Devic's syndrome in systemic lupus erythematosus and probable antiphospholipid syndrome

S. Ferreira, P. Marques, E. Carneiro1, D. D'Cruz2 and G. Gama

Internal Medicine Department (B) and 1 Neuroradiology Department, São João Hospital, Porto, Portugal and 2 The Lupus Research Unit, The Rayne Institute, St Thomas' Hospital, London SE1 7EH, UK

Correspondence to: S. A. M. P. Ferreira, Serviço de Medicina B, Hospital São João, Alameda Prof. Hernâni Monteiro, 4200 Porto, Portugal. E-mail: susanaferreira14{at}hotmail.com

Neuropsychiatric lupus is common and results in significant morbidity [1, 2]. Antiphospholipid antibodies (aPL) may play a major role and are associated with transverse myelitis [2–4], often with a significant response to anticoagulation [4, 5]. Devic's syndrome is described in multiple sclerosis (MS) [6] and has rarely been associated with systemic lupus erythematosus (SLE) [5, 7–9]. We present a 44-yr-old woman with SLE who developed neuromyelitis optica and probable antiphospholipid syndrome (APS).

She was healthy until 1990 when schizophrenia was diagnosed. Two years later, SLE was diagnosed based on arthralgias, malar rash, photosensitivity, thrombocytopenia and positive antinuclear (ANA) and anti-DNA antibodies. She remained in remission on corticosteroids but developed diabetes mellitus, hypertension, hyperlipidaemia and osteoporosis. Her aPL had always been negative; she had a previous non-complicated pregnancy and no miscarriages or thrombosis.

In 2003, pulmonary tuberculosis was diagnosed and standard therapy was started but the patient was later switched to rifampicin, pyrazinamide and streptomycin, following a Stevens–Johnson reaction to isoniazid. Immunological markers substantially increased (anti-DNA 1/1280) and anti-histone antibodies were detected. Proteinuria (2.6 g/day), leucocyturia and renal failure (creatinine clearance 14 ml/min) were documented 2 months later and nephritis WHO class IV was diagnosed. She was successfully treated with intravenous (i.v.) cyclophosphamide 1 g/m2 and prednisolone 1.5 mg/kg/day.

She was well until the current admission, when she suddenly lost right eye vision and progressively developed bilateral paraesthesiae, lower extremity weakness, right hemiparesis and left arm monoparesis. She was oriented, apyrexial, normotensive and cushingoid, with malar rash, palpable purpura on the feet and extensive livedo reticularis. The cranial nerves were normal apart from decreased right visual acuity and optic disc pallor. She had decreased power (4/5) in the right limbs and left upper extremity and a sensory level at T4. A right Babinski sign was present but the other reflexes were normal. Treatment was commenced with aspirin 100 mg once daily (od), enoxaparin 50 mg subcutaneous twice daily, methylprednisolone 500 mg i.v. od for 5 days and prednisolone 60 mg oral od thereafter.

Laboratory tests showed a high erythrocyte sedimentation rate (ESR; 113 mm/h), a low complement concentration, strongly positive ANA and anti-DNA antibodies and negative anti-histone antibodies. Anticardiolipin antibodies were only positive once and lupus anticoagulant was negative. Cerebrospinal fluid (CSF) examination was sterile, with mild lymphocytic pleocytosis and oligoclonal bands.

Magnetic resonance imaging (MRI) revealed right frontal infarction with a haemorrhagic area and small ischaemic lesions in the corpus callosum and the left frontal lobe (Fig. 1A). The optic nerves had normal appearance. Spinal MRI showed T2-high signal and T1-low signal lesions without enhancement after gadolinium administration (Fig. 1B).



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FIG. 1. (A) Brain MRI. Axial T2-weighted images showing right frontal lobe ischaemic infarction with a haemorrhagic area and small areas of increased signal in the corpus callosum and in the left frontal lobe white matter consistent with microinfarcts. (B) Spinal MRI. Sagittal T2-weighted images showing lesions of abnormal increased signal at the level of C2–C6 and T1–T3, compatible with transverse myelitis.

 
Right visual evoked potentials were delayed and had short amplitude; electromyography revealed axonal sensory and motor neuropathy. The following were negative: urinalysis, 24-h proteinuria, chest X-ray, echocardiography and carotid Doppler ultrasound.

In view of the MRI findings and the inconsistent aPL positivity, aspirin and heparin were stopped, and plasmapheresis (five daily sessions) followed by i.v. immunoglobulin (0.4 g/kg/day for 5 days) were given. There was significant improvement but the visual loss and paraesthesiae persisted. Despite persistent active serology (anti-DNA >1/1000), she remained clinically stable on treatment with cyclophosphamide, clopidogrel, rifampicin and levofloxacin.

Devic's neuromyelitis optica was first described in the 19th century and it remains controversial whether it can be distinguished from MS [6]. There are interesting reports to indicate the association of Devic's syndrome with SLE—‘lupoid sclerosis’ [5, 7–9]. An extensive review of the literature on SLE patients with optic neuropathy shows that, from 1973 to 1997, out of 51 SLE patients with optic neuropathy, 41.1% presented signs of spinal cord involvement [8]. aPL have been associated with transverse myelitis and optic neuropathy [2–4], but have rarely been described in Devic's syndrome.

It is not clear whether the pathophysiology of isolated neuromyelitis optica (primary Devic's syndrome) is similar to or different from that occurring in MS, SLE and APS (secondary Devic's syndrome) [10]. Giorgi and Bonomo suggested a common pathogenic factor [10] but further investigation is needed. The underlying mechanisms are still uncertain [7, 8, 10], but it is possible that both an immunological/inflammatory response and thrombotic/ischaemic phenomena might be involved.

In our patient, the high anti-DNA titre and ESR, low complement and CSF examination were consistent with active lupus. However, she was already immunosuppressed, nephritis was responding to standard treatment and optic vasculitis is usually bilateral [8]. Although she does not fulfil the classification criteria, she has many features of APS: stroke, transverse myelitis, abrupt-onset, unilateral and irreversible optic neuritis, livedo reticularis and thrombocytopenia. In a similar previous case, a good response to anticoagulation was observed despite the absence of aPL [5].

Devic's syndrome carries a poor prognosis since it is often refractory [5, 7–9] and optic neuropathy is a significant cause of blindness in SLE [8]. Early recognition and treatment with high-dose i.v. corticosteroids, immunosuppression, plasmapheresis or i.v. immunoglobulin may be effective [4, 7] but, in some cases, combined therapy with anticoagulation might be beneficial [4, 5].

The authors have declared no conflicts of interest.

References

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Accepted 5 January 2005