International Journal of Rheumatic Diseases 2014; 17: 483–485
CORRESPONDENCE
A case of migrating bone marrow edema syndrome in a patient with Behcet’s disease Dear Editor, Bone marrow edema syndrome (BMES) refers to a transient clinical condition of unknown pathogenicity.1 In general, the course is self-limiting and symptoms resolve spontaneously over 6–12 months.2 Because of the lack of a specific diagnostic test and similar symptoms and imaging findings to those of other entities, differentiation of BMES from avascular necrosis (AVN), neoplasm and osteomyelitis is difficult.3 Early diagnosis is important for preventing overtreatment of benign conditions and for starting proper management in serious cases.1,3,4 Here, we present the first case of migrating BMES within the same foot in a patient with Behcet’s disease (BD). A 38-year-old woman with BD visited our clinic in February 2013 with a 10-day history of left ankle pain. She reported severe, progressive pain and tenderness in the left ankle. She had no history of a traumatic event. In 2009, she had been diagnosed with BD on the basis of findings of recurrent oral aphthous ulcers, genital aphthous ulcers, erythema nodosum and arthritis.5 She had been prescribed colchicine 0.6 mg daily, sulfasalazine 500 mg daily, and acetaminophen 1300 mg daily for 4 years. However, her drug compliance was poor, and she complained constantly of recurrent oral and genital ulcers. She took steroids only when the oral and genital ulcers were aggravated. She had a history of thyroid papillary carcinoma and had undergone a total thyroidectomy and radioiodine ablation 6 years before admission. She reported that she had been hospitalized for similar left ankle pain in November 2003 and July 2004. The magnetic resonance imaging (MRI) images obtained in 2003 demonstrated diffuse high signal intensity on T2-weighted images of the lateral portion of the calcaneus (Fig. 1a,b). Under consideration of a diagnosis of osteomyelitis, she had been treated with antibiotics for 50 days. The pain had subsided after 1 month. In 2004, the left foot and ankle pain developed again, and MRI revealed newly developed bone marrow edema at the talus and distal tibia, and the size
(a)
(b)
(c)
(d)
Figure 1 Magnetic resonance imaging (MRI) obtained in November 2003 demonstrate ill-defined low signal intensity on an axial T1-weighted image (a) and high signal intensity on an axial fat-suppressed T2-weighted image (b) in the lateral portion of the calcaneus of the left ankle (arrows), suggesting a bone marrow edema-like lesion. A coronal fat-suppressed T2-weighted MRI obtained in June 2004 (c) showed that the previous bone marrow edema-like lesion on the lateral portion of the calcaneus had decreased markedly (arrow) and that a new lesion had developed on the inferior portion of the talus and distal tibia (arrow in d).
of the previous lesion in the calcaneus had markedly decreased (Fig. 1c,d). Her doctor had suspected a recurrence of osteomyelitis and recommended a surgical
© 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd
Correspondence
biopsy; however, she refused the biopsy and the pain slowly subsided. On the most recent admission, joint examination of the left ankle and foot showed severe tenderness without local heat or swelling. Electrolyte levels, liver and renal function tests, urinalysis, C-reactive protein, erythrocyte sedimentation rate and coagulation tests were normal. Tests for lupus anticoagulant, anti-b2 glycoprotein, and anti-cardiolipin antibody produced negative results. She had a low protein S activity – 63% when she was first diagnosed with BD – and this remained low at 62% (normal, 71–103%). A radiograph of the left ankle did not show any abnormal lesions. A bone scan showed abnormally increased uptake in the left calcaneus and the absence of a cold spot. MRI revealed ill-defined, high signal intensity bone marrow edema on the lateral portion of calcaneus on fat-suppressed T2-weighted images (Fig. 2a). There were no findings of synovitis and no definite doubleline sign representing osteonecrosis on T2-weighted images. Considering the recurrence of the lesions, the migrating feature of the bone marrow edema, and the clinical symptoms without fever or leukocytosis, migrating BMES was the most likely diagnosis instead of osteomyelitis or osteonecrosis. We decided to treat her symptomatically with a nonsteroidal anti-infalmmatory drug without any antibiotics. We considered adding an anticoagulant, but she declined it because of severe dyspepsia. The patient’s symptoms gradually subsided. Re-evaluation of the MRI images after 1 and 3 months showed decreased size and extent of the bone marrow (a)
(b)
edema (Fig. 2b,c). There was no symptom recurrence at the 6-month follow-up visit. The recurrence of symptoms in an adjacent joint or intra-articular migration in the same joint is a characteristic clinical and radiological feature of migrating BMES.6 Migration of BMES lesions within different compartments of the same joint is rare, and development of BMES in the foot is even rarer.6,7 The present case is distinctive because the signs of BMES occurred in a patient with BD, and BMES recurred in the same foot three times. BMES involves diffuse subacute ischemia and is resolved completely in most patients who have a sufficient repair mechanism.3 Many hypotheses have been proposed to explain the pathogenesis of BMES, but the exact etiology remains unknown.1 Theories include thromboembolism, obstruction of arteriolar inflow or venous outflow, injury to the vessel wall secondary to vasculitis, altered lipid metabolism and reduced fibrinolysis.1,4 Deficiency of protein S, a cardinal cofactor in the inactivation of the coagulation pathway, increases the risk of thromboembolism and osteonecrosis.8 Although the association between BD and BMES remains unclear and we cannot discount the possibility of coincidence, we estimate that the uncontrolled disease activity, blood flow obstruction induced by vasculitis and protein S deficiency may have all played roles in the development of recurrent BMES in our patient. It is debatable whether BMES represents a distinct disease or whether it is indicative of early AVN.4,9 Although early interventions such as core decompression, rotational osteotomy, vascularized bone graft and electrical stimulation are optimal treatment methods for
(c)
Figure 2 Axial fat-suppressed T2weighted magnetic resonance images obtained in February (a), March (b) and May (c) in 2013 demonstrate an illdefined bone marrow edema on the medial portion of the calcaneus (arrows), which sequentially decreased in size and extent.
484
International Journal of Rheumatic Diseases 2014; 17: 483–485
Correspondence
AVN, BMES is a self-limiting disease; therefore, surgical intervention is usually not warranted.1,7 However, some researchers emphasize that BMES should be considered as a marker of the potential for progression to advanced AVN and that careful examination for AVN is necessary when BMES is detected.4,9 We think that recurrent BMES may progress to AVN in patients with BD because of ischemic changes and thrombus formation caused by vasculitis and protein S deficiency.8,10 Therefore, BMES should be closely monitored in a patient with BD, especially when accompanied by protein S deficiency. Early treatment with an anti-coagulant or anti-platelet therapies should be considered in BMES patients with risk factors such as BD or other forms of vasculitis. Further studies are needed to elucidate the triggering factors or causes of recurrent BMES in a patient with BD. This work was supported by INHA UNIVERSITY HOSPITAL research grant. Hea Yoon KWON1, Won PARK1, Seong Ryul KWON1, Mie Jin LIM1, Yeo Ju KIM2, KoWoon JOO1, Jun Hyeok LIM1 and Kyong-Hee JUNG1 1
Division of Rheumatology, Department of Internal Medicine and 2Department of Radiology, Inha University Hospital, Incheon, Korea Correspondence: Professor Kyong-Hee Jung email: [email protected]
REFERENCES 1 Korompilias AV, Karantanas AH, Lykissas MG, Beris AE (2009) Bone marrow edema syndrome. Skeletal Radiol 38, 425–36.
International Journal of Rheumatic Diseases 2014; 17: 483–485
2 Gaeta M, Mazziotti S, Minutoli F, Vinci S, Blandino A (2002) Migrating transient bone marrow edema syndrome of the knee: MRI findings in a new case. Eur Radiol 12 (Suppl.3), 40–2. 3 Hofmann S, Kramer J, Vakil-Adli A, Aigner N, Breitenseher M (2004) Painful bone marrow edema of the knee: differential diagnosis and therapeutic concepts. Orthop Clin North Am 35, 321–33. 4 Watson RM, Roach NA, Dalinka MK (2004) Avascular necrosis and bone marrow edema syndrome. Radiol Clin North Am 42, 207–19. 5 Davatchi F, Assaad-Khalil S, Calamia KT et al. (2013) The International Criteria for Behcet’s Disease (ICBD): a collaborative study of 27 countries on the sensitivity and specificity of the new criteria. J Eur Acad Dermatol Venereol 28, 338–47. 6 Aigner N, Meizer R, Petje G, Meizer E, Abdelkafy A, Landsiedl F (2008) Natural course of intra-articular shifting bone marrow edema syndrome of the knee. BMC Musculoskelet Disord 9, 45. 7 Koo K, Kim T (2007) Distinguishing transient bone marrow edema syndrome of the hip from femoral head osteonecrosis. Semin Arthroplasty 18, 198–202. 8 Orth P, Anagnostakos K (2013) Coagulation abnormalities in osteonecrosis and bone marrow edema syndrome. Orthopedics 36, 290–300. 9 Fernandez-Canton G, Casado O, Capelastegui A, Astigarraga E, Larena J, Merino A (2003) Bone marrow edema syndrome of the foot: one year follow-up with MR imaging. Skeletal Radiol 32, 273–8. 10 Chang HK, Choi YJ, Baek SK, Lee DH, Won KS (2001) Osteonecrosis and bone infarction in association with Behcet’s disease: report of two cases. Clin Exp Rheumatol 19, 51–4.
485
Copyright of International Journal of Rheumatic Diseases is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
CORRESPONDENCE
A case of migrating bone marrow edema syndrome in a patient with Behcet’s disease Dear Editor, Bone marrow edema syndrome (BMES) refers to a transient clinical condition of unknown pathogenicity.1 In general, the course is self-limiting and symptoms resolve spontaneously over 6–12 months.2 Because of the lack of a specific diagnostic test and similar symptoms and imaging findings to those of other entities, differentiation of BMES from avascular necrosis (AVN), neoplasm and osteomyelitis is difficult.3 Early diagnosis is important for preventing overtreatment of benign conditions and for starting proper management in serious cases.1,3,4 Here, we present the first case of migrating BMES within the same foot in a patient with Behcet’s disease (BD). A 38-year-old woman with BD visited our clinic in February 2013 with a 10-day history of left ankle pain. She reported severe, progressive pain and tenderness in the left ankle. She had no history of a traumatic event. In 2009, she had been diagnosed with BD on the basis of findings of recurrent oral aphthous ulcers, genital aphthous ulcers, erythema nodosum and arthritis.5 She had been prescribed colchicine 0.6 mg daily, sulfasalazine 500 mg daily, and acetaminophen 1300 mg daily for 4 years. However, her drug compliance was poor, and she complained constantly of recurrent oral and genital ulcers. She took steroids only when the oral and genital ulcers were aggravated. She had a history of thyroid papillary carcinoma and had undergone a total thyroidectomy and radioiodine ablation 6 years before admission. She reported that she had been hospitalized for similar left ankle pain in November 2003 and July 2004. The magnetic resonance imaging (MRI) images obtained in 2003 demonstrated diffuse high signal intensity on T2-weighted images of the lateral portion of the calcaneus (Fig. 1a,b). Under consideration of a diagnosis of osteomyelitis, she had been treated with antibiotics for 50 days. The pain had subsided after 1 month. In 2004, the left foot and ankle pain developed again, and MRI revealed newly developed bone marrow edema at the talus and distal tibia, and the size
(a)
(b)
(c)
(d)
Figure 1 Magnetic resonance imaging (MRI) obtained in November 2003 demonstrate ill-defined low signal intensity on an axial T1-weighted image (a) and high signal intensity on an axial fat-suppressed T2-weighted image (b) in the lateral portion of the calcaneus of the left ankle (arrows), suggesting a bone marrow edema-like lesion. A coronal fat-suppressed T2-weighted MRI obtained in June 2004 (c) showed that the previous bone marrow edema-like lesion on the lateral portion of the calcaneus had decreased markedly (arrow) and that a new lesion had developed on the inferior portion of the talus and distal tibia (arrow in d).
of the previous lesion in the calcaneus had markedly decreased (Fig. 1c,d). Her doctor had suspected a recurrence of osteomyelitis and recommended a surgical
© 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd
Correspondence
biopsy; however, she refused the biopsy and the pain slowly subsided. On the most recent admission, joint examination of the left ankle and foot showed severe tenderness without local heat or swelling. Electrolyte levels, liver and renal function tests, urinalysis, C-reactive protein, erythrocyte sedimentation rate and coagulation tests were normal. Tests for lupus anticoagulant, anti-b2 glycoprotein, and anti-cardiolipin antibody produced negative results. She had a low protein S activity – 63% when she was first diagnosed with BD – and this remained low at 62% (normal, 71–103%). A radiograph of the left ankle did not show any abnormal lesions. A bone scan showed abnormally increased uptake in the left calcaneus and the absence of a cold spot. MRI revealed ill-defined, high signal intensity bone marrow edema on the lateral portion of calcaneus on fat-suppressed T2-weighted images (Fig. 2a). There were no findings of synovitis and no definite doubleline sign representing osteonecrosis on T2-weighted images. Considering the recurrence of the lesions, the migrating feature of the bone marrow edema, and the clinical symptoms without fever or leukocytosis, migrating BMES was the most likely diagnosis instead of osteomyelitis or osteonecrosis. We decided to treat her symptomatically with a nonsteroidal anti-infalmmatory drug without any antibiotics. We considered adding an anticoagulant, but she declined it because of severe dyspepsia. The patient’s symptoms gradually subsided. Re-evaluation of the MRI images after 1 and 3 months showed decreased size and extent of the bone marrow (a)
(b)
edema (Fig. 2b,c). There was no symptom recurrence at the 6-month follow-up visit. The recurrence of symptoms in an adjacent joint or intra-articular migration in the same joint is a characteristic clinical and radiological feature of migrating BMES.6 Migration of BMES lesions within different compartments of the same joint is rare, and development of BMES in the foot is even rarer.6,7 The present case is distinctive because the signs of BMES occurred in a patient with BD, and BMES recurred in the same foot three times. BMES involves diffuse subacute ischemia and is resolved completely in most patients who have a sufficient repair mechanism.3 Many hypotheses have been proposed to explain the pathogenesis of BMES, but the exact etiology remains unknown.1 Theories include thromboembolism, obstruction of arteriolar inflow or venous outflow, injury to the vessel wall secondary to vasculitis, altered lipid metabolism and reduced fibrinolysis.1,4 Deficiency of protein S, a cardinal cofactor in the inactivation of the coagulation pathway, increases the risk of thromboembolism and osteonecrosis.8 Although the association between BD and BMES remains unclear and we cannot discount the possibility of coincidence, we estimate that the uncontrolled disease activity, blood flow obstruction induced by vasculitis and protein S deficiency may have all played roles in the development of recurrent BMES in our patient. It is debatable whether BMES represents a distinct disease or whether it is indicative of early AVN.4,9 Although early interventions such as core decompression, rotational osteotomy, vascularized bone graft and electrical stimulation are optimal treatment methods for
(c)
Figure 2 Axial fat-suppressed T2weighted magnetic resonance images obtained in February (a), March (b) and May (c) in 2013 demonstrate an illdefined bone marrow edema on the medial portion of the calcaneus (arrows), which sequentially decreased in size and extent.
484
International Journal of Rheumatic Diseases 2014; 17: 483–485
Correspondence
AVN, BMES is a self-limiting disease; therefore, surgical intervention is usually not warranted.1,7 However, some researchers emphasize that BMES should be considered as a marker of the potential for progression to advanced AVN and that careful examination for AVN is necessary when BMES is detected.4,9 We think that recurrent BMES may progress to AVN in patients with BD because of ischemic changes and thrombus formation caused by vasculitis and protein S deficiency.8,10 Therefore, BMES should be closely monitored in a patient with BD, especially when accompanied by protein S deficiency. Early treatment with an anti-coagulant or anti-platelet therapies should be considered in BMES patients with risk factors such as BD or other forms of vasculitis. Further studies are needed to elucidate the triggering factors or causes of recurrent BMES in a patient with BD. This work was supported by INHA UNIVERSITY HOSPITAL research grant. Hea Yoon KWON1, Won PARK1, Seong Ryul KWON1, Mie Jin LIM1, Yeo Ju KIM2, KoWoon JOO1, Jun Hyeok LIM1 and Kyong-Hee JUNG1 1
Division of Rheumatology, Department of Internal Medicine and 2Department of Radiology, Inha University Hospital, Incheon, Korea Correspondence: Professor Kyong-Hee Jung email: [email protected]
REFERENCES 1 Korompilias AV, Karantanas AH, Lykissas MG, Beris AE (2009) Bone marrow edema syndrome. Skeletal Radiol 38, 425–36.
International Journal of Rheumatic Diseases 2014; 17: 483–485
2 Gaeta M, Mazziotti S, Minutoli F, Vinci S, Blandino A (2002) Migrating transient bone marrow edema syndrome of the knee: MRI findings in a new case. Eur Radiol 12 (Suppl.3), 40–2. 3 Hofmann S, Kramer J, Vakil-Adli A, Aigner N, Breitenseher M (2004) Painful bone marrow edema of the knee: differential diagnosis and therapeutic concepts. Orthop Clin North Am 35, 321–33. 4 Watson RM, Roach NA, Dalinka MK (2004) Avascular necrosis and bone marrow edema syndrome. Radiol Clin North Am 42, 207–19. 5 Davatchi F, Assaad-Khalil S, Calamia KT et al. (2013) The International Criteria for Behcet’s Disease (ICBD): a collaborative study of 27 countries on the sensitivity and specificity of the new criteria. J Eur Acad Dermatol Venereol 28, 338–47. 6 Aigner N, Meizer R, Petje G, Meizer E, Abdelkafy A, Landsiedl F (2008) Natural course of intra-articular shifting bone marrow edema syndrome of the knee. BMC Musculoskelet Disord 9, 45. 7 Koo K, Kim T (2007) Distinguishing transient bone marrow edema syndrome of the hip from femoral head osteonecrosis. Semin Arthroplasty 18, 198–202. 8 Orth P, Anagnostakos K (2013) Coagulation abnormalities in osteonecrosis and bone marrow edema syndrome. Orthopedics 36, 290–300. 9 Fernandez-Canton G, Casado O, Capelastegui A, Astigarraga E, Larena J, Merino A (2003) Bone marrow edema syndrome of the foot: one year follow-up with MR imaging. Skeletal Radiol 32, 273–8. 10 Chang HK, Choi YJ, Baek SK, Lee DH, Won KS (2001) Osteonecrosis and bone infarction in association with Behcet’s disease: report of two cases. Clin Exp Rheumatol 19, 51–4.
485
Copyright of International Journal of Rheumatic Diseases is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
