+
MODEL
Pediatrics and Neonatology (2013) xx, 1e4
Available online at www.sciencedirect.com
ScienceDirect journal homepage: http://www.pediatr-neonatol.com
CASE REPORT
Musculoskeletal Sepsis Associated with Deep Vein Thrombosis in a Child Chih-Ying Lee a, Yu-Sheng Lee a,b,*, Pei-Chen Tsao a,b, Mei-Jy Jeng a,b,c, Wen-Jue Soong a,b,c a
Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan Department of Pediatrics, Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan c Institute of Emergency and Critical Care Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan b
Received Apr 10, 2013; received in revised form Aug 23, 2013; accepted Sep 14, 2013
Key Words deep vein thrombosis; methicillin-resistant Staphylococcus aureus; myositis; osteomyelitis
Deep vein thrombosis (DVT) is a rare disease in pediatric patients. We report a pediatric patient who developed DVT in association with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia complicated with septic arthritis, osteomyelitis, and myositis extensively. It is crucial to consider musculoskeletal infection associated with DVT in any child who presents with severe swollen limbs and limitations of motion. Prompt antibiotic and anticoagulant treatments should be initiated to reduce the risk of fatal complications. Copyright ª 2013, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. All rights reserved.
1. Introduction Deep vein thrombosis (DVT) is a relatively rare disease in pediatric patients.1,2 According to previous studies, venous thromboembolic disease has an annual incidence of 1 per
* Corresponding author. Department of Pediatrics, Taipei Veterans General Hospital, Number 201, Shih-Pai Road, Section 2, Taipei 112, Taiwan. E-mail address: [email protected] (Y.-S. Lee).
100,000 and 0.74 per 100,000 in Singapore and Hong Kong Chinese children (< 15 years of age), respectively.3,4 The most important risk factor for DVT in children is the presence of a central venous line. In addition to infection, trauma and congenital heart disease are also common risk factors. The Virchow triad, including venous stasis, endothelial damage, and a hypercoagulation state, is the pathophysiology in venous thromboembolic disease. Outcomes of DVT in children may differ depending on anatomic sites, hemorrhage, superior vena cava syndrome, renal insufficiency, limb gangrene, and recurrent DVT. Herein, we report a pediatric patient with exceptionally extensive
1875-9572/$36 Copyright ª 2013, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. All rights reserved. http://dx.doi.org/10.1016/j.pedneo.2013.09.004
Please cite this article in press as: Lee C-Y, et al., Musculoskeletal Sepsis Associated with Deep Vein Thrombosis in a Child, Pediatrics and Neonatology (2013), http://dx.doi.org/10.1016/j.pedneo.2013.09.004
+
MODEL
2
C.-Y. Lee et al
regional septic arthritis, osteomyelitis, and myositis complicated with septic DVT secondary to communityassociated methicillin-resistant Staphylococcus aureus (CA-MRSA). After a complete course of antibiotics plus anticoagulation treatments, without surgical intervention, this patient recovered fully. No complications were noted during the following 2 years.
2. Case Report A previously healthy 23-month-old boy with an initial presentation of intermittent high fever up to 39.5 C for 3 days was sent to the emergency room (ER) of our hospital. According to the statement of the patient’s mother, he had suffered from a mild cough, decreased activity, poor appetite accompanied with vomiting, and right lower extremity pain that had been ongoing for approximately 2 days. The patient had no known history of major trauma prior to this episode. Physical examination at the ER revealed a mildly injected throat and bilateral coarse breathing sounds. The white blood cell count was 29,500/CUMM with a band of 1% and segment of 84%. The level of C-reactive protein (CRP) was 35.7 mg/L (normal 0e5 mg/L). The urine analysis results were negative. A chest radiograph showed mild bilateral infiltration. The patient was then admitted to the ward under the suspicion of a lower respiratory tract infection. Pain and swelling over the right hip with weakness of the right lower extremity were noted on the 3rd day after admission. A physical examination showed local heat, tenderness, and erythematous changes over the right hip joint and inguinal area, accompanied by right lower extremity swelling and edema. The range of motion of the patient’s right lower extremity was limited. Doppler ultrasonography of the limbs showed DVT of the right femoral vein. Laboratory examinations revealed: D-dimer 6.62 ug/ mL (normal < 0.55 mg/mL), fibrinogen 527 mg/dL (normal 200e400 mg/dL), fibrin degradation products 16.54 mg/mL (normal < 5 mg/mL). The osteomyelitis scan showed an increased signal over the right hip region (Figure 1). A magnetic resonance imaging (MRI) study of the lower extremities revealed thrombophlebitis of the right femoral vein, septic arthritis over the right hip joint, osteomyelitis
Figure 1
over the right femoral bone, and myositis (Figure 2A and B). The coagulation profile and immunity tests from this patient all showed no abnormal findings: a protein C functional assay of 63% and a protein S functional assay of 161%. Antibiotic treatment with Unasyn (ampicillin þ sulfactum, 25 mg ampicillin/kg/dose, q6h) was given after hospital admission. A blood culture revealed MRSA on the 3rd day after admission. MRSA was sensitive to gentamycin, vancomycin, linezolid, trimethoprim/sulfamethoxazole and resistant to oxacillin, ampicillin, clindamycin, penicillin-G, ceftriaxone, tetracycline, and cefazolin. Antibiotic treatment was therefore shifted to vancomycin (10 mg/kg/dose, q6h) because of diffuse soft tissue infection and bacteremia. Owing to the rise in CRP to 14.7 mg/dL and intermittent fever that persisted after 4 days of vancomycin treatment, the antibiotic regimen was switched to daptomycin (10 mg/kg/dose, qd), according to the recommendation of a pediatric infectious disease specialist because of poor clinical response and elevated laboratory parameters. A pediatric orthopedist was also consulted and he suggested no indication of surgical intervention due to the fact that no motion limitations were observed clinically and no pus formation was observed according to the image. Antibiotic treatment with daptomycin was provided for 6 weeks and follow-up blood culture showed no bacteria growth. After DVT was diagnosed by Doppler ultrasonography of the limbs, low molecular weight heparin (LMWH) was administered for 2 weeks, and then shifted to the oral form antithrombotic agent, warfarin. Warfarin was given for nearly 5.5 months and the dosage was adjusted to keep the International Normalized Ratio (INR) at approximately 2e2.5. The total duration of the anticoagulant therapy, including LMWH and warfarin, was 6 months. An MRI study was performed 1 month later after antibiotic and anticoagulant treatment, and it showed a regressive change. Recanalization of the femoral vein was noted on the Doppler ultrasonography of the limbs after 40 days of treatment. The Doppler ultrasonography of the limbs was followed 3 months later after completion of warfarin treatment, and it showed partial residual thrombosis of the right femoral vein. This patient experienced no major complications during the entire course of antibiotic and anticoagulant treatment.
Osteomyelitis scan: increased blood pool and Ga-67 in the right hip region, compatible with cellulitis.
Please cite this article in press as: Lee C-Y, et al., Musculoskeletal Sepsis Associated with Deep Vein Thrombosis in a Child, Pediatrics and Neonatology (2013), http://dx.doi.org/10.1016/j.pedneo.2013.09.004
+
MODEL
Septic thrombosis in a child
Figure 2 Magnetic resonance imaging showed (A) deep vein thrombosis (DVT): thrombosis of the right femoral vein, suggestive of thrombophlebitis and (B) septic arthritis, osteomyelitis, and myositis: thickening and contrast enhancement in the synovial in the right hip joint, bone marrow enhancement in the metaphysic and extending to the proximal third of diaphysis, swelling, and increased enhancement in the muscles (including gluteal muscles, vastus muscles, and part of the adductor muscles) and fascia.
The follow-up musculoskeletal examination at the outpatient clinic showed normal strength and range of motion in the child’s joints.
3. Discussion Venous thromboembolism is a rare disorder in children. The National Hospital Discharge Survey reported that the
3 incidence rate in the USA was 0.49 per 10,000 per year. Epidemiological data have also revealed that the age distribution of this condition is bimodal, especially in the neonatal and adolescent period.5,6 Venous thrombosis with osteomyelitis occurs rarely, but may be life-threatening.7,8 The pathogenesis of venous thromboembolism consists of venous stasis, endothelial damage, and the hypercoagulation state, which is called the Virchow triad.9,10 The most important predisposing factor for DVT is implantation of a central venous catheter.11 The previous literature reported that approximately 89% of venous thromboembolism cases in newborns are associated with an intravascular catheter.12 In addition, infection and trauma are also the etiologies of endothelial damage, especially minimal trauma as a risk factor for septic thrombosis in children.10 CA-MRSA is the most common pathogen involved in venous thrombosis with osteomyelitis.7,13e15 In our case, there was no central venous catheter implantation. However, infection of local soft tissue was diagnosed and blood culture revealed MRSA, which are consistent with previous reports. We observed that diffuse soft tissue infection as septic arthritis, osteomyelitis, and myositis can be associated with DVT in children. According to the study of Huang and Chen,16 CA-MRSA infections have been increasingly reported in pediatric patients since 2000 in Taiwan and the isolation rate from pediatric CA-S. aureus infections has recently been more than 50%. Skin and soft-tissue infection was the most common presentation of CA-MRSA infection in Taiwanese children and accounted for 83% of all reported cases. CAMRSA clinical isolates were also resistant to multiple antibiotics, including clindamycin (> 90%), erythromycin (> 90%), and chloramphenicol (57e65%), but were less resistant to gentamicin (21e34%). All CA-MRSA isolates were susceptible to vancomycin and teicoplanin and > 90% were susceptible to ciprofloxacin, fusidic acid, minocycline, and rifampicin. The majority of CA-MRSA isolates in Taiwan belonged to the sequence type (ST) 59 lineage, defined by multilocus sequence typing, and the most common molecular characteristics of CA-MRSA clinical isolates were ST59/ pulsed-field gel electrophoresis type D/staphylococcal chromosomal cassette mec VT/PantoneValentine leukocidin (PVL)-positivity.16 Vascular complications, such as DVT, were more common and more severe in patients with MRSA musculoskeletal infections compared with methicillin-sensitive S. aureus infections, especially for those with pulmonary involvement. MRSA infections also presented with significantly higher inflammatory markers and increased lengths of hospital stays. A number of factors may predispose to the development of DVT in osteomyelitis caused by S. aureus. Bacterial adhesion to thrombogenic surfaces plays an important pathogenic role. S. aureus release various exotoxins, which act on cell membranes and produce aggregation of platelets and smooth muscle spasm, both of which predispose to thrombosis, whereas the enzyme coagulase interacts with fibrinogen and causes plasma clotting. Besides, leukocidin, a multicomponent protein toxin and the product of the PVL gene, may also be the responsible toxin associated with DVT.14 The molecular characteristic in CAMRSA may be associated with the disease spectrum, severity, and prognosis. Although our patient did not
Please cite this article in press as: Lee C-Y, et al., Musculoskeletal Sepsis Associated with Deep Vein Thrombosis in a Child, Pediatrics and Neonatology (2013), http://dx.doi.org/10.1016/j.pedneo.2013.09.004
+
MODEL
4 receive a further molecular examination, we suggest that further investigation to explore the molecular characteristics in CA-MRSA infection may provide valuable information in clinical practice. The clinical presentations of fever with unilateral pain and swelling are often noted in DVT patients,8,13 but the condition can also be asymptomatic. The femoral and popliteal veins are most commonly affected,7,13 and our patient suffered from right femoral vein involvement. The predominance of DVT in males has been noted,7,13,14 and our case supported this tendency. The Doppler ultrasonography is the most common applicable diagnostic tool among DVT patients. However, magnetic resonance angiography or computed tomography is needed in some cases, especially when thrombosis extends to the visceral vessels. The laboratory examinations of CRP, erythrocyte sedimentation, and D-dimer revealed elevated levels.7,15 A coagulation profile should be evaluated, because protein C deficiency is a risk for venous thromboembolism in children.2 The results of the current patient’s coagulation profile all showed negative findings. The treatment of musculoskeletal sepsis associated with DVT is composed of antibiotic and anticoagulation treatment. Vancomycin is the first choice of antibiotic treatment for treating MRSA, and its dose should be adjusted depending on a patient’s blood culture results. Daptomycin may be effective against Gram-positive pathogens in bone and joint infections or bacteremia in a pediatric patient, when first-line treatment has failed. Anticoagulation treatment was performed, comprising LMWH followed with either LMWH or warfarin. The suggested length of treatment is reported to be 2.5e10 months,7,8 (at least 3 months is recommended).17 Warfarin treatment should be adjusted to keep the INR between 2.0 and 3.0. The current patient underwent anticoagulation therapy with LMWH followed by oral warfarin for 6 months. This regimen was consistent with previous recommendations. Inferior vena cava filters may play a role in treatment of DVT under some clinical conditions.17,18 Thrombolytic agents are reserved for limb salvage or hemodynamically unstable cases.17 Surgical therapy for DVT may be indicated when anticoagulation therapy is ineffective or contraindicated.8 However, our patient did not receive this invasive procedure. Some previous reports in the literature revealed complications of septic pulmonary emboli.7,8,13e15 Dyspnea, hemoptysis, and pleuritic chest pain are common symptoms, with signs of crepitations, tachycardia, and cyanosis.17 The incidence of pulmonary complications is low, but the mortality rates can be high.8,11,17 The ventilation/perfusion scan is a recommended test for the possibility of pulmonary emboli in children.10,17 In conclusion, DVT is uncommon in pediatric patients, but it should be considered in children with musculoskeletal infections accompanied with swollen extremities and motion limitations. Minor trauma is a potential risk factor for the disease. Early recognition and prompt treatment comprising antibiotic and anticoagulant therapy should be initiated as
C.-Y. Lee et al soon as DVT is suspected; and a delay in diagnosis may contribute to serious sequelae and even fatal consequences.
References 1. Clark DJ. Venous thromboembolism in paediatric practice. Paediatr Anaesth 1999;9:475e84. 2. Walsh S, Phillips F. Deep vein thrombosis associated with pediatric musculoskeletal sepsis. J Pediatr Orthop 2002;22:329e32. 3. Lee AC, Li CH, Szeto SC, Ma ES. Symptomatic venous thromboembolism in Hong Kong Chinese children. Hong Kong Med J 2003;9:259e62. 4. Molina JA, Jiang ZG, Heng BH, Ong BK. Venous thromboembolism at the National Healthcare Group, Singapore. Ann Acad Med Singapore 2009;38:470e8. 5. Stein PD, Kayali F, Olson RE. Incidence of venous thromboembolism in infants and children: data from the National Hospital Discharge Survey. J Pediatr 2004;145:563e5. 6. van Ommen CH, Heijboer H, Bu ¨ller HR, Hirasing RA, Heijmans HS, Peters M. Venous thromboembolism in childhood: a prospective two-year registry in The Netherlands. J Pediatr 2001;139:676e81. 7. Gonzalez BE, Teruya J, Mahoney Jr DH, Hulten KG, Edwards R, Lamberth LB, et al. Venous thrombosis associated with staphylococcal osteomyelitis in children. Pediatrics 2006;117: 1673e9. 8. Prasad R, Mishra OP, Pant P. Deep vein thrombosis with Staphylococcus aureus septicemia. Indian Pediatr 2007;44: 43e5. 9. Goldenberg NA, Bernard TJ. Venous thromboembolism in children. Hematol Oncol Clin North Am 2010;24:151e66. 10. Newgard CD, Inkelis SH, Mink R. Septic thromboembolism from unrecognized deep venous thrombosis in a child. Pediatr Emerg Care 2002;18:192e6. 11. Andrew M, David M, Adams M, Ali K, Anderson R, Barnard D, et al. Venous thromboembolic complications (VTE) in children: first analyses of the Canadian Registry of VTE. Blood 1994;83: 1251e7. 12. Schmidt B, Andrew M. Neonatal thrombosis: report of a prospective Canadian and international registry. Pediatrics 1995; 96:939e43. 13. Bouchoucha S, Benghachame F, Trifa M, Saied W, Douira W, Nessib MN, et al. Deep venous thrombosis associated with acute hematogenous osteomyelitis in children. Orthop Traumatol Surg Res 2010;96:890e3. 14. Mantadakis E, Plessa E, Vouloumanou EK, Michailidis L, Chatzimichael A, Falagas ME. Deep venous thrombosis in children with musculoskeletal infections: the clinical evidence. Int J Infect Dis 2012;16:e236e43. 15. Crary SE, Buchanan GR, Drake CE, Journeycake JM. Venous thrombosis and thromboembolism in children with osteomyelitis. J Pediatr 2006;149:537e41. 16. Huang YC, Chen CJ. Community-associated meticillin-resistant Staphylococcus aureus in children in Taiwan, 2000s. Int J Antimicrob Agents 2011;38:2e8. 17. Blann AD, Lip GY. Venous thromboembolism. BMJ 2006;332: 215e9. 18. Kuhfahl KJ, Fasano C, Deitch K. Scapular abscess, septic emboli, and deep vein thrombosis in a healthy child due to community-acquired methicillin-resistant Staphylococcus aureus: case report. Pediatr Emerg Care 2009;25:677e80.
Please cite this article in press as: Lee C-Y, et al., Musculoskeletal Sepsis Associated with Deep Vein Thrombosis in a Child, Pediatrics and Neonatology (2013), http://dx.doi.org/10.1016/j.pedneo.2013.09.004
MODEL
Pediatrics and Neonatology (2013) xx, 1e4
Available online at www.sciencedirect.com
ScienceDirect journal homepage: http://www.pediatr-neonatol.com
CASE REPORT
Musculoskeletal Sepsis Associated with Deep Vein Thrombosis in a Child Chih-Ying Lee a, Yu-Sheng Lee a,b,*, Pei-Chen Tsao a,b, Mei-Jy Jeng a,b,c, Wen-Jue Soong a,b,c a
Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan Department of Pediatrics, Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan c Institute of Emergency and Critical Care Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan b
Received Apr 10, 2013; received in revised form Aug 23, 2013; accepted Sep 14, 2013
Key Words deep vein thrombosis; methicillin-resistant Staphylococcus aureus; myositis; osteomyelitis
Deep vein thrombosis (DVT) is a rare disease in pediatric patients. We report a pediatric patient who developed DVT in association with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia complicated with septic arthritis, osteomyelitis, and myositis extensively. It is crucial to consider musculoskeletal infection associated with DVT in any child who presents with severe swollen limbs and limitations of motion. Prompt antibiotic and anticoagulant treatments should be initiated to reduce the risk of fatal complications. Copyright ª 2013, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. All rights reserved.
1. Introduction Deep vein thrombosis (DVT) is a relatively rare disease in pediatric patients.1,2 According to previous studies, venous thromboembolic disease has an annual incidence of 1 per
* Corresponding author. Department of Pediatrics, Taipei Veterans General Hospital, Number 201, Shih-Pai Road, Section 2, Taipei 112, Taiwan. E-mail address: [email protected] (Y.-S. Lee).
100,000 and 0.74 per 100,000 in Singapore and Hong Kong Chinese children (< 15 years of age), respectively.3,4 The most important risk factor for DVT in children is the presence of a central venous line. In addition to infection, trauma and congenital heart disease are also common risk factors. The Virchow triad, including venous stasis, endothelial damage, and a hypercoagulation state, is the pathophysiology in venous thromboembolic disease. Outcomes of DVT in children may differ depending on anatomic sites, hemorrhage, superior vena cava syndrome, renal insufficiency, limb gangrene, and recurrent DVT. Herein, we report a pediatric patient with exceptionally extensive
1875-9572/$36 Copyright ª 2013, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. All rights reserved. http://dx.doi.org/10.1016/j.pedneo.2013.09.004
Please cite this article in press as: Lee C-Y, et al., Musculoskeletal Sepsis Associated with Deep Vein Thrombosis in a Child, Pediatrics and Neonatology (2013), http://dx.doi.org/10.1016/j.pedneo.2013.09.004
+
MODEL
2
C.-Y. Lee et al
regional septic arthritis, osteomyelitis, and myositis complicated with septic DVT secondary to communityassociated methicillin-resistant Staphylococcus aureus (CA-MRSA). After a complete course of antibiotics plus anticoagulation treatments, without surgical intervention, this patient recovered fully. No complications were noted during the following 2 years.
2. Case Report A previously healthy 23-month-old boy with an initial presentation of intermittent high fever up to 39.5 C for 3 days was sent to the emergency room (ER) of our hospital. According to the statement of the patient’s mother, he had suffered from a mild cough, decreased activity, poor appetite accompanied with vomiting, and right lower extremity pain that had been ongoing for approximately 2 days. The patient had no known history of major trauma prior to this episode. Physical examination at the ER revealed a mildly injected throat and bilateral coarse breathing sounds. The white blood cell count was 29,500/CUMM with a band of 1% and segment of 84%. The level of C-reactive protein (CRP) was 35.7 mg/L (normal 0e5 mg/L). The urine analysis results were negative. A chest radiograph showed mild bilateral infiltration. The patient was then admitted to the ward under the suspicion of a lower respiratory tract infection. Pain and swelling over the right hip with weakness of the right lower extremity were noted on the 3rd day after admission. A physical examination showed local heat, tenderness, and erythematous changes over the right hip joint and inguinal area, accompanied by right lower extremity swelling and edema. The range of motion of the patient’s right lower extremity was limited. Doppler ultrasonography of the limbs showed DVT of the right femoral vein. Laboratory examinations revealed: D-dimer 6.62 ug/ mL (normal < 0.55 mg/mL), fibrinogen 527 mg/dL (normal 200e400 mg/dL), fibrin degradation products 16.54 mg/mL (normal < 5 mg/mL). The osteomyelitis scan showed an increased signal over the right hip region (Figure 1). A magnetic resonance imaging (MRI) study of the lower extremities revealed thrombophlebitis of the right femoral vein, septic arthritis over the right hip joint, osteomyelitis
Figure 1
over the right femoral bone, and myositis (Figure 2A and B). The coagulation profile and immunity tests from this patient all showed no abnormal findings: a protein C functional assay of 63% and a protein S functional assay of 161%. Antibiotic treatment with Unasyn (ampicillin þ sulfactum, 25 mg ampicillin/kg/dose, q6h) was given after hospital admission. A blood culture revealed MRSA on the 3rd day after admission. MRSA was sensitive to gentamycin, vancomycin, linezolid, trimethoprim/sulfamethoxazole and resistant to oxacillin, ampicillin, clindamycin, penicillin-G, ceftriaxone, tetracycline, and cefazolin. Antibiotic treatment was therefore shifted to vancomycin (10 mg/kg/dose, q6h) because of diffuse soft tissue infection and bacteremia. Owing to the rise in CRP to 14.7 mg/dL and intermittent fever that persisted after 4 days of vancomycin treatment, the antibiotic regimen was switched to daptomycin (10 mg/kg/dose, qd), according to the recommendation of a pediatric infectious disease specialist because of poor clinical response and elevated laboratory parameters. A pediatric orthopedist was also consulted and he suggested no indication of surgical intervention due to the fact that no motion limitations were observed clinically and no pus formation was observed according to the image. Antibiotic treatment with daptomycin was provided for 6 weeks and follow-up blood culture showed no bacteria growth. After DVT was diagnosed by Doppler ultrasonography of the limbs, low molecular weight heparin (LMWH) was administered for 2 weeks, and then shifted to the oral form antithrombotic agent, warfarin. Warfarin was given for nearly 5.5 months and the dosage was adjusted to keep the International Normalized Ratio (INR) at approximately 2e2.5. The total duration of the anticoagulant therapy, including LMWH and warfarin, was 6 months. An MRI study was performed 1 month later after antibiotic and anticoagulant treatment, and it showed a regressive change. Recanalization of the femoral vein was noted on the Doppler ultrasonography of the limbs after 40 days of treatment. The Doppler ultrasonography of the limbs was followed 3 months later after completion of warfarin treatment, and it showed partial residual thrombosis of the right femoral vein. This patient experienced no major complications during the entire course of antibiotic and anticoagulant treatment.
Osteomyelitis scan: increased blood pool and Ga-67 in the right hip region, compatible with cellulitis.
Please cite this article in press as: Lee C-Y, et al., Musculoskeletal Sepsis Associated with Deep Vein Thrombosis in a Child, Pediatrics and Neonatology (2013), http://dx.doi.org/10.1016/j.pedneo.2013.09.004
+
MODEL
Septic thrombosis in a child
Figure 2 Magnetic resonance imaging showed (A) deep vein thrombosis (DVT): thrombosis of the right femoral vein, suggestive of thrombophlebitis and (B) septic arthritis, osteomyelitis, and myositis: thickening and contrast enhancement in the synovial in the right hip joint, bone marrow enhancement in the metaphysic and extending to the proximal third of diaphysis, swelling, and increased enhancement in the muscles (including gluteal muscles, vastus muscles, and part of the adductor muscles) and fascia.
The follow-up musculoskeletal examination at the outpatient clinic showed normal strength and range of motion in the child’s joints.
3. Discussion Venous thromboembolism is a rare disorder in children. The National Hospital Discharge Survey reported that the
3 incidence rate in the USA was 0.49 per 10,000 per year. Epidemiological data have also revealed that the age distribution of this condition is bimodal, especially in the neonatal and adolescent period.5,6 Venous thrombosis with osteomyelitis occurs rarely, but may be life-threatening.7,8 The pathogenesis of venous thromboembolism consists of venous stasis, endothelial damage, and the hypercoagulation state, which is called the Virchow triad.9,10 The most important predisposing factor for DVT is implantation of a central venous catheter.11 The previous literature reported that approximately 89% of venous thromboembolism cases in newborns are associated with an intravascular catheter.12 In addition, infection and trauma are also the etiologies of endothelial damage, especially minimal trauma as a risk factor for septic thrombosis in children.10 CA-MRSA is the most common pathogen involved in venous thrombosis with osteomyelitis.7,13e15 In our case, there was no central venous catheter implantation. However, infection of local soft tissue was diagnosed and blood culture revealed MRSA, which are consistent with previous reports. We observed that diffuse soft tissue infection as septic arthritis, osteomyelitis, and myositis can be associated with DVT in children. According to the study of Huang and Chen,16 CA-MRSA infections have been increasingly reported in pediatric patients since 2000 in Taiwan and the isolation rate from pediatric CA-S. aureus infections has recently been more than 50%. Skin and soft-tissue infection was the most common presentation of CA-MRSA infection in Taiwanese children and accounted for 83% of all reported cases. CAMRSA clinical isolates were also resistant to multiple antibiotics, including clindamycin (> 90%), erythromycin (> 90%), and chloramphenicol (57e65%), but were less resistant to gentamicin (21e34%). All CA-MRSA isolates were susceptible to vancomycin and teicoplanin and > 90% were susceptible to ciprofloxacin, fusidic acid, minocycline, and rifampicin. The majority of CA-MRSA isolates in Taiwan belonged to the sequence type (ST) 59 lineage, defined by multilocus sequence typing, and the most common molecular characteristics of CA-MRSA clinical isolates were ST59/ pulsed-field gel electrophoresis type D/staphylococcal chromosomal cassette mec VT/PantoneValentine leukocidin (PVL)-positivity.16 Vascular complications, such as DVT, were more common and more severe in patients with MRSA musculoskeletal infections compared with methicillin-sensitive S. aureus infections, especially for those with pulmonary involvement. MRSA infections also presented with significantly higher inflammatory markers and increased lengths of hospital stays. A number of factors may predispose to the development of DVT in osteomyelitis caused by S. aureus. Bacterial adhesion to thrombogenic surfaces plays an important pathogenic role. S. aureus release various exotoxins, which act on cell membranes and produce aggregation of platelets and smooth muscle spasm, both of which predispose to thrombosis, whereas the enzyme coagulase interacts with fibrinogen and causes plasma clotting. Besides, leukocidin, a multicomponent protein toxin and the product of the PVL gene, may also be the responsible toxin associated with DVT.14 The molecular characteristic in CAMRSA may be associated with the disease spectrum, severity, and prognosis. Although our patient did not
Please cite this article in press as: Lee C-Y, et al., Musculoskeletal Sepsis Associated with Deep Vein Thrombosis in a Child, Pediatrics and Neonatology (2013), http://dx.doi.org/10.1016/j.pedneo.2013.09.004
+
MODEL
4 receive a further molecular examination, we suggest that further investigation to explore the molecular characteristics in CA-MRSA infection may provide valuable information in clinical practice. The clinical presentations of fever with unilateral pain and swelling are often noted in DVT patients,8,13 but the condition can also be asymptomatic. The femoral and popliteal veins are most commonly affected,7,13 and our patient suffered from right femoral vein involvement. The predominance of DVT in males has been noted,7,13,14 and our case supported this tendency. The Doppler ultrasonography is the most common applicable diagnostic tool among DVT patients. However, magnetic resonance angiography or computed tomography is needed in some cases, especially when thrombosis extends to the visceral vessels. The laboratory examinations of CRP, erythrocyte sedimentation, and D-dimer revealed elevated levels.7,15 A coagulation profile should be evaluated, because protein C deficiency is a risk for venous thromboembolism in children.2 The results of the current patient’s coagulation profile all showed negative findings. The treatment of musculoskeletal sepsis associated with DVT is composed of antibiotic and anticoagulation treatment. Vancomycin is the first choice of antibiotic treatment for treating MRSA, and its dose should be adjusted depending on a patient’s blood culture results. Daptomycin may be effective against Gram-positive pathogens in bone and joint infections or bacteremia in a pediatric patient, when first-line treatment has failed. Anticoagulation treatment was performed, comprising LMWH followed with either LMWH or warfarin. The suggested length of treatment is reported to be 2.5e10 months,7,8 (at least 3 months is recommended).17 Warfarin treatment should be adjusted to keep the INR between 2.0 and 3.0. The current patient underwent anticoagulation therapy with LMWH followed by oral warfarin for 6 months. This regimen was consistent with previous recommendations. Inferior vena cava filters may play a role in treatment of DVT under some clinical conditions.17,18 Thrombolytic agents are reserved for limb salvage or hemodynamically unstable cases.17 Surgical therapy for DVT may be indicated when anticoagulation therapy is ineffective or contraindicated.8 However, our patient did not receive this invasive procedure. Some previous reports in the literature revealed complications of septic pulmonary emboli.7,8,13e15 Dyspnea, hemoptysis, and pleuritic chest pain are common symptoms, with signs of crepitations, tachycardia, and cyanosis.17 The incidence of pulmonary complications is low, but the mortality rates can be high.8,11,17 The ventilation/perfusion scan is a recommended test for the possibility of pulmonary emboli in children.10,17 In conclusion, DVT is uncommon in pediatric patients, but it should be considered in children with musculoskeletal infections accompanied with swollen extremities and motion limitations. Minor trauma is a potential risk factor for the disease. Early recognition and prompt treatment comprising antibiotic and anticoagulant therapy should be initiated as
C.-Y. Lee et al soon as DVT is suspected; and a delay in diagnosis may contribute to serious sequelae and even fatal consequences.
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Please cite this article in press as: Lee C-Y, et al., Musculoskeletal Sepsis Associated with Deep Vein Thrombosis in a Child, Pediatrics and Neonatology (2013), http://dx.doi.org/10.1016/j.pedneo.2013.09.004
