POEMS syndrome is a rare variation of multiple myeloma with concomitant paraneoplasia. Elevated levels of vascular endothelial growth factor (VEGF) can be detected in almost all patients.
What is POEMS syndrome?
POEMS syndrome is a paraneoplastic disorder. The acronym POEMS stands for the English names of the symptoms polyneuropathy, endocrinopathy, M gradient, skin changes, and organomegaly. It is not yet known how POEMS syndrome develops. The syndrome most commonly occurs between the ages of 50 and 60. It is often confused with chronic inflammatory demyelinating polyneuropathy. This is a dangerous misdiagnosis, because the therapy of chronic inflammatory demyelinating polyneuropathy is absolutely ineffective in POEMS syndrome. POEMS syndrome is treated with high-dose chemotherapy and stem cell transplantation.
Causes
The origin of the multisystem disease is still unclear. However, the cytokine VEGF appears to play a critical role in pathogenesis. In patients with POEMS syndrome, serum VEGF levels are markedly elevated. It also correlates with disease activity. This means that the higher the VEGF level, the more pronounced the symptoms. VEGF is an endothelial growth factor that is normally required for the formation of new vessels and new endothelial cells. In POEMS syndrome, the increased serum VEGF level appears to be due to increased plasma cell activity. At higher levels, VEGF apparently increases vascular permeability. This results in fluid retention in the tissues, leading to nerve damage.
Symptoms, complaints, and signs
POEMS syndrome is a multisystem disorder. Accordingly, the disease has many faces. Not every patient also presents with every symptom. Many patients complain of symptoms that can be attributed to peripheral nerve damage. This damage is also called peripheral polyneuropathy. There are sensory disturbances in the extremities (acroparesthesia), as well as insensations and motor deficits. Later, pressure sensitivity of the nerves also becomes apparent. This can manifest itself, for example, as calf pressure pain. Nutritional disorders in the form of skin damage can also result from damage to the autonomic nerves. Likewise, in all patients the syndrome manifests itself through a monoclonal plasma cell disease. In this case, the composition of the proteins in the blood plasma changes. In most cases, an immunoglobulin increases pathologically. One of the most common monoclonal plasma cell diseases occurring in POEMS syndrome is multiple myeloma. In most cases, it is an IgG plasmacytoma. The plasma cells in the bone marrow proliferate and produce complete or incomplete immunoglobulins of type G. The destructive spread of the cell clones into the bones displaces the other hematopoietic stem cells. This results in anemia with symptoms such as fatigue, susceptibility to infection, and impaired concentration. Since fewer platelets are also produced, patients have an increased tendency to bleed. The immunoglobulins also inhibit the activity of osteoblasts in the bones. Dissolution of the bone occurs with a subsequent increase in blood calcium levels. Osteolysis is noticeable in patients in the form of back pain or shoulder pain. The hypercalcemia can damage the kidney. Eventually, even renal insufficiency develops. Many patients with POEMS syndrome also have Castleman’s disease. Here, one or more lymph nodes are enlarged due to hyperplasia. Endocrinopathy may also develop during the course of the disease. In an endocrinopathy, hormone production, hormone regulation or hormone action are disturbed. Known endocrinopathies are Graves’ disease, type 2 diabetes mellitus, Cushing’s syndrome, hypothyroidism and hyperthyroidism. In many patients, the disease initially manifests itself in the form of skin lesions. These vary from patient to patient and have neither a clearly defined appearance nor a preferred location.
Diagnosis and course of the disease
For diagnostic purposes, the symptoms of POEMS syndrome can be divided into mandatory criteria, major criteria, and minor criteria. For the diagnosis of POEMS syndrome to be made, the two mandatory criteria must be met.In addition, one major and one minor criterion each must be present. The two mandatory criteria are peripheral polyneuropathy and plasma monoclonal cell disease. Major criteria include elevated serum VEGF level, Castleman disease, and sclerotic bone lesions. Secondary criteria include organomegaly, skin changes, erythrocytosis, thrombocytosis, endocrinopathy, and congestive papules and excess volume outside the vessels.
Complications
POEMS syndrome does not necessarily lead to complications or discomfort in every case. In many cases, affected individuals can live a symptom-free life. However, paralysis and other sensory disturbances do occur because of the syndrome in most cases. It may also affect the patient’s daily life, making them dependent on other people for help in their lives. Furthermore, pain may occur in the calves. The nerves themselves are irreversibly damaged and cannot be restored. Likewise, patients suffer from concentration disorders and also fatigue due to POEMS syndrome. Due to the weakened immune system, patients are not infrequently susceptible to infections and various diseases. Back pain can also occur with this disease. If POEMS syndrome is not treated, it usually results in kidney problems and, in the worst case, kidney failure. POEMS syndrome cannot be treated causally. For this reason, only the symptoms are treated. The life expectancy of the affected person is usually reduced by POEMS syndrome.
When should you see a doctor?
People who suffer from extremity discomfort and have sensory disturbances should see a doctor. If there are disorders of the musculoskeletal system, insensitivity or unsteadiness of gait, a doctor is needed. If there is pain on pressure, complications with locomotion or restriction of movement, a doctor is needed. If the discomfort persists for an extended period of time or spreads, the affected person needs help. A susceptibility to infection, pain in the back or shoulders indicate health impairments that need to be investigated and treated. An increased tendency to bleed should be presented to a physician. If existing bleeding cannot be stopped, seeking medical treatment is necessary. Fatigue, exhaustion and a drop in physical as well as mental performance levels should be discussed with a physician. Disturbances in concentration as well as attention, a reduced sense of well-being and a decrease in the quality of life should be discussed with a physician. If the affected person suffers from disturbances in urination or pain in the area of the kidneys, a comprehensive examination is necessary to clarify the cause. Blood in the urine or a general feeling of malaise is considered worrisome. If the affected person suffers from enlarged lymph and a feeling of illness over a longer period of time, consultation with a physician is advisable.
Treatment and therapy
The treatment of POEMS syndrome is based on the guidelines for the therapy of plasmacytoma. This is multimodal and interdisciplinary. The disease is not curable but is treatable. The goals of therapy are to attenuate symptoms and prolong survival. In addition, possible complications should be prevented. In plasmacytoma from stage II and in patients over 65 years of age, chemotherapy is given according to the Alexanian regimen with melphalan and prednisone. This should result in a decrease in the immunoglobulin concentration in the blood and a 50 percent reduction in plasma cells in the bone marrow. With this partial normalization of laboratory values, the patient’s condition also improves. Alternatively, thalidomide or bortezomib can be used as chemotherapeutic agents. In younger patients, the gold standard is autogenous stem cell transplantation from bone marrow. This must be combined with myeloablative high-dose chemotherapy. More gentle is allogeneic stem cell transplantation from histocompatible bone marrow. However, the recurrence rate is higher here. Patients also receive biphosphonates to attenuate bone dissolution. Pamidronate is infused monthly for this purpose. Hypercalcemia is also treated with medication.
Outlook and prognosis
The prognosis for patients with POEMS syndrome is difficult.In many cases, the signs and symptoms present are misinterpreted as chronic inflammatory demyelinating polyneuropathy. The problem is that treatment against it remains ineffective. Symptomatic treatment of the syndrome that is actually present is omitted. This can lead to dramatic consequences for those affected. The paraneoplastic POEMS syndrome reduces the survival time in any case. The leading symptoms are polyneuropathy, organomegaly, endocrinopathy, M gradient and skin changes. However, these symptoms usually become more frequent later in life. In this respect, the limitation of life in POEMS syndrome need not always be considered serious. Since the causes for the development of POEMS syndrome are unknown, targeted prevention at a younger age is often not possible. Multimodal therapies are most often used to treat POEMS syndrome. These aim to improve the quality of life. Currently, the only therapeutic options are administration of high-dose chemotherapeutic agents, or for younger affected individuals, stem cell transplantation as the gold standard. If left untreated, the prognosis of POEMS syndrome worsens. Renal symptoms and renal insufficiency may develop. These can only be resolved by dialysis or organ transplantation. There may also be an increased tendency to bleed, or a weakened immune system in affected individuals. Treatment strives to prevent complications, and prolong survival.
Prevention
To date, it is not clear how or why POEMS syndrome develops. Therefore, effective preventive measures do not exist.
Follow-up
In most cases, patients with POEMS syndrome do not have any special options for aftercare, as this disease should primarily be treated comprehensively and properly by a physician. Only with early detection and subsequent treatment of the disease can further complications be prevented. The earlier a doctor is consulted, the better the further course of this disease usually is. As a rule, those affected by POEMS syndrome are dependent on taking various medications that can permanently alleviate the symptoms. It is always important to ensure that the medication is taken correctly and also that the correct dosage is given. If there are any questions or if anything is unclear, a doctor should always be consulted first. In many cases, patients are also dependent on help and care from their own family due to the disease. In this context, loving and intensive conversations also have a positive effect on the further course of the disease and can prevent depression or other mental illnesses. In some cases, however, POEMS syndrome reduces the life expectancy of the affected person.
Here’s what you can do yourself
This disorder has many faces, so it may have taken a long time to be diagnosed. This is just as stressful for many patients as the therapies that now follow or even the fact of being dependent on the help of others. Therefore, it is definitely advisable to seek psychotherapeutic support during this time. Many patients also find it relieving to join a self-help group. Since POEMS syndrome is a variant of multiple myeloma, a list of all self-help groups can be found on the Internet on the website of “Myelom Deutschland” (www.myelom-deutschland.de/selbsthilfegruppen/). Since POEMS syndrome is associated with susceptibility to infections, those affected can help themselves by strengthening their immune system with a healthy lifestyle. On the one hand, this means that patients should not smoke and drink as little alcohol as possible so as not to cause additional damage to their bodies. On the other hand, a healthy lifestyle also includes a diet that contains sufficient vitamins and minerals. A regular sleep-wake cycle and plenty of exercise in the fresh air also support the immune system. Because eighty percent of all immune cells are located in the intestine, the administration of probiotics is also recommended. These are dietary supplements containing living microorganisms. They multiply in the intestine and are said to help maintain the immune system there.