In the latest Case Record of the Massachusetts General Hospital, a 53-year-old woman was admitted to the hospital because of erythroderma and lymphadenopathy for 18 months, associated with alopecia, recurrent skin infections, peripheral-blood eosinophilia, and elevated IgE levels. Diagnostic procedures were performed. Idiopathic hypereosinophilic syndrome is defined by an eosinophil count of more than 1500 per cubic millimeter for at least 6 months, without an identifiable cause, and the resulting tissue damage. Examples of cutaneous manifestations are angioedema, urticaria, and erythroderma. Skin-biopsy specimens show nonspecific perivascular infiltrates of eosinophils and mononuclear cells. Persistent eosinophilia may also be due to neoplastic or paraneoplastic causes.
• What is the differential diagnosis of erythroderma?
The differential diagnosis of erythroderma is extensive, but the majority of cases can be attributed to a preexisting dermatitis, such as psoriasis, atopic dermatitis, or allergic contact dermatitis. Second most common are idiopathic cases of erythroderma, with no cause found despite extensive evaluation. Erythroderma is also frequently attributable to medications; in such cases, symptoms typically begin as morbilliform eruptions shortly after the start of a new medication and progress to erythroderma. Five percent of cases of erythroderma are ultimately shown to be a type of cutaneous T-cell lymphoma (e.g., the Sezary syndrome). On rare occasions, erythroderma could be attributed to the hypereosinophilic syndrome, paraneoplastic syndromes, or unusual presentations of common entities such as scabies or dermatophytosis.
• What is the Sezary syndrome?
The Sezary syndrome is a leukemic form of cutaneous T-cell lymphoma, defined by the presence of erythroderma covering at least 80% of the body-surface area, lymphadenopathy, and the presence of clonally related neoplastic T cells with cerebriform nuclei (Sezary cells) in the blood, skin, and lymph nodes. Other cutaneous findings are alopecia, ectropion, palmoplantar keratoderma, and often excoriations due to intense pruritus. Patients with the Sezary syndrome have an increased susceptibility to infections and frequently have hypereosinophilia.
Morning Report Questions
Q: What features are necessary in order for a diagnosis of the Sezary syndrome to be made?
A: For a diagnosis to be made, there must be a clonal rearrangement of the T-cell receptor in the blood, as well as 1000 or more Sezary cells per liter of blood, a high CD4+ T-cell count (with a CD4:CD8 ratio of greater than or equal to 10), or an increased CD4+ T-cell count with an abnormal immunophenotype (>40% CD4+CD7− or >30% CD4+CD26−). The results of skin biopsies are often nonspecific in cases of erythroderma related to the Sezary syndrome.
Q: What are the options for treatment of the Sezary syndrome?
A: Two options for the initial treatment of the Sezary syndrome that are not profoundly immunosuppressive are extracorporeal photopheresis, often in combination with interferon or bexarotene, and the use of histone deacetylase inhibitors, such as vorinostat or romidepsin. The overall response rate for extracorporeal photopheresis alone in patients with the Sezary syndrome ranges from 18 to 67%. Pegylated liposomal doxorubicin is an effective agent, with response rates of 30 to 80% and complete response rates of 20 to 60%; it causes myelosuppression and has a risk of cardiomyopathy at lifetime doses exceeding 400 mg per square meter of body-surface area. Combination chemotherapy regimens such as cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) have response rates of 66 to 80% but also are associated with a significant risk of infection and a short duration of response. Denileukin diftitox is a fusion protein of the interleukin-2 receptor ligand fused to diphtheria toxin that targets cells expressing CD25 as part of the high-affinity interleukin-2 receptor. It has response rates in patients with cutaneous T-cell lymphoma of up to 50%, with a 10% complete response rate. The monoclonal antibody alemtuzumab, which targets CD52 expressed on both T and B lymphocytes, is one of the few agents that have been studied in patients with the Sezary syndrome. Low-dose alemtuzumab (10 mg or 15 mg delivered subcutaneously three times a week) was found to have an overall response rate of 86% and a complete response rate of 21% in a trial involving 14 patients with the Sezary syndrome.