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Sézary Syndrome

Last updated Dec. 22, 2018

Approved by: Krish Tangella MD, MBA, FCAP

Sézary Syndrome (SS) is a rare, aggressive form of T-cell non-Hodgkin’s lymphoma that can affect the skin. It generally occurs in adults over the age of 50 years.

What are the other Names for this Condition? (Also known as/Synonyms)

  • Sézary Disease
  • SS (Sézary Syndrome)

What is Sézary Syndrome? (Definition/Background Information)

  • Sézary Syndrome (SS) is a rare, aggressive form of T-cell non-Hodgkin’s lymphoma that can affect the skin. It generally occurs in adults over the age of 50 years
  • Sézary Syndrome can originate and spread, either within the lymph nodes, or in other regions, such as the skin, thyroid gland, bone, breast, testes, and the gastrointestinal tract
  • Sézary Syndrome can result in the formation of skin lesions (red itchy rashes) that may ulcerate and cause secondary infections. Generalized symptoms, such as weight loss, fatigue, anemia, fever, and night sweats can also be present
  • Sézary Syndrome is normally diagnosed using a biopsy of the involved skin or using a biopsy of the swollen lymph nodes or affected organ. Other examinations and tests may be performed to assess the severity and spread of the condition
  • The treatment depends upon the stage of Sézary Syndrome. It may be skin-directed treatment (such as the use of topical medications, phototherapy, or local radiation therapy), or mostly systemic therapy (through a combination of chemotherapy, radiation therapy, and surgery), since other organs are involved
  • The prognosis depends on many factors including the type of lymphoma, progression of the condition, response to treatment, and overall health of the individual. In general, the prognosis of Sézary Syndrome is poor despite treatment

General information on lymphoma and lymphocytes:

  • Lymphoma is a type of cancer stemming from uncontrollably dividing lymphocytes (type of white blood cells). There are two types of lymphomas:
    • Hodgkin lymphoma
    • Non-Hodgkin lymphoma
  • Lymphocytes are the main white blood cells found in the lymph, which is the fluid of the lymphatic system; just as blood is the fluid of the circulatory system
  • Lymphocytes are made in bone marrow, and can develop into either B-cells or T-cells. T-cells mature in the thymus; Sézary Syndrome arises from cancerous T-cells
  • Lymph results from filtration of blood as it travels to and from tissues. Lymph is colorless because it lacks red blood cells; instead, it contains lymphocytes. It is central to the immune system
  • There are 3 different kinds of lymphocytes:
    • T-lymphocytes or T cells: They help combat infections and abnormalities within the cells (cell-mediated immunity). They fight viruses and cancerous cells
    • B-lymphocytes or B cells: They produce antibodies that are bodily defense proteins, which target foreign invaders outside the cells (humoral immunity). They fight bacterial cells, cell fragments, and other immunogenic elements
    • Natural killer cells or NK cells: They perform diverse functions related to both cell-mediated and humoral immunity. They also scout for cancer cells, a process called immune surveillance

Who gets Sézary Syndrome? (Age and Sex Distribution)

  • Sézary Syndrome is a rare type of lymphoma that generally affects adults over the age of 50 years. The condition has never been reported in children, indicating that it typically does not occur in them
  • Both males and females are affected, though there is a male predominance
  • All races and ethnic groups can be affected
  • About 1 in 20 cases of cutaneous T-cell lymphoma is Sézary Syndrome

What are the Risk Factors for Sézary Syndrome? (Predisposing Factors)

The risk factors for Sézary Syndrome include:

  • Cigarette smoking for 40 years or more
  • Skin conditions such as eczema
  • Family history of multiple myeloma
  • Individuals in occupations such as painting, carpentry, farming, and pottery and ceramics
  • Viral infections
  • Caucasians

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one's chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Sézary Syndrome? (Etiology)

Lymphocytes are a type of white blood cells that are responsible for providing immunity in the human body. B-cells and T-cells are the two different types of lymphocytes. When under certain circumstances, the lymphocytes grow and multiply abnormally, it leads to a condition called as lymphoma, which is a most common type of cancer. There are 2 types of lymphoma:

  • Hodgkin lymphoma
  • Non-Hodgkin lymphoma

The cause of Sézary Syndrome is generally unknown. There may be certain genetic mutations/defects, such as translocation, which is a juxtaposition of regions of chromosomes resulting in:

  • Change of regulatory elements of certain cancer-causing genes called as oncogenes, which can lead to increased production of their mRNA (overexpression), thus increasing their protein levels
  • Exchange of protein coding regions of gene, giving rise to new proteins that can stimulate the inappropriate growth of cells

It is believed that the abnormal development of lymphocytes gives rise to cancerous cells leading to the formation of this condition. Nevertheless, how this occurs and the factors that cause it remain under investigation.


  • Sézary Syndrome is non-contagious and is not transmitted from one individual to another. One cannot contract the condition through close physical interaction with the affected individuals
  • When the tumor is primarily confined to skin, it is known as Mycosis Fungoides; but, when the tumor cells enter into blood, it is called Sézary Syndrome

What are the Signs and Symptoms of Sézary Syndrome?

There are 3 key features that define Sézary Syndrome and these include:

  • Severe itching
  • Red skin
  • Enlarged lymph nodes

Other signs and symptoms may include:

  • The presence of a skin nodule, patch, or rash
  • The lesion usually occur as well-circumscribed patches and plaques
  • Palmoplantar keratoderma, which is a thickening of the skin of the palms and soles; peeling of skin on the palms and soles
  • Abnormality of the fingernails and toenails
  • Abnormality of the eyelids; it may be turned outwards (known as ectropion)
  • Hair loss is a common symptom
  • The skin lesions can grow, ulcerate, and spread to other parts of the body
  • The skin signs and symptoms may occur all over the body

Sézary Syndrome affects many body systems and organs outside the skin. In such cases, the following general signs and symptoms may be seen, which include:

  • Individuals may not be able to maintain their body temperature
  • Unintentional weight loss; changes in appetite
  • Fatigue and weakness, headache
  • High temperatures and excessive night sweats (may be recurrent)
  • Anemia (low red blood cell count)
  • Low lymphocyte count, established by a blood test
  • Frequent infections
  • Trouble breathing
  • Low blood pressure
  • Back pain
  • Swelling of the legs
  • Abdominal pain and swelling; constipation
  • Frequent urination

Depending upon the specific organ or area involved, the signs and symptoms may include:

  • ‘Non-painful’ swelling of lymph nodes in the neck, armpits, or groin
  • Associated autoimmune disorders, which can cause joint and muscle pain, heat intolerance, recurrent rashes, abdominal pain, and a general feeling of illness
  • If the lymphoma involves the brain, then neurological symptoms such as:
    • Confusion
    • Tinnitus
    • Hearing and visual impairment
  • If the lymphoma involves the gastrointestinal tract, then GI symptoms such as:
    • Ulcers
    • Diarrhea
    • Inflammation
    • GI bleeding
  • The cancerous cells may be found in the blood, lymph nodes, liver, spleen, and bone marrow
  • Involvement of the bone
  • Liver and spleen enlargement
  • Joint inflammation and fluid accumulation (edema) can occur, if the lymphoma involves the joints

How is Sézary Syndrome Diagnosed?

Sézary Syndrome diagnosis is performed by obtaining biopsy samples from the affected region and examining them under a microscope to detect the cancerous cells. General methods to aid in the study-diagnosis include:

  • A thorough physical examination and a complete medical history, which is very important
  • Blood tests that may include:
    • Complete blood cell count (CBC) blood test
    • Absolute lymphocyte count on peripheral blood
    • Liver function blood test (LFT)
    • Lactate dehydrogenase (LDH) blood test
  • If the lymphoma involves the lymph nodes then, biopsies of enlarged lymph nodes are taken and examined in a lab to determine if the cells are malignant or benign. The biopsies may be performed under general or local anesthesia. Normally, the entire lymph node is removed to help determine the subtype of lymphoma
  • Biopsy from the affected area or a skin biopsy:
    • A biopsy of the tumor is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis
    • Biopsy specimens are studied initially using Hematoxylin and Eosin staining. The pathologist then decides on additional studies depending on the clinical situation
    • Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, molecular testing, flow cytometric analysis and very rarely, electron microscopic studies, to assist in the diagnosis
    • Radiological imaging may be performed to determine the extent of lymphoma in the body including:
      • X-ray of the affected region
      • Ultrasound scan of the affected region
      • Computerized tomography (CT) scan of the affected region
      • Vascular radiological studies
      • Whole body bone scan
      • Whole body CT-PET scans to determine how far the lymphoma has spread, by checking the size and metabolic rate (a reflection of uncontrolled growth) of lymph nodes, throughout the body. This can also help determine, if the cancer has spread to other organ systems
      • Brain MRIs are used if neurological symptoms are present, which can help determine if the cancer has spread to the brain, or to tissues that cover the brain
  • Bone marrow aspiration and biopsy is performed and sent to a laboratory for a pathological examination, to determine if the bone marrow is involved. Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, histochemical stains, molecular testing, and very rarely electron microscopic studies. However, a bone marrow biopsy is not needed in the early stages of the condition
  • Flow cytometry to identify cells as they flow through an instrument, called a flow cytometer. Flow cytometry measures the number and percentage of cells in a blood sample, and cell characteristics such as size, shape, and the presence of biomarkers on the cell surface. This method helps to sub-classify the condition and also to detect residual levels of disease after treatment. This tool can help in diagnosing relapse and restart treatment as needed
  • Fluorescence in situ hybridization (FISH): It is a test performed on the blood or bone marrow cells to detect chromosome changes (cytogenetic analysis) in blood cancer cells. The test helps in identifying genetic abnormalities that may not be evident with an examination of cells under a microscope
  • Immunophenotyping to identify a specific type of cell in a sample, which can help determine the best treatment course to be followed
  • Polymerase chain reaction (PCR): It is used to measure the presence of certain biomarkers in blood or bone marrow cells. The test is ultrasensitive and detects extremely low amounts of biomarkers remaining in blood, which can be missed by cytogenetic methods, such as FISH, karyotype, or flow cytometry. PCR allows a more sensitive follow-up of patients in remission and can help determine whether additional treatment is necessary
  • Lumbar puncture to determine if the brain is involved
  • In addition, the cerebrospinal spinal fluid (CSF) may be collected by inserting a needle in the spine and subjected to microscopic, flow cytometric, PCR, and biochemical analysis, to diagnose central nervous system (CNS) involvement, if any
  • Exploratory laparoscopy (diagnostic laparoscopy) may be required, if gastrointestinal symptoms are present. In this procedure, the abdomen is examined using a minimally-invasive technique, and a tissue biopsy and tissue for culture obtained. Minimally-invasive approaches help decrease complications and the length of stay at the hospital. A diagnostic laparoscopy is also helpful in staging of the tumor. Nevertheless, this procedure is not very much used

Note: Differential diagnoses, to eliminate other tumor types are often considered, before arriving at a definitive diagnosis.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Sézary Syndrome?

The complications due to Sézary Syndrome may include:

  • Involvement to local and distant organs: It can spread from the lymph nodes to other parts of the body
  • Loss of function of the organ/area to which the cancer has spread
  • Secondary bacterial infections are common
  • Individuals are at a higher risk for developing other cancers
  • Weakened immune system (or immunosuppression) can be a complication of Sézary Syndrome, which can become more severe during treatment. Due to this, individuals are more vulnerable to infections; there is an increased risk of developing serious complications from such infections
  • If the condition spreads to the brain and central nervous system, it can give rise to:
    • Inflammation of the meninges or brain (that can be lethal)
    • Headache
    • Vision changes
    • Facial numbness
  • If the abdomen is affected, it can cause intestinal obstruction that results in urine outflow obstruction and kidney damage
  • Risk of development of other types of lymphomas
  • Occasionally, Sézary Syndrome can transform into a more aggressive form of lymphoma

There may be complications related to chemotherapy used in treating the condition, which may include:

  • Side effects such as dizziness, vomiting, appetite loss, mouth ulcers, and hair loss
  • By damaging healthy cells, the individual is more open or vulnerable to secondary infections
  • The treatment can also cause infertility in men and women. Hence, measures to protect the individual’s fertility must be considered, before starting chemotherapy

How is Sézary Syndrome Treated?

Once a definitive diagnosis of Sézary Syndrome has been made, staging is used to describe how far the cancer has spread. The staging can help describe:

  • How many lymph nodes are affected
  • Their locations in the body
  • And, if other organs are being affected

Staging is important because different treatment regimens are necessary, depending on the progression of the lymphoma. The staging of Sézary Syndrome is as follows:

Stage I Sézary Syndrome: Presence of non-cancerous, but abnormal lymphocytes in blood.

  • Stage IA: The skin lesions (patches, papules, plaques) cover less than 10% of the body area
  • Stage IB: The skin lesions cover more than 10% of the body area

Stage II Sézary Syndrome: Presence of non-cancerous, but abnormal lymphocytes in blood.

  • Stage IIA: The skin lesions (patches, papules, plaques) can cover any percentage of the body area. The cancer has not affected the lymph nodes, but they are enlarged
  • Stage IIB: The presence of single or multiple tumors, over 1 cm in size (or larger), on the skin. The cancer has not affected the lymph nodes, but they may be enlarged

Stage III Sézary Syndrome:

  • Presence of non-cancerous, but abnormal lymphocytes in blood
  • The skin is red and the skin lesions (patches, papules, plaques) may be found almost on the entire body
  • The cancer has not affected the lymph nodes, but they may be enlarged

Stage IV Sézary Syndrome:

  • The skin is red on most part of the body surface; the skin lesions (patches, papules, plaques) or tumors cover most part of the body area
  • The cancer may have affected the lymph nodes, which may be enlarged
  • There may be the presence of cancerous lymphocytes in blood

The treatment is dependent upon the stage and location of the tumor. There are 2 main treatment protocols for Sézary Syndrome and these include:

  • Skin-directed therapy
  • Systemic therapy

Skin-directed therapies are used (and often in combination) when the tumor is mainly confined to the skin. This may include the following treatment measures:

  • Sunlight therapy (or exposure to ultraviolet light)
  • Use of topical steroids and chemotherapy
  • Systemic chemotherapy
  • Radiation therapy to affected (local) skin area
  • Other systemic treatment measures, such as the use of interferons, retinoids, etc.
  • Biological therapy

Systemic therapy is generally used for higher or advanced stage tumors. A combination of treatment measures may be effectively used to treat the condition. It may include the following:

  • Chemotherapy: This approach uses a combination of drugs to kill the cancerous cells and can be used in patients, for all stages of Sézary Syndrome
    • There can be severe side effects including fatigue, nausea, hair loss, anemia, high risk of infection, and drug-specific reactions
    • Many T-cell lymphomas can be resistant to chemotherapy. It can also damage healthy cells
    • Chemotherapy can be administered as a pill, liquid, shot, or intravenously

Note: Men and women in child-bearing age would greatly benefit from counseling regarding fertility issues. Some chemotherapy agents can cause infertility in both men and women. There can be permanent damage to the testicles and ovaries, harming their ability to produce sperms or ova. In men, sperm banking can be considered before initiating therapy. In women, in many cases, due to urgency of starting chemotherapy, it is often difficult to perform ovum banking. However, if there is sufficient time prior to chemotherapy, ovum banking may be performed. The healthcare provider may help assess the risk-benefit analysis, depending upon each individual’s specific circumstances.

  • Radiation: Radiation therapy is the use of high-energy radiation waves to kill cancer cells, by destroying their DNA
    • This treatment modality is generally used for early stage lymphomas. It is most commonly used in combination with chemotherapy
    • The radiation may be administered by a machine placed outside the body, or by placing a radioactive material inside the body
    • The side effects of radiation therapy include nausea, vomiting, fatigue, pain, risk of cancer later in life, and risk of heart disease
    • Radiation can damage healthy cells in addition to cancer cells, causing further complications
  • Surgery: After initial biopsies to diagnose Sézary Syndrome, surgery is a very uncommon treatment option, because lymphomas are systemic and might have already spread to more than one lymph node in most patients. Under such circumstances, removing all the affected lymph nodes would be extremely difficult
  • Supportive treatment: Steroids, blood transfusions, anti-nausea medications, and antibiotics, may be used as supportive therapy. In combination with other treatment measures, these can help combat the symptoms of immunodeficiency

If Sézary Syndrome is not fully responsive to treatment, or if the chance of recurrence is high, then bone marrow transplantation or stem cell transplantation can be considered.

  • Bone marrow transplantation: Typically systemic cases of MF may be treated by administering high doses of chemotherapy or radiotherapy. But, high doses of chemotherapy drugs will also damage the bone marrow, preventing it from making any blood cells. Hence, before starting high-dose chemotherapy, the physicians may take out some of the patient’s bone marrow and freeze/preserve it. Collecting the bone marrow is called a bone marrow harvest. The bone marrow is then stored. After high dose chemotherapy or radiation, the bone marrow is thawed and injected back into patient through a drip (transfusion). This is called an autologous bone marrow transplant. Sometimes bone marrow donated by another matching person (usually a brother or sister) is used, if the condition recurs following transplant using one’s own cell. This is called as allogeneic bone marrow transplant
  • Stem cell transplantation: This procedure is similar to bone marrow transplantation and involves the transplantation of healthy blood-forming stem cells into the body. The procedure is also called hematopoietic progenitor cell transplantation. Stem cells can be collected from the bone marrow, circulating (peripheral) blood, and umbilical cord blood. It may either involve an autologous stem cell transplantation, where stem cells are harvested from individuals before treatment and transplanted back into the patient after treatment, or involve an allogeneic stem cell transplantation, where stem cells donated by another matching person (usually a brother or sister) is used, if the condition recurs after stem cell transplant using one’s own cell. This is called as allogeneic stem cell transplant

Note: Allogeneic bone marrow and allogeneic stem cell transplants may have more side effects and complications, and this treatment may not be suitable for every individual. If allogeneic transplants come from a healthy donor with no malignant cells, then the chances of recurrence of the condition may be reduced.

  • In order to prevent infections because the immune system is weakened by Sézary Syndrome or by its treatment, the patient is kept in an isolated ward and treated with appropriate antibiotics
  • Nowadays targeted therapies are being developed that can selectively kill the cancer cells. Many of them are in the stage of clinical trials
  • Clinical trials: There may be some newer treatment options, currently on clinical trials, which can be considered for some patients depending on their respective risk factors

You healthcare provider will determine the best course of treatment depending on your individual circumstances. Also, follow-up care with regular screening and check-ups are important post-treatment.

How can Sézary Syndrome be Prevented?

Currently, the cause of Sézary Syndrome is unknown. Hence, there are no known methods to prevent the tumor occurrence. Eliminating the modifiable risk factors may help in preventing the condition. The following general factors may be considered:

  • Avoid or stop smoking
  • Undertaking appropriate and prompt treatment for skin conditions, such as eczema, or viral infections
  • Using suitable protective wear (face masks, hand gloves, protective clothing) and adhere to proper safety practices, especially if you are a painter, carpenter, farmer, or working in the ceramics industry
  • Healthy diet and exercise, as well as avoidance of unnecessary exposure to chemicals, may help decrease cancer risk
  • In order to avoid a relapse, or be prepared for a recurrence, the entire diagnosis, treatment process, drugs administered, etc. should be well-documented and follow-up measures initiated

Regular medical screening at periodic intervals with blood tests, scans, and physical examinations, are mandatory. Often several years of active vigilance are crucial and necessary.

What is the Prognosis of Sézary Syndrome? (Outcomes/Resolutions)

  • Sézary Syndrome is an aggressive cancer with a poor prognosis. The average survival period after diagnosis of the condition is between 2-4 years
  • However, the prognosis depends upon a set of several factors, which include:
    • Stage of tumor: With lower-stage tumors, when the tumor is confined to site of origin, the prognosis is usually excellent with appropriate therapy. In higher-stage tumors, such as tumors with metastasis, the prognosis is poor
    • Overall health of the individual: Individuals with overall excellent health have better prognosis compared with those with poor health
    • Age of the individual: Older individuals generally have poorer prognosis than younger individuals
    • The size of the tumor: Individuals with small-sized tumors fare better than those with large-sized tumors
    • Individuals with bulky disease have a poorer prognosis
    • Involvement of vital organs may complicate the condition
    • The surgical resectability of the tumor (meaning, if the tumor can be removed completely) - it is a rare option
    • Whether the tumor is occurring for the first time, or is a recurrent tumor. Recurring tumors have worse prognosis compared to tumors that do not recur
    • Response to treatment: Tumors that respond to treatment have better prognosis compared to tumors that do not respond to treatment
    • Progression of the condition makes the outcome worse (progressive Sézary Syndrome): This condition is known to progress rapidly
  • An early diagnosis and prompt treatment of the tumor generally yields better outcomes than a late diagnosis and delayed treatment
  • The combination chemotherapy drugs used, may have some severe side effects (such as cardio-toxicity). This chiefly impacts the elderly adults, or those who are already affected by other medical conditions. Tolerance to the chemotherapy sessions is a positive influencing factor
  • Progression to bone marrow failure is usually associated with short survival

Additional and Relevant Useful Information for Sézary Syndrome:

  • T-cell lymphomas are less common than B-cell lymphomas
  • Treatment for Sézary Syndrome can cause physical and emotional distress; supportive care and encouragement, help positively and can bring a measure of relief to the patients

The following article link will help you understand leukemia and lymphoma (blood cancer):


What are some Useful Resources for Additional Information?

References and Information Sources used for the Article:

Helpful Peer-Reviewed Medical Articles:

Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: Feb. 18, 2016
Last updated: Dec. 22, 2018