What Is Sézary Syndrome?

Sézary syndrome is a type of cutaneous T-cell lymphoma. It is a rare cancer that begins in the T lymphocytes­ (T-cells), a type of white blood cell. Sézary cells are cancerous and can be found in the blood, skin, and lymph nodes. Sézary cancer can spread to other organs.

Sézary syndrome is extremely rare. It makes up only 3% to 5% of cutaneous T-cell lymphomas. The condition is sometimes called Sézary erythroderma or Sézary’s lymphoma.

Keep reading to learn more about Sézary syndrome, including symptoms, causes, treatment, and more.

Sézary Syndrome Symptoms

Sézary syndrome is characterized by an itchy red rash that covers up to 80% of the body. This rash is called erythroderma. Sometimes the skin rash is in the form of thick patches called plaques, and/or tumors. Plaques are often located on the palms of the hands and soles of the feet, but they can show up anywhere on the body.

Additional signs and symptoms might include:

• Skin swelling
• Enlarged lymph nodes
• Abnormalities of the fingernails and toenails
• Ectropion: Lower eyelids that turn outward away from the eye
• Hair loss
• Body temperature problems
• Enlarged spleen
• Problems with the lungs, liver, and gastrointestinal tract

Sézary syndrome also increases your risk of other lymphomas and cancers. 

It is also possible for Sézary syndrome to present without erythroderma. The research shows that this is rare, but the prognosis tends to be better for people without skin involvement.

Sezary syndrome is staged using the same system as another type of cutaneous T-cell lymphoma called mycosis fungoides.

Sézary Syndrome vs. Mycosis Fungoides

Mycosis fungoides and Sézary syndrome are the two most common types of cutaneous T-cell lymphoma. Much like Sézary syndrome, mycosis fungoides causes a red rash on the skin. Sézary syndrome is considered a variant of mycosis fungoides, but these two cancers are generally classified as different conditions.

In both conditions, T-cell lymphocytes become cancerous and affect skin cells. In mycosis fungoides, the symptoms are limited to the skin.

If these cancerous T-cells are found in blood, they are called Sézary cells and the condition is classified as Sézary syndrome. With Sézary syndrome, there is not only skin involvement but also cells spread through the blood. The cancerous cells may also be found in the lymph nodes and other body tissues.

Mycosis fungoides is staged in phases. 

• Premycotic phase: At this early stage, the rash presents in areas that have not been exposed to sunlight. There are no other symptoms. The rash can last for months or even years. It is often hard to diagnose mycosis fungoides this early.
• Patch phase: At this stage, the rash is thin and red and can be mistaken for eczema.
• Plaque phase: In this phase, a rash appears as papules (small raised bumps) or hardened lesions.
• Tumor phase: This is the phase where tumors form on the skin and some develop ulcers or become infected.

According to the Cleveland Clinic, some experts classify Sézary syndrome as the most advanced stage of mycosis fungoides. Other experts consider Sézary syndrome a separate condition. Neither theory has been confirmed.

Causes

Research shows that Sézary syndrome affects 0.1 per million persons. Cutaneous T-cell lymphomas affect around 10 out of every million people.

An exact cause for Sézary syndrome is unknown. However, most people who develop the condition show chromosomal abnormalities in the DNA of cancerous cells. These abnormalities are not seen in healthy cells.

DNA defects are not inherited and are considered “somatic” because they occur over a person’s lifetime. People with Sézary syndrome have deletions of DNA from chromosomes 10 and 17 or duplications of DNA on chromosomes 8 and 17. Researchers don’t know whether these abnormalities play any role in the development of Sézary syndrome. 

Risk Factors

There is no known inheritance pattern linked to Sézary syndrome. The condition occurs spontaneously in people with no history of the condition. 

Older age might be a risk factor for Sézary syndrome. Anyone can develop the condition, but it’s more likely to affect people over age 60.

With cutaneous T-cell lymphomas, men are more frequently affected. Risk increases with age, with people ages 70 and up having the highest risk.

Blacks have higher incidence rates than Whites; they also tend to be diagnosed at earlier ages and the condition is more aggressive.

Diagnosis

A diagnosis of Sézary syndrome starts with a physical examination of the skin and a medical history, including symptoms. Because Sézary syndrome is such a rare condition, a hematopathologist or dermatopathologist should confirm your diagnosis.

Additional testing to confirm a diagnosis of Sézary syndrome might include:

• Biopsy: A biopsy of the skin, lymph nodes, or bone marrow takes a tissue sample to look for signs of cancer. As with other cancers, a biopsy is the most accurate way to confirm a diagnosis. A pathologist examines the tissue sample under a microscope to look for cancer cells.
• Blood work: A complete blood count and blood smear check red and white blood cells, platelets, and hemoglobin. Blood flow cytometry can identify the kinds of cells in blood or a bone marrow sample, including cancer cells.
• Immunotyping: This test uses a blood or tissue sample to look for markers on cell surfaces and identify different types of lymphomas.
• T-cell (TCR) gene rearrangement test: Using a blood or bone marrow sample, this test looks for problems in the genes that control T-cell function.
• Imaging: Computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) scans can help to determine if cancer has spread to lymph nodes and organs.

Treatment 

Treatment for Sézary syndrome depends on different factors including your age, any other health problems, and the stage at the time of diagnosis.

Your treatment options might include:

Symptom Relief

Medications such as gabapentin and mirtazapine can help manage skin pain and itch. Strong topical steroids can also help.

Anti-staphylococcus antibiotics are prescribed to people whose skin has become infected, cracked, or bleeding.

Long-Term Disease Control

Long-term disease control might include extracorporeal photopheresis and total skin electron beam therapy.

Extracorporeal photopheresis removes blood using a special machine and isolates the white blood cells. The blood cells are then exposed to 8-methoxypsoralen followed by UVA irradiation treatment before the blood is returned to the body.

Total skin electron beam therapy is a type of radiation therapy that treats a person’s entire skin surface. Some newer research shows low-dose total skin electron beam therapy (TSEBT) to be effective for some people in achieving long-term remission.

Long-term remission is uncommon with Sézary syndrome, and TSEBT is a promising treatment that researchers will continue to look at. 

Systemic Therapy

Systemic therapies may be used. One example out of several options is low-dose methotrexate. Methotrexate interferes with folic acid metabolism in cancer cells and is often given to people with cutaneous T-cell lymphomas.

Monoclonal Antibodies

Monoclonal antibodies such as alemtuzumab target CD52 (antigens present on lymphocytes) to deplete circulating T-cells and B-cells. It has been prescribed off-label to treat Sézary syndrome. Other such medications are also used.

Allogeneic Stem Cell Transplantation

Allogeneic stem cell transplantation involves transferring stem cells from a healthy person to the body of someone with Sézary syndrome after high-intensity chemotherapy or radiation therapy. Research shows that allogeneic stem cell transplantation may result in long-term remission in some types of cutaneous T-cell lymphomas.

Prognosis

Sézary syndrome is a very aggressive cancer. Treatment can slow down the disease or cause it to go into remission.

According to the Cleveland Clinic, 24% of people diagnosed with the condition will survive for at least five years after the start of the condition. But for many people with Sézary syndrome, a weakened immune system can make them vulnerable to serious infections and other cancers. 

The best way to improve your prognosis is to see your doctor right away for early diagnosis and treatment. Your doctor is in the best position to answer any questions about your specific outlook with Sézary syndrome.

Summary

Sézary syndrome is a rare type of T-cell lymphoma in which the cancerous Sézary cells are seen in the blood, skin, and lymph nodes. Symptoms include a widespread itchy red rash. It is diagnosed via blood tests, biopsy, imaging, and immunotyping.

Treatment may include extracorporeal photopheresis, total skin electron beam therapy, methotrexate, or stem cell transplant. The condition can be fatal if not treated.

A Word From Verywell

There is currently no definitive cure for Sézary syndrome. Your outlook is often dependent on the stage of the disease at the time you are diagnosed. Other factors that affect your outlook include your age, your overall health, and how well you respond to treatment.

Palliative care can help you to manage symptoms while you treat Sézary syndrome. It can be a valuable resource for alleviating symptoms and treatment side effects and educating you about your illness, treatments, and disease progression. It can also help you cope with feelings and challenges, as well as help in identifying and accessing additional resources.

Talk to your doctor if you want to know more about palliative care and what your options might be.

Frequently Asked Questions

How do you identify a Sézary syndrome rash?

People with Sézary syndrome have erythroderma, a red, very itchy rash that covers large areas of the body. There are Sézary cells in the rash even though the skin cells are not cancerous. The skin problems result from the Sézary cells that enter the bloodstream into the skin.

The Sézary rash is sometimes confused with other skin conditions, including psoriasis or eczema. A person might also experience similar symptoms to other skin conditions, including redness, itchiness, and raised patches called plaques. These plaques can also appear on the palms and soles. The skin may peel and might be inflamed and painful.

A biopsy of the affected skin can confirm the type of rash and its source.

What tests do doctors use to diagnose Sézary syndrome?

A diagnosis of Sézary syndrome starts with an examination of skin and a review of symptoms. Blood work can identify markers on the surface of blood cells. Other testing includes imaging (CT, MRI, or PET) and biopsy.

Imaging can check if cancer has spread to other organs. Lymph node, bone marrow, and skin biopsies take a sample of tissue to examine under a microscope to look for cancer cells. A biopsy is the most accurate way to confirm Sézary syndrome.

What is the survival rate of Sézary syndrome?

Sézary syndrome is a very aggressive cancer, and without treatment, it will be fatal. But treatment can slow down disease progression or cause the disease to go into remission.

Average survival with Sézary syndrome is around two to four years, but this rate is improving due to better and newer treatment options. The five-year survival rate is reported to be around 24%. See your doctor right away to start treatment to ensure the best prognosis and outlook. 

How different is mycosis fungoides?

Like Sézary syndrome, mycosis fungoides is a type of cutaneous T-cell lymphoma. With mycosis fungoides, T-cell lymphocytes become cancerous and affect the skin.

A sign of mycosis fungoides is a red rash on the skin that worsens with phases and eventually causes patches, plaques, and/or tumors on the skin. Some experts think Sézary syndrome is advanced mycosis fungoides, but no clinical study has confirmed this.