What Is POEMS Syndrome

Introduction 

Definition of POEMS syndrome 

POEMS syndrome is a complex disorder that can affect multiple systems of the body. It is a result of when abnormal levels of plasma cells are produced causing the body to accidentally attack normal cells of the immune system.¹ POEMS syndrome is an acronym for Polyneuropathy, Organomeagly, Endocrinopathy, Monoclonal Protein, and Skin changes.

Plasma cells are a key component of the immune system. They are a type of white blood cell called B lymphocytes that are produced in the bone marrow. They are responsible for attacking and destroying bacteria and viruses when they enter the body.

POEMS syndrome is a rare disorder affecting approximately 0.3 in every 100,000 individuals, and it is more commonly seen in males in their 50s and 60s,  according to a national survey conducted in 2003 in Japan. It was thought to most commonly affect patients of Japanese descent, however, as more research comes to light, it has been reported that populations within countries like France, the USA, China, and India are also significantly affected by POEMS syndrome.²

The exact cause is not fully understood but research suggests that a cytokine (a chemical messenger), called Vascular Endothelial Growth Factor (VEGF), released from plasma cells plays a role in this disease.³

Clinical features 

Each major feature of POEMS syndrome is defined below:

Polyneuropathy

Polyneuropathy, also known as peripheral neuropathy, is a disorder of the peripheral nervous system. Polyneuropathy is the most common symptom associated with POEMS syndrome, affecting the majority of patients.¹

Two components comprise the nervous system: the central nervous system, consisting of the brain and spinal cord, and the peripheral nervous system, which includes nerves that branch out of the spinal cord and extend to the rest of the body. 

The peripheral nervous system can be subdivided into two subsystems: somatic and autonomic. They can be further subdivided into different types of nerves: 

• Sensory: Carrys sensory information like touch, vision, taste, and smell to the brain
• Autonomic: Regulates unconscious processes like our heartbeat, digestion, and respiration 
• Motor: Responsible for voluntary movement

Nerve damage and symptoms

When these nerves are damaged by polyneuropathy, it can cause pain, numbness, or tingling in the extremities such as the hands, feet, and arms.¹

If the motor nerves are damaged, it may cause the muscles to weaken or even become paralysed. 

Sensory nerve damage causes many symptoms such as losing our ability to feel touch, vibrations, pain, or temperature changes. This can seriously damage your quality of life. Although pain is an unpleasant signal, it is essential for our survival and promotes avoidance behaviour. If we are unable to feel pain, we may cause damage to our body without realising it.

Organomegaly

Organomegaly refers to the unusual enlargement of the organs. Common organs affected include:¹

• Liver (hepatomegaly)
• Spleen (splenomegaly)
• Lymph nodes (lymphadenopathy)

Endocrinopathy

Endoocrinophathy refers to the abnormal production of hormones like sex hormones, insulin, and thyroid hormones, resulting in diseases like polycystic ovary syndrome (PCOS), hypothyroidism (underactive thyroid glands), and diabetes mellitus. 

Patients are most commonly affected with hypothyroidism.⁴

Males may experience enlarged breasts and erectile dysfunction (inability to maintain an erection during sex). Females can experience irregular or absent periods and unusual milk discharge from the nipples.¹

Effects on the endocrine system

Diseases affecting the endocrine system can affect the individual physiologically and psychologically. As there is a hormonal balance with these conditions, they can cause problems in growth and development, metabolism, mood, and sexual function.⁵

Monoclonal protein

Monoclonal proteins are produced by plasma cells in the bloodstream.

The overproduction of monoclonal proteins released from plasma cells can cause tumours and cause your bones to harden or thicken.¹

Skin Changes

POEMS syndrome can cause abnormalities of the skin, these include:

• Hyperpigmentation (dark patches on the skin)
• Excessive hair growth
• Nail changes (white discolouration or clubbed fingernails)
• Less or more sweating than usual
• Thickening of the skin

Diagnosis 

A variety of diagnostic tools are used to confirm the diagnosis of POEMS syndrome. Using a single diagnostic tool can be challenging and can easily lead to a misdiagnosis. 

Not all of the five characteristics of POEMS syndrome must be present to make a diagnosis.⁶ A diagnosis is made if the symptoms meet specific diagnostic criteria. 

The diagnosis must have all of the following:²

• Polyneuropathy
• Monoclonal plasma cell disorder

And 1 or more of these  features:

• Castleman’s disease
• High levels of VEGF
• Sclerotic (rigid) bone changes
• Any one or more of the features of POEMS syndrome

Clinical evaluation 

A clinical evaluation may be required, which consists of a physical examination and a review of the medical history. 

Laboratory tests

Your healthcare provider will request a blood or urine sample to identify elevated levels of M protein and VEGF. High levels of VEGF increase the amount of molecules, like drugs, nutrients, and water, passing through the blood vessels. This is known as vascular permeability and causes fluid accumulation. 

Imaging studies 

Diagnostic imaging tools like MRI, CT, and X-ray scans allow us to see whether your bones have hardened or thickened. This is caused by the M protein.

Treatment 

The main goal of treatment is to slow the growth of plasma cell neoplasms and the release of pro-inflammatory (increased inflammation can lead to unpleasant symptoms and life-threatening conditions) and pro-angiogenic cytokines (accelerating blood vessel formation).

As soon as a diagnosis is confirmed, you should expect to start treatment right away. Your condition can progressively worsen if you don’t receive any treatment. 

Treatment for this disease has greatly improved since the 1980s and many go on to lead a normal life, with a median survival of 14 years.¹

Treatment may consist of radiation therapy, stem cell transplant, drug treatment, and surgery. Your healthcare provider will discuss the best course of treatment for you.

Symptomatic management

Pain relief for neuropathy

You may be given pain relief medications to manage nerve pain. Common over-the-counter painkillers like paracetamol and ibuprofen do not typically work with nerve pain so other medicines like tramadol are used as they are stronger and more effective. Painkillers like tramadol are only prescribed for a short period as they can be addicting.

Caution is required as you may experience mild adverse side effects like constipation and dizziness. 

Addressing endocrine abnormalities

Medication is typically the first line of therapy for individuals with endocrine abnormalities.  Medication can help rebalance hormonal levels and manage symptoms. 

If you have PCOS, typical treatments may consist of lifestyle changes and medications. 

Immunomodulatory therapy 

The use of immunomodulatory drugs, like Thalidomide and Lenalidomide, are greatly effective in the treatment of multiple myeloma (MM), a type of blood cancer developed in the plasma cells. Immunomodulatory drugs may prove effective for the treatment of POEMS syndrome.

You may be given a single treatment or a combination of immunomodulatory drugs. One study found that the use of lenalidomide greatly improved the symptoms and showed a decrease in polyneuropathy, organomegaly, and excess fluid buildup.⁷

The choice of treatment will be discussed with your doctor and reviewed based on how well you respond to treatments. Other immunomodulatory drugs like thalidomide and bortezomib have been shown to worsen neuropathy so they are not often used in patients with POEMS syndrome. 

Chemotherapy and stem cell transplantation

You may receive chemotherapy to destroy the plasma cell neoplasm andmanage symptoms. In addition to your chemotherapy, autologous stem cell transplantation (ASCT) may be offered in combination to improve overall outcomes.⁸

If diagnosis reveals frequent bone changes in your body or the bone marrow is damaged, this means that your body cannot produce healthy blood cells. ASCT is used to effectively bring your blood count back to normal, improving neuropathy and overall enhancing your quality of life.¹

Supportive care 

Physical therapy 

Doing gentle physical activity like stretching and yoga may help manage your symptoms.

Management of associated complications

Addressing other complications associated with POEMS syndrome should be a priority for patients. Discussing your symptoms and your overall condition with your doctor can help them decide the appropriate course of treatment to address any concerns. 

Prognosis 

Variability in outcomes 

The prognosis for POEMS syndrome is good in comparison with multiple myeloma. The management and therapies for POEMS syndrome have greatly improved since the 1980s, when the median survival was 33 months. Today, approximately 82% of newly diagnosed patients can expect to livefor more than 10 years. 

Patients with nail clubbing or peripheral fluid overload after treatment have shorter survival expectations, approximately 31 months and 79 months respectively. 

Treatments to address this problem through clinical trials have not yet been discussed and are potentially challenging due to the complexity of this disease.⁷

Impact on quality of life 

You may experience discomfort, shock, denial, or anxiety along with physical pain. If you are experiencing difficulties, speak to your healthcare provider so they know how to best support you. They may refer you to a psychologist. Some of the ways you can take care of yourself are by doing activities that you enjoy doing or joining a support group.

Long-term monitoring and follow-up

Scheduling follow-up appointments is necessary to see how well you are doing after your treatment. It’s recommended to follow up at least every 3 months for several years so that doctors can monitor your condition. If there's a relapse, they can treat and manage your condition as soon as possible. 

FAQs

Is POEMS syndrome a type of cancer?

No, not all plasma cell disorders are cancerous, they can also be benign (non-cancerous). 

Summary

POEMS syndrome is a chronic and rare disorder affecting multiple systems of the body, predominantly affecting the nerves in the extremities such as the hands, feet, and legs. POEMS syndrome is an acronym for polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes.

Not all 5 of these characteristics must be present to make a diagnosis. A thorough diagnosis using a wide range of diagnostic tools like imaging techniques and blood tests will be used to decide the appropriate treatment. 

The type of therapy will be chosen depending on how localised the abnormal plasma cells are. Treatments consist of radiotherapy, chemotherapy, surgery, and stem cell transplant, and improvements in the condition are usually gradual. Treatment has advanced since the 1980s and will continue to accelerate as more research on POEMS syndrome continues.