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American Journal of Hematology Feb 2014POEMS syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell... (Review)
Review
DISEASE OVERVIEW
POEMS syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell disorder (PCD), sclerotic bone lesions, elevated vascular endothelial growth factor, and the presence of Castleman disease. Minor features include organomegaly, endocrinopathy, characteristic skin changes, papilledema, extravascular volume overload, and thrombocytosis. Diagnoses are often delayed because the syndrome is rare and can be mistaken for other neurologic disorders, most commonly chronic inflammatory demyelinating polyradiculoneuropathy. POEMS syndrome should be distinguished from the Castleman disease variant of POEMS syndrome, which has no clonal PCD and typically little to no peripheral neuropathy but has several of the minor diagnostic criteria for POEMS syndrome.
DIAGNOSIS
The diagnosis of POEMS syndrome is made with three of the major criteria, two of which must include polyradiculoneuropathy and clonal PCD, and at least one of the minor criteria.
RISK STRATIFICATION
Because the pathogenesis of the syndrome is not well understood, risk stratification is limited to clinical phenotype rather than specific molecular markers. The number of clinical criteria is not prognostic, but the extent of the PCD is. Those patients with an iliac crest bone marrow biopsy that does not reveal a plasma cell clone are candidates for local radiation therapy; those with a more extensive or disseminated clone will be candidates for systemic therapy.
RISK-ADAPTED THERAPY
For those patients with a dominant sclerotic plasmacytoma, first line therapy is irradiation. Patients with diffuse sclerotic lesions or disseminated bone marrow involvement and for those who have progression of their disease 3-6 months after completing radiation therapy should receive systemic therapy. Corticosteroids are temporizing, but alkylators are the mainstay of treatment, either in the form of low dose conventional therapy or high dose with stem cell transplantation. The benefit of anti-VEGF antibodies is conflicting. Lenalidomide shows promise with manageable toxicity. Thalidomide and bortezomib also have activity, but their benefit needs to be weighed against their risk of exacerbating the peripheral neuropathy. Prompt recognition and institution of both supportive care measures and therapy directed against the plasma cell result in the best outcomes.
Topics: Bone Marrow; Castleman Disease; Diagnosis, Differential; Humans; POEMS Syndrome; Risk Factors; Treatment Outcome
PubMed: 24532337
DOI: 10.1002/ajh.23644 -
BMC Neurology Jun 2021This study aimed to investigate the frequency and risk factors for cerebral artery stenosis and occlusion in patients with polyneuropathy, organomegaly, endocrinopathy,...
BACKGROUND
This study aimed to investigate the frequency and risk factors for cerebral artery stenosis and occlusion in patients with polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome.
METHODS
We reviewed results of magnetic resonance angiography (MRA) or computed tomography angiography (CTA) in 61 patients with POEMS syndrome seen between 2010 and 2017. Stenosis or occlusion was assessed in the initial MRA/CTA. Multivariate analysis was used to identify risk factors for artery stenosis/occlusion. In an autopsy case, pathologic examination was conducted of the occluded middle cerebral arteries.
RESULTS
Stenosis (> 50 %) or occlusion of the major cerebral arteries was found in 29 (47.5 %) patients on the initial MRA/CTA. The internal carotid artery was involved most frequently (32.8 %), followed by the anterior (21.3 %) and middle (16.4 %) cerebral arteries. The basilar (1.3 %) and vertebral (3.6 %) arteries were rarely affected. Cerebral infarction developed in eight (13.1 %) patients. The serum vascular endothelial growth factor (VEGF) level was an independent predictor for stenosis/occlusion (odds ratio, 1.228; 95 % confidence interval, 1.042-1.447; P = 0.014). An autopsy study showed occluded middle cerebral arteries by fibrous and myxomatous thickening of intima with splitting of the internal elastic lamina. Follow-up MRA in 23 patients showed improved, worsened, and unchanged stenosis in 20.7 %, 8.7 %, and 69.6 %, respectively.
CONCLUSIONS
Cerebral large-vessel stenosis or occlusion is frequently seen in approximately half of patients with POEMS syndrome. Vasculopathy was related to serum VEGF levels and thereby disease activity. Assessment of cerebral vessels is recommended in these patients to improve management.
Topics: Cerebrovascular Disorders; Humans; Infarction, Middle Cerebral Artery; POEMS Syndrome
PubMed: 34167480
DOI: 10.1186/s12883-021-02260-2 -
JCI Insight Oct 2022POEMS syndrome is a rare monoclonal plasma cell disorder, with unique symptoms distinct from those of other plasma cell neoplasms, including high serum VEGF levels....
POEMS syndrome is a rare monoclonal plasma cell disorder, with unique symptoms distinct from those of other plasma cell neoplasms, including high serum VEGF levels. Because the prospective isolation of POEMS clones has not yet been successful, their real nature remains unclear. Herein, we performed single-cell RNA-Seq of BM plasma cells from patients with POEMS syndrome and identified POEMS clones that had Ig λ light chain (IGL) sequences (IGLV1-36, -40, -44, and -47) with amino acid changes specific to POEMS syndrome. The proportions of POEMS clones in plasma cells were markedly smaller than in patients with multiple myeloma (MM) and patients with monoclonal gammopathy of undetermined significance (MGUS). Single-cell transcriptomes revealed that POEMS clones were CD19+, CD138+, and MHC class IIlo, which allowed for their prospective isolation. POEMS clones expressed significantly lower levels of c-MYC and CCND1 than MM clones, accounting for their small size. VEGF mRNA was not upregulated in POEMS clones, directly indicating that VEGF is not produced by POEMS clones. These results reveal unique features of POEMS clones and enhance our understanding of the pathogenesis of POEMS syndrome.
Topics: Humans; POEMS Syndrome; Plasma Cells; Vascular Endothelial Growth Factor A; Single-Cell Analysis; Immunoglobulin lambda-Chains; Immunoglobulin Light Chains; Clone Cells; Multiple Myeloma; Amino Acids
PubMed: 36129760
DOI: 10.1172/jci.insight.151482 -
Internal Medicine (Tokyo, Japan) Nov 2004
Topics: Humans; POEMS Syndrome; Platelet Aggregation Inhibitors; Ticlopidine; Vascular Endothelial Growth Factors
PubMed: 15609693
DOI: 10.2169/internalmedicine.43.1014 -
American Journal of Hematology Jul 2011POEMS syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell... (Review)
Review
DISEASE OVERVIEW
POEMS syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell disorder (PCD), sclerotic bone lesions, elevated vascular endothelial growth factor, and the presence of Castleman disease. Minor features include organomegaly, endocrinopathy, characteristic skin changes, papilledema, extravascular volume overload, and thrombocytosis. Diagnoses are often delayed because the syndrome is rare and can be mistaken for other neurologic disorders, most commonly chronic inflammatory demyelinating polyradiculoneuropathy. POEMS syndrome should be distinguished from the Castleman disease variant of POEMS syndrome, which has no clonal PCD and typically little to no peripheral neuropathy but has several of the minor diagnostic criteria for POEMS syndrome.
DIAGNOSIS
The diagnosis of POEMS syndrome is made with three of the major criteria, two of which must include polyradiculoneuropathy and clonal plasma cell disorder, and at least one of the minor criteria.
RISK STRATIFICATION
Because the pathogenesis of the syndrome is not well understood, risk stratification is limited to clinical phenotype rather than specific molecular markers. The number of clinical criteria is not prognostic, but the extent of the plasma cell disorder is. Those patients with an iliac crest bone marrow biopsy that does not reveal a plasma cell clone are candidates for local radiation therapy; those with a more extensive or disseminated clone will be candidates for systemic therapy.
RISK-ADAPTED THERAPY
For those patients with a dominant sclerotic plasmacytoma, first line therapy is irradiation. Patients with diffuse sclerotic lesions or disseminated bone marrow involvement and for those who have progression of their disease 3 to 6 months after completing radiation therapy should receive systemic therapy. Corticosteroids are temporizing, but alkylators are the mainstay of treatment, either in the form of low dose conventional therapy or high dose with stem cell transplantation. The benefit of anti-VEGF antibodies is conflicting. Lenalidomide shows promise with manageable toxicity. Thalidomide and bortezomib also have activity, but their benefit needs to be weighed against their risk of exacerbating the peripheral neuropathy. Prompt recognition and institution of both supportive care measures and therapy directed against the plasma cell result in the best outcomes.
Topics: Castleman Disease; Diagnosis, Differential; Humans; POEMS Syndrome; Risk Factors; Time Factors
PubMed: 21681783
DOI: 10.1002/ajh.22050 -
Heliyon Oct 2023POEMS syndrome is a rare and complex plasma cell disorder characterized by polyneuropathy, organomegaly, endocrinopathy, high M protein levels, and skin changes....
BACKGROUND
POEMS syndrome is a rare and complex plasma cell disorder characterized by polyneuropathy, organomegaly, endocrinopathy, high M protein levels, and skin changes. Understanding of POEMS syndrome has advanced rapidly since the 21st century. This study aims to summarize and evaluate the research status of POEMS syndrome in the past 23 years through a bibliometric and visualization analysis, and identify research focuses and emerging hotspots for the future.
METHODS
POEMS syndrome-related articles published between January 1, 2000, and March 8, 2023, were systematically retrieved from the Web of Science Core Collection. Data processing and visualization analysis were carried out using a combination of R software, HistCite, VOSviewer, and CiteSpace.
RESULTS
Since entering the 21st century, 3677 authors from 1125 institutions in 68 countries/regions have published 830 original and review articles on POEMS syndrome in 408 journals so far, among which the USA, Japan, and China published the most articles, and Mayo Clinic, Udice French Research Universities, and Peking Union Medical College listed the top three most prolific institutions. However, collaborative research across countries and groups in the study of POEMS syndrome remain significantly limited. Angela Dispenzieri ranked first in POEMS syndrome research from every aspect of authors, producing the most papers and contributing the most-cited article, followed by Satoshi Kuwabara and Sonoko Misawa. was the most productive journal on POEMS syndrome. "endothelial growth factor" was the keyword with the highest occurrence except for "POEMS syndrome", and "bevacizumab", "lenalidomide", "dexamethasone", and "management" were recognized as emerging topics.
CONCLUSION
This study utilized bibliometric and visualization analysis to systematically summarize the research of POEMS syndrome in the first two decades of the 21st century, offering a data-based and objective perspective on the field of POEMS syndrome and guiding researchers in the identification of novel research directions.
PubMed: 37842561
DOI: 10.1016/j.heliyon.2023.e20612 -
International Journal of Retina and... Jan 2021POEMS (polyneuropathy, organomegaly, endocrinopathy, myeloma protein, skin changes) syndrome is a rare blood disorder with multi-system involvement. The cause is...
BACKGROUND
POEMS (polyneuropathy, organomegaly, endocrinopathy, myeloma protein, skin changes) syndrome is a rare blood disorder with multi-system involvement. The cause is unknown. It is marked by elevated plasma cells, platelets, & VEGF (vascular endothelial growth factor) levels. 52% of patients develop optic disc edema which may be vision threatening but the exact etiology of optic disc edema is uncertain. We report a rare finding of peripheral retinal leakage in POEMS syndrome.
CASE PRESENTATION
A 60 year-old female with POEMS syndrome presented with bilateral blurred vision. Fundi showed grade 3 disc edema OU. Lumbar puncture showed normal opening pressure. CSF analysis showed elevated proteins with no cells. MRI brain and MR Venogram head were unremarkable. Wide field fluorescein angiography demonstrated multifocal tiny vascular leakage and significant anterior temporal leakage.
CONCLUSION
The authors hypothesize the disc edema in POEMS syndrome may be caused by increased vascular permeability at the optic disc secondary to increased VEGF (vascular endothelial growth factor) levels. Though disc leakage is a well-documented finding in fundus fluorescein imaging, peripheral retinal leakage in POEMS syndrome is not reported.
PubMed: 33436019
DOI: 10.1186/s40942-020-00278-1 -
Clinical Lymphoma, Myeloma & Leukemia May 2022POEMS syndrome, a rare plasma cell disorder, is challenging both in the diagnostic and therapeutic management. We present real word retrospective analysis of 108 cases...
POEMS syndrome, a rare plasma cell disorder, is challenging both in the diagnostic and therapeutic management. We present real word retrospective analysis of 108 cases analyzing clinical features and therapeutic modes. We compare our results with the available literature. This is the first description with such wide use of proteasome inhibitors in first line treatment. POEMS (Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) syndrome is a rare and challenging plasma cell disorder, both in the diagnostic and therapeutic management of the disease. Currently, the literature on POEMS is sparse with most evidence being case reports and small case studies. We present a retrospective real world experience of 108 patients with POEMS. We analyzed the clinical features and therapeutic interventions. Regarding clinical features, our findings demonstrated that skin lesions, thrombocythemia and polycythemia were present less frequently than reported previously. Regarding clinical interventions, this is one of the largest analyses of front line treatment in POEMS and the first one to include frequent utilization of proteasome inhibitors (37%). Bortezomib monotherapy was the most effective therapy achieving complete remission/very good partial remissions (CR/VGPR) in 69% of patients. Thirty percent of patients proceeded to planned autologous stem cell transplant (ASCT) as part of the front-line treatment resulting in statistically superior progression-free (PFS) and overall survival (OS) compared to non-ASCT treated patients (P= .003). In multivariate analysis, anemia, thrombocytopenia, and as age over 60 were associated with a negative impact on patient outcomes.
Topics: Humans; POEMS Syndrome; Paraproteinemias; Proteasome Inhibitors; Retrospective Studies; Transplantation, Autologous
PubMed: 34844892
DOI: 10.1016/j.clml.2021.10.007 -
Actas Dermo-sifiliograficas Mar 2017POEMS syndrome is a paraneoplastic manifestation associated with hematopoietic disorders such as multiple myeloma and Castleman disease. POEMS is an acronym for the main...
POEMS syndrome is a paraneoplastic manifestation associated with hematopoietic disorders such as multiple myeloma and Castleman disease. POEMS is an acronym for the main clinical features of the syndrome, namely, Polyneuropathy, Organomegaly, Endocrinopathy, M protein, and Skin abnormalities. Glomeruloid hemangiomas are considered to be a specific clinical marker of POEMS syndrome. However, while they are not pathognomonic, their presence should raise suspicion of this syndrome or alert clinicians to its possible future development, as these lesions can appear years before the onset of the syndrome. We report the cases of 2 women with plasma cell dyscrasias and sudden onset of lesions with a vascular appearance and histologic findings consistent with glomeruloid hemangioma. Recognition of this vascular tumor is important for the early diagnosis of POEMS syndrome.
Topics: Aged, 80 and over; Dermoscopy; Female; Hemangioma; Humans; Middle Aged; Multiple Myeloma; POEMS Syndrome; Paraneoplastic Syndromes; Plasmacytoma; Positron Emission Tomography Computed Tomography; Skin Neoplasms
PubMed: 27208909
DOI: 10.1016/j.ad.2015.10.020 -
Clinical Neurophysiology Practice 2020We detailed the electrophysiological patterns of peripheral nerve temporal dispersion across spectrum of POEMS syndrome and Castleman disease (CD).
OBJECTIVE
We detailed the electrophysiological patterns of peripheral nerve temporal dispersion across spectrum of POEMS syndrome and Castleman disease (CD).
METHODS
Compound muscle action potentials (CMAP) duration of 3 patients with POEMS syndrome and 2 with hyaline vascular type CD without clonal plasma cell dyscrasia were retrospectively analysed.
RESULTS
Median and ulnar nerves distal CMAP duration were prolonged in all patients irrespective of plasma cell dyscrasia or M protein. All lower limbs distal CMAP responses were absent. Greatest distal CMAP duration prolongation was observed in median nerves for POEMS syndrome (17.0 ms, 158% upper limit normal) and in ulnar nerves for CD (9.8 ms, 47% upper limit normal). Distal/proximal CMAP duration ratio of <0.7 were seen in 33% of median and ulnar nerves studied among POEMS syndrome. Among nerves with ratio >0.7, all had distal CMAP duration prolongation (Range 7%-158% of upper limit normal).
CONCLUSIONS
Abnormal distal CMAP dispersion is not uncommon in POEMS syndrome and CD without clonal plasma cell dyscrasia or M protein. POEMS syndrome has greater distal CMAP duration in median and ulnar nerves, particularly in median nerve that can reach up to 150% of upper limit normal, compared to <50% in CD.
SIGNIFICANCE
Detailed electrophysiological analysis of distal CMAP duration may help in distinguishing POEMS syndrome and CD.
PubMed: 32613149
DOI: 10.1016/j.cnp.2020.05.001