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July 21, 2020; 95 (3) Article

Clinical characteristics, risk factors, and outcomes of POEMS syndrome

A longitudinal cohort study

View ORCID ProfileStephen Keddie, David Foldes, Francisca Caimari, Stephanie E. Baldeweg, Joshua Bomsztyk, Oliver J. Ziff, Janev Fehmi, Aviva Cerner, Zane Jaunmuktane, Sebastian Brandner, Kwee Yong, Hadi Manji, Aisling Carr, Simon Rinaldi, Mary M. Reilly, Shirley D'Sa, View ORCID ProfileMichael P. Lunn
First published June 30, 2020, DOI: https://doi.org/10.1212/WNL.0000000000009940
Stephen Keddie
From the MRC Centre for Neuromuscular Disease, Neuroimmunology and CSF Laboratory (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), Institute of Neurology, Cancer Division (D.F., J.B., A.C., K.Y., S.D.), Department of Endocrinology (F.C., S.E.B., M.P.L.), and Division of Neuropathology, National Hospital for Neurology and Neurosurgery (Z.J., S.B.), University College London NHS Foundation Trust (S.K.), National Hospital for Neurology and Neurosurgery; Department of Neuromuscular Diseases (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), UCL Queen Square Institute of Neurology; and Department of Clinical Neurosciences (J.F., S.R.), John Radcliffe Hospital, Oxford, UK.
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David Foldes
From the MRC Centre for Neuromuscular Disease, Neuroimmunology and CSF Laboratory (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), Institute of Neurology, Cancer Division (D.F., J.B., A.C., K.Y., S.D.), Department of Endocrinology (F.C., S.E.B., M.P.L.), and Division of Neuropathology, National Hospital for Neurology and Neurosurgery (Z.J., S.B.), University College London NHS Foundation Trust (S.K.), National Hospital for Neurology and Neurosurgery; Department of Neuromuscular Diseases (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), UCL Queen Square Institute of Neurology; and Department of Clinical Neurosciences (J.F., S.R.), John Radcliffe Hospital, Oxford, UK.
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Francisca Caimari
From the MRC Centre for Neuromuscular Disease, Neuroimmunology and CSF Laboratory (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), Institute of Neurology, Cancer Division (D.F., J.B., A.C., K.Y., S.D.), Department of Endocrinology (F.C., S.E.B., M.P.L.), and Division of Neuropathology, National Hospital for Neurology and Neurosurgery (Z.J., S.B.), University College London NHS Foundation Trust (S.K.), National Hospital for Neurology and Neurosurgery; Department of Neuromuscular Diseases (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), UCL Queen Square Institute of Neurology; and Department of Clinical Neurosciences (J.F., S.R.), John Radcliffe Hospital, Oxford, UK.
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Stephanie E. Baldeweg
From the MRC Centre for Neuromuscular Disease, Neuroimmunology and CSF Laboratory (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), Institute of Neurology, Cancer Division (D.F., J.B., A.C., K.Y., S.D.), Department of Endocrinology (F.C., S.E.B., M.P.L.), and Division of Neuropathology, National Hospital for Neurology and Neurosurgery (Z.J., S.B.), University College London NHS Foundation Trust (S.K.), National Hospital for Neurology and Neurosurgery; Department of Neuromuscular Diseases (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), UCL Queen Square Institute of Neurology; and Department of Clinical Neurosciences (J.F., S.R.), John Radcliffe Hospital, Oxford, UK.
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Joshua Bomsztyk
From the MRC Centre for Neuromuscular Disease, Neuroimmunology and CSF Laboratory (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), Institute of Neurology, Cancer Division (D.F., J.B., A.C., K.Y., S.D.), Department of Endocrinology (F.C., S.E.B., M.P.L.), and Division of Neuropathology, National Hospital for Neurology and Neurosurgery (Z.J., S.B.), University College London NHS Foundation Trust (S.K.), National Hospital for Neurology and Neurosurgery; Department of Neuromuscular Diseases (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), UCL Queen Square Institute of Neurology; and Department of Clinical Neurosciences (J.F., S.R.), John Radcliffe Hospital, Oxford, UK.
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Oliver J. Ziff
From the MRC Centre for Neuromuscular Disease, Neuroimmunology and CSF Laboratory (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), Institute of Neurology, Cancer Division (D.F., J.B., A.C., K.Y., S.D.), Department of Endocrinology (F.C., S.E.B., M.P.L.), and Division of Neuropathology, National Hospital for Neurology and Neurosurgery (Z.J., S.B.), University College London NHS Foundation Trust (S.K.), National Hospital for Neurology and Neurosurgery; Department of Neuromuscular Diseases (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), UCL Queen Square Institute of Neurology; and Department of Clinical Neurosciences (J.F., S.R.), John Radcliffe Hospital, Oxford, UK.
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Janev Fehmi
From the MRC Centre for Neuromuscular Disease, Neuroimmunology and CSF Laboratory (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), Institute of Neurology, Cancer Division (D.F., J.B., A.C., K.Y., S.D.), Department of Endocrinology (F.C., S.E.B., M.P.L.), and Division of Neuropathology, National Hospital for Neurology and Neurosurgery (Z.J., S.B.), University College London NHS Foundation Trust (S.K.), National Hospital for Neurology and Neurosurgery; Department of Neuromuscular Diseases (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), UCL Queen Square Institute of Neurology; and Department of Clinical Neurosciences (J.F., S.R.), John Radcliffe Hospital, Oxford, UK.
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Aviva Cerner
From the MRC Centre for Neuromuscular Disease, Neuroimmunology and CSF Laboratory (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), Institute of Neurology, Cancer Division (D.F., J.B., A.C., K.Y., S.D.), Department of Endocrinology (F.C., S.E.B., M.P.L.), and Division of Neuropathology, National Hospital for Neurology and Neurosurgery (Z.J., S.B.), University College London NHS Foundation Trust (S.K.), National Hospital for Neurology and Neurosurgery; Department of Neuromuscular Diseases (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), UCL Queen Square Institute of Neurology; and Department of Clinical Neurosciences (J.F., S.R.), John Radcliffe Hospital, Oxford, UK.
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Zane Jaunmuktane
From the MRC Centre for Neuromuscular Disease, Neuroimmunology and CSF Laboratory (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), Institute of Neurology, Cancer Division (D.F., J.B., A.C., K.Y., S.D.), Department of Endocrinology (F.C., S.E.B., M.P.L.), and Division of Neuropathology, National Hospital for Neurology and Neurosurgery (Z.J., S.B.), University College London NHS Foundation Trust (S.K.), National Hospital for Neurology and Neurosurgery; Department of Neuromuscular Diseases (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), UCL Queen Square Institute of Neurology; and Department of Clinical Neurosciences (J.F., S.R.), John Radcliffe Hospital, Oxford, UK.
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Sebastian Brandner
From the MRC Centre for Neuromuscular Disease, Neuroimmunology and CSF Laboratory (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), Institute of Neurology, Cancer Division (D.F., J.B., A.C., K.Y., S.D.), Department of Endocrinology (F.C., S.E.B., M.P.L.), and Division of Neuropathology, National Hospital for Neurology and Neurosurgery (Z.J., S.B.), University College London NHS Foundation Trust (S.K.), National Hospital for Neurology and Neurosurgery; Department of Neuromuscular Diseases (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), UCL Queen Square Institute of Neurology; and Department of Clinical Neurosciences (J.F., S.R.), John Radcliffe Hospital, Oxford, UK.
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Kwee Yong
From the MRC Centre for Neuromuscular Disease, Neuroimmunology and CSF Laboratory (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), Institute of Neurology, Cancer Division (D.F., J.B., A.C., K.Y., S.D.), Department of Endocrinology (F.C., S.E.B., M.P.L.), and Division of Neuropathology, National Hospital for Neurology and Neurosurgery (Z.J., S.B.), University College London NHS Foundation Trust (S.K.), National Hospital for Neurology and Neurosurgery; Department of Neuromuscular Diseases (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), UCL Queen Square Institute of Neurology; and Department of Clinical Neurosciences (J.F., S.R.), John Radcliffe Hospital, Oxford, UK.
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Hadi Manji
From the MRC Centre for Neuromuscular Disease, Neuroimmunology and CSF Laboratory (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), Institute of Neurology, Cancer Division (D.F., J.B., A.C., K.Y., S.D.), Department of Endocrinology (F.C., S.E.B., M.P.L.), and Division of Neuropathology, National Hospital for Neurology and Neurosurgery (Z.J., S.B.), University College London NHS Foundation Trust (S.K.), National Hospital for Neurology and Neurosurgery; Department of Neuromuscular Diseases (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), UCL Queen Square Institute of Neurology; and Department of Clinical Neurosciences (J.F., S.R.), John Radcliffe Hospital, Oxford, UK.
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Aisling Carr
From the MRC Centre for Neuromuscular Disease, Neuroimmunology and CSF Laboratory (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), Institute of Neurology, Cancer Division (D.F., J.B., A.C., K.Y., S.D.), Department of Endocrinology (F.C., S.E.B., M.P.L.), and Division of Neuropathology, National Hospital for Neurology and Neurosurgery (Z.J., S.B.), University College London NHS Foundation Trust (S.K.), National Hospital for Neurology and Neurosurgery; Department of Neuromuscular Diseases (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), UCL Queen Square Institute of Neurology; and Department of Clinical Neurosciences (J.F., S.R.), John Radcliffe Hospital, Oxford, UK.
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Simon Rinaldi
From the MRC Centre for Neuromuscular Disease, Neuroimmunology and CSF Laboratory (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), Institute of Neurology, Cancer Division (D.F., J.B., A.C., K.Y., S.D.), Department of Endocrinology (F.C., S.E.B., M.P.L.), and Division of Neuropathology, National Hospital for Neurology and Neurosurgery (Z.J., S.B.), University College London NHS Foundation Trust (S.K.), National Hospital for Neurology and Neurosurgery; Department of Neuromuscular Diseases (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), UCL Queen Square Institute of Neurology; and Department of Clinical Neurosciences (J.F., S.R.), John Radcliffe Hospital, Oxford, UK.
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Mary M. Reilly
From the MRC Centre for Neuromuscular Disease, Neuroimmunology and CSF Laboratory (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), Institute of Neurology, Cancer Division (D.F., J.B., A.C., K.Y., S.D.), Department of Endocrinology (F.C., S.E.B., M.P.L.), and Division of Neuropathology, National Hospital for Neurology and Neurosurgery (Z.J., S.B.), University College London NHS Foundation Trust (S.K.), National Hospital for Neurology and Neurosurgery; Department of Neuromuscular Diseases (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), UCL Queen Square Institute of Neurology; and Department of Clinical Neurosciences (J.F., S.R.), John Radcliffe Hospital, Oxford, UK.
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Shirley D'Sa
From the MRC Centre for Neuromuscular Disease, Neuroimmunology and CSF Laboratory (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), Institute of Neurology, Cancer Division (D.F., J.B., A.C., K.Y., S.D.), Department of Endocrinology (F.C., S.E.B., M.P.L.), and Division of Neuropathology, National Hospital for Neurology and Neurosurgery (Z.J., S.B.), University College London NHS Foundation Trust (S.K.), National Hospital for Neurology and Neurosurgery; Department of Neuromuscular Diseases (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), UCL Queen Square Institute of Neurology; and Department of Clinical Neurosciences (J.F., S.R.), John Radcliffe Hospital, Oxford, UK.
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Michael P. Lunn
From the MRC Centre for Neuromuscular Disease, Neuroimmunology and CSF Laboratory (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), Institute of Neurology, Cancer Division (D.F., J.B., A.C., K.Y., S.D.), Department of Endocrinology (F.C., S.E.B., M.P.L.), and Division of Neuropathology, National Hospital for Neurology and Neurosurgery (Z.J., S.B.), University College London NHS Foundation Trust (S.K.), National Hospital for Neurology and Neurosurgery; Department of Neuromuscular Diseases (S.K., O.J.Z., H.M., A.C., M.M.R., M.P.L.), UCL Queen Square Institute of Neurology; and Department of Clinical Neurosciences (J.F., S.R.), John Radcliffe Hospital, Oxford, UK.
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Citation
Clinical characteristics, risk factors, and outcomes of POEMS syndrome
A longitudinal cohort study
Stephen Keddie, David Foldes, Francisca Caimari, Stephanie E. Baldeweg, Joshua Bomsztyk, Oliver J. Ziff, Janev Fehmi, Aviva Cerner, Zane Jaunmuktane, Sebastian Brandner, Kwee Yong, Hadi Manji, Aisling Carr, Simon Rinaldi, Mary M. Reilly, Shirley D'Sa, Michael P. Lunn
Neurology Jul 2020, 95 (3) e268-e279; DOI: 10.1212/WNL.0000000000009940

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Abstract

Objective POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin lesions) is a paraneoplastic disorder resulting in severe neurologic disability. Understanding the clinical, laboratory, neurophysiologic, and histopathologic features as well as treatment responses of POEMS will assist in more accurate and timely diagnosis, risk stratification, and effective management.

Methods This was a retrospective longitudinal cohort study from 1998 to March 2019, with 7,184 person-months of follow-up time. Hospital databases were used to collate presenting features, investigations, therapies, and response.

Results One hundred patients were included with a median follow-up time of 59 months (range, 1–252). Mean symptom onset to diagnosis was 15 months (range, 1–77), with 54% of patients initially misdiagnosed with chronic inflammatory demyelinating polyneuropathy. Median number of multisystem features at diagnosis was 7. Ninety-six (96%) presented with neuropathy, which was length-dependent in 93 (93%) and painful in 75 (75%). At diagnosis, 35% of patients were wheelchair or bedbound, with median Overall Neuropathy Limitation Score of 6, improving to 3 following treatment (p < 0.05). Five-year survival was 90% and 82% at 10 years, with 5- and 10-year progression-free survival of 65% and 53%. Nontreatment with autologous stem cell transplantation, nonhematologic response, and non–vascular endothelial growth factor response are significant risk factors in multivariate analysis to predict progression or death. Risk factors are incorporated to develop a risk score enabling stratification of high- and low-risk cases.

Conclusions POEMS syndrome is a rare multisystem condition with delayed diagnosis and poor neurologic function at presentation. Therapy has favorable outcomes. Patients at high risk of death or progression can be identified, which may allow for more active monitoring and influence management.

Glossary

ASCT=
autologous stem cell transplantation;
CI=
confidence interval;
CIDP=
chronic inflammatory demyelinating polyneuropathy;
CR=
complete response;
HR=
hazard ratio;
IQR=
interquartile range;
M-protein=
monoclonal protein;
mRS=
modified Rankin Scale;
NE=
not evaluable;
NR=
no response;
ONLS=
Overall Neuropathy Limitation Score;
OS=
overall survival;
PFS=
progression-free survival;
PR=
partial response;
SFLC=
serum free light chains;
SPE=
serum protein electrophoresis;
SUV=
standardized uptake value;
sVEGF=
serum vascular endothelial growth factor;
UCLH=
University College London Hospital;
VEGF=
vascular endothelial growth factor

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received July 17, 2019.
  • Accepted in final form December 27, 2019.
  • © 2020 American Academy of Neurology
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Disputes & Debates: Rapid online correspondence

  • Author response: Clinical characteristics, risk factors, and outcomes of POEMS syndrome: A longitudinal cohort study
    • Stephen Keddie, Neurology SpR, Research Fellow, University College London Hospital National Hospital for Neurology and Neurosurgery
    • Michael P. Lunn, Professor of Neurology & Neuroimmunology Laboratory Clinical Lead, University College London Hospital National Hospital for Neurology and Neurosurgery
    Submitted August 06, 2020
  • Reader response: Clinical characteristics, risk factors, and outcomes of POEMS syndrome: A longitudinal cohort study
    • Chiara Briani, Neurologist, Department of Neurosciences, University of Padova (Padova, Italy)
    • Renzo Manara, Neuroradiologist, Neuroradiology, University of Padova (Padova, Italy)
    • Annalisa Angelini, Pathologist, Cardiovascular Pathology, University of Padova (Padova, Italy)
    Submitted July 21, 2020
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