Raised VEGF: High sensitivity and specificity in the diagnosis of POEMS syndrome

Abstract

Objective: To investigate the sensitivity and the specificity of serum vascular endothelial growth factor (sVEGF) for the diagnosis of polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome in patients with a neuropathy (NP) and to identify confounding causes of raised vascular endothelial growth factor (VEGF) in this context to improve accuracy.

Methods: We studied the specificity and sensitivity of sVEGF for the diagnosis of POEMS syndrome in a cohort of 195 consecutive patients with an NP in serum samples from June 2009 to November 2013, including 27 untreated patients with POEMS syndrome. We then studied VEGF in other neuropathies and analyzed causes of elevated VEGF in a multiple logistic regression analysis in a larger cohort of 236 patients including 168 with a non-POEMS NP and 68 without NP.

Results: The sensitivity of elevated sVEGF for the diagnosis of POEMS was 100%. Its specificity was 91% in patients with an NP and 92% in patients with an NP and a paraproteinemia. sVEGF was much higher in POEMS before treatment. sVEGF was not significantly elevated in any non-POEMS NP or hematologic disease group. Multiple logistic regression showed that anemia with low iron was a significant predictor for elevated sVEGF and that chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea-hypopnoea syndrome were significant predictors for very elevated sVEGF.

Interpretation: We confirmed the high sensitivity and specificity of an elevated VEGF for the diagnosis of POEMS. However, VEGF testing should be repeated, particularly after acute illnesses. Raised sVEGF should be interpreted with caution unless anemias with low iron, sleep apnea, COPD, cancers, vasculitis, and chronic inflammatory diseases are excluded.

Classification of evidence: This study provides class IV evidence that elevated sVEGF levels accurately identifies patients with POEMS syndrome.

Figure 1. Serum vascular endothelial growth factor (sVEGF) concentrations in different NP groups

1,000 pg/mL (very elevated sVEGF); 771 pg/mL (elevated sVEGF). *p < 0.0001 in comparison with each other group; **p < 0.05 in comparison with other inflammatory/paraproteinemic NPs and other noninflammatory NPs; ***p < 0.05 in comparison with other noninflammatory NPs. Anti-MAG = anti-myelin-associated glycoprotein; CIDP = chronic inflammatory demyelinating polyneuropathy; NP = neuropathy; POEMS = polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes; VEGF = vascular endothelial growth factor.

Figure 2. Distribution of serum vascular endothelial growth factor (sVEGF) in different neuropathy groups

1,000 pg/mL (very elevated sVEGF); 771 pg/mL (elevated sVEGF). Anti-MAG = anti-myelin-associated glycoprotein; CIDP = chronic inflammatory demyelinating polyneuropathy; NP = neuropathy; POEMS = polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes; VEGF = vascular endothelial growth factor.

Figure 3. sVEGF concentrations in anemia and hypoxemic diseases

(A) Serum VEGF in anemia with and without iron deficiency. (B) Serum VEGF in hypoxemic diseases. 1,000 pg/mL (very elevated sVEGF); 771 pg/mL (elevated sVEGF). COPD = chronic obstructive pulmonary disease; OSAHS = obstructive sleep apnoea-hypopnea syndrome; sVEGF = serum vascular endothelial growth factor.