Lupus (2015) 24, 90–93 http://lup.sagepub.com
CASE REPORT
Recurrent spontaneous subdural hematoma secondary to immune thrombocytopenia in a patient with overlap syndrome KG Goh1 and SG Ong2 1
Department of Medicine, University Malaya Medical Centre, Kuala Lumpur, Malaysia; and 2Department of Medicine, Kuala Lumpur Hospital, Kuala Lumpur, Malaysia
Patients with autoimmune connective tissue disease may manifest as overlap syndrome with features of systemic lupus erythematosus (SLE), systemic sclerosis, rheumatoid arthritis and myositis. Those presenting with active SLE can present with immune thrombocytopenia (IT) and may be complicated with subdural hematoma which, though rare, is potentially lifethreatening. We report here a patient with overlap syndrome who had recurrent spontaneous subdural hematoma due to severe thrombocytopenia which did not respond to corticosteroids and azathioprine. Her platelet count became normal with three doses of low-dose intravenous cyclophosphamide (IV CYC) given at 3-weekly intervals. She remained in remission with maintenance therapy with azathioprine. Lupus (2015) 24, 90–93. Key words: Systemic lupus erythematosus; recurrent subdural hematoma; immune thrombocytopenia
Introduction Overlap syndrome is a heterogeneous multi-systemic autoimmune connective tissue disease. Patients with overlap syndrome present with clinical features of systemic lupus erythematosus (SLE), systemic sclerosis, polymyositis and rheumatoid arthritis. Due to severe thrombocytopenia, patients can present with intracranial hemorrhage which is potentially fatal,1 or subdural hematoma (SDH) which is rare2 and usually caused by traumatic brain injury, and occurs more commonly in the very young or elderly.3 We present here a case of overlap syndrome with recurrent SDH as a result of severe thrombocytopenia, which to the best of our knowledge is the first reported case.
Case report A 22-year-old woman presented to the medical ward with a 1-week history of generalized headache and vomiting. The headache had become Correspondence to: Swee Gaik Ong, Department of Medicine, Kuala Lumpur Hospital, Jalan Pahang, 50586 Kuala Lumpur, Malaysia. Email: [email protected] Received 8 February 2014; revised: 23 March 2014; 31 August 2014; accepted 10 September 2014
progressively more severe, with a pain score of 8 out of 10. She had 4–5 episodes of vomiting per day, which was not associated with nausea. There were no other signs of raised intracranial pressure such as visual disturbances or altered level of consciousness. She could not recall any recent head trauma and she denied consuming any drugs or traditional remedies. Physical examination revealed an alert, smallbuilt young lady. She weighed 35 kg. She was afebrile, pulse rate was 82 beats per minute and blood pressure was 100/75 mm Hg. There was no neck stiffness and neurological examination was unremarkable. She had microstomia, Raynaud’s phenomenon, sclerodactyly, digital pitting scars, tight and waxy skin of the limbs with patchy ‘salt-andpepper’ appearance, and fine crepitations in both lung bases. There was no lymphadenopathy or hepatosplenomegaly. Her previous clinic records showed she had been diagnosed as having cutaneous lupus erythematosus based on a skin biopsy 2 years ago. In addition, she had pulmonary fibrosis identified from high-resolution computed tomography (CT) of the thorax. There was no pulmonary hypertension on echocardiography. Her blood results showed platelet count of 3 109/l, hemoglobin concentration of 7.7 g/dl and white blood count of 2.87 109/l. Reticulocyte count was normal at 2.3% (0.5–2.5%).
! The Author(s), 2014. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav
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10.1177/0961203314554248
Recurrent spontaneous subdural hematoma secondary to IT in a patient with overlap syndrome KG Goh and SG Ong
91
Peripheral blood smear showed hypochromic microcytic red blood cells and marked reduction in platelets of 2560 (speckled pattern) and anti-dsDNA was negative. Anti-SSA and anti-RNP antibodies were positive. Urine analysis was normal. In view of the sudden onset of headache and severe thrombocytopenia, a CT brain was performed. It showed subdural hematoma at the right temporo-parietal region which extended to the tentorium cerebelli and posterior interhemispheric fissure. However there was no midline shift (Figure 1). She remained alert throughout her stay in the ward with a Glasgow Coma Scale (GCS) of 15/15. She did not develop any signs of raised intracranial pressure or focal neurological deficit. Hence she was treated conservatively by the neurosurgical team. Given the hematological abnormalities, a bone marrow aspiration and trephine biopsy was done which showed mild trilineage myelodysplasia with no evidence of hematological malignancy.
Figure 1 Non-enhanced CT brain showed subdural hematoma (arrow) at the right temporo-parietal region with extension to the tentorium cerebelli and posterior interhemispheric fissure. There was no midline shift.
The above findings demonstrated a lupus flare with severe thrombocytopenia complicated by SDH. As she had features of both SLE and systemic sclerosis, a diagnosis of overlap syndrome was established. She was transfused with 4 units of platelet concentrate and given intravenous (IV) methylprednisolone 500 mg daily for 3 days together with intravenous immunoglobulin (IVIG) at 0.4 g/kg/ day for 5 days, followed by 40 mg of oral prednisolone. Platelet count rose to 49 109/l on day 2 of treatment and it reached 189 109/l on day 14. By then her headache had resolved and she was discharged for follow-up at the clinic. Our patient defaulted follow-up, and after 9 months she presented with a new episode of generalized headache. She denied traumatic injury to the head. Once again she had severe thrombocytopenia (4 109/l) with an elevated ESR of 86 mm/hr. CT brain showed SDH, this time involving the left temporo-parietal region, with no midline shift (Figure 2). She received 4 units of platelet concentrate, IVIG and IV methylprednisolone, followed by oral prednisolone of 40 mg od. Platelet count rose to 72 109/l on day 2 and 115 109/l on day 10 of treatment, respectively. Azathioprine 50 mg daily was added for steroid-sparing effect and was increased to 75 mg (at 2 mg/kg/day) daily 2 weeks later.
Figure 2 Non-enhanced CT brain showing subdural hematoma (arrows) involving the left temporo-parietal region, with no midline shift. Lupus
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Recurrent spontaneous subdural hematoma secondary to IT in a patient with overlap syndrome KG Goh and SG Ong
92
We tapered the dose of prednisolone gradually over the ensuing 3 months. Nevertheless, once prednisolone was reduced to 25 mg daily, the platelet count began to drop below 150 109/l. It even plummeted to as low as 35 109/l. Given the inadequate response to prednisolone and azathioprine, the latter was discontinued. Our patient was then treated with IV methylprednisolone 250 mg daily for three doses, followed by low-dose IV cyclophosphamide (IV CYC) 500 mg. Prednisolone was increased back to 30 mg daily. On day 5 of treatment, platelet count had risen to 148 109/l. The patient subsequently received two further cycles of IV CYC at 3-weekly intervals. Her platelet count was maintained above 150 109/l throughout the 6-week course of IV CYC therapy. Given her favorable response and achievement of remission induction with three doses of IV CYC, it was decided that further treatment with IV CYC was no longer necessary and instead she was commenced on azathioprine. Meanwhile, the dose of oral prednisolone was gradually tapered. Platelet count remained normal for the subsequent 12 months and she was maintained on azathioprine 75 mg daily and prednisolone 2.5 mg daily. To date, she continues to be well with no further flares of lupus or progression of systemic sclerosis.
Discussion Hematological abnormalities including immune thrombocytopenia (IT) are frequent among patients with SLE. The degree of thrombocytopenia is variable, but profound thrombocytopenia as illustrated in our patient is uncommon. There are several mechanisms involved in the pathogenesis of thrombocytopenia in SLE, but the most common mechanism is immune-mediated platelet destruction. Bone marrow evaluation is occasionally necessary in SLE patients with unexplained cytopenias. Our patient’s bone marrow biopsy showed mild trilineage dysplasia, a finding that had been described in SLE patients. Voulgarelis et al. examined bone marrow biopsies of 40 SLE patients with cytopenias and found bone marrow changes which among others included bone marrow necrosis, bone marrow hypocellularity, stromal changes, distortion of bone marrow microarchitecture as well as dysplastic changes of all hemopoietic lineages.4 Spontaneous intracranial hemorrhage is the most feared complication of IT as it is potentially fatal. In a review of 26 cases of SLE with intracranial hemorrhage, Gao et al. found that
thrombocytopenia was an independent risk factor for this group of patients.5 The most common form of intracranial hemorrhage as a result of thrombocytopenia is intracerebral hemorrhage. Subdural hematoma is less common, and while it remains a rare entity in the setting of IT, has been reported to occur in 0.65% to 26% of patients with thrombocytopenia.3 Given the fact that thrombocytopenia in the setting of SLE is largely immune mediated, the mainstay of drug therapy is systemic corticosteroids. Since our patient had severe thrombocytopenia which was complicated by life-threatening bleeding manifestation, urgent treatment with combination pulsed IV methylprednisolone and IVIG, together with platelet transfusion was instituted at an early stage. The aims of treatment were to rapidly increase the platelet count to a safe level and prevent further bleeding. In patients who fail to respond to systemic corticosteroids, require moderate doses of corticosteroids to maintain the platelet count, or develop undesirable side effects from corticosteroids, other agents are deemed necessary. These include rituximab, mycophenolate mofetil and more recently, thrombopoeitin receptor agonist.6–8 Splenectomy remains an option for refractory thrombocytopenia if medical therapies fail. Intermittent IV CYC is a cytotoxic agent which was initially used in treating lupus nephritis.9 Nonetheless, its use in the treatment of thrombocytopenia is considered ‘off label’.10 More recently, Park et al. demonstrated two patients with SLE who achieved successful remission of IT with lowdose IV CYC.11 To date, there is still no consensus about the ideal treatment dose of cyclophosphamide, frequency of dosing or duration of treatment in treating IT. In our patient, azathioprine had failed to maintain the platelet count when prednisolone was tapered. However, her thrombocytopenia demonstrated remarkable improvement with three cycles of low-dose IV CYC. Platelet count remained normal in the subsequent 12 months while she was receiving maintenance therapy with azathioprine and prednisolone. Of note, she did not experience any acute side effects of IV CYC. The potential benefit of pulse IV CYC in the treatment of IT has to be judiciously weighed against its short- and long-term adverse effects which include infection, gonadal failure and malignancy. It was noteworthy that both episodes of spontaneous SDH were associated with increased activity of SLE as demonstrated by leukopenia and raised ESR.
Lupus Downloaded from lup.sagepub.com at UNIV PRINCE EDWARD ISLAND on February 5, 2015
Recurrent spontaneous subdural hematoma secondary to IT in a patient with overlap syndrome KG Goh and SG Ong
93
Spontaneous recurrent SDH as a consequence of recurrent thrombocytopenia is extremely rare, particularly in the setting of connective tissue disease. We successfully induced remission for IT with short-course low-dose IV CYC in a patient who failed to respond to corticosteroids and azathioprine. Hence we propose that treatment regime using short-course low-dose IV CYC followed by azathioprine is strongly considered in the management of IT for patients with connective tissue disease.
Funding This research received no specific grant from any agency.
Conflict of interest statement The authors have no conflicts of interest to declare.
References
2 Panicker JN, Pavithran K, Thomas M. Management of subdural hematoma in immune thrombocytopenic purpura: Report of seven patients and a literature review. Clin Neurol Neurosurg 2009; 111: 189–192. 3 Meena AK, Murthy JM. Subdural haematoma in a patient with immune thrombocytopenic purpura. Neurol India 1999; 47: 335–337. 4 Voulgarelis M, Giannouli S, Tasidou A, et al. Bone marrow histological findings in systemic lupus erythematosus with hematologic abnormalities: A clinicopathological study. Am J Hematology 2006; 81: 590–597. 5 Gao N, Wang ZL, Li MT, et al. Clinical characteristics and risk factors of intracranial hemorrhage in systemic lupus erythematosus. Lupus 2013; 22: 453–460. 6 Jovancevic B, Lindholm C, Pullerits R. Anti B-cell therapy against refractory thrombocytopenia in SLE and MCTD patients: Longterm follow-up and review of the literature. Lupus 2013; 22: 664–674. 7 Alkaabi JK, Alkindi S, Riyami NA, et al. Successful treatment of severe thrombocytopenia with romiplostim in a pregnant patient with systemic lupus erythematosus. Lupus 2012; 21: 1571–1574. 8 Vasoo S, Thumboo J, Fong K-Y. Refractory immune thrombocytopenia in systemic lupus erythematosus: Response to mycophenolate mofetil. Lupus 2003; 12: 630–632. 9 Hui M, Garner R, Rees F, et al. Lupus nephritis: A 15-year multicentre experience in the UK. Lupus 2013; 22: 328–332. 10 Aringer M, Burkhardt H, Burmester GR, et al. Current state of evidence on ‘‘off-label’’ therapeutic options for systemic lupus erythematosus, including biological immunosuppressive agents in Germany, Austria and Switzerland - a consensus report. Lupus 2012; 21: 386–401. 11 Park H-J, Kang M-I, Kang Y, et al. Two cases of refractory thrombocytopenia in systemic lupus erythematosus that responded to intravenous low-dose cyclophosphamide. J Korean Med Sci 2013; 28: 472–475.
1 Liliang P-C, Tsai Y-D, Liang C-L, et al. Chronic subdural haematoma in young and extremely aged adults: A comparative study of two age groups. Injury 2002; 33: 345–348.
Lupus Downloaded from lup.sagepub.com at UNIV PRINCE EDWARD ISLAND on February 5, 2015
CASE REPORT
Recurrent spontaneous subdural hematoma secondary to immune thrombocytopenia in a patient with overlap syndrome KG Goh1 and SG Ong2 1
Department of Medicine, University Malaya Medical Centre, Kuala Lumpur, Malaysia; and 2Department of Medicine, Kuala Lumpur Hospital, Kuala Lumpur, Malaysia
Patients with autoimmune connective tissue disease may manifest as overlap syndrome with features of systemic lupus erythematosus (SLE), systemic sclerosis, rheumatoid arthritis and myositis. Those presenting with active SLE can present with immune thrombocytopenia (IT) and may be complicated with subdural hematoma which, though rare, is potentially lifethreatening. We report here a patient with overlap syndrome who had recurrent spontaneous subdural hematoma due to severe thrombocytopenia which did not respond to corticosteroids and azathioprine. Her platelet count became normal with three doses of low-dose intravenous cyclophosphamide (IV CYC) given at 3-weekly intervals. She remained in remission with maintenance therapy with azathioprine. Lupus (2015) 24, 90–93. Key words: Systemic lupus erythematosus; recurrent subdural hematoma; immune thrombocytopenia
Introduction Overlap syndrome is a heterogeneous multi-systemic autoimmune connective tissue disease. Patients with overlap syndrome present with clinical features of systemic lupus erythematosus (SLE), systemic sclerosis, polymyositis and rheumatoid arthritis. Due to severe thrombocytopenia, patients can present with intracranial hemorrhage which is potentially fatal,1 or subdural hematoma (SDH) which is rare2 and usually caused by traumatic brain injury, and occurs more commonly in the very young or elderly.3 We present here a case of overlap syndrome with recurrent SDH as a result of severe thrombocytopenia, which to the best of our knowledge is the first reported case.
Case report A 22-year-old woman presented to the medical ward with a 1-week history of generalized headache and vomiting. The headache had become Correspondence to: Swee Gaik Ong, Department of Medicine, Kuala Lumpur Hospital, Jalan Pahang, 50586 Kuala Lumpur, Malaysia. Email: [email protected] Received 8 February 2014; revised: 23 March 2014; 31 August 2014; accepted 10 September 2014
progressively more severe, with a pain score of 8 out of 10. She had 4–5 episodes of vomiting per day, which was not associated with nausea. There were no other signs of raised intracranial pressure such as visual disturbances or altered level of consciousness. She could not recall any recent head trauma and she denied consuming any drugs or traditional remedies. Physical examination revealed an alert, smallbuilt young lady. She weighed 35 kg. She was afebrile, pulse rate was 82 beats per minute and blood pressure was 100/75 mm Hg. There was no neck stiffness and neurological examination was unremarkable. She had microstomia, Raynaud’s phenomenon, sclerodactyly, digital pitting scars, tight and waxy skin of the limbs with patchy ‘salt-andpepper’ appearance, and fine crepitations in both lung bases. There was no lymphadenopathy or hepatosplenomegaly. Her previous clinic records showed she had been diagnosed as having cutaneous lupus erythematosus based on a skin biopsy 2 years ago. In addition, she had pulmonary fibrosis identified from high-resolution computed tomography (CT) of the thorax. There was no pulmonary hypertension on echocardiography. Her blood results showed platelet count of 3 109/l, hemoglobin concentration of 7.7 g/dl and white blood count of 2.87 109/l. Reticulocyte count was normal at 2.3% (0.5–2.5%).
! The Author(s), 2014. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav
Downloaded from lup.sagepub.com at UNIV PRINCE EDWARD ISLAND on February 5, 2015
10.1177/0961203314554248
Recurrent spontaneous subdural hematoma secondary to IT in a patient with overlap syndrome KG Goh and SG Ong
91
Peripheral blood smear showed hypochromic microcytic red blood cells and marked reduction in platelets of 2560 (speckled pattern) and anti-dsDNA was negative. Anti-SSA and anti-RNP antibodies were positive. Urine analysis was normal. In view of the sudden onset of headache and severe thrombocytopenia, a CT brain was performed. It showed subdural hematoma at the right temporo-parietal region which extended to the tentorium cerebelli and posterior interhemispheric fissure. However there was no midline shift (Figure 1). She remained alert throughout her stay in the ward with a Glasgow Coma Scale (GCS) of 15/15. She did not develop any signs of raised intracranial pressure or focal neurological deficit. Hence she was treated conservatively by the neurosurgical team. Given the hematological abnormalities, a bone marrow aspiration and trephine biopsy was done which showed mild trilineage myelodysplasia with no evidence of hematological malignancy.
Figure 1 Non-enhanced CT brain showed subdural hematoma (arrow) at the right temporo-parietal region with extension to the tentorium cerebelli and posterior interhemispheric fissure. There was no midline shift.
The above findings demonstrated a lupus flare with severe thrombocytopenia complicated by SDH. As she had features of both SLE and systemic sclerosis, a diagnosis of overlap syndrome was established. She was transfused with 4 units of platelet concentrate and given intravenous (IV) methylprednisolone 500 mg daily for 3 days together with intravenous immunoglobulin (IVIG) at 0.4 g/kg/ day for 5 days, followed by 40 mg of oral prednisolone. Platelet count rose to 49 109/l on day 2 of treatment and it reached 189 109/l on day 14. By then her headache had resolved and she was discharged for follow-up at the clinic. Our patient defaulted follow-up, and after 9 months she presented with a new episode of generalized headache. She denied traumatic injury to the head. Once again she had severe thrombocytopenia (4 109/l) with an elevated ESR of 86 mm/hr. CT brain showed SDH, this time involving the left temporo-parietal region, with no midline shift (Figure 2). She received 4 units of platelet concentrate, IVIG and IV methylprednisolone, followed by oral prednisolone of 40 mg od. Platelet count rose to 72 109/l on day 2 and 115 109/l on day 10 of treatment, respectively. Azathioprine 50 mg daily was added for steroid-sparing effect and was increased to 75 mg (at 2 mg/kg/day) daily 2 weeks later.
Figure 2 Non-enhanced CT brain showing subdural hematoma (arrows) involving the left temporo-parietal region, with no midline shift. Lupus
Downloaded from lup.sagepub.com at UNIV PRINCE EDWARD ISLAND on February 5, 2015
Recurrent spontaneous subdural hematoma secondary to IT in a patient with overlap syndrome KG Goh and SG Ong
92
We tapered the dose of prednisolone gradually over the ensuing 3 months. Nevertheless, once prednisolone was reduced to 25 mg daily, the platelet count began to drop below 150 109/l. It even plummeted to as low as 35 109/l. Given the inadequate response to prednisolone and azathioprine, the latter was discontinued. Our patient was then treated with IV methylprednisolone 250 mg daily for three doses, followed by low-dose IV cyclophosphamide (IV CYC) 500 mg. Prednisolone was increased back to 30 mg daily. On day 5 of treatment, platelet count had risen to 148 109/l. The patient subsequently received two further cycles of IV CYC at 3-weekly intervals. Her platelet count was maintained above 150 109/l throughout the 6-week course of IV CYC therapy. Given her favorable response and achievement of remission induction with three doses of IV CYC, it was decided that further treatment with IV CYC was no longer necessary and instead she was commenced on azathioprine. Meanwhile, the dose of oral prednisolone was gradually tapered. Platelet count remained normal for the subsequent 12 months and she was maintained on azathioprine 75 mg daily and prednisolone 2.5 mg daily. To date, she continues to be well with no further flares of lupus or progression of systemic sclerosis.
Discussion Hematological abnormalities including immune thrombocytopenia (IT) are frequent among patients with SLE. The degree of thrombocytopenia is variable, but profound thrombocytopenia as illustrated in our patient is uncommon. There are several mechanisms involved in the pathogenesis of thrombocytopenia in SLE, but the most common mechanism is immune-mediated platelet destruction. Bone marrow evaluation is occasionally necessary in SLE patients with unexplained cytopenias. Our patient’s bone marrow biopsy showed mild trilineage dysplasia, a finding that had been described in SLE patients. Voulgarelis et al. examined bone marrow biopsies of 40 SLE patients with cytopenias and found bone marrow changes which among others included bone marrow necrosis, bone marrow hypocellularity, stromal changes, distortion of bone marrow microarchitecture as well as dysplastic changes of all hemopoietic lineages.4 Spontaneous intracranial hemorrhage is the most feared complication of IT as it is potentially fatal. In a review of 26 cases of SLE with intracranial hemorrhage, Gao et al. found that
thrombocytopenia was an independent risk factor for this group of patients.5 The most common form of intracranial hemorrhage as a result of thrombocytopenia is intracerebral hemorrhage. Subdural hematoma is less common, and while it remains a rare entity in the setting of IT, has been reported to occur in 0.65% to 26% of patients with thrombocytopenia.3 Given the fact that thrombocytopenia in the setting of SLE is largely immune mediated, the mainstay of drug therapy is systemic corticosteroids. Since our patient had severe thrombocytopenia which was complicated by life-threatening bleeding manifestation, urgent treatment with combination pulsed IV methylprednisolone and IVIG, together with platelet transfusion was instituted at an early stage. The aims of treatment were to rapidly increase the platelet count to a safe level and prevent further bleeding. In patients who fail to respond to systemic corticosteroids, require moderate doses of corticosteroids to maintain the platelet count, or develop undesirable side effects from corticosteroids, other agents are deemed necessary. These include rituximab, mycophenolate mofetil and more recently, thrombopoeitin receptor agonist.6–8 Splenectomy remains an option for refractory thrombocytopenia if medical therapies fail. Intermittent IV CYC is a cytotoxic agent which was initially used in treating lupus nephritis.9 Nonetheless, its use in the treatment of thrombocytopenia is considered ‘off label’.10 More recently, Park et al. demonstrated two patients with SLE who achieved successful remission of IT with lowdose IV CYC.11 To date, there is still no consensus about the ideal treatment dose of cyclophosphamide, frequency of dosing or duration of treatment in treating IT. In our patient, azathioprine had failed to maintain the platelet count when prednisolone was tapered. However, her thrombocytopenia demonstrated remarkable improvement with three cycles of low-dose IV CYC. Platelet count remained normal in the subsequent 12 months while she was receiving maintenance therapy with azathioprine and prednisolone. Of note, she did not experience any acute side effects of IV CYC. The potential benefit of pulse IV CYC in the treatment of IT has to be judiciously weighed against its short- and long-term adverse effects which include infection, gonadal failure and malignancy. It was noteworthy that both episodes of spontaneous SDH were associated with increased activity of SLE as demonstrated by leukopenia and raised ESR.
Lupus Downloaded from lup.sagepub.com at UNIV PRINCE EDWARD ISLAND on February 5, 2015
Recurrent spontaneous subdural hematoma secondary to IT in a patient with overlap syndrome KG Goh and SG Ong
93
Spontaneous recurrent SDH as a consequence of recurrent thrombocytopenia is extremely rare, particularly in the setting of connective tissue disease. We successfully induced remission for IT with short-course low-dose IV CYC in a patient who failed to respond to corticosteroids and azathioprine. Hence we propose that treatment regime using short-course low-dose IV CYC followed by azathioprine is strongly considered in the management of IT for patients with connective tissue disease.
Funding This research received no specific grant from any agency.
Conflict of interest statement The authors have no conflicts of interest to declare.
References
2 Panicker JN, Pavithran K, Thomas M. Management of subdural hematoma in immune thrombocytopenic purpura: Report of seven patients and a literature review. Clin Neurol Neurosurg 2009; 111: 189–192. 3 Meena AK, Murthy JM. Subdural haematoma in a patient with immune thrombocytopenic purpura. Neurol India 1999; 47: 335–337. 4 Voulgarelis M, Giannouli S, Tasidou A, et al. Bone marrow histological findings in systemic lupus erythematosus with hematologic abnormalities: A clinicopathological study. Am J Hematology 2006; 81: 590–597. 5 Gao N, Wang ZL, Li MT, et al. Clinical characteristics and risk factors of intracranial hemorrhage in systemic lupus erythematosus. Lupus 2013; 22: 453–460. 6 Jovancevic B, Lindholm C, Pullerits R. Anti B-cell therapy against refractory thrombocytopenia in SLE and MCTD patients: Longterm follow-up and review of the literature. Lupus 2013; 22: 664–674. 7 Alkaabi JK, Alkindi S, Riyami NA, et al. Successful treatment of severe thrombocytopenia with romiplostim in a pregnant patient with systemic lupus erythematosus. Lupus 2012; 21: 1571–1574. 8 Vasoo S, Thumboo J, Fong K-Y. Refractory immune thrombocytopenia in systemic lupus erythematosus: Response to mycophenolate mofetil. Lupus 2003; 12: 630–632. 9 Hui M, Garner R, Rees F, et al. Lupus nephritis: A 15-year multicentre experience in the UK. Lupus 2013; 22: 328–332. 10 Aringer M, Burkhardt H, Burmester GR, et al. Current state of evidence on ‘‘off-label’’ therapeutic options for systemic lupus erythematosus, including biological immunosuppressive agents in Germany, Austria and Switzerland - a consensus report. Lupus 2012; 21: 386–401. 11 Park H-J, Kang M-I, Kang Y, et al. Two cases of refractory thrombocytopenia in systemic lupus erythematosus that responded to intravenous low-dose cyclophosphamide. J Korean Med Sci 2013; 28: 472–475.
1 Liliang P-C, Tsai Y-D, Liang C-L, et al. Chronic subdural haematoma in young and extremely aged adults: A comparative study of two age groups. Injury 2002; 33: 345–348.
Lupus Downloaded from lup.sagepub.com at UNIV PRINCE EDWARD ISLAND on February 5, 2015
