Postgrad. med. J. (July 1967) 43, 467-480.

Rheumatic feverA clinico-pathological conference held at the Royal Alexandra

Hospital for Sick Children, Brighton, on Tuesday, 8 February 1966

CHAIRMAN: R. KEMBALL-PRICEM.D., F.R.C.P.

Consultant Physician, Brighton andLewes Hospitals

R. KEMBALL-PRICE: Ladies and Gentlemen, thisevening's subject for discussion is the problem ofrheumatic fever and we are particularly fortunatein having Dr Michael Joseph here as guest speaker.Dr Joseph has for some years been a member ofthe consultant staff of Guy's Hospital, where heworks as a paediatrician with a special interest incardiology. More recently he has been appointedas Consultant Paediatrician to the Brompton Hos-pital and so you will appreciate that his experienceand knowledge of heart disease in children is quiteextensive. We are particularly pleased to welcomehim here tonight because he comes, not simply asa visitor from London, but as a friend of many inBrighton whom he has met at the regular heartclinics that are held at the Children's Hospital. Iam quite sure that we shall have an entertainingand instructive session this evening.And now, to start the proceedings, I should like

to ask Dr Nash to present the details of his patientwho forms the subject of this clinico-pathologicalconference.

F. W. NASH: This young boy, Vasfi M., died inour hospital on 25 May 1965, at the age of 92years, during his fourth attack of rheumatic fever.The first attack had occurred some 5 years pre-viously.The social background of the family is of some

importance and the medical details would be in-complete without telling you a little about it.Vasfi was a member of a Turkish Cypriot familywhich came to Britain in 1952. The parents andfive other children (with ages ranging from 4 to 20years) live in a small three-roomed basement flat inLondon. One of the children, a girl 13 years old,has so far had two attacks of rheumatic fever.There was also another child who died frommiliary tuberculosis in 1959. Although the family is

Requests for reprints should be sent to Dr F. W. Nash,Royal Alexandra Hospital for Sick Children, Dyke Road,Brighton, 1.

GUEST SPEAKER: MICHAEL JOSEPHM.D., M.R.C.P., D.C.H.

Consultant Paediatrician to Guy'sHospital and the Brompton Hospital

over-crowded and living conditions are not verygood, there is no real shortage of money, for bothparents and the two eldest children are out atwork. One of the important aetiological factors inour patient's illness appears to have been aninability to spend the family income properly andto make adequate use of available medical andsocial facilties. This was largely due to intellectuallimitations of both parents and recurrent spells ofdepression on the part of the mother.

In 1959, when he was aged 4 years, Vasfi wasadmitted to the Westminster Children's Hospitalwith a chest infection complicated by congestiveheart failure and this illness was subsequentlydiagnosed, in retrospect, as rheumatic fever onthe basis of the appearance of cardiac enlarge-ment and established mitral incompetence. Twoyears later (1961) the boy was investigated inGuy's Hospital for an obscure illness which mighthave been subacute bacterial endocarditis, thougha firm diagnosis was never established. Soon after-wards he had an atypical attack of rheumatic feverwith pain and swelling of a single joint (the rightknee), and some pyrexia. There was no history ofa preceding throat infection. The heart enlargedfurther and signs of mitral stenosis appeared inaddition to those of incompetence. The illness wastreated with prednisone as well as aspirin andpenicillin. Interestingly, the highest ASO titre wasonly 280 units. A comment appears in the notesthat the parents had been very lax over giving theirchild prophylactic oral penicillin.

In 1962 there was yet another illness with in-volvement of the right knee associated withpyrexia, a raised ESR, but a normal ASO titre (166units). Rheumatic fever was again diagnosed andon this occasion steroids were not given becauseof cardiac enlargement. After discharge fromhospital an attempt was made to give prophylacticpenicillin (Triplopen) by injections, but Vasfi fre-quently failed to attend for this treatment. Even-tually, in September 1962, he was admitted to a

Rheumatic fever

boarding school for physically handicapped child-ren (Staplefield School). He remained an activechild with only slight limitation of exercisetolerance and was generally very fit, though exam-inations showed that the heart was large and themurmurs persisted. Oral penicillin was givenregularly whilst he was at school and he had asupply to take home for the holidays, but we donot know that he had it regularly whilst at home.My first contact with Vasfi was on 21 May when

I was asked to see him at the school. He had beenunwell for 3 days with a sore throat, raised tem-perature and vague pains in his joints. When Iexamined him he appeared to be a very anxiousboy, but not extremely ill-temperature 102°F,pulse rate 120/min, respiratory rate 30/min.There was no evidence of congestive heart failure,though the heart was considerably enlarged andthere were clear signs of mitral stenosis with in-competence and also aortic incompetence. Bothknee joints were slightly swollen, but not tender orreddened; however, there was some redness andtenderness over the inner side of the left ankle.Admission to hospital was discussed with theschool doctor, but we decided against it at thisstage because of the boy's anxiety about himselfand the separation it would involve. I recommendedincreasing the dose of aspirin to 60 grains/day andgiving intramuscular instead of oral penicillin,because a throat swab taken at the beginning of hisillness produced a growth of haemolytic strepto-coccus (though not of Lancefield Group A).

Later that night Vasfi suddenly became very illwith high pyrexia (104°F) and he was transferredto the Children's Hospital early the next morning.He was then clearly in early congestive heartfailure; there was no clinical evidence of peri-carditis. After treatment with digoxin andprednisone, whilst being nursed in an oxygen tent,he improved a little. Throughout the following day(24 May), the child remained quite ill. In theevening of the 24 May he complained of someabdominal pain and had a haemoptysis of about2 or 3 oz. Signs of consolidation in the left lowerlobe were noted and, although a pulmonaryembolus may have been the cause of the newsymptoms, it was decided to give him chlor-amphenicol since there was a possibility that hewas developing pneumonia in addition to therheumatic carditis. The boy seemed much morecomfortable for a time and he even had a chatwith the night sister when she was doing herrounds but, quite suddenly, at about 01.30 hourson the 25 May, he slumped forward in his bed anddied.R. KEMBALL-PRICE: Thank you, Dr Nash. Now

would Dr Rubin please tell us something about

the X-rays of this boy. Afterwards I shall ask DrTrott to describe the post-mortem findings andDr Elliott will discuss the histology.

J. RUBIN: There are two films (supine andlateral) which were taken on 22 May 1966; Ibelieve this was 3 days before the child died. Theyshow that the heart is severely enlarged with quitedefinite pulmonary congestion as revealed bygeneralized pulmonary vascular plethora (Fig. 1).The appearances are really those of early con-gestive heart failure.

FIG. 1.

A small pericardial effusion cannot be excluded.The left costophrenic recess is less well illuminatedthan the right and this may be due to slight pleuralreaction, but there is no obvious pleural effusionat the time of this portable X-ray examination.

P. TROTr: At post-mortem the principal findingswere in the heart. This was grossly enlarged andweighed 330 g, which is at least double the normalweight for a heart in a boy of this age. Theincrease in size was predominantly due to a grosslyenlarged left ventricle which was dilated and hada very thick wall (1-2 cm), somewhat thicker thana normal adult's left ventricle. The myocardiumwas generally pale but there were no rheumatic

468

A clinico-pathological conferencenodules to be seen macroscopically. The pul-monary, tricuspid and aortic valves were normalto the naked eye, but the mitral valve was verymuch dilated and admited three fingers. The sur-face of the valve was pink and oedematous andthere were many pale grey bead-like vegetationson the auricular surface, some of which hadextended to the margin of the valve giving it anextremely irregular and rigid appearance. In therespiratory tract the tonsils were enlarged to abouttwice the normal size, the trachea and mainbronchi were filled with a pink watery fluid andthe lungs were grossly congested and oedematous,particularly in the left lower lobe. The liver wasenlarged to about twice the normal size and itscut surface was dark red in colour. All the otherorgans were apparently normal.The conclusion is that the child died from heart

failure due to acute-on-chronic rheumatic carditis.

R. I. K. ELLIOTT: The question that we have totry to answer histologically is whether this child'sterminal illness was still basically rheumatic; notas simple, in fact, as it sounds. We all know thatthe classical lesion in rheumatic disease is theAschoff nodule; but the trouble about classicalthings is that nowadays one sees them only inruins: the ravages in this instance being those oftherapy, rather than time. But quite apart from

modifications due to treatment, the Aschoff noduleis not a structure readily pinned down: it developsand changes, so that even in the florid untreateddisease one sees a collection of stages rather thana single unvarying pattern. For a picture of thehistological ingredients of this lesion, it is easier totake a small focus from a rheumatoid nodule,which is similar, but more stereotyped; and morereadily available. In such a focus, taken from anadult patient (Fig. 2), one finds a central area offibrinoid material surrounded by a radial palisadeof mononuclear cells, which merges without adistinct border into the surrounding fibrous tissue.

In this child's myocardium, low-power exam-ination shows extensive fibrosis, patchily distri-buted, heaviest beneath the endocardium and atthe sites of attachment of the valves. In the fibroustissue are cellular infiltrates, roughly fusiform,with indistinct boundaries. Under the high power,they show a central area of fibrinoid materialsimilar to that of the rheumatoid nodule, butsmaller. Round it, you can trace a stragglingpalisade (Fig. 3). The cells are fewer and lessregularly disposed than in the rheumatoid nodule,but they are of the same type, somewhere betweena histiocyte and a fibroblast. In some foci, a fewlymphocytes are also present in this zone. By com-parison with a rheumatoid nodule, the cellularreaction is feeble-this I interpret as the effect of

FIG. 2. A small rheumatoid focus in the joint capsule in severe rheumatoid arthritis, showing acentral fibrinoid lake with a palisaded border of histiocytes and fibroblasts. (x 128).

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Rheumatic fever

FIG. 3. An Aschoff node from the patient's myocardium; with some fibrinoid staining presentcentrally, but reduced cellular infiltration as a result of treatment. (x 128).

FIG. 4. Renal medulla showing the edge of the infarcted area: viable tubules on right, dilated vesselscentrally, necrotic tissue on left. (x 32).

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A clinico-pathological conferencesteroid therapy-nevertheless, it is clear that weare dealing with reactions of a similar type. It isnot difficult to find a number of lesions of thiskind scattered through the excessive fibrous tissuein this boy's myocardium and I think the con-clusion must be that in spite of treatment therewas still active rheumatic disease in progress in hisfinal illness, and that this was a major factor inhis death.Apart from the myocardial lesions, there is not

a great deal to show in other organs. In one of thesections of kidney there is a focus of pyramidalnecrosis (Fig. 4); although several kidney sectionswere examined, no other necrotic areas were found.In the lungs, as Dr Trott described, there was asevere degree of oedema and congestion, and thehistology confirms this; detailed examination alsoshows occasional necrotic foci surrounded byheavy inflammatory infiltration. It is tempting toregard these as a form of Aschoff body but theusual view is that Aschoff lesions are found onlyin the myocardium. Finally, there are quite fre-quent multinucleate giant cells in the alveoli, oftenassociated with fibrinoid exudate (Fig. 5). Thiscombination of findings: oedema, congestion,fibrinoid exudate and giant cells, constitute themain features of rheumatic pneumonitis, and con-firms further that the rheumatic process was themajor cause of his death.

R. KEMBALL-PRICE: Thank you, Dr Elliott.Now that we have had the clinical and patho-logical presentation of this interesting case, per-haps Dr Joseph would open the discussion.

M. C. JOSEPH: Dr Kemball-Price, Ladies andGentlemen. First of all I would like to thank DrMann and Dr Nash for inviting me down here tojoin you in this interesting clinico-pathologicaldiscussion and, secondly, I would like to thankDr Kemball-Price for the kind remarks he madeabout me.Could I perhaps at this stage just start with

something fundamental and go over some of thepoints in rheumatic fever from a clinical aspectwhich were first described and well documentedby Duckett Jones (1944), who, you may remember,made a long-term follow up study of 1000 patientswith rheumatic fever. He was the first to describewhat he considered to be the major and minorcriteria of the disease. Now he did this, not becausehe thought this was necessarily the whole truth,but because he felt that when people were des-cribing rheumatic fever it was as well to havesome sort of agreement on the criteria needed fora reasonably firm diagnosis. These criteria couldthen be used as a future basis for comparison withdifferent series. Duckett Jones (1944) divided boththe clinical and laboratory findings into major and

FIG. 5. Lung in rheumatic pneumonia, showing fibrinoid material and giant cells in two alveoli.(x320).

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Rheumatic' fever

minor groups (Table 1). He suggested that thepresence of one major plus two minor criteriamade the diagnosis of rheumatic fever highlylikely. Now, there have been some suggestedalterations to these criteria (Table 1) and one ofthese (and I would like to hear your views aboutit) was that a recurrence should be consideredminor (Royal College of Physicians, 1957), thoughsurely a recurrence should persuade us very hardthat we might be dealing with a second attack ofrheumatic fever. Another suggestion was thaterythema marginatum should be major.

TABLE 1Criteria for diagnosis of rheumatic fever

(based on Duckett Jones, 1944)

Major Minor

Arthralgia FeverCarditis Abdominal painRecurrences* Precordial painNodules EpistaxisChorea Pulmonary

manifestationsRashesLaboratory evidence(ESR, WBC, ASO)

Duckett Jones recommends one major and twominor criteria.

* Royal College of Physicians (1957) regards recurrencesas a minor criterion and considers that the presence of twomajor or one major and two minor criteria indicates a highpossibility of rheumatic fever.

Arthralgia describes the symptom of pain in ajoint without objective evidence of joint involve-ment. It is a difficult symptom to evaluate becauseit is so common in young children. In 1957 a Com-mittee of the Royal College of Physicians sug-gested that arthralgia be classified as a minorcriterion and arthritis as a major criterion. So, onthe whole, if one uses these criteria as a guide, Ithink one can indicate the diagnosis with morecertainty when two major criteria are present(Royal College of Physicians, 1957). But one isstill left in doubt without necropsy evidence of thereliability of these particular criteria. You can getnearer the diagnosis if a nodule is present whichcan be examined histologically, and I would liketo hear Dr Elliott's views about this.Now there is one particular combination which

is difficult and that is when you have a combina-tion of arthritis (major), fever (minor) and a raisedsedimentation rate (minor). On the basis ofDuckett Jones' criteria you would be correct indiagnosing rheumatic fever-but there are other

conditions which can simulate this, such asrheumatoid arthritis or disseminated lupus erythe-matosus, so that when you have this particularcombination the criteria are less reliable, but itseems reasonably good for everything else.

Next; let us discuss this particular child. Weknow that initially, I think when he was aged 4years, he had arthritis. That is correct isn't it?

F. W. NASH: I think his first illness was said tobe a chest infection followed by the carditis which,in retrospect, was diagnosed as rheumatic fever.

M. C. JOSEPH: He had this at the age of 4 years,didn't he?

F. W. NASH: Yes.

M. C. JOSEPH: A chest infection?

F. W. NASH: Yes. Now we haven't access to theoriginal notes, but there is no mention of arthritisin the summary of his first illness. But he did havearthritis, limited to one joint, in a second attackand also in his third attack. He also suffered a longillness which was investigated as subacute bacterialendocarditis, but it seems that his terminal illnesswas the only one in which more than one joint wasaffected.

M. C. JOSEPH: As regards the question ofarthritis, we know that it may be absent in rheu-matic fever and it is said to be less common inchildhood (Wood, 1956), but joint pain occurredin 90% of 457 initial attacks of rheumatic fever inpatients under the age of 17 years (Massell, 1958).On the basis of the pathological findings you

seem to have demonstrated the presence of therheumatic process very clearly, and we cannotargue about this, but one of the points of aclinico-pathological conference is to go back overthe clinical side and see where we might have gonewrong. I think we have here a good illustrationthat throughout the history this has not beentypical. The boy had undoubted carditis, but Ibelieve he did not have a raised ASO titre eachtime he showed activity. The ASO titre is almostalways over 400 units when you have other reason-able evidence of rheumatic fever, but there is nodoubt that with two or even three major featuresyou do sometimes find an ASO titre of 125 or less.Massell (1958) has stated that the titre was at least400 units in more than 90% of proven cases andthat less than 125 units was strong evidence againstrheumatic fever, especially if the illness was of lessthan 4 months' duration; he regarded 160-320units as borderline. This boy may have had a

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A clinico-pathological conference

sensitizing infection when he had a chest infection,yet he never showed this response in his blood.Going back and arguing against myself, could

this boy have had a non-streptococcal infection ofhis lungs at the age of 4 years unrelated to rheu-matic fever, and then when he was seen at the ageof 5 years the anatomical cardiac condition wasrecognized, but the mitral incompetence mighthave been congenital in origin? Well, I think with-out any more data it would have been a veryreasonable diagnosis and I believe he was goingto be investigated, wasn't he, at another hospitalfor his heart condition on the grounds that itmight not be rheumatic? I am not certain aboutthis. However, it seems that subsequently he hadarthritis; he had evidence of cardiac involvementand he had four attacks and this is where, I think,the criterion of recurrence is largely usefulalthough, of course, rheumatoid arthritis andlupus also characteristically recur. Abdominal painis a useful minor criterion and, I think, it remindsus that rheumatic fever sometimes masquerades asappendicitis; it is said that some patients havehad normal appendices removed and a few dayslater additional features have appeared whichmake the diagnosis of rheumatic fever evident. I,myself, have no experience of patients with pre-cordial pain, but presumably this is a reflection ofpericarditis. Epistaxis, when it does occur, is saidto be useful in diagnosis. I was interested to hearthat this child had pulmonary manifestationsproven histologically. On a clinical basis this isclassified as a minor criterion, but I think it isdifficult to establish whether the radiologicalchanges can be recognized during life as distinctiveof a rheumatic process. Rheumatic pneumonitis isa rare manifestation only occurring in 1-2% ofactive cases (Wood, 1956). Chorea speaks for itself,but about one-third of patients with chorea sub-sequently develop rheumatic heart disease (Ash,1948). The arthritis and arthralgia we have alreadyreferred to, but I would like to point out that it iseasy to talk about arthritis and arthralgia,although, when it comes to the actual child, hetells his mother that he has pain and she interpretsits site, but when you actually ask the child hepoints somewhere else. So that I think it is verydifficult to be certain on the history. Objectively,if you see the child at the time of the acute attack(more often you see the child a day or two afterwhen the 'arthritis' is subsiding), the joint is sopainful that if a lower limb joint is involved, thechild has to be off his feet and in bed. However,you do get intermediate grades of severity whichare a problem in diagnosis.

Carditis is next on our list. Both from a dis-ability and a killing point of view, as in this child,

this is the most important single aspect. Perhapswe could just talk about that for a few minutes.What do we mean by carditis? Perhaps a betterterm is 'cardiac involvement' (Table 2). Tachy-cardia is often mentioned, but is not evidence ofcarditis; it is part of the general disease process.So what are the real features that one looks for as

TABLE 2Cardiac involvement in 457 initial attacks of rheumatic

fever (exclusive of pure chorea), Massell (1958)Per cent

Mitral regurgitation 38Mitral and aortic regurgitation 12Aortic regurgitation alone 4Pericarditis 6Prolonged PR interval 25Cardiac failure 8

evidence of cardiac involvement? Firstly, mur-murs, which may be systolic or diastolic. Thesystolic murmur, which may be evidence of mitralincompetence (organic or functional), is pan-systolic. It occurs at the apex, is conducted intothe axilla, is blowing in character and at leastgrade two out of six in intensity. Then there aretwo types of diastolic murmur, one of which isrumbling, situated at the apex and resembles therumbling murmur of mitral stenosis. This is some-times called a Carey Coombe's murmur. Anothercategory of diastolic murmur is that of aorticregurgitation, commonly a quiet (grade 2-3 out of6) blowing murmur occurring immediately afterthe second sound along the left sternal border.Now either of these two diastolic murmurs is goodevidence of carditis. Because children so oftenhave systolic murmurs which are of no significanceit can be difficult to interpret a murmur. If it is anew one, or it changes during the course of theillness, then this may be worth-while evidence ofcardiac involvement, but you are still left with thedifficulty that anaemia may give rise to a systolicmurmur. Now, anaemia is common in childrenand it occurs also in rheumatic fever; it is par-ticularly likely to be present in those children of asocial class which is more likely to be subject torheumatic fever. Cardiac enlargement (not in-cluded by Massell) is another piece of evidenceand this may be detected on clinical grounds or,better still, radiologically, but it may be difficultto differentiate from pericardial effusion. Peri-carditis is further evidence of cardiac involvementand this may be in the form of a friction rub, orclinical and radiological evidence of an effusion,or electrocardiographic evidence of pericarditis.There is one more electrocardiographic change

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Rheumatic feverwhich is useful; that is a lengthening of the P-Rinterval. There are tables available which indicatethe percentiles at varying ages (McCammon,1961): borderline lengthening (less than the 90thpercentile) is only helpful if you know that it is anew finding.

In practice in the home one may be faced witha child who is a little off-colour, who has not'snapped out' of his sore throat in the usual wayand it is difficult to put your finger on anythingmore specific. I think it is this group of patientswhich needs to be more fully investigated, or havea period of observation in hospital in order tomake a more certain diagnosis.One more point I would just like to bring up

concerning this particular patient is to ask whywe failed here. How did we allow him to succumb?It seems that Dr Nash had the care of this childright at the end of a period after he had beenexposed to four attacks of rheumatic fever, eachone damaging his heart further. He was left witha heart with severe mitral incompetence whichfinally ended in cardiac failure with, in addition,pulmonary manifestations of the rheumatic pro-cess. One other point Dr Nash has already madeis this difficulty of being certain that the childtook his prophylactic penicillin. We are not certainabout that, are we?

F. W. NASH: We are certain that he did not getit regularly until he went away to school and thenhe did get it regularly.M. C. JOSEPH: Did he get an attack while he

was on regular prophylactic penicillin?F. W. NASH: No, except his last attack. During

this last illness he was still on oral penicillin. Theonly proviso I have to make is that we do notknow the details of what he had during schoolholidays. It is quite likely, I would have thought,that the parents had not kept it going during theholidays, but he was on prophylactic penicillinand he developed an illness with a sore throatwhilst he was still on it.

M. C. JOSEPH: I think this is a very importantpoint. It seems that he was not taking penicillinall the time or, perhaps, adequate blood levels werenot achieved. It must be very rare for the organismto be insensitive to penicillin and perhaps DrElliott will tell us about this.

R. I. K. ELLIOTT: It is so rare that I would preferto say that he was not taking it.

F. W. NASH: Well, he was taking it all right. Ihave no doubt about that.

R. I. K. ELLIOTT: Then perhaps he was not takingsufficient.

F. W. NASH: This is possible. I mean, no onebelieves, I am sure, that oral penicillin preventsevery invasion with the haemolytic streptococcus,it simply reduces the likelihood, doesn't it? If youexamine control studies you find that the incidenceof infection and of relapses of rheumatic fever ismuch lower in the treated group than in the un-treated group.

M. C. JOSEPH: This is a very good point, isn'tit? You just do better, but do not achieve completeprophylaxis. I suppose this might be one example.However, I would like to hear other people'sviews about this.

R. KEMBALL-PRICE: May I thank all thespeakers so far, especially Dr Joseph for his mostinteresting comments on rheumatic fever and dis-cussion of this particular patient.And now Dr Trevor Mann has a contribution to

make; he is going to say something about thedifferential diagnosis of rheumatic fever.

TREVOR P. MANN: To overlook rheumatic feverin a child may have life-long repercussions for thatindividual; to misdiagnose the condition may alsohave serious and long-lasting effects on the childand perhaps on his family. The assessment of achild with possible rheumatic fever is, therefore, amost responsible task for the physician and thereare no specific laboratory tests to assist one.Fortunately its recognition in childhood is, in themajority of instances, relatively straight-forwardespecially if one bears in mind the major andminor criteria which we have just heard aboutfrom Dr Joseph.

If one was writing about the differential diag-nosis of rheumatic fever in Finals, or let us saythe Membership examination, one would certainlyconsider acute leukaemia, rheumatoid arthritis(Still's Disease), anaphylactoid purpura (Henoch-Schonlein syndrome), and acute osteomyelitis withor without joint involvement, all of which canmimic rheumatic fever quite closely, especiallyearly in the illness. Some reference would alsohave to be made to rarer disorders such as dis-seminated lupus erythematosus, subacute bacterialendocarditis, brucellosis and, in coloured children,to sickle cell anaemia, which in the African is agreat imitator rather as syphilis used to be whenit was prevalent. A few years ago one would havegiven poliomyelitis some prominence in the differ-ential diagnosis and even today this conditionmust be considered in countries where the infec-tion remains endemic.

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A clinico-pathological conference

There are atypical ways in which rheumaticfever may present which, at times, may makethings difficult for the physician or even thesurgeon! Thus, as Dr Joseph has reminded us,abdominal pain may be an early and impressivesymptom, so much so that the child may find hisway into a surgical ward as a possible 'acuteabdomen'.

I am going to confine my remarks on differentialdiagnosis to the first group of disorders because inall of these pain in and around joints may be anearly and impressive feature. I shall conclude bymentioning one other disorder of a non-specificnature which may confuse the diagnostician.Acute leukaemia may present with joint pains

and, as I shall illustrate shortly, these, at times,may be migratory and simulate very closely thearthralgia of rheumatic fever. There may beassociated fever to add to the clinician's difficul-ties with diagnosis. When leukaemia starts in thisway there may be no initial anaemia or thrombo-cytopenia and so pallor and bruising, which aresuch constant presenting features in the ordinaryrun of cases, may be absent. Here, now, is a briefaccount of the early illness in a child with acutelymphatic leukaemia with osseous involvementwhere for obvious reasons rheumatic fever,glandular fever and Still's disease were all con-sidered in turn as the clinical picture unfurled.

Case reportA.A. Female. Aged 9 years. Illness began with sore

throat, enlarged neck glands and abdominal pain. Sheresponded to a course of tetracycline and returned to schoolafter 4 days.

Three days later recurrence of fever (101°F). Complainedof pain in hips, knees, shoulders, elbows and wrists. Painflitted from one joint to another and lasted several hours ineach joint; never more than two were affected at once.General Practitioner at first suspected rheumatic fever andprescribed aspirin and penicillin. No response and followingday neck pain was experienced. Marked hepato-spleno-megaly noted at this stage. Blood count: Haemoglobin92%. White cells 16,000/mm3-atypical mononuclear cells6%. Paul Bunnell screening test positive; full test negative.Antistreptolysin O titre 123 units.

Comment. In this child hepato-splenomegaly was astriking early finding and pointed to a diagnosis other thanrheumatic fever. However, such gross changes in thelymphatic system are unusual in children with acuteleukaemia presenting with skeletal involvement. Note themisleadingly high haemoglobin value, a not uncommoninitial finding in cases of this kind.

Turning now to Still's disease, this disordermay come to our notice in two contrasting ways.A child may simply complain of pain and swellingin one joint, often the knee. There may be noassociated ill health or fever. These youngstersnot infrequently find their way to an OrthopaedicClinic, sometimes with a tentative diagnosis oftuberculous arthritis, a rare disorder nowadays in

this country. In contradistinction, Still's diseasemay present as an acute febrile illness withmultiple joint involvement and the clinical picture,initially, can resemble rheumatic fever, especiallyif there should be changing heart murmurs. It isworth bearing in mind that rheumatic fever isexceedingly unusual under 5 years of age whereas'rheumatoid', especially the acute form, quitecommonly affects the pre-school child and mayoccur in early infancy. In Still's disease, especiallythe acute febrile form, the small joints of thefingers and toes, both proximal and distal, maybecome swollen and painful, an infrequent hap-pening in rheumatic fever. One must rememberthat unusual joints may be affected in rheumatoidarthritis, such as those of the cervical spine leadingto pain and stiffness in the neck. Again, one orother temporo-mandibular joints may be involvedproducing discomfort and limitation of movementon opening the mouth. In Still's disease there mayalso be changes in the lymphatic system (especiallyin young patients) with localized or generalizedlymphadenopathy. The spleen, too, may be en-larged at the same time. The pericardium is some-times affected and a friction sound may then beheard perhaps accompanied by a complaint ofretro-sternal pain which can at times be severe.Pericarditis can occur, too, in rheumatic fever.Although endocarditis does not occur in 'rheuma-toid' cases, systolic murmurs may yet be heard,even changing ones. These variable bruits may berelated to anaemia and tachycardia. On the labora-tory side the total white count is generally low in'rheumatoid' whereas in rheumatic fever an initialpolymorpho-leucocytosis is usual although by nomeans constant. The anti-streptolysin O titre maybe of some help in differentiating these two dis-orders, an elevated and often rising value beingfound in rheumatic fever but not in Still's disease.Incidentally, it is unusual in 'rheumatoid' to obtaina history of a preceding sore throat but this is afairly constant finding in rheumatic fever, thelatent period between the onset of infection andthe appearance of rheumatic symptoms being 1-6weeks. Finally, the response to salicylates inadequate dosage may prove helpful. In rheumaticfever the effect on the joint picture and fever isimmediate (24-48 hr) and dramatic whereas inStill's disease there may be some relief of pain butthe response is not striking and remittent feveroften continues.

Anaphylactoid purpura may manifest itself inseveral ways and when joint symptoms are a pro-minent early feature rheumatic fever may besimulated. In this condition there is often a historyof a preceding infection, even a sore throat. Thejoints most frequently affected are the knees and

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ankles, sometimes the wrists. Swelling, tendernessand loss of joint mobility may occur. However,local heat is unusual and the pains are not migra-tory in character. In cases presenting with jointinvolvement diagnosis may be straightforwardwhen there are, in addition, other suggestive fea-tures such as colicky abdominal pain, perhapsassociated with the passage of blood in the stools,or the characteristic haemorrhagic skin lesionsdistributed about the elbows, buttocks, knees,ankles and feet. One should remember that theeruption of anaphylactoid purpura may beurticarial or erythematous at first although theindividual lesions soon become purpuric andoccasionally necrotic. Sometimes the tell-tale rashis late in appearing and the differential diagnosismay at first be wide in a child with the Henoch-Schonlein syndrome and include not only rheu-matic fever but also rheumatoid arthritis, intus-susception and even acute glomerulo-nephritis,depending on the initial pattern of symptoms andclinical manifestations. Perhaps the most difficultcondition at times to differentiate from rheumaticfever is acute osteomyelitis, especially in the earlystages of the illness. I can best illustrate this pointby giving two case reports.

Case reportsC.J.A. Male. Aged 11 years. Admitted with 3-day

history of chills, anorexia, vomiting and swelling and heatof both knees. No recent sore throat although very sus-ceptible to tonsillitis. Had received several doses of aspirinbefore admission.

Examination. Temperature 105°F. Pulse 130. Tonsilsenlarged with white exudate on both sides. Cardio-vascularsystem normal. Presumed subcutaneous nodule left elbow.Vague tenderness both shoulder joints; no swelling orredness. Hips tender on palpation. Both knees tender,swollen and hot; no erythema.

Shortly before admission several epistaxes. Haemoglobin75 %. White cells 4000/mm3-polymorphs 85 %. CorrectedESR 22 mm/hr.An initial diagnosis of rheumatic fever was made and the

child started on aspirin grains 20, 4-hourly and prophylacticpenicillin V, 125 mg b.d. orally. The temperature fell tonormal, by crisis, within 48 hr, but the boy remained ill.A red, tender swollen area then appeared over the medialaspect of the upper end of the left tibia. The diagnosis wasthen revised to acute osteomyelitis and a sub-periostealabscess was drained from which staphylococcus pyogeneswas isolated.

Comment. The apparent response to salicylates was dueto temporary suppression of fever by oral penicillin. Intreating rheumatic fever prophylactic penicillin should on noaccount be started until the response to salicylates has beenadequately assessed. The initial white cell count in this boywas misleadingly low for acute osteomyelitis and rheumaticfever alike. A temperature as high as 105°F is unusual inrheumatic fever.

M.H. Male. Aged 6 years. Six days before admissionfebrile head cold with associated cough. Three days later,having returned to school, became febrile again and com-plained of pain in the left knee. Following day, temperature

101°F. Left knee hot and painful. Aspirin and penicillinprescribed by General Practitioner. Forty-eight hours laterdeveloped painful right ankle; left knee more painful. Atthis stage referred to hospital. Family history of rheumaticfever.

Examination (on admission). Temperature 101°F. Pulse120. Left knee warm; no active movements and all passivemovements limited by pain and muscle spasm. No rednessor swelling at this joint. Small clean cut lower part of knee.Tender erythematous area over lower part of right fibula.Grade 2/6 ejection murmur at apex. Haemoglobin 83 %.White cells 14,200/mm3-polymorphs 88 %. CorrectedESR 27 mm/hr. Antistreptolysin O titre 388 units.The differential diagnosis was between rheumatic fever

and acute osteomyelitis. The boy was treated initially withlarge doses of aspirin. After 48 hr the temperature hadsettled but the left knee remained hot and painful. In orderto exclude an osteomyelitis of the upper end of the left tibiathe area was explored with negative findings. However,swabs taken from the wound subsequently grew staphylo-coccus pyogenes (the admission blood culture was negative)and a course of erythromycin was started. His anti-strepto-lysin O titre fell to 50 units 8 days after admission. Severalweeks later X-ray changes consistent with a healing osteo-myelitis in the upper third of the left tibia and the lower endof the shaft of the right fibula.

Comment. The first antistreptolysin O titre was marginallyraised. The fall to 50 units in just over a week was very muchagainst a rheumatic aetiology.The last thing I want to mention, because it

tends to get left out of the textbooks, is that it canbe quite difficult to differentiate rheumatic feverfrom vague febrile myalgias which are probablycaused by non-specific virus infections. I haveseen two children at home recently with fever anda history of joint pains who had responded to fulldoses of aspirin by the time I examined them. Inone case there was a family history of rheumaticfever and this child had quite an impressivesystolic murmur which I now regard as innocent.The only thing to do in the absence of continuingrheumatic manifestations, especially signs of activecarditis, is to stop the salicylates, and with thechild in bed to watch his behaviour and tempera-ture chart. If fever and joint pains do not recurwithin a few days of stopping treatment then theyoung patient can be mobilized. At this stage itwould be wise to check the sedimentation rate anddetermine the anti-streptolysin O titre before con-tinuing with convalescence.

Perhaps the doctors who were looking after thetwo patients I have just mentioned would like tosay something. Dr Hartsilver?

J. HARTSILVER: Well, I was called to see a girlof 11 years, about 2 weeks ago, with a complaintof sickness and abdominal pain and, on enquiry, Ifound the child had had some liver sausage andI made a provisional diagnosis of food poisoning.I felt the child's abdomen, because sometimes onemay be caught out with an acute abdomen in thatway, and felt nothing abnormal so I put the child

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on a sulphadimidine mixture because there hadbeen a few cases in my practice of food poisoning.But just before I went out of the house I was toldthat the child had had a sore throat and had goneswimming with the school and, subsequently, hadpains flitting from one joint to another. I havealways regarded pain in joints changing over likethat as very strongly suspicious of rheumatic fever,so I revised my ideas at once and said the childhad better keep to bed and also put her onpenicillin and aspirin which is not the correct thingto do, but I thought so at the time. Now, sub-sequently the temperature came down: I forgot tomention the temperature was 101-102°F. The jointpains disappeared completely; there was no fur-ther nausea and the child seemed perfectly well,but because of the joint pains flitting from onejoint to another I still felt unhappy. I felt all overfor nodules and listened to the heart for changingheart sounds which is another important sign ofrheumatic fever. Also, this child twitched a littleat the mouth, but I happened to remember thatwe had had that twitch before, for she was anervous child, and the mother corroborated thatshe was not making any purposeless movementssuggestive of chorea. Well then, the question aroseas to whether the child, although she seemed well,should be regarded as having rheumatic fever ornot and I felt influenced in favour of rheumaticfever when I heard that another boy in the class atschool the child attended had tonsillitis.

I informed the School Medical Officer accord-ing to the Ministry of Health brochure (thebrochure that has just appeared on RheumaticFever), in which it is advised that where there isany shadow of a doubt, the Principal SchoolMedical Officer should be informed with a viewto swabbing throats; though I think it was notdone in this case. In future I shall take a cultureevery time to see if there is a haemolytic strepto-coccus. Because of the doubt about the diagnosisI asked Dr Mann if he would be good enough tocome and see my patient, and he very kindlysuggested that the child should be regarded withsuspicion and be kept under observation. At thepresent time-2 weeks later-there are no signs ofrheumatic fever, no heart signs and no nodules;but the question is whether that child should bekept in bed longer or allowed to go about in thenormal way. Well now, I think the thing to do isto keep her under observation and gradually gether up. Dr Mann suggested that the penicillin andsalicylates should be left off and that he would beinterested to know whether any signs of rheumaticfever have recurred. Well, there have been no jointpains and what I propose is that this patient beseen periodically; the mother will certainly let me

know if there is any malaise of any sort whichmight lead one to suspect a recurrence.

T. P. MANN: Perhaps I could just say that thischild had been on penicillin and Disprin for 5days when I saw her. I am interested to hear that4 days later, when off this treatment, there hasbeen no recurrence of arthralgia. The pains werein both wrists, left elbow, shoulders and knees-quite a disseminated affection of joints. I think theother thing we should consider, just to add to whatDr Hartsilver has said, is to do a full white count,ESR and an ASO titre within the next 48 hr. Ifthe ASO titre is, say, 800 units or something ofthat order, then it would be very much in favourof this being rheumatic fever. The other case wasone I saw with Dr Alexander of Newhaven, an8-year-old child. I don't know whether he wouldlike to say something about that one? Well, thischild had been poorly for 4 days when I first sawher; she had become mopey, listless and developedpains in her knees, shins and feet. She was put tobed, examined by Dr Barton (Dr Alexander'spartner), and was found to have a temperature of103 F. There were no other abnormal signs exceptthat she complained of pains in her elbows andwrists. There was a possible scarlatiniform rashabout the ankles, so he put her on aspirin,gr. 10 t.d.s., and there was great improvementwithin 24 hr. I saw her 4 days later, after she hadbeen on salicylates, and there were no abnormalsigns. I should mention that there had been avague history of sore throat 2 weeks previously.With this child, too, there was the remains of arash over the left ankle which I thought at firstwas purpuric and I wondered about anaphylactoidpurpura, but we looked at this very carefully andI don't think it really was purpuric. By the time Isaw the girl it really was not possible to make afirm diagnosis and, as the child had been onsalicylates for 4 days, I suggested stopping thetreatment and seeing what happened. That was 8days ago and perhaps Dr Alexander could tell uswhat has happened in the meantime.

R. ALEXANDER: We are waiting for an ASOtitre.

T. P. MANN: Is the ESR raised?

R. ALEXANDER: It has not come through yet.T. P. MANN: Is the child better?

R. ALEXANDER: Quite.

T. P. MANN: Could I, perhaps, ask Dr Josephwhat he makes of this type of case? Do you see

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Rheumatic feverthese children; because I am quite sure thatgeneral practictioners see them and we, too, see theodd one with this sort of syndrome-fever, jointpains, limb pains and response to aspirin.M. C. JOSEPH: Yes, I indicated earlier that I

think this is a very difficult situation and I don'tconsider it too diffuse to say that if there is clinicalsuspicion of rheumatic fever one should investigatefurther as you have here. There is bound to be agroup of patients who, on clinical grounds, youhave doubts about but have not got enoughweighty evidence to say 'this is rheumatic fever',and I think that it is this group that needs, as Imentioned, further laboratory and perhaps electro-cardiographic and radiological investigation. Youwill obviously say 'we can't do that on everypatient who has a bit of pain in or near a joint',and I would just say: 'Well, if you clinicallysuspect rheumatic fever you should'. But if onedoesn't clinically suspect the disease and if one issatisfied on the basis of the clinical findings, thenthere is no need to investigate further.The really difficult situation is when you are in

the country and you may be 50 miles away fromlaboratory help; but it is, I think, this very groupthat needs this extra help.Could I just make one or two comments about

some of the discussion earlier on? Dr Mann men-tioned two points-one was about the response ofrheumatoid arthritis versus rheumatic fever tosalicylates. I get the impression that it is the feverthat responds in both, but not the arthritis ofrheumatoid, though it is still the fever thatresponds. I am making this point because I thinkit is sometimes misunderstood and said ratherloosely that if you give salicylates and the patientresponds, or the symptoms improve, then it ismore likely to be rheumatic fever than rheumatoidarthritis. It should be made clear that in bothconditions the fever responds, but in rheumaticfever the fever and the joint involvement respond,whereas in rheumatoid arthritis or in lupuserythematosus the joints do not improve dramatic-ally within the first 24 hr; I mean you certainlyalleviate the pain to a certain extent, but it is notthe really striking response as in rheumatic fever.The other point is the question of the family

history; I do agree about this and I should haveput it in. It has, I believe, been recommendedrecently that this is a genuine minor criterionbecause it is very useful; a fact well brought outin this particular child, wasn't it, whose sister,now aged 13, has had what seems to be typicalrheumatic fever. This is really a soil as well as aseed disease; you have to have the streptococciaround, but you also have to have a type of patientwho is susceptible.

Another matter I just wonder about in DrMann's very interesting case of osteomyelitis,which is an important differential diagnosis, ishow long it took for the temperature to drop. Wasit a sudden fall?-because usually osteomyelitistakes 2-3 days for the temperature to respond andI think sometimes this is a useful point in thedifferential diagnosis, though one must admit it isusually a differentional diagnosis in retrospect.

T. P. MANN: Well, to answer the last questionfirst-the temperature came down by crisis from104 to 96°F in a matter of just over 24 hr-a verydramatic response. It stayed down for 48 hr andthen spiked up to about 101 °F.

This point about Still's disease-I would saythere are some children with Still's disease, par-ticularly younger ones, with a very fulminatingpicture with a septic sort of temperature chart and,if you put them on full doses of salicylates, Iwould say that the joints won't respond very much-they may have less pain, but I think the physicalsigns will be just as apparent 48 hr later and Ithink that in this group the temperature may comedown, but the joints very often are quite un-influenced by salicylates and even by steroids. Ifyou give them steroids after a week or so if theyare doing badly quite a few of them do notrespond dramatically even to the right sort oftreatment.

R. KEMBALL-PRICE: Time is getting on andmost of you have not had any opportunity ofspeaking yet so it is open for free discussion nowif anyone else would like to speak.

L. B. PETERS: Perhaps I should mention thatthe tonsils of this child were twice as large asnormal. Now I know that tonsillectomy medicallyis rather inclined to be a dirty word these days,but I often wonder whether in the case ofrheumatic disease if you remove the tonsils youmay prevent secondary cardiac complications. CanI ask if there was anything pathological in thesetonsils at post-mortem and whether Dr Josephfeels that this has any significance?M. C. JOSEPH: Can I be outspoken about size

and say that I do not know what 'normal' is interms of size of the tonsils. By this I mean that ifyou look at 500 normal children, say aged 5-7years, I am sure you will find that the tonsils areanything from tiny little peas to huge giants, aren'tthey? Would you agree with that? And, therefore,I don't want to use the term 'enlarged' as beingpathological just because I don't think I can tell.There is also some evidence that you and I any-how are hopeless at saying what size the tonsils

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A clinico-pathological conferenceare; an E.N.T. surgeon and his colleague gottogether and said: 'Let us say what size thesetonsils are prior to operation', and when theanaesthetist had anaesthetized, they all graded thetonsils. After enucleation the tonsils were weighedand there was a complete lack of correlation withwhat had been forecast. In other words, I wouldlike to suggest that size perhaps is less importantthan whether the tonsils look unhealthy, arefibrosed or have exudate on them and whetherthere is adenitis (by which I mean palpable tenderglands bigger than you would expect). PersonallyI find it very difficult to evaluate diseased tonsilsin the way that I have mentioned and if I was inany doubt I would ask my E.N.T. colleague whathe thought about them. But there is a suggestionthat if you remove the tonsils you have merelyremoved only one source of infection; that it ispossible to get pharyngitis instead of tonsillitis. Ibelieve that at this very moment the College ofGeneral Practitioners has a large research projecton in which they are trying to assess which groupof patients is benefitted by tonsillectomy. One isvery confused really as to the good or harm onedoes in advising parents to have a child's tonsilsremoved. I don't honestly know the answer to yourspecific point, Dr Peters. It might have done aworld of good in this particular patient if we couldbe reasonably certain that the tonsils were diseasedand a source of endogenous streptococcal infec-tion, but one would have hoped that the penicillinmight have eradicated this. I entirely agree withyou. It is a very good point to have brought upand one which we have not talked about so far-as to whether indeed these tonsils, as a source ofinfection and no longer protecting the patient,might have been better out of the way.R. KEMBALL-PRICE: Would anyone else like to

say something? Dr Elliott?R. I. K. ELLIOTT: Yes, just one point-a thing

which came up when I was doing something quitedifferent. I went through a series of post-mortemscarried out at the Royal Sussex County Hospitalover the last 50 years (up to 1956), and the thingwhich struck me was the change in the pattern ofcardiac deaths. Over the 50-year period, deathsdue to coronary heart disease showed a strikingincrease, whereas deaths due to rheumatic heartdisease showed a numerically similar decrease;and, what is more, at the beginning of this periodall the cases who were dying of rheumatic heartdisease were young patients aged 20-30 years withsevere, active carditis; but the patients who havedied in recent years who came under this headingwere all in the late stages of chronic valvulardisease-in other words it does seem that over the

last 50 years the incidence in severity of activerheumatic carditis has decreased very consider-ably. I wonder whether Dr Joseph would like tocomment on this point which ties in with what hewas saying about the social background.M. C. JOSEPH: One of the things that strikes one

is that it is said that the incidence of rheumaticfever is declining, but talking to Dr Mann andDr Nash over the past 3-4 years (and I am sureour colleagues will substantiate this), there seemto have been quite a few patients-anyhow in thisarea-who have had rheumatic fever. We alsohave had an increase, not during the last 3 monthsbut prior to that, either with rheumatic manifesta-tions, chorea or rheumatic fever, although I believethere is some evidence that acute carditis duringthe active rheumatic process is probably less thanit used to be.R. KEMBALL-PRICE: I was very interested in the

slide that Dr Elliott showed of the active myo-carditis because I think with the obvious signs ofold endocarditis people are sometimes apt toforget the permanent damage that may be doneto the myocardinm; and we see cases which, aftersuccessful mitral valvotomy, rapidly go intofailure. There seems little doubt that this is dueto the state of the myocardium which has beendamaged by chronic disease from the rheumaticprocess.Now I wonder if anybody else would like to

comment?

QUESTIONER: This child had steroids in thesecond illness, I believe. How long did the childhave them and do you think that if they had beencontinued the outlook would have been anybetter?

F. W. NASH: If my memory serves me right, Ithink he had steroids over a period of about 6-8weeks. This was at the Evelina Hospital (Guy's)and they noted that towards the end of this periodof treatment he was getting mooned and his heartwas enlarging fairly rapidly. Because of this theydecided not to go on with steroids. In any eventit is not now generally accepted policy to continueindefinitely with steroids because of the hazardsof the treatment itself; one feels that if therheumatic process has become inactive as far asone can tell by ordinary clinical and laboratoryinvestigations, then there is really no object incontinuing with steroid therapy in what is believedto be a hypersensitivity phenomenon; but there is,of course, some advantage to be gained by long-term penicillin prophylaxis to try to prevent in-fection with haemolytic streptococci. Would youagree with these general comments, Dr Joseph?

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480 Rheumatic feverM. C. JOSEPH: Yes, certainly. I don't quite

know what the cardiac enlargement was due to-whether it was heart failure or continuation ofrheumatic activity or both; one just cannot tell.The rationale of using steroids is really because

fundamentally they suppress the inflammatoryprocess and in particular prevent the sequelae. Inactual fact, I think it is very well documentedthat if you have two groups of patients and yougive steroids to one and not to the other the signsof carditis diminish much more rapidly in thegroup treated with steroids so that they do seemto have an important anti-inflammatory effect. Theuse of steroids is also considered of special im-portance in the prevention of fibrosis and its end-results, and this is why there is all this argumentstill as to whether steroids should be given toevery patient with rheumatic fever or only tothose who have, as far as one can tell, evidence ofcarditis. There are some people who say everypatient who has rheumatic fever also has carditisbut that you and I cannot always detect it, but Idon't know how we prove this point without post-mortem evidence.

R. KEMBALL-PRICE: I think it might be relevanthere to mention the differentiation of pericardialeffusion and heart failure in the course of rheu-matic fever because they have certain points ofsimilarity. In both you have cardiac enlargementon X-ray and you may also have engorged neckveins and an enlarged liver, but the prognosis ofheart failure in the course of rheumatic fever isfar worse than that of pericardial effusion. About10 years ago Gerald Thomas (1954) as a result ofhis experience at Taplow, laid down certain pointsof differentiation, and there were ten that he men-tioned. First was the time of onset, in thatpericarditis and effusion tend to occur early inthe attack whereas heart failure tends to comelate. The temperature is practically always raisedwith pericarditis and is often normal in the state

of heart failure. The sedimentation rate is alwaysup with pericarditis and may be normal at thetime when heart failure develops; the same is trueof leucocytosis. Oedema and ascites are bothcommon in heart failure but are not seen withpericardial effusion. In addition, a pleural effusionis common with a pericardial effusion and it is rarein heart failure. And then again in pericarditis arapid change in the heart size on X-ray is in favourof fluid coming and going rather than the cardiacsize changing. Furthermore, the hilar congestionof pulmonary oedema is common in heart failurebut is not commonly seen with pericardial effusion.Finally, we find that heart failure tends to respondto digitalis whereas a pericardial effusion is un-affected by this treatment.Well now would anybody else like to speak?

Perhaps as it is getting late we ought to end ourproceedings, but before doing so I should like tothank all the speakers, particularly Dr Joseph whohas made such a useful contribution to our know-ledge about rheumatic fever. Thank you, DrJoseph.

AcknowledgmentWe are grateful to the Nestle Company who financed the

Clinico-pathological Conference.

ReferencesASH, R. (1948) The first ten years of rheumatic infection in

childhood. Amer. Heart J. 36, 89.JoNES, T. DUCKETT (1944) The diagnosis of rheumatic fever.

J. Amer. med. Ass. 126, 481.MCCAMMON, R.W. (1961) A longitudinal study of electro-

cardiographic intervals in healthy children. Acta paediat.(Uppsala), 50, Suppl. 126, 313.

MASSELL, B.F. (1958) The diagnosis and treatment ofrheumatic fever and rheumatic carditis. Med. Clin. N.Amer. Sept. 1958, p. 1343.

ROYAL COLLEGE OF PHYSICIANS, Report of Rheumatic FeverCommittee, July 1957.

THOMAS, G. (1954) Heart failure in children with activerheumatic carditis. Brit. med. J. ii, 250.

WOOD, P. (1956) Diseases of the Heart and Circulation, 2ndedn. Eyre & Spottiswoode, London.