Granulomatous relationship to · Granulomatous myopathy: its relationship to sarcoidosis andpolymyositis FIG. 1 Case 1. Section ofquadriceps muscle showing a typical granuloma with

Journal of Neurology, Neurosurgery, and Psychiatry, 1975, 38, 1090-1099

Granulomatous myopathy:its relationship to sarcoidosis and polymyositis

R. H. HEWLETT AND BETTY BROWNELL

From the Department of Neuropathology, Frenchay Hospital, Bristol, England, andDepartment of Anatomical Pathology, Stellenbosch University Medical School,

Tygerberg Hospital, Tiervlei, Cape, S. Africa

SYNOPSIS In three cases of generalized muscle weakness, muscle biopsy revealed well-defined, non-caseating epithelioid granulomata with giant cells. In one of these patients there was, in addition, ahigh serum CPK and histological evidence of widespread muscle cell degeneration and regeneration,apparently unrelated to the granulomatous process. In a re-examination of the histopathology ofthese cases, using biopsy material from a fourth case of proven sarcoidosis as a standard, it was con-cluded that there are no special features of the granulomatous/giant cell process which permit theseparation of the case of presumed polymyositis. However, it appeared that granulomata per se donot exert a significant ill effect on surrounding muscle cells, and that evidence ofwidespread degenera-tion of muscle cells is the important point of distinction.

The syndrome of slowly progressive proximalmuscle weakness associated with the biopsydemonstration of skeletal muscle granulomatahas for long been a source of particular interestto clinicians and pathologists alike (Dyken, 1962;Gardner-Thorpe, 1972). The apparent need toprovide a firm diagnosis of sarcoidosis, usuallyin the absence of organ involvement elsewhere,has caused stress to be laid on the interpretationof the muscle biopsy. This report presents theclinical and pathological findings in four cases of'granulomatous myopathy', three of whom ex-hibited a clinical picture suggestive of chronicpolymyositis, while the last showed severe musclewasting together with a lymphadenopathy laterproven to be sarcoidosis.

CASE 1

A 29 year old bantu female suffered generalized achesand pains, particularly in the hands and feet, whichhad commenced 12 months earlier, and for the pre-vious five months she had noticed generalized weak-ness which progressed until she was unable to walk,get out of a chair unaided, or lift her arms to combher hair. She thought that some areas of her skin werediscoloured, with darkening of the face and lighten-(Accepted 25 June 1975.)

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ing of the neck and forearms. She was anorexic andhad lost weight over the past three months beforeadmission. She denied any previous major illnesssuch as tuberculosis.On examination, she was apyrexial but looked ill.

General examination was negative except for patchypigmentation of the skin of the neck, and obviousgeneralized muscular weakness, most marked prox-imally. Tendon jerks were present but diminished.The following investigations were reported as nor-

mal: haemoglobin, WBC, blood urea and electro-lytes, serum proteins, serum and urinary calcium,aspartate transaminase, LDH, aldolase and CPK,WR, ASOT, latex fixation, LE cells, porphyrinsscreening, and glucose tolerance. The ECG was alsonormal, as were the CSF and a liver biopsy. The ESRwas 97 mm in the first hour, the chest radiographshowed possible widening of the mediastinum, andelectromyography of the quadriceps femoris andbiceps humeri muscles revealed a myopathic pattern.

MUSCLE BIOPSY (quadriceps femoris muscle) Thestriking lesion consisted of multiple granulomata,varying in size from 200-700 ,um, and situated in con-nective tissue septa and within muscle fasciculi (Fig.1). Giant cells were prominent, but no caseation orother necrosis was apparent. There were a number ofmyopathic changes including central nuclei andvacuolation, and also perifascicular atrophy which

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Granulomatous myopathy: its relationship to sarcoidosis and polymyositis

FIG. 1 Case 1. Section of quadriceps muscle showing a typical granuloma with giant cells.Haematoxylin anzd eosin, x 160.

in one section was grouped enough to suggest dener-vation. Silver preparations revealed peripheral nerveinvolvement by a granuloma, at one point, withaxonal beading and fragmentation. A minor lympho-cytic infiltrate was present, usually in relation to thegranulomata, and extending locally among adjacentmuscle cells. Blood vessels were generally normal,and stains for tubercle bacilli and fungi were non-contributory.

COURSE AND MANAGEMENT The patient was put onto prednisone 60 mg daily for one week, and this wasreduced to 40 mg for three weeks and she was dis-charged on 30 mg daily, having shown a markedimprovement in muscle power.

CASE 2

A white female, aged 72 years, was first seen in 1972having at that time a nine months' history of an achein the left arm, followed by progressive weakness ofthe limb. At the same time she noticed difficulty in

climbing stairs, and over the past few months she haddeveloped a tendency to choke when eating. Uponquestioning, she admitted to having been feeling ex-ceptionally tired for the past three years.

Examination revealed slight facial weakness andpoor movement of the palate. Speech was normal,and the sternomastoid muscles did not show anyweakness. There was marked wasting of the bicepsand brachialis muscles bilaterally, and generalizedweakness of the arms and legs, more apparent proxi-mally. The reflexes were normal and sensation wasunimpaired. There was no sign of muscular tender-ness.

She had suffered a myocardial infarction two yearspreviously, and had developed mild congestive car-diac failure as a consequence. This was treated withdiuretics only.The following investigations were reported as

normal: haemoglobin, WBC, serum proteins, serumcalcium, blood sugar, serum CPK, blood urea andelectrolytes. The chest radiograph showed generalizedpulmonary fibrosis, and the heart was slightly en-

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R. H. Hewlett and Betty Brownell

FIG. 2 Case 2. Section ofdeltoid muscle showing asmall epithelioidgranu-loma surrounded by normalmuscle fibres. Haema-toxylin and eosin, x 400.

FIG. 3 Case 2. Longi-tudinal section of deltoidmuscle showing nerveaxons emerging from agranuloma. Note irregularaxonal thickening, anddegenerate telodendria.Schofield's modification ofBielschowsky's silver stain,x 400.

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FIG. 4 Case 2. Cryostat section of deltoid muscle showing enclosed type I cells and a small area of typegrouping. Lactic dehydrogenase stain, x 160.

larged. Electromyography of the deltoid and quadri-ceps femoris muscle was also normal. An edrophon-ium test was negative.

MUSCLE BIOPSY (deltoid muscle) Scattered through-out the specimen, and sparse enough to require manysections for their demonstration, were tiny epitheli-oid granulomata (Fig. 2) measuring approximately200 Ftm in diameter, apparently situated betweencells, and unassociated with any myopathic changesin the surrounding muscle fibres. The remainder ofthe sample appeared to be normal with regard tofibre size and blood vessels, but silver preparationsdemonstrated a generalized axonal degeneration ofterminal nerve fibres and motor endplates (Fig. 3).Sometimes these terminal axons could be seen to beemerging from a granuloma. Histochemistry re-vealed increased numbers of enclosed cells and smallareas of fibre type grouping, both with regard to typeI fibres (Fig. 4). The routine methods for the demon-stration of bacilli and fungi were negative.

COURSE AND MANAGEMENT The patient was dis-charged from hospital without any specific therapy.

She was seen again a year later, when it was thoughtthat her muscle weakness had progressed. The serumCPK was still normal. She was put on to 15 mgprednisone thrice daily for six months then reducedto 5 mg thrice daily. Two years later (March 1975),without prednisone, there was marked wasting of theupper limb muscles, especially the left deltoid, and adistinctly waddling gait. She was now unable toclimb stairs or to get out of the bath unaided.Steroids were discontinued on account of severeosteoporosis.

CASE 3

This young coloured male, aged 21 years, was re-ferred by a country practitioner because his com-plaint of low back ache had failed to respond tovarious drugs (including anti-rheumatic therapy).Steroids had not been tried. His symptoms were ofsix months' duration, and included a feeling of weak-ness and fatigue in the muscles of the neck, shoulders,arms, and thighs. Exertion made his conditionworse and rest improved it. He said he tended tostumble and fall easily, and that he had difficulty in

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FIG. 5 Case 3. Section ofquadriceps muscle showingfibre-size variation, central nuclei, and degeneratingcells. Haematoxylin and eosin, x 160.

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*:::.:::::* ~ ~ ~ ~ ~~~~.:.. .::. .:::*~~~~~~~~~~~~~~~.FIG. 6. Case 3. Section ofquadriceps muscle showing a single tiny granuloma. Haematoxylin and eosin,x 640.

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Granulomatous myopathy: its relationship to sarcoidosis andpolymyositis

arising from the ground. On questioning, he ad-mitted slight difficulty in swallowing solid food.

Examination revealed a slenderly built patientwith minimal signs of proximal muscle wasting. Theskin above the right eye was slightly erythematous.Physical signs were confined to the locomotor system,where an obvious weakness of the proximal muscleswas easily demonstrable: the patient could barelylift his arms above shoulder level, and was unable toget up off the floor without assistance. Passive limbmovements suggested stiffness of the muscles, but thereflexes, although somewhat diminished, werepresent and equal.The following investigations were reported as

normal: haemoglobin, WBC, liver function tests,blood urea, thyroid function tests, LE cells, radio-graphy of chest and spine, and liver biopsy. The ESRwas 27 mm in the first hour, the serum CPK 1 103IU/l (normal 0-100), LDH 1 312 IU/l (normal 0-200),and electromyography showed a myopathic pattern.

MUSCLE BIOPSY (quadriceps femoris muscle) Therewas evidence of a generalized myopathic process,with fibre-diameter variation, central nucleation,vacuolation, degeneration and phagocytosis, andalso regeneration of muscle cells (Fig. 5). Granulo-mata composed of well-defined epithelioid cells werescattered sparsely through the specimen, and

measured 200-600 ,um, although very tiny lesions(80 ltm) could be seen (Fig. 6), apparently emanatingfrom within muscle cells. Except for a few lympho-cytes within and around the granulomata, there wasno inflammatory cell infiltrate and intramuscularblood vessels were normal. Stains for tuberclebacilli and fungi were negative.

COURSE AND MANAGEMENT Prednisone 60 mg perday was started, and during the next six weeks theserum CPK fell to 167 IU/l, muscle power greatlyimproved, and the patient was discharged on 20 mgprednisone a day.

CASE 4

A coloured male, aged 23 years, had apparently beendiagnosed as having sarcoidosis a year earlier, on thebasis of a febrile illness, radiological changes in thelungs, and an adenopathy. He had been put on tosteroids at one stage, but it is not known how muchor for how long. He had improved on this therapyinitially, but then stopped attending the outpatientdepartment. He returned to hospital because ofgeneralized weakness and tingling sensations in bothfeet.On examination, he was found to be almost

cachectic, with stocking-distribution sensory changes

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FIG. 7 Case 4. Section ofquadriceps muscle showing multinucleate cells. Haematoxy-lin and eosin, x 400.

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in both lower limbs, and absent knee and ankle re-flexes. He was quite unable to walk. There was ageneralized lymphadenopathy, bilateral parotidgland enlargement, and tender, swollen joints (knee,elbow).

LABORATORY INVESTIGATIONS The blood haemo-globin, serum electrolytes, serum proteins, and theCSF were normal. Serum alkaline phosphatase wasmarkedly raised (1 960 IU/l) and the aspartate trans-aminase and LDH were slightly elevated. The serumCPK was normal. The ESR was 120 mm in the firsthour, and the WBC 18 000/mm3 (lymphocytes 21 %Y,monocytes 11 , eosinophils 2%4, neutrophils 66%4).The ASO titre was 833 units. Chest radiographyshowed some pulmonary fibrosis suggestive of healedtuberculosis, and there was slight ECG evidence ofleft ventricular hypertrophy. A lymph node biopsy(done concurrently with the muscle biopsy) showedfloridgranulomatous inflammation without caseation.Asteroid bodies were easily seen.

MUSCLE BIOPSY (quadriceps femoris muscle) Mul-tiple granulomata, ranging in size from 100-800 ,umin diameter, were apparent in many sections. Thelarger lesions showed multinucleate cells surroundedby epithelioid cells and lymphocytes, and wereassociated with obvious atrophy of adjacent musclefibres. Occasional isolated lymphorrhages could beseen, but except for the muscle cells undergoing anapparent 'compressive' destruction by the granulo-mata, degenerative changes elsewhere were notapparent. Of particular interest were a number ofmuscle fibres in which a process of multinucleationand enlargement quite unlike simple fibre regenera-tion, could be seen to be taking place (Fig. 7). Inwhat is presumed to be the early phase of this pro-cess, there was a clear demarcation between the cyto-plasm of the invading cell and the muscle sarcoplasm,but when the whole structure was enlarged, thecontent of the cell became homogeneous. Histo-chemistry showed intense staining of epithelioidcells with the reduced NAD technique, evidence ofmyosin ATP-ase activity in multinucleate giant cells,preservation of fibre identity among those cellsundergoing atrophy on the periphery of granulo-mata, and a general type II fibre atrophy throughoutthe rest of the sample. Routine methods for thedemonstration of tubercle bacilli and fungi were non-contributory.

COURSE AND MANAGEMENT The patient was put backon to 45 mg prednisone daily and showed improve-ment in muscle power and sensation. The serumalkaline phosphatase level fell and the lympha-denopathy was observed to diminish. He was dis-charged on maintenance therapy.

DISCUSSION

Examination of the literature shows very well theevolution of thought with regard to sarcoidosisand granulomatous lesions in skeletal muscle.Initially, the involvement ofmuscle in sarcoidosiswas thought to be rare, and Ricker and Clark(1949), in a study of 300 cases, found skeletalmuscle lesions in 10% of live patients and in twoout of 22 necropsies. Longcope and Freiman(1952), in their excellent and widely quoted paper,do not refer specifically to muscle involvementor to clinically demonstrable muscle weakness.Then there appeared the papers of Myers et al.

(1952), Powell (1953), Phillips and Phillips (1956)and Wallace et al. (1958), from which it was con-cluded that sarcoidosis of muscle was relativelycommon, that it might be asymptomatic, andthat its incidence appeared to vary directly withorgan involvement elsewhere. It was pointed outthat, because lesions were sparsely distributed, anumber of sections might be required in order todemonstrate a granuloma.Next it became apparent that sarcoidosis

might seem to involve skeletal muscle in isolationand, in an important paper, Harvey (1959) re-ported, for the first time, the occurrence of amyopathic syndrome on the basis of sarcoidosis.Brun (1961) described a case of 'chronic poly-myositis' as a result of muscular sarcoidosis, andCrompton and MacDermott (1961) describedthree cases of sarcoidosis producing progressivemuscular weakness and wasting, in one of whomnecropsy showed apparent regression of themuscle lesions. In 1964, Hinterbuchner andHinterbuchner, expanding the concepts ofHarvey (1959) and Brun (1961), proposed aclassification for the various expressions of sar-coidosis of muscle:

1. Asymptomatic (microscopic granulomata)2. Palpable nodules3. Myopathic form

a. Pure myopathic without clinical evidenceof sarcoidosis

b. Myopathic with other organ involve-ment

Thereafter, save for the sporadic account(Talbot, 1967), interest in sarcoid myopathyseems to have waned, and Scadding (1967) sum-marized the situation '. . . many cases of sarcoi-dosis involving muscles have been reported ...

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In most cases the clinical picture was that of apolymyositis with widespread weakness, usuallywith wasting. . .' The report ofLynch and Bansal(1973) entitled 'Granulomatous polymyositis' isa good example of this syndrome; a 56 year oldwoman with a long history of progressive muscleweakness, having no demonstrable evidence ofsarcoidosis elsewhere, a normal serum creatinephosphokinase, and a biopsy revealing musclegranulomata without evidence of generalizedmuscle cell degeneration. We do not support theuse ofthe term 'polymyositis' outside the contextofan inflammatory or necrotizing myopathy withwidespread degeneration and regeneration ofmuscle cells and laboratory evidence of a col-lagen disease; and it is in relation to the collagen-oses that we have attempted to re-examine theclinical and pathological findings in these fourpatients. In these circumstances, the real prob-lem becomes one of distinguishing the myopathyof sarcoidosis from that of the collagenoses inthe face of clinically identical syndromes, whichmay also have a similar response to steroidtherapy.

Case 4 undoubtedly suffers from sarcoidosis,having a chronic illness with arthritis, parotitis,and lymphadenopathy, in addition to peripheralneuropathy, generalized muscular wasting, and amyopathic EMG. The granulomatous processhas resulted in considerable local destruction ofmuscle cells but generalized myopathic changes,such as necrosis, phagocytosis, and infiltrationby inflammatory cells, are lacking. The normalCPK excludes significant damage to muscletissue. Case 2 probably represents the other endof the spectrum of sarcoid myopathy: muscularweakness and wasting of many months duration,generalized pulmonary fibrosis, unremarkablelaboratory tests (including EMG, serum CPK),and sparse, small muscle granulomata with nomyopathicchanges whatever. Case 1 demonstratesan intermediate form, with severe muscle weak-ness (although little evidence of wasting), noother demonstrable organ or tissue involvement,a normal serum CPK, myopathic EMG, andlarge well-developed skeletal muscle granulo-mata with some myopathic changes in the formof central nuclei, vacuolation, and the occasionalregenerating cell, and, in addition, some evidenceof intramuscular nerve involvement.Case 3 is different from the others in two res-

pects: his biopsy specimen showed widespreadand severe myopathic changes with degenerationand regeneration of muscle cells but sparse,poorly developed granulomata, and the serumCPK was greatly elevated.

Is there, therefore, any sound histopatho-logical basis for the distinction between thesarcoid and inflammatory myopathies (leavingaside the semantic problem implicit in the termgranuloma)? Clearly, the granuloma itself can-not be of much help, for it has been reported inmyositis complicating thymoma (Namba et al.,1974), in carcinoma (Symmers, 1951), and invarious collagenoses (Adams et al., 1962). Acareful study of the granulomata in this seriesdid not reveal any useful differences betweenthose found in cases 1, 2, and 4 on the one hand,and those in case 3 on the other, except that thelatter had much fewer definitive lesions. And,while we agree with Longcope and Freiman(1952) and others that the well-developed granu-loma is primarily an interstitial lesion, exerting adestructive effect by compression (Adams et al.,1962), yet we were able to find in cases 3 and 4evidence of an apparent intracellular origin (orextension of very small lesions). It was not pos-sible to distinguish between small and mediumepithelioid fusions and multinucleate muscle cells.Of considerably more interest and possible

significance is the presence of widespread musclecell degeneration and regeneration unassociatedwith the immediate effects of the granuloma.Evidence of a generalized myopathy was appar-ent only in case 3 where muscle cell necrosis,phagocytosis, vacuolation, and regenerationwere readily identifiable, and even without thegranulomata would have constituted-takinginto account the myopathic EMG and greatlyelevated serum CPK-perfectly adequate groundsfor the diagnosis of polymyositis.We have been impressed, while studying the

literature, by the virtual absence of any specificaccount of a generalized myopathy in the docu-mented material: most authors comment uponthe presence of local fibre degeneration oratrophy occurring as a direct result of the granu-lomatous focus, but only Crompton and Mac-Dermott (1961) describe a case with histologicalevidence of a diffuse myopathic process (theircase 2), and it is interesting to note that thispatient's muscles examined at necropsy, while

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exhibiting a diffuse inflammatory infiltrate, didnot show any sign of the granulomatous processapparent in the biopsy sample taken four monthspreviously.Apart from the report by Lynch and Bansal

(1973), there do not appear to be any otherstudies of the histochemistry of granulomatousmyopathy: these authors noted the preservationof both types of muscle fibre, adjacent to andremote from the granulomatous foci, and theyconcluded that nothing useful could be learnedof the histochemical characteristics of those cellsmaking up granulomata. In our own series,histochemistry was performed on two of the fourcases, one of whom (case 4) was accepted ashaving sarcoidosis. In this subject, we were in-terested to observe the weak myosin ATP-asestaining of large multinucleate cells within somegranulomata, although we did not ascribe anyspecificity to this finding other than support forour contention that such cells cannot be posi-tively identified as either Langhans or myogenicgiant cells. Epithelioid cells stained intensely withoxidative enzyme methods, whether situatedwithin a muscle fasciculus or a septum.The histochemical pattern, on the other hand,

revealed, in both patients, an apparent loss of thenormal mosaic pattern, with significant numbersof enclosed type I cells in case 2, and a type IIfibre atrophy in case 4. Type II fibre atrophy isnow accepted as being a common and non-specific change, apparently reflecting the 'selec-tive susceptibility' of this cell species (Engel,1970). This finding is particularly common in thecollagenoses, including polymyalgia rheumaticaand rheumatoid arthritis (Brooke and Kaplan,1972), but its pathogenesis remains obscure. Intwo of our patients on whom nerve preparationswere made (cases 1 and 2), there was evidence ofterminal axonal degeneration, sometimes associ-ated with obvious involvement of nerve fibres bythe granulomatous process. These interesting anddifficult-to-interpret findings, however, unfor-tunately contribute little to the attempt toseparate, on morphological grounds, case 3 fromthe others, but there remains one outstandingdistinguishing feature, and that is the greatlyelevated serum CPK in this patient.Of the literature on granulomatous myopathy

due to sarcoidosis, only the papers by Talbot(1967), Gardner-Thorpe (1972), and Lynch and

Bansal (1973) provide details of the estimationsof this enzyme, and all were normal. We considerit significant that the considerable destruction ofmuscle cells by granulomatous foci, apparent inthe biopsy from case 4, was not associated with arise in serum CPK, while case 3, whose muscleshowed sparse, small foci of epithelioid cells,exhibited a very high enzyme level which fellrapidly on steroid therapy. This suggests that thenature of the pathological process is different,and that granulomata alone cannot contributesignificantly to muscle cell dysfunction.

In this re-examination of the biopsy materialfrom four cases of granulomatous myopathy, wehave to conclude that, despite its apparentacceptance, genuine granulomatous inflamma-tion complicating the picture of polymyositismust be a rare event. In a combined series ofsome 370 consecutive muscle biopsies examinedby us (Cape Town and Bristol), muscle granulo-mata were encountered in only the four casesdescribed, but, since so few patients with sus-pected sarcoidosis are investigated for skeletalmuscle lesions, no useful assumption can bemade about their incidence. Despite Gardner-Thorpe's (1972) assertion that other organ in-volvement can usually be found in muscularsarcoidosis if one's search is thorough enough,case 3 remains unresolved. Clinical and labora-tory studies failed to provide collateral evidenceof sarcoid, and we were unable to convince our-selves of that point upon which the diagnosis ofothers has hinged-namely, the reliable dis-tinction of myogenic and epithelioid giant cells,by whatever histological detail or method. It didappear, however, that the necrotizing element ofthis patient's myopathy, coupled with the highserum CPK, constituted reasonable grounds forconsidering a collagen disorder to be the under-lying pathological process of significance in hisillness.

We are grateful to Professor Walter Gordon, of GrooteSchuur Hospital, Cape Town, for permission to publishdetails from the first case, and to Professor H. W. Weber,of Stellenbosch University Medical School, for materialand clinical details from cases 3 and 4. Dr R. LangtonHewer kindly allowed us to use the details of case 2.

REFERENCES

Adams, R. D., Denny-Brown, D., and Pearson, C. M. (1962).Sarcoidosis (Boeck-Besnier-Schaumann disease). In Di-seases of Muscle, pp. 453-457. Hoeber: New York.

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Brooke, M. H., and Kaplan, H. (1972). Muscle pathology inrheumatoid arthritis, polymyalgia rheumatica and poly-myositis. Archives of Pathology, 94, 101-118.

Brun, A. (1961). Chronic polymyositis on the basis of sarcoi-dosis. Acta Psychiatrica et Neurologica Scandinavica, 36,515-523.

Crompton, M. R., and MacDermott, V. A. (1961). Sarcoi-dosis associated with progressive muscular wasting andweakness. Brain, 84, 62-74.

Dyken, P. R. (1962). Sarcoidosis of skeletal muscle-a casereport and review of the literature. Neurology (Minneap.),12, 643-651.

Engel, W. K. (1970). Selective and non-selective vulnerabilityof muscle fiber types. Archives of Neurology, 22, 97-117.

Gardner-Thorpe, C. (1972). Muscle weakness due to sarcoidmyopathy: 6 case reports and an evaluation of steroidtherapy. Neurology (Minneap.), 22, 917-928.

Harvey, J. C. (1959). A myopathy of Boeck's sarcoid. Ameri-can Journal of Medicine, 27, 356-363.

Hinterbuchner, C. N., and Hinterbuchner, L. P. (1964). Myo-pathic syndrome in muscular sarcoidosis. Brain, 87, 355-366.

Longcope, W. T., and Freiman, D. G. (1952). Study of sar-coidosis based on combined investigations of 160 casesincluding 30 autopsies from Johns Hopkins Hospital andMassachusetts General Hospital. Medicine (Balt.), 31, 1-132.

Lynch, P. G., and Bansal, D. V. (1973). Granulomatouspolymyositis. Journal of the Neurological Sciences, 18, 1-9.

Myers, G B., Gottlieb, A. M., Mattman, P. E., Eckley, G. M.and Chason, J. L. (1952). Joint and skeletal muscle mani-festations in sarcoidosis. American Journal of Medicine, 12,161-169.

Namba, T., Brunner, N. G., and Grob, D. (1974). Idiopathicgiant cell polymyositis. Archives ofNeurology, 31, 27-30.

Phillips, R. W., and Phillips, A. M. (1956). The diagnosis ofBoeck's sarcoid by skeletal muscle biopsy. Archives ofInternal Medicine, 98, 732-736.

Powell, L. W. (1953). Sarcoidosis of skeletal muscle-reportof 6 cases and review of the literature. American Journal ofClinical Pathology, 23, 881-889.

Ricker, W., and Clark, M. (1949). Sarcoidosis. A clinico-pathologic review of 300 cases, including 22 autopsies.American Journal of Clinical Pathology, 19, 725-749.

Scadding, J. G (1967). Sarcoidosis, pp. 22-25. Eyre andSpottiswoode: London.

Symmers, W. St. C. (1951). Localised tuberculoid granulomasassociated with carcinoma. Their relationship to sarcoi-dosis. American Journal of Pathology, 27, 493-521.

Talbot, P. S. (1967). Sarcoid myopathy. British Medical Jour-nal, 4, 465-466.

Wallace, S. C., Latte, R., Malia, J. P., and Ragan, C. (1958).Muscle involvement in Boeck's sarcoid. Annals of InternalMedicine, 48, 497-511.

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Granulomatous relationship to · Granulomatous myopathy: its relationship to sarcoidosis andpolymyositis FIG. 1 Case 1. Section ofquadriceps muscle showing a typical granuloma with