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POEMS Syndrome

Joanna L Chan, MD, Resident Physician, Department of Dermatology, University of Texas Southwestern Medical Center
Wingfield Rehmus, MD, MPH, ; Alexa F Boer Kimball, MD, MPH, Associate Professor of Dermatology, Harvard University School of Medicine; Vice Chair, Department of Dermatology, Massachusetts General Hospital; Director of Clinical Unit for Research Trials in Skin (CURTIS), Department of Dermatology, Massachusetts General Hospital

Updated: Sep 25, 2009

Introduction

Background

Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a rare multisystemic disease that occurs in the setting of a plasma cell dyscrasia. The pathophysiologic link between the constellation of symptoms and the underlying disease is not well understood, but the link may be related to changes in the levels of a cytokine or a growth factor. POEMS syndrome was first described by Crow in 1956 and then by Fukase in 1968. The syndrome was termed Crow-Fukase syndrome (by which it is known in Japan) by Nakanishi in a study of 102 cases in Japan.

In 1980, the acronym POEMS was coined by Bardwick et al based on the 5 main features of the disease, namely, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes.

No specific case definition exists for POEMS syndrome; however, most authors agree that patients with POEMS syndrome should have 3 or more of the 5 features. Some authors have proposed that the presence of 2 major criteria, including a monoclonal plasma-proliferative disorder and polyneuropathy, in addition to the existence of 1 minor criterion, is sufficient for diagnosis. The suggested minor criteria include sclerotic bone lesions, organomegaly, edema, endocrinopathy, papilledema, and skin changes. However, the findings of a retrospective analysis of 629 patients using these criteria suggest that this approach may be inadequate for excluding other disease processes that may account for symptoms and that atypical presentations of POEMS may be misdiagnosed.1,2

The polyneuropathy associated with POEMS syndrome is a bilateral symmetric disturbance. It involves both motor and sensory nerves, begins distally, and has a progressive proximal spread. Associated cranial or autonomic nerves are not involved. Both demyelination and axonal degeneration are noted.

The liver, the lymph nodes, and the spleen are the organs most frequently involved. Enlargement of the lymph nodes and spleen is secondary to changes consistent with Castleman disease (giant angiofollicular hyperplasia, multicentric plasma cell variant) in most patients. Approximately 15% of patients with POEMS syndrome have concomitant evidence of Castleman disease. Hepatomegaly is not associated with any defined histologic or pathophysiologic changes.

Multiple endocrinopathies have been associated with POEMS syndrome, and most patients have more than 1 endocrine abnormality. Many of the abnormalities noted can be explained by elevations in estrogen levels. Impotence and gynecomastia are common among men. Amenorrhea is common among women. Diabetes mellitus and glucose intolerance are also noted in many patients. Other associated endocrinopathies include hypothyroidism, hyperprolactinemia, and hypoparathyroidism.

POEMS syndrome is seen in the setting of a plasma cell dyscrasia. Although many plasma cell disorders have been reported in patients with POEMS syndrome, most patients are seen with osteosclerotic myeloma or monoclonal gammopathy of unknown significance.

The M proteins most frequently found are the immunoglobulin A (IgA)–gamma and immunoglobulin G (IgG)–gamma light chains. In a case report of one patient with POEMS syndrome,3 serum electrophoresis demonstrated an M-band with isolated IgA heavy chain but no abnormal light chain, which could suggest abnormal secretion of monoclonal protein or the rare possibility of coincidental heavy-chain disease in association with POEMS syndrome. A single case of POEMS syndrome in association with Waldenström macroglobulinemia,4 characterized by immunoglobulin M–kappa paraproteinemia, has been reported. Classic multiple myeloma has not been associated with the disease. The type of plasma cell disorder has not been shown to be correlated with the constellation of symptoms noted in patients with POEMS syndrome.

Multiple dermatologic changes have been associated with POEMS syndrome. The most common changes include hyperpigmentation, skin thickening, sclerodermoid changes, and hypertrichosis. Other skin changes, including whitening of the proximal nail (Terry nails), peripheral edema, hyperhidrosis, clubbing of the fingers, Raynaud phenomenon, and angiomas, have been observed.

Other signs and symptoms associated with POEMS syndrome include papilledema, anasarca, pleural effusions, ascites, fever, thrombosis, renal insufficiency, and diarrhea.

Pathophysiology

The pathophysiology of POEMS syndrome is not well understood. In all patients, a plasma cell disorder underlies the development of the syndrome; however, the mechanism by which this occurs is unknown. Elevations of cytokines, such as interleukin (IL)–1beta, IL-6, and tumor necrosis factor (TNF)–alpha, have all been noted.

Most recently,5 significant elevations in vascular endothelial growth factor (VEGF) levels have been noted. Increases in VEGF levels have been postulated to lead to enhanced vascular permeability, leading to the associated edema, increased endoneural pressure, and deposition of plasma cell–derived material. As myelin is exposed to serum cytokines and complement, demyelination can occur. In one case report of a patient with POEMS syndrome and bilateral cystoid macular edema, macular thickness varied with serum VEGF levels. After vitrectomy and an intraocular triamcinolone injection, decreased macular thickness was associated with lower intraocular VEGF levels. The authors proposed that elevated VEGF levels may be causally related to cystoid macular edema in persons with POEMS syndrome. Stimulated vascular proliferation has also been postulated to result in some of the skin changes associated with the disease.

VEGF may also play a role in bone metabolism, as suggested by a study of 2 patients who received high-dose therapy (HDT) with autologous stem cell transplantation. In this study by Kastritis et al,6 decreasing VEGF levels corresponded with both clinical improvement and the normalization of bone metabolism as measured by multiple remodeling indices.

In a study of 22 patients with POEMS, hyperalgesia was correlated with an elevation of proinflammatory cytokines (IL-1beta, IL-6, and TNF-alpha), in addition to the electrophysiologic reduction of sensory nerve action potentials and the histopathologic loss of myelinated fibers.7 Serum levels of other growth factors, including epidermal growth factor, fibroblast growth factor, and platelet-derived growth factor, are not increased in patients with POEMS syndrome. Because POEMS syndrome is associated with Castleman disease and angioma formation, a role for human herpesvirus 8 (HHV-8) has been postulated; however, early studies have not demonstrated an association.

Frequency

International

POEMS syndrome is rare. Several hundred cases have been described in the literature; however, the incidence may be underreported because the syndrome may go unrecognized.

Mortality/Morbidity

The morbidity associated with POEMS syndrome depends on the systems involved and ranges from skin pigment alteration to debilitating weakness and loss of function. The median survival period for patients with POEMS syndrome is 8 years. The natural course of POEMS syndrome is chronic, with a reported median survival of approximately a decade (8-13.8 y). In their review, Miralles and colleagues8 reported a 5-year survival rate of 60%.

Overall shorter survival has been associated with extravascular volume overload (eg, effusions, edema, ascites) and fingernail clubbing. Cardiorespiratory failure, renal failure, infection, and progressive inanition are among the most common causes of death. The neurologic sequelae of POEMS syndrome cause approximately 50% of the patients with POEMS syndrome to become bedridden. Death may also occur as a consequence of decubitus ulcers and thromboses due to inactivity, organomegaly, and endocrinopathy, rather than as a consequence of the aggressiveness of the monoclonal protein.

Race

No specific racial association has been identified, although a preponderance of cases have been reported in the Japanese literature.

Sex

POEMS syndrome is slightly more prevalent among men than women, with a male-to-female ratio of 2.5:1.

Age

The onset of POEMS syndrome occurs most frequently in the fifth or sixth decade of life, with a mean patient age at onset of 48 years for men and 59 years for women.  In 2007 and 2008, however, POEMS syndrome has been reported to occur in two 15-year old patients.9,10

Clinical

History

Presenting symptoms vary based on the organ systems involved.

  • Frequent presentations include the following:
    • Symmetric distal weakness and paresthesia
    • Painful diarrhea
    • Peripheral edema
  • Patients may also report the following:
    • Impotence
    • Gynecomastia
    • Amenorrhea
    • Shortness of breath
    • Hypertrichosis
    • Hyperpigmentation
    • Hyperhidrosis
    • Raynaud phenomenon
    • Loss of function because of skin tightening
    • Edema
    • Diarrhea
    • Rarely, bone pain and fractures

Physical

  • Skin manifestations
    • Diffuse hyperpigmentation and lower extremity edema are seen in more than 90% of patients.
    • Hypertrichosis is seen in 80% of patients and can be diffuse but is usually most pronounced over the face, the limbs, and the chest.
    • Skin thickening with sclerodermoid changes and tightening, which can limit function, is seen in approximately 77% of patients.
    • Angiomas are often present and may progress rapidly.
    • Nail changes are noted, with whitening of the proximal nails and possible clubbing.
    • Many other skin changes have also been observed in persons with POEMS syndrome; these changes include alopecia, flushing, ichthyosis, Sweetlike lesions, and vasculitis.
    • Mucous membrane involvement has not been reported.
  • Neurologic manifestations
    • Motor deficiency follows decreased perception of pinprick and vibration sensation.
    • Both motor and sensory deficits are reported and are characterized by distal, symmetric, and progressive involvement associated with gradual proximal spread.
    • Some loss of temperature sensation and nociception has been reported.
    • Deep tendon reflexes are diminished, but cranial nerve examination results are normal.
  • Cardiovascular manifestations
    • Rarely, macroangiopathy affecting coronary and lower limb arteries may be associated with POEMS syndrome, which has resulted in reported cases of cerebrovascular manifestations in the absence of vascular risk factors.
    • Acute ischemic stroke has been reported rarely in patients with POEMS syndrome, and one case series of such patients described a particular association with end artery border-zone infarctions and elevated fibrinogen levels, which may be implicated in the pathogenesis of cerebrovascular events.7
    • Other authors suggest that patients with POEMS syndrome who had ischemic stroke had elevated fibrinogen levels in the absence of increased acute-phase reactants.8 This counterpoint suggests that increased fibrinogen may be more a consequence of the chronic release of proinflammatory cytokines characteristic of POEMS syndrome and of the inflammatory response following a stroke, rather than to its actual pathogenesis.
  • Endocrine manifestations
    • In a series of 170 patients, 84% had a recognized endocrinopathy, the most common of which was hypogonadism associated with depressed testosterone levels, gynecomastia, or elevated prolactin levels.
    • Other abnormalities included hypothyroidism, abnormal glucose metabolism, adrenal insufficiency, hypocalcemia
    • Many patients may exhibit evidence of multiple endocrinopathies in the 4 major endocrine axes (ie, gonadal, thyroid, adrenal, and glucose).11
  • Pulmonary manifestations
    • Approximately a quarter of patients will develop respiratory symptoms within 2 years of diagnosis.
    • Patients may develop restrictive lung disease, pulmonary hypertension, respiratory muscle weakness, and an isolated diminished diffusing capacity.
    • Radiographic findings such as pleural effusions and diaphragm elevation may be seen in nearly a quarter of patients.12
  • Other extracutaneous manifestations
    • Hepatomegaly, splenomegaly, and lymphadenopathy occur in patients with organomegaly.
    • Patients with endocrine involvement may have gynecomastia.
    • Strokes have been reported rarely in patients with POEMS syndrome, which is postulated to result from an intracranial vasculopathic process.13
    • Patients with POEMS syndrome have been shown to have bilateral optic disc edema and bilateral cystoid macular edema. Authors suggest that these findings may reflect increased vascular permeability.14,15

Causes

  • All cases of POEMS syndrome are associated with a plasma cell disorder.
  • The syndrome has been seen in association with osteosclerotic myeloma, monoclonal gammopathy of unknown significance, and Waldenström macroglobulinemia, but not with classic multiple myeloma.
  • The reason plasma cells in some dyscrasias produce factors that cause POEMS syndrome while others do not is not clear.
  • The mechanism by which plasma cells lead to POEMS syndrome is not understood; however, elevations in IL-1beta, IL-6, TNF-alpha, and VEGF levels have been implicated.

Differential Diagnoses

Hirsutism

Other Problems to Be Considered

Chronic inflammatory demyelinating polyradiculoneuropathy
Cryoglobulinemia
Amyloidosis, Nodular Localized Cutaneous
Multiple Myeloma
Monoclonal gammopathy of undetermined significance
Waldenstrom Hypergammaglobulinemia
Scleroderma
Raynaud Phenomenon

Workup

Laboratory Studies

  • When POEMS syndrome is suggested clinically, perform a range of laboratory studies to define the extent of involvement and to establish whether other organ systems are involved.
  • Patients commonly have thrombocytosis with or without polycythemia.
  • Hypercalcemia and renal insufficiency are rarely present.
  • Generally, the M protein is IgG-gamma or IgA-gamma and small in size (median, 1.1 g/dL).
  • Serum protein immunoelectrophoresis is used to define the nature and the extent of the monoclonal gammopathy.
  • Thyrotropin levels, fasting blood glucose levels, a glucose tolerance test, and estrogen levels can be used to screen for endocrinopathy.
  • In patients with neuropathy, cerebrospinal fluid test results either are in the reference range or may show elevated levels of protein.
  • Erythrocyte sedimentation rate results are in the reference range or slightly elevated.
  • Cerebrospinal fluid may demonstrate a cytoalbuminologic dissociation.
  • For research purposes, cytokine and growth factor levels can be measured. Based on past studies, TNF-alpha, IL-6, IL-1beta, and VEGF levels are usually elevated, while epidermal growth factor, fibroblast growth factor, and platelet-derived growth factor levels are within the reference range.

Imaging Studies

  • Plain film radiographs are useful for locating lytic bone lesions caused by osteosclerotic myeloma.
  • At least 95% of patients have osteosclerotic lesions, with more than half the patients having multiple lesions. Both osteosclerotic and osteolytic lesions may be present and may be of modest size.

Procedures

  • Bone marrow biopsy may be indicated because as many as 10% of patients have marrow involvement with plasma cells.
  • Lymph node biopsy is indicated in patients with lymphadenopathy and, in most patients, demonstrates findings of Castleman disease. HHV-8 has been demonstrated within the lymphocytes of some of these lymph node biopsy specimens, in addition to being present within endothelial cells and lymphocytes in the glomeruloid hemangioma skin biopsy specimen.16,17 Within the HHV-8 genome, a viral homologue to human IL-6 is present, which is believed to induce angiogenesis and hematopoiesis. However, some patients test negative for HHV-8,18 so the complete role of this virus in the pathogenesis of Castleman disease is unknown.
  • Electromyography exhibits findings consistent with polyneuropathy, prominent demyelination, and features of axonal degeneration. One study demonstrated a statistically significant pattern of lower limbs having absent or attenuated amplitudes of compound muscle action potentials and absent sensory nerve action potentials compared with upper limbs. Intermediate nerves segments exhibited abnormal conduction slowing compared with distal portions. These patterns may aid in early diagnosis.
  • Nerve biopsies usually reveal evidence of both axonal degeneration and demyelination, characterized by uncompacted myelin lamina without immunoglobulin deposition and minimal cellular infiltration.

Histologic Findings

The histopathologic changes seen in the sclerodermoid lesions are nonspecific, showing hyperpigmentation of the basal layer with an inflammatory infiltrate or dermal fibrosis. Other reports have noted vascular prominence. Sweat glands and collagen are normal, differentiating this condition from scleroderma. A skin biopsy of hyperpigmented lesional skin may demonstrate a nonspecific inflammatory infiltrate composed of a lymphoplasmacytic population.19

Most angiomas seen in persons with POEMS syndrome are histologically consistent with cherry angiomas. The angiomas in a small proportion of patients have the appearance of a glomeruloid hemangioma. This finding may be strongly suggestive of POEMS syndrome, but it is not pathognomonic because the presence of this pathologic entity has been reported in a patient without POEMS syndrome. Multiple ectatic vascular spaces with luminal clusters of congested capillaries are noted in the lesions. The capillaries are surrounded by pericytes and resemble renal glomeruli, hence the term glomeruloid hemangioma.

Treatment

Medical Care

The treatment of POEMS syndrome depends on the treatment of the underlying plasma cell disorder. Most patients are treated with a combination of medical, surgical, and adjuvant therapies.

  • The current mainstays of treatment for patients with diffuse disease include combinations of corticosteroids, low-dose alkylators, and peripheral blood stem cell transplantation following high-dose chemotherapy. Some caution should be used in selecting the chemotherapeutic regimen to avoid worsening of the polyneuropathy.
  • Widespread osteosclerotic lesions may benefit from systemic therapy, with approximately half the patients benefiting from melphalan and prednisone. Although about a quarter of patients respond to corticosteroids, relapses are common without additional treatment of the underlying plasma cell disorder. Intravenous immunoglobulin and plasmapheresis have not shown therapeutic benefit.
  • Some patients may consider high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation. Preliminary studies report a mortality rate of 7.4% associated with the procedure, in addition to significant peritransplantation morbidity that often requires intubation, but nearly all survivors experienced benefit. A case report described the successful treatment of a patient with multicentric Castleman disease and POEMS syndrome with autologous hematopoietic stem cell transplantation, with subsequent improved nerve conduction and normalization of serum protein electrophoresis results.20
  • Treatment with high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation may result in clinical improvements of polyneuropathy.21
  • Relapse after successful auto peripheral blood stem cell transplantation has been reported.22
  • In a series of 30 POEMS syndrome patients treated at the Mayo Clinic in Rochester, Minn, engraftment syndrome was reported in approximately half the patients, with symptoms including fever (93%), diarrhea (77%), weight gain (53%), and rash (43%), in addition to a 3% treatment-related mortality rate. Baseline splenomegaly was predictive of a complicated peritransplantation course.23
  • Kojima et al24 describe clinical remission of more than 20 months for one patient who received high-dose chemotherapy with autologous CD34+ -purged stem cells.
  • The clinical course of one patient improved after administration of thalidomide, which has well-described antiangiogenetic, antiproliferative, and anticytokine characteristics.25
  • A case report of one patient with POEMS syndrome and elevated VEGF levels describes successful treatment with bevacizumab, an antiangiogenesis monoclonal antibody directed against VEGF. This treatment was associated with reduced edema and less painful neuropathy.26 Another patient treated with bevacizumab (10 mg/kg) twice monthly had decreased pain after one month, with improvements in breathing and walking within 10 weeks. These subjective changes were associated with a drop in VEGF levels and clinical improvements measured by pulmonary function tests, electromyographic studies, and nerve conduction studies. In this patient, neither hepatomegaly nor skin abnormalities were modified.27
  • Responses to bevacizumab reportedly have been variable. In one patient treated 7 years after diagnosis, no clinical improvement was reported despite lowered VEGF levels, which the authors thought may be due to aberrant angiogenesis that had already developed systemically.28 Another POEMS patient treated with 2 courses of bevacizumab (5 mg/kg) had decreased VEGF levels but worsening paresis, and this patient developed severe capillary leak syndrome with edema, ascites, and pleural effusion. These authors encourage caution prior to starting bevacizumab therapy because a sudden decrease in VEGF levels may result in apoptosis of endothelial cells, possibly increasing capillary leakiness.29 This approach is supported by another report of a patient treated by bevacizumab who developed diarrhea, generalized edema, pulmonary hypertension, and systemic inflammation and who subsequently died from multiorgan failure.
  • One patient improved after receiving 9 cycles of lenalidomide given daily for 21 days of a 28-day cycle with once-weekly dexamethasone. The dosage of lenalidomide was gradually increased from 15 mg to the standard 25-mg dose. Lenalidomide is cytotoxic to malignant plasma cells in addition to being immune modulatory.30 In 2009, a case report also described lenalidomide therapy in a patient with kappa restriction.31
  • Sanada et al32 report the clinical remission and correspondingly decreased VEGF serum concentrations of one patient with POEMS syndrome and renal lesions after treatment with high-dose melphalan therapy followed by autologous blood stem cell transplantation.
  • A single patient with POEMS syndrome associated with 2 monoclonal gammopathies (IgG-kappa and IgA-gamma) has been reported, in whom high doses of all-trans -retinoic acid was potentially beneficial.33
  • Two case reports describe successful therapy with bortezomib.34,35
  • For patients with POEMS and pulmonary hypertension, high-dose steroid treatment appears to provide improvement as confirmed by sequential hemodynamic studies.36,37

Surgical Care

Surgical excision of isolated plasmacytomas may result in complete resolution of the syndrome.

  • Radiation therapy of solitary osteosclerotic lesions is first-line therapy for patients with an isolated plasmacytoma.
  • Radiation therapy in dosages of 40-50 cGy to limited areas can improve osteosclerotic lesions in more than half the patients. More than 6 months may elapse before clinically apparent improvement is observed, with benefit observed even 2-3 years after therapy. Other authors recommend systemic therapy for patients whose disease process fails to stabilize 3-6 months after completing radiation therapy.

Consultations

Care of patients with POEMS syndrome is coordinated through many specialists because of the extent of possible symptoms associated with the disorder.

  • Once the diagnosis is clinically suggested, the patient should be evaluated by a neurologist, a hematologist, a dermatologist, and an endocrinologist to define the extent of disease.
  • Referral to a pulmonologist or a nephrologist should be guided by the patient's symptomatology.
  • A surgeon or a radiation oncologist may be needed for coordination of treatment.

Medication

The goal of pharmacotherapy is to reduce morbidity in patients whose disease does not respond to surgical removal or radiation therapy of the plasmacytoma.

Corticosteroids

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. In addition, they modify the body's immune response to diverse stimuli.


Prednisone (Deltasone, Orasone, Meticorten)

Useful in many inflammatory and autoimmune conditions. Must be metabolized to the active metabolite prednisolone for effect. Conversion may be impaired by liver disease. May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

Dosing

Adult

40-80 mg PO qd or divided bid; taper slowly; extended therapy is required in many patients; qod dosing may decrease adverse reactions

Pediatric

Not established

Interactions

Coadministration with estrogens may decrease clearance; when used with digoxin, digitalis toxicity secondary to hypokalemia may increase; phenobarbital, phenytoin, and rifampin may increase the metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics; coadministration with ritonavir may significantly increase serum concentrations of prednisone; concomitant therapy with montelukast may result in severe peripheral edema; clarithromycin may increase risk of psychotic symptoms

Contraindications

Documented hypersensitivity; viral, fungal, tubercular skin, or connective-tissue infections; peptic ulcer disease; hepatic dysfunction; hypertension; diabetes; do not administer vaccinations for immunization during treatment

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

May unmask hypertension or diabetes or exacerbate peptic ulcer disease and tuberculosis; long-term sequelae associated with long-term steroid use include osteoporosis, cataracts, and pituitary-hypothalamic axis suppression; with high doses, patients may develop a steroid psychosis and are at increased risk of infections, particularly when oral steroids are used in conjunction with other immunosuppressants; frequently monitor patient's blood sugar level, blood pressure, and weight; monitor for Cushing syndrome

Follow-up

Further Outpatient Care

Even if the plasmacytoma completely responds to treatment, patients need long-term follow-up care because some symptoms, such as neurologic defects and functional loss due to tightening of the skin, may be permanent.

Prognosis

The prognosis depends on the extent of the underlying plasma cell disorder and its response to treatment.

  • The prognosis is best for patients with a single lytic lesion.
  • The prognosis is worst for patients with a plasma cell disorder involving the bone marrow.
  • Patients with multiple lytic bone lesions have an intermediate prognosis.
  • When the plasma cell disorder responds to treatment, all other symptoms usually improve or resolve completely.
  • Reduced survival times are associated with the presence of cough, and respiratory weakness decreased mean survival time from 139 months to 87 months in one study.12

References

  1. Ofran Y, Yishay O, Elinav E, Eran E. POEMS syndrome: failure of newly suggested diagnostic criteria to anticipate the development of the syndrome. Am J Hematol. Aug 2005;79(4):316-8. [Medline].

  2. Morizane R, Sasamura H, Minakuchi H, Takae Y, Kikuchi H, Yoshiya N, et al. A case of atypical POEMS syndrome without polyneuropathy. Eur J Haematol. May 2008;80(5):452-5. [Medline].

  3. Min JH, Hong YH, Lee KW. Electrophysiological features of patients with POEMS syndrome. Clin Neurophysiol. Apr 2005;116(4):965-8. [Medline].

  4. Pavord SR, Murphy PT, Mitchell VE. POEMS syndrome and Waldenström's macroglobulinaemia. J Clin Pathol. Feb 1996;49(2):181-2. [Medline].

  5. Watanabe O, Arimura K, Kitajima I, Osame M, Maruyama I. Greatly raised vascular endothelial growth factor (VEGF) in POEMS syndrome. Lancet. Mar 9 1996;347(9002):702. [Medline].

  6. Kastritis E, Terpos E, Anagnostopoulos A, Xilouri I, Dimopoulos MA. Angiogenetic factors and biochemical markers of bone metabolism in POEMS syndrome treated with high-dose therapy and autologous stem cell support. Clin Lymphoma Myeloma. Jul 2006;7(1):73-6. [Medline].

  7. Koike H, Iijima M, Mori K, Yamamoto M, Hattori N, Watanabe H, et al. Neuropathic pain correlates with myelinated fiber loss and cytokine profile in POEMS syndrome. J Neurol Neurosurg Psychiatry. Apr 3 2008;[Medline].

  8. Miralles GD, O'Fallon JR, Talley NJ. Plasma-cell dyscrasia with polyneuropathy. The spectrum of POEMS syndrome. N Engl J Med. Dec 31 1992;327(27):1919-23. [Medline].

  9. Lanza C, Misericordia M, Fabrizzi G. POEMS syndrome in a 15-year-old boy: radiological findings. Pediatr Radiol. Nov 2007;37(11):1147-50. [Medline].

  10. Sevketoglu E, Hatipoglu S, Ayan I, Dogan O, Salihoglu B. Case report: POEMS syndrome in childhood. J Pediatr Hematol Oncol. Mar 2008;30(3):235-8. [Medline].

  11. Gandhi GY, Basu R, Dispenzieri A, Basu A, Montori VM, Brennan MD. Endocrinopathy in POEMS syndrome: the Mayo Clinic experience. Mayo Clin Proc. Jul 2007;82(7):836-42. [Medline].

  12. Allam JS, Kennedy CC, Aksamit TR, Dispenzieri A. Pulmonary manifestations in patients with POEMS syndrome: a retrospective review of 137 patients. Chest. Apr 2008;133(4):969-74. [Medline].

  13. Garcia T, Dafer R, Hocker S, Schneck M, Barton K, Biller J. Recurrent strokes in two patients with POEMS syndrome and Castleman's disease. J Stroke Cerebrovasc Dis. Nov-Dec 2007;16(6):278-84. [Medline].

  14. Wiaux C, Landau K, Borruat FX. Unusual cause of bilateral optic disc swelling: POEMS syndrome. Klin Monatsbl Augenheilkd. Apr 2007;224(4):334-6. [Medline].

  15. Chong DY, Comer GM, Trobe JD. Optic disc edema, cystoid macular edema, and elevated vascular endothelial growth factor in a patient with POEMS syndrome. J Neuroophthalmol. Sep 2007;27(3):180-3. [Medline].

  16. Hudnall SD, Chen T, Brown K, Angel T, Schwartz MR, Tyring SK. Human herpesvirus-8-positive microvenular hemangioma in POEMS syndrome. Arch Pathol Lab Med. Aug 2003;127(8):1034-6. [Medline].

  17. Papo T, Soubrier M, Marcelin AG, Calvez V, Wechsler B, Huraux JM, et al. Human herpesvirus 8 infection, Castleman's disease and POEMS syndrome. Br J Haematol. Mar 1999;104(4):932-3. [Medline].

  18. Obermoser G, Larcher C, Sheldon JA, Sepp N, Zelger B. Absence of human herpesvirus-8 in glomeruloid haemangiomas associated with POEMS syndrome and Castleman's disease. Br J Dermatol. Jun 2003;148(6):1276-8. [Medline].

  19. Colaco SM, Miller T, Ruben BS, Fogarty PF, Fox LP. IgM-lambda paraproteinemia with associated cutaneous lymphoplasmacytic infiltrate in a patient who meets diagnostic criteria for POEMS syndrome. J Am Acad Dermatol. Apr 2008;58(4):671-5. [Medline].

  20. Ganti AK, Pipinos I, Culcea E, Armitage JO, Tarantolo S. Successful hematopoietic stem-cell transplantation in multicentric Castleman disease complicated by POEMS syndrome. Am J Hematol. Jul 2005;79(3):206-10. [Medline].

  21. Imai H, Kusuhara S, Nakanishi Y, Teraoka Escaño MF, Yamamoto H, Tsukahara Y, et al. A case of POEMS syndrome with cystoid macular edema. Am J Ophthalmol. Mar 2005;139(3):563-6. [Medline].

  22. Giglia F, Chiapparini L, Fariselli L, Barbui T, Ciano C, Scarlato M. POEMS syndrome: relapse after successful autologous peripheral blood stem cell transplantation. Neuromuscul Disord. Dec 2007;17(11-12):980-2. [Medline].

  23. Dispenzieri A, Lacy MQ, Hayman SR, Kumar SK, Buadi F, Dingli D, et al. Peripheral blood stem cell transplant for POEMS syndrome is associated with high rates of engraftment syndrome. Eur J Haematol. May 2008;80(5):397-406. [Medline].

  24. Kojima H, Katsuoka Y, Katsura Y, Suzuki S, Suzukawa K, Hasegawa Y, et al. Successful treatment of a patient with POEMS syndrome by tandem high-dose chemotherapy with autologous CD34+ purged stem cell rescue. Int J Hematol. Aug 2006;84(2):182-5. [Medline].

  25. Sinisalo M, Hietaharju A, Sauranen J, Wirta O. Thalidomide in POEMS syndrome: case report. Am J Hematol. May 2004;76(1):66-8. [Medline].

  26. Badros A, Porter N, Zimrin A. Bevacizumab therapy for POEMS syndrome. Blood. Aug 1 2005;106(3):1135. [Medline].

  27. Dietrich PY, Duchosal MA. Bevacizumab therapy before autologous stem-cell transplantation for POEMS syndrome. Ann Oncol. Mar 2008;19(3):595. [Medline].

  28. Kanai K, Kuwabara S, Misawa S, Hattori T. Failure of treatment with anti-VEGF monoclonal antibody for long-standing POEMS syndrome. Intern Med. 2007;46(6):311-3. [Medline].

  29. Straume O, Bergheim J, Ernst P. Bevacizumab therapy for POEMS syndrome. Blood. Jun 15 2006;107(12):4972-3; author reply 4973-4. [Medline].

  30. Dispenzieri A, Klein CJ, Mauermann ML. Lenalidomide therapy in a patient with POEMS syndrome. Blood. Aug 1 2007;110(3):1075-6. [Medline].

  31. Sethi S, Tageja N, Arabi H, Penumetcha R. Lenalidomide Therapy in a Rare Case of POEMS Syndrome with Kappa Restriction. South Med J. Sep 4 2009;[Medline].

  32. Sanada S, Ookawara S, Karube H, Shindo T, Goto T, Nakamichi T, et al. Marked recovery of severe renal lesions in POEMS syndrome with high-dose melphalan therapy supported by autologous blood stem cell transplantation. Am J Kidney Dis. Apr 2006;47(4):672-9. [Medline].

  33. Authier FJ, Belec L, Levy Y, Lefaucheur JP, Defer GL, Degos JD, et al. All-trans-retinoic acid in POEMS syndrome. Therapeutic effect associated with decreased circulating levels of proinflammatory cytokines. Arthritis Rheum. Aug 1996;39(8):1423-6. [Medline].

  34. Tang X, Shi X, Sun A, et al. Successful bortezomib-based treatment in POEMS syndrome. Eur J Haematol. Aug 6 2009;[Medline].

  35. Kaygusuz I, Tezcan H, Cetiner M, Kocakaya O, Uzay A, Bayik M. Bortezomib: A New Therapeutic Option for POEMS Syndrome. Eur J Haematol. Sep 3 2009;[Medline].

  36. Jouve P, Humbert M, Chauveheid MP, Jaïs X, Papo T. POEMS syndrome-related pulmonary hypertension is steroid-responsive. Respir Med. Feb 2007;101(2):353-5. [Medline].

  37. Rached S, Athanazio RA, Dias SA Jr, Jardim C, Souza R. Systemic corticosteroids as first-line treatment in pulmonary hypertension associated with POEMS syndrome. J Bras Pneumol. Aug 2009;35(8):804-8. [Medline].

  38. Cabezas-Agricola JM, Lado-Abeal JJ, Otero-Anton E, Sanchez-Leira J, Cabezas-Cerrato J. Hypoparathyroidism in POEMS syndrome. Lancet. Mar 9 1996;347(9002):701-2. [Medline].

  39. Calonje E, Wilson-Jones E. Vascular tumors. In: Elder D, Elenitsas R, Jaworsky C, eds. Lever's Histopathology of the Skin. 8th ed. Philadelphia, Pa: Lippincott-Raven; 1997:890-1.

  40. Di Napoli M, Arakelyan A. POEMS syndrome, fibrinogen, and ischemic stroke: a critical point of view. Arch Neurol. Jan 2004;61(1):155; author reply 155-6. [Medline].

  41. Dispenzieri A, Gertz MA. Treatment options for POEMS syndrome. Expert Opin Pharmacother. Jun 2005;6(6):945-53. [Medline].

  42. Dispenzieri A, Kyle RA. Neurological aspects of multiple myeloma and related disorders. Best Pract Res Clin Haematol. 2005;18(4):673-88. [Medline].

  43. Dispenzieri A, Kyle RA, Lacy MQ, Rajkumar SV, Therneau TM, Larson DR, et al. POEMS syndrome: definitions and long-term outcome. Blood. Apr 1 2003;101(7):2496-506. [Medline].

  44. Dispenzieri A, Moreno-Aspitia A, Suarez GA, Lacy MQ, Colon-Otero G, Tefferi A, et al. Peripheral blood stem cell transplantation in 16 patients with POEMS syndrome, and a review of the literature. Blood. Nov 15 2004;104(10):3400-7. [Medline].

  45. Donofrio PD. Immunotherapy of idiopathic inflammatory neuropathies. Muscle Nerve. Sep 2003;28(3):273-92. [Medline].

  46. Erro ME, Lacruz F, Aymerich N, Ayuso T, Soriano G, Gállego J, et al. Acute carotid obliteration: a new vascular manifestation in POEMS syndrome. Eur J Neurol. Jul 2003;10(4):383-4. [Medline].

  47. Fishel B, Brenner S, Weiss S, Yaron M. POEMS syndrome associated with cryoglobulinemia, lymphoma, multiple seborrheic keratosis, and ichthyosis. J Am Acad Dermatol. Nov 1988;19(5 Pt 2):979-82. [Medline].

  48. Goebels N, Walther EU, Schaller M, Pongratz D, Mueller-Felber W. Inflammatory myopathy in POEMS syndrome. Neurology. Nov 14 2000;55(9):1413-4. [Medline].

  49. Imai N, Kitamura E, Tachibana T, Konishi T, Suzuki Y, Serizawa M. Efficacy of autologous peripheral blood stem cell transplantation in POEMS syndrome with polyneuropathy. Intern Med. 2007;46(3):135-8. [Medline].

  50. Kang K, Chu K, Kim DE, Jeong SW, Lee JW, Roh JK. POEMS syndrome associated with ischemic stroke. Arch Neurol. May 2003;60(5):745-9. [Medline].

  51. Kim SK, Park IK, Park BH, Park W, Lee HS, Kim TH, et al. A case report: isolated a heavy chain monoclonal gammopathy in a patient with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin change syndrome. Int J Clin Pract Suppl. Apr 2005;(147):26-30. [Medline].

  52. Kuwabara S, Hattori T, Shimoe Y, Kamitsukasa I. Long term melphalan-prednisolone chemotherapy for POEMS syndrome. J Neurol Neurosurg Psychiatry. Sep 1997;63(3):385-7. [Medline].

  53. Kuwabara S, Misawa S, Kanai K, Kikkawa Y, Nishimura M, Nakaseko C, et al. Autologous peripheral blood stem cell transplantation for POEMS syndrome. Neurology. Jan 10 2006;66(1):105-7. [Medline].

  54. Mokhlesi B, Jain M. Pulmonary manifestations of POEMS syndrome: case report and literature review. Chest. Jun 1999;115(6):1740-2. [Medline].

  55. Samaras P, Bauer S, Stenner-Liewen F, Steiner R, Zweifel M, Renner C, et al. Treatment of POEMS syndrome with bevacizumab. Haematologica. Oct 2007;92(10):1438-9. [Medline].

  56. Shibata M, Yamada T, Tanahashi N, Koto A, Kuramochi S, Fukushima S, et al. POEMS syndrome with necrotizing vasculitis: a novel feature of vascular abnormalities. Neurology. Feb 8 2000;54(3):772-3. [Medline].

  57. Soubrier M, Dubost JJ, Serre AF, Ristori JM, Sauvezie B, Cathebras P, et al. Growth factors in POEMS syndrome: evidence for a marked increase in circulating vascular endothelial growth factor. Arthritis Rheum. Apr 1997;40(4):786-7. [Medline].

  58. 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. Dec 1994;97(6):543-53. [Medline].

  59. Vélez D, Delgado-Jiménez Y, Fraga J. Solitary glomeruloid haemangioma without POEMS syndrome. J Cutan Pathol. Jul 2005;32(6):449-52. [Medline].

  60. Warren KJ. POEMS syndrome in a patient with diabetic ketoacidosis: case report and review. Cutis. Jun 1998;61(6):329-34. [Medline].

Keywords

Crow-Fukase syndrome, Takatsuki syndrome, PEP, polyneuropathy endocrinopathy plasma cell dyscrasia, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes, Castleman disease, Castleman's disease, Takatsuki syndrome

Contributor Information and Disclosures

Author

Joanna L Chan, MD, Resident Physician, Department of Dermatology, University of Texas Southwestern Medical Center
Joanna L Chan, MD is a member of the following medical societies: American Academy of Dermatology and American Society for Dermatologic Surgery
Disclosure: Nothing to disclose.

Coauthor(s)

Wingfield Rehmus, MD, MPH, 
Wingfield Rehmus, MD, MPH is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

Alexa F Boer Kimball, MD, MPH, Associate Professor of Dermatology, Harvard University School of Medicine; Vice Chair, Department of Dermatology, Massachusetts General Hospital; Director of Clinical Unit for Research Trials in Skin (CURTIS), Department of Dermatology, Massachusetts General Hospital
Alexa F Boer Kimball, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Medical Editor

Neil Shear, MD, Professor and Chief of Dermatology, Professor of Medicine, Pediatrics and Pharmacology, University of Toronto Faculty of Medicine; Head of Dermatology, Sunnybrook Women's College Health Sciences Center and Women's College Hospital, Canada
Neil Shear, MD is a member of the following medical societies: American Academy of Dermatology, American Society for Clinical Pharmacology and Therapeutics, Canadian Dermatology Association, Canadian Medical Association, Ontario Medical Association, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Pharmacy Editor

Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center
Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Warren R Heymann, MD, Head, Division of Dermatology, Professor, Department of Internal Medicine, University of Medicine and Dentistry of New Jersey
Warren R Heymann, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

CME Editor

Glen H Crawford, MD, Assistant Clinical Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, The Pennsylvania Hospital
Glen H Crawford, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Phi Beta Kappa, and Society of USAF Flight Surgeons
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

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