Pathogenesis Of POEMS Syndrome Research Articles

Diagnosis and management of POEMS syndrome

POEMS syndrome is a plasma cell neoplasm that presents with peripheral neuropathy, organomegaly, fluid retention, skin manifestations, osteosclerotic lesions, and λ-type M-proteinemia. The pathogenesis of POEMS syndrome is poorly understood, as the genetic profile of plasma cells in POEMS syndrome differs from that of myeloma. In most cases, POEMS syndrome is difficult to distinguish from chronic inflammatory demyelinating polyneuropathy (CIDP). Consequently, it is essential not to miss characteristic signs of POEMS syndrome such as M-protein, VEGF, pleural effusion, and osteosclerotic lesions. Novel agents for myeloma, such as thalidomide, lenalidomide, and bortezomib, are effective. For younger patients, these agents followed by autologous transplantation with high-dose melphalan is the standard of care. More relapses are now being reported in results of long-term observation, and treatment strategies for relapsed disease must be established.

Alterations in choroidal vascular structures due to serum levels of vascular endothelial growth factor in patients with POEMS syndrome

A higher serum vascular endothelial growth factor (VEGF) level can cause choroidal thickening in the choroid of patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. We aimed to determine whether fluctuations in serum VEGF levels affect choroidal vascular structures in patients with POEMS syndrome. This retrospective observational case series examined 17 left eyes of 17 patients with POEMS syndrome. Enhanced depth imaging optical coherence tomography (EDI-OCT) images were obtained, and serum VEGF levels were measured at baseline and 6 months after transplantation with dexamethasone (n = 6), thalidomide (n = 8), or lenalidomide (n = 3). EDI-OCT images were binarized using ImageJ software, and we calculated the areas of the whole choroid and the luminal and stromal areas. Subsequently, we determined whether the choroidal vascular structure had changed significantly between baseline and 6 months after treatment. Six months after treatment, serum VEGF levels and the whole choroid, luminal, and stromal areas had decreased significantly compared to the baseline values (all, P < 0.001). The mean luminal area to the whole choroidal area ratio at 6 months after treatment was 0.70 ± 0.03, which was significantly smaller than the ratio at baseline (0.72 ± 0.03; P < 0.001). Whole choroid and luminal area fluctuations were significantly positively correlated with fluctuations in serum VEGF levels (r = 0.626, P = 0.007 and r = 0.585, P = 0.014, respectively). Choroidal thickening induced by VEGF might be caused by increases in the choroidal vessel lumen area. These results may offer insights into the pathogenesis of POEMS syndrome and the role of serum VEGF in choroidal vascular structure, which may apply to other ocular diseases.

Update on the POEMS syndrome.

POEMS syndrome is an acronym for polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes. It is a rare paraneoplastic disorder related to plasma cell neoplasm. However, its pathophysiology has not yet been clearly elucidated. The production of pro-inflammatory cytokines is thought to play an important role in the pathogenesis of POEMS syndrome. Vascular endothelial growth factor level reflects disease activity, which is helpful for the diagnosis and evaluation of treatment response. Conventional agents such as corticosteroids and melphalan are effective and safe combination regimens. Autologous hematopoietic stem cell transplantation is another option for high-risk transplant-eligible patients. Radiotherapy is effective in patients with localized lesions. The anti-myeloma agents lenalidomide, thalidomide, and bortezomib have shown good treatment outcomes for POEMS syndrome; however, large-scale studies with long-term follow-up are required. Early identification and active treatment can improve the outcomes of POEMS syndrome patients.

Lenalidomide Treatment for a POEMS Syndrome Patient with Massive Pericardial Effusion as the First Manifestation

To show the successful handle of a very rare complication of POEMS syndrome. We report a case of POEMS syndrome wherein the first symptom was recurrent massive pericardial effusions. The patient was misdiagnosed as having tuberculous pericarditis and received anti-tuberculosis treatment for nearly 20 months without effect. She suffered painful pericardiocentesis every 2 to 3 months until the POEMS syndrome diagnosis was confirmed when she appeared with polyneuropathy combined with cervical lymph node biopsy, indicating Castleman disease, serum monoclonal immunoglobulin of IgG λ type, and markedly elevated serum VEGF. Lenalidomide and dexamethasone treatments were introduced, and her pericardial fluid significantly reduced. Massive pericardial effusion is a rare manifestation of POEMS syndrome. POEMS syndromes with polyserositis are easily misdiagnosed as tuberculous polyserous effusions in China. Recognition of the possible pathogenesis of POEMS syndrome with a large amount of pericardial effusion will help to identify POEMS syndrome in an early stage.

Correlation of changes in serum level of VEGF and peripapillary retinal thickness in patients with POEMS syndrome

AimTo determine whether changes in the serum levels of vascular endothelial growth factor (VEGF) after thalidomide therapy will affect the peripapillary retinal thickness (pRT) associated with optic disc oedema (ODE)...

Clinical, electrophysiological and VEGF 2-year response after lenalidomide or stem cell transplantation in patients with POEMS syndrome

POEMS syndrome is a rare multisystem disease characterised by polyneuropathy (P), organomegaly (O), endocrinopathy (E), monoclonal gammopathy (M) and skin changes (S).1 A usually severe demyelinating and axonal neuropathy is...

Glomeruloid haemangiomas associated with generalized oedema in a patient with atypical POEMS syndrome.

A 55-year-old woman was admitted for evaluation of progressive generalized oedema and mild kidney dysfunction (serum creatinine 1.12 mg/dL; blood urea nitrogen 45 mg/dL). On admission, generalized oedema, transudative pleural effusion, collapsed inferior vena cava and low fractional excretion of sodium (0.14%) suggested severe volume depletion due to plasma extravasation; however, its aetiology could not be attributed to decreased colloid osmotic pressure (serum total protein 6.4 g/dL). Further examination of the patient revealed hepatosplenomegaly, slowing of nerve conduction velocities, albuminocytological dissociation in the cerebrospinal fluid, and multiple cherry-red papules on the neck and chest (Figure 1). These features were suggestive of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome, also called osteosclerotic myeloma or Crow–Fukase syndrome. However, this case did not entirely fulfil the diagnostic criteria because monoclonal plasma cell disorders were not detected [1]. The skin biopsy revealed lesions consistent with glomeruloid haemangiomas (Figure 2), which is considered to be a specific marker for POEMS syndrome [2]. Furthermore, the serum level of vascular endothelial growth factor (VEGF), which is involved in the pathogenesis of POEMS syndrome [1], was extremely elevated to 16 300 pg/mL. These findings led us to make a diagnosis of atypical POEMS syndrome and speculate that microvascular hyperpermeability induced by excess VEGF resulted in generalized oedema and effusions associated with severe volume depletion [3,4]. In patients with oedema and effusions of unknown cause, one should consider the possibility of disorders associated with VEGF overproduction including POEMS syndrome. Fig. 1 Multiple eruptive cherry-red papules on the neck. Fig. 2 (a) Dermal lesions showing vascular structures with capillary loops, resembling renal glomeruli (haematoxylin–eosin stain). (b) Endothelial cells stained for CD 31.

Síndrome de POEMS: a propósito de un caso

POEMS syndrome is a rare multisystemic disorder characterized by polyneuropathy (P), organomegaly (O), endocrinopathy (E), blood dyscrasia with M-protein band (M), and skin changes (S). The pathogenesis of POEMS syndrome is not completely understood. This paraneoplastic syndrome may be associated to bone lesions that are characteristically sclerotic or lytic with sclerotic halo and negative at bone scintigraphy. We report a case of a 37-year-old man with several manifestations of POEMS syndrome who presented bone lesions characteristic of osteosclerotic myeloma confirmed by bone biopsy.

Autologous Peripheral Blood Stem Cell Transplantation for POEMS Syndrome

Background: POEMS syndrome is a rare plasma cell disorder characterized by polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes associated with multiorgan involvement and monoclonal plasma cell dyscrasia. The pathogenesis of POEMS syndrome is not well understood, but overproduction of vascular endothelial growth factor (VEGF) probably secreted by plasma cells is considered to be responsible. High-dose melphalan (Mel) with autologous stem cell transplantation (ASCT) has been recently considered to be an effective strategy, but its treatment related mortality is considered to be high. Here, we report the results of ASCT for POEMS syndrome.Methods: Between January 2004 and June 2008, twelve patients with POEMS syndrome underwent ASCT at Chiba University Hospital and were retrospectively analyzed in the study. Conditioning treatment for ASCT was Mel 200 mg/m2, while Mel dose was reduced to 140 mg/m2 if a patient had poor performance status (PS).Results: Ten out of twelve patients were male and their median age was 48 years (range 34–61). Median time from first symptom and diagnosis to ASCT was 21 and 10 months, respectively. Seven patients received induction therapy before preparation of ASCT, thalidomide-dexamethasone in four, intravenous Mel in two, and bevacizumab followed by thalidomide in one patient. Peripheral blood stem cells were mobilized by cyclophosphamide/G-CSF in nine cases and G-CSF alone in three. Median serum VEGF level before ASCT was 2835 pg/ml (range; 334–5300). Median number of infused CD34+ cells was 2.3 × 106/kg (range; 2.1–4.3 × 106/kg). Eleven patients were conditioned with Mel 200 mg/m2, while one patient with poor PS (Karnofsky score 30%) received Mel 140 mg/m2. Median time to neutrophil recovery (>500/mm3) was 13 days post transplant (range 9–17 days). Only two patients developed respiratory distress during neutrophil engraftment period. Both cases were successfully treated with corticosteroid therapy, none of them required intubation. During a median follow up period of 16.5 months (range 2–54), there was no transplant related death. Neurologic improvement was significantly observed in all patients and median post transplantation serum VEGF level was decreased to 330 pg/ml (range 87–3250). Only one patient experienced relapse of polyneuropathy at 43 months post transplant following reincrease of serum VEGF level.Conclusions: ASCT is an effective therapy for POEMS syndrome. Despite previous published reports arousing potential risk of life-threatening engraftment syndrome, treatment related mortality and periengraftment pulmonary complications were significantly low in our patient series. We speculate that stabilization of serum VEGF level by induction therapy before ASCT could play a potential role for reducing the risk of peritransplant complications.

Restrictive usage of monoclonal immunoglobulin λ light chain germline in POEMS syndrome

AbstractPOEMS syndrome is a rare plasma cell disorder characterized by peripheral neuropathy, monoclonal gammopathy, and high levels of serum vascular endothelial growth factor, the pathogenesis of which remains unclear. A unique feature of this syndrome is that the proliferating monoclonal plasma cells are essentially λ-restricted. Here we determined complete nucleotide sequences of monoclonal immunoglobulin λ light chain (IGL) variable regions in 11 patients with POEMS syndrome. The V-region of the Igλ gene of all 11 patients was restricted to the Vλ1 subfamily. Searching for homologies with IGL germlines revealed that 2 germlines, IGLV1-44*01 (9/11) and IGLV1-40*01 (2/10), were identified, with an average homology of 91.1%. The IGLJ3*02 gene was used in 11 of 11 re-arrangements with an average homology of 92.2%. These data suggest that the highly restricted use of IGL Vλ1 germlines plays an important role in the pathogenesis of POEMS syndrome.

Ratio of serum vascular endothelial growth factor to platelet count correlates with disease activity in a patient with POEMS syndrome

Vascular endothelial growth factor (VEGF) is known to be involved in the pathogenesis of POEMS (polyneuropathy, organomegaly, endocrine disorder, M-protein, and skin lesion) syndrome. Because platelets have recently been recognized as transporters of VEGF, enhanced blood coagulation activity in this syndrome may accelerate vasopermeability by releasing VEGF from platelets in vivo. Here we report a case of POEMS syndrome with anasarca showing a high ratio of serum VEGF to platelet count, indicative of massive VEGF release from aggregated platelets in vivo. Changes in the ratio clearly reflected disease activity. This observation suggests that the ratio of serum VEGF to platelet count is more precise in monitoring disease activity than serum VEGF alone, and that VEGF released in vivo is critically involved in the pathogenesis of POEMS syndrome, causing hypervasopermeability.

Circulating levels of MMP-1, -2, -3, -9, and TIMP-1 are increased in POEMS syndrome.

The authors quantitatively measured levels of matrix metalloproteinases (MMP), tissue inhibitor of metalloproteinases (TIMP), and vascular endothelial growth factor (VEGF) in blood samples of POEMS syndrome. Circulating levels of MMP-1, -2, -3, -9, and TIMP-1 were more increased in patients with POEMS syndrome than in patients with other neurologic disorders or in healthy controls. Serum levels of VEGF and TIMP-1 were strongly correlated with each other. Increased circulating levels of MMP-1, -2, -3, -9, and TIMP-1 may lead to a better understanding the pathogenesis of POEMS syndrome.