Skin disease of penis and male genitalia is linked to atopy and circumcision: caseload in a male genital dermatology clinic.

BACKGROUND/OBJECTIVES: Male genital dermatoses are a common and underappreciated cause of morbidity. Its prevalence and the characteristics of patients presenting with these conditions are poorly understood. The aim of the study was to ascertain which dermatoses were referred to the Male Genital Dermatology Clinic in Melbourne, Australia and to determine whether circumcision and atopy are associated with male genital skin disease. METHOD: This was a retrospective review of 331 new patients who attended the clinic from 2004 to 2012. Descriptive statistics were obtained to determine the frequency of diagnoses made in the clinic and to record the proportions of circumcised and atopic patients. RESULTS: The most common primary diagnoses were irritant contact dermatitis (n = 67), dysaesthesia (n = 60), psoriasis (n = 31), lichen sclerosus (n = 28), unknown (n = 19), genital warts (n = 18), normal anatomic variant (n = 17), other infection (n = 17), eczema (n = 16) and lichen planus (n = 16). For the 10 most commonly observed conditions, more than 70% of patients were uncircumcised and more than 69% of these patients had a history of atopy. CONCLUSIONS: The diagnoses made were described, including their associations with non-circumcision and atopy. Several of these observations have not been recognised before in the literature. We discuss lessons learned in the management of male genital disease and its psychosocial impact.

PDGFR Inhibition Results in Pericyte Depletion and Hemorrhage into the Corpus Luteum of the Rat Ovary.

The growth plate, ovary, adrenal gland, and rodent incisor tooth are sentinel organs for antiangiogenic effects since they respond reliably, quantitatively, and sensitively to inhibition of the vascular endothelial growth factor receptor (VEGFR). Here we report that treatment of rats with platelet-derived growth factor receptor beta (PDGFRß) inhibitors that target pericytes results in severe ovarian hemorrhage with degeneration and eventual rupture of the corpus luteum. Evaluation of the growth plate, adrenal gland, and incisor tooth that are typical target organs for antiangiogenic treatment in the rodent revealed no abnormalities. Histologically, the changes in the ovary were characterized by sinusoidal dilatation, increased vessel fragility, and hemorrhage into the corpus luteum. Immunocytochemical staining of vessels with alpha smooth muscle actin and CD31 that recognize pericytes and vascular endothelium, respectively, demonstrated that this effect was due to selective pericyte deficiency within corpora lutea. Further experiments in which rats were treated concurrently with both PDGFRß and VEGFR inhibitors ablated the hemorrhagic response, resulting instead in corpus luteum necrosis. These changes are consistent with the notion that selective pericyte loss in the primitive capillary network resulted in increased vessel fragility and hemorrhage, whereas concomitant VEGFR inhibition resulted in vessel regression and reduced vascular perfusion that restricted development of the hemorrhagic vessels. These results also highlight the utility of the rodent ovary to respond differentially to VEGFR and PDGFR inhibitors, which may provide useful information during routine safety assessment for determining target organ toxicity.

Review of the effects of anti-angiogenic compounds on the epiphyseal growth plate.

The formation of new blood vessels from a pre-existing vascular bed, termed "angiogenesis," is of critical importance for the growth and development of the animal since it is required for the growth of the skeleton during endochondral ossification, development and cycling of the corpus luteum and uterus, and for the repair of tissues during wound healing. "Vasculogenesis," the de novo formation of blood vessels is also important for the proper function and development of the vascular system in the embryo. New blood vessel formation is a prominent feature and permissive factor in the relentless progression of many human diseases, one of the most important examples of which is neoplasia. It is for this reason that angiogenesis is considered to be one of the hallmarks of cancer. The development of new classes of drugs that inhibit the growth and proper functioning of new blood vessels in vivo is likely to provide significant therapeutic benefit in the treatment of cancer, as well as other conditions where angiogenesis is a strong driver to the disease process. During the preclinical safety testing of these drugs, it is becoming increasingly clear that their in vivo efficacy is reflected in the profile of "expected toxicity" (resulting from pharmacology) observed in laboratory animals, so much so, that this profile of "desired" toxicity may act as a signature for their anti-angiogenic effect. In this article we review the major mechanisms controlling angiogenesis and its role during endochondral ossification. We also review the effects of perturbation of endochondral ossification through four mechanisms-inhibition of vascular endothelial growth factor (VEGF), pp60 c-Src kinase and matrix metalloproteinases as well as disruption of the blood supply with vascular targeting agents. Inhibition through each of these mechanisms appears to have broadly similar effects on the epiphyseal growth plate characterised by thickening due to the retention of hypertrophic chondrocytes resulting from the inhibition of angiogenesis. In contrast, in the metaphysis there are differing effects reflecting the specific role of these targets at this site.