Clinical characteristics and long-term outcome of patients with POEMS syndrome in China

POEMS syndrome is a rare plasma cell dyscrasia characterized by polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes. This study reviewed the clinical characteristics and long-term outcome of 99 consecutive Chinese patients with newly diagnosed POEMS syndrome in a single institute. The median age of 99 patients was 45 years, and the ratio of men/women was 1.4. The median time from onset of symptoms to diagnosis was 18 months. The typical five features of peripheral neuropathy, organomegaly, endocrinopathy, M protein, and skin change remained to be essential for patients with POEMS syndrome in China. The unusual features like pulmonary hypertension (36%) and renal impairment (37%) were not uncommon in China. Eighty-three percent patients were alive after follow-up time of 25 months, and 10% patients had survived more than 60 months. Melphalan-based therapy (OR, 0.076; 95% CI, 0.02–0.285) and normal renal function (OR, 0.246; 95% CI, 0.076–0.802) were independent prognostic factors for the survival of patients with POEMS syndrome. In conclusion, POEMS syndrome in Chinese patients was a multi-systemic disease with clinical features similar to non-Chinese ones. Active therapy can effectively improve the prognosis of patients with POEMS syndrome.     

POEMS syndrome. Study of a patient with proteinuria, microangiopathic glomerulopathy, and renal enlargement

We studied a patient with POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal [M]-protein, skin changes) who was also found to have renal enlargement and microangiopathic glomerulopathy. The latter finding is unusual in POEMS syndrome patients, and the associated symptoms can lead to confusion in diagnosis. We emphasize the importance of considering POEMS syndrome in the differential diagnosis of patients who have unexplained neuropathy, scleroderma-like skin changes, and/or monoclonal gammopathy.     

POEMS syndrome, osteosclerotic myeloma and Castleman's disease: a case report

Abstract Peripheral neuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes are often the presenting features of the POEMS syndrome. Approximately 50% of these are associated with osteosclerotic myeloma, a rare variant of multiple myeloma and some with Castlemanapos;s disease, an unusual lympho-proliferative disorder. The underlying pathogenetic mechanisms have not been elucidated but amelioration of symptoms with the disappearance of the M-component suggests possible etiopathogenic mechanisms. We present a 40-year-old woman with manifestations of all three disorders. (Aust NZ J Med 1991; 21:454–456.).     

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.     

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.     

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.     

POEMS综合征5例临床分析

背景：POEMS综合征是一组以多发性周围神经病为突出表现的临床症候群。该病少见且临床表现复杂、无特异性，极易漏诊或误诊。目的：总结POEMS综合征的临床特点，提高对该病的认识。方法：回顾性分析上海仁济医院2001年5月-2007年5月5例确诊的POEMS综合征患者的临床表现、实验室检查结果、治疗方案和预后情况。结果：5例POEMS综合征患者的主要临床表现发生率分别为周围神经病变、内分泌异常和皮肤改变100％．脏器肿大80％，M蛋白阳性60％。经激素或免疫抑制剂治疗，出院时4例患者好转，1例恶化，但至随访结束时仅1例维持好转。结论：POEMS综合征临床表现复杂。随着其诊断和治疗的进展，患者预后将明显改善。     

Calciphylaxis in a patient with POEMS syndrome without renal failure and/or hyperparathyroidism. A case report

POEMS (Crow-Fukase) syndrome is a rare plasma cell lymphoproliferative disorder associated with polyneuropathy (P), organomegaly (O), endocrinopathy (E), monoclonal (M) gammopathy and skin (S) abnormalities. The latter are usually not specific and include hyperpigmentation, hypertrichosis, cutaneous angioma and skin-thickening. A 45-year-old Italian woman was admitted to hospital because of muscle weakness, marked fatigue and paresthesia of the upper and lower extremities. Two and a half years earlier, a POEMS syndrome had been diagnosed on the basis of a history of organomegaly and mild lymphadenopathy, IgA-lambda monoclonal gammopathy, hypothyroidism, severe lower and upper limb sensory-motor peripheral neuropathy and a single osteosclerotic lesion in the left humerus. Eight weeks later, she developed skin lesions bioptically shown to be due to calciphylaxis-induced cutaneous vasculitis. To our knowledge, this is the first case of POEMS syndrome with this peculiar type of vasculitis. The absence of predisposing conditions, namely renal failure, hyperparathyroidism or clotting disorders renders the pathogenetic mechanism(s) of this severe type of vasculitis more intriguing.     

POEMS (polyneuropathy,organomegaly, endocrinopathy,M‐protein and skin changes) syndrome in China

Background/Aim: The clinical characteristics of POEMS (polyneuropathy, organomegaly, endocrinopathy, M‐protein and skin changes) syndrome in China are largely unknown. This work thus studied the clinical manifestations of POEMS syndrome in China. Methods: We retrospectively reviewed the medical records of 82 patients with POEMS syndrome in our hospital and made a comparison with those reported outside China. Results: There were 82 patients. Forty (49%) were 45 years old or younger. Sensorimotor deficits were the common initial symptoms. The clinical manifestations are as follows: (i) peripheral neuropathy and abnormal electromyogram were seen in all patients (100%); (ii) organomegaly was present in 72 patients (88%); 61 of them (74%) had splenomegaly; (iii) endocrinopathy was present in 74 cases (90%); hypothyroidism was seen in 51 of 70 patients (73%); (iv) 60 patients (73%) had monoclonal plasmaproliferative disorder; only 22 of 40 (55%) had M‐protein; (v) skin changes were seen in 71 patients (87%); (vi) 68 patients (83%) had oedema and effusions; of these, hydropericardium was seen in 23 patients (28%); (vii) 35 of 55 patients (64%) had abnormal electrocardiogram and only 21 of 46 (46%) had bone lesions in X‐ray. Conclusions: POEMS syndrome in China has its own distinctive features, parts of which are commoner in the young people, the higher frequency of splenomegaly, hypothyroidism, hydropericardium and abnormal electrocardiogram, as well as the lower M‐protein and bone lesions in X‐ray.     

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.     

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.     

Solitary plasmacytoma of the skull revealed by a mononeuritis multiplex associated with immune complex vasculitis

We describe a patient with solitary plasmacytoma of the skull, in whom mononeuritis multiplex was the presenting manifestation. Some features of the POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal [M] protein, skin changes), including thrombocytosis, were found. Muscle and nerve biopsies disclosed a small vessel hypersensitivity-type vasculitis and complement-fixing immune complex deposits in vessel walls. Removal of the plasmacytoma resulted in clinical improvement and clearance of the vasculitis and immune complex deposits.     

POEM syndrome

This article summarizes the clinical, radiological and laboratory features of syndrome, which is known by the acronym "POEMS". POEMS syndrome is a rare multisystemic syndrome with plasma cell dyscrasia. POEMS is characterized by the combination of polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes. Other signs are frequently observed in affected patients, such as peripheral edema, arteriopathy, nephropathy, thrombocytosis and osteosclerotic lesions. The plasma cell dyscrasia in POEMS syndrome differs from the dyscrasia found in multiple myeloma. It has been suggested that pleiotropic cytokines which act in synergy on immune, nervous, endocrine and vascular systems could play a pathogenic role in POEMS syndrome.     

Pulmonary manifestations of POEMS syndrome: case report and literature review.

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.     

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.     

Pachymeningeal involvement in POEMS syndrome: dramatic cerebral MRI improvement after lenalidomide therapy

POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome is a rare multisystemic disease associated with plasma cell dyscrasia and increased serum or plasma vascular endothelial growth factor (VEGF) levels, the latter likely responsible for several POEMS syndrome manifestations. Whereas peripheral neuropathy is the main neurological feature and a mandatory diagnostic criterium, central nervous system involvement is less common except for papilledema and stroke. We recently reported the frequent occurrence at brain MRI of cranial pachymeningeal involvement ina series of POEMS syndrome patients. Meningeal histopathology revealed hyperplasia of meningothelial cells, neovascularization, and obstructive vessel remodeling without inflammatory signs pointing to a role of VEGF in the meningeal manifestations. Here, we report the dramatic pachymeningeal improvement in patients undergoing lenalidomide therapy. These findings support the therapeutic role of lenalidomide and might shed further light on the pathophysiology of the disease     

Multiple angiogenetic factors are upregulated in POEMS syndrome

Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is a multisystem disorder associated with plasma cell dyscrasia. Elevated serum levels of vascular endothelial growth factor (VEGF), which strongly promotes neovascularization and vasopermeability, are considered to be responsible for the characteristic symptoms such as angiomata, pleural effusion/ascites, edema, and organomegaly in the disorder. To study whether other angiogenetic factors are upregulated in POEMS syndrome, we measured serum levels of basic fibroblast growth factor and hepatocyte growth factor (HGF), as well as VEGF, in 17 patients with POEMS syndrome. All these factors were significantly upregulated in the POEMS syndrome patients. After the treatment with anti-VEGF antibody, the levels of HGF did not change, suggesting that elevation of HGF levels is not secondary to VEGF overproduction. These results suggest that different angiogenetic factors might contribute to the pathogenesis of POEMS syndrome, and this fact might contribute to the insufficient clinical effects obtained by suppression of VEGF alone.     

Pulmonary manifestations in patients with POEMS syndrome: a retrospective review of 137 patients

BACKGROUND: POEMS syndrome is a monoclonal plasma cell disorder characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes. Rare reports of pulmonary manifestations of POEMS syndrome such as pulmonary hypertension exist; however, a comprehensive review of the pulmonary manifestations of POEMS syndrome is lacking. METHODS: Retrospective review of patients with a diagnosis of POEMS syndrome at our institution between 1975 and 2003. Demographics, signs and symptoms, test findings (ie, radiographs, pulmonary function tests, and echocardiography), and survival data were extracted. Kaplan-Meier survival analysis was performed. In addition, categoric variables were compared using the Pearson chi(2) test or Fisher exact test, where appropriate. RESULTS: The study comprised 137 patients (66% male) with a mean age of 51.6 years. Respiratory symptoms were common within 2 years of diagnosis (28%). The median overall survival time was 147 months. Pulmonary manifestations of POEMS syndrome included pulmonary hypertension, restrictive lung disease, respiratory muscle weakness, and an isolated diminished diffusing capacity. Significant radiographic findings such as pleural effusions, diaphragm elevation, and increased cardiac silhouette were seen in 23% of patients. When separated by the presence or absence of respiratory muscle weakness, the median survival time was 87 vs 139 months, respectively (p < 0.05). The presence of cough was associated with reduced survival time. CONCLUSIONS: Pulmonary manifestations of POEMS are common, and both symptomatic and asymptomatic respiratory involvements are frequent on presentation in patients with POEMS syndrome. Respiratory muscle weakness and cough portend a poorer prognosis. These results suggest the need for increased awareness of the association between POEMS syndrome and pulmonary disease to guide appropriate screening and supportive therapy.