Systemic 5-fluorouracil induced lupus erythematosus: a review of the literature

Drug-induced subacute cutaneous lupus erythematosus (SCLE) is the most common subtype of drug-induced systemic lupus erythematosus and has been associated with more than 100 drugs. It presents weeks to months after initiation of the culprit medication. The eruption is typically in a photodistribution and it is marked by positive serology to anti-Ro (SSA) antibody. Systemic 5-fluorouracil (5-FU) is a less-common culprit of drug-induced SCLE and its occurrence is likely dependent on exposure to ultraviolet light. Herein, we present a review of drug-induced lupus induced by the pyrimidine analog, 5-FU, and its prodrugs, capecitabine and uracil-tegafur. The search was carried out using the following terms: (PubMed: keywords included drug-induced lupus, 5-fluorouracil, subacute cutaneous lupus erythematosus, capecitabine, uracil-tegafur, discoid lupus, systemic lupus erythematosus)

Phototesting and photoprotection in LE

Photosensitivity and induction of skin lesions following UV radiation is a common problem of patients with cutaneous and systemic forms of lupus erythematosus. The detrimental effect of UV radiation to patients with lupus erythematosus was already recognized in the last century. Skin lesions can now be provoked under standardized conditions allowing the diagnosis and classification of patients with photosensitive disorders. The aim of this review is to give an overview on the history, test procedure and test results in patients with lupus erythematosus

Comparison of structural magnetic resonance imaging findings between neuropsychiatric systemic lupus erythematosus and systemic lupus erythematosus patients: A systematic review and meta-analysis

Introduction: Neuropsychiatric systemic lupus erythematosus is often clinically challenging to diagnose, treat and monitor. Although brain magnetic resonance imaging is frequently performed before lumbar puncture in neuropsychiatric systemic lupus erythematosus, it is not clear from the literature whether specific brain magnetic resonance imaging findings are associated with distinct clinical features of neuropsychiatric systemic lupus erythematosus. Methods: We conducted a systematic review and meta-analysis on published studies of neuropsychiatric systemic lupus erythematosus including brain magnetic resonance imaging and the 1999 American College of Rheumatology-defined clinical neuropsychiatric systemic lupus erythematosus syndromes to determine their relationship. Pooled prevalence and risk ratio for distinct neuropsychiatric systemic lupus erythematosus associations were determined with 95% confidence intervals. Results: Of 821 studies screened, 21 fulfilled inclusion criteria. A total of 818 participants were evaluated (91% female) with 1064 neuropsychiatric systemic lupus erythematosus episodes assessed. Neuropsychiatric systemic lupus erythematosus features included headache (24%), seizures (19%), cerebrovascular disease (18%), cognitive dysfunction (15%) and acute confusional state (14%). Normal magnetic resonance imaging was significant for anxiety disorder (risk ratio: 9.00; 95% confidence interval: 2.40, 33.79), autonomic disorder (risk ratio: 7.00; 95% confidence interval: 0.51, 96.06) and plexopathy (risk ratio: 5.00; 95% confidence interval: 0.81, 31.00). Highest risk ratio of neuropsychiatric systemic lupus erythematosus syndrome with abnormal magnetic resonance imaging was observed for cerebrovascular disease (risk ratio: 0.15; 95% confidence interval: 0.10, 0.24) and demyelination (risk ratio: 0.11; 95% confidence interval: 0.02, 0.72). Conclusion: Normal magnetic resonance imaging in neuropsychiatric systemic lupus erythematosus was the most significant correlate from our meta-analysis for psychological symptoms including anxiety and peripheral nerve features of autonomic disorder and plexopathy. The main abnormal brain magnetic resonance imaging correlates included cerebrovascular disease and demyelination. Brain magnetic resonance imaging correlates poorly with neuropsychiatric systemic lupus erythematosus features, and specific clinical symptoms should be the main determinants of performing magnetic resonance imaging rather than presence of neuropsychiatric systemic lupus erythematosus per se

Cancer complicating systemic lupus erythematosus--a dichotomy emerging from a nested case-control study

We determined whether any individual cancers are increased or decreased in a cohort of 595 patients with systemic lupus erythematosus (SLE) followed for up to 32 years at the University College London Hospitals Lupus Clinic, looking for any associated clinical or serological factors and the prognosis after cancer diagnosis

Cognitive dysfunction improves in systemic lupus erythematosus: Results of a 10 years prospective study

Objective Cognitive impairment (CI) has been described in 3–80% of Systemic lupus erythematosus (SLE) patients but only short-term studies evaluated its over-time changes, suggesting that CI is usually a stable finding. We aimed at evaluating the changes of SLE-related CI in a 10-years prospective single center cohort study. Methods We evaluated 43 patients (M/F 5/38; mean age = 45.7±10.1 years; mean disease duration = 230.8±74.3 months) at baseline (T0) and after 10 years (T1). A test battery designed to detect fronto-subcortical dysfunction across five domains (memory, attention, abstract reasoning, executive and visuospatial function) was administered. A global cognitive dysfunction score (GCD) was obtained and associated with clinical and laboratory features. Results Prevalence of CI was 20.9% at T0 and 13.9% at T1 (P = NS). This impairment was prevalently mild at T0 (55.5%) and mild or moderate at T1 (36.3% for both degrees). After 10 years, CI improved in 50% of patients, while 10% worsened. Impaired memory (P = 0.02), executive functions (P = 0.02) and abstract reasoning (P = 0.03) were associated with dyslipidemia at T0. Worsening of visuospatial functions was significantly associated with dyslipidemia and Lupus Anticoagulant (P = 0.04 for both parameters). Finally, GCD significantly correlated with chronic damage measured by SLICC/damage index at T0 (r = 0.3; P = 0.04) and T1 (r = 0.3; P = 0.03). Conclusions For the first time, we assessed CI changes over 10-years in SLE. CI improved in the majority of the patients. Furthermore, we observed an improvement of the overall cognitive functions. These results could suggest that an appropriate management of the disease during the follow-up could be able to control SLE-related CI

Aplastic Crisis as Primary Manifestation of Systemic Lupus Erythematosus

Aplastic crisis is an unusual feature of systemic lupus erythematosus (SLE). We report the case of a 54-year-old woman presenting with both (extravascular) Coombs-positive hemolytic anemia and laboratory findings of bone marrow hyporegeneration with concomitant severe neutropenia. A bone marrow biopsy confirmed aplastic crisis. Diagnostic work-up revealed soaring titers of autoantibodies (anti-nuclear, anti-double-stranded DNA, anti-cardiolipin-IgM, and anti-beta 2-glykoprotein-IgM antibodies), indicating a connective tissue disease as the most plausible reason for bone marrow insufficiency. As the criteria for SLE were fulfilled, we initiated an immunosuppressive therapy by steroids, which led to a rapid complete hematologic and clinical remission in our patient. In this case, we could report on one of the rare cases of SLE-induced aplastic crisis showing that this condition can be entirely reversed by immunosuppressive treatment and that SLE-induced aplastic crisis yields a good prognosis. In conclusion, in a case of aplastic crisis, physicians should be aware that SLE can be a rare cause that is accessible to specific treatment

Investigating lupus retention in care to inform interventions for disparities reduction: an observational cohort study.

BACKGROUND:Systemic lupus erythematous (SLE) disproportionately impacts patients of color and socioeconomically disadvantaged patients. Similar disparities in HIV were reduced through a World Health Organization-endorsed Care Continuum strategy targeting "retention in care," defined as having at least two annual visits or viral load lab tests. Using similar definitions, this study aimed to examine predictors of lupus retention in care, to develop an SLE Care Continuum and inform interventions to reduce disparities. We hypothesized that Black patients and those residing in disadvantaged neighborhoods would have lower retention in care. METHODS:Abstractors manually validated 545 potential adult cases with SLE codes in 2013-2014 using 1997 American College of Rheumatology (ACR) or 2012 Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) criteria. We identified 397 SLE patients who met ACR or SLICC criteria for definite lupus, had at least one baseline rheumatology visit, and were alive through 2015. Retention in care was defined as having two ambulatory rheumatology visits or SLE labs (e.g., complement tests) during the outcome year 2015, analogous to HIV retention definitions. Explanatory variables included age, sex, race, ethnicity, smoking status, neighborhood area deprivation index (ADI), number of SLE criteria, and nephritis. We used multivariable logistic regression to test our hypothesis and model predictors of SLE retention in care. RESULTS:Among 397 SLE patients, 91% were female, 56% White, 39% Black, and 5% Hispanic. Notably, 51% of Black versus 5% of White SLE patients resided in the most disadvantaged ADI neighborhood quartile. Overall, 60% met visit-defined retention and 27% met complement lab-defined retention in 2015. Retention was 59% lower for patients in the most disadvantaged neighborhood quartile (adjusted OR 0.41, CI 0.18, 0.93). No statistical difference was seen based on age, sex, race, or ethnicity. More SLE criteria and non-smoking predicted greater retention. CONCLUSIONS:Disadvantaged neighborhood residence was the strongest factor predicting poor SLE retention in care. Future interventions could geo-target disadvantaged neighborhoods and design retention programs with vulnerable populations to improve retention in care and reduce SLE outcome disparities

Macrophage Activation Syndrome as Onset of Systemic Lupus Erythematosus: A Case Report and a Review of the Literature

Macrophage activation syndrome (MAS) is a potentially fatal condition. It is a rare complication of several autoimmune disorders, including systemic lupus erythematosus (SLE) and systemic juvenile idiopathic arthritis (sJIA). The incidence of MAS associated with SLE is about 0.9–4.6% [1]. MAS is a multifarious disease, presenting with several signs and symptoms, including high fever, hepatomegaly, splenomegaly, hemorrhagic manifestations (e.g., purpura), and dysfunction of the central nervous system, like lethargy. Furthermore, MAS is characterized by several alterations in laboratory tests, including pancytopenia, hypofibrinogenemia, hypertriglyceridemia, and hyperferritinemia. MAS is classified among the group of hemophagocytic lymphohistiocytosis (HLH), which includes familial HLH and secondary HLH. Secondary HLH is triggered by several causes, including infection, drugs, malignancy, and rheumatic disorder [2]. We report a rare case of MAS that occurred as first manifestation of SLE treated with high dose intravenous methylprednisolone and oral cyclosporine

Influence of 1 Alpha, 25-Dihydroxyvitamin D3 on T helper 17 cells and related cytokines in systemic lupus erythematosus

Background: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Emerging data suggests that T helper 17 (Th17) cells play a pathogenic role in SLE and the increased number of these cells correlates with disease activity. In recent years, 1α, 25-dihydroxyvitamin D3 (1,25VitD3) has been considered as an immunomodulatory factor. Objective: To investigate the effect of 1,25VitD3 on Th17 cells and on the expression of related cytokines in SLE patients. Method: Thirty SLE patients (newly diagnosed or in remission) were sampled for 10 ml whole blood to isolate peripheral blood mononuclear cells (PBMCs) using Ficoll-Hypaque density gradient centrifugation. Isolated cells were cultured in the presence and absence of 50 nM 1,25VitD3. After incubation, cells were harvested and stimulated for 4-5 hours with phorbol myristate acetate (PMA) and ionomycin in the presence of brefeldin A. IL-17 secreting cells were analyzed by flowcytometry. RNA was extracted from cultured cells, cDNA was synthesized, and the expression levels of IL-6, IL-17, IL-23 and TGF-β genes were assessed by real-time PCR. Results: The percentage of Th17 cells (CD3+CD8- IL-17+ T cells) decreased significantly in 1,25VitD3-treated cells (3.67 ± 2.43%) compared to untreated cells (4.65 ± 2.75%) (p=0.003). The expression of TGF-β up regulated (1.38-fold) and the expression of IL-6 (50%), IL-17 (27%) and IL-23 (64%) down regulated after 1,25VitD3 treatment. Conclusion: This study showed that 1,25VitD3 modulates Th17 related pathways in SLE patients and revealed the immunomodulatory effect of 1,25VitD3 on the Th17 mediated autoimmunity. © 2015, Shiraz University of Medical Sciences. All rights reserved