Document RJ5yRBdr2G2bdZRROw94MrLMX

I lt UNION CARBIDE CORPORATION P.,0. BOX 8361, SOUTH CHARLESTON, WV Health, Safety & Environmental Affaire Department August 24, 1981 25303 Robert C. Maynard, Esq. Squire, Sanders & Dempsey 1800 Union Commerce Bldg. Cleveland, Ohio 44115 Re; Bumbarger vs. UCC et al Dear Mr. Maynard: My letter dated August 6, 1981 states that polyvinyl chloride disease is not an identified syndrome in the litera ture and cites The Society of the Plastics Industry file which you have. A further search of MEDLARS has been made. This search unearthed one reference to polyvinyl chloride disease, "Classi fication and Nomenclature of Progressive Systemic Sclerosis (Scleroderma)" by G. P. Rodnan, Stephanie Jablonska and Thomas A. Medsger, Jr. in Clinics in Rheumatic Diseases. Volume 5, No. 1, April, 1979. A quick check of the references cited in the article (Veltman, Suciu and Selikoff) shows that the authors erroneously converted the term "vinyl chloride disease" to "polyvinyl chloride disease". The article is not without merit for our cause however, in that the authors title their discussion of vinyl chloride as "Chemical Induced Scleroderma-Like Conditions". This appears to distinguish the vinyl chloride induced disease from the much more serious "progressive systemic sclerosis" or "systemic sclero derma" and other types of scleroderma. I am attaching a copy of the article for your information. UCC 049242 Robert C. Maynard, Esq. August 24, 1981 Page 2 If the case progresses to a point where medical experts required they should be made aware of this reference. Very truly yours, /UUA RNWjr/dh R. N. Wheeler, Jr,*' Assistant Director of Product Safety Attachments CC: M. G. Manetti, Esq. L. A. Crisorio ucc 049243 Nrti.-v T!,,-inrv.t n.ilin >, s___,-( t. 1 ' ). W , li I . - 1 Classification and Nomenclature of Progressive Systemic Sclerosis (Scleroderma) GERALD P. RODNAN STEPHANIE JABLONSKA THOMAS A. MEDSGER Jr The term scleroderma (meaning hardening or the skin) has traditionally been applied to a heterogeneous group of conditions, consisting, on one hand, of a cluster of disorders designated collectively its localized or focal scleroderma in which there is more circumscribed or patchy fibrosis limited to the dermis and immediately subjacent tissues, and, on the other, of a generalized multi-organ disorder of connective tissue known as progressive systemic sclerosis or systemic scleroderma (PSS) (Goetz, 1945), which incorporates symmetrical thickening of the skin with fibrosis and degenera tive changes in the synovium, digital arteries, and certain internal organs, notably the oesophagus and intestinal tract, lungs, heart, and kidney (Tuffanelliand Winkelmann, 1961; Jablonska, 1975; Rodnan, 1979). Vascular abnormalities, affecting chiefly the microcirculation and small arteries, con stitute a prominent feature of the disease (Maricq and LcRoy, Chapter S). Progressive systemic sclerosis is variably; severe and variably progressive, with a spectrum ranging from widespread cutaneous thickening (I'SS with diffuse scleroderma) with rapidly advancing visceral involvement to a form which is distinguished by much more restricted skin change--often confined to the fingers and face--and the passage of a prolonged period of lime (often several decades) before the full expression of characteristic internal mani festations (CREST syndrome variant) (Table 1) (Rodnan, 1979). Certain components of progressive systemic sclerosis are also encoun tered in a number of `overlap' syndromes, such as mixed connective tissue disease (Sharp et al, 1972) and sclcrodermatoniyositis (Tuffanclli and Win kelmann, 1962). Mixed connective tissue disease is a recently recognized connective tissue disease `overlap' syndrome in which there is an admixture of features typical of PSS (sclerodermatous changes in the hands, oesophageal dysfunction, and Raynaud's phenomenon) with various mani festations of systemic lupus erythematosus and polymyositis; this disorder is marked hy extremely high litres of antibody (hacinagglutination) reactive ( ' Clinics in Rheumatic Harases--Vui. J. No. t, April I '17*1. 5 % 6 GERALD V. RODMAN, STEPHANIE JABLONSRA AND THOMAS A. MEDSGER Table I. ('luuijiratimi nfsrlrrtulrrma 1. Progressive systemic sclerosis (a) With symmetric, diffuse involvement of the skin (scleroderma}--affecting trunk, face, and proaimal as well as distal pontons or the cxircmitic*. and a tendency toward the relatively early appearance of disease of the oesophagus, intestine, heart, long, and kidney--classical dims* (b) With relatively limited involvemen! of the skin--often confined to the Ungers and face. Prominence of C'aktnosis, Ksynsud's phenomenon, faophageal dysfunction, Jdcrodsctyly, Telangiectasia. and prolonged delay in appearance of distinctive internal manifesta tions (iitrinding severe pulntauuiry arterial hypertension and biliary cirrhosis)---CAES? (c) 'Overlap' syndromes, skMm( sekfivlvnuatomyositia ami mired connective tissue dis ease 2. l.ocalircd (focal) forms of scleroderma (a) Morphoca 1. I1a<|uc-likc morphoca 2. Guttate morphoca 1. Generalised morphoca 4. Less typical forms: subcutaneous morphoca, keloid morphoca 5. ? Superficial primary atrophic morphoca (atrophoderma Paiini-Pierini) (h) Linear scleroderma, with or without melorheostosit (e) Scleroderma rn roup Jc sabre. with or without facial hemiatrophy 3. Chemical-induced sckrodctma-like conditions (a) Polyvinyl chloride disease (b) ? Trichlorcthylenc-induced sderoderma (c) Bleomycin-induced fibrosis 4. I'oMiutphilic fasciitis with nuclear ribonuclcoprotcin (Sharp ct aI, 1976; Chubick and Gilliam, 1978). Progressive systemic sclerosis has been described in people ofall races and appears to be global in distribution. In view of the difficulty of delecting the disease in ils milder form (CREST syndrome), there is reason to believe that recent estimates of the incidence of PSS (4.5 to 12 cases per million populalittn per year) arc falsely low. T!IE CREST SYNDROME In reviewing the older literature dealing wilh PSS, it is clear that the form of the disease which is now generally designated as the CREST syndrome was formerly known under (lie term ocrosclerosit (Scllei, 1931,1934; O'Leary and Waismnn, 1943). Recognition of this variant dates back to 1893, when 11ulchinson described a woman who had experienced episodes ofRaynaud's phenomenon `almost from childhood* and was first noted to have tightness of the skin in Iter hands when she was 41 (Hutchinson, 1893)*. When seen at ' ft.ifl it emtied ilic iHViniciHx- uf a `special vaiicly' nf sckrinkrinu liiuiteil lit Hie lingers hi u wum.iii whtt hail liad repealed episodes nf cohl-irtducctf Raynaud's phenomenon since childIhmhI as cjiK as IK?I (Hall, )H?i); fmtr yean talci thi* same tulluu inUixluccd lle term xitffttt/uttyi/f (Hall, |H?5|. CLASSIFICATION AND NOMENCLATURE OP PSS 7 age 50 this patient had gangrene of the tip of a forefinger (and had suffered from the same in several other lingers) and it was noted that Iter face was `board-like*. Hutchinson suggested that this case `forms one of the most definite connecting links between Raynaud's disease and disuse scleroderma*. Three years later Hutchinson reported another patient with 'aero-scleroderma' and flexion contractures of the fingers which had developed in the wake of long-standing Raynaud's phenomenon. The face of this young woman was `dotted with stigmata* and its features contracted; licr lips were thin and failed to cover her teeth, and there was `evident loss of mobility* of the facial skin (Hutchinson, 1896). Soon after this, the occurrence of subcutaneous calcinosis (a prominent feature in many cases of the CREST syndrome), first noted by. Weber in 1878, was emphasized by Thibiergc and Weissenbach and the association between calcinosis and sderoderma lias long been known, and is still refer red to, as the Thibierge-Weissenbach syndrome (Thibiergc and Weissen bach, 1910,1911). Hie calcinosis found in the CREST syndrome tends to be much more extensive and exuberant and the telangiectasia much more florid than that encountered in individuals with PSS and diffuse sderoderma. O'Leary and Waisman defined acroscterosis as a syndrome which `com bines the features of Raynaud's phenomena with a characteristic scleroderma of the distal parts of the extremities and of the face and neck' (O'Leary and Waisman, 1943). They provided a richly detailed account of their experience with 64 patients with this disorder, which included descrip tion of the characteristic calcinosis and telangiectasia of CREST syndrome, ns well as notation of oesophageal involvement (including two cases of stricture). In describing tliv condition of the skin, they slate: `Alter the development of the cutaneous changes on the hands, forearms, face and upper part of (he chest, further extension is unusual, although the vas omotor phenomena persist and the sclerosis and other trophic disturbances may increase. The topographic localization or restriction is an essential feature of acroscterosis, being one of the characteristics which distinguish it sharply from progressive diffuse scleroderma.' Although Scllei argued that acroscterosis be considered a disorder unre lated to diffuse scleroderma, this distinction was criticized by Goetz, wiio wondered whether the two conditions `arc not after all only mere variations in the course of one disease' (Goetz, 1945), a view which has now hecn accepted by many other authors (Rothman and Walker. (949; Lcinwaml, Durycc and Richter, 1954; Jabfonska, Bubnowand Luka.siak, J9.S8, 1959; Farmer, Gifford and Hines, 196(1; Tuffonclfi und Winkclmann, 1902; Har nett, 1974*; Jabfonska, 1975; Rodnan, t979). Attention was rc-drawn to acroscterosis in recent times by reports which suggested that the combination of calcinosis (C), Raynaud's phenomenon (R), sclcrodactyly (S) and telangiectasia (Y) (thus the original acronym of CRST syndrome) represented a benign variant associated with a more * We consider both type 1 and type 2 scleroderma with systemic involvement ( progressive systemic sclerosis) of Darnell (1074) as well as many instances of chronic Raynaud's disease wilh chronic visceral sclerosis of Winkclmann (l*)71) lo represent tin: l ULST syndiontv. 1 i% ucc 049245 b lirKAU) I*. KOUNAN, STI-PIIANII! JAItl.ONSKA AND THOMAS A. MF.DSGIiR favourable prognosis than ilio classical farm of the disease (i.c. PSS .with ilillnse sclciodcima) (WiiitcihatiCT, I')<)). Raynaud's phenomenon, alone or in vomhitiaiton with swollen, puffy fingers, is llie initial manifestation in t he great majority of these eases. In one large series the mean age at the time of initial diagnosis was 49 years, or an average of ten years after appearance or the first symptoms (Rodnan, Medsger and Buckingham, 1975). During the interim these individuals were commonly thought to have 'Raynaud's disease' or 'primary' Raynaud's phenomenon. Although the life span of patients with the CREST syndrome is significantly longer than that of individuals with PSS and diffuse scleroderma (O'Leary and Waisman, 1943; Farmer, Gifford and Hines, I960; Medsger ct al, 1971; Rodnan, Medsger and Buckingham, 1975) and although the illness of the former is often very mild and only very slowly progressive, prolonged observation has disclosed that the CREST syndrome is by no means an entirely benign disorder. In addition to the frequent development of oesophageal dysfunction indistinguishable in its pathogenesis from that occurring in the classical form of PSS (hence the insertion r E, for `esophagus', to form the acronym CREST syndrome), these individuals are liable to develop severe pulmonary hypertension (Salerni ct al, 1977) and a peculiar form of biliary cirrhosis (Reynolds ct al, 1971). Many also show evidence of Sjogren's syndrome (Cipulctfi et al, 1977). The relative frequency with which one secs patients with the various forms of scleroderma will depend on ihe nature of one's clinical practice and the attendant patterns of referral. Dermatologists tend to have moreexperience with localized scleroderma, while rheumatologists, being sub-specialists in internal medicine, arc more likely lo see chiefly pnlicnls with PSS and related disorders in which there is a predominance of visceral dysfunction. In our experience at the University of Pittsburgh during the period 1972 to 1978, the number or newly examined cases of PSS with diffuse scleroderma (135) proved lo be almost exactly equal to the number with CREST syn drome (138). In both of these groups, the ratio of women to men affected was slightly greater than 4:1 (Table 2). LOCALIZED SCLERODERMA The tightening and hardening of the integument that occurs in the several varieties of localized scleroderma may be indistinguishable from that found in PSS, but certain pathological as well as clinical differences separate these disorders (Jabtonska, 1975; Rodnan, 1979; see also Chapter. 13, by Jablonska and Rodnan). In contrast to PSS, localized scleroderma is more common in children than adults, lends to run a much milder course and is never lethal. After a more or less protracted period, spontaneous recovery, partial t>r complete, is not infrequent. In our experience there has been no convincing evidence of Raynaud's phenomenon or of internal involvement in individuals with isolated plaque-like or guttate morphoea or linear scleroderma, or of transition of these conditions to PSS, although one of us (S.J.) has observed the development of a diminution in oesophageal peri- CLASStFICATtON AND NOMENCLATURE OF ESS 9 stiilsis and a reduction in (wlmonary diffusing capacity in a few children with extensive generalized morphoea and symmetrical cutaneous changes. CHEMICAL-INDUCED SCLERODERMA-LIKE CONDITIONS A peculiar osteolysis of the distal phalanges (aero-osteolysis) has been recognized in a small percentage of workmen who clean reactor-vessels containing Ihe polymerizing agent vinyl chloride (CHjClICI) (Sclikoff and Hammond, !975;Sucioct ai, 1975; Vcltmanctal, 1975). These individuals also develop Raynaud's phenomenon, nodular induration of the skin of the hands and forearms, synovial thickening of the proximal intcrphalangea! joints and an unusual form of hepatic and pulmonary tibrosis. Nailfold microvascularabnormalitieswhichmimicthoscencounteredinPSShavcbcen observed but the relationship, if any, between these disorders is still obscure. Cross-link analysis and measurement of hydroxyprolinc formation (organ culture) have indicated that there is an excess in new collagen production (Jayson et al, 1976). The development of a disorder with some features similar to those of polyvinyl chloride disease has recently been reported in a man who had had prolonged exposure lo high concentrations of trichlorethytenc, a structurally similar chemical (Siahan, Burton and Heaton, 1978). TaMr 2. ftthrivefrequencyofdiffuse trierwlemaandofCRBSTsyndrome andratios ofwomen to men in patients with progressive systemic sclerosis seen for first lime at the University of Pittsburgh Medical Center during the perioti /V72 to I97H No. patients Women Men W/M PSS with diffuse scleroderma 13S 1 to 25 PSS with CREST 138 Iff syndrome 27 Total 273 221 52 4.4 4.1 4.3 Administration of the fumoricidal drug bleomycin often leads to the development of nodules and/or plaques of thickened skin, the result of an increase of dense collagen in the dermis (Cohen et al, 1973). On occasion . there may be more generalized induration of the dermis, closely similar to that found in PSS. The association of these changes with pulmonary fibrosis and with Raynaud's phenomenon is of great interest and constitutes an additional point of close similarity to naturally occurring PSS. The dermal fibrosis tends to recede following discontinuation of bleomycin. Culture of skin fibroblasts from a young man with bleomycin-induced diffuse thicken ing of the skin has yielded evidence of an increased synthesis of dermal collagen, similar to that found in individuals with PSS (Finch ct al, 1979). 9VZ6M3 00n \ IQ GERALD P. RODNAN, STEPHANIE JABLONSXA AND THOMAS A. MUDSOER EOSINOPHILIC FASCIITIS Eosinophilic fasciitis is a recently recognized scleroderma-like disorder chiefly affecting adults, the onset of which is characterized by pain, swelling and tenderness of the hands and the forearms and the feet and legs. This is soon followed by the development of severe induration of the skin and subcutaneous tissues of these parts with marked limitation of motion of the hands and feet (Shulnian, I *>77; Barnes ct al, 1979). Striking flexion con tractures of the lingers occur, forming in a period of only a few weeks. Carpal tunnel syndrome is an early feature in many cases. The induration may remain confined to the extremities or spread to affect variably extensive portions of the trunk as well as the face. Raynaud's phenomenon and internal manifestations of progressive systemic sclerosis are conspicuously absent. Striking peripheral eosinophilia is found during I he early slagcs of this disorder, often 30 per cent or more of the total leucocytes, and liypergammaglobulinacmia (IgG) is common (Rodnanctal, I97S). 11 biological diagnosis is best established using a deep wedge biopsy which includes skin, subcutis, fascia and muscle. Inflammation and fibrosis are found in all layers (including the dermis) but this is most impressive in the fascia, which may be thickened many-fold (Barnes et al, 1979). Large numbers of lymphocytes, plasma cells, histiocytes and eosinophils arc pres ent in the affected areas. The disease tends to be self-limited, with spontane ous and often complete remission after periods of two or more years being the rule. Corticosteroids, in small doses, generally provide substantial symp tomatic relief and readily obliterate the eosinophilia. Tablr 3. Dormer in which there tire skin changes that may resemble scleroderma Cpseudotckroderma*) A. Oedcmatuus 1. Scicinterna (scleredema aduttorum of Buschke) (A. Buschke, 1900) 2. Selemmyiocdcma (litturn myatdcmatuMis. papular mucinosis) 8. Indurative 1. Carcinoid syndrome 2. Phenylketonuria 3. Porphyria cutanea tarda 4. Confcnil.il porphyria 5. Primary and multiple myeloma-associated amyloidosis 6. Acromegaly C. Atrophic |. Werner's syndrome (O. Werner. I9(M) Progeria > Rollimtind's syndrome (Rnthmund-Thompson syndrome) (A. Rothmund Jr, 1868; M. S. Thompson. 192.1) 4 Air.niffnull I is chronica atrophicans 5. Lichen seleiosuset sttophieus 6. Lipiutropliy--ol the ankles, annular, panatrophy Gowers CLASSIFICATION AND NOMENCLATURE OP l*SS 1l The aetiology of eosinophilic fasciitis is unknown, although it has been noted that the illness is often preceded hy umiMtally strenuous exertion, Eosinophilia, the raised scrum IgG levels, and the identification of immunoglobulin and complementcomponent C3 in the inflamed fascia raise the possibility that a humoral immune mechanism may be involved in pathogenesis. Eosinophilic fasciitis should always be considered in any individual with symmetrical scicrodcrma-like thickening and induration of the skin of the forearms and/or legs who has pcripltcral eosinophilia and fails to exhibit Raynaud's phenomenon. PSEUDOSCLERODERMA There are a number of diseases in which one is confronted with skin changes that may resemble those ofscleroderma. Ordinarily there is little difficulty iu differentiation since these maladies lack the visceral components of PSS and display other characteristic diagnostic features of their own. A list of these conditions, to which the term pseudoscleroderma has been applied, is given inTablc3(Jablonska, 1975; Rodnan, 1979; see also Chapter 14, by Flcischmajer and Pollock). REFERENCES Bill, B. (1821) Cur presentation. Stance du 10 juin (I). Compte Rendu des Stances de la Socitlf de Biotogie, 13,43-S2. Ban, D. (1873) Case presentation. Bulletin et Mtmoire de la Socitlf Midicale des lldpitaui de Paris, 11,96. Bancs, E. L., Rodnan, G. P., Medsger, T. A. A Short, D. (1979) Eosinophilic fasciitis: a pathologic study of twenty cases. American Journal ofPathology. 96,493-51*. Barnett, A. J. (1974) Scleroderma (Progressive Systemic Sclerosis). Springfield, IHinois: Charles C Thomas. Chubtck, A. A Gittiam, J. N. (1978) A reviewof miicd connective tissue disease. International Journal ofDermatology, 17, 123-133. Gpolctli, J. F., Buckingham. R. B.. Barnet, E. L, Peel, R. L, Mahmood, K.. Ggnetti, F. E.. Pierce, J. M., Rabin, B. S. A Rodnan, G. P. (1977) SjSgren't syndrome in progressive systemic tdcrosis (scleroderma). Annals ofInternal Medicine, 87,535-541. Cohen, I.S.. Mosher. M U . O'Keefe. E. J.. Klaus. S. N.A IXConti. R. C.( 1973) Cutaneous tonicity of bleomycin therapy. A rehives ofDermatology, 107, 553-555. Farmer, R. G., Gifford, R. W. JrA Hines, E. A. Jr (1960) Prognostic significance of Raynaud's phenomenon and other clinical characteristics of systemic scleroderma. A study of 271 eases. Circu/rMKWi. 21, 1088-1095. Finch. W. R., Rodnan, G. P., Buckingham, R. B.. Winkelitein, A. A Prince, R. K. (1979) Skin filrroblast activity in bleomycin induced scleroderma. Arthritis and Rheumatism, 12. 608-609 (abstract). Gaels, R. H. (1945) The pathology ofprogressive systemic sclerosis (generalized scleroderma) with special reference to changes in the fiscera. Clinical Proceedings. The Journal of the Cape Town Post-Graduate Medical A.tstxiafion. 4. 337-392. tlutch'msoft, J. (tK93) Inherited liability to Raynaud's phenomena, with great prooencsx to chilblains--gradual increase or liability to paroxysmal local asphyxia--acro-sphacclu* with sell'rollermb --checks affected. Archives ofSurgery (London). 4, 312-313. Hutchinson, J. (1896) Aero-scleroderma following Raynaud's phenomenon. Clinical Journal (London), 7, 240. Jablonska, S. (Ed.) (1975) Scletoderma and Pseudoscleroderma. 2nd Edition, Warsaw: polish Medical Publishers. LbZ6M) OQfi i 12 GERALD T. RODNAN, STENIANIE JABLONSKA AND THOMAS A. MBDSGSR Jablonska, S.. Rnhnow. B. A Lukasiak, B. (I9J8) Raynaud's syndrome; acroademah; sckrodctou. British Journal of Dcrnuuuiogy. 70, 37-43. Jablonska. S,, Buhnow, B. A Lukasiak, B. (1939) Acrosrlcroab: a disease mf gtnrrit or a variety of diffuse scleroderma? British Journal of Dermatology, 71,123-133. Jayion, M. I. V.. Bailey. A. J.. Black. C. A Lloyd-Jones. K. (1976) Collagen studies k) acto-ostcolysis. Proceedings ofthe Royal Society ofMedicine, (9, 293-297. Leinwand, I., Duryee, A. W. A Richter, M. N. (1934) Scleroderma (baaed on a study of over 130 cam). Anneli ofIrnrmal Medicine, 41,1003-1041. Mcdsgcr, T. A., Mari, A. T.. Rodnan, G. P, Bcoedck, T. G. A Robinson, H. (1971) Survival with tytiemic aclerotir (tdcrodctma). A life-table analysis of 309 patients. Annals of Internal Methane. 75, 369-376. O'Leary, P. A. A Waiaman, M. (1943) Acrosckrosif. Archive* ofDermatologyand Syphiloiogy (Chicago). 47, 382-397. Rcynohfc. T. D.. Denison, E. K.. Frank], H. D., Licberman, F. L. A Peters, R. L. (1971) Primary biliary cirrhosis with scleroderma, Raynnud'a phenomenon and telangiectasia. New syndrome. American Jottmef ofMedicine, 50,302-312. Rodnan. G. P. (1979) Progressive systemic sclerosis (scleroderma). In Arthritis and ABied Ctmtltnnns, 9th Edition (Ed.) McCarty, D. i. Jr. Philntfclpliia: lata and litbiger, pp, 762-809. i Rodnan, G. P., Mcdsgcr, T. A. Jr A Buckingham, R. B. (1975) Progressive systemic sclerosis--CREST syndrome: observations on natural history and late coni|dicatiuns in 90 psUctUi. Arthritis and Rheumatism, IS, 423 (abstract). Rodnan. G. P,, Di Bartolomeo, A. G,, Medsger, T. A. A Barnet, E. L. (1973) Eosinophilic fasciitis: report of seven cases ofa newly waiptited sdcrodcrma-like syndrome. Arthritis and M-anninri. 18. 422-423 (abstract). Rothman. S. A Walker. S. (1949) Scleroderma. Medical Oinks ofNorth America, 33,33-77. Saihan, E. M., Burton, I.LA Heaton, K. W. (1978) A new syndrome with pigmentation, scleroderma, gynaccomastia, Raynaud's phenomenon and peripheral neuropathy. British Journal of Dermatology, *9, 437-440. Salcrni. R.. Rodnan, G. P.,leon, D. F. A Shaver, J. A. (1977) Pulmonary Hypertension In the CREST syndrome variant of progressive systemic sclerosis {scleroderma). Annals of Internal tMiiiw, 80. 394-399. Selikoft. I. J. A I lammond, 1;. C. (Editors and Contcrence Chairmen) (1973) Toxicity of vmyt chtoridc-pofyvinyl chtoridc. Annals ofthe New York Academy ofSciences, 244.1-337. Scllei. J. (1931) Die Akrosklcrosis (Skleiodaktyiic) und dertn Symptomenkompies nebtt ncueren Untcnuchungeo bci Sklerodermie. Arthlv file Dtrmaiologie und Syphilis, 143, 343-365. Scllci. 1.(1934) The diagnosis and treatment ofscleroderma and acrosderotts and someoftheir kindred diseases. British Journal of Dermatology and Syphilis, 44, 323-336. Sharp. G. C. Irvin, W. S.. Tan, E. M.. Gould, R. G. A Holman, H. R. (1972) Mixed connective tissue disease--an apparently distinct rheumatic disease syndrome associated with a specific antibody to an eatractable nuclear antigen (ENA). American JournalofMedicine, 51. 148-159. Sharp. G. C.. Irvin. W. S.. May, C. J.. I tolman. 11. R,, McDuffie. F. C.Hcss. I*. V. A Schmid, F. R. (1976) Association of antibodies to rilNinudcoprofcin and Sm antigens with mixed connectivc-tissuc disease, systemic lupus erylbeinalusus and other rheumatic diseases. New England Journal ofMedicine. 295, 1149-1154. Shulman. L E. (1977) Diffuse fasciitis with cosioophilia: a new syndrome. Arthritis and Rheumatism, 2D, S205-S215 (supplement}. Sucio, |,, Prodan.L. Ilea, E-, Paduraru. A. A Pascu.L. (1975) Clinical manifestalinm in vinyl chloride poisoning. Annals ofthe New York Academy ofSciences, 244, 53-69. Thihicrgr. G. A Weissenbach. R.-J. (19111) Une forme dcconcrs'limwealcairessous-oilandes cn rclarion avee la nirnsknuic. Ituttrlin et MJtnnircdrlaSttckiJ MJilicaie ties lliipitaus tie I'urts. .W, 111-14. Thibicigc, G. A WcisscmImcIi, R.-J. (1911) Concretions calcaitcs sous-tiilances el sclcrmk-r- nnc Annith'S de Dermatologic et Srphitigraphir, 2. 129-155. I ullanclli. IJ. L. A K. (1961) Systemic scleroderma. A clinical study of 727 cases. Archives of Dermatology, 84, 359-371. Tu'fanelli, D. L. A Winkclmann, R. K. (1962) Scleroderma and its relationship to the *col- CLASSIFICATION AND NOMENCLATURE OF PSS 13 lagcnosei': dermalomyosilU, lupus erythematosus, rheumatoid arthritis and Sjogren's syndrome. American Journal ofthe Medical Sciences. 243. 133-146. Vehman, G.. Lsngc. C.-E . JOhe. S.. Stein, G. A Dachncr, U. (1975) CUnical manifestatkins and course of vinyl chloride disease. Annals ofthe New York Academy ofSciences, 244, 6*17* Winkclmann, R, K. (1971) Classification and pathogenerit of scleroderma. Mayo Clinic Proceedings, 44.83-91. Wintcrbauer, R. H. (1964) Multiple telangiectasia, Raynaud's phenomenon, sclerodactyly, and subcutaneous calcinosis: a syndrome mimicking hereditary hcmorrhsgic iclangicctasia. Bulletin ofthe Johns Hopkins Hospital, 114, 361-383. a l % ucc 049248