A Case of Inclusion Body Myositis with Benign Monoclonal Gammopathy Successfully Responding to Repeated Immunoabsorption

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J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.68.2.230 on 1 February 2000. Downloaded from 230 J Neurol Neurosurg Psychiatry 2000;68:230–233

SHORT REPORT

A case of inclusion body myositis with benign monoclonal gammopathy successfully responding to repeated immunoabsorption

T Nakayama, E Horiuchi, T Watanabe, S Murayama, H Nakase

Abstract al postulated the diagnostic criteria of inclusion A 69 year old woman with inclusion body body myositis.1 They diagnosed patients who myositis is described. She presented with exhibited all the above pathological features as benign monoclonal gammopathy. She was deﬁnite inclusion body myositis and if the resistant to steroid therapy, but responded muscle only showed inﬂammation without the to repeated immunoabsorption. Up to other pathological features, as possible inclu- now, there has been no established sion body myositis. Dalakas et al reported that therapy for inclusion body myositis, in- inclusion body myositis was often associated cluding IVIg. It is suggested that immuno- with monoclonal gammopathies.2 We exam- absorption could be an alternative therapy ined a 69 year old woman with inclusion body for inclusion body myositis, when it was myositis associated with IgG-ã, BJP-ã type accompanied by immunological abnor- benign monoclonal gammopathy, which was mality. successfully treated with repeated immunoab- (J Neurol Neurosurg Psychiatry 2000;68:230–233) sorption.

Keywords: inclusion body myositis, benign monoclonal gammopathy, steroid therapy, immunoabsorption, IgG Case report A 69 year old woman developed muscle weakness from 66 years of age. There was no family Inclusion body myositis is a common acquired history of neuromuscular disorders and no myopathy in patients older than 50. The char- consanguinity. She was employed at a clothing acteristic pathological features are inflamma- shop as a deskworker. History disclosed tion, vacuolated muscle fibres, amyloid depos- dysaesthesia on the palmer side of her right its and 15–18 nm tubulo filaments.1 Mendell et second to fourth fingers at 67. She was http://jnnp.bmj.com/ Department of Neurology, Toranomon 50 mg Hospital, 2–2–2, 30 mg Toranomon, Prednisolone 20 mg Minato-ku, Tokyo 105–8470, Japan T Nakayama Methotraxate 5 mg E Horiuchi

T Watanabe Immunoabsorption on September 30, 2021 by guest. Protected copyright. H Nakase Standing up Department of with assistance Impossible Impossible Impossible Possible Neurology, Division of Neuroscience, MMT of glu max 2– 2– 2+ 3– Graduate school of Medicine, University of Tokyo, 7–3–1, Hongo, Hamstrings 2+ 2– 2+ 3 3+ Bunkyo-ku, Tokyo 113–0033, Japan Serum IgG (mg/dl) 2337 877 650 616 500 S Murayama

Correspondence to: M-protein (mg/dl) 1017 761 725 468 404 Dr H Nakase, Department of Neurology, Urine (+) (+) (–) (–) (–) (–) Toranomon Hospital, 2–2–2, M-protein (mg/dl) Toranomon, Minato-ku, Tokyo 105–8470, Japan email [email protected] % Creatine-urine 50% 48% 49% 51%

Received 5 March 1999 and 12/96 5/97 6/97 7/97 8/97 in revised form 15 July 1999 Figure 1 Clinical course of the patient. MMT=Manual muscle strength test; arrows indicate immunoabsorption Accepted 16 August 1999 treatments; clinical improvements are underlined. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.68.2.230 on 1 February 2000. Downloaded from A case of inclusion body myositis with benign monoclonal gammopathy 231 http://jnnp.bmj.com/

Figure 2 (A) Haematoxylin-eosin stain. (×33); Increase of connective tissue, variation in muscle fibre size, round muscle fibres in some groups, and increase of intermyonuclei are found. Some basophilic round nuclei in some regeneration fibres and rimmed vacuoles in a few muscle fibres are present. One basophilic fibre mononuclear infiltration is seen. (B) Muscle MRI of the right thigh muscle; T2 weighted images. The left image shows muscle atrophy in the thigh before prednisolone

therapy. After repeated immunoabsorption, progression of muscle atrophy is not shown in the ight image. on September 30, 2021 by guest. Protected copyright. diagnosed with carpal tunnel syndrome from ing results: neck flexion 3, extension 4, arm 4, the delayed distal latency of the right median forearm 4, hip extension 3-, hip flexion 2+, nerve shown in a nerve conduction study. knee extension 2+, knee flexion 2-, ankle Endoscopic ligament resection was performed dorsiflexion 4, ankle planter flexion 5-), and and her dysaesthesia disappeared. dysaesthesia at the bilateral palmer site of the At 66 years of age, she noticed weakness in second to fourth fingers. Laboratory studies her thigh muscles. At 67, she needed support showed the following; creatine kinase and standing up from a chair. At 68, she went up lactate dehydrogenase were moderately in- stairs one step at a time and she walked more creased to 550IU/l and 400IU/l, homogeneous slowly than before. Later she could not go up type of antinuclear antibody was detected at 40 stairs and needed help with housework. She times dilution, IgG and BJP monoclonal gam- could not stand up from a squat position, so maglobulins were detected. IgG was 650 she was admitted to our hospital in September mg/dl, IgA was 78.2 mg/dl, and IgM was 114 1996. mg/dl.. Urinalysis gave a %creatine : creatinine On admission, her weight had decreased by 6 ratio of 50%. Bone marrow aspiration showed kg over 3 years. Neurological examination hypocellular bone marrow and its plasma cell showed atrophy of her hip and hamstring mus- concentration was 8.2%. Bone radiography cles, proximal dominant muscle weakness showed osteolytic lesions on the left temporal (manual muscle strength test gave the follow- bone, the right fifth and sixth ribs and the left J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.68.2.230 on 1 February 2000. Downloaded from 232 Nakayama, Horiuchi, Watanabe, et al

second and third ribs. Therefore, we concluded similar to that before therapy; progression of that her gammopathy was benign monoclonal muscle atrophy was not shown (fig 1 B). gammopathy of uncertain significance (MGUS) from the Southwestern Oncology Group criteria for multiple myeloma. Discussion Needle electromyography showed early re- Many studies have reported myopathy associ- cruitment of all examined muscles and at ated with MGUS or multiple myeloma voluntary contraction polyphasic, low ampli- Teleman-Toppet et al reported myositis with 3 tude, and short duration unit potentials were perifascicular atrophy associated with MGUS. revealed. At rest, a fibrillation and positive Kiprov et al performed combination therapy of sharp wave was shown. We concluded that plasma exchange and treatment with pred- these were myogenic changes. Muscle CT nisolone and cyclophosphamide for three cases showed severe atrophy of the bilateral gluteus of inflammatory myositis with perifascicular 4 maximum muscle and the hamstrings. Moder- atrophy associated with IgG-ã type MGUS. ate atrophy of the paraspinal and bilateral pos- The treatment produced clinical improvement terior tibial muscles was also found. in all three patients. Examination of muscle Left semitendinosus muscle biopsy was per- biopsy specimens by direct immunofluores- formed. Haematoxylin-eosin staining showed cence showed linear deposits of IgG-ã along increased connective tissue, variation in muscle the sarcolemmal basement membrane. Muscle fibre size, round muscle fibres in some groups, biopsy specimens after treatment showed no and increased intermyonuclei. We found ba- immune deposits. Sheehan-Dare and Simmons sophilic round nuclei in some regenerating treated amyloid myopathy in association with fibres; therefore, internuclear inclusions were IgG-ã chain myeloma by melphalan and 5 suspected (fig 1 A). Immunocytochemistry prednisolone which resulted in the remission showed mononuclear infiltration around one of both the myeloma and myopathy. Eymard et basophilic fibre, prominent CD3 positive T al reported that plasmapheresis and immuno- cells, and dominant CD 8 positive cells. suppressive agents produced partial clinical Gomori-trichrome stain showed rimmed vacu- improvement of late onset rod myopathy with 6 oles in a few muscle fibres. Tiny deposits of MGUS, however, therapy interruption led to tau-positive profiles were detected. Character- remission. As shown above, reduction of serum istic filamentous inclusions were not disclosed monoclonal gammaglobulin by chemotherapy, by electron microscopy in the cytoplasm or plasma exchange, or immunoabsorption im- myonuclei. We concluded that the patient had proved the myositis. inclusion body myositis by the clinical criteria Dalakas et al reported that inclusion body Mendel .2 myositis was often associated with monoclonal et al 2 Prednisolone (50 mg/day) was given from gammaglobulin, but there was no report of December 1996. Muscle power increased, but plasma exchange or immunoabsorption to on tapering prednisolone the power decreased inclusion body myositis with gammopathy. again. The %creatine : creatinine ratio of about Chad et al reported that plasma exchange pro- 50% did not alter with the tapering of duced no improvement of inclusion body 7 prednisolone. Steroid myopathy was excluded. myositis in Sjögren’s syndrome but no control In April 1997, prednisolone was tapered to study was performed. Dalakas et al concluded 8 http://jnnp.bmj.com/ 30 mg/day and methotraxate at 5 mg/week was that plasmapheresis was not helpful for inclu- administered. Her hip flexor power was de- sion body myositis because plasmapheresis was creased to 2- and we concluded that immuno- ineVective in a double blind controlled study suppressive therapy with prednisolone and conducted in polymyositis and dermatomyosi- methotraxate had little eVect. tis. Dalakas reported that IVIg treatment Next we examined monoclonal gammopa- produced only modest improvement for inclu- 9 thy; we started immunoabsorption at the end of sion body myositis and the eYcacy of IVIg 910 May 1997, 2–3 times a month. After the fourth remains debatable. on September 30, 2021 by guest. Protected copyright. absorption, monoclonal gammaglobulin in the We examined inclusion body myositis with urine disappeared and that in serum reduced. MGUS. Repeated immunoabsorption reduced After the seventh absorption her knee flexion urinary and serum monoclonal gammaglobulin power was increased to 3-. After the ninth and her muscle weakness was improved. The absorption, she could flex the knee at a right good response to immunoabsorption was simi- angle, and keep her leg up in a prone position; lar to that of myositis with monoclonal with assistance she could stand up from a chair, gammaglobulin. It would be useful to look hard and her creatine kinase concentration reduced for immunological abnormalities such as to 50IU/l. We tapered prednisolone gradually MGUS or multiple myeloma in patients with to 20 mg/day from the the seventh absorption inclusion body myositis and, if there, to onwards and she showed no progression of consider immunoabsorption or plasmaphore- muscle weakness. She was discharged from our sis. hospital at the end of August 1997 and we continued absorption once a month, because 1 Griggs RC, Askanas V, DiMauro S, et al. Inclusion myositis and myopathies. Ann Neurol 1995;38:705–13. monoclonal gammaglobulin in her urine reap- 2 Dalakas MC, Illa I, Gallardo E, et al. Inclusion bosy myosi- peared 3 to 4 weeks after absorption. Her clini- tis and paraproteinemia: incidence and immunopathologic cal course is shown below (fig 2) In April 1998, correlations. Ann Neurol 1997;41:100–4. 3 Telerman-Toppet N, Wittek M, Bacq M, et al. Benign she had maintained the strength of her monoclonal gammopathy and relasping polymyositis. Mus- cle Nerve 1982;5:490–1. hamstring muscles. Muscle MRI of her thigh 4 Kiprov DD, Miller RG. Polymyositis associated with mono- muscle showed muscle atrophy of the thigh clonal gammopathy. Lancet 1984;ii:1183–6. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.68.2.230 on 1 February 2000. 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5 Sheehan-Dare RA, Simmons AV. Amyloid myopathy and 8 Dalakas MC. Clinical, immunopathologic, and therpeutic myeloma: response to treatment. Postgrad Med J 1987, considerations of inﬂamatory myopathies. Clin Neurophar- 63:141–2. macol 1992;15:327–51. 6 Eymard B, Brouet JC, Collin H, et al. Late-onset rod 9 Dalakas MC, Sonies B, Dambrosia J, et al. Treatment of myopathy associated with monoclonal gammopathy. Neu- inclusion-body myositis with IVIg: a double-blind, placebo- romusc Disord 1993;3:557–60. controlled study. Neurology 1997;48:712–16. 7 Chad D, Good P, Adalman L, et al. Inclusion body myositis 10 Barohn RJ. The therapeutic dilemma of inclusion body associated with Sjögren syndrome. Arch Neuro 1982;39:186. myositis. Neurology 1997;48:567–8. http://jnnp.bmj.com/ on September 30, 2021 by guest. Protected copyright.