Anna Bogaczewicz

Exacerbations of bipolar disorder triggered by chloroquine in systemic lupus erythematosus—a case report

Despite precise definitions and exclusions for 19 syndromes of neuropsychiatric systemic lupus erythematosus (NPSLE), under some circumstances it appears to be difficult to differentiate whether neuropsychiatric symptoms are caused by SLE or by other reasons such as primary mental disorders or substance-induced mood disorders, especially induced by glucocorticoids or antimalarials. We report the case of a male patient with SLE who presented with an exacerbation of bipolar disorder triggered by chloroquine. Firstly, when the patient was diagnosed with SLE, he underwent six months of therapy with chloroquine without any psychiatric symptoms. Later, the SLE returned and the patient was prescribed chloroquine again, without any mental illness. When the third exacerbation of SLE occurred, it coincided with a severe depressive episode with psychotic features that became aggravated for the first time after the administration of chloroquine. The chloroquine was subsequently replaced with hydroxychloroquine for the next six months without any behavioral problems, following which, the SLE and mood disorder were in remission. Later, a bipolar disorder relapse occurred, manifested by a manic episode, and in the following three months, despite psychiatric treatment, a manic episode with psychotic features developed four days after chloroquine was prescribed for arthritis. It was the second time that the mood disorder was exacerbated by chloroquine. Since that time, chloroquine has been withdrawn. Currently the patient is undergoing treatment with hydroxychloroquine and psychiatric drugs with good response. Our case points out that although chloroquine-induced psychosis is rare, patients presenting with behavioral changes need physicians’ attention in order to diagnose early and efficiently treat encountered mood disorders.

Toll-like receptor 4 gene polymorphism 1196 C/T does not influence the risk of neuropsychiatric systemic lupus erythematosus in Polish population – a preliminary report

Objective Recent data indicate that Toll-like receptors (TLRs) participate in various neuropathologic conditions, including ictogenesis, myelin disruptions associated with chronic alcohol abuse, behavioral and cognitive dysfunctions associated with alcohol-induced neuroinflammatory damage, and activation of microglia to reduce amyloid β deposits. As seizures and depression are well known neuropsychiatric syndromes in systemic lupus erythematosus (SLE) the aim of the study was to investigate whether TLR4 gene polymorphism 1196C/T (rs4986791, Thr399Ile) was a candidate for susceptibility of development of neuropsychiatric systemic lupus erythematosus (NPSLE). Methods The study covered 60 patients with SLE and 100 healthy individuals. TLR4 1196C/T genotyping was performed by real-time polymerase chain reaction with the SimpleProbe. Results The SLE group comprised 86.7% of patients with wild-type homozygotes CC and 13.3% heterozygotes CT and no homozygotes TT. The control group consisted of 85% wild-type homozygotes CC, 15% heterozygotes CT and no homozygotes TT. The frequencies of genotype and allele distribution in SLE patients did not differ significantly from those of the control subjects. The probability of describing the possible risk of SLE imputed to genotype did not significantly differ in comparison with the healthy individuals (p = 0.77, odds ratio = 0.87, 95% confidence interval 0.34–2.19). A significant genotype association of genotype CC with arthritis was found in SLE patients (p = 0.02). It was further confirmed by a significant association of a dominant allele C with arthritis (p = 0.02). No association between CC and CT genotypes of TLR4 1196C/T and NPSLE was found. Allele distribution of TLR4 1196C/T also was not associated with NPSLE. No other significant differences were found in genotype and allele frequencies regarding clinical manifestation of SLE patients. Conclusion In the Polish population of SLE patients, 1196C/T polymorphism of TLR4 gene does not increase the risk of development of NPSLE; however, genotype CC and a dominant allele C is associated with arthritis in the course of SLE.

Cambridge Neuropsychological Test Automated Battery in assessment of cognitive parameters in patients with systemic lupus erythematosus in relation to autoantibody profile.

Objectives To relate the cognitive parameters of systemic lupus erythematosus (SLE) patients in remission to their profile of autoantibodies. Material and methods The study included 32 patients with SLE in remission, with mild disease activity as indicated by SELENA-SLEDAI < 6. For neuropsychological assessment, the Cambridge Neuropsychological Test Automated Battery (CANTAB) was applied, using motor screening (MOT), big little circle (BLC), paired associated learning (PAL), stockings of Cambridge (SOC), and graded naming tests (GNT). Detection of autoantibodies against dsDNA, nucleosome (aNuc), Sm, and anticardiolipin (aCL: IgG and IgM) was performed with immunoassays. Results The SLE patients demonstrated standard scores below norms, matched according to age and gender, in the following tests: GNT (–0.87 ±0.85), SOC PSMM (–0.47 ±0.97), PAL (–1.88 ±3.58), and BLC (–0.31 ±1.90). GNT scores under –0.5 were found significantly more frequently in SLE patients, seen in roughly 66% of test subjects. Values for PAL and mean subsequent thinking time of stockings of Cambridge (SOC MSTT) were found to be lower than –0.5 in approximately half of the patients. Mean error of motor screening (MOT ME) was found to negatively correlate with mean latency of motor screening (MOT ML) (r = –0.55). PAL significantly correlated with SOC MSTT (r = 0.38) and with GNT (r = 0.36). Anti-dsDNA antibody level correlated negatively with MOT ME (r = –0.46). Anti-Nuc antibodies correlated with MOT ML (r = 0.41) but negatively correlated with MOT ME (r = –0.58). The levels of anti-Sm, anti-CL IgM and IgG did not correlate significantly with the outcomes of CANTAB. The age of the patients correlated negatively with MOT ME (r = –0.36), positively with BLC (r = 0.53) and negatively with SOC MSTT (r = –0.43). The level of anti-Nuc antibodies correlated with anti-dsDNA level (r = 0.62) and of anti-CL IgM with anti-Sm (r = 0.39) and anti-CL IgG (r = 0.87). Conclusions CANTAB reveals a decrease in selected cognitive functions in patients with SLE. ACL IgG and anti-dsDNA antibodies indicated SLE patients prone to develop a decrease in cognitive functions.

Chloroquine-induced subacute paranoid-like disorder as a complication of dermatological treatment

A 29-year-old female patient with systemic lupus erythematosus (SLE) was referred to our Department of Dermatology and Venereology in response to psychiatric symptoms that developed 3 days after commencement of chloroquine treatment. The following criteria of the American College of Rheumatology were fulfilled: malar rash, photosensitivity, leukopenia (WBC 2.7 9 10/lL), and the positive antinuclear antibodies (titer 1/1280). Anti-SS-A (60 kDa) antibodies were strongly positive. Creatinine, liver function tests, electrolytes, glucose, and lipids were within normal limits. One year previously, the patient had received prednisone 40 mg daily for 1 month in response to leukopenia, which was found to be the predominant manifestation of SLE. Owing to a good therapeutic response (WBC 5.8 9 10/lL), the dose of prednisone was gradually tapered to 5 mg daily over the following 6 months. She also received cholecalciferol supplementation at a daily dose of 2000 IU to prevent osteoporosis and 20 mg of omeprazole to avoid glucocorticoid-induced gastritis. Methylprednisolone aceponate was applied topically for facial lesions. The patient was advised to use sunscreens and to avoid sun exposure, as well as any drugs containing estrogens, procainamide, or hydralazine. After 6 months, when the patient was receiving prednisone 5 mg every other day, she reported an aggravation of SLE with leukopenia (WBC 3.7 9 10/lL) and an eruption of erythematous macules and papules in an annular pattern, distributed on the back of the trunk and on the upper part of the chest. Although the skin lesions resembled subacute cutaneous lupus erythematosus, they were not sharply defined, and there was no scaling, no central regression, and no telangiectasia. The treatment was changed to 15 mg of prednisone daily in a tapering dose together with topical clobetasol propionate, and clinical improvement was observed 2 weeks later. One month later, all drug

EPA-1255 – Behavioral symptoms in patients with systemic lupus erythematosus induced by chloroquine-a report of two cases

Introduction It is difficult to differentiate whether neuropsychiatric symptoms are caused by systemic lupus erythematosus (SLE) or psychiatric background, coexisting disorders or drug-induced side effects. The aim of this paper is to present two cases of psychotic symptoms (bipolar and paranoid disorder) induced by chloroquine. Results Case 1: Severe depressive episode with psychotic features appeared in the context of third SLE exacerbation and chloroquine treatment. Hydroxychloroquine was used instead and symptoms resolved. Later, manic episode (with psychotic features) emerged several days after chloroquine was prescribed for concomitant arthritis. Since that time, chloroquine has been withdrawn. Currently the patient is undergoing treatment with hydroxychloroquine and psychiatric drugs with good response. Case 2: The second patient started to suffer from headaches and being lightheaded three days after chloroquine administration and within next few days feeling of derealization and poorly defining persecutory delusions accompanied by strong anxiety with occasional visual illusions occurred with clear consciousness. After eighteen days chloroquine was withdrawn and after two days all the symptoms resolved. Conclusions Clinicians should be vigilant for possible psychiatric disorder when using chloroquine in patients with SLE. Such cases are probably rare and may include both paranoid and bipolar spectrum disorders. Studies on interactions of chloroquine with brain neurotransmitter systems are needed. Hydroxychloroquine may represent lower risk considering psychiatric complications. Mechanism of the difference is currently not known.

EPA-1252 – Cognitive decline correlates with anticardiolipin antibodies and anti-dsdna in patients with systemic lupus erythematosus

Introduction Cognitive dysfunction (CD) affects 10-36% of patients with systemic lupus erythematosus (SLE). Its pathogenesis comprise direct neurocytoxicity, vasculopathy, thrombosis, hipercholesterolemia and atherosclerosis. The aim of this study was to evaluate CD in SLE patients and to investigate whether it is influenced by selected immunological and cardiological parameters. Methods Thirty-two SLE patients in remission were enrolled. Anti-cardiolipin and anti-dsDNA antibodies were estimated using immunoenzymatic techniques. Transthoracic echocardiography was performed using Acuson CV70. Since at least some tests proposed by the American College of Rheumatology for neuropsychological evaluation have Polish language version, we have used the Cambridge Neuropsychological Test Automated Battery (Cantab) that employs non-verbal stimuli and requires non-verbal responses. The following Cantab tests were used: Motor screening (MOT); Big little circle (BLC); Paired associated learning (PAL); Stockings of Cambridge (SOC); Graded naming test (GNT). Results In SLE results obtained in BLC, PAL, SOC PSMM, and GNT were lower than those of controls. SOC Mean initial thinking time correlated with ACL IgG (r=0.42; p=0.42) and anti-dsDNA antibodies (r=0.47, p=0.23) and, also, with aorticdiameter (r=0.48; p=0.036). SOC Mean subsequent thinking time negatively correlated with Left-ventricular-end-systolic diameter (r=-0.5; p=0.02). GNT correlated positively with posterior-wall-systolic-diameter (r=0.45; p=0.049) and interventricular-septum-systolic diameter (r=0.61; p=0.005). Conclusions SLE patients are cognitively compromised. Immunological and cardiological correlates may indicate underlying vascular brain damage. Biological explanation of the observed correlates is, however, unclear and possible causality needs further studies to become elucidated.