Donata Marra

Bio: Donata Marra is an academic researcher from Pierre-and-Marie-Curie University. The author has contributed to research in topics: Hydroxychloroquine & Mental health. The author has an hindex of 4, co-authored 5 publications receiving 343 citations.

Very low blood hydroxychloroquine concentration as an objective marker of poor adherence to treatment of systemic lupus erythematosus.

Abstract: Objective: Poor adherence to treatment is very difficult to diagnose accurately. Hydroxychloroquine (HCQ) has a long elimination half-life and its concentration in whole blood can be measured easily. We evaluated the utility of a very low blood HCQ concentration as a marker of poor compliance in patients with systemic lupus erythematosus (SLE). Methods: We determined HCQ concentrations on a blinded basis in 203 unselected SLE patients. At the end of the study, patients were informed of the results and retrospectively interviewed about their adherence to treatment. Results: 14 patients (7%) said they had stopped taking HCQ (n=8) or had taken it no more than once or twice a week (n=6). Their mean HCQ concentration was 26 ± 46 ng/mL [0-129]. In contrast, the other patients had a mean HCQ concentration of 1079 ng/mL [205-2629]. The principal barriers to adherence were related to HCQ treatment characteristics. Adherence subsequently improved in 10 of the 12 patients whose blood HCQ concentrations were remeasured. Conclusions: Very low whole-blood HCQ concentrations are an objective marker of prolonged poor compliance in SLE patients. Regular drug assays might help physicians to detect noncompliance and serve as a basis for counseling and supporting these patients.

Adherence to treatment in systemic lupus erythematosus patients

Abstract: Adherence is defined as "the extent to which a person's behaviour coincides with medical or health advice." Poor adherence to therapeutic regimens is a common and expensive problem in patients with chronic diseases including systemic lupus erythematosus (SLE) and is associated with a higher risk of flares, morbidity, hospitalisations and poor renal outcome. Non-adherence to the treatment is multifactorial for most patients and varies according to unintentional or intentional patterns. The rates of non-adherence in SLE patients range from 3% to 76% depending on the assessment methods, which are all subject to limitations. Indeed, poor adherence to therapeutic regimens is difficult to evaluate. Two studies have shown that undetectable blood hydroxychloroquine (HCQ) concentration may be a simple, objective and reliable marker of non-adherence in SLE patients. The accurate diagnosis of non-adherence may prevent one from incorrectly interpreting disease manifestations as a lack of response. It may then avoid an unnecessary or even dangerous treatment escalation.

Malignant catatonia due to anti-NMDA-receptor encephalitis in a 17-year-old girl: case report

Abstract: Anti-NMDA-Receptor encephalitis is a severe form of encephalitis that was recently identified in the context of acute neuropsychiatric presentation. Here, we describe the case of a 17-year-old girl referred for an acute mania with psychotic features and a clinical picture deteriorated to a catatonic state. Positive diagnosis of anti-NMDA-receptor encephalitis suggested specific treatment. She improved after plasma exchange and immunosuppressive therapy. Post-cognitive sequelae (memory impairment) disappeared within 2-year follow-up and intensive cognitive rehabilitation.

Plasma exchange in patients with stuporous catatonia and systemic lupus erythematosus.

Abstract: gomery-Asberg Depression Rating Scale, the Brief Psychiatric Rating Scale and the SLE Disease Activity Index (SLEDAI) [6] . Because of their clinical specificity, the CRS and the SLEDAI were the primary variables. For the comparison of preand postclinical scores, we used a nonparametric test which needs a minimum of 5 patients to reach a 0.05 significance. During the course of the study, 5 patients were admitted with SLE and catatonia. These 5 patients, all female, met the inclusion criteria. All of them (or their families on their behalf) agreed to PE. Three of the patients were teenagers who had been hospitalized for several weeks without any improvement, receiving a treatment regimen combining psychotropic medications, corticoids and immunosuppressors. Three patients exhibited life-threatening complications: 2 were severely malnourished and the third had a pulmonary infection and skin lesions due to immobility. One patient showed a severe renal involvement. The last patient was included because of resistance after 3 weeks of treatment. Table 1 summarizes the demographic, clinical and biological characteristics, and treatments of all subjects both before and after PE. All patients had severe depression with psychotic and catatonic features. The number of catatonic signs ranged from 6 to 12, with staring, negativism and withdrawal being present in all 5 patients, and catalepsy, stupor, mutism and refusal to eat in 4. Regarding SLE, the clinical and biological manifestations varied across individuals and included asthenia (n = 5), polyarthralgia (n = 3), renal involvement (n = 3), cutaneous lesions (n = 3), weight loss (n = 2), myalgia (n = 1), generalized adenopathy (n = 1) and melena (n = 1). One patient had an abnormal neurological examination limited to moderate ataxia. All patients had biological features of SLE. Routine biological and hematological tests showed anemia (n = 3), thrombocytopenia (n = 2), lymphopenia (n = 2) and proteinuria (n = 3). The cerebrospinal fluid showed biochemical abnormalities in 3 patients but none of them had monoclonal immunoglobulin G or cell increase. MRI scans showed abnormalities in 3 patients, including cortical atrophy (n = 2) and T 2 -weighted hyperintensities of the frontal lobes (n = 1). The mean number of PE that patients received was 7.2 (range: 3–11). We found a significant improvement for all clinical variables. Mean CRS and SLEDAI scores before PE were 15 (range: 11–16) and 18.8 (range: 12–22), respectively. Both scores dramatically decreased after PE to a mean of 1.2 (range: 0–6) and 3.4 (range: 0–12), respectively (Wilcoxon paired test: Z = –2.032, p = 0.042). In particular, 3 patients very much improved on the Clinical Global Impression Scale after the first week of PE. The biological variables paralleled clinical improvement. At follow-up, 4 patients were still doing well; in particular, all the teenagers were able to return to school with minimal treatment for SLE. The last patient (case 4) died in her local hospital as a consequence of a septic shock 3 months after discharge. To date, only a few case studies have reported the possible use of PE in neuropsychiatric SLE [7, 8], but catatonia was not explored. Therapeutic approaches to catatonia are mainly symptomatic. It is recommended (a) to use high doses of benzodiazepines or sedative drugs, and (b) to apply ECT in case of resistance or life-threatening conditions [1] . However, treatment of associated disorders may improve psychomotor symptoms as well. This is important when there are organic causes. Therefore, etiopathogenic investigations are mandatory when catatonia occurs [9] . In the cases studied here, benzodiazepines were inefficient, and ECT was not considered because of the associated SLE. The report that PE was an efficient treatment option for pediatric autoimmune neuropsychiatric disorders associCatatonia is a rare but severe psychiatric condition. The most frequent causes are psychiatric diseases (e.g. schizophrenia), but organic causes should be considered as well (e.g. Wilson’s disease) [1] . The recommended treatments are symptomatic and include the use of sedative drugs and electroconvulsive therapy (ECT) [1] . Although rare cases of catatonia have been described in systemic lupus erythematosus (SLE) [2] , catatonia was not included in the recent nomenclature of neuropsychiatric SLE [3] . In a recent report, we showed that plasma exchanges (PE) could be an efficient treatment option for catatonic manifestations of SLE, avoiding the use of ECT [4] . The aim of the present study was to assess the efficacy of PE for severely resistant patients with catatonia and SLE in an open trial. The consecutive patients were recruited at Pitié-Salpêtrière Hospital from 2001 to 2004. For inclusion, the diagnosis of SLE was based on the revised criteria of the American College of Rheumatology [3] . The diagnosis of catatonia was made based on at least two catatonic motor signs, or one catatonic motor sign (catalepsy, stupor, posturing, waxy flexibility, staring, stereotypies, psychomotor excitement, automatic compulsive movements, muscular rigidity, echopraxia) combined with a nonmotor catatonic symptom indicative of severely impaired behavioral and emotional functioning (withdrawal, mutism, mannerism, echolalia, incontinence, verbigeration, refusal to eat) [5] . Clinical examinations by a psychiatrist and a physician specializing in internal medicine were repeated as needed. Psychiatric diagnoses were based on DSM-IV criteria. Additional investigations always included routine hematological tests, immunological investigations, studies of cerebrospinal fluid, electroencephalography, and neuroimaging. All patients received a symptomatic psychiatric treatment (benzodiazepine for motor symptoms, antidepressant for depression, atypical neuroleptic for psychosis and mood stabilizer for bipolarity) combined with (a) high-dose intravenous methylprednisone (1 g/day ! 3) followed by oral prednisone (1 mg/kg/day), and (b) monthly pulse cyclophosphamide (0.7 g/m 2 ) or azathioprine (2– 3 mg/kg/day). In case of life-threatening conditions, severe complications of SLE or resistance to pharmacotherapy for 3 weeks, patients were asked to receive PE and written consent was obtained (from them or their families). PE (60 ml/kg) was given 2–3 times per week. Treatment efficacy was monitored using the Clinical Global Impression-Severity Scale, the Global Assessment of Functioning Scale, the modified Bush-Francis Catatonia Rating Scale (CRS) [5] , the Mont-

2019 update of the EULAR recommendations for the management of systemic lupus erythematosus

Abstract: Our objective was to update the EULAR recommendations for the management of systemic lupus erythematosus (SLE), based on emerging new evidence. We performed a systematic literature review (01/2007-12/2017), followed by modified Delphi method, to form questions, elicit expert opinions and reach consensus. Treatment in SLE aims at remission or low disease activity and prevention of flares. Hydroxychloroquine is recommended in all patients with lupus, at a dose not exceeding 5 mg/kg real body weight. During chronic maintenance treatment, glucocorticoids (GC) should be minimised to less than 7.5 mg/day (prednisone equivalent) and, when possible, withdrawn. Appropriate initiation of immunomodulatory agents (methotrexate, azathioprine, mycophenolate) can expedite the tapering/discontinuation of GC. In persistently active or flaring extrarenal disease, add-on belimumab should be considered; rituximab (RTX) may be considered in organ-threatening, refractory disease. Updated specific recommendations are also provided for cutaneous, neuropsychiatric, haematological and renal disease. Patients with SLE should be assessed for their antiphospholipid antibody status, infectious and cardiovascular diseases risk profile and preventative strategies be tailored accordingly. The updated recommendations provide physicians and patients with updated consensus guidance on the management of SLE, combining evidence-base and expert-opinion.

The Risk of Toxic Retinopathy in Patients on Long-term Hydroxychloroquine Therapy

Abstract: Importance Hydroxychloroquine sulfate is widely used for the long-term treatment of autoimmune conditions but can cause irreversible toxic retinopathy. Prior estimations of risk were low but were based largely on short-term users or severe retinal toxicity (bull’s eye maculopathy). The risk may be much higher because retinopathy can be detected earlier when using more sensitive screening techniques. Objectives To reassess the prevalence of and risk factors for hydroxychloroquine retinal toxicity and to determine dosage levels that facilitate safe use of the drug. Design, Setting, and Participants Retrospective case-control study in an integrated health organization of approximately 3.4 million members among 2361 patients who had used hydroxychloroquine continuously for at least 5 years according to pharmacy records and who were evaluated with visual field testing or spectral-domain optical coherence tomography. Exposure Hydroxychloroquine use for at least 5 years. Main Outcomes and Measures Retinal toxicity as determined by characteristic visual field loss or retinal thinning and photoreceptor damage, as well as statistical measures of risk factors and prevalence. Results Real body weight predicted risk better than ideal body weight and was used for all calculations. The overall prevalence of hydroxychloroquine retinopathy was 7.5% but varied with daily consumption (odds ratio, 5.67; 95% CI, 4.14-7.79 for >5.0 mg/kg) and with duration of use (odds ratio, 3.22; 95% CI, 2.20-4.70 for >10 years). For daily consumption of 4.0 to 5.0 mg/kg, the prevalence of retinal toxicity remained less than 2% within the first 10 years of use but rose to almost 20% after 20 years of use. Other major risk factors include kidney disease (odds ratio, 2.08; 95% CI, 1.44-3.01) and concurrent tamoxifen citrate therapy (odds ratio, 4.59; 95% CI, 2.05-10.27). Conclusions and Relevance These data suggest that hydroxychloroquine retinopathy is more common than previously recognized, especially at high dosages and long duration of use. While no completely safe dosage is identified from this study, daily consumption of 5.0 mg/kg of real body weight or less is associated with a low risk for up to 10 years. Knowledge of these data and risk factors should help physicians prescribe hydroxychloroquine in a manner that will minimize the likelihood of vision loss.

The British Society for Rheumatology guideline for the management of systemic lupus erythematosus in adults

Abstract: NICE has accredited the process used by the BSR to produce its guidance on the management of systemic lupus erythematosus in adults. Accreditation is valid for 5 years from 10 June 2013. More information on accreditation can be viewed at www.nice.org.uk/accreditation. For full details on our accreditation visit: www.nice.org.uk/accreditation. Rheumatology Research Group, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Rheumatology Department, City Hospital, Sandwell and West Birmingham Hospitals NHS Trust, Rheumatology Department, University Hospitals Birmingham NHS Foundation Trust, Birmingham, Royal National Hospital for Rheumatic Diseases, Bath, Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute for Inflammation and Repair, University of Manchester, Manchester Academic Health Sciences Centre, The Kellgren Centre for Rheumatology, NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester, Louise Coote Lupus Unit, Guy’s Hospital, London, Laurie Pike Health Centre, Modality Partnership, Birmingham, Department of Rheumatology, Freeman Hospital, Newcastle upon Tyne, Department of Medicine, University of Cambridge, Lupus and Vasculitis Unit, Addenbrooke’s Hospital, Cambridge, Lupus Research Unit, The Rayne Institute, St Thomas’ Hospital, Division of Women’s Health, King’s College London, Section of Renal Medicine and Vascular Inflammation, Division of Immunology and Inflammation, Department of Medicine, Imperial College London, London, LUPUS UK, Romford, Essex and Centre for Rheumatology, University College London, London, UK