DIAB-6431; No. of Pages 3 diabetes research and clinical practice xxx (2015) xxx.e1–xxx.e3
Contents available at ScienceDirect
Diabetes Research and Clinical Practice journ al h ome pa ge : www .elsevier.co m/lo cate/diabres
Brief report
Diabetes myonecrosis – A rare complication T. Joshi a,*, E. D’Almeida b, J. Luu a a b
John Hunter Hospital, Department of Endocrinology and Diabetes, New Lambton, NSW, Australia John Hunter Hospital, Department of Nephrology, New Lambton, NSW, Australia
article info
abstract
Article history:
We report a patient with very rare complication of poorly controlled diabetes. Diabetes
Received 9 June 2015
myonecrosis is a self-limiting condition with unclear pathogenesis and it most commonly
Accepted 20 June 2015
affects the quadriceps muscle. Physicians should consider this diagnosis in diabetic patients
Available online xxx
presenting with sudden onset, non-traumatic muscular pain. # 2015 Elsevier Ireland Ltd. All rights reserved.
Keywords: Diabetes Muscle Myonecrosis Complications
1.
Introduction
Diabetes mellitus is associated with a wide-range of microvascular and macrovascular complications. Diabetes myonecrosis is a rare complication [1] first reported by Angerall and Stener in 1965 [2]. Since then, only a few cases have been reported in the literature [1–7]. Previous reports have used various terms for this condition including aseptic myonecrosis, aseptic diabetes muscle infarction, ischemic myonecrosis, and tumoriform focal muscle infarction [1]. Patients with this condition usually present with acute pain and swelling in limb muscles without any external injury [1,4]. Diabetes myonecrosis can be diagnosed with magnetic resonance imaging (MRI) showing hyperintensity in T2-weighted images and isointensity or hypointensity on T1-weighted images in the affected muscles. However, the diagnosis of diabetes myonecrosis is often delayed due to lack of awareness. Here, we discuss a case of a 59-year-old male with type 2 diabetes
mellitus presenting with classical features of diabetic myonecrosis.
2.
Clinical case
A 59-year-old male presented with severe pain in left thigh that was gradually progressive in intensity over 2–3 weeks. He had no fever or rash or arthralgia. There was no history of preceding trauma to the limb. His past medical history was significant for poorly controlled type 2 diabetes mellitus, diagnosed two years ago. He was managed with oral hypoglycemic agents. He was also diagnosed to have proliferative retinopathy, stage 5 chronic kidney disease and erectile dysfunction. Physical examination revealed a swollen, tender, distal lateral left thigh. The skin over the involved thigh was erythematous. Pedal pulses were palpable bilaterally. Left thigh movement was restricted in flexion. There was no knee or hip joint effusion.
* Corresponding author at: Byrne House John Hunter Hospital, New Lambton, NSW 2305, Australia. Tel.: +61 4 11863273; fax: +61 2 49223368. E-mail address: [email protected] (T. Joshi). http://dx.doi.org/10.1016/j.diabres.2015.06.004 0168-8227/# 2015 Elsevier Ireland Ltd. All rights reserved.
Please cite this article in press as: Joshi T, et al. Diabetes myonecrosis – A rare complication. Diabetes Res Clin Pract (2015), http://dx.doi.org/ 10.1016/j.diabres.2015.06.004
DIAB-6431; No. of Pages 3
e2
diabetes research and clinical practice xxx (2015) xxx.e1–xxx.e3
Investigations revealed an elevated creatinine kinase of 649 U/L (reference range 1–185 U/L) and an elevated erythrocyte sedimentation rate of 64 mm/h. Hemoglobin was 98 g/L and white cell count was 7.3 109/L. Vasculitic and autoimmune screen were negative. Serum urea was raised at 22.2 mmol/L (reference range 3.6–8.4) with serum creatinine of 540 mmol/L (reference range 60–120; eGFR 9 mL/min/ 1.73 m2) consistent with stage 5 chronic kidney disease. HbA1c was 74 mmol/mol (NGSP 8.9%) suggestive of poor glycemic control. Ultrasound of the thigh revealed diffuse subcutaneous edema. Duplex ultrasound showed normal flow in proximal iliac, femoral, and popliteal arteries with only minimal plaque formation. MRI scan revealed extensive swelling and edema in the left vastus medialis, intermedius and lateralis muscles with sparing of rectus femoris, suggestive of myositis or myonecrosis (Fig. 1a and b). He was initially commenced on antibiotics for possible infective myositis and subsequently prednisolone for possible vasculitic myonecrosis. Due to a poor response to treatment we proceeded to muscle biopsy. Muscle biopsy demonstrated myofibre necrosis with evidence of regeneration, suggestive of chronic ischemia. There was no evidence of vasculitis and blood vessels were normal in appearance (Fig. 1e and f). A diagnosis of diabetic myonecrosis was made and he was subsequently managed conservatively with analgesia and physiotherapy. He was commenced on insulin therapy and glycemic control was optimized. Over the next few months, there was significant improvement in muscle strength and
function of the left thigh with decreased swelling. Repeat MRI three months later showed resolution of edema and swelling with minor residual signal changes in vastus lateralis and medialis (Fig. 1c and d).
3.
Discussion
Diabetic myonecrosis has been reported in both type 1 and type 2 diabetes [1,3]. Risk factors include long duration of diabetes and poor glycemic control. There is a slight female preponderance (61.5%) [1]. Patients usually have other associated microvascular complications, most commonly nephropathy. Most commonly muscles affected are: quadriceps 62%, hip adductors 13%, hamstrings 8%, hip flexors 2%, calf muscles and upper limb involvement is rare. Bilateral involvement is seen in 8.4% [1]. The reason for predominant involvement of quadriceps is not clear but it has been postulated to be related to the level of mechanical load sustained by this muscle group [3]. The clinical picture is of sudden onset pain with absence of constitutional symptoms and no history of preceding trauma. The affected area appears swollen, warm, and tender [1,4]. Blood tests show an elevated CK and ESR in 50% [1] of cases. The imaging modality of choice is MRI with characteristic finds of hypointense or iso intense images on T1, increased intensity on T2 suggestive of edema and gadolinium enhanced images showing central non enhancing areas with peripheral enhancement suggestive of central necrosis
Fig. 1 – (a) Initial MRI-T1 image. (b) Initial MRI-T2 image showing hyperintensity in vastus lateralis and medialis muscles. (c) MRI (3 months post)-T1 image showing resolution. (d) MRI (3 months post)-T2 image showing resolution, with some residual changes in vastus laterialis. (e) Microscopic: Paraffin H&E 40X: vacuolated myofibres with interspersed inflammatory cells and fibrosis. (f) Microscopic: Frozen H&E 40X: regenerating myofibres and pale anuclear myofibres with chronic inflammation and fibrosis. Please cite this article in press as: Joshi T, et al. Diabetes myonecrosis – A rare complication. Diabetes Res Clin Pract (2015), http://dx.doi.org/ 10.1016/j.diabres.2015.06.004
DIAB-6431; No. of Pages 3 diabetes research and clinical practice xxx (2015) xxx.e1–xxx.e3
surrounded by viable muscle fibers and inflammatory infiltrate [5]. Muscle biopsy is not routinely required but may be considered when the diagnosis is unclear or atypical presentation [6]. Excisional biopsy should be avoided due to the complications of hematoma, infection and delayed healing associated with it in patients with diabetes myonecrosis [6]. When performed, muscle biopsy shows large areas of necrosis and edema along with collagen and granular tissue [1]. Perivascular and endomysial lymphohistiocytic infiltrate has been reported [4]. In later stages, myofibre regeneration, mononuclear infiltrate and fibrosis is seen [1]. The differential diagnoses include pyomyositis, necrotizing fasciitis, acute compartment syndrome, deep venous thrombosis, dermatomyositis, soft tissue abscess, primary muscle lymphoma, and sarcoma [1,4]. These can be differentiated clinically and on MRI. The exact pathogenesis of diabetic myonecrosis is unknown, but postulated mechanisms include hypoxia-reperfusion injury, atherosclerotic occlusion, vasculitis with thrombosis, atheroembolism of small vessels, and hypercoagulability [1,3]. Diabetes myonecrosis is usually self-limited condition and management is conservative [1]. Short-term prognosis is good but long-term prognosis is poor, with most patients deceased within 5 years due to diabetic complications [3,7]. Recurrence is seen in approximately half of cases [1].
4.
Conclusion
Diabetes myonecrosis is a rare complication of poorly controlled diabetes with only a few reported cases. Physicians should have a high index of suspicion for diabetes myonecrosis in patients with poorly controlled diabetic presenting with sudden onset, non-traumatic limb pain. Patients usually have other microvascular complications, particularly nephropathy. MRI is the imaging investigation of choice. Blood investigations are rarely differentiating. Muscle biopsy is not routinely indicated but appropriate in cases of atypical presentation or progression. Treatment is mainly conservative. Short-term prognosis is good but longterm prognosis is poor. Recurrence is common.
e3
Author contributions TJ researched data and wrote the manuscript. JL and ED reviewed and edited the manuscript.
Conflict of interest The authors report no conflict of interest.
Funding There was no funding support for this study.
Acknowledgements The authors thank Dr. Min-Xin Wang and Prof. Roger Pamphlett, Department of Neurology, University of Sydney, for assisting with histology.
references
[1] Trujillos-Santos AJ. Diabetic muscular infarction. Diabetes Care 2003;26(January):211–5. [2] Angerall L, Stener B. Tumoriform focal muscular degeneration in two diabetic patients. Diabetologia 1965;1:39–42. [3] Habib G, Nashashibi M, W. Saliba, Haj S. Diabetic muscular infarction: emphasis on pathogenesis. Clin Rheumatol 2003;22(December):450–1. [4] Rashidi A, Bahrani O. Diabetic myonecrosis of the thigh. JCEM 2011;96(August (8)):2310–1. [5] Kattapuram T, Suri R, Rosol MS, Rosenberg AE, Kattapuram SV. Idiopathic and diabetic skeletal muscle infarction: evaluation by magnetic resonance imaging. Skelet Radiol 2005;34(April):203–9. [6] Keller DR, Erpelding M, Grist T. Diabetic muscular infarction: preventing morbidity by avoiding excisional biopsy. Arch Int Med 1997;157(July (14)):1611–2. [7] Hoyt J, Wittich CM. Diabetic myonecrosis. JECM 2008;93(10):3690.
Please cite this article in press as: Joshi T, et al. Diabetes myonecrosis – A rare complication. Diabetes Res Clin Pract (2015), http://dx.doi.org/ 10.1016/j.diabres.2015.06.004
Contents available at ScienceDirect
Diabetes Research and Clinical Practice journ al h ome pa ge : www .elsevier.co m/lo cate/diabres
Brief report
Diabetes myonecrosis – A rare complication T. Joshi a,*, E. D’Almeida b, J. Luu a a b
John Hunter Hospital, Department of Endocrinology and Diabetes, New Lambton, NSW, Australia John Hunter Hospital, Department of Nephrology, New Lambton, NSW, Australia
article info
abstract
Article history:
We report a patient with very rare complication of poorly controlled diabetes. Diabetes
Received 9 June 2015
myonecrosis is a self-limiting condition with unclear pathogenesis and it most commonly
Accepted 20 June 2015
affects the quadriceps muscle. Physicians should consider this diagnosis in diabetic patients
Available online xxx
presenting with sudden onset, non-traumatic muscular pain. # 2015 Elsevier Ireland Ltd. All rights reserved.
Keywords: Diabetes Muscle Myonecrosis Complications
1.
Introduction
Diabetes mellitus is associated with a wide-range of microvascular and macrovascular complications. Diabetes myonecrosis is a rare complication [1] first reported by Angerall and Stener in 1965 [2]. Since then, only a few cases have been reported in the literature [1–7]. Previous reports have used various terms for this condition including aseptic myonecrosis, aseptic diabetes muscle infarction, ischemic myonecrosis, and tumoriform focal muscle infarction [1]. Patients with this condition usually present with acute pain and swelling in limb muscles without any external injury [1,4]. Diabetes myonecrosis can be diagnosed with magnetic resonance imaging (MRI) showing hyperintensity in T2-weighted images and isointensity or hypointensity on T1-weighted images in the affected muscles. However, the diagnosis of diabetes myonecrosis is often delayed due to lack of awareness. Here, we discuss a case of a 59-year-old male with type 2 diabetes
mellitus presenting with classical features of diabetic myonecrosis.
2.
Clinical case
A 59-year-old male presented with severe pain in left thigh that was gradually progressive in intensity over 2–3 weeks. He had no fever or rash or arthralgia. There was no history of preceding trauma to the limb. His past medical history was significant for poorly controlled type 2 diabetes mellitus, diagnosed two years ago. He was managed with oral hypoglycemic agents. He was also diagnosed to have proliferative retinopathy, stage 5 chronic kidney disease and erectile dysfunction. Physical examination revealed a swollen, tender, distal lateral left thigh. The skin over the involved thigh was erythematous. Pedal pulses were palpable bilaterally. Left thigh movement was restricted in flexion. There was no knee or hip joint effusion.
* Corresponding author at: Byrne House John Hunter Hospital, New Lambton, NSW 2305, Australia. Tel.: +61 4 11863273; fax: +61 2 49223368. E-mail address: [email protected] (T. Joshi). http://dx.doi.org/10.1016/j.diabres.2015.06.004 0168-8227/# 2015 Elsevier Ireland Ltd. All rights reserved.
Please cite this article in press as: Joshi T, et al. Diabetes myonecrosis – A rare complication. Diabetes Res Clin Pract (2015), http://dx.doi.org/ 10.1016/j.diabres.2015.06.004
DIAB-6431; No. of Pages 3
e2
diabetes research and clinical practice xxx (2015) xxx.e1–xxx.e3
Investigations revealed an elevated creatinine kinase of 649 U/L (reference range 1–185 U/L) and an elevated erythrocyte sedimentation rate of 64 mm/h. Hemoglobin was 98 g/L and white cell count was 7.3 109/L. Vasculitic and autoimmune screen were negative. Serum urea was raised at 22.2 mmol/L (reference range 3.6–8.4) with serum creatinine of 540 mmol/L (reference range 60–120; eGFR 9 mL/min/ 1.73 m2) consistent with stage 5 chronic kidney disease. HbA1c was 74 mmol/mol (NGSP 8.9%) suggestive of poor glycemic control. Ultrasound of the thigh revealed diffuse subcutaneous edema. Duplex ultrasound showed normal flow in proximal iliac, femoral, and popliteal arteries with only minimal plaque formation. MRI scan revealed extensive swelling and edema in the left vastus medialis, intermedius and lateralis muscles with sparing of rectus femoris, suggestive of myositis or myonecrosis (Fig. 1a and b). He was initially commenced on antibiotics for possible infective myositis and subsequently prednisolone for possible vasculitic myonecrosis. Due to a poor response to treatment we proceeded to muscle biopsy. Muscle biopsy demonstrated myofibre necrosis with evidence of regeneration, suggestive of chronic ischemia. There was no evidence of vasculitis and blood vessels were normal in appearance (Fig. 1e and f). A diagnosis of diabetic myonecrosis was made and he was subsequently managed conservatively with analgesia and physiotherapy. He was commenced on insulin therapy and glycemic control was optimized. Over the next few months, there was significant improvement in muscle strength and
function of the left thigh with decreased swelling. Repeat MRI three months later showed resolution of edema and swelling with minor residual signal changes in vastus lateralis and medialis (Fig. 1c and d).
3.
Discussion
Diabetic myonecrosis has been reported in both type 1 and type 2 diabetes [1,3]. Risk factors include long duration of diabetes and poor glycemic control. There is a slight female preponderance (61.5%) [1]. Patients usually have other associated microvascular complications, most commonly nephropathy. Most commonly muscles affected are: quadriceps 62%, hip adductors 13%, hamstrings 8%, hip flexors 2%, calf muscles and upper limb involvement is rare. Bilateral involvement is seen in 8.4% [1]. The reason for predominant involvement of quadriceps is not clear but it has been postulated to be related to the level of mechanical load sustained by this muscle group [3]. The clinical picture is of sudden onset pain with absence of constitutional symptoms and no history of preceding trauma. The affected area appears swollen, warm, and tender [1,4]. Blood tests show an elevated CK and ESR in 50% [1] of cases. The imaging modality of choice is MRI with characteristic finds of hypointense or iso intense images on T1, increased intensity on T2 suggestive of edema and gadolinium enhanced images showing central non enhancing areas with peripheral enhancement suggestive of central necrosis
Fig. 1 – (a) Initial MRI-T1 image. (b) Initial MRI-T2 image showing hyperintensity in vastus lateralis and medialis muscles. (c) MRI (3 months post)-T1 image showing resolution. (d) MRI (3 months post)-T2 image showing resolution, with some residual changes in vastus laterialis. (e) Microscopic: Paraffin H&E 40X: vacuolated myofibres with interspersed inflammatory cells and fibrosis. (f) Microscopic: Frozen H&E 40X: regenerating myofibres and pale anuclear myofibres with chronic inflammation and fibrosis. Please cite this article in press as: Joshi T, et al. Diabetes myonecrosis – A rare complication. Diabetes Res Clin Pract (2015), http://dx.doi.org/ 10.1016/j.diabres.2015.06.004
DIAB-6431; No. of Pages 3 diabetes research and clinical practice xxx (2015) xxx.e1–xxx.e3
surrounded by viable muscle fibers and inflammatory infiltrate [5]. Muscle biopsy is not routinely required but may be considered when the diagnosis is unclear or atypical presentation [6]. Excisional biopsy should be avoided due to the complications of hematoma, infection and delayed healing associated with it in patients with diabetes myonecrosis [6]. When performed, muscle biopsy shows large areas of necrosis and edema along with collagen and granular tissue [1]. Perivascular and endomysial lymphohistiocytic infiltrate has been reported [4]. In later stages, myofibre regeneration, mononuclear infiltrate and fibrosis is seen [1]. The differential diagnoses include pyomyositis, necrotizing fasciitis, acute compartment syndrome, deep venous thrombosis, dermatomyositis, soft tissue abscess, primary muscle lymphoma, and sarcoma [1,4]. These can be differentiated clinically and on MRI. The exact pathogenesis of diabetic myonecrosis is unknown, but postulated mechanisms include hypoxia-reperfusion injury, atherosclerotic occlusion, vasculitis with thrombosis, atheroembolism of small vessels, and hypercoagulability [1,3]. Diabetes myonecrosis is usually self-limited condition and management is conservative [1]. Short-term prognosis is good but long-term prognosis is poor, with most patients deceased within 5 years due to diabetic complications [3,7]. Recurrence is seen in approximately half of cases [1].
4.
Conclusion
Diabetes myonecrosis is a rare complication of poorly controlled diabetes with only a few reported cases. Physicians should have a high index of suspicion for diabetes myonecrosis in patients with poorly controlled diabetic presenting with sudden onset, non-traumatic limb pain. Patients usually have other microvascular complications, particularly nephropathy. MRI is the imaging investigation of choice. Blood investigations are rarely differentiating. Muscle biopsy is not routinely indicated but appropriate in cases of atypical presentation or progression. Treatment is mainly conservative. Short-term prognosis is good but longterm prognosis is poor. Recurrence is common.
e3
Author contributions TJ researched data and wrote the manuscript. JL and ED reviewed and edited the manuscript.
Conflict of interest The authors report no conflict of interest.
Funding There was no funding support for this study.
Acknowledgements The authors thank Dr. Min-Xin Wang and Prof. Roger Pamphlett, Department of Neurology, University of Sydney, for assisting with histology.
references
[1] Trujillos-Santos AJ. Diabetic muscular infarction. Diabetes Care 2003;26(January):211–5. [2] Angerall L, Stener B. Tumoriform focal muscular degeneration in two diabetic patients. Diabetologia 1965;1:39–42. [3] Habib G, Nashashibi M, W. Saliba, Haj S. Diabetic muscular infarction: emphasis on pathogenesis. Clin Rheumatol 2003;22(December):450–1. [4] Rashidi A, Bahrani O. Diabetic myonecrosis of the thigh. JCEM 2011;96(August (8)):2310–1. [5] Kattapuram T, Suri R, Rosol MS, Rosenberg AE, Kattapuram SV. Idiopathic and diabetic skeletal muscle infarction: evaluation by magnetic resonance imaging. Skelet Radiol 2005;34(April):203–9. [6] Keller DR, Erpelding M, Grist T. Diabetic muscular infarction: preventing morbidity by avoiding excisional biopsy. Arch Int Med 1997;157(July (14)):1611–2. [7] Hoyt J, Wittich CM. Diabetic myonecrosis. JECM 2008;93(10):3690.
Please cite this article in press as: Joshi T, et al. Diabetes myonecrosis – A rare complication. Diabetes Res Clin Pract (2015), http://dx.doi.org/ 10.1016/j.diabres.2015.06.004
