Document RpJwMDbv5Lka4MJjJx6vnzG5E

\' OC?BTR 76-483 C. ON THE SO-CALLED VINYL CHLORIDE DISEASE j (a new occupational disease [Dber die sog. Vinylchlorid-Krankheit (eine neue Berufskrankheit)] S. Juhe, C.-E. Lange, G. Stein and G Veltman u U 0 JL- 7f Berufsdermatosen i Vol. 22, 1974, pp. 4-22.. i ----------------- -- RECEIVED DEC 20 1976 MCOINNSTMAtNTO COM N12N* v ST. LOUIS TRANSLATED FOR EPA BY SCXTRAN (SCIENTIFIC TRANSLATION SERVICE) SANTA BARBARA, CALIFORNIA f'ATICrUL TRANSLATIONS CENTER This trcrcfctton is b3ir.^ frrnislicd for pni-t3 cso and rvi2;rrh on:y. !t nay net fca soUl or pusushed-ia cay form without tfts psrmission of tfcs author. Paps ~~ vMZ. nl.Vi.-T tfiSlftiS RSV 0018179 ON THE SO-CALLED VINYL CHLORIDE DISEASE* (a new occupational disease) S. Juhe, C.-E. Lange, G. Stein and G. Veltman University Skin Clinic; Bonn. Introduction In recent decades the plastics industry has marketed a multitude of synthetic products. Their production and processing requires* continuous and effective observation and testing because of the possible of health-damaging effects. Most of the injuries which have become known from the individual types of plastics are either acute toxic dermatoses (e. g., from methyl methacrylate in the product ion of polymethylmethacrylate -- Plexiglas), where there can occasionally be percutaneous penetration (e. g.v for acrylonitrile in the manufacture of polyacrylonitrile -- Dralon) or results of inhalation and absorption of the corresponding plastic vapors (e. g., pulmonary edema after inhalation of Teflon vapors) which can occur in the polymerization or even in the processing of plastics [24]. Quantitatively, the starting material (the so-called monomer) plays the most important part in the origin of these disease syndromes. Another possibility for injury arises from the presence of the so-called adjuvants or additives needed for the p'rogress of the chemical process, such as the plasticizers, hardeners, fillers, smoothers, catalysts, stabilizers or antioxidants. Furthermore, toxic intermediates' ^Lecture held at the Lower Rhine association for natural and healing sciences, Bonn on June 13, 1973. RSV 0018180 can occur during the production process. Even with the largely inactive end products, one must take hyper* sensitivity into account or, if finely divided plastic masses have penetrated into the organism and remain there for a long time, foreign body reactions (e. g., after excessive use of hairsprays with polyvinylpyrollidine particles: diffuse interstitial pulmonary fibrosis resembling the Hamman-Rich syndrome) and perhaps even a carcinogenic effect. Finally, one must consider the possibility of damage from monomers even when there is decomposition of the polymers (degradation) in processing or application of the end product due to high temperature or other causes [14], A disease picture which we were able to observe in Germany for the first time last year also belongs in this group of diseases [11, 12, 20, 21]. It appears predominantly but,, as we assume today, not solely in autoclave workers in, tha industry manufacturing polyvinyl chloride (FVC). It had become well known in the foreign literature as "occupational acroosteolysis" or "occupational acroosteolysis syndrome" [2,3 4,6,7,9,22, 23,25]. Today, however, on the basis of our more extensive investigations [13, 15] we believe that this is a very complex syndrome. It is probably triggered by long-term exposure to vinyl chloride (VC), and ,is expressed in a connective tissue process which is not yet explained, with fibrosing of the skin and the vascular system, and' probably also in the parenchymatous organs, the lungsand liver, which we studied. Thus, this syndrome gains the character of a systemic disease, with serious prognosis in the advanced stage. It extends, therefore, far beyond the disease picture previously described under the name of "occupational acroosteolysis" Thus, we have separated our* selved from this symptom-linked designation and called the 2 RSV 0018181 new comprehensive syndrome the "so-called vinyl chloride disease ([16] -- extensive presentation and more literature citations). Polyvinylchloride Manufacture VC (CH2"CHC1) is a colorless gas with an aromatic odor and narcotic action, which is heavier than air. The maximum worksite concentration was established.as 100 ppm in 1970 [-10]. The polymerization of VC to PVC goes on in large autoclaves in which the reaction mixture of water, the so-called additives, and the VC is kept in motion by a rotating propellor at 50-55*C until the desired degree of polymerization is attained. In the suspension process, the reaction mixture, after the excess VC is sucked away, is pumped into a mixture holder and, through other supply tanks, introduced to centrifuges in which the polymer is separated frqm the aqueous phase. After drying and separation by particle size, one obtains the finished powdery white polymer. In the emulsion process, the reaction mixture, with other additives (emulsifiers) is sprayed into a spray-drying tower containing hot air, so that the polymer in the sprayed emulsion droplets is immediately dried and separated at the filters [3, 6, 7]. After the reaction mixture is drained off, the autoclave is opened and sprayed with water, using a high-pressure gun. If it is not clean after that, it is filled with water. After the water is drained, one or two workers climb into the autoclave and remove the coatings on the inner wall,' which are often quite solid, with trowels or occasionally evan with hammers and chisels. VC and other gaseous compounds can get into the work area air with the following opportunities: 3 RSV 0018182 1. Amounts of gas perceptible by odor escape from the mixing and storage tanks, from the centrifuges and at the spraydrying tower, as well as from the inlet and outlet lines, the drying system and*the sieving system. (The odor threshold may be about 50-100 ppm, but, of course, it is subject to individual variation.) 2. On each cleaning of the autoclave with the water spray gun, the residual gas escapes into the autoclave. This can be a considerable amount, so that it is possible to reach the concentration at which the autoclave workers experience a prenarcotic syndrome (numbness, dizziness, nausea [18, 19]. 3. In particular, the workers who clean the inner walls of the .autoclaves with trowel and chisel are exposed to the gases which diffuse out of the wall deposits or occur in holes in the polymer deposits. The air analyses near the inner wall of the reactor, i. e., in the region where the hands and faces of the workers are exposed, showed concentrations of 600-1,000 ppm. 4. large amounts of gas are liberated through leaks (at the valves, for instance) on loaded autoclaves and through insufficient VC recovery. The predominant portion of the residual gas from auto claves consists of VC (chemical analysis: 90% VC, 8.5% carbon dioxide, small amounts of vinyl acetate, trichloro ethylene and nitrogen," traces of argon) [5]. 4 RSV 0018183 Our Observations and Study Results Since the beginning of 1972 we have investigated 10 workers, aged 29 - 40 years, at a plant producing FVC. They had come to us because of the clinical skin changes. They had worked from 1 3/4 to 12 years, and the average latent period to the appearance of the first symptoms was about 2 years. The general complaints included increased sweating (7 patients); frequent feeling of dizziness (5 patients); occasional nausea at the work place (3 patients); reduced vision; poor hearing; and headaches. As the_ first symptoms of the disease, 7 patients noted increased feeling of coldness in the region of individual fingers or hand, connected with numbness and itching. Pressure sensitivity at the finger tips, looseness of the nails, and club-like swelling of individual fingertips were each noted by one patient. For 6 patients, the skin symptoms started on fingers 1-3 of the right hand, and only for 3' patients on the 2d or 2d and 3d fingers of the left hand. They can be arranged as follows (Table 1). Table 1. SUMMARY OF THE CLINICAL SKIN CHANGES IN 10 PATIENTS WITH THE SO-CALLED VINYL CHLORIDE DISEASE No. l 2 J4 ( 7 9 it Patient sO..5a. D.Z J.F. H.D. A. W. H.A. SMc.WC. K.H. Cold Sensitivity (R: with Raynaud syndrome + + + no + 00 -- -- 00 + 00 -- Drumstick finger + + _ + + + + Hourglass nail KoilcnyAia + + Sclerodermic skin changes + av. -- + .+ " P+- + Sum | 76 8 5 RSV 0018184 .1 In 7 patients there was increased sensitivity to cold in the hands, and usually in the feet as well. With 4 of these it was even possible to provoke a Raynaud phenomenon repeatedly in cold exposure tests (Figure 1, p. 7, top). 2. In 7 patients there were drumstick-like, clubby swellings of the terminal phalanges of one or of almost all fingers. In correlation with the X-ray changes yet to be presented, these were predominantly on the fingers of the right hand (Figure 2, p. 7, center). 3. The nails of the fingers affected were curved up in an hourglass shape (see Figure 2) except for one patient in which koilonychia developed. But in contrast to "true" drumstick fingers, we found not only a clubby swelling, but a distinct shortening of the terminal phalanges and of the finger nails. 4. Eight patients had the very characteristic skin changes, similar to sclerodermia: infiltrations which were very firm, relatively sharply bounded, whitish to ivory-colored, usually raise'd above the skin level, and of the size of cereal grains to small nodules, or even more, plate shaped (Figure 3). We saw such indurations most often above the basal joints of the fingers and in the immediate vicinity of the Proc. styloideus ulnae, at the ulnar side of the back of the hand, and at the distal third of the inner side of the lower arm, with distinct reduction proximally, and less frequently on the extensor sides of the fingers, distal to the olecranon and in the face (malar and zygomal bone regions). Samples were excised from the right or left hand of all patients. In all, even those who showed clinically only a Raynaud syndrome without palpable infiltrations, there were essentially the same changes (Table 2); more or less expressed, distinct hyperorthokeratosis (Figure 4); increasing narrowing of the epidermis with gradual flattening of the epidermis-cutis 6 RSV 0018185 I Figure 1. j i j I i I I I Figure 2. Figure 3. Captions on this page illegible in German text. 7 RSV 0018186 i Tabic 2. HISTOLOGIC CHANGES IN THE SKIN OF 10 PATIENTS WITH SO-CALLED VINYL CHLORIDE DISEASE. No. Patient Epidermis Cutis Cutis (a s hyper- 1. * 2. ortho Collagen Elastic Fibers keratosis; a: a: . reduction b: atrophy) multipli b: fragment cation; ation >: homogen ization A Cutis 3. Vessels A Tissue Status t fa- J. (U I O.Z. 4 S.W. A -A A -- S AD. --A A tA ft A . ft A --A --A ft A A capillaries edema in central with endo corium, perivascular thelial swell infiltrates ing in the subepithelial boundary layers normal sclerotic normal collagenous connective tissue very densely packed occasional expanded capillaries in the upper corium normal vessel walls swollen in central and upper corium severe edema in corium BSV 0018187 / Tabic 2. Continued. No. c 7 t 'O m Patient Epidermis Cutis Cutis [a s hyper- 1- 2. ortho- Collagen Elastic ceratosis; & 9 Fibers b: atrophy) Multipli a: reduction cation; b: fragment bs homogen ation ization Cutis 3. Vessels b a b b normal H. A, b 'i -- b normal M.C K.W. K.K. .1 b ft --' --- a b a b Distinct wall thickening of central and deep corium -- partial wall thickening b a b capillaries expanded and increased in upper corium Tissue Status corium edema; loose, predominantly lympho cytic infiltration slight lymphocytic infiltration moderate edema; loose lymphocytic infil tration normal deeper corium sclerotic RSV 0018188 i 4> Figure 4. Hyperorthokeratosis. Increased and expanded capillaries, some with endothelial swelling and a loose, sparse, predominantly lymphocytic infiltration. Broadened collagenous bundles with few nuclei, (hematoxylin-eosin stain;. _ boundary, in which the papillary bodies vanish first, while the retial patterns can remain for a longer period. The cutis occasionally shows considerable broadening with multiplication of usually nucleus-poor, swollen and/or homogeneous collagenous bundles with the skin appendages being "walled about", or with the sweat glands being pushed higher on (pressure) atrophy of the sebaceous glands and hair follicles (Figures 5 and 6). The elastic fibers show distinct to considerable rarefaction, splitting up, and fragmentation (Figures 7 and 8). In the subepidermal boundary layers, one sees multiplied and expanded capillaries with endothelial swelling. Likewise, the vessels of the central and lower corium occasionally show distinct wall thickening. The entire cutis shows moderate intracellular edema and a loose,, usually sparse, predominantly lymphocytic infiltration occasionally between the collagenous bundles and with some regularity around the vessels. 10 RSV 0018189 Figure 5 Swollen and homogeneous collagenous bundles. (Hematoxylin-eosin stain). Figure 6. Multiplication of the expanded, swollen and homogenized collagenous bundle with the sweat glands "walled off". (Hematoxylin-eosin stain). 11 RSV 0018190 Figure 7 Severe rarefaction and fragmentation of the elastic fibers. (Elastic staining). Figure 8. Almost complete rarefaction and splitting up of the elastic fibers. (Elastic staining). RSV 0018191 12 Table 3. BONE CHANGES IN 10 PATIENTS WITH THE SO-CALLED VINYL CHLORIDE DISEASE Hand Skeleton Foot Skeleton Other Skeleton No. Patient Osteo porosis Marginal defects Banded Osteo Marginal Banded Arthritis Bone osteo porosis defects osteo- Cysts (atrophy) (Proc. ung.) lyses (atrophy) [Proc. ung.) lyses [terminal [terminal phalanges) phalanges) 1 S.G. -- + 4. -- <+> 44 2 O.S. 4 4' + + -7- ' -- 4 3 r.z. + -- ---- -- ------ 4 j.p . -- 4 ---- -- ---- -- . 5 H.D. -- -- 4-- 4---- -- 6 A.W. -- 4 -- -- -- -- + 4' 7 H.A. 4 4 +-- ---- 4 --. 8 M.C. 9 S.W. -- + + + -- <> -- -- -- + -- + ------ 4 10 K.H. + -- 4-- ---- 4 4 5 6 6 2 1(2) 0 4s RSV 0018192 i \ t r I i, ,i The bone changes were particularly impressive (Table 3). They appear to be the major symptom, and have led to the name of "occupational acroosteolyses" in the Anglo-American literature Figure 9. Banded osteolyses in the bases of the Proc. unguiculares of the 2d-4th fingers of the left and the lst-3d and 5th fingers of the right hand, which extend into the shaft In some terminal phalanges. Some small bone fragments or sequesters can be detected in the resorption bands. A "fracture line" runs through the Proc. unguicularis of the 4th finger at the right (1962). Typical banded or striped osteolyses appeared in the hands of 6 patients at the bases of the Process! unguiculares, predom inantly in the first through third fingers on both sides, with shortening of the terminal phalanges affected. In some cases the Proc. unguiculares separated by the osteolyses show small bone fragments or sequestered bones (Figures 9 and 10). Six patients showed bone defects at the margins of the Proc. unguiculares, and 5 a diffuse bone atrophy in the hand skeleton* 14 RSV 0018193 Figure 10. . Control picture 10 years after the first invest igation (3 years after termination of work in occupation). The Proc. unguiculares have in part built up again. On the other hand, the osteolysis has advanced farther proximally in the shaft. The Process! sit at the stumps of the terminal phalanges with a gap which is still clearly detect able. The "fracture line" running through the Proc. unguicularis of the 4th finger of the right hand is no longer demonstrable. The terminal phalanx of the 5th finger of the right hand appears as a structurally intact but shortened terminal phalanx. One patient had, instead of an acroosteolysis, a distinct fungiform broadening of the Proc. unguicularis with zones of condensation at the transition of the Proc. unguicularis to the shaft, broadening of the shaft, and also shortening of the finger terminal phalanges. In the foot skeleton, unspecific changes such as atrophy and small marginal defects of the Proc. unguicularis appear in 4 cases; and typical marginal separations of the Proc. unguicularis of both big toes in one case. The ileosacral joints of 4 patients showed unsharp contours and sclerosing. Many cystic lightenings appeared in the region of the caput humeri and of the 15 RSV 0018194 Proc. styloideus ulnae In five patients. Banded osteolyses of PVC workers have been described by several authors. There are also literature reports of the bone margin defects mentioned, of the osteoporosis, and of the sclerosing of the ileosacral joint. Because of the small number of patients, we cannot yet decide whether the striking frequency of bone cysts is characteristic of the syndrome in our patients. In order to clarify the question of reversibility of the acroosteolyses, observations already published and discussed by us on the observation of one patient for a course of illness which has been longer than ten years [12, 20, 21] may contribute. According to that, the osteolytic process proceeds from distal to proximal in the terminal phalanges. At the same time there is partial bone development in the region of the Proc. unguiculares and fusing of .the "fracture fragments". The terminal phalanges remain shortened, however, and there has not yet been restitutio ad integrum. The previously mentioned principal symptoms, Raynaud syndrome, skin indurations and bone lesions <-- even though only rarely banded osteolyses in this, form -- recall to the derma tologist the long-known syndrome of progressive sclerodermia, in which the corresponding connective tissue alterations regularly occur, also in the internal organs in the sense of visceral participation, especially for the lungs, heart, upper gastrointestinal tract and kidneys. For that reason, we have carried out careful studies on all patients, with particular attention to the vascular system, the blood-forming system, the liver, spleen, lungs, the nerve system and digestive tract, as well as to exclude an autoaggression disease. Here, we were able to collect many findings, described for the first time, on various organ systems (Table 4): thrombo cytopenia, splenomegaly, limitation of liver function, 16 RSV 0018195 y 44 1 RSV 0018196 TABLE 4. SUMMARY OF THE MOST IMPORTANT FINDINGS IN ALL THE PATIENTS WITH THE SO-CALLED VINYL CHLORIDE DISEASE Skin changes No. Patient a) clinical b) histol- Circulatory oglcal disturbance 1 so. * as 1 D.Z. 4 i. r. 5 HD. 4 A.W. 7 H.A. M.C. 9 SLW. 19 K.H. 11 L.M. 4 4 4 .4 4 + + 4 4 4 4 4 4 4 4 4 4 4 4' n r.s - -- u SK. _ t '4 Sum S 12 4 '4 4 cm 4() 4(2) 4 4<*) 4 4- Bone Throrobo- changes cytopenia 44 44 4 4 44 4 44 4 44 4 4 44 444 . 4 7a Splenomegaly (2) 4 4 4 44 44 4 4* 4+41 444 44 44 u Liver ch an ge s /entilation and/ or diffu sion dist urbance 4 4 4 4 Esophageal varices .4 Portal'fibr.1 4 4 4 Esophageal varices portal fibr. Esophageal p^tVF'hbr. Esophageal varices portal fibr. U 4 4 4 4 4 4 4 4 4 II g 4 130ooo--toooo >4 4+ * 90000--ooo A ++ -<90000__________ 9 + as for as the costal arch ' 44 -- Enlargement beyond the costal arch ___________________________ L* Enlargement beyond the costal arch *flbr. - fibrosis. periportal fibrosis, portal hypertonia, esophageal varices, partial insufficiency with indications of restrictive changes. These results, as well as the fact that we could detect three other autoclave workers who showed no clinical skin changes and no acroosteolyses, but a striking agreement with the previously collected internal findings, stimulated us to a very attentive search directed toward possible other patients. As a result, we now have study findings from 45 (of a total of 128) workers in this FVC-manufacturing plant. Ihey are sumnarized in Table 5 [15]. Table 5. FREQUENCY OF CLINICAL, SCINTIGRAPHIC, X-RAY FINDINGS AND PATHOLOGIC LABORATORY FINDINGS IN 45 WORKERS AT A PLANT MANUFACTURING PVC. 1. Sclerodermia-like changes 8 investigated .2. Raynaud syndrome 4 investigated' 3. Acroosteolysis of the hands 6 investigated 4. Increased liver enzyme values (transaminases, LDH, AP, SP) 8 investigated 5. Increased BSP retention 23 investigated (7-27 percent retention after 45 minutes) 6. Thrombocytopenia (17,000 - 140,000/u) 37 investigated 7. Splenomegaly (scintigraphy) 25 investigated 8. Varices of esophagus and/or 7 investigated gastric fundus (MDP, splenoportography) - Studies of the vascular system for diagnostic and patho genetic. explanation of the previously mentioned symptoms led to the following findings: The skin temperature of the hands was reduced in 6 patients (up to 10C below the normal). In the cold exposure test, the rewarming time was extended in 9 patients (up to 60 minutes). 18 RSV 0018197 A Raynaud syndrome could be triggered for individual or all fingers of both hands in 4 of them. . There was no oscillo graphic or plethysmographic indication for reduced circulation of the extremities. Distinct vessel changes could be demonstrated by arterio graphy in 7 patients with acroosteolyses and sclerodermia-like changes or Raynaud syndrome. They extend from a slight narrowing of the vascular lumens for the finger arteries through distinct -delay of the filling time, extensive stenoses and total closings in the region of the basal and middle phalanx, especially in the fingers with acroosteolyses, to complete segmentary occlusions or even failure of filling of the arteries along the whole length of the finger. The other fingers show a distinctly denser vascular net. Investigations by capillary microscopy on 4 patients who showed clinical circulatory disturbances but no Raynaud syndrome showed ampulla-Like expansions of the capillary loops, such as are described in the Raynaud syndrome. To the extent that we can yet judge, there appears to be a relation between the duration of exposure and the extent of the angiographic findings, to the extent that the patient exposed more than 11 years showed the most severe changes (Prof. Dr. Schlftssel, Prof. Dr. Schober, Siegburg City Hospital; Private Lecturer Dr. Belz, Radiographic Clinic, (Dr. P. Thum, Director)). In almost all those studied we found slight to severe thrombopenia with values between 17,000 and 140,000 per pi, with the lower limit of normality at 150,000 per Pi. These reduced thrombocyte numbers actually appear to be the first symptom which can be objectively determined. This may be of importance for future continuous industrial medical studies. The blood picture and the bone marrow studies showed, aaide from an occasional slight reticulocytosis between 16 and 20Z, no indication of injury to the blood-forming system. 19 RSV 0018198 In particular, there were no signs of osteomyelosclerosis or fibrosis (Medical Clinic; Prof. Dr. H.-J. Dengler, Director). More than half of the patients investigated so far showed splenomegaly with occasional enlargement extending beyond the costal arch (scintigraphic findings)(Dr. Schneider, Institute for Clinical and Experimental Nuclear Medicine; Prof. Dr. C. Winkler, Director). The hypersplenism resulting from this might perhaps be responsible for the thrombopenia regularly observed, even though thrombopenia oecurs without splenomegaly and there is no direct relation between the severity of the thrombopenia and the extent of the splenomegaly. Liver damage can be demonstrated just as often with 'normal palpation findings, based on the laboratory chemical^ X-ray, scintigraphic, laparoscopic and histologic findings: Slight to moderate increased BSP retention (maximum: 26.5%; upper boundary range in 14 patients between 5 and 7Z in 14 patients; slight increase of the transaminases in the range of 20-32 mU/ml (6 patients) and of the alkaline phosphatase up to 86 raU/ml (4 patients). In 6 patients there were also slight changes in the coagulogram (Institute for Experimental Hematology and Blood Transfusion Methods; Prof. Dr. H. Egli, Director). In striking contrast to these changes, which were discrete ' except for the increased BSP retention, the laparoscopic picture showed netlike or superficial capsular fibrosis. In individual cases there was arching or protrusion of the surface and histologically, a distinct periportal, septal and intra lobular fibrosing in the sense of a chronically toxic liver injury, such as can occur after long-term intoxication with chlorinated hydrocarbons [15]. 20 RSV 0018199 The deviations in the electrophoretic pattern could be explained in the same way (differing increase of the immunoglobulins in changing composition, reduction of the 0-1-A complement fraction). The esophageal varices seen in 7 patients (gastrointestinal series; Radiologic Clinic) might be direct hemodynamic and life*threatening consequences of the liver changes. Changes in the respiratory tract could also be established with striking frequency. Most of the patients (8) showed functional disturbances in the sense of partial insufficiency and indications of predominantly restrict ive changes (Prof. Dr. Schwabe, Medical Clinic). Review and Discussion These findings justify our opinion that this is a new occupational disease. We concede that the name "so-called vinyl chloride disease" cannot be certain until accurate work-site analyses and, if possible, animal experimental investigations have finally confirmed our suspicion. There are already bases for arguing that VC could be of causative significance for the appearance of this disease pictures 1. Gas analyses which have been published have shown that the residual gas in question consists of 90 VC while other gases such as vinyl acetate or trichloroethylene occur only in amounts which hardly come into question as causes for such damages 2. The various additives can be eliminated as causes because the bone changes, themselves rare, were observed in various countries by various authors for the same production process. But it can hardly be assumed that any additive which might have been used at random here 21 RSV 0018200 would have led to these'striking changes. 3. The narcotic action of VC is well known. In the case history, one of the workers we studied reported that at times VC occurs at various points in the production process in such quantities as to cause lassitude, dizziness and nausea. 4. The occurrence of the Raynaud syndrome has been observed in plants which make only the monomer, but not 'PVC. The pathogenesis is not yet explained. In all of the organ systems which We studied, there was change in the connective tissue or the vascular connective tissue. Because . of the high morbidity for predominantly young men in only a single very special occupational sector and the complex nature -of the disease picture, we would prefer to believe in a toxic occurrence. The cause of the thrombocytopenia still remains unclear. The question of why the disease picture can occur with or without circulatory disturbances, skin and bone changes, can perhaps be explained from the activity at work. All the patients who have these changes were active as autoclave cleaners for at least some time. Now if, as assumed, this substance has a toxic action percutaneously and by inhalation, then the close contact with the polymer deposits on manual inner cleaning of the autoclaves would have considerable importance in the origin of the disease particular. In addition, we have as yet found sclerodermia-like skin changes only in the areas of the unclothed skin parts. 22 RSV 0018201 In view of the visceral involvement and particularly in respect to the question of portal fibrosis, the prognosis must be made only with reservation. At least, the reversibility of the clinical phenomena, which has been repeatedly advanced in the literature cannot yet be confirmed. The existing findings also provide extensive differential diagnostic delimitation from progressive sclerodermia, with which it has been brought into close connection because it is also a disease affecting the vascular connective tissue system: 1. In our patients, " we do not see the findings described as early symptoms of progressive sclerodermia: shortening and sclerosing of the tongue ligaments and esophageal sclerosis. 2. As far as is known now, the skin changes appear only on the uncovered parts of the body. 3*. The disease picture does not lead to the severe sclerodermic changes with their sequelae, such as the claw position of the hand, atrophy and the cone-like narrowering of the finger. On the contrary, there is club-like swelling and shortening of the terminal finger phalanges with narrowing of the nail plates. 4. In contrast to progressive sclerodermia, in which the changes of the elastic fibers are less expressed, the histologic picture shows distinct to considerable fragment ation and rarefaction of the elastic fibers. 23 RSV 0018202 5. Searches for antinuclear factors, LE cells and rheumatic factors, often pathologic in progressive sclerodermia, gave no indication for the presence of an autoimmune disease. 6. In progressive sclerodermia, the bone changes begin at the distal end of the Proc. unguicularis with bone atrophy, rarefaction or osteolysis. This advances proximally and leads to the picture of "pointed terminal phalanges". Banded acroosteolyses are exceptional in progressive sclerodermia. 7. When internal organs are involved, the heart, lungs and kidneys are more involved than the liver and spleen in progressive sclerodermia. 8. In the early stages of the so-called vinyl chloride disease there is apparently a certain capability for recovery, particularly of the skin phenomena. In the advanced stage, we must consider the prognosis as more serious than had been assumed before, in view of the hemodynamic sequelae which have become known (esophageal varices). It is not comparable, however, with the fatal outcome of progressive sclerodermia. Preventive measures should start with improvement of the working conditions: gas analyses at the work site, develop ment of better ventilation systems to take away the vapors or smoke, automatic cleaning equipment for the autoclaves, avoid ance of high temperatures (above 350C) which can cause decom position of the plastic. Furthermore, persons with liver disease should not be hired. It would also be reasonable for the workers to have regular followup studies with thrombocyte determination. The industries which do further processing -- 24 RSV 0018203 especially those in which there is danger of renewed degradation in the production processes -- should be included. The problem for insurance law is clear. The disease picture must be recognized as an indemnifiable occupational disease in the sense of the 7th Decree on extension of accident insurance to occupational diseases, under part A of the attached list: diseases caused by chemical substances* According to our information, this is to occur through the union also. Summary A survey is presented on a syndrome seen for the first time in Germany. That syndrome called "occupational acroosteol'ysis" so far, is diagnosed mostly in autoclave workers in the industry producing PVC. Results are reported on detailed examinations on lesions of the skin, bones, vascular and hemo poietic systems, liver, spleen and lungs* These results suggest that this very complex syndrome (systemic disease) is due to prolonged exposure to vinyl chloride* The connective tissue undergoes an unknown alteration, together with fibrosation of the skin and of the vascular system, and perhaps of the lungs and liver as well. The author suggests that the syndrome be renamed "vinyl chloride disease"* On the strength of the legal regulations in the German Federal Republic, this syndrome should be reco^iized as an indemnifiable- occupational disease. 25 l RSV 0018204