Early VEGF testing in inflammatory neuropathy avoids POEMS syndrome misdiagnosis and associated costs

BACKGROUND: Prompt diagnosis and early treatment prevents disability in Polyneuropathy Organomegaly Endocrinopathy Monoclonal-protein and Skin Changes (POEMS) syndrome. Delay in diagnosis is common with 55% of patients initially incorrectly diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Patients are often treated with intravenous immunoglobulin which is both expensive and ineffective in the treatment of POEMS. Testing patients with acquired demyelinating neuropathy with serum vascular endothelial growth factor (VEGF) more accurately identifies POEMS syndrome than the current standard of care. Incorporating VEGF testing into screening could prevent misdiagnosis and reduce costs. METHODS: We used observed treatment information for patients in the University College London Hospital's POEMS syndrome database (n=100) and from the National Immunoglobulin Database to estimate costs associated with incorrect CIDP diagnoses across our cohort. We conducted a model-based cost-effectiveness analysis to compare the current diagnostic algorithm with an alternative which includes VEGF testing for all patients with an acquired demyelinating neuropathy. RESULTS: Treatment associated with an incorrect CIDP diagnosis led to total wasted healthcare expenditures of between £808 550 and £1 111 756 across our cohort, with an average cost-per-POEMS-patient misdiagnosed of £14 701 to £20 214. Introducing mandatory VEGF testing for patients with acquired demyelinating neuropathy would lead to annual cost-savings of £107 398 for the National Health Service and could prevent misdiagnosis in 16 cases per annum. CONCLUSIONS: Misdiagnosis in POEMS syndrome results in diagnostic delay, disease progression and significant healthcare costs. Introducing mandatory VEGF testing for patients with acquired demyelinating neuropathy is a cost-effective strategy allowing for early POEMS diagnosis and potentially enabling prompt disease-directed therapy

POEMS neuropathy: optimising diagnosis and management

POEMS syndrome is a rare and disabling autoinflammatory condition characterised by a typical peripheral neuropathy and the presence of a monoclonal plasma cell disorder. The acronym 'POEMS' represents the complex and multisystem features of the disease, including polyneuropathy, organomegaly, endocrinopathy, a monoclonal plasma cell disorder and skin disease. The diagnosis of POEMS is a significant challenge because of the heterogeneity of clinical presentations and variation of POEMS features. Patients are often misdiagnosed with another cause of inflammatory neuropathy and receive one or more ineffective immunomodulatory medications, resulting in delayed diagnosis and further clinical deterioration before a diagnosis is made. University College London Hospitals sees one of the largest reported POEMS cohorts in Europe, and runs a multispecialist clinic to assist with diagnosis, treatment and ongoing support. This review draws upon our experience to present the typical features of POEMS syndrome and highlight diagnostic conundrums commonly experienced, supplemented with clinical cases. We provide an investigative guide for clinicians when considering POEMS as the diagnosis, and propose a treatment algorithm that centres on the site and degree of monoclonal cell proliferation

High rates of venous and arterial thrombotic events in patients with POEMS syndrome: results from the UCLH (UK) POEMS Registry

Arterial and venous thromboses occur in patients with POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein level, and skin changes) syndrome at a previously reported rate of 20%. We reviewed the University College London Hospitals (UCLH) POEMS Registry to determine the rate of venous thromboembolism (VTE), arterial events, and risk factors. This registry, established in 1999 and comprising 103 patients at the time of this study, is the largest single-center cohort in Europe. Of the 83 assessable patients, median age at presentation was 52 years (range, 31-84). Twenty-five patients experienced clinically apparent arterial or venous events, and 2 had concurrent arterial and venous thromboses. Eleven patients had VTEs, including deep vein thrombosis (DVT; 3 of 11), pulmonary embolism (4 of 11), and peripherally inserted central catheter–associated DVT, which occurred during autologous stem cell transplantation (3 of 11). Sixteen patients experienced arterial events: stroke (7 of 16), peripheral arterial occlusion (5 of 16), myocardial infarction (3 of 16), and microvascular disease (1 of 16), with no discernible relationship with thrombocytosis or polycythemia. Thirty percent of POEMS patients have arterial and venous thromboses, higher than previously reported. There were more arterial than venous events, and most occurred during active disease, before the start of chemotherapy, indicating the need for a preemptive approach to thromboprophylaxi

IgM paraprotein-associated peripheral neuropathy: small CD20-positive B-cell clones may predict a monoclonal gammopathy of neurological significance and rituximab responsiveness

IgM paraprotein‐associated peripheral neuropathy (PN) in patients without overt evidence of lymphoma is a recognised clinical entity of unknown aetiology. Interrogating the bone marrow B‐cell or plasma cell clones underlying paraproteinemic neuropathies may improve our understanding of both pathogenesis and treatment options. This retrospective observational analysis of IgM paraprotein‐associated PN identified five patients with small pathological MYD88 L265P and CD20‐positive B‐cell clones in their bone marrow using multi‐parametric flow cytometry, who have shown durable neurological response to rituximab. We posit that multi‐parametric flow cytometry may be instrumental in identifying the cellular source of the paraprotein in IgM paraprotein‐associated PN, and thus directing appropriate immunomodulatory therapy. Further understanding of these small pathological B‐cell clones may also provide additional insight into mechanisms of monoclonal gammopathy of clinical significance overall

Spinal disease in myeloma: cohort analysis at a specialist spinal surgery centre indicates benefit of early surgical augmentation or bracing

BACKGROUND: Multiple myeloma osteolytic disease affecting the spine results in vertebral compression fractures. These are painful, result in kyphosis, and impact respiratory function and quality of life. We explore the impact of time to presentation on the efficacy of spinal treatment modalities. METHODS: We retrospectively reviewed 183 patients with spinal myeloma presenting to our service over a 2 year period. RESULTS: Median time from multiple myeloma diagnosis to presentation at our centre was 195 days. Eighty-four patients (45.9 %) were treated with balloon kyphoplasty and the remainder with a thoracolumbar-sacral orthosis as per our published protocol. Patients presenting earlier than 195 days from diagnosis had significant improvements in patient reported outcome measures: EuroQol 5-Dimensions (p < 0.001), Oswestry Disability Index (p < 0.001), and Visual Analogue Pain Score (p < 0.001) at follow-up, regardless of treatment. Patients presenting after 195 days, however, only experienced benefit following balloon kyphoplasty, with no significant benefit from non-operative management. CONCLUSION: Vertebral augmentation and thoracolumbar bracing improve patient reported outcome scores in patients with spinal myeloma. However, delay in treatment negatively impacts clinical outcome, particularly if managed non-operatively. It is important to screen and treat patients with MM and back pain early to prevent deformity and improve quality of life

Early VEGF testing in inflammatory neuropathy avoids POEMS syndrome misdiagnosis and associated costs.

BACKGROUND: Prompt diagnosis and early treatment prevents disability in Polyneuropathy Organomegaly Endocrinopathy Monoclonal-protein and Skin Changes (POEMS) syndrome. Delay in diagnosis is common with 55% of patients initially incorrectly diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Patients are often treated with intravenous immunoglobulin which is both expensive and ineffective in the treatment of POEMS. Testing patients with acquired demyelinating neuropathy with serum vascular endothelial growth factor (VEGF) more accurately identifies POEMS syndrome than the current standard of care. Incorporating VEGF testing into screening could prevent misdiagnosis and reduce costs. METHODS: We used observed treatment information for patients in the University College London Hospital's POEMS syndrome database (n=100) and from the National Immunoglobulin Database to estimate costs associated with incorrect CIDP diagnoses across our cohort. We conducted a model-based cost-effectiveness analysis to compare the current diagnostic algorithm with an alternative which includes VEGF testing for all patients with an acquired demyelinating neuropathy. RESULTS: Treatment associated with an incorrect CIDP diagnosis led to total wasted healthcare expenditures of between £808 550 and £1 111 756 across our cohort, with an average cost-per-POEMS-patient misdiagnosed of £14 701 to £20 214. Introducing mandatory VEGF testing for patients with acquired demyelinating neuropathy would lead to annual cost-savings of £107 398 for the National Health Service and could prevent misdiagnosis in 16 cases per annum. CONCLUSIONS: Misdiagnosis in POEMS syndrome results in diagnostic delay, disease progression and significant healthcare costs. Introducing mandatory VEGF testing for patients with acquired demyelinating neuropathy is a cost-effective strategy allowing for early POEMS diagnosis and potentially enabling prompt disease-directed therapy

Prevalence and course of endocrinopathy in POEMS syndrome

CONTEXT: POEMS syndrome is a rare multisystem disorder characterised by polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma-proliferative disorder and skin changes among other features. OBJECTIVE: To describe the prevalence and course of the endocrine dysfunction in the context of POEMS. DESIGN: Cohort study with systematic review of the endocrinopathy in POEMS. SETTING: 75 patients with POEMS were evaluated by the multidisciplinary team at our tertiary specialist centre. PATIENTS: Endocrine data was available for 59 patients who attended the clinic from 06/1999 to 05/2018. INTERVENTIONS: All patients had regular endocrine screening including testing for diabetes, pituitary and thyroid dysfunction and assessment of bone metabolism. MAIN OUTCOME MEASURE: Prevalence and survival time to develop endocrinopathy in POEMS. RESULTS: Thirty-four (63%) patients presented with an endocrinopathy at point of POEMS diagnosis and 54 (92%) had at least one endocrine abnormality at follow-up. The median follow-up was 4.4[1.5, 7.9] years. The most common endocrine abnormality was hypogonadism in 68%, followed by hyperprolactinaemia (56%), hypothyroidism (54%), abnormal glucose metabolism (24%), adrenal insufficiency (17%) and high IGF-1 levels (15%). Spontaneous resolution of endocrine abnormalities at the end of follow-up was observed: 14% in hypogonadism, 42% in hyperprolactinaemia, 34% in hypothyroidism and 38% in high IGF-1 levels. CONCLUSIONS: Endocrinopathy was found in 63% of patients at diagnosis and in 92% of patients during follow-up in our cohort, therefore patients with POEMS should be systematically assessed for endocrinopathy. The most common deficiencies were hypogonadism and hypothyroidism, however normalisation of the endocrinopathy can occur so on-going treatment should remain under review