Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, and Skin changes – these are the key elements that form the acronym POEMS syndrome. This rare paraneoplastic syndrome arises due to an underlying plasma cell neoplasm. Often, the path to diagnosis is complex, resembling the unfolding of a cryptic “Diagnosis Poem,” as it can easily be mistaken for other neurological conditions, most notably chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Understanding the diagnostic criteria and nuances of POEMS syndrome is crucial for timely and effective management.
The syndrome is characterized by a constellation of both major and minor criteria. For a definitive diagnosis of POEMS syndrome, clinicians look for the presence of at least three major criteria, with two being mandatory: polyradiculoneuropathy and a clonal plasma cell disorder. The other major criteria include sclerotic bone lesions, elevated levels of vascular endothelial growth factor (VEGF), and the presence of Castleman disease. These major criteria are fundamental clues in deciphering the “diagnosis poem” of POEMS.
Complementing these major indicators are several minor features that further paint the clinical picture. Organomegaly, encompassing the enlargement of organs such as the liver, spleen, or lymph nodes, is a significant minor criterion. Endocrinopathy, indicating dysfunction of endocrine glands and potentially leading to conditions like diabetes or hypothyroidism, is another key feature. Characteristic skin changes, which can manifest as hyperpigmentation, hypertrichosis, or glomeruloid hemangiomas, also contribute to the diagnostic puzzle. Other minor criteria include papilledema (swelling of the optic disc), extravascular volume overload (leading to edema or ascites), and thrombocytosis (elevated platelet count). The presence of these minor criteria, in conjunction with the major ones, helps to solidify the diagnosis of POEMS syndrome.
It is important to differentiate POEMS syndrome from the Castleman disease variant of POEMS syndrome. This variant lacks a clonal plasma cell disorder and typically presents with minimal peripheral neuropathy, setting it apart from the classic POEMS syndrome. However, the Castleman disease variant often shares several of the minor diagnostic criteria, making careful evaluation of the complete clinical picture essential for accurate diagnosis and appropriate management strategies.
Risk stratification in POEMS syndrome remains challenging due to an incomplete understanding of its pathogenesis. Currently, risk assessment relies primarily on clinical phenotype rather than specific molecular markers. Identified risk factors that may indicate a poorer prognosis include low serum albumin levels, older age at diagnosis, the presence of pleural effusion, pulmonary hypertension, and reduced estimated glomerular filtration rate (eGFR). These clinical indicators help in gauging the severity and potential progression of the syndrome.
Therapeutic approaches for POEMS syndrome are risk-adapted and depend on the nature and extent of the underlying plasma cell neoplasm. For patients presenting with a dominant sclerotic plasmacytoma, localized irradiation is typically the first-line therapy. However, for individuals with diffuse sclerotic lesions, disseminated bone marrow involvement, or disease progression following radiation therapy, systemic therapy becomes necessary. While corticosteroids may offer temporary relief, alkylating agents form the cornerstone of systemic treatment. These can be administered as low-dose conventional therapy or high-dose therapy in conjunction with stem cell transplantation. Emerging therapies, such as lenalidomide, show promise with manageable toxicity profiles. Thalidomide and bortezomib also demonstrate activity against POEMS syndrome, but their potential to exacerbate peripheral neuropathy necessitates a careful risk-benefit assessment. Ultimately, prompt diagnosis, coupled with the initiation of both supportive care measures and targeted therapy aimed at the plasma cell disorder, is paramount to achieving the most favorable outcomes for patients navigating the complexities of POEMS syndrome.
