288
Letters to the Editor / Joint Bone Spine (2015) 287–295
References [1] Odvina CV, Zerwekh JE, Rao DS, et al. Severely suppressed bone turnover: a potential complication of alendronate therapy. J Clin Endocrinol Metab 2005;90:1294–302. [2] Mashiba T, Hirano T, Turner CH, et al. Suppressed bone turnover by biphosphonate increases microdamage accumulation and reduces some biomechanical properties in dog rib. J Bone Miner Res 2000;15:613–20. [3] Abrahamsen B, Eiken P, Eastell R. Subtrochanteric and diaphyseal femur fractures in patients treated with alendronate: a register-based national cohort study. J Bone Miner Res 2009;24:1095–102. [4] Black DM, Kelly MP, Genant HK, et al. Bisphosphonates and fractures of the subtrochanteric or diaphyseal femur. N Engl J Med 2010;362:1761–71. [5] Neviaser AS, Lane JM, Edobor-Osula F, et al. Low-energy femoral fractures associated with alendronate use. J Orthop Trauma 2008;22:346–50. [6] Glorieux FH, Bishop NJ, Plotkin H, et al. Cyclic administration of pamidronate in children with severe osteogenic imperfecta. N Engl J Med 1998;339:947–52. [7] Whyte MP, Wenkert D, Clements KL, et al. Biphosphonate-induced osteopetrosis. Engl N J Med 2003;349:457–63. [8] Shane E, Burr D, Abrahamsen B, et al. Atypical subtrochanteric and diaphyseal femoral fractures: second report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 2014;29:1–23. [9] Bissonnette L, April PM, Dumais R, et al. Atypical fracture of the tibial diaphysis associated with biphosphonate therapy. A case report. Bone 2013;56:406–9. [10] Meier RPH, Lorenzini KI, Uebelhart B, et al. Atypical femoral fracture following biphosphonate treatment in a woman with osteogenesis imperfect. A case report. Acta Orthop 2012;83:548–50. Fig. 2. AP and lateral radiographs of the right tibia showing complete fracture of the mid-shaft tibia and fibula with oblique and transverse component and posterior spike.
fractures in children. The fractures observed in the patient reported here may be regarded as true atypical fractures since, even though the ASBMR task force criteria for atypical fracture [8] were not designed for application to fractures occurring in bones other than the femur, the fractures seen here shared certain features of atypical femoral fractures, including prodromal symptoms, and transverse, non-comminuted fracture following minimal trauma; additionally, the fracture affected both cortices and was associated with a medial spike; finally, was located in the mid-tibial diaphysis, and displayed thickening of the anterior cortex. Involvement of the anterior cortex rather than the lateral cortex as reported in atypical femoral fractures may be related to differences in geometry and in stress distribution along these bones. Atypical femoral fractures occur in the lateral cortex, where the greatest tension loading is exerted. Likewise, stress fractures of the anterior cortex of the tibial midshaft result from tension stress rather than compression [9]. But we cannot say with absolute certainty that this fracture is due to the treatment with biphosphonate because the osteogenesis imperfect itself could have contributed to the occurrence of this stress fracture, but the absent of an obvious trauma and the radiographic features make us think that this is an atypical fracture secondary to biphosphonate treatment. The literature contains only one report of a patient with osteogenesis imperfecta displaying atypical fracture associated with bisphosphonate therapy [10]; since this patient was 75 years old, the results cannot usefully be compared with those of the present study. The possible appearance of atypical fractures should be borne in mind when dealing with children receiving bisphosphonate therapy, and any unexplained pain should prompt examination using sensitive techniques such as scintigraphy or MRI. We consider that we have to make a careful selection of patients (multiple fracture or low BMD) due to the possible occurrence of these fractures or other complications related to the prolonged treatment with biphosphonates. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article
Pedro Carpintero a,∗ Jose-Antonio Del Fresno a Jorge Ruiz-Sanz a Paula Jaenal b a Orthopaedic Department, University Hospital Reina Sofia, Menendez Pidal Avenue, 14004 Cordoba, Spain b Pediatric Department, University Hospital Reina Sofia, Cordoba, Spain ∗ Corresponding
author. Tel.: +957218248; fax: +954218248. E-mail address: [email protected] (P. Carpintero) Accepted 22 October 2014 Available online 24 December 2014 http://dx.doi.org/10.1016/j.jbspin.2014.10.014
Catastrophic antiphospholipid syndrome presenting with bilateral massive adrenal haemorrhage. A case report
a r t i c l e
i n f o
Keywords: Catastrophic antiphospholipid syndrome Adrenal haemorrhage
A 55-year-old man with primary antiphospholipid syndrome (APS) since 1983 (three episodes of deep vein thrombosis, persistent lupus anticoagulant, and high titers of IgG anticardiolipin and anti-2 -glycoprotein I antibodies) presented with a sudden intense left flank pain. Two days before admission, warfarin had been discontinued and replaced by enoxaparin for a planned surgery. Physical examination revealed tachycardia (100 b/min) and a tender abdomen. CT-scan showed a massive left adrenal haemorrhage (AH) (Fig. 1A). INR value was 2.4. Enoxaparin was discontinued. The following day, general condition worsened. Blood pressure was 80/54 mmHg, heart rate 138 beats/min. Flank and abdominal pain persisted. Several splinter haemorrhages were noted. Haemoglobin (Hb) level dropped from 13.6 to 7 g/dL and platelet count from 180 000 to 60 000/mm3 , with no schizocytes.
Letters to the Editor / Joint Bone Spine (2015) 287–295
Fig. 1. Serial coronal abdominal CT-scan. A. The day of admission, showing left adrenal haemorrhage (9 cm × 5 cm). B. Three days after admission, showing increased left adrenal haemorrhage (13.5 cm × 10 cm). C. Four days after admission, showing the development of a right adrenal haemorrhage. *: hematoma in the left adrenal gland; ¤: hematoma in the right adrenal gland.
289
when active bleeding is documented whereas surgery is susceptible to increase bleeding by removing the hematoma compression effect [9]. In CAPS, these procedures may precipitate thrombotic events. AH complicating APS is thought to be a haemorrhagic infarction complicating adrenal vein thrombosis [2,4]; this was suspected in our patient, as his right adrenal gland seemed to be swollen before bleeding. Thus, we initially chose to continue heparin therapy despite the presence of massive adrenal hematomas that could also be attributed to anticoagulation itself. Several days after initiation of corticosteroids and IVIg, assuming that the risk of thrombotic complication has diminished, anticoagulation was discontinued for a few days. This case report of CAPS and bilateral AH leading to simultaneous life-threatening haemorrhage and thrombosis illustrate how anticoagulation can be a major challenge during the treatment of CAPS. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.
References
Fig. 2. Frontal abdominal CT-scan four days after admission, showing massive bilateral adrenal haemorrhage. *: hematoma in the left adrenal gland; ¤: hematoma in the right adrenal gland.
A second CT-scan (Fig. 1B) showed worsening of the left AH. Intravenous hydrocortisone (50 mg/6 h) and hydration improved the general condition. Unfractionated heparin (UFH) was started, targeting serum UFH level between 0.4 and 0.5 UI/mL, despite the haemorrhage, because catastrophic antiphospholipid syndrome (CAPS) was suspected. Anticoagulation was associated with platelets and red cells transfusions, IV immunoglobulin (IVIg) and methylprednisolone (1 mg/kg/d). The following day, he developed of a right flank pain revealing a right AH (CT-scan: Figs. 1C and 2). Four days after admission, as repeated transfusions were needed to maintain Hb > 7 g/dL, UFH was stopped, for three days and then resumed as haemoglobin level remained above 8.5 g/dL and platelet count > 100 000/mm3 . Livedo reticularis developed and skin biopsy showed numerous microthrombi in capillaries, supporting the diagnosis of CAPS. The patient discharged one month later with enoxaparin, secondarily replaced by warfarin. After a one-year follow-up, the patient is doing well with hydrocortisone supplementation and warfarin. Adrenal hematomas are slowly diminishing. Antiphospholipid syndrome is one of the most frequent causes of bilateral AH [1–4]. Our patient fulfils the classification criteria for a probable CAPS [5–7]: two organs involved in less than a week, histological evidence of small vessel occlusion, presence of antiphospholipid antibodies. Anticoagulation is the only treatment that seems to prevent death from CAPS [5,6,8]. However, experts recommend that treatment of life-threatening CAPS should combine anticoagulation, corticosteroids and IVIg or plasma exchange (PE) [3,6,8]. Management of our patient was particularly challenging given the large retroperitoneal haemorrhage but anticoagulation remains essential in this situation. Intra-arterial embolization could be used
[1] Espinosa G, Santos E, Cervera R, et al. Adrenal involvement in the antiphospholipid syndrome: clinical and immunologic characteristics of 86 patients. Medicine (Baltimore) 2003;82:106–18. [2] Ramon I, Mathian A, Bachelot A, et al. Primary adrenal insufficiency due to bilateral adrenal haemorrhage-adrenal infarction in the antiphospholipid syndrome: long-term outcome of 16 patients. J Clin Endocrinol Metab 2013;98:3179–89. [3] Costedoat-Chalumeau N, Arnaud L, Saadoun D, et al. Catastrophic antiphospholipid syndrome. Rev Med Interne 2012;33:194–9. [4] Vella A, Nippoldt TB, Morris JC. Adrenal haemorrhage: a 25-year experience at the Mayo Clinic. Mayo Clinic Proc 2001;76:161–8. [5] Asherson R, Cervera R, de Groot P, et al. Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines. Lupus 2003;12:530. [6] Asherson RA, Cervera R, Piette JC, et al. Catastrophic antiphospholipid syndrome: clues to the pathogenesis from a series of 80 patients. Medicine (Baltimore) 2001;80:355–77. [7] Erkan D, Espinosa G, Cervera R. Catastrophic antiphospholipid syndrome: updated diagnostic algorithms. Autoimmun Rev 2010;10:74–9. [8] Saadoun D, Piette J-C, Wahl D, et al. Management of antiphospholipid syndrome. Rev Med Interne 2012;33:217–22. [9] Chan YC, Morales JP, Reidy JF, et al. Management of spontaneous and iatrogenic retroperitoneal haemorrhage: conservative management, endovascular intervention or open surgery? Int J Clin Pract 2008;62:1604–13.
Adrien Michon a,∗ Luc Darnige b Jacques Pouchot a Jean-Benoît Arlet a a Service de médecine interne, hôpital européen Georges-Pompidou, Assistance Publique des hôpitaux de Paris, université Paris Descartes, Sorbonne Paris Cité, 20, rue Leblanc, 75015 Paris, France b Service d’hématologie biologique, hôpital européen Georges-Pompidou, Assistance Publique des hôpitaux de Paris, université Paris Descartes, Sorbonne Paris Cité, 75015 Paris, France ∗ Corresponding
author. Tel.: +33 1 56 09 27 19; fax: +33 1 56 09 38 16. E-mail address: [email protected] (A. Michon) Accepted 22 October 2014 Available online 29 December 2014
http://dx.doi.org/10.1016/j.jbspin.2014.10.016
Letters to the Editor / Joint Bone Spine (2015) 287–295
References [1] Odvina CV, Zerwekh JE, Rao DS, et al. Severely suppressed bone turnover: a potential complication of alendronate therapy. J Clin Endocrinol Metab 2005;90:1294–302. [2] Mashiba T, Hirano T, Turner CH, et al. Suppressed bone turnover by biphosphonate increases microdamage accumulation and reduces some biomechanical properties in dog rib. J Bone Miner Res 2000;15:613–20. [3] Abrahamsen B, Eiken P, Eastell R. Subtrochanteric and diaphyseal femur fractures in patients treated with alendronate: a register-based national cohort study. J Bone Miner Res 2009;24:1095–102. [4] Black DM, Kelly MP, Genant HK, et al. Bisphosphonates and fractures of the subtrochanteric or diaphyseal femur. N Engl J Med 2010;362:1761–71. [5] Neviaser AS, Lane JM, Edobor-Osula F, et al. Low-energy femoral fractures associated with alendronate use. J Orthop Trauma 2008;22:346–50. [6] Glorieux FH, Bishop NJ, Plotkin H, et al. Cyclic administration of pamidronate in children with severe osteogenic imperfecta. N Engl J Med 1998;339:947–52. [7] Whyte MP, Wenkert D, Clements KL, et al. Biphosphonate-induced osteopetrosis. Engl N J Med 2003;349:457–63. [8] Shane E, Burr D, Abrahamsen B, et al. Atypical subtrochanteric and diaphyseal femoral fractures: second report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 2014;29:1–23. [9] Bissonnette L, April PM, Dumais R, et al. Atypical fracture of the tibial diaphysis associated with biphosphonate therapy. A case report. Bone 2013;56:406–9. [10] Meier RPH, Lorenzini KI, Uebelhart B, et al. Atypical femoral fracture following biphosphonate treatment in a woman with osteogenesis imperfect. A case report. Acta Orthop 2012;83:548–50. Fig. 2. AP and lateral radiographs of the right tibia showing complete fracture of the mid-shaft tibia and fibula with oblique and transverse component and posterior spike.
fractures in children. The fractures observed in the patient reported here may be regarded as true atypical fractures since, even though the ASBMR task force criteria for atypical fracture [8] were not designed for application to fractures occurring in bones other than the femur, the fractures seen here shared certain features of atypical femoral fractures, including prodromal symptoms, and transverse, non-comminuted fracture following minimal trauma; additionally, the fracture affected both cortices and was associated with a medial spike; finally, was located in the mid-tibial diaphysis, and displayed thickening of the anterior cortex. Involvement of the anterior cortex rather than the lateral cortex as reported in atypical femoral fractures may be related to differences in geometry and in stress distribution along these bones. Atypical femoral fractures occur in the lateral cortex, where the greatest tension loading is exerted. Likewise, stress fractures of the anterior cortex of the tibial midshaft result from tension stress rather than compression [9]. But we cannot say with absolute certainty that this fracture is due to the treatment with biphosphonate because the osteogenesis imperfect itself could have contributed to the occurrence of this stress fracture, but the absent of an obvious trauma and the radiographic features make us think that this is an atypical fracture secondary to biphosphonate treatment. The literature contains only one report of a patient with osteogenesis imperfecta displaying atypical fracture associated with bisphosphonate therapy [10]; since this patient was 75 years old, the results cannot usefully be compared with those of the present study. The possible appearance of atypical fractures should be borne in mind when dealing with children receiving bisphosphonate therapy, and any unexplained pain should prompt examination using sensitive techniques such as scintigraphy or MRI. We consider that we have to make a careful selection of patients (multiple fracture or low BMD) due to the possible occurrence of these fractures or other complications related to the prolonged treatment with biphosphonates. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article
Pedro Carpintero a,∗ Jose-Antonio Del Fresno a Jorge Ruiz-Sanz a Paula Jaenal b a Orthopaedic Department, University Hospital Reina Sofia, Menendez Pidal Avenue, 14004 Cordoba, Spain b Pediatric Department, University Hospital Reina Sofia, Cordoba, Spain ∗ Corresponding
author. Tel.: +957218248; fax: +954218248. E-mail address: [email protected] (P. Carpintero) Accepted 22 October 2014 Available online 24 December 2014 http://dx.doi.org/10.1016/j.jbspin.2014.10.014
Catastrophic antiphospholipid syndrome presenting with bilateral massive adrenal haemorrhage. A case report
a r t i c l e
i n f o
Keywords: Catastrophic antiphospholipid syndrome Adrenal haemorrhage
A 55-year-old man with primary antiphospholipid syndrome (APS) since 1983 (three episodes of deep vein thrombosis, persistent lupus anticoagulant, and high titers of IgG anticardiolipin and anti-2 -glycoprotein I antibodies) presented with a sudden intense left flank pain. Two days before admission, warfarin had been discontinued and replaced by enoxaparin for a planned surgery. Physical examination revealed tachycardia (100 b/min) and a tender abdomen. CT-scan showed a massive left adrenal haemorrhage (AH) (Fig. 1A). INR value was 2.4. Enoxaparin was discontinued. The following day, general condition worsened. Blood pressure was 80/54 mmHg, heart rate 138 beats/min. Flank and abdominal pain persisted. Several splinter haemorrhages were noted. Haemoglobin (Hb) level dropped from 13.6 to 7 g/dL and platelet count from 180 000 to 60 000/mm3 , with no schizocytes.
Letters to the Editor / Joint Bone Spine (2015) 287–295
Fig. 1. Serial coronal abdominal CT-scan. A. The day of admission, showing left adrenal haemorrhage (9 cm × 5 cm). B. Three days after admission, showing increased left adrenal haemorrhage (13.5 cm × 10 cm). C. Four days after admission, showing the development of a right adrenal haemorrhage. *: hematoma in the left adrenal gland; ¤: hematoma in the right adrenal gland.
289
when active bleeding is documented whereas surgery is susceptible to increase bleeding by removing the hematoma compression effect [9]. In CAPS, these procedures may precipitate thrombotic events. AH complicating APS is thought to be a haemorrhagic infarction complicating adrenal vein thrombosis [2,4]; this was suspected in our patient, as his right adrenal gland seemed to be swollen before bleeding. Thus, we initially chose to continue heparin therapy despite the presence of massive adrenal hematomas that could also be attributed to anticoagulation itself. Several days after initiation of corticosteroids and IVIg, assuming that the risk of thrombotic complication has diminished, anticoagulation was discontinued for a few days. This case report of CAPS and bilateral AH leading to simultaneous life-threatening haemorrhage and thrombosis illustrate how anticoagulation can be a major challenge during the treatment of CAPS. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.
References
Fig. 2. Frontal abdominal CT-scan four days after admission, showing massive bilateral adrenal haemorrhage. *: hematoma in the left adrenal gland; ¤: hematoma in the right adrenal gland.
A second CT-scan (Fig. 1B) showed worsening of the left AH. Intravenous hydrocortisone (50 mg/6 h) and hydration improved the general condition. Unfractionated heparin (UFH) was started, targeting serum UFH level between 0.4 and 0.5 UI/mL, despite the haemorrhage, because catastrophic antiphospholipid syndrome (CAPS) was suspected. Anticoagulation was associated with platelets and red cells transfusions, IV immunoglobulin (IVIg) and methylprednisolone (1 mg/kg/d). The following day, he developed of a right flank pain revealing a right AH (CT-scan: Figs. 1C and 2). Four days after admission, as repeated transfusions were needed to maintain Hb > 7 g/dL, UFH was stopped, for three days and then resumed as haemoglobin level remained above 8.5 g/dL and platelet count > 100 000/mm3 . Livedo reticularis developed and skin biopsy showed numerous microthrombi in capillaries, supporting the diagnosis of CAPS. The patient discharged one month later with enoxaparin, secondarily replaced by warfarin. After a one-year follow-up, the patient is doing well with hydrocortisone supplementation and warfarin. Adrenal hematomas are slowly diminishing. Antiphospholipid syndrome is one of the most frequent causes of bilateral AH [1–4]. Our patient fulfils the classification criteria for a probable CAPS [5–7]: two organs involved in less than a week, histological evidence of small vessel occlusion, presence of antiphospholipid antibodies. Anticoagulation is the only treatment that seems to prevent death from CAPS [5,6,8]. However, experts recommend that treatment of life-threatening CAPS should combine anticoagulation, corticosteroids and IVIg or plasma exchange (PE) [3,6,8]. Management of our patient was particularly challenging given the large retroperitoneal haemorrhage but anticoagulation remains essential in this situation. Intra-arterial embolization could be used
[1] Espinosa G, Santos E, Cervera R, et al. Adrenal involvement in the antiphospholipid syndrome: clinical and immunologic characteristics of 86 patients. Medicine (Baltimore) 2003;82:106–18. [2] Ramon I, Mathian A, Bachelot A, et al. Primary adrenal insufficiency due to bilateral adrenal haemorrhage-adrenal infarction in the antiphospholipid syndrome: long-term outcome of 16 patients. J Clin Endocrinol Metab 2013;98:3179–89. [3] Costedoat-Chalumeau N, Arnaud L, Saadoun D, et al. Catastrophic antiphospholipid syndrome. Rev Med Interne 2012;33:194–9. [4] Vella A, Nippoldt TB, Morris JC. Adrenal haemorrhage: a 25-year experience at the Mayo Clinic. Mayo Clinic Proc 2001;76:161–8. [5] Asherson R, Cervera R, de Groot P, et al. Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines. Lupus 2003;12:530. [6] Asherson RA, Cervera R, Piette JC, et al. Catastrophic antiphospholipid syndrome: clues to the pathogenesis from a series of 80 patients. Medicine (Baltimore) 2001;80:355–77. [7] Erkan D, Espinosa G, Cervera R. Catastrophic antiphospholipid syndrome: updated diagnostic algorithms. Autoimmun Rev 2010;10:74–9. [8] Saadoun D, Piette J-C, Wahl D, et al. Management of antiphospholipid syndrome. Rev Med Interne 2012;33:217–22. [9] Chan YC, Morales JP, Reidy JF, et al. Management of spontaneous and iatrogenic retroperitoneal haemorrhage: conservative management, endovascular intervention or open surgery? Int J Clin Pract 2008;62:1604–13.
Adrien Michon a,∗ Luc Darnige b Jacques Pouchot a Jean-Benoît Arlet a a Service de médecine interne, hôpital européen Georges-Pompidou, Assistance Publique des hôpitaux de Paris, université Paris Descartes, Sorbonne Paris Cité, 20, rue Leblanc, 75015 Paris, France b Service d’hématologie biologique, hôpital européen Georges-Pompidou, Assistance Publique des hôpitaux de Paris, université Paris Descartes, Sorbonne Paris Cité, 75015 Paris, France ∗ Corresponding
author. Tel.: +33 1 56 09 27 19; fax: +33 1 56 09 38 16. E-mail address: [email protected] (A. Michon) Accepted 22 October 2014 Available online 29 December 2014
http://dx.doi.org/10.1016/j.jbspin.2014.10.016
