diagnosing poems syndrome

The most commonly used diagnostic criteria are Dispenzieri's criteria (originally published in 2003, and revised in 2007). They have come under some criticism, and Misawa and Kuwabara have proposed different criteria. (I have included a brief sketch of the history of POEMS diagnostic criteria, and a bibliography of articles cited on this page.)

If you have corrections or suggestions, please let me know. I have started writing descriptions of each of the diagnostic criteria, but those will take me some time to finish!

Harry A Ide
last revised 1 March 2015

Dispenzieri's criteria

The commonly used current diagnostic criteria require meeting

(a) two mandatory major criteria
(b) one other major criterion
(c) one minor criterion

(See for example, Dispenzieri 2014 p.215; Li 2013 also uses these criteria.)

Dispenzieri also recognizes a Castleman disease variant of POEMS syndrome, without evidence of a clonal plasma cell disease (Dispenzieri 2014 pp.215, 218).

mandatory major criteria 1. polyneuropathy (typically demyelinating)
2. monoclonal plasma cell-proliferative disorder (almost always λ light-chain)

other major criteria 3. Castleman disease
4. sclerotic bone lesions
5. elevated VEGF (vascular endothelial growth factor)

minor criteria 6. organomegaly (splenomegaly, hepatomegaly, or lymphadenopathy)
7. extravascular volume overload (edema, pleural effusion, or ascites)
8. endocrinopathy (adrenal, thyroid, pituitary, gonadal, parathyroid, pancreatic (but not diabetes mellitus or thyroid abnormalities alone))
9. skin changes (hyperpigmentation, hypertrichosis, glomeruloid hemangiomata, plethora, acrocyanosis, flushing, white nails)

other symptoms & signs   clubbing, weight loss, hyperhidrosis, pulmonary hypertension, restrictive lung disease, thrombotic diatheses, diarrhea, low vitamin B12 values

Misawa and Kuwabara criteria

These criteria introduce two levels of confidence in a POEMS diagnosis:

for a definite diagnosis: all three major criteria, and one minor criterion
for a probable diagnosis: two of the major criteria, and one minor criterion

They also recognize a Castleman disease variant of POEMS syndrome, without evidence of a clonal plasma cell disease (Misawa 2013 p.320).

To make comparison easier, I've numbered these criteria as in the Dispenzieri criteria above.

major criteria 1. polyneuropathy
2. monoclonal plasma cell proliferative disorder (M-protein, or monoclonal plasma cell proliferation in bone marrow biopsy or biopsy of a plasmacytome or sclerotic lesion)
5. elevated serum or plasma VEGF levels

minor criteria 4. sclerotic bone lesions
3. Castleman disease
6. organomegaly (hepatosplenomegaly or lymphadenopathy)
7. edema (edema, pleural effusions, or ascites)
8. endocrinopathy (adrenal, thyyroid, pituitary, gonadal, parathyroid, or pancreatic, but not diabetes mellitus or thyroid abnormalities alone
9. skin changes (hyperpigmentation, hypertrichosis, plethora, cyanosis, hemangiomata, or white nails)
10. papilledema
11. thrombocytosis and/or polycythemia


Nakanishi et al. 1984 'provisionally' (p.714) divided symptoms into seven groups: (1) polyneuropathy (including peripheral neuropathy, papilledema, and increased CSF protein), (2) anasarca (including peripheral edema, ascites, and pleural effusions), (3) skin changes (hyperpigmentation, hypertrichosis, and thickening), (4) endocrinopathy (including gynecomastia, impotence, amenorrhea, and glucose intolerance), (5) dysglobulinemia (including M protein and bone lesions), (6) organomegaly (including hepatomegaly, splenomegaly, and lymphadenopathy), and (7) other (including slight fever, hyperhidrosis, and finger clubbing)
They found all patients had symptoms in at least three of the categories: polyneuropathy, dysglobulinemia, and one other (p.714)
Ji et al. 2012 cite this discussion as proposing diagnostic criteria, with '[a]t least three of these six criteria [excluding 'other'] ... required for diagnosis' (p.1)
Bardwick (1980)
Bardwick et al. proposed the name 'POEMS', not as stating diagnostic criteria, but '[t]o facilitate recognition of the most constant and important features of this syndrome' (p.311)
They recognized other features, including sclerotic skeletal lesions, and anasarca
Dispenzieri's original criteria (2003)
Dispenzieri et al. 2003 p.2497
These required both polyneuropathy and monoclonal plasmaproliferative disorder, and either sclerotic bone lesion, Castleman disease, organomegaly, edema, endocrinopathy, skin changes, or papilledema
Yishay et al. 2005 (3 patients who met the criteria were stable, 5 'developed the full-blown syndrome', and 4 developed other diseases that accounted for their clinical findings': essential mixed cryoglobulinemia, acute inflammatory demyelinating polyneuropathy, polyarthritis nodosa (2 patients); vasculitis or κ light chain gammopathy should preclude a POEMS diagnosis 'prior to development of all features')
Charli-Joseph et al. 2011 (criticism of the 2003 [sic] criteria, based on 2 cases: (1) polyneuropathy, no serum M-protein on SPEP [no mention of immunoelecrophoresis], Castleman's, hepato-splenomegaly, ascites, hypothyroidism, skin lesions (including mixed features of tufted-type and glomeruloid-type hemangiomas); (2) polyneuopathy, no M-protein on SPEP [no mention of immunoelectrophoresis or other tests], Castleman's, organomegaly, volume overload,endocrinopathy, glomeruloid hemangiomas--this article suggests that (a) the monoclonal gammopathy criterion be replaced by: monoclonal gammopathy OR multicentric Castleman's OR Sjogrens disease, and (b) glomeruloid hemangiomas plus other characteristics -> incomplete POEMS syndrome
Dispenzieri 2007 p.286 (these are the criteria I listed above)
Beside adding the second set of mandatory criteria (in a deliberate attempt to make the criteria narrower (p.286), and adding VEGF, this alters the list of "skin changes" slightly, from 'hyperpigmentation, hypertrichosis, plethora, hemangiomata, white nails' to the list above; Kuwabara 2012 and Misawa 2013 quote the revised criteria with the original list of skin changes--I assume that difference isn't significant.
criticism of the revised criteria
Morizane 2008 (a case with no neuropathy five years after skin lesions, but small serum and urine IgA-λ m-protein, osteosclerotic lesions, elevated VEGF, splenamegaly, mild pitting edema in lower extremities, hypothalamic gonadal hypofunction, hemangiomas ('lesions suggestive of glomeruloid hemangiomas'), and 'bilateral papillary edemas')
Ono 2013 (a case with polyneuropathy, IgA-λ monoclonal plasma cell proliferative disorder, skin lesions, but not Castleman's, sclerotic lesions, or elevated VEGF [plasma VEGF of 36 pg/mL])
Misawa 2013 p.320 proposes the criteria listed above based on these three criticisms:
(1) earlier diagnosis will be possible if monoclonal plasma cell proliferative disease and polyneuropathy aren't required, since early on patients may lack evidence of monoclonal plasma cell proliferative disease (citing Nakanishi 1984), and some patients do not have evident neuropathy (Morizane 2008)
(2) Castleman disease is different enough from POEMS (in neuropathy, frequency of clonal plasma cell disorder, and cytokines) that it should not be a major criterion for typical POEMS
(3) osteosclerotic lesions duplicate plasma cell proliferative disease, since the sclerotic lesions usually show diffuse light-chain-restricted plasma cells
Dispenzieri's most recent discussion
Dispenzieri 2014 (a) still requires both peripheral neuropathy and a plasma cell clone for 'standard POEMS syndrome', but (b) recognizes a 'Castleman disease variant of POEMS' for patients who don't have both those features, but have other POEMS features (p.218)


Bardwick 1980
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 Jul;59(4):311-22.
Charli-Joseph 2011
Charli-Joseph Y, Fernández-Sánchez M, Saeb-Lima M, Orozco-Topete R. 'POEMS syndrome: are current diagnostic criteria too exclusive?' Journal of the American academy of dermatology 2011 Aug;65(2):415-7.
Dispenzieri 2003
Dispenzieri A, Kyle RA, Lacy MQ, Rajkumar SV, Therneau TM, Larson DR, Greipp PR,Witzig TE, Basu R, Suarez GA, Fonseca R, Lust JA, Gertz MA. 'POEMS syndrome: definitions and long-term outcome.' Blood 2003 Apr 1;101(7):2496-506.
Dispenzieri 2007
Dispenzieri A. 'POEMS syndrome.' Blood reviews 2007 Nov; 21(6): 285-99
Dispenzieri 2014
Dispenzieri A. 'POEMS syndrome: 2014 update on diagnosis, risk-stratification, and management.' American journal of hematology 2014 Feb;89(2):214-23.
Kuwabara 2012
Kuwabara S, Dispenzieri A, Arimura K, Misawa S, Nakaseko C. 'Treatment for POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome.' Cochrane Database Syst Rev 2012 Jun 13;6:CD006828.
Li 2013
Li J, Zhou DB. 'New advances in the diagnosis and treatment of POEMS syndrome.' British journal of haematology 2013 May;161(3):303-15. doi: 10.1111/bjh.12236.
Misawa 2013
Misawa S, Kuwabara S. 'Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (Crow-Fukase) syndrome: diagnostic criteria and treatment perspectives'. Clinical & experimental neuroimmunology 4 (2013) 318-325.
Morizane 2008
Morizane R, Sasamura H, Minakuchi H, Takae Y, Kikuchi H, Yoshiya N, uchi A, Konishi K, Okamoto S, Itoh H. 'A case of atypical POEMS syndrome without polyneuropathy.' European journal of haematology 2008 May;80(5):452-5.
Nakanishi 1984
Nakanishi T, Sobue I, Toyokura Y, Nishitani H, Kuroiwa Y, Satoyoshi E, Tsubaki T, Igata A, Ozaki Y. 'The Crow-Fukase syndrome: a study of 102 cases in Japan.' Neurology 1984 Jun;34(6):712-20.
Ono 2013
Ono S, Otsuka A, Miyachi Y, Kabashima K. 'Incomplete POEMS syndrome presenting for years solely with scleredema and hyperpigmentation.' Journal of dermatology 2013 Jan;40(1):77-8.
Yishay 2005
Yishay O, Eran E. 'POEMS syndrome: failure of newly suggested diagnostic criteria to anticipate the development of the syndrome.' American journal of hematology 79 (2005) 316-318.

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