Paraneoplastic Syndrome – Sign of Leser-Trelat
Paraneoplastic syndromes are rare disorders that are triggered by an altered immune system response to a neoplasm. They are defined as clinical syndromes involving non-metastatic systemic effects that accompany malignant disease. In order for any cutaneous alterations to be considered a paraneoplastic syndrome there are six criteria that must be met: (1) onset near the beginning of the neoplasia; (2) both following parallel courses; (3) the dermatosis must not be part of a genetic syndrome; (4) the dermatosis accompanies a specific tumor; (5) the cutaneous disease is common; (6) there is a strong degree of correlation with the neoplasia.
The sign of Leser-Trélat (LT) is a paraneoplastic syndrome characterized by a sudden eruption of multiple seborrheic keratoses or a rapid increase in the number and size of preexisting seborrheic keratoses, with or without associated pruritis. It is most commonly linked with adenocarcinomas of the gastrointestinal tract, but also of the breast, lung, ovary, uterus, kidney, liver and pancreas. There are also cases reported in association with squamous cell carcinomas, leukemias and lymphomas.
It is speculated the eruption of seborrheic keratoses in LT is driven by endogenous mediators of hyperproliferative skin disease such as epidermal growth factor (EGF), transforming growth factor-alpha (TGF-α) or amphiregulin. These factors are thought to function in a local autocrine manner or travel through the circulation to affect the epidermis in a diffuse manner. A reduction in host defenses and the rupture in epidermal cellular turnover are two other proposed mechanisms for LT.
The reliability of LT as a true paraneoplastic syndrome has been questioned due to the common occurrence of seborrheic keratoses among the elderly. This generation also has a greater incidence of the malignancies associated with LT, such as leukemias and lymphonas, allowing for a higher likelihood of coincidence. A florid eruption of seborrheic keratoses has also been reported in nonmalignant conditions such as HIV infection, pregnancy and after heart transplantation. Additionally, LT is a very rare occurrence and no guidelines exist to define a time frame or what constitutes a significant increase in number and size of the seborrheic keratoses.
Evidence favoring a link between LT and underlying malignancy includes reports of LT occurring simultaneously with more traditional paraneoplastic presentations, such as acanthosis nigricans and tripe palms. Regardless of its acceptance in the literature, a florid eruption of seborrheic keratoses warrants investigation for underlying malignancy by utilizing appropriate imaging techniques and tumor-screening tests.
Treatment of LT is directed toward the underlying malignancy, with approximately 50% of patients experiencing resolution of the seborrheic keratoses after the initiation of chemotherapy or radiation. Curettage, laser therapy, cryosurgery, electrocautery or excision may also be employed in resistant cases or symptomatic lesions. Because pruritus can be severe, symptomatic treatment must also be addressed in these patients.
The patient was started on prednisone 40 mg daily and hydroxyzine 25-50 mg daily. A twice daily application of CeraVe mixed with clobetasol 0.05% solution was prescribed to alleviate the intense pruritis associated with her condition. A Medi-Port was placed and oncology began to administer 5-florouracil and cisplatin. After the first cycle of chemotherapy a striking improvement was noted in her skin with a decrease in both the size and number of seborrheic keratoses, as well as a slight improvement in the coarse texture of her palms. Additionally, her dysphagia and recent abdominal pain had almost completely resolved. The patient is currently being tapered off of the prednisone and is continuing with chemotherapy. Topical 40% urea cream has recently been added to alleviate the xerosis and scaling associated with the shedding of the seborrheic keratoses.
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