Feature Article

Diabetic Myonecrosis: An Indian Experience

Dayanidhi Meher, MD, DM, Vivek Mathew, MD, DM, Raiz Ahmed Misgar, MD, DM, Satinath Mukherjee, MD, DM, Subhankar Chowdhury, DM, MRCP, and Jyothi Chowdhury, MBBS, DTM&H

iabetic myonecrosis is an perception test revealed moder- muscles mainly in its lower half. under-recognized and ate . There A post-gadolinium contrast study Dunder-reported complication was no evidence of nephropathy or showed mild enhancement, and of longstanding . In this case retinopathy. there was no area of pus collec- series, we have attempted to report Laboratory investigations tion. Adjacent subcutaneous tissue the clinical and radiological revealed poor glycemic control was edematous. A muscle characteristics of six patients with (fasting plasma glucose [FPG] 327 revealed infiltration of lymphocytes diabetic myonecrosis along with a mg/dl, postprandial plasma glucose and plasma cells. There was evidence review of existing literature. [PPG] 417 mg/dl) and dyslipidemia of degeneration and in the (total cholesterol 206 mg/dl, triglyc- muscle fibers (Figure 2). Case Report 1 erides 156 mg/dl, LDL cholesterol She was managed with bed rest, A 53-year-old woman presented with 141 mg/dl, and HDL cholesterol 34 , and optimal glycemic painful swelling of the right thigh that mg/dl). Her serum control. The pain and swelling had been present for the past 9 days. (CK) was 311 U/l (normal < 167 U/l), resolved completely within 4 weeks. The pain was of acute onset, dull- and her serum lactic dehydrogenase She came to us again 2 years later aching, and constant and was suf- (LDH) was 394 U/l (normal 240–480 with recurrence of myonecrosis on ficient to make her nonambulatory. U/l). Total leukocyte and differ- the opposite thigh (Figure 3). There was no history of trauma or ential counts were normal. Lupus fever. She had been diagnosed with anticoagulant and antiphospholipid Case Report 2 1 year ago and hyper- antibodies were negative. A 37-year-old woman with type 2 tension 5 years ago. Ultrasonography showed an ill- diabetes for 8 years presented to us On examination, her right thigh defined hypoechoeic area measuring with painful swelling of the left thigh was swollen with a diffuse, indurated 25 × 15 cm² over the lateral aspect of for the past week. She was afebrile, tender mass over the anterolateral the right mid-thigh. Magnetic reso- and there was no history of local aspect (Figure 1). The margins were nance imaging (MRI; T2-weighted trauma. There was no weakness in not distinct, and there were no other short TI inversion recovery images) the left thigh, but movement was signs of inflammation or pus forma- showed heterogenous and hyperin- restricted because of severe pain. She tion. She was afebrile. A vibration tense areas involving the anterior and medial group of right thigh

In Brief

Diabetic myonecrosis is an uncommon muscular complica- tion of diabetes with significant morbidity. Clinical features and radiological findings are helpful in the diagnosis of myonecrosis. Management is conservative and Figure 2. Case report 1: muscle biopsy Figure 1. Case report 1: right thigh focused on symptomatic relief and of right thigh showing infiltration of showing diffuse swelling (white arrow) control of diabetes. inflammatory cells with muscle fiber anterolaterally. degeneration (white arrow).

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ous and had curtailed her day-to-day control and recovered in a period activities. The right thigh was swollen of 4 weeks. uniformly and was tender. She had microalbuminuria, bilat- Case Report 5 eral NPDR with clinically significant A 55-year-old man with type 2 diabe- macular edema, and DSPN. She had tes for 10 years presented with painful a history of foot ulcer. swelling of the right thigh for the past Laboratory investigation revealed 2 days. His evaluation revealed micro- poor glycemic control, leukocytosis, vascular complications in the form elevated ESR, and dyslipidemia. of bilateral NPDR and DSPN. There Serum CK and LDH levels were was no evidence of nephropathy. Figure 3. Case report 1: swollen left MRI and ultrasonography of thigh (white arrow) with scar on right within normal limits. Serum anti- the right thigh was suggestive of thigh (black arrow) from previous nuclear antibody, rheumatoid factor, biopsy. and antiphospholipid antibodies myonecrosis. He was managed with bed rest, had received antibiotics, which did were not detected. analgesics, and optimal glycemic not relieve her symptoms. Ultrasonography showed control and recovered in a period Her glycemic control was poor hypoechoic areas in the muscle of 4 weeks. (FPG 289 mg/dl, PPG 389 mg/dl, and minimal fluid collection in the A1C 9.2%). Other laboratory find- intermuscular spaces. Culture of the Case Report 6 ings revealed a hemoglobin level of aspirated fluid was sterile. MRI was A 56-year-old woman with type 2 10.2 g/dl, erythrocyte sedimentation suggestive of diabetic myonecrosis. diabetes for 25 years presented with rate (ESR) of 32 mm/hour, serum The patient was managed with rapid-onset spontaneous painful creatinine of 2.1 mg/dl, total choles- bed rest, analgesics, and optimal swelling of the right thigh and leg terol of 211 mg/dl, LDL cholesterol glycemic control and recovered in a for 2 weeks. On examination, there of 112 mg/dl, and triglyceride level period of 4 weeks. was a diffuse swelling over the right of 287 mg/dl. There was no evidence thigh and leg. Case Report 4 of systemic inflammation, and She was on and anti- A 55-year-old man with type 2 dia- muscle enzymes (CK and LDH) hypertensive drugs. Her glycemic betes for 12 years and poor glycemic were normal. control was poor (FPG 292 mg/dl, control presented with bilateral pain- She had microvascular com- PPG 401 mg/dl, A1C 10.2%). She had ful thigh swelling of 4 days’ duration. plications in the form of diabetic microvascular complications in the The swelling was asymmetrical and nephropathy (chronic kidney form of (CKD more prominent on the left side. disease [CKD] stage 3), bilateral stage 3) and DSPN. He had micro- and macrovas- severe nonproliferative diabetic Fundus examination was nor- cular complications in the form of retinopathy (NPDR), and dis- mal. Total leucocyte count, ESR, nephropathy, DSPN, bilateral mild tal symmetrical polyneuropathy and muscle enzymes (CK and LDH) NPDR, and coronary heart disease. (DSPN). Ultrasonography showed a were normal. MRI (Figure 4) and diffuse hypoechoic area covering the Laboratory investigations did not anterolateral aspect of the left thigh. reveal any evidence of inflammation. MRI revealed features suggestive of Serum CK and LDH levels were muscle inflammation. within normal limits. She was managed with bed rest, Venous Doppler of the lower analgesics, and optimal glycemic limbs was normal. Ultrasonography control and recovered in a period showed a diffuse hypoechoic area in of 6 weeks. the quadriceps muscles bilaterally. Because he could not afford an MRI Case Report 3 study, a bilateral muscle biopsy was A 53-year-old woman with type 2 dia- performed and revealed degenera- Figure 4. Case report 6: T2 MRI (fat betes for 5 years presented with pain tion and necrosis of muscle fibers. suppressed) of both thighs with right in her right thigh of 5 days’ duration. He was managed with bed rest, thigh showing increased signal intensity The pain was abrupt and spontane- analgesics, and optimal glycemic over quadriceps muscles.

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Table 1. Characteristics of Our Patients With Diabetic Myonecrosis Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Age (years) 53 37 53 55 55 56 Sex Female Female Female Male Male Female Duration of diabetes 1 8 5 12 10 25 (years) Local trauma None None None None None None Fever None None None None None None Neuropathy Present Present Present Present Present Present Nephropathy Absent Present Present Present Absent Present Retinopathy Absent Present Present Present Present Absent Leucocytosis Absent Absent Present Absent Absent Absent ESR Normal Elevated Elevated Normal Normal Normal Muscle enzymes Elevated Normal Normal Normal Normal Normal Ultrasonography of Hypoechoeic Hypoechoeic Hypoechoeic Hypoechoic Hypoechoic Hypoechoic muscles Muscles involved Quadriceps Quadriceps Quadriceps Bilateral Quadriceps Quadriceps, quadriceps calf muscles Biopsy Necrosis Necrosis Necrosis Necrosis ND ND Resolution time (weeks) 4 6 4 4 4 3 ND, not done ultrasonography revealed features about it compared to other compli- typically includes an abrupt onset of suggestive of myonecrosis involv- cations of diabetes. Hence, there is diffuse painful swelling of involved ing the right thigh and leg. She was often a delay in diagnosis, which in muscles and occasionally a palpable managed with bed rest, analgesics, turn increases the morbidity associ- mass without antecedent trauma or 3 and optimal glycemic control and ated with the disease. Women with infection. Bilateral involvement is recovered in a period of 3 weeks. longstanding are the seen in 8–10% of cases.4,5 An increase Table 1 presents a summary of most common patients to develop in the dimensions of the thigh may be the patients in these six case reports. this disease. In patients with type 2 diabetes, older individuals are the initial presenting feature. Fever Overview of Myonecrosis more commonly affected.4,5 Diabetic and other signs of inflammation are Diabetic myonecrosis is a complica- myonecrosis is usually seen in usually absent. tion of longstanding diabetes. Since patients with longstanding diabetes Thigh muscles are commonly its first description by Angervall and who are on insulin therapy and have affected, with the quadriceps being 1 Stener in 1965, ~ 100 cases have been multiple micro- and macrovascular the most frequently involved muscle 2 reported in the literature. Diabetic 4–6 complications. group.7 Vastus lateralis and vastus myonecrosis is also known as spon- The diagnosis criteria for medialis are the most commonly taneous diabetic muscle infarction diabetic myonecrosis are summa- affected muscle sites.8 Involvement (DMI), aseptic myonecrosis, ischemic rized in Table 2 and discussed in of calf and upper-extremity muscle myonecrosis, and tumoriform focal detail below. muscular degeneration. groups has also been documented.4,8,9 Diabetic myonecrosis is rare, and Clinical presentation With time, the swelling localizes, there is a relative lack of awareness Clinical presentation of myonecrosis and the predominant symptom

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coursing through the lesion, lack of Table 2. Criteria for Diagnosis of Diabetic Myonecrosis a predominately anechoic region, Clinical features: and absence of motion or swirling • Abrupt onset of severe pain and swelling of affected area of fluid with transducer pressure.18 • Usually asymmetrical The advantages of ultrasonography • Absence of fever and other signs of inflammation include easy availability, nonin- • History of trauma usually absent vasiveness, early diagnosis, and • Diabetes with end-organ damage exclusion of other causes such as Laboratory features: soft-tissue . • Normal leucocyte count Imaging studies may be quite • Normal or mildly elevated ESR useful in the diagnosis of diabetic • Normal or mildly elevated muscle enzymes myonecrosis and can simultaneously Radiological features: exclude other differential diagnoses • Ultrasound: well-marginated, hypoechoic, intramuscular lesion with no such as , abscess, fracture, features of abscess* tropical , necrotizing *Internal linear structures that suggest muscle fibers coursing through the lesion, fasciitis, diabetic lumbar plexopathy, lack of a predominately anechoic region, and absence of motion or swirling and . of fluid with transducer pressure are suggestive of myonecrosis and rule out MRI studies show increased soft-tissue abscess. signal intensity from the affected

muscle area in T2-weighted, may be pain with restriction of Galtier-Dereure et al.16 have inversion recovery, and gadolinium- movement.10 shown a high prevalence of enhanced images and isointense or

antiphospholipid antibodies in hypointense areas on T1-weighted Pathophysiology of myonecrosis patients with type 1 or type 2 images. The pathological basis of Possible pathological mechanisms diabetes and end-organ complica- these findings is the presence of revolve around diabetic microangi- tions. The coexistence of diabetes increased water content resulting opathy, with thrombosis, and antiphospholipid antibod- from edema.19 Other findings include hypoxia-reperfusion injury, and ies increases hypercoagulability diffuse enlargement of affected mus- 11,12 atherosclerotic occlusion. Patients and puts patients at high risk for cles, ill-defined borders secondary generally have end-organ complica- thrombotic complications and dia- to loss of the normal fatty intra- tions of diabetes, suggesting the role betic myonecrosis. Vasculitis with muscular septa, and hemorrhagic of small vessel disease and atheroscle- fibrinoid necrosis, although reported foci.20 The disadvantages of MRI rosis as an underlying pathology. in diabetic myonecrosis, is rare.17 include its high cost, lack of univer- Cases of diabetic myonecrosis sal availability, and nonspecificity. also have been reported with cirrho- Laboratory investigations Many MRI findings seen in diabetic sis and antiphospholipid antibody and radiology myonecrosis can also be found in syndrome. Diabetes is a proinflam- Laboratory evaluation shows an other inflammatory myopathies. matory state, with increased activity elevated ESR in half of the cases.4 Computed tomography (CT) scans of factor VII, plasminogen activator Leucocytosis is generally absent. show diffuse muscular enlargement inhibitor-1, and thrombomodulin. Serum levels of muscle enzymes such with diminished attenuation of the This in turn creates a hyperco- as CPK and LDH are usually normal affected muscle, increased attenu- agulable state.5,13,14 The or mildly elevated.8 Serum levels of ation of the subcutaneous fat, and abnormalities associated with cir- aspartate and alanine transaminases thickening of subcutaneous fascial rhosis may put patients at risk for are generally normal. planes and skin.21 hematoma formation and infection. Bedside ultrasonography is Because MRI and CT scans are Ischemia and associated edema may the first-line imaging diagnostic nonspecific, many patients also are aggravate the local pressure effect, modality in diabetic myonecrosis. subjected to biopsy. Findings on which may further compromise Ultrasonography generally reveals a muscle biopsy depend on the stage blood flow to the affected muscles.15 well-marginated, hypoechoic, intra- of the myonecrosis. Early on, light Hence, ischemia and edema may muscular lesion with the following microscopy shows large areas of form a vicious circle leading to wors- additional features: internal linear muscle necrosis and edema, phago- ening of diabetic myonecrosis. structures that suggest muscle fibers cytosis of the necrotic muscle fibers,

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and variable presence of granular Doppler studies may be required to diabetes complications. All of our tissue and collagen. At a later stage, rule out deep-vein thrombosis. patients had neuropathy and dia- there is a fibrous replacement of betic dyslipidemia. Nephropathy was the necrotic tissue, myofiber regen- Treatment and prognosis present in five cases, and retinopathy eration, and mononuclear cell Treatment for diabetic myonecrosis was present in four cases. infiltration.22 Small vessel walls are is generally conservative and sup- All of our patients presented with often hyalinized and thickened with portive. Bed rest is usually advised, typical clinical features of diabetic evidence of atherosclerosis. Some although there are conflicting myonecrosis such as abrupt onset small vessels may be occluded with reports on the benefits of physical of pain and swelling in the affected fibrin or calcium fragments. therapy.8,12,15 Nonsteroidal anti- muscles. Fever has been reported in Conflicting reports suggest that inflammatory drugs and narcotics ~ 10% of patients with diabetic myo- biopsy may be associated with may be used for inflammation and necrosis, but none of our patients hematoma formation, infection, and pain control. Good glycemic control had a fever. an extended recovery period.15,17,23 during the hospital stay is recom- Diabetic myonecrosis has a pre- Cultures for and fungi mended. Anticoagulants may be used dilection for thigh muscles. In our are generally negative unless there only if a patient has a hypercoagu- series, all six patients had involve- is a complicated myonecrosis.6 lable state such as antiphospholipid ment of the quadriceps, and one However, because biopsy is invasive syndrome. In general, surgical patient (case report 6) had involve- and noninvasive investigations such interventions should be avoided ment of calf muscles in addition to as ultrasound are easily available, unless there is a complicated diabetic the quadriceps. One of our patients biopsy should be reserved for cases myonecrosis with abscess formation had bilateral involvement (case in which the clinical presentation is or peripheral arterial compromise.14 report 4). In the literature, bilat- atypical or the diagnosis uncertain Generally, the short-term progno- eral involvement was reported in or when appropriate treatment fails sis is good for diabetic myonecrosis. 8–10% of cases. to elicit clinical improvement.15,19,24 The swelling and pain lessen, and Plasma levels of muscle enzymes patients become mobile in 1–2 were elevated in only one of our Differential diagnosis months. However, patients usu- patients (case report 1). Leucocytosis Other conditions that may mimic ally have associated micro- and and elevated ESR were reported myonecrosis include soft-tissue macrovascular complications that in ~ 8 and 52% of patients, respec- abscess, necrotizing fasciitis, pyomyo- affect the long-term prognosis and tively. We noted leucocytosis in case sitis, dermatomyositis, benign muscle elevate 5-year mortality.3,4 Patients report 3 and elevated ESR in case tumors, lymphomas, , are known to have recurrences, reports 2 and 3. diabetic amyotrophy, drug-induced and most events occur within a We managed our patients with myositis, , muscle period of 2 months after the initial bed rest and analgesics. Glycemic rupture, hematoma, ruptured Baker’s presentation. control was optimized. All of our cyst, deep-vein thrombosis, diabetic patients had complete resolution of lumbosacral plexopathy, and throm- Experience with diabetic myonecrosis myonecrosis without any complica- bophlebitis. Clinical presentation, Diabetic myonecrosis has been more tions in 4.16 ± 0.96 weeks. laboratory investigations, MRI, and frequently reported in women. Four In diabetic myonecrosis, recur- sonographic features, along with (66.6%) of the patients in our series rence was reported in ~ 47% of the course of the disease, all help in described above were women. The patients. The majority (81%) of these differentiation. Soft-tissue mean age at presentation was 51.5 ± patients have recurrences in a differ- on ultrasound are anechoic or 7.2 years (range 37–56 years), which is ent muscle. In our series, one patient hypoechoic, well defined, and show higher than noted in a previously pub- (case report 1) had recurrence of 5 posterior acoustic enhancing and lished review. The fact that all of our myonecrosis in the opposite thigh 2 intrinsic motion of fluid. Patients patients had type 2 diabetes may have years after the first presentation. with pyomyositis generally will have contributed to the higher mean age. systemic symptoms with fever and The mean duration of diabetes, Conclusion leucocytois. ESR, CPK, and LDH from initial diagnosis to the first epi- Diabetic myonecrosis is an uncom- are generally elevated. Blood cul- sode of myonecrosis, was 10.16 ± mon complication of longstanding tures and local tissue cultures may 8.23 years (range 1–25 years). Our diabetes. Patients may present with grow Staphylococcus aureus. Venous patients had multiple end-organ pain and swelling of involved muscle

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groups, leading to significant mor- myonecrosis. Case Rep Endocrinol Article ID 21Grigoriadis E, Fam AG, StarokM, Ang 624020, 2011 (doi:10.1155/2011/624020) LC: infarction in dia betes bidity. Management is conservative, mellitus. J Rheumatol 27:1063–1068, 2000 10Umpiérrez GE, Stiles RG, Kleinbart with good short-term prognosis. The J, Krendel DA, Watts NB: Diabetic muscle 22Rocca PV, Alloway JA, Nashel DJ: long-term prognosis of these patients infarction. Am J Med 101:245–250, 1996 Diabetic muscular infarction. Semin Arthritis is poor, in part because many of them 11Scully RE, Mark EJ, McNelly WF, Rheum 22:280–287, 1993 Ebeling SH, Phillips LD: Case 29–1997: 23Delaney-Sathy LO, Fessell DP, already have micro- and macrovascu- case records of the Massachusetts General Jacobson JA, Hayes CW: Sonography of lar complications of diabetes. Hospital. N Engl J Med 337:839–845, 1997 diabetic muscle infarction with MR imaging, 12Habib G, Nashashibi M, Walid S: CT, and pathologic correlation. AJR Am J References Diabetic muscular infarction: emphasis on Roentgenol 174:165–169, 2000 pathogenesis. Clin Rheumatol 22:450–451, 24 1 Barohn RJ, Kissel JT: Case of the Angervall L, Stener B: Tumoriform 2003 month: painful thigh mass in a young focal muscular degeneration in two diabetic 13 woman: diabetic muscle infarction. Muscle patients. Diabetologia 1:39–42, 1965 Palmer GW, Greco TP: Diabetic thigh muscle infarction in association with anti- Nerve 15:850–855, 1992. 2Maclsaac RJ, Jerums G, Scurrah L: phospholipid antibodies. Semin Arthritis Diabetic muscle infarction. Med J Aust Rheum 30:272–280, 2001 177:323–324, 2002 14Bjornskov EK, Carry MR, Katz FH, Dayanidhi Meher, MD, DM, is 3Wintz RL, Pimstone KR, Nelson SD: Leflowitz J, Ringel SP: Diabetic muscle a postdoctoral trainee; Satinath Detection of diabetic myonecrosis: compli- infarction: a new perspective on pathogenesis cation is often-missed sign of underlying an management. Neuromusc Disord 5:39–45, Mukherjee, MD, DM, is a profes- disease. Postgrad Med 119:66 –69, 2006 1995 sor; and Subhankar Chowdhury, 15 4Trujillo-Santos AJ: Diabetic muscle Chester CS, Banker BQ: Focal infarc- DM, MRCP, is a professor and head infarction: an underdiagnosed complication tion of muscle in diabetics. Diabetes Care of long-standing diabetes. Diabetes Care 9:623–630, 1986 of the Department of Endocrinology 26:211–215, 2003 16Galtier-Dereure F, Biron C, Vies M, and Metabolism at the Institute of 5Mancillas-Adame LG, González- Bourgeois V, Schved JF, Bringer J: Vascular Post-Graduate Medical Education González JG, Jáquez-Quintana JO, complications of diabetes mellitus: what role Cardoza-Torres MA, García Ade L: Diabetic for phospholipid-binding antibodies? Lupus and Research in Kolkata, India. 7:469–470, 1998 myonecrosis in a patient with hepatic cirrho- Raiz Ahmed Misgar, MD, DM, sis: a case report and review of the literature. 17Chason DP, Fleckenstein JL, Burns DK, J Med Case Rep 3:9305, 2009 Rojas G: Diabetic muscle infarction: radio- is a consultant in endocrinology in

6 logic evaluation. Skeletal Radiol 25:127–132, Kashmir, India. Vivek Mathew, MD, Rajiv R, Davidson MB: Diabetic muscle 1996 infarction: a rare complication of diabetes DM, is an assistant professor in the mellitus. Endocrinologist 14:167–170, 2004 18Nagdev A, Murphy M, Sisson C: Bedside ultrasound for the detection of dia- Department of Endocrinology at St. 7Chow KM, Szeto CC, Wong TY, Leung betic myonecrosis. Am J Emerg Med 26:969. Johns Medical College in Bangalore, FK, Cheuk A, Li PK: Diabetic muscle infarc- e3–969.e4, 2008 tion (Letter). Diabetes Care 25:1895, 2002 Karnataka, India. Jyothi Chowdhury, 19Sharma P, Mangwana S, Kapoor RK: 8Bunch TJ, Birskovich LM, Eiken PW: Diabetic muscle infarction: atypical MR MBBS, DTM&H, is a consul- Diabetic myonecrosis in a previously healthy appearance. Skeletal Radiol 29:477–480, 2000 tant pathologist at the Nightingale woman and review of a 25-year Mayo Clinic 20 experience. Endocr Pract 8:343–346, 2002 Levinsohn EM, Bryan PJ: Computed Diagnostic & Medicare Center tomography in unilateral extremity swell- 9Mukhopadhyay P, Barai R, Philips ing of unusual cause. J Comp Assist Tomogr in Shakespeare Sarani, Kolkata, CA, Ghosh J, Saha S: An unusual case of 3:67–70, 1979 West Bengal.

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