Ocular Manifestations of Polyneuropathy, Organomegaly, Endocrinopathy, Myeloma Protein, and Skin Changes (POEMS) Syndrome
Disease Entity
Disease
POEMS Syndrome is a hematologic condition that is characterized by aberrant production of plasma cells[1]. The acronym POEMS stands for Polyneuropathy, Organomegaly, Endocrinopathy, Myeloma protein, and Skin changes (POEMS)[1]. While the pathogenesis is still unclear, studies have demonstrated that it can lead to severe progressive decline in function in multiple organ systems[1]. POEMS Syndrome has potential ocular manifestations, including papilledema, retinal detachment, and central retinal artery occlusion (CRAO)[2].
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[3]. 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[3].
The main ocular manifestation of POEMS syndrome is papilledema[2]. Lam et al. have determined that papilledema occurs in nearly 50% of known POEMS cases[2]. 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[2]. A common competing hypothesis states that increased vascular permeability due increased VEGF or cytokine production leads to optic nerve swelling[2].
Etiology
The incidence and prevalence of POEMS syndrome are not as clear as it is a rare condition[1]. In Japan, the alleged country of origin, the prevalence is approximately 0.3 per 100,000 people[1]. With an unclear pathogenesis, risk factors for the disease are also largely unknown[1].
Signs
Patient Exam[4]
- Signs of Elevated Intracranial Pressure:
- Headache
- Nausea and Vomiting
- Diplopia
- Ataxia
- Altered Consciousness
Possible Fundus Findings[4]:
- 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[4] | Symptoms: Central visual loss.
Fundoscopy: Intraretinal cystoid macular edema and thickening[5] |
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[6] |
| Serous Macular Detachment[4] | Painless Loss of Vision, Blurry Vision[7] | Test of Choice: Binocular ophthalmoscopy and OCT[7]
Findings: Loss of foveal fundus reflex, elevation of the retina by subretinal fluid seen on OCT[7] |
| Venous Sinus Thrombosis[4] | Papilledema, Headache (Thunderclap, migraine, cluster), Cranial Nerve Involvement including non-localizing sixth nerve palsy, Altered Consciousness[8] | Test of Choice: Computed tomography (CT) or CT venography or Magnetic Resonance Imaging (MRI) and MR Venography (MRV). May require catheter angiography.[9]
Radiographic findings: Occlusion/thrombus in cerebral veins and sinuses [9] |
| Central Retinal Artery Occlusion (CRAO)[4] | Acute, monocular painless of vision[10] | Tests of Choice: Fundus examination, fluorescein angiography, OCT[11]
Findings in descending order of prevalence[11]:
|
| Uveitis[4] | Pain, redness, photophobia, anterior or posterior chamber cells, loss of vision[12] | 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[13]
Findings: Anterior uveitis, vitreitis, retinitis, exudative retinal detachment, disc atrophy or edema, and chorioretinal scarring[13] |
Diagnosis
POEMS Syndrome[1]:
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[1]. Not all features need to be present to make the diagnosis.
The diagnosis of POEM syndrome may include the following tests[1]:
- 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[1]:
- Mandatory Major Criteria (Both are required)
- Polyradiculoneuropathy
- Monoclonal plasma cell disorder
Other major criteria (At least one is required)[1]:
- 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[14].
Differential diagnosis
The differential diagnosis of POEMS syndrome includes the following conditions[3]:
- 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.
Management
General treatment
The treatment for POEMS syndrome is collaborative with hematology and oncology[15]. Generally, the first step in therapy is to determine the level of systemic involvement using systemic markers, including symptoms and bone health[15]. For non-metastatic disease, radiotherapy is first-line[15]. For those determined to have more systemic disease, a combination of chemotherapy and autologous stem cell transplantation has been considered[15]. Most drug agents are either alkylating agents, such as melphalan or cyclophosphamide, or anti-cytokine agents, such as thalidomide and bevacizumab[15].
In the treatment of the patient’s papilledema, the first line therapy is to address the underlying cause in POEMS[16]. Standard medical and surgical treatments of papilledema may be necessary however[16].
Prognosis
The median time of onset of disease to diagnosis of POEMS syndrome is nearly 13-18 months[3]. The median survival with therapy is approximately 14 years[3]. Common causes of death include cardiorespiratory failure, progressive inanition, infection, capillary leak-like syndrome, and renal failure[3].
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 Dispenzieri, A. (2019). POEMS Syndrome: 2019 Update on diagnosis, risk-stratification, and management. American Journal of Hematology, 94(7), https://doi.org/10.1002/ajh.25495
- ↑ 2.0 2.1 2.2 2.3 2.4 Lam, C, & Margolin, E. (2016). A case of POEMS and chronic papilledema with preserved optic nerve function. Canadian Journal of Ophthalmology, 51, 6-8.
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 Nozza, A. (2017) POEMS syndrome: an update. Mediterranean journal of hematology and infectious diseases, 9(1), e2017051. https://doi.org/10.4084/MJHID.2017.051
- ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 Jindahra, P., Dejthevaporn, C., Niparuck, P. et al. Atypical central retinal artery occlusion as the first presentation of POEMS syndrome: a case report. BMC Neurol 18, 64 (2018). https://doi.org/10.1186/s12883-018-1071-y
- ↑ Musat, O., Cernat, C., Labib, M., Gheorghe, A., Toma, O., Zamfir, M., & Boureanu, A. M. (2015). DIABETIC MACULAR EDEMA. Romanian journal of ophthalmology, 59(3), 133–136.
- ↑ Gundogan, F. C., Yolcu, U., Akay, F., Ilhan, A., Ozge, G., & Uzun, S. (2016). Diabetic Macular Edema. Pakistan journal of medical sciences, 32(2), 505–510. https://doi.org/10.12669/pjms.322.8496
- ↑ 7.0 7.1 7.2 Jalali S. (2003). Retinal detachment. Community eye health, 16(46), 25–26.
- ↑ Luo, Y., Tian, X., & Wang, X. (2018). Diagnosis and Treatment of Cerebral Venous Thrombosis: A Review. Frontiers in aging neuroscience, 10, 2. https://doi.org/10.3389/fnagi.2018.00002
- ↑ 9.0 9.1 Ferro, J.M., Canhão, P. Cerebral Venous Sinus Thrombosis: Update on Diagnosis and Management. Curr Cardiol Rep 16, 523 (2014). https://doi.org/10.1007/s11886-014-0523-2
- ↑ Hayreh S. S. (2018). Central retinal artery occlusion. Indian journal of ophthalmology, 66(12), 1684–1694. https://doi.org/10.4103/ijo.IJO_1446_18
- ↑ 11.0 11.1 11.2 Varma, D. D., Cugati, S., Lee, A. W., & Chen, C. S. (2013). A review of central retinal artery occlusion: clinical presentation and management. Eye (London, England), 27(6), 688–697. https://doi.org/10.1038/eye.2013.25
- ↑ Rathinam, S. R., & Babu, M. (2013). Algorithmic approach in the diagnosis of uveitis. Indian journal of ophthalmology, 61(6), 255–262. https://doi.org/10.4103/0301-4738.114092
- ↑ 13.0 13.1 Al-Dhibi, H. A., Al-Mahmood, A. M., & Arevalo, J. F. (2014). A systematic approach to emergencies in uveitis. Middle East African journal of ophthalmology, 21(3), 251–258. https://doi.org/10.4103/0974-9233.134687
- ↑ Saeed-Abdul-Rahman, I., & Al-Amri, A. M. (2012). Castleman disease. The Korean journal of hematology, 47(3), 163–177. https://doi.org/10.5045/kjh.2012.47.3.163
- ↑ 15.0 15.1 15.2 15.3 15.4 Dispenzieri, A. How I treat POEMS syndrome. Blood. 2012; 119(24): 5650-5658. Doi: 10.1182/blood-2012-03-378992
- ↑ 16.0 16.1 Rigi, M., Almarzouqi, S.J., Morgan, M.L., Lee, A. G. (2015). Papilledema: epidemiology, etiology, and clinical management. Eye and brain, 7, 47-57. https://doi.org/10.2147/EB.S69174
