The POEMS syndrome (coined to refer to polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) remains poorly understood. Ambiguity exists over the features necessary to establish the diagnosis, treatment efficacy, and prognosis. We identified 99 patients with POEMS syndrome. Minimal criteria were a sensorimotor peripheral neuropathy and evidence of a monoclonal plasmaproliferative disorder. To distinguish POEMS from neuropathy associated with monoclonal gammopathy of undetermined significance, additional criteria were included: a bone lesion, Castleman disease, organomegaly (or lymphadenopathy), endocrinopathy, edema (peripheral edema, ascites, or effusions), and skin changes. The median age at presentation was 51 years; 63% were men. Median survival was 165 months. With the exception of fingernail clubbing (P = .03) and extravascular volume overload (P = .04), no presenting feature, including the number of presenting features, was predictive of survival. Response to therapy (P < .001) was predictive of survival. Pulmonary hypertension, renal failure, thrombotic events, and congestive heart failure were observed and appear to be part of the syndrome. In 18 patients (18%), new disease manifestations developed over time. More than 50% of patients had a response to radiation, and 22% to 50% had responses to prednisone and a combination of melphalan and prednisone, respectively. We conclude that the median survival of patients with POEMS syndrome is 165 months, independent of the number of syndrome features, bone lesions, or plasma cells at diagnosis. Additional features of the syndrome often develop, but the complications of classic multiple myeloma rarely develop.

Introduction

Associations between plasma cell dyscrasia and peripheral neuropathy are well recognized.1 One third to one half of patients with osteosclerotic myeloma have neuropathy,2-4 and one half of patients with myeloma and peripheral neuropathy have osteosclerotic lesions.5 These figures contrast distinctly with the 1% to 8% incidence of neuropathy in patients with classic multiple myeloma.6,7 

In 1956, the interaction of plasma cell dyscrasia and peripheral neuropathy was shown to be more complex with Crow's1description of 2 patients with osteosclerotic plasmacytomas with neuritis and other “striking features,” which included clubbing, skin pigmentation, dusky discoloration of the skin, white fingernails, mild lymphadenopathy, and ankle edema. Scheinker's autopsy case in 1938 was the first report of what we now call POEMS syndrome, Crow-Fukase syndrome, PEP syndrome (plasma cell dyscrasia, endocrinopathy, and polyneuropathy), or Takatsuki syndrome.8,9 The patient was a 39-year-old man with a solitary plasmacytoma, sensorimotor polyneuropathy, and localized patches of thickened and deeply pigmented skin on the chest.3,10 Subsequently, others reported patients with osteosclerotic myeloma and peripheral neuropathy with organomegaly, skin changes, endocrinopathy, edema, hypertrichosis, gynecomastia, and ascites.2-4,9,11-18 In a 1977 review by Iwashita et al,3 30 patients with osteosclerotic myeloma and peripheral neuropathy, as compared with 29 patients without peripheral neuropathy, had a higher incidence of hyperpigmentation, edema, skin thickening, hepatomegaly, hypertrichosis, and clubbing. In 1980, Bardwick et al19 coined the acronym POEMS to represent a syndrome characterized by polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes. Not represented in the acronym are several important features, including sclerotic bone lesions, Castleman disease, papilledema, pleural effusion, edema, ascites, and thrombocytosis.8,20-22 

No single test establishes the diagnosis of POEMS syndrome. Seemingly disparate signs and symptoms must be linked to establish the diagnosis. Although several series have been reported,8,19,22ambiguity exists about the number of features necessary for diagnosis, effective therapies, and prognosis. The interconnections between POEMS syndrome, osteosclerotic myeloma, and Castleman disease are still under investigation. Cytokines have been implicated in the pathogenesis of the disease.23-25 POEMS appears to be mediated by an imbalance of proinflammatory cytokines. Interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α inconsistently have been reported to be increased in association with the syndrome.26-28Preliminary data suggest that vascular endothelial growth factor is an excellent candidate as a pathogenic factor in POEMS29,30; it induces a rapid and reversible increase in vascular permeability, is a growth factor for endothelial cells, and is considered important in angiogenesis.27 

In a retrospective review of a single institution's experience, we defined the minimal criteria required for the diagnosis of POEMS syndrome, described the natural history of the disease, and studied whether pulmonary hypertension, restrictive lung disease, thrombosis, cardiomyopathy, and glomerulonephritis are true associations.

Patients and methods

The Mayo Clinic dysproteinemia database was queried for all patients with POEMS syndrome or osteosclerotic myeloma. One reviewer (A.D.) abstracted data. Through December 1998, 99 patients were identified who met the minimal criteria for study inclusion. The diagnosis had been made at our institution in 80 patients and elsewhere in 19 patients. All 99 patients had both major criteria and one minor criterion for the diagnosis of POEMS syndrome (Table1).

Table 1.

Criteria for the diagnosis of POEMS syndrome*

Major criteria Polyneuropathy 
 Monoclonal plasmaproliferative disorder 
Minor criteria Sclerotic bone lesions 
 Castleman disease 
 Organomegaly (splenomegaly, hepatomegaly, or lymphadenopathy) 
 Edema (edema, pleural effusion, or ascites) 
 Endocrinopathy (adrenal, thyroid, pituitary, gonadal, parathyroid, pancreatic
 Skin changes (hyperpigmentation, hypertrichosis, plethora, hemangiomata, white nails) 
 Papilledema 
Known associations Clubbing 
 Weight loss 
 Thrombocytosis 
 Polycythemia 
 Hyperhidrosis 
Possible associations Pulmonary hypertension 
 Restrictive lung disease 
 Thrombotic diatheses 
 Arthralgias 
 Cardiomyopathy (systolic dysfunction) 
 Fever 
 Low vitamin B12values 
 Diarrhea 
Major criteria Polyneuropathy 
 Monoclonal plasmaproliferative disorder 
Minor criteria Sclerotic bone lesions 
 Castleman disease 
 Organomegaly (splenomegaly, hepatomegaly, or lymphadenopathy) 
 Edema (edema, pleural effusion, or ascites) 
 Endocrinopathy (adrenal, thyroid, pituitary, gonadal, parathyroid, pancreatic
 Skin changes (hyperpigmentation, hypertrichosis, plethora, hemangiomata, white nails) 
 Papilledema 
Known associations Clubbing 
 Weight loss 
 Thrombocytosis 
 Polycythemia 
 Hyperhidrosis 
Possible associations Pulmonary hypertension 
 Restrictive lung disease 
 Thrombotic diatheses 
 Arthralgias 
 Cardiomyopathy (systolic dysfunction) 
 Fever 
 Low vitamin B12values 
 Diarrhea 

POEMS indicates polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes.

*

Two major criteria and at least 1 minor criterion are required for diagnosis.

Osteosclerotic lesion or Castleman disease is usually present.

Because of the high prevalence of diabetes mellitus and thyroid abnormalities, this diagnosis alone is not sufficient to meet this minor criterion.

All patients (or their physicians) for whom no follow-up data were available in the preceding year were contacted. Death certificates were sought for deceased patients for whom there was inadequate information. Follow-up data were available for 93 patients (94%). Median follow-up was 70.6 months (range, 0.2 to 304 months). Twenty-four patients (24%) were evaluated from 1960 to 1985, 33 (33%) from 1986 to 1990, and 42 (42%) from 1991 to 1998. The Mayo Foundation Institutional Review Board approved the study in accordance with Minnesota state law.

The definitions of response to treatment were based on both patient and physician reports of improvement rather than on strictly defined objective criteria. Patients who had little or no residual neuropathy and otherwise regained a normal sense of well-being and function were classified as having had a very good response. Those who had improvement in their neuropathy but still perceived themselves to have a significant handicap were classified as having had a good response. Patients whose deterioration stabilized during or after treatment but did not derive any subjective or objective improvement were classified as having stable disease. Patients who continued to deteriorate despite therapy were deemed refractory.

Curves for overall survival and time to the development of new syndrome features were plotted according to the method of Kaplan and Meier31 and were compared by the log-rank test.32 Survival was calculated from the time of diagnosis. Prognostic factors for overall survival and risk of developing additional features were determined by the Cox proportional hazards model in the analysis of covariates.33 Variables analyzed in these models include the following: age, sex, organomegaly, papilledema, skin abnormalities, endocrine abnormalities, edema, weight loss, lymphadenopathy, Castleman disease, number of POEMS features, thrombocytosis, hemoglobin level, type of immunoglobulin heavy chain, bone marrow plasmacytosis, serum M-protein level, urine M-protein level, number of bone lesions, and type of treatment.

Results

Presenting features

Patient characteristics are shown in Tables2 and 3. Thirty-one patients (31%) were 45 years or younger; 62 (63%) were men. Table 3 compares the findings in this study with those of the 2 other largest patient series.8,22 The most notable differences among the studies are the high frequency of accompanying bone lesions in the present study (97% compared with 54% to 68%) and the lower frequency in the present study of edema and effusions (29% compared with 66% to 89%) and organomegaly (50% compared with 68% to 78%). In contrast to the other studies in Table3, the present series cites only the features present at diagnosis rather than features observed during disease evolution and progression.

Table 2.

Presenting clinical characteristics of 99 patients with POEMS syndrome

Characteristic%
Median age, y (range) 51 (30-83)  
Race  
 African American  8  
 Asian  0  
 Hispanic 
 Non-Hispanic white 89  
Male sex 63  
Patients with given no. of classic POEMS features*  
 2 features 
 3 features 32  
 4 features 31  
 5 features 29 
Patients with given no. of revised POEMS features  
 3 features  6  
 4 features 19  
 5 features 32 
 6 features 17  
 7 features 16  
 8 features  7  
 9 features  2  
Laboratory value  
 Albumin less than 3.0 g/dL (range) 24 (2.3-4.5)  
 Bone marrow plasma cells more than 10% (range) 14 (0-40)  
 Calcium more than 10.5 mg/dL (range) 0 (7.8-10.2)  
 Creatinine more than 1.5 mg/dL (range) 2 (0.5-1.9)  
 Erythrocyte sedimentation rate more than 29 mm/h (range) 16 (1-58)  
 Hemoglobin less than 11 g/dL (range) 4 (10.4-18.4)  
 Hemoglobin more than 16 g/dL (range) 16 (10.4-18.4)  
 Leukocytes more than 10 500/μL (range) 21 (3700-17 600)  
 Platelets more than 450 × 103/μL (range) 54 (111-1163)  
 Serum M-spike more than 2.0 g/dL (range) 7 (0.00-4.1)  
 Urine M-spike more than 0.5 g/24 h (range) 0 (0.00-0.45)  
 Urine protein more than 1.0 g/24 h (range) 5 (0.02-3.2) 
Characteristic%
Median age, y (range) 51 (30-83)  
Race  
 African American  8  
 Asian  0  
 Hispanic 
 Non-Hispanic white 89  
Male sex 63  
Patients with given no. of classic POEMS features*  
 2 features 
 3 features 32  
 4 features 31  
 5 features 29 
Patients with given no. of revised POEMS features  
 3 features  6  
 4 features 19  
 5 features 32 
 6 features 17  
 7 features 16  
 8 features  7  
 9 features  2  
Laboratory value  
 Albumin less than 3.0 g/dL (range) 24 (2.3-4.5)  
 Bone marrow plasma cells more than 10% (range) 14 (0-40)  
 Calcium more than 10.5 mg/dL (range) 0 (7.8-10.2)  
 Creatinine more than 1.5 mg/dL (range) 2 (0.5-1.9)  
 Erythrocyte sedimentation rate more than 29 mm/h (range) 16 (1-58)  
 Hemoglobin less than 11 g/dL (range) 4 (10.4-18.4)  
 Hemoglobin more than 16 g/dL (range) 16 (10.4-18.4)  
 Leukocytes more than 10 500/μL (range) 21 (3700-17 600)  
 Platelets more than 450 × 103/μL (range) 54 (111-1163)  
 Serum M-spike more than 2.0 g/dL (range) 7 (0.00-4.1)  
 Urine M-spike more than 0.5 g/24 h (range) 0 (0.00-0.45)  
 Urine protein more than 1.0 g/24 h (range) 5 (0.02-3.2) 

POEMS encompasses polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes.

*

According to Bardwick et al.19 

According to Table 1.

Table 3.

Comparison of clinical characteristics of patients in the present series and 2 previous series3-150

CharacteristicPresent study, % N = 99Soubrier et al,22 %
N = 25
Nakanishi et al,8%
N = 102
Polyneuropathy    
 Peripheral neuropathy 100 100 100  
 Cerebrospinal fluid protein more than 50 mg/dL 1003-152 1003-152 973-152 
Organomegaly 50 NR NR 
 Hepatomegaly 24 68 78 
 Splenomegaly 22 52 35 
 Lymphadenopathy 26 52 61  
 Castleman disease 11 24 19 
Endocrinopathy 67 NR NR  
 Gonadal axis abnormality 55 NR NR  
 Adrenal axis abnormality 16 NR NR  
 Increased prolactin value NR NR  
 Gynecomastia or galactorrhea 18 NR NR  
 Diabetes mellitus 36 25 
 Hypothyroidism 14 36 NR 
 Hyperparathyroidism NR NR  
Monoclonal plasma cell dyscrasia 100 100 75  
 M component on serum protein electrophoresis 54 100 70  
Skin changes 68 NR NR 
 Hyperpigmentation 46 48 93  
 Acrocyanosis and plethora 19 NR NR 
 Hemangioma/telangiectasia 32 NR 
 Hypertrichosis 26 24 74 
 Thickening 28 61  
Papilledema 29 40 55 
Extravascular volume overload 29 NR NR 
 Peripheral edema 24 80 89  
 Ascites 32 52 
 Pleural effusion 24 35  
Bone lesions 97 68 54  
 Osteosclerotic only3-151 47 41 56 
 Mixed sclerotic and lytic3-151 51 59 31  
 Lytic only3-151 13  
 Solitary lesion3-151 45 41 45 
 2 or 3 lesions3-151 23 NR NR  
 More than 1 lesion3-151 54 59 45  
 More than 3 lesions3-151 32 NR NR  
Other features    
 Weight loss more than 10 pounds 37 NR NR 
 Fatigue 31 NR NR  
 Thrombocytosis: platelet count more than 450 × 103/μL 54 88 NR  
 Polycythemia: hemoglobin more than 15 g/dL in women and more than 17 g/dL in men 18 12 19  
 Clubbing 32 49 
CharacteristicPresent study, % N = 99Soubrier et al,22 %
N = 25
Nakanishi et al,8%
N = 102
Polyneuropathy    
 Peripheral neuropathy 100 100 100  
 Cerebrospinal fluid protein more than 50 mg/dL 1003-152 1003-152 973-152 
Organomegaly 50 NR NR 
 Hepatomegaly 24 68 78 
 Splenomegaly 22 52 35 
 Lymphadenopathy 26 52 61  
 Castleman disease 11 24 19 
Endocrinopathy 67 NR NR  
 Gonadal axis abnormality 55 NR NR  
 Adrenal axis abnormality 16 NR NR  
 Increased prolactin value NR NR  
 Gynecomastia or galactorrhea 18 NR NR  
 Diabetes mellitus 36 25 
 Hypothyroidism 14 36 NR 
 Hyperparathyroidism NR NR  
Monoclonal plasma cell dyscrasia 100 100 75  
 M component on serum protein electrophoresis 54 100 70  
Skin changes 68 NR NR 
 Hyperpigmentation 46 48 93  
 Acrocyanosis and plethora 19 NR NR 
 Hemangioma/telangiectasia 32 NR 
 Hypertrichosis 26 24 74 
 Thickening 28 61  
Papilledema 29 40 55 
Extravascular volume overload 29 NR NR 
 Peripheral edema 24 80 89  
 Ascites 32 52 
 Pleural effusion 24 35  
Bone lesions 97 68 54  
 Osteosclerotic only3-151 47 41 56 
 Mixed sclerotic and lytic3-151 51 59 31  
 Lytic only3-151 13  
 Solitary lesion3-151 45 41 45 
 2 or 3 lesions3-151 23 NR NR  
 More than 1 lesion3-151 54 59 45  
 More than 3 lesions3-151 32 NR NR  
Other features    
 Weight loss more than 10 pounds 37 NR NR 
 Fatigue 31 NR NR  
 Thrombocytosis: platelet count more than 450 × 103/μL 54 88 NR  
 Polycythemia: hemoglobin more than 15 g/dL in women and more than 17 g/dL in men 18 12 19  
 Clubbing 32 49 

NR indicates not reported.

F3-150

The percentage of patients with the given characteristic is shown. Percentages are based on the total number of patients in the series, with the exception of cerebrospinal fluid protein, which includes the actual number tested.

F3-151

Percentage of patients with bone lesions.

F3-152

Only 28, 23, and 73 patients, respectively, were tested; percentage represents percent positive of those tested.

Polyneuropathy

Peripheral neuropathy is the dominant clinical feature of this disorder (Table 3). By definition, all patients in this series had a peripheral neuropathy. Although neuropathy is typically the presenting symptom, in the present series 5 patients (5%) had a known plasma cell dyscrasia before the onset of the neuropathy.8,22 All patients in this series had increased cerebrospinal fluid protein, increased cerebrospinal fluid opening pressures, and a normal cell count.8,22 Thirty-one patients (31%) had sural nerve biopsy; in most cases, the findings were those of a demyelinating process with axonal loss.

Organomegaly

Fifty patients (50%) had organomegaly. Twenty-six patients (26%) had lymphadenopathy. Of these 26, 15 underwent biopsy: 11 had Castleman disease, and 4 had reactive changes. Twenty-four patients (24%) had hepatomegaly, and 22 (22%) had splenomegaly. No patient had massive lymphadenopathy or organomegaly. The percentage of patients with organomegaly in our series seems lower than that in other series (Table 3).

Endocrinopathy

Endocrine abnormality is a defining feature of POEMS.19 In the present study, 66 patients (67%) had at least one endocrine abnormality at presentation. Later in the course of disease, endocrine abnormalities developed in 7 other patients (7%). Most patients did not have a thorough endocrine evaluation, lowering the reported incidence. Because both diabetes mellitus and hypothyroidism are common endocrine abnormalities, care was taken to assign them as part of the syndrome only if there appeared to be a clear temporal relationship. The overall prevalence of endocrinopathy was similar to that previously reported by others (Table3).22,34 

Hypogonadism was most common, though laboratory data were too sparse to determine whether there was primary or secondary failure. Forty-four men (71%) had erectile dysfunction. Twenty-eight of these men had serum testosterone levels measured; all but 4 had low levels. Of those not reporting sexual dysfunction, 5 had low serum testosterone levels. Of the 19 men who had serum prolactin levels measured, none had high levels. Seventeen men had gynecomastia; none of the 4 men tested had high serum estradiol levels. The sexual history of women was less reliably ascertained. Two women had irregular menses, one of whom also had galactorrhea. Serum estradiol levels were normal in all 4 women tested. Among the 25 patients with measured serum prolactin levels, levels were high (range, 26 to 58 μg/mL [26 to 58 ng/L]; normal, less than 23 μg/mL [23 ng/L]) in 3 men and 2 women.

Fourteen patients (14%) had hypothyroidism requiring treatment. Another 12 patients (12%) had mild increases in thyroid-stimulating hormone (5.8 to 13.4 mU/L [5.8 to 13.4 μU/mL]; normal, 0.3 to 5.0 mU/L [0.3 to 5.0 μU/mL]) and normal thyroxine levels; these patients were not treated and therefore not considered to have an endocrine abnormality in this series. The hypothyroidism was primary in 9 patients and secondary in 3. In 3 patients, hypothyroidism was the only endocrine abnormality. The remainder had gonadal or adrenal dysfunction or both. In 6 other patients, hypothyroidism developed during the course of disease; they were not included among those considered to have an endocrine abnormality at presentation (Table 3).

Three patients (3%) had diabetes mellitus, having high fasting glucose and glycosylated hemoglobin levels. Of the 35 patients who had adrenal-pituitary testing, 16 (16%) had abnormalities of the adrenal-pituitary axis at presentation. In another 5 patients, adrenal insufficiency developed later in the course of disease. In total, 9 patients had primary adrenal dysfunction, 3 had secondary adrenal dysfunction, and 10 had insufficient data to make the distinction.

Serum levels of parathyroid hormone were measured in 4 patients and were found to be increased in 3. In one patient hypoparathyroidism was diagnosed 84 months after POEMS syndrome was diagnosed.

Monoclonal plasmaproliferative disorder

By definition, all patients had evidence of a monoclonal plasmaproliferative disorder. Eighty-four patients (85%) had a detectable monoclonal protein in their serum on analysis by immunofixation. These findings are similar to those of Nakanishi et al,8 who found an M component to be present in 75% of patients. The serum protein electrophoresis patterns of 24 of our patients were normal; patterns of 7 patients appeared polyclonal. Had immunofixation not been done, the monoclonal protein would have been missed in these 31 patients. Although 40 patients had a detectable monoclonal protein in their urine, in only 3 patients did urine screening identify a monoclonal plasmaproliferative disorder that had not been detected in the serum. The quantity of monoclonal protein was small in both serum and urine, with a median serum M-spike of 11 g/L (1.1 g/dL) (range, 0.0 to 41 g/L [4.1 g/dL]; only 7 patients had an M-spike more than 20 g/L [2 g/dL]) (Table 2). The median total urine protein was 100 mg per 24 hours.

All patients had a monoclonal λ light chain. Forty-four patients had an immunoglobulin A (IgA) λ, 40 had an IgG λ, and 1 had an IgM λ. For the 12 patients who did not have a monoclonal protein in their serum or urine, a clonal λ plasmaproliferative disorder was demonstrated by immunohistochemical staining of biopsy specimens from sclerotic bone lesions or bone marrow.

Of 90 patients who had a bone marrow biopsy performed, the most common interpretation was “nondiagnostic,” with the predominant feature being a hypercellular or “reactive-appearing” marrow. Twenty-one patients had a normal-appearing marrow. Only 4 patients had more than 20% plasma cells; none of these 4 patients had lytic bone disease or anemia. In 25 patients, there was only a slight increase in plasma cells (Tables 2 and 3). Our finding that 14% of patients had a bone marrow plasmacytosis more than 10% is similar to the 5% to 20% previously reported.8,22 

Skin changes

Skin changes were documented in 67 patients (68%) (Table3). The most common abnormality was hyperpigmentation (46 patients), followed by acrocyanosis and plethora (19 patients). The latter 2 features were not well-captured in the other large series, but they are described elsewhere.1,8,22,35 Five patients had skin thickening. Multiple hemangiomas were documented in 9 patients; vascular changes similar to those in Kaposi sarcoma were seen in one of these patients. A necrotizing vasculitis along with hyperpigmentation was present in another patient. Of the 26 patients with hypertrichosis, only 5 had no endocrine abnormality, and only 4 had no other skin abnormalities. The hypertrichosis was either generalized or limited to body parts, such as the extremities or face. Twenty-nine patients had 2 or 3 coexistent skin abnormalities. Although white nails can occur in patients with POEMS syndrome, no mention of this finding was made regarding the patients we studied.

Edema and effusions

On presentation, 29 patients (29%) had some form of extravascular volume overload. Peripheral edema, ascites, and pleural effusions were present in 24, 7, and 3 patients, respectively (Table 3). One patient had a pericardial effusion. The incidence of edema and effusions was lower in our series than in other series; however, if one includes patients in whom edema or effusions developed during the course of disease, the numbers increase to 29, 15, and 9, respectively.

Sclerotic bone lesions

On presentation, 95 patients had at least one abnormality detected on radiographic bone survey (Table 3). Of the 4 patients not presenting with a bone lesion, all had 4 or 5 features of POEMS syndrome, including a clonal plasmaproliferative disorder. In one patient, a sclerotic bone lesion developed 18 months later, yielding a total of 96 patients (97%) with abnormal findings on bone radiography. Of the patients with abnormal findings, all but 2 had sclerotic bone lesions. The radiographs for these 2 patients could not be located to establish whether there was any element of sclerosis associated with the lytic lesions. These 2 patients had solitary lytic lesions. In our experience, lytic lesions in patients with POEMS syndrome tend to have a sclerotic rim. Forty-nine patients had lesions with mixed sclerotic and lytic components. Forty-three patients had a solitary lesion, 22 had 2 or 3 lesions, and 31 had more than 3 lesions (Table 3). These findings are consistent with those of previous publications.8,22 Twenty-two patients underwent biopsy of a sclerotic lesion; results were diagnostic in 20.

Papilledema

Papilledema was observed in 29 patients (29%) (Table 3). In other series, papilledema has been observed in 40% to 55% of patients.8,22 

Other established features

Thirty-seven patients (37%) had lost more than 10 pounds of body weight at presentation. Thirty-one patients (31%) complained of significant fatigue. Five patients (5%) had recognized clubbing at diagnosis, one of whom had coincident restrictive lung disease. Patients with clubbing seemed to have more extensive disease: all had organomegaly, endocrinopathy, skin changes, peripheral neuropathy, and plasmaproliferative disorder; in all but one of these patients, additional POEMS features developed over time. Thirteen patients (13%) complained of generalized bone pain or arthralgia; only 3 of these patients had diffuse sclerotic lesions. Fifty-three patients (54%) had thrombocytosis, and 18 (18%) had polycythemia (hemoglobin more than 150 g/L [15 g/dL] in women and more than 170 g/L [17 g/dL] in men).

Unusual features

Data from case reports and small series suggest that pulmonary hypertension, congestive heart failure, thrombosis, and renal failure may be part of the POEMS syndrome (Table 1).7,29,36-76 In the present series, 47 patients had one or more of these features.

Fourteen patients had lung disease other than effusion during the course of their illness; 3 had effusion, one of whom also had other pulmonary manifestations. Five patients had pulmonary hypertension. Five patients had restrictive lung disease. In 4 patients, respiratory failure or insufficiency developed within several months before death; 17% of deaths were due to respiratory failure.

Four patients died of complications of renal failure between 34 and 120 months after diagnosis. The renal failure occurred within 6 months before death in 3 patients and 3 years before death in 1. There was associated ascites in 3 of the 4 patients. No renal biopsies were performed. All patients who died of renal failure had coexistent ascites and a capillary leaklike syndrome.

Congestive heart failure and cardiomyopathy were among the presenting features in 3 patients. After treatment of the plasma cell dyscrasia with either radiation or combination chemotherapy, cardiac symptoms resolved in all 3 patients. In 4 other patients, congestive heart failure developed at 12, 30, 56, and 192 months. Each of the cardiac events occurred during a POEMS exacerbation. Two patients had pericarditis within a few months of presentation.

Twenty-one thrombotic events (10 venous, 11 arterial) occurred in 18 patients. Seven patients had 8 thrombotic events predating their diagnosis with POEMS. Eleven patients had 13 events after diagnosis.

Survival and prognostic features

Overall median survival was 165 months (Figure1). Only fingernail clubbing and extravascular volume overload (edema, effusion, or ascites) were prognostic for survival. Patients with clubbing or extravascular volume overload had a median survival of 31 and 79 months, respectively. These variables were independent of each other, and their corresponding proportional hazard ratios for death were 4.0 (P = .03) and 2.1 (P = .04). Patients who received radiation therapy and those who had a very good or good response to treatment also had superior survival (Figure 2).

Fig. 1.

Overall survival for 99 patients with POEMS syndrome evaluated at a single institution.

Fig. 1.

Overall survival for 99 patients with POEMS syndrome evaluated at a single institution.

Fig. 2.

Survival on the basis of treatment with radiation.

P < .04 for comparison of the 2 groups.

Fig. 2.

Survival on the basis of treatment with radiation.

P < .04 for comparison of the 2 groups.

When we used the criteria of Bardwick et al,19 median survival for patients with 2, 3, 4, and 5 features at presentation was more than 174, 85, more than 302, and 96 months, respectively; 29%, 50%, 23%, and 34% of the patients in the respective groups have died. When we used the 9 major and minor criteria in Table 1, median survival for patients with 3, 4, 5, 6, 7, 8, and 9 features was more than 174, 85, more than 302, 49, more than 197, 103, and 50 months, respectively (P = not significant) (Figure3); 17%, 47%, 25%, 53%, 25%, 29%, and 100% of the patients in the respective groups have died. In toto, 35 patients have died (Table 4). The most commonly identified causes of death were cardiorespiratory failure and infection. No patient died of classic myeloma—that is, progressive bone marrow failure or hypercalcemia. All patients who died of renal failure had coexistent ascites and a capillary leaklike syndrome.

Fig. 3.

Survival on the basis of number of features at presentation.

P = not significant. MS indicates median survival; Pts, patients.

Fig. 3.

Survival on the basis of number of features at presentation.

P = not significant. MS indicates median survival; Pts, patients.

Table 4.

Causes of death among 35 patients

Cause of deathNo. of patients4-150
Cardiac event 74-151, 
Respiratory failure 6 
Infection 4  
POEMS 3  
Cancer 34-153 
Renal failure 44-155 
Unknown 
Other 5# 
Cause of deathNo. of patients4-150
Cardiac event 74-151, 
Respiratory failure 6 
Infection 4  
POEMS 3  
Cancer 34-153 
Renal failure 44-155 
Unknown 
Other 5# 
F4-150

The deaths of 2 patients were attributed to more than 1 cause.

F4-151

Includes 3 patients with congestive heart failure.

Includes 1 patient who died of cardiorespiratory arrest.

F4-153

Includes acute myelogenous leukemia, cholangiocarcinoma, and cancer not otherwise specified.

F4-155

Includes 1 patient who died of shock and renal failure.

#Includes suicide, cachexia, inanition, shock, and stroke.

Long-term follow-up of patients with POEMS syndrome

Not only are the number of features present at diagnosis not prognostic of survival (Figure 3), but patients often accumulate additional features of POEMS syndrome over time (Table5). In our cohort, the median time between onset of symptoms and diagnosis was 15 months (range, 3-120 months). The respective median times in months from the initial occurrence of symptoms to diagnosis for patients with 2, 3, 4, and 5 features at presentation were 11 (range, 5-60); 13 (range, 3-60); 15 (range, 3-48); and 21 (range, 3-120). Moreover, during follow-up additional classic POEMS characteristics developed in 18 patients; possible POEMS features (congestive heart failure and thrombosis) developed in 7 other patients.

Table 5.

Acquisition of POEMS syndrome features over time

Patient characteristicsInitial POEMS featuresSubsequently acquired POEMS featuresTTP, yFU, yResponse
to therapy
Current status
No.SexAge, yPOEMSAB, no.CPap
66     Diff   Hypothyroid, hypoadrenal at 126 mo; ascites, pulmonary hypertension at 156 mo 10.5 14.5 V gd Alive 
34     2 or 3   Ascites, Budd-Chiari at 149 mo; pleural effusion at 156 mo 12.4 13.4 V gd Alive 
34    Diff   Detectable monoclonal protein in serum at 39 mo; hypothyroid at 60 mo; ascites and hepatomegaly at 87 mo 5.0 7.8 Stable Dead 
46   Diff   Pulmonary hypertension and effusion at 36 mo; hypothyroid at 52 mo; acrocyanosis at 54 mo 3.0 5.8 Good Alive 
58   Diff  Pap Hypothyroid at 9 mo; ascites and renal failure
at 12 mo 
0.8 3.3 Good Dead 
43    2 or 3   Hypoadrenal at 4 mo 0.3 1.0 Refr Alive 
50      Pericardial effusion at 1 mo 0.1 0.2 Refr Dead 
38     CHF, hypogonad, hypothyroid, hypoadrenal, peripheral edema, acrocyanosis, hypertrichosis, hyperpigmentation at 192 mo 16.0 16.4 V gd Alive 
33    Pap Peripheral edema at 90 mo 7.5 9.5 V gd Alive 
10 56   2 or 3   Diabetes mellitus at 94 mo 7.8 9.1 V gd Alive 
11 44    Pap Ascites and CHF at 56 mo 4.7 5.0 Good Dead 
12 51   Diff  Clubbing, ascites, and renal failure at 52 mo 4.3 4.9 ND Dead 
13 61   2 or 3   Ascites at 1 mo 0.1 0.7 ND Alive 
14 57 Diff   Ascites at 22 mo; renal failure and oxygen dependence at 117 mo 1.8 10.0 V gd Dead 
15 50  2 or 3  Pap Ascites at 12 mo; respiratory failure at 66 mo 1.0 5.7 Good Dead 
16 51  2 or 3   Hepatomegaly and hepatic dysfunction at 30 mo 2.5 2.8 Good Dead 
17 39    Lymphadenopathy at 17 mo; restrictive lung disease at 36 mo 1.4 1.4 Good Alive 
18 64 Diff  Pap Hypoparathyroid at 84 mo 7.0 14.6 Good Alive 
Patient characteristicsInitial POEMS featuresSubsequently acquired POEMS featuresTTP, yFU, yResponse
to therapy
Current status
No.SexAge, yPOEMSAB, no.CPap
66     Diff   Hypothyroid, hypoadrenal at 126 mo; ascites, pulmonary hypertension at 156 mo 10.5 14.5 V gd Alive 
34     2 or 3   Ascites, Budd-Chiari at 149 mo; pleural effusion at 156 mo 12.4 13.4 V gd Alive 
34    Diff   Detectable monoclonal protein in serum at 39 mo; hypothyroid at 60 mo; ascites and hepatomegaly at 87 mo 5.0 7.8 Stable Dead 
46   Diff   Pulmonary hypertension and effusion at 36 mo; hypothyroid at 52 mo; acrocyanosis at 54 mo 3.0 5.8 Good Alive 
58   Diff  Pap Hypothyroid at 9 mo; ascites and renal failure
at 12 mo 
0.8 3.3 Good Dead 
43    2 or 3   Hypoadrenal at 4 mo 0.3 1.0 Refr Alive 
50      Pericardial effusion at 1 mo 0.1 0.2 Refr Dead 
38     CHF, hypogonad, hypothyroid, hypoadrenal, peripheral edema, acrocyanosis, hypertrichosis, hyperpigmentation at 192 mo 16.0 16.4 V gd Alive 
33    Pap Peripheral edema at 90 mo 7.5 9.5 V gd Alive 
10 56   2 or 3   Diabetes mellitus at 94 mo 7.8 9.1 V gd Alive 
11 44    Pap Ascites and CHF at 56 mo 4.7 5.0 Good Dead 
12 51   Diff  Clubbing, ascites, and renal failure at 52 mo 4.3 4.9 ND Dead 
13 61   2 or 3   Ascites at 1 mo 0.1 0.7 ND Alive 
14 57 Diff   Ascites at 22 mo; renal failure and oxygen dependence at 117 mo 1.8 10.0 V gd Dead 
15 50  2 or 3  Pap Ascites at 12 mo; respiratory failure at 66 mo 1.0 5.7 Good Dead 
16 51  2 or 3   Hepatomegaly and hepatic dysfunction at 30 mo 2.5 2.8 Good Dead 
17 39    Lymphadenopathy at 17 mo; restrictive lung disease at 36 mo 1.4 1.4 Good Alive 
18 64 Diff  Pap Hypoparathyroid at 84 mo 7.0 14.6 Good Alive 

A indicates anasarca, edema, ascites, or pleural effusion; B, bone lesions; C, Castleman disease; CHF, congestive heart failure; Diff, diffuse; E, endocrinopathy; FU, follow-up; M, monoclonal plasma cell dyscrasia; ND, no data; O, organomegaly (including hepatomegaly, splenomegaly, and lymphadenopathy); P, peripheral neuropathy; Pap, papilledema; Refr, refractory disease; S, skin changes; TTP, time to progression; and V gd, very good.

Seven patients had only 2 of the 5 POEMS features as described by Bardwick et al,19 namely, the monoclonal plasmaproliferative disorder and peripheral neuropathy. All 7 patients had at least 1 osteosclerotic bone lesion; in fact, 6 had more than 1 lesion. Additional POEMS features subsequently developed in 2 (Table5).

Among the 32 patients with 3 features of POEMS, additional features developed in 5 patients 9 to 60 months after the original diagnosis. Among the 31 patients with 4 features of POEMS, other features subsequently developed in 6. Finally, among the 29 patients with all 5 features, other POEMS features developed in 4.

Presenting features were evaluated for their value in predicting the development of other POEMS features. On univariate analysis, the only factors predictive of the development of additional POEMS features were a serum M-spike of more than 1 g/dL (P = .04), the presence of a monoclonal protein in the urine (P = .05), and the absence of radiation therapy (P = .02). On multivariate analysis, only the presence of a urinary monoclonal protein was predictive of the development of additional features (proportional hazards, 4.82; confidence interval, 1.71-13.8;P = .003). Among the 18 patients in whom additional POEMS-associated features developed over time, those patients with the fewest POEMS features as described by Bardwick et al19 had the highest risk of additional features developing (29% vs 14%).

Therapy

Patients were either treated by Mayo Clinic physicians or referred for treatment to their local physicians. Because this was a retrospective analysis, it was difficult to draw firm conclusions regarding therapy. However, we found that 73 patients (74%) had at least some response to therapy (Table 6). Fourteen patients were refractory to the treatments chosen. Sixty-four patients were treated with 70 courses of radiation, 48 with melphalan and prednisone, 15 with alkylator-based combination chemotherapy, 41 with prednisone or dexamethasone alone, 30 with plasmapheresis, and 9 with intravenous immunoglobulin.

Table 6.

Response to therapy in patients with POEMS syndrome

TreatmentNo. of patientsResponse to treatment, %
ImprovedStableProgressionUnknown
Radiation 706-151 54 16 26  
Melphalan and prednisone 48 44 12 12 31  
Combination chemotherapy6-150 15 27 33 33  
Cyclosporine or azathioprine 100 0  
Cyclosporine or azathioprine, plus prednisone 50 17 33 
Prednisone or dexamethasone 41 15 20 59 
Plasmapheresis 16 12 87 0  
Plasmapheresis plus prednisone 14 21 14 64  
Intravenous immunoglobulin 89 11 
TreatmentNo. of patientsResponse to treatment, %
ImprovedStableProgressionUnknown
Radiation 706-151 54 16 26  
Melphalan and prednisone 48 44 12 12 31  
Combination chemotherapy6-150 15 27 33 33  
Cyclosporine or azathioprine 100 0  
Cyclosporine or azathioprine, plus prednisone 50 17 33 
Prednisone or dexamethasone 41 15 20 59 
Plasmapheresis 16 12 87 0  
Plasmapheresis plus prednisone 14 21 14 64  
Intravenous immunoglobulin 89 11 
F6-150

Includes vincristine, carmustine, melphalan, cyclophosphamide, and prednisone; vincristine, doxorubicin, and dexamethasone; cyclophosphamide, doxorubicin, vincristine, and prednisone; and cyclophospharnide-based chemotherapy.

F6-151

Sixty-four patients were treated with 70 courses of radiation.

A response was defined as stabilization or improvement of symptoms as reported by the patient or the treating physician. Radiation therapy was effective; at least half of patients so treated responded. Only those patients with a solitary lesion or a dominant lesion were treated with radiation. Of the 13 patients who did not respond to radiation, 9 had received less than 4000 cGy. Responses were often inapparent until 3 to 6 months after treatment. Some patients showed continued improvement 1 to 2 years after radiation treatment. Responses of organomegaly and skin changes generally antedated a response of neuropathy.

Clinical responses to prednisone and a combination of melphalan and prednisone occurred in approximately 22% to 56% of patients. Patients receiving plasmapheresis, cyclosporine, or azathioprine responded only if they were also receiving prednisone, suggesting that these agents themselves are ineffective. No response was observed with intravenous immunoglobulin.

Discussion

Clinical features

All patients with POEMS syndrome have peripheral neuropathy and a monoclonal plasma cell dyscrasia or Castleman disease. Hepatomegaly, splenomegaly, lymphadenopathy, endocrinopathy, skin changes, papilledema, peripheral edema, ascites, sclerotic bone lesions, clubbing, polycythemia, thrombocytosis, and fatigue are all features of the syndrome.8,22 

The neuropathy is symmetrical and ascending, with either an insidious or rapidly progressing onset. Patients often describe numbness and dysesthesias followed by a progressive ascending weakness that overshadows the sensory impairment. In most patients, it is the presenting symptom; however, in one series edema preceded neuropathy in 12% of patients and coincided with it in 14%.8 In our series, 5 patients had a known antecedent plasmaproliferative disorder. The neuropathy is seldom painful, and autonomic involvement is rare.5 It is typically a chronic, large-fiber sensorimotor neuropathy. Most authors have not found monoclonal immunoglobulin associated with nerve specimens,8,36,37,77 except for Adams and Said78 and Broussolle et al.79 

The estimate that 11% to 30% of POEMS patients have Castleman disease is conservative because many patients do not undergo lymph node biopsy.8,22 The association between the 2 disorders is well recognized but poorly understood.8,22,38,47,65,80-114 

Endocrine abnormalities are defining features of the syndrome.19 Primary and secondary hypothyroidism, hypogonadism, adrenocortical insufficiency, and diabetes mellitus have been described.19,22,86,97,115,116 Parathyroid hormone abnormalities were found in 4 of our patients and have been reported previously.2,100,117,118 

Papilledema, which occurs in 29% to 55% of patients, may be asymptomatic or may cause headache, transient obscurations of vision, scotomata, enlarged blind spots, or progressive constriction of the visual field.8,22,38,119 

Sclerotic bone lesions occur in most patients. They may be solitary or multiple. In the series of Soubrier et al,22 prognosis was significantly better for patients with solitary bone lesions. In our series, survival was independent of the number of bone lesions. However, response to therapy was better in patients with radiated dominant bone lesions.

Clubbing may occur in up to 13% of patients.1,120 It is unclear whether the clubbing observed in patients with POEMS syndrome is a function of undiagnosed pulmonary hypertension121; regardless, our data demonstrate that the presence of clubbing bodes a poor prognosis.

Minimal criteria for the diagnosis and evolution of disease

A table and comparisons of the largest series of patients with the syndrome are provided in “Results.” In Table 1 we list the features associated with POEMS and set forth a proposed model of the minimal criteria needed to establish the diagnosis. Relapse and additional new features can occur even in patients who have responded.7,17,35,48,118,122-125 In our series, this occurred in 18% to 25% of patients, depending on whether one considers congestive heart failure and thrombotic abnormalities to be part of the syndrome. New features can develop more than 10 years after the initial presentation.35 We therefore propose the concept that 2 major criteria and at least 1 minor criterion should be met to establish the diagnosis of POEMS syndrome.

Survival

The prognosis for patients with POEMS has been reported to be poor, with median survivals estimated to be 12 to 33 months.2,8,9 However, this has not been our experience. In the present series, median survival was 165 months. Reports of patients who have had the disease for more than 5 years are not unusual.7,17,35,118,123,125 In one study, 7 of 15 patients were alive for more than 5 years, with 1 patient living for 25 years.126 

Our data and those of others demonstrate that survival is not affected by the number of POEMS features,22 although clubbing and extravascular volume overload are associated with shorter survival. In the present series, 35 patients have died. Even patients with multiple bone lesions or those with more than 10% plasma cells do not progress to overt multiple myeloma. Bone fractures rarely develop. The neuropathy may be unrelenting and contribute to progressive inanition and eventual cardiorespiratory failure and pneumonia. Stroke and myocardial infarction, which may or may not be related to the POEMS syndrome, also are observed causes of death.

Less-recognized features

Less-recognized phenomena may be pulmonary hypertension, restrictive lung disease, cardiomyopathy, and an increased incidence of arterial and venous thrombosis.

At least 13 cases of pulmonary hypertension in patients with POEMS syndrome have been reported in previous series.36-45 In the present series, we report an additional 5. Moreover, restrictive lung disease was recognized in another 5% of our patients, and 20% of deaths were related to respiratory failure. In a series of 20 patients with POEMS followed up during a 10-year period, 25% had pulmonary hypertension.43 

Cardiomyopathy and congestive heart disease were observed in 7 of our patients. These conditions have been reported in 3 other cases.7,42,46 

Both arterial and venous thromboses have been described in patients with POEMS syndrome. In our series, there were 18 patients with stroke, myocardial infarction, and Budd-Chiari syndrome. Lesprit et al26 observed 4 of 20 patients to have arterial occlusion. An additional 15 patients with gangrene, ischemia, myocardial infarction, splenic infarcts, and strokes have been reported.47-60 Vasospastic angina,61,62pulmonary embolism, and Budd-Chiari syndrome also have been described.63,64 

In 4 of our patients, renal failure developed as a preterminal event. The renal histologic characteristics of patients with POEMS have been described.29,36,48,65-76 Almost one half of these patients had coexistent Castleman disease. Light-chain deposition is not observed. Instead, membranoproliferative features and evidence of endothelial injury are characteristic.36,48,66,71-73 

Treatment strategies

Because the pathogenesis of this multisystem disease is unclear, treatment is not standardized. The λ light chain has been implicated because less than 5% of patients with POEMS syndrome have monoclonal κ.5,8,9,34,78,104,124,127,128 The hypothesis implicating vascular endothelial growth factor25,28,30,37,65,99,126,129-131 eventually may be validated, providing a uniform target for therapy. To avoid the risk of systemic alkylator exposure, most would agree that for an isolated plasmacytoma, radiation is the preferred treatment.3,11,79,120,132 Systemic and skin symptoms tend to respond sooner than do symptoms of neuropathy, with the former beginning to respond within 1 month and the latter within 3 to 6 months. Besides radiation, many strategies have been used, including plasmapheresis, intravenous immunoglobulin, interferon alfa, corticosteroids, alkylators, azathioprine, autologous stem cell transplantation, tamoxifen, and transretinoic acid.3,7,8,11,20,21,48,63,71,79,96,97,100,105-107,118,120,122,125,127,130,132-144On the basis of our experience and reports in the literature,105,125,134 neither plasmapheresis nor intravenous immunoglobulin is effective treatment. Alkylators with or without corticosteroids are effective in some patients.7,100,105 High-dose chemotherapy with autologous stem cell support may be considered.143-146 

Screening for the syndrome

Screening for POEMS syndrome with serum protein electrophoresis alone is inadequate. Immunofixation of serum and urine and metastatic bone survey are essential for all patients with unexplained peripheral neuropathy. If the index of suspicion is high enough, bone marrow aspirate and biopsy with immunostaining may be required. The predominance of monoclonal λ cannot be overemphasized. Skin, viscera, lymph nodes, and optic fundi should be examined carefully. If the diagnosis is strongly suspected, a thorough endocrine evaluation should be performed. If the patient has respiratory symptoms, pulmonary function testing and echocardiography should be performed.

Final comments

We propose that the diagnosis of POEMS syndrome be predicated on the presence of major and minor criteria. Two major criteria and at least one minor criterion should be satisfied to differentiate this syndrome from neuropathy associated with monoclonal gammopathy of undetermined significance, myeloma, and Waldenström disease. Primary systemic amyloidosis also should be excluded. The major criteria include a polyneuropathy and a clonal plasmaproliferative disorder (almost always λ). The minor criteria include osteosclerotic bone lesions; Castleman disease; papilledema; organomegaly, including lymphadenopathy; edema, pleural effusion, or ascites; endocrinopathy; and skin changes.

Survival for patients with POEMS syndrome is better than previously reported, with median survival of 165 months, regardless of how many syndrome features, bone lesions, or plasma cells are present at diagnosis. Patients do not have the usual complications of classic multiple myeloma. Radiation and chemotherapy are the most useful therapies. Ultimately, manipulation of the cytokine milieu may be the treatment of choice.

Prepublished online as Blood First Edition Paper, November 27, 2002; DOI 10.1182/blood- 2002-07-2299.

Supported in part by grants CA62242 and CA91561 from the National Institutes of Health.

The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked “advertisement” in accordance with 18 U.S.C. section 1734.

References

References
1
Crow
R
Peripheral neuritis in myelomatosis.
Brit Med J.
2
1956
802
804
2
Driedger
H
Pruzanski
W
Plasma cell neoplasia with osteosclerotic lesions: a study of five cases and a review of the literature.
Arch Intern Med.
139
1979
892
896
3
Iwashita
H
Ohnishi
A
Asada
M
Kanazawa
Y
Kuroiwa
Y
Polyneuropathy, skin hyperpigmentation, edema, and hypertrichosis in localized osteosclerotic myeloma.
Neurology.
27
1977
675
681
4
Mangalik
A
Veliath
AJ
Osteosclerotic myeloma and peripheral neuropathy: a case report.
Cancer.
28
1971
1040
1045
5
Kelly
JJ
Jr
Kyle
RA
Miles
JM
Dyck
PJ
Osteosclerotic myeloma and peripheral neuropathy.
Neurology.
33
1983
202
210
6
Evison
G
Evans
KT
Sclerotic bone deposits in multiple myeloma [letter].
Br J Radiol.
56
1983
145
7
Reitan
JB
Pape
E
Fossa
SD
Julsrud
OJ
Slettnes
ON
Solheim
OP
Osteosclerotic myeloma with polyneuropathy.
Acta Med Scand.
208
1980
137
144
8
Nakanishi
T
Sobue
I
Toyokura
Y
et al
The Crow-Fukase syndrome: a study of 102 cases in Japan.
Neurology.
34
1984
712
720
9
Driedger
H
Pruzanski
W
Plasma cell neoplasia with peripheral polyneuropathy: a study of five cases and a review of the literature.
Medicine.
59
1980
301
310
10
Scheinker
I
Myelom und Nervensystem: Über eine bisher nicht beschriebene mit eigentümlichen Hautveränderungen einhergehende Polyneuritis bei einem plasmazellulären Myelom des Sternums.
Deutsche Zeitschrift für Nervenheilkunde.
147
1938
247
273
11
Morley
JB
Schwieger
AC
The relation between chronic polyneuropathy and osteosclerotic myeloma.
J Neurol Neurosurg Psychiatry.
30
1967
432
442
12
Shimpo
S
Solitary myeloma causing polyneuritis and endocrine disorders [in Japanese].
Nippon Rinsho.
26
1968
2444
2456
13
Mayo
CM
Daniels
A
Barron
KD
Polyneuropathy in the osteosclerotic form of multiple myeloma.
Trans Am Neurol Assoc.
93
1968
240
242
14
Fukase
M
Kakimatsu
T
Nishitani
H
et al
Report of a case of solitary plasmacytoma in the abdomen presenting with polyneuropathy and endocrinological disorders [abstract].
Clin Neurol.
9
1969
657
15
Imawari
M
Akatsuka
N
Ishibashi
M
Beppu
H
Suzuki
H
Syndrome of plasma cell dyscrasia, polyneuropathy, and endocrine disturbances: report of a case.
Ann Intern Med.
81
1974
490
493
16
Getaz
P
Handler
L
Jacobs
P
Tunley
I
Osteosclerotic myeloma with peripheral neuropathy.
S Afr Med J.
48
1974
1246
1250
17
Waldenström
JG
Adner
A
Gydell
K
Zettervall
O
Osteosclerotic “plasmocytoma” with polyneuropathy, hypertrichosis and diabetes.
Acta Med Scand.
203
1978
297
303
18
Moya-Mir
MS
Martin-Martin
F
Barbadillo
R
et al
Plasma cell dyscrasia with polyneuritis and dermato-endocrine alterations: report of a new case outside Japan.
Postgrad Med J.
56
1980
427
430
19
Bardwick
PA
Zvaifler
NJ
Gill
GN
Newman
D
Greenway
GD
Resnick
DL
Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes: the POEMS syndrome: report on two cases and a review of the literature.
Medicine.
59
1980
311
322
20
Milanov
I
Georgiev
D
Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome.
Can J Neurol Sci.
21
1994
60
63
21
Longo
G
Emilia
G
Torelli
U
Skin changes in POEMS syndrome.
Haematologica.
84
1999
86
22
Soubrier
MJ
Dubost
JJ
Sauvezie
BJ
POEMS syndrome: a study of 25 cases and a review of the literature. French Study Group on POEMS syndrome.
Am J Med.
97
1994
543
553
23
Watanabe
O
Arimura
K
Kitajima
I
Osame
M
Maruyama
I
Greatly raised vascular endothelial growth factor (VEGF) in POEMS syndrome [letter].
Lancet.
347
1996
702
24
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.
21
1998
1390
1397
25
Soubrier
M
Dubost
JJ
Serre
AF
et al
Growth factors in POEMS syndrome: evidence for a marked increase in circulating vascular endothelial growth factor.
Arthritis Rheum.
40
1997
786
787
26
Lesprit
P
Authier
FJ
Gherardi
R
et al
Acute arterial obliteration: a new feature of the POEMS syndrome?
Medicine.
75
1996
226
232
27
Soubrier
M
Guillon
R
Dubost
JJ
et al
Arterial obliteration in POEMS syndrome: possible role of vascular endothelial growth factor.
J Rheumatol.
25
1998
813
815
28
Feinberg
L
Temple
D
de Marchena
E
Patarca
R
Mitrani
A
Soluble immune mediators in POEMS syndrome with pulmonary hypertension: case report and review of the literature.
Crit Rev Oncog.
10
1999
293
302
29
Soubrier
M
Sauron
C
Souweine
B
et al
Growth factors and proinflammatory cytokines in the renal involvement of POEMS syndrome.
Am J Kidney Dis.
34
1999
633
638
30
Hashiguchi
T
Arimura
K
Matsumuro
K
et al
Highly concentrated vascular endothelial growth factor in platelets in Crow-Fukase syndrome.
Muscle Nerve.
23
2000
1051
1056
31
Kaplan
EL
Meier
P
Nonparametric estimation from incomplete observations.
J Am Stat Assoc.
53
1958
457
481
32
Peto
R
Peto
J
Asymptotically efficient rank in variant test procedures.
J R Stat Soc A.
135
1972
185
198
33
Cox
DR
Regression models and life tables.
J R Stat Soc B.
34
1972
187
202
34
Takatsuki
K
Sanada
I
Plasma cell dyscrasia with polyneuropathy and endocrine disorder: clinical and laboratory features of 109 reported cases.
Jpn J Clin Oncol.
13
1983
543
555
35
Sakemi
H
Okada
H
An autopsy case of Crow-Fukase syndrome which developed 18 years after the first manifestation of plasmacytoma.
Intern Med.
31
1992
50
54
36
Viard
JP
Lesavre
P
Boitard
C
et al
POEMS syndrome presenting as systemic sclerosis: clinical and pathologic study of a case with microangiopathic glomerular lesions.
Am J Med.
84
1988
524
528
37
Rose
C
Zandecki
M
Copin
MC
et al
POEMS syndrome: report on six patients with unusual clinical signs, elevated levels of cytokines, macrophage involvement and chromosomal aberrations of bone marrow plasma cells.
Leukemia.
11
1997
1318
1323
38
Brazis
PW
Liesegang
TJ
Bolling
JP
Kashii
S
Trachtman
M
Burde
RM
When do optic disc edema and peripheral neuropathy constitute poetry?
Surv Ophthalmol.
35
1990
219
225
39
Mufti
GJ
Hamblin
TJ
Gordon
J
Melphalan-induced pulmonary fibrosis in osteosclerotic myeloma.
Acta Haematol.
69
1983
140
141
40
Ribadeau-Dumas
S
Tillie-Leblond
I
Rose
C
et al
Pulmonary hypertension associated with POEMS syndrome.
Eur Respir J.
9
1996
1760
1762
41
Okura
H
Gohma
I
Hatta
K
Imanaka
T
Thiamine deficiency and pulmonary hypertension in Crow-Fukase syndrome.
Intern Med.
34
1995
674
675
42
Iwasaki
H
Ogawa
K
Yoshida
H
et al
Crow-Fukase syndrome associated with pulmonary hypertension.
Intern Med.
32
1993
556
560
43
Lesprit
P
Godeau
B
Authier
FJ
et al
Pulmonary hypertension in POEMS syndrome: a new feature mediated by cytokines.
Am J Respir Crit Care Med.
157
1998
907
911
44
Kishimoto
S
Takenaka
H
Shibagaki
R
Noda
Y
Yamamoto
M
Yasuno
H
Glomeruloid hemangioma in POEMS syndrome shows two different immunophenotypic endothelial cells.
J Cutan Pathol.
27
2000
87
92
45
Paciocco
G
Bossone
E
Erba
H
Rubenfire
M
Reversible pulmonary hypertension in POEMS syndrome: another etiology of triggered pulmonary vasculopathy?
Can J Cardiol.
16
2000
1007
1012
46
Shimizu
N
Goya
M
Akimoto
H
et al
Cardiomyopathy in a case of Crow-Fukase syndrome.
Jpn Heart J.
38
1997
877
880
47
Forster
A
Muri
R
Recurrent cerebrovascular insult—manifestation of POEMS syndrome? [in German].
Schweiz Med Wochenschr.
128
1998
1059
1064
48
Stewart
PM
McIntyre
MA
Edwards
CR
The endocrinopathy of POEMS syndrome.
Scott Med J.
34
1989
520
522
49
Hori
T
Tsuboi
Y
Okubo
R
Hirooka
M
Yamada
T
Crow-Fukase syndrome associated with Castleman disease showing hypertrophic cranial pachymeningitis and bilateral internal carotid artery occlusion [in Japanese].
Rinsho Shinkeigaku.
39
1999
456
460
50
Manning
WJ
Goldberger
AL
Drews
RE
et al
POEMS syndrome with myocardial infarction: observations concerning pathogenesis and review of the literature.
Semin Arthritis Rheum.
22
1992
151
161
51
Solomons
RE
Gibbs
DD
Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes: the POEMS syndrome.
J R Soc Med.
75
1982
553
555
52
Semble
EL
Challa
VR
Holt
DA
Pisko
EJ
Light and electron microscopic findings in POEMS, or Japanese multisystem syndrome.
Arthritis Rheum.
29
1986
286
291
53
Tobin
MJ
Fitzgerald
MX
The Japanese plasma cell dyscrasia syndrome: case report and theory of pathogenesis.
Postgrad Med J.
58
1982
786
789
54
Rushton
D
Peripheral sensorimotor neuropathy associated with a localized myeloma.
Br Med J.
2
1965
203
205
55
Amiel
JL
Machover
D
Droz
JP
Plasma cell dyscrasia with arteriopathy, polyneuropathy, and endocrine syndrome: a Japanese disease in an Italian patient [in French].
Ann Med Interne.
126
1975
745
749
56
Huth
M
Gordon
D
Verrier
ED
Otto
CM
Aortic valvular fibroma as a source of systemic emboli in POEMS syndrome.
J Am Soc Echocardiogr.
4
1991
401
404
57
Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 10-1987. A 59-year-old woman with progressive polyneuropathy and monoclonal gammopathy.
N Engl J Med.
316
1987
606
618
58
Virmani
R
Popovsky
MA
Roberts
WC
Thrombocytosis, coronary thrombosis and acute myocardial infarction.
Am J Med.
67
1979
498
506
59
Zenone
T
Bastion
Y
Salles
G
et al
POEMS syndrome, arterial thrombosis and thrombocythaemia.
J Intern Med.
240
1996
107
109
60
Bova
G
Pasqui
AL
Saletti
M
Bruni
F
Auteri
A
POEMS syndrome with vascular lesions: a role for interleukin-1β and interleukin-6 increase—a case report.
Angiology.
49
1998
937
940
61
Mochizuki
Y
Yoshihashi
H
Oishi
M
et al
Crow-Fukase syndrome: a case associated with vasospastic angina.
Acta Neurol.
16
1994
170
176
62
Kato
T
Kaneko
E
Numano
F
et al
Vasospastic angina in Crow-Fukase syndrome.
Am Heart J.
124
1992
505
507
63
Kuwabara
S
Hattori
T
Shimoe
Y
Kamitsukasa
I
Long term melphalan-prednisolone chemotherapy for POEMS syndrome.
J Neurol Neurosurg Psychiatry.
63
1997
385
387
64
Wong
VA
Wade
NK
POEMS syndrome: an unusual cause of bilateral optic disk swelling.
Am J Ophthalmol.
126
1998
452
454
65
Nakazawa
K
Itoh
N
Shigematsu
H
Koh
CS
An autopsy case of Crow-Fukase (POEMS) syndrome with a high level of IL-6 in the ascites: special reference to glomerular lesions.
Acta Pathol Jpn.
42
1992
651
656
66
Navis
GJ
Dullaart
RP
Vellenga
E
Elema
JD
de Jong
PE
Renal disease in POEMS syndrome: report on a case and review of the literature.
Nephrol Dial Transplant.
9
1994
1477
1481
67
Nakamoto
Y
Imai
H
Yasuda
T
Asakura
K
Miura
AB
Nishimura
S
Mesangiolytic glomerulonephritis associated with Takatsuki's syndrome: an analysis of five renal biopsy specimens.
Hum Pathol.
20
1989
243
251
68
Nakamoto
Y
Imai
H
Yasuda
T
Wakui
H
Miura
AB
A spectrum of clinicopathological features of nephropathy associated with POEMS syndrome.
Nephrol Dial Transplant.
14
1999
2370
2378
69
Fukatsu
A
Ito
Y
Yuzawa
Y
et al
A case of POEMS syndrome showing elevated serum interleukin 6 and abnormal expression of interleukin 6 in the kidney.
Nephron.
62
1992
47
51
70
Fukatsu
A
Tamai
H
Nishikawa
K
et al
The kidney disease of Crow-Fukase (POEMS) syndrome: a clinico-pathological study of four cases.
Clin Nephrol.
36
1991
76
82
71
Sano
M
Terasaki
T
Koyama
A
Narita
M
Tojo
S
Glomerular lesions associated with the Crow-Fukase syndrome.
Virchows Arch A Pathol Anat Histopathol.
409
1986
3
9
72
Takazoe
K
Shimada
T
Kawamura
T
et al
Possible mechanism of progressive renal failure in Crow-Fukase syndrome.
Clin Nephrol.
47
1997
66
67
73
Mizuiri
S
Mitsuo
K
Sakai
K
et al
Renal involvement in POEMS syndrome.
Nephron.
59
1991
153
156
74
Kubota
T
Yoshizawa
N
Takeuchi
A
Niwa
H
Microangiopathic hypothesis of POEMS tissue lesions.
Clin Nephrol.
38
1992
115
118
75
Modesto-Segonds
A
Rey
JP
Orfila
C
Huchard
G
Suc
JM
Renal involvement in POEMS syndrome.
Clin Nephrol.
43
1995
342
345
76
Fam
AG
Rubenstein
JD
Cowan
DH
POEMS syndrome: study of a patient with proteinuria, microangiopathic glomerulopathy, and renal enlargement.
Arthritis Rheum.
29
1986
233
241
77
Bergouignan
FX
Massonnat
R
Vital
C
et al
Uncompacted lamellae in three patients with POEMS syndrome.
Eur Neurol.
27
1987
173
181
78
Adams
D
Said
G
Ultrastructural characterisation of the M protein in nerve biopsy of patients with POEMS syndrome.
J Neurol Neurosurg Psychiatry.
64
1998
809
812
79
Broussolle
E
Vighetto
A
Bancel
B
Confavreux
C
Pialat
J
Aimard
G
P.O.E.M.S. syndrome with complete recovery after treatment of a solitary plasmocytoma.
Clin Neurol Neurosurg.
93
1991
165
170
80
Shirabe
S
Kishikawa
M
Mine
M
Miyazaki
T
Kuratsune
H
Tobinaga
K
Crow-Fukase syndrome associated with extramedullary plasmacytoma.
Jpn J Med.
30
1991
64
66
81
Thajeb
P
Chee
CY
Lo
SF
Lee
N
The POEMS syndrome among Chinese: association with Castleman's disease and some immunological abnormalities.
Acta Neurol Scand.
80
1989
492
500
82
Papo
T
Soubrier
M
Marcelin
AG
et al
Human herpesvirus 8 infection, Castleman's disease and POEMS syndrome.
Br J Haematol.
104
1999
932
933
83
Vital
C
Gherardi
R
Vital
A
et al
Uncompacted myelin lamellae in polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes syndrome: ultrastructural study of peripheral nerve biopsy from 22 patients.
Acta Neuropathol.
87
1994
302
307
84
Yang
SG
Cho
KH
Bang
YJ
Kim
CW
A case of glomeruloid hemangioma associated with multicentric Castleman's disease.
Am J Dermatopathol.
20
1998
266
270
85
Kobayashi
H
Ii
K
Sano
T
Sakaki
A
Hizawa
K
Ogushi
F
Plasma-cell dyscrasia with polyneuropathy and endocrine disorders associated with dysfunction of salivary glands.
Am J Surg Pathol.
9
1985
759
763
86
Bitter
MA
Komaiko
W
Franklin
WA
Giant lymph node hyperplasia with osteoblastic bone lesions and the POEMS (Takatsuki's) syndrome.
Cancer.
56
1985
188
194
87
Lapresle
J
Lacroix-Ciaudo
C
Reynes
M
Madoule
P
Crow-Fukase syndrome (POEMS syndrome) and osseous mastocytosis secondary to Castleman's angiofollicular lymphoid hyperplasia [in French].
Rev Neurol.
142
1986
731
737
88
Gherardi
R
Baudrimont
M
Kujas
M
et al
Pathological findings in three non-Japanese patients with the POEMS syndrome.
Virchows Arch A Pathol Anat Histopathol.
413
1988
357
365
89
Dworak
O
Tschubel
K
Zhou
H
Meybehm
M
Angiofollicular lymphatic hyperplasia with plasmacytoma and polyneuropathy: a case report with immunohistochemical study [in German].
Klin Wochenschr.
66
1988
591
595
90
Rolon
PG
Audouin
J
Diebold
J
Rolon
PA
Gonzalez
A
Multicentric angiofollicular lymph node hyperplasia associated with a solitary osteolytic costal IgG λ myeloma. POEMS syndrome in a South American (Paraguayan) patient.
Pathol Res Pract.
185
1989
468
475
91
Carcaterra
A
Santini
R
Sozzi
G
Zuccoli
E
Crow-Fukase syndrome (POEMS syndrome): the first Italian presentation of a case and review of the literature [in Italian].
G Ital Dermatol Venereol.
125
1990
97
103
92
Chan
JK
Fletcher
CD
Hicklin
GA
Rosai
J
Glomeruloid hemangioma: a distinctive cutaneous lesion of multicentric Castleman's disease associated with POEMS syndrome.
Am J Surg Pathol.
14
1990
1036
1046
93
Munoz
G
Geijo
P
Moldenhauer
F
Perez-Moro
E
Razquin
J
Piris
MA
Plasmacellular Castleman's disease and POEMS syndrome.
Histopathology.
17
1990
172
174
94
Gherardi
RK
Malapert
D
Degos
JD
Castleman disease-POEMS syndrome overlap.
Ann Intern Med.
114
1991
520
521
95
Myers
BM
Miralles
GD
Taylor
CA
Gastineau
DA
Pisani
RJ
Talley
NJ
POEMS syndrome with idiopathic flushing mimicking carcinoid syndrome.
Am J Med.
90
1991
646
648
96
Coto
V
Auletta
M
Oliviero
U
et al
POEMS syndrome: an Italian case with diagnostic and therapeutic implications.
Ann Ital Med Int.
6
1991
416
419
97
Bosco
J
Pathmanathan
R
POEMS syndrome, osteosclerotic myeloma and Castleman's disease: a case report.
Aust N Z J Med.
21
1991
454
456
98
Mandler
RN
Kerrigan
DP
Smart
J
Kuis
W
Villiger
P
Lotz
M
Castleman's disease in POEMS syndrome with elevated interleukin-6.
Cancer.
69
1992
2697
2703
99
Emile
C
Danon
F
Fermand
JP
Clauvel
JP
Castleman disease in POEMS syndrome with elevated interleukin-6 [letter].
Cancer.
71
1993
874
100
Judge
MR
McGibbon
DH
Thompson
RP
Angioendotheliomatosis associated with Castleman's lymphoma and POEMS syndrome.
Clin Exp Dermatol.
18
1993
360
362
101
Del Rio
R
Alsina
M
Monteagudo
J
et al
POEMS syndrome and multiple angioproliferative lesions mimicking generalized histiocytomas.
Acta Derm Venereol.
74
1994
388
390
102
Bhatia
M
Maheshwari
MC
Angiofollicular lymphoid hyperplasia presenting as POEMS syndrome.
J Assoc Physicians India.
42
1994
751
752
103
Adelman
HM
Cacciatore
ML
Pascual
JF
Mike
JM
Alberts
WM
Wallach
PM
Case report: Castleman disease in association with POEMS.
Am J Med Sci.
307
1994
112
114
104
Pareyson
D
Marazzi
R
Confalonieri
P
Mancardi
GL
Schenone
A
Sghirlanzoni
A
The POEMS syndrome: report of six cases.
Ital J Neurol Sci.
15
1994
353
358
105
Ku
A
Lachmann
E
Tunkel
R
Nagler
W
Severe polyneuropathy: initial manifestation of Castleman's disease associated with POEMS syndrome.
Arch Phys Med Rehabil.
76
1995
692
694
106
Huang
CC
Chu
CC
Poor response to intravenous immunoglobulin therapy in patients with Castleman's disease and the POEMS syndrome.
J Neurol.
243
1996
726
727
107
Chang
YJ
Huang
CC
Chu
CC
Intravenous immunoglobulin therapy in POEMS syndrome: a case report.
Zhonghua Yi Xue Za Zhi.
58
1996
366
369
108
Belec
L
Salmon-Ceron
D
Blanche
P
Dreyfus
F
Zuber
M
Sicard
D
POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes), multicentric Castleman disease, renal chromophobe carcinoma and herpes virus type 8 infection [in French].
Ann Pathol.
19
1999
373
374
109
Belec
L
Mohamed
AS
Authier
FJ
et al
Human herpesvirus 8 infection in patients with POEMS syndrome-associated multicentric Castleman's disease.
Blood.
93
1999
3643
3653
110
Belec
L
Authier
FJ
Mohamed
AS
Soubrier
M
Gherardi
RK
Antibodies to human herpesvirus 8 in POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes) syndrome with multicentric Castleman's disease.
Clin Infect Dis.
28
1999
678
679
111
Gaba
AR
Stein
RS
Sweet
DL
Variakojis
D
Multicentric giant lymph node hyperplasia.
Am J Clin Pathol.
69
1978
86
90
112
Hineman
VL
Phyliky
RL
Banks
PM
Angiofollicular lymph node hyperplasia and peripheral neuropathy: association with monoclonal gammopathy.
Mayo Clin Proc.
57
1982
379
382
113
Black
DA
Forgacs
I
Davies
DR
Thompson
RP
Pseudotumour cerebri in a patient with Castleman's disease.
Postgrad Med J.
64
1988
217
219
114
Feigert
JM
Sweet
DL
Coleman
M
et al
Multicentric angiofollicular lymph node hyperplasia with peripheral neuropathy, pseudotumor cerebri, IgA dysproteinemia, and thrombocytosis in women: a distinct syndrome.
Ann Intern Med.
113
1990
362
367
115
Sasano
T
Sakurai
SI
Hara
Y
Improvement in gonadotropin secretion after corticosteroid therapy in a case of POEMS syndrome.
Endocr J.
45
1998
413
419
116
Shichiri
M
Iwashina
M
Imai
T
Marumo
F
Hirata
Y
Abnormal FSH hypersecretion as an endocrinological manifestation of POEMS syndrome.
Endocr J.
45
1998
131
134
117
Ludescher
C
Grunewald
K
Fend
F
Dietze
O
Thaler
J
Schmid
KW
Osteosclerotic myeloma with polyneuropathy and hypocalcemia.
Blut.
58
1989
207
210
118
Cabezas-Agricola
JM
Lado-Abeal
JJ
Otero- Anton
E
Sanchez-Leira
J
Cabezas-Cerrato
J
Hypoparathyroidism in POEMS syndrome.
Lancet.
347
1996
701
702
119
Bolling
JP
Brazis
PW
Optic disk swelling with peripheral neuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS syndrome).
Am J Ophthalmol.
109
1990
503
510
120
Davis
LE
Drachman
DB
Myeloma neuropathy: successful treatment of two patients and review of cases.
Arch Neurol.
27
1972
507
511
121
Martinez-Lavin
M
Vargas
AS
Cabre
J
et al
Features of hypertrophic osteoarthropathy in patients with POEMS syndrome: a metaanalysis.
J Rheumatol.
24
1997
2267
2268
122
Crisci
C
Barbieri
F
Parente
D
Pappone
N
Caruso
G
POEMS syndrome: follow-up study of a case.
Clin Neurol Neurosurg.
94
1992
65
68
123
Rongioletti
F
Gambini
C
Lerza
R
Glomeruloid hemangioma: a cutaneous marker of POEMS syndrome.
Am J Dermatopathol.
16
1994
175
178
124
Simmons
Z
Wald
J
Albers
JW
Feldman
EL
The natural history of a “benign” rib lesion in a patient with a demyelinating polyneuropathy and an unusual variant of POEMS syndrome.
Muscle Nerve.
17
1994
1055
1059
125
Silberstein
LE
Duggan
D
Berkman
EM
Therapeutic trial of plasma exchange in osteosclerotic myeloma associated with the POEMS syndrome.
J Clin Apheresis.
2
1985
253
257
126
Gherardi
RK
Belec
L
Soubrier
M
et al
Overproduction of proinflammatory cytokines imbalanced by their antagonists in POEMS syndrome.
Blood.
87
1996
1458
1465
127
Saida
K
Kawakami
H
Ohta
M
Iwamura
K
Coagulation and vascular abnormalities in Crow-Fukase syndrome.
Muscle Nerve.
20
1997
486
492
128
Miralles
GD
O'Fallon
JR
Talley
NJ
Plasma-cell dyscrasia with polyneuropathy: the spectrum of POEMS syndrome.
N Engl J Med.
327
1992
1919
1923
129
Hitoshi
S
Suzuki
K
Sakuta
M
Elevated serum interleukin-6 in POEMS syndrome reflects the activity of the disease.
Intern Med.
33
1994
583
587
130
Orefice
G
Morra
VB
De Michele
G
et al
POEMS syndrome: clinical, pathological and immunological study of a case.
Neurol Res.
16
1994
477
480
131
Saida
K
Ohta
M
Kawakami
H
Saida
T
Cytokines and myelin antibodies in Crow-Fukase syndrome.
Muscle Nerve.
19
1996
1620
1622
132
Philips
ED
el-Mahdi
AM
Humphrey
RL
Furlong
MB
Jr
The effect of the radiation treatment on the polyneuropathy of multiple myeloma.
J Can Assoc Radiol.
23
1972
103
106
133
Ako
S
Kaneko
Y
Higuchi
M
et al
Crow-Fukase syndrome: immunoadsorption plasmapheresis effectively lowers elevated interleukin-6 concentration.
Nephrol Dial Transplant.
14
1999
419
422
134
Atsumi
T
Kato
K
Kurosawa
S
Abe
M
Fujisaku
A
A case of Crow-Fukase syndrome with elevated soluble interleukin-6 receptor in cerebrospinal fluid: response to double-filtration plasmapheresis and corticosteroids.
Acta Haematol.
94
1995
90
94
135
Benito-Leon
J
Lopez-Rios
F
Rodriguez-Martin
FJ
Madero
S
Ruiz
J
Rapidly deteriorating polyneuropathy associated with osteosclerotic myeloma responsive to intravenous immunoglobulin and radiotherapy.
J Neurol Sci.
158
1998
113
117
136
Henze
T
Krieger
G
Combined high-dose 7S-IgG and dexamethasone is effective in severe polyneuropathy of the POEMS syndrome.
J Neurol.
242
1995
482
483
137
Rotta
FT
Bradley
WG
Marked improvement of severe polyneuropathy associated with multifocal osteosclerotic myeloma following surgery, radiation, and chemotherapy.
Muscle Nerve.
20
1997
1035
1037
138
Donofrio
PD
Albers
JW
Greenberg
HS
Mitchell
BS
Peripheral neuropathy in osteosclerotic myeloma: clinical and electrodiagnostic improvement with chemotherapy.
Muscle Nerve.
7
1984
137
141
139
Parra
R
Fernandez
JM
Garcia-Bragado
F
Bueno
J
Biosca
M
Successful treatment of peripheral neuropathy with chemotherapy in osteosclerotic myeloma.
J Neurol.
234
1987
261
263
140
Antela Lopez
A
Requena Caballero
I
Masa Vazquez
L
Antela Carrera
C
Barrio Gomez
E
Polyneuropathy associated with osteosclerotic myeloma: excellent response to chemotherapy [in Spanish].
Neurologia.
5
1990
102
106
141
Rousseau
JJ
Franck
G
Grisar
T
Reznik
M
Heynen
G
Salmon
J
Osteosclerotic myeloma with polyneuropathy and ectopic secretion of calcitonin.
Eur J Cancer.
14
1978
133
140
142
Reulecke
M
Dumas
M
Meier
C
Specific antibody activity against neuroendocrine tissue in a case of POEMS syndrome with IgG gammopathy.
Neurology.
38
1988
614
616
143
Rovira
M
Carreras
E
Bladé
J
et al
Dramatic improvement of POEMS syndrome following autologous haematopoietic cell transplantation.
Br J Haematol.
115
2001
373
375
144
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.
28
2001
305
309
145
Dispenzieri
A
Lacy
MQ
Litzow
MR
et al
Peripheral blood stem cell transplant (PBSCT) in patients with POEMS syndrome [abstract].
Blood.
98
2001
391b
146
Jaccard
A
Royer
B
Bordessoule
D
Brouet
JC
Fermand
JP
High-dose therapy and autologous blood stem cell transplantation in POEMS syndrome.
Blood.
99
2002
3057
3059

Author notes

Angela Dispenzieri, Division of Hematology and Internal Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905; e-mail:dispenzieri.angela@mayo.edu.