Ocular Manifestations of Polyneuropathy, Organomegaly, Endocrinopathy, Myeloma Protein, and Skin Changes (POEMS) Syndrome

Article initiated by:

Arjun V Jogimahanti, Subahari Raviskanthan, MBBS

All authors and contributors:

Peter W. Mortensen, MD, Andrew Go Lee, MD, Nagham Al-Zubidi, MD, Subahari Raviskanthan, MBBS

Assigned editor:

Danah Albreiki, MBBS FRCSC

Review:

Assigned status Update Pending

 by Danah Albreiki, MBBS FRCSC on November 16, 2020.

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Contributing Editors:	add

Disease

POEMS Syndrome is a hematologic condition that is characterized by aberrant production of plasma cells. The acronym POEMS stands for Polyneuropathy, Organomegaly, Endocrinopathy, Myeloma protein, and Skin changes (POEMS). While the pathogenesis is still unclear, studies have demonstrated that it can lead to severe progressive decline in function in multiple organ systems. POEMS Syndrome has potential ocular manifestations, including papilledema, retinal detachment, and central retinal artery occlusion (CRAO).

Pathophysiology

The pathogenesis of POEMS syndrome remains ill-defined but recent research has demonstrated that inflammatory cytokines and growth factors play a significant role in the development of this condition. These cytokines (e.g., Tumor Necrosis Factor-Alpha (TNF-α), Interleukin-1 (IL1), Interleukin-6 (IL6), and Vascular Endothelial Growth Factor (VEGF) are often elevated during symptomatic periods of the disease.

The main ocular manifestation of POEMS syndrome is papilledema. Lam et al. have determined that papilledema occurs in nearly 50% of known POEMS cases. The reason for disc swelling is unclear. Many experts believe that increased CSF proteins, due to increased concentration of immunoglobulin in the plasma, leads to a type of communicating hydrocephalus. A common competing hypothesis states that increased vascular permeability due increased VEGF or cytokine production leads to optic nerve swelling.

Etiology

The incidence and prevalence of POEMS syndrome are not as clear as it is a rare condition. In Japan, the alleged country of origin, the prevalence is approximately 0.3 per 100,000 people. With an unclear pathogenesis, risk factors for the disease are also largely unknown.

Signs

Papilledema:

            Patient Exam

•   Signs of Elevated Intracranial Pressure:

•   Headache

•   Nausea and Vomiting

•   Diplopia

•   Ataxia

•   Altered Consciousness      

            Possible Fundus Findings⁴:

•   Elevation and blurring of optic disc

•   Venous congestion

•   Retinal Hard Exudates

•   Splinter Hemorrhages and Infarcts

Finding	Presenting Symptoms and signs	Imaging/ Tests
Cystoid Macular Edema	Symptoms: Central visual loss. Fundoscopy: Intraretinal cystoid macular edema and thickening	Test of Choice: Lens-aided slit-lamp biomicroscopy of the posterior pole Ophthalmoscopic and optical coherence tomography (OCT) findings: Macular thickening, exudates, and cystoid changes
Serous Macular Detachment	Painless Loss of Vision, Blurry Vision	Test of Choice: Binocular ophthalmoscopy and OCT Findings: Loss of foveal fundus reflex, elevation of the retina by subretinal fluid seen on OCT
Venous Sinus Thrombosis	Papilledema, Headache (Thunderclap, migraine, cluster), Cranial Nerve Involvement including non-localizing sixth nerve palsy, Altered Consciousness	Test of Choice: Computed tomography (CT) or CT venography or Magnetic Resonance Imaging (MRI) and MR Venography (MRV). May require catheter angiography. Radiographic findings: Occlusion/thrombus in cerebral veins and sinuses
Central Retinal Artery Occlusion (CRAO)	Acute, monocular painless of vision	Tests of Choice: Fundus examination, fluorescein angiography, OCT Findings in descending order of prevalence: 1.     Cherry-Red Spot 2.     Retinal opacity in the posterior pole 3.     Pallor 4.     Retinal Arterial Attenuation Fluorescein angiography demonstrates poor filling of central retinal artery. OCT demonstrates inner retinal thickening from ischemic retina.
Uveitis	Pain, redness, photophobia, anterior or posterior chamber cells, loss of vision	Test of Choice: Slit lamp biomicroscopy, dilated Fundus Examination and OCT may show inflammatory signs (e.g., anterior chamber cell and flare), CME or serous detachments as above Findings: Anterior uveitis, vitreitis, retinitis, exudative retinal detachment, disc atrophy or edema, and chorioretinal scarring

Diagnosis

POEMS Syndrome:

A patient with POEMS may have a variable initial presentation, but the four most common symptoms and signs, based on a large series of retrospective studies, include polyneuropathy, organomegaly, volume overload, and endocrine abnormalities. Not all features need to be present to make the diagnosis.

The diagnosis of POEM syndrome may include the following tests:

•   Physical Examination evaluating for lymphadenopathy, organomegaly, and edema

•   Complete neurological exam

•   EMG condition tests

•   Detailed neurological history

•   Sural Nerve Biopsy

•   Endocrine Profile, including sexual and menstrual function

•   Serum Protein Electrophoresis (SPEP) and immunofixation

Diagnostic Criteria for POEMS Syndrome:

•   Mandatory Major Criteria (Both are required)

•   Polyradiculoneuropathy

•   Monoclonal plasma cell disorder

Other major criteria (At least one is required):

•   Castleman Disease

•   Sclerotic Bone Lesions

•   VEGF elevation

•   Minor Criteria (At least One is required)

•   Organomegaly (Splenomegaly, Hepatomegaly, or Lymphadenopathy)

•   Extravascular Volume Overload

•   Endocrinopathy

•   Skin changes

•   Papilledema

•   Thrombocytosis or Polycythemia

Note: This is a condition related to excessive B-cell and plasma cell proliferation in lymphatic tissue. The findings range from asymptomatic discrete lymphadenopathy to major hematologic systemic effects with lymphadenopathy.

Differential diagnosis

The differential diagnosis of POEMS syndrome includes the following conditions:

•   Multiple Myeloma

•   Chronic Inflammatory Demyelinating Polyneuropathy

•   Monoclonal gammopathy of undetermined significance (MGUS)

•   Solitary Plasmacytomas

•   Plasma Cell Leukemia

•   AL Amyloidosis

These other diseases must be carefully considered and evaluated before diagnosing a patient with POEMS syndrome.

General treatment

The treatment for POEMS syndrome is collaborative with hematology and oncology. Generally, the first step in therapy is to determine the level of systemic involvement using systemic markers, including symptoms and bone health. For non-metastatic disease, radiotherapy is first-line. For those determined to have more systemic disease, a combination of chemotherapy and autologous stem cell transplantation has been considered. Most drug agents are either alkylating agents, such as melphalan or cyclophosphamide, or anti-cytokine agents, such as thalidomide and bevacizumab.

Papilledema:

In the treatment of the patient’s papilledema, the first line therapy is to address the underlying cause in POEMS. Standard medical and surgical treatments of papilledema may be necessary however.

Prognosis

The median time of onset of disease to diagnosis of POEMS syndrome is nearly 13-18 months. The median survival with therapy is approximately 14 years. Common causes of death include cardiorespiratory failure, progressive inanition, infection, capillary leak-like syndrome, and renal failure.