Rheumatology Advance Access originally published online on April 25, 2006
Rheumatology 2006 45(7):913-915; doi:10.1093/rheumatology/kei263
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LETTER TO THE EDITOR |
Sustained improvement of a girl affected with Devic's disease over 2 years of mycophenolate mofetil treatment
Department of Pediatrics, Clinica Pediatrica I, University of Florence, Florence, Italy
Correspondence to: F. Fernanda, Department of Pediatrics, Rheumatology Unit, University of Florence, Anna Meyer Children's Hospital, Via Pico della Mirandola 24, 50132 Florence, Italy. E-mail: falcini{at}unifi.it
SIR, We report a 9-yr-old girl with a severe relapsing–remitting course of neuromyelitis optica (NMO) [1–3] who had a dramatic and sustained improvement over a 2-yr period of treatment with mycophenolate mofetil (MMF), the prodrug of mycophenolic acid.
A 9-yr-old Caucasian girl, previously healthy, was admitted to A. Meyer Children's Hospital in November 2001, complaining of motor alterations and headache. Pregnancy and delivery had been uneventful. Psychomotor development was normal. The family medical history was negative for neurological and autoimmune diseases. No recent history of fever, respiratory or gastrointestinal symptoms were recorded.
On admission she was alert and afebrile, with respiratory rate and blood pressure within the normal range. She reported pain in her right eye, weakness in both legs and gait difficulties. Routine blood tests were normal, including thyroid function and functional clotting tests. Extensive autoimmune disease work-up resulted negative for systemic lupus erythematosus (SLE), Sjögren syndrome and antiphospholipid syndrome [4, 5].
Whilst MRI of the brain did not disclose any alterations, a spinal MRI showed multiple hyperintense T2 in the upper cervical region, predominating in the cervical and upper dorsal region (C2–D3) (Fig. 1A and B). A large hyperintense lesion with mild mass effect was detected, extending from the high cervical level through the conus medullaris. Mild gadolinium enhancement was seen in spinal cord lesions. The cerebral spinal fluid analysis showed pleocytosis, more than 50 x 103/µl leucocytes, predominantly neutrophils, and the absence of oligoclonal bands. Seven months later (June 2002), the girl developed visual impairment. Reduction both in visual activity and visual field was detected on ocular evaluation, and the diagnosis of retrobulbar optic neuritis in the right eye was made. Gadolinium enhancement was observed in the right optic nerve (Fig. 1C and D).
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Due to the clinical and MRI findings, Devic's disease was diagnosed. Three courses of high-dose pulse corticosteroid (30 mg/kg/day) followed by oral administration (2 mg/kg/day) were helpful in inducing complete remission of ocular and motor symptoms. The girl was discharged on a low oral dose of steroids (1 mg progressively tapered to 0.5 mg/kg). Several months later (November 2002), a new severe optic myelitis attack with visual loss prompted us to restart pulse methylprednisolone and then oral prednisone treatment. Following vertebral crash steroids were quickly tapered. Azathioprine (2.5 mg/kg/day) was added to a low oral dose (0.5 mg/kg/day) of steroids, but the patient experienced two additional relapses of optic neuritis with worsening of visual acuity (1/25 and 1/30, respectively, in the right eye), both associated with a reduced visual field. After wash-out of azathioprine, MMF (2 g/day) was then introduced 16 months after the onset of symptoms (March 2003), and corticosteroids were progressively tapered and withdrawn. Subsequently, the girl experienced an impressive clinical remission, with no relapses of optic neuritis and motor alterations over the following 2 yr.
At the 2-yr follow-up, MRI showed a significant reduction in previously detected lesions with no new alterations, and the last ophthalmological evaluation of visual acuity and the visual field showed complete recovery.
Our patient is the first case of severe relapsing NMO who dramatically improved on MMF, achieving sustained remission over a 2-yr follow-up. The high dose of steroids provided was able to induce a partial response and initial improvement of her symptoms but relapse on any attempt at withdrawal. After vertebral crash, azathioprine was then added as steroid sparing drug. However, within steroid tapering the patient flared again.
MMF provided prompt, impressive and persistent control of disease activity. Over 2 yr, no relapses of visual disturbances or motor deficits have been observed despite the progressive tapering and withdrawal of steroids.
The typical MRI features detected on admission showed a significant regression 2 yr later, and no new findings of NMO were added.
NMO is frequently associated with vasculitis or thyroid disease; thus, at the onset and during follow-up, complete screening for systemic vasculitic is recommended. Supporting the diagnosis of primary optical neuromyelitis, at the 2-yr follow-up our patient has not yet developed any other autoimmune diseases.
The observation that several diseases may share common pathogenetic pathways suggests the possibility of using common therapeutic strategies in different autoimmune diseases [6].
MMF, a non-competitive inhibitor of the enzyme inosine 5'-monophosphate dehydrogenase, controls lymphocyte proliferation and T-cell-dependent antibody responses through purine synthesis inhibition [7]. Having been used effectively as an immunosuppressant in transplantation medicine, it has recently attracted interest as therapeutic agent for several autoimmune diseases, including refractory immune thrombocytopenia, autoimmune inflammatory myopathy and autoimmune hepatitis [7, 8]. It has been proved to be effective and well tolerated in SLE nephritis, in adults as well in childhood, avoiding potential side-effects, such as amenorrhoea and sterility, in long-term administration [9].
In NMO, approaches combining steroids and steroid-sparing drugs, such as cyclophosphamide and/or azathioprine, were unsuccessful in preventing relapses [9]; evidence for the efficacy of monthly intravenous immunoglobulins in addition to steroids and azathioprine is still limited to anecdotal cases [10]. Plasmapheresis promptly instituted when flares occur has also been useful in ameliorating optic and motor findings, but is unable to reduce the recurrence of attacks.
Pending further controlled studies to confirm this observation, based on the clinical and MRI outcome at 2 yr in the case described above, MMF might be considered a safe and effective alternative immunosuppressive approach in preventing relapses of Devic's disease.
The authors have declared no conflicts of interest.
References
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