Iman M. Amin

Treatment of dystrophic epidermolysis bullosa with bone marrow non‐hematopoeitic stem cells: a randomized controlled trial

Patients with dystrophic epidermolysis bullosa (DEB) have mutations in type VII collagen gene. Type VII collagen is synthesized by keratinocytes and fibroblasts. Based on the ability of bone marrow non‐hematopoeitic stem cells (NHBMSC) to develop into fibroblasts, we decided to investigate the use of NHBMSC in the treatment of recessive DEB (RDEB). This study included fourteen patients with RDEB; the first seven of them were given cyclosporine after the infusion of NHBMSC. As cyclosporine has been used for the treatment of RDEB we decided not to use cyclosporine for the second group of seven patients. Skin biopsies from the lesions were studied by electron microscopy before and after treatment. The number of new blisters decreased significantly after treatment in both groups (p = 0.003 and 0.004 respectively) and the rate of healing of new blisters became significantly faster after treatment in both groups (p < 0.001) with no significant difference between the two groups. Electron microscopic examination revealed increased number of anchoring fibrils after treatment in both groups. No major side effects were reported during the 1‐year follow‐up period. Our findings highlight the efficacy as well as the safety of NHBMSC in the treatment of RDEB.

Skin tags, leptin, metabolic syndrome and change of the life style

BACKGROUND Skin tags (STs), are papillomas commonly found in the neck and in the axillae of middle-aged and elderly people. Metabolic syndrome (MS) is a complex of interrelated risk factors for cardiovascular disease and diabetes. Epidemiologic studies of different ethnic populations have indicated that hyperleptinaemia and leptin resistance are strongly associated with MS. AIM To study the possible relation of skin tags and leptin levels to MS guided by the International Diabetes Federation (IDF) diagnostic criteria. METHODS This study included 80 participants, 40 ST patients and 40 apparently healthy controls. Age, sex, waist circumference (WC), body mass index (BMI), smoking status, fasting glucose level, insulin level and insulin resistance were estimated as well as cholesterol, triglycerides, HDL, criteria of MS, and leptin levels. RESULTS The univariate analysis showed that WC, BMI, fasting glucose, insulin levels, insulin resistance, cholesterol, triglycerides, HDL, and leptin levels were significantly higher in ST patients compared to controls (P<0.001). The multivariate analysis between MS components and ST showed that only high triglyceride levels (OR 1.205/95% CI 1.044-1.391/P=0.011) and low HDL levels (OR 0.554/95% CI 0.384-0.800/P=0.002) were significantly associated with ST. Multivariate linear regression analysis of the predictors of high plasma leptin levels, showed that high triglyceride levels (OR 0.287/95% CI 0.410-3.56/P=0.014), and low HDL levels (OR -0.404/95% CI -8.7 to -2.08/P=0.002) were significant predictors. CONCLUSION The results of this study suggested that the presence of both ST and hyperleptinaemia in patients with STs may be associated with high levels of triglycerides and low levels of HDL and this could suggest that changing the life style of patients with ST may have a beneficial role.

Mycophenolate mofetil: a novel immunosuppressant in the treatment of dystrophic epidermolysis bullosa, a randomized controlled trial

Background: No effective treatment has been found for epidermolysis bullosa dystrophica (EBD). Objective: To evaluate the efficacy and safety mycophenolate mofetil (MMF) in treating EBD. Methods: This randomized controlled double-blinded study included 35 patients with severe generalized EBD. Patients were randomly divided into two groups: group I (18 patients) received cyclosporine therapy (5 mg/kg/day) and group II (17 patients) received MMF therapy (500–1500 mg/day). Clinical assessment was made weekly for 3 months from the start of the treatment. Patients were assessed by measuring the extent of the disease, the % of improvement, assessing the number of new blister formation and the time of complete healing of new blisters. Side effects were recorded when detected. Results: The % of improvement in the disease extent was statistically significantly higher (p = 0.009) in group I (mean ± SD: 59.21 ± 22.676) than in group II (mean ± SD: 44.03 ± 25.71). As regards the number of new blisters and the rate of healing of blisters, there was no statistically significant difference between both groups (p = 0.693 and 0.404, respectively). No serious side effects were reported. Conclusion: MMF seems to be a good therapeutic option for the long-term treatment of EBD, it can be a good alternative for patients who cannot tolerate cyclosporine.

Insulin-like growth factor-1 in psoriatic plaques treated with PUVA and methotrexate

Background  The pathogenesis of psoriasis is thought to depend on the activation of immune cells and their secreted cytokines, chemokines and growth factors like IGF‐1 which may contribute to the epidermal hyperplasia of psoriasis. Treatment of psoriasis with PUVA and methotrexate are associated with clinical improvement and decrease in epidermal hyperplasia.

Tissue level of nuclear factor-erythroid2-related factor2 and melanocyte-stimulating hormone in vitiligo patients

BackgroundThe pathogenesis of vitiligo is believed to depend on the presence of intrinsic/extrinsic metabolic defects in the melanocytes themselves or in the epidermal melanin unit, leading to oxidative stress, which further leads to melanocyte damage. The transcription factor, nuclear factor-erythroid 2-related factor 2 (Nrf-2), is a central regulator of the cellular antioxidant response and is a key factor for cytoprotection in various aspects. &agr;-Melanocyte-stimulating hormone (&agr;MSH) also plays an additional antioxidant role beyond its effect on the stimulation of melanogenesis. ObjectiveTo assess the level of Nrf-2 and &agr;MSH in lesional and perilesional vitiligo skin and to study their relationship with the extent and activity of the disease. Patients and methodsFor 22 vitiligo patients, the vitiligo disease activity score and levels of lesional and nonlesional Nrf-2 and &agr;MSH mRNA were determined by reverse transcription-PCR. Skin biopsies from 10 healthy volunteers served as controls for Nrf-2 and &agr;MSH mRNA levels in normal skin. ResultsLesional skin of vitiligo patients showed a significantly lower expression of Nrf-2 mRNA levels in comparison with nonlesional biopsies from the patients and with normal skin of the controls (P=0.001 and 0.000, respectively). Moreover, Nrf-2 mRNA in nonlesional skin of patients was significantly lower than that in the controls (P<0.01). The same trend was found in the levels of &agr;MSH mRNA, which were significantly decreased in the lesional and perilesional biopsies versus the control group (P=0.000 and 0.000). No significant correlation was detected between the levels of Nrf-2 mRNA and the levels of &agr;MSH mRNA in lesional vitiligo skin. The levels of Nrf-2 and &agr;MSH mRNA were not affected by the activity of the disease, presence of stress, or the extent of the disease. ConclusionThe reduction of both Nrf-2 and &agr;MSH mRNA levels in vitiligo lesions may play a role in the pathogenesis of vitiligo; yet, their levels are not markers of disease activity or severity. Moreover, the downregulation of their levels in perilesional skin of vitiligo patients may be a requisite for disease initiation when they reach levels that allow loss of self-tolerance.

Toll-like receptor (TLR)7 expression in mycosis fungoides and psoriasis: a case–control study

Toll‐like receptors (TLRs) have been implicated in various dermatological diseases. TLR agonists have the capacity to potently activate the innate immune cells of patients with advanced, refractory, cutaneous T‐cell lymphoma (CTCL).

Histopathological evidence of involvement of eccrine sweat glands in adverse cutaneous drug reactions

BackgroundInvolvement of eccrine sweat glands in adverse cutaneous drug reactions (ACDRs) has not received sufficient interest. ObjectiveTo examine histopathological changes in eccrine sweat glands in ACDRs. Patients and methodsForty ACDR cases were recruited. Lesional and nonlesional biopsies underwent thorough histopathological evaluation of the eccrine apparatus. ResultsThe eccrine apparatus was involved in 97.5% of lesional skin biopsies, secretory coils most frequently, and in 42.1% of apparently normal skin biopsies, and the difference was statistically significant (P<0.05). The most frequently encountered changes in lesional skin included acrosyringial necrosis, intraductal inflammatory cell infiltrate, and hydropic degeneration of the secretory coils. ConclusionThe invariable involvement of the eccrine sweat apparatus in ACDRs appears to be largely secondary to different mediators of the inflammatory process rather than events primarily and directly caused by the inciting drugs.

Assessment of Tissue Level of Histone Deactylase-2 (HDAC-2) in Patients With Mycosis Fungoides

Background: Histone deactylases (HDAC) have a role in the pathogenesis of mycosis fungoides (MF) through their actions on different apoptosis pathways. Objective: To assess the possible role played by HDAC-2 in MF by estimating the tissue expression of HDAC2 mRNA in different stages of MF. Methods: This study included 28 MF patients and 30 controls. The HDAC-2 levels were detected by real-time polymerase chain reaction (PCR). Correlations of HDAC-2 levels with clinical presentation and different stages of MF were analyzed. Results: Mean HDAC-2 level was significantly higher in patients (P < .001) than in controls. HDAC-2 highest mean value was significantly detected in patients with stage IIb, and the lowest mean value was detected in patients with stage Ia (P < .001). Conclusion: Up-regulation of tissue HDAC-2 in MF patients might develop a new approach in the understanding of the pathogenesis of MF. Histone deactylases are important targets for molecular cancer therapeutics.

Morphometry of pilosebaceous unit and immunohistochemical expression of substance P and neurokinin-1 receptor in acne vulgaris

BackgroundAcne vulgaris is a distressing condition that affects the pilosebaceous follicles. Neuropeptides, notably substance P (SP), are considered to play a role in the pathophysiology of acne. ObjectiveTo study the pilosebaceous units (PSUs) and the expression of SP and its receptor neurokinin-1 (NK-1R) in comedonal and inflammatory acne lesions in comparison with controls and to verify the relation of the expression of this neuropeptide and its receptor with stress. Patients and methodsA total of 30 patients with acne vulgaris and 20 age-matched and sex-matched healthy controls were the participants of this study. Perceived Stress Scale was carried out for every patient. Skin biopsies were taken from comedonal lesions, inflammatory lesions, and normal control skin. Biopsies were subjected to routine hematoxylin and eosin staining for morphometric evaluation of PSUs and sebocytes as well as immunohistochemical staining for the detection of SP and NK-1R. ResultsSignificantly larger PSUs and sebocytes were detected in acne lesions compared with the controls (P<0.0001). Both SP and NK-1R showed significantly higher expression in acne lesions compared with the controls (P<0.0001), being significantly higher in inflammatory lesions compared with comedonal lesions (P<0.0001). Both SP and NK-1R showed a significant direct correlation with Perceived Stress Scale in both comedonal and inflammatory lesions (P<0.05). ConclusionSP and its receptor NK-1R seem to be important in the regulation of sebaceous gland function and provide a new insight into the involvement of the cutaneous nervous system in the pathogenesis of acne.

Serum and tissue transforming growth factor β1 expression in vitiligo

BackgroundVitiligo is believed to result from progressive autoimmune-mediated loss of melanocytes. Although a number of studies suggest the involvement of several autoimmune influencing cytokines in the pathogenesis of vitiligo, these reports are still limited and contradictory. ObjectiveTo examine the degree of expression of transforming growth factor &bgr;1 (TGF-&bgr;1) in both the serum and the tissue of vitiligo patients and their relation to disease development, progression, and severity. Patients and methodsIn this case control study, 20 vitiligo patients and 10 age-matched and sex-matched controls were recruited. TGF-&bgr;1 levels were detected in serum and lesional as well as nonlesional specimens of cases and controls. The relations of TGF-&bgr;1 levels with disease parameters including disease extent, type, and vitiligo disease activity score were analyzed statistically. ResultsSerum and tissue levels of TGF-&bgr;1 were significantly lower in patients than the controls (P=0.001 and P<0.001, respectively). There was no significant difference between the TGF-&bgr;1 levels between the lesional and the nonlesional skin of patients (P=0.634). ConclusionDownregulation of serum and tissue TGF-&bgr;1 may result in the loss of peripheral tolerance mediated by T regulatory cells and should be further investigated as a prerequisite for disease initiation in susceptible individuals.