Original Article

Plasma-Cell Dyscrasia with Polyneuropathy — The Spectrum of Poems Syndrome

G. Diego Miralles, M.D., Judith R. O'Fallon, Ph.D., and Nicholas J. Talley, M.B., Ph.D., F.R.A.C.P.

N Engl J Med 1992; 327:1919-1923December 31, 1992

Abstract

Abstract

Background.

The POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome and osteosclerotic myeloma (polyneuropathy and sclerotic bone lesions) may both be manifestations of plasma-cell dyscrasia, but the interrelation of these diseases is not clear. We therefore set out to define the clinical spectrum of disease in patients with plasma-cell dyscrasia and polyneuropathy who have the complete or incomplete form of the POEMS syndrome or osteosclerotic myeloma.

Full Text of Background....

Methods.

Among 2714 patients with plasma-cell dyscrasia who were identified between 1973 and 1989, we reviewed the cases of those with polyneuropathy and plasma-cell dyscrasia who fulfilled the criteria for the POEMS syndrome or osteosclerotic myeloma.

Full Text of Methods....

Results.

Thirty-eight patients (1.4 percent) with a median age of 51 years were identified, 22 of whom were male. By definition, all had polyneuropathy (37 combined sensorimotor, and 1 primarily motor). Other findings included osteosclerotic bone lesions (82 percent), skin abnormalities (58 percent), lymphadenopathy (42 percent), papilledema (37 percent), peripheral edema (29 percent), hepatomegaly (24 percent), splenomegaly (21 percent), and ascites (11 percent). Thirty-three patients (87 percent) had an abnormal M protein in serum or urine (17 had IgA-λ, and 12 IgG-λ). Five patients fulfilled all the criteria for the POEMS syndrome. The estimated five-year survival in the 38 patients was 60 percent, which was significantly better than the 20 percent survival in 869 patients with multiple myeloma (P<0.05). The clinical course was similar among the patients with the complete form of the POEMS syndrome and those with the incomplete form.

Full Text of Results....

Conclusions.

Plasma-cell dyscrasia with polyneuropathy is a rare multisystem disease that often presents with osteosclerotic bone lesions. The differentiation of the POEMS syndrome from so-called osteosclerotic myeloma with peripheral neuropathy appears to have no clinical value. (N Engl J Med 1992;327:1919–23.)

Full Text of Conclusions....

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Media in This Article

Figure 1Survival Curves for 38 Patients with Plasma-Cell Dyscrasia and Polyneuropathy and 869 Patients with Multiple Myeloma.

Figure 2Survival Curves for 5 Patients Who Had All Five Features of the POEMS Syndrome and 33 Patients Who Did Not.

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Article

IN tertiary care centers, up to 10 percent of all patients with idiopathic peripheral neuropathy have an underlying plasma-cell dyscrasia.1 , 2 Osteosclerotic myeloma is a plasma-cell dyscrasia characterized by sclerotic bone lesions and progressive demyelinating polyneuropathy; it differs from multiple myeloma, in which lytic bone lesions are typical.1 2 3 4 5 6 7 Although multiple myeloma is defined by the presence of bone marrow plasmacytosis with more than 10 percent plasma cells, the bone marrow in osteosclerotic myeloma usually contains less than 5 percent plasma cells.2 , 7 The proliferation of plasma cells in osteosclerotic myeloma is usually detected in either affected bone or lymph nodes. Bone biopsy of the sclerotic lesions typically reveals a plasmacytoma with polymorphic plasma cells.8 , 9 The proliferation of plasma cells in lymph nodes presents a specific histologic picture, characterized by large follicles with intervening sheaths of plasma cells and blood vessels; these plasma cells prove to be monoclonal when analyzed with lambda or kappa light-chain antiserum.8 , 10 Patients with plasma-cell dyscrasia can also present with a variable constellation of features, including polyneuropathy, organomegaly (lymphadenopathy, splenomegaly, or hepatomegaly), endocrinopathy (typically, hypogonadism or hypothyroidism), monoclonal gammopathy, and skin changes; this has been termed the "POEMS syndrome," but whether this syndrome is a distinct variant of osteosclerotic myeloma is unclear.5 6 7 , 11 12 13 14 15 16 17 18 19 20 21 The relation between the POEMS syndrome and osteosclerotic myeloma is uncertain. We therefore attempted to describe the clinical and laboratory features of the POEMS syndrome and osteosclerotic myeloma and to compare the prognosis of these diseases with that of classic multiple myeloma.

Methods

A retrospective analysis of 2714 patients with plasma-cell dyscrasia who were seen at the Mayo Clinic between January 1973 and April 1989 was performed with a computer search of medical records. The study was approved by the institutional review board of the Mayo Clinic. A retrospective analysis was necessary because of the rarity of this disorder. Criteria for entry in the study included all of the following: clinically apparent polyneuropathy or polyradiculopathy, confirmed by needle electromyography and nerve-conduction studies; the absence of secondary causes, such as amyloidosis, and of other diseases, such as nerve-root or spinal cord compression; pathological findings of either an underlying plasmacytoma in the bone biopsy or plasma-cell proliferation with characteristic histologic features of angiofollicular hyperplasia in the lymph-node—biopsy specimen; normal results of bone marrow biopsy (to exclude patients with multiple myeloma); and the exclusion of other malignant bony lesions on the basis of bone biopsy.

Thirty-eight patients with polyneuropathy who fulfilled the criteria were identified; these included 16 patients whose cases have been reported previously.7 , 22 , 23 All the diagnoses were made at the Mayo Clinic, and follow-up was begun at the time of the diagnosis.

A variety of treatments were used, including irradiation with or without prednisone or chemotherapeutic agents. Clinical and laboratory follow-up was done through chart review and telephone communication with either the patients' local physicians or the patients themselves. The clinical response to treatment was classified as follows: no response was considered to have occurred if the patient's condition continued to deteriorate; a partial response was considered to have occurred if the progression of the disease was stopped or slowed by treatment; and a complete response was considered to have occurred if there was substantial functional improvement as compared with the patient's pretreatment status.

The Kaplan–Meier survival curve24 was constructed for the entire group of patients and plotted against the survival curve for 869 patients with multiple myeloma who had previously been studied at our institution.25 To identify prognostic factors for this disease, we defined 10 dichotomous (i.e., yes/no) variables quantifying possible prognostic factors before the study began, calculated the Kaplan–Meier survival curves for the two values of each variable, and tested for equality among the variables using the log-rank test.26

Results

Thirty-eight patients who fulfilled the entry criteria were identified (1.4 percent of the patients with plasma-cell dyscrasia). The clinical and biochemical characteristics of the patients at presentation are shown in Table 1Table 1Clinical and Biochemical Characteristics of the 38 Patients with Plasma-Cell Dyscrasia and Polyneuropathy.*, according to the number of features of the POEMS syndrome. The ratio of males to females was 22 to 16, and the median age was 51 years (range, 32 to 83). All the patients had polyneuropathy by definition: 37 had a combined sensorimotor neuropathy, and 1 had primarily motor neuropathy. Thirty-three patients (87 percent) had an abnormal M protein in serum or urine, the most common of which was IgAλ. Thirty-six patients had bone lesions; of these, 31 (86 percent) had sclerotic bone lesions. Twenty-two patients had skin abnormalities, the most common of which was hyperpigmentation (45 percent). Other findings included hypertrichosis, thickened skin, Raynaud's phenomenon, and clubbing; one patient had idiopathic flushing. Additional abnormalities found on physical examination are listed in Table 1.

Polycythemia was noted in 37 percent, anemia in 11 percent (hemoglobin value, <11.6 g per deciliter for female patients and <12.9 g per deciliter for male patients), leukocytosis in 24 percent (white-cell count, >10.9×10³ per cubic millimeter), and thrombocytosis in 76 percent (platelet count, >451×10³ per cubic millimeter for female patients and >370×10³ per cubic millimeter for male patients). Six patients (16 percent) had elevated erythrocyte-sedimentation rates. Nine patients (24 percent) had decreased serum levels of vitamin B₁₂ (<168 ng per liter [<124 pmol per liter]). Seven patients (18 percent) had hypothyroidism, and two (5 percent) had elevated serum prolactin levels (>20 ng per milliliter). Six patients (27 percent of the men) had decreased total serum testosterone levels (<298 ng per deciliter [<10.3 nmol per liter]); of these, four were impotent, two had gynecomastia, and four also had elevated gonadotropin levels, indicating primary hypogonadism. The level of cerebrospinal fluid protein was elevated in all 23 patients tested (>45 mg per deciliter). None of the patients had serious hyperglycemia. Only five patients fulfilled all the criteria for the POEMS syndrome.

The patients were followed until March 1989 or until death. The length of follow-up ranged from 4 to 184 months (median, 48). One patient was lost to follow-up after 35 months. The patients' responses to therapy are summarized in Table 2Table 2Treatment of and Outcome in the 38 Patients with Plasma-Cell Dyscrasia and Polyneuropathy.*. In the 13 patients with one bone lesion each, treatment consisted of local irradiation alone, and if no response was observed, other agents were added. In the 23 patients with more than one bone lesion each, the treatment depended on the physician's individual preference.

In 20 of the 38 patients, the clinical course was characterized by a slow but unrelenting progression of the polyneuropathy despite therapy, and none of the 38 patients had spontaneous improvement. Five patients had substantial improvement of their polyneuropathy in response to treatment. Four of 22 patients had improvement of their dermatologic abnormalities. Six patients with resistant disease were treated with plasmapheresis, which was not beneficial in any case; four of these patients died. An additional eight patients died during the follow-up period, and the causes of death are summarized in Table 2.

The survival rate was better among the patients with plasma-cell dyscrasia and polyneuropathy than among the 869 patients with multiple myeloma (Fig. 1Figure 1Survival Curves for 38 Patients with Plasma-Cell Dyscrasia and Polyneuropathy and 869 Patients with Multiple Myeloma.). The estimated five-year survival rate was 60 percent in the patients with plasma-cell dyscrasia, as compared with 20 percent in those with multiple myeloma (P<0.05). There was no evidence that the survival rate was significantly (P<0.05) associated with the presence of multiple bone lesions, hyperpigmentation, any skin changes, hepatosplenomegaly, lymphadenopathy, papilledema, IgA-λ, IgG-λ, age, or sex. The survival rate in the 5 patients with all five features of the POEMS syndrome did not differ significantly from that in the 33 patients with four or fewer features of the disease (P = 0.99) (Fig. 2Figure 2Survival Curves for 5 Patients Who Had All Five Features of the POEMS Syndrome and 33 Patients Who Did Not.).

Discussion

Plasma-cell dyscrasias associated with peripheral polyneuropathy include nonmalignant IgG, IgA, and IgM monoclonal gammopathies; multiple myeloma; Waldenström's macroglobulinemia; amyloidosis; osteosclerotic myeloma; and the POEMS syndrome. Osteosclerotic myeloma is characterized by a plasmacytoma — which is usually but not always found in sclerotic bone lesions — peripheral polyneuropathy, and monoclonal protein. In this study, however, 84 percent of the patients who fulfilled the criteria for osteosclerotic myeloma also had multiorgan involvement, and five of them met all the criteria for the POEMS syndrome. This finding suggests that a distinction between osteosclerotic myeloma and the POEMS syndrome may be artificial.

Nerve infiltration is the cause of the polyneuropathy that occurs in amyloidosis and in some cases of multiple myeloma. The polyneuropathy associated with plasma-cell dyscrasia is mainly of the demyelinating type, in which pain and autonomic involvement are rare. Typically, distal symmetric sensory symptoms are followed by motor weakness with progressive proximal involvement. Although the pathogenesis of the nerve damage is unclear,6 , 23 , 27 some patients with IgM monoclonal gammopathy have a glycoprotein associated with the M protein on the myelin sheaths,28 29 30 31 and recent reports suggest that the nerve injury may be mediated by complement.32 , 33 No direct correlation has been observed between the levels of the M protein and the severity of the neuropathy; some patients have neuropathy without detectable M protein. Papilledema was present in 37 percent of our patients, but there was no other evidence of elevated intracranial pressure. The mechanism of the papilledema is unknown, but it might be due to increased capillary permeability.34

Bone lesions were present in 36 patients; these were usually sclerotic and painless, in contrast to the painful lytic bone lesions that occur in multiple myeloma.3 , 4 Since bone lesions can be representative of the tumor mass, it is conceivable that their number is related to the prognosis. However, we found no correlation between the number of bone lesions and the clinical course. Bone lesions do not occur in all cases, since the proliferation of plasma cells may be confined to the lymph nodes.

Among the most striking findings were the skin changes, which included hyperpigmentation, hypertrichosis, thickened skin, Raynaud's phenomenon, clubbing, and in one case, idiopathic flushing.22 The skin findings are sometimes confused with the changes seen in scleroderma. One report suggested that a vasculopathy is the underlying process responsible for the skin changes,34 but other authors have not been able to confirm any characteristic histologic abnormality of the skin.12 Hepatomegaly, splenomegaly, and lymphadenopathy are unusual in classic multiple myeloma, but they were not uncommon in this series, which is consistent with other data.6

The most striking hematologic abnormality in our series was thrombocytosis, which was present in 76 percent of the patients; the platelet count usually returned to normal after treatment of the underlying disease. One patient had multiple thrombotic events, which were attributed to the thrombocytosis and polycythemia. The M protein was detectable in nearly 90 percent of the patients, in contrast to previous studies, in which it was undetectable in up to 25 percent of patients.5 6 7 In 5 percent of our patients, however, M protein was first detected during follow-up. When detected, it was composed of lambda chains in all but two patients, and it was fairly evenly distributed between IgA and IgG; M protein was rarely present in the urine.

Diabetes mellitus was not part of this syndrome, although an association with plasma-cell dyscrasia has been reported.5 , 6 Hypothyroidism was the most frequent endocrine abnormality in our series. The endocrine changes remain unexplained, although it has been postulated that antibodies directed against specific endocrine organs may be involved.31

The natural history of the patients with plasma-cell dyscrasia and polyneuropathy in this study was characterized by an earlier presentation (median age, 51 years) and slower progression (median survival, 97 months) than in classic multiple myeloma, which presents later (median age, 64 years) and has a shorter median survival (30 to 35 months).1 , 25 Progressive worsening of the polyneuropathy was the usual outcome in this series. No particular clinical or laboratory features were predictive of survival. Plasmapheresis, which in previous reports had been considered beneficial,35 , 36 did not help the six patients in whom it was used; this finding may be biased, since these patients did not respond to any treatment.

We conclude that patients with unexplained peripheral sensorimotor polyneuropathy should undergo as part of their diagnostic evaluation serum protein electrophoresis and a metastatic bone survey. Patients with the complete POEMS syndrome appear to have the same clinical outcome as those with the incomplete form, and there seems to be no clinical value in differentiating between the POEMS syndrome and osteosclerotic myeloma. In view of these findings, and because the terms in the literature are so confusing, we believe that the terms "POEMS syndrome" and "osteosclerotic myeloma" should not be used to describe the syndrome of plasma-cell dyscrasia with polyneuropathy.

Presented in part at the 1990 American College of Physicians Meeting, Chicago, April 1990, and the American Federation for Clinical Research Midwest Regional Meeting, Chicago, December 1989.

Supported in part by the Mayo Clinic.

We are indebted to Drs. R.A. Kyle and D.A. Gastineau for their critiques of earlier drafts and to Elaine Rodgers for assistance in the preparation of the manuscript.

Source Information

From the Division of Gastroenterology and Internal Medicine (G.D.M., N.J.T.), the Cancer Statistics Unit (J.R.O.), and the Department of Health Sciences Research (N.J.T.), Mayo Clinic and Mayo Foundation, Rochester, Minn. Address reprint requests to Dr. Talley at the Mayo Clinic, 200 First St. SW, Rochester, MN 55905.

References

References

1. 1

   Kyle RA, Bayrd ED. The monoclonal gammopathies: multiple myeloma and related plasma-cell disorders. Springfield, Ill.: Charles C Thomas, 1976.
   

2. 2

   Wiernik PH, Canellos GP, Kyle RA, Schiffer CA, eds. Neoplastic diseases of the blood. 2nd ed. New York: Churchill Livingstone, 1991.
   

3. 3

   Odelberg-Johnson O. Osteosclerotic changes in myelomatosis: report of a case . Acta Radiol 1959;52:139–44.
   CrossRef | Web of Science | Medline

4. 4

   Evison G, Evans KT. Bone sclerosis in multiple myeloma . Br J Radiol 1967;40:81–9.
   CrossRef | Web of Science | Medline

5. 5

   Crow RS. Peripheral neuritis in myelomatosis . BMJ 1956;2:802–4.
   CrossRef | Web of Science | Medline

6. 6

   Driedger H, Pruzanski W. Plasma cell neoplasia with peripheral polyneuropathy: a study of five cases and a review of the literature . Medicine (Baltimore) 1980;59:301–10.
   Web of Science | Medline

7. 7

   Kelly JJ Jr, Kyle RA, Miles JM, Dyck PJ. Osteosclerotic myeloma and peripheral neuropathy . Neurology 1983;33:202–10.
   Web of Science | Medline

8. 8

   Kojima M, Sakuma H, Mori N. Histopathological features of plasma cell dyscrasia with polyneuropathy and endocrine disturbances, with special reference to germinal center lesions . Jpn J Clin Oncol 1983;13:557–75.
   Web of Science | Medline

9. 9

   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.
   Web of Science | Medline

10. 10

    Semble EL, Challa VR, Holt DA, Pisko EJ. Light and electron microscopic findings in POEMS, or Japanese multisystem syndrome . Arthritis Rheum 1986;29:286–91.
    CrossRef | Web of Science | Medline

11. 11

    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 (Baltimore) 1980;59:311–22.
    Web of Science | Medline

12. 12

    Nakanishi T, Sobue I, Toyokura Y, et al. The Crow-Fukase syndrome: a study of 102 cases in Japan . Neurology 1984;34:712–20.
    Web of Science | Medline

13. 13

    Hafler DA, Johnson D, Kelly JJ, Panitch H, Kyle R, Weiner HL. Monoclonal gammopathy and neuropathy: myelin-associated glycoprotein reactivity and clinical characteristics . Neurology 1986;36:75–8.
    Web of Science | Medline

14. 14

    Besinger UA, Toyka KV, Anzil AP, et al. Myeloma neuropathy: passive transfer from man to mouse . Science 1981;213:1027–30.
    CrossRef | Web of Science | Medline

15. 15

    Morley JB, Schwieger achéal. The relation between chronic polyneuropathy and osteosclerotic myeloma . J Neurol Neurosurg Psychiatry 1967;30:432–42.
    CrossRef | Web of Science | Medline

16. 16

    Shimpo S. Solitary myeloma causing polyneuritis and endocrine disorders . Nippon Rinsho 1968;26:2444–56.
    Medline

17. 17

    Waldenstrom JG, Adner A, Gydell K, Zettervall O. Osteosclerotic "plasmocytoma" with polyneuropathy, hypertrichosis and diabetes . Acta Med Scand 1978;203:297–303.
    CrossRef | Web of Science | Medline

18. 18

    Aguayo A, Thompson DW, Humphrey JG. Multiple myeloma with polyneuropathy and osteosclerotic lesions . J Neurol Neurosurg Psychiatry 1964; 27:562–6.
    CrossRef | Web of Science | Medline

19. 19

    Reitan JB, Pape E, Fossa SD, Julsrud OJ, Slettnes ON, Solheim OP. Osteosclerotic myeloma with polyneuropathy . Acta Med Scand 1980;208:137–44.
    CrossRef | Web of Science | Medline

20. 20

    Mayo CM, Daniels A, Barron KD. Polyneuropathy in the osteosclerotic form of multiple myeloma . Trans Am Neurol Assoc 1968;93:240–2.
    Medline

21. 21

    Shelley WB, Shelley ED. The skin changes in the Crow-Fukase (POEMS) syndrome: a case report . Arch Dermatol 1987;123:85–7.
    CrossRef | Web of Science | Medline

22. 22

    Myers BM, Miralles GD, Taylor CA, Gastineau DA, Pisani RJ, Talley NJ. POEMS syndrome with idiopathic flushing mimicking carcinoid syndrome . Am J Med 1991;90:646–8.
    Web of Science | Medline

23. 23

    Kelly JJ Jr, Kyle RA, Miles JM, O'Brien PC, Dyck PJ. The spectrum of peripheral neuropathy in myeloma . Neurology 1981;31:24–31.
    Web of Science | Medline

24. 24

    Kaplan EL, Meier P. Nonparametric estimation from incomplete observations . J Am Stat Assoc 1958;53:457–81.
    CrossRef | Web of Science

25. 25

    Kyle RA. Multiple myeloma: review of 869 cases . Mayo Clin Proc 1975;50: 29–40.
    Web of Science | Medline

26. 26

    Mantel N. Evaluation of survival data and two new rank order statistics arising in its consideration . Cancer Chemother Rep 1966;50:163–70.
    Medline

27. 27

    Meier C. Polyneuropathy in paraproteinaemia . J Neurol 1985;232:204–14.
    CrossRef | Web of Science | Medline

28. 28

    Latov N, Sherman WH, Nemni R, et al. Plasma-cell dyscrasia and peripheral neuropathy with a monoclonal antibody to peripheral-nerve myelin . N Engl J Med 1980;303:618–21.
    Full Text | Web of Science | Medline

29. 29

    Julien J, Vital C, Vallat J-M, Lagueny A, Deminiere C, Darriet D. Polyneuropathy in Waldenstrom's macroglobulinemia: deposition of M component on myelin sheaths . Arch Neurol 1978;35:423–5.
    Web of Science | Medline

30. 30

    Braun PE, Frail DE, Latov N. Myelin-associated glycoprotein is the antigen for a monoclonal IgM in polyneuropathy . J Neurochem 1982;39:1261–5.
    CrossRef | Web of Science | Medline

31. 31

    Reulecke M, Dumas M, Meier C. Specific antibody activity against neuroendocrine tissue in a case of POEMS syndrome with IgG gammopathy . Neurology 1988;38:614–6.
    Web of Science | Medline

32. 32

    Latov N, Gross RB, Kastelman J, et al. Complement-fixing antiperipheral nerve myelin antibodies in patients with inflammatory polyneuritis and with polyneuropathy and paraproteinemia . Neurology 1981;31:1530–4.
    Web of Science | Medline

33. 33

    Monaco S, Bonetti B, Ferrari S, et al. Complement-mediated demyelination in patients with IgM monoclonal gammopathy and polyneuropathy . N Engl J Med 1990;322:649–52.
    Full Text | Web of Science | Medline

34. 34

    Trentham DE, Masi AT, Marker HW. Polyneuropathy and anasarca: evidence for a new connective-tissue syndrome and vasculopathic contribution . Ann Intern Med 1976;84:271–4.
    Web of Science | Medline

35. 35

    Silberstein LE, Duggan D, Berkman EM. Therapeutic trial of plasma exchange in osteosclerotic myeloma associated with the POEMS syndrome . J Clin Apheresis 1985;2:253–7.
    CrossRef | Medline

36. 36

    Dyck PJ, Low PA, Windebank AJ, et al. Plasma exchange in polyneuropathy associated with monoclonal gammopathy of undetermined significance . N Engl J Med 1991;325:1482–6.
    Full Text | Web of Science | Medline

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6. 6

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   CrossRef

7. 7

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8. 8

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9. 9

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   CrossRef

10. 10

    DANIEL A. ARBER. 2009. Bone Marrow. , 1536-1593.
    CrossRef

11. 11

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12. 12

    D. Abe, C. Nakaseko, M. Takeuchi, H. Tanaka, C. Ohwada, E. Sakaida, Y. Takeda, K. Oda, S. Ozawa, N. Shimizu, S. Masuda, R. Cho, M. Nishimura, S. Misawa, S. Kuwabara, Y. Saito. (2008) Restrictive usage of monoclonal immunoglobulin   light chain germline in POEMS syndrome. Blood 112:3, 836-839
    CrossRef

13. 13

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    CrossRef

14. 14

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15. 15

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16. 16

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17. 17

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    CrossRef

18. 18

    Apar Kishor Ganti, Iraklis Pipinos, Eliad Culcea, James O. Armitage, Stefano Tarantolo. (2005) Successful hematopoietic stem-cell transplantation in multicentric Castleman disease complicated by POEMS syndrome. American Journal of Hematology 79:3, 206-210
    CrossRef

19. 19

    S-K Kim, I-K Park, B-H Park, W. Park, H-S Lee, T-H Kim, J-B Jun, S-C Bae, D-H Yoo, W-S Uhm. (2005) A case report: isolated α heavy chain monoclonal gammopathy in a patient with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin change syndrome. International Journal of Clinical Practice 59, 26-30
    CrossRef

20. 20

    John J. Kelly, Donald S. Karcher. (2005) Lymphoma and peripheral neuropathy: A clinical review. Muscle & Nerve 31:3, 301-313
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21. 21

    Jun Ozaki, Hirokazu Okumura, Kouji Iwamoto, Shigeru Shimadoi, Shinichi Yamanaka, Shigeki Ohtake, Shinji Nakao. (2004) Refractory Crow-Fukase Syndrome (POEMS Syndrome) Successfully Treated with High-Dose Melphalan followed by Autologous Peripheral Blood Stem Cell Transplantation. International Journal of Hematology 79:1, 95-99
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22. 22

    Denis Mulleman, Cédric Gaxatte, Gaëlle Guillerm, Xavier Leroy, Anne Cotten, Bernard Duquesnoy, René-Marc Flipo. (2004) Multiple myeloma presenting with widespread osteosclerotic lesions. Joint Bone Spine 71:1, 79-83
    CrossRef

23. 23

    D. Cocito, L. Durelli, G. Isoardo. (2003) Different clinical, electrophysiological and immunological features of CIDP associated with paraproteinaemia. Acta Neurologica Scandinavica 108:4, 274-280
    CrossRef

24. 24

    Peter D. Donofrio. (2003) Immunotherapy of idiopathic inflammatory neuropathies. Muscle & Nerve 28:3, 273-292
    CrossRef

25. 25

    M. E. Erro, F. Lacruz, N. Aymerich, T. Ayuso, G. Soriano, J. Gallego, J. A. Villanueva. (2003) Acute carotid obliteration: a new vascular manifestation in POEMS syndrome. European Journal of Neurology 10:4, 383-384
    CrossRef

26. 26

    Y. T. Ma, S. J. Weatherby, D. G. Rao, J. B. Winer, C. Craddock, A. C. Williams. (2003) Facial flushing and localized Castleman's disease: an extension of the POEMS syndrome phenotype. Journal of Internal Medicine 253:2, 247-248
    CrossRef

27. 27

    Devinder Singh, Jyoti Wadhwa, Lalit Kumar, Vinod Raina, Amit Agarwal, Vinod Kochupillai. (2003) POEMS Syndrome: Experience with Fourteen Cases. Leukemia & Lymphoma 44:10, 1749-1752
    CrossRef

28. 28

    L Zumo, R.P Grewal. (2002) Castleman's disease-associated neuropathy: no evidence of human herpesvirus type 8 infection. Journal of the Neurological Sciences 195:1, 47-50
    CrossRef

29. 29

    Edward J Dropcho. (2002) Remote Neurologic Manifestations of Cancer. Neurologic Clinics 20:1, 85-122
    CrossRef

30. 30

    Matthew P. Wicklund, John T. Kissel. (2001) Paraproteinemic neuropathy. Current Treatment Options in Neurology 3:2, 147-156
    CrossRef

31. 31

    Valeria Ascoli, Sabina Signoretti, Andrea Onetti-Muda, Edoardo Pescarmona, Carlo Della-Rocca, Francesco Nardi, Claudio Maria Mastroianni, Roberta Gastaldi, Alessandra Pistilli, Gianluca Gaidano, Antonino Carbone, Francesco Lo-Coco. (2001) Primary effusion lymphoma in HIV-infected patients with multicentric Castleman's disease. The Journal of Pathology 193:2, 200-209
    CrossRef

32. 32

    Stacy A. Rudnicki, Josep Dalmau. (2000) Paraneoplastic syndromes of the spinal cord, nerve, and muscle. Muscle & Nerve 23:12, 1800-1818
    CrossRef

33. 33

    Haruki Koike, Gen Sobue. (2000) Crow-Fukase syndrome. Neuropathology 20:s1, 69-72
    CrossRef

34. 34

    Cabot, Richard C.Scully, Robert E., Mark, Eugene J., McNeely, William F., Ebeling, Sally H.Phillips, Lucy D.Ellender, Stacey M., Rosier, Randy N.Rosenberg, Andrew E.. (2000) Case 9-2000. New England Journal of Medicine 342:12, 875-883
    Full Text

35. 35

    Robert Weinstein. (2000) Therapeutic apheresis in neurological disorders. Journal of Clinical Apheresis 15:1-2, 74-128
    CrossRef

36. 36

    Martin Soubrier, Catherine Sauron, Bertrand Souweine, Claire Larroche, Bertrand Wechsler, Loïc Guillevin, Jean Charles Piette, Hugues Rousset, Patrice Deteix. (1999) Growth factors and proinflammatory cytokines in the renal involvement of POEMS syndrome. American Journal of Kidney Diseases 34:4, 633-638
    CrossRef

37. 37

    Zachary Simmons. (1999) Paraproteinemia and neuropathy. Current Opinion in Neurology 12:5, 589-595
    CrossRef

38. 38

    Brigitte Erbslöh-Möller, Boris Perras, Klaus Sack. (1999) POEMS-Syndrom mit Niereninsuffizienz. Medizinische Klinik 94:3, 159-164
    CrossRef

39. 39

    Osamu Watanabe, Ikuro Maruyama, Kimiyoshi Arimura, Isao Kitajima, Hitoshi Arimura, Mitsuya Hanatani, Katsuhiko Matsuo, Takayo Arisato, Mitsuhiro Osame. (1998) Overproduction of vascular endothelial growth factor/vascular permeability factor is causative in crow-fukase (POEMS) syndrome. Muscle & Nerve 21:11, 1390-1397
    CrossRef

40. 40

    Mathias Cohnen, Michael Uppenkamp, Peter Meusers, Günter Brittinger. (1998) POEMS-Syndrom. Medizinische Klinik 93:11, 678-682
    CrossRef

41. 41

    Vincent A. Wong, N.Kevin Wade. (1998) POEMS syndrome: an unusual cause of bilateral optic disk swelling. American Journal of Ophthalmology 126:3, 452-454
    CrossRef

42. 42

    J Benito-León, F López-Rı́os, F.J Rodrı́guez-Martı́n, S Madero, J Ruiz. (1998) Rapidly deteriorating polyneuropathy associated with osteosclerotic myeloma responsive to intravenous immunoglobulin and radiotherapy. Journal of the Neurological Sciences 158:1, 113-117
    CrossRef

43. 43

    Ropper, Allan H., Gorson, Kenneth C., . (1998) Neuropathies Associated with Paraproteinemia. New England Journal of Medicine 338:22, 1601-1607
    Full Text

44. 44

    Cabot, Richard C.Scully, Robert E., Mark, Eugene J., McNeely, William F., Ebeling, Sally H.Phillips, Lucy D., Gominak, Stasha C.Cros, Didier P.. (1998) Case 13-1998. New England Journal of Medicine 338:17, 1212-1219
    Full Text

45. 45

    Martha Q. Lacy, Morie A. Gertz, Curtis A. Hanson, David J. Inwards, Robert A. Kyle. (1997) Multiple myeloma associated with diffuse osteosclerotic bone lesions: A clinical entity distinct from osteosclerotic myeloma (POEMS syndrome). American Journal of Hematology 56:4, 288-293
    CrossRef

46. 46

    Paul Joseph Tuite, Vera Bril. (1997) POEMS syndrome in a 24-year-old man associated with vitamin B12 deficiency and a solitary lytic bone lesion. Muscle & Nerve 20:11, 1454-1456
    CrossRef

47. 47

    Francisco T. Rotta, Walter G. Bradley. (1997) Marked improvement of severe polyneuropathy associated with multifocal osteosclerotic myeloma following surgery, radiation, and chemotherapy. Muscle & Nerve 20:8, 1035-1037
    CrossRef

48. 48

    Colin H. Chalk. (1997) ACQUIRED PERIPHERAL NEUROPATHY. Neurologic Clinics 15:3, 501-528
    CrossRef

49. 49

    C Rose, M Mahieu, E Hachulla, T Façon, PY Hatron, F Bauters, B Devulder. (1997) Le POEMS syndrome. La Revue de Médecine Interne 18:7, 553-562
    CrossRef

50. 50

    F. Gohlke, E. Märker-Hermann, S. Kanzler, M. Mitze, K. -H. Meyer Zum Büschenfelde. (1997) Autoimmune findings resembling connective tissue disease in a patient with castleman's disease. Clinical Rheumatology 16:1, 87-92
    CrossRef

51. 51

    François-Jerome Authier, Laurent Belec, Yves Levy, Jean-Pascal Lefaucheur, Gilles-Louis Defer, Jean-Denis Degos, Romain K. Gherardi. (1996) All-trans-retinoic acid in poems syndrome. Therapeutic effect associated with decreased circulating levels of proinflammatory cytokines. Arthritis & Rheumatism 39:8, 1423-1426
    CrossRef

52. 52

    Philippe Lesprit, Francois-Jerôme Authier, Romain Gherardi, Laurent Bélec, Daniel Paris, Didier Melliere, Annette Schaeffer, Bertrand Godeau. (1996) Acute Arterial Obliteration: A New Feature of the POEMS Syndrome?. Medicine 75:4, 226-232
    CrossRef

53. 53

    S. Schey. (1996) Osteosclerotic myeloma and ‘POEMS’ syndrome. Blood Reviews 10:2, 75-80
    CrossRef

54. 54

    George F. Duna, Joseph M. Cash. (1996) RHEUMATIC MANIFESTATIONS OF DYSPROTEINEMIAS AND LYMPHOPROLIFERATIVE DISORDERS. Rheumatic Disease Clinics of North America 22:1, 39-51
    CrossRef

55. 55

    E Andrés, F Courouau, G Kaltenbach, F Maloisel, M Imler. (1996) Syndrome POEMS: rôles et intérêts de l'interleukine 6. La Revue de Médecine Interne 17:2, 145-149
    CrossRef

56. 56

    John T. Kissel, Jerry R. Mendell. (1996) Neuropathies associated with monoclonal gammopathies. Neuromuscular Disorders 6:1, 3-18
    CrossRef

57. 57

    Meletios A. Dimopoulos, Christos Papadimitriou, Nafsika Sakarellou, Peter Athanassiades. (1995) 9Complications and supportive therapy of multiple myeloma. Baillière's Clinical Haematology 8:4, 845-852
    CrossRef

58. 58

    Aubrey Ku, Elisabeth Lachmann, Richard Tunkel, Willibald Nagler. (1995) Severe polyneuropathy: Initial manifestation of Castleman's disease associated with POEMS syndrome. Archives of Physical Medicine and Rehabilitation 76:7, 692-694
    CrossRef

59. 59

    Enzo Pascali. (1995) Diagnosis and treatment of primary amyloidosis. Critical Reviews in Oncology/Hematology 19:3, 149-181
    CrossRef

60. 60

    Charles Perniciaro. (1995) POEMS syndrome. Seminars in Dermatology 14:2, 162-165
    CrossRef

61. 61

    Norman Latov. (1995) Pathogenesis and therapy of neuropathies associated with monoclonal gammopathies. Annals of Neurology 37:S1, 32-42
    CrossRef

62. 62

    Christian A. Gericke, Rolf Zschenderlein, Albert C. Ludolph. (1995) Amyotrophic lateral sclerosis associated with multiple myeloma, endocrinopathy and skin changes suggestive of a POEMS syndrome variant. Journal of the Neurological Sciences 129, 58-60
    CrossRef

63. 63

    Zachary Simmons, John Wald, James W. Albers, Eva L. Feldman. (1994) The natural history of a ?benign? rib lesion in a patient with a demyelinating polyneuropathy and an unusual variant of poems syndrome. Muscle & Nerve 17:9, 1055-1059
    CrossRef

64. 64

    D. Pareyson, R. Marazzi, P. Confalonieri, G. L. Mancardi, A. Schenone, A. Sghirlanzoni. (1994) The POEMS syndrome: Report of six cases. The Italian Journal of Neurological Sciences 15:7, 353-358
    CrossRef

65. 65

    R. K. Gherardi, S. Chouab, D. Malapert, L. Blec, L. Intrator, J.-D. Degos. (1994) Early weight loss and high serum tumor necrosis factor-? levels in polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes syndrome. Annals of Neurology 35:4, 501-505
    CrossRef

66. 66

    Kazuki Yasuda, Yutaka Yatomi, Teruhiko Matsushima, Akiko Yoneyama, Masaaki Higashihara, Kiyoshi Kurokawa, Kazuhiko Nakahara. (1994) A case of POEMS syndrome with thrombocytopenia and biliverdinaemia. British Journal of Haematology 86:2, 389-390
    CrossRef

67. 67

    Romain K. Gherardi, Denis Malapert, Jean-Denis Degos, Zachary Simmons, Mark B. Bromberg, Eva L. Feldman, Mila Blaivas, A. Arturo Leis, Jeremy M. Shefner, Eric L. Logigian, T. P. Links, J. H. van der Hoeven, Carlayne E. Jackson, Richard J. Barohn, Walter G. Bradley, Helena Pihko, John W. Dunne, Edward G. Stewart-Wynne, Koyotoshi Kaneko, Osamu Yamazaki, Tadashi Miyatake, Said R. Beydoun. (1993) Letters to the editor. Muscle & Nerve 16:10, 1129-1137
    CrossRef

68. 68

    Cabot, Richard C.Scully, Robert E., Mark, Eugene J., McNeely, William F., McNeely, Betty U., Ropper, Allan H.McKee, Ann C.. (1993) Case 21-1993. New England Journal of Medicine 328:21, 1550-1558
    Full Text

69. 69

    Robert Weinstein, P. T. Sachiko Sato, Kimaada Shelton, Nancy Hartigan, Allan H. Ropper, Michael Hayes, Kathleen Cardillo. (1993) Successful management of paraprotein-associated peripheral polyneuropathies by immunoadsorption of plasma with staphylococcal protein A. Journal of Clinical Apheresis 8:2, 72-77
    CrossRef