Author Of 2 Presentations
P0430 - Anti-TNF induced lupus-like disease and progressive multifocal leukoencephalopathy: a unifying underlying mechanism? (ID 1144)
Abstract
Background
Anti-TNF agents have revolutionized the treatment of chronic inflammatory disorders. Nevertheless, several adverse reactions are well recognized including increased rates of infections, lupus-like disease and demyelinating lesions. Progressive multifocal leukoencephalopathy (PML) is a rare but severe demyelinating disease caused by the reactivation and access to the brain of the ubiquitous polyomavirus JC (JCV), which targets oligodendrocytes. It is most commonly associated with immunosuppression, malignancies and systemic lupus erythematosus (SLE).
Objectives
We present the development of both SLE and PML as a result of etanercept treatment for underlying psoriatic arthritis suggesting a need for careful evaluation and close neurological surveillance in patients receiving anti-TNF treatment.
Methods
A brain MRI including MR spectroscopy was performed. To further investigate the lesion, a stereotactic brain biopsy was accomplished, followed by immunohistochemistry.
Results
A 65-year-old female was admitted in the hospital because of a gradual onset of right homonymous hemianopsia. She had a history of psoriatic arthritis treated with etanercept monotherapy for five years. Two years prior to the current admission she developed photosensitivity and antibodies against Ro/SSA and La/SSB. With a presumable diagnosis of anti-TNF induced SLE, etanercept was discontinued and hydroxychloroquine was prescribed. A year later, personality changes were reported and 8 months later, visual disturbances. On current admission, neurological examination revealed a Babinski sign on the right side as well as limb-kinetic apraxia on both sides. MRI showed a T2-hyperintense, non-enhancing, parieto-occipital subcortical lesion of the left hemisphere, spreading through the spleen of the corpus callosum to the right hemisphere. Spectroscopy was compatible with a diagnosis of grade III glioma. Pathology of the brain specimen revealed a demyelinating, macrophage-rich lesion with lysis of Simian-Virus-40 positive glial cells. A diagnosis of PML was made.
Conclusions
In summary, a case of anti-TNF induced lupus which soon developed signs of PML is presented. Induction of type I interferon responses and B cell activation previously shown to be induced by anti-TNF treatment might be involved in mobilization of CD34+ B cell precursors harboring JC virus, a mechanism previously postulated for PML development. Moreover, decreased toll-like receptor signaling and dampened plasmacytoid dendritic cell activation following hydroxychloroquine treatment, could be an alternative explanation. Since the use of immunosuppressive therapy is a known predisposing factor for development of PML, careful evaluation and close neurological surveillance is mandatory.
P0508 - Unusual associations of Scleroderma-specific autoantibodies with MS-like disease. Case series and literature review. (ID 1792)
Abstract
Background
Scleroderma-associated autoantibodies are traditionally detected in patients with Systemic Sclerosis (SSc) and/or myositis. The association of these autoantibodies with Central Nervous System (CNS) manifestations is extremely rare.
Objectives
We report 6 cases of Scleroderma-specific autoantibodies detected through extensive diagnostic evaluation in patients with Multiple Sclerosis (MS)-like clinical and imaging characteristics.
Methods
6 patients with demyelinating lesions atypical for MS in CNS Magnetic Resonance Imaging (MRI) underwent complete evaluation by both Neurology and Rheumatology Specialists. Comprehensive laboratory testing was performed to exclude potential MS mimics. Based on clinical, laboratory or imaging characteristics not typical for MS, testing for several autoantibodies was conducted with commercially available EUROLINE kits.
Results
We report 6 patients (5 females), 24 to 62 years old, 3 with optic neuritis (ON) (1 relapsing) and 3 with pyramidal and sensory clinical findings (2 with progressive course). Apart from arthralgias (3/6) and shortness of breath (1/6) no other signs of SSc were documented. 4/6 had positive anti-PM/Scl-100 antibodies, 1 had anti-Scl-70 and 1 anti-RNAP-III. No other autoantibodies including those against Myelin Oligodendrocyte Glycoprotein and Aquaporin-4 were detected along with no other abnormal laboratory values. Cerebrospinal fluid oligoclonal bands were: type 2 in 2/6 and type 4 in 1/6. Of the ONs, 1 (with anti-RNAP-III) had also brain lesions (one 15mm in diameter) and one cervical spine lesion. All other 3 patients had brain (1 diffuse, 1 one single 16mm lesion) and spinal cord lesions (none transverse) in MRI. The McDonald 2017 diagnostic criteria for MS were fulfilled for 3/6 but 0/6 fulfilled classification criteria for SSc. 5/6 received high-doses of IV methylprednisolone with good clinical response and no adverse effects. 1/6 received Interferon-β (IFN-β) which was discontinued due to myalgias. 1/6 receives cyclophosphamide and 1/6 mycophenolate mofetil.
Conclusions
Detection of SSc-specific autoantibodies in patients with CNS demyelination is extremely rare and it may imply an underlying autoimmune dysregulation distinct from MS. Given the potential exacerbation of systemic autoimmunity by IFN-β and the risk for renal crisis following high doses of corticosteroids, testing for SSc-specific autoantibodies could be useful in the diagnostic evaluation of atypical CNS demyelinating lesions.