POEMS Syndrome

5/16/00 (Del Rio)

Group: Tuesday Interns

RE: A 24 year old African American fe male with undiagnosed fever and renal insufficiency.

Question: What is the POEMS syndrome?

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[Link Directly to Fulltext Article in OVID]

Unique Identifier: 20143022

Authors: Shibata M. Yamada T. Tanahashi N. Koto A. Kuramochi S. Fukushima S. Fukuuchi Y.

Institution: Department of Neurology, School of Medicine, Keio University, Tokyo, Japan.

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Unique Identifier: 20142172

Authors: Kishimoto S. Takenaka H. Shibagaki R. Noda Y. Yamamoto M. Yasuno H.

Institution: Department of Dermatology, Kyoto Prefectural University of Medicine, Japan. sabkishi@derm.kpu-m.ac.jp

Abstract: The case of a Japanese woman with glomeruloid hemangioma, an initial marker for POEMS syndrome, is reported. Her: cutaneous lesions were multiple and consisted of glomeruloid hemangiomas, cherry-type capillary hemangiomas, and a: mixture of both. The specimens of glomeruloid hemangiomas were studied by paraffin section immunohistochemistry with: a large panel of antibodies and electron microscopy, respectively. The lesions, whose size ranged from minute foci to: large nodules, were composed of anastomosing vascular channels resembling renal glomeruli and had irregular lumina,: often featuring capillaries and sinusoid-like spaces. The vascular channels were lined by a single layer of endothelial cells,: which showed two types of cells. The capillary-type endothelium possessed large vesicular nuclei with open chromatin: and large amount of cytoplasm. The sinusoidal endothelium possessed small basal nuclei with dense chromatin as well as: scant amount of cytoplasm. The former cells had a characteristic CD31+/CD34+/UEA I+/CD68- phenotype. Some of: these cells ultrastructurally showed intracytoplasmic lumen formation. The latter cells had a characteristic: CD31+/CD34-/UEA I-/CD68+ phenotype. The present study shows that glomeruloid hemangioma has unique: morphologic and immunologic features that differ from the traditional hemangiomas as well as littoral cell angioma of the: spleen.

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Unique Identifier: 20073931

Authors: Chang SE. Choi JH. Sung KJ. Moon KC. Koh JK. Ro JY.

Institution: Department of Dermatology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea.

Abstract: A diffuse xanthomatous infiltration was detected on a biopsy of the hyperpigmented patches in a 40-year-old man with: POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, Skin changes) syndrome. Multiple biopsies of: the hyperpigmented patches showed diffuse or perivascular foamy histiocytes in the upper and mid dermis, a sparse: infiltrate of lymphocytes, fibrosis, hyperpigmentation of the basal layer, and capillary proliferation. The foamy cells were: positive for periodic acid-Schiff (PAS) with diastase, oil red-O, and CD68. To our knowledge, this is the first case with: foamy histiocytes without xanthomatous-appearing skin lesions in POEMS syndrome. It would be worth searching for: xanthomatous histiocytes in the hyperpigmented skin of patients with POEMS syndrome.

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Unique Identifier: 99455928

Authors: Nakamoto Y. Imai H. Yasuda T. Wakui H. Miura AB.

Institution: Kichijoji Asahi Hospital, Musashino, Tokyo, Japan.

Abstract: BACKGROUND: In POEMS syndrome, substantial involvement of the kidney can occur and is reflected by: proteinuria, haematuria, renal dysfunction, and renal failure requiring dialysis therapy. The mechanism by which renal: dysfunction is induced and progresses to end-stage renal disease remains obscure. A pathogenic role of cytokines and: growth factors has recently been implicated. METHODS: We reviewed cases of 52 Japanese patients with confirmed: renal pathology who were reported in the literature, and personally analysed renal tissues from 22 subjects including nine: patients of our own. Interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) were measured in our cases.: RESULTS: Despite relatively mild renal symptomatology, about half of the cases had azotaemia with creatinine levels: above 1.5 mg/dl and the BUN/creatinine ratio markedly raised by volume contraction or wasting. One-tenth of patients: were placed on haemodialysis because of advanced or end-stage renal disease. Bilateral and unilateral contracted: kidneys were found in four and two cases respectively. Pathological analyses disclosed two major changes: glomerular: alterations and endarteritis-like lesions of renal small arteries. The former included glomerular enlargement, cellular: proliferation, mesangiolysis and marked swelling of endothelial-mesangial cells. This structural disorganization led to a: reduction in renal function to some degree by impairing the glomerular circulation. Vasculopathy of the small artery: probably resulted in progressive renal damage and ultimately to kidney contraction. Serum IL-6 was elevated in about: 40% of cases. IL-6 levels were found to be high in the ascites of three patients who were examined. In different studies,: an increased level of VEGF was found in the peripheral blood (75-100%; overall 92.3%), but no apparent correlation: with glomerular alterations was observed. CONCLUSION: POEMS nephropathy can be one cause of end-stage renal: disease with variable intrarenal pathological changes of a microangiopathic nature which have differential influences on: renal function. A pathogenic role for VEGF in POEMS syndrome appears to be likely, but its causal relation to the: nephropathy awaits further investigation.

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[Link Directly to Fulltext Article in OVID]

Unique Identifier: 99304922

Authors: Mokhlesi B. Jain M.

Institution: Department of Medicine, Northwestern University Medical School, Chicago, IL 60611, USA.

Abstract: Phrenic nerve paresis is an unusual complication of POEMS (polyneuropathy, organomegaly, endocrinopathy,: M-protein spike and skin changes) syndrome. In this report, we describe a case of POEMS syndrome in which a: 56-year-old woman presented with dyspnea and ventilatory failure due to bilateral phrenic nerve paralysis. To our: knowledge, only one other case of phrenic neuropathy in POEMS syndrome has been reported.

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Unique Identifier: 99208438

Authors: Belec L. Authier FJ. Mohamed AS. Soubrier M. Gherardi RK.

Institution: Laboratoire de Virologie, CHU Broussais-Hotel Dieu, Paris, France. laurent.belec@brs.ap-hop-paris.fr

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Unique Identifier: 99272406

Authors: Belec L. Mohamed AS. Authier FJ. Hallouin MC. Soe AM. Cotigny S. Gaulard P. Gherardi RK.

Institution: Groupe d'Etude et de Recherche sur le Nerf Et le Muscle (GERMEN, EA 2347), Faculte de Medecine de Creteil,: Universite Paris XII-Val de Marne, France.

Abstract: The polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes (POEMS) syndrome is a rare: multisystemic disorder associated with osteosclerotic myeloma and multicentric Castleman's disease (MCD). Human: herpesvirus type 8 (HHV-8) DNA sequences have been detected in lymph nodes of about 40% of human: immunodeficiency virus (HIV)-negative patients with MCD, and in bone marrow stromal cells of patients with multiple: myeloma. Considering these data, we investigated the presence of HHV-8 in 18 patients with POEMS syndrome (9: with MCD), by nested polymerase chain reaction (N-PCR) to detect DNA sequenses in various cells and tissues: obtained by biopsy or at autopsy (13 patients, of whom 7 had MCD), and by an immunofluorescence assay to detect: anti-HHV-8 IgG antibodies in blood (18 patients, of whom 9 had MCD). Detection of HHV-8 DNA was performed: using three different N-PCR, targeting nonoverlapping regions in open reading frame (ORF) 25 and ORF26. Seven of: 13 (54%) POEMS patients had HHV-8 DNA sequences in their tissues, as assessed by all three N-PCR, and 9 of 18: (50%) had circulating anti-HHV-8 antibodies. HHV-8 was mainly detected in the subset of POEMS patients with MCD: (6 of 7 [85%] for DNA sequences; 7 of 9 [78%] for antibodies). The percentage of positive N-PCR was higher in: lymph nodes than in bone marrow samples (P <.02). Sequencing of amplicons showed a homogeneous restricted: variability in the ORF26 region, characteristic of the minority subgroup B defined by Zong, and responsible for isoleucine: and glycine substitutions at amino acid positions 134 and 167. These findings strongly suggest an association of HHV-8: infection with POEMS syndrome-associated MCD.

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Unique Identifier: 99191497

Authors: Longo G. Emilia G. Torelli U.

Institution: Department of Medical Sciences, University of Modena, Italy.

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Unique Identifier: 98285862

Authors: Pasqui AL. Bova G. Saletti M. Bruni F. Di Renzo M. Auteri A.

Institution: U.O. Immunologia Clinica, Policlinico Le Scotte , I-53100 Siena, Italy. defranco@unisi.it

Abstract: We describe here the case of a 60 years man with POEMS syndrome associated with renal tumor and vascular lesions.: The patient had osteosclerotic myeloma IgA-lambda, polyneuropathy, endocrinopathy and skin changes. In addition, he: developed renal clear cell carcinoma and gangrena of lower limbs. The humoral study showed thrombocytosis, high levels: of IL-1beta and IL-6 and of some coagulative/fibrinolytic and endothelial factors (von Willebrand factor,: plasmin-antiplasmine complexes, plasminogen activator). We suggest the hypothesis that these factors are capable of: determining some manifestations of POEMS syndrome.

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Unique Identifier: 98176787

Authors: Lesprit P. Godeau B. Authier FJ. Soubrier M. Zuber M. Larroche C. Viard JP. Wechsler B. Gherardi R.

Institution: Departement de Pathologie, Hopital Henri Mondor, Creteil, France.

Abstract: POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome is a: rare variant of plasma cell dyscrasia with multiple systemic manifestations. We followed the progress of 20 patients with: POEMS syndrome in our institution over a 10-yr period. Pulmonary hypertension (PH) was observed in five patients.: All patients suffered dyspnea on exertion, which always appeared during an exacerbation of POEMS syndrome. The: typical echocardiographic signs of PH were observed in all of these patients, and the median pulmonary-artery systolic: pressure was 57 mm Hg (range, 50 to 65 mm Hg). Mean pulmonary-artery pressure during right side heart: catheterization in two patients was 32 mm Hg. No other explanation for the PH could be found. Overproduction of: cytokines was found in all cases, with high serum concentrations of interleukin-1beta, interleukin-6, tumor necrosis: factor-alpha, and vascular endothelial growth factor. We suggest that PH should be added to the list of symptoms of: POEMS syndrome. Cytokines may mediate POEMS syndrome-associated PH, as proposed for the other systemic: manifestations of this disorder.

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Unique Identifier: 98106262

Authors: Narvaez JA. Majos C. Narvaez J. Valls C. Fernandez-Cabrera L.

Institution: Department of CT and MR Imaging, Institut de Diagnostic per la Imatge, Hospital Duran i Reynals, Ciudad Sanitaria y: Universitaria de Bellvitge, Autovia de Castelldefels km. 2'7, E-08907 L'Hospitalet de Llobregat, Barcelona, Spain.

Abstract: POEMS syndrome is a multisystemic disorder related to a plasma cell dyscrasia. Radiologically, this syndrome is: characterized by sclerotic focal bone lesions with a normal radionuclide bone scan. We report a case of POEMS: syndrome with an expansile lytic lesion in the sternum showing periosteal reaction and soft tissue mass, which revealed: locally increased uptake of radiotracer in bone scintigraphy. These unusual findings and the differential diagnosis are: discussed.

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Unique Identifier: 98055572

Authors: Lacy MQ. Gertz MA. Hanson CA. Inwards DJ. Kyle RA.

Institution: Division of Hematology and Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.

Abstract: Multiple myeloma usually is characterized by the development of lytic bone lesions. Osteosclerotic myeloma is a rare: entity characterized by a single or multiple osteosclerotic bone lesions and often accompanied by a demyelinating: polyneuropathy. Multiple myeloma associated with widespread osteosclerotic lesions seen on radiographic studies is: exceedingly rare. We describe 3 such cases and review 12 other cases described in the literature. Overall, the patients: described herein had a clinical course that resembled multiple myeloma more than osteosclerotic myeloma. However,: some patients had features of both diseases. Although rare, multiple myeloma should be included in the differential: diagnosis of widespread osteosclerotic bone lesions. [References: 19]

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Unique Identifier: 97466920

Authors: Kuwabara S. Hattori T. Shimoe Y. Kamitsukasa I.

Institution: Department of Neurology, School of Medicine, Chiba University, Japan.

Abstract: The effects of long term melphalan-prednisolone (MP) therapy was studied on 12 patients with POEMS: (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome. Six were treated with MP: every six weeks for 16 to 52 months; three also with cyclophosphamide, and three with localised irradiation for: osteoclastic lesions. Five of the six survived during the follow up period and showed various degrees of lessening of their: neuropathy and other symptoms. There were no serious side effects. The other six patients received treatments that: included corticosteroids, short term chemotherapy, or irradiation, but not long term chemotherapy. Five showed transient: lessening of their non-neurological symptoms, and one, obvious neurological improvement. Five of these six patients died: from nine to 70 months after POEMS onset. The findings suggest that long term MP therapy may be an effective: treatment for the POEMS syndrome.

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Unique Identifier: 97407638

Authors: Rose C. Zandecki M. Copin MC. Gosset P. Labalette M. Hatron PY. Jauberteau MO. Devulder B. Bauters F. Facon: T.

Institution: Laboratoire d'Hematologie A, CHU, Lille, France.

Abstract: POEMS syndrome is a multisystemic disorder characterized by the association of polyneuropathy, organomegaly,: endocrinopathy, M protein, skin changes and various other systemic clinical signs. The pathophysiology of this syndrome: remains largely unknown. In order to gain insight into its pathophysiology, we studied the clinical characteristics and: performed serum analysis (auto-antibodies, cytokine levels) and phenotypic and cytogenetic studies of bone marrow: plasma cells (BMPC) in six patients with unequivocal POEMS syndrome. Two unusual clinical signs were present in: these patients: pulmonary hypertension (two patients) and diffuse cutaneous necrosis (one patient). No auto-antibodies: against peripheral nerve (PN) antigens (SGPG and SGLPG glycolipids, GM1, GD1a, GD1b and GT1b gangliosides): were found. Sequential evaluations of serum cytokines (IL-1-beta, IL-6 and TNF-alpha) showed a moderate to marked: elevations of IL-6 and TNF-alpha in all patients (up to six-fold for TNF-alpha and 16-fold for IL-6). Using in situ: hybridization of these cytokines mRNAs on lymph node specimens of two patients who had an angiofollicular lymph: node hyperplasia, a strong positivity was found with the IL-1-beta antisense probe in lymph node macrophages. On skin: biopsy a high number of cells expressing TNF-alpha mRNA was observed in the dermis. The biological features of: BMPC: phenotype (expression of CD19 and CD56 antigens), kinetics (Ki-67 index), karyotype, DNA content and: chromosomal in situ hybridization remained those of BMPC found in monoclonal gammopathy of undetermined: significance. We conclude that POEMS syndrome is a hypercytokinemic syndrome in which BMPC are not of: malignant type. Macrophages are involved in this syndrome and their role has to be further investigated as well as: treatments which act through an anti-cytokine mechanism.

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Unique Identifier: 97379998

Authors: Rotta FT. Bradley WG.

Institution: Department of Neurology, University of Miami School of Medicine, Florida 33101, USA.

Abstract: We describe a patient with a 3 year history of progressive polyneuropathy that rendered him severely quadriparetic and: bedridden. Work up revealed an IgG lambda monoclonal spike and multifocal osteosclerotic myeloma. Remarkable: improvement followed combined treatment with surgical excision, radiation therapy, and chemotherapy using: chlorambucil, danazol, and hydrocortisone. Hence, we believe that aggressive local therapy associated with systemic: chemotherapy should be considered in severely affected patients with multifocal osteosclerotic myeloma and peripheral: neuropathy.

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Unique Identifier: 97063196

Authors: Duna GF. Cash JM.

Institution: The Cleveland Clinic Foundation, Ohio, USA.

Abstract: Rheumatic manifestations may be the presenting features of dysproteinemias and lymphoproliferative disorders. Disease: or therapy-related complications may mimic a number of primary rheumatic syndromes. This article emphasizes clinical: aspects pertaining to prompt diagnosis and therapy. [References: 107]

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Unique Identifier: 97096255

Authors: Mandler RN. King MK.

Institution: Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque 87131, USA.

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Unique Identifier: 97020223

Authors: Ribadeau-Dumas S. Tillie-Leblond I. Rose C. Saulnier F. Wemeau JL. Hatron PY. Wallaert B.

Institution: Service de Pneumologie et Immuno-allergologie, Hopital Calmette and INSERM U416, Institut Pasteur, Lille, France.

Abstract: Pulmonary hypertension (PH) is an uncommon but lethal complication of some connective tissue diseases. We describe: two cases of PH associated with plasma cell dyscrasia, with polyneuropathy (P), organomegaly (O), endocrinopathy (E),: M protein (P) and skin changes (S) described as POEMS syndrome. Two patients, one female and one male, were: hospitalized for dyspnoea. Both had a history of POEMS syndrome a few years previously. PH was diagnosed from: cardiac catherization, and complete investigations did not reveal other underlying disease. In Case No. 1, mean: pulmonary artery pressure was 40 mmHg and pulmonary vascular resistance was 775 dyne x s x cm-5 x m2, with a: significant reversibility to vasodilators. Nifedipine and fluindrone treatment was initiated. The patient was still alive 18: months later. In Case No. 2, mean pulmonary artery pressure was 28 mmHg and pulmonary vascular resistance was 243: dyne x s x cm-5x m2, with a slight reversibility to vasodilators. The patient died 6 months later. Our observations suggest: that pulmonary hypertension (PH) may be associated with the POEMS syndrome, and that patients suffering from the: POEMS syndrome and dyspnoea should be tested for PH. [References: 17]

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Unique Identifier: 96408326

Authors: Schey S.

Institution: Guy's and St Thomas' Trust, London.

Abstract: Metabolic bone disease is a major cause of morbidity and mortality in patients suffering from multiple myeloma. This: usually results from an imbalance between the osteoclast and osteoblast activity of bone resorption and formation due to: the secretion of an osteoclast-activating factor by the myeloma cells. This generally takes the form of lytic lesions,: hypercalcaemia and osteoporosis but, in a minority of patients, osteosclerosis is a striking feature. In a proportion of: patients with gammopathy and the osteosclerotic form of the disease, there appears to be an association with other: symptom complexes including Polyneuropathy, organomegaly, endocrine changes, and skin abnormalities. This article: summarizes the clinical, radiological and laboratory features of this syndrome, which is known by the acronym: 'POEMS'. It is important to recognize this condition, as it carries a better prognosis than the more common lytic form of: the disease and because vincristine, and agents frequently used to treat this condition, may severely exacerbate the: neuropathy and should be avoided. This syndrome is also important because it may give some insight into the: pathophysiology of the plasma-cell dyscrasias. [References: 50]

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Unique Identifier: 96406851

Authors: Zenone T. Bastion Y. Salles G. Rieux C. Morel D. Felman P. Espinouse D. Bryon PA. Coiffier B.

Institution: Department of Haematology, Centre Hospitalier Lyon-Sud, Pierre-Benite, France.

Abstract: The case of a 22-year-old man with polyneuropathy, endocrinopathy, skin change and monoclonal gammopathy of: IgG-lambda type is described. There was no solitary plasmocytoma, osteosclerotic myeloma or Castleman's disease.: However, significant thrombocytosis occurred and the patient developed arterial thrombosis, these were attributed to: essential thrombocythaemia in the absence of other aetiological factors.

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Unique Identifier: 96320248

Authors: Authier FJ. Belec L. Levy Y. Lefaucheur JP. Defer GL. Degos JD. Gherardi RK.

Institution: Groupe d'Etude et de Recherche sur le Muscle et le Nerf (Germen, Universite Paris XII, France.

Abstract: Chronically elevated serum levels of proinflammatory cytokines is a feature of the syndrome known as POEMS (plasma: cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal [M] protein, skin changes). A patient: had a POEMS syndrome with thrombocytosis and biclonal gammopathy and was treated as follows: all-trans-retinoic: acid (tretinoin) at 90 mg/day for 50 days, no treatment for 70 days, readministration of tretinoin at 75 mg/day for 180: days. Focal bone lesion irradiation was performed from day 26 to day 50. Serum levels of interleukin-6 (IL-6), tumor: necrosis factor alpha (TNF alpha), and IL-1 beta normalized within 7 days after the first administration of tretinoin,: transiently increased at the time of radiotherapy, increased again after withdrawal of the tretinoin, and decreased again: after its reintroduction. The platelet count and gammopathy paralleled the changes in the cytokine levels. This study: documents in vivo the ability of all-trans-retinoic acid to down-regulate the release of IL-6, IL-1 beta, and TNF alpha,: and illustrates its potential as a therapeutic agent in conditions associated with chronic overproduction of proinflammatory: cytokines.

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Unique Identifier: 96264447

Authors: Pavord SR. Murphy PT. Mitchell VE.

Institution: Department of Haematology, Leicester Royal Infirmary.

Abstract: A 58 year old man presented with a three year history of impotence, night sweats and ankle swelling. On examination,: the patient fulfilled the diagnostic criteria for POEMS syndrome, but was unusual in that he also had underlying: Waldenstrom's macroglobulinaemia with IgM kappa paraproteinaemia. The patient was treated with intermittent: chlorambucil and made a good recovery. POEMS syndrome has been described in association with osteosclerotic: myeloma and Castleman's disease. The paraprotein involved is usually IgG or IgA with lambda light chains. This case: indicates that the presence of lambda light chains is not essential for the pathogenesis of POEMS syndrome. It also: emphasises the diversity of plasma cell dyscrasias that can manifest as POEMS syndrome.

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Unique Identifier: 96190062

Authors: Gherardi RK. Belec L. Soubrier M. Malapert D. Zuber M. Viard JP. Intrator L. Degos JD. Authier FJ.

Institution: Groupe d'Etude et de Recherche sur le Nerf le Muscle, GERMEN, Faculte de Medecine de Creteil-Paris XII, Paris,: France.

Abstract: The polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes (POEMS) syndrome is a rare: multisystem disorder of obscure pathogenesis associated with osteosclerotic myeloma. Circulating levels of: proinflammatory cytokines (tumor necrosis factor-alpha (TNF-alpha) interleukin-1 beta [IL-1 beta], IL-2, IL-6, and: interferon-gamma [IFN-gamma]), anti-inflammatory cytokines (transforming growth factor beta 1 [TGF beta 1], IL-4,: IL-10, and IL-13), the cytokine carrier protein alpha 2 macroglobulin, IL-1 receptor antagonist (IL-1ra), soluble TNF: receptors (sTNFr) p55 and p75, and soluble IL-6 receptor (sIL-6r) were determined in 15 patients with POEMS: syndrome and 15 with multiple myeloma. Patients with POEMS syndrome had higher serum levels of IL-1 beta,: TNF-alpha, and IL-6 and lower serum levels of TGF beta 1 than did patients with multiple myeloma. Serum levels of: IL-2, IL-4, IL-10, IL-13, IFN-gamma, alpha 2 macroglobulin, and sIL-6r were similar in both groups. IL-1ra and: sTNFrs were increased in POEMS syndrome, but out of proportion to the increase of IL-1 beta and TNF-alpha.: Serial evaluations in 1 patient showed that proinflammatory cytokine serum levels paralleled disease activity assessed by: platelet count and neurologic involvement. Our results suggest that the manifestations of POEMS syndrome might be: regarded as the result of a marked activation of the proinflammatory cytokine network (IL-1 beta, IL-6, and TNF-alpha): associated with a weak or even decreased (TGF beta 1) antagonistic reaction insufficient to counteract the noxious: effects of cytokines.

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Unique Identifier: 95361238

Authors: Modesto-Segonds A. Rey JP. Orfila C. Huchard G. Suc JM.

Institution: Laboratoire d'Immunologie, CHU Rangueil, Toulouse, France.

Abstract: We describe a patient with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal: gammopathy and skin changes) who was found to have renal involvement with particular renal pathological findings. So: far, 17 other cases, most of them from Japan, of POEMS syndrome with renal involvement, have been published.: Clinical features are variable: acute renal failure with anasarca or moderate chronic renal insufficiency with mild: proteinuria. This latter presentation often passes unnoticed. There is no severe hypertension, no microangiopathic: hemolytic anemia. Renal biopsy shows prominent glomerular changes which are unusual and distinct from: membranoproliferative glomerulonephritis (MPGN) and from glomerular thrombotic microangiopathy (TMA). Mesangial: proliferation and thickening of the capillary wall with double contour on light microscopy suggest an MPGN. By: immunofluorescent microscopy, no immunoglobulins or complement deposits were found. The occurrence of: mesangiolytic lesions has led to the term of "mesangiolytic glomerulonephritis". The presence, on electron microscopy, of: lucent subendothelial spaces could indicate TMA. But there are neither thrombi nor arteriolar changes. We are inclined to: consider that the microangiopathic lesions are due to chronic injury of glomerular endothelial cells, exacerbated at: outbreaks of the disease. Increased production of IL 6 could support the efficacy of corticosteroid therapy, particularly in: acute clinical situations. [References: 21]

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Unique Identifier: 95367464

Authors: Perniciaro C.

Institution: Department of Dermatology, Mayo Clinic Jacksonville, FL 32224, USA.

Abstract: The principal features of POEMS syndrome are osteosclerotic bone lesions, peripheral sensorimotor neuropathy, and: elevated levels of a monoclonal protein in the serum or urine. Skin lesions are present in the majority of patients with: POEMS syndrome. Diffuse hyperpigmentation is the most common cutaneous finding. Hemangiomas with: histopathological features resembling renal glomeruli are the most specific skin lesions.

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Unique Identifier: 95234515

Authors: Cuellar ML. Garcia C. Molina JF.

Institution: Louisiana State University School of Medicine, Department of Medicine, New Orleans 70112, USA.

Abstract: The introduction of newer technology in the past few years, especially the use of second-generation enzyme-linked: immunosorbent assays, recombinant immunoblot assays, reverse transcriptase, and DNA amplification, have clearly: defined the role of hepatitis C virus as the most important etiologic factor in the development of mixed cryoglobulinemia.: This has led to a better understanding of the pathogenic mechanisms involved in disease expression, particularly vasculitis,: and also has provided a rationale for the use of interferon alfa and other antiviral drugs in the therapy of these disorders.: The clinical manifestations of the syndrome also have been well characterized, as well as some of the risk factors. There: also has been an improvement in our understanding of the pathogenic mechanisms involved in multiple myeloma and: related monoclonal gammopathies, as well as several attempts to improve early recognition of bone disease with magnetic: resonance imaging. The susceptibility gene for familial Mediterranean fever has been better characterized, as have risk: factors for colchicine toxicity. The role of cytokines has been better delineated for both monoclonal gammopathies and: POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome. [References: 66]

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Unique Identifier: 95213169

Authors: Pareyson D. Marazzi R. Confalonieri P. Mancardi GL. Schenone A. Sghirlanzoni A.

Institution: Istituto Nazionale Neurologico, C. Besta, IRCCS, Milano.

Abstract: We report six patients affected by POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal: gammopathy, and Skin changes), a peculiar multiorgan disease frequently associated with osteosclerotic myeloma or: other plasma cell disorders. Sensorimotor polyneuropathy was associated with multisystem involvement in all of the: patients, with osteosclerotic myeloma in 2 cases, monoclonal gammopathy of undetermined significance in 2 cases and: Castleman's disease in the final two. In all of the patients, sural nerve biopsy findings were consistent with a mixed, axonal: and demyelinating neuropathy. Increased levels of Interleukin-6 were found in two cases, but the pathogenesis of the: disease is far from established.

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Unique Identifier: 95115939

Authors: Navis GJ. Dullaart RP. Vellenga E. Elema JD. de Jong PE.

Institution: Department of Internal Medicine, State University Hospital, Groningen, The Netherlands.

Abstract: POEMS syndrome is a multisystem disorder associated with plasma cell dyscrasias. This report describes a patient with: POEMS-associated renal disease and reviews the literature on biopsy-proven renal involvement in POEMS syndrome.: Our patient had glomerulonephritis with membranoproliferative features on light-microscopy without characteristic: findings on immunofluorescence, and with ultrastructural evidence of glomerular microangiopathy. Ultrastructural evidence: of microangiopathy was also found in vasa nervorum. In 20 other cases of POEMS-associated renal disease, 16 had: glomerular disease. Light-microscopy showed membranoproliferative-like glomerulopathy in 14 patients and glomerular: microangiopathy in two. Ultrastructural evidence of microangiopathy was present in all 15 patients in whom: electron-microscopy was done. Thus, in most patients with POEMS-associated glomerular disease a characteristic: lesion is present with evidence of endothelial injury. As endothelial damage is also found in endoneural vessels,: generalized endothelial injury may play a role in non-renal manifestations of POEMS syndrome. In previous reviews: manifestations of the POEMS syndrome were similar for patients with or without myeloma. Among patients with: biopsy-proven glomerular disease, however, myeloma patients are underrepresented. Whether this represents a sampling: error or has true pathophysiological significance remains to be established. [References: 25]

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[Link Directly to Fulltext Article in OVID]

Unique Identifier: 95077020

Authors: Soubrier MJ. Dubost JJ. Sauvezie BJ.

Institution: Rheumatology Service, Hopital G. Montpied, Clermont-Ferrand, France.

Abstract: OBJECTIVE: To determine whether there are peculiarities of the POEMS syndrome (a multisystemic disorder: associated with polyneuropathy, organomegaly, endocrinopathy of various forms, production of a monoclonal [M]: component, and skin changes) in Caucasian patients, especially signs and symptoms absent in other series; and to attempt: a reappraisal of the neuropathy and endocrinopathy to find a unifying mechanism. DESIGN: A retrospective,: cooperative study compared 25 cases, observed over a 15-year period, with two published series of patients, one of: Japanese patients and one of American patients, and with a review of the literature on non-Asian cases. Details were: obtained of patients' medical history, physical examination, immunochemical and hormonal testing, roentgenographic: examination, computed tomography imaging, and electromyography. RESULTS: The main features of the syndrome: found in these patients were those first described in Japan: polyneuropathy, enlargement of the lymph nodes, liver, and: spleen, endocrine disturbances, low concentration of the monoclonal component, hyperpigmentation, and hypertrichosis.: Three other symptoms were found more frequently than previously reported: skin angiomas, scleroderma changes of the: hands, and thrombocytosis. Electromyography and nerve biopsy showed a variety of abnormalities ranging from: demyelination to axonal degeneration. Nerve deposits of immunoglobulin were absent. Organomegaly seemed to be: heterogeneous. Pathologic findings in the enlarged lymph nodes and spleen were compatible with Castleman's disease.: Liver biopsies were usually normal. The endocrine changes were surprisingly diverse, with some observations combining: unrelated primary and secondary insufficiencies. No single hypothesis emerged regarding their mechanism. All M: components had a lambda-light chain. An IgG M component was found more frequently in solitary lesions. An IgA M: component was found more frequently in patients without bone lesions. Sedimentation rate was usually normal.: Radiotherapy of solitary plasma-cytomas was followed by dramatic improvement of extramedullary signs and symptoms: in all cases. CONCLUSIONS: The symptoms, clinical course, and management of the patients reported here were: similar to those observed in the literature. This study confirms the existence of a close link between symptoms and: lambda-light-chain production. There are indications that a plasma cell growth factor that does not cross-react with: interleukin-6 (IL-6) may be involved. [References: 110]

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Unique Identifier: 94236514

Authors: Milanov I. Georgiev D.

Institution: University Hospital IV kilometer, III Neurological Clinic, Sofia, Bulgaria.

Abstract: A patient with a three year history of POEMS syndrome-polyneuropathy, hepatosplenomegaly M-protein, skin: changes, optic disc edema, peripheral oedema, pleuritis, lymphadenopathy, and osteosclerotic myeloma is described.: The patient had a twenty year history of psoriasis and impotence was the first sign of the disease. The pathophysiology of: this multisystem disorder is unknown, although the M-protein is essential. No improvement was found after radiation,: chemotherapy and steroid treatment.

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Unique Identifier: 94206026

Authors: Gherardi RK. Chouaib S. Malapert D. Belec L. Intrator L. Degos JD.

Institution: Departement de Pathologie (Maladies Neuro-Musculaires), Hopital Henri Mondor, Creteil, France.

Abstract: We studied tumor necrosis factor-alpha (TNF-alpha) levels in serial serum samples from 3 consecutive patients who had: a complete form of POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes) syndrome and: early weight loss. Serum TNF-alpha levels were compared with those of 10 patients with multiple myeloma (5) or: Waldenstrom's macroglobulinemia (5). Elevated serum levels of TNF-alpha were found in the patients with POEMS: syndrome (two- to eightfold increase in 10 of 11 samples) and not in those with other malignant plasma cell dyscrasias.: These results are in keeping with the hypothesis of a role for nonimmunoglobulinic mediators in the pathogenesis of the: POEMS syndrome, and are consistent with previous reports of TNF-alpha overproduction in inflammatory: demyelinating neuropathies and cachectic states.

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Unique Identifier: 92309266

Authors: Murphy N. Schumacher HR Jr.

Institution: Department of Medicine, University of Pennsylvania, School of Medicine, Philadelphia 19104.

Abstract: POEMS syndrome [plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal (M): protein, skin changes] although mimicking the connective tissue diseases in several ways has not been reported in a: patient who also meets criteria for the diagnosis of systemic lupus erythematosus (SLE). We describe a patient with: POEMS syndrome and SLE and review the similarities and differences between POEMS syndrome and other: connective tissue disorders.

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Unique Identifier: 92080367

Authors: Leung NW. Lam CW. Pang JC.

Institution: Department of Medicine, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin.

Abstract: A 40 year old Chinese woman presented with anasarca and later developed features of POEMS syndrome. These are: peripheral neuropathy (P), organomegaly (O), endocrine dysfunction (E), monoclonal gammopathy (M), and skin: changes (S) which are usually associated with plasma cell dyscrasia. In our patient, monoclonal gammopathy was not: detected on immunofixation electrophoresis and was revealed only after analysis of kappa/lambda light chain ratio of the: raised serum IgA immunoglobulin. Needle liver biopsy of her grossly enlarged liver showed marked accumulation of: glycogen and presence of giant mitochondria in the hepatocytes, a feature not previously reported.

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Unique Identifier: 92049959

Authors: Mizuiri S. Mitsuo K. Sakai K. Hayashi I. Suzuki T. Nagai Y. Ohara T. Hasegawa A. Kawamura S.

Institution: Department of Nephrology, Toho University School of Medicine, Tokyo, Japan.

Abstract: We describe a patient with POEMS syndrome whose renal biopsy specimen also showed nephropathy.: Immunoelectron microscopy of the renal biopsy revealed the localization of immunoglobulin (IgA and lambda light chain): in the subendothelial space of the glomerular capillaries, a previously unrecognized finding. We conclude that the renal: pathology in POEMS syndrome is unusual and distinct from microangiopathic glomerular involvement or idiopathic: mesangiocapillary glomerulonephritis.

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Unique Identifier: 92035805

Authors: Fukatsu A. Tamai H. Nishikawa K. Matsukawa W. Yoshida F. Matsuo S. Takeda A. Kodera K. Morozumi K. Ito Y.: et al.

Institution: 3rd Department of Internal Medicine, Nagoya University School of Medicine, Japan.

Abstract: We studied four cases of Crow-Fukase syndrome with renal dysfunction. Kidney specimens obtained by needle biopsy: showed glomerular lesions resembling those seen in conditions characterized by microangiopathy. Common glomerular: findings by light microscopy were mesangial expansion and narrowing of the capillary lumina. An enlarged subendothelial: space and mesangial area with deposition of amorphous material as well as swelling and vacuolization of endothelial cells: were observed by electron microscopy. In an active phase, severe mesangial edema and segmental mesangiolysis, and in: a late stage, mesangial cell interposition and sclerosis were seen. Tests by immunofluorescence microscopy for the: presence of immunoglobulins A, M, G, lambda and kappa light chains, C3, and C4 were negative. Decay accelerating: factor was found in glomeruli and in the vascular pole. Other findings included lymph node angiosclerosis, peripheral: nerve microangiopathy and hemangioma formation with endothelial cell proliferation. These observations suggest that: chronic endothelial injury constitutes the basic pathology of Crow-Fukase syndrome. Hemodialysis was required to: manage anasarca in three of the patients although serum creatinine levels were below 5.0 mg/dl. Urinalysis revealed mild: abnormalities and did not reflect the severity of the glomerular lesion. Corticosteroids given to three of the patients were: effective in controlling fever and the lymphadenopathy; in two cases the corticosteroids induced a recovery of renal: function. Thus Crow-Fukase syndrome may be due to chronic endothelial injury; the clinical symptoms and renal: involvement respond to corticosteroid therapy.