Case of Acute Disseminated Encephalomyelitis Associated with Cytomegalovirus Reactivation in an Immunocompromised Systemic Lupus Erythematosus Patient

We present a case of an immunocompromised systemic lupus erythematosus female patient admitted to our hospital for general impairment, monoparesis, and temporary cognitive disability. The case represented a significant diagnostic and therapeutic challenge primarily because of a wide range of differential diagnosis options (CNS lupus, ischemic cerebrovascular disease, viral meningoencephalitis, progressive multifocal leukoencephalopathy, limbic encephalitis, and acute disseminated encephalomyelitis—ADEM). Brain MRI findings were compatible with ADEM, and microbiological tests showed a cytomegalovirus infection (CMV) which is rarely associated with ADEM despite the increasing number of immunocompromised patients prone to symptomatic CMV reactivation. Our patient was treated with intravenous methylprednisolone, immunoglobulin (IVIG), along with antiviral therapy resulting in a favorable therapeutic effect. In conclusion, only a few described ADEM cases have been associated with CMV, and none of them, to the best of our knowledge, in an immunocompromised patient. In this case, a multidisciplinary approach and broad diagnostic considerations were decisive for successful treatment and outcome.

Formal neurocognitive function and anti-N-methyl-D-aspartate receptor antibodies in paediatric lupus

ObjectiveSLE is a chronic multisystem autoimmune inflammatory disease impacting a number of organs, including the central nervous system (CNS). The pathophysiology of CNS lupus is multifactorial, making diagnosis problematic. Neurocognitive (NC) testing and specific biomarkers to identify the development of neuropsychiatric (NP) symptoms in lupus are needed. Paediatric patients with SLE have high incidence of NP disease . While serum anti-N-methyl-D-aspartate receptor (NMDAR) antibodies have shown promise as a biomarker of NP in adults with SLE, much less is known with regard to paediatric patients with SLE.MethodsWe performed a cross-sectional study in paediatric patients with SLE. Serum NMDAR antibodies were measured and compared with levels in patients with juvenile idiopathic arthritis (JIA). Formal NC testing was performed in accordance with the Childhood Arthritis & Rheumatology Research Alliance neuropsychological core test battery. NC functioning was compared in the two groups and with NMDAR antibody levels.ResultsSerum NMDAR antibody levels were significantly higher in paediatric patients with SLE compared with patients with JIA. There were no significant correlations between NMDAR antibody levels and any measure of NC functioning. In an exploratory examination of anti-ribosomal P (RibP) antibody and NC functioning in a subset of patients with SLE, RibP antibody-positive patients exhibited worse scores for Verbal Memory Index and Design Fluency Test Switching compared with RibP antibody-negative patients. A globally significant association between disease status and NC functioning was observed. Specifically, patients with SLE had lower scores compared with patients with JIA for full-scale IQ, letter–word recognition, reading fluency and calculation skills after adjusting for multiple comparisons.ConclusionThese collective results suggest that although serum NMDAR may serve as a biomarker, formal NC testing is superior in identifying paediatric patients with SLE with NP manifestations. RibP also may potentially serve as a biomarker of NP manifestations in paediatric patients with SLE. Additional and longitudinal studies are needed.

Prevalence of progressive multifocal leukoencephalopathy (PML) in adults and children with systemic lupus erythematosus

ObjectiveTo define the risk of progressive multifocal leukoencephalopathy (PML) in SLE.MethodsThis is a retrospective observational study to evaluate PML cases in patients with SLE admitted to two large academic hospitals. Using electronic medical record (EMR) data, International Classification of Diseases (ICD) codes identified PML cases among patients with SLE, rheumatoid arthritis (RA) (controls), had renal transplant and with HIV. Medication exposure was reviewed.ResultsA total of 5409 Columbia University Medical Center (CUMC) patients and 2046 Northwell Health patients were identified using one ICD code for SLE. Of 7455 patients, three had an ICD code for PML. On EMR review, however, PML was substantiated in only one fatal SLE case with significant immunosuppressant use and severe lymphopenia (<0.5 cells x 109/L); one patient was evaluated for PML but cerebrospinal fluid (CSF) was negative for JC virus and improved with treatment of central nervous system (CNS) lupus. EMR data were very limited for the third patient and diagnosis could not be confirmed. None of the 13 342 patients with RA ICD codes had PML. Of the 5409 patients with an SLE ICD code at CUMC, 212 also had a renal transplant ICD code, and 83 had concomitant HIV/AIDS. Based on inpatient pharmacy records of 5409 hospitalised patients at CUMC, 59.2% were treated with steroids, and 16.09% with immunosuppressants (7.76% mycophenolate, 3.42% cyclophosphamide, 2.88% azathioprine and 2.03% rituximab). No patients with paediatric SLE (pSLE) (n=538) had PML. The combined prevalence of PML in hospitalised patients with SLE at the two hospitals was 13–27/100 000 patients.ConclusionAmong 7455 adult patients with SLE ICD codes, there were two PML cases, with only one confirmed case associated with severe lymphopenia and immunosuppressants, corresponding to a prevalence of 13–27 per 100 000 patients. No PML cases in pSLE were found. A high index of suspicion in patients with SLE and CNS manifestations is required for the prompt diagnosis of PML.

The Wolf’(s)-B(r)ain- The Past, Present, Future of CNS Lupus

Systemic Lupus Erythematosus is a long-studied condition with protean manifestations, yet, with so much known about the pathogenesis and treatment aspects still in the dark. In this review article, we try to sum up all the knowledge we have till date, the practice essentials used to date and the future research directions, all of which ultimately lead to a better understanding of the disease and its management.

Balancing immunosuppression and infection: recurrent enterovirus encephalitis in SLE

A young woman with systemic lupus erythematosus (SLE) developed recurrent enterovirus meningoencephalitis while taking prednisolone, azathioprine and rituximab. After reducing the immunosuppression, she developed a central nervous system (CNS) flare of SLE, with enterovirus still present in the cerebrospinal fluid (CSF). There are no evidence-based specific treatments for enterovirus encephalitis, but she responded well to intravenous immunoglobulin alongside pulsed methylprednisolone and rituximab. This case highlights the difficulties in managing people with co-existing infective and autoimmune conditions, especially if each affects the CNS. A viral infection and SLE flare can resemble one another clinically, although here the radiological differentiation of CNS lupus versus enterovirus encephalitis helped to guide the diagnosis.

A retrospective study of mucocutaneous lesions of SLE patients and their systemic implications

<p class="abstract"><strong>Background:</strong> SLE is a systemic disease with multiorgan involvement occuring very rarely, if so, it has a very grave prognosis if not detected early. Our study enlightens about the evolution of mucocutaneous lesions which can serve as an eye opener for early detection of systemic involvement.</p><p class="abstract"><strong>Methods:</strong> A descriptive study was conducted in the Department of Dermatology at a tertiary care centre from May 2017 to April 2018 retrospectively. From 15 confirmed cases of SLE a critical retrospective analysis of symptom complex evolution was done and thus a clinical correlation of evolution of mucocutaneous lesions and systemic involvement was attempted.<strong></strong></p><p class="abstract"><strong>Results:</strong> Out of the fifteen patients in our study comprising various age groups (4-51 years), mean age group was 29.76 years. 14 (93%) were female patients and 1 (6.6%) male patient. Oral ulcerations, Non-scarring alopecia and vasculitic lesions were predominant (3 patients-80%) followed by photosensitivity and cheilitis (9 patients- 60%). Systemic involvement was present in 9 (60%), out of which one (6%) patient had lupus nephritis and 3 patients (20%) had CNS lupus, 2 (13%) had chronic unilateral scleritis, 2 (13%) had interstitial lung disease, one (6%) had coronary heart disease. Mucocutaneous lesions preceded the systemic involvement in 88.8% of cases, with mean duration being 3 years (4 months – 10 years).</p><p class="abstract"><strong>Conclusions:</strong> Mucocutaneous lesions could serve as an eye opener for diagnosis of SLE, which is always a diagnosis made out of high degree of suspicion apart from certain mucocutaneous lesions serving as an ominous sign of system involvement in SLE.</p><p class="abstract"> </p>

Effects of conventional immunosuppressive therapy on functional and pathological features of CNS lupus in NZB/W mice

Neurological involvement is one of the most devastating complications of the disease, systemic lupus erythematosus (SLE). To understand the effect of the drugs, cyclophosphamide (CY) and prednisolone (PD) on CNS manifestations, the New Zealand Black/White (NZB/W) lupus mice, were given a cocktail of both drugs by intraperitoneal injections daily from 22 to 44 weeks of age. The treatment prolonged survival (10% of the treated 20 NZB/W mice died compared to 50% of the 30 NZB/W mice, with no mortality in the control NZW mice). Real-time PCR analysis showed a three- to fifteen-fold increase in the expression of GFAP, vimentin and syndecan4 in the cerebral cortex of 44 week NZB/W mice. These alterations were prevented by CY and PD treatment. Immunostaining revealed increased GFAP expression in NZB/W mice compared to congenic, nondiseased NZW mice, which was prevented by treatment. In addition, concomitant changes were observed in the expression of extracellular matrix proteins, collagen IV and fibronectin. To determine the impact of these alterations on the neurological manifestations of SLE, behavior was studied in these mice. The NZB/W mice were spontaneously less active in the open field and exhibited a decrease in distance traveled (58% of control, p<0.01) and ambulatory measurements (52% of control, p<0.01). They took more time (8.8+1.2min) to escape from the maze compared to the control NZW mice (2.6+0.8min). Even more striking was that the behavioral deficits were alleviated in these mice by CY and PD treatment. These results support the hypothesis that increased astrogliosis and altered extracellular matrix proteins may be two of the critical factors that mediate lupus brain disease.