Psychosis in systemic lupus erythematosus (SLE): 40-year experience of a specialist centre

Abstract Objectives The long-term outcome of psychosis in association with systemic lupus erythematosus (SLE) has been insufficiently characterised. We used a specialist centre cohort of patients with SLE and psychosis to investigate their clinical outcome and phenotypic and laboratory characteristics. Methods Retrospective cohort study of 709 SLE patients seen at a specialist centre between January 1978 and November 2018. Clinical, biochemical and immunological characteristics (Bonferroni corrected), and serum neuronal surface antibody profile using novel cell-based assays, were compared between patients with and without psychosis. Results Eighteen (18/709, 2.5%) patients developed lupus psychosis over a mean ± SD of 17.5 ± 11.0 years follow-up. Psychosis fully remitted in 66.7% (12/18) with a combination of antipsychotic (in 38.9%) and immunosuppressive therapy (methylprednisolone 72.2%, cyclophosphamide 55.6%, rituximab 16.7%, plasma exchange 27.8%, prednisolone 50%). Patients who developed lupus psychosis may be more likely to have anti-RNP antibodies (50.0% vs 26.5%) and less likely to have anti-cardiolipin antibodies (5.6% vs 30.0%), but this was not significant in our small sample. Neuronal surface autoantibody tests found GABABR autoantibodies in 3/10 (30.0%) lupus psychosis patients compared with only 3/27 (11.1%) in age- and sex-matched SLE controls using fixed cell-based assays (P =0.114). However, GABABR antibodies were not replicated using a live cell-based assay. NMDAR-antibodies were not detected with fixed or live cell assays in any samples. Conclusion Lupus psychosis is rare but treatable. In this rare sample of eighteen patients from a 40-year cohort, no significant biomarker was found, but some preliminary associations warrant further exploration in a larger multicentre analysis.

[1]  F. Piehl,et al.  Absence of Neuronal Autoantibodies in Neuropsychiatric Systemic Lupus Erythematosus , 2020, Annals of neurology.

[2]  I. Bruce,et al.  Psychosis in Systemic Lupus Erythematosus: Results From an International Inception Cohort Study , 2019, Arthritis & rheumatology.

[3]  N. Harrison,et al.  DMARDs for mental health symptoms in RA , 2018, Nature Reviews Rheumatology.

[4]  Y. Joo,et al.  Prevalence, risk factors, and impact on mortality of neuropsychiatric lupus: a prospective, single-center study , 2018, Lupus.

[5]  M. Leboyer,et al.  Cell- and Single Molecule-Based Methods to Detect Anti-N-Methyl-D-Aspartate Receptor Autoantibodies in Patients With First-Episode Psychosis From the OPTiMiSE Project , 2017, Biological Psychiatry.

[6]  E. Mann,et al.  Pathogenic potential of antibodies to the GABAB receptor , 2017, Epilepsia open.

[7]  M. Etemadifar,et al.  Neuropsychiatric manifestations in patients with systemic lupus erythematosus: A study from Iran , 2016, Advanced biomedical research.

[8]  Melvyn W B Zhang,et al.  A meta-analysis of serum and cerebrospinal fluid autoantibodies in neuropsychiatric systemic lupus erythematosus. , 2016, Autoimmunity reviews.

[9]  D. Gladman,et al.  Mood Disorders in Systemic Lupus Erythematosus: Results From an International Inception Cohort Study , 2015, Arthritis & rheumatology.

[10]  Chih-Min Liu,et al.  Negative symptoms in neuropsychiatric systemic lupus erythematosus. , 2015, The Journal of neuropsychiatry and clinical neurosciences.

[11]  B. Volpe,et al.  Brain metabolism and autoantibody titres predict functional impairment in systemic lupus erythematosus , 2015, Lupus Science & Medicine.

[12]  S. Muller,et al.  Neuropsychiatric systemic lupus erythematosus: pathogenesis and biomarkers , 2014, Nature Reviews Neurology.

[13]  D. Kullmann,et al.  Clinical relevance of serum antibodies to extracellular N-methyl-d-aspartate receptor epitopes , 2014, Journal of Neurology, Neurosurgery & Psychiatry.

[14]  T. Kano,et al.  Identification of novel autoantibodies to GABA(B) receptors in patients with neuropsychiatric systemic lupus erythematosus. , 2014, Rheumatology.

[15]  D. Roccatello,et al.  Autoantibodies involved in neuropsychiatric manifestations associated with systemic lupus erythematosus: a systematic review , 2014, Journal of Neurology.

[16]  J. Hanly Diagnosis and management of neuropsychiatric SLE , 2014, Nature Reviews Rheumatology.

[17]  B. Lennox,et al.  Antibodies to the N-Methyl-D-Aspartate Receptor and Other Synaptic Proteins in Psychosis , 2014, Biological Psychiatry.

[18]  C. Foocharoen,et al.  Characteristics, treatments and outcome of psychosis in Thai SLE patients. , 2012, Journal of psychosomatic research.

[19]  R. Omdal,et al.  Systemic lupus erythematosus, the brain, and anti-NR2 antibodies , 2012, Journal of Neurology.

[20]  S. Chate,et al.  Psychosis in Patients with Systemic Lupus Erythematosus , 2012, Indian journal of psychological medicine.

[21]  A. Vincent,et al.  Neue serologische Marker zur Differentialdiagnose der Autoimmun-Enzephalitis/New serological markers for the differential diagnosis of autoimmune limbic encephalitis , 2011 .

[22]  P. Thuras,et al.  Deficits in GABAB receptor system in schizophrenia and mood disorders: A postmortem study , 2011, Schizophrenia Research.

[23]  D. Kullmann,et al.  N-methyl-d-aspartate antibody encephalitis: temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes , 2010, Brain : a journal of neurology.

[24]  Neil J Scolding,et al.  Neurolupus , 2010, Practical Neurology.

[25]  D. Friedman,et al.  Antibodies to the GABAB receptor in limbic encephalitis with seizures: case series and characterisation of the antigen , 2010, The Lancet Neurology.

[26]  I. Bruce,et al.  Prospective analysis of neuropsychiatric events in an international disease inception cohort of patients with systemic lupus erythematosus , 2009, Annals of the rheumatic diseases.

[27]  D. Isenberg,et al.  Psychosis due to systemic lupus erythematosus: characteristics and long-term outcome of this rare manifestation of the disease. , 2008, Rheumatology.

[28]  J. Hanly,et al.  Neuropsychiatric events in systemic lupus erythematosus: attribution and clinical significance. , 2004, The Journal of rheumatology.

[29]  M. Kopelman,et al.  A psychiatric perspective on the therapy of psychosis in systemic lupus erythematosus , 2003, Lupus.

[30]  C. Lau,et al.  Treatment of lupus psychosis with oral cyclophosphamide followed by azathioprine maintenance: an open-label study. , 2003, The American journal of medicine.

[31]  O. Nived,et al.  Outcome of neuropsychiatric systemic lupus erythematosus within a defined Swedish population: increased morbidity but low mortality. , 2002, Rheumatology.

[32]  Caroline Gordon,et al.  The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. , 1999, Arthritis and rheumatism.

[33]  N. Brot,et al.  Association between lupus psychosis and anti-ribosomal P protein antibodies. , 1987, The New England journal of medicine.

[34]  J F Fries,et al.  The 1982 revised criteria for the classification of systemic lupus erythematosus. , 1982, Arthritis and rheumatism.

[35]  C. Brook,et al.  Psychosis in Systemic Lupus Erythematosus (SLE) and the Response to Cyclophosphamide , 1969, Proceedings of the Royal Society of Medicine.

[36]  F. Cendes,et al.  Acute psychosis in systemic lupus erythematosus , 2007, Rheumatology International.

[37]  J. Ioannidis,et al.  Accuracy of anti-ribosomal P protein antibody testing for the diagnosis of neuropsychiatric systemic lupus erythematosus: an international meta-analysis. , 2006, Arthritis and rheumatism.