key: cord-343018-8ghon5nb authors: Rajabally, Yusuf A.; Goedee, H. Stephan; Attarian, Shahram; Hartung, Hans‐Peter title: Management challenges for chronic dysimmune neuropathies during the COVID‐19 pandemic date: 2020-04-24 journal: Muscle Nerve DOI: 10.1002/mus.26896 sha: doc_id: 343018 cord_uid: 8ghon5nb Since March 2020, the COVID‐19 pandemic has led to the need to re‐think the delivery of services to patients with chronic dysimmune neuropathies. Telephone/video consultations have become widespread but have compounded concerns about objective evaluation. Therapeutic decisions need, more than ever before, to be considered in the best interests of both patients, and society, while not denying function‐preserving/restoring treatment. Immunoglobulin therapy and plasma exchange, for those treated outside of the home, expose patients to the hazards of hospital or outpatient infusion centers. Steroid therapy initiation and continuation pose increased infectious risk. Immunosuppressant therapy similarly becomes highly problematic, with the risks of treatment continuation enhanced by uncertainties regarding duration of the pandemic. The required processes necessitate considerable time and effort especially as resources and staff are re‐deployed to face the pandemic, but are essential for protecting this group of patients and as an integral part of wider public health actions. month ago. Social distancing suggests that decisions can no longer be based solely on the affected individual, but also on the need to protect that individual's immediate family and society at large. Opinions and recommendations on the diagnosis, monitoring, and treatment of chronic dysimmune neuropathies during the current pandemic are here offered. These are summarized in Tables 1 and 2 . Current international measures to curb the progression of the pandemic will have to be maintained for an indeterminate period of time, albeit in different forms. Many uncertainties will remain, although several changes in our practice, aimed at offering optimal care to our patients as neurologists while adhering to our public health responsibilities as physicians, have become essential and urgent. We discuss these crucial changes in practice and their implementation in routine clinical care. Prompt identification of a treatable disorder such as CIDP is highly desirable. Delays in treatment initiation may result in worse prognosis due to axonal loss. 2 CIDP, however, may present with widely varying disability and modes of progression. Whereas decision-making may be easier in patients with severe impairment, often of rapid onset, many patients present with slowly progressive, moderate deficits. Difficulties with tasks involving hand and arm function that nevertheless remain partially preserved, or with lower limb function not impacting independent mobility, require particular attention and caution. In such patients, the urgency of diagnosis should be balanced against the risks of hospital/medical facility attendance for clinical evaluation and diagnostic tests. These tests themselves, usually considered helpful, 3 now require consideration of their benefit-to-risk ratio. The American Suggested clinical management guidance for incident patients with CIDP, MMN, and anti-MAG neuropathy during the COVID-19 pandemic 11 and its derivative the Overall Neuropathy Limitation Scale (ONLS) 12 are easy and rapid to administer. 13 Rasch-built scales, including the inflammatory Rasch-built Overall Disability Scale (I-RODS) 14 and its equivalent for MMN, the MMN-RODS, 15 have been proposed, and are now frequently used. 13 The COVID-19 pandemic has resulted in several new issues directly impacting the treatment of dysimmune neuropathies. These relate not only to the patients themselves, including their age, medical history, personal and familial circumstances, but also to the disease subtype, the resulting severity of disability, and the treatments. CIDP is known to affect more commonly elderly subjects, particularly males. 19 This group is at higher risk of severe COVID-19 infection and fatal outcome. 20 The need for treatment for a newly identified patient with chronic dysimmune neuropathy also concurrently infected by COVID-19 will likely be a rare occurrence, and treatment delay is probably appropri- Also of concern, the infection risk with immunosuppressants probably lasts for several months after interruption (although there are only few studies of single agents used for sufficiently long to confirm this). Despite little available data comparing corticosteroids vs other immunosuppressants for infection risk, the benefit of the former is generally well-accepted for CIDP, thereby offering potential justification, as opposed to the latter. Use of long-term methotrexate, cyclosporine, azathioprine, or mycophenolate mofetil exposures, often of unproven benefit as usually used in conjunction with continuing first-line agents, now, therefore, carry unacceptable risks. Although it has been suggested that the infectious risk may be highest with cyclophosphamide, it may also be that previous use of three or more immunosuppressants carries an even greater risk. 33 This is a situation not infrequently encountered in subjects with CIDP. The discovery of new antinodal and paranodal antibodies in a small proportion of patients with CIDP, most often refractory to IVIg, poses a rarely encountered, but genuine clinical problem. 34 Some such patients may respond to corticosteroid therapy and others only to rituximab. With regards to rituximab, for which the efficacy has also been described in CIDP without paranodal antibodies, 35 and while randomized controlled trial evidence is awaited, 36 There is no current evidence for routine use of any treatment in anti-MAG neuropathy. 40 However, in selected patients with severe and rapidly progressive disease, rituximab may be of benefit and is used by many. Again, precisely defining severity and speed of decline becomes essential through detailed remote consultation, with only severe disability justifying treatment consideration. In the setting of the pandemic, it may in such patients, be advisable to attempt IVIg in the first instance, which could produce short-term benefit, before considering rituximab. "CIDP-like" phenotypes have rarely been described in patients with anti-MAG antibodies. 41 For such patients, first-line CIDP treatment (principally IVIg and plasma exchange), rather than rituximab, may be justified. In the wider setting of paraproteinemic neuropathy, greater collaborative neuro-hematologic interaction has become essential in current times, with careful multidisciplinary decisions. Treatment recommendations are summarized in Tables 1 and 2 . Many weeks of profound uncertainty are ahead of us. Lockdown measures are hoped to effectively reduce COVID-19 transmission rates, but what the future holds for the management of patients with chronic dysimmune neuropathies is unknown. Issues with reliability, availability, and generalization of testing persist worldwide and will necessarily impact on future practice. 42 In the case of patients at high risk of severe infection and death from COVID-19, but who will remain seronegative, the question of when the re-implementation of routine face-to-face consultations, usual hospital or infusion center treatment and use of immune suppressive therapies, particularly corticosteroids, will become safe again, is, disturbingly, unanswered. Immunomodulatory and particularly immunosuppressive therapies may compromise the immune system's ability to effectively fight off infection with COVID-19, and this concern will persist for an indeterminate time and impact upon patient management. In practice, a focus on the severity of the clinical picture and especially of disability, acuteness of the presentation, and likelihood of treatment efficacy, are all essential in making diagnostic decisions. Therapy needs to be focused first and foremost on not exposing the patient, family, and society to harm. This involves choosing the least dangerous option when essential, not hesitating to alter previously Remote assessments of these patients may be a part of clinical care for the foreseeable future, and prioritizing clinical judgement over use of test results for patients affected by chronic dysimmune neuropathy has never been more important. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. On being a neurologist in Italy at the time of the COVID-19 outbreak Clinical and electrophysiologic correlates of IVIg responsiveness in CIDP European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society -first revision Guidance for Managing NCS/EMG Testing Requests During COVID-19 Derivation and validation of diagnostic criteria for chronic inflammatory demyelinating polyneuropathy CIDP diagnostic pitfalls and perception of treatment benefit Multifocal motor neuropathy Epidemiology of chronic inflammatory neuropathies in southeast England Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan. China Correlation of the patient's reported outcome Inflammatory-RODS with an objective metric in immune-mediated neuropathies Randomized controlled trial of intravenous immunoglobulin versus oral prednisolone in chronic inflammatory demyelinating polyradiculoneuropathy A modified peripheral neuropathy scale: the Overall Neuropathy Limitations Scale Outcome measures for chronic inflammatory demyelinating polyneuropathy in research: relevance and applicability to clinical practice Rasch-built Overall Disability Scale (R-ODS) for immune-mediated peripheral neuropathies Rasch-built Overall Disability Scale for Multifocal motor neuropathy COVID-19 is catalyzing the adoption of teleneurology Modifying the Medical Research Council grading system through Rasch analyses Reference values of grip strength, prevalence of low grip strength, and factors affecting grip strength values in Chinese adults Epidemiologic variability of chronic inflammatory demyelinating polyneuropathy with different diagnostic criteria: study of a UK population Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study Prevalence of underlying diseases in hospitalized patients with COVID-19: a systematic review and meta-analysis Rapid assessment of regional SARS-CoV-2 community transmission through a convenience sample of healthcare workers, the Netherlands Subcutaneous immunoglobulin for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (PATH): a randomised, double-blind, placebo-controlled, phase 3 trial Long-term immunoglobulin therapy for chronic inflammatory demyelinating polyradiculoneuropathy Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy Intravenous immunoglobulin versus intravenous methylprednisolone for chronic inflammatory demyelinating polyradiculoneuropathy: a randomised controlled trial Pulsed high-dose dexamethasone versus standard prednisolone treatment for chronic inflammatory demyelinating polyradiculoneuropathy (PREDICT study): a double-blind, randomised, controlled trial Association of cumulative steroid dose with risk of infection after treatment for severe acute graft-versus-host disease Incidence of infections associated with oral glucocorticoid dose in people diagnosed with polymyalgia rheumatica or giant cell arteritis: a cohort study in England Treatments for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): an overview of systematic reviews A novel treatment approach to the novel coronavirus: an argument for the use of therapeutic plasma exchange for fulminant COVID-19 Unconventional treatments for chronic inflammatory demyelinating polyneuropathy Severe infections in sarcoidosis: incidence, predictors and long-term outcome in a cohort of 585 patients Autoantibodies in chronic inflammatory neuropathies: diagnostic and therapeutic implications Rituximab in refractory chronic inflammatory demyelinating polyneuropathy. Muscle Nerve. 2020 Efficacy and safety of rituximab in refractory CIDP with or without IgG4 autoantibodies (RECIPE): protocol for a double-blind, randomized, placebo-controlled clinical trial Severe infections in patients with anti-neutrophil cytoplasmic antibody-associated vasculitides receiving rituximab: a meta-analysis Subcutaneous immunoglobulin in CIDP and MMN: a different long-term clinical response? Intravenous immunoglobulin as short-and long-term therapy of multifocal motor neuropathy: a retrospective study of response to IVIg and of its predictive criteria in 40 patients Immunotherapy for IgM anti-myelinassociated glycoprotein paraprotein-associated peripheral neuropathies Heterogeneity of polyneuropathy associated with anti-MAG antibodies The laboratory diagnosis of COVID-19 infection: current issues and challenges Management challenges for chronic dysimmune neuropathies during the COVID-19 pandemic