POEMS: Into the Multisystem Disorder
Summary of Disease
POEMS syndrome is a multisystem disorder mainly linked to plasma cell dyscrasia, plasma cell overgrowth in the bone marrow1 where the bone appears denser than normal2. Its precise cause is still unclear. The name of this rare disease, POEMS, is an acronym that encompasses its five most common manifestations. POEMS stands for Polyneuropathy (damaged peripheral nerves), Organomegaly (organ enlargement), Endocrine gland abnormalities, Monoclonal-protein abnormalities (clonal plasma cell dyscrasia), and Skin changes3. While POEMS encompasses a wide range of symptoms, it is rare for patients with the disease to present all of them1. Nevertheless, polyneuropathies, abnormalities of peripheral nerves resulting in motor disability, are the most common manifestation of the disease3.
Symptoms
The predominant symptoms are those outlined by the POEMS acronym. Sensorimotor Polyneuropathy may include weakening, numbness, tingling of the limbs, progressive immobility, or difficulty breathing7. Organ enlargement is predominantly seen in the spleen, liver, or lymph nodes7 (which may be presented as Castleman disease). Endocrine gland abnormalities may be presented as hypothyroidism (could be presented as low energy), dysfunction of sex hormones, and metabolic issues. Monoclonal-protein (a type of antibody) abnormalities might be one of the key symptoms for diagnosis. M-protein abnormalities are mostly exhibited by increased levels of bone marrow plasma cells which produce monoclonal protein and are characterized as plasma cell dyscrasia4. Skin changes are mostly seen as hyperpigmented skin1, darkening of the skin, excessive hair growth, “white fingernails”, acrocyanosis (bluish skin on hands and feet), or skin flushing8. Other major criteria are sclerotic bone lesions (hardening of the bone) and vascular endothelial growth factor (VEGF) elevation9.
“POEMS has been seen twice as often in men than women 6 .”
Other symptoms worth mentioning that belong to minor criteria include papilledema (swelling of the optic disc 10), thrombocytosis (excessive number of platelet counts in blood and increased clothing11), and fatigue.
Etiology and Pathology
POEMS is characterized as a paraneoplastic syndrome, a disorder rooted in abnormal immune system responses to uncontrolled growth of plasma cells8. This is noted as a clonal plasma cell disorder, in which a single cell proliferates and may be producing excessive amounts of monoclonal proteins8.
POEMS is also associated with overproduction of proinflammatory cytokines, including interleukin (IL)-6, IL-1beta, and tumor necrosis factor (TNF)-alpha4 which are molecules that are integral parts of the signaling pathways in our body’s immune response. Additionally, this syndrome is associated with increased vascular endothelial growth factor (VEGF)4, a signaling protein that stimulates new blood vessel formation. The increase in VEGF in POEMS has seemed to be associated with edemas (different kinds of swelling) associated with POEMS syndrome and may play a role in the aberrant bone metabolism underlying the bone lesions seen in some patients4. The increased exposure of myelin (lipid layer surrounding nerves) to these proinflammatory cytokines has been suggested to lead to demyelination causing peripheral neuropathy in POEMS4. While these factors: elevated IL-6, IL-1beta, TNF-alpha, and VEGF, are associated with POEMS characteristics, the exact pathogenesis of this disease, particularly the role of plasma cells, is still not well understood.
Epidemiology
Since this syndrome’s exact origins are still not well understood, risk factors of POEMS have mostly been observable characteristics of the disease rather than protein markers that can be measured in the blood. Risk factors include pectoral effusion (a build-up of fluid in the lungs), pulmonary hypertension, reduced estimated glomerular filtration (eGFR) of kidneys, a marker for kidney function, and increased age5.
POEMS has been seen twice as often in men than women. On average, men are diagnosed around the age of 50 and women around the age of 606.
Diagnosis
Evidently, the broadly variable manifestations of POEMS, which are often non-specific, makes it difficult to diagnose. In addition, it is a rare disease that can be difficult to distinguish from similar neurologic disorders such as chronic inflammatory demyelinating polyradiculoneuropathy and the Castleman disease variant of POEMS5. The Castleman disease variant has no clonal plasma cell dyscrasia and no peripheral neuropathy but can present some of the minor characteristics of POEMS7.
“The broadly variable manifestations of POEMS, which are often non-specific, makes POEMS difficult to diagnose.”
Diagnosis can be made typically when the patient presents three major criteria: two symptoms related to polyneuropathy and one related to clonal plasma cell dyscrasia5. At least one of the minor criteria symptoms must also be present for diagnosis8. The most common way to detect the disease’s major characterizations is through a computerized tomography (CT) scan12. Bone marrow and lymph node biopsies may also be done for those presenting presumed sclerotic bone lesions and Castleman disease respectively12. Additionally, bone marrow biopsy can be used to further identify monoclonal abnormalities of POEMS8. Minor characterizations such as thrombosis and other major characterizations such as endocrine gland abnormalities can be detected with blood work9.
Treatment and Prognosis
Due to the wide range of manifestations of POEMS syndrome, treatments are based on the characteristics that each patient presents. There is currently no known cure for the disease; hence patients are treated with risk-adapted therapy5 to address the specific presented symptoms. The conventional therapy for patients with POEMS is radiotherapy but can include chemotherapy, or combined therapy. Surgery may also be an option for patients with plasmacytomas13 (plasma cell tumor from plasma cell dyscrasia). Those with sclerotic lesions, extensive bone marrow involvement, and a progression of POEMS within 3-6 months following radiation therapy are commonly treated with systemic therapy (treatment targeting the whole body14). In this scenario, systemic therapy consist of IV corticosteroids and alkylators which may be administered at low does directly into the bloodstream along with conventional therapies or in high doses with blood stem cell transplantation; another option is to use conventional therapies5.
The prognosis for POEMS syndrome ranges just like its wide range of symptoms. Prognosis typically depends on the extent of the morbidity associated with the affected systems. Commonly, POEMS is a chronic syndrome with a reported approximate median survival of around 8-13.8 years4.
Lina Lombo
Works Cited:
1. Peggs KS, Paneesha S, Kottaridis PD, et al. Peripheral blood stem cell transplantation for POEMS syndrome. Bone Marrow Transplant. 2002;30(6):401-404. doi:10.1038/sj.bmt.1703670
2. Related Diseases | Leukemia and Lymphoma Society of Canada. Accessed October 14, 2020. https://www.llscanada.org/disease-information/myeloma/related-diseases
3. POEMS syndrome | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. Accessed October 14, 2020. https://rarediseases.info.nih.gov/diseases/7411/poems-syndrome
4. Chan JL, Kubicki MN. POEMS Syndrome: Background, Pathophysiology, Etiology. Published September 17, 2020. Accessed October 14, 2020. https://emedicine.medscape.com/article/1097031-overview#a5
5. Dispenzieri A. POEMS Syndrome: 2019 Update on diagnosis, risk-stratification, and management. Am J Hematol. 2019;94(7):812-827. doi:10.1002/ajh.25495
6. Myeloma Canada | Related Disorders. Accessed October 14, 2020. https://www.myelomacanada.ca/en/about-multiple-myeloma/what-is-myeloma/related-disorders
7. POEMS syndrome - Symptoms and causes - Mayo Clinic. Accessed October 14, 2020. https://www.mayoclinic.org/diseases-conditions/poems-syndrome/symptoms-causes/syc-20352678
8. Dispenzieri A. POEMS syndrome. Blood Rev. 2007;21(6):285-299. doi:10.1016/j.blre.2007.07.004
9. Zhao G, Deng Y-C, Kang J, et al. POEMS syndrome associated with Castleman disease: a case report and literature review. Neuroimmunol Neuroinflammation. 2014;1(1):40. doi:10.4103/2347-8659.135577
10. Papilledema - an overview | ScienceDirect Topics. Accessed October 14, 2020. https://www.sciencedirect.com/topics/medicine-and-dentistry/papilledema
11. Thrombocytosis & High Platelet Count Treatment & Diagnosis. Accessed October 14, 2020. https://my.clevelandclinic.org/health/diseases/13350-thrombocytosis
12. Rahul K, Handa N, Chandrashekhara SH, Usha T, Singh A. An atypical case of POEMS syndrome with an osteolytic bone lesion. J Clin Diagnostic Res. 2015;9(6):XD01-XD02. doi:10.7860/JCDR/2015/12998.6099
13. Suh YG, Kim YS, Suh CO, et al. The role of radiotherapy in the management of POEMS syndrome. Radiat Oncol. 2014;9(1):265. doi:10.1186/s13014-014-0265-8
14. Systemic Therapy | Moffitt. Accessed October 14, 2020. https://moffitt.org/treatments/systemic-therapy/
Cite This Article:
Lombo L., Chowdhury F., Nakhoul R., Liang A. POEMS: Into the Multisystem Disorder. Illustrated by D.Amin Rare Disease Review. November 2020. DOI:10.13140/RG.2.2.26235.95527.
