POEMS syndrome

Introduction to POEMS Syndrome POEMS syndrome is a rare multisystem disease with unclear etiology and pathogenesis. It is mainly characterized by polyneuropathy (P), organmegamega (o), endocrinopathy (E). Monoclonal gamma globulin disease (M, also known as M-protein) and skin changes (Skinchanges, S). The disease was first described by Crow in 1956, followed by Fukase in 1968, and Nakanishi et al. referred to it as Crow-Fukase syndrome. Takatsuki first confirmed and comprehensively described the disease, so it is also known as Takatsuki syndrome. Bardwick et al. combined the first letters of the above five main manifestations into POEMS syndrome. POEMS syndrome patients are often accompanied by osteosclerotic bone damage, biopsy can be seen in malignant plasma cells, so it is a special type of plasma cell disease, and POEMS syndrome may be a paraneoplastic syndrome. basic knowledge The proportion of illness: 0.0025% Susceptible people: no special people Mode of infection: non-infectious Complications: multiple myeloma

Causes of POEMS syndrome

(1) Causes of the disease

The etiology of this disease is unclear. The latest research suggests that human herpesvirus type 8 (HHV-8) infection is associated with POEMS syndrome-related multicentric Castleman disease (MCD), and 18 cases of Belec et al. HHV-8 infection in patients with POEMS syndrome (9 with MCD) was investigated, 7/13 (54%) detected HHV-8 DNA sequence, and 9/18 (50%) detected circulating anti-HHV- Of the 8 antibodies, 6/7 (85%) of the POEMS patients with MCD detected DNA sequences, 7/9 (78%) detected antibodies, and MCD was an undefined non-neoplastic lymphoid proliferation. The disease, characterized by vascular follicular lymph node proliferation in primary polylytic organs, may be associated with various immunodeficiency states, including rheumatoid arthritis, Hodgkin's disease, and B-cell non-Hodgkin's lymphoma, human immunodeficiency Human immunodeficiency virus (HIV) infection and POEMS syndrome, HHV-8 infection was first discovered in acquired immunodeficiency syndrome (AIDS), and non-AIDS-related Kaposi sarcoma (Kaposis sarcoma). Primary exudative lymphoma (primary ef Fusion lym-phoma), MCD lymph node and peripheral blood mononuclear cells and multiple myeloma bone marrow dendritic cells, a substance similar to human interleukin-6 (IL-6) is present in the HHV-8 genome, while IL -6 as a growth factor may play a role in the pathogenesis of Kaposi sarcoma, primary exudative lymphoma, multiple myeloma, MCD and POEMS syndrome.

(two) pathogenesis

Unclear pathogenesis, proinflammatory cytokines and vascular endothelial growth factor (VEGF) overproduction may play an important role in the pathogenesis of this disease, excessive production of pro-inflammatory cytokines and The weakening of the antagonistic response is related to the disease. These pro-inflammatory cytokines mainly include IL-1, TNF- and IL-6, which are functionally related to each other. IL-1 and TNF-a have mutual stimulation effects. It can stimulate the production of IL-6. IL-6 is rarely directly toxic. It is involved in pathogenesis as an important cofactor. IL-1 is an early inflammatory mediator produced by mononuclear macrophages, acting on almost all tissues. Including immune, neurological and endocrine systems, which have a wide-ranging effect on various systems when released in the blood circulation, IL-1a is mainly present in cells, while IL-1 is mainly secreted into extracellular fluids, Gherardi et al., 14/ In 15 patients with POEMS syndrome, serum IL-1 levels increased, 10 patients had increased TNF-, 10 patients had increased IL-6 levels, serum IL-1, TNF- and IL-6 levels were higher than those without neuropathy. Tumor patient The levels of IL-2 and interferon gamma (IFN-) are normal, and the level of metastatic growth factor 1 (TGF-1) is low. The primary site of activation and the cause of activation of these cytokines have not been determined. Lymph nodes may be excessive IL-1. The site of production, but more likely reflects the systemic activation of the monocyte/macrophage system. Similarly, normal levels of IL-2 and TNF-[alpha] suggest activation of macrophages rather than activation of T cells.

However, activation of cytokine production is associated with plasma cell cloning or its secretory product, as patients with POEMS syndrome with solitary plasmacytoma can be completely relieved after surgery or local radiotherapy, so some people suspect that monoclonal gamma globulin disease or its lambda Light chain triggers mononuclear/macrophage system production, pro-inflammatory cytokines, and may also be the production of IL-6, IL-1 and TNF- in bone marrow cells of patients with multiple myeloma. Tumor cells themselves can also be produced. The cytokine, TGF-1, is one of the inhibitory cytokines. In vitro animal experiments indicate that inhibition of TGF-1 production is associated with severe systemic inflammatory responses, and TGF-1 has been shown to antagonize pro-inflammatory cytokines. And as an inactivation factor for monocytes/macrophages, by reducing the production of hydrogen peroxide and nitric oxide and the production of IL-6 and TNF-, IL-1, TNF-a and IL-6 Overproduction and a decrease in TGF-1 levels reflect an imbalance in cytokine production and its antagonism, ie, TGF-1 is insufficient to buffer the deleterious effects of cytokines.

Because TNF-, IL-1 and IL-6 have overlapping biological activities and synergistic effects, it is difficult to attribute one symptom to the role of a single cytokine, however, studies suggest that TNF- levels increase for a long time. With inflammatory demyelinopathy, hepatosplenomegaly, endocrine disorders (including low testosteroneemia, gonadotropin-releasing release, adrenal insufficiency, hypothyroidism and hyperprolactinemia), skin changes (eg Hairy, clubbing) and other clinical manifestations (such as edema, lipase inhibition with weight loss, hypertriglyceridemia and diarrhea), elevated levels of IL-1 can act on the central nervous system, causing anorexia and brown Activation of sympathetic nerves in adipose tissue leads to cachexia; activation of the opioid pro-opiomelanocortin gene, which leads to skin pigmentation, and excessive production of IL-1 may also explain multiple endocrine abnormalities (including impaired glucose tolerance, Behavioral and mental disorders and accelerated atherosclerosis), elevated levels of IL-6 and plasma cell proliferation and gamma globulin disease, thrombocytosis, Castlerman's disease, hemangioma and Related to vascular glomerular lesions, IL-1 and TNF- are strong osteoclast activating factors, while TGF- can stimulate osteogenesis, but the latter is associated with the observed bone sclerosis. Not consistent, however, it is curious that low concentrations of IL-1 can stimulate bone formation in vitro, and IL-1 can up-regulate TGF- surface receptors, so osteosclerosis may be due to local cytokine-induced complex metabolic disorders of bone. To.

Recently, it has been recognized that the overproduction of vascular endothelial growth factor is involved in the pathogenesis of this disease. Vascular endothelial growth factor is a powerful, multifunctional cytokine that induces angiogenesis and enhanced microvascular permeability, so it is also called vascular permeability factor. Vascular permeability factor (VPF), which directly and selectively acts on vascular endothelial cells through two vascular endothelial growth factor receptors. The origin of vascular endothelial growth factor is unclear. Vascular endothelial growth factor can be secreted by tumor cells. It can also be secreted by plasma cells and macrophages in chronic inflammatory lesions. Bone damage may be a source of elevated vascular endothelial growth factor levels, as vascular endothelial growth factor levels decrease after local excision and radiotherapy, and vascular endothelial growth factor also It may be secreted by swollen lymph nodes, because in a group of reported cases in Japan, 19/30 lymph node specimens are damaged by Castleman's disease, and elevated levels of vascular endothelial growth factor may also be caused by circulating and proliferation of plasma cells in the bone.

The physiological role of vascular endothelial growth factor may explain the organ enlargement, edema, skin damage and multiple neuropathy in this disease. The enlarged organs are usually liver, spleen and lymph nodes, and common vascular follicular lymph nodes proliferate. It is characterized by obvious vascular proliferation, lymphoid sinus cell proliferation and large mature plasma cells. Vascular endothelial growth factor is a mitogenic factor of dermal microvascular endothelial cells, which can explain skin thickening. The pathology of a patient with skin thickening shows arterioles and Capillary wall thickening but no obvious necrotizing vasculitis, suggesting the presence of low-level occlusive microvascular disease or vascular disease, vascular endothelial growth factor may cause multiple neuropathy, but may not be direct, because the nervous system is not Expression of vascular endothelial growth factor messenger RNA and vascular endothelial growth factor receptor, vascular endothelial growth factor may affect the blood-nerve barrier by increasing microvascular permeability, resulting in increased intra-neuronal pressure after edema, increased blood-nerve barrier permeability, Serum components that are toxic to nerves such as complement and thrombin may cause Damaged, vascular endothelial growth factor can also cause an increase in bone density, which can explain changes in osteosclerosis, osteogenesis depends on angiogenesis, osteoblasts and bone tissue express vascular endothelial growth factor, the latter is an important regulator of osteoblast differentiation Vascular endothelial growth factor can also promote mesangial proliferation and glomerular capillary thickening, and the role of vascular endothelial growth factor in endocrine expression remains unclear.

IL-1 and IL-6 can stimulate vascular endothelial growth factor production, and the combined effects of vascular endothelial growth factor and cytokines are thought to play a special role in the production of various clinical manifestations of this disease.

POEMS syndrome prevention

There is no effective protective measure for this disease, and early detection and early treatment is the best preventive measure.

POEMS syndrome complications Complications Multiple myeloma

Almost all cases have plasma cell proliferative diseases, the most common is sclerosing myeloma, followed by extramedullary plasmacytoma, osteolytic multiple myeloma is rare, followed by endocrine dysfunction, heart failure and cachexia.

POEMS syndrome symptoms common symptoms sensory disturbance amenorrhea thyroid function hypothyroidism thrombocytopenia lymphadenopathy

The onset of the disease is insidious, and the progress is slow. The main clinical manifestations can be summarized into the following 6 groups.

1. Progressive multiple peripheral neuropathy is often the first symptom, which is characterized by symmetric movement of the limbs, sensory disturbance, lower limbs than upper limbs, distal end more severe, often with foot drop, muscle atrophy and tendon reflex weakened or disappeared, set Type of sensory disorder, some patients only have dyskinesia, and cranial nerve damage is mainly optic disc edema.

2. The swelling of the organs is mainly liver and/or splenomegaly, but the liver function is normal, and there are few manifestations of esophageal varices and hypersplenism. Some patients may have lymphadenopathy.

3. The skin changes with diffuse pigmentation (93%), mainly in the limbs and head and face, the areola is black, and there is thickening of the skin, necrosis and hairy (81%). Some patients may have similar dermatomyositis or hard. The skin of the skin disease changes.

4. Endocrine changes manifest as endocrine gland dysfunction, male breast development, impotence, female breast enlargement, galactorrhea, amenorrhea, may also be associated with impaired glucose tolerance and hypothyroidism, edema is more common, mostly depressed, and often For the first symptom, some patients may have pleural effusion, ascites, hypothermia (76%), hyperhidrosis (66%) and clubbing (56%), similar to proliferative glomerulonephritis, acute arterial occlusion , pulmonary hypertension, thrombocytosis and true erythrocytosis, occasionally pericardial effusion.

5. The most common plasma cell proliferative disease is osteosclerotic myeloma, followed by extramedullary plasmacytoma, and osteolytic multiple myeloma is rare.

6. Clinical auxiliary examination features

(1) Serological examination: serum protein electrophoresis may have M protein (75%), but the increase is not significant, mostly IgG, a few are IgA, most of which are -type light chain, rarely chain, some patients can There are double clones (biclonal), polyclonal albumen (polyclonal albumen), anti-nuclear antibodies and rheumatoid factor can be positive.

(2) Cerebrospinal fluid examination: cerebrospinal fluid protein is elevated and the number of cells is normal.

(3) Urine test: There may be a Bence-Jones protein.

(4) bone marrow puncture: visible plasma cell hyperplasia, ossifying myeloma when the proportion of plasma cells is more than 5%, multiple myeloma (osteolytic) more than 10%, lymph node biopsy can be seen plasmacytoma or plasma cells Hyperplasia.

(5) X-ray examination: including bone hardening changes, osteolytic changes or both, of which bone hardening is the most common, mainly involving the pelvis, clavicle, ribs, humerus, femur, thoracolumbar vertebrae and skull, X-ray findings Bone hyperplasia or destruction.

(6) EMG examination: neurogenic damage, slowing of both motor and sensory conduction.

POEMS syndrome check

1. Serological examination of blood M protein positive up to about 75%, due to the low value, often need to be detected by immunoelectrophoresis.

2. Half of the blood patients have low T3T4, and the increase of erythrocyte sedimentation rate and immunoglobulin increase are also common.

3. Lumbar puncture cerebrospinal fluid pressure is slightly increased or normal, protein quantitation is often increased, cell count is normal or slightly increased.

4. Half of the patients with bone marrow puncture showed a slight increase in plasma cells (2% to 5%), and the proportion of plasma cells in patients with myeloma was significantly increased (>10%).

5. Nerve conduction velocity The movement of the limbs, the sensory nerve conduction velocity is slowed down or significantly slowed down, and the bilateral common peroneal nerve conduction velocity is often unable to be elicited.

6. The sural nerve biopsy showed varying degrees of segmental demyelination and/or axonal degeneration.

Diagnostic identification of POEMS syndrome

The syndrome is complicated and diverse due to multiple organ damage. It is often difficult to diagnose early. It must be diagnosed with more than 3 of the main clinical manifestations. Among them, multiple peripheral neuropathy, visceral enlargement and blood M protein positive are especially Important, therefore, for patients with unexplained peripheral nerve damage in the early stage, edema (mainly with lower limbs, face), and patients with enlarged organs should consider the possibility of this syndrome, and conduct relevant tests as soon as possible to facilitate diagnosis.

However, the misdiagnosis rate of this syndrome is high, the main reasons are: rational understanding and perceptual knowledge are not enough, the diagnosis often unilaterally focuses on the specialist disease, neglecting detailed medical history inquiry and comprehensive physical examination.

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