CD4+ T-cell Subsets and Cytokine Signature in Pemphigus Foliaceus Clinical Stratification beyond the th1/Th2 Paradigm.

BACKGROUND: T helper interplay and cytokines monitoring in auto-immune skin disorders such as Pemphigus Foliaceus [PF] may play a central role in predicting the clinical stratification of the pathology. OBJECTIVES: In order to assess the CD4+ T cell imbalance, [i] this study aims to assess the related immune cells [Th1, Th2, Th17, and Treg cells] as well as the related cytokines [IL-1ß, IFNγ, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-17F, IL- 22, TNF-ß, and TNFα] in peripheral blood, and [ii] their respective transcription factors in the lesioned skin of PF endemic patients during the clinical course. METHODS: Peripheral blood of 22 PF patients was analyzed by flow cytometry to assess the functional associations of Th cell subpopulations and their characteristic cytokines by multiplex bead assay of 14-plex cytokines. Skin mRNA expression of their associated transcription factors was analyzed using the TaqMan detection system. RESULTS: Our findings revealed that the CD4+ T cell subtypes in PF patients compared to Healthy Controls [HC] were characterized by [i] a similar Th1/Th2 ratio and increased Th17/Treg ratio and [ii] significantly higher plasma levels of Th-17 specific cytokines; IL- 6, IL-8, IL-17A. Higher percentages in Th17 and Treg subtypes and a significant increase in plasma IL-17F levels were maintained in relapsing PF patients, arguing the pivotal role of Th17 cells in PF pathogenesis. Furthermore, our findings pointed out the major contribution of the pro-inflammatory cytokine IL-6. Indeed, in addition to being involved in the initial stages of disease development, IL-6 seems to also be involved in the maintenance of the pathophysiological process, probably through its effect on Th17 differentiation. The skin-relative mRNA expression levels of FOXP3 and TBET were significantly higher in relapsing PF patients compared to de novo PF patients. CONCLUSION: Our results highlight the central role played by Th17 lymphocytes and their related pro-inflammatory cytokines during the clinical course of the disease, reversing the Th1/Th2 dichotomy in PF.

Unilateral hyperpigmented lesion of the breast.

Muco-cutaneous melanosis is a benign entity with no progression. Although, dermoscopic features may help to differentiate melanosis from malignant pigmented diseases, histopathology remains crucial for the confirming of melanosis of the nipple and areola. Herein, we represent a new case of melanosis of the areola and we describe its clinico-pathological aspects.

Multiple asymptomatic papules following breast cancer treatment.

Acquired lymphangiectasia (AL) represents superficial lymphatic dilatation caused by different processes. It is a consequence of lymphatic damage by an external cause; leading to obstruction of local lymphatic drainage.1 We report a case of AL of the breast in a 45-year-old woman mimicking warts.

Fat necrosis: A neglected side effect of intramuscular injections.

Panniculitis has various etiologies. One of the less common causes is trauma and hence traumatic fat necrosis (FN). These soft tissue injuries usually appear on the shins, thighs, breasts, arms, and buttocks. FN is mainly caused by trauma and may be associated with other conditions such as pancreatic disease. FN arising after intramuscular injections is uncommon and usually appears as firm, encapsulated, mobile, nontender, and solitary or multiple subcutaneous nodules. We report an interesting case of FN caused by intramuscular injections of cefazolin and meglumine antimoniate (MA) in a 38-year-old female patient. MA is regarded as the first-line systemic treatment for cutaneous leishmaniasis (CL). However, these drugs are not devoid of various potentially adverse reactions.

Kaposiform hemangioendothelioma with fatal income: Kasabach-Merritt phenomenon and hypercalcemia.

Kaposiform hemangioendothelioma is a rare, borderline tumor that typically occurs during early childhood. Kasabach-Merritt phenomenon is a complication characterized by a consumptive coagulopathy resulting from the localized intravascular coagulation. Hypercalcemia generation is a rare association that was related in our case to parathyroid hormone-related protein produced by this angioma.

Date seed oil inhibits hydrogen peroxide-induced oxidative stress in human epidermal keratinocytes.

BACKGROUND: Oxidative stress has been implicated in various skin diseases through the generation of reactive oxygen species and the depletion of endogenous antioxidant systems. The administration of antioxidants is reportedly helpful, notably to enhance the healing process. To protect the skin against oxidative damages, we have studied the effect of new oil: "date seed oil" (DSO). This oil, may serve as a potential source of natural antioxidants such as phenols and tocopherols. METHODS: Here, we report the protective effect of DSO against hydrogen peroxide (H(2)O(2))-induced oxidative stress in terms of lipid peroxidation, depletion of endogenous antioxidant defense enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) using normal human epidermal keratinocytes (NHEK). RESULTS: In the investigated model system, DSO has significant chemoprotective effect, by inhibition of damage caused by H(2)O(2) compared with cells without such addition endowing with a radical scavenging ability. Treatment of NHEK with DSO inhibited H(2)O(2)-induced lipid peroxidation. In addition, this oil inhibited H(2)O(2)-induced depletion of antioxidant defense components, such as SOD, CAT and GPx. CONCLUSIONS: Our findings demonstrate that DSO is an efficient extract that is able to prevent keratinocytes oxidative damage induced by H(2)O(2) exposure and may thus be a potential promising candidate, as a chemopreventive agent, in the development of keratinocytes-related pathologies.

Date seed oil inhibits hydrogen peroxide-induced oxidative stress in normal human epidermal melanocytes.

The administration of antioxidants has been shown to enhance repair and healing processes in cutaneous tissue. Date seed oil (DSO) extract, which might be a potential source of natural antioxidants such as phenols and tocopherols, has been reported to be beneficial in the reduction of chemically induced oxidative stress in normal human skin. In this study, we investigated the protective effects of DSO against hydrogen peroxide (H(2)O(2))-induced oxidative stress in terms of lipid peroxidation, depletion of such endogenous antioxidant defense enzymes as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) using normal human epidermal melanocytes (NHEM). The results showed that DSO, endowed with a radical scavenging ability, decreased oxidative injury by inhibition of damage caused by H(2)O(2). Treatment of NHEM with DSO inhibited H(2)O(2)-induced lipid peroxidation. In addition, the extract inhibited H(2)O(2)-induced depletion of antioxidant defense components, such as SOD, CAT, and GPx. Our findings demonstrate that DSO is an efficient extract able to prevent melanocytes oxidative damage induced by H(2)O(2) exposure. Thus it may be a potential promising candidate, as a chemopreventive agent, in the development of melanocyte-related pathologies like vitiligo and melanoma.

A comparative study of oxidant-antioxidant status in stable and active vitiligo patients.

The pathogenetic mechanisms in vitiligo have not been completely clarified. One of the major hypotheses in the pathogenesis of vitiligo is the oxidative stress hypothesis. The active or stable phase of vitiligo is defined on the basis of the progression or appearance of new lesions in the last 3 months and the absence of new lesions or their progression in the last 6 months, respectively. Eighteen patients with active vitiligo, 18 patients with stable vitiligo, and 40 controls were included in this study. We examined serum levels of malondialdehyde, selenium, vitamin E and A, and the erythrocyte activities of glutathione peroxidase, superoxide dismutase, and catalase. Our results revealed a significantly higher level of serum malondialdehyde, selenium in patients with active disease compared with the controls. Significant higher increase in erythrocytes superoxide dismutase activities was observed in active vitiligo group, erythrocyte glutathione peroxidase activity was decreased significantly in active disease, whereas erythrocyte catalase activity and plasma vitamin E and A levels were not different in vitiligo patients as compared with controls. Our study shows that oxidative stress is involved in the pathophysiology of both active and stable vitiligo but increased imbalance of antioxidants was observed in the blood of active vitiligo patients.