THE EXPERIMENTAL USE OF LIPOCAIC IN THE TREATMENT OF PSORIASIS A PRELIMINARY REPORT1,2

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1 THE EXPERIMENTAL USE OF LIPOCAIC IN THE TREATMENT OF PSORIASIS A PRELIMINARY REPORT1,2 C. DUNCAN STEWART, M.D., D. E. CLARK, M.S., M.D., L. R. DRAGSTEDT, PH.D., M.D. AND S. WILLIAM BECKER, M.S., M.D. (Received for publiction June 21, 1939) The role of lipid metbolism in reltion to psorisis hs been the subject of numerous investigtions since the work of GrUtz nd BUrger (1) who found extreme hyper-cholesterolemi ssocited with the disese. They expressed the belief tht disturbnce of ft metbolism ws the cuse of the skin lesions nd obtined beneficil effects with low ft diets. Gte, Chnil, Vllet nd Humbert (2) found n increse in serum cholesterol in 70 per cent of their ptients who showed clinicl evidence of psorisis. Puly (3) observed derngement of lipid metbolism in ptients with psorisis, but did not consider this s the cuse of the disese. He ws of the opinion, however, tht n ltered ft metbolism my ply n importnt role in the pthogenesis of psorisis. The cholesterol tolernce test s used by Grütz nd Burger (1) ws employed in ten psoritic ptients by Rosen, Rosenfeld nd Krsnow (4). On the bsis of this test the uthors could not ssume tht disturbnce of ft metbolism ws present, lthough they showed tht hypo-cholesterolemi existed in ptients with psorisis. Hering (5) fter studying this question denied tht there ws ny reltionship between ft metbolism nd psorisis. More recently Mdden (6) concluded tht 1 This work hs been ided by grnts from the Josih Mcy, Jr. Foundtion, the Dougls Smith Foundtion for Medicl Reserch of The University of Chicgo, The Eli Lilly Compny, nd the Committee on Reserch in Endocrinology of the Ntionl Reserch Council. 2 From the Deprtment of Surgery, nd the Section of Dermtology of the Deprtment of Medicine, the University of Chicgo. 219

2 220 THE JOURNAL OF INVESTIGATIVE DERMATOLOGY hypercholesterolemi does not exist in psorisis nd tht the cholesterol tolernce test ws of no vlue. He found tht low ft diets were of definite vlue in 68 per cent of ptients with psorisis, but believed tht the fvorble effect of the diet could be explined on the bsis of generl relignment of metbolism nd tissue function rther thn on the bsis of restortion of disturbed ft metbolism. LIPOCAIC The recent report by Drgstedt, Prohsk nd Hrms (7) showed tht the pncres mnufctures, in ddition to insulin, nother hormone which seems to be concerned in some wy with the metbolism of ft. It hd been discovered by Fisher (8) tht completely depncretized dogs dequtely treted with insulin usully filed to survive more thn two or three months. At utopsy the most obvious chnge ws extensive ftty infiltrtion of the liver. The ddition of rw pncrese to the diet ws found by Mcleod nd his ssocites (12), t bout the sme time, to prevent the development of liver chnge nd to permit survivl for long periods of time, Drgstedt, Prohsk nd Hrms (7) reported tht 1 to 1.5 grms of neutrl lcoholic extrct of pncres, rendered free of ft by extrction with ether, ws effective in preventing the deposition of ft in the liver of depncretized dogs. They concluded tht the ction of this pncretic extrct ws due to the presence of n internl secretion, hormone to which they gve the nme "lipocic." There is very little known concerning the function of this new hormone. Together with insulin it seems to be essentil for life nd in its bsence specific defect is produced. As ws noted before, this is mnifested by extreme infiltrtion of the liver with ft nd very pronounced decrese in concentrtion of ft in the blood (9). The dministrtion of lipocic produces mrked elevtion in the blood lipids nd t the sme time cuses disppernce of the lrge mount of ft in the liver. There is some evidence which suggests tht under the influence of lipocic this ft is in prt converted into glucose. Sufficient evidence, however, hs not yet been obtined s to whether this new hormone hs to do with oxidtion of ft or is minly concerned with ft trnsporttion (9).

3 USE OF LIPOCAIC IN TREATMENT OF PSORIASIS 221 Mny theories hve been dvnced s to the cuse of psorisis, but t the present time the cuse still remins unknown nd the tretment unstisfctory s regrds cure, lthough relief cn usully be obtined. Our determintion to investigte the effect of lipocic in the tretment of psorisis ws bsed lrgely on our success in considerbly reducing the blood lipids in ptients with xnthom. This work will be published t future dte. Lipocic possibly cn estblish the sme metbolic stte in ptient s low-ft diet, but hs the dvntges tht ptient cn et regulr diet nd does not need hospitliztion for dietry regultion. Mdden (6) believed hospitliztion to be the most importnt fctor in the effect of diet on psorisis. Schmberg (10) lso observed the benefit of hospitliztion when he did his work on the effect of low protein diet in psorisis. EXPERIMENTAL Six cses form the bsis of this pper. Although the series is smll due to the difficulty of obtining sufficient lipocic, which t present is vilble oniy for experimentl use, it seemed worthwhile to mke preliminry report of our results to dte. Of the six cses presented three were children nd three were dults. The sex ws eqully divided. The selection of ptients ws bsed merely upon their willingness to cooperte nd the vilble supply of lipocic. The ptients were instructed to stop ll previous therpeutic mesures. No dietry or other restrictions were imposed. The sole tretment consisted of the orl dministrtion of lipocic cpsules three times dily; no locl pplictions were used. The number of cpsules (7- grins ech) ingested per dy vried from 8 to 14. The mount of lipocic contined in ech cpsule ws equivlent to 25 grms of rw pncres. The ptients returned without brekfst t intervls of two weeks, when the clinicl progress ws noted nd blood ws drwn for determintion of totl lipids. The determintions of the totl blood serum lipids were mde by modifiction of the Wilson method (11), s follows: Three cubic centimeters of blood serum were mixed with bout 60 cubic centimeters of "lcohol-ether" (3 prts of dehydrted lcohol nd 1 prt ether). The mixture ws shken thoroughly nd llowed to stnd for 24 hours. Severl

4 222 THE JOURNAL OF INVESTIGATIVE DERMATOLOGY glss beds were dded to prevent bumping nd the extrction mixture ws refluxed in wter bth for twenty minutes. The extrct ws filtered while still hot through ft free filter pper into 125 cubic centimeter Erlenmeyer flsk. The protein precipitte ws wshed severl times with smll portions of the mixture of lcohol nd ether. The filtrte ws evported to dryness in ir t room temperture. The totl lipid ws then determined by the grvimetric method. The residue ws suspended in 4 to 5 cubic centimeters of distilled wter nd 1 drop of concentrted HC1 (sp. gr. 1.18) ws dded to insure cidity. The cidified suspended residue ws then extrcted with bout 10 cubic centimeters of petroleum ether by heting on the hot plte until bout 5 cubic centimeters of the solvent remined. After the lyers hd seprted the superntnt fluid ws trnsferred with smll rubber bulbed pipette to tred weighing bottle. The extrction ws repeted 5 times. The petroleum ether solution ws then evported to dryness in ir t room temperture. The weighing flsk ws plced in the blnce room nd llowed to come to constnt weight. The flsk ws weighed nd the tre substrcted to obtin the number of milligrms of ft contined in 3 cubic centimeters of serum. By this method the norml rnge of totl lipids is milligrms per 100 cubic centimeters of serum. Most of the determintions were run in duplicte. REPORT OF CASES Cse 1. B. H., white girl ged 10 yers ws first seen on November 3, 1938, with modertely severe psorisis vulgris involving the sclp, bck, scrl region, nd extremities which hd been present for two yers. She hd hd no previous tretment. The totl blood serum lipids ws 770 mgs. per 100 cc. Tretment ws immeditely begun with 8 cpsules of lipocic dily. By December 7th there ws very little improvement in the psorisis nd the lipocic ws incresed to 10 cpsules dily. The totl blood serum lipids on this dte ws 830 mgs. per 100 cc. Two weeks lter, s there ws still no chnge in the eruption, the lipocic ws incresed to 12 cpsules dily. The totl blood serum lipids t this time ws 833 mgs. per 100 cc. From this dte on there ws stedy improvement in the eruption, ccompnied lso by decrese in the serum lipids, which reched level of 650 mgs. per 100 cc. Lipocic ws then grdully decresed until it ws discontinued entirely on My 15, At this time there were only few slightly seling lesions remining. The vlue for totl blood serum lipids ws 785 mgs. per 100 cc. Cse 2. R. L., white boy ged 12 yers, presented himself on November 5, 1938, with modertely severe psorisis vulgris of seven months' durtion involving the sclp, lower bck nd extremities. There ws moderte pruritus. He hd been treted with vrious ointments nd injections without benefit. The blood serum t this time showed the totl lipids to be 860 mgs. per 100 cc. The ptient ws strted immeditely on 10 cpsules of lipocic dily. Improvement ws stedy nd by Jnury 1, 1939, there were only few lesions remining on the lower extremities. Within two weeks fter beginning lipocic the totl

5 USE OF LIPOCAIC IN TREATMENT OF PSORIASIS 223 blood serum lipids hd fllen to 600 mgs. per 100 cc. nd lter reched the low level of 500 mgs. per cent. In Februry the number of cpsules dministered ws decresed nd on Mrch 26, 1939, they were discontinued ltogether. Finl observtion on April 28, 1939, reveled one smll, slightly scly lesion on ech knee. The totl blood serum lipids t this exmintion ws 500 mgs. per 100 cc., lthough the ptient hd received no lipocic for one month. Cse 3. B. H., white girl ged 10 yers. This ptient ws first seen on December 12, 1938, with severe generlized psorisis vulgris (fig. 1) which hd been present since the ge of five yers. Numerous nd vried tretments hd been dministered from time to time with occsionl temporry improvement. The eruption hd never entirely disppered. The initil totl blood-scrnm I ii:y. gi? Fzo. 1. CAsE 3. PHOTOGRAPH OF LEszoNs ON KNEEs BEFORE STARTING TREATMENT WITH LIP0cAIC lipids figure ws 600 mgs. per 100 cc. Ten cpsules of lipocic were given dily, beginning December 13, Two sveeks lter there ws centrl clering (fig. 2) of the lesions nd the totl lipid vlue ws 533 mgs. per cent. From this time on there ws stedy improvement so tht by Mrch 11, 1939, there were only few lesions with prcticlly no scles (fig. 3). The lipocic ws then reduced nd on My 19, 1939, discontinued entirely. Finl observtion on this dte reveled the skin to be completely norml except for two smll, slightly scly lesions below the left elbow. The totl blood serum lipids ws 485 mgs. per 100 cc. serum. One month fter discontinuing lipocic, few recurrent lesions ppered (fig. 4). Cse 4. J. W., white mn ged 21 yers, first presented himself on Jnnry 11, 1939, with generlized psorisis of the guttte type which hd been present for three nd one-hlf yers. There ws moderte pruritus. Previous tretment

6 224 THE JOURNAL OF INVESTIGATIVE DERMATOLOGY hd consisted of crude col tr ointment. About three yers previous to this time the ptient hd hd complete remission lsting for six months. Totl blood serum lipids t this time ws 700 mgs. per 100 cc. Tretment ws strted -! ' i't' 7 j %;P,#!t: '. FIG. 2. CASE 3. PHOTOGRAPH OF LESIONS ON KNEES 14 DAYS AFTER BEGINNING LIP0cAIc FIG. 3. CASE 3. PHOTOGRAPH OF LESIONS ON KNEEs 90 DAYS AFTER BEGINNING LIP0cAIc with 12 cpsules of lipocic dily. Within one week there ws slight improvement nd the pruritus hd decresed. The totl blood serum lipids ws 560 mgs. per 100 cc. Following this observtion there ws no further improvement in the eruption, even though the lipocic ws incresed to 14 cpsules dily on Februry 14, The ptient ws seen lst on Mrch 15, 1939, fter which he filed

7 USE OF LIPOCAIC IN TREATMENT OF PSORIASIS 225 to return. His psorisis hd remined sttionry since the first week of tretment. Cesc 5. C. C., white womn ged 34 yers, ws first seen on Februry 14, 1939, with generlized psorisis vulgris which hd been present since the ge of.4 Fzu. 4. CASE 3. PHOTOGRAPH OF KNEES ONE MONTH AFTER DISCONTINUING LIP0CAIc, SHOWING RECURRENCE OF A SMALL LESION ON RIGHT KNEE, WHICH WAS NOT PRESENT AT THE TIME LIP0CAIC WAs STOPPED 15 yers. No tretment hd been given for the pst few yers. The totl blood serum lipids t this visit ws 710 mgs. per 100 cc. Tretment ws begun with 12 cpsules of lipocic dily. This ptient obtined mrked nd stedy improvement under therpy, nd on April 13, 1939 prcticlly ll tht remined of the eruption ws residul pigmenttion. The ptient volunteered the informtion tht she ws less nervous since tking the lipocic, nd the lesions were less

8 TABLE I Results of lipocic in psorisis S CASE 1 CASE 2 I I 3.; d -t o P5-0 O ci n..c.2 n -C g Slightly im Slightly im- I proved proved Sttionry Sttioory Sttionry Sttionry Improved Improved Sttionry Mrkedly improved Lesions lmost gone 6 Slightly improved Sttionry Mrkedly improve improved Very few lesions Slight exeerhtion L Improved Improved One smll lesion on ech leg Sttionry Sttionry CASE 3 CASE 4 CASE 5.. I - 1 : ; C j ;. n g n. g 0.5).2 n. 0 n n. HO Slightly im Slightly im- 670 proved proved improved Sttionry Improved Strionry Improved Sttionry 12 Mrkedly improved 6 Lesions lmost gone I Finl observtion Sttionry 14 Sttionry C 55 C.0 C 12 Improved 12 t Mrkedly improved Lesions lmost gone Cler except residul pigmenttion Sttionry * 0 4; -o H- O CASE C.0 g C Slightly improved Sttionry Finl Only few slightly obser- scly lesions revtion mining. Lipocic discontinued Only one smll slightly scly lesion on ech knee * Totl blood lipid in mg.per 100 cc. of serum. Ech cpsule is equivlent to 25gm. of fresh rw pncres. Entirely cler except for two smll lesions on left rm. Lipocic discontinued Slight improvement for first week; then sttionry. Ptient not coopertive. Tretment stopped Ernption cored. Resid- Ptient still under ul pigmenttion. tretment Lipocic stopped H z 14 4 CI) H H 4-4 -*1 H H

9 USE OF LIPOCAIC IN TREATMENT OF PSORIASIS 227 pruritic. The totl blood serum lipids t this time ws 565 mgs. per 100 cc. Lipocic ws then grdully reduced until on My 19, 1939, it ws discontinued entirely. The skin t this time ws entirely cler except for some remining pigmenttion. The totl blood serum lipids ws 465 mgs. per cent. It is interesting to note tht for bout one week during Mrch, 1939, the ptient received no lipocic nd stted tht she becme more nervos, the lesions becme prominent, nd were more pruritic. Cse 6. E. F., white mn ged 32 yers, ws first seen My 8, 1939, t which time he presented lesions on the sclp, plms, soles nd genitli of one yer's durtion. There were lso mild symptoms of psorisis rthropthic. No tretment hd been received. Totl blood serum lipids t this time ws 965 mgs. per 100 cc. Tretment ws strted with 12 cpsules of lipocic dily. Two weeks lter there ws slight improvement of the hnds. The totl blood serum lipids t this time ws 1000 mgs. per cent. The ptient ws next observed pproximtely one month fter the beginning of tretment. At this visit no further improvement ws noted nd the ptient complined of mild joint pins. The totl blood serum lipids ws 750 mgs. per 100 cc. This ptient is still under tretment. The ccompnying tble illustrtes the clinicl course of the eruption, long with chnges in blood lipids (tble I). COMMENT In our experience the norml totl serum lipid vlue rnged from mgs. per 100 cc. by the method used. In the six ptients whom we studied, three hd n initil lipemi, two were within norml limits nd one hd subnorml reding. No correltion between the initil totl lipid figure nd the response to lipocic therpy could be formulted. Regrdless of whether their totl lipids were elevted, ll ptients experienced slight improvement fter one or two weeks of tretment. However, subsequent improvement ppered to depend upon mintining the serum lipids t the lower limits of norml or below. This is well illustrted by the fct tht no ptient showed significnt improvement until the totl serum lipids hd reched level of 650 mgs. per 100 cc. or less. In the one cse in which there ws n initil subnorml vlue it will be noted tht t the time of gretest improvement the serum lipids were decresed below the initil figure. Cse 1 illustrtes this point very definitely. Mrked improvement here ws not noted until fter three months of therpy, when, under incresed dosge of lipocic the serum

10 228 THE JOURNAL OF INVESTIGATIVE DERMATOLOGY lipids fell to 650 mgs. per 100 cc. Prior to this time, the lowest level hd been 730 mgs. per 100 cc. of serum. The one cse in which filure to respond ws seen (cse 4) is somewht difficult to explin. The totl serum lipids ws 650 mgs. per 100 cc. or less during the entire course, except for one occsion. However, the ptient ws lost from observtion fter only two months of tretment, which in our opinion is too short period to judge the effect of lipocic therpy. It is interesting to note tht this ws our one cse of guttte psorisis. Mdden (6) stted tht the guttte lesions clered fster thn the inveterte plques when treted with low ft diet. Heling in most lesions begn centrlly. In cse 5 fter clering of the lesions there ws definite residul pigmenttion. One noteworthy fct ws the stubbornness with which the lst few remining lesions persisted. These usully proved resistnt to further lipocic therpy. Pruritus when present ws usully promptly relieved by tretment. We relize of course tht it is difficult if not impossible to evlute ny therpeutic procedure from such smll series of cses, nd prticulrly in disese chrcterized by spontneous remissions. However, it should be borne in mind tht these ptients clered during the winter months, seson when psorisis is generlly most severe. It must lso be remembered tht these ptients were not hospitlized or restricted in ny mnner, dietry or otherwise, nd tht no locl therpy of ny kind ws pplied. Wht the future course will be for these ptients cnnot be foretold s yet. Two ptients who were completely relieved, nd who hve not received lipocic for severl months hve noticed lesions beginning to repper. The tendency to relpse is of course well known. There is possibility, however, tht once psoritic is free of lesions he cn be kept free by smll dily mintennce dose of lipocic. This remins to be determined. In view of our results we feel justified in greeing with those uthors who mintin tht in psorisis there is present disturbnce of the lipid metbolism.

11 USE OF LIPOCAIC IN TREATMENT OF PSORIASIS 229 In closing it must be stressed tht we do not offer lipocic s cure for psorisis, but on the bsis of our study thus fr it promises to be vluble djunct in the tretment of this disese. As this work continues we shll report lrger series of ptients, together with the ultimte outcome of those who hve been relieved. SUMMARY 1. Six ptients with psorisis re presented who were treted with lipocic. Four showed mrked improvement, one filed to respond to lipocic therpy nd the other one hs shown slight improvement fter four weeks of tretment. 2. Before tretment ws strted, three ptients hd lipemi, two hd blood lipid vlues within norml limits, nd one showed subnorml lipid vlue. 3. Lipocic is shown to lower the blood serum lipids to norml or below norml level in ptients with psorisis. 4. This study lends support to the ide tht psorisis is ssocited with dernged ft metbolism. 5. Lipocic promises to be vluble djunct in the tretment of psorisis. Medicl-Professionl Bldg., Corpus Christi, Texs. 905 Est 59th &., Chicgo. BIBLIOGRAPHY (1) GRUTZ, 0., AND BURGER, M.: Die Psorisis ls Stoffwechselproblem. Kim. Wchnschr. 12: (Mr. 11) (2) GATE, J., CRANIAL, G., VALLET, A., AND HUMBERT, P.: Recherches Sur l Cholestérolémi dns le Psorisis. Ann. de Dermt. et Syph. 9: (June) (3) PULAY, E.: Le "psorisis vulgris" et son tritement. Bull. Soc. frnc. de dermt. et syph. 43: (July) (4) ROSEN, I., ROSENFELD, H., AND KRASNOW, F.: Studies in Psorisis. Arch. Dermt. & Syph. 35: (June) (5) fleeing, H.: Experimentelie Beitrge zum Fettstoffwechsel der Psorisis Vulgris. Dermt. Wchnschr. 106: , (6) MADDEN, J. F.: Cholesterol Blnce nd Low Ft Diet in Psorisis. Arch. Dermt. & Syph. 39: (Feb.) (7) DRAGSTEDT, L. R., VAN PROHASKA, J., AND HARMS, H. P.: Observtions on

12 230 THE JOURNAL OF INVESTIGATIVE DERMATOLOGY Substnce in Pncres (A Ft Metbolizing Hormone) Which Permits Survivl nd Prevents Liver Chnge in Depncretized Dogs. Amer. Jour. of Phys. 117: (Sept.) (8) FISRER, N. F.: Attempts to Mintin the Life of Totlly Pncretestnized Dogs Indefinitely by Insulin. Amer. Jour, of Phys. 67: (Nov.) (9) DRAGSTEDT, L. R., et L: Lipocic nd Ftty Infiltrtion of the Liver in Pncretic Dibetes, Arch. Tnt. Med. (in press). (10) SCJIAMBERG, J. F.: The Dietry Tretment of Psorisis. J. A. M. A. 98: (My 7)1922. (11) WiLson, W. R., AND HANNNR, J. P.: Chnges of Totl Lipid nd Iodine Number of Blood Ft in Alimentry Lipemi. Jour. Biol. Chem. 106: (My) (12) ALLAN, F. N., BowIE, J. J., MACLEOn, J. J. R., AND Roninson, W. L.: Behvior of Depncretized Dogs Kept Alive with Insulin: Brit. J. Exper. Pth. 5: 75, 1924.

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