¹Associate Professor, Dr.VithalraoVikhe Patil Foundation’s College of Nursing, Ahmednagar, Maharashtra, India.

²Community Health Officer, Nashik, Maharashtra, India.

*Corresponding Author E-mail: tusharskedar1212@gmail.com

ABSTRACT:

The purpose of this review is to provide the latest information on POEMS syndrome. The authors conducted a literature search of available sources describing the issue of POEMS syndrome with special focus on syndrome and made a comparison and evaluation of relevant findings. The results of this review indicate that POEMS syndrome is associated with a group of disorders known as monoclonal gammopathies or plasma cell dyscrasias. These disorders are characterized the uncontrolled growth of a single clone (monoclonal) of plasma cells, which results in the abnormal accumulation of M-proteins (also known as immunoglobulin) in the blood which has a significant impact on the quality of life of both the patients and his/her family. Diagnoses are often delayed because the syndrome is rare and can be mistaken for other neurologic disorders, most commonly chronic inflammatory demyelinating polyradiculoneuropathy. Therefore, early and proper diagnosis and treatment are necessary in order to reduce or even eliminate both symptoms and social burden of the patient.

KEYWORDS: POEMS syndrome, Plasma dyscrasias, Immunoglobulin.

INTRODUCTION:

POEMS syndrome is a rare paraneoplastic syndrome due to an underlying plasma cell disorder (PCD). The acronym, which was coined by Bardwick in 1980, refers to several, but not all, of the features of the syndrome: polyradiculoneuropathy, organomegaly, endocrinopathy, monoclonal PCD, and skin changes. There are three important points that relate to this memorable acronym:

(a) not all of the features within the acronym are required to make the diagnosis; (b) there are other important features not included in the POEMS acronym, including papilledema, extravascular volume overload, sclerotic bone lesions, thrombocytosis/erythrocytosis (PEST), elevated vascular endothelial growth factor (VEGF) levels, a predisposition toward thrombosis, and abnormal pulmonary function tests; and (c) there is a Castleman disease variant of POEMS syndrome may is associated with a clonal PCD.

Other names of the POEMS syndrome that are less frequently used are osteosclerotic myeloma, Takatsuki syndrome or Crow‐Fukase syndrome. The disease was initially thought to be more common in patients of Japanese descent given the largest initial reports from Japan. However, over the years, large series have also been reported from France, the United States, China, and India.¹

A national survey was conducted in Japan in 2015 using an established epidemiological method. The estimated number of patients with POEMS were 392 (95% confidence interval [CI] 320–464), and the prevalence was 0.3 per 100,000. Detailed clinical profiles were available for 167 patients. Median age at onset was 54 years (range, 21–84 years), and the ratio of male to female was 1.5. All patients showed polyneuropathy; 89% had monoclonal plasma cell proliferation; and 84% had elevated vascular endothelial growth factor level in whom pretreatment serum or plasma was available (n = 87). Other common features were skin changes (84%), edema/effusion (81%), and organomegaly (76%). A total of 160 patients were treated with any of the following: radiation, corticosteroids, melphalan, thalidomide, lenalidomide, bortezomib, or autologous stem cell transplantation. Primary therapeutic options were thalidomide (n = 86) and autologous stem cell transplantation (n = 71). Thirty-nine patients (24%) were initially treated with corticosteroid alone. The 10-year overall survival was 93% (95% CI 86%–96%).²

What is POEMS Syndrome?

POEMS syndrome is a rare blood disorder that damages your nerves and affects other parts of your body. POEMS stands for these signs and symptoms: Polyneuropathy. Numbness, tingling and weakness in your legs — and over time, maybe in your hands and difficulty breathing.

POEMS syndrome is a rare multisystem disorder. POEMS syndrome is an extremely rare multisystem disorder. POEMS is an acronym that stands for polyneuropathy, disease affecting many nerves; organomegaly, abnormal enlargement of an organ; Endocrinology, disease affecting certain hormone – producing gland that help to regulate sexual function, and metabolic function, Monoclonal gammopathy or M protein; and skin abnormalities. POEMS syndrome is paraneoplastic syndrome caused by plasma cell dyscrasia related to changes in the level of a cytokine or a growth factor.³

Etiology:

· The cause of POEMS syndrome is Unknown

· Genetics

· Environmental and developmental factors

· Race-no specific racial association has been identified, although a preponderance of cases have been reported in the Japanese literature.

· Sex- Slightly more prevalent among men than women, with a male-to-female ratio of 2.5:1.

· Age-The onset of POEMS syndrome occurs most frequently in the fifth or sixth decade of life, with a mean patient age at onset of 48 years for men and 59 years for women.⁴

Pathophysiology:

The pathophysiology of POEMS syndrome is not clearly understood. Aa plasma cell disorder underlies the development of the syndrome; however, the mechanism by which this occurs is unknown. Elevations of cytokines, such as interleukin (IL)–1beta, IL-6, and tumor necrosis factor (TNF)–alpha, have all been noted. Most recently, significant elevations in vascular endothelial growth factor (VEGF) levels have been noted. Increases in VEGF levels have been postulated to lead to enhanced vascular permeability, leading to the associated edema, increased endo neural pressure, and deposition of plasma cell–derived material. As myelin is exposed to serum cytokines and complement, demyelization can occur.⁵

Affected populations:

POEMS syndrome affected men more often than women and usually occurs during the forties or fifties, although it has been reported in individuals in their twenties. The disorder was originally thought to be more common in Japan than in United states & Europe. Making it difficult to determine the true frequency in the general population. ⁶

Clinical Manifestation:

1. Polyneuropathy- Numbness, tingling and weakness in your legs — and over time, maybe in your hands and difficulty breathing. This is an essential feature in the diagnosis of POEMS syndrome.

2. Organomegaly- Enlarged spleen, liver or lymph nodes.

3. Endocrinopathy/edema- Abnormal hormone levels that can result in an underactive thyroid (hypothyroidism), diabetes, sexual problems, fatigue, swelling in your limbs, and problems with metabolism and other essential functions.

4. Monoclonal-protein- Abnormal bone marrow cells (plasma cells) that produce a protein (monoclonal protein) that can be found in the bloodstream. This is an essential feature in the diagnosis of POEMS syndrome. Monoclonal-protein is often associated with unusual bone hardening or thickening.

5. Skin changes- More colour than normal on your skin, red spots, possibly thicker skin, and increased facial or leg hair.

Other symptoms and signs -

· Weight loss and fatigue

· Extrvascular fluid overload with ascites, peripheral oedema and pleural effusion (accumulation of fluid in the abdominal cavity, limbs and lung lining respectively)

· Arterial and venous thromboses (blood clots)

· Pulmonary disease:

· Restrictive lung disease

· Pulmonary hypertension

· Respiratory muscle weakness.⁷

Diagnostic Evaluation:

To diagnose POEMS, need:

a) Both mandatory major criteria,

b) At least 1 of the other major criteria,

c) AND at least 1 of the minor criteria.

Other diagnostic test:

· Blood tests.

· Full blood count: which may show thrombocytosis

+/-polycythaemia

· Endocrine panels may show abnormalities including deranged thyrotropin, glucose, and oestrogen

· Serum or urine electrophoresis to test for the monoclonal immunoglobulin

· X-ray of bones in almost all patients show osteosclerotic lesions, which are often multiple

· Biopsy of an enlarged lymph node may show Castleman disease

· Lumbar puncture in those with neuropathy may show increased protein in the cerebrospinal fluid

· Nerve conduction studies may show changes of demyelination and axonal degeneration

· Bone marrow examination may show involvement with plasma cells

· Lymph node biopsy of enlarged nodes

· Skin biopsy results are usually nonspecific

· Scleroderma-like lesions show nonspecific hyperpigmentation of the basal layer with inflammatory infiltrate or dermal fibrosis. Sweat glands and collagen are normal, which differentiates it from scleroderma.

· Hyperpigmented lesions show nonspecific inflammatory infiltrate of lymphocytes and plasma cells

· Angiomas include strawberry naevus, lobular capillary angioma, and in around 3%, glomeruloid haemangioma (this is especially characteristic of POEMS syndrome and shows enlarged vascular spaces filled with coiled capillaries surrounded by pericytes, which look like kidney glomerulus).⁸

Management:

As reported by Dispenzieri et al Mayo Clinic treatment regimens are tailored to treat the clinical manifestations and prognosis for the rate of progression of the POEMS syndrome in each patient. In rare cases, patients may have minimal or no symptoms at presentation or after successful treatment of their disorder. These patients may be monitored every 2–3 months for symptoms and disease progression. Otherwise, treatment is divided based on the local versus systemic spread of its clonal plasma cells. Patients with one or two plasmacytoma bone lesions and no clonal plasma cells in their bone

marrow biopsy specimens are treated by surgical removal or radiotherapy of their tumors. These treatments can relieve many of the syndromes clinical manifestations including neuropathies, have a 10-year overall survival of 70% and a 6-year progression-free survival of 62%. Patients with >2 plasmacytoma bone lesions and/or increases in bone marrow clonal plasma cells are treated with a low-dose or high-dose chemotherapy regimen, i.e. a corticosteroid such as dexamethasone plus an alkylating agents such as melphalan. Dosage regimens are selected on the basis of patient tolerance. Hematological response rates to the dexamethasone/melphalan regimens have been reported to be in the 80% range with neurological response rates approaching 100%. Patients successfully treated with the high-dose dexamethasone/melphalan regimen have been further treated with autologous stem cell transplantation. In 59 patients treated with the chemotherapy/ transplantation regimen, the Mayo Clinic reported progression-free survival rates of 98%, 94%, and 75% at

1, 2, and 5 years, respectively.

Other treatment regiments are being studied. Immunomodulatory imide drugs such as thalidomide and lenalidomide have been used in combination with dexamethasone to treat POEMS syndrome patients. While the mechanism of action of these immunomodulators are not clear, they do inhibit the production of cytokines suspected of contributing to POEMS syndrome such as VEGF, TNFα, and IL-6 and stimulate T cells and NK cells to increase their production of interferon gamma and interleukin 2 (see immunomodulatory imide drug's mechanism of action). A double blind study of 25 POEMS syndrome patients found significantly better results (VEGF reduction, neuromuscular function improvement and quality of life improvement) in patients treated with thalidomide plus dexamethasone compared to patients treated with a thalidomide placebo plus dexamethasone.

Since VEGF plays a central role in the symptoms of POEMS syndrome, some have tried bevacizumab, a monoclonal antibody directed against VEGF. While some reports were positive, others have reported capillary leak syndrome suspected to be the result of overly rapid lowering of VEGF levels. It therefore remains doubtful as to whether this will become part of standard treatment for POEMS syndrome. ⁹

Complications:

Complications of POEMS syndrome depends on the symptoms a person experiences. The treatment may cause complication of their own . In some people with POEMS syndrome nerve damage and weakness gets worse over time and can severely limit mobility. If too much fluids up near the lungs or chest cavity, it can cause chest pain and breathing trouble. Effective treatment will stop the nerve damage and help alleviate other symptoms of the disease as well. Nerve damage may slowly improve over time.¹⁰

Prognosis:

POEMS Syndrome is a chronic disease. The median survival is around a decade (8-14 years), which is three times longer than patients with multiple myeloma. However, many patients are bedridden due to neuropathy (50%).¹¹

CONCLUSION:

In conclusion POEMS syndrome is an important paraneoplastic syndrome associated with a clonal plasma cell neoplasm. Making the diagnosis can be a challenge, but a good history and physical examination followed by appropriate testing most notably radiographic assessment of bones, measurement of VEGF, and careful analysis of a bone marrow biopsy can differentiate this syndrome from other conditions like CIDP, immunoglobulin light chain amyloidosis, and MGUS neuropathy. Once the diagnosis is made, attention to supportive care and treatments that are active in MM are essential; however, application of neurotoxic MM therapies should be used in the context of a clinical trial or at the time of relapsed or resistant disease. Cause is remaining unknown but family history is prevalent in this disorder. Each patient is unique, the individual or family should work with a clinician to determine an appropriate treatment plan.

CONFLICT ON INTEREST:

Nil.

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Received on 28.07.2021 Modified on 07.08.2021

Int. J. Nur. Edu. and Research. 2021; 9(4):505-508.

DOI: 10.52711/2454-2660.2021.00119

Veerabhadrappa G Mendagudli1*, Tushar S Kedar2