# POEMS Syndrome



## ndlemons (Aug 21, 2009)

Does anybody have an ICD-9 code for POEMS Syndrome?

It's also called Crow-Fuakse Syndrome, Takatsuki Disease, and PEP Syndrome


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## KimberlyLanier (Aug 21, 2009)

I have been on the internet searching for a Diagnosis Code this is all the infomation I could find on it. I know now that POEMS stands for 
POEMS syndrome (POEMS (polyneuropathy, organomegaly, endocrinopathy, presence of a monoclonal band and skin changes)

Maybe you can figure something out.  

Wow at some of the Diagnosis's that we have to struggle with.
Good Luck

Kimberly CPC


By

Andrew S Chi and Santosh Kesari



Historical note and nomenclature
  A paper titled “Peripheral neuritis in myelomatosis” appeared in the British Medical Journal in 1956. The author, RS Crow, was a medical senior registrar. He described 2 patients with multiple myeloma and peripheral neuropathy. Both patients presented with peripheral neuropathy, had lytic and sclerotic bone lesions, skin pigmentation, and normal sedimentation rates (Crow 1956). In 1968 Shimpo described a patient with plasmacytoma, polyneuritis, and endocrine abnormalities (Shimpo et al 1968). In 1973 Yodoi described the association of myeloma, polyneuropathy, endocrinopathy, and skin pigmentation. He then postulated this to be a new syndrome (Yodoi et al 1973). Takatsuki later reviewed 32 patients with polyneuropathy, endocrinopathy, and a plasma cell disorder (Takatsuki et al 1977). In 1980 Bardwick and colleagues described similar findings in American patients, and coined the syndrome POEMS (polyneuropathy, organomegaly, endocrinopathy, presence of a monoclonal band and skin changes) (Bardwick et al 1980). Its various eponyms are Crow-***ase syndrome, Takatsuki syndrome, plasma cell dyscrasia, endocrine disturbances, and polyneuropathy syndrome (also called PEP syndrome), and Japanese multisystem syndrome.




Clinical manifestations
  POEMS syndrome is a rare, incompletely understood multisystem disease caused by an underlying plasma cell dyscrasia. Patients usually present around 40 to 50 years of age. In 4 separate studies, the median ages were 46 years (Nakanishi et al 1984), 51 years (Miralles et al 1992), 55.3 years (Driedger and Pruzanski 1979), and 51 years (Dispenzieri et al 2003). The age of onset ranges from 20 to 83 years. Men are involved more often than women, with a ratio approximating 2 to 1. Although most cases have been reported from Japan, increasing numbers are being reported worldwide.

  The acronym POEMS refers to polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes, although many other features may be intermixed including sclerotic bone lesions, Castleman disease, peripheral edema, papilledema, thrombocytosis, renal disease, and various other systemic manifestations. Recently, new criteria for the diagnosis of POEMS syndrome were proposed from a retrospective study of 99 patients (Dispenzieri et al 2003). Two major criteria and one minor criterion are necessary for diagnosis. Polyneuropathy and a clonal plasmaproliferative disorder (usually either osteosclerotic myeloma or Castleman disease) are required as the two major criteria (Table 1). POEMS syndrome has also been reported with connective tissue disorders, nonhematological malignancies, and following exposure to toxins (Nakanishi et al 1984). Rarely, the initial manifestation suggests a connective tissue disease, and patients with POEMS syndrome have presented with histologically-proven scleroderma (Toussaint et al 2000; Eidner et al 2001).



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 diathesis

• Arthralgias

• Cardiomyopathy (systolic dysfunction)

• Fever

• Low vitamin B12 values

• Diarrhea




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

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

** Osterosclerotic lesion or Castleman disease is almost always present.

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

(Dispenzieri et al 2003)



  Polyneuropathy. The most common initial manifestation of POEMS syndrome is polyneuropathy, and is present in all patients with the disease. Symptoms typically start with distal numbness, tingling, prickly pain, or aches (Kelly et al 1981), and progress in a "glove and stocking distribution" with motor involvement following the sensory symptoms. The neuropathy involves small and large fibers equally.

  Distal, insidiously progressive weakness is usually the predominant deficit at the initial examination. Deep tendon reflexes are lost early. Progression varies among patients, causing some to be bed-bound and ultimately can lead to death. In advanced stages, marked atrophy of distal muscles occurs. Pure motor or pure sensory syndromes have been described. Sphincter dysfunction and cranial nerve involvement are rare. Polyneuropathy may precede the discovery of the paraproteinemic state or involvement of other systems.

  Electrophysiologic studies reveal demyelinating and axonal features with prolonged distal motor latencies and marked slowing of conduction velocities (from segmental demyelination); reduced motor amplitudes, fibrillations, positive sharp waves, and enlarged, polyphasic motor unit action potentials (from axonal damage). Recently, several electrophysiologic patterns were identified in patients with POEMS syndrome which are distinct from other types of polyneuropathies. Nerve conduction slowing is typically predominant in the intermediate rather than distal nerve segments, is more severe and frequent in the lower rather than upper limbs, motor rather than sensory fibers is more greatly affected, and conduction block is infrequent (6%) relative to other demyelinating diseases (Sung et al 2001; Min et al 2004). Dying-back or Wallerian degeneration seen in axonal neuropathies affects primarily the terminal nerve segments, and the immune-mediated neuropathies predominantly affect the extreme proximal and distal nerve segments.

  Cerebrospinal fluid shows a moderate to marked elevation of protein. In 102 patients with POEMS syndrome, 97% had elevated cerebrospinal fluid protein (greater than 50 mg/dL), and 30% had levels greater than 200 mg/dL (Nakanishi et al 1984). Similar results were later noted in 109 patients (Takatsuki and Sanada 1983).

  Peripheral nerve biopsies most often show a mixture of axonal degeneration and segmental demyelination. Mononuclear cell infiltration is rarely seen, with case reports of a few scattered mononuclear cells in the endoneurium as well as in the perivascular spaces of the endoneurium and epineurium (Vital et al 2003). Immunoglobulin deposits have been reported in the endoneurium which have corresponded to the monoclonal antibody in the serum (Hyman and Westrick 1986; Adams and Said 1998), however, most authors have not found monoclonal immunoglobulin deposits in peripheral nerve specimens. Amyloid deposition is absent.

  Uncompacted myelin lamellae (UML) are present in peripheral nerve biopsy specimens of most patients with POEMS syndrome (Vital et al 2003). Vital and colleagues found that a high percentage of myelinated fibers (1% to 7%) had features of uncompacted myelin lamellae in patients with POEMS syndrome (Vital et al 2003). Uncompacted myelin lamillae have also been described in Charcot-Marie-Tooth 1B syndrome, hereditary neuropathy with predisposition to pressure palsies, chronic inflammatory demyelinating polyneuropathy, and Guillain-Barre Syndrome (Vital et al 1994), however only in rare cases of CMT1B disease are uncompacted myelin lamellae found with such a high frequency as in POEMS syndrome (Vital et al 2003). Based on this observation, Vital and colleagues have proposed that the demonstration of numerous uncompacted myelin lamillae on a thorough ultrastructural examination of a peripheral nerve biopsy can be highly suggestive of POEMS syndrome (Vital et al 2003).

  In osteosclerotic myeloma, nearly 50% of patients have a peripheral neuropathy. In the most common form of myeloma, osteolytic myeloma, the clinical features of neuropathy are infrequent, occurring in less than 5% of patients (Silverstein and Doniger 1963). When electrophysiology and histology are performed in clinically asymptomatic patients with osteolytic myeloma, this figure may reach 40% to 60% (Hesselvik 1969;(Walsh 1971). The neuropathy is usually sensorimotor and demonstrates similarities to carcinomatous neuropathy and those of primary systemic amyloidosis. Electrophysiology reveals an axonopathy in all 3 conditions (Kelly et al 1981). Occasionally, entrapment neuropathies may occur from primary amyloidosis. An inflammatory myopathy associated with POEMS has recently been described (Goebels et al 2000).

  Central nervous system involvement is rare. There are several case reports of cerebral infarctions (Forster and Muri 1998, Kang et al 2003), as well as a description of an acute carotid obliteration (Erro et al 2003). Others have reported pachymeningitis, amyotrophic lateral sclerosis, and white matter edema (Gericke et al 1995; Tsunoda et al 1995; Mandler and King 1996). Papilledema has been described with relative frequency, in 62% of patients in one series (Nakanishi et al 1984), and is attributed to the elevated cerebrospinal fluid protein. Ophthalmological and orbital involvement has included oscillopsia with blurred vision (Charif et al 2000), proptosis (Gandhi et al 2001), optic disk drusen and peripapillary choroidal neovascularisation (Diduszyn et al 2002).

  Organomegaly. The commonly enlarged organs in POEMS are the liver, spleen, and lymph nodes. Eighty-three percent of patients present with an enlarged liver (Nakanishi et al 1984), 24% an enlarged spleen (Miralles et al 1992), and 42% with enlarged lymph nodes (Takatsuki et al 1977). Enlargement of the kidneys, thyroid, parotid (Ratnatunga et al 1997), and heart (Tanus and Miller 1992) have also been reported.

  Endocrinopathy. Endocrine disturbances vary among reported series. Underactivity rather than overproduction of hormones predominates. The hypothalamo-pituitary axis is commonly involved. Men can develop impotence, gynecomastia, testicular atrophy, reduced testosterone level, and elevated estrogen, follicle stimulating, and luteinizing hormone. Women can experience amenorrhea with decreased luteinizing and follicle stimulating hormone levels. Diabetes mellitus occurs in nearly 50% of cases. Hypothyroidism, hyperprolactinemia, hypoadrenalism (Addison disease), and hypoparathyroidism may occur.

  Immunologic.   According to the new criteria for POEMS syndrome, all patients by definition have a clonal plasmaproliferative disorder (Dispenzieri et al 2003). The plasma clones are almost always lambda light chains of either IgG or IgA type. However, IgG kappa chains (Romas et al 1992), IgE (Fishkin et al 1972) and IgM (Fujii et al 1991) bands have been reported. Rarely, the monoclonal immunoglobulin may be produced in excess amount leading to light chain deposition with systemic effects (Lambotte et al 2001). The amount of monoclonal protein in the serum is typically small and in bone marrow specimens the plasma cell population is usually 10% or less (Nakanishi et al 1984; Soubrier et al 1994; Dispenzieri et al 2003). The monoclonal protein can usually be detected in the serum or urine by immunofixation, however in a recent series of 99 patients, 12% of cases were diagnosed only by immunohistochemical staining of bone marrow or sclerotic bone lesion specimens demonstrating a clonal plasma cell disorder.

  POEMS syndrome is associated with a variety of plasma cell disorders, including multiple myeloma (usually the osteosclerotic type), plasmacytoma, monoclonal gammopathy of uncertain significance, Waldenstroms macroglobulinemia, and lymphoproliferative disorders (Nakanishi et al 1984; Soubrier et al 1994; Kihara et al 2002). Castleman disease is clearly associated with POEMS syndrome; however, the nature of the correlation is not well understood. Castleman disease is found in 11% to 30% of POEMS patients (Soubrier et al 1994; Dispenzieri et al 2003; Belec et al 1999). 

  Dermatologic. Cutaneous findings include pigmentation, hypertrichosis, thickened skin, hyperhidrosis, thin white nails (Terry nails), “clubbing”, sclerodermatous changes with Raynaud phenomenon, alopecia, and edema of the skin. Lesions may resemble generalized histiocytomas (Del Rio et al 1994). Glomeruloid hemangiomas (hemangiomas with histological resemblance to renal glomeruli), which vary from pinhead to pea size (Rongioletti et al 1994; Perniciaro 1995), are specific cutaneous markers for POEMS syndrome (Chan et al 1990; Tsai et al 2001). These have immunologic features that differ from traditional hemangiomas and littoral angiomas of the spleen (Kishimoto et al 2000). Although rare, histologically proven vasculitic lesions have been described (Sharabi et al 2000).

  Skeletal. Radiographic changes of multiple myeloma are present in nearly 50% of POEMS syndrome patients. They may be osteosclerotic, or a mixture of osteosclerotic and osteolytic (Takatsuki and Sanada 1983). In 102 patients, 56 presented with lesions on radiological study. Of these, 31 were sclerotic and 17 were mixed. Seventy-three percent of these 56 patients had monoclonal gammopathy (Nakanishi et al 1984). A case of destructive polyarthritis with multicentric Castleman disease has been described (Carpentier-Planchon 2000).


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