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Lingual thrombosis in a woman with antiphospholipid syndrome
Case Report
www. AJOG.org
Lingual thrombosis in a woman with antiphospholipid syndrome Jovana P. Lekovic, MD; Constantin M. Friedman, MD; Maria T. DeSancho, MD, MSc
C ASE R EPORT A 28-year-old female, gravida 3 P 1, 34 weeks pregnant, presented to the labor and delivery suite with a 10 day history of lingual vesicular lesions and mouth soreness. She had a history of herpes simplex virus infection, with relatively frequent outbreaks, usually on her lower lip but never on her tongue. Her primary care physician had started her on valacyclovir orally for a presumed herpes outbreak. However, the lingual lesion became very
From the Department of Obstetrics and Gynecology, New York Presbyterian HospitalWeill Cornell Medical College, New York, NY (Dr Lekovic); and Department of Pathology (Dr Friedman) and Division of Hematology and Oncology (Dr DeSancho), Department of Medicine, Weill Cornell Medical College, New York, NY. The authors report no conflict of interest. Reprints: Maria T. DeSancho, MD, MSc, Department of Medicine, Division of Hematology and Oncology, Weill Cornell Medical College, 1305 York Ave., New York, NY 10021. [email protected] 0002-9378/free © 2013 Mosby, Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajog.2013.01.002
A 28-year-old woman, 34 weeks pregnant, with previously diagnosed antiphospholipid syndrome, presents with vesicular tongue lesions treated as herpes outbreak and new onset of preeclampsia. Tongue biopsy preformed postpartum after induction of labor for preeclampsia reveals tongue infarction. Key words: antiphospholipid syndrome, preeclampsia, thrombophilia, tongue thrombosis
painful and she was having difficulty tolerating oral fluid or food intake. Her past medical history was significant for a second-trimester fetal demise 4 years previously. She was subsequently found to have persistently positive lupus anticoagulant and high-titer antiphospholipid antibodies (aPLs), and the diagnosis of antiphospholipid syndrome (APS) was made. She became pregnant again while on aspirin 81 mg and prophylactic enoxaparin 40 mg subcutaneously (SC) daily. She had an uneventful second pregnancy and delivered at 37 weeks of gestation. She had postpartum thromboprophylaxis with enoxaparin 40 mg SC daily for 6 weeks. During the current, third pregnancy, she was managed with a prophylactic dose of enoxaparin 40 mg SC and aspirin 81 mg daily. The
enoxaparin dose was increased to 60 mg SC daily because her antifactor Xa activity was found to be decreased at 32 weeks of gestation. On examination, purple discoloration and blisters were noted on the right lateral aspect of the tongue and on the superior and inferior surfaces (Figure, A). Her blood pressure was elevated to 140/92 mmHg, and urinalysis demonstrated 30 mg of protein. Platelets were decreased to 111,000/L. Concern for preeclampsia prompted hospital admission for 24-hour urine protein collection and observation. The treatment with valacyclovir for the lingual lesion was continued. The following day, her 24-hour urine protein collection demonstrated significant proteinuria (360 mg per 24 hours), and her platelet count dropped
FIGURE
Lingual lesion
A
B
C
A, Lingual lesion on presentation. B, Pathological findings. C, Lingual lesion resolved on follow-up visit. Lekovic. Pregnant woman with lingual thrombosis. Am J Obstet Gynecol 2013.
APRIL 2013 American Journal of Obstetrics & Gynecology
e3
Case Report to 80,000/L. Her blood pressure remained elevated, and she was induced with oxytocin for presumed atypical hemolysis-elevated liver enzymes-low platelets syndrome (HELLP). She had an uncomplicated labor and delivered vaginally a healthy male baby with Apgar scores of 9 and 9 for 1 and 5 minutes, respectively, and weighing 2890 g. Placental pathology demonstrated decidual vasculopathy and 3-vessel cord with focal myonecrosis. Persistence of the painful lingual lesion despite treatment prompted a lingual biopsy, which revealed recent thrombi in small- to medium-sized vessels, leading to ischemic necrosis of the adjacent striated muscle and adjacent acute inflammation. Mucosal necrosis and ulceration were also noted (Figure, B); these findings were consistent with lingual infarction. The patient was restarted on therapeutic enoxaparin at 60 mg every 12 hours. On a follow-up visit 2 weeks postpartum, her lingual lesion was markedly improved, and the lesion completely resolved 4 weeks after delivery (Figure, C). APS is a clinicopathological diagnosis characterized by the presence of vascular thrombosis and/or pregnancy morbidity along with positive antibodies directed against phospholipids or phospholipidbinding proteins (aPLs), present on confirmatory testing after 12 weeks.1 Arterial infarction and the subsequent gangrene of the tongue has previously been described in patients with systemic lupus erythematosus,2 atrial fibrillation, giant cell arteritis,3 or radiation but never in patients with APS. In addition, liver, bone, and gut infarction in association with APS and HELLP syndrome
e4
www.AJOG.org have been reported.4 Thrombotic microangiopathy is a pathological feature of catastrophic antiphospolipid syndrome (when 3 or more organ systems are affected by thromboses in less than a week), however, with high frequency of kidney, skin, pulmonary, and central nervous system involvement,5 whereas tongue pathology has never been reported before. Other unusual sites of thrombosis have been reported in pregnant women with APS, including cerebral venous sinus thrombosis in the first trimester of pregnancy6 and ovarian vein thrombosis in the postpartum period.7 Hepatic infarction, a rare condition caused by the dual blood supply to the liver, acute noninflammatory pancreatitis,8 nonbacterial thrombotic endocarditis,9 Snedon’s syndrome (noninflammatory occlusive arteriopathy of small- and mediumsized arteries of the skin and the brain leading to cerebrovascular disease and livedo reticularis),10 avascular bone necrosis,11 and adrenal vein thrombosis resulting in Addison’s disease12 have also been reported. We believe that any unusual lesion in a pregnant patient with APS, a condition with high morbidity and mortality, should be investigated thoroughly to establish an accurate diagnosis and initiate f prompt therapeutic intervention. ACKNOWLEDGMENTS Contributions to this work were made by the following authors: Dr Lekovic was involved in the literature search, data collection, and writing the report; Dr Friedman performed the pathology analysis and provided pathology photographs; and Dr DeSancho was involved in the literature search, editing the report, and supervision.
American Journal of Obstetrics & Gynecology APRIL 2013
REFERENCES 1. American College of Obstetricians and Gynecologists Practice Bulletin. Antiphospholipid syndrome. Available at: http://www.acog.org/ Resources_And_Publications/Practice_Bulletins/ Committee_on_Practice_Bulletins_—_Obstetrics/ Antiphospholipid_Syndrome. Accessed Dec. 2, 2012. 2. Korn S, Huppert A, Spitzer S, DeHoratus R. Systemic lupus erythematosus presenting with lingual Infarction. J Rheumatol 1988;15: 1281-3. 3. Pedersen AT, Jepsen FL. Lingual infarction in giant cell arteritis: a case report. J Laryngol Otol 1983;97:479-83. 4. Koenig M, Roy M, Baccot S, Cuilleron M, de Filippis JP, Cathébras P. Thrombotic microangiopathy with liver, gut, and bone infarction (catastrophic antiphospholipid syndrome) associated with HELLP syndrome. Clin Rheumatol 2005;24:166-8. 5. Asherson R, Carvera R, Piette J, et al. Catastrophic antiphospolipid syndrome: clues to the pathogenesis from a series of 80 patients. Medicine (Baltimore) 2001;80:355-77. 6. Hanprasertpong T, Hanprasertpong J, Riabroi K. Cerebral venous sinus thrombosis in early pregnancy: an unusual presentation of primary antiphospholipid syndrome. J Obstet Gynaecol Res 2009;35:1125-8. 7. André M, Delèvaux I, Amoura Z, et al. Ovarian vein thrombosis in the antiphospholipid syndrome. Arthritis Rheum 2004;50:183-6. 8. Uthmal I, Khamashta M. The abdominal manifestations of the antiphospholipid syndrome. Rheumatology 2007;46:1641-7. 9. Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006;4:295-306. 10. Francès C, Piette JC. The mystery of Sneddon syndrome: relationship with antiphospholipid syndrome and systemic lupus erythematosus. J Autoimmun 2000;15:139-43. 11. Gorshtein A, Levy Y. Orthopedic involvement in antiphospholipid syndrome. Clin Rev Allergy Immunol 2007;32:167-71. 12. Uthman I, Salti I, Khamashta M. Endocrinologic manifestations of the antiphospholipid syndrome. Lupus 2006;15:485-9.
www. AJOG.org
Lingual thrombosis in a woman with antiphospholipid syndrome Jovana P. Lekovic, MD; Constantin M. Friedman, MD; Maria T. DeSancho, MD, MSc
C ASE R EPORT A 28-year-old female, gravida 3 P 1, 34 weeks pregnant, presented to the labor and delivery suite with a 10 day history of lingual vesicular lesions and mouth soreness. She had a history of herpes simplex virus infection, with relatively frequent outbreaks, usually on her lower lip but never on her tongue. Her primary care physician had started her on valacyclovir orally for a presumed herpes outbreak. However, the lingual lesion became very
From the Department of Obstetrics and Gynecology, New York Presbyterian HospitalWeill Cornell Medical College, New York, NY (Dr Lekovic); and Department of Pathology (Dr Friedman) and Division of Hematology and Oncology (Dr DeSancho), Department of Medicine, Weill Cornell Medical College, New York, NY. The authors report no conflict of interest. Reprints: Maria T. DeSancho, MD, MSc, Department of Medicine, Division of Hematology and Oncology, Weill Cornell Medical College, 1305 York Ave., New York, NY 10021. [email protected] 0002-9378/free © 2013 Mosby, Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajog.2013.01.002
A 28-year-old woman, 34 weeks pregnant, with previously diagnosed antiphospholipid syndrome, presents with vesicular tongue lesions treated as herpes outbreak and new onset of preeclampsia. Tongue biopsy preformed postpartum after induction of labor for preeclampsia reveals tongue infarction. Key words: antiphospholipid syndrome, preeclampsia, thrombophilia, tongue thrombosis
painful and she was having difficulty tolerating oral fluid or food intake. Her past medical history was significant for a second-trimester fetal demise 4 years previously. She was subsequently found to have persistently positive lupus anticoagulant and high-titer antiphospholipid antibodies (aPLs), and the diagnosis of antiphospholipid syndrome (APS) was made. She became pregnant again while on aspirin 81 mg and prophylactic enoxaparin 40 mg subcutaneously (SC) daily. She had an uneventful second pregnancy and delivered at 37 weeks of gestation. She had postpartum thromboprophylaxis with enoxaparin 40 mg SC daily for 6 weeks. During the current, third pregnancy, she was managed with a prophylactic dose of enoxaparin 40 mg SC and aspirin 81 mg daily. The
enoxaparin dose was increased to 60 mg SC daily because her antifactor Xa activity was found to be decreased at 32 weeks of gestation. On examination, purple discoloration and blisters were noted on the right lateral aspect of the tongue and on the superior and inferior surfaces (Figure, A). Her blood pressure was elevated to 140/92 mmHg, and urinalysis demonstrated 30 mg of protein. Platelets were decreased to 111,000/L. Concern for preeclampsia prompted hospital admission for 24-hour urine protein collection and observation. The treatment with valacyclovir for the lingual lesion was continued. The following day, her 24-hour urine protein collection demonstrated significant proteinuria (360 mg per 24 hours), and her platelet count dropped
FIGURE
Lingual lesion
A
B
C
A, Lingual lesion on presentation. B, Pathological findings. C, Lingual lesion resolved on follow-up visit. Lekovic. Pregnant woman with lingual thrombosis. Am J Obstet Gynecol 2013.
APRIL 2013 American Journal of Obstetrics & Gynecology
e3
Case Report to 80,000/L. Her blood pressure remained elevated, and she was induced with oxytocin for presumed atypical hemolysis-elevated liver enzymes-low platelets syndrome (HELLP). She had an uncomplicated labor and delivered vaginally a healthy male baby with Apgar scores of 9 and 9 for 1 and 5 minutes, respectively, and weighing 2890 g. Placental pathology demonstrated decidual vasculopathy and 3-vessel cord with focal myonecrosis. Persistence of the painful lingual lesion despite treatment prompted a lingual biopsy, which revealed recent thrombi in small- to medium-sized vessels, leading to ischemic necrosis of the adjacent striated muscle and adjacent acute inflammation. Mucosal necrosis and ulceration were also noted (Figure, B); these findings were consistent with lingual infarction. The patient was restarted on therapeutic enoxaparin at 60 mg every 12 hours. On a follow-up visit 2 weeks postpartum, her lingual lesion was markedly improved, and the lesion completely resolved 4 weeks after delivery (Figure, C). APS is a clinicopathological diagnosis characterized by the presence of vascular thrombosis and/or pregnancy morbidity along with positive antibodies directed against phospholipids or phospholipidbinding proteins (aPLs), present on confirmatory testing after 12 weeks.1 Arterial infarction and the subsequent gangrene of the tongue has previously been described in patients with systemic lupus erythematosus,2 atrial fibrillation, giant cell arteritis,3 or radiation but never in patients with APS. In addition, liver, bone, and gut infarction in association with APS and HELLP syndrome
e4
www.AJOG.org have been reported.4 Thrombotic microangiopathy is a pathological feature of catastrophic antiphospolipid syndrome (when 3 or more organ systems are affected by thromboses in less than a week), however, with high frequency of kidney, skin, pulmonary, and central nervous system involvement,5 whereas tongue pathology has never been reported before. Other unusual sites of thrombosis have been reported in pregnant women with APS, including cerebral venous sinus thrombosis in the first trimester of pregnancy6 and ovarian vein thrombosis in the postpartum period.7 Hepatic infarction, a rare condition caused by the dual blood supply to the liver, acute noninflammatory pancreatitis,8 nonbacterial thrombotic endocarditis,9 Snedon’s syndrome (noninflammatory occlusive arteriopathy of small- and mediumsized arteries of the skin and the brain leading to cerebrovascular disease and livedo reticularis),10 avascular bone necrosis,11 and adrenal vein thrombosis resulting in Addison’s disease12 have also been reported. We believe that any unusual lesion in a pregnant patient with APS, a condition with high morbidity and mortality, should be investigated thoroughly to establish an accurate diagnosis and initiate f prompt therapeutic intervention. ACKNOWLEDGMENTS Contributions to this work were made by the following authors: Dr Lekovic was involved in the literature search, data collection, and writing the report; Dr Friedman performed the pathology analysis and provided pathology photographs; and Dr DeSancho was involved in the literature search, editing the report, and supervision.
American Journal of Obstetrics & Gynecology APRIL 2013
REFERENCES 1. American College of Obstetricians and Gynecologists Practice Bulletin. Antiphospholipid syndrome. Available at: http://www.acog.org/ Resources_And_Publications/Practice_Bulletins/ Committee_on_Practice_Bulletins_—_Obstetrics/ Antiphospholipid_Syndrome. Accessed Dec. 2, 2012. 2. Korn S, Huppert A, Spitzer S, DeHoratus R. Systemic lupus erythematosus presenting with lingual Infarction. J Rheumatol 1988;15: 1281-3. 3. Pedersen AT, Jepsen FL. Lingual infarction in giant cell arteritis: a case report. J Laryngol Otol 1983;97:479-83. 4. Koenig M, Roy M, Baccot S, Cuilleron M, de Filippis JP, Cathébras P. Thrombotic microangiopathy with liver, gut, and bone infarction (catastrophic antiphospholipid syndrome) associated with HELLP syndrome. Clin Rheumatol 2005;24:166-8. 5. Asherson R, Carvera R, Piette J, et al. Catastrophic antiphospolipid syndrome: clues to the pathogenesis from a series of 80 patients. Medicine (Baltimore) 2001;80:355-77. 6. Hanprasertpong T, Hanprasertpong J, Riabroi K. Cerebral venous sinus thrombosis in early pregnancy: an unusual presentation of primary antiphospholipid syndrome. J Obstet Gynaecol Res 2009;35:1125-8. 7. André M, Delèvaux I, Amoura Z, et al. Ovarian vein thrombosis in the antiphospholipid syndrome. Arthritis Rheum 2004;50:183-6. 8. Uthmal I, Khamashta M. The abdominal manifestations of the antiphospholipid syndrome. Rheumatology 2007;46:1641-7. 9. Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006;4:295-306. 10. Francès C, Piette JC. The mystery of Sneddon syndrome: relationship with antiphospholipid syndrome and systemic lupus erythematosus. J Autoimmun 2000;15:139-43. 11. Gorshtein A, Levy Y. Orthopedic involvement in antiphospholipid syndrome. Clin Rev Allergy Immunol 2007;32:167-71. 12. Uthman I, Salti I, Khamashta M. Endocrinologic manifestations of the antiphospholipid syndrome. Lupus 2006;15:485-9.