Total Serum Procollagen Type 1 Amino-terminal Extension Of Meaning Peptide (total P1NP) In POEMS Syndrome Diagnosis And Follow-up

BACKGROUNDPOEMS syndrome, a rare plasma cell dyscrasia, typically presents with polyneuropathy, organomegaly, endocrinopathy, monoclonal immunoglobulinemia and skin changes. No gold diagnostic standard exists. VEGF distinguishes itself among myriads of serum/plasma markers with its well-established role in following the disease activity individually, although its broad serum/plasma range is self-limiting in quantifying the disease severity; a baseline level is required for patient follow-ups. Its meticulously checked contributions in other more common processes like prostatic cancer and colorectal cancer further prevents its confirming POEMS syndrome alone. Recent reports of its somehow silenced voices in a few relapsing cases are quite encouraging, for both challengers and defenders of its utility in the diagnosis and follow-up of this mysterious syndrome. Depressive state has succeeded in frustrating both of them, but its hosting a vast majority of their beloved patients has fired a question:Beat it or spare it?PURPOSES1. Calculating the value of serum P1NP in differentiating POEMS syndrome from disorders sharing some major or minor components of its diagnostic criteria, such as other plasma cell dyscrasias(AL type amyloidosis, multiple myeloma), Castleman’s disease, CIDP, polyserositis secondary to hemodynamic compromise, inflammatory or neoplastic processes.2. Describing the relationship between serum P1NP and disease activity of POEMS syndrome.3. Probing into the depressive state complicating POEMS syndrome for its current status, risk factors and prognostic factors.METHODSPOEMS syndrome patients were consecutively recruited and each one was matched with a control of the same age and gender. Serum samples of every subject at his/her first visit and follow-ups, if any, and relevant medical records were collected. Serum P1NP was measured by electrochemiluminescence immunoassay and serum VEGF by ELISA. Whole-body bone X-rays of the untreated POEMS patients were performed. We use Receiver Operating Curve (ROC) to analyze sensitivity and specificity of either serum P1NP or serum VEGF in diagnosing POEMS syndrome. Compare the serum P1NP levels of different lesions on whole-body bone X-ray of the untreated POEMS syndrome and those of normal controls. Search for the clinical manifestations that parallel with serum P1NP level in untreated patients. Compare serum P1NP with serum VEGF for patient follow-ups. Measure the depressive state of untreated POEMS patients using PHQ-9(Patient Health Questionnarie) and follow them up at least three months later, through telephone or in the clinic.RESULTS(For POEMS patients with renal function within normal limits) Serum P1NP combined with serum VEGF yield a higher sensitivity and specificity for diagnosing POEMS syndrome.Negative whole-body bone X-ray does not exclude osteosclerotic lesions. Serum P1NP parallel with VEGF in follow-ups except for its possible earlier detection of relapses.Higher serum P1NP level statistically parallel with more advanced serum M protein (p=0.012), osteosclerosis on X-ray(p=0.039), pitting edema(p=0.050), ascites(p=0.006), pleural efrusions(p=0.015), PHQ-9score(p=0.020), pulmonary hypertension (p=0.004)Depressive state complicates72%untreated POEMS syndrome patients. Pulmonary arterial hypertension[OR=43.028,95%CI(2.782,665.523)] andhypothyroidism[OR=35.478,95%CI(1.162,1083)] may be risk factors for depression in POEMS syndrome. The degree of improvement of depressive state parallel with the degree of improvement of overall neuropathy limitations scale.CONCLUSIONSSerum P1NP sensitizes VEGF in POEMS syndrome diagnosis and maybe relapse detection. Serum P1NP specifies VEGF in POEMS syndrome diagnosis and bone lesions types on whole-body bone X-ray.Serum P1NP level, as well as serum VEGF level, waxes and wanes with disease activity. A higher serum P1NP level indicate more M protein, more advanced osteosclerotic lesions, more severe endocrinopathy, and more extravascular volume overload of POEMS syndrome.Most untreated POEMS syndrome patients suffer from depressive state, for which pulmonary arterial hypertension and hypothyroidism may be risk factors. It improves with the resolution of the peripheral neurological dysfunction.