie PL. MacDonald KL. Osterholm MT: An investigation of the cause of the eosinophiliamyalgia syndrome associated with tryptophan use. N Engl J Med 1990:323:357-365.
