Document Ne8ZbvNqo1pdX03DY2zLMk0Ey

"VINYL-CHLORIDE DISEASE SIMULATING SCLERODERMA" Joseph Bretza, M.D. 2nd Year Fellow, Rheumatology-Immunology University of California Medical Center Irvine 101 City Drive South Orange, California 92668 1976 - 1978 Staff Internist USPHS Indian Hospital Claremore, Oklahoma and Instructor in Medicine University of Oklahoma Tulsa Medical College John A. Goldman, M.D. Associate Professor of Medicine Division of Rheumatology-Immunology Emory University School of Medicine 69 Butler Street, S.E., Atlanta, Georgia 30303 "VINYL-CHLORIDE DISEASE SIMULATING SCLERODERMA" Joseph Bretza, M.D. and John A. Goldman, M.D. University of Oklahoma Tulsa Medical College Department of Internal Medicine Claremore Indian Hospital and Emory University School of Medicine Division of Rheumatology-Immunology Atlanta, Georgia ABSTRACT Progressive systemic sclerosis early in its course, especially prior to distinctive internal organ involvement, can be difficult to distinguish from vinyl chloride disease. This 50 year old male de veloped classic scleroderma while employed in a polyvinyl chloride plant. Early in his disease he displayed a number of features com mon to both disorders, including acroosteolysis, sclerodactyly, polygammopathy and circulating immune complexes. His characteristic vis ceral involvement was the cardinal feature which distinguished him from the pseudoscleroderma of vinyl-chloride disease. GTR 676 INTRODUCTION Vinyl-Chloride (VC) disease is a multi-system disorder afflicting skin, vessels, bone, lung and liver which occurs in plastic industry workers exposed to high concentrations of the VC monomer. Polyvinyl chloride (PVC), the polymerized resin of VC, is the chemical used in the fabrication of numerous plastic products from pipes to phonograph records. Although epidemiological studies strongly implicate prolong ed VC exposure in the pathogeneses of vinyl-chloride disease there is uncertainty as to whether the polymerized PVC is completely inert.1 2 Pneumoconiosis secondary to PVC has been reported. In addition, the level of residual VC monomer in PVC powder has been reported to con tain 1000-5000 parts per million of VC per weight, which prior to 1974 far exceeded the rigid present-day standards of one part per million. 3 * 4 Various authors have also reported cases of VC disease in workers who never had prolonged, intimate contact with gaseous VC monomer. 1*5 * 6 A certain genetic predisposition is felt to be involved since less than 3% of reactor-vessel cleaners developed VC disease in spite of similar chemical and physical insults. Due to the differences in prognosis between these two syndromes, it is important to be cognizant of the overlapping features between oc cupational pseudoscleroderma and true progressive systemic sclerosis, (PSS). GTR 677 CASE REPORT This 60 year old native Indian was in good health until December 1970, when he developed arthralgias in his hands, wrists, knees and back. His symptoms began five months after he started working at a petroleum plant that was engaged in the fabrication of plastic pipes from PVC fluff. The patient's job was a "blenderman", in which he mixed PVC powder with organic solvents. He was required to wear a mask but seldom complied with this regulation. His foreman related that af ter a few months of shoveling the powder into the mixer he was furnished with rubber gloves because his fingertips showed unusual sensitivity to the powder by becoming painful and beginning to peel. Because his sen sitivity reaction did not respond to wearing gloves, he was temporarily transferred to other jobs in the plant, including custodial work and packing. A physical examination done by the company physician one month after he started working was normal. The review of systems at that time was also negative with the patient not mentioning any rheumatic complaints or symptoms of Raynaud's phenomenon. In July 1971, he voluntarily resigned, which, according to his plant health records, was due to his "constant arthritic complaints." In April 1972 he consulted a physician for the first time, complain ing of "heartburn, arthritis and cold hands." The physical examination was normal except for sclerodactyly. A skin biopsy was consistent with either scleroderma or vinyl-chloride disease. Laboratory data revealed a polyclonal gammopathy and a negative antinuclear antibody and rheuma toid factor. The chest x-ray, barium swallow and gastrointestinal series GTR 678 were normal. Two years later he was hospitalized for treatment of peri carditis. In April, 1975, it was first noted that he had 1-15 rbc's/hpf in his urine with a normal blood pressure. One and one-half years later "interstitial fibrosis" was noted on his x-ray for the first time. He had smoked cigarettes for forty years. In May, 1977, he noted a rash on his legs which a skin biopsy docu mented as leucocytoclastic vasculitis. He complained of "rny arms and face are getting tight with my fingers drawing up." He voiced concern over increasing heartburn and his Raynaud's with three color changes which occurred daily. There was no family history of acroosteolysis, but his sister has stage IV, class IV rheumatoid arthritis. Physical examination revealed taut facial and peri-oral skin with a decreased oral opening and acroosclerosis of the forearm and hands. The blood pressure was 118/72 mmHg. No calcinosis or telangiectasias were present. The contractures of 30 degrees at the PIP and DIP joints and shortening of the phalanges gave the appearance of "claw-hands." Laboratory data revealed numerous rbc's and red cell casts on urinalysis. The creatinine clearance collected while the patient was on no medica tions was 41 ml/min and the 24 hour urine protein was 591 mg. The plate- 33 let counts up to 1975 averaged 102,000/mm (98,000 to 106,000/mm ) and 3 thereafter were normal. The WBC was 7800/mm and hot was 3735- The anti nuclear antibody was 1:320 in a homogenous pattern, the rheumatoid fac tor was 1:80 and the Westergren sedimentation rate was 88 mm/hr. Cryofibrinogens were present in trace amounts and cold agglutinins were nega tive. Cryoglobulins at 72 hours, checked three times, and hepatitis anti gen were negative. The Cg, and total hemolytic complements were normal. GTR 679 Antibodies to native-DNA were normal and to ENA not present. No parapro teins were present on immunoelectrophoresis. Circulating immune complex es were positive by platelet aggregation at 1/16. His HLA typing was A 28; AW 31; B5; BW 40. The pulmonary function tests showed severe re strictive lung disease with a DLCO 34% of normal. Arterial blood gases at rest showed a PC^ of 32 mmHg and pH 7.42. His liver chemistries were normal. The renal biopsy showed glomerulosclerosis, interstitial inflamma tion and fibrosis, focal tubular atrophy and arterial and arteriolar sclerosis. Electron microscopy showed half the glomeruli to be obsolete. Uninvolved glomeruli were normal without the presence of immune deposits. The tubular architecture showed moderate distortion with prominent tubu lar atrophy, dilitation, tubular dropout and interstitial fibrosis. Small arteries showed thickening with a homogenous eosinophilic intima and some of the afferent arterioles showed hyaline sclerosis. The small bowel x-rays did not reveal any flocculation. The barium swallow with fluoroscopy showed esophageal reflux and esophageal manometry demonstra-: ted absent lower esophageal sphincture pressure. Roentgenograms of the hands showed dissolution of the bones at the distal phalangeal tuffs and cystic changes of the distal radius and ulna and carpal bones. (Figure 1). This patient's vasculitis rash subsided spontaneously. The patient con tinues with intermittent periods of occult hematuria but has remained normotensive with stable renal function over the last four years. GTR 680 DISCUSSION Vinyl chloride is a volatile, odorless, flammable gas that has gained prominence by its untoward clinical reactions: (1) Its carcino genic potential via the known association with angiosarcomas of the liver; (2) its anaesthetic potential with acute exposure; (3) its muta genic capability as demonstrated in animals^ and by an epidemiological Q study in humans; and (4) its ability to produce the so-called vinylchloride disease which is reminiscent of an incomplete form of sclero derma. The first hint of the toxocologic potential of VC came in 1963 with the report of Raynaud's phenomenon in polymerizer vessel cleaners by Lucite, et al. In 1966, VC disease was recognized as a clinical entity with the report by Cordier et al of a complex syndrome that de veloped in workers engaged in the direct manufacture of PVC from VC monomer.The period of exposure to the noxious gas before the onset symptoms varied widely from as short as one month to as long as eleven years.The most characteristic finding in VC disease is acroosteolysis, which consists of resorption of the terminal tufts in the hands and feet. (Figure 1). Acroosteolysis however, has multiple etiologies, including scleroderma. (Table 1). The similarities between VC disease and PSS are more than macroscopic, since skin biopsies, angiographic studies, and wide-field capil lary microscopy^ show indistinguishable patterns. (Table 2). Some au thorities have tried to differentiate the two entities in the early sta ges by the excess of inflammatory cells in skin biopsies and by the ab sence of acral ulcerations and telangiectases in patients with VC disease, 15 but no universally accepted criteria exists. As the natural history of GTR 681 of this patient's illness unfolded it became clear that he suffered from progressive systemic sclerosis. His exposure to PVC as opposed to VC monomer mitigated against the diagnosis of VC disease but more important ly, his viscereal involvement (renal, cardiac, esophageal) proved most crucial in arriving at the correct diagnosis. This patient's family history of connective tissue disease plus his HLA antigen B5 which has been reported with increased frequency in Behcet's disease plus his HLA Bw 40 in which some authors report with increased frequency in rheumatoid arthritis 17 suggests an inherited tendency toward an aberrant immune re sponse. However, a recent study has shown no significant increase in the frequency of any major HLA antigen in scleroderma. Nevertheless, even though no increase of any major histocompatibility antigens has been identified yet in scleroderma, the HLA typing of patients with VC disease might be of interest to determine whether any immune response genes are associated with the "peculiar idiosyncrasy" of such a small fraction of workers to develop VC disease. Previous studies aimed at trying to deter mine why less than 3% of VC workers develop this disorder have shown no relation between the occurrence of the severity of the disease and those patterns known to influence the vascular response: smoking, coffee and 19 alcohol. Since the latent period before the onset of symptoms of VC disease has been reported to be as long as eleven years 12 there is the distinct possibility that new cases will continue to arise in the future mimick ing scleroderma. Prognostically it is important to recognize the pivo tal visceral involvement that occurs in PSS since the renal disease car ries the potential for devastating consequences. Being able to make the GTR 682 diagnosis of VC disease, has practical application since the patient may be compensated by local workmen's compensation laws. Epidemiologically, the occurrence of VC disease signifies the possibility that other workers may be at risk if environmental safety standards for VC have broken down. On a wider scale the clinical and histologic similarities between PSS and VD disease (graph 2) suggests that VC disease might serve as a model to gain insight into the etiology and pathogenesis of scleroderma. GTR 683 ACKNOWLEDGEMENTS We express appreciation to Pat Fair, Jennie Crook, Donna Guthrie and Rebecca Cochran for secretarial assistance in the preparation of this manuscript. We thank Benjamin Spargo, M.D. of the University of Chicago for electron microscopy and immunofluorescence. We are grate ful to Helen Casey, Ph.D. and Ruth Gogel of the Perinatal Virology Branch of the Center for Disease Control, Atlanta, Georgia, for plate let aggregation studies. Presented at the Thirteenth Annual Meeting of the PSPHS Professional Association, held in Atlanta, Georgia from March 27th to March 30th, 1978. GTR 684 TABLE 1 VISCERAL INVOLVEMENT (renal, gi, cardiac) CALCINOSIS TELANGIECTASES ANTINUCLEAR ANTIBODY THROMBOCYTOPENIA DECREASED COMPLEMENT CRYOGLOBULINS CIRCULATING COMPLEXES INCREASED GAMMAGLOBULIN ACROOSTEOLYSIS RAYNAUD'S SCLERODACTYLY DIGITAL ARTERY LESIONS (ANGIO) PULMONARY/HEPATIC FIBROSIS t SCLERODERMA + VINYL-CHLORIDE DISEASE t +- +- + i -+ -+ -+ ++ ++ ++ ++ ++ ++ ++ GTR 685 GTR 686 TABLE 2 - CAUSE OF ACROOSTEOLYSIS. i IMFE.CILQU2. LEPROSY YAWS physical/chemical agents THERMAL INJURY POLYVINYL CHLORIDE ERGOTISM MISCELLANEOUS SYRINOMYELIA LESCH-NYHAM SYNDROME Rothmund's syndrome PACHYDERMOPERIOSTOSIS OSTEOPERIOSTOSIS TABES FAMILIAL EMDQ.CRIHE DIABETES MELLITUS HYPERPARATHYROIDISM DEGENERATIVE ARTERIOSCLEROSIS BUERGER'S DISEASE PROGERIA COLLAGEN DISEASED RHEUMATOID VASCULITIS SCLERODERMA SARCOID PSORIASIS RAYNAUD'S DISEASE Figure la. X-rays of the hands of the patient showing digital tuft resorption and cystic changes of the distal radius ulna and carpal bones, especially of the left hand. Figure lb. Close-up of the digital tuft resorption of the second, third and fourth fingers of the left hand. Figure lc. Close-up of the cystic changes of the distal radius ulna and carpal bones. GTR 687 ASSIGNMENT OF COPYRIGHT I (we) certify that I am (we are) the author(s) of the article en titled "Vinyl-Chloride Disease Simulating Scleroderma," which is submit ted for publication in the Journal of Occupational Medicine, a periodical published by the American Occupational Medical Association (AOMA) an Illinois not-for-profit corporation, and further certify that neither the said article nor any substantial portion thereof has been published here tofore by me (us) or with my (our) approval, that I (we) have made no prior assignment of the copyright in the said article or any portion thereof. In consideration for the editing, review, and publication of the aforesaid article, I (we) do hereby transfer, assign and convey to the AOMA all rights, title and interest In and to the copyright In the said article. GTR 688 REFERENCES 1. O'Conner RB: A New Occupational Disease is Born. J Occup Med 12: 234, 1970. 2. Szende B, Lapis K, Nemes A, Pinter A: Pneumoconiosis Caused by the Inhalation of Polyvinylchloride Dust. Med Lavoso 61: 433-436, 1970. 3. Barnes AN: Vinyl Chloride and the Production of PVC. Proc R Soc Med 69: 277-281, 1975. 4. Haley TJ: Vinyl Chloride - How many unknown problems. J Toxicol Environ Health 1: 47-73, 1975. 5. Stewart JD, Williams MD, McLachlan MS: Acroosteolysis in a Polyvinyl Chloride Worker with an Atypical Industrial History. J Soc Occup Med 25: 103-109, 1975. 6. Walker AE: Clinical Aspect of Vinyl Chloride Disease -- Skin. Proc R Soc Med 69: 286-288, 1976. 7. Humberman E, Bartsch H, Sach L: Vinyl Chloride and mutations in mam mals. Int J Cancer 16: 639, 1975. 8. Infante PF, Wagoner JK, McMichael AJ, Waxweiler RJ, Falk H: Genetic Risks of Vinyl Chloride 1: 734-735, 1976. 9. Sucia I, Dregman I, Valeskai: Investigation of the Diseases Caused t*y Vinyl Chloride. Med Intern 15: 867-968, 1963. 10. Cordier JM, Fievaz C, LeFebre MJ, Sevrin A: Acroosteolysis and Skin Lesions Among Workers Engaged in Cleaning Reactors. Cal Med Travail 4: 14-19, 1966. 11. Juhe S, Lange CE, Stein G, Veltman G: The So Called Vinyl Chloride Disease. Ger Weekly 98: 2034-2037,1974. English Translation via EPA, US Department of Commerce TR75-6; PB 258838-T, 1975. GTR 689 12. Jayson MI, Bailey AJ, Black C, Jones KL: Collagent Studies in Acroosteolysis. Proc R Soc Med 69: 295-296, 1976. 13. Veltman G, Lange CE, Juhe S, Stein G, Bactiner U: Clinical Mani festations and Course of Vinyl Chloride Disease. Ann N Y Acad Sci 246: 6-17, 1975. 14. Maricq HZ, Johnson MN, Whetstone CL, LeRoy CE: Capillary Abnormali ties in Polyvinyl Chloride Production Workers. JAMA 236: 1368-1371, 1976. 15. Jablonska D: Scleroderma and Pseudoscleroderma. New York: Dowden, Hutchinson and Ross, Inc: 1975, pp. 192-195. 16. Ritzman ES: HLA Patterns and Disease Association. JAMA 236: 23052309, 1976. 17. Seignalet J, Clot J, Sany J, Serro H: HLA Antigens in Rheumatoid Arthritis. Vox Sang 23: 468-471, 1972. 18. Birnbaum NS, Rodnan GP, Rabron BS, Bassion S: Histocompatibility Antigens in Progressive Systemic Sclerosis (Scleroderma). J Rheum 4: 425-428, 1977. 19. Dodson VN, Bertrum DD, Whitehouse WM, Nasr AN, Magnuson HJ: Occu pational Acroosteolysis - A Clinical Study. Arch Environ Health 22: 83-91, 1971. GTR 690