□ CASE REPORT □

Multifocal Diabetic Muscle Infarction: A Rare Complication of Poorly Controlled Mellitus

Wafa Chebbi 1,SaidaJerbi2, Rym Klii 3,WafaAlaya1, Sarra Mestiri 4, Baha Zantour 1 and Mohamed Habib Sfar 1

Abstract

Diabetic muscle infarction (DMI) is a rare complication of long-standing poorly controlled diabetes melli- tus. We herein describe the case of a 56-year-old man with a 10-year history of poorly controlled type 2 dia- betes mellitus with multiple microvascular and macrovascular complications who presented with the sudden onset of left thigh pain and swelling. MRI suggested muscle infarction. A muscle demonstrated co- agulation in the with inflammation and infarction in the walls of small blood vessels. Physicians should consider DMI in the differential diagnosis of patients with diabetes who present with pain- ful, swollen muscles without systemic signs of infection.

Key words: diabetes mellitus, muscle infarction, magnetic resonance imaging

(Intern Med 53: 2091-2094, 2014) (DOI: 10.2169/internalmedicine.53.2322)

vious amputation of the right fifth toe due to peripheral arte- Introduction rial disease. He denied any history of traumatic injury, ani- mal bites or muscular injections into the left thigh. On a Diabetic muscle infarction (DMI) is a rare and often un- physical examination, he was found to be afebrile with dif- recognized complication of diabetes mellitus. It typically oc- fuse swelling of the left proximal thigh and a 10×15-cm pal- curs in patients with poorly controlled and multi- pable, tender mass in the posteromedial region of the af- complicated diabetes (1, 2). The typical clinical presentation fected extremity. The patient’s thigh was warm to the touch, includes indurate muscle pain primarily localized in the without erythema or skin changes. There were no systemic lower limbs with acute onset (1). We herein report a case of symptoms. The laboratory data were significant for a blood multifocal DMI occurring in a 56-year-old man with type 2 glucose level of 270 mg/dL and a HbA1c level of 11.6%, as diabetes and degenerative complications and discuss its shown in the Table. A complete blood count revealed nor- clinical features, pathogenesis, diagnosis and prognosis. mocytic normochromic anemia with moderate leukocytosis. The serum creatinine kinase (CK) level was elevated at 852 Case Report IU/L. In addition, a biological inflammatory syndrome was detected (erythrocyte sedimentation rate: 135 mm/h, CRP: A 56-year-old man with a 10-year history of poorly con- 84.6 mg/L, fibrinogen: 6.8 mg/L). However, the serum cre- trolled was evaluated for acute recurrent atinine level was normal (0.9 mg/dL), and blood cultures pain lasting for one month in his left thigh, which was and antiphospholipid antibodies were negative. Ultra- swollen and caused him great difficulty in moving. The pa- sonography demonstrated extensive subcutaneous edema of tient had multiple diabetic complications, including microal- the posterior and medial compartment of the left thigh. buminuria, nonproliferative retinopathy, sensory polyneuro- Color Doppler ultrasonography revealed no evidence of deep pathy confirmed on and a history of pre- venous thrombosis. The patient was initially treated with in-

１Department of Internal Medicine, University Hospital Taher Sfar, Tunisia, ２Department of Radiology, University Hospital Taher Sfar, Tunisia, ３Department of Internal Medicine, University Hospital Fattouma Bourguiba, Tunisia and ４Department of Pathology, University Hospital Farhat Hached, Tunisia Received for publication December 15, 2013; Accepted for publication February 25, 2014 Correspondence to Dr. Wafa Chebbi, [email protected]

2091 Intern Med 53: 2091-2094, 2014 DOI: 10.2169/internalmedicine.53.2322

Table. Laboratory Findings on Admission

Parameters Value Normal range Complete blood count Hematocrit (%) 33 .5 36-54 hemoglobin (g/dL) 10.6 12-18 Mean corpuscular volume (μm3) 86 80-100 Leucocytes (× 103/mm3)124-10 Neutrophils (× 103/mm3) 8.9 2-6.9 Lymphocytes (× 103/mm3) 2.2 0.6-3.4 Platelets (× 103/mm3) 210 150-400 Blood chemistry Glucose (mg/dL) 270 62-109 Hemoglobin A1C (%) 11.6 4.3-5.7 Creatinine (mg/dL) 0.9 0.6-1.2 Creatinine kinase (IU/L) 852 24-170 Lactate dehydrogenase (IU/L) 240 230-460 Proteins (g/L) 72 61-79 Albumin (g/L) 24 39-46 Erythrocyte sedimentation rate (mm/h) 135 <10 CRP (mg/L) 84.6 <6 Uric acid (mg/L) 6.8 2-7.5 Total cholesterol (mg/dL) 185 96.6-201 Triglycerides (mg/dL) 97.4 44.8-150.5 HDL-Cholesterol(mg/dL) 49.8 35-85.4 Figure 1. Coronal T2-weighted fat-suppressed MRI showing Blood extensive involvement of the thigh with diffuse hyperintensity International normalized ratio 1.03 0.8 -1.2 Prothrombin ratio (%) 100 70-100 of the rectus femoris, gracilis, sartorius and adductor muscles. Activated partial thromboplastin time /control 30s /30s Protein C (%) 100 70-120 Protein S (%) 90 65-140 Anti-thrombin III 110 80-120 Fibrinogen (g/L) 6.8 2-4 D-dimer (μg/L) 370 ” Immnochemistry Anticardiolipin antibodies Discussion Ig M (U/mL) (-) <10 Ig G (U/mL) (-) < 10 The present patient exhibited typical features of DMI, in- b2-glycoprotein-I antibodies Ig M (U/mL) (-) <10 cluding acute onset of focal leg pain, followed by tenderness Ig G (U/mL) (-) <10 and swelling. MRI visualized the multifocal infarct, and a Antinuclear antibodies (-) <1:40 Antineutrophil cytoplasmic antibodies (-) - muscle biopsy confirmed hemorrhagic necrosis of the mus- cle. The patient had poorly controlled diabetes mellitus and was hyperglycemic at the time of infarction. travenous antibiotics for a presumptive diagnosis of pyo- DMI is a rare complication that is usually reported in as- myositis or necrotizing fasciitis, with no improvements in sociation with long-standing poorly controlled diabetes mel- his condition. Magnetic resonance imaging (MRI) was per- litus, particularly , with known late complica- formed, which disclosed isointense swelling on T1-weighted tions, such as nephropathy, retinopathy and neuropa- images and diffuse hyperintensity on T2-weighted images of thy (1-3). Although first described in 1965, less than 200 the rectus femoris, gracilis, sartorius and adductor muscles cases have been reported in the literature (1, 4). The paucity (Fig. 1). MRI performed with intravenous gadolinium re- of cases may be the result of unfamiliarity with this rare vealed non-enhancing large areas in the left adductor mus- condition among clinicians. The patient described in this cle, indicative of necrosis, surround by peripheral enhance- case report had uncontrolled type 2 diabetes mellitus with ment (Fig. 2). An examination of a biopsy specimen of the associated microvascular and macrovascular complications, left thigh muscle showed diffuse edema with hemorrhage, which have been reported previously to be risk factors for large patchy areas of coagulation necrosis and inflammation DMI (1-5). surrounding blood vessels, consistent with an ischemic proc- The typical presentation of DMI includes acute onset pain ess (Fig. 3). A culture of the biopsy specimen was negative. in the affected muscle, local swelling and, occasionally, a Based on these findings, the patient was diagnosed with palpable mass, without any prior history of DMI. Complete bed rest was advised, and the patient was trauma (1, 3, 4, 6). Fever is uncommon, and, if present, one given symptomatic treatment with , antiplatelets should actively look for an infective pathology (7). The and subcutaneous injection. After two weeks of hos- thigh muscles are affected in 81% to 87% of cases, and the pitalization, his symptoms regressed; he was able to walk calf in 13% to 19% of cases, with bilateral involvement in and subsequently discharged. In addition, a significant im- approximately 40% of patients (8). The most commonly in- provement was obtained in various blood parameters (CRP: volved muscles are the quadriceps (62%), hip adductors 18 mg/L, CK: 102 IU/L), with a stable glycemic profile. No (13%), hamstrings (8%) and hip flexor muscles (2%). DMI recurrence of symptoms was observed during six months of of the calf and upper extremity muscles is less common (9). follow-up. In the present case, the area of infarction was multifocal, in-

2092 Intern Med 53: 2091-2094, 2014 DOI: 10.2169/internalmedicine.53.2322

Figure 3. Histologic appearance of muscle tissue showing co- Figure 2. Axial fat-suppressed gadolinium-enhanced T1- agulation necrosis with hemorrhage (Hematoxylin and Eosin weighted image demonstrating areas of diffuse enhancement of staining; ×100). the left thigh muscles (*). Other areas show focal rim enhance- ment with a low-signal-intensity center (arrow). Presumably, these areas represent focal necrosis within the muscle. due to the rarity of the condition, the association between antiphospholipid antibody syndrome and DMI has not been volving more than three muscle groups in the thigh. proven (10). In the present case, no abnormalities in the co- Laboratory studies generally demonstrate an elevated agulation system or levels of phospholipid antibodies were erythrocyte sedimentation rate and normal or mildly elevated detected. white blood cell count in affected patients. Measurements of The mainstay of treatment for DMI involves early recog- CK may be normal or elevated depending on the timing of nition, bed rest, analgesics and aggressive control of diabe- blood sampling and amount of muscle involved (10). tes mellitus. Other modalities suggested to be beneficial in- MRI is the diagnostic test of choice for DMI and makes clude the administration of low-dose aspirin, pentoxifylline, it possible to confirm the diagnosis without performing a nifedipine, dipyridamole, nonsteroidal agents and anticoagu- muscular biopsy. MRI typically shows isointense swelling lants. However, there are no randomized control trials to on T1-weighted images and diffuse heterogeneous hyperin- support the use of these agents (6, 10, 12). In general, the tensity on T2-weighted images of the affected muscle, with short-term prognosis is reported to be benign, although the surrounding subfascial and subcutaneous edema. Gadolinium long-term outcome is discouraging. Several patients have contrast reveals non-enhancing areas surrounded by periph- been reported to have died within two years after being di- eral enhancement (11). MRI also makes it possible to ex- agnosed with DMI, mostly due to vascular complications as- clude other diseases that mimic DMI, which can be difficult sociated with diabetes mellitus (1). In one study, the progno- to diagnose clinically. The differential diagnosis includes sis of DMI among patients with diabetes mellitus was re- deep venous thrombosis, , , pyo- ported to be similar to that observed after myocardial infarc- myositis, spontaneous hematomas, , necrotic fascii- tion, with both conditions invariably involving significant tis, myositis, , and primary lym- vascular injury (13). phoma (1-3, 5). In conclusion, DMI is a rare but significant complication The gold standard for diagnosis is a biopsy of the muscle, of diabetes mellitus with an overall poor long-term outcome. although this procedure carries a risk of delayed healing and The incidence of this condition is likely to increase as a re- superimposed infection. Muscle are reserved for pa- sult of the increasing global prevalence of diabetes. Physi- tients in whom the diagnosis is uncertain and those with an cians should consider DMI in the differential diagnosis of atypical presentation or who do not improve with appropri- patients with diabetes who present with painful, swollen ate treatment (2, 5). Typical biopsy findings reveal muscle muscles without systemic signs of infection. MRI is the di- fiber necrosis, inflammatory cell infiltration and microvascu- agnostic test of choice for evaluating DMI. lar abnormalities, as observed in this current case (5). The pathogenesis of DMI remains unclear. It has been The authors state that they havenoConflictofInterest(COI). suggested that reperfusion injury after muscle ischemia re- sults in muscle infarction, as almost all patients with DMI References experience microangiopathic complications of diabetes mel- litus. In addition, the presence of endothelial dysfunction in 1. Kapur S, Brunet JA, McKendry RJ. Diabetic muscle infarction: patients with diabetes mellitus in addition to hypercoagula- case report and review. J Rheumatol 31: 190-194, 2004. bility resulting from alterations in the coagulation- 2. Trujillo-Santos AJ. Diabetic muscle infarction: an underdiagnosed complication of long-standing diabetes. Diabetes Care 26: 211- fibrinolytic system has been proposed (6, 10, 12). However,

2093 Intern Med 53: 2091-2094, 2014 DOI: 10.2169/internalmedicine.53.2322

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