Multiple Sclerosis and Related Disorders (2015) 4, 281–283
Available online at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/msard
CASE REPORT
Transverse myelitis presenting in a patient with Hughes-Stovin syndrome Jason Margoleskyn, Leticia Tornes1, Aram Vosoughi University of Miami Miller School of Medicine, Department of Neurology, Professional Arts Center, 1150 NW 14th St, Suite 609, Miami, FL 33136, United States Received 12 February 2015; received in revised form 21 March 2015; accepted 4 April 2015
KEYWORDS Hughes-Stovin syndrome; Behcet's disease; Transverse myelitis
1.
Introduction
Hughes-Stovin syndrome (HSS) is a lymphocytic vasculitis defined by the constellation of venous thrombosis and multiple pulmonary artery aneurysms. Aneurysmal rupture with massive hemorrhage is a frequent fatal event. HSS is thought of as a forme fruste of Behcet's disease (BD), sharing similar histological findings, but without other associated manifestations that characterize BD. Classically patients with HSS do not have oral and genital ulcers, inflammatory eye disease, skin pathergy, nor do they develop neurological manifestations that can arise with n
Corresponding author. Tel.: +305 790 4246. E-mail addresses: [email protected] (J. Margolesky), [email protected] (L. Tornes). 1 Tel.: +305 243 2279. http://dx.doi.org/10.1016/j.msard.2015.04.004 2211-0348/& 2015 Elsevier B.V. All rights reserved.
BD. We report a case of a steroid responsive transverse myelitis (TM) in a patient with HSS.
2.
Case report
In 2009, a then 38 year old woman (a Jehova's Witness) developed a deep vein thrombosis (DVT). In March 2012 she was admitted to an outside institution for recurrent hemoptysis. Her workup included bronchoscopy and video assisted thoracoscopic surgery with lung biopsy. No clear etiology was offered. In May 2012, she presented to our hospital for recurrent hemoptysis. We requested the previously obtained pathology specimen for review. CT-angiogram (CTA) of her chest visualized multiple pulmonary artery aneurysms, areas of pulmonary infarction, and a right ventricular cardiac thrombus. A rheumatologic panel including ANA, anti-dsDNA,
282
J. Margolesky et al. weakness. There was diffuse hyper-reflexia with bilateral Hoffman signs and a Babinski sign on the left. On sensory exam there was a high thoracic sensory level to pinprick on the right and reduced vibration sense in the left leg. The findings are consistent with corticospinal tract, spinothalamic tract, and dorsal column dysfunction. A normal cranial nerve exam and proximal upper extremity exam helped to localize the lesion to the thoracic spinal cord. Magnetic resonance imaging (MRI) brain, cervical spine and thoracic spine were obtained with and without gadolinium. Remarkable findings included non enhancing areas of hyperintensity on T2-weighted images in the thoracic cord at levels T1–T8 (Figure 2). Rheumatologic work up was again unremarkable. Nutritional studies were normal. Antiphospholipid syndrome, IgG4 related disease, thyroid disease and Lyme disease were ruled out. Lumbar puncture was obtained and cerebral spinal fluid analysis including cell count, glucose, protein, VDRL, microbial cultures, viral PCR studies, and oligoclonal bands were unremarkable. Her TM was presumed to be an inflammatory manifestation of her known diagnosis. She received a five day course of IV methylprednisolone, 1 g per day, with improvement in symptoms. She was maintained on azathioprine 50 mg daily. Three weeks later, MRI showed resolution of the thoracic lesions. At outpatient follow up in October 2014 she had persistent paresthesias but a normal neurological exam aside from decreased vibratory sensation in both lower extremities.
3.
Figure 1 H & E stain showing lymphocytic vasculitis at 10 and 40 magnifications.
anti- smith, anti-RNP, anti-SMRNP, anti-centromere, antichromatin, anti-ribosomal, ANCA (MPO and PR3), Scl 70, SSA and SSB, Jo1, RF, C3, C4 and ACE was obtained and was unremarkable. Pathology's review diagnosed a lymphocytic vasculitis (Figure 1) and the diagnosis of HSS was made. She did not undergo anticoagulation due to risk of massive hemorrhage in the setting of hemoptysis in a person who does not wish to receive blood transfusions. Catheter angiography was performed and two pulmonary artery aneurysms were embolized and an intra-vena cava filter was placed. She was initially treated with prednisone 60 mg and cyclophosphide 50 mg daily. The prednisone was tapered over 12 months. Cyclophosphamide was increased to 100 mg daily and continued at that dose for 12 months; it was then replaced by azithioprine 50 mg daily. She remained clinically stable until June 2014. While standing in her kitchen she developed bilateral lower extremity paresthesias described as heat, tightness, and tingling. She noted bilateral leg weakness and difficulty walking. There was no associated back pain, fever, or change in bowel or bladder function. She presented to the emergency room the following afternoon with persistent symptoms. Her exam revealed difficulty with fine rapid movements in her hands, mild bilateral iliopsoas and left hamstring
Discussion
Hughes and Stovin (1959) described four patients with a syndrome of deep vein thrombosis and pulmonary artery aneurysms , the now eponymous HSS. As a rarely reported disease epidemiological data is limited. There seems to be a male predilection; age of onset in the second to fifth decade; and cases have been reported from diverse geographic locations (Khali and Saleem, 2011). Hughes-Stovin syndrome has no formal diagnostic criteria or pathognomonic laboratory finding, but classically is characterized by venous thrombosis and multiple pulmonary artery aneurysms. These pathologies can present in any venous or arterial system in the body (including previously reported hepatic artery aneurysm) (Herb et al., 1998). Other presenting symptoms can include cough, hemoptysis, fever, dyspnea, chest pain and signs of pulmonary hypertension. HSS and BD have similar histopathological findings. Both conditions are associated with a lymphocytic vasculitis and destruction of arterial walls due to vasculitic involvement of the vaso vasorum (Erkan et al., 2004). Behcet's disease (Al-Araji and Kidd, 2009) is an autoinflammatory disorder also associated with aneurysm formation and thromboses, but with the additional classic constellation of recurrent painful oral and genital ulcers, inflammatory ophthalmic lesions, skin lesions and positive skin pathergy testing. BD can have neurological manifestations, that come in two main flavors: vascular-inflammatory disease and cerebral venous sinus thrombosis. Cognitive dysfunction, meningoencephalitis, peripheral neuropathy, demyelinating lesions, and TM have been described.
Transverse myelitis
283 azathioprine regimen she developed a steroid responsive TM. In classic HSS, the development of any neurological manifestation is beyond the spectrum on the syndrome. In NeuroBehcet's disease, spinal cord involvement has been reported in 10% of cases clinically and 28% of cases at autopsy were found to have spinal cord lesions (Al-Araji and Kidd, 2009). Review of the literature did not reveal previously reported cases of patients with HSS developing TM (or any other systemic manifestations more typical of BD). In terms of the ongoing debate regarding HSS as a truncated version of BD, this case supports the concept of the two syndromes as a spectrum of a unified disorder. A similar pathophysiology underlies the two syndromes and BD may represent a more complete phenotype with multisystem involvement of the inflammatory process. With the development of TM our patient's constellation of symptoms no longer meets the classic definition of HSS nor does it fulfill the formal diagnostic criteria of BD. With TM, her diagnosis has shifted on the HSS-BD spectrum towards BD.
4.
Conclusion
Hughes-Stovin syndrome may be a forme fruste of BD. We should be aware that the truncated classic form of HSS can blossom into a disease that extends beyond thromboembolic disease and pulmonary artery aneurysms, into an inflammatory central nervous system process. Typical acute management of inflammatory processes was effective in our case. Strict adherence to immunosuppressant therapy may prevent such progression. Future case reports of patient's with HSS developing unexpected complications will help further elucidate the natural history of the disease and will help define the risk of HSS shifting down the spectrum towards BD.
Conflict of interest and funding source Figure 2 Sagittal and axial T2 weighted MRI images showing thoracic level hyperintense lesions.
Hughes-Stovin syndrome is treated (Khali and Saleem, 2011) with immunosuppressants. Pulmonary artery aneurysms can be treated with embolization procedures. In the setting of thromboembolic disease, the risk of anticoagulation must be weighed against the risk of hemorrhage. It seems that thromboembolic disease will continue to progress with anticoagulation alone and that immunosuppressant therapy is more effective in this regard. Our patient carried the diagnosis of HSS based on her history of thrombotic events and multiple pulmonary artery aneurysms. The diagnosis was supported by histological evidence of a lymphocytic vasculitis. Her course had been stabilized with immunosuppressive therapies. With non-adherence to her
We have no conflicts of interest to mention and no sources of funding.
References Al-Araji A, Kidd D. Neuro-Behcet's disease: epidemiology, clinical characteristics, and management. Lancet Neurol 2009;8(2):192–204. Erkan D, Yazici Y, Sanders A, Trost D, Yazici H. Is Hughes-Stovin syndrome Behcet's disease? July–August. Clin Exp Rheumatol 2004;22(4 Suppl. 34):S64–8. Herb S, Hetzel M, Hetzel J, Friedrih J, Weber J. An unusual case of Hughes-Stovin syndrome. May. Eur Respir J 1998;11(5):1191–3. Hughes J, Stovin P. Segmental pulmonary artery aneurysms with peripheral venous thrombosis. Br J Dis Chest 1959;53:19–27. Khali U, Saleem T. Hughes-Stovin syndrome. April 13. Orphanet J Rare Dis 2011:6–15.
Available online at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/msard
CASE REPORT
Transverse myelitis presenting in a patient with Hughes-Stovin syndrome Jason Margoleskyn, Leticia Tornes1, Aram Vosoughi University of Miami Miller School of Medicine, Department of Neurology, Professional Arts Center, 1150 NW 14th St, Suite 609, Miami, FL 33136, United States Received 12 February 2015; received in revised form 21 March 2015; accepted 4 April 2015
KEYWORDS Hughes-Stovin syndrome; Behcet's disease; Transverse myelitis
1.
Introduction
Hughes-Stovin syndrome (HSS) is a lymphocytic vasculitis defined by the constellation of venous thrombosis and multiple pulmonary artery aneurysms. Aneurysmal rupture with massive hemorrhage is a frequent fatal event. HSS is thought of as a forme fruste of Behcet's disease (BD), sharing similar histological findings, but without other associated manifestations that characterize BD. Classically patients with HSS do not have oral and genital ulcers, inflammatory eye disease, skin pathergy, nor do they develop neurological manifestations that can arise with n
Corresponding author. Tel.: +305 790 4246. E-mail addresses: [email protected] (J. Margolesky), [email protected] (L. Tornes). 1 Tel.: +305 243 2279. http://dx.doi.org/10.1016/j.msard.2015.04.004 2211-0348/& 2015 Elsevier B.V. All rights reserved.
BD. We report a case of a steroid responsive transverse myelitis (TM) in a patient with HSS.
2.
Case report
In 2009, a then 38 year old woman (a Jehova's Witness) developed a deep vein thrombosis (DVT). In March 2012 she was admitted to an outside institution for recurrent hemoptysis. Her workup included bronchoscopy and video assisted thoracoscopic surgery with lung biopsy. No clear etiology was offered. In May 2012, she presented to our hospital for recurrent hemoptysis. We requested the previously obtained pathology specimen for review. CT-angiogram (CTA) of her chest visualized multiple pulmonary artery aneurysms, areas of pulmonary infarction, and a right ventricular cardiac thrombus. A rheumatologic panel including ANA, anti-dsDNA,
282
J. Margolesky et al. weakness. There was diffuse hyper-reflexia with bilateral Hoffman signs and a Babinski sign on the left. On sensory exam there was a high thoracic sensory level to pinprick on the right and reduced vibration sense in the left leg. The findings are consistent with corticospinal tract, spinothalamic tract, and dorsal column dysfunction. A normal cranial nerve exam and proximal upper extremity exam helped to localize the lesion to the thoracic spinal cord. Magnetic resonance imaging (MRI) brain, cervical spine and thoracic spine were obtained with and without gadolinium. Remarkable findings included non enhancing areas of hyperintensity on T2-weighted images in the thoracic cord at levels T1–T8 (Figure 2). Rheumatologic work up was again unremarkable. Nutritional studies were normal. Antiphospholipid syndrome, IgG4 related disease, thyroid disease and Lyme disease were ruled out. Lumbar puncture was obtained and cerebral spinal fluid analysis including cell count, glucose, protein, VDRL, microbial cultures, viral PCR studies, and oligoclonal bands were unremarkable. Her TM was presumed to be an inflammatory manifestation of her known diagnosis. She received a five day course of IV methylprednisolone, 1 g per day, with improvement in symptoms. She was maintained on azathioprine 50 mg daily. Three weeks later, MRI showed resolution of the thoracic lesions. At outpatient follow up in October 2014 she had persistent paresthesias but a normal neurological exam aside from decreased vibratory sensation in both lower extremities.
3.
Figure 1 H & E stain showing lymphocytic vasculitis at 10 and 40 magnifications.
anti- smith, anti-RNP, anti-SMRNP, anti-centromere, antichromatin, anti-ribosomal, ANCA (MPO and PR3), Scl 70, SSA and SSB, Jo1, RF, C3, C4 and ACE was obtained and was unremarkable. Pathology's review diagnosed a lymphocytic vasculitis (Figure 1) and the diagnosis of HSS was made. She did not undergo anticoagulation due to risk of massive hemorrhage in the setting of hemoptysis in a person who does not wish to receive blood transfusions. Catheter angiography was performed and two pulmonary artery aneurysms were embolized and an intra-vena cava filter was placed. She was initially treated with prednisone 60 mg and cyclophosphide 50 mg daily. The prednisone was tapered over 12 months. Cyclophosphamide was increased to 100 mg daily and continued at that dose for 12 months; it was then replaced by azithioprine 50 mg daily. She remained clinically stable until June 2014. While standing in her kitchen she developed bilateral lower extremity paresthesias described as heat, tightness, and tingling. She noted bilateral leg weakness and difficulty walking. There was no associated back pain, fever, or change in bowel or bladder function. She presented to the emergency room the following afternoon with persistent symptoms. Her exam revealed difficulty with fine rapid movements in her hands, mild bilateral iliopsoas and left hamstring
Discussion
Hughes and Stovin (1959) described four patients with a syndrome of deep vein thrombosis and pulmonary artery aneurysms , the now eponymous HSS. As a rarely reported disease epidemiological data is limited. There seems to be a male predilection; age of onset in the second to fifth decade; and cases have been reported from diverse geographic locations (Khali and Saleem, 2011). Hughes-Stovin syndrome has no formal diagnostic criteria or pathognomonic laboratory finding, but classically is characterized by venous thrombosis and multiple pulmonary artery aneurysms. These pathologies can present in any venous or arterial system in the body (including previously reported hepatic artery aneurysm) (Herb et al., 1998). Other presenting symptoms can include cough, hemoptysis, fever, dyspnea, chest pain and signs of pulmonary hypertension. HSS and BD have similar histopathological findings. Both conditions are associated with a lymphocytic vasculitis and destruction of arterial walls due to vasculitic involvement of the vaso vasorum (Erkan et al., 2004). Behcet's disease (Al-Araji and Kidd, 2009) is an autoinflammatory disorder also associated with aneurysm formation and thromboses, but with the additional classic constellation of recurrent painful oral and genital ulcers, inflammatory ophthalmic lesions, skin lesions and positive skin pathergy testing. BD can have neurological manifestations, that come in two main flavors: vascular-inflammatory disease and cerebral venous sinus thrombosis. Cognitive dysfunction, meningoencephalitis, peripheral neuropathy, demyelinating lesions, and TM have been described.
Transverse myelitis
283 azathioprine regimen she developed a steroid responsive TM. In classic HSS, the development of any neurological manifestation is beyond the spectrum on the syndrome. In NeuroBehcet's disease, spinal cord involvement has been reported in 10% of cases clinically and 28% of cases at autopsy were found to have spinal cord lesions (Al-Araji and Kidd, 2009). Review of the literature did not reveal previously reported cases of patients with HSS developing TM (or any other systemic manifestations more typical of BD). In terms of the ongoing debate regarding HSS as a truncated version of BD, this case supports the concept of the two syndromes as a spectrum of a unified disorder. A similar pathophysiology underlies the two syndromes and BD may represent a more complete phenotype with multisystem involvement of the inflammatory process. With the development of TM our patient's constellation of symptoms no longer meets the classic definition of HSS nor does it fulfill the formal diagnostic criteria of BD. With TM, her diagnosis has shifted on the HSS-BD spectrum towards BD.
4.
Conclusion
Hughes-Stovin syndrome may be a forme fruste of BD. We should be aware that the truncated classic form of HSS can blossom into a disease that extends beyond thromboembolic disease and pulmonary artery aneurysms, into an inflammatory central nervous system process. Typical acute management of inflammatory processes was effective in our case. Strict adherence to immunosuppressant therapy may prevent such progression. Future case reports of patient's with HSS developing unexpected complications will help further elucidate the natural history of the disease and will help define the risk of HSS shifting down the spectrum towards BD.
Conflict of interest and funding source Figure 2 Sagittal and axial T2 weighted MRI images showing thoracic level hyperintense lesions.
Hughes-Stovin syndrome is treated (Khali and Saleem, 2011) with immunosuppressants. Pulmonary artery aneurysms can be treated with embolization procedures. In the setting of thromboembolic disease, the risk of anticoagulation must be weighed against the risk of hemorrhage. It seems that thromboembolic disease will continue to progress with anticoagulation alone and that immunosuppressant therapy is more effective in this regard. Our patient carried the diagnosis of HSS based on her history of thrombotic events and multiple pulmonary artery aneurysms. The diagnosis was supported by histological evidence of a lymphocytic vasculitis. Her course had been stabilized with immunosuppressive therapies. With non-adherence to her
We have no conflicts of interest to mention and no sources of funding.
References Al-Araji A, Kidd D. Neuro-Behcet's disease: epidemiology, clinical characteristics, and management. Lancet Neurol 2009;8(2):192–204. Erkan D, Yazici Y, Sanders A, Trost D, Yazici H. Is Hughes-Stovin syndrome Behcet's disease? July–August. Clin Exp Rheumatol 2004;22(4 Suppl. 34):S64–8. Herb S, Hetzel M, Hetzel J, Friedrih J, Weber J. An unusual case of Hughes-Stovin syndrome. May. Eur Respir J 1998;11(5):1191–3. Hughes J, Stovin P. Segmental pulmonary artery aneurysms with peripheral venous thrombosis. Br J Dis Chest 1959;53:19–27. Khali U, Saleem T. Hughes-Stovin syndrome. April 13. Orphanet J Rare Dis 2011:6–15.
