Document rxyrrwXMmNgoo71QZ5Z5DVyQG

Reprinted Irom Ihe Archivtt ot Environmental Health January 1071. Velum* 22 Copyright 1071. American Medical Association Occupational Acroosteolysis : IIL A Clinical Study Vernon N. Dodson, MD; Bertram D. Dinrnan, MD; Walter M, Whitehouae, UD; ' Ahmed N. M. Near. MD, PhD; end Harold J. Magnuson, MD, MPH, Ann Arbor, Mkh So <0 S*' ' . '*, * V * *e y *A` e*a -t * 83 Occupational Acroosteolysis III. A Clinical Study Vernon N. Dodton, MD; Bertram D. Dinman. MU; Walter M. Whitthoute, MD; Ahmed N. M. Naur, MU. PhD; and Harold J. Magnuton. MD. MPH, Ann Arbor, Mich Four subjects with acroosteolysis wsrs studied clinically. All had osteotyllc lesion*. especially In the distal phalanges ol th* hands, and Raynaud'* phenomenon. Afl had worked m polyvinyl chloride re*ctor-vasil dear****. with hand *craping being ft* common mod* ol operation. Raynaud's phe nomenon antecaded osteolytic lesiona. On* ol ih* subject* waa In nagathm calcium and phoaphorua balance. Ptathysroographlc abnormalltlea were praaant In three. Esophageal motility was normaL' ScinMacana ol the hand* using sodium fluoride labaliad with radloacfiva fluorine (`TJ reverted variable uptake* In Via linger* which correlated with the radiographic laalon*. A wide variety ol clinical laboratory parameters were normal. Occ'Ut PATIONAL acroofiteolysi* f AOL) consists primarily of Raynaud's phenome non and osteolysis of the distal phalanges in the hands. Suciu et at first described Ray naud's phenomenon in polyvinyl workers in 1963.1 Osteolytic lesions were reported in other cases.* T Other associated clinical fea tures such as hepatomegaly, the cutaneous Stigmata of scleroderma, hypothroid param eters, and numerous abnormal laboratory tests have been reported.' 7 Epidemiologically, patients with AOL arc associated with the manufacture of vinyl chloride polymers, more specifically with the hand cleaning of the polymerisation reactors. This paper reports the results of intensive clinical investigation or four patients with AOL. Three four polio is wore selected from those cmploycre of 32 p.^nts engaged in the manufacture * f vinyl chloride polyiners throughout Ilx* United Slates. Methods Each patient was admitted to the CJinicnl Research Unit. University of Michigan Hospital, for a two-week period where detailed medi cal histories war* investigated and physical examination* performed. Detail* of th* work histories and environment*! exposures were de rived from In-plant epidemiological sIndies car ried out jointly by the Institute of Environ, mental and Industrial Health of the University of Michigan and th* Manufacturing Chemist*' Association. Table 1 list* the laboratory param eters applied. In addition, calrium and phos phorus balance studies were carried out. using a dietary history to establish a constant cal cium-phosphorus intake to which each patient wes accustomed. Daily 24-hour urine specimens were collected, and stool specimen* were pooled every throe days for calcium and phoaphorua determinations. Appropriate correctional com putation* for uneaten foods'ware made. Cat*, chotamine* and S-hydroxyindole acetic add were determined on 24-hour urine collections, often partitioned by six-hour units and usually collected on days of provocative cold stresses during pleihytmographic determination*. Numerous roentgenofreptile techniques were introduced, ranging from skeletal survey films to barium swallow radiographs and hone xerog raphy. Brans of the hands and sacral regie;.., using sodium flurick' labelled with ndinsitvi fluorine (>*F). were undertaken in two of the patients. Plethysmography of-the forearms and hands, using the method of Zwdfler ri ol. sw employed.* Esophageml motility studies r;r' made, using Salndin et iTs technique.* Results Subinil(H) ftr imhlHnltun KrI* Murvh 24. U7t>, hiiftilnl Vrom the wlioti t*f (JitviiitlltMtiil und Knviitm- mcnUl Mnlrint him) Ih* Dtfmrinigtfii of !ntnif| Mdirint 1V. mm! Hit trtxtiltil* af tinvi* romiiciilHl himI liMlitMrinl IIvmIiIi (l)n.. Dininiut mihI NuntI, the Dfrpnrltiipnt rf Kii*mktmcnUl unci In- ffiHlriitt Hmllh, of I'liMir Mpnllh <|)r. M x niNKlmikI IIip lJk*|Milnkrnt af IttitHiltiKy (|)r, WhiU4Hbi. llnivrnilv f Amt AHnit. Ht`|irinl ivtitiols (< Inmlilutr iH Kuvinmm4*rtn| itml Iliiibffsiiy l .M'l'tii^in. Ann AiImh'. Mkl -IrtllH lltr |kNM*t.uii. History.--Blanching of the hands wits the find sign of AOL. In two of the men, the onset was gradual over i firw weeks, and in two it whs abrupt, tut sltown in Table 2. ('-old was the inciting factor In all owk T1v blanching was associated with cither tin gling of the luuirix or lendcriwss of llttfingrrti|K. Tie |x>lyvinyl work cxisauirc to first lilaiM'tiing ranged front ' rum In W ,\trh h'.nt imn //e'ttfih \*tti '*'* /tin /* t ILLEGIBLE DOCUMENT R&S 028270 :it;^l tej pmat t wf% ' vr-%::pr- - -; \ '^f t k-v '-* f---3 \ M ~ `>V '\- . - *&k V 4 > s 1 -/' Y-rM m r ar fc v S 1 \ ; r- ik*u\ ,- ta mv. jsr .-^ Fig 1.---Not* trantver** defects In distal phalange* of nng*r* on* to four on laft hand and finger* on* to three on right hand. Marginal defect I* praient In diatal portion of dittal phalanx of right fifth lingar (cate 1). TxMo 1.--Laboratory Iniattigathrt of AOL patSanta Biochemistry Sodium Calcium Pots ftturn Phosphorus Carbon dioxide Choletlarol Chloride Clucot* (fatting) Bilirubin dir*ct/toUi Urn nitrogen Crestfnfn* ToUl t^rum protein Electrophoresis tarum Albumin 0-1 m-2 P y MagnOftnim Lipid* Photphoiipld* Triglycerides Catacholamlna* Noroplnaphrin* Eplnaphrin* Serum Enzym** Alkaline phonphatas* Threonine aldolase Acid phosphate** Made dehydrogenate Serum glutamic oxaloacetic Irinumindtk Olutamk dehydrogenase Serum gfcitamtc pyruvic transaminase Leucine omlnopaplldas* Lactic da hydros*n*t isogram Aldotaso S 'Nucleotidase Croatin* phospboklnas* Sarin* dahydrotas* IsocUrate dahydroganasa Immunological T**ta Vanaraal Msaaso Kasaarch Antlnudtir factor Laboratory LEcaS Direct Coomb's Cryoglobulins Immunophor-x1* kA Latax-rhaumatotd factor Cold agghiUnln* kM IfiO months. The length of the Interval bore > relationship to the mode of onset or the severity of the symptoms. A raromary of the habits and dietary history of these patients is detailed in Table 3. Three of the four men were cigarette smokers with smoking histories of nine (case 1), 1* (ease 4), and 25 (case 2) pack-years. Half drank coffee (three or nine cups per day). All were casual tea drinkers. Three drank between three and 18 bottles of beer each month. One (case 4) drank 120 cans of beer per mc'Si but no whiskey while the others consumed less than four Fig 2.--Hand* (how further resorption of bon*, resitting In thotlaning of tormina) phalange* of alt finger* except laft fifth and right `fourth, latter having davafopad banavarm defect. Right fifth finger ha* shown additional resorption of dittal phalangeal Up. Softttaeuo clubbing'I* relaxed to shortened phalange* (cat* 1). Bo CO R&S 028272 86 OCCUPATIONAL ACnOOSTFOLYSIO-POPSON FT AL Table 5.--Physical Findings on Patents With /OL imrns which were rametimr* PttyiiCil Findings Case : Sfcln Dorsel-tMckcning bends Blanching Without cold With cold Joints Synoriaf thickening Incidents! + + PIPt 34P| Knees Dupuytren's . conlricluftf Finfer R 2 end 3 l 3 end 4 Alio fingers, t Proximal intsrphalsngtal. t MsUcarpophslsngssl. Cdtc 2 CdK 3 + + _ i ++ PIPf -- _ em Thickening Shorten of wrist ing of extensors tingsr Ups ' C> 4 + + al. --' parlilioni'd in six-hour incre ments (Table 6t. Oi1 |xitiert's third-period value of 2.8 occurred during o cold stress while plethysmogra phy was being done (case 11. Another patient's third value of 1.6 did not increase under similar cold stress (case 2I. Plethysmogrnphic studio: revealed normal pulse vol umes in all but one patient (case 2). All patients ex cept one (rase 3) showed di minished pulse volumes with cold stress typical at the Raynaud's phenomenon observed in other dis ease- Esophageal motor activity was normal fn all subjects as shown by banun fluoro scopy and Saladln's et al motility technique.* . Radiological Findings.--The radiographic findings of the four patients analyzed are summarized in the case report-. Report of Cases . C*SS 1.--X-ray films made elsewhere prior to the patient's hospitalisation at the University of Michigan exhibited normal hands on Oct 20. - IMS, and. in 1967, showed marginal bone de Fig 3.--Eroiiva and sclerotic change* In lacro-.iiac fects of the right third and left second, third, Joint* bilaterally (cam 1). and fourth distal phalange* and distal fragmen Ftg 4.--Errwivs lesions ct ot calcii posterior to bony pur (case 1). tation of the distal phalanx of the left first digit On Aug 6. 1967, transverse defects were noted on the distal phalange* of the left fingers one to four and right one to three, with resorp tion of thedistal portion of the distal phalanx . of die right fifth finger. The appearance of the hands on Oct IS, 1967, whan the patient was - lint aeeh, W shewn in Fig 1., Some reparativ* changes'worn noted in comparison with the - previous fibm,'with persistent transverse de fects in fingers one to (our on the led and one Mo three on Uni right with a marginal defect fat ' the distal portion of :he distal phalanx of the right fifth finger. Further check-up examination i was obtained on dan 9, 1969, and Oct 24. 1969, the letter bein^x shown In Fig 2. 'During this prrmd of time,' there has been further resorption of hone, rtnulllng in shorten ing of the terminal phalangiv ,of all fingers esre|>l IIn- k-fl fifth, which hue' remained unin. . vnlvrri, and lie- right fourth, which him miin- tsimri its length but tnn- <levelo|Hd n tninwi rw Att h Fniiru* llrallh--W 73. Jim 1971 R&S 028273 ns s.--left hand shows marginal defect at tip of distal .phalanx of second finger, with transverse defect In distal phalanx of third finger. Right hand shows transverse defects In distal phalanges of second and third fingers and an additional distal marginal defect of second finger (top [case 2J). Scintigram shows uptake of sodium fluoride *T (bottom). Fig 6. Sacro-lliee Joints show erosive and sclerotic Changes, owe marked on left (ease 2). ter* Knriimi II,tilth--IW 22. Jan lull BEST AVAILABLE COPY 3J </> oto 00 s 4* as OCCUPATIONAL ACnOOSTKOLYSIS--liOnSON ET AL Table 8,--f/vs-hjrdroxjrlndote Acetic Acid end Catecholamine Studies In Pallants With AOL Cate I Case 2 Case 3 C*K 4 Urinary Excretion fiv*-hy< iroitym<lote acetic acid 8em-2pm 2pm-8pm 8pm2am ?am-8m Total (1) total (2) Total(3) Catecholamine Epinephrine Norepinephrine Urine Creat- Urine Creat Urine Creel- Urine Creat- Mg Volume mine mb Volume inine M Volume Jnme Mg Votume mine 0.78 390 0.36 2.0 265 0.59 0.92 460 0.42 2.2 240 0.54 2.80 730 0.62 1.2 300 0.69 ' 0.89 1*0 0.12 1.-6 210 0.48 5.39 1.720 1.52 '7.0 1.0! 5 2.30 ...5.8 . 2,170 1.47 ... ... ...4.0 1,720 1.46 a*. a*. 7.6 23.6 6.1 390 0.30 1,208 0,97 4)6 0.33 430 0 34 2.444 1.94 V ... ... ... defect. The right fifth finger hat ihown addi tional resorption of the phalangal tip. Softtissue dubbing is noted in the ahortened phalange*. Some sclerosis in noted along the margin* adjacent to the transverse defect*. This patient also showed extensive erosive nnd srlerotic change* in the aacro-iliac joint*, as seen in Fig 3. An erosive lesion whs also found in the plantar surface of thu o* odd*, i* depicted in Fig 4. CUB 2.--This |Wtient had an extensive skele tal survey on Feh 8.1968. with positive findings limited to the hands and pelvis. As shown in Fig IS, thfe leit hand revealed a marginal defect at the tip of the distal phalanx of the second finger while the third finger showed a transverse defect in the distal pha lanx. At the same time, the right hand present ed transverse lytic defects in the distal pha langes of the second and third fingers and an additional distal marginal defect of the so,nnd finger. Figure 5 compares a typical *<xtium fluo ride lkF scintiscan of the hands and the corre sponding roentgenograms. A slight increase in sodium fluoride "F uptake is seen in the distal phalanges of (he left third and right second nnd third finger* while the uptake is diminished over the distal phalange* of the left fifth and right fourth and fifth fingers. Generally', uptake* over the remaining hone* of the hands are uniform. The sacra-iliac joints also displayed extensive erosive and sclerotic change, more marked on the left, as shown in Fig 6, Cass 3.--Extensive skeletal survey on this Fig 7,--Hands `how shortening and widening o4 distal phalanges of *11 lingers, with resultant clubbing ot soft tissues (case 3). Arrh Enrfrtm llenlth--Vo! 22, Jtttt 1971 best available copy OCVVPATIOXAl. ACIt(X)STK()I.YStS--DODSOX KT AL 8 loljcnl un Miirt-h 18. 1968, showed shortening widening of the distal ph.iljingim of nit fingers (Fife 7). with resultiuil HuNiing of llv jutft tissur-s. The change* wrrv inti-rptfled ns I hi- rnd #lii|tiii of hivling of A01-. Ttu- wu-rti-iliao joint* showed erosive and wlemlic change*, more marked on the right (Fig H). Review of previous x-ruy films mode else where indicated that some Mucru-ilinc joint change* were present on .April 8. 19?i9, and that the hnnd* hod not changed in apiienranee since October 1906. CASE 4.--Review of previous x-ray films made of this patient indicated that no abnor mality of the hands was present on Feb 20. 1967, or Jan 23. 1968. On July IS, 1968, films of the sacro-iliac joints exhibited erosive and scle rotic changes, and the hands revealed marginal defect of the distal phalanges of the left third and the right fourth fingers, alight irregularity of distal phalanx ef tha right fifth fingvr, and transverse defects of the distal phalanges of the thumbs bilaterally. Skeletal survey on Oct JO, 1968. noted sepa ration of the Up of the styloid process of the right ulna, marked resorptive and sclerotic changes of the sacro-iliac joints (Fig 9), and soma progression of the hand involvement, with transverse defects now involving the distal phalanges of the left digits one to three and Fkl S.--Saero-ihee joints Shoe arotit* ch/nges, mors merited on right (csss 3r. : ceooc Fig 10.--Hand* show transverse defects In distal phalanges of left finger* one to three and right Angers one and four, with so additional marginal detset ef left second Anger (csss 4). Fig 9.--Sacro iliac joints shew erosive and scierqoc changes bilaterally (case 4). R&S 028275 Anh Hntiwn Ihiillh . IW Jim nr,' BEST AVAILABLE COPY 90 OCCUPATIONAL ACflOOSTZOLYSIS--DODSON ET AL right digits one and (our end on additional At first glance, it appeared that there was marginal defect of the left second digit (Fig a rich history of heart disease or hyperten 10). Irregularity of the lower pole of the right sion or both in the parents of these men. patella wan also noted. Comparison of them with healthy male Comments chemical workers not involved in polyvinyl chloride manufacture and matched in age Raynaud's phenomenon was the first manifestation noted by these subjects and in the majority of the cases reported. Harris and Adams1 reported one case in which distal digit shortening occurred first, while suggests a significant correlation by the x` test, using Yate's correction. Whether such an observation suggests a hereditary frailty to explain the susceptibility of those individ uals developing AOL is speculative. The * Wilson et al4 noted this in five of his 31 number of observations is too small to sup cases. This suggests that the vascular lesion port seriously such a contention at this time. tends to antecede the bone changes in most The extent and character of other muscu individuals. None of these patients exhibited lar skeletal findings such as tendon and Raynaud's phenomenon of the feet, which synovial thickening confirm the findings of confirms Wilson et al's experience. All of others. these individuals had been "reactor dean* We are able to offer no suitable explana era" ie, they spent some hours each week tion for the frequent episodes of intermittent cleaning the polyvinyl chloride polymeriza orthostatic tinnitus described by three of tion kettles shortly prior to or at the time of these men. the onset of their disease. No consistent relationship was found between the occur rence of severity of either Raynaud's phe nomenon or the osteolytic lesions and those Suciu et al described liver enlargement, various vague asthenic symptoms, and mani festations of hypothyroidism. Such findings were not present in these men or had they habit patterns which have been drawn to been in the past influence vascular reponses, eg, cigarette Die radiological findings in occupational smoking and the ingestion of alcohol, coffee, AOL have been reviewed recently on the, or tee. Likewise, neither the bone lesions basis of the epldemiological investigation of nor Raynaud's phenomenon seemed to cor the polyvinyl chloride industry. Workers in relate with the daily consumption of milk or other countries have described lytic lesions dietary calcium. Dallas and Nordin1* have in the distal phalanges of the hands, styloid shown that while dietary deficiencies or cal- processes of the ulna and radius, and the dum may or may not potentiate osteoporo saoo-iliac joints.1-** sis of various types, an adequate calcium These four patients demonstrate the en intake of 15 mg/kg is protective. Only one tire spectrum of radiographic hand changes patient Cease 2) had Im than this amount in occupational AOL from the earliest mar <5.8 mg/kg). Since such dietary histories ginal erosion of the distal phalanx through have been shown to be quite reliable,11 their the extensive transverse defect, with ulti habitual calcium intakes do not appear to be mate heating resulting in a short and wide a consistent causative factor in their cases. . phalanx. The fact that all four showed sac-, Likewise, the calcium-phosphorus balance ro-iliac Involvement suggests'that the. inci studies on these men reveal no clear-cut dence of involvement at thla silo is probably abnormality or pattern. This result might be higher than previously suspected. anticipated since these men have been away The additional smaller abnormalities 3J from reactor cleaning for several months, found in the ulnar styloid, os colds, and flo cn and the mass of involved bone is slight lower |wle of the patella suggest that these compared to the entire skeleton. However, it on-os might well be evaluated in other cows roo co should be pointed out that a two-week bal os they appear in order to get a more accur ance period is a short observation period ate estimate of their incidence. ro though Dray were plucrd on calcium and The sodium fluoride '"K scintiscan data Ni o> plmsphnrus intakes romparnliU* to Iheir usu suggests that the* more advanced osteolytic al ruling habits to obviate disrupt ion of cimnges with transverse defects al Ibis lime their *Vt!idy dale." wi-re picking up nsire fluorine and pnJsililv Arrh Eniinm IInil A--IV :*i. Jon mi "V"