Rheumatology Advance Access originally published online on November 22, 2007
Rheumatology 2008 47(1):107-109; doi:10.1093/rheumatology/kem264
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Aggressive CNS lupus vasculitis in the absence of systemic disease activity
1Department of Molecular Neuroscience and Centre for Neuromuscular Disease, Institute of Neurology and the National Hospital for Neurology & Neurosurgery, 2Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, Queen Square, 3Department of Neuropathology, Institute of Neurology, Queen Square House, London WC1N 3BG and 4Centre For Rheumatology Research, University College London, The Windeyer Building, 46 Cleveland Street, London W1T 4JF, UK
Correspondence to: M. G. Hanna, Department of Molecular Neuroscience and Centre for Neuromuscular Disease, Institute of Neurology and the National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK. E-mail: m.hanna{at}ion.ucl.ac.uk
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SIR, A 35-yr-old woman was diagnosed with systemic lupus erythematosus (SLE) at age 25 when she presented with fever, arthralgia, alopecia, photosensitive rash and oral ulceration associated with high-titre anti-nuclear antibodies (ANA) (1:320). Double-stranded DNA (dsDNA) antibodies were 20 IU/ml [normal range (NR) <50] and IgG anti-cardiolipin antibodies became elevated (35 U/ml, NR <5 U/ml). Two months later, while there continued to be active systemic disease activity [1] and strongly positive ANA, she developed mononeuritis multiplex and had four generalized tonic–clonic seizures and was treated with carbamazepine (800 mg/day). She was treated with prednisolone (25 mg/day) and hydroxychloroquine (400 mg/day) and over the next decade her SLE remained quiescent, except for the development of hypertension, a transient bullous rash and osteopenia. Immunosuppression and carbamazepine were discontinued at the age of 30 yrs.
She was admitted to the hospital with a 2-month history of fever, nausea, abdominal pain and diarrhoea. There was a fever (37.8°C) and diffuse abdominal tenderness with no masses or organomegaly. She was normotensive with a normal cardiovascular and respiratory examination. There was no alopecia, lymphadenopathy, rash, arthritis or synovitis. Anti-dsDNA antibodies (DNA ELISA 45, NR 0–50 IU/ml), antiphospholipid (APL) antibodies (IgG 1.9, IgM 2.3, NR 0–5 U), complement C3 (1.6, NR 0.9–1.80 g/l) and C4 (0.20, NR 0.10–0.40 g/l) were all normal. ANA were positive at low titre (1:10) and anti-Ro antibodies undetectable. Chest X-ray, echocardiogram and blood cultures were unremarkable. An abdominal ultrasound suggested cholecystitis and i.v. cefuroxime was commenced. She then had a secondary generalized tonic–clonic seizure. Post-ictally, there was a mild left hemiparesis with brisk left upper limb reflexes.
An MRI brain (Fig. 1A) showed abnormalities highly suggestive of herpes simplex virus (HSV) encephalitis. Immunological markers for active SLE, including ANA, dsDNA, anti-Ro and APL antibodies, remained within normal limits. The serum C-reactive protein was elevated (121.8 mg/l) as was the erythrocyte sedimentation rate (ESR) (>120 mm/h), consistent with the diagnosis of cholecystitis. There was a normochromic, normocytic anaemia (Hb 9.1 g/l), normal platelet count and APTT. Cerebrospinal fluid (CSF) was sterile with a slightly elevated protein (0.71 g/l), normal glucose (CSF 3.3 mmol/l, serum 6.0 mmol/l) and 2 lymphocytes/ml present. HSV PCR was negative and oligoclonal bands were absent.
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The clinical course deteriorated over the next 2 days with persistent fever, a worsening left hemiparesis and coma, despite treatment with i.v. aciclovir. An EEG confirmed generalized non-specific encephalopathic slowing and excluded continuous non-convulsive seizure activity. Repeat MRI brain (Fig. 1B) showed marked progression. The complete absence of systemic SLE autoimmune activity (i.e. negative ANA, dsDNA antibodies and normal complement levels) was striking and the cause of the problem remained obscure. Due to the rapid deterioration and lack of a response to aciclovir, a right temporal lobe brain biopsy was performed. This was consistent with active small vessel lymphocytic vasculitis (Fig. 1E–G). She was treated with i.v. methylprednisolone (1 g daily for 3 days) and monthly i.v. cyclophosphamide (750 mg) for 6 months. There was marked improvement in clinical condition and MRI appearances (Fig. 1C and D). She relapsed 6 months later without elevation of ESR, ANA or antineutrophil cytoplasmic antibody (ANCA), requiring a further course of cyclophosphamide, again with a good recovery, and is currently maintained on azathioprine (2 mg/kg) and phenytoin (200 mg/day).
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The American College of Rheumatology recognizes 19 SLE neuropsychiatric syndromes [2] including psychosis, stroke, seizures and subtle abnormalities of cognitive function. Independent predictors of neuropsychiatric damage include systemic disease activity, Caucasian ethnicity and the presence of APL and anti-Ro antibodies [3]. Vasculitis is a rare manifestation, occurring in less than 7% of neuropsychiatric lupus [4, 5]. CNS SLE vasculopathy is usually a non-inflammatory process affecting small arterioles and capillaries leading to micro-infarcts and haemorrhages [6]. CNS vasculitis presenting without systemic SLE activity is extremely rare.
The initial MRI brain in our patient showed abnormal signal in both hippocampi, unusual for SLE [7] but a common feature of viral encephalitis [8]. The clinical and radiological deterioration and the lack of response to aciclovir prompted the early decision to proceed to brain biopsy, enabling the correct diagnosis of CNS vasculitis to be made and for immunosuppression to commence [9].
This case highlights the importance of considering active CNS lupus even in the absence of both clinical systemic activity and immunological markers for SLE. A high index of clinical suspicion led to the correct diagnosis of CNS SLE vasculitis.
Disclosure statement: The authors have declared no conflicts of interest.
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[Abstract/Free Full Text]
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