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Mycosis fungoides, the most common form of cutaneous T-cell lymphoma, has a higher incidence and poorer prognosis in African-Americans. The factors that may be contributing to this disparity are presented in the context of a health disparities framework that includes discussion of patient-related factors such as race/ethnicity, socioeconomic status, and biological differences, provider-related factors such as patient-provider communication and the competing demands for providers' time, and health care system-related factors such as access to health care and workforce diversity. The changing demographics of the USA emphasize the need to understand and address health disparities in mycosis fungoides and other dermatologic diseases. The framework presented here can be used to examine disparities in other dermatologic conditions and advance health disparities research in dermatology. [ABSTRACT FROM AUTHOR]

Keloids are progressively expanding scars, mostly prevalent in individuals of African descent. Previous data identified increased mast cell number and activation state in keloids suggesting a role in disease progression. The major eicosanoid secreted by mast cells is prostaglandin D2 ( PGD2), a relatively unstable pro-inflammatory mediator which can be spontaneously converted to 15-deoxy-(Delta12,14)-prostaglandin J2(15d-PGJ2) or enzymatically metabolized to 9α,11β- PGF2 by aldo-keto reductase 1C3 ( AKR1C3). In this work, we investigated the possible role of PGD2 and its metabolites in keloids using CRL1762 keloid fibroblasts ( KF) and immunohistochemical staining. Our data suggested approximately 3-fold increase of tryptase-positive mast cell count in keloids compared with normal skin. Furthermore, AKR1C3 was overexpressed in the fibrotic area of keloids while relatively weak staining detected in normal skin. Metabolism of PGD2 to 9 α,11 β- PGF2 by both, KF and normal fibroblasts, was dependent on AKR1C3 as this reaction was attenuated in the presence of the AKR1C3 inhibitor, 2′-hydroxyflavanone, or in cells with decreased AKR1C3 expression. 15d- PGJ2, but not the other tested PGs, inhibited KF proliferation, attenuated KF-mediated collagen gel contraction and increased caspase-3 activation. In addition, treatment with 15d- PGJ2 activated P38- MAPK, induced reactive oxygen species and upregulated superoxide dismutase-1 ( SOD-1). Finally, inhibition of P38- MAPK further augmented 15d- PGJ2-induced caspase-3 cleavage and attenuated its effect on SOD-1 transcription. This work suggests that localized dual inhibition of AKR1C3 and P38- MAPK may inhibit keloid progression. Inhibiting AKR1C3 activity may generate oxidative environment due to redirection of PGD2 metabolism towards 15d- PGJ2 while inhibition of P38- MAPK will sensitize keloid cells to ROS-induced apoptosis. [ABSTRACT FROM AUTHOR]