HI In sezary syndrome an erythrodermic form of cutaneous T-Cell lymphoma (CTCL), a term that collectively includes all cutaneous lymphomas arising from T lymphocytes. The syndrome is named after Albert Sézary, a French dermatologist born in 1880. It is also called Sezary syndrome. T lymphocytes are circulating immune cells that mature in the thymus. In Sézary syndrome, malignant T lymphocytes in the peripheral blood clonally match malignant T cells found in the skin. Sézary syndrome is a disease of older adults. Epidemiological data is not available in New Zealand. Worldwide, incidence appears to be 0.8–0.9 per million with a male to female ratio of 2:1. It is not an inherited disease. The cause of Sézary syndrome remains largely unclear. The malignant T cells in the skin and blood have the following characteristics: CD4 positive: this indicates they are central memory T cells A significant percentage exhibit loss of CD26 and CD7 Abnormal clonal Th2 cells Reduced Th1 (T-helper) cells This contributes to endogenous immunosuppression. Skin signs Patients with Sézary syndrome present with diffusely red, thickened and scaly skin. Pruritus (itch) is common, often severe, and can be difficult to manage. Other features may include: Slowly-developing generalised induration (firmness of the skin) Lichenification (increased skin markings due to scratching and rubbing) Lichenification (increased skin markings due to scratching and rubbing) Scaly papules due to follicular prominence Thickened nails Ectropion (drooping of lower eyelid) Diffuse or patchy alopecia (hair loss) These symptoms often lead to lack of sleep, anxiety and depression. Very rarely, Sézary syndrome has been reported to present with pruritus, Sézary cells on biopsy of normal-looking skin, and no visible rash. Sézary syndrome should be considered in any erythrodermic patient. Diagnosis requires clinicopathological correlation. Skin biopsy If possible, select an area of indurated skin for biopsy. Multiple biopsies are useful especially if morphology varies. Features on light microscopy may include: Atypical lymphocytes infiltrating dermis Epidermotropism (cells migrating to epidermis) Lymphocytes with a single cerebriform nucleus (not diagnostic) Pautrier microabscesses, or intra-epidermal aggregates of atypical cells Immunohistochemistry stains positive for CD3+ and CD4+ cells Blood tests Sézary cells are large atypical mononuclear cells with a large cerebriform nuclei. They are found in large numbers in the peripheral blood of patients with Sézary syndrome. Smaller numbers may be found in healthy patients or those with other diseases. Flow cytometry can demonstrate CD4+CD7- and CD4+CD26- T cells, which are characteristic of Sézary syndrome. T-cell antigens may also be absent (CD2, CD3, CD4 and/or CD5). The CD4:CD8 ratio is 10, but is not diagnostic. Lymph node biopsy Excisional biopsies are required to distinguish between dermatopathic lymph node changes and reactive lymph node changes. T-cell receptor (TCR) gene rearrangement tests T-cell receptor (TCR) gene rearrangement tests may be performed on the skin specimen, circulating blood and lymph nodes. This test evaluates clonality of the cells, which should be similar in the 3 sites. Differential diagnosis of Sézary syndrome Other diagnoses considered in an erythrodermic patient may include: Mycosis fungoides (another form of CTCL) Psoriasis Pityriasis rubra pilaris Atopic dermatitis Other forms of dermatitis Treatment for Sézary syndrome is determined by the stage of disease and comorbidities. TNMB criteria for staging CTCL are skin (T), lymph node (N), visceral involvement (M), blood (B). Sézary syndrome is classified as at least T4B2 (T4 erythroderma and B2 peripheral blood involvement). Classification also depends on lymph node or internal organ involvement: Stage IVA1: no internal organ involvement. Lymph nodes may be uninvolved or enlarged but with only minor histological abnormalities Stage IVA2: histologically abnormal lymph node involvement without internal organ involvement Stage IVB: internal organ involvement with or without lymph node involvement There is no standard therapy for Sézary syndrome. Patients are prescribed topical and systemic medications. They may also receive UVB or PUVA phototherapy, and/or radiotherapy (localised superficial rays or total skin electron Extracorporeal photopheresis (ECP) ECP is an immune-sparing therapy in which a photosensitizing agent (psoralen/8-methoxsalen) is combined with UVA to treat peripheral bloodwhich is extracted, irradiated and returned to the patient. It is the preferred first line therapy in early stages. Side effects include headache, fatigue, itch and transient hypotension (low blood pressure) with possible syncope (collapse). Response rates are improved when combined with biological response modifiers. ECP is currently not available in New Zealand but is available in Australia. Biological response modifiers Biologics are preferably used in conjunction with photopheresis. However, they can be used as part of single or multi-agent regimes if ECP is not available. They include: Denileukin diftitox (Ontak®), a protein combining Interleukin-2 and Diphtheria toxin approved in the treatment of cutaneous T-cell lymphoma that have the high affinity component of the IL-2 receptor Alemtuzumab (Campath-1H) is a monoclonal antibody directed against the lymphocytic antigen CD52 expressed on B- and T-cells. It has been used successfully off-label in Sezary syndrome. Other biologics are under investigation in this disease. Other medications used in Sézary syndrome Medications are often used in combination. Conventional sedating antihistamines to reduce the impact of pruritus Interferons: interferon alpha and gamma Retinoids: oral bexarotene, acitretin, isotretinoin Low dose methotrexate Histone deacetylase inhibitors: oral vorinostat or intravenous romidepsin Chemotherapy for Sézary syndrome Examples of chemotherapy agents used for Sézary syndrome are: Pegylated liposomal doxorubicin Gemcitabine Fludarabine Cladribine Pentostatin Sézary syndrome is usually aggressive and prognosis is generally poor with a median survival between 2–4 years. Patients may respond transiently but relapse is often inevitable. The occasional patient has gone into remission after treatment. Patients usually succumb to opportunistic infections due to immune suppression. Regards DR DE