polyneuropathy , organomegaly , endocrinopathy , monoclonal protein , skin changes ( poems ) is a rare disease associated with plasma cell dyscrasia , which is generally lambda - chain restricted . high serum vascular endothelial growth factor ( vegf ) levels have been included into the five major diagnostic criteria ( polyneuropathy , monoclonal plasma cell - proliferative disorder , sclerotic bone lesions , castleman 's disease and elevated serum vegf levels ) of poems syndrome . several lines of evidence suggest that vegf is central to the pathogenesis of this paraneoplastic disorder : ( i ) whilst interleukin ( il ) 6 , tumour necrosis factor ( tnf )  and il-1 levels may or may not be elevated in poems syndrome , vegf serum levels are always significantly elevated in this disease as compared to myeloma patients and control subjects , ( ii ) pathological changes in poems syndrome consist of microangiopathy combining neoangiogenesis and increased vascular permeability induced by excessive vegf expression and ( iii ) there is a consistent relationship between serum vegf levels and the activity of the disease before therapy , whilst a decrease or normalization of vegf serum levels has been observed in patients experiencing remission after treatment with high - dose chemotherapy and autologous stem - cell transplantation ( asct ) . current therapeutic approaches in poems syndrome have mostly been aimed at the eradication of the plasma cell clone , using steroids , alkylating agents , asct or surgery and/or radiotherapy in the case of solitary plasmacytoma . recent reports have highlighted that clinical improvement is better correlated with the drop in serum vegf levels than with haematological remission . accordingly , another tempting approach to therapy in poems syndrome is to specifically target vegf over - expression . we report the case of a 57-year - old woman treated with bevacizumab , an anti - vegf monoclonal antibody , as first line treatment for poems syndrome . the patient had a 24-month - long history of severe polyneuropathy , organomegaly , ascites , pleural effusion , skin pigmentation and papilloedema with a world health organization ( who ) status of 3 . there was a 5-fold increase of free light lambda chains in the serum , without bence - jones proteinuria . multiple myeloma and solitary plasmacytoma were ruled out by blood marrow smear , bone mri and positron emission tomography ( pet ) scan . renal features included hypertension , moderate renal failure ( glomerular filtration rate 44 ml / min ) and mild proteinuria ( 1 g / day ) . endothelial cells swelling , capillary membrane double contours , widening of the subendothelial spaces and mesangiolysis  with negative immune - complex staining , which prompted the diagnosis of poems syndrome . the patient received six courses of bevacizumab ( 5 mg / kg , q 14 days ) with good tolerance . serum vegf levels dropped rapidly to a nadir of 40 pg / ml ( figure 1 ) , but her clinical condition worsened unremittingly : 4 months after bevacizumab therapy , the patient displayed high output cardiac failure , severe pulmonary hypertension and bilateral pleural effusions culminating in acute respiratory distress syndrome . the patient received 1 mg / kg / day of prednisone along with intensive support care . steroids were tapered over a 6-month period and maintained at 10 mg / day . over that period , clinical status improved steadily : complete clearance of pleural effusions ( figure 2 ) , significant diminution of pulmonary hypertension and objective improvement in polyneuropathy . in parallel , free serum lambda chain levels fell from 118 to 38 mg / l and then stabilized at about 50 mg / l for up to 1 year on low - dose prednisone therapy . in sharp contrast , serum vegf levels increased progressively to 2000 pg / ml ( figure 1 ) . evolution of serum vegf levels and free serum lambda light chains during bevacizumab and steroid therapy . we here report the case of a patient with poems syndrome treated with bevacizumab . in spite of complete vegf blockade , so far , only seven reports are available to evaluate treatment with bevacizumab in poems syndrome . two patients had previously been unsuccessfully treated by alkylating agents , one had relapsed after conventional chemotherapy   and one after bone marrow transplantation . another patient received both bevacizumab and cyclophosphamide simultaneously   and two were treated with bevacizumab before asct . in all patients , vegf blood levels dropped significantly with conflicting clinical outcomes : clinical condition worsened rapidly in three patients , leading to death in a few weeks , whilst the other four patients experienced clinical improvement , although long - term information is missing . although vegf is a likely pathogenic factor in poems syndrome , the discrepancy in response to serum vegf blockade raises the question of the pathophysiological impact of the inhibition of this cytokine in this disease . other cytokines such as il-1 , il-6 and tnf- may contribute to the pathogenesis of poems syndrome , explaining that targeting vegf alone can be ineffective , while prednisone  given its non - specific effect on cytokine release  can be effective . alternatively , the contradictory effects of bevacizumab in these eight patients may depend on the duration of the disease . indeed , the four patients who responded to bevacizumab therapy had a short duration of disease compared to the other four patients . it has been hypothesized that aberrant angiogenesis due to high vegf levels could lead to abnormal vessels no longer sensitive to anti - vefg therapy . thus , a non - return point in the reversibility of blood vessel damage may explain different outcomes . some authors have suggested that the rapid decrease of vegf levels after chronic vegf over - expression could be deleterious . straume et al . suggested that a sudden drop in vegf may accelerate neurological damage and endothelial apoptosis , explaining the rapid decline of clinical condition in their patient . in this journal , a french group   reported findings of thrombotic microangiopathy on renal biopsy in six patients treated with bevacizumab for cancer , suggesting a potential endothelial toxicity of bevacizumab . thus , an abrupt drop in vegf levels may aggravate endothelial lesions , explaining a potential worsening in patients with poems syndrome treated with bevacizumab . our case , along with the seven patients previously reported , sheds light on the complexity of the pathophysiology of poems syndrome . the beneficial impact of bevacizumab in four poems patients provides a proof of concept for vegf blockade . this case report , which documents clinical worsening despite complete serum vegf blockade , but dramatic improvement on steroids , clearly establishes that vegf blockade should not be considered a panacea for treatment nor a reliable marker to predict remission in poems syndrome .
polyneuropathy , organomegaly , endocrinopathy , monoclonal protein , skin changes ( poems ) syndrome is a systemic condition related to plasma cell dyscrasia . 
 increased vascular permeability is responsible for some of the hallmarks of this disorder that may include renal microangiopathy . 
 several lines of evidence suggest that vascular endothelial growth factor ( vegf ) is central to the pathogenesis of poems syndrome . 
 thus , specifically targeting vegf over - expression seems to be a promising treatment . 
 anti - vegf therapies are yielding conflicting results . 
 we report on a patient with poems syndrome treated with bevacizumab , an anti - vegf monoclonal antibody . 
 sequential monitoring of serum vegf showed sustained normalization of serum vegf levels , without any beneficial effect on the patient 's condition . 
 indications of this treatment should be chosen carefully .