J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.48.3.270 on 1 March 1985. Downloaded from Journal ofNeurology, Neurosurgery, and Psychiatry 1985;48:270-273

Short report Inclusion body myositis: a case with associated collagen vascular disease responding to treatment

RJM LANE, JJ FULTHORPE, P HUDGSON UK From the Regional Neurological Centre, Newcastle General Hospital, Newcastle-upon-Tyne, elec- SUMMARY Patients with inclusion body myositis demonstrate characteristic histological and muscle and are generally considered refractory to treatment. tronmicroscopical abnormalities in autoimmune A patient with inclusion body myositis is described with evidence of associated disease, who responded to steroids.

muscles. He felt that his legs were quite normal. He denied guest. Protected by copyright. The diagnosis of inclusion body myositis depends symptoms. There was no relevant family or of the characteristic any sensory ultimately on the demonstration drug history. dis- intracytoplasmic and intranuclear filamentous inclu- On examination, he had a prominent bluish/purple sions, and cytoplasmic vacuoles originally described colouration of the knuckles, thickening of the skin on the by Chou in 1968.' However, reviews of reported dorsum of the hands and a slight heliotrope facial rash. The features which facial muscles were slightly wasted and he had marked cases have also emphasised clinical sternomastoids, deltoids, appear to distinguish inclusion body myositis from weakness and wasting of the Prominent among spinatti, biceps and triceps, with relative preservation of other forms of polymyositis.2-7 distal muscles. All upper limb reflexes were grossly these are the lack of associated skin changes or other bulk, power and to diminished or absent. In contrast, the stigmata or collagen vascular disease and failure reflexes in the lower limbs were entirely normal. All mod- respond to steroids. alities of sensation were intact throughout. We report a patient who, while showing the his- The erythrocyte sedimentation rate was consistently tological and electronmicroscopic features of inclu- normal (10-12 mm/hr) as were the serum muscle enzyme sion body myositis had the typical rash of der- levels (CK 33.5 u/l-normal <50; aldolase 1.4-normal <5). matomyositis, an autoimmune diathesis with pul- Autoantibody screen showed positive immunofluorescence to thyroid cytoplasmic antigen but was negative to gastric monary involvement, and unequivocal clinical smooth muscle to steroids. parietal cell, nuclear, mitochondrial and improvement in response antigens. The Rose-Waaler test was negative. A chest radiograph showed reticular and micronodular Case report shadowing in both lungs, particularly at the bases. Vital http://jnnp.bmj.com/ 1 of value), FEV,/FVC was referred in May capacity was 3-1 (82% predicted DC (X23980), a 53-year-old man, was 0-63 (normal >0.75) and single-breath CO transfer 1977 with a six month history of dyspnoea on exertion, a of expected value, at 3-11 the dorsum of his factor was reduced to 33% purple discolouration of the skin over mmol min-' kPa-'. The arterial blood gases were normal fingers and hands, arthralgia involving the metacar- tests were considered con- and Raynaud's at rest. The pulmonary function pophalangeal joints of the right hand, sistent with the chest radiograph findings, indicating diffuse phenomenon. He denied dysphagia but had lost 4-5 kg in aware of interstitial pulmonary fibrosis. weight over this period. He had also become Motor and sensory nerve conduction velocity measure-

shoulder-girdle on September 29, 2021 by considerable wasting of his upper arms and ments were normal throughout. Concentric needle elec- tromyograms of the right biceps, triceps, quadriceps and Address for reprint requests: Dr RJM Lane, Regional Neurological tibialis anterior showed no spontaneous activity, and voli- Centre, Newcastle General Hospital, Westgate Road, Newcastle tional activity was also normal (Dr DD Barwick). upon Tyne, NE4 6BE, UK. Muscle biopsies were obtained from the left quadriceps was virtually 1984. and left deltoid. Muscle from the quadriceps Received 23 March 1984 and in revised form 15 August from moderate, non-specific Type 2 fibre Accepted 18 August 1984. normal, apart 270 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.48.3.270 on 1 March 1985. Downloaded from Inclusion body myositis: a case with associated collagen vascular disease responding to treatment 271

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Fig (a) Section from left deltoid showing perivascular and interstitial inflammatory cell infitration, marked increase in variation in fibre diameters and replacement ofmuscle with fat andfibrous tissue. (H & E. IOO,u marker). (b) Representative area from (a) showing sub-sarcolemmal vacuoles with basophilic inclusions (arrows). (H & E. 5O,u marker). (c) Intranuclearfdaments in a nearby nucleus. (O-5,u marker). (d) Membranous whorls forming aggregates, corresponding to the basophilic masses in a http://jnnp.bmj.com/ sub-sarcolemmal vacuole. (1 ,u marker). atrophy. However, the deltoid biopsy specimen showed filaments in random orientation. The filaments measured marked fibrosis with striking perivascular and endomysial 20 nm in diameter. In addition, numerous osmiophilic lymphocytic infiltrations, and gross variation in muscle membranous whorls were observed (fig (d)), correspond- fibre diameters (fig (a)). Some of the atrophic fibres were ing to the basophilic masses in the vacuoles seen by light was angulated, but there no evidence of fibre type grouping microscopy. on September 29, 2021 by or grouped fibre atrophy on histochemical stains. Under The patient was treated with prednisone 20 mg tds and high power, some 5% of the fibres showed conspicuous azathioprine 50 mg tds. On review one month later, he felt vacuoles, some containing basophilic masses at their much better and his strength had improved. Over the suc- peripheries (fig (b)). These could be seen in more detail in ceeding month his skin rash gradually faded and the the toluidine blue-stained sections prepared for electron- steroids were reduced to 30 mg daily. This resulted in a microscopy. Electronmicroscopic examination revealed return of his symptoms and progressive exertional dysp- the presence of both cytoplasmic and intranuclear (fig (c)) noea. Reinstitution of prednisone 20 mg tds again pro- J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.48.3.270 on 1 March 1985. Downloaded from 272 Lane, Fulthorpe, Hudgson duced significant improvement to his arm and shoulder ances, however, are characteristic. There are cyto- strength and reduction of his dyspnoea. Further improve- plasmic and intranuclear masses of randomly orien- ment in breathing followed addition of a beclomethasone tated filaments, reported to be between 10-25 nm in inhaler to his regime. Attempts at steroids reduction some diameter and about 1-3,u in length, and membran- five months after starting treatment once more resulted in ous osmiophilic whorls within the vacuoles, which deterioration, particularly in his breathing but his condi- to correspond to the basophilic masses tion had stabilised after six months of treatment on high- are believed dose steroids. seen by light microscopy. Unfortunately, in February 1978 he suddenly developed Our patient thus conforms to the histopathologi- a right hemiplegia and dysphasia and eventually suc- cal criteria for the diagnosis of inclusion body cumbed to a suppurative bronchopneumonia. myositis. However, previous reviews have emphas- ised the absence of skin changes or other stigmata of Discusson collagen vascular disease in most cases and response to treatment in inclusion body myositis has been Since Chou originally described "myxovirus-like almost uniformly unsuccessful. The histopathologi- structures and accompanying nuclear changes in a cal changes of inclusion body myositis have been patient with chronic polymyositis", inclusion body reported, however, in patients with der- myositis has emerged as an apparently distinct matomyositis8 9 scleroderma,'0 coeliac disease,'" and pathological entity. Furthermore, the clinical fea- Sjogren's syndrome.'2 In addition several authors tures in the majority of more than forty cases have reported modest clinical response to administ- reported to date, have conformed to a pattern dis- ration of steroids;45"1 but in other instances no tinct from that normally encountered in autoim- treatment was given.34 Our patient undoubtedly had mune polymositis.2-7 a collagen vascular disorder, with the typical skin Typically, inclusion body myositis presents with changes of dermatomyositis, thyroid cytoplasmic slowly progressive, sometimes asymmetrical, pain- antibodies and a chest radiograph and pulmonary guest. Protected by copyright. less weakness which often affects the distal limb diffusion disorder indicating interstitial pulmonary muscles as much, or even more prominently, than fibrosis of the type sometimes encountered in lupus the proximal. Facial muscle weakness and dysphagia erythematosus or systemic sclerosis. He showed sub- may be early manifestations. There has been some stantial improvement in muscle strength with steroid debate regarding the sex ratio in inclusion body treatment and relapsed transiently when the dose myositis. Reviews of reported cases revealed a con- was decreased. siderable male predominance, contrasting with the Clearly therefore, this case calls into question the female predominance in autoimmune myositis.34 status of inclusion body myositis as a separate The condition tends to affect an older population nosological entity. It also emphasises the importance than autoimmune polymyositis, although it may also of at least attempting therapy in this condition. occur in younger patients, who are more often female, and a bimodal age-sex distribution has been We thank Dr C Strang for allowing us to report this suggested.6 Serum muscle enzymes are generally case. Dr Lane is a Wellcome Senior Research Fel- normal, or only moderately raised. low in Clinical Sciences. Electromyography often reveals predominant changes of denervation with fibrillations and large References prolonged duration polyphasic potentials with late 'Chou SM. Myxovirus-like structures and accompanying

on volitional activity, but in some cases http://jnnp.bmj.com/ components nuclear changes in chronic polymyositis. Arch Pathol the changes may be predominantly myopathic. 1968;86:649-58. Muscle biopsy findings in inclusion body myositis 2 Carpenter S, Karpati G, Heller I, Eisen A. Inclusion are said to be diagnostic.2-7 By light microscopy, body myositis: A distinct variety of idopathic 5-10% of the fibres reveal single or multiple inflammatory myopathy. Neurology (Minneap) membrane-lined vacuoles, often containing 1978;28:8-17. basophilic masses, and occasionally eosinophilic 3 Danon MJ, Reyes MG, Perurena OH, Masden JC, Man- inclusions. The vacuoles are typically acid phosphat- aligod JR. Inclusion-body myositis. A corticosteroid- resistant idiopathic inflammatory myopathy. Arch ase negative, indicating that they are probably not on September 29, 2021 by autophagic. In addition to necrosis, phagocytosis Neurol 1982;39:760-4. 4 Julien J, Vital CL, Vallat JM, Lagueny A, Sapina D. and replacement of muscle by fat and fibrous tissue Inclusion body myositis. Clinical biological and ultras- in chronic cases, most cases of inclusion body tructural study. J Neurol Sci 1982;55: 15-24. myositis reveal lymphocytic inflammatory cell infil- 5 Mikol J, Felten-Papaiconomou A, Ferchal F, et al. trates, although these may be sparse or even absent Inclusion-body myositis: Clinicopathological studies in some cases. The electronmicroscopic appear- and isolation of an adenovirus Type 2 from muscle J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.48.3.270 on 1 March 1985. Downloaded from

Inclusion body myositis: a case with associated collagen vascular disease responding to treatment 273 biopsy specimen. Ann Neurol 1982;55:15-24. Sato T, Tsubaki T. Characteristics of virus-like struc- 6 Sawchak JA, Kula RW, Sher JH, Shafig SA, Clark LM. tures in polymyositis. ibid, 280-283. Clinicopathologic investigations in patients with inclu- '° Marie L. (1980) Contribution a l'Etude d'une Nouvelle sion body myositis. Neurology (NY) 1983;33: (suppi Entite Clinico-pathologique: la myosite A 2), 237: (abs.) inclusions-a propos d' une Observation associee a 7Eisen A, Berry K, Gibson G. Inclusion body myositis une Scl6rodermie Generalisee, un Syndrome de (IBM): Myopathy or neuropathy? Neurology (NY) Kleinefelter. These, Paris-Sud. 1983;33: 1109-114. Hughes JT, Esiri MM. Ultrastructural studies in human Chou JM. (1972). Prospects of viral etiology in polymyositis. J Neurol Sci 1975;25:347-60. polymyositis. In: BA Kakulas, ed. 2nd International 12 Chad D, Good P, Adelman L, Bradley WG, Mills J. Congress on Muscle Diseases Part 2. Amsterdam: Inclusion body myositis associated with Sjogren' s syn- Excerpta Medica, 17-28. drome. Arch Neurol 1982;39:186-8. guest. Protected by copyright. http://jnnp.bmj.com/ on September 29, 2021 by