Sézary syndrome

ALSO KNOWN AS: Baccaredda-Sézary syndrome, cutaneous T-cell lymphoma, T-cell erythroderma, Sézary-Baccaredda syndrome, Sézary-Bouvrain syndrome, Sézary’s disease, Sézary erythroderma

RELATED CONDITIONS: Mycosis fungoides; some experts consider Sézary syndrome to be an advanced form of mycosis fungoides, while others consider it a separate disease.

DEFINITION: Sézary syndrome is a variant of cutaneous T-cell lymphoma (CTCL). In this disease, T lymphocytes (the cells that help the immune system by killing bacteria in the body) become cancerous, affecting the skin and blood. After these cancerous cells enter the bloodstream, the disease may spread to other organs. It is named for Albert Sézary, A. Baccaredda, and Yves Bouvrain, who first described it in 1938.

Risk factors: There are no known risk factors for Sézary syndrome. Exposure to certain chemicals or viruses has been thought to increase risk, but these ideas have not been proven. Older populations and men are more likely to be diagnosed with Sézary syndrome, and most patients show some indication of chromosomal abnormalities.

Etiology and the disease process: Sézary syndrome develops slowly, usually over years. In the early stages, the skin itches and forms dry, dark patches. Then tumors, called mycosis fungoides, form on the skin, and the skin may become infected. When many tumor cells appear in the blood and travel throughout the body, this disease has progressed into Sézary syndrome. The disease may then spread to the lymph nodes or other organs such as the lungs, liver, or spleen.

Incidence: Each year, approximately 3,000 cases of cutaneous T-cell lymphoma are diagnosed in the United States. Fifteen percent become Sézary syndrome. Most cases appear in people who are over the age of fifty. Men get this disease more often than women, and Black Americans develop it more often than members of other ethnicities.

Symptoms: Symptoms include itching; a dry, red skin rash; skin tumors; and enlarged lymph nodes.

Screening and diagnosis: A physical exam is the general screening tool for this disease. If Sézary syndrome is suspected, blood tests or skin biopsies may be used to confirm the diagnosis. Other tests, such as X-rays, computed tomography (CT) scans, magnetic resonance imaging (MRI), or lymph node biopsies, may be used to see if the disease has spread to other parts of the body.

Sézary syndrome involves these stages:

• Stage I: Only parts of the skin are affected with a red, scaly rash. There are no tumors, and lymph nodes are normal.
• Stage II: Either the lymph nodes are normal or enlarged but have no cancerous cells, and the skin has a red, scaly rash but no tumors, or the lymph nodes are normal or enlarged but do not contain cancerous cells, although the skin has tumors.
• Stage III: Most of the skin is affected by a red, scaly rash, but the lymph nodes, either normal or enlarged, do not contain cancerous cells.
• Stage IV: In addition to the skin rash, either cancer cells are in the lymph nodes or cancer cells have spread to other organs.
• Recurrent: The cancer has been previously treated but has returned, either where it began or in another area of the body.

Treatment and therapy: The three treatments generally used for Sézary syndrome are radiation therapy, chemotherapy, and phototherapy. Others include immunotherapy, extracorporeal photopheresis, and histone deacytlase inhibitors.

In radiation therapy for this disease, a special type of radiation that only penetrates the outer layers of the skin (total skin electron beam radiation) may be directed to the entire body to kill cancer cells in the skin. Another method is to direct radiation only to small areas of skin that are highly affected.

Chemotherapy for this disease may involve traditional systemic chemotherapy (putting chemicals that kill cancer cells into the bloodstream by mouth or intravenously) or a topical cream that contains chemicals that kill cancer cells.

With one type of phototherapy for this cancer (PUVA therapy, psoralen plus ultraviolet light A), patients are given certain drugs that make cancer cells sensitive to light; then a laser light is shone on the skin to kill the cancer cells. In another type of phototherapy (extracorporeal photochemotherapy), patients are given certain drugs; then, some of the blood cells are taken out of the body, exposed to a special light, then reinserted into the body. Sometimes patients who are treated with phototherapy need to avoid sunlight.

Other treatments, such as steroid creams, may be used to ease the itching and swelling of the skin with this disease. In 2018, the US Food and Drug Administration approved Mogamulizumab, a monoclonal antibody that targets cancer cells, for the treatment of Sézary syndrome. Doctors also found success in combining the drug with other treatments. Similarly, Magrolimab, an anti-CD-47 monoclonal antibody, was also being investigated as an adjunct treatment to Mogamulizumab. CAR-T Cell Therapy, a proven treatment method for blood cancers, was also being explored as a treatment option. 

Prognosis, prevention, and outcomes: Sézary syndrome is difficult to cure, and no way of preventing it is known, but treatments can relieve symptoms. The stage of the disease at diagnosis significantly affects the prognosis. Overall, five-year survival rates have shown to vary according to study and stage of the disease, but they are anywhere between 20 and 85 percent, with average median survival times of four years. Patients whose disease progresses into Stage IV often succumb to infection due to their compromised immune systems.

Bibliography

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“How Long Will I Live With CTCL?” HealthTree, healthtree.org/cutaneous-t-cell-lymphoma/community/how-long-will-i-live-with-cutaneous-t-cell-lymphoma. Accessed 15 June 2024.

"Mycosis Fungoides (Including Sézary Syndrome) Treatment.” National Cancer Institute, 25 Mar. 2022, www.cancer.gov/types/lymphoma/patient/mycosis-fungoides-treatment-pdq. Accessed 15 June 2024.

Quadri, Imran, et al. "Advancements in the Treatment of Mycosis Fungoides and Sézary Syndrome: Monoclonal Antibodies, Immunotherapies, and Janus Kinase Inhibitors." Frontiers in Immunology, vol. 14, 2023, p. 1291259, doi:10.3389/fimmu.2023.1291259. Accessed 15 June 2024.

“Sézary Syndrome: Symptoms, Treatment & Prognosis.” Cleveland Clinic, 17 Nov. 2023, my.clevelandclinic.org/health/diseases/8493-sezary-syndrome. Accessed 15 June 2024.

Siegel, Richard S., et al. “Primary Cutaneous T-Cell Lymphoma: Review and Current Concepts.” Journal of Clinical Oncology, vol. 18.15, 2000, pp. 2908–25.

Tan, Sharlene. “What Is Sézary Syndrome?” WebMD, 29 Feb. 2024, www.webmd.com/cancer/lymphoma/what-to-know-about-sezary-syndrome. Accessed 15 June 2024.

Vakiti, Anusha. “Sezary Syndrome - StatPearls.” NCBI, 24 Sept. 2022, www.ncbi.nlm.nih.gov/books/NBK499874. Accessed 15 June 2024.

Zackheim, Herschel S., ed. Cutaneous T-Cell Lymphoma: Mycosis Fungoides and Sézary Syndrome. Boca Raton: CRC, 2005.