POEMS syndrome: update on diagnosis, risk-stratification, and management

DISEASE OVERVIEW: POEMS syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell disorder (PCD), sclerotic bone lesions, elevated vascular endothelial growth factor, and the presence of Castleman disease. Minor features include organomegaly, endocrinopathy, characteristic skin changes, papilledema, extravascular volume overload, and thrombocytosis. Diagnoses are often delayed because the syndrome is rare and can be mistaken for other neurologic disorders, most commonly chronic inflammatory demyelinating polyradiculoneuropathy. POEMS syndrome should be distinguished from the Castleman disease variant of POEMS syndrome, which has no clonal PCD and typically little to no peripheral neuropathy but has several of the minor diagnostic criteria for POEMS syndrome. DIAGNOSIS: The diagnosis of POEMS syndrome is made with 3 of the major criteria, two of which must include polyradiculoneuropathy and clonal plasma cell disorder, and at least one of the minor criteria. RISK STRATIFICATION: Because the pathogenesis of the syndrome is not well understood, risk stratification is limited to clinical phenotype rather than specific molecular markers. The number of clinical criteria is not prognostic, but the extent of the plasma cell disorder is. Those patients with an iliac crest bone marrow biopsy that does not reveal a plasma cell clone are candidates for local radiation therapy; those with a more extensive or disseminated clone will be candidates for systemic therapy. RISK-ADAPTED THERAPY: For those patients with a dominant sclerotic plasmacytoma, first line therapy is irradiation. Patients with diffuse sclerotic lesions or disseminated bone marrow involvement and for those who have progression of their disease 3 to 6 months after completing radiation therapy should receive systemic therapy. Corticosteroids are temporizing, but alkylators are the mainstay of treatment, either in the form of low dose conventional therapy or high dose with stem cell transplantation. The benefit of anti-VEGF antibodies is conflicting. Lenalidomide shows promise with manageable toxicity. Thalidomide and bortezomib also have activity, but their benefit needs to be weighed against their risk of exacerbating the peripheral neuropathy. Prompt recognition and institution of both supportive care measures and therapy directed against the plasma cell result in the best outcomes.     

POEMS syndrome: 2011 update on diagnosis, risk-stratification, and management

DISEASE OVERVIEW: POEMS syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell disorder (PCD), sclerotic bone lesions, elevated vascular endothelial growth factor, and the presence of Castleman disease. Minor features include organomegaly, endocrinopathy, characteristic skin changes, papilledema, extravascular volume overload, and thrombocytosis. Diagnoses are often delayed because the syndrome is rare and can be mistaken for other neurologic disorders, most commonly chronic inflammatory demyelinating polyradiculoneuropathy. POEMS syndrome should be distinguished from the Castleman disease variant of POEMS syndrome, which has no clonal PCD and typically little to no peripheral neuropathy but has several of the minor diagnostic criteria for POEMS syndrome. DIAGNOSIS: The diagnosis of POEMS syndrome is made with three of the major criteria, two of which must include polyradiculoneuropathy and clonal plasma cell disorder, and at least one of the minor criteria. RISK STRATIFICATION: Because the pathogenesis of the syndrome is not well understood, risk stratification is limited to clinical phenotype rather than specific molecular markers. The number of clinical criteria is not prognostic, but the extent of the plasma cell disorder is. Those patients with an iliac crest bone marrow biopsy that does not reveal a plasma cell clone are candidates for local radiation therapy; those with a more extensive or disseminated clone will be candidates for systemic therapy. RISK-ADAPTED THERAPY: For those patients with a dominant sclerotic plasmacytoma, first line therapy is irradiation. Patients with diffuse sclerotic lesions or disseminated bone marrow involvement and for those who have progression of their disease 3 to 6 months after completing radiation therapy should receive systemic therapy. Corticosteroids are temporizing, but alkylators are the mainstay of treatment, either in the form of low dose conventional therapy or high dose with stem cell transplantation. The benefit of anti-VEGF antibodies is conflicting. Lenalidomide shows promise with manageable toxicity. Thalidomide and bortezomib also have activity, but their benefit needs to be weighed against their risk of exacerbating the peripheral neuropathy. Prompt recognition and institution of both supportive care measures and therapy directed against the plasma cell result in the best outcomes.     

POEMS syndrome: 2014 Update on diagnosis,risk‐stratification,and management

Disease overview: POEMS syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell disorder (PCD), sclerotic bone lesions, elevated vascular endothelial growth factor, and the presence of Castleman disease. Minor features include organomegaly, endocrinopathy, characteristic skin changes, papilledema, extravascular volume overload, and thrombocytosis. Diagnoses are often delayed because the syndrome is rare and can be mistaken for other neurologic disorders, most commonly chronic inflammatory demyelinating polyradiculoneuropathy. POEMS syndrome should be distinguished from the Castleman disease variant of POEMS syndrome, which has no clonal PCD and typically little to no peripheral neuropathy but has several of the minor diagnostic criteria for POEMS syndrome. Diagnosis: The diagnosis of POEMS syndrome is made with three of the major criteria, two of which must include polyradiculoneuropathy and clonal PCD, and at least one of the minor criteria. Risk stratification: Because the pathogenesis of the syndrome is not well understood, risk stratification is limited to clinical phenotype rather than specific molecular markers. The number of clinical criteria is not prognostic, but the extent of the PCD is. Those patients with an iliac crest bone marrow biopsy that does not reveal a plasma cell clone are candidates for local radiation therapy; those with a more extensive or disseminated clone will be candidates for systemic therapy. Risk‐adapted therapy: For those patients with a dominant sclerotic plasmacytoma, first line therapy is irradiation. Patients with diffuse sclerotic lesions or disseminated bone marrow involvement and for those who have progression of their disease 3–6 months after completing radiation therapy should receive systemic therapy. Corticosteroids are temporizing, but alkylators are the mainstay of treatment, either in the form of low dose conventional therapy or high dose with stem cell transplantation. The benefit of anti‐VEGF antibodies is conflicting. Lenalidomide shows promise with manageable toxicity. Thalidomide and bortezomib also have activity, but their benefit needs to be weighed against their risk of exacerbating the peripheral neuropathy. Prompt recognition and institution of both supportive care measures and therapy directed against the plasma cell result in the best outcomes. Am. J. Hematol. 89:214–223, 2014. © 2014 Wiley Periodicals, Inc.     

POEMS syndrome: Update on diagnosis,risk‐stratification,and management

Disease overview: POEMS syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell disorder (PCD), sclerotic bone lesions, elevated vascular endothelial growth factor, and the presence of Castleman disease. Minor features include organomegaly, endocrinopathy, characteristic skin changes, papilledema, extravascular volume overload, and thrombocytosis. Diagnoses are often delayed because the syndrome is rare and can be mistaken for other neurologic disorders, most commonly chronic inflammatory demyelinating polyradiculoneuropathy. POEMS syndrome should be distinguished from the Castleman disease variant of POEMS syndrome, which has no clonal PCD and typically little to no peripheral neuropathy but has several of the minor diagnostic criteria for POEMS syndrome. Diagnosis: The diagnosis of POEMS syndrome is made with three of the major criteria, two of which must include polyradiculoneuropathy and clonal plasma cell disorder, and at least one of the minor criteria. Risk stratification: Because the pathogenesis of the syndrome is not well understood, risk stratification is limited to clinical phenotype rather than specific molecular markers. The number of clinical criteria is not prognostic, but the extent of the plasma cell disorder is. Those patients with an iliac crest bone marrow biopsy that does not reveal a plasma cell clone are candidates for local radiation therapy; those with a more extensive or disseminated clone will be candidates for systemic therapy. Risk‐adapted therapy: For those patients with a dominant sclerotic plasmacytoma, first line therapy is irradiation. Patients with diffuse sclerotic lesions or disseminated bone marrow involvement and for those who have progression of their disease 3–6 months after completing radiation therapy should receive systemic therapy. Corticosteroids are temporizing, but alkylators are the mainstay of treatment, either in the form of low dose conventional therapy or high dose with stem cell transplantation. Lenalidomide shows promise with manageable toxicity. Thalidomide and bortezomib also have activity, but their benefit needs to be weighed against their risk of exacerbating the peripheral neuropathy. The benefit of anti‐VEGF antibodies is conflicting. Prompt recognition and institution of both supportive care measures and therapy directed against the plasma cell result in the best outcomes. Am. J. Hematol. 90:951–962, 2015. © 2015 Wiley Periodicals, Inc.     

How I treat POEMS syndrome

POEMS syndrome is a paraneoplastic syndrome whose acronym stands for less than half of the defining features of the disease, that is, polyradiculoneuropathy, organomegaly, potentially including coexisting Castleman disease, endocrinopathy, monoclonal plasma cell neoplasm, and skin changes. The other important features include papilledema, extravascular volume overload, sclerotic bone lesions, thrombocytosis, elevated VEGF, and abnormal pulmonary function. The diagnosis is based on having both the polyradiculoneuropathy and the monoclonal plasma cell disorder, and at least 1 of the other 3 major criteria (Castleman disease, sclerotic bone lesions, or elevated VEGF) and at least one minor criterion. The diagnosis is often delayed with intervening incorrect diagnoses of chronic inflammatory demyelinating polyradiculoneuropathy, myeloproliferative disorder, and monoclonal gammopathy of undetermined significance. Prompt treatment directed at the underlying plasma cell clone produces dramatic responses in the majority of patients. Although there are no randomized clinical trial data to direct best therapy, for patients with disseminated disease, high-dose chemotherapy with peripheral blood transplantation has yielded durable benefit, whereas radiation therapy is typically effective for patients with a more localized presentation. More universal recognition of and more scientific inquiry into the underpinnings of the disease will provide direction toward the best treatment strategies in the future.     

POEMS syndrome: A multisystem clonal disorder

Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome is a rare condition defined by monoclonal plasma cell disorder, peripheral neuropathy, and other systemic symptoms. The pathophysiology of POEMS syndrome is unknown, but the overproduction of vascular endothelial growth factor (VEGF) appears to be an important contributory element. The diagnosis of POEMS syndrome requires the presence of both mandatory criteria (ie, polyneuropathy and a monoclonal plasma cell disorder), at least one major criterion (ie, osteosclerotic bone lesions, Castleman disease, or elevated serum or plasma levels of vascular endothelial growth factor), and at least one of the six minor criteria. POEMS syndrome lacks a standard treatment, but patients with limited sclerotic bone lesions are typically treated with radiation therapy. In contrast, those with widespread lesions receive chemotherapy and hematopoietic stem cell transplantation.     

POEMS syndrome

POEMS syndrome is a rare paraneoplastic syndrome secondary to a plasma cell dyscrasia. Recognition of the complex of a combination of peripheral neuropathy, organomegaly, endocrinopathy, monoclonal plasmaproliferative disorder, skin changes, papilledema, extravascular volume overload (peripheral edema, pleural effusions, ascites), sclerotic bone lesions, thrombocytosis, Castleman disease is the first step in effectively managing the disease. A rise in the blood levels of vascular endothelial growth factor is usually confirmatory. More than 95% of patients will have monoclonal lambda sclerotic plasmacytoma(s) or bone marrow infiltration. In patients with a dominant sclerotic plasmacytoma, first line therapy should include radiation to the lesion. Retrospective analysis and personal experience would dictate that systemic therapy be considered for patients with diffuse sclerotic lesions or absence of any bone lesion and for those who have not demonstrated stabilization of their disease 3 to 6 months after completing radiation therapy. For those patients with diffuse disease, systemic therapy is indicated. Useful approaches include therapy with corticosteroids, low dose alkylator therapy, and high dose chemotherapy with peripheral blood stem cell transplant. Until the pathogenesis is fully understood, these are the mainstays of treatment for patients with POEMS syndrome. The role of anti-VEGF therapies, immune modulatory drugs, and proteasome inhibitors has not yet been defined, but drugs with known high rates of treatment related neuropathy should not be considered as first line therapy.     

A case of atypical POEMS syndrome without polyneuropathy

POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, Skin changes) syndrome is a rare hematological disease associated with overproduction of pro-inflammatory cytokines. Under the current nomenclature and diagnostic criteria for POEMS syndrome, the presence of characteristic polyneuropathy is required for diagnosis. We report a 43-year-old Japanese woman with organomegaly, endocrinopathy, M-protein, skin lesions, as well as typical renal lesions and sclerotic bone lesions. Of note, neurological examinations and peripheral nerve conduction tests were normal in this patient. In view of the overwhelming number of otherwise characteristic signs and symptoms, we made a provisional diagnosis of 'atypical POEMS syndrome without polyneuropathy'. If further similar cases are reported in the future, reconsideration of the nomenclature and/or diagnostic criteria for POEMS syndrome may be required.     

Peripheral blood stem cell transplantation in 16 patients with POEMS syndrome, and a review of the literature

POEMS syndrome is characterized by peripheral neuropathy (PN), a clonal plasma cell disorder (PCD), organomegaly, endocrinopathy, skin changes, edema, sclerotic bone lesions, and thrombocytosis. Based on the improved response rates observed with peripheral blood stem cell transplantation (PBSCT) in patients with other PCDs, autologous PBSCT may be an attractive treatment option for this syndrome. Sixteen patients with POEMS syndrome have undergone PBSCT at Mayo. Of these patients, 15 had a severe rapidly progressive sensorimotor PN (9 were wheelchair dependent) and 14 were male. Median age was 51 years (range, 19-62 years). The median number of prior therapies was 3 (range, 0-7). From first symptoms and from diagnosis of POEMS the times to transplantation were 42 months and 5 months (ranges, 8-185 months and 2-149 months), respectively. There were 15 patients who had significantly abnormal pretransplant pulmonary function tests. There was one transplant-related death. During the peritransplant period, 5 patients required intubation for respiratory compromise, including one who required intubation during his stem cell mobilization period. Another patient required noninvasive biphasic positive airway pressure throughout his course. Of the 14 evaluable patients, all have had neurologic improvement or stabilization. Other features have improved substantially. PBSCT for POEMS syndrome is effective therapy but may also be associated with significant morbidity.     

46-year-old patient with polyneuropathy, hepatosplenomegaly, endocrinopathy, M-gradient, skin manifestations, sclerotic bone changes and therapy refractory ascites]

The POEMS syndrome is a rare multisystemic disorder with polyneuropathy, organomegaly, endocrinopathy of various forms, production of monoclonal (M) component, and skin changes. We describe a 46-year-old man who developed ascites one year after the onset of peripheral neuropathy with accompanying muscle atrophies and increasing weakness. Extensive evaluation revealed that the patient had no underlying liver disease, malignancy, infection, or cardiac or renal disease. The ascites initially responded to high-dose corticosteroid therapy. The patient had many clinical features of the described POEMS syndrome including sclerotic bone lesions, a persistent lambda-paraprotein and refractory ascites. In this case ascites was a main presenting feature. Thus, the POEMS syndrome must be added to the list of rare causes of refractory ascites.     

High-dose therapy and autologous blood stem cell transplantation in POEMS syndrome

We treated 5 patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome and multifocal bone lesions or diffuse bone marrow plasmacytic infiltration with high-dose therapy (HDT) and autologous blood stem cell transplantation. In all cases, the treatment produced remission of plasma cell proliferation associated with marked improvement in the patients' performance status, neurologic symptoms, and other manifestations of the syndrome. HDT with stem cell support should be investigated further as a therapeutic option in patients with POEMS syndrome and disseminated plasma cell dyscrasia.     

Moyamoya Disease-like Cerebrovascular Stenotic Lesions Are an Important Phenotype of POEMS Syndrome-associated Vasculopathy

A 41-year-old woman was diagnosed with polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome based on polyneuropathy, hepatosplenomegaly, sclerotic bone lesions, IgA-λ M-protein, and an elevated level of serum vascular endothelial growth factor. One month after the initiation of lenalidomide-dexamethasone with prophylactic aspirin, she developed facial paralysis, dysarthria, and left hemiplegia. Multiple cerebral infarctions and internal carotid artery stenosis were detected. Five months after switching to pomalidomide-dexamethasone, she again developed cerebral infarction. Progressed stenotic lesions in the bilateral internal carotid artery terminal portions were detected, showing a moyamoya disease-like appearance. Quasi-moyamoya disease can be an important phenotype of systemic vasculopathies of POEMS syndrome.     

POEMS syndrome: failure of newly suggested diagnostic criteria to anticipate the development of the syndrome

POEMS syndrome is a unique clinical entity. Although it's a diagnosis of exclusion, it was previously described by the presence of several typical characteristics as paraproteinemia, polyneuropathy, organomegaly, endocrinopathy, and skin changes. Recently, new criteria were proposed, and the presence of two major and one minor criterion was claimed to suffice for a diagnosis. Both methods considered other important characteristics germane to the syndrome unessential for diagnosis. Retrospective evaluation of patients with lymphoproliferative disease was carried out to reveal the presence of the syndrome according to these different methods. Patients' clinical progression during follow-up will be used to validate the criteria's sensitivity and specificity. Six hundred twenty-nine consecutive files of patients with paraproteinemia who were followed-up at a tertiary medical center were reviewed. Of 12 patients who fulfilled the new criteria for diagnosis of POEMS, 3 remain stable during long-term follow-up and only 5 finally developed the full-blown syndrome. Four patients developed other diseases that accounted for their clinical findings. Patients presenting with neuronal vasculitic changes on biopsy, kappa light-chain monoclonal gammopathy, and cryoglobulinemia were unlikely to develop POEMS syndrome, even though they fulfilled the newly suggested criteria. Although they are not in the criteria, sclerotic bone lesions were found only in patients who eventually developed the full syndrome. The diagnosis of POEMS syndrome according to the newly suggested criteria should not be definitive in the presence of atypical clinical features of the syndrome.     

Peripheral blood stem cell transplant for POEMS syndrome is associated with high rates of engraftment syndrome

Polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes (POEMS) syndrome is a devastating syndrome, characterized by peripheral neuropathy, organomegaly, endocrinopathy, monoclonal plasma cells, skin changes, papilledema, volume overload, sclerotic bone lesions, thrombocytosis and high vascular endothelial growth factor (VEGF). High-dose chemotherapy with autologous peripheral blood stem cell transplantation (ASCT) ultimately yields excellent clinical responses, but there can be considerable peritransplant morbidity. We have treated 30 POEMS patients with ASCT at Mayo Clinic, Rochester. During transplant period, patients had high rates of fever, diarrhea, weight gain and rash (93%, 77%, 53% and 43%, respectively). Only 13% remained outpatient, and median time to discharge from hospital was transplant day 17 (range 0-175). Splenomegaly was the baseline factor that best predicted for a complicated peritransplant course. Depending on the definition used, approximately 50% of patients satisfied criteria for engraftment syndrome. Earlier and more aggressive use of corticosteroids may be associated with less complicated post-transplant courses. Median overall survival has not been reached; the treatment-related mortality was 3%. In addition, important clinical improvements and reductions in plasma VEGF levels can occur in the absence of significant decrease in the monoclonal protein. Unraveling the mechanisms of the syndrome both in the context of ASCT and in general are challenges for the future.     

Dramatic improvement of POEMS syndrome following autologous haematopoietic cell transplantation

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, serum monoclonal protein and skin changes) is a rare plasma cell disorder of unknown pathogenesis and is diagnosed by the demonstration of a plasma cell proliferation at the biopsy of an osteoesclerotic lesion. When the lesions are in a limited area, radiation therapy is usually highly effective. Patients with disseminated disease require systemic chemotherapy, which is not effective in most cases. A patient with severe widespread POEMS syndrome resistant to melphalan who experienced a dramatic improvement after high-dose melphalan followed by autologous haematopoietic cell transplantation (AHCT) is reported. We believe that this is the first reported case of POEMS syndrome treated with AHCT, a procedure that could be considered in similarly affected patients.     

POEMS syndrome in systemic lupus erythematosus.

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.     

POEMS syndrome: definitions and long-term outcome

The POEMS syndrome (coined to refer to polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) remains poorly understood. Ambiguity exists over the features necessary to establish the diagnosis, treatment efficacy, and prognosis. We identified 99 patients with POEMS syndrome. Minimal criteria were a sensorimotor peripheral neuropathy and evidence of a monoclonal plasmaproliferative disorder. To distinguish POEMS from neuropathy associated with monoclonal gammopathy of undetermined significance, additional criteria were included: a bone lesion, Castleman disease, organomegaly (or lymphadenopathy), endocrinopathy, edema (peripheral edema, ascites, or effusions), and skin changes. The median age at presentation was 51 years; 63% were men. Median survival was 165 months. With the exception of fingernail clubbing (P =.03) and extravascular volume overload (P =.04), no presenting feature, including the number of presenting features, was predictive of survival. Response to therapy (P <.001) was predictive of survival. Pulmonary hypertension, renal failure, thrombotic events, and congestive heart failure were observed and appear to be part of the syndrome. In 18 patients (18%), new disease manifestations developed over time. More than 50% of patients had a response to radiation, and 22% to 50% had responses to prednisone and a combination of melphalan and prednisone, respectively. We conclude that the median survival of patients with POEMS syndrome is 165 months, independent of the number of syndrome features, bone lesions, or plasma cells at diagnosis. Additional features of the syndrome often develop, but the complications of classic multiple myeloma rarely develop.     

Successful Treatment of a Patient with POEMS Syndrome by Tandem High-Dose Chemotherapy with Autologous CD34+ Purged Stem Cell Rescue

A 36-year-old man was admitted because of numbness and muscle weakness in the lower extremities. He had gait disturbance, malaise, and body weight loss. Based on the existence of monoclonal gammopathy, the proliferation of abnormal plasma cells in the bone marrow, the presence of sclerotic bone lesion, polycythemia, mild splenomegaly, and an elevated level of serum vascular endothelial growth factor (VEGF) (14,900 pg/mL; normal, 62-707), he was diagnosed as having peripheral neuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. Following 2 courses of conventional chemotherapy with doxorubicin and dexamethasone, peripheral blood stem cells were mobilized by high-dose etoposide (500 mg/m(2) x 3 days) and granulocyte colony-stimulating factor. After purging by CD34+ selection using the CliniMACS device, the selected cells (12.4 x 10(6)/kg) were cryopreserved. He was then treated with tandem high-dose chemotherapy (HDC) (melphalan 100 mg/m(2) x 2 days) with autologous stem cell rescue. After the first course of HDC, the serum level of VEGF normalized and the minimal residual disease in the bone marrow was reduced below the detection limit of CDR3 analysis by polymerase chain reaction. The patient has been in remission for more than 20 months. He has gradually recovered from the neurological symptoms and now has no impairments of daily living. Our experience suggests that autologous purged stem cell transplantation should be considered as the treatment of choice for POEMS syndrome.     

Development of POEMS syndrome after an initial manifestation of solitary plasmacytoma

A 44-year-old male was admitted for numbness in the left arm. CT showed a tumor impacting on the spinal cord with an adjacent thoracic vertebral osteosclerotic lesion. The histopathology of the tumor showed diffuse proliferation of atypical plasma cells with expressed vascular endothelial growth factor (VEGF), which is a known etiological factor in POEMS syndrome. Though serum VEGF (sVEGF) level was elevated, a diagnosis of solitary plasmacytoma with an osteosclerotic lesion was made as the patient presented no polyneuropathy, organomegaly, endocrinopathy, or skin changes. The patient experienced muscle weakness of the lower limbs and skin pigmentation/hemangioma one year after irradiation of the osteosclerotic lesion. Laboratory tests revealed hypothyroidism, hyperglycemia, serum monoclonal gammopathy, further elevation of sVEGF, and increased atypical bone marrow plasma cells. CT imaging showed splenomegaly, and a nerve conduction test revealed demyelinating motor peripheral neuropathy. The patient was therefore diagnosed with POEMS syndrome. Plasmacytoma is very rare as an initial manifestation of POEMS syndrome. Patients presenting with plasmacytoma with an osteosclerotic lesion should be carefully observed and evaluated for the expression of sVEGF and development of POEMS syndrome, as most bone plasmacytomas in POEMS syndrome patients are reported to be osteosclerotic. This is to our knowledge the first case of osteosclerotic plasmacytoma that progressed to POEMS syndrome, with an increase of sVEGF.     

Clinical Manifestation of POEMS Syndrome with Features of Connective Tissue Disease

The POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes) syndrome is a rare plasma cell disease with multiorgan involvement and varying clinical manifestations. We report a 38-year-old man who presented with scleroderma-like skin changes of the hands and feet, sicca and Raynaud’s syndrome, pleural effusions, glomerulopathy, polyneuropathy, hepatosplenomegaly and lymphadenopathy. Steroid treatment was started on the assumption of a connective tissue disease and led to a temporary improvement. During the further course of the disease, hypothyreosis, monoclonal gammopathy and osteosclerotic bone lesions were detected, leading to the diagnosis of POEMS syndrome. This case emphasises the need to consider POEMS syndrome as a differential diagnosis in patients with signs of connective tissue disease and polyneuropathy. Received: 21 February 2000 / Accepted: 6 September 2000