TOX expression and role in CTCL.

BACKGROUND: Cutaneous T-cell lymphomas (CTCL) are skin malignancies including mycosis fungoides (MF) and CD30(+) lymphoproliferative disorders (LPD). In early disease, CTCL can be difficult to diagnose, especially in MF for which there is no reliable diagnostic marker. MF/CTCL have increased expression of thymocyte selection-associated HMG box protein (TOX). Although TOX has been proposed to be a diagnostic marker for MF, further validation studies are needed. Moreover, it is unclear what drives TOX expression or its role in MF/CTCL. OBJECTIVE: We hypothesize evaluation of TOX levels across a spectrum of CTCL, including MF precursor (large plaque parapsoriasis, LPP), will help elucidate the implications of altered TOX expression. MATERIALS AND METHODS: TOX staining was performed in MF, CD30(+) LPD, LPP as well as benign inflammatory dermatoses (BID) and normal skin (NS). CTCL cell lines were utilized to evaluate the regulation of TOX. RESULTS: Positive TOX expression was identified in 73.6% of MF cases and in 31.6% of BID/NS. TOX had a positive predictive value (PPV) for MF of 86.7% and a negative predictive value (NPV) of 48.1%. TOX expression in MF was detected more commonly in Black patients (P = 0.015) and less commonly in transformed MF (P = 0.045). LPP had positive TOX staining in 70.0%. In CTCL cells, GATA3 knockdown decreased TOX mRNA and protein expression. TOX expression also decreased in the presence of CTCL therapeutics. CONCLUSION: Our data indicate that TOX is useful as a diagnostic marker in MF. Moreover, TOX expression was evident in LPP, indicating it may have a previously unappreciated role in the development of MF. Finally, our data suggest that GATA3 regulates TOX, revealing insight into TOX regulation.

Scurvy presenting as painful gait with bruising in a young boy.

A case of scurvy occurred in an apparently well-nourished 5-year-old boy with normal growth parameters. Only after the diagnosis of scurvy was raised on clinical grounds did we discover the peculiar dietary habits that were responsible for his deficiency of ascorbic acid. His case is a reminder to the clinician that nutritionally based disease may occur in any socioeconomic setting and that nutritional screening remains an important part of every child's general health care.

Treatment of cutaneous sarcoidosis with chloroquine. Review of the literature.

Systemic corticosteroids may be either contraindicated or not efficacious in treating the cutaneous manifestations occurring in 20% to 35% of patients with systemic sarcoidosis. Chloroquine phosphate has been reported to be a valuable alternative therapy for cutaneous lesions of sarcoidosis. With a judiciously determined daily dosage and regular 6-month ophthalmologic follow-up examinations, the risk of developing retinopathy can be avoided, because the daily dosage rate rather than total dose accumulation determines the development of chloroquine-induced retinopathy. We reviewed the efficacy and safety of chloroquine and its role in the treatment of cutaneous sarcoidosis.

Localized heat urticaria.

Localized heat urticaria is one of the rarest of the physical urticarias, characterized by well-defined urticarial lesions sharply confined to sites of heat exposure. We describe a case of localized heat urticaria in a 40-year-old woman. Because of the rarity of this disorder, much remains to be elucidated. The clinical features, pathogenesis and therapy are reviewed.

Idiopathic leukonychia totalis and partialis in a 12-year-old patient.

Leukonychia totalis and partialis are uncommon nail findings characterized by the complete or partial whitening of the nail plate. Most cases of true leukonychia are inherited. We present a rare case of a young man with persistent, progressive, acquired leukonychia totalis and partialis.

Intravascular large cell lymphoma: a patient with asymptomatic purpuric patches and a chronic clinical course.

Intravascular large cell lymphoma (malignant angioendotheliomatosis) is a rare, multifocal, intravascular neoplasm of lymphoid cells that preferentially involves the vasculature of the skin and central nervous system. We describe a 54-year-old man with asymptomatic purpuric patches on the lower extremities for 10 years duration and a more recent lesion on the right arm. A biopsy specimen showed intravascular collections of tumor cells with irregular nuclear contours and prominent nucleoli. These cells were leukocyte common antigen (CD45), CD20, and CDW75 positive, but CD3, CD43, CD45RO, and cytokeratin negative. Polymerase chain reaction analysis of the skin for immunoglobulin heavy chain gene rearrangement detected a clonal population of B cells, supporting the diagnosis of a B-cell lymphoma. Peripheral blood showed no abnormal circulating cells. This case of malignant angioendotheliomatosis is unusual for its prolonged clinical course and presence of purpuric patches.

The North American experience with photopheresis.

Photopheresis or extracorporeal photochemotherapy (ECP) is a novel immunomodulatory therapy based upon pheresis of light-sensitive cells. Whole blood is removed from patients who have previously ingested the photosensitizing agent 8-methoxypsoralen (8-MOP) followed by leukapheresis and exposure of the 8-MOP containing white blood cells (WBCs) extracorporeally to an ultraviolet A (UVA) light source prior to their return to the patient. In 1988, the Food and Drug Administration (FDA) approved photopheresis for the treatment of cutaneous T-cell lymphoma (CTCL). Treatment of CTCL with photopheresis has been reported in over 300 patients worldwide. Photopheresis has also demonstrated encouraging results in the treatment of solid organ transplant rejection, graft versus host disease, scleroderma, and other autoimmune diseases although fewer patients have been studied. This review will focus on the North American experience with photopheresis.

Mycosis fungoides d'embleé: CD30-negative cutaneous large T-cell lymphoma.

The d'embleé variant of mycosis fungoides initially described patients with a rapid onset of tumors without progression through patch- and plaque-stage disease. We report a case of a patient with the clinical presentation of mycosis fungoides d'embleé and correlate the histologic and immunophenotypic data with those of a more updated classification scheme.

Long-term follow-up of patients with cutaneous T-cell lymphoma treated with extracorporeal photochemotherapy.

BACKGROUND: Few studies have assessed the long-term outcome of patients with cutaneous T-cell lymphoma (CTCL) treated with extracorporeal photochemotherapy (ECP). OBJECTIVE: Our objective was to assess the efficacy, safety, and survival of a cohort of patients with refractory T-cell lymphoma in various stages of cutaneous involvement who were treated with ECP. METHODS: Twenty patients who had received at least 6 months of ECP between September 1988 and April 1991 were reevaluated and the data analyzed statistically to obtain outcome data through December 1995. RESULTS: A complete response (disappearance of all lesions) was obtained in five patients (25%) and a partial response (disappearance of at least 50% of lesions) in five patients (25%). Of the 10 responders, seven (70%) were weaned from ECP. Two of seven patients had a relapse. Ten patients (50%) showed no response to ECP. No statistically significant differences between responders and nonresponders were found with respect to demographic, clinical, or laboratory variables. Seven patients died of causes directly related to CTCL and two patients died of unrelated causes. Median survival time for the entire cohort was 96 months (range, 16 to 152 months). An assessment of early response after 6 to 8 months of ECP had a sensitivity of 100% and a specificity of 90% for predicting long-term (> 4 years) outcome. Adverse effects were minimal. CONCLUSION: ECP is a safe effective alternative therapy for CTCL that is refractory to other therapies; it can induce a long-term, disease-free remission in a minority of patients. Response in the first 6 to 8 months of treatment predicts long-term outcome.