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American Journal of Hematology Jul 2019Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes (POEMS) syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major... (Review)
Review
DISEASE OVERVIEW
Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes (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. Risk factors include low serum albumin, age, pleural effusion, pulmonary hypertension, and reduced eGFR.
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. 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: Adrenal Cortex Hormones; Allografts; Bortezomib; Castleman Disease; Diagnosis, Differential; Humans; POEMS Syndrome; Risk Assessment; Risk Factors; Stem Cell Transplantation; Thalidomide; Vascular Endothelial Growth Factor A
PubMed: 31012139
DOI: 10.1002/ajh.25495 -
Annals of Hematology Mar 2022Although Castleman disease was first described in 1956, this disease includes various conditions, including unicentric Castleman disease with hyaline vascular histology,... (Review)
Review
Although Castleman disease was first described in 1956, this disease includes various conditions, including unicentric Castleman disease with hyaline vascular histology, human herpesvirus-8 (HHV-8) related multicentric Castleman disease, idiopathic multicentric Castleman disease, and mimics of Castleman disease associated with other conditions. To date, Castleman disease remains incompletely understood due to its rareness and difficulties in clinical and pathological diagnosis. TAFRO syndrome was reported in Japan in 2010. Because lymph node histology is similar in patients with TAFRO syndrome and Castleman disease, TAFRO syndrome is described as a related disorder of Castleman disease. Clinically, however, these conditions differ markedly. Although elevated interleukin-6 (IL-6) expression is characteristic of Castleman disease, increased expression of IL-6 may occur in patients with other diseases, making elevated IL-6 unsuitable for differential diagnosis. Further understanding of these disorders requires the identification of novel disease-specific biomarkers. This review article therefore outlines the characteristics of Castleman disease and TAFRO syndrome.
Topics: Animals; Castleman Disease; Cytokine Release Syndrome; Diagnosis, Differential; Humans; Interleukin-6; Lymph Nodes
PubMed: 35044513
DOI: 10.1007/s00277-022-04762-6 -
Blood Research Apr 2022POEMS syndrome is an acronym for polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes. It is a rare paraneoplastic disorder related to... (Review)
Review
POEMS syndrome is an acronym for polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes. It is a rare paraneoplastic disorder related to plasma cell neoplasm. However, its pathophysiology has not yet been clearly elucidated. The production of pro-inflammatory cytokines is thought to play an important role in the pathogenesis of POEMS syndrome. Vascular endothelial growth factor level reflects disease activity, which is helpful for the diagnosis and evaluation of treatment response. Conventional agents such as corticosteroids and melphalan are effective and safe combination regimens. Autologous hematopoietic stem cell transplantation is another option for high-risk transplant-eligible patients. Radiotherapy is effective in patients with localized lesions. The anti-myeloma agents lenalidomide, thalidomide, and bortezomib have shown good treatment outcomes for POEMS syndrome; however, large-scale studies with long-term follow-up are required. Early identification and active treatment can improve the outcomes of POEMS syndrome patients.
PubMed: 35483922
DOI: 10.5045/br.2022.2022001 -
Journal of Neurology Jan 2019POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) is a rare paraneoplastic syndrome, caused by a plasma cell proliferative disorder,... (Review)
Review
POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) is a rare paraneoplastic syndrome, caused by a plasma cell proliferative disorder, which is most commonly lambda restricted. The neurological hallmark, which forms one of the mandatory criteria for diagnosis, is a subacute onset demyelinating neuropathy, which can be rapidly disabling and painful. A number of multi-system features are also characteristic of this disorder, and certainly not restricted to those included in its acronym, which though limited, remains a useful and memorable name, helping distinguish POEMS syndrome from other paraproteinaemic neuropathies. The discovery of vascular endothelial growth factor (VEGF) in association with POEMS syndrome has been extremely useful in aiding clinical diagnosis, and monitoring response to treatment, as well as helping understand the underlying mechanism of disease. Interestingly, however, treatment targeting VEGF has been disappointing, suggesting other disease mechanisms or inflammatory processes are also important. Current understanding of the pathogenesis of POEMS syndrome is outlined in detail in the accompanying article by Cerri et al. Here, we review the clinical features of POEMS syndrome, differential diagnosis and available treatment options, based on current literature.
Topics: Humans; POEMS Syndrome
PubMed: 30498913
DOI: 10.1007/s00415-018-9110-6 -
Muscle & Nerve Feb 2021Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is characterized by progressive weakness and sensory loss, often affecting patients' ability to walk and... (Review)
Review
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is characterized by progressive weakness and sensory loss, often affecting patients' ability to walk and perform activities of daily living independently. With the lack of a diagnostic biomarker, the diagnosis relies on clinical suspicion, clinical findings, and the demonstration of demyelinating changes on electrodiagnostic (EDx) testing and nerve pathology. As a result, patients can often be misdiagnosed with CIDP and unnecessarily treated with immunotherapy. Interpreting the EDx testing and cerebrospinal fluid findings in light of the clinical phenotype, recognizing atypical forms of CIDP, and screening for CIDP mimickers are the mainstays of the approach to patients suspected of having CIDP, and are detailed in this review. We also review the currently available treatment options, including intravenous immunoglobulin (IVIg), corticosteroids (CCS), and plasma exchange (PE), and discuss how to approach treatment-refractory cases. Finally, we emphasize the need to adopt objective outcome measures to monitor treatment response.
Topics: Adrenal Cortex Hormones; Amyloid Neuropathies; Cerebrospinal Fluid; Charcot-Marie-Tooth Disease; Diagnosis, Differential; Diagnostic Errors; Disease Progression; Electrodiagnosis; Humans; Immunoglobulin G; Immunoglobulins, Intravenous; Immunologic Factors; Infusions, Subcutaneous; Medical Overuse; Neural Conduction; Outcome Assessment, Health Care; POEMS Syndrome; Paraneoplastic Polyneuropathy; Paraproteinemias; Peripheral Nerves; Plasma Exchange; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
PubMed: 32914902
DOI: 10.1002/mus.27046 -
Blood Cancer Journal Apr 2022Monoclonal gammopathy associated with dermatological manifestations are a well-recognized complication. These skin disorders can be associated with infiltration and... (Review)
Review
Monoclonal gammopathy associated with dermatological manifestations are a well-recognized complication. These skin disorders can be associated with infiltration and proliferation of a malignant plasma cells or by a deposition of the monoclonal immunoglobulin in a nonmalignant monoclonal gammopathy. These disorders include POEMS syndrome, light chain amyloidosis, Schnitzler syndrome, scleromyxedema and TEMPI syndrome. This article provides a review of clinical manifestations, diagnostics criteria, natural evolution, pathogenesis, and treatment of these cutaneous manifestations.
Topics: Amyloidosis; Humans; Monoclonal Gammopathy of Undetermined Significance; Paraproteinemias; Plasma Cells; Skin Diseases
PubMed: 35411042
DOI: 10.1038/s41408-022-00661-1 -
American Journal of Hematology Jul 2021POEMS syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell...
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.
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. Risk factors include low serum albumin, age, pleural effusion, pulmonary hypertension, and reduced eGFR.
RISK-ADAPTED THERAPY
For those patients with a dominant 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. 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; Disease Management; Humans; POEMS Syndrome; Risk Assessment; Risk Factors
PubMed: 34000085
DOI: 10.1002/ajh.26240 -
Journal of Neuroimmune Pharmacology :... Dec 2021Autoimmune neurological disorders are commonly treated with immunosuppressive therapy. In patients with refractory conditions, standard immunosuppression is often... (Review)
Review
Autoimmune neurological disorders are commonly treated with immunosuppressive therapy. In patients with refractory conditions, standard immunosuppression is often insufficient for complete recovery or to prevent relapses. These patients rely on other treatments to manage their disease. While treatment of refractory cases differs between diseases, intravenous immunoglobulin, plasma exchange (PLEX), and immune-modulating treatments are commonly used. In this review, we focus on five autoimmune neurological disorders that were the themes of the 2018 Midlands Neurological Society meeting on PLEX in refractory neurology: Autoimmune Encephalitis (AE), Multiple Sclerosis (MS), Neuromyelitis Optica Spectrum disorders (NMOSD), Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) and Myasthenia Gravis (MG). The diagnosis of inflammatory neuropathies is often challenging, and while PLEX can be very effective in refractory autoimmune diseases, its ineffectiveness can be confounded by misdiagnosis. One example is POEMS syndrome (characterized by Polyneuropathy Organomegaly, Endocrinopathy, Myeloma protein, Skin changes), which is often wrongly diagnosed as CIDP; and while CIDP responds well to PLEX, POEMS does not. Accurate diagnosis is therefore essential. Success rates can also differ within 'one' disease: e.g. response rates to PLEX are considerably higher in refractory relapsing remitting MS compared to primary or secondary progressive MS. When sufficient efforts are made to correctly pinpoint the diagnosis along with the type and subtype of refractory autoimmune disease, PLEX and other immunotherapies can play a valuable role in the patient management.
Topics: Humans; Immunoglobulins, Intravenous; Multiple Sclerosis; Neuromyelitis Optica; Plasma Exchange; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
PubMed: 34599742
DOI: 10.1007/s11481-021-10004-9 -
The Malaysian Journal of Pathology Dec 2017POEMS syndrome is the syndrome of Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein and typical Skin changes. A 65-year-old lady presented with the...
POEMS syndrome is the syndrome of Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein and typical Skin changes. A 65-year-old lady presented with the 2-day-history of inability to walk, 4-month-history of progressive worsening of muscle weakness of both lower limbs and 1-year-history of progressive worsening of bilateral numbness of lower limbs. Nerve conduction study revealed generalized sensorimotor demyelinating polyneuropathy. She was initially treated as chronic inflammatory demyelinating polyradiculoneuropathy with intravenous immunoglobulin (IVIG) and high-dose prednisolone. However, she had no significant neurological improvement despite getting standard therapy. In addition to peripheral neuropathy, the presence of hepatosplenomegaly, skin changes, polycythaemia and thrombocytosis prompted for further investigations. She was diagnosed as POEMS syndrome based on the presence of two mandatory major criteria [polyneuropathy, monoclonal plasma cell proliferative disorder (lambda)], one major criterion (sclerotic bone lesions) and three minor criteria (organomegaly, skin changes and thrombocytosis/polycythaemia). She received treatment with melphalan and prednisolone. She achieved clinical improvement and partial response (haematologic and radiological) after six cycles of therapy. We highlight the awareness of this rare syndrome, for patients presenting with peripheral neuropathy and not responding to its standard therapy, by recognizing other associated clinical manifestations and proceeding further diagnostic work-up.
Topics: Aged; Anti-Inflammatory Agents; Female; Humans; Melphalan; Myeloablative Agonists; POEMS Syndrome; Prednisolone
PubMed: 29279594
DOI: No ID Found -
HemaSphere Nov 2022Polyneuropathy Organomegaly, Endocrinopathy, Monoclonal protein and Skin changes syndrome is a rare multisystem condition with a range of manifestations which are often... (Review)
Review
Polyneuropathy Organomegaly, Endocrinopathy, Monoclonal protein and Skin changes syndrome is a rare multisystem condition with a range of manifestations which are often overlooked as trivial comorbidities, until their whole triggers the possibility of the diagnosis. The diagnosis is typically delayed by 12-16 months, by which time patients can be severely disabled. There are no established consensus guidelines. We provide clinicians a comprehensive blueprint for managing POEMS from diagnostic suspicion through the work-up, selection of therapy, follow-up, and treatment of relapse based on published evidence and our large single-center experience. A multidisciplinary approach is essential including expert hematologists, neurologists, histopathologists, radiologists, and neurophysiologists. The aim of treatment is to eradicate the underlying plasma cell dyscrasia, but there are limited trial data to guide treatment decisions. Supportive care considerations include management of endocrinopathy, neuropathy, thrombosis, and infection. Response assessment is centered on clinical, neuropathy, hematological, vascular endothelial growth factor, and radiological criteria. Future clinical trials are welcomed in this setting where evidence is limited.
PubMed: 36340912
DOI: 10.1097/HS9.0000000000000796