310 Ann Rheum Dis 2001;60:310–312

MASTERCLASS Ann Rheum Dis: first published as 10.1136/ard.60.4.310 on 1 April 2001. Downloaded from An unexpected cause of muscle pain in diabetes

L Silberstein, K E Britton, F P Marsh, M J Raftery, D D’Cruz

Abstract She was given intravenous albumin and diuret- Diabetic muscle infarction is a rare ics. Although no specific treatment for the condition which may present to a rheuma- swelling of the leg was prescribed, the symp- tologist. It was first reported in 1965. Two toms gradually improved. She did, however, illustrative cases are described here and develop contractures in the muscles the mechanisms of pathogenesis dis- requiring physiotherapy. At the time of dis- cussed. Analysis of the published data, charge she could walk with a stick. results of the muscle biopsies, and a She presented again five months later with a technetium-99m sestamibi scan suggest one week history of painful swelling of the that the condition, which occurs against a opposite thigh. On this occasion, there were no background of diabetic microangiopathy, precipitating factors. The medial compartment can be triggered by an ischaemic event of the right thigh was markedly swollen. There and causes extensive muscle necrosis was no neutrophilia or CK rise. A CT scan through hypoxia-reperfusion injury and showed generalised swelling of the anterior and compartment syndrome. medial groups of muscle and connective tissue (Ann Rheum Dis 2001;60:310–312) from the distally. The patient underwent surgical debridement of the mass. The sartorius muscle was necrotic Diabetic muscle infarction is a rare cause of and was excised. Swollen but viable muscles in acute severe muscle pain in patients with the adductor and quadriceps compartments diabetes mellitus. The diVerential diagnosis were noted. Histological examination showed includes focal or systemic myositis, localised widespread necrosis. The vessels had lumenal abscess, haematoma, deep venous thrombosis, stenosis and calcification consistent with long- osteomyelitis, and a muscle tumour (sarcoma standing diabetes. or lymphoma). We describe two illustrative In view of the worsening renal failure, patients and discuss the investigations and pos- peritoneal dialysis was started. She remained http://ard.bmj.com/ sible pathogenesis of this condition. well for the next four years, but her condition later deteriorated and she died from a compli- Case 1 cation of peritoneal dialysis. A 46 year old West Indian woman with a 14 year history of type II diabetes mellitus complicated by diabetic nephropathy and pro- Case 2

liferative retinopathy presented to a local A 55 year old Afro-Caribbean man with a 24 on September 27, 2021 by guest. Protected copyright. hospital with a painful swollen left leg after an year history of type II diabetes complicated by insulin injection into the left peripheral neuropathy, proliferative retinopa- area. Deep venous thrombosis was excluded by thy, and nephropathy requiring continuous Doppler ultrasound, and a computed tomogra- ambulatory peritoneal dialysis (CAPD) pre- phy (CT) scan showed swelling of the left vas- sented to his local hospital with a tender swell- tus medialis muscle. The erythrocyte sedimen- ing on his left upper lateral thigh. Serial blood tation rate (ESR) was raised at 130 mm/1st h, and fungal cultures, cryoglobulins, ANA, anti- St Bartholomew’s and the Royal London antineutrophil cytoplasmic antibodies dsDNA, and ANCA were all negative. A biopsy School of Medicine (ANCA), antinuclear antibodies (ANA), and showed striated muscle exhibiting infarction and Dentistry, London, rheumatoid factor were negative. Muscle bi- and infiltration by neutrophils. The UK opsy showed chronic inflammation. She re- showed lumenal thrombosis and organisation, L Silberstein ceived treatment with steroids and antituber- and small arterioles showed fibrinoid necrosis. K E Britton culous drugs, but did not improve. Six weeks Stains for bacteria and fungi were negative. F P Marsh M J Raftery later she was transferred to this hospital for The patient was given fusidic acid and D D’Cruz further assessment. flucloxacillin and gradually improved. Clinically she was afebrile and markedly Two months later he re-presented with pain- Correspondence to: overloaded with fluid. There was swelling and ful well defined swelling in the left thigh. C Dr D D’Cruz, The Lupus Research Unit, The Rayne tenderness of the left compart- reactive protein (CRP) on admission was 60 Institute, St Thomas’s ment and proximal weakness of the left leg. mg/l (reference range 0–10 mg/l) and rose to Hospital, Lambeth Palace Investigations showed no neutrophilia, creatine 105 mg/l one week later. He was given intra- Road, London SE1 7EH, kinase (CK) 202 IU/l (reference range 0–170 venous flucloxacillin and ciprofloxacin for four UK IU/l), ESR 97 mm/1st h, and albumin 16 g/l. A weeks, but failed to improve and the entire Accepted 20 October 2000 renal biopsy confirmed diabetic nephropathy. mass was excised. Histological findings were

www.annrheumdis.com Muscle pain in diabetes 311

two weeks after discharge showed increased blood flow to the aVected area of the muscle with slightly increased tracer uptake in the soft tissues and normal uptake in the skeletal

system. Ann Rheum Dis: first published as 10.1136/ard.60.4.310 on 1 April 2001. Downloaded from The patient was readmitted a month later with worsening pain in the right thigh. Serial CK measurements remained normal. He was given a small dose of steroids and his condition improved. A 99mTc-sestamibi scan showed increased vascularity at the lesion in the right thigh, seen on the bone scan, and the presence of living muscle (fig 2). Over the next three months he was admitted several times with infection of the fascial spaces of the hand and CAPD peritonitis; he died from the complications of diabetes.

Discussion

Figure 1 T2 weighted magnetic resonance image. An Diabetic muscle infarction is a rare complica- increased signal density in the right can be seen. tion of diabetes, which should be suspected in any diabetic subject with atypical severe muscular pain. It was first described in 1965 by Angerall and Stener as a “tumoriform focal muscular degeneration”1 and since then has been reported in a total of 86 patients.1–33 Sixty five patients had type I diabetes, 19 patients had type II diabetes, and in two patients the type was not specified. The male/female ratio was almost equal (44/42), with an age range of 19–81 years. Most patients had longstanding diabetes and extensive end-organ damage due to microvascular disease. The condition presents as an atraumatic swelling of the limb, commonly the thigh. The onset of pain is usually gradual, but can be sudden. The swelling is exquisitely tender. It

resolves within a few weeks, but frequently http://ard.bmj.com/ recurs. The white cell count and the level of CK are normal or slightly raised. Muscle biopsy typically shows large confluent areas of muscle necrosis and oedema.2 The best imag-

ing results are with T2 weighted MRI scans, Figure 2 Dynamic 99mTc-sestamibi scan. Increased tracer which have a fairly characteristic, but non-

uptake at the site of the lesion in the right thigh is seen. specific appearance showing the absence of a on September 27, 2021 by guest. Protected copyright. discrete mass and increased signal within the similar to the previous biopsy, but arteriolar aVected muscle.3 fibrinoid necrosis was more marked. The diVerential diagnosis includes a muscle Ten months later the patient was admitted tumour (sarcoma or lymphoma), localised with pain and swelling of the opposite thigh, abscess, haematoma, focal or systemic myosi- which had developed over a few weeks. On tis, deep venous thrombosis, and osteomyelitis. examination he had a large discrete swelling on The management should include bed rest, the lateral aspect of the right thigh which was analgesia, tight metabolic control, and physio- warm and exquisitely tender. He had a mild therapy.24 neutrophilia, markedly raised CRP of 132 mg/l, Various mechanisms of pathogenesis have but normal CK. A plain x ray examination of been proposed. Earlier reports focused on dia- the right was normal, apart from wide- betic microangiopathy, atheromatosis,1 and spread vascular calcification. Doppler ultra- embolisation of atheromatous material from sound showed no evidence of a deep vein ulcerated aortic plaques as the causes of muscle thrombosis. A magnetic resonance imaging infarction.5 In the presence of diabetic micro- (MRI) scan of the showed an area of vascular disease, a thromboembolic event is increased signal density in the right vastus lat- more likely to lead to infarction because of eralis compartment consistent with oedema of impaired collateral circulation.6 However, later the muscle (fig 1). He was treated with intra- reports showed that only a minority of cases venous antibiotics and analgesia. His symp- had a vascular occlusion which would corre- toms gradually improved, he no longer re- spond to the extent of muscle necrosis. The quired opiates, and could walk with a stick. A above concept was therefore modified, suggest- technetium (Tc) labelled bone scan performed ing that an initial ischaemic event itself does

www.annrheumdis.com 312 Silberstein, Britton, Marsh, et al

not cause infarction but leads to it by produc- 4 Jelinek JS, Murphey MD, Aboulafia AJ, Dussault RG, Kap- lan PA, Snearly WN. Muscle infarction in patients with ing muscle oedema which increases the pres- diabetes mellitus: MR imaging findings. Radiology 1999; sure within a fascial compartment and causes 211:241–7. 7 5 Banker BQ, Chester CS. Infarction of thigh muscle in the further ischaemia. diabetic patient. Neurology 1973;23:667–77.

We suggest that hypoxia-reperfusion injury 6 Becker BN, Otley CC, McNeill DB, Weintraub ID, Harrel- Ann Rheum Dis: first published as 10.1136/ard.60.4.310 on 1 April 2001. Downloaded from son JM. Microangiopathic ischaemic myopathy of semi- may have an important role in the pathogenesis membranosus muscle in patient with diabetes mellitus. of diabetic muscle infarction. The likely Diabetes Care 1992;15:586–7. sequence of events leading to muscle necrosis is 7 Chester CS, Banker BQ. Focal infarction of muscle in diabetics. Diabetes Care 1986;9:623–20. as follows. Compartment syndrome, precipi- 8 Aboulafia AJ, Monson DK, Kennon RE. Clinical and radio- tated by a small thrombotic/embolic event or logical aspects of diabetic muscle infarction. Rational approach to diagnosis and treatment. J Bone Joint Surg Br intramuscular insulin injection, produces is- 1999;81:323–6. chaemic muscle damage. This leads to a potent 9 Eady JL, Cobbs KF. Diabetic muscle infarction. 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