transverse myelitis in systemic lupus erythematosus filereumatol clin. 2007;3(2):73-7 73 mielitis...

Reumatol Clin. 2007;3(2):73-7 73

Mielitis transversa en lupus eritematoso sistémico

Objetivo: La mielitis transversa aguda (MTA) es una rara complicación en los pacientes con lupus eritematososistémico (LES). Revisamos nuestra serie de pacientescon LES para determinar la prevalencia de MTA y analizar las características clínicas, las pruebascomplementarias, la evolución y la respuesta altratamiento.Pacientes y método: Se identificó a 6 pacientes con MTAque se sometieron a valoración clínico-neurológica,resonancia magnética y estudio electrofisiológico yrecibieron el mismo tratamiento. Realizamos un estudioestadístico descriptivo.Resultados: Observamos una prevalencia de MTA del0,92% de nuestros pacientes con LES. El 83,3%presentaba anticuerpos antifosfolipídicos y/oanticoagulante lúpico. La resonancia magnética confirmóel diagnóstico en 5 de los 6 casos; 3 de los 5 pacientes conanticuerpos antifosfolipídicos fueron anticoagulados oantiagregados, con buena evolución neurológica; 2 deellos han quedado sin secuelas.Conclusiones: Encontramos una prevalencia similar a laobservada en otras series, en torno al 1%. La altaprevalencia de anticuerpos antifosfolipídicos en lospacientes, con buen resultado en los antiagregados oanticoagulados, indica un importante papel patogénico enel desarrollo de la MTA, y nos hace plantearnos laimportancia de añadir al tratamiento estándar terapiaantiagregante o anticoagulante.

Palabras clave: Mielitis transversa. Lupus eritematososistémico. Anticuerpos antifosfolipídicos.

Introduction

Neuropsychiatric manifestations are present in up to 60%of patients with systemic lupus erythematosus (SLE).Acute transverse myelitis (ATM), a very uncommonneurological manifestation, occurs in 1%-2%. The physiopathologic mechanism of ATM in SLE isunknown, though inflammatory and arterial thromboticphenomena have been proposed. A greater prevalence of

Correspondence: Dra. M.L. Velloso Feijoo.Avda. Ramón Carande, 7, portal 4, 2.o A. 41013 Sevilla. España.E-mail: [email protected]

Manuscript received September 11, 2006; accepted for publication January31, 2007.

Objective: Transverse myelitis (TM) is a rarecomplication in patients with systemic lupuserithematosus (SLE). We reviewed a series of our SLEpatients to determine the prevalence of TM, and evaluatethe clinical characteristics, medical tests, evolution, andresponse to the treatment.Patients and method: Six patients with TM wereidentified and underwent a neurological evaluation, MRI,electrophysiologic study, and were all subjected to thesame treatment. A descriptive statistical study wasconducted.Results: We observed a prevalence of 0.92% in ourpatients with SLE. Eighty-three point three per cent hadantiphospholipid antibodies and/or lupus anticoagulant.The MRI confirmed the diagnosis in 5 cases. Of the 5 patients with antiphospholypid antibodies, 3 wereanticoagulated or took aspirin with a good neurologicaloutcome, leaving 2 of them without posteriorcomplications.Conclusions: We found a prevalence similar to thatobserved in other series, around 1%. The high prevalenceof antiphospholypid antibodies in these patients, withgood outcome in those anticoagulated or treated withantiplatelet agents suggests an important pathogenic rolein the development of TM, and emphasized thepossibility of adding to the standard treatment,antiplatelet agents, or anticoagulation.

Key words: Transverse myelitis. Systemic erithematosuslupus. Antiphospholipid antibodies.

Transverse Myelitis in Systemic Lupus Erythematosus

María Luisa Velloso Feijoo, Francisco García Hernández, Celia Ocaña Medina, Rocío González León,Rocío Garrido Rasco, and Julio Sánchez Román

Unidad de Colagenosis, Servicio de Medicina Interna, Hospital Universitario Virgen del Rocío, Sevilla, Spain

Original Articles

Document downloaded from http://www.elsevier.es, day 30/06/2017. This copy is for personal use. Any transmission of this document by any media or format is strictly prohibited.Document downloaded from http://www.elsevier.es, day 30/06/2017. This copy is for personal use. Any transmission of this document by any media or format is strictly prohibited.

antiphospholipid antibodies has been described in patientswith SLE and ATM than in the general population ofpatients with SLE,1-3 something that could have importantimplications to decide whether if these patients are suitablefor anticoagulant treatment or not.Different authors have proposed different treatmentregiments for this entity, based on high-dose steroids,combined or not with immunosuppresants and/orplasmapheresis.The main objective of the present study is to determinethe prevalence of ATM in our series of patients with SLEand to describe their clinical characteristics as well as thefindings of complementary testing as well as the evolutionand the response to treatment.

Patients and Methods

From a total population of 650 patients with SLE,classified according to the ACR criteria and attended atthe Unit of Collagenosis of the Hospital Virgen del Rocíoin Sevilla, 6 patients with ATM were identified in thelast 10 years.The diagnosis of ATM was done according to the clinicalcharacteristics that reflected spinal cord lesion, such assensory and/or motor sphincter dysfunction, documentedwith the magnetic resonance imaging (MR) findings, andother tests. Patients were studied through a clinical and neurologicalevaluation, MR and an electrophysiologic study. ELISA(enzyme-linked immunosorbent assay) was employed for thedetermination of anticardiolipin antibodies and normalvalues were 0 to 20 and 0 to 10 units GPL and MPL forIgG and IgM isotypes, respectively. All patients weretreated using the same therapeutic scheme. A descriptive statistical analysis was carried out, takinginto account numerical and qualitative variables, expressedas means ± standard deviations and expressed throughTables and percentages. The most relevant patient data reviewed is presented in Table 1.

Results

In our series of patients with SLE, ATM was seen witha frequency of 0.92%; 66.6% of patients were women;mean age at the onset of ATM was 37.33±10.367 years.The clinical characteristics related to lupus were varied.All patients had skin and joint affection; 50% had lunginvolvement; 33.3% had presented serositis in somemoment of their evolution; 83.3% had some typo ofcytopenia and 16.7% had presented autoimmune hemolyticanemia.We proved the presence of antinuclear antibodies (ANA)in all patients, with diverse immunofluoresence patterns:

Velloso Feijoo ML et al. Transverse Myelitis in Systemic Lupus Erythematosus

74 Reumatol Clin. 2007;3(2):73-7

speckled (present in 83.3%), diffuse (66.7%), cytoplasmic(50%), nucleolar (50%), anti-Sm antibodies (33.3%), andnuclear (16.7%). Anti-DNA antibodies were positive in50%. As for the presence of antihospholipid antibodies, 83.3%(5 of 6 patients) had positive results for anticardiolipinantibodies and/or lupus anticoagulant: IgG anticardiolipinantibodies in 60% and IgM in 40% and lupus anticoagulant(elongated partial thromboplastin time without correctionafter the addition of normal plasma) in 33.3%. Only 1patient had presented a previous thrombotic event, namelya deep venous thrombosis. The time since onset of SLE, when ATM appeared, was27±27,821 months; it was the first manifestation of SLEin 1 of the 6 patients. The start of the manifestation was acute in 50% of casesand subacute in the rest. In 33.3%, ATM was manifestedas a Brown-Sequard syndrome. In the majority ofpatients (5 out of 6) a sensitive level was present: 4 inthe dorsal spine and 1 in the lumbar spine. Sphincterdysfunction was present in 50% and 1 patient had acase of optic neuritis; 33.3% of cases were associatedto fever. RM confirmed the diagnosis in 83.3% of cases, showingwidening and an increase in signal of the spinal cord tissue,on T2 (Figure 1). An electrophysiologic study was carriedout in 5 of 6 patients; they all showed alterations compatiblewith sensorymotor demyelinating axonal neuropathy. As mentioned, the same therapeutic scheme was employedin all patients, consisting in 3 bolus doses of 1 gmethylprednisolone on 3 consecutive days when startingwith the manifestations and 6 bolus doses ofcyclophosphamide at 15 mg/kg, monthly during the first6 months and 6 trimestral doses during the following 18months. After the pulse therapy, patients received oralsteroids at a dose of 0.5-1 mg/kg/day of prednisone orthe equivalent, in a descending pattern until a maintenancedose of 10-15 mg/day was reached; 16.7% of the patientsreceived antiplatelet therapy and 33.3% receivedanticoagulation. One of the latter presented a subduralhematoma that forced the suspension of oral anticoagulants.The evolution of the hematoma was favorable, but a newbout of ATM developed (the only patient that presentedrecurrence) 8 months later; anticoagulation was restored,with a good response. Response to treatment was favorablein 83.3% of cases, with a very heterogeneous time ofrecuperation; 50% of patients remained asymptomatic andwithout sequelae. The mean follow-up time of thesepatients up until currently was 8 years. A patient withchronic hepatitis C infection died as a consequence of theprogressive deterioration of liver function. Apart fromstandard therapy, 3 of the 5 patients positive forantiphospholipid antibodies received antiplatelet ofanticoagulant therapy, with a favorable evolution of theneurological clinical signs and symptoms; 2 of themremained without sequelae.



Reumatol Clin. 2007;3(2):73-7 75

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Discussion

ATM is a rare but serious complication in patients withSLE. Its low prevalence is estimated approximately 1%-2% of this patient population, and this is confirmedonce more in our series of patients, which was around1%. Our patients developed it in the first 6 years since diseasediagnosis, coinciding with the start of the disease in oneof them, circumstance that has been mentioned in somestudies in which it is communicated in up to 39% ofcases in which ATM was the initial manifestation ofSLE.1,2

The clinical spectrum of the disease is varied4 and wefound no trace of the underlying disease associated in acharacteristic manner to ATM. The case of the patient with chronic hepatitis C infection,who died due to liver dysfunction, a special mention isdeserved because it is the first communicated case in themedical literature of interferon-alpha induced SLE inpatients with hepatitis C.5

One of our patients developed optic neuromyelitis,described by Devic in 1894 and related to the presence ofantiphospholipid antibodies.6

Through MR, considered the best imaging technique forATM,7 the diagnosis was confirmed in 5 of 6 patients.Nonetheless, in close to 40% of ATM there are nodemonstrable alterations through MR: Mok et al8 observedMR alterations in 56%, Kovacs et al2 in 70%, and D´Cruzet al1 in 93%. There is no consensus for the treatment of thismanifestation of SLE, probably due to its scarce incidence,though the majority of the authors coincide in theimportance of its early installation.9 The use of steroidsat a high dose is recommended, associated to the use ofimmunosuppressants. Kovacs et al2 observed that theclinical manifestations of ATM improve with theadministration of intravenous methylprednisolone, butthe results are better if pulse cyclophosphamide is added.In a clinical trial published by Barile et al10 in patientswith SLE and neurological manifestations,cyclophosphamide is more efficacious than the use ofmethylprednisolone, used in a dose of 0.75 g/m2 bodysurface monthly during 1 year and every 3 months foranother year. Mok et al8 pointed out that cyclophosphamideseems to be more effective than azathioprine regardingthe remaining functional situation. Several authors have shown the that the strong associationbetween ATM and the presence of antiphospholipidantibodies,1-3,9 larger than in the general population ofSLE patients (estimated in 30%-50%). It seems veryprobable that they have an important role in thepathogenesis of this disease, through their interactionwith the spinal phospholipids.11 Thrombosis of the spineblood vessel would explain a larger dorsal affection becausethe vessels are smaller but, in the few autopsy studies

published, necrosis of the spine has been shown, but nothrombosis of the spinal vessels. In any case, it is difficultto precise if it is a thrombotic phenomenon or aninflammatory one, or a combination of both. The role of anticoagulation is a controversial topic, stillnot having been resolved in the ATM associated toSLE. It seems reasonable to install it in patients withantiphospholipid antibodies due to their prothromboticpower. The high prevalence of antiphospholipidantibodies in our patients (83.3%), with a good outcomein those that underwent anticoagulant or antiplatelettherapy, indicating the important role these antibodiesplay in the pathogenesis and development of ATM andforces us to consider adding anticoagulant or antiplatelettherapy to the standard therapy with steroids andimmunosuppresants.Controlled studies are needed to approach the developmentof therapeutic strategies, attending specially the need foanticoagulation and antiplatelet therapy.

References

1. D´Cruz DP, Mellor-Pita S, Joven B, Sana G, Allason J, Taylor J, et al.Transverse myelitis as the first manifestation of systemic lupus erithematosusor lupus-like disease: good functional outcome and releance of antiphospholipidantibodies. J Rheumatol. 2004;31:280-5.

2. Kovacs B, Lafferty Brent LH, deHoratius RJ. Transverse myelopathy insystemic lupus erythematosus: an analisis of 14 cases and review of theliterature. Ann Rheum Dis. 2000;59:120-4.

3. Lavalle C, Pizarro S, Drenkard C, Sánchez-Guerrero J, Alarcón-Segovia D.Transverse myelitis: a manifestation of systemic lupus erythematosus stronglyasociated with antiphospholipid antibodies. J Rheumatol. 1990; 17:34-7.

4. Chan KF, Boey ML. Transverse myelopathiy in SLE: clinical features andfunctional outcomes. Lupus. 1996;5:294-9.

5. Sánchez Román J, Castillo Palma MJ, García Díaz E, Ferrer Ordínez JA.Lupus eritematoso sistémico inducido por interferón alfarrecombinante. MedClin (Barc). 1994;102:198.

6. Ferreira S, Marquez P, Carneiro E, D’Cruz D, Gama G. Devic´s syndromeand probable antiphospholipid syndrome. Rheumatology. 2005;44:693-5.

7. Boumpas DT, Patronas NJ, Dalakas MC, Hakim CA, Klippel JH, BalowJE. Acute transverse myelitis in systemic lupus erythematosus: magnetic


76 Reumatol Clin. 2007;3(2):73-7

Figure. Magnetic resonance indicating a widening and increase inintensity of signal in the cervical spinal cord on T2.


resonance imaging and review of the literature. J Rheumatol. 1990;17:89-92.

8. Mok CC, Lau CS, Chan EY, Wong RW. Acute transverse myelopathy insystemic lupus erythematosus: clinical presentation, treatment and outcome.J Rheumatol. 1998;25:467-73.

9. Sherer Y, Hassin S, Shoenfeld Y, Levy Y, Lionel A, Ohry A, et al. Transversemyelitis in patients with antiphospholipid antobodies, the importance ofearly diagnosis and treatment. Clin Rheumatol. 2002;21:207-10.

10. Barile-Fabris L, Ariza-Andraca R, Olquin-Ortega L, Jara LJ, Fraga MouretA, Miranda-Limon JM, et al. Controlled clinical trial of IV cyclophosphamide versus IV methylprednisolone in severe neurologicalmanifestations in systemic lupus erythematosus. Ann Rheum Dis.2005;64:620-5.

11. Chapman J, Cohen-Armon M, Shoenfeld Y, Korczyn AD. Antiphospholipidantibodies permeabilize and depolarize brain synaptoneurosomes. Lupus.1999;8:127-33.


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