Relapsing Disease Course Research Articles

Paediatric Acquired Demyelinating Syndromes

Paediatric acquired demyelinating syndromes (ADS) are characterised by neurological deficits persisting for at least 24 hours, involving the optic nerve, spinal cord or brain with a clinical spectrum of diagnoses including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD) and MOG-Ab associated disease (MOGAD). Important strides have been made in delineating MS from other ADS subtypes over the past decade, including the discovery of serum aquaporin-4 (AQP4) and Myelin oligodendrocyte glycoprotein (MOG) antibodies (Ab). Both genetic (e.g. human leukocyte antigen, HLA-DRB1*1501 allele) and environmental risk factors (e.g. low serum vitamin D levels and prior exposure to Epstein–Barr virus) may contribute to risk of MS in children. Some of these risk factors not only confer increased susceptibility to MS but may also affect the disease course. Paediatric AQP4-Ab NMOSD is a rare disease worldwide but variations in incidence/prevalence have been described among different geographic regions and ethnicities. One-third of children who present with an ADS have MOG-Ab, and approximately half of patients with MOG-Ab have a relapsing disease course. It seems there is no racial or gender predominance in MOGAD, which is in contrast to the female and non-white predominance seen in both MS and NMOSD.‎ In this review, we examine the current literature regarding the epidemiology and demographics of these different ADS entities with a particular focus on the genetic and environmental risk factors for MS in children. While insights into disease pathophysiology in paediatric ADS have led recent therapeutic advances, well designed, collaborative large scale epidemiological studies are likely to provide the critical next step to a personalised approach to these conditions.

Initial visit symptoms in probable Behçet's syndrome is predictive of ISG criteria fulfillment in Behçet's syndrome: data from New York and Amsterdam cohorts.

Behçet's syndrome (BS) is a systemic vasculitis with heterogeneous clinical presentation and a relapsing disease course. The International Study Group (ISG) criteria are most often used for classification. A significant proportion of patients is classified as probable BS because they do not fulfil the criteria at initial presentation. The aim of this study is to explore clinical BS symptoms present at initial patient visit predictive of ISG criteria diagnosis during follow-up. Patients classified as probable BS at initial visit were included. Follow-up ISG status (defined as meeting criteria ISG+ vs. not meeting criteria ISG-) was abstracted from last visit. Univariable logistic regression was used to screen initial visit clinical features and symptoms with follow-up ISG status. All variables that passed screening at p<0.10 were included in the final multivariable model, which was then used to create a probability risk score. 189 patients were included (169 from New York and 20 from Amsterdam). 71 (37.6%) patients were classified as ISG+ during follow-up. In the final model, presence of morning stiffness, genital ulcers, skin lesions, and eye disease were associated with increased odds of ISG+, adjusting for age, symptom duration and family history. This was used to create a probability risk score. Over a third of patients with suspected or probable BS developed new manifestations over time that led to classification as ISG+ BS. The presence of morning stiffness, genital ulcers, skin lesions and eye disease at initial visit were independently associated with significantly higher odds for developing ISG+ Behçet's during follow-up.

Tre-P-22 - The primary cutaneous CD30- positive lymphoproliferative diseases; the own observations of the center, prospects of therapy

Primary cutaneous T-cell lymphomas are the heterogeneous group of T-cell lymphoproliferative diseases (LPD), which are developed mainly in the skin and characterized by diagnostic features, clinical course and therapeutic approach. Primary cutaneous anaplastic lymphoma (с-ALCL) and lymphomatoid papulosis (LyP) are diagnosed In a quarter of cases of all T-cell skin lymphomas. The tumor cells in primary cutaneous CD30-positive skin lymphomas express CD30 in more than 75% of cases. The majority of patients with cutaneous CD30+ LPD have an indolent course with a favorable prognosis, the resistant course of disease develops in about 30% of cases and fatal cases from lymphoma are registered in 8% of cases. Most commonly, the treatment of these forms of LPD includes the surgical removal, radiation therapy or small doses of methotrexate, the systemic chemotherapy is used to generalize the process. Recently, monoclonal antibodies have been included in clinical practice for the treatment of skin lymphomas, one of which is brentuximab vedotin, the use of which has shown a rather high efficiency in the treatment of CD30 + skin lymphomas: more than 2/3 of the patients responded to the treatment, despite the many lines of therapy (median of prior effect is 3.1 for c-ALCL). The general group of patients with cutaneous T-cell lymphomas and who received the consultative-diagnostic or inpatient treatment at the National Research Centre of Hematology includes 328 patients. Among them the CD30-positive cutaneous LPD were verified in 33 patients (10%): 16 patients with LyP, 17 patients with c-ALCL. The eruptions were regressed on its own without specific therapy in 75% of patients with LyP and 4 patients received the treatment. As well as one patient with the relapsing course of disease, with a long period of self-regression of the papules, with the lack of the treatment effect (phototherapy and low-dose methotrexate) received brentuximab vedotin (BV). The complete clinical response was achieved after the first cycle of monotherapy with BV and persists for more than a year. Patients with c-ALCL more frequently needed the specific therapy (76% of patients), only 4 patients were observed with the self-regression of the papules within 6-9 weeks. Most patients received the interferon alfa therapy with the complete clinical response; the rest patients - local radiation therapy, the small doses of methotrexate. The systemic chemotherapy was done to the 5 patients. Considering the common process, however 2 of them died from infectious complications during the chemotherapy, 2 patients had early recurrence and only 1 patient is in the long-lasting complete remission after the high-dose of chemotherapy. In summary, the primary cutaneous CD30 + lymphoproliferative diseases cover a spectrum of benign condition with the so-called "malignant" phenotype. LyP and c-ALCL have a favorable prognosis, 5-year survival rate is exceeding 95%, photo- and immunotherapy are successfully used in the treatment, while the use of systemic chemotherapy should be avoided (shortening of the remissions duration, progression of the infectious complications). The use of targeted therapy (brentuximab vedotin) increases the therapeutic ability in the situations where the routine treatment options are ineffective.

Myelin oligodendrocyte glycoprotein (MOG) antibody-mediated disease: The difficulty of predicting relapses

BackgroundWhile many patients with myelin oligodendrocyte glycoprotein antibody-mediated disease (MOG-AD) will have a monophasic course, 30-80% of patients will relapse after the initial attack. It is not known which factors predict relapse. Here we describe our clinical experience with MOG-AD and evaluate for factors that correlate with relapsing disease. MethodsThis was a retrospective, multi-institutional study of 54 patients with MOG-AD, including 17 children and 37 adults. Mann-Whitney U and Fischer's Exact tests were used for comparisons and logistic regression for correlations. ResultsIncident attack phenotype included acute disseminated encephalomyelitis (15%), unilateral optic neuritis (ON; 39%), bilateral ON (24%), transverse myelitis (TM; 11%) and ON with TM (11%). Pediatric patients were more likely than adults to present with ADEM (p = .009) and less likely to present with unilateral ON (p = .04). 31 patients (57%) had a relapsing disease course, with time to first relapse of 8.2 months and median annualized relapse rate of 0.97 months. In 40% of patients (n = 22) the first relapse occurred following the withdrawal of treatment for the incident attack. 5 patients converted to seronegative at follow up, 2 of whom later relapsed. Logistic regression revealed no significant relationship between age, gender, race, presentation phenotype, antibody titer, or cerebrospinal fluid results with risk of relapse. For patients who started disease modifying therapy (DMT) prior to the first relapse (n = 11), 64% remained monophasic. 50% (n = 15) of patients on DMT continued to have disease activity, requiring treatment adjustment. ConclusionsIt is difficult to predict which patients with MOG-AD will relapse. Research is needed to determine the optimal timing and choice of treatment.

P-OT003. A case series of familial neuromyelitis optica spectrum disorder (NMOSD)

Introduction . Evidence of familial neuromyelitis optica spectrum disorder (NMOSD) have been limited, reported to comprised of 3% of total cases (Matiello et al., 2010). We report a case series of possible familial NMOSD involving only 1 generation, namely 3 out of the 6 female siblings. Results . All 3 patients were female Malaysian Chinese with age of disease onset of 39, 56, and 57 years respectively. Two of them demonstrated AQP4 seropositivity while one passed away without being tested. Their presenting features were optic neuritis (ON) plus transverse myelitis (TM) in Patient 1 and TM in both Patient 2 and Patient 3. Subsequent relapses involved both ON and TM over years. They demonstrated relapsing disease course with annualized relapse rates of 0.67, 0.55 and 0.20 respectively. Both Patient 2 and Patient 3 demonstrated longitudinally extensive transverse myelitis on spinal MRI with normal MRI brain. Apart from serum anti-Ro positivity hence Sjogren’s Syndrome in Patient 3, comprehensive workups for other aetiologies of myelitis were negative. Both Patient 2 and Patient 3 responded well with intravenous methylprednisolone (IVMP) during acute attacks/relapses, followed by long term maintenance therapy of prednisolone plus Mycophenolate Mofetil (MMF). Patient 3 received 1 cycle of add-on therapeutic plasma exchange once during a relapse with severe LETM. During the last follow-up, (i) Patient 1 demonstrated right eye blindness, (ii) Patient 2 demonstrated impaired colour vision of right eye, and (iii) Expanded Disability Status Scale was 1 in all 3 patients. Both Patient 2 and Patient 3 fulfilled the 2015 international consensus diagnostic criteria for NMOSD. Patient 1 passed away in 1989 without undergoing detailed para-clinical and neuroimaging investigations. Conclusion . Familial NMOSD may still be recognized despite an onset within the same generation with heterogenous phenotypic presentations, provided fulfilment of the international consensus diagnostic criteria.

Novel Targeted Biological Agents for the Treatment of Atopic Dermatitis

Atopic dermatitis (AD) is a common inflammatory dermatologic disease clinically characterized by intense itch, recurrent eczematous lesions, and a chronic or relapsing disease course. Mild-to-moderate AD can be controlled by using moisturizers and topical immunomodulators such as topical corticosteroids and calcineurin inhibitors. If topical therapies fail, phototherapy and systemic immunosuppressant therapies, such as ciclosporin, methotrexate, and azathioprine, can be considered. However, relapse and side effects could still occur. The pathogenesis of AD involves epidermal barrier dysfunction, skin microbiome abnormalities, and cutaneous inflammation. Inflammatory mediators, such as interleukin (IL)-4, IL-13, IL-31, IL-33, IL-17, IL-23, and thymic stromal lymphopoietin, are involved in AD development. Therefore, a series of biological agents targeting these cytokines are promising approaches for treating AD. Dupilumab is the first biological agent approved for the treatment of AD in patients aged 6 years and older in the United States. Tralokinumab, lebrikizumab, and nemolizumab have also been confirmed to have significant efficacy against AD in phase III or IIb clinical trials. Also, fezakinumab was effective in severe AD patients in a phase IIa trial. However, phase II trials of ustekinumab, tezepelumab, etokimab, secukinumab, and omalizumab have failed to meet their primary endpoints. Phase II trials of GBR 830 and KHK 4083 are ongoing. In general, further studies are needed to explore new therapeutic targets and improve the efficacy of biological agents.

POS0338 STEROID-SPARING EFFECT OF ANAKINRA IN GIANT-CELL ARTERITIS: A CASE SERIES WITH CLINICAL, BIOLOGICAL AND ICONOGRAPHIC LONG-TERM ASSESSMENTS

Background:The treatment of giant cell arteritis (GCA) relies on corticosteroids but is burdened by a high rate of relapses and adverse effects. Anti-interleukin-6 treatments show a clear benefit with a significant steroid-sparing effect, but late relapses occur after treatment discontinuation. In addition to interleukin-6, interleukin-1 also appears to play a significant role in GCA pathophysiology.Objectives:We report herein the efficacy of anakinra, an interleukin-1 receptor antagonist, in 6 GCA patients exhibiting corticosteroid dependence or resistance, specifically analyzing the outcome of aortitis in 4 of them, and including the long-term follow-up of 2 previously described patients (1).Methods:This retrospective study analyzed the cases of all GCA patients treated with anakinra from the French Study Group for Large Vessel Vasculitis.Patients had to satisfy the following two criteria to be enrolled in this retrospective study. First, their diagnosis of GCA should be based on the fulfillment of at least 3 criteria of the American College of Rheumatology (ACR) for GCA or on the satisfaction of 2 of these criteria along with the demonstration of LVI on imaging. Second, patients should have received anakinra because of corticosteroid dependence or resistance.Corticosteroid dependence was defined as ≥2 relapses or the combination of 2 of the following criteria: a daily dose of oral prednisone &gt;20 mg/day (or 0.3 mg/kg) at 6 months; a daily dose of oral prednisone &gt;10 mg/day (or 0.2 mg/kg) at 12 months; and/or a treatment maintained &gt;24 months because of a relapsing disease course. Corticosteroid resistance was defined as persistent increased inflammatory parameters at month 3 despite a steroid dosage over 0.5 mg/kg.Results:After a median duration of anakinra therapy of 19 [18–32] months, all 6 patients exhibited complete clinical and biological remission. Among the 4 patients with large-vessel involvement, 2 had a disappearance of aortitis under anakinra, and 2 showed a decrease in vascular uptake. After a median follow-up of 56 [48–63] months, corticosteroids were discontinued in 4 patients, and corticosteroid dosage could be decreased to 5 mg/day in 2 patients. One patient relapsed 13 months after anakinra introduction in the context of increasing the daily anakinra injection interval to every 48 hours. Three patients experienced transient injection-site reactions, and 1 patient had pneumonia.Figure 1.Steroid dosages before and after the introduction of anakinra in 6 patients with giant-cell arteritis and corticosteroid dependence or resistance. The black arrow indicates the time of anakinra introduction.Conclusion:In this short series, anakinra appears to be an efficient and safe steroid-sparing agent in refractory GCA, with a possible beneficial effect on large-vessel involvement.

Clinical significance of anti-Ro52 (TRIM21) antibodies in adult patients with connective tissue diseases

ObjectivesClinical significance of anti-Ro52 antibodies in connective tissue diseases (CTD) is controversial. Anti-Ro52 antibodies might be associated with a more severe CTD phenotype, especially interstitial lung disease (ILD). The aims of this study were to evaluate ILD prevalence and severity, the prevalence of micro- or macroangiopathy and CTD-associated cancers in CTD with anti-Ro52 antibodies. MethodsCTD patients with anti-Ro52 antibody screening by immunoblot at diagnosis were enrolled. Two groups were retrospectively formed according to the presence of anti-Ro52 antibodies with an unbiased 1:1 matching on CTD types. Unsupervised multiple correspondence analysis and hierarchical clustering analysis were used to aggregate anti-Ro52 positive patients in subgroups. Results408 CTD patients were included. Anti-Ro52 antibodies were detected in 33 % of CTD patients. Anti-Ro52 antibodies were associated with ILD at CTD diagnosis (47.8% vs. 23.0%, OR 3.3 95% IC 1.4 to 8.0, p = 0.008), even after adjusting for the presence of anti-Ro60 antibodies, especially in patients with antisynthetase syndrome, primary Sjögren syndrome and systemic sclerosis. Micro- or macroangiopathy was more frequent in anti-Ro52 positive CTD patients (18.6% vs. 9.7%, p = 0.02) and CTD patients with anti-Ro52 antibodies experienced more frequent relapses and required more immunosuppressive drugs. Clusters 4 and 5 identified anti-Ro52 positive CTD patients with severe ILD and with clinical features of systemic sclerosis or antisynthetase syndrome respectively. ConclusionsWe found that anti-Ro52 antibodies were independently associated with ILD in CTD patients irrespective of CTD type. Anti-Ro52 antibodies could be associated with severity and a more relapsing disease course in CTD patients.

Course of Disease in Patients with Microscopic Colitis: A European Prospective Incident Cohort Study.

The disease course of microscopic colitis [MC] is considered chronic but benign. However, this assumption is based on mainly retrospective studies, reporting on incomplete follow-up of selective cohorts. Systematic, prospective and unbiased data to inform patients and healthcare professionals on the expected course of the disease and real-life response to therapy are warranted. A prospective, pan-European, multi-centre, web-based registry was established. Incident cases of MC were included. Data on patient characteristics, symptoms, treatment and quality of life were systematically registered at baseline and during real-time follow-up. Four disease course phenotypes were discriminated and described. Among 381 cases with complete 1-year follow-up, 49% had a chronic active or relapsing disease course, 40% achieved sustained remission after treatment and 11% had a quiescent course. In general, symptoms and quality of life improved after 3 months of follow-up. A relapsing or chronic active disease course was associated with significantly more symptoms and impaired quality of life after 1 year. A minority of MC patients follow a quiescent disease course with spontaneous clinical improvement, whereas the majority suffer a chronic active or relapsing disease course during the first year after diagnosis, with persisting symptoms accompanied by a significantly impaired quality of life.

IgA vasculitis (Henoch-Schönlein purpura): refractory and relapsing disease course in the adult population.

BackgroundThe disease course of adult immunoglobulin A (IgA) vasculitis (IgAV; Henoch–Schönlein purpura) has not been well defined.MethodsIn a retrospective survey, we studied 85 adult IgAV patients with extended follow-up (median 43 months) for 67 patients.ResultsOnly 33 of 67 (49%) achieved complete remission. Ongoing renal disease was the most common persistent organ manifestation, but extra-renal disease activity was also present in >50% of patients not achieving complete remission. Twenty-nine of 67 (43%) had relapsing disease, with 18/67 (27%) experiencing several relapses. Skin disease was the most common feature in relapsing patients, followed by nephritis. At 4 years of follow-up, 6 of 29 (21%) experienced progressive disease and 10/29 (34%) relapsing disease. Five of 67 (7%) developed nephritis after diagnosis, within the first 6 months of follow-up. At final follow-up, 10 of 67 (15%) had chronic kidney disease Stage ≥G3a, 18 (27%) haematuria and 13 (19%) proteinuria. No therapy appeared particularly effective and only 6/17 patients treated with mycophenolate mofetil experienced a good response.ConclusionsThe disease course of adult IgAV is different from that seen in children, with higher frequency of persisting and relapsing disease. Renal disease is the main determinant of ongoing disease activity, but extra-renal features were seen in >50% of patients with chronic disease activity. No clear conclusions on use or choice of immunosuppressive agent could be made based on our experience.

Patients with a relapsing course of steroid-responsive encephalopathy associated with autoimmune thyroiditis exhibit persistent intrathecal CD4+ T-cell activation.

Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT) is a rare condition defined by encephalopathy with acute or subacute onset, the presence of serum anti-thyroid antibodies, and reasonable exclusion of alternative causes. Despite having strong response towards corticosteroid treatment, some patients exhibit a chronic-relapsing course and require long-term immunosuppression. Markers for early identification of those patients are still absent. Thus, we aimed to characterise clinical as well as laboratory parameters of our local SREAT cohort. We retrospectively evaluated a cohort of 22 SREAT patients treated in our hospital from January 2014. A total of 14 patients with a monophasic disease course and eight patients with multiple relapses were identified. Neither baseline characteristics nor routine cerebrospinal fluid (CSF) parameters were able to distinguish between those patient groups. Flow cytometry following initial relapse therapy showed treatment-resistant sequestration of activated CD4+ T cells in patients with a relapsing disease course, whereas other lymphocyte subsets showed uniform changes. Such changes were also present in long-term follow-up CSF examination. Our findings indicate a potential biomarker for risk stratification in patients with SREAT. Currently, it remains unclear whether the observed two phenotypes are different spectra of SREAT or represent separate diseases in terms of pathophysiology.

Silent New Brain MRI Lesions in Children with MOG-Antibody Associated Disease.

Anti-myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) antibodies are associated clinically with either a monophasic or relapsing disease course. We investigated the frequency and clinical importance of acquired asymptomatic brain magnetic resonance imaging (MRI) lesions in a prospective incident cohort of 74 MOG-IgG positive children with serial MRI scans over a median of 5 years from presentation. Silent new lesions were detected in 14% of MOG-IgG positive participants, most commonly within the first months post-onset, with a positive predictive value for clinically relapsing disease of only 20%. Detection of asymptomatic lesions alone need not prompt initiation of chronic immunotherapy. ANN NEUROL 2021;89:408-413.

Cornelian Cherry Iridoid-Polyphenolic Extract Improves Mucosal Epithelial Barrier Integrity in Rat Experimental Colitis and Exerts Antimicrobial and Antiadhesive Activities In Vitro.

Background and Aims Inflammatory bowel disease pharmacotherapy, despite substantial progress, is still not satisfactory for both patients and clinicians. In view of the chronic and relapsing disease course and not always effective treatment with adverse effects, attempts to search for new, more efficient, and safer substances are essential and reasonable. This study was designed to elucidate the impact of cornelian cherry iridoid-polyphenolic extract (CE) and loganic acid (LA) on adherent-invasive E. coli growth and adhesion in vitro and to assess the effect of pretreatment with CE or LA on the course of intestinal inflammation in rat experimental colitis compared with sulfasalazine. Methods Antibacterial and antiadhesive activities of CE and LA were assessed using microdilution, Int407 cell adherence, and yeast agglutination assays. The colitis model was induced by 2,4,6-trinitrobenzenesulfonic acid. Studied substances were administered intragastrically for 16 days prior to colitis induction. Body weight loss; colon index; histological injuries; IL-23, IL-17, TNF-α, and chemerin levels; and STAT3, Muc2, and TFF3 mRNA expression were evaluated. Results Only CE exerted antimicrobial and antiadhesive activities in vitro and alleviated colonic symptoms. CE coadministrated with sulfasalazine was more effective than single compounds in reversing increased concentrations of TNF-α, IL-17, and chemerin and decreased Muc2 mRNA expression. Conclusions CE exerted a protective effect against experimental colitis via impaired mucosal epithelial barrier restoration and intestinal inflammatory response attenuation and given concomitantly with sulfasalazine counteracted colitis in a more effective way than sulfasalazine alone, which indicates their synergistic interaction. The beneficial effect of CE may also be due to its bacteriostatic and antiadhesive activities.

Satralizumab in the treatment of neuromyelitis optica spectrum disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare and debilitating autoimmune astrocytopathy with apredominantly relapsing disease course. Satralizumab, a humanized monoclonal antibody, was designed to treat NMOSD by targeting the IL-6 receptor. Satralizumab builds on positive experiences of off-label usetocilizumab in recentyears. Before 2019, no medications were approved for the treatment of NMOSD. In 2020, satralizumab became the third compound to enter the US market, adding to the complement inhibitor eculizumab and the CD19 inhibitor inebilizumab. Here, we review the two randomized, double-blind, Phase III trials that investigated the subcutaneous administration of satralizumab as add-on treatment and monotherapy. Both studies revealed positive effects concerning the reduction of relapse risk for AQP4seropositive NMOSD patients and generally good tolerability.

E.U. paediatric MOG consortium consensus: Part 1 - Classification of clinical phenotypes of paediatric myelin oligodendrocyte glycoprotein antibody-associated disorders.

Over the past few years, increasing interest in the role of autoantibodies against myelin oligodendrocyte glycoprotein (MOG-abs) as a new candidate biomarker in demyelinating central nervous system diseases has arisen. MOG-abs have now consistently been identified in a variety of demyelinating syndromes, with a predominance in paediatric patients. The clinical spectrum of these MOG-ab-associated disorders (MOGAD) is still expanding and differs between paediatric and adult patients. This first part of the Paediatric European Collaborative Consensus emphasises the diversity in clinical phenotypes associated with MOG-abs in paediatric patients and discusses these associated clinical phenotypes in detail. Typical MOGAD presentations consist of demyelinating syndromes, including acute disseminated encephalomyelitis (ADEM) in younger, and optic neuritis (ON) and/or transverse myelitis (TM) in older children. A proportion of patients experience a relapsing disease course, presenting as ADEM followed by one or multiple episode(s) of ON (ADEM-ON), multiphasic disseminated encephalomyelitis (MDEM), relapsing ON (RON) or relapsing neuromyelitis optica spectrum disorders (NMOSD)-like syndromes. More recently, the disease spectrum has been expanded with clinical and radiological phenotypes including encephalitis-like, leukodystrophy-like, and other non-classifiable presentations. This review concludes with recommendations following expert consensus on serologic testing for MOG-abs in paediatric patients, the presence of which has consequences for long-term monitoring, relapse risk, treatments, and for counselling of patient and families. Furthermore, we propose a clinical classification of paediatric MOGAD with clinical definitions and key features. These are operational and need to be tested, however essential for future paediatric MOGAD studies.

Longer-term effects of intravenous immunoglobulin treatment in chronic inflammatory demyelinating polyneuropathy: Who benefits?

Intravenous immunoglobulins (IVIg) represent an established cornerstone for the immunotherapy of chronic inflammatory demyelinating polyneuropathy (CIDP). Efficacy of IVIg for CIDP was proven in a large phase III trial. Yet, data on longer-term efficacy and effects in distinct subgroups are scarce. Our trial investigates the long-term efficacy of IVIg treatment in CIDP patients.In this observational real-world study, we retrospectively analyzed 49 CIDP patients receiving continuous IVIg treatment with a mean initial dosage of 87 g (1 g/kg body weight) every 4 weeks over a mean time of 45 months between 2010 and 2018. INCAT-Scores before the start of treatment and at the end of the observation period were compared.Over the observation period, IVIg treatment led to a median improvement of one INCAT score point. Subgroup analyses revealed a more pronounced improvement of INCAT scores in female CIDP patients, individuals with relapsing disease courses, patients with more pronounced motor impairment (higher initial INCAT scores) and in the cohort without need for concomitant other immunotherapies.These data argue for sustained beneficial effects of longer-term immunotherapy with IVIg in CIDP, particularly in females and relapsing disease forms with higher disease activity.

Working ability in individuals with different disease courses of multiple sclerosis: Factors beyond physical impairment

BackgroundExperiencing a decrease in working ability or even becoming unemployed is common in patients with multiple sclerosis (MS) and has a detrimental impact on the individual's quality of life, self-esteem, and on society's economic burden. Physical disability is still considered the most important predictor for patients’ inability to work. This study aims to confirm and extend findings from prior studies indicating the additional importance of other demographical and clinical information accessible within a routine patient evaluation, placing particular emphasis on the inclusion of cognitive and neuropsychiatric measures, as well as on potential disease course differences. Methods159 MS patients (84 with a relapsing disease course (RMS); 75 with a progressive disease course (PMS)) were examined with the Brief International Cognitive Assessment for MS (BICAMS) battery, mood and fatigue questionnaires, and screened for subjectively experienced cognitive problems as well as for various person- and disease-related information (age, sex, education, age at diagnosis, disease duration, immunotherapy, number and nature of comorbidities, smoking and alcohol intake, sleep disturbances). These measures, along with Expanded Disability Status Scale (EDSS) scores were compared between unemployed, part- and full-time working patients. Significant variables were further entered into hierarchical regression models predicting employment status (employed vs. unemployed) as well as weekly hours at work in each disease subtype, respectively. ResultsIn patients with RMS, unemployed patients had higher EDSS scores, reported a higher number of comorbidities, more frequent past depressive episodes, a higher level of fatigue, and performed worse on the Symbol-Digit Modalities Test (SDMT) and the Brief Visuospatial Memory Test revised (BVMT-R). Besides EDSS, unemployment was predicted by SDMT, while weekly hours at work were further determined by the number of comorbidities, BVMT-R, and disease duration. In patients with PMS, unemployed patients also had higher EDSS scores, were younger at diagnosis, and showed a decreased performance in SDMT and the Rey Verbal Learning and Memory Test German version (Verbaler Lern- und Merkfaehigkeitstest; VLMT). Employment status as well as weekly working hours were both predicted by VLMT, educational level, and disease duration beyond EDSS in patients with PMS, while depressive episodes additionally impacted on employment status. ConclusionsObjectively assessed cognitive functions, neuropsychiatric symptoms (i.e. a history of depressive episodes, fatigue) as well as some specific clinical data (disease duration, comorbidities) add substantial value in the evaluation of working ability beyond physical disability. Since unemployment is associated with different major factors among disease courses, more comprehensive and customized assessments are needed to refine characterization of individual work ability and to adjust interventional strategies targeting employment maintenance.

Patient perspective on decisions to switch disease-modifying treatments in relapsing-remitting multiple sclerosis

BackgroundThere are now large cohorts of people with relapsing-remitting multiple sclerosis (pwRRMS) who have taken several Disease-Modifying Treatments (DMTs). Studies about switching DMTs mostly focus on clinical outcomes rather than patients' decision-making. Neurologists are now required to support decisions at various times during the relapsing disease course and they do so with concerns about DMTs risks. This qualitative study investigates how pwRRMS weigh up the pros and cons of DMTs, focusing on perceptions of effectiveness and risks when new treatments are considered. ObjectiveTo increase understanding of people's experiences of decision-making when switching DMTs. Methods30 semi-structured interviews were conducted with pwRRMS in England. 16 participants had switched DMT and their experiences were compared with those who had only taken one DMT. Interviews were analysed thematically to answer: what main factors influence people's decision-making to switch DMTs and why? ResultsOf the 16 participants with experience of switching DMT, eight had taken two or more DMTs; eight had taken three or more. Two was the DMT median. This study demonstrated that despite the term "switching" implying that similar treatments are inter-changeable, for pwRRMS taking new treatments involves different emotions, routines, risks, prognosis and communication experiences. Two meta themes identified were: 1) A distinctive, rapid and emotional decision-making process where old emotions related to MS prognosis are revisited. 2) Switching has a different impact on communication for escalation or de-escalation processes. ConclusionSwitching DMT involves different routines, risks, prognosis and communication experiences. These decisions are emotionally difficult because of the fear about transitioning to secondary progressive MS, and DMT effectiveness uncertainty. Patient centred decision aids should include information about first and consecutive treatment decisions.

Food allergy and atopic dermatitis.

Atopic dermatitis (AD), characterized by intense pruritus, eczematous lesions, and a relapsing disease course, is a chronic inflammatory skin disease that affects both children and adults. AD often begins in infancy and is associated with atopic diseases in the personal or family history.1 Environmental factors may trigger AD by affecting the skin barrier and by triggering inflammation. The elicitation of T-helper type 2 cytokines further impairs the epidermal barrier and leads to the penetration of irritants and allergens into the epidermis and thereby perpetuating inflammation. The presence of AD and its severity has been shown to positively correlate with risk of developing food allergy (FA). Children with AD are estimated to be six times more likely to develop FA compared with their healthy peers. It has been reported that nearly 40% of children with moderate-to-severe AD have immunoglobulin E (IgE) mediated FA compared with only 6% in the general population. Although analysis of experimental data has linked skin inflammation in AD to FA, with food challenges reproducing symptoms and avoidance diets improving AD, elimination diets are not known to cure AD and may have unfavorable consequences, such as loss of tolerance, which leads to immediate-type allergy, including anaphylaxis, nutritional deficiencies, growth failure, and reduction of quality of life for the patient and family. Exacerbation of AD can be inaccurately attributed to foods. Individuals with AD are often sensitized to foods with positive testing results, however, able to tolerate the food. In light of widespread ordering and commercial availability of serum specific IgE for FA, testing for FA is recommended only if, from a detailed clinical history, immediate-type allergic symptoms occur with ingestion of food, or in infants with AD who do not improve with optimal skin care.

Evolving Cognitive Dysfunction in Children with Neurologically Stable Opsoclonus-Myoclonus Syndrome.

Cognitive and acquired neurodevelopmental deficits have been reported in children with opsoclonus–myoclonus syndrome (OMS) and are known to be associated with more severe and relapsing disease course. However, there is a paucity of data regarding cognitive dysfunction in children with stable neurological disease. We report three children with OMS and evolving cognitive dysfunction in the context of a mild disease course. The children’s ages at disease onset were between 17 and 35 months and they were followed up for 4–10 years. Neuroblastoma was identified in one child. OMS severity scores ranged between 8 and 12/15 at presentation. They underwent immunotherapy and all were in remission by 7 months (range 4–13 months), with treatment maintained for 1 year. One child remained relapse-free, while two others had one clinical relapse each and were immunotherapy-responsive again. In all cases, evolving cognitive dysfunction was reported despite being in remission and stable off treatment for a median of 20 months (range of 12–31 months; two OMS scores of 0/15 and one of 2/15). In children with OMS who have completed treatment and have made full or near full neurological recovery, concerns remain regarding long-term outcome in terms of future learning and cognitive development.