Poems Syndrome
What is Poems Syndrome ?
POEMS syndrome is DEFINED by polyneuropathy, endocrinopathy, monoclonal gammopathy and skin impairment. It represents a rare multisystemic disorder.
It has been noted that the peak incidence of POEMS syndrome is in the fifth and sixth decade and it is more prevalent in Japanese population.
The synonymes for POEMS syndrome Crow-Fukase syndrome and Takatsuki syndrome.
It is a paraneoplastic disorder due to underlying plasma cells dyscrasia.
The acronym POEMS syndrome has been introduced in 1980 by Bardwick etdue to the main clinical characteristics such as polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin impairment.
The major criteria that define this syndrome are Castelman’s disease, sclerotic bone defects or increased vascular endothelial growth factor level.
Other minor criteria are organomegaly, extravascular volume overload, endocrinopathy, skin disorder, papilledema, thrombocytosis and polycythemia.(1)
Clinical Presentation
POEMS syndrome has been associated with coronary and lower limb ischemic disease, as well as acute ischemic stroke. Osteosclerotic bone lesions are additional manifestation of POEMS syndrome.
Additional clinical findings in POEMS syndrome are papilledema, extracellular volume overload, sclerotic bone defects, thrombocytosis, eryhthrocytosis, increased levels of vascular endothelial growth factor (VEGF), pathological pulmonary function tests as well as higher risk for thrombosis.
In the majority of patients there is a peripheral neuropathy. Its symptoms are often present in the feet and are in the form of paresthesia and the feeling of coldness.
In certain patients, severe pain may be present associated with weakness. There might be present an inability to climb stairs, stand up or hold certain objects.
The neuropathy is alike the chronic inflammation in demyelineting polyneuropathy with the motor predominance. In the evaluation of the liquor there are increased levels of proteins. Nerve biopsy shows an axonal degeneration linked with demyelinating process.
In half of the patient there is an enlarged liver that is palpable upon clinical examination. Ocassionaly, splenomegaly and lymphadenectomy may be evident. Furthermore, there are present testicular atrophy and gynecomastia.
In approximatelly 50% of patients there are skin changes (hyperpigmentation, hemangiomas, plethora and acrocyanosis).
In 90% of individuals there are osteosclerotic bone defects in the form of solitary lesions.
In patients with papilledema there are symptoms headache, transient obscure vision spots, progressive constriction of visual field.
Ascites and pleural effusion may be present in certain individuals.
Renal failure is not rare condition in patients with POEMS syndrome as well a light chain deposition.
POEMS syndrome is of chronic and progressive course.
Pathogenesis
The exact POEMS syndrome pathogenesis is still not fully understood. Its clinical course has been associated with the higher level of serum or plasma vascular endothelial growth factor (VEGF).
It has been concluded that M protein may be involved in the pathogenesis of POEMS syndrome. Certain genes that encode immunoglobulin lambda light chain variable (IGLV) region may be involved in the onset of this syndrome.
Certain clinical manifestations of POEMS syndrome have been linked to microangiopathy, neovascularization and enhanced vasopermeability. In this syndrome, it has been concluded that the tissue vascular permeability is in correlation with VEGF level.
It has been noted that VEGF released from plasma cells or white blood cells may cause the onset of edema. It may even lead to microangiopathy or macroangiopathy that may cause such diverse clinical presentation of POEMS syndrome.
POEMS syndrome may be linked to cerebral infarction due to cerebral vasculopathy. It has been as well associated with the presence of arterial and venous thrombosis that causes cerebral infarction.
MRI of POEMS syndrome has shown a high frequency of pachymeningeal enhancement.
Diagnosis
The diagnosis of POEMS syndrome is based upon a clinical investigation and characteristic laboratory findings. There are found: a lambda-restricted monoclonal protein, thrombocytosis, anasarca, or papilledema. Additional investigations include radiographic imaging of bones, measurement of VEGF levels and specific evaluation of bone marrow biopsy.
In most cases, diagnosis of POEMS syndrome may be suspected according to its clinical course, especially in the presence of peripheral neuropathy, refractory ascites and peripheral oedema. No single test is sufficient to establish a diagnosis of POEMS syndrome.
The most prominent clinical characteristic is the presence of chronic progressive polyneuropathy with motor disability.
There is still not known a specific test for this syndrome.
Nowadays, there is available screening test such as serum or urine immunofixation electrophoresis.
In order to provide an accurate diagnosis of POEMS syndrome, the presence of at least three major criteria and one minor is necessary. (2)
Increased level of serum and plasma VEGF levels may be helpful in the diagnosis of POEMS syndrome.
In POEMS syndrome, temporary remission may result after the radiotherapy directed at the plasmocytoma. The syndrome may be due to the fact of the circulating immunoglobulins with the findign of excess vascular endothelial growth factor as well as elevated IL1-b, IL-6 and TNF-a.
Differential diagnosis
It is necessary to differentiate POEMS syndrome from light chain amyloidosis and multiple myeloma. Such conditions are plasma cell disorders as well. Peripheral neuropathies such as lambda chain-restricted M protein and elevated serum VEGF concentration.
Treatment
In case of the local presentation of the disease, radiotherapy is of help. If POEMS syndrome is characterized by the disseminate disease, bone marrow involvement by clonal plasma cells, or the progression of the disease after 3-6 months, the adequate therapy is the systemic one or autologous stem cell transplantation.
Corticosteroids and alkylators are administered in certain cases. Certain level of lenalidomide has shown efficacy with treatable toxicity.
There are supportive measures such as physical therapy and exercise that are included in the treatment of neuropathy. It is recommended to include physical activity in those individuals such as bicycle riding, walking or even standing.
In the regulation of electrolyte disbalances such as ascites and pleural effusion, diuretics may be effective (mostly furosemide and spironolactone). In case of refractory ascites, paracentesis may be performed.
In individuals with hypothyroidism or adrenal insufficiency, hormone replacement therapy may be necessary.
In case of patients with solitary bone lesions, radiation might be effective in certain percentage. (R)
Prognosis
The clinical progress of POEMS syndrome is chronic. The estimated median survival is 4 times shorter than in individuals with multiple myeloma.
In patients with POEMS syndrome the most frequent death causes are cardiorespiratory insufficiency, systemic infection and renal failure.
References
- Warsame R. POEMS Syndrome: an Enigma.Curr Hematol Malig Rep. 2017 Mar 15.
- Dispenzieri A. POEMS syndrome: update on diagnosis, risk-stratification, and management.Am J Hematol. 2015 Oct;90(10):951-62.
