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Devic’s Syndrome as Initial Presentation of Systemic Lupus Erythematosus
CASE REPORT
Devic’s Syndrome as Initial Presentation of Systemic Lupus Erythematosus Shabana Karim, MD and Vikas Majithia, MD
Background: Devic’s syndrome or neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system associated with optic neuritis, myelitis involving 3 or more contiguous spinal cord segments, and seropositivity for NMO-IgG antibody. Case: A 22-year-old African American woman P1G0 at 22 weeks of gestation presented with weakness for 1 week. The weakness initially started in the left lower extremity and then involved the other extremities. She also had horizontal diplopia, temporal headache, and arthralgias. On physical examination, she had a discoid rash behind the left ear, muscle strength 3/5 in the upper and 0/5 in the lower extremities, and hyporeflexia. She had lymphopenia, a highly positive antinuclear antibody, and SS-A/ SS-B antibodies. The magnetic resonance imaging of the patient showed abnormal cord signal within brain and cervical and thoracic spine. Salivary gland biopsy revealed mild lymphoplasmacytic inflammation. The NMO antibody was positive. A diagnosis of Devic’s syndrome associated with probable systemic lupus erythematosus (SLE) was made. She was treated with pulse IV solumedrol and plasmapheresis for 4 days. The patient improved clinically with treatment, but the fetus developed bradycardia, which was treated with IV dexamethasone. Discussion and Conclusion: There is a debate about the relationship of NMO with autoimmune disorders, such as SLE or Sjogren syndrome. If clinically evident SLE or Sjogren or positive autoantibodies coexist with NMO signs and symptoms, the neurologic process could be an independent association due to NMO or may be a vasculitic complication of the systemic disease. Our case highlights these issues, difficulty in making a correct diagnosis, and choosing the appropriate management. Further case studies are needed to explore these important issues. Key Indexing Terms: Devic’s syndrome; Systemic lupus erythematosus; Neuromyelitis optica IgG; Optic neuritis; Transverse myelitis. [Am J Med Sci 2009;338(3):245–247.]
D
evic’s syndrome or neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system associated with optic neuritis, myelitis involving 3 or more contiguous spinal cord segments, and seropositivity for NMO-IgG antibody. Presentation with more severe attack, absence of oligoclonal banding and no elevation of albumin levels in the cerebrospinal fluid (CSF), and magnetic resonance imaging (MRI) evidence of contiguous longitudinally extensive lesion during acute attacks distinguishes this syndrome from multiple sclerosis. There is a debate about the relationship of NMO with autoimmune disorders. Recent studies have demonstrated that
NMO-IgG are found more often in patients with NMO symptoms who have clinical or serological evidence of systemic lupus erythematosus (SLE).
CASE REPORT A 22-year-old African American woman, at 22 weeks of gestation with first pregnancy, presented with left-sided weakness for 1 week. The weakness initially started in the lower extremity and then gradually progressed to involve all the other extremities. She also had horizontal diplopia, right-sided temporal headache, and arthralgia. She otherwise denied fever, chills, night sweats, sore throat, shortness of breath, cough, chest pain, nausea, vomiting, diarrhea, and dysuria. She denied contact with any sick person. She had no history of dry eyes or dry mouth. On physical examination, she was afebrile and tachycardic. She was well built, well nourished, and in no acute distress. Systemic examination, including eyes, ENT, respiratory, cardiovascular (except for tachycardia), and abdominal examination, was within normal limits. She had a discoid rash behind the left ear. On musculoskeletal examination, she had no signs of joint inflammation. She had significant weakness and was completely flaccid in the lower extremities, with her motor strength rated as 0/5. She was able to move her upper extremities against gravity but not against resistance, with her motor strength rated as 3/5. She also had generalized hyporeflexia. She was alert and oriented, and the cranial nerves were intact. Her coordination was intact, although she was slow to perform task. Laboratory assessment revealed normal chemistry, renal and hepatic function tests, coagulation tests (prothrombin time, partial thromboplastin time), thyroid-stimulating hormone, rheumatoid factor, and C-reactive protein. Hepatitis panel, antineutrophil cytoplasmic antibodies panel, antiphospholipid antibody panel, lupus anticoagulant, HIV, and rapid plasma reagin were negative. Her erythrocyte sedimentation rate was 35. She had lymphopenia, a highly positive antinuclear antibody (ANA) with positive anti–SS-A and anti–SS-B antibodies. MRI of the brain showed abnormal signal and thickening within the hypothalamus, proximal infundibulum, and anterior corpus callosum extending to involve cervical spinal cord consistent with edema (Figure 1). MRI of the thoracic cord demonstrated abnormal signal from thoracic segments 9 through 11 (Figure 2). Salivary gland biopsy revealed focal mild lymphoplasmacytic inflammation (Figure 3).
Course The patient had progressive lower and upper extremity weakness, diplopia, discoid rash, and arthralgia, along with lymphopenia. Her ANA, anti–SS-A, and anti–SS-B were positive; MRI was highly suggestive of transverse myelitis affecting multiple contiguous segments. A diagnosis of NMO secondary to underlying connective tissue disease was suspected. The NMO antibodies were checked, which came out to be positive. On the basis of the findings, a diagnosis of Devic’s syndrome in association with SLE was made. The patient was treated with pulse IV solumedrol and plasmapheresis for 4 days. The patient improved clinically with treatment, but the fetus developed bradycardia because ofo third-degree congenital heart block, which was treated with IV dexamethasone.
DISCUSSION From the Division of Rheumatology, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi. Submitted January 6, 2009; accepted in revised form April 1, 2009. Correspondence: Shabana Karim, MD, Division of Rheumatology, Department of Medicine, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216 (E-mail: [email protected]).
Devic’s syndrome or NMO is an inflammatory demyelinating disease of the central nervous system that causes optic neuritis and myelitis, usually involving the 3 or more contiguous spinal cord, an initial nondiagnostic brain MRI, and seropositivity for NMO-IgG antibody.1 The patient typically com-
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Karim and Majithia
FIGURE 3. Salivary gland biopsy revealed focal mild lymphoplasmacytic inflammation.
FIGURE 1. MRI of the brain showing abnormal signal and thickening within the hypothalamus, proximal infundibulum, and anterior corpus callosum extending to involve cervical spinal cord consistent with edema.
plained of bilateral simultaneous visual loss and pain with eye movement, paraparesis or quadriparesis, loss of sensation below the site of inflammation, bladder and bowel retention or incontinence, and painful spasm of 1 or more limbs. Spinal cord lesion may ascend into the brain stem and cause respiratory failure. It has recently been distinguished from multiple sclerosis on the basis of more severe attacks, no fever at onset, nondiagnostic brain MRI, lower frequency CSF oligoclonal banding, no elevation of albumin levels in the CSF, and an MRI
FIGURE 2. MRI of the thoracic cord demonstrated abnormal signal from thoracic segments 9 through 11.
246
evidence of contiguous, longitudinally extensive lesion during acute attacks.1,2 CSF analysis is of little benefit in making the diagnosis. The association of NMO with serum NMO-IgG antibody was first reported in 2004. It is unclear whether NMO-IgG causes NMO or is simply a marker of the disease. Recent studies have demonstrated that NMO-IgG is detected more commonly in patients with NMO symptoms who have clinical or serological evidence of SLE or Sjogren syndrome than in those who do not.3 There is a debate about the relationship of NMO with autoimmune disorders, such as SLE or Sjogren syndrome. If clinically evident SLE or Sjogren or positive autoantibodies coexist with NMO signs and symptoms, the neurologic process could be an independent association due to NMO or may be a vasculitic complication of the systemic disease. A lot of times, it is difficult to make the correct diagnosis of the underlying disease because of lack of complete presentation at the onset, as is demonstrated in our case. A recent review suggests an existence of NMO spectrum disorders with positive ANA and SS-A antibodies but not fulfilling a clinical picture of these disorders as well as a strong association of NMO and SLE/Sjogren syndrome patients with myelitis.4 It suggested that the neurologic process may be directly related to NMO antibodies and not a vasculopathic complication of the underlying disease.4 It is not possible to exactly place this case in either of those categories. In this patient, features suggestive of SLE include a definite discoid rash, lymphopenia along with positive ANA and SS-A antibodies, which are not well-characterized findings in the NMO spectrum disorders. Sjogren syndrome was less likely due to an absence of dry eyes, dry mouth, and nondiagnostic lip biopsy. She certainly did not fulfill the American College of Rheumatism classification criteria for SLE or Sjogren disorders at the time of presentation, but the criteria have limited specificity for diagnosing SLE especially at initial presentation and are not recommended to be used exclusively in this manner. It is quite likely that this patient will develop other features of SLE or related autoimmune syndromes in the future, and the course can be better predicted. Another issue here is the development of overlapping autoimmune disorders during pregnancy. A number of factors could have lead to that, specifically exposure to new antigens from fetus during her second trimester with breakdown of placental barrier and maternal immunological tolerance as well Volume 338, Number 3, September 2009
Devic’s Syndrome and Systemic Lupus Erythematosus
as pregnancy associated hormonal changes. The development of fetal bradycardia is also suggestive of anti-SSA–associated congenital heart block, which responded well to treatment with dexamethasone. NMO is one of the rarest and most serious neurologic manifestation associated with autoimmune disorders, including SLE. Rapid diagnosis and early initiation of aggressive treatments are essential. Different authors recommend various treatment regimens, including high-dose intravenous cyclophosphamide and/or pulse intravenous methylprednisolone, a combination of oral prednisolone and azathioprine and/or plasmapheresis, and more recently Rituxan.5,6 However, the prognosis is often poor, only a few patients attain complete recovery.
CONCLUSION Our case highlights these issues related to occurrence of this serious neurologic disease, difficulty in making a correct diagnosis of the underlying connective tissue disease, and choosing the appropriate management in these patients. The available literature does not completely address these ques-
© 2009 Lippincott Williams & Wilkins
tions. Further case studies, trials, and reviews are needed to explore these important issues. REFERENCES 1. Wingerchuk DM, Hogancamp WF, O’Brien PC, et al. The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology 1999;53: 1107–14. 2. Bonnet F, Mercie P, Morlat P, et al. Devic’s neuromyelitis optica during pregnancy in a patient with systemic lupus erythematosus. Lupus 1999;8:244 –7. 3. Kinney EL, Berdoff RL, Rao NS, et al. Devic’s syndrome and systemic lupus erythematosus. Arch Neurol 1979;36:643– 4. 4. Sean JP, Vanda AL, Jerome DS, et al. Neuromyelitis optica and non-organ-specific autoimmunity. Arch Neurol 2008;65:78 – 83. 5. Neuromyelitis Optica Information Page: National Institute of Neurologic Disorders and Stroke; March 05, 2007. 6. Julius B, Douglas K. Optic neuritis and recurrent myelitis in a woman with systemic lupus erythematosus. Nat Clin Pract Rheum 2008;4: 381– 6.
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Devic’s Syndrome as Initial Presentation of Systemic Lupus Erythematosus Shabana Karim, MD and Vikas Majithia, MD
Background: Devic’s syndrome or neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system associated with optic neuritis, myelitis involving 3 or more contiguous spinal cord segments, and seropositivity for NMO-IgG antibody. Case: A 22-year-old African American woman P1G0 at 22 weeks of gestation presented with weakness for 1 week. The weakness initially started in the left lower extremity and then involved the other extremities. She also had horizontal diplopia, temporal headache, and arthralgias. On physical examination, she had a discoid rash behind the left ear, muscle strength 3/5 in the upper and 0/5 in the lower extremities, and hyporeflexia. She had lymphopenia, a highly positive antinuclear antibody, and SS-A/ SS-B antibodies. The magnetic resonance imaging of the patient showed abnormal cord signal within brain and cervical and thoracic spine. Salivary gland biopsy revealed mild lymphoplasmacytic inflammation. The NMO antibody was positive. A diagnosis of Devic’s syndrome associated with probable systemic lupus erythematosus (SLE) was made. She was treated with pulse IV solumedrol and plasmapheresis for 4 days. The patient improved clinically with treatment, but the fetus developed bradycardia, which was treated with IV dexamethasone. Discussion and Conclusion: There is a debate about the relationship of NMO with autoimmune disorders, such as SLE or Sjogren syndrome. If clinically evident SLE or Sjogren or positive autoantibodies coexist with NMO signs and symptoms, the neurologic process could be an independent association due to NMO or may be a vasculitic complication of the systemic disease. Our case highlights these issues, difficulty in making a correct diagnosis, and choosing the appropriate management. Further case studies are needed to explore these important issues. Key Indexing Terms: Devic’s syndrome; Systemic lupus erythematosus; Neuromyelitis optica IgG; Optic neuritis; Transverse myelitis. [Am J Med Sci 2009;338(3):245–247.]
D
evic’s syndrome or neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system associated with optic neuritis, myelitis involving 3 or more contiguous spinal cord segments, and seropositivity for NMO-IgG antibody. Presentation with more severe attack, absence of oligoclonal banding and no elevation of albumin levels in the cerebrospinal fluid (CSF), and magnetic resonance imaging (MRI) evidence of contiguous longitudinally extensive lesion during acute attacks distinguishes this syndrome from multiple sclerosis. There is a debate about the relationship of NMO with autoimmune disorders. Recent studies have demonstrated that
NMO-IgG are found more often in patients with NMO symptoms who have clinical or serological evidence of systemic lupus erythematosus (SLE).
CASE REPORT A 22-year-old African American woman, at 22 weeks of gestation with first pregnancy, presented with left-sided weakness for 1 week. The weakness initially started in the lower extremity and then gradually progressed to involve all the other extremities. She also had horizontal diplopia, right-sided temporal headache, and arthralgia. She otherwise denied fever, chills, night sweats, sore throat, shortness of breath, cough, chest pain, nausea, vomiting, diarrhea, and dysuria. She denied contact with any sick person. She had no history of dry eyes or dry mouth. On physical examination, she was afebrile and tachycardic. She was well built, well nourished, and in no acute distress. Systemic examination, including eyes, ENT, respiratory, cardiovascular (except for tachycardia), and abdominal examination, was within normal limits. She had a discoid rash behind the left ear. On musculoskeletal examination, she had no signs of joint inflammation. She had significant weakness and was completely flaccid in the lower extremities, with her motor strength rated as 0/5. She was able to move her upper extremities against gravity but not against resistance, with her motor strength rated as 3/5. She also had generalized hyporeflexia. She was alert and oriented, and the cranial nerves were intact. Her coordination was intact, although she was slow to perform task. Laboratory assessment revealed normal chemistry, renal and hepatic function tests, coagulation tests (prothrombin time, partial thromboplastin time), thyroid-stimulating hormone, rheumatoid factor, and C-reactive protein. Hepatitis panel, antineutrophil cytoplasmic antibodies panel, antiphospholipid antibody panel, lupus anticoagulant, HIV, and rapid plasma reagin were negative. Her erythrocyte sedimentation rate was 35. She had lymphopenia, a highly positive antinuclear antibody (ANA) with positive anti–SS-A and anti–SS-B antibodies. MRI of the brain showed abnormal signal and thickening within the hypothalamus, proximal infundibulum, and anterior corpus callosum extending to involve cervical spinal cord consistent with edema (Figure 1). MRI of the thoracic cord demonstrated abnormal signal from thoracic segments 9 through 11 (Figure 2). Salivary gland biopsy revealed focal mild lymphoplasmacytic inflammation (Figure 3).
Course The patient had progressive lower and upper extremity weakness, diplopia, discoid rash, and arthralgia, along with lymphopenia. Her ANA, anti–SS-A, and anti–SS-B were positive; MRI was highly suggestive of transverse myelitis affecting multiple contiguous segments. A diagnosis of NMO secondary to underlying connective tissue disease was suspected. The NMO antibodies were checked, which came out to be positive. On the basis of the findings, a diagnosis of Devic’s syndrome in association with SLE was made. The patient was treated with pulse IV solumedrol and plasmapheresis for 4 days. The patient improved clinically with treatment, but the fetus developed bradycardia because ofo third-degree congenital heart block, which was treated with IV dexamethasone.
DISCUSSION From the Division of Rheumatology, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi. Submitted January 6, 2009; accepted in revised form April 1, 2009. Correspondence: Shabana Karim, MD, Division of Rheumatology, Department of Medicine, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216 (E-mail: [email protected]).
Devic’s syndrome or NMO is an inflammatory demyelinating disease of the central nervous system that causes optic neuritis and myelitis, usually involving the 3 or more contiguous spinal cord, an initial nondiagnostic brain MRI, and seropositivity for NMO-IgG antibody.1 The patient typically com-
The American Journal of the Medical Sciences • Volume 338, Number 3, September 2009
245
Karim and Majithia
FIGURE 3. Salivary gland biopsy revealed focal mild lymphoplasmacytic inflammation.
FIGURE 1. MRI of the brain showing abnormal signal and thickening within the hypothalamus, proximal infundibulum, and anterior corpus callosum extending to involve cervical spinal cord consistent with edema.
plained of bilateral simultaneous visual loss and pain with eye movement, paraparesis or quadriparesis, loss of sensation below the site of inflammation, bladder and bowel retention or incontinence, and painful spasm of 1 or more limbs. Spinal cord lesion may ascend into the brain stem and cause respiratory failure. It has recently been distinguished from multiple sclerosis on the basis of more severe attacks, no fever at onset, nondiagnostic brain MRI, lower frequency CSF oligoclonal banding, no elevation of albumin levels in the CSF, and an MRI
FIGURE 2. MRI of the thoracic cord demonstrated abnormal signal from thoracic segments 9 through 11.
246
evidence of contiguous, longitudinally extensive lesion during acute attacks.1,2 CSF analysis is of little benefit in making the diagnosis. The association of NMO with serum NMO-IgG antibody was first reported in 2004. It is unclear whether NMO-IgG causes NMO or is simply a marker of the disease. Recent studies have demonstrated that NMO-IgG is detected more commonly in patients with NMO symptoms who have clinical or serological evidence of SLE or Sjogren syndrome than in those who do not.3 There is a debate about the relationship of NMO with autoimmune disorders, such as SLE or Sjogren syndrome. If clinically evident SLE or Sjogren or positive autoantibodies coexist with NMO signs and symptoms, the neurologic process could be an independent association due to NMO or may be a vasculitic complication of the systemic disease. A lot of times, it is difficult to make the correct diagnosis of the underlying disease because of lack of complete presentation at the onset, as is demonstrated in our case. A recent review suggests an existence of NMO spectrum disorders with positive ANA and SS-A antibodies but not fulfilling a clinical picture of these disorders as well as a strong association of NMO and SLE/Sjogren syndrome patients with myelitis.4 It suggested that the neurologic process may be directly related to NMO antibodies and not a vasculopathic complication of the underlying disease.4 It is not possible to exactly place this case in either of those categories. In this patient, features suggestive of SLE include a definite discoid rash, lymphopenia along with positive ANA and SS-A antibodies, which are not well-characterized findings in the NMO spectrum disorders. Sjogren syndrome was less likely due to an absence of dry eyes, dry mouth, and nondiagnostic lip biopsy. She certainly did not fulfill the American College of Rheumatism classification criteria for SLE or Sjogren disorders at the time of presentation, but the criteria have limited specificity for diagnosing SLE especially at initial presentation and are not recommended to be used exclusively in this manner. It is quite likely that this patient will develop other features of SLE or related autoimmune syndromes in the future, and the course can be better predicted. Another issue here is the development of overlapping autoimmune disorders during pregnancy. A number of factors could have lead to that, specifically exposure to new antigens from fetus during her second trimester with breakdown of placental barrier and maternal immunological tolerance as well Volume 338, Number 3, September 2009
Devic’s Syndrome and Systemic Lupus Erythematosus
as pregnancy associated hormonal changes. The development of fetal bradycardia is also suggestive of anti-SSA–associated congenital heart block, which responded well to treatment with dexamethasone. NMO is one of the rarest and most serious neurologic manifestation associated with autoimmune disorders, including SLE. Rapid diagnosis and early initiation of aggressive treatments are essential. Different authors recommend various treatment regimens, including high-dose intravenous cyclophosphamide and/or pulse intravenous methylprednisolone, a combination of oral prednisolone and azathioprine and/or plasmapheresis, and more recently Rituxan.5,6 However, the prognosis is often poor, only a few patients attain complete recovery.
CONCLUSION Our case highlights these issues related to occurrence of this serious neurologic disease, difficulty in making a correct diagnosis of the underlying connective tissue disease, and choosing the appropriate management in these patients. The available literature does not completely address these ques-
© 2009 Lippincott Williams & Wilkins
tions. Further case studies, trials, and reviews are needed to explore these important issues. REFERENCES 1. Wingerchuk DM, Hogancamp WF, O’Brien PC, et al. The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology 1999;53: 1107–14. 2. Bonnet F, Mercie P, Morlat P, et al. Devic’s neuromyelitis optica during pregnancy in a patient with systemic lupus erythematosus. Lupus 1999;8:244 –7. 3. Kinney EL, Berdoff RL, Rao NS, et al. Devic’s syndrome and systemic lupus erythematosus. Arch Neurol 1979;36:643– 4. 4. Sean JP, Vanda AL, Jerome DS, et al. Neuromyelitis optica and non-organ-specific autoimmunity. Arch Neurol 2008;65:78 – 83. 5. Neuromyelitis Optica Information Page: National Institute of Neurologic Disorders and Stroke; March 05, 2007. 6. Julius B, Douglas K. Optic neuritis and recurrent myelitis in a woman with systemic lupus erythematosus. Nat Clin Pract Rheum 2008;4: 381– 6.
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