POEMS syndrome …

Neuroimmunology

Updated 08.10.2023
Released 05.08.1995
Expires For CME 08.10.2026

POEMS syndrome

Authors: Joan Blade MD PhD, M Teresa Cibeira MD PhD

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Editor: Francesc Graus MD PhD

POEMS syndrome

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Introduction

Overview

POEMS syndrome is a rare multisystem disease with unknown pathogenesis; it is classified as a plasma cell dyscrasia. Although neuropathy is the dominant clinical feature, the syndrome is characterized by a constellation of manifestations, including but not limited to those referred by the acronym: polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes. In this article, the authors discuss the biological basis, clinical presentation, diagnosis, and treatment options, including autologous peripheral blood stem cell transplantation and other emerging therapies.

Key points

	• POEMS syndrome is a rare multisystem disease caused by an underlying plasma cell dyscrasia.
	• The acronym POEMS refers to polyneuropathy (dominant clinical feature), organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes, although many other features may be intermixed.
	• The diagnosis is made based on a composite of clinical and lab features. An accurate differential diagnosis should be made to avoid misdiagnosis and improper therapeutic management.
	• Treatment targets the underlying plasma cell clone with a risk-adapted therapy.

Historical note and terminology

The first case of what we now know as POEMS syndrome was reported in 1938 by Scheinker (86). Almost 20 years later, Crow described two patients with multiple myeloma and peripheral neuropathy in his paper titled “Peripheral neuritis in myelomatosis.” Both patients presented with peripheral neuropathy and had lytic and sclerotic bone lesions, skin pigmentation, and normal sedimentation rates (14). Twelve years later, other author described a patient with plasmacytoma, polyneuritis, and endocrine abnormalities (92). In 1973, Yodoi described the association of myeloma, polyneuropathy, endocrinopathy, and skin pigmentation and postulated this to be a new syndrome (112). A few years later, Takatsuki and coworkers reviewed 32 patients with polyneuropathy, endocrinopathy, and a plasma cell disorder (98). In 1980, Bardwick and colleagues described similar findings in American patients and coined the term POEMS (polyneuropathy, organomegaly, endocrinopathy, presence of a monoclonal band and skin changes) (06). It has also been referred as Crow-Fukase syndrome, Takatsuki syndrome, PEP syndrome (plasma cell dyscrasia, endocrine disturbances and polyneuropathy), osteosclerotic myeloma, and Japanese multisystem syndrome.

Clinical manifestations

Presentation and course

The acronym POEMS refers to polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes. However, many other features may be intermixed, including sclerotic bone lesions, Castleman disease, peripheral edema, papilledema, thrombocytosis, respiratory dysfunction, renal disease, and various other systemic manifestations. Each one of these manifestations is described below.

Polyneuropathy. The most common manifestation of POEMS syndrome is peripheral neuropathy, and it is present in all patients with the disease. Symptoms typically start with distal and symmetrical numbness, tingling, prickly pain, or aches in the feet (52), and progress in a "glove and stocking distribution" with motor involvement following the sensory symptoms and leading to progressive weakness. The neuropathy involves small and large fibers equally.

Deep tendon reflexes are lost early. Progression varies among patients, causing some to be bedbound, and ultimately can lead to death. In advanced stages, marked atrophy of distal muscles occurs. Pure motor or pure sensory syndromes have been described. Sphincter dysfunction and cranial nerve involvement are rare.

Electrophysiologic studies reveal demyelinating and axonal features with prolonged distal motor latencies and marked slowing of conduction velocities (from segmental demyelination), reduced motor amplitudes, fibrillations, positive sharp waves, and enlarged, polyphasic motor unit action potentials (from axonal damage). Several electrophysiologic patterns were identified in patients with POEMS syndrome, which are distinct from other types of polyneuropathies. Nerve conduction slowing is typically predominant in the intermediate rather than distal nerve segments, is more severe and frequent in the lower rather than upper limbs, motor rather than sensory fibers are more greatly affected, and conduction block is infrequent (6%) relative to other demyelinating diseases (96; 73). In this sense, a greater axonal loss, greater slowing of the intermediate nerve segments, less common temporal dispersion and conduction block, and absent sural sparing can be very useful to differentiate POEMS from chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), with which it is often confused (71).

Cerebrospinal fluid shows a moderate to marked elevation of protein. In 102 patients with POEMS syndrome, 97% had elevated cerebrospinal fluid protein (greater than 50 mg/dL), and 30% had levels greater than 200 mg/dL (78). Similar results were noted in another series with 109 patients (97).

Peripheral nerve biopsies most often show a mixture of axonal degeneration and segmental demyelination. Mononuclear cell infiltration is rarely seen, with case reports of a few scattered mononuclear cells in the endoneurium as well as in the perivascular spaces of the endoneurium and epineurium (102; 103). Immunoglobulin deposits rarely have been described in the endoneurium that have corresponded to the monoclonal antibody in the serum (44; 01). Amyloid deposition is absent. Uncompacted myelin lamellae are highly present in peripheral nerve biopsy specimens of most patients with POEMS syndrome, so their demonstration on a thorough ultrastructural examination can be strongly suggestive of this disease (102; 103). Also, a greater axonal degeneration and epineurial neovascularization compared to CIDP, which has greater endoneurial inflammation and onion-bulb formation, may help to differentiate between these two commonly confused entities (81).

Ocular manifestations include blurred vision, diplopia, and ocular pain (50). Bilateral optic disc edema (papilledema) is the most common ocular finding (52%), whereas proptosis (33), peripapillary choroidal neovascularization (18), and peripheral retinal leakage (10) are less frequent. Measure of lumbar puncture opening pressure (50), optical coherence tomography (30), and fundus fluorescein angiography (10) have been used to evaluate and monitor these ophthalmologic findings in POEMS.

Organomegaly and Castleman disease. Liver (83%), spleen (24%), and lymph nodes (42%) are the commonly enlarged organs in POEMS syndrome (98; 78; 74). In total, 50% of patients from a large Mayo Clinic series had organomegaly (24). Histologic examination of enlarged lymph nodes may show Castleman disease or reactive changes. Enlargement of other organs, such as kidneys, thyroid, parotid, and heart, has also been reported.

Castleman disease (CD), also known as angiofollicular lymph node hyperplasia, is a rare lymphoproliferative disorder whose presentation may range from a single enlarged lymph node or region of lymph nodes (unicentric Castleman disease [UCD]) to multiple masses (multicentric Castleman disease [MCD]) that can be associated to a multiple manifestations such as B symptoms, autoimmune phenomena, or POEMS syndrome. The latest association is known as POEMS-MCD and should be distinguished from human herpes virus-8 associated MCD and idiopathic MCD (22).

Endocrinopathy. Endocrine abnormalities vary among reported series, usually due to hormone insufficiency involving the four major endocrine axes (gonadal, thyroid, glucose metabolism, and adrenal). In one large series from the Mayo Clinic, 84% of patients had a recognized endocrinopathy, hypogonadism being the most common (34). Men can develop impotence, gynecomastia, testicular atrophy, and reduced testosterone level as well as elevated estrogen, follicle-stimulating hormone, and luteinizing hormone. Women can experience amenorrhea with decreased luteinizing and follicle-stimulating hormone levels. Diabetes mellitus occurs in nearly 50% of cases. In another series, hypogonadism was followed by hyperprolactinemia (56%), hypothyroidism (54%), abnormal glucose metabolism (24%), adrenal insufficiency (17%; Addison disease), and hypoparathyroidism (09). Hypothyroidism has been associated with inferior survival (110). Spontaneous resolution of endocrine abnormalities can occur, so on-going treatment should remain under review.

Monoclonal plasma cell disorder. According to the new criteria for POEMS syndrome, all patients by definition have a clonal proliferative disorder (19). In a previously published Mayo Clinic series, a serum or urine monoclonal (M)-protein was found in 88% of patients, usually of small size (median serum M-spike of 11 g/L), with the light chain being almost always of lambda type and the associated heavy chain of IgA or IgG isotype (24). However, IgG kappa chains, IgE, and IgM bands have also been reported. In patients without M-protein by immunofixation, clonality can be demonstrated by immunohistochemical staining of bone marrow or sclerotic bone lesions, although bone marrow plasma cell population is usually 10% or less (24). Dao and colleagues studied the bone marrow histopathology in pretreatment samples from 67 patients with POEMS syndrome (16). Based on their findings, the constellation of monotypic (lambda-restricted) plasma cells, lymphoid aggregates rimmed by plasma cells, and megakaryocyte hyperplasia is considered highly suggestive of this diagnosis, especially in the proper clinical context. In those patients without clonal plasma cells on their bone marrow biopsy, histologic evaluation of a bone lesion should be considered.

Less frequently, POEMS syndrome can be associated with multiple myeloma (usually the osteosclerotic type), plasmacytoma, Waldenström macroglobulinemia, or lymphoproliferative disorders (78; 57). Castleman disease is also clearly associated with POEMS syndrome (11% to 30% of cases) as previously described, although the nature of the correlation is not well understood (22).

Skin changes. Cutaneous findings are present in 68% of patients and include hyperpigmentation, hypertrichosis, thickened skin, hyperhidrosis, thin white nails (Terry nails), “clubbing,” sclerodermatous changes with Raynaud phenomenon, alopecia, and edema of the skin. Lesions may resemble generalized histiocytomas (17). Glomeruloid hemangiomas, characterized by its histological resemblance to renal glomeruli, are specific cutaneous markers for POEMS syndrome and have immunologic features that differ from traditional hemangiomas and littoral angiomas of the spleen (58; 101). Although rare, histologically proven vasculitic lesions have also been described (89).

Osteosclerotic bone lesions. Bone lesions have been described in 50% to 96% of patients with POEMS syndrome as either purely sclerotic or mixed sclerotic and lytic on radiographic bone surveys (97; 78; 24). In a retrospective study, computed tomography (CT) assessment demonstrated a high sensitivity in identifying sclerotic lesions (38). In this study, skeletal survey had a false negative rate of 36%, whereas CT showed at least one lesion in all evaluated patients, the most common pattern being multiple small lesions of less than 1 cm; CT also proved to be useful in the response evaluation. Larger lesions had lytic centers with sclerotic margins and used to be 18F- fluorodeoxyglucose (FDG) avid by positron emission tomography (PET). Although only able to detect metabolic active bone lesions, PET has shown to contribute to the diagnosis, evaluation, and monitoring response to treatment in patients with high baseline FDG uptake (02; 93; 38). Finally, a case of POEMS syndrome with destructive polyarthritis and multicentric Castleman disease has been described (11).

Vascular manifestations. Both arterial and venous thromboses have been described in up to 30% of patients with POEMS syndrome (84; 72). In the United Kingdom registry, arterial events were more frequent and included strokes, peripheral arterial occlusions, myocardial infarctions, and microvascular disease, whereas venous events consisted of deep vein thromboses (DVT), pulmonary embolisms, and peripherally inserted central catheter-associated deep vein thromboses (84). Mellors and colleagues analyzed a retrospective cohort of 230 patients with POEMS syndrome and identified thrombocytosis, polyglobulia, extravascular volume overload, and splenomegaly as risk factors for arterial events, whereas hyperprolactinemia was considered a risk factor for venous thrombosis (72). Moreover, thrombosis recurrence was observed in 21% of patients. On the other hand, it has been suggested that vasculopathy might be induced by the overproduction of cytokines and systemic inflammation due to POEMS syndrome (32). According to all these findings, antiplatelet prophylaxis in all patients with POEMS syndrome and consideration of anticoagulation in those with risk factors for thrombosis has been recommended (84; 72).

Anecdotally, cardiomegaly was postulated to have been part of organomegaly in a 51-year-old woman and improved after treatment of the POEMS syndrome (91), and pericarditis leading to tamponade with elevated IL-6 in the pericardial fluid was described in a study (90).

Respiratory manifestations. In a large series of 137 patients with POEMS syndrome from the Mayo Clinic, 28% presented with pulmonary manifestations, including pulmonary hypertension, restrictive lung disease, respiratory muscle weakness, and an isolated diminished diffusing capacity (03). In a series of 154 patients, pulmonary hypertension was identified in 27% and was associated with signs of extravascular volume overload; although reversible with treatment, pulmonary hypertension was associated with worse survival (68). Pleural effusions, pulmonary edema, and chylothorax have also been reported (61; 15).

Extravascular volume overload. Extravascular volume overload is present in approximately one third of patients, mainly as peripheral edema (24% of patients) and less frequently as ascites (7%) or pleural effusion (3%) (24).

Hematologic manifestations. Polycythemia and mainly thrombocytosis are common findings in POEMS syndrome (24). In this sense, megakaryocyte hyperplasia and megakaryocyte clustering were found in the bone marrow biopsy of 54% and 93% patients, in the absence of JAK2V617F mutation (16). Anemia is infrequent (hemoglobin lower than 110 g/L in fewer than 5% of patients), and none of the patients in the Mayo Clinic series progressed to overt multiple myeloma (24). There is a well-acknowledged prothrombotic state as previously discussed (see vascular manifestations).

Renal manifestations. Renal involvement is considered a rare complication in POEMS syndrome (24). However, in a large series of patients from China, impairment of renal function was found to be common (22.4%), mostly moderate (77.6% had estimated glomerular filtration rate of 30 to 59 mL/min/1.73 m2) and reversible after treatment in 66% of cases (111). In this study and consistently with previous reports, renal pathologic findings consisted of glomerular changes with marked endothelial proliferation and capillary collapse (77; 111).

Psychiatric involvement. The incidence of depression is reported as 38%, with extent of neuropathy, upper limb function, and ascites reported as significant independent predictors (115).

Prognosis and complications

In the first published series of patients with POEMS syndrome, the mean survival was 33 months in 102 patients (78), and the estimated 5-year survival was 60% in another series with 38 patients (74). In a large series of 291 patients from the Mayo Clinic, a 10-year overall survival of 62% was reported confirming the very good long-term outcomes of patients with this disease (59). On the multivariate analysis, younger age, albumin greater than 32 g/L, and attainment of complete hematologic response were factors associated with superior overall survival (59; 60).

Clinical vignette

A 43-year-old woman without relevant past medical history complained of paresthesia and neuropathic pain in her legs under her knees leading to progressive difficulty in walking over the previous 6 months.

Electrophysiologic studies demonstrated a demyelinating sensory-motor polyneuropathy, and the patient progressively developed asthenia and dyspnea on exertion. The diagnosis of rheumatic polymyalgia had been suspected, and the patient had received treatment with prednisone and intravenous immunoglobulin without improvement.

On physical examination, she presented with peripheral edema in her legs, moderate hepatomegaly, and skin lesions consisting of telangiectasias and acrocyanosis. Laboratory examinations revealed thrombocytosis of 550 x109/L, a serum IgA-lambda monoclonal spike of 7.5 g/L (Bence Jones protein was negative) with 9% plasma cells in the bone marrow aspirate, and hyperprolactinemia together with a subclinical hypothyroidism. No VEGF was available at that time (in 2001). Radiological skeletal survey showed sclerotic bone lesions in both humeri and proximal left femur.

Sclerotic bone lesions in the right humerus

Sclerotic bone lesions (see arrows) in the right humerus. (Contributed by Joan Blade.)

Echocardiography suggested a severe pulmonary hypertension that was confirmed by hemodynamic studies, and lung function test showed a severe restrictive lung disease. She also presented bilateral papilledema by funduscopy. A CT scan found homogeneous liver enlargement without lymphadenopathy.

This patient fulfilled both mandatory major criteria (polyneuropathy and monoclonal gammopathy), one additional major criterion (sclerotic bone lesions), and at least five minor criteria for POEMS syndrome as well as associated pulmonary hypertension.

Given her poor performance status at presentation, she was considered not to be a good transplant candidate and received cyclophosphamide and prednisone together with supportive therapy (diuretics and anticoagulation). Clinical improvement was evident after two cycles of chemotherapy, and she was eventually able to receive high-dose melphalan and stem cell rescue. After transplant, the patient achieved a complete hematologic response and mild improvement of polyneuropathy as well as a significant clinical improvement of the remaining clinical features of the disease. This response lasted for 12 years.

Biological basis

Etiology and pathogenesis

Although the underlying plasma cell dyscrasia in POEMS syndrome suggests an antibody-mediated etiopathogenesis, the features of the disease are not explained by immune-mediated processes alone. Pathologic review of affected organs does not support paraprotein deposition as a mechanism of disease either (78; 102; 103), even though the association between monoclonal plasma cells and activity of the disease is well established (51). Overproduction of proinflammatory cytokines and angiogenic growth factors, mainly vascular endothelial growth factor (VEGF), are believed to play an important pathogenic role (109). However, there is no unifying explanation for all the features of POEMS syndrome, and the pathogenesis remains unknown.

Regarding vascular endothelial growth factor, significantly elevated serum levels have been found in POEMS syndrome, higher than in other monoclonal gammopathies and other neurologic diseases (Watanabe et al 1996, 107), and decreased levels in correlation with response to conventional therapy have been described (107; 85). VEGF is secreted by platelets during platelet aggregation (40) and possibly by plasma cells (107). Interestingly, some studies suggested that the major source of serum VEGF were polyclonal plasma cells, whereas POEMS clones might produce proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6), which in turn induce VEGF production (37; Wang et a 2016; 45). This could lead to aggregation of platelets on vascular walls and elevated local VEGF concentration, promoting vascular permeability, angiogenesis, and monocyte and macrophage migration. These mechanisms could explain the arterial obliteration, microthrombosis, edema, organomegaly, pulmonary hypertension, skin changes, and neuropathy. Overexpression of VEGF is thought to affect peripheral nerves by causing endoneurial edema and microangiopathy of endoneurial vessels (85). Glomeruloid hemangiomas, thought to be highly specific for POEMS syndrome, are believed to be a reactive endothelial proliferation in response to angiogenic stimuli (101). However, the cause of VEGF overproduction remains to be elucidated. Agents that specifically reduce VEGF levels, such as ticlopidine (70) and bevacizumab (05), have been reported to improve disease symptoms, but the response appears to be inconsistent (87), suggesting that other angiogenic growth factors might be playing a role (109).

Nagao and colleagues performed a comprehensive genetic analysis of plasma cells from 20 patients with POEMS syndrome, including whole exome sequencing, targeted sequencing, and RNA sequencing (76). They identified 20 mutations in seven recurrently mutated genes (not including any of the driver gene mutations frequently found in multiple myeloma) as well as a specific transcription profile. In contrast, Chen and colleagues performed a similar analysis and revealed heterogeneous genomic profiles of bone marrow plasma cells that might share similarities to other plasma cell disorders (12).

Diagnostic workup

The diagnosis of POEMS syndrome is based on a combination of clinical and laboratory features and requires a good history and physical examination, including a whole neurologic and skin evaluation. The following studies should be performed in a patient with clinical suspicion of POEMS syndrome (23; 22).

	• Blood test with a complete blood count, sedimentation rate, electrolytes, urea, creatinine, liver function tests, 24-hour urine total protein, and serum and urine immunoglobulin electrophoresis and immunofixation.
	• Serum VEGF measurement.
	• Endocrine screening, including testing for diabetes and pituitary and thyroid dysfunction as well as assessment of bone metabolism.
	• In the presence of a monoclonal band and a neuropathy, bone marrow aspiration is required to search for a plasma cell malignancy.
	• If no serum or urine monoclonal protein is detected and the clinical suspicion for POEMS syndrome is high, immunohistochemical staining of biopsy specimens from skeletal lesions or bone marrow is indicated.
	• Electromyography is needed to determine the nature of the polyneuropathy.
	• A skeletal survey for osteolytic or osteosclerotic lesions should be undertaken in all patients. CT imaging and PET/CT should be considered.
	• Enlarged lymph nodes should be biopsied to diagnose lymphoproliferative disorders and neoplastic conditions. In this sense, 18F-FDG PET/CT may be useful in detecting and selecting bone lesions and lymph nodes for biopsy (02).
	• According to clinical symptoms, echocardiography to assess right ventricular systolic and pulmonary artery pressures, as well as pulmonary function tests including DLCO, might be needed.

New criteria for the diagnosis of POEMS syndrome were proposed from a retrospective study of 99 patients (24). Clinical features were divided into mandatory major, major, and minor criteria (Table 1). Both mandatory major criteria, together with at least one of three major and one of the six minor criteria are necessary for the diagnosis.

Table 1. Criteria for the Diagnosis of POEMS Syndrome

Mandatory major criteria
	• Polyneuropathy • Monoclonal plasma cell-proliferative disorder
Major criteria
	• Sclerotic bone lesions • Castleman disease • Increased levels of VEGF
Minor criteria
	• Organomegaly (splenomegaly, hepatomegaly, or lymphadenopathy) • Extravascular volume overload (edema, pleural effusion, or ascites) • Endocrinopathy (adrenal, thyroid, pituitary, gonadal, parathyroid, pancreatic) • Skin changes (hyperpigmentation, hypertrichosis, plethora, glomeruloid hemangiomata, acrocyanosis, flushing, white nails) • Papilledema • Thrombocytosis or polycythemia
Other known associations
	• Clubbing • Weight loss • Hyperhidrosis • Pulmonary hypertension or restrictive lung disease • Thrombotic diathesis • Low vitamin B12 values • Diarrhea
* Diabetes mellitus and thyroid abnormalities are not sufficient alone to meet the minor criterion due to their high prevalence.
Adapted from (24)

Management

The aim of therapy in POEMS syndrome is to eradicate the plasma cell clone in order to obtain improvement of the clinical manifestations of the disease, particularly the peripheral neuropathy. Due to the low frequency of this disease, few controlled clinical trials and even fewer randomized trials have been conducted. Consequently, there is no consensus regarding standard therapeutic regimens for POEMS syndrome. Most of the recommendations for treatment are based on small series of patients and experienced groups (20; 63; 22; 54; 49; 55). A systematic review of the most commonly used therapies for POEMS syndrome has also been published (31). In order to choose the appropriate treatment, bone marrow plasma cell infiltration and the number of osteosclerotic bone lesions should be taken into account (46; 22). Evaluation of response after treatment should consider different aspects of the disease (22): hematologic response (using a modified amyloid response criteria), organ response (mainly restricted to the dominant symptoms such as peripheral neuropathy, pulmonary function and extravascular overload), VEGF response, and PET/CT response (in patients with at least one FDG-avid lesion at diagnosis).

Patients with a limited number of osteosclerotic bone lesions (one to three) or with multiple small lesions in a limited area and without bone marrow involvement by clonal plasma cells can be treated with radiation therapy. The median radiation dose used in the Mayo Clinic series was 45 Gy (range, 35 to 54 Gy). In the same study, around half of the patients experienced significant symptom improvement and durable responses, with time to response of neurologic symptoms being about 3 to 6 months after treatment (43).

Systemic therapy targeting the underlying plasma cell clone is mandatory if the patient has bone marrow involvement by clonal plasma cells or more than three bone lesions. However, despite bone marrow involvement, radiation therapy can be considered in two situations: a) as primary therapy if the bone lesion is reasonably large and consider addition of systemic therapy depending on response at 6 to 12 months after radiation, or b) as adjuvant therapy in patients with large bony lesions with a significant lytic component and no response at 6 months after completing systemic therapy (22). Corticosteroids alone or in combination with alkylator-based therapies with melphalan or cyclophosphamide as well as immunosuppressant agents, such as cyclosporine or azathioprine with prednisone, have been of limited benefit (24; 69). The first therapeutic approach to show dramatic responses in this disease was high-dose melphalan with autologous stem cell transplant (ASCT) (42; 82; 48). Dispenzieri and colleagues reported responses in 14 of 16 patients who received this treatment, with neuropathy improvement in all of them, although with significant morbidity and transplant-related mortality in one patient (27). An update of this series with 59 patients who received an ASCT at the Mayo Clinic and a median follow-up of 45 months, showed a hematologic response rate of 78% (including 57% complete responses) and clinical improvement in 92% of patients (29). In this study, the 5-year progression-free survival and overall survival were 75% and 94%, respectively, and factors associated with progression were younger age (below 50 years), IgG-lambda isotype, presence of FDG-avid lesions on baseline PET, and lack of complete hematologic response (29). Similar results were reported in a large series of patients from the EBMT registry (13). No differences were observed between cyclophosphamide plus G-CSF versus G-CSF alone as a mobilization regimen of peripheral blood progenitors in a retrospective Italian study (04). Induction chemotherapy before ASCT is not mandatory, but it might help to obtain a rapid response, allowing some patients to undergo transplant in a better condition (46). Transplant-associated complications include engraftment syndrome, recognized in 37% of patients in the Mayo Clinic series (29), which could make it advisable to avoid the use of G-CSF after transplant according to previous experience in patients with MM (36; 39). Also, pulmonary complications requiring mechanical ventilation occurred in a third of patients in one series, with transplant-related mortality up to 7.5%, so an accurate pulmonary evaluation before ASCT is essential (27; 62). Finally, engraftment failure occurred in three of 123 patients in the EBMT registry (13) (stem cell backup recommended according to personal experience).

For those patients who are not candidates for radiation therapy nor for high-dose chemotherapy and ASCT, there is no consensus on the best treatment option. VEGF responses were reported with thalidomide plus dexamethasone, but it is not recommended as first-line therapy due to its potential neurotoxicity (75). Promising responses have been published with lenalidomide plus dexamethasone becoming a safe and effective treatment option even in the setting of newly diagnosed disease (83; 47; 113; 65; 79; 67) and in thalidomide-refractory patients (95). In this sense, Li and colleagues reported the results of a prospective phase 2 trial with 46% hematologic complete responses as well as neurologic and VEGF response rates of 95% and 83%, respectively, with a 3-year progression-free survival of 75%. Thrombotic risk associated with this regimen and the disease itself should be considered, and the type of prophylaxis should be individualized according to the risk of falls due to the neuropathy (22). The role of bortezomib to treat POEMS syndrome as a single agent, in combination with dexamethasone, or with cyclophosphamide and dexamethasone has also been supported by a number of case reports and a small series of patients with no significant neurologic worsening (105; 114; 41). More recently, the anti-CD38 monoclonal antibody daratumumab has been used in POEMS syndrome both alone (66; 100) and in combination, either with bortezomib-dexamethasone (56) or with lenalidomide-dexamethasone (53; 35), even followed by ASCT (99), in the context of POEMS-MCD (88), and in the presence of 17p deletion (80). The investigation of other new agents, such as pomalidomide or ixazomib (21), or even anti-B-cell maturation antigen (BCMA) chimaeric antigen receptor (CAR-T) cell therapy (108), is warranted. In contrast, the anti-VEGF monoclonal antibody bevacizumab is formally discouraged due to an observed increase in number of early deaths after its administration (94; 87).

Last but not least, a multidisciplinary approach including supportive care and emotional support is essential given the systemic nature of the disease and the common significant physical limitations it entails (08). In this sense, interventions such as analgesics for neuropathic pain, neurorehabilitation, orthopedic devices, or occupational therapy can be of great help in managing neuropathy. Dialysis may also be needed for advanced renal disease, antiplatelet agents in cases of thrombocytosis, phlebotomy for polyglobulia, and endocrine interventions for the specific disturbances. Finally, it is important to be aware of ineffective therapies such as intravenous immunoglobulins and plasma exchange, and to treat patients in the context of clinical trials whenever possible.

References

01: Adams D, Said G. Ultrastructural characterization of the M protein in nerve biopsy of patients with POEMS syndrome. J Neurol Neurosurg Psychiatry 1998;64(6):809-12. PMID 9647319
02: Alberti MA, Martinez-Yelamos S, Fernandez A, et al. 18F-FDG PET/CT in the evaluation of POEMS syndrome. Eur J Radiol 2010;76(2):180-2. PMID 19581061
03: Allam JS, Kennedy CC, Aksamit TR, Dispenzieri A. Pulmonary manifestations in patients with POEMS syndrome: a retrospective review of 137 patients. Chest 2008;133(4):969-74. PMID 18198255
04: Autore F, Piccirillo N, Nozza A, et al. Peripheral blood hematopoietic stem cell mobilization regimens in POEMS syndrome: a retrospective study at 2 hematologic Italian centers. Biol Blood Marrow Transplant 2019;25(12):2514-16. PMID 31445184
05: Badros A, Porter N, Zimrin A. Bevacizumab therapy for POEMS syndrome. Blood 2005;106(3):1135. PMID 16033956
06: Bardwick PA, Zvaifler NJ, Gill GN, et al. Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes: The POEMS syndrome. Medicine 1980;59:311-22. PMID 6248720
07: Barry JC, Gleichmann M, Wilhelm H. Bilateral optic disc edema in polyneuropathy, organomegaly, endocrinopathy, monoclonal proteins and skin changes (POEMS syndrome). Klin Monatsbl Augenheilkd 1999;215(1):59-63. PMID 10448640
08: Bou Zerdan M, George TI, Bunting ST, Chaulagain CP. Recent advances in the treatment and supportive care of POEMS syndrome. J Clin Med 2022;11(23):7011. PMID 36498588
09: Caimari F, Keddie S, Lunn MP, D’Sa S, Baldeweg SE. Prevalence and course of endocrinopathy in POEMS. J Clin Endocrinol Metab 2019;104(6):2140-6. PMID 30239770
10: Carey AR, Jeyaseelan P. Peripheral retinal leakage in POEMS syndrome. Int J Retina Vitreous 2021;7(1):6. PMID 33436019
11: Carpentier-Planchon V. A unique case of destructive polyarthritis associated with multicentric Castleman’s disease. Clin Imaging 2000;24(4):193-6.
12: Chen J, Gao XM, Zhao H, et al. A highly heterogeneous mutational pattern in POEMS syndrome. Leukemia 2021;35(4):1100-7. PMID 33262528
13: Cook G, Lacobelli S, van Biezen A, et al. High-dose therapy and autologous stem cell transplantation in patients with POEMS syndrome: a retrospective study of the Plasma Cell Disorder sub-committee of the Chronic Malignancy Working Party of the European Society for Blood & Marrow Transplantation. Haematologica 2017;102(1):160-7. PMID 27634201
14: Crow RS. Peripheral neuritis in myelomatosis. BMJ 1956;2:802-4. PMID 13364332
15: Cui RT, Yu SY, Huang XS, et al. Incidence and risk factors of pleural effusions in patients with POEMS syndrome. Hematol Oncol 2015;33(2):80-4. PMID 24519469
16: Dao LN, Hanson CA, Dispenzieri A, Morice WG, Kurtin PJ, Hoyer JD. Bone marrow histopathology in POEMS syndrome: a distinctive combination of plasma cell, lymphoid, and myeloid findings in 87 patients. Blood 2011;117(24):6438-44. PMID 21385854
17: Del Rio AM, Monteagudo J, Torremorell D, et al. POEMS syndrome and multiple angioproliferative lesions mimicking generalized histiocytomas. Acta Derm Venereol 1994;74:388-90. PMID 7817680
18: Diduszyn JM, Quillen DA, Cantore WA, Gardner TW. Optic disk drusen, peripapillary choroidal neovascularization, and POEMS syndrome. Am J Ophthalmol 2002;133(2):275-6. PMID 11812439
19: Dispenzieri A. POEMS syndrome: 2011 update on diagnosis, risk-stratification, and management. Am J Hematol 2011;86(7):591-601. PMID 21681783
20: Dispenzieri A. How I treat POEMS syndrome. Blood 2012;119(24):5650-8. PMID 22547581
21: Dispenzieri A. POEMS syndrome: 2019 update on diagnosis, risk stratification and management. Am J Hematol 2019;94(7):812-27. PMID 31012139
22: Dispenzieri A, Fajgenbaum DC. Overview of Castleman disease. Blood 2020;135(16):1353-64. PMID 32106302
23: Dispenzieri A, Kourelis T, Buadi F. POEMS syndrome: diagnosis and Investigative work-up. Hematol Oncol Clin North Am 2018;32(1):119-39.** PMID 29157614
24: Dispenzieri A, Kyle RA, Lacy MQ, et al. POEMS syndrome: definitions and long-term outcome. Blood 2003;101(7):2496-506. PMID 12456500
25: Dispenzieri A, Lacy MQ, Hayman SR, et al. Peripheral blood stem cell transplant for POEMS syndrome is associated with high rates of engraftment syndrome. Eur J Haematol 2008;80(5):397-406. PMID 18221391
26: Dispenzieri A, Mauermann M, LaPlant B, et al. A prospective pilot study of ixazomib, lenalidomide, and dexamethasone for patients with newly diagnosed or relapsed/refractory POEMS syndrome. Blood 2019;134(suppl1):1846.
27: Dispenzieri A, Moreno-Aspitia A, Suarez GA, et al. Peripheral blood stem cell transplantation in 16 patients with POEMS syndrome, and a review of the literature. Blood 2004;104(10):3400-7. PMID 15280195
28: Driedger H, Pruzanski W. Plasma cell neoplasia with osteosclerotic lesions. A study of five cases and study of the literature. Arch Intern Med 1979;139:892-6. PMID 223510
29: D'Souza A, Lacy M, Gertz M, et al. Long-term outcomes after autologous stem cell transplantation for patients with POEMS syndrome (osteosclerotic myeloma): a single-center experience. Blood 2012;120(1):56-62. PMID 22611150
30: Ecsedy M, Schneider M, Nemes J, Nemeth J, Recsan Z. Optical coherence tomography features of POEMS syndrome and Castleman disease-associated papillopathy. Ocul Immunol Inflamm 2014;22(6):454-60. PMID 24564641
31: Faizan U, Sana MK, Farooqi MS, Hashmi H. Efficacy and safety of regimens used for the treatment of POEMS syndrome – a systematic review. Clin Lymphoma Myeloma Leuk 2022;22(1):e26-33. PMID 34507924
32: Fu FW, Rao J, Zheng YY, Wang HL, Yang JG, Zheng GQ. Ischemic stroke in patients with POEMS syndrome: a case report and comprehensive analysis of literature. Oncotarget 2017;8(51):89406-24. PMID 29179528
33: Gandhi D, Vashisht S, Mahajan A, Kapoor A, Berry M. Proptosis with orbital soft tissue and bone changes and unilateral papilledema: unusual presentation of POEMS syndrome. Neurology 2001;56(6):807-10.
34: Gandhi GY, Basu R, Dispenzieri A, Basu A, Montori VM, Brennan MD. Endocrinopathy in POEMS syndrome: the Mayo Clinic experience. Mayo Clin Proc 2007;82(7):836-42. PMID 17605964
35: Gavriatopoulou M, Ntanasis-Stathopoulos I, Fotiou D, et al. Upfront daratumumab with lenalidomide and dexamethasone for POEMS syndrome. Hemasphere 2020;4(3):e381. PMID 32647800
36: Gertz MA, Gastineau DA, Lacy MQ, et al. SCT without growth factor in multiple myeloma: engraftment kinetics, bacteremia and hospitalization. Bone Marrow Transplant 2011;46(7):956-61. PMID 20972466
37: Gherardi RK, Belec L, Soubries M, et al. Overproduction of proinflammatory cytokines imbalanced by their antagonists in POEMS syndrome. Blood 1996;87:1458-65. PMID 8608236
38: Glazebrook K, Guerra Bonilla FL, Johnson A, Leng S, Dispenzieri A. Computed tomography assessment of bone lesions in patients with POEMS syndrome. Eur Radiol 2015;25(2):497-504. PMID 25253619
39: Gutiérrez-García G, Rovira M, Magnano L, et al. Innovative strategies minimize engraftment syndrome in multiple myeloma patients with novel induction therapy following autologous hematopoietic stem cell transplantation. Bone Marrow Transplant 2018;53(12):1541-7. PMID 29706650
40: Hashiguchi T, Arimura K, Matsumuro K, et al. Highly concentrated vascular endothelial growth factor in platelets in Crow-Fukase syndrome. Muscle Nerve 2000;23(7):1051-6. PMID 10882999
41: He H, Fu W, Du J, Jiang H, Hou J. Successful treatment of newly diagnosed POEMS syndrome with reduced-dose bortezomib based regimen. Br J Haematol 2018;181(1):126-8. PMID 28146276
42: Hogan WJ, Lacy MQ, Wiseman GA, Fealey RD, Dispenzieri A, Gertz MA. Successful treatment of POEMS syndrome with autologous hematopoietic progenitor cell transplantation. Bone Marrow Transplant 2001;28(3):305-9. PMID 11536000
43: Humeniuk MS, Gertz MA, Lacy MQ, et al. Outcomes of patients with POEMS syndrome treated initially with radiation. Blood 2013;122:66-73. PMID 23699599
44: Hyman BT, Westrick MA. Multiple myeloma with polyneuropathy and coagulopathy. A case report of the polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin change (POEMS) syndrome. Arch Intern Med 1986;146(5):993-4. PMID 3083799
45: Isshiki Y, Oshima M, Mimura, N, et al. Unraveling unique features of plasma cell clones in POEMS syndrome with single-cell analysis. JCI Insight 2022;7(20):e151482. PMID 36129760
46: Jaccard A. POEMS syndrome: therapeutic options. Hematol Oncol Clin North Am 2018;32(1):141-51.** PMID 29157615
47: Jaccard A, Lazareth A, Karlin L, et al. A prospective phase II trial of lenalidomide and dexamethasone (LEN-DEX) in POEMS syndrome. Blood 2014;124:36.
48: Jaccard A, Royer B, Bordessoule D, Brouet JC, Fermand JP. High-dose therapy and autologous blood stem cell transplantation in POEMS syndrome. Blood 2002;99(8):3057-9. PMID 11929800
49: Jurczyszyn A, Olszewska-Szopa M, Vesole D. POEMS syndrome-clinical picture and management. Current knowledge. Clin Lymphoma Myeloma Leuk 2023;23(8):575-82. PMID 37210272
50: Kaushik M, Pulido JS, Abreu R, et al. Ocular findings in patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome. Ophthalmology 2011;118(4):778-82. PMID 21035860
51: Kawajiri-Manako C, Mimura N, Fukuyo M, et al. Clonal immunoglobulin λ light-chain gene rearrangements detected by next generation sequencing in POEMS syndrome. Am J Hematol 2018;93(9):1161-8. PMID 30015379
52: Kelly JJ, Kyle RA, Myles JM, et al. The spectrum of peripheral neuropathy in myeloma. Neurology 1981;31:24-31. PMID 6256682
53: Khan M, Stone K, van Rhee F. Daratumumab for POEMS syndrome. Mayo Clin Proc 2018;93(4):542-4. PMID 29622102
54: Khouri J, Nakashima M, Wong S. Update on the diagnosis and treatment of POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome: a review. JAMA Oncol 2021;7(9):1383-91. PMID 34081097
55: Khwaja J, D'Sa S, Lunn MP, Sive J. Evidence-based medical treatment of POEMS syndrome. Br J Haematol 2023;200(2):128-36. PMID 35934319
56: Khwaja J, Keh R, Smyth D, Lunn MP, D’Sa S, Sive J. Daratumumab-bortezomib-dexamethasone use in relapsed POEMS syndrome. EJHaem 2022;3(3):1021-4. PMID 36051015
57: Kihara Y, Hori H, Murakami H, et al. A case of POEMS syndrome associated with reactive amyloidosis and Waldenstrom's macroglobulinaemia. J Intern Med 2002;252(3):255-8. PMID 12270006
58: Kishimoto S, Takenaka H, Shibagaki R, Noda Y, Yamamoto M, Yasuna H. Glomeruloid hemangioma in POEMS syndrome shows two different immunophenotypic endothelial cells. J Cutan Pathol 2000;27(2):87-92. PMID 10678704
59: Kourelis TV, Buadi FK, Kumar SK, et al. Long-term outcome of patients with POEMS syndrome: an update of the Mayo Clinic experience. Am J Hematol 2016a;91(6):585-9.** PMID 26972803
60: Kourelis TV, Buadi FK, Gertz MA, et al. Risk factors for and outcomes of patients with POEMS syndrome who experience progression after first line treatment. Leukemia 2016b;30:179-85. PMID 26669974
61: Kudo Y, Miura H, Nakajima E, Takahashi H, Aoki A, Ikeda N. Chylothorax in POEMS syndrome. Tohoku J Exp Med 2014;232(1):43-6. PMID 24477187
62: Kuwabara S. New strategy of treatment for POEMS syndrome--autologous peripheral blood stem cell transplantation and thalidomide therapy. Brain Nerve 2008;60(6):627-33. PMID 18567358
63: Kuwabara S, Dispenzieri A, Arimura K, Misawa S. Treatment for POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome. Cochrane Database Syst Rev 2012;(6):CD006828. PMID 22696361
64: Lee LN, Jan IS, Tien HF, Lin JS, Lo SC, Cheng WC. Laboratory and clinical characterization of monoclonal gammopathy in Taiwanese. J Formos Med Assoc 2002;101(2):91-7. PMID 12099210
65: Lestang E, Caristan A, Néel A, et al. Lenalidomide as frontline therapy in polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes syndrome: a retrospective case series of eight patients. Leuk Lymphoma 2015;56(6):1895-6. PMID 25347429
66: Leung B, Nelson T, Willenberg R, Burford M. Failure of daratumumab therapy for polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes syndrome. J Clin Neuromuscul Dis 2021;23(1):56-8. PMID 34431806
67: Li J, Huang XF, Cai QQ, et al. A prospective phase II study of low dose lenalidomide plus dexamethasone in patients with newly diagnosed polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. Am J Hematol 2018;93(6):803-9. PMID 29603764
68: Li J, Tian Z, Zheng HY, et al. Pulmonary hypertension in POEMS syndrome. Haematologica 2013;98(3):393-8. PMID 22983590
69: Li J, Zhang W, Jiao L, et al. Combination of melphalan and dexamethasone for patients with newly diagnosed POEMS syndrome. Blood 2011;117(24):6445-9. PMID 21393478
70: Matsui H, Udaka F, Kubori T, Oda M, Nishinaka K, Kameyama M. POEMS syndrome demonstrating VEGF decrease by ticlopidine. Intern Med 2004;43(11):1082-3. PMID 15609708
71: Mauermann ML, Sorenson EJ, Dispenzieri A, et al. Uniform demyelination and more severe axonal loss distinguish POEMS syndrome from CIDP. J Neurol Neurosurg Psychiatry 2012;83(5):480-6. PMID 22396441
72: Mellors PW, Kourelis T, Go RS, et al. Characteristics and risk factors for thrombosis in POEMS syndrome: a retrospective evaluation of 230 patients. Am J hematol 2022;97(2):209-15. PMID 34822175
73: Min JH, Hong YH, Lee KW. Electrophysiological features of patients with POEMS syndrome. Clin Neurophysiol 2005;116(4):965-8. PMID 15792906
74: Miralles GD, O'Fallon JR, Talley NJ. Plasma cell dyscrasia with polyneuropathy. The spectrum of POEMS syndrome. N Engl J Med 1992;327(27):1919-23. PMID 1333569
75: Misawa S, Sato Y, Katayama K, et al. Safety and efficacy of thalidomide in patients with POEMS syndrome: a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol 2016;15(11):1129-37. PMID 27496680
76: Nagao Y, Mimura N, Takeda J, et al. Genetic and transcriptional landscape of plasma cell in POEMS syndrome. Leukemia 2019;33(7):1723-35. PMID 30635632
77: Nakamoto Y, Imai H, Yasuda T, et al. A spectrum of clinicopathological features of nephropathy associated with POEMS syndrome. Nephrol Dial Transplant 1999;14(10):2370-8. PMID 10528660
78: Nakanishi T, Sobue I, Toyokura Y, et al. The Crow-Fukase syndrome: a study of 102 cases in Japan. Neurology 1984;34:712-20. PMID 6539431
79: Nozza A, Terenghi F, Gallia F, et al. Lenalidomide and dexamethasone in patients with POEMS syndrome: results of a prospective, open-label trial. Br J Haematol 2017;179(5):748-55. PMID 29048107
80: Oyama T, Taoka K, Chiba A, et al. Daratumumab plus lenalidomide and dexamethasone for relapsed POEMS syndrome with bone plasmacytoma harboring 17p deletion. Int J Hematol 2023;117(3):463-7. PMID 36202948
81: Piccione EA, Engelstad J, Dyck PJ, et al. Nerve pathologic features differentiate POEMS syndrome from CIDP. Acta Neuropathol Commun 2016;4(1):116. PMID 27799073
82: Rovira M, Carreras E, Blade J, et al. Dramatic improvement of POEMS syndrome following autologous haematopoietic cell transplantation. Br J Haematol 2001;115(2):373-5. PMID 11703338
83: Royer B, Merlusca L, Abraham J, et al. Efficacy of lenalidomide in POEMS syndrome: a retrospective study of 20 patients. Am J Hematol 2013;88:207-12. PMID 23335406
84: Sayar Z, Weatherill A, Keddie S, et al. High rates of venous and arterial thrombotic events in patients with POEMS syndrome: results from the UCLH (UK) POEMS registry. Blood Adv 2020;4(10):2139-42. PMID 32421810
85: Scarlato M, Previtali SC, Carpo M, et al. Polyneuropathy in POEMS syndrome: role of angiogenic factors in the pathogenesis. Brain 2005;128(Pt 8):1911-20. PMID 15975949
86: Scheinker Y. Myelom und Nerveensystem: Über eine bisher nicht beschriebene mit eigentümlichen Haut-veränderungen einhergehende Polyneuritis bei einem plasmazellulären Myelom des Sternums. Dtsch Z Nervenheilkd 1938;147:247.
87: Sekiguchi Y, Misawa S, Shibuya K, et al. Ambiguous effects of anti-VEGF monoclonal antibody (bevacizumab) for POEMS syndrome. J Neurol Neurosurg Psychiatry 2013;84(12):1346-8. PMID 23463868
88: Sevindik OG, Mutlu YG, Aydin BB, Serin I. First-line usage of daratumumab, lenalidomide, dexamethasone (DRd) combination in a case of Castleman disease variant of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome (CD-POEMS). Hemasphere 2022;6(7):e728. PMID 35747589
89: Sharabi Y, Raanani P, Shenkar A, Thaler M, Grossman E. Plasma cell dyscrasia with polyneuropathy--POEMS syndrome presenting with vasculitic skin lesions and responding to combination chemotherapy. Leuk Lymphoma 2000;40(1-2):209-13. PMID 11426623
90: Shikama N, Isono A, Otsuka Y, Terano T, Hirai A. A case of POEMS syndrome with high concentration of interleukin-6 in pericardial fluid. J Intern Med 2001;250(2):170-3. PMID 11489068
91: Shimizu N, Goya M, Akimoto H, et al. Cardiomyopathy in a case of Crow-Fukase syndrome. Jpn Heart J 1997;38(6):877-80. PMID 9486942
92: Shimpo S, Nishitani H, Tsunematsu T, Kawaguchi Y, Ito K. Solitary plasmacytoma with polyneuritis and endocrine disturbances. Nippon Rinsho 1968;26:2444-56. PMID 5752014
93: Stefanelli A, Treglia G, Leccisotti L, et al. Usefulness of F-18 FDG PET/CT in the follow-up of POEMS syndrome after autologous peripheral blood stem cell transplantation. Clin Nucl Med 2012;37(2):181-3. PMID 22228347
94: Straume O, Bergheim J, Ernst P. Bevacizumab therapy for POEMS syndrome. Blood 2006;107(12):4972-73. PMID 16754779
95: Suichi T, Misawa S, Nagashima K, et al. Lenalidomide treatment for thalidomide-refractory POEMS syndrome: a prospective single-arm clinical trial. Intern Med 2020;59(9):1149-53. PMID 32009091
96: Sung JY, Kuwabara S, Ogawara K, Kanai K, Hattori T. Patterns of nerve conduction abnormalities in POEMS syndrome. Muscle Nerve 2002;26(2):189-93. PMID 12210381
97: Takatsuki K, Sanada I. Plasma cell dyscrasia with polyneuropathy and endocrine disorder: clinical and laboratory features of 109 reported cases. Jpn J Clin Oncol 1983;13:543-55. PMID 6315993
98: Takatsuki K, Uchiyama T, Sagawa K, et al. Plasma cell dyscrasia with polyneuropathy and endocrine disorder: review of 32 patients, in Topics in Hematology. Excerpta Medica, International congress series 415. Amsterdam: Elsevier Publishing Co., 1977:454-7.
99: Taenaka R, Shimokawa S, Katayama A, et al. Successful treatment with daratumumab, lenalidomide and dexamethasone therapy followed by autologous stem cell tranaplantation for newly diagnosed polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome: a case report. J Med Case Rep 2022;16(1):311. PMID 35978379
100: Tiew HW, Sampath VS, Gallardo CA, et al. Single-agent daratumumab for refractory POEMS syndrome. Am J Hematol 2022;97(6):E189-91. PMID 35253931
101: Tsai CY, Lai CH, Chan HL, Kuo Tt. Glomeruloid hemangioma--a specific cutaneous marker of POEMS syndrome. Int J Dermatol 2001;40(6):403-6. PMID 11589746
102: Vital C, Bouillot S, Vital A. Significance of uncompacted myelin lamellae in POEMS syndrome. Muscle Nerve 2003a;27(2):253-4. PMID 12548537
103: Vital C, Vital A, Ferrer X, et al. Crow-Fukase (POEMS) syndrome: a study of peripheral nerve biopsy in five new cases. J Peripher Nerv Syst 2003b;8(3):136-44. PMID 12904234
104: Wang C, Huang XF, Cai QQ, et al. Remarkable expression of vascular endothelial growth factor in bone marrow plasma cells of patients with POEMS syndrome. Leuk Res 2016;50:78-84. PMID 27697660
105: Warsame R, Kohut IE, Dispenzieri A. Successful use of cyclophosphamide, bortezomib, and dexamethasone to treat a case of relapsed POEMS. Eur J Haematol 2012;8(6):549-50. PMID 22416898
106: Watanabe O, Arimura K, Kitajima I, Osame M, Maruyama I. Greatly raised vascular endothelial growth factor (VEGF) in POEMS syndrome. Lancet 1996;347(9002):702. PMID 8596427
107: Watanabe O, Maruyama I, Arimura K, et al. Overproduction of vascular endothelial growth factor/vascular permeability factor is causative in Crow-Fukase (POEMS) syndrome. Muscle Nerve 1998;21(11):1390-7. PMID 9771661
108: Xu J, Wang Q, Xu H, et al. Anti-BCMA CAR-T cells for treatment of plasma cell dyscrasia: case report on POEMS syndrome and multiple myeloma. J Hematol Oncol 2018;11(1):128. PMID 30348186
109: Yamada Y, Sawai S, Misawa S, et al. Multiple angiogenetic factors are upregulated in POEMS syndrome. Ann Hematol 2013;92(2):245-8. PMID 23053181
110: Yang H, Zhao H, Gao X, et al. Endocrine evaluation in POEMS syndrome: a cohort study. Front Endocrinol (Lausanne) 2020;11:536241. PMID 33193075
111: Ye W, Wang C, Cai QQ, et al. Renal impairment in patients with polyneuropathy, organomegaly, endocrinopathy , monoclonal gammopathy and skin changes syndrome: incidence, treatment and outcome. Nephrol Dial Transplant 2016;31(2):275-83. PMID 26130736
112: Yodoi J, Takatsuki K, Wakisaka K. Association of myeloma, polyneuropathy, pigmentation and gynaecomastia. A possible new syndrome [abstract]. Acta Hematol Jap 1973;36:363.
113: Zagouri F, Kastritis E, Gavriatopoulou M, et al. Lenalidomide inpatients with POEMS syndrome: a systematic review and pooled analysis. Leuk Lymphoma 2014;55:2018-23. PMID 24295131
114: Zeng K, Yang JR, Li J, et al. Effective induction therapy with subcutaneous administration of bortezomib for newly diagnosed POEMS syndrome: a case report and a review of the literature. Acta Haematol 2013;129(2):101-5. PMID 23171959
115: Zhang L, Zhou YL, Zhang W, et al. Prevalence and risk factors for depression in newly diagnosed patients with POEMS syndrome. Leuk Lymphoma 2014;55(12):2835-41. PMID 24524304

Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Authors

Joan Blade MD PhD

Dr. Blade of Hospital Clinic of Barcelona received honorariums for educational lectures from Janssen, Celgene/BMS, and Sanofi.
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M Teresa Cibeira MD PhD

Dr. Cibeira of Hospital Clinic of Barcelona received honorariums as guest speaker and advisory board member from Janssen and Sanofi.
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Editor

Francesc Graus MD PhD

Dr. Graus, Emeritus Professor, Laboratory Clinical and Experimental Neuroimmunology, Institut D’Investigacions Biomédiques August Pi I Sunyer, Hospital Clinic, Spain, has no relevant financial relationships to disclose.
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Former Authors

Hassan Fathallah-Shaykh MD (original author), Aashit Shah MD, Nirjal Nikhar MD, Andrew S Chi MD, Santosh Kesari MD PhD, Jai Grewal MD, and Harpreet K Grewal MD

Patient Profile

Age range of presentation: 19 to 65+ years
Sex preponderance: male>female, >2:1
Heredity: none
Population groups selectively affected: Japanese
Occupation groups selectively affected: none selectively affected

ICD & OMIM codes

ICD-9: Hemangioma any site: 228.0

Monoclonal gammopathy: 273.1

Idiopathic progressive polyneuropathy: 356.4

Hepatomegaly: 789.1
ICD-10: Hemangioma, any site: D18.0

Monoclonal gammopathy: D47.2

Polyneuropathy, unspecified: G62.9

Hepatomegaly and splenomegaly, not elsewhere classified: R16

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POEMS syndrome

Associated Disorders

Amyotrophic lateral sclerosis
Anemia
Arterial thrombosis
Ascites
Castleman disease
- Coronary artery thrombosis
- Lymphadenopathy
- Lymphoproliferative disorders
- Monoclonal gammopathy
- Multiple myeloma
- Papilledema
- Plasmacytoma
- Polycythemia
- Pulmonary hypertension
- Renal failure
- Thrombocytosis
- Ulcerative colitis
- Waldenstrom macroglobulinemia

Differential Diagnosis

chronic inflammatory demyelinating polyneuropathy
asymptomatic monoclonal gammopathies
symptomatic monoclonal gammopathies
various skeletal abnormalities
diabetes
- porphyria
- heavy metal toxicity
- sarcoidosis
- paraneoplastic disorders
- hereditary demyelinating states
- osteosclerotic myeloma
- Paget disease
- osteoblastic solid tumors
- prostate metastasis
- lymphoma
- systemic mastocytosis
- osteolytic myeloma
- osseous metastasis
- histiocytosis X
- solitary plasmacytoma
- Castleman disease
- sarcoidosis
- metastatic neoplastic disease

POEMS syndrome …

POEMS syndrome

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Diagnostic workup

Table 1. Criteria for the Diagnosis of POEMS Syndrome

Management

Media

References

Contributors

Authors

Editor

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview.
Start a Free Account
to access the full version.

Questions or Comment?

Also in This Category

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Paraneoplastic syndromes

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Progressive encephalomyelitis with rigidity and myoclonus and glycine receptor antibodies

Hypothyroidism

Giant cell arteritis

POEMS syndrome

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Diagnostic workup

Table 1. Criteria for the Diagnosis of POEMS Syndrome

Management

Media

References

Contributors

Authors

Editor

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Neuropathies associated with cytomegalovirus infection

Clinical evaluation of peripheral neuropathies

Paraneoplastic syndromes

Anti-IgLON5 disease

Anti-LGI1 encephalitis

Progressive encephalomyelitis with rigidity and myoclonus and glycine receptor antibodies

Hypothyroidism

Giant cell arteritis

This is an article preview.
Start a Free Account
to access the full version.