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217

SARCOIDOSISBy W. M. MACLEOD, M.B.E., M.R.C.P.

Chest Physician, Southampton

Just over 50 years ago a young policeman con-sulted Professor C. Boeck on account of a trouble-some skin disease. The rash was peculiar. It hadstarted on his brow and spread in the course oftwo years to produce scattered well-definednodules on his face, scalp and trunk and on theextensor aspects of his limbs. The lesions variedin size from that of a pea to that of a large bean.Most of them were yellowish-brown in colour,though some of the larger ones had a bluish-redtint. In addition to the rash, Boeck noticed thatthe cubital and femoral groups of glands weregreatly enlarged and the axillary group was alsoeasily palpable. Histologically the appearanceresembled a sarcoma. This latter observation,together with the indolent clinical progress, ledBoeck to call the disease' multiple benign sarkoid '(Boeck, I899).The picture that Boeck recoided is now known

to be but one facet of a disease characterized bydisseminated granulomatous lesions which mayaffect most structures of the body. From hisoriginal annotation the term 'sarcoidosis' hasdeveloped, and in the English-speaking countrieshas come to stay as a convenient, though notinformative, title for this interesting disease group.

Jonathan Hutchinson (I898) is credited withthe first report of this condition. In 1878 hereported an anomalous disease of the skin andfingers. Twenty years later he published detailsof four similar cases. The first concerned a Mrs.Mortimer and he called the condition Mortimer'sdisease.

Following these earlier papers there have beennumerous accounts illustrating various clinicalfeatures under a variety of headings and eponyms.The underlying common pathological develop-ment was suggested by Schaumann in 1914(Schaumann, I924), but the fuller appreciation ofthe pleomorphic clinical features is moie recent.For a more detailed historical account see thepapers of Hunter (1936) and Freiman (1948).The latter paper has a'most helpful list of referenceson all aspects of the disease.

Sarcoidosis is a disseminated granuloma ofmultiple aetiology which, affecting most parts of

the body, clinically presents with predominantinvolvement of the lymph glands, lungs, skin, eyesand bones.The foci, irrespective of their situation, have

a characteristic histological pattern (Ricker andClark, 1949), though the picture is not specificfor this disease (frQntispiece). The lesions arecomposed of large epithelioid cells with abundantacidophilic cytoplasm and large ovoid vesicularnuclei. The cells at times tend to be arranged'concentrically. Giant cells are often present andare either of the Langhans or foreign body types.They may show inclusion bodies. There areusually a few lymphocytes scattered at the peri-phery of the lesion, the whole being bound bya reticulum. As the lesions grow they fuse, buttheir multi-focal development remains recogniz-able. In common with the typical clinical features,many authorities will accept variations of the usualpattern. Giant cells may be numerous andlymphocytes moderately increased in number.Those workers who consider sarcoidosis closelyrelated to tuberculosis will even allow minimalcaseation as distinct from the more usual centralfibrillary necrosis (Rubin and Pinner, I944).

The' foci may resolve, may remain stationaryfor months or even many years, or may heal,forming hyaline fibrous nodules. The organsinvolved frequently show enlargement, but it isnot rare to find scarcely palpable lymph glandswith their normal structure almost 'entirelyreplaced by sarcoid tissue.

It has been well recognized for many yearsthat a low skin sensitivity to tuberculin is a frequentoccurrence in sarcoidosis. Wells and Wylie (1949)have shown that there is present in the serum ofsome cases of sarcoidosis a tuberculin-neutralizingfactor. While this factor is also found in serafrom other diseases, such as kala-azar, and insome apparently normal sera, they believe that itspresence in sarcoidosis may be significant. Apositive skin reaction to i in Io,ooo O.T. mightcall for a careful review of the evidence, but in thepresence of the characteristic clinical picture,especially if backed by histological examination,it should not negative the diagnosis.



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2I8 POSTGRADUATE MEDICAL JOURNAL April 1952

Lemming (1940) was the first of several obser-vers who inoculated patients suffering from sar-coidosis with B.C.G. In general, it was found thatconversion to a positive tuberculin reaction wasdifficult to achieve, and that when it occurred itwas of short duration. This response has beenused to support the tuberculous aetiology of thedisease. Israel and his associates (I950), con-firming Lemming's results, point out that thesepatients also respond unusually to other inocula-tions such as pertussis vaccine, and that tuberculinanergy is only one feature of a wider interferenceof their immunologic mechanisms.Lemming (I942) also noted that the lesion at

the site of the B.C.G. inoculation, or in the drain-ing glands, showed a typical sarcoid picture. Thishistological pattern response is a non-specific one.Kveim (I941) has claimed that his inoculumderived from a proven sarcoid lymph gland pro-duces a specific skin reaction in this condition.The delayed interval of its appearance and itsduration are characteristic. Nelson (I949) hasrecently discussed this test, and notes that amongother substances normal splenic extracts may givesimilar results; The microscopy of the papulesformed shows appearances of sarcoidosis. Nelson'sresults were not confirmed by Danbolt (I95I),who strongly supports the specificity of Kveim'stest.

Clinical FeaturesIn England, judged by the comparatively small

number of series published, it would appear thatall sections of the population are equally liable tothe disease. In America, on the other hand, thereis a much greater incidence among negroes. Bothsexes are affected, though it is less common inmales. This bias is very evident in the group ofcases presenting with erythema nodosum, suchcases being nearly always found in women ofchild-bearing age. The majority of all groupsare noted in young and middle-aged adults, butcases have been reported in children and infants,and are not rare in the very old.One of the most striking features of the disease

is the great disproportion between the symptomsand the extent of the lesions. It is well knownthat a grossly abnormal lung picture often accom-panies a reasonably fit and uncomplaining patientwho has innocently attended for mass X-ray.

General symptoms are not a prominent featurein the earlier stages of the disease. Loss of weightis slight and notable fever uncommon, thoughoccasionally it may accompany a fairly acuteonset of the disease with marked enlargement ofthe liver and spleen. The E.S.R. is often normal,and a raised total serum globulin with reversal ofthe albumin-globulin ratio is not an essential

feature: when found it is in no way specific to thedisease. Other biochemical investigations areusually normal unless the localization of thedisease is such as to affect function, for example inthe rare involvement of the kidneys.

It is usual for sarcoidosis to present as a localdisease affecting one organ or one particularstructure. The chest physician, the dermatologistand the ophthalmologist are those who mostfrequently see the presenting features. As isevident from the historical appreciation of thedisease so, even today, the clinician is apt to focushis attention on but one aspect of the disease.The danger lies in his treating this fragmentwithout due regard for the whole patient andallthe structures affected.

It is simplest to consider the main features ingroups.

The Lymph GlandsIt is probably true to say that in every case of

sarcoidosis at least one group of glands is diseased.Generalized gross enlargement of the peripheralglands is not common. When it occurs there isusually enlargement of the liver and spleen andaccompanying symptoms of ill health and fever.This is an uncommon presentation. As a ruleone group of glands is picked out. These maybe superficial, such as the cervical group, but themediastinal and broncho-pulmonary glands arefrequently involved. Occasionally the mediastinalgroups are particularly noticeable, showing agreatly enlarged broad upper mediastinal shadowon the X-ray (Fig. 2). This picture is commonto many lymphadenopathies.

It is more usual, however, for the emphasis tobe on the broncho-pulmonary groups. Theresulting gross bilateral hilar enlargement, oftenwith well-maiked circular contours in a com-paratively well patient is, in England, almostdiagnostic of sarcoidosis (Fig. 3). In any case ofsuspected sarcoidosis, where confirmatory evidenceis required, a careful examination of all peripheralgroups should be made, as even hardly palpableglands may show the characteristic histology.The LungsSometimes a patient showing only broncho-

pulmonary adenopathy will, in the course of amonth or two, develop radiological evidence ofpulmonary dissemination (Fig. 4). As the lungfoci are chalked in, the hilar shadows are smudgedout. The glands return to a more normal size,though still diseased. These changes are notaccompanied by any subjective change in thewell-being of the patient, and it is remarkable howdense an infiltration may be present before slightshortness of breath is noted. The lung changes



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April 1952 MACLEOD: Sarcoidosis 219

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FIG. 2.-X-ray showing wide upper mediastinal shadow. The right hilarshadow is also prominent. There is only slight mottling in the lungfields.

may develop while the glands remain prominent,or they may be present without any known pre-ceding adenopathy. Their main characteristic isthat of multiple scattered foci without, as a rule,any major areas of confluence. The very finemottling seen in some cases of miliary tuberculosisis not usual, but all other vaiiations of size, densityand distribution may occur. None are diagnostic.The changes, generally bilateral, may be confinedto one lung or lobe. Pulmonary tuberculosis maybe closely mimicked, though cavitation, if present,is an interesting rarity.

In favourable cases the mottling reaches itszenith after several months and then, remainingunchanged for an interval which may be as longas two or three years, it clears sometimes with re-markable speed over a few weeks, but as a rule asslowly as it had previously progressed.

Persistence of the infiltration is unfortunate as itis a prelude to disseminated pulmonary fibrosis andassociated emphysema. These late changes arerecognizable by the complaint of increasingbreathlessness. Right-sided cardiac failure mayensue. An appreciable number of cases develop

phthisis-variously estimated at IO to 25 per cent.Such definite tuberculous change may involve onlypart of the sarcoid disease, and is usually accom-panied by a change from tuberculin anergy tosensitivity. A similar change in tuberculin sen-sitivity may occur in cases which are progressingfavourably.

Direct involvement of the larger bronchi is rare,and their compression by enlarged glands also veryuncommon. Both these features are notablydifferent to the behaviour of proven tuberculousinfection. Pleural effusions are also most unusualthough cases are occasionally seen which presentin such a way.The course of the lung disease is so variable and

unpredictable that the prognosis of any particularcase is difficult to determine. A rough clinical im-pression suggests that about half of the casespresenting with lung disease will resolve apparentlycompletely. Dense infiltrations can eventuallyclear even though they have been present for twoor three years. However it is true that the longerthe disease is present the more likely will fibrosisdevelop.

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220 POSTGRADUATE MEDICAL JOURNAL April 1952

FIG. 3.-X-ray showing the characteristic bilateral tuberous enlargement of the hilarshadows. The lung fields are clear.

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shadows. The lungfieldsareclear.

In assessing the progress of lung disease, symp-toms are of little value as they are present to asignificant degree only in the advanced fibroticcases or in those developing complications such ascaseating tuberculosis or right heart failure. Wedepend almost entirely on the X-ray appearances.The case illustrated in Figs. 5 and 6 gives anunusual opportunity for relating the disease,present in the lung in a comparatively early stage,to that seen in the X-ray. There is a remarkabledifference in the relative densities, though this is-exaggerated as the lung biopsy is not inflated. Thecommon fallacies of X-ray interpretation are wellknown, though they are sometimes convenientlyforgotten. It is commonly accepted that a clearingof the picture is, in the absence of symptoms, areturn of the lung to a normal state. While this is apractical, and probably correct belief, we must re-member that there are at present few physiologicallong-term studies of these recovered cases. Thelungs illustrated in Fig. 4 cleared after the in-

filtrations had persisted for one year. Six monthsafter a normal picture was obtained, a punchbiopsy of a normal sized liver showed activesarcoid lesions.

In most cases of sarcoidosis there are no factorswhich allow prognostic grouping. There are,however, two types of the disease which canreasonably be separated on this account. Berylliumis responsible for a condition so similar in manyrespects to other forms of sarcoidosis that we mayspeak of beryllium sarcoid. This is discussedfurther below, but one of its distinctive features isthe rarity of resolution and consequent poor prog-nosis. A second group of cases present witherythema nodosum. These cases, in contra-distinction to the former group, have an excellentoutlook and clearing of the infiltrations is therule.

All aspects of pulmonary sarcoidosis are con-sidered in detail by Scadding in the Bradshawlecture for I949 (Scadding, 1950).



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April I952 MACLEOD: Sarcoidosis 22r

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FIG. 4.-Same case as Fig 3 nine months later. The hilar shadows are almost normal.

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The SkinIt is usual in discussing the skin changes

associated with sarcoidosis to consider them inthree groups. The first and perhaps the com-monest is Boeck's' multiple benign sarkoid,' or as hetermed it later' miliary lupoid.' Secondly there isthe subcutaneous sarcoid of Darier and Roussy(1904), and lastly lupus pernio, first described byBesnier in I889. The first two groups may beassociated with each other, but lupus perniogenerally appears on its own. Multiple benignsarcoid is formed by nodules or plaques. Thelesions are at first reddish or bluish-red, darkeningto yellowish-brown. On pressure they show smallgieyish-yellow foci from which appearance derivesthe name miliary lupoid. They are very variablein number, size and distribution, being mostcommonly seen on the face, back or trunk and ex-tensor aspects of the limbs. The lesions maypersist unchanged or resolve with scar formation,

Ulceration does not occur. The subcutaneoussarcoid lesions of Darier-Roussy are much lessfrequent. The deposits are more deeply-seated,comparatively few in number, of normal skincolour or dull bluish-red, and in size as big as awalnut. They may be accompanied by the lesionsof the Boeck type.Lupus pernio is distinct from the preceding

types and appears as a rule on its own. It ischaracterized by symmetrical erythematous areaswith bluish-red infiltrated thickened plaques.Telangiectases may be prominent and ulceration iscommon. It affects especially the nose, face, ears,fingers and back of hands. In old lesions tissueloss with atrophy, ulceration and scarring isnoticeable.

The EyeIritis is the most frequent and important of all

ocular sarcoid lesions. Characteristically it is aB2



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FIG. 5.-X-ray of left mid-zone showing sarcoid infil-tration, part of which is in the apex of left lowerlobe.

painless nodular iritis with only slight inflam-matory symptoms (Woods, I95I). The nodulesare larger, pinker and more irregular than miliarytubercles. Large 'mutton fat' keratic depositsare common. l'he disease is chronic, with re-missions, and may heal with hyalinization or com-plete regression. Unfortunately theie is a seriousrisk of phthisis bulbi with complete blindness.

Occasionally the eye lesions are accompanied byenlargement of the lacrimal, salivary and ceivicallymph glands. Such cases have been reported asuveo-parotitis and in some instances Mikuliczsyndrome.Bones

Holt and Owens (1949) in their excellent surveyof skeletal sarcoidosis say that a reticular patternresulting from the destruction of the finer tra-beculae is the most characteristic and commonestX-ray finding. It is seen especially in the phal-anges and is almost specific for sarcoidosis. Thischange may be accompanied by the often-men-tioned 'punched out' cystic spaces (Figs. 7 and8). The disease in the bone starts in the medullarycavity and the earliest change noted is a mottledrarefaction or stippled pattern in the phalanges.This tends to be more marked at the distal endsof the proximal and middle phalanges and theproximal ends of the distal phalanges, though any

part of the skeleton may be involved. Thelacunae formed enlarge and coalesce to form theclassical cysts in various shapes and sizes. Holtand Owens' paper well illustrates these changes.They estimate the incidence of bone changes ataround 15 per cent., but this is a rough figure andmuch depends on the thoroughness with whichthe lesions are sought. They also reaffirmSchaumann's original observation (Schaumann,1924) that extensive sarcoid infiltration of thebone marrow may be present without any clinicalor radiological evidence of disease. Finger swell.ings, when present, are generally painless. Thebone disease may heal with resolution or fibroticpersistence of the ' cysts.' Occasionally spon-taneous fractures and gross finger deformity mayensue.

The Nervous SystemColover (1948) has reviewed the changes that

are sometimes found in the nervous system. Thecranial nerves are most often involved, especiallythe seventh on one or both sides, sometimesaccompanied by parotid enlargement. The opticnerve and the glosso-pharyngeal and vagus, withaffection of the pharynx and vocal cords, are alsoliable to infiltration. The peripheral nerves maybe affected. Meningo-encephalitis and myelitishave been seen.

The HeartSarcoid infiltration of the myocardium is not

common. Most of the cases reported have beenin the American literature, and like the diseaseitself in that country, most instances have been innegroes. Clinically it may be suspected in thepresence of various arrythmias or unexplainedtachycardia. It has been responsible for severalcases of sudden death in apparently healthypeople (Simkins, I951).Other Organs

It is common for the liver to show foci evenwhen it is of normal size and there is, as a rule, nodetectable impairment of function. The spleenshares the involvement of other lymphatic struc-tures, is often palpable and may rarely be verylarge. The kidneys are seldom clinically recog-nized as being affected. Many other parts of thebody on occasions may be diseased, including thenose, larynx, tonsils and adenoids, epididymis,testes and breasts. The pituitary and thyroidhave also shown infiltration.

Criteria of DiagnosisThe factors necessary before making the diag-

nosis of sarcoidosis in any case will depend on thestandards and beliefs of the observer, and thepurpose for which the diagnosis is required.



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Apr'tI5 MACLEOD: Sarcoidosis 2

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FIG. 6.-Same case as ig. 5. Section from iopsy of apex of lefloelb soin ueru sroi oi.Fr opaiowith X-ray.".:."'H:-iiiiii~bi4-!i:iin

In all cases it is essential that there are presentsome of the accepted proven clinical features.A single bizarre lesion, even with the standardhistological appearances, is not adequate. On theother hand, in clinical practice, it may be sufficientto note the typical X-ray picture of the lungs andmediastinum together with the state of the patient,to make a sufficiently assured diagnosis for thewell-being and treatment of the patient. How-ever, most clinicians would agree that, especiallyin the present state of our knowledge of thisdisease, wherever possible biopsy evidence shouldsupport the clinical picture. This has been foundmost often in the superficial lymph glands, evenwhere they are hardly enlarged. The skin, theliver, the tonsil, the nasal mucosa and sternalmarrow have also been found convenient sites.The case illustrated in Fig. 2 was diagnosed bybiopsy of a mediastinal gland removed at the timeof ligature of ductus arteriosus, As similar

changes are found in the mediastinal glands inpulmonary tuberculosis, the diagnosis was onlyaccepted after further clinical development. Thelung is also a rare source of biopsy material(Fig. 6).AetiologyThe agent responsible for the development of

sarcoidosis is unknown. In England it is gener-ally held that most cases are a result of a peculiarreaction to the tubercle bacillus. This view hasmany antagonists, especially on the Continent.The high incidence of tuberculin anergy, the

finding of tubercle bacilli, sometimes only afterprolonged search, in cases fulfilling other criteriaof sarcoidosis are evidence used to support thetuberculous aetiology. Kyrle's inoculation experi-ments with tubercle bacilli (Kyrle, I92I), thepapules and glands developed by B.C.G. in sar-coid patients, and the changes found in the glands



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FIG. 7.-X-ray of big toe showing( cyst' in terminal phalanx.

draining caseous tuberculous lesions are factswhich show that the tubercle bacillus can producethe 'sarcoid' histological picture without thebacillus being demonstrable and without caseation.But perhaps the most convincing evidence is theclinical experience that all gradations from openpulmonary tuberculosis on the one hand, to clas-sical sarcoidosis on the other, are not infrequentlymet.None of this evidence is absolute and all has

been refuted to the satisfaction of the opponentsof the tuberculous basis of sarcoidosis. Therarity of sarcoid infiltration of the bronchi, pleurajoints and adrenals, in spite of its wide dissemina-tion, are also notable and perhaps unexpecteddifferences.Some authorities hold that the disease is due

to a specific but unknown virus. Kveim's test,discussed earlier, is claimed to support this view.Others believe that various fungi are responsible.The chronic granuloma associated with beryl-

lium poisoning is very similar to sarcoidosis,though Hardy (1951) believes that the two con-ditions can be separated both by their histologicalappearances and by their clinical behaviour. Thechronic beryllium disease is characterized by severe

respiratory disability early on, and by the pre-valence of gastro-intestinal symptoms. It has abad prognosis.A dual aetiology has been suggested. The work

of Kallos (Warfinge, 1943) lends support to thisidea. White rats are endemically infected withbartonella. If they are inoculated with virulenttubercle bacilli their tissues respond in a sarcoid

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changes in distal end of proximal

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FIG. 8.rX-ray showing cystic sarcoidchanges in distal end of proximalphalanx of index finger. Thereare also less obvious changes inproximal end of same phalanxin middle finger.

manner. If, however, the rats' bartonella infectionis countered effectively and their reticulo-endo-thelial system blocked with indian ink, then thetubercle bacilli produce caseating tuberculosis.The group of cases presenting with erythema

nodosum is also worth commenting on in this con-nection. This type of sarcoidosis is almost con-fined to women of child-bearing age. After theinitial febrile reaction, with the typical and non-specific rash, the course is that of pulmonarysarcoidosis with an excellent prognosis. It iswidely held that erythema nodosum is a sen-sitivity response to a variety of agents, the tuberclebacillus, the streptococcus, sulphathiazole, etc. Ifthe tubercle bacillus is responsible for the ery-thema group it is difficult to understand how thebody can react with low skin sensitivity to tubercu-lin at the same time as the erythema nodosum is inevidence. We can postulate that some otherproduct of the tubercle bacillus is causing theerythema nodosum or, as is more likely, someother substance is present, perhaps from a strepto-coccus, which is not only responsible for theerythema, but also modifies the body's reaction tothe tubercle bacillus in this very peculiar way. It



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April I952 MACLEOD: Sarcoidosis25is all unproven conjecture. At present we mayconclude that there are several agents responsible,and as Scadding suggests (i950) we may speak oftuberculous sarcoidosis, of beryllium sarcoidosis,or of sarcoidosis due to any other agent that maypossibly in the future be shown to cause it.

TreatmentIn assessing the effectiveness of any particular

line of therapy we depend on observations oflocalized disease, especially in the lungs, skin oreyes. The difficulties are at once apparent. Theprogress of the local lesion is not necessarily atrue indicator of the state of the generalizeddisease. It is a frequent observation that decreasein the size of the hilar glands is succeeded by lungdissemination. Uveitis may heal only to be fol-lowed years later by other overt lesions in the skin,lungs or elsewhere. The unpredictable variationsin the natural course of the local disease have beenmentioned above. The whole disease may, withevanescent,symptoms, apparently resolve in a year,for example the erythema nodosum group. Incontrast the beryllium cases progress relentlesslyvith little relief. One of Boeck's original casesdying of carcinoma 29 years after the originaldiagnosis well illustrates the extreme chronicity ofsome cases (Danbolt, 1936). At autopsy the scarsof the initial lesions on the cheeks were accom-panied by more recent active skin disease, andsimilar foci were found in bones, lymphatic glands,lungs and spleen.With such variety of behaviour before us de-

manding caution, we can more reasonably ap-preciate the value of any therapeutic measureagainst the whole disease process. At the sametime we should remember that death usually re-sults from lung involvement and distress fromblindness and skin deformity. If treatment iseffective in these sites alone it is still of greatbenefit to the patient, although it is true thatthe local lesion may not reflect the thera-

peutic response of the disease as a whole.Most workers have treated a few cases with

streptomycin and P.A.S. in similar dosage to thatused for pulmonary tuberculosis. In general theirresults suggest that this treatment has little or noeffect on the course of the disease.

Calciferol has given much more encouragingresults. Scadding (1950) reports its use in pul-monary disease. He gave 50,000 to 150,000 unitsdaily, depending on the tolerance of the patient.He concluded that it was well worth further in-vestigation. It cannot be expected to help in thelong-standing fibrotic lesions, but infiltrations ofseveral years' persistence may clear, and in doubtthere is little to lose by careful trial. Favourableresults are also reported in treatment of the skinlesions.

Recently cases have been treated by cortisoneand A.C.T.H. (Siltzbach et al., I951; Lovelock etal., I95I; Small, 1951). It is much too early todetermine the true value of these measures. Thereis often prompt and encouraging response withrapid decrease in the size of liver and spleen, and ageneral sense of well being. If respiratory dis-ability was present it may show improvement.Unfortunately, the duration of the benefit in somecases is disappointing, relapse occurring a few weeksafter the cessation of treatment. The results maywell depend on the age of the lesion and thecausative agent.

I have reviewed the main features of sarcoidosisand have considered its diagnosis, aetiology andtreatment. There is still much that is uncertainand unknown about this fascinating group ofdiseases. In advancing our knowledge and in-creasing our experience of this condition we shouldavoid, on the one hand, a too rigid limitation of cri-teria, and on the other we should hesitate to includeborderline cases unsupported by sufficient evidence.

I am indebted to Dr. J. G. Scadding for thefrontispiece and for Figs. 7 and 8, and to Dr. J.Clegg for Figs. 5 and 6.

BIBLIOGRAPHY

BESNIER, E. (1889), Ann. Dermat. Syph., 0o, 333.BOECK, C. (1899), J. Cutan. G.U. Dis., 17, 543.COLOVER, J. (I948), Brain, 71, 451.DANBOLT, N., and HVAL, E. (1936), Acta. Derm. Venereol., 17,

477.DANBOLT, N. (1951), Ibid., 31, I84.DARIER J., and ROUSSY, G. (90o ), Ann. Dermat. Syph., 5, 144.FREIMAN, D. G. (1948), New Eng. J. Med., 239, 664, 709, 743.HARDY, H. L. (I95I), Proc. R. Soc. Med., 44, 257.HOLT, J. F., and OWENS, W. I. (I949), Radiology, 53, ii. --HUNTER, F. T. (1936), New Eng. J. Med., 214, 346.HUTCHINSON, J. (1878), 'Illustrations of Clinical Surgery,'

p. 42.HUTCHINSON, J. (1898), Arch. Surg., 9, 307.ISRAEL, H. L., SONES, M., STEIN, S. C., ARONSEN, J. D.

(195c), Amer. Rev. Tuberc., 62, 408.KVEIM, A. (I941), Nord. Med., 9, 169.KYRLE, T. (192t), Arch. f. Dermat. Syph., 131, 33.

LEMMING, R. (1940), Acta. Med. Scand., 103, 400.LEMMING, R. (1942), Ibid., IIo, I5I.LOVELOCK, F. J., and STONE, D. J. (I95I), J. Amer. med. Ass.,

I47, 930.NELSON, C. T. (1949), Arch. Derm. Syph., 60, 377.RICKER, W., and CLARK, M. (I949), Amer. J. Clin. Path., I9,

725.RUBIN, E. H., and PINNER, M. (1944), Amer. Rev. Tuberc., 49,146.SCADDING, J. G. (1950), Brit. Med. J., i, 745.SCHAUMANN, J. (I924), Brit. J. Derm. Syph., 36, 515.SILTZBACH, L. E., POSNER, A., MEDINE, M. M. (I95I),.. Amer. med. Ass., 147, 927.SIMKINS, S. (i951), Ibid., 146, 794.SMALL, M. J. (i95I), Ibid, 147. 932.

-WARFINGE, L. E. (I943), Acta. Med. Scand., 14, 259.WELLS, A. Q., and WYLIE, J. A. H. (I949), Lancet, i, 439.

- WOODS, A. C. (I949), Trans. Amer. Acad. Ophthal. Otolaryng.,March, 333.



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tba~ * · 217 SARCOIDOSIS By W. M. MACLEOD, M.B.E., M.R.C.P. Chest Physician, Southampton Just over...

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