Ann. rheum. Dis. (1960), 19, 174.

ARTICULAR MANIFESTATIONS OF ERYTHEMANODOSUM*

BY

LESLIE H. TRUELOVERheumatic Diseases Unit, Northern General Hospital, Edinburgh

Erythema nodosum was first distinguished fromother forms of erythema by Willan (1808), andHebra (1860) amplified Willan's account of thecondition as follows:

" . . . tumours of a pale red colour, raised abovethe level of the skin, and either semi-globular oroval in form. These swellings are tender onpressure, and are observed chiefly on the lower limbs.In some cases, the outbreak of this form of erythemais preceded by slight febrile disturbance, and even byshivering. . . They have at first a pale rose redcolour, with a slight tinge of yellow. Afterwardsthey become dark red, then livid; and when the redcolour has faded, a yellowish coloration remainsfor a considerable time."

Neither author mentioned arthritic manifestations,but Mackenzie (1886) reported a study of 108 casesof erythema nodosum in 34 of whom there weresymptoms of joint involvement. Various authorshave subsequently confirmed the association. Lof-gren (1946) reviewed 178 cases oferythema nodosum;57 per cent. of his patients complained of painfuljoints at the outset, and 27 per cent. had actual jointswelling. In this series L6fgren classified theaetiology as tuberculous in 104 patients and asstreptococcal in thirty. In a subsequent investiga-tion (LUfgren, 1953a), he studied 212 patients withbilateral hilar gland enlargement associated with anegative or weakly positive reaction to tuberculin;113 of them had erythema nodosum as a presentingsymptom, 101 with arthralgia and 78 with actualjoint swelling. James (1959) analysed 200 patientswith histological evidence of sarcoidosis in the formof non-caseating giant-cell systems; 62 of them(31 per cent.) had erythema nodosum and of theseforty (64 per cent.) suffered from polyarthralgia.These patients had no joint effusions and the arthral-gia settled without sequel. All but three had bi-lateral enlargement of the hilar glands.

* Paper read at a meeting of the Heberden Society on December 5,1959.

Although the presence of symptoms in the jointsin association with erythema nodosum is so wellauthenticated in the literature, there are no accountsof the actual duration and severity apart from generalstatements such as that of L6fgren (1953a) that"the symptoms being mild in type generally subsidewithin a couple of weeks".

In James's series the onset of arthralgia precededthe appearance of the skin lesion in 25 of the 62patients concerned. This precedence, which wasfirst described by Mackenzie (1886), leads suchpatients to be referred from time to time to rheumaticclinics, and a review of the records over a 10-yearperiod at the Rheumatic Unit of the NorthernGeneral Hospital prompted an inquiry into thepossible variations in the clinical picture.

Material and MethodsThe series consisted of all the patients with erythema

nodosum who had been referred to the Rheumatic Unitduring a period of 10 years. There were thirty suchpatients and 23 were reviewed personally. To thesewere added eleven in whom arthralgia had been an earlyand prominent symptom but who had been referred tothe Respiratory Diseases Unit of the hospital, and fourof these were seen personally. The mean duration offollow-up was 41 years, being less than 1 year in sevencases, from 1 to 5 years in 25 cases, and 6 years or morein nine cases.

Classification of cases according to possible aetiologicalfactors was difficult and patients were therefore dividedinto two main groups: those with bilateral enlargementof the hilar glands (25) and those without (14). Twopatients were not x-rayed in the early stages ofthe disease.These two groups were further subdivided according towhether or not a sore throat had preceded the onset ofother symptoms. Eight of the group with hilar glandenlargement, and four of the group without, gave ahistory of such a preceding infection.The sensitized sheep cell test was performed by the

method of Ball (1950) modified by the use of M.R.C.haemagglutination plates in place of test tubes. Com-parison with the results in this laboratory using Ball'soriginal method showed that higher titres were recorded

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ARTICULAR MANIFESTATIONS OF ERYTHEMA NODOSUMon the plates. In order to retain both the specificityand sensitivity of the test it has been considered advisableto designate a titre of 1/128 as the lowest indicating apositive result in rheumatoid arthritis. The results ofthe sheep cell test in 200 relatives of patients with rheuma-toid arthritis (Bremner, Alexander, and Duthie, 1959)were used as controls.The erythrocyte sedimentation rate (E.S.R.) was

measured in venous blood collected in Wintrobe'santicoagulant. Westergren tubes were used and the fallin millimetres was read at the end of one hour.

Results

Age and Sex.-The distribution of patients withregard to age at onset in the two main groups isshown in Fig. 1. The average age of the 25 patientswith bilateral hilar gland enlargement was 32 years,only three patients being in the fifth decade. Theaverage age of the second group, those withouthilar gland enlargement, was 39, but the variationin age was much greater and extended from 15 to77 years.The preponderance of women was striking. There

were only five men in the whole series, three beingin the group with bilateral hilar gland enlargement.

Involvement of the Joints.-The results of thesurvey as regards clinical involvement of the jointsare summarized in Table I. As might be expectedin a rheumatic unit, the joint symptoms preceded theonset of the skin lesions in the majority of cases.In one case the appearance of the skin lesion pre-ceded the onset of arthralgia by 3 days and in fivecases they coincided. On the average, however,there was a 2 weeks' interval between the two,the range being up to 7 weeks. The symptomsconsisted of pain and stiffness. Morning stiffnesswas a striking feature in many patients and was aspecific complaint in fourteen cases. Abnormal

TABLE I

CLINICAL FEATURES

Length of Time (wks) Mean Range

Interval between Onset ofArthralgia andAppearance of Rash.2 0-7

Duration ofArthralgia. 26 2-100+

Duration of Rash 3 3 days-6 weeks

Knees 87Ankles 67Wrists 51

Joints Involved (per cent. of cases) .. Fingers 36Shoulders 36Elbows 26Hips 23

physical signs in the joints consisted of swelling andtenderness (present in 27 cases), and effusion (presentin thirteen cases). Involvement of the knees wasalmost universal, next in order were the ankles,wrists, fingers, shoulders, elbows, and hips.The duration of the joint symptoms was very

variable. In three cases symptoms lasted for only2 weeks, and in twelve cases they lasted to the endof the follow-up period. In eighteen cases (44 percent.), symptoms lasted for less than 6 weeks, andin a further twelve for less than 6 months. Ineight of the twelve patients who complained ofarthralgia at the time of review symptoms hadcontinued on and off throughout the follow-upperiod. Four of these twelve patients made a goodinitial recovery, but three had further attacks oferythema nodosum. None of these three showedhilar gland enlargement and sensitivity to strepto-cocci or sulphonamide drugs was the probable causeof the recurrence in two. Amongst the eightpatients with persistent symptoms, two had furtherattacks of erythema nodosum and one of these had a

Bilateral Hilar Gland Enlargement000 0)000 00 oocnoo--oco0 0 0

00 s

00

0000 0

o - Present

* Absent

0

10 20 30 40 50Age (yrs)

60 70 so

Fig. 1.-Relationship between age at onset and presence or.absence of bilateral hilar gland enlargement.7

A

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ANNALS OF THE RHEUMATIC DISEASES

condition clinically and radiologically indistin-guishable from rheumatoid arthritis. This patientalso had a positive sheep cell test and a review ofthe history suggested that she was suffering fromrheumatoid arthritis in which erythema nodosumhad twice occurred as a complication associated withstreptococcal or sulphonamide sensitivity. A fur-ther patient had evidence of an erosive arthritis,but in this case the sheep cell test was negative andthe onset of the arthritis was immediately precededby the erythema nodosum. Only one of the remain-ing patients showed radiological abnormalities. Thiswas a woman, now aged 53, who showed changescompatible with a minor degree of generalizedosteo-arthritis and in whom this condition may wellhave been the cause of her persistent joint pain.An attempt was made to find out whether any

features in the early stages of the illness were asso-ciated with undue prolongation of joint symptoms.There was some distinction between those patientswho had objective signs, such as joint tenderness orswelling, when first seen and those with arthralgiaonly. Fourteen patients had no objective signs ofjoint involvement in the early stages, and only twoof these continued to have symptoms to the end ofthe follow-up period. The mean duration of symp-toms in the remaining twelve was 5{ weeks. In27 patients joint swelling or tenderness was presentwhen they were first seen and nine of these hadsymptoms to the end of the follow-up period. Inthe remaining eighteen the average duration ofsymptoms was 11 weeks.A similar analysis of patients in whom sore throat

was an early symptom showed that this also was afactor associated with longer duration of symptoms.Twelve patients had a sore throat initially and, ofthese, seven still had symptoms at the end of thefollow-up period. The mean duration of symptomsin the remaining five was 13 weeks. Sore throatwas not a prominent early symptom in 28 patientsand, of these, five still had symptoms at the end ofthe follow-up period. The mean duration ofsymptoms in the remaining 23 was 8 weeks.

Six patients had more than one attack of erythemanodosum. Five of these had symptoms persistingto the end of the follow-up period and three hadsigns of joint swelling or tenderness.

The Skin Lesion.-This was in accordance withthe classical descriptions and was confined to thelower legs in the majority of cases. In sevenpatients there were lesions morphologically typicalof erythema nodosum on the arms as well as on thelegs, and in two further cases there was an addi-tional rash on the body which was classified as

erythema multiforme. The skin lesions werepresent for an average period of 3 weeks, the rangebeing from 3 days to 6 weeks. Some patientsshowed successive crops of lesions arising duringthis 6 weeks' period.

Cardiac Involvement.-In eight of the 41 casescardiac murmurs were heard on first examination,but none was considered to be of pathologicalsignificance, all being systolic in timing and usuallyheard in the pulmonary area. At the time offollow-up only four patients were found to havemurmurs, and in three the murmur had been presentat the first examination. None was consideredto be organic in origin.

Erythrocyte Sedimentation Rate.-The behaviourof the E.S.R. is summarized in Table II. It washigh in the early stages, rising to over 60 in fifteenof the 27 cases in which it was recorded initially,and was normal in only one case. The E.S.R.remained raised for a mean period of 16 weeks.In ten cases out of the 27 it fell to normal within6 weeks. The relation between the duration ofraised E.S.R. and duration of symptoms varied. Infive patients the E.S.R. remained raised after thesymptoms had subsided, and in seven the E.S.R.became normal at the same time as the symptomsdisappeared. In one case, however, the E.S.R.remained raised for 10 weeks after the symptomshad subsided, and in fifteen patients the symptomspersisted after the E.S.R. had become normal, inseven of them for more than 6 months.

TABLE II

CHANGES IN CHEST X RAYS AND ERYTHROCYTESEDIMENTATION RATE

Duration of Signs (wks) Mean Range No. of Cases

Bilateral Hilar Enlargement .. 40 8-100 25

Elevation of Erythrocyte Sedimen- 12 9

Maximum Erythrocyte Sedimenta- 60 15

Radiological Examcation.-In 27 patients thehands and feet were x-rayed at the time of review.None showed changes such as the circumscribedareas of rarefaction described as typical of sar-coidosis.

Bilateral enlargement of the hilar glands was seenin 25 patients; the duration is summarized in

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ARTICULAR MANIFESTATIONS OF ER YTHEMA NODOSUM

Table II. The mean duration of hilar gland en-largement was 40 weeks, the range being from8 to 100 weeks. In nineteen patients the x rayhad become normal within one year. Thirteenpatients also showed radiological evidence ofinvolvement ofthe lung fields. This consisted for themost part of diffuse mottling. The duration ofx-ray signs showed no constant relationship to theduration of joint symptoms. In eight cases thex-ray signs cleared before the arthralgia ceased andin sixteen cases the arthralgia subsided first. It isworthy of note that none of the patients had per-sistent x-ray changes at the end of the follow-upperiod. Those who had had involvement of thelung fields did not differ from the rest of the seriesin regard to duration of joint symptoms or systemicdisturbance.

Three patients were considered to have signs ofprimary tuberculous infection at the time that theerythema nodosum developed. One of these had afurther attack of erythema nodosum 4 years later

80

70

60

0

Z 40w0.

3'..I

201/'

/120 . I s

Negativ

and on that occasion developed bilateral hilargland enlargement.

Sensitivity to Tuberculin.-The sensitivity tointradermal injection of tuberculin was determinedin twenty cases. The reaction was positive at adilution of 1/1,000 in five cases, and at a dilutionof 1/100 in nine cases. The remaining six casesfailed to react. Eighteen of the patients whosesensitivity to tuberculin was determined wereamongst the group with bilateral enlargementof the hilar glands and only five of these failed toreact to a dilution of at least 1/100.

Sensitized Sheep Cell Test.-This test was per-formed on 22 patients at the time of review. Theresults of the test are illustrated in Fig. 2, where theyare compared with those obtained from 200 relativesof patients with rheumatoid arthritis. Twelve ofthe erythema nodosum patients show a titre of1/32 or higher compared with eighteen of the 200controls. There is no relation between these titres

0---*Normal' sera

0-0 Erythema

C~~~~~~~~~~~~

IFe I

Nodosum sera (22)

Positive

Fig. 2.-Results of sensitized sheep cell test (S.S.C.T.) compared with the results in a "normal" series of 200 relatives of patients withrheumatoid arthritis.

< 1/16 1/16 1/32 1/64 1/128 1/256 1/512 1/1024S.SC.T. TITRE

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ANNALS OF THE RHEUMATIC DISEASES

and such factors as duration of symptoms, durationof raised E.S.R., or presumed aetiological factors.The difference between the two groups at the levelstated is highly significant (Xc = 27 68), but inview of the small numbers no importance can beattached to the shape of the curve.

Treatment.-During the acute stage of the illnessthis consisted of rest in bed and aspirin by mouthin a dose of 60 to 80 gr. a day. Five cases weretreated with steroid hormones in the early stagesfor periods up to a maximum of 6 weeks. In eachof these there was a rapid regression of the skinlesion and the temperature became normal. Thereis no evidence to suggest that the subsequent clinicalcourse of these patients differed from that of therest of the series.

DiscussionA study of the symptoms and signs in these 41

patients reveals a clinical syndrome of fairly uniformpattern, particularly with regard to involvement ofthe joints. Certain variations within this pattern areworthy of note. In patients with bilateral enlarge-ment of the hilar glands the age at onset was lowerthan in the remainder, being mainly confined to thethird and fourth decades, but the two groups didnot differ significantly in other respects. Preciseaetiological classification was difficult, but theresults suggest a relationship between erythemanodosum and joint manifestations which is in-dependent of possible aetiological factors such asdrug-sensitivity or streptococcal or tuberculousinfection. In three patients, in which a diagnosis ofprimary tuberculosis was made, the clinical picturediffered in no particular respect from that seen inthe remainder of the series. In those patients inwhom sore throat was an early manifestation, orin whom objective signs in the joints were observed,the disease tended to run a more protracted course,irrespective of whether the hilar glands were en-larged or not.The predominance of women in the series was

striking. This conforms with the observation ofJames (1959), who found that 70 per cent. of hiscases of sarcoidosis with erythema nodosum werewomen, whereas the sex incidence of sarcoidosis asa whole was more equal.The systemic disturbance, usually marked at the

onset, quickly subsided in the majority of cases,and in two-thirds the E.S.R. had returned to normalwithin 4 months. The absence of serious pul-monary involvement was worthy of note. In thisrespect there may be some difference betweenpatients with bilateral hilar gland enlargement anderythema nodosum and a similar group of patients

without erythema nodosum who might be classifiedas cases of sarcoidosis on the grounds of low sen-sitivity to tuberculin and histological evidence ofa sarcoid type of reaction. Lofgren (1953b), inhis study of 212 patients with bilateral enlargementof the hilar glands, found a tendency to persistenceof pulmonary lesions in only 8 per cent. of caseswith erythema nodosum compared with 28 per cent.of cases discovered on routine x-ray examinationor on investigation of symptoms other than those oferythema nodosum. However, he considered thatthe difference might be due to earlier diagnosis in thecase of the patients with erythema nodosum.Scadding (1956), in a series of 102 cases of sar-coidosis, found that a good prognosis could be givento those patients who first came under observationwith enlarged hilar lymph nodes only. In the presentseries no patient showed clinical evidence of rheu-matic heart disease, and none developed activepulmonary tuberculosis.From the point of view of joint involvement, there

was again no significant difference between thepatients with bilateral hilar gland involvement andthose without.No crippling form of arthritis developed, even

amongst those patients with prolonged signs. Twopatients, however, did show an erosive arthritis,mainly affecting the hands, but one of these mayhave been a case of rheumatoid arthritis in whomerythema nodosum occurred as an incidental com-plication. In this case the erythema nodosum wasassociated with an exacerbation of joint symptoms.Among the remaining ten patients with prolongedsymptoms, only five had actual joint swelling ortenderness and this was relatively mild, only one ortwo joints being involved, though the symptomswere sufficiently troublesome for them to continuetaking moderate doses of aspirin.The results of this study indicate that the prog-

nosis in patients presenting with erythema nodosumand arthralgia, with or without bilateral hilar glandenlargement, is excellent, although joint symptomsmay persist in some for many months, especiallyif sore throat precedes the onset. There is noevidence to support the view that rheumatic fever,tuberculosis, or progressive sarcoidosis occur com-monly amongst these patients. Thus treatmentshould be on simple conservative lines. Rest in bedneed not be unduly prolonged. Adequate doses ofaspirin will suffice to control symptoms in themajority of cases and steroids are rarely indicated.Treatment in the form of prophylactic penicillin oranti-tuberculous drugs will be required only in rareinstances with unequivocal evidence of rheumaticcarditis or active tuberculosis.

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ARTICULAR MANIFESTATIONS OF ER YTHEMA NODOSUM

Summary(1) 41 patients with erythema nodosum in whom

arthralgia was an early and prominent symptomhave been followed for an average period of 4j years.The clinical course of these patients is described withparticular reference to signs and symptoms affectingthe joints.

(2) The condition was essentially benign, althoughjoint symptoms persisted in some patients for manymonths. These were particularly liable to persistwhere sore throat was an early symptom, whereswelling or effusion was noted in the early stages, orwhere erythema nodosum was recurrent.

(3) No evidence was seen in this series to supportthe idea that rheumatic fever, tuberculosis, orprogressive sarcoidosis occur commonly amongthese patients.

(4) The results of the sensitized sheep cell test(S.S.C.T.) performed at the time of review, showedagglutination at higher titres within the sero-negative range than the results in a control group.

It is a pleasure to acknowledge the help and advicegiven me by Dr. J. J. R. Duthie during the course of thissurvey. I should also like to thank my colleagues of theRespiratory Diseases Unit for permission to see theircases and, in particular, Dr. A. C. Douglas for his help.During the period when this work was done, the

Rheumatic Unit was in receipt of grants from the NuffieldFoundation, the Medical Research Council, and BootsPure Drug Company Limited.

REFERENCESBall, J. (1950). Lancet, 2, 520.Bremner, J. M., Alexander, W. R. M., and Duthie, J. J. R (1959).

Ann. rheum. Dis., 18, 279.Hebra, F. (1860). "Acute Exantheme und Hautkrankheiten", in

"Handbuch der speciellen Pathologie und Therapie", ed.R. Virchow, vol. 3, pt. 1, p. 201. Enke, Erlangen.

James, D. G. (1959). Quart. J. Med., 28, 109.Lofgren, S. (1946). Acta med. scand., Suppl. 174.

(1953a). Ibid., 145, 424.(1953b). Ibid., 145, 465.

Mackenzie, S. (1886). Brit. med. J., 1, 741.Scadding, J. G. (1956). Proc. roy. Soc. Med., 49, 799.Willan, R. (1808). "On Cutaneous Diseases", vol. 1, p. 483.

London.

Manifestations articulaires de l'eytheme noueuxRESUMf

(1) On a suivi l'evolution clinique de 41 maladesatteints d'erytheme noueux, chez qui l'arthralgie avaite un sympt6me precoce et prominent, pendant uneperiod de 4 ans et demi en moyenne. On decritl'evolution clinique de ces malades, avec reference par-ticuliere aux signes et sympt6mes articulaires.

(2) L'affection fut essentiellement benigne, bien queles sympt6mes articulaires aient persisted chez quelquesmalades pendant plusieurs mois. Cette tendance a lapersistence de la symptomatologie articulaire fut noteparticulierement chez ceux qui avaient debuted par uneangine, par une tumefaction ou un epanchement, ouchez ceux dont l'erytheme noueux fut recurrent.

(3) Dans cette serie on ne trouva rien A l'appui de latheorie que le rhumatisme articulaire aigu, la tuberculose

ou la sarcoidose progressive surviennent souvent chezces malades.

(4) Des reactions avec des globules de mouton sen-sibilisees, effectuees durant une revue des malades,accuserent des agglutinations a des titres supdrieurs, endedans des limites sdro-ndgatives, que ceux des temoins.

Manifestaciones articulates del eritema nudosoSUMARIO

(1) Se sigui6 el curso clinico de 41 enfermos coneritema nudoso, en los cuales la artralgia fue un sintomaprecoz y destacado, durante un periodo medio detiempo de 4 afios y medio. Es descrita la evoluci6nclinica de estos enfermos con especial referencia a lossintomas y signos articulates.

(2) La afecci6n fue esencialmente benigna, aunque lossintomas articulates persistieron en algunos enfermosdurante muchos meses. Fueron particularmente pro-pensos a esta persistencia de la sintomatologia articularaquellos casos en que una angina fue un sintoma precoz,o en que una hinchaz6n o un derrame aparecier6n en losestadios iniciales, o finalmente en que el eritema nudosofue recurrente.

(3) En esta serie no apareci6 ningun dato que justi-fique la idea de que el reumatismo poliarticular agudo,la tuberculosis o la sarcoidosis progresiva afecten confrecuencia a estos enfermos.

(4) Las reacciones con gl6bulos de carnero sensibili-zados, efectuadas durante la revision de los enfermos,acusaron aglutinaciones a titulos mayores, dentro de lanorma sero-negativa, que en los testigos.

DISCUSSION

DR. B. ANSELL (Taplow) asked whether any secondattacks of erythema nodosum were again associated witharthritis.

PROF. S. J. HARTFALL (Leeds) asked whether anyantistreptolysin titres were carried out.DR. J. S. LAWRENCE (Manchester) asked whether the

seasonal incidence was significant.DR. A. ST. J. DIXON (London) said he was glad to hear

that attention had been drawn to the fact that the arth-ralgia of erythema nodosum sometimes remained afterall objective signs had disappeared, because somepatients had been labelled psychoneurotic because ofthis complaint. He asked whether any observationshad been made of "T"-wave changes in the electro-cardiograms. He said that these had been reported aspart of the syndrome and had in the past caused con-fusion with rheumatic carditis.DR. A. G. S. HILL (Stoke Mandeville) said that Dr.

Wilkinson at Stoke Mandeville had found positive sheepcell tests in a small proportion of patients; these sub-sequently became negative as the condition subsided.In this condition he had noticed a period of 2 or 3 weeksof general malaise before anything else happened. Thiscaused a diagnostic problem. He wondered whether thepolyarthralgia was ever seen without erythema nodosum,and whether this was one of the benign polyarthritides.

PROF. E. G. L. BYWATERS (London) said that they sawa fair amount in children at Taplow and in adults atHammersmith. In general it seemed that the joint

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ANNALS OF THE RHEUMATIC DISEASESmanifestations were much more common in adults andless common in children. He did not know whether anyinformation existed on the histological appearances. Ithad been thought that the occasional abdominal pain orjoint manifestations might be panniculitis occurring indeep spots, similar to panniculitis in superficial areas.There was a widespread feeling that erythema nodosumand joint pain entailed an association with rheumaticfever. He had seen only one case in which there wasrheumatic carditis. Finally, he asked what the speaker'sregime of treatment was, particularly in cases with apositive Mantoux.

DR. TRUELOVE replied that second attacks wereobserved in four patients, and that all four had persistedwith signs at the end of the follow-up, two of them havinghad three attacks. Antistreptolysin titres were not done,and the seasonal incidence had not been worked out.Nor had electrocardiograms been done routinely, so thathe could give no information about "T"-wave changes.

In reference to sheep cell titres, he emphasized thatthe sheep cell tests shown had been done at the end of thefollow-up period. He had no conclusive information onwhat the titres were at the beginning, although he hadseen positive readings in a number of patients. He hadthe impression that these patients did not need specifictreatment, except rest in bed and salicylates, but in

patients treated with steroids the erythema nodosum hadsubsided more quickly than in the others. Steroids weregiven only for short periods up to 6 weeks, and there didnot appear to be much distinction between those treatedwith steroids and those without.

PROF. E. G. L. BYWATERS (London) asked if PAS orINAH had been used.

DR. TRUELOVE replied that these drugs were given topatients with bilateral hilar gland enlargement.

DR. J. J. R. DUTHIE (Edinburgh) said that they hadwondered whether if steroids were given to patients withsarcoidosis they should be "covered" with antibiotics,but that their colleagues, the chest physicians, hadassured them that this was no longer necessary.

PROF. E. G. L. BYWATERS (London) said that it wassometimes difficult to know whether a patient hadsarcoidosis or tuberculosis. There were Mantoux-positive cases of sarcoidosis and sometimes Mantoux-negative tuberculosis patients, at least for a while. Hethought the question of giving antibiotics was veryimportant, and felt that cortisone should not be givento any great extent to such patients without "covering"it with suitable antibiotics.

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