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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 -
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 -
Nature Reviews. Disease Primers Nov 2021Castleman disease (CD), a heterogeneous group of disorders that share morphological features, is divided into unicentric CD and multicentric CD (MCD) according to the... (Review)
Review
Castleman disease (CD), a heterogeneous group of disorders that share morphological features, is divided into unicentric CD and multicentric CD (MCD) according to the clinical presentation and disease course. Unicentric CD involves a solitary enlarged lymph node and mild symptoms and excision surgery is often curative. MCD includes a form associated with Kaposi sarcoma herpesvirus (KSHV) (also known as human herpesvirus 8) and a KSHV-negative idiopathic form (iMCD). iMCD can present in association with severe syndromes such as TAFRO (thrombocytopenia, ascites, fever, reticulin fibrosis and organomegaly) or POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder and skin changes). KSHV-MCD often occurs in the setting of HIV infection or another cause of immune deficiency. The interplay between KSHV and HIV elevates the risk for the development of KSHV-induced disorders, including KSHV-MCD, KSHV-lymphoproliferation, KSHV inflammatory cytokine syndrome, primary effusion lymphoma and Kaposi sarcoma. A CD diagnosis requires a multidimensional approach, including clinical presentation and imaging, pathological features, and molecular virology. B cell-directed monoclonal antibody therapy is the standard of care in KSHV-MCD, and anti-IL-6 therapy is the recommended first-line therapy and only treatment of iMCD approved by the US FDA and EMA.
Topics: Antibodies, Monoclonal; Castleman Disease; HIV Infections; Herpesvirus 8, Human; Humans; Sarcoma, Kaposi
PubMed: 34824298
DOI: 10.1038/s41572-021-00317-7 -
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 -
Blood Advances Dec 2020Castleman disease (CD) includes a group of rare and heterogeneous disorders with characteristic lymph node histopathological abnormalities. CD can occur in a single...
Castleman disease (CD) includes a group of rare and heterogeneous disorders with characteristic lymph node histopathological abnormalities. CD can occur in a single lymph node station, which is referred to as unicentric CD (UCD). CD can also involve multicentric lymphadenopathy and inflammatory symptoms (multicentric CD [MCD]). MCD includes human herpesvirus-8 (HHV-8)-associated MCD, POEMS-associated MCD, and HHV-8-/idiopathic MCD (iMCD). The first-ever diagnostic and treatment guidelines were recently developed for iMCD by an international expert consortium convened by the Castleman Disease Collaborative Network (CDCN). The focus of this report is to establish similar guidelines for the management of UCD. To this purpose, an international working group of 42 experts from 10 countries was convened to establish consensus recommendations based on review of treatment in published cases of UCD, the CDCN ACCELERATE registry, and expert opinion. Complete surgical resection is often curative and is therefore the preferred first-line therapy, if possible. The management of unresectable UCD is more challenging. Existing evidence supports that asymptomatic unresectable UCD may be observed. The anti-interleukin-6 monoclonal antibody siltuximab should be considered for unresectable UCD patients with an inflammatory syndrome. Unresectable UCD that is symptomatic as a result of compression of vital neighboring structures may be rendered amenable to resection by medical therapy (eg, rituximab, steroids), radiotherapy, or embolization. Further research is needed in UCD patients with persisting constitutional symptoms despite complete excision and normal laboratory markers. We hope that these guidelines will improve outcomes in UCD and help treating physicians decide the best therapeutic approach for their patients.
Topics: Antineoplastic Agents; Castleman Disease; Consensus; Herpesvirus 8, Human; Humans; Rituximab
PubMed: 33284946
DOI: 10.1182/bloodadvances.2020003334 -
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