THE DIFFERENTIAL DIAGNOSIS OF RHEUMATIC FEVERBY

K. A. HALLIDIE-SMITH and E. G. L. BYWATERSFrom the Rheumatism Research Unit (Medical Research Council), Canadian Red Cross Memorial Hospital, Taplow

(RECEIVED FOR PUBLICATION JANUARY 29, 1958)

Since the efficacy of continuous daily sulphona-mide or penicillin administration in the preventionof attacks of rheumatic fever has now been estab-lished, and the measure recommended not onlynationally but by international committees (WorldHealth Organization, 1957), it has become increas-ingly important to recognize even mild cases ofrheumatic fever. At the same time it is equallyessential to avoid diagnosing this erroneously, sincethe resulting continuous daily prophylaxis isundesirable from the point of view both of thepatient and of the tax-payer. We thought thereforethat an account of our observations at this NationalCentre for Juvenile Rheumatism over the last nineyears would be useful, since over this period therehas accumulated considerable experience not onlyof rheumatic fever, but also of many conditionswhich masquerade as such.Out of such prolonged experience at the House of

the Good Samaritan in Boston, Duckett Jones (1944)was able to formulate a set of diagnostic criteriawhich have proved extremely useful in a modifiedform (Rheumatic Fever Committee Joint Report,1955) for ensuring in a large therapeutic trial thatcases from many different centres were of the samegeneral type. He realized that cases of other diseaseswere as far as possible to be ruled out. It was realizedfurther that many cases of genuine rheumatic fever,if first observed late in the course of the disease, orif mild, could not be fitted in and would have to becalled 'probable rheumatic fever'. Furthermore,some of the criteria depend upon continuous clinicalobservation or laboratory tests usually possible inhospital, but only comparatively rarely made in thiscountry in the average general practice. In this centrethen, a discharge diagnosis of rheumatic fever hasbeen made on unformulated but rather wider groundsthan those of the Duckett Jones criteria, so that of2,214 patients admitted to the unit over the nine-yearperiod, 959 were discharged with the diagnosis ofrheumatic fever. Nearly two thirds of these satisfieddiagnostic criteria comparable to those of Duckett

Jones, save that chorea was excluded as a majorcriterion and past rheumatic fever as a minorcriterion. In addition, 42 cases were discharged witha diagnosis of 'possible rheumatic fever' and 202 witha diagnosis of Still's disease, the remaining 1,011cases being various other miscellaneous disorders.

Group A. Erroneous Initial Diagnoses in RheumaticFever Cases

A one-in-six sample of these patients ultimatelydiagnosed as rheumatic fever was taken, consistingof those with surnames beginning with the initialsA, B and C admitted between July, 1947, and June,1956. In this group of 160 rheumatic fever patients,12 were found definitely to have been initially other-wise diagnosed, though subsequently all satisfiedDuckett Jones' criteria for the diagnosis of rheumaticfever. All were children between the ages of 6 and12 years, apart from the patient initially thought tohave sub-acute bacterial endocarditis, and only inthat patient and the child thought to be a case ofStill's disease was the ultimate diagnosis not madebefore transfer here. All patients have been regularlyfollowed up since discharge, for periods between18 months and seven years.

Poliomyelitis. These two children complained of feverand limb pains and one had neck stiffness. Normalcerebrospinal fluid was found and in both significantheart murmurs became audible subsequently.

Pneumonia. This 9-year-old girl gave a history ofgeneral malaise and limb pains. On admission to thereferring hospital, she was febrile and was found to haveimpaired percussion note and crepitations in the rightmid-zone. Following subsidence of the chest signs shedeveloped significant heart murmurs, and later rheumaticnodules.

Meningitis. This child had a sore throat followed bylimb pain and headache. Normal cerebrospinal fluid wasobtained and she subsequently developed polyarthritisand heart block.

Rubella. This 7-year-old girl had a sudden onset ofabdominal pain and a rubella-like rash. There was, how-

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ever, a normal white count and no accompanyinglymphadenopathy; she subsequently developed peri-carditis and endocarditis.

Dysentery. This girl complained of abdominal pain,diarrhoea and limb pains. Stool culture was negative.She complained of limb pains after the diarrhoea settledand an organic mitral pansystolic murmur developed.

Subacute Bacterial Endocarditis. This young adultfemale with known rheumatic heart disease gave a five-dayhistory of general malaise, generalized aches and painsand fever. She subsequently developed polyarthritis anda raised antistreptolysin-0 titre; repeated blood cultureswere negative and there were no embolic manifestations.She responded to bed rest and salicylates.

Appendicitis. These two children both complained ofabdominal pain. Normal appendices were removed, butthey both subsequently developed polyarthritis andorganic heart murmurs.

Suppurative Arthritis of Hip. This 9-year-old boy hada four weeks' history of pain in one hip with inguinaladenitis and fever. He subsequently developed poly-arthritis and a mitral pansystolic murmur.

Still's Disease. This boy presented with a three months'history of polyarthritis, fever, rash and general malaise.It was not until after 10 weeks in this hospital that hedeveloped heart lesions, by which time the arthritis hadsettled leaving no residua.

Fallen Arches. This 6-year-old boy had complained ofpain in his feet for four weeks and had been treated withremedial exercises. He developed polyarthritis, and had araised E.S.R. and A.S.O. titre.

Group B. Unsubstantiated Admission Diagnosis ofRheumatic Fever

This group consisted of all patients admittedbetween July, 1947, and October 31, 1956, with thepresumed diagnosis of rheumatic fever, but in whomthis diagnosis was not substantiated. Only thosewere included in whom there was fairly certainevidence from the referring letter or history on entrythat they were thought to have rheumatic fever; theynumbered 196.These 196 admissions consisted of 171 children

under the age of 17 years, and 25 adults. Follow-uphas varied from none in a small minority to severalyears in some instances. There has been no evidentrheumatic activity at these check-ups, and no patienthas developed organic heart disease under out-patient observation. None of the patients either onlong or short term follow-up has been re-admittedwith rheumatic fever. They may be divided into sevenbroad groups which can be further subdivided asshown in Table 1. The various groups will now beconsidered in more detail:

TABLE 1

FINAL DIAGNOSIS OF 196 CASES REFERRED AS RHEU-MATIC FEVER IN WHOM THIS DIAGNOSIS WAS NOT

CONFIRMEDFunctional (8):

Physiological tachycardiaHysteria.Neurosis and depression

Traumatic and Postural (11):SprainsSlipped femoral epiphysisTorn cartilage, osteochondritis dissecans, chest deformity and

back ache-1 eachInfections (91):Upper respiratory tractLower respiratory tractBone andl jointBlood strlamrUsinary -actPericarditisSpecific fevers

Connective rissue Disorders (42):Still's and rheumatoid arthritisSchonlein-Henoch purpuraErythema nodosumVisceral Itipus erythematosusPeriarteritis nodosum.Penicillin sensitivityGranuloma annulare

Rheumatic and Congenital Heart Disease (9):CongenitalRheumatic

Blood Dyscrasias (2):Iron deficiency anaemiaAleukaemic stem-celled leukaemia

Others (33):Arthritis.ArthralgiaLimb painsFeverGout and syphilis

Total

332

52

4

45101044216

24852

5915

3

1

19

I. Functional. This group comprised six childrenand two young adults. The three patients withphysiological tachycardia were all children. The firsthad a history of recent sore throat and the referringdoctor thought he had detected clinical signs ofcardiac enlargement with persistent tachycardia.The second child had complained of limb pains forsix weeks and was noted to have an evening tempera-ture up to 98 8°F. and persistent tachycardia of130-140 per minute. The third child had a recenthistory of cold and cough with persistent tachycardia.Nothing abnormal could be found in any of thesepatients, and, although the pulse rate was elevatedby day, the sleeping pulse was within the normalrange (Nelson, 1954).The two young female adults complained of limb

pains and general ill-health; one had had rheumaticfever as a child; she showed hysterical manifestationssuch as hyperventilation and no organic signs werefound. The other patient also had nothing organicdemonstrable, and was referred to a psychiatristwho diagnosed neurosis and depression.The other three children all complained of pains

in joints or limbs for which no organic cause wasfound. One had a functional wrist drop, the secondhysterical gait, and the third, with an unhappy homebackground, admitted to exaggerating his symptoms

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ll. Traumatic and Postural. All the patients in thisgroup were children, and all complained of jointpains; three patients had a history of rheumatic fever.In eight patients there was a definite history oftrauma with objective signs in a single joint (knee inthree cases, ankle in two, hip in two and elbow inone) with radiological evidence of slipped epiphysisin the two patients with hip involvement and ofosteochondritis dissecans in the patient with elbowinvolvement. In the other five patients, there werenormal serological findings, normal hearts andabsence of other joint involvement. One patient gavea history of rheumatic fever previously, and of recentjoint pains, low grade fever and suspectedpresystolic murmur; she was found to have a normalheart and normal temperature range, but a consider-able degree of sternal deformity and scoliosis.Another girl had also had rheumatic fever andcomplained of pains in her back and thighs. Nosigns of rheumatic activity were found, but the back-ache was thought to be postural following her periodof prolonged bedrest. The last patient gave a historyof painful swelling of both knees following a sorethroat. She had a normal heart and there was noevidence of rheumatic activity. Both knees tended tolock in flexion and to extend suddenly with a click,suggesting meniscus lesions. Exploration of the kneejoints revealed torn cartilages, which were thoughtto be due to a congenital defect.

SLIPPED FEMORAL EPIPHYSIS. (i) This girl, aged 13, wasreferred with the following letter from her family doctor,'Rheumatic fever 18 months ago. Now complains of painin joints, right foot swollen. Systolic murmur at apexwhich has just appeared. I should be grateful if you wouldtake her in for recurrence of rheumatic fever'. The historyobtained on transfer here was of trauma to the right thighone month previously, since when she had limped andnoticed pain in the feet, knee and hip on the affected side,with recent swelling of the foot. On examination, move-ments of the right hip were restricted and painful andthere was slight swelling of the right foot. A radiographof the right hip showed slipped femoral epiphysis. Therewas evidence of mitral and aortic valve disease but thiswas thought to be inactive and she was transferred to anorthopaedic hospital for operation. She has now beenfollowed up for five years and there has been no freshrheumatic activity.

(ii) J.H., aged 14, was admitted with painful swelling ofthe elbow for two weeks. He had had rheumatic feverwith carditis two years previously. After admission nofurther joints became involved and there was no evidenceof recent streptococcal infection or carditis; but radio-graphy showed osteochondritis dissecans affecting thecapitellum.

III. Infections. (a) UPPER RESPIRATORY TRACTINFECTIONS. Of this large group, 45 (43 children andtwo young adults) were diagnosed as upper respira-tory tract infections. The presumptive diagnosis ofrheumatic fever was based on preceding upperrespiratory tract infection followed by limb or jointpains, fever and general malaise in 33 patients. Therewere 12 patients in the whole group who did notcomplain of pain and in eight of them an organicsystolic murmur was initially suspected, as in 16 ofthose who did complain of limb and joint pains.Three had had previous rheumatic fever. In all thesepatients, rheumatic activity was thought unlikelybecause of the absence of abnormal physical signsother than those of a present upper respiratory tractinfection in some cases, and because of normal orrapidly settling sedimentation rate and negativeevidence of streptococcal infection, except for twochildren (one with raised A.S.T.) whose throat swabsgrew group A haemolytic streptococci.

(b) LOWER RESPIRATORY TRACT INFECTIONS. Allthese patients were children and the typical sympto-matology differed from the upper respiratory tractgroup in that fever and cough were the presentingsymptoms; pain, complained of by four children,was confined to chest or shoulder. Two children (onewith primary tuberculosis and the other with bron-chiectasis) had persistently elevated sedimentationrates and in four patients an organic systolic murmurwas queried but not confirmed here. There wasradiological proof of diagnosis in six cases (two,primary tuberculosis; one, bronchiectasis and three,lobar pneumonia). The remaining four children werediagnosed as bronchitis or resolving pneumonia inview of the chest signs on admission and the absenceof cardiac involvement or streptococcal infection.LEFT LOWER LOBE PNEUMONIA. This girl, aged 8, had

had rheumatic fever and chorea five years previously. Shehad a sore throat one week before present admissionfollowed by general malaise and fever. Her doctorqueried precordial friction rub and thought she liad had arelapse of acute rheumatism. This was not confirmed herebut there were early signs of pneumonia at the left baseand a subsequent radiograph showed consolidation of theleft lower lobe. She responded to penicillin therapy.

(c) BONE AND JOINT INFECTIONS. Four of these 10patients (nine children and a young adult male)complained of multiple joint pains and fever, butsubjective and objective signs eventually becamelocalised to one joint and diagnosis was confirmedby obtaining pus on drilling or by periosteal changeson radiographic examination. The six other patientshad pain and swelling of a single joint with fever, anddiagnostic proof by aspiration of purulent fluid infive cases and radiological changes in three (periostitisin two and Brodie's abscess in the third).

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J.W., aged 15, was admitted to another hospital withfever and pain in the right knee. White blood cells were8,000 per c.mm. with 80% polymorphs. Osteomyelitiswas queried and she was given a short course of peni-cillin, but she then developed pain in other joints and wasthought to have rheumatic fever. She was put on tosalicylates and transferred here. She continued to run alow grade pyrexia and high E.S.R. and a bony swellingof the lower end of the right femur became apparent.White blood cells at this time were 5,000 per c.mm. with50% polymorphs. Radiographs showed marked bonychanges of osteomyelitis and the femur was subsequentlydrilled.

(d) BLOOD STREAM INFECTIONS. Three of thesecases were children and the fourth a young adultfemale. All complained of multiple acute painfulswollen joints, fever and general malaise. In one boyan organic mitral systolic murmur was suspected.Ultimate diagnosis was based on a positive bloodculture (staphylococci in two cases and streptococciin two cases), rapid response to chemotherapy andabsence of cardiac involvement.

(e) URINARY TRACT INFECTIONS. These fourpatients (all children) complained of limb pains andgeneral malaise and were referred with low gradefever and a suspected organic systolic murmur in onecase. All had Esch. coli urinary infections and one hada hydronephrosis. No other abnormal physical signswere found, and there was no evidence of carditisor of streptococcal infection.

(f) PERICARDITIS. One of these children presentedwith shoulder pain and fever, and the referringdoctor thought that organic systolic and diastolicmurmurs were present. On admission here she wasfound to have pericardial and pleural effusions withpericardial friction, but no evidence of endocarditis.There was no evidence of streptococcal infection. AMantoux test at 1:1,000 was positive and radio-graphs showed enlarged hilar glands on one side.Symptoms and signs resolved after prolonged bedrest, and follow-up for two years showed satisfactoryprogress. The other child complained of generalmalaise and chest pain and his general practitionerfound him to be febrile and thought that an organicsystolic murmur was present. On admission, he hada pericardial effusion and friction rub, but noevidence of endocarditis. There was no evidence ofstreptococcal infection, but a Mantoux test at1:10,000 was positive. In both these cases, thetentativediagnosis on discharge was tuberculous pericarditis,but in view of their satisfactory progress in hospitaland at follow-up, in retrospect they may both havebeen cases of benign non-specific pericarditis.

(g) SPECIFIC FEVERS. This group comprised 13children and three girls aged 18-19 years. Fivechildren had an acute episode of fever, limb pains

and general malaise. This fever settled quickly afteradmission, no abnormal physical signs were elicitedand there was no abnormal serology. They werethought to be cases of influenza, though no sero-logical proof of diagnosis was sought.Four patients had a discharge diagnosis of

glandular fever. They all had fever and limb painsand in two of them an organic systolic murmur wasquestioned by the referring doctor. They werediagnosed after development of generalized lymph-adenopathy and splenomegaly, abnormal mono-nuclear leucocytes in the peripheral blood and apositive Paul Bunnell titre in one case. No abnormalcardiac signs were noted and findings reverted tonormal quite quickly.An example of this group was a girl, aged 10. She

was admitted with a history of sore throat three weekspreviously and five days' fever and joint pains. Onadmission here she had a fever of 99°F. but no abnormalphysical signs. Erythrocyte sedimentation rate was15 mm./hr. and a white cell count was normal. Five daysafter admission, a white cell count showed a relativelymphocytosis of 60% and a week later 230% abnormalmononuclears were noted in a total of 15,850 W.B.C. perc.mm. Paul Bunnell titre was positive (1:224).

Six patients had acute histories with fever andmuscle and joint pains in each case, but rapidlychanging physical signs, finally developing featurestypical of measles, poliomyelitis, meningitis (noorganism isolated but response to chloramphenicoltherapy), infective hepatitis, erysipelas and para-typhoid fever.The paratyphoid fever patient, an 18-year-old girl, had

had rheumatic fever previously, leaving established mitraland aortic valve lesions. She gave a three-day history offever, headache, generalized aches and pains with vomit-ing and diarrhoea for two days. The doctor thought shehad had fresh rheumatic activity and put her on tosalicylates. On admission here, vomiting and diarrhoeawas a noticeable feature, and Paratyphosus B was isolatedfrom blood, urine and faeces. She responded to treatmentwith chloramphenicol.The patient with poliomyelitis, aged 4 years, was

referred with the following letter from the general prac-titioner: 'History of tonsillitis two days previously. Onadmission she developed severe rheumatic pains in thearms and shoulders. Refuses to move the right armbecause of the pain. C.N.S., all reflexes present andequal.' On admission here she was found to be febrilewith slight neck stiffness and a flaccid paralysis of theright arm. The cerebrospinal fluid showed changesconsistent with poliomyelitis.The last patient in this group, a 13-year-old boy, had an

acute onset of high fever, pain and weakness in one hip.There was no evidence of cardiac involvement nor ofstreptococcal infection and no further joints becameinvolved; it was thought that he might have had radiculitisof virus origin.

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IV. Connective Tissue Disorders. (a) STILL'S DISEASEAND RHEUMATOID ARTHRITIS. These 24 cases (threeof whom were over 16 years of age) all presentedwith joint pains and the majority had had objectivejoint signs prior to admission; fever and generalmalaise were also presenting features. Eighteen hadhad acute symptoms and signs for over a monthprior to admission here. Persistence of 'active' joints,swinging fever and in some cases lymphadenopathyor typical Still's rash, with confirmation by biopsyof synovial membrane in less classical cases, fur-nished the eventual diagnosis. Of these patients, fivehad pericarditis and in three patients a significantsystolic murmur was thought to be present by thereferring doctor. This latter finding was not con-firmed here. It is of interest to note that while 16 ofthe 18 with symptoms of over one month's durationwere thought to be Still's disease on entry to thishospital, all those six with histories of under onemonth's duration were thought to be rheumaticfever when first admitted; underlining the consider-able difficulty in the early recognition of Still'sdisease. The following case history illustrates thispoint:

J.F., aged 11. Nine days before admission here hedeveloped pains in his thighs after playing football. Nextday the left ankle and right toe became swollen andpainful. The general practitioner found his E.S.R. to be72 mm./hr. and put him on salicylates. On admission herethe right big toe and left ankle were hot and swollen, andthe right hip painful. E.S.R. was 60 mm./hr.; heart andelectrocardiogram normal. He was thought to be a caseof rheumatic fever and put on cortisone. Despite highdosage, acute arthritis persisted and the left elbow alsobecame involved. Persistent joint involvement with softtissue thickening and raised E.S.R. with no evidence ofendocarditis, favoured the alternative diagnosis of Still'sdisease which has been confirmed by the subsequentprogress of the patient.

(b) SCHONLEIN-HENOCH PURPURA. Of the eightcases with Schonlein-Henoch purpura, five hadpolyarthritis and three had limb pains; abdominalpain was a prominent feature in four cases. In sixpatients there was history of preceding upperrespiratory tract infection. In all cases the diagnosiswas eventually clarified by the appearance of typicalpetechiae.

(c) ERYTHEMA NODOSUM. There were two adultsand three children in this group. Four patients hadjoint pains and two had joint swelling together withfever. All developed lesions typical of erythemanodosum and the illness settled spontaneously,without an obvious cause having been discovered.Radiographs of the chest were normal and throatand nose swabs negative with no rise in antistrepto-lysin-O titre. The fifth patient gave a history of

severe sore throat and fever treated with sulpha-thiazole, and he subsequently developed lesionstypical of erythema nodosum. Sulphathiazole wassuggested as the provocative agent after exclusion oftuberculosis.

(g) GENERALIZED LuPus ERYTHEMATOSUS. Twoyoung females were eventually diagnosed as acutelupus erythematosus. These patients both had jointpains and pericarditis. Eventual diagnosis was madein the first patient by the development of typical skinlesions with biopsy proof and L.E. cells found inperipheral blood. In the second patient proof waseventually found at autopsy. In neither was thediagnosis obvious at the time of transfer.

(e) PERIARTERITIS NODOSA. In this child of I1, asore throat was followed two weeks later by poly-arthritis, fever and rash of multiform type. Ontransfer here she had a patchy reticular erythema,pericarditis, polyarthritis and muscle pains. Skinbiopsy showed changes typical of periarteritisnodosa. Subsequent follow-up has confirmed thisdiagnosis.

(f) PROBABLE PENICILLIN SENSITIVITY. This 5-year-old boy presented with pains in his knees andswelling of his face following an upper respiratorytract infection treated with penicillin. There was noevidence of arthritis, carditis or streptococcalinfection on transfer, and he was thought to besensitive to penicillin.

(g) GRANULOMA ANNULARE. This patient, a 6-year-old boy, gave a history of nodules on elbows, wrists,toes and neck, and pain in his knees, for six months.On admission here he had a normal E.S.R. and anti-streptolysin-O titre. Nodule biopsy resembledgranuloma annulaire, though there is no record ofhis subsequent progress.

V. Rheumatic and Congenital Heart Disease.(a) CONGENITAL HEART DISEASE. These two childrenwere referred on account of general malaise and thediscovery of abnormal heart murmurs. One hadsigns typical of coarctation of the aorta, and theother, aged 4, was admitted with a history of asevere febrile cold following which a heart murmurhad been noted. On admission here there was noevidence of rheumatic activity, but cardiovascularfindings were those of patent ductus arteriosus, whichwas subsequently confirmed at operation two yearslater.

(b) RHEUMATIC HEART DISEASE. This group com-prised six children and a 19-year-old girl, all ofwhomhad had rheumatic fever previously with establishedrheumatic heart disease. The recent history was ofjoint or limb pains, general malaise and tachycardia.All had normal sedimentation rate, antistrepto-

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lysin-O titre and sleeping pulse, and there was no,evidence of active rheumatism.

VI. Blood Dyscrasias. (a) IRON DEFICIENCY ANAEMIA.This 14-year-old girl presented with general malaiseand odd aches and pains; the referring doctorthought there was a significant heart murmur. Shewas found to have severe iron deficiency anaemiaand an innocent basal systolic murmur. Despitefull investigation, no satisfactory explanation wasfound other than inadequate diet.

(b) ALEUKAEMIC STEM-CELLED LEUKAEMIA. This6-year-old girl was admitted from another hospitalwith a diagnosis of rheumatic fever. There was onemnonth's history of general malaise with joint pains,fever, tachycardia and swelling of the left knee.E.S.R. was 32 mm./hr.; Hb., 13 * 8%; W.B.C.,7,000/mm3 (pblymorphs, 82%, leucocytes, 16%,monocytes, 2%). There was an unsatisfactoryresponse to salicylates. She was thought here to be acase of rheumatic fever until, following progressiveweight loss, mild generalized lymphadenopathy andanaemia, the bone marrowwas examined and showeda picture of aleukaemic stem-celled leukaemia.Radiographs of the long bones showed mildgeneralized osteoporosis with coarse mottling.

VII. Others. This group consisted of 25 childrenand eight adults. In only one patient, an adult male,aged 42, could a definite diagnosis be made. He hadpolyarthritis and a basal diastolic murmur. Thesefindings were confirmed here. He had a raised serumuric acid and radiological changes characteristic ofgout; the Wassermann reaction was positive,accounting for the aortic incompetence. In the other32 patients, the provisional diagnosis of rheumaticfever was not confirmed but no satisfactory alterna-tive diagnosis could be found. Follow-up has variedfrom none, in a small minority, to seven years, andin no case have rheumatic fever-like episodesrecurred, nor has any cardiac abnormality developed.They are grouped according to their main symptom-atology as follows:

(a) ARTHRITIS OF UNEXPLAINED ORIGIN. Thesepatients, four children and one young female adult,gave a history ofjoint swellings but had no abnormalphysical signs on admission here. No evidence ofstreptococcal infection was found (normal anti-streptolysin-O titre and negative nose and throatswabs) and normal E.S.R. Short term follow-up wassatisfactory.

(b) ARTHRALGIA. These patients gave a history ofjoint pains dating over several weeks or months andwhen examined by the family doctor there was eithera slight rise in temperature, tachycardia or a sus-pected organic murmur. Three patients gave a

history of recent upper respiratory tract infection.Clinical and serological examinations were negativein all these patients. Short term follow-up wassatisfactory.

(c) LIMB PAIN. These patients all complained oflimb pains, four following an upper respiratory tractinfection. In four cases the referring doctor queriedan organic systolic murmur; another patient had hadrheumatic fever previously, and in another there wasa strong family history of rheumatic fever. In otherpatients, low grade fever and/or tachycardia werementioned in the referring letter. When admittedhere, all investigations were negative.

(d) FEVER. These patients were referred on accountof unexplained febrile illnesses during which thegeneral practitioner thought that an organic murmurwas present. This finding was not confirmed here,and the cause of the preceding febrile episode wasnever established.

Observations

From the above analysis, it may be seen that manydiagnoses may be confused with that of rheumaticfever. In Group B on closer study, four generalcategories of diagnostic errors became evident:1. Those cases who would fulfil the Duckett Jonescriteria but in whom further observation anddevelopment of fresh features provided the ultimatecorrect diagnosis. 2. Those who would have fulfilledthe criteria if all points in the history and clinicalexamination could have been corroborated. 3. Thosein whom there were never even questionably suffi-cient criteria. 4. Those in whom the diagnosis mighthave been rejected or the correct one established ifthe referring doctor had had the facilities and leisurefor carrying out further investigations.The majority in the first category are found in the

connective tissue diseases, notably rheumatoidarthritis. The early acute stage of this disease closelyresembles rheumatic fever, especially in children,with pericarditis, salicylate-responding pyrexia andtransient joint involvement; the Rose Waaler test isusually negative. Only continued observation of thesubsequent course of the disease, or the developmentof endocarditis, erythema marginatum or choreaprovides a solution. Even chorea may be seen inacute lupus erythematosus.The seconc category comprised both those in

whom the referring doctor's findings were not sub-stantiated here, or were not felt to be significantin the diagnosis of rheumatic fever, and also casesin which other points were elicited that had eitherbeen missed before or developed subsequently. Ingreater detail these notably concern the following:

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(1) History. A careful history is an essential in theexclusion or confirmation of the less typical formsof acute rheumatism. In several instances therelationship to trauma was missed; in a large numberit seemed that complaints of limb or joint painscontributed too prominently towards the proposedinitial diagnosis of rheumatic fever, since they werenot complained of on transfer here and did not recur.A previous history. of rheumatic fever or a familyhistory of the illness often seemed to swing thebalance disproportionately in favour of a pre-sumptive diagnosis of rheumatic fever.

(2) Fever. Temperatures of 98- 8°-99 -4°F. wereoften cited as being a significant feature. As anisolated finding in a child, this is probably of littleconsequence, since a normal child's temperature mayoften reach these levels at some time in the 24 hours.

(3) Tachycardia. This was a feature often stressedin referring letters, particularly in the group whichpresented primarily with limb and joint pains.Tachycardia out of proportion to the temperaturehas not been a common finding here, usually occur-ring only in those children with severe rheumaticfever or cardiac failure; in a few cases of acuterheumatism there has been a sinus bradycardia in theearly stages. Even mild apprehension can causetachycardia in a nervous child, but the sleeping pulsewill be within normal range for the age group.

(4) Systolic Murmur. The presence of an organicsystolic murmur was initially queried in a total of48 patients, half of whom were in the upper respira-tory tract infection group. A systolic murmur can bedemonstrated in a high percentage of infants(Hallidie-Smith, unpublished work) and most normalchildren (Lessof and Brigden, 1957). These murmursare usually best heard down the left sternal edge orjust internal to the apex. They may be fairly localizedor propagated out of the apex and up to the neck.The innocent systolic murmur never fills systole(Lessof and Brigden, 1957), and is usually maximalin early or mid systole. The character may be lowpitched and musical, or rather more high pitchedand blowing (Friedman, Robie and Harris, 1949).The precise aetiology of these murmurs has not beenestablished, but they are thought to be related toflow of blood in the great vessels and are accentuatedin the febrile child whose cardiac output is increased.In contrast, the organic systolic murmur is smoothand high-pitched, filling systole. It is best heard at,or just internal to, the apex, and is propagatedoutwards to the axilla.The last category comprises those in whom the

error of diagnosis might not have been made if the

referring doctor had been able to carry out furtherinvestigations toward an alternative diagnosis, sincethere was often insufficient evidence for suggestingthe diagnosis as it stood. The sedimentation rate is ofparticular value. A normal rate (less than 15 mm./hr.Westergren) at the onset of the disease, would makethe diagnosis of active acute rheumatism very un-likely, although it may remain above this level for aslittle as two weeks. A search for evidence of apreceding streptococcal infection by isolation of theorganism in throat or nose swab, or demonstrationof a rise in antistreptolysin-O titre, is of some helpin doubtful cases.

In other published series (McCue and Galvin,1948; Lewy, 1952; McCue, 1954; Saslaw, Hernandezand Werblow, 1954; Wedum and Rhodes, 1955)similar points have been made about history-taking,examination and evaluation of physical signs; ineach, a large proportion of cases were referred with aprovisional diagnosis of rheumatic fever, whicheither could not be substantiated or was supersededby an alternative diagnosis, sometimes only aftercareful observation over a period of time. The goodlong-term prognosis noted in the group with upperrespiratory tract infection followed by fever and limbpains is confirmed by these writers and by Kaiser(1943). In the series referred to, the overall pattern ofdifferential diagnosis approximates to our own withcertain exceptions, in part explained by the differentgeographical distributions of disease, e.g. sickle cellanaemia, and in part by the fact that some series onlydealt with out-patient referrals. Amongst other lesscommon diseases not listed in our series, but notedin the literature with reference to the differentialdiagnosis of rheumatic fever, are cat scratch fever(Lyon, 1956); meningococcaemia (Daniels, 1948);miliary tuberculosis (Freud, Weisz and Brunhofer,1950); ascariasis (Doumer, Lorriaux and Belbenoit,1951); juvenile hyperparathyroidism (Bogdonoff,Woods, White and Engel, 1956); Weber Christianpanniculitis (Brudno, 1950); Hodgkin's disease(Paquet and Delage, 1957); berylliosis (Sprague andHardy, 1954), sarcoidosis (Myers, Gottlieb, Matt-man, Eckley and Chason, 1952); hepatitis (Martini,1950), and irritable hip syndrome (Caravias, 1956).This last interesting entity has also been noted here.The symptoms are fever, general malaise and suddenonset of severe pain confined to the hip, all settlingspontaneously and thought to be due to synovitis.

SummaryThe differential diagnosis of rheumatic fever is

discussed from the experience at Taplow over anine-year-period from 1947 to 1956. The originaldiagnosis is reviewed in a sample of those cases

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DIFFERENTIAL DIAGNOSIS OF RHEUMATIC FEVER 357ultimately diagnosed as rheumatic fever, and 12cases are described which were originally diagnosedotherwise.A larger series of 196 patients is described who

were originally thought to have rheumatic fever, butin whom this diagnosis was eventually not sub-stantiated. This series is subdivided into seven maindiagnostic disease groups, which are discussed indetail and illustrated. The pointers in clinicalinvestigation that led to the eventual diagnosis arelisted and common erroneous interpretations ofhistory, fever, tachycardia and systolic murmurs arediscussed.Thus the differential diagnosis of rheumatic fever

still may present considerable difficulties, particu-larly in its milder forms. Some of these difficulties areinsurmountable. Others could be overcome by morerigid adherence to diagnostic criteria, by morecritical examination of the problems presenting, andby increased awareness of the significance of thephysical signs elicited. Fuller investigations at anearly stage in the disease, notably sedimentation rateand a search for streptococcal infection, would behelpful in the less obvious cases.

We are indebted to Dr. Wallace Brigden, Dr. Reginald

Lightwood, Dr. Gerald Thomas and Dr. Paul Wood fortheir guidance and participation over the years.

REFERENCESBogdonoff, M. D., Woods, A. H., White, J. E., and Engel, F. L. (1956).

Amer. J. Med., 21, 583.Brudno, J. C. (1950). New EngI. J. Med., 243, 513.Caravias, D. E. (1956). Arch. Dis. Childh., 31, 415.Daniels, W. B. (1948). Arch. intern. Med., 81, 145.Doumer, E., Lorriaux, A. and Belbenoit, C. (1951). Bull. Soc. med.

H6p. Paris, 67, 801.Freud, P., Weisz, A. and Brunhofer, A. (1950). Amer. J. Dis. Child.,

79, 676.Friedman, S., Robie, W. A. and Harris, T. N. (1949). Pediatrics,

4, 782.Hallidie-Smith, K. A. Unpublished work.Jones, T. Duckett (1944). J. Amer. med. Ass., 126, 481Kaiser, A. D. (1943). N. Y. St. J. Med., 43, 1937.Lessof, M. and Brigden, W. (1957). Lancet, 2, 673.Lewy, F. J. (1952). Ann. intern. Med., 36, 1042.Lyon, R. (1956). Lancet, 2, 555.McCue, C. M. (1954). J. Pediat., 44, 290.-and Galvin, L. F. (1948). Ibid., 33, 467.Martini, G. A. (1950). Dtsch. med. Wschr., 75, 1464.Myers, G. B., Gottlieb, A. M., Mattman, P. E., Eckley, G. M. and

Chason, J. L. (1952). Amer. J. Med., 12, 161.Nelson, W. E. (1954). Textbook of Pediatrics, 6th ed., p. 854.

Saunders, Philadelphia.Paquet, E. and Delage, J. M. (1957). Canad. med. Ass. J., 76, 927.Rheumnatic Fever Comsnittee Joint Report (1955). Rheumatic Fever

Working Party of the Medical Research Council of GreatBritain and the Subcommittee of Principal Investigators of theAmerican Council on Rheumatic Fever and Congenital HeartDisease, American Heart Association. Brit.-med. J., 1, 555.

Saslaw, M. S., Hernandez, F. A. and Werblow, S. C. (1954). J.Pediat., 44, 414.

Sprague, H. B. and Hardy, H. L. (1954). Circulation (N. Y.), 10, 129.Wedum, B. G. and Rhodes, P. H. (1955). J. Amer. med. Ass., 157,

981.World Health Organization. (1957). Report of the Committee on

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