Sézary disease

Overview

Sézary disease, also known as Sézary syndrome, is a rare and aggressive form of cutaneous T-cell lymphoma (CTCL), a type of non-Hodgkin lymphoma that primarily affects the skin. It is characterized by the triad of generalized erythroderma (widespread redness and scaling of the skin), lymphadenopathy (enlarged lymph nodes), and the presence of malignant T-cells, known as Sézary cells, in the blood. Sézary disease typically affects older adults and is considered a leukemic variant of mycosis fungoides, another type of CTCL. The disease is chronic and progressive, requiring long-term management and often systemic therapy.

Causes

The exact cause of Sézary disease is unknown. It arises from the malignant transformation of mature CD4+ T-cells, which are part of the immune system. These abnormal T-cells preferentially migrate to the skin and circulate in the blood, causing systemic symptoms. Although the precise triggers remain unclear, several factors are believed to contribute to its development:

• Genetic mutations: Alterations in tumor suppressor genes and oncogenes may contribute to malignant T-cell proliferation

• Immune dysregulation: Dysfunction of the immune surveillance system may fail to eliminate abnormal cells

• Environmental exposures: Long-term exposure to certain chemicals or infectious agents may play a role, though evidence is limited

Sézary disease is not contagious and does not appear to run in families.

Symptoms

The symptoms of Sézary disease are systemic and affect the skin, lymphatic system, and blood. They can severely impact a patient’s quality of life. Common symptoms include:

Skin Symptoms:

• Generalized erythroderma (red, inflamed skin covering >80% of the body)

• Severe pruritus (itching)

• Scaling, dryness, and thickening of the skin

• Swelling of the face and eyelids (facial edema)

• Hair loss, especially eyebrows and eyelashes

• Nail dystrophy

Systemic Symptoms:

• Lymphadenopathy (enlarged lymph nodes)

• Presence of Sézary cells in the peripheral blood

• Fatigue and malaise

• Immunosuppression leading to recurrent infections

• Weight loss in advanced cases

Due to the leukemic nature of the disease, Sézary cells can affect various organs, especially in advanced stages, leading to complications.

Diagnosis

Diagnosing Sézary disease requires a combination of clinical examination, laboratory tests, and histopathological analysis. Diagnostic criteria include:

• Blood tests: Detection of a high count of Sézary cells (abnormal T-cells) in peripheral blood using flow cytometry and blood smears

• Skin biopsy: Histological examination of affected skin to identify atypical lymphocytes in the epidermis and dermis

• Lymph node biopsy: To assess involvement by malignant T-cells

• Immunophenotyping: Sézary cells typically express CD3+, CD4+, CD7-, CD26- surface markers

• T-cell receptor gene rearrangement studies: Used to confirm clonality of the malignant cells

Diagnosis can be challenging and is often delayed, as early symptoms may mimic other inflammatory skin conditions such as eczema or psoriasis.

Treatment

There is no definitive cure for Sézary disease, and treatment is aimed at controlling symptoms, improving quality of life, and slowing disease progression. Management is often personalized and may include:

Skin-Directed Therapies:

• Topical corticosteroids

• Phototherapy (PUVA or narrowband UVB)

• Total skin electron beam therapy (TSEBT)

Systemic Therapies:

• Oral retinoids (e.g., bexarotene)

• Interferon-alpha to stimulate immune response

• Histone deacetylase (HDAC) inhibitors (e.g., vorinostat, romidepsin)

• Monoclonal antibodies (e.g., mogamulizumab targets CCR4+ T-cells)

• Extracorporeal photopheresis (ECP) – a process where blood is treated with light-sensitive agents and exposed to UV light

• Systemic chemotherapy for advanced or refractory cases

Stem Cell Transplant:

• Allogeneic hematopoietic stem cell transplant may be considered in selected younger patients with aggressive disease and poor response to conventional therapies

Prognosis

The prognosis for Sézary disease varies depending on age, overall health, and how early the disease is diagnosed and treated. It is generally considered an aggressive form of CTCL with a median survival of 2 to 4 years from diagnosis. Prognostic factors associated with worse outcomes include high blood tumor burden, extensive lymph node involvement, and immune suppression.

With advancements in targeted therapies and immunomodulatory treatments, outcomes are gradually improving. Supportive care, including infection prevention, skin care, and psychosocial support, is crucial for maintaining quality of life. Ongoing clinical trials offer hope for more effective treatments in the future.