Search

The retinoid X receptor (RXR)-agonist bexarotene and the histone deacetylase inhibitor (HDACI) vorinostat are each established monotherapies for cutaneous T-cell lymphomas (CTCLs). We investigated the combination of HDACI and retinoic acid receptor (RAR)/RXR agonists in vitro and in a phase I, multicenter, open-label, two-part dose-escalation study. The combination of bexarotene with a HDACI in vitro leads to cooperative activation of gene transcription and reduction of cell viability in human tumor cell lines. The primary clinical objective was to determine the maximum tolerated dose (MTD) of bexarotene plus vorinostat in 23 patients with CTCLs. The MTD for part I was established at vorinostat 200 mg/day plus bexarotene 300 mg/m2/day. The MTD for part II was not reached. Four patients had an objective response and seven patients experienced pruritus relief. We conclude that concomitant administration of vorinostat and bexarotene is feasible only if lower doses of each drug are administered relative to the product label monotherapy doses. [ABSTRACT FROM AUTHOR]

The CD30-positive cutaneous lymphoproliferative disorders (CLPD) include lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large T-cell lymphoma (cALCL). Despite the malign-appearing histology, an excellent prognosis and spontaneous regression of single lesions characterize LyP. Even after years of clinical remission newly erupting lesions often harbor a T-cell clone identical to the initial one. This fact raises the question whether the clonal T-cell population persists in the peripheral blood. Therefore we investigated genomic DNA of 126 samples of lesional skin and peripheral blood from 31 patients with CLPD, obtained during both active disease and clinical remission. We performed molecular genetic analysis by combining T-cell receptor (TCR)-γ PCR with the GeneScan technique and assessed the TCR repertoire in selected blood samples by β-variable complementarity-determining region 3 (CDR3) spectratyping qualitatively and quantitatively. We were able to detect a clonal T-cell population in 36/43 (84%) skin samples and in 35/83 (42%) blood samples. Comparison of the compartments in each patient demonstrated different T-cell clones in skin and blood, suggesting a reactive nature of the clonal T cells in the blood. Moreover, CDR3 spectratyping revealed a restricted T-cell repertoire in the blood, suggesting T-cell stimulation by an unknown antigen.Journal of Investigative Dermatology (2009) 129, 89–98; doi:10.1038/jid.2008.204; published online 17 July 2008 [ABSTRACT FROM AUTHOR]

Cutaneous leishmaniasis is an infectious disease caused by several Leishmania species. It is transmitted to humans by the bite of the infected female phlebotomus sandfly. Today, more than 1 billion people in leishmaniasis endemic areas are at risk of infection. More than 1.5 million new cases of cutaneous leishmaniasis occur every year. On the basis of two cases, we show that cutaneous leishmaniasis is still an imported tropical disease in Germany. However, due to the increasing intercontinental travel, cases may increase. Therefore, cutaneous leishmaniasis should be considered in the differential diagnosis in patients with nonhealing wounds, ulcers, papules or nodules and the corresponding travel history., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Tumor necrosis factor (TNF)-alpha antagonists have considerably improved the therapeutic approach to chronic inflammatory disorders including psoriasis vulgaris. Recently, some cases of highly aggressive hepatosplenic T-cell lymphoma (HSTCL) have developed in patients with inflammatory bowel diseases (IBD) being treated with infliximab or adalimumab. Analysis of the published data suggests that the emergence of HSTCL is favored by the combination of purine analogues and infliximab or adalimumab in the therapy of a granulomatous inflammation involving Vdelta1(+)gammadelta T cells. Because psoriasis vulgaris is different from IBD in regard to the type of inflammation, the concomitant therapies used and the tissue-specific subsets of gammadelta T cells, the use of infliximab or adalimumab in psoriasis may not necessarily be associated with an increase in the risk of HSTCL.

Background: The most common type of primary cutaneous T cell-lymphomas (CTCLs), which are characterised by a clonal proliferation of malignant skin-homing CD4(+) lymphocytes, is mycosis fungoides (MF) and its rare leukaemic variant Sézary syndrome (SS)., Objective: Zanolimumab is a high affinity human monoclonal IgG1k antibody, targeting the CD4-molecule. It exhibits cytotoxic and antiproliferative effects and has previously shown efficacy in CTCLs., Methods: Literature and reference research was done by using Pubmed and updates of ongoing studies were taken from American Society of Clinical Oncology (ASCO) and American Society of Hematology (ASH )annual meeting abstracts., Results: This article gives an overview about efficacy, tolerability and safety as well as chemistry, pharmacodynamics and pharmacokinetics of zanolimumab in the treatment of CTCLs.

The lymph nodes are generally the first extracutaneous manifestation in patients with cutaneous T-cell lymphoma (CTCL); however, their early involvement is difficult to assess. The aim of our study was to define the diagnostic and prognostic value of T-cell clonality analysis for a more precise assessment of lymph node involvement in CTCL. T-cell clonality was determined by 2 independent polymerase chain reaction (PCR) assays, namely a recently developed T-cell receptor-beta (TCR-beta) PCR technique as well as an established TCR-gamma PCR. T-cell clonality was found in 22 of 22 lymph nodes with histologically detectable CTCL involvement as well as in 7 of 14 histologically noninvolved dermatopathic lymph nodes. The clonal T-cell populations in the lymph nodes were in all cases identical to those detected in the corresponding skin lesions, identifying them as the tumor cell population. T-cell clonality was not found in any of the 12 dermatopathic lymph nodes from 12 patients with inflammatory skin diseases. Clonal T-cell detection in 7 of 14 dermatopathic lymph nodes of patients with CTCL was associated with limited survival (74 months; confidence interval [CI], 66-82 months) as in patients with histologically confirmed lymph node involvement (41 months; CI, 35-47 months), whereas all patients without T-cell clonality in the lymph nodes (7 patients) were alive at the last follow-up. Thus, T-cell clonality analysis is an important adjunct in differentiating benign dermatopathic lymphadenitis from early CTCL involvement.

A woman developed widespread contact dermatitis after temporary tattooing with henna, caused by paraphenylenediamine (PPD) which had been added to the henna as an enhancer. The patient recovered after treatment; a week later an acute generalized rebound occurred after she wore dark clothing (black chador). Patch tests revealed type-IV allergy to PPD, along with multiple sensitisations to other textile dyes (disperse orange 3, para-aminoazobenzole, Bismark brown R). Temporary henna tattoos are not always harmless holiday souvenirs. The addition of color enhancers such as PPD into henna may lead to multiple contact allergies to other textile dyes.