Progressive Multifocal Leukoencephalopathy in Systemic Lupus Erythematosus: A Consequence of Patient-Intrinsic or -Extrinsic Factors?

Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease of the central nervous system (CNS) caused by reactivation of the polyomavirus JC (JCV) typically in immunocompromised individuals. The risk of PML among rheumatic diseases may be higher for systemic lupus erythematosus (SLE), without, however, a clear association with the type and intensity of background therapy. We present the development and outcome of PML in a 32-year-old female lupus patient under mild immunosuppressive treatment, yet with marked B-cell lymphopenia in the peripheral blood and bone marrow (<1% of total lymphocytes). Despite treatment with the immune checkpoint inhibitor pembrolizumab, the patient showed progressive neurological and brain imaging deterioration and eventually died 15 months after PML diagnosis. To unveil possible underlying genetic liabilities, whole exome sequencing was performed which identified deleterious variants in GATA2 and CDH7 genes, which both have been linked to defective T- and/or B-lymphocyte production. These findings reiterate the possible role of disease-/patient-intrinsic factors, rather than that of drug-induced immunosuppression, in driving immune dysregulation and susceptibility to PML in certain patients with SLE.

Remission or low disease activity at pregnancy onset are linked to improved foetal outcomes in women with systemic lupus erythematosus: results from a prospective observational study.

OBJECTIVES: Systemic lupus erythematosus (SLE) patients show variably increased risk for pregnancy complications. We analysed pregnancy outcomes (foetal and maternal), patterns of disease activity and use of medications in a contemporary Caucasian SLE population. METHODS: Prospective observational study, involving hospital units and private rheumatologists in Greece, of incident pregnancies (period 2015-2018) in women with SLE. Clinical and obstetrical monitoring was performed at regular intervals up to 9 months post-partum. Regression and mixed model analyses were used to determine predictors for adverse foetal outcomes and flares. RESULTS: We monitored 82 pregnancies in 64 SLE patients. Foetal loss, prematurity and small for gestational age neonate occurred at 15.8%, 34.1% and 8.5%, respectively; 53.7% of pregnancies were complicated with at least one adverse outcome. Patients with antiphospholipid antibodies (aPL) had increased risk (odds ratio [OR] 5.67, p=0.015), whereas those at low disease activity at pregnancy onset were protected (OR 0.20, p=0.024) against foetal complications. Persistent activity and glucocorticoid intake during pregnancy also predicted poor foetal outcomes. SLE patients experienced an average 1.08 mild/moderate and 0.27 severe flares. The latter occurred more frequently post-partum, in patients with alopecia (OR 8.92, p=0.003), hypocomplementaemia (OR 10.34, p=0.038) and nephritis (OR 7.32, p=0.052). Lupusactivity post-labour was paralleled by decreased use of hydroxychloroquine, glucocorticoids and azathioprine. CONCLUSIONS: In SLE women, foetal complications are common especially in the presence of aPL and increased activity, which corroborates the importance of pregnancy planning and tight disease control at pregnancy onset. Flares, mostly mild or moderate, can occur both during and after pregnancy.

Central nervous system tuberculosis reactivation following intravenous iron supplementation.

Patients with inflammatory bowel disease (IBD) are often treated with tumor necrosis factor (TNF)-alpha inhibitors and are therefore at higher risk for tuberculosis (TB) reactivation. IBD patients also frequently have iron deficiency which is often treated with intravenous iron supplementation. Iron plays an important role in mycobacterial infections, and reactivation of TB has been rarely reported after iron repletion. We present a case of a 63-year-old male with a history of Crohn's disease, on treatment with adalimumab for 2 years. The patient presented with malaise, mild lethargy, low-grade fever, and hyponatremia within a week after the first dose of intravenous iron. He was diagnosed with central nervous system TB (positive cerebrospinal fluid polymerase chain reaction and culture) and responded to treatment with a four-drug regimen. The timing of TB reactivation (within a week after intravenous iron administration) suggests that iron repletion contributed to the clinical reactivation of TB. Biological plausibility and prior similar clinical observations further support the causality of this association. Considering the frequency of iron deficiency in IBD, we believe that it is worthy to further explore the potential association between intravenous iron administration and the timing of TB reactivation in patients being treated with TNF-alpha inhibitors.

Birth Registry of Women With Systematic Lupus Erythematosus: The Greek Experience.

Pregnancy in women with SLE (Systematic Lupus Erythematosus) is considered of "high risk" since it has been related with adverse events both in the mother and the foetus. Many studies have reported relapse of the disease during the pregnancy and the first trimester post-labour, while others have found no difference in terms of frequency and type of relapses. Moreover, adverse obstetrical events like recurrent pregnancy loss, preeclampsia, prematurity, intrauterine growth restriction and neonatal lupus syndrome tend to occur more often in patents with SLE. However, most of these data regarding the burden and pregnancy outcomes in SLE come from retrospective studies of previous decades, and in non-Caucasian patients. To this end, more recent studies have suggested overall improved outcomes of pregnancy, still their results are often conflicting. The purpose of this study is to record, through a prospective observational (non-interventional) study, the contemporary prognosis of pregnancy in women with SLE who are followed-up by private and hospital physicians in Greece. In particular, we aim to establish a registry to study the course of the disease during pregnancy, the outcome of pregnancy and the possible negative or positive prognostic factors, the effect of drugs on pregnancy and the foetus.