1.ATCLIFFE: August 1950 - Postgraduate Medical Journalpmj.bmj.com/content/postgradmedj/26/298/436.full.pdf · t36 1.ATCLIFFE: Intermittent ... nameof Leo Buerger. ... exercises consisting

t36 1.ATCLIFFE: Intermittent Claudication August 1950

FIG. 2.-Juvenile obliterative arteritis-Later stage.(By courtesy of the Editors of the ' _'ournal of Bone andJ7oint Surgery ')

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437

INTERMITTENT CLAUDICATIONA REVIEW

Bv .A. HALL RATCLIFFE, M.A., B.Sc., D.PHIL.Lecturer in Experimental Methods, Department of Surgery, University of Manchester

PART I

HISTORICALIntroduction

Intermittent claudication, now recognized asone of the most constant symptoms of obliterativearterial disease, may be defined as a discomfort ofvarying severity, produced by exercising a muscleunder ischaemic conditions and being rapidlyrelieved by rest. The original report of thephenomenon appears to be that of the veterinarysurgeon Boullay (I83I), who observed it in asix-year-old mare. According to Boullay the causewas obliteration of the femoral arteries; when theanimal was at rest the collateral blood supply wasadequate, but when it trotted the blood supplywas insufficient. The result was ' une douleurprofonde.'The clinical picture was described by Charcot

(i858) in a 54-year-old man having an aneurysmof the right common iliac artery with obliterationof the distal part of the vessel. Strangely enoughthis is the least common site of obstruction of avessel supplying the leg and the occurrence ofsuch a case is still considered worthy of comment(Boyd and Jepson, 1950). Further examples ofintermittent claudication were given by Marinesco(I896) and Erb (I898).

Classification of Occlusive Arterial DiseaseThe medical literature of the igth century

abounds with clinical reports of occlusive arterialdisease leading to gangrene and resultant amputa-tion. Each individual author appears to havenoticed some distinctive feature with consequentjustification for the coining of a new term todescribe the general clinical condition. Brown,Allen and Mahorner (I928) give a list of no fewerthan 34 names which have been coined in this way.The first attempt at investigation was that of

von Winiwarter in i879. He studied the vesselsin a leg amputated for gangrene, and noted theproliferation of the intima, the presence of acellular mass gradually producing occlusion ofthe vessel, and the presence of thrombi in thevessels. The thrombi appear to have been re-

gvrded as adventitious, as von Winiwarter con-cluded that the final obliteration of the vessel wasthe direct result of the cellular proliferation. Theterm applied to this condition was ' endarteritisobliterans.' This classic article has been used asa stepping stone by many writers since its pub-lication and, in consequence of the deductionsmade from the report, it should be emphasized atthis point that von Winiwarter's patient was 57years of age. The significance of this will beshown later.The next important advance in the appreciation

of occlusive vascular disease is associated with thename of Leo Buerger. In I908 he made a reportbased on the study of the arteries ..nd veins in i Iamputated limbs. A series of papers by the sameauthor culminated in a monograph which appearedin 1924. Buerger distinguished two main con-ditions and called them ' thromboangiitisobliterans' and ' ateriosclerosis obliterans.' Theformer condition has acquired the name Buerger'sdisease.The distinction between the two diseases rested

chiefly on the age of the patient. Thromboangiitisobliterans was diagnosed in individuals below theage of 45 and arteriosclerosis obliterans over theage of 55. Between those two ages there existeda mixed group the nature of whose condition wasdifficult to ascertain. An additional distinctionwzs the presence of superficial phlebitis in 30 percent. of cases of thromboangiitis obliterans; thisadjunct was never observed in arteriosclerosisobliterans.The tacit acceptance of these definitions has led

to the widespread idea that two very distinctforms of occlusive vascular disease exist, oneoccurring in young men in whom arterioscleroticchanges are completely absent; the other occur-ring in later life, arteriosclerotic changes beingdiagnostic. Here a reference to Buerger (I908)himself is worthy of note. The original patho-logical study led Buerger to the conclusion thatthromboangiitis obliterans was an acute inflam-matory condition with a sequel of thrombosis.The intimal proliferation reported by von Wini-warter (I879) was not considered important, the



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438 POSTGRADUATE MEDICAL JOURNAL August 1950

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FIG. I.-Juvenile obliterative arteritis-Early stage.

changes observed being in Buerger's opinion dueto arteriosclerosis.De Takats (I934) added two further groups to

Buerger's nomenclature. Under the heading of' acute vascular occlusion ' he listed patients withthrombotic or embolic block of a main vessel ofthe limb, irrespective of cause. He revived theterm ' endarteritis obliterans ' and applied it to' the obliterative healed stage of many differentchemical and bacterial injuries that affect theintima.' This group included lesions due to frostbite, syphilis, tuberculous arteritis and poisoningby metals such as lead and arsenic.

Whatever the views as to the nature of theunderlying arterial lesion, all writers are agreedthat the principal symptom causing the patient toseek medical advice is the onset of intermittentclaudication. It was present in approximately 8oper cent. of the cases reported.

TreatmentIf the Igth century may be said to be noted for

the variety of the terminology applied to occlusivevascular disease, then the first part of the 2oth

century can with equal justice be said to be notedfor the multiplicity of treatments.

Repeated intravenous injections of varioussolutions, which it was considered might halt theprogress of arterial disease, have been tried.Steel (1921) considered that there was a reductionin clotting time of the blood which resulted inthrombosis. He therefore advocated the use ofsodium citrate. Koga (1913) felt that the viscosityof the blood was increased in thromboangiitisobliterans and advised carrying out the appropriatedilution with Ringer's solution. Silbert (I935)reported the results of treatment of 524 cases ofocclusive vascular disease with hypertonic (5 percent.) salt solution and recorded improvement in434 cases.Ambard, Boyer and Schmid (1926) found that

pain was relieved and the colour of the skinimproved following the subcutaneous injectionof io units of insulin daily. Barker, Brown andRoth (I935) obtained results with various tissueextracts in alleviating the pain of intermittentclaudication.

Various substances have been used to produce



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August 1950 RATCLIFFE: Intermittent Claudication 439

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FIG. 3.-Primary popliteal thrombosis.

vasodilatation. Goodman and Gottesman (1923)suggested the use of non-specific protein for thispurpose. Good results have been reported in alimited number of cases by Brown, Allen andMahorner (1928) from the Mayo Clinic, and A. W.Allen (1930) from the Massachussets GeneralHospital. Papaverine hydrochloride has beenused by Allen and MacLean (I935) in cases ofsudden arterial occlusion. The tetraethylam-monium compounds have been suggested as vaso-dilators in peripheral vascular disease (Lyons et al.,1947) although their action has been shown to becapricious (Boyd et al., I948).

Buerger (1924) devised a series of posturalexercises consisting primarily of elevating thelegs at an angle of 450 for two minutes followedby the patient sitting on the edge of the bed withhis feet hanging down for a further two minutes.During this period the patient was supposed tocarry out a routine of dorsiflexion, extension,inversion and eversion of the feet and flexion andextension of the toes. After this he lay flat in bed,with radiant heat treatment, for five minutes.

Physiotherapy has been advised by several

writers, the most popular form being short-wavediathermy (Wright, I938). A thermo-regulatedfoot cradle was produced by Starr (I93I). Contrastbaths were recommended by Brown et al. (I928).The legs were immersed for one-minute periodsalternately in hot (I00° to iio0F.) and cold (400to 5o°F.) water for a total of 15 minutes threetimes a day.

Another form of mechanical treatment was'passive vascular exercise ' or ' Pavaex ' therapy.Here the leg under treatment was inserted throughan airtight seal into a glass boot and subjectedfirstly to a negative pressure to fill the capillariesand secondly to a positive pressure to empty them.This system appears to have been developed moreor less coincidentally by Landis and Gibbon(I933a and b) and Herrman and Reid (I934).The former used a negative pressure of from 8oto I20 mm. of mercury for 25 seconds followedby a positive pressure of 6o to 8o mm. for fiveseconds; the latter used 8o mm. negative and20 mm. positive pressure at a rate variable fromtwo to four cycles a minute. Reports on thesuccess of ' Pavaex ' vary from the enthusiastic to



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440 POSTGRADUATE MEDICAL JOURNAL August fg95

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FIG. 4.-Senile obliterative arteritis-Diffuse obliterative arteritis.(By courtesy of the Editors of the 'Journal of Bone and Jotnt Surgery ')

the very critical. Investigators include de Takats(1934), Collens and Wilensky (I936) and Conway(1936) in addition to the originators of thetechnique.

Surgical measures for the treatment of occlusivevascular disease have also been many and varied.Perhaps the most revolutionary was the suggestionput forward by Lewis and Reichert (1926) thatthe femoral artery should be ligated distal to theorigin of the profunda before the popliteal arterybecame thrombosed; by this means it was con-sidered that the collateral circulation would beincreased. Femoral vein ligation was tried, butGinsburg (I917), reviewing the subject, con-sidered the results far from satisfactory. Lilienthal(1907). carried out an end-to-end anastomosis ofthe femoral artery and vein, but the patient diedthree days after the operation. The procedure wasperformed successfully by Meyer (I925) withreported good result. The rationale of arterio-venous anastomosis was considered to be invalidby Buerger (I924) on the grounds that a venousthrombosis is not uncommonly present.The hypothesis that occlusive vascular disease

might be due to an excess of circulating adrenalin(Josue, I903) was advanced as a reason forunilateral adrenalectomy. Reviewing i io cases,Herzberg (1926) condemned the procedure.A local vasodilatation and relief of pain as a

result of periarterial sympathectomy was describedby Leriche and Heitz (I917). Although theoperation has been performed by many surgeons,the clinical results do not appear to have beensuccessful. Brown and Rowntree (I925), in aseries of 17 cases, were unable to demonstrate anyvasodilatation. Allen (1930) considered thatthe procedure was not worthwhile on clinicalgrounds.Lumbar ganglionectomy was advocated by Adson

and Brown (I932) in cases where a preliminarynerve block resulted in a rise of skin temperatureof the extremities of 30C. or greater. Good resultsfrom the operation have been recorded by Telfordand Stopford (I933), Flothow and Swift (I933),Diez (I934), Atlas (I94I), van Ouwerkerk (I946)and many others. Atlas (1942), however, soundeda warning note on the subject. He pointed outthat in certain cases the main effect of sympathei.-



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Alugust 1950 RATCLIFFE: Intermittent Clatudication 44!.

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FIG. 5.-Senile obliterative arteritis-Secondary popliteal thrombosis.(By courtesy of the Editors of td. '.Yournal oJ Bon: and 7oint Surgery ')

tomy is to open up arteriovenous shunts in theskin with disastrous results.

Pain-relieving procedures consisting of destruc-tion of peripheral nerves by section (Laskey andSilbert, 1933), crushing or alcohol injection(Smithwick and White, 1930, 1935) have also beendescribed.

PART II

THE MECHANISM OF PAIN ININTERMITTENT CLAUDICATION

Although from the time of Boullay (1831) itwPs realized that the underlying cause of thesyndrome of intermittent claudication was arterialdeficiency, the reason whv this should cause painwas not clear. Various theories have been advancedfrom time to time:

Muscular SpasmIt wvas observed bv the earlier clinicians that

after a patient with intermittent claudication hadexercised there was sometimes a palpable changein the consistency of the- calf m-useles. Tlhis

suggested that the ultimate cause of the pain wasmuscle spasm. Charcot ki858) and Marinesco(I896) went so far as to comparc the state of themuscle with cadaveric rigidity. Support was givento the muscular spasm hypothesis by Erb (I898).Two facts make the theory untenable; the paindoes not vary with each individual muscle con-traction, and the change in muscular consistencyis far from constant.

Arterial SpasmOppenheim (I900) described cases where inter-

mittent claudication was present without obviousarterial disease. He considered this to be due toarterial spasm. From this it was but a short stepto the assumption that the pain in all intermittentclaudication is angiospastic in origin, despite thephvsiological concept that the response to muscleexercise is vasodilatation. Veal and McFetridge(1936), by arteriographic studies, showed thatexercise pain did in fact occur with the vesselsdilated.

Certain anomalous cases of intermittent claudi-cation, with disappearance of the limb -pulses



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442 POSTGRADUATE MEDICAL JOURNAL August I950

........ZJ

FIG. (,.-Senile obliterative arteritis-Secondary femoral thrcmbosis.

after exercise, although no arterial disease wasdemonstrable (Pearl, 1937), are most probably dueto a thrombotic lesion proximal to the femoralartery (Boyd and Jepson, 1950).

Muscular IschaemiaZak (1921) showed that repeated opening and

closing of the hand in a normal upper extremityproduced symptoms akin to intermittent claudica-tion if the brachial artery was artificially com-pressed. Detailed investigation of this pheno-menon was carried out by Lewis and his co-workers (1929); a review of the work was made byLewis (1942).The concept advanced by Lewis was that the

immediate cause of the claudication pain was notoxygen lack but the accumulation of metabolitesacting on sensory nerves. The particular sub-stance responsible is designated as 'factor P.' Theobservations which support this idea may besummarized briefly as follows:

(a) The intensity of the claudication pain doesnot increase and diminish as the muscle contractsand relaxes but is-a steady ache.

(b) With a test involving a standard rate ofwork done by normal subjects with the circulationoccluded, it was found that pain began some 35seconds after exercise started, becoming intoler-able after a further minute. If the circulation isrestored the pain disappears within 3 seconds; ifthe circulation is not restored the pain persists.

(c) If the circulation is completely occluded theonset of the pain depends on the total work done;if the rate at which the work is done is increasedthe time of onset of the pain is reduced in propor-tion. If the circulation is incompletely occludedthe total amount of work required to produce painincreases as the rate of work is reduced (Katz,Lindner and Landt, 1934). The explanation isthat, with the circulation only party occluded,reducing the rate of exercise allows a greater timebetween muscle contractions for the metabolitesto be removed.

(d) After the claudication pain has becomeestablished, if the circulation is restored for aninterval just sufficient to remove the pain, and theexperiment repeated, it is found that the amountof -work which causes pain has been reduced.



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RATCLIFFE: Intermittent Claudication

This suggests the carry-over of metabolites fromthe previous experiment.The composition of ' factor P ' has not yet been

determined. Katz, Lindner and Landt (I935)believe it to be a non-volatile acid. In parenthesisit may be noted that Buerger (1924) suggestedthat the failure to remove lactic acid from themuscle might be the cause of claudication pain.

PART III

THE WORK OF THE MANCHESTERNEUROVASCULAR TEAM

A study of the underlying causes, methods ofinvestigation and treatment of intermittent claudi-cation was begun in 1947 in the neurovascularclinic at the Manchester Royal Infirmary. Theconclusions reached at the end of the first twoyears have been reported by Boyd, Hall Ratcliffe,Jepson and James (I949), together with an analysisof 276 cases followed up for a minimum period ofsix months. A review of this and subsequentpublications is given below.

A Classification of Occlusive Arterial DiseaseThe arteriographic findings and clinical features

in over a thousand patients with deficiency ofcirculation in the lower limbs investigated duringthe last three years have been reviewed by Boyd(1950). The arterial lesions may be classified underfour main headings:

(i) Traumatic thrombosis.(2) Juvenile obliterative arteritis.(3) Primary popliteal thrombosis.(4) Senile obliterative arteritis.

(i) TRAUMATIC THROMBOSISThe designation of this group is self-explanatory,

the arterial thrombosis being directly due to grosstrauma.

(2) JUVENILE OBLITERATIVE ARTERITISHere the degenerative process begins in the

small arteries of the feet (Figs. i and 2). Althoughthere are quiescent periods the disease inevitablyascends the limb, eventually resulting in gangrene.The condition is bilateral, although one limb maybe affected a considerable time before the other.A patchy superficial phlebitis usually precedes thearterial changes. A fungus infection of the feetis an almost constant finding. That certain fungigive rise to toxins which affect the endotheliumof blood vessels has been shown by Thompson(i944) and it may well be that this is the causativefactor. An unusually high occurrence of patchysuperficial phlebitis and juvenile obliterativearteritis was seen among troops in Egypt underconditions where fungus infection was rampant.

A careful distinction must be made betweenthis condition and the distal form of senileobliterative arteritis, which is clinically similarbut is not accompanied by superficial phlebitis orfungus infection.

(3) PRIMARY POPLITEAL THROMBOSISArteriographic studies show that the lesion is

confined to the popliteal artery (Fig. 3). Thethrombus may extend from the level of the kneejoint upwards to the adductor opening or down-wards to the bifurcation of the artery, or occasion-ally in both directions. The constancy with whichthe thrombosis starts at the level of the knee jointsuggests that repeated minor traumata may be thecausative factor. Arteriograms of patients knownto have sustained traumatic thrombosis of thepopliteal artery from posterior dislocation of theknee joint are indistinguishable from those ofprimary popliteal thrombosis.

Histologically there is no evidence of inflam-matory changes in the arterial wall (Boyd, 1938).The lumen is found to be occluded by healthyclot in various stages of organization.Primary popliteal thrombosis follows a benign

course and there has been no further evidence ofarterial lesions in patients who have been seen byBoyd ten years after the onset of the condition.This course differs greatly from the after-historiesof patients with juvenile obliterative arteritis.

In this series patients under the age of 35 fallinto the categories of primary popliteal throm-bosis or juvenile obliterative arteritis. It is con-sidered that, in spite of the marked clinical dif-ference, these two conditions have in the past beengrouped together under the general term' throm-boangiitis obliterans,' although it is felt that somereported series contain a generous admixture ofthe distal type of senile obliterative arteritisdescribed below.

(4) SENILE OBLITERATIVE ARTERITISOver go per cent. of the patients in this series

are included in this group. It must be emphasizedthat senile obliterative arteritis is not solely con-fined to the elderly. Atheroma has been recordedin young children, and it is far from rare in thethird and fourth decades; it accounts for prac-tically all occlusive arterial disease over the ageof 40 years. Senile obliterative arteritis may beof the diffuse form; there may be secondarythrombosis of a major vessel ; or the lesion mayaffect only the feet.

(a) Diffuse Obliterative Arteritis. Arteriographyshows partial occlusion and irregularity of themain vessels and larger branches (Fig. 4). In themost common group the small branches areabundant and the collateral circulation is markedly

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developed. Less frequently there seems to bea paucity of muscular branches wvhich appear toend abruptly; the collateral circulation is poorlydeveloped and theie is pronounced musclewasting.

(b) Secondary Popliteal Thrombosis. Before theseverity of the intermittent claudication compelspatients with senile obliterative arteritis to seekadvice, nearly half of them have experienced asecondary popliteal thrombosis, usuallv associatedwith some definite incident of over-exertion. Asin the primary type the thrombosis begins behindthe knee joint and usually extends upwards tothe adductor opening (Fig. 5), although sometimesit may spread downwards or in both directions.The effect of the secondary popliteal throm-

bosis depends on the degree of development ofthe collateral circulation. If the arterial diseaseis of long standing the collaterals are probablywell developed, whereas a thrombosis occurringearly in the disease is bound to lead to severeischaemia.

(c) Secondary Femoral Thrombosis. Thrombosisof the superficial femoral artery occurred in 13per cent. of the patients with senile obliterativearteritis. The thrombosis begins in the region ofthe adductor opening (Fig. 6); the proximal ex-tension is limited by the brisk flow of bloodthrough the profunda femoris.

Clinically a secondary femoral thrombosis is tobe suspected in a patient complaining of inter-mittent claudication in the calf and yet having anapparently healthy limb. In general the higherthe arterial block the less marked are the effectson tlle peripheral circulation.

(d) Distal Type. The distal type of senileobliterative arteritis affects the feet and often thehands. It occurred in approximately io per cent.of the cases in this series. Proximal spread of thelesion is uncommon and the condition rarelyleads to more than superficial necrosis or the lossof the terminal phalanges of the toes.

In young people the condition can be dis-tinguished from juvenile obliterative arteritis bythe lack of patchy superficial phlebitis and fungusinfection. Juvenile obliterative arteritis does notaffect the hands.

In the elderly patient clinical recognition isimportant. The sudden appearance of ischaemicchanges in the feet is usually regarded as hopeless,whereas in fact this type generally respondsreadily to treatment.

Investigation and Clinical TypingPatients complaining of intermittent claudica-

tion are first seen in the Neurovascular Clinic.Investigation, therefore, was designed to enablethe surgeon to decide whether treatment can be

given as an out-patient or whether admission forfurther study is desirable. The informationrequired consists of the clinical history and generaldata, the diagnosis of the nature of the causativelesion, the muscle group affected and the degreeof severity of the condition.

CLINICAL HISTORY AND GENERAL DATASince peripheral vascular disease is part of a

general degenerative process the patient must beassessed as a whole. A detailed examination ofthe cardiovascular system is not possible in theout-patient clinic, but where operative procedureis contemplated, is carried out when the patientis admitted.During the out-patient investigation the data

are entered on a standard pro-forma. A recordis made of the location of pain, the date when itwas first noticed, whether the onset was gradualor sudden; the distance walked originally andat the time of examination, whether the changewas gradual or sudden; any history of injury,frostbite or phlebitis; the amount of tobaccosmoked; the parents' age and cause of death.Clinical data include general health, state of heartand blood pressure, nutrition of the limb, musclewasting or other degenerative changes.

THE CAUSATIVE LESIONOscillometric readings are taken above and

below the knee and above the ankle. The oscillo-meter is not a'precision instrument, but it doesallow assessment of main vessel changes. Oscil-lations are reduced in an arteriosclerotic limb andare absent below a main vessel block.

THE MUSCLE GROUP AFFECTEDThe muscle group most affected by the is-

chaemic changes may be found from the surfacerepresentation of the'claudication pain. This wasworked out by Jepson by injecting the appropriatemuscle group, in himself and volunteers, with 6per cent. saline after first infiltrating the skin anddeep fascia with local anaesthetic. Three referenceareas were demonstrated. Injection of the gastroc-nemius produced a pain in the mid-calf extendingbehind the knee to the back of the thigh; fromthe mid-calf downwards to the instep; theanterior tibial and peroneal muscles on the antero-lateral surface of the leg.

ASSESSMENT OF SEVERITY: CLINICAL TYPINGThe patients' walking ability is tested on a

'claudicometer.' This consists of an endless beltdriven by an electric motor at a speed rangingfrom one to four and a half miles per hour; atachometer gives the speed and distance traversed.The patient steps on to the belt, which is moving

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towards him at the slowest rate; the speed is thenadjusted until the patient considers he is walkingat his normal rate. When the claudication painbegins the distance is noted by the observer. Thepatient is not allowed to rest, but is urged to con-tinue walking as far as possible, meanwhile de-scribing the subjective phenomena. The distanceat which the patient eventually halts is also noted.From the data obtained it is possible to classifythe severity of the condition as belonging to oneof three types.The rationale of the classification depends on

a consideration of the events taking place in amuscle during exercise. The blood supply toa muscle at rest is scanty, but it increases consider-ably with exercise (Krogh, 1922). If the muscleis exercised under ischaemic conditions pain results(Lewis et al., 1929). Though the exact mechanismof the vasodilatation and the production of painhas not been fully described, it cannot be doubtedthat the initiating event is the accumulation ofmetabolites in the contracting muscle (Hamnilton,1947).With continuing exercise the level of meta-

bolites will become steady when the rate ofelimination is equal to the rate of production.With normal blood supply, stabilization takes placebelow the threshold of pain, but in the claudicantwith reduced blood supply the pain threshold isreached before stabilization. The level at whichequilibrium is attained depends on the relationbetween blood supply and demand, and it is thislevel which determines the severity of the painand the clinical type of claudication.

Type i. In this type the blood supply anddemand are about equal. Before maximum vaso-dilatation is achieved the pain threshold is crossed,but equilibrium is eventually reached below thethreshold. On walking, the Type i claudicantcomplains of the onset of pain, but on continuingto walk he announces, usually with some surprise,that the pain has disappeared. That the equili-brium is just below the pain threshold can bedemonstrated by increasing the rate of walkingabove the normal, causing the pain,to return.

Type 2. Here equilibrium is reached above thethreshold of pain. On continuing to walk after theonset of the claudication the patient says that theintensity of the pain remains much the same.Eventually he stops walking, not because of anyincrease in intensity but because of the persistenceof the pain. Naturally the patient with the lessintense pain tends to walk further than the patientwith the more severe pain.

Type 3. -Equilibrium is never reached with thistype; the deficiency of blood supply is such thatthe pain becomes intolerable before that point.The Type 3 patient, on being urged on after the

onset of claudication, states that the pain is growingworse, and he halts a short distance further on,obviously in extreme pain.

TreatmentLack of knowledge of the etiology of arterial

disease limits the treatment of intermittent claudi-cation to alleviation of the subjective manifestationswhich interfere with the daily life of the patient.As the pain is due to an imbalance between bloodsupply and demand the logical treatment wouldbe to increase the blood supply to the requiredlevel or, if this is not possible, to reduce thedemand. In practice the problem is more com-plex; many factors must be considered and eachcase assessed individually.

FACTORS INFLUENCING THE CHOICE OF TREATMENT(a) Clinical Type. Failure to recognize that there

are different grades of claudication has made theassessment of treatment virtually impossible. Thegeneral principles of treatment indicated in eachclinical type can, however, be defined clearly.In Type I patients blood supply and demand arevery nearly equal.. The slightest increase in bloodsupply brings about complete relief from claudica-tion, and it appears that additional exercise willdo this. In consequence the patient will respondto any treatment in which he has confidence.The gap between supply and demand is greater inthe Type 2 patient. Generally the supply can beincreased to meet the demand, though in the moresevere cases the demand may be reduced. In theType 3 patient the supply cannot be increased tobridge the gap and relief from pain can be securedonly by reducing the demand.

(b) Age. The younger the patient the morenecessary it is to secure the greatest ,possibleincrease in blood supply, not only to improve thenutrition of the limb but also to retard degenerativechanges and postpone the need for amputation,

(c) Type of Arterial Disease. With diffuseobliterative arteritis and calcification of the mainvessels, loss of life through coronary thrombosisor cerebral complications is more likely than lossof the limb through gangrene. It is felt thatsympathectomy should only be advised in thiscondition when there is good reason to believethe limb to be in danger.

Patients with a main vessel thrombosis, especi-ally the superficial femoral, are prone to furthermassive thrombosis and gangrene. An effort toimprove the blood flow is strongly advocated- inType 3 patients in these groups, together withmeasures for the relief of pain, and in all patientswith superficial femoral thrombosis.

(d) Associated Conditioms. In patients pastmiddle-age, arterial lesions resulting in inter-

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mittent claudication are often only part of ageneralized degenerative change. Apart fromgeneral conditions contra-indicative of a par-ticular treatment, it is advisable to ascertain thatclaudication really is the limiting factor. It isunwise, for instance, to carry out an operation forthe relief of claudication if the patient is broughtto a standstill by osteoarthritis of the knee joint.

Diabetes, unless mild and well controlled,accounts for rapid progress in arterioscleroticchanges and in the development of peripheralgangrene and must be excluded before decisionsare made as to treatment.

METHODS OF TREATMENTOnly those methods of treatment whose success

has justified their retention are reviewed. Forothers which were tried and abandoned, referenceshould be made to the original papers.

Assessment of results has been made on thepatient's ability to walk a minimum of half a mile;beyond this distance he is classed as improved,short of it as unimproved. This method has beenadopted on the grounds that a patient's walkingdistance may be doubled-e.g. from ioo yards to200 yards-and still not be of economic value.Assessment has been limited in this review, tothose patients for whom the procedure was under-taken with a view to relieving their claudication.For exarnple, the results of lumbar ganglionectomyare reviewed on Type 2 patients, although it wasalso performed on Type 3 patients with poor limbnutrition.Lumbar Ganglionectomy. The quickest and most

certain method of improving the blood supply tothe limb is lumbar ganglionectomy. Release ofnormal tone increases the blood flow even if thereis no evidence of abnormal vasoconstriction. Inorder to be sure of denervating the whole limbit is necessary to remove the first three lumbarganglia and the intervening chain (Hall Ratcliffeand Jepson, I950). Of 52 Type 3 patients in thisseries, 47 were improved by the operation.

Paravertebral Block with i o per cent. Phenol.In patients in whom lumbar ganglionectomy wascontra-indicated on the grounds of age or generalcondition, chemical destruction of the ganglia hasproved of value. The method advocated byHaxton (I949) has been employed. Of i8 Type 2patients, I4 were improved by this method.

Vitamin E (a-tocopherol) Therapy. a-tocopheroltherapy has been employed in cases whereoperative procedures were considered inadvisable.Patients were given daily doses of syntheticoc-tocopherol (Ephynal, Roche). A controlledseries has been reported by Hall Ratcliffe (I949).Of 4I Type 2 patients fulfilling the experimentalcriteria, 34 were improved, while of 25 controlsonly 5 were improved.

Tenotomy of the Tendo Achillis. This procedurehas been carried out in Type 3 patients in whomthe reference areas of the pain show beyond doubtthat claudication in the gastrocnemius or soleus isthe limiting factor. The disability is slight and inmost.cases the gait is improved; the slight limpcaused by the tenotomy replaces the severe limpof the claudication.The operation was performed on i8 Type 3

patients and all were improved.Division of the External Popliteal Nerve. Three

Type 3 patients had no calf pain, the referencearea being that of the anterior tibial-peronealgroup. The external popliteal nerve was infil-trated with 2 per cent. novocain, after which thepain was relieved and all were able to walk morethan half a mile in comfort. They each agreedthat the foot-drop was infinltely preferable to theclaudication pain and that the nerve should bedivided. This was done and so far they haveremained satisfied.

AcknowledgmentAcknowledgment is freely and gladly given to

Professor A. M. Boyd and my fellow workers inthe Manchester neurovascular team.

BIBLIOGRAPHY

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Am. Your. Med. Sci., I89, 36.BOULLAY, P. (I83I), Ar,:hives Ginerales de Medicine, 27, 425.BOYD, A. M. (1938), St. Bartholomew's Hospital Reports, 71, I51.BOYD, A. M. (I950), Practitioner, I64, 488.BOYD, A. M., CRAWSHAW, G. R., HALL RATCLIFFE, A.,

and JEPSON, R. P. (1948), Lancet, i, I5.130YD, A. M., HALL RATCLIFFE, A., JEPSON, R. P., and

JAMES, G. W. H. (I949), Jour. Bone Jt. Surgery, 31B, 325.BOYD A. M., and JEPSON, R. P. (1950), Brit. Med. Jour., i, 1457.

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21, 343-GINSBURG, N. (1917), Am. J7our. Med. Sci., I54, 328.GOODMAN, C., and GOTTESMAN, J. (I923), Med. J7our. New

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August 1950 LOXTON: Advances in Treatment of Rheumatoid Arthritis

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(abs. World Surg. (I947), I, 149).PEARL, F L. (1937), Am. Jour. Med. Sci., I94, 505.SILBERT, S. (I935), Surg. Gynec. Obstet., 6i, 214.SMITHWICK, R. H., and WVHITE, J. C. (1930), Ibid., 51, 394.SMITHWICK, R. H., and WHITE, J. C. (I935), Ibid., 6o, iio6.STARR, I. Jr. (193I), Proc. Soc. Exper. Biol. Med., 28, I1I.STEEL, W. A. (I921), Med. Rec. New York, 99, 370.De TAKATS, G. (I934), Jour. Am. Med. Assoc., 103, 1920.TELFORD, E. D., and STOPFORD, J. S. B. (I933), Brit. Med.

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Sci., 192, 113.von VINIWARTER, F. (1879), Arch. f. klin. Chir., 23, 202.WRIGHT, I. S. (1938), Arch. Phys. Therap., I9, i61.ZAK, E. (192I), quoted by BUERGER (1924).

RECENT ADVANCES IN THE TREATMENT OFRHEUMATOID ARTHRITIS

By GEOFFREY LOXTON, M.B., M.R.C.P.Consultant Physician, Woolwich Group of Hospitals, South-East Region

Since the announcement by Hench and hiscollaborators at the Mayo Clinic that cortisone(17 - hydroxy - i i - dehydrocortico - sterone, Com-pound E) and ACTH (pituitary adenocortico-trophic hormone) can produce dramatic improve-ment in patients suffering from rheumatoidarthritis, the medical and lay press have shown aburst of interest in the treatment of this tragicand ancient disease. The general physician andendocrinologist, who in the past were often loathto admit cases to their beds,..now all seem keen'to have a go.' It is therefore important that theproblems arising from these new forms of treat-ment should be viewed with a proper sense ofperspective. To do this a brief description ofmodem views on the aetiology, diagnosis andnatural history of the disease is necessary. Wemust also reconsider our methods of assessingimprovement and cure.

Aetiology

The cause of rheumatoid arthritis is unknown,though most workers agree that heredity andphysical or emotional strain may be contributoryfactors. The disease is commoner in womenthan in men, in the poor than in the rich, in coldwet climates than in warm dry climates. We shalldiscuss not only these factors, but also the follow-ing suggested causes: focal sepsis, bacterial orvirus infection, bacterial or virus sensitivity,vitamin deficiency, endocrinological factors andthe general adaptation syndrome of Selye.

Focal sepsis if always sought is not commonlyfound. Finding and clearing it rarely cures. Itcannot therefore be regarded as a constant aetio-logical factor.The disease has many of the characteristics of

a chronic infection, fever, malaise, wasting and, a



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