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Πέμπτη 25 Ιουλίου 2019

Kasr AL-Ainy’s psoriasis unit protocol for the treatment of psoriasis, part II: biological therapies
Hoda Rasheed, Hesham A.Z AEl-Moaty, Mohamed H.M El-Komy, Heba Mashaly, Khadiga S Sayed, Vanessa Hafez, Marwa S El-Mesidy, Eman R Said, Marwa A Amer, Aya M AlOrbani, Dina G Saadi, Mona El-Kalioby, Reem O Eid, Yousra Azzazi

Journal of the Egyptian Women�s Dermatologic Society 2019 16(2):73-80

Psoriasis is a chronic multisystem inflammatory disease affecting primarily the skin and joints but also involves several comorbidities. The disease affects between 0.2 and 4% of the population worldwide. The Kasr Al-Ainy Psoriasis Unit developed a protocol of therapy for psoriasis. Part I discussed the topical and systemic therapies. This part discusses the biological therapy. Biological therapies for psoriasis are agents that can specifically target an immune mediator and block specific molecular steps important in the pathogenesis of psoriasis. Despite the cost, the use of biological therapies in psoriasis is sometimes necessary. However, the adequate choice of biologic in the proper indication is mandatory for cost–benefit balance for the patient. Physicians using biological therapies should be familiar with complications. The protocol offers regional physicians a practical algorithm for choice of biological therapies in psoriasis and a full workup before therapy and during follow-up. Authors highlight the safety and efficacy data of biologic therapies available in the Egyptian market, with special focus on particular situations (hepatitis, tuberculosis, and demyelinating disorders). 

Immunohistochemical study of Wnt5a expression in cutaneous and oral lichen planus
Rania A.R Eltatawy, Ghada F.R Hassan, Asmaa M.A Qandeel, Dareen A Mohammed

Journal of the Egyptian Women�s Dermatologic Society 2019 16(2):81-88

Background Lichen planus (LP) is an inflammatory disease that affects the skin, mucous membranes, and skin appendages. Although the exact cause of LP is unclear, it was thought to be a T cell-mediated autoimmune disease. Wnt5a is one of the most extensively studied Wnt proteins, which has an important role in stimulating inflammation, cellular proliferation, differentiation, apoptosis, migration, and polarity. Objective To study the immunohistochemical expression of Wnt5a in patients with cutaneous and oral LP in comparison with healthy participants to study its possible role in the pathogenesis of the disease. Patients and methods Sixty patients with cutaneous and oral LP were included in this study, in addition to 40 healthy skin and oral mucosa specimens serving as controls. Punch biopsies of 3 mm were taken from lesional skin and control skin and were immunohistochemically stained for Wnt5a expression. Results There was a statistically significant increase in Wnt5a expression in cutaneous and oral LP lesions compared with normal controls. Moreover, Wnt5a expression was increased in hypertrophic and oral types of LP when compared with other types: classic, atrophic, and actinic. Moreover, a statistically higher expression of Wnt5a was found in hepatitis C antibodies-positive patients when compared with hepatitis C antibodies-negative patients. Conclusion Expression of Wnt5a was significantly increased in patients with LP than in controls, and this supports that Wnt5a might be involved in the pathogenesis of LP. Overexpression of Wnt5a in hypertrophic and oral types of lichen may predispose to malignant transformation. Therefore, these patients should be followed up regularly. 

Topical tranexamic acid with microneedling versus microneedling alone in treatment of melasma: clinical, histopathologic, and immunohistochemical study
Fatma Y Saleh, Eman S Abdel-Azim, Maha H Ragaie, Mary G Guendy

Journal of the Egyptian Women�s Dermatologic Society 2019 16(2):89-96

Background Melasma is an acquired disorder of symmetrical hypermelanosis that involves sun-exposed areas of the skin. Although multiple therapeutic modalities have previously been tried, successful, truly effective treatment options for this condition have been few and quite elusive. Objectives To compare the therapeutic efficacy of topical tranexamic acid (TXA) with microneedling versus microneedling alone in the treatment of melasma and to evaluate the changes that occur clinically, histologically, and immunohistochemically. Patients and methods This study was conducted on 42 patients with melasma, randomly divided into two groups. In group I, each patient was subjected to a series of six sessions of skin microneedling and TXA application, whereas in group II, six sessions of microneedling alone were performed, with 2-week interval. Results Clinically, the mean melasma area and severity index (MASI) score was significantly decreased in both groups with statistically significant higher reduction scores in group I compared with group II. Histopathologically, epidermal hyperpigmentation and dermal melanophages were significantly reduced after treatment with more obvious reduction in group I. The number of melanoma antigen recognized by T cells-1-positive cells showed significant reduction in both groups; this reduction was statistically higher in group I than group II. Conclusions Although microneedling alone produced significant lightening effect, topical TXA combined with microneedling achieved more satisfactory results. 

Role of chemokine ligand 22 in narrow-band ultraviolet B-induced pigmentation in vitiligo: an immunohistochemical study
Azza G Antar Farag, Mostafa A Hammam, Dalia R Al-Sharaky, Reem A Hassan, Eman N ElShafey, Nehal A Ali

Journal of the Egyptian Women�s Dermatologic Society 2019 16(2):97-104

Background Chemokine ligand 22 (CCL22) is a heparin-binding immunomodulator protein that plays an important role in a variety of autoimmune diseases. Narrow-band ultraviolet B (NB-UVB) therapy was considered a cornerstone in the treatment of vitiligo. However, the mechanism of action of NB-UVB in vitiligo has not been completely elucidated. Objective To study the hypothesized role of CCL22 in vitiligo etiopathogenesis and to detect its possible role in NB-UVB-induced pigmentation in vitiligo through its lesional immunohistochemical evaluation in patients with vitiligo before and after ultraviolet B phototherapy. Patients and methods A total of 33 patients with vitiligo versus 20 patients of age-matched, sex-matched, and skin phototype-matched healthy controls were enrolled in this case–control study. Patients were treated with NB-UVB three sessions weekly for 12 weeks. Vitiligo Area Scoring Index score was evaluated before and after NB-UVB sessions. For patients with vitiligo, baseline CCL22 immunohistochemical staining was estimated, and compared with that of controls and with its posttreatment data in those patients. Results Baseline CCL22 immunohistochemical studied parameters were insignificantly lower in patients with vitiligo than controls except its cellular localization (P<0.001). After 12 weeks of NB-UVB, these CCL22 immunohistochemical parameters were significantly up-regulated (P<0.001). Although there was a negative correlation between the improvement in Vitiligo Area Scoring Index score and CCL22 H score, this correlation could not reach level of significance (r=0.086, P=0.653). Conclusion Although we could not confirm that CCL22 protein has an active role in the pathogenesis and development of vitiligo, we concluded that CCL22 chemokine may take part in photo-induced melanogenesis. Yet, the mechanism of NB-UVB-induced pigmentation is still far from being clarified, and further studies are needed. 

MicroRNA-146a and Forkhead box protein 3 expressions in nonsegmental vitiligo: an insight into disease pathogenesis
Arwa M Hassan, Yomna M. El-Hamd Neinaa, Amal S El-Bendary, Soha S Zakaria

Journal of the Egyptian Women�s Dermatologic Society 2019 16(2):105-111

Background Autoimmune destruction of melanocytes is the principal hypothesis in vitiligo pathogenesis. MicroRNA-146a (miRNA-146a) is considered an essential regulator of posttranscriptional gene expression, suggesting a potential role in autoimmune diseases. Forkhead box protein 3 (Foxp3) is a crucial transcription factor that controls regulatory T cells, which play a critical role in avoiding autoimmunity. Objective To evaluate the possible role and relationship of miRNA-146a and Foxp3 in the pathogenesis of nonsegmental vitiligo. Patients and methods A total of 50 patients with nonsegmental vitiligo and 25 healthy controls were enrolled in this study. History taking and thorough general and dermatological assessments of vitiligo patients were done including evaluation of Vitiligo Area Scoring Index and Vitiligo Index of Disease Activity scores. Relative levels of miRNA-146a and Foxp3 expressions were analyzed in the peripheral blood mononuclear cells of all participants by real-time reverse transcriptase-PCR. Results The relative levels of miRNA-146a expressions showed significant upregulation, whereas that of Foxp3 showed significant downregulation, in patients with vitiligo compared with healthy controls. In patients with vitiligo, there was negative correlation between relative levels of miRNA-146a and Foxp3 expressions. Furthermore, vitiligo activity assessed by Vitiligo Index of Disease Activity score correlated positively with miRNA-146a expressions and negatively with Foxp3 expressions. However, no significant correlation between their expressions and disease severity assessed by Vitiligo Area Scoring Index score was detected. Conclusion Both miRNA-146a and Foxp3 may be implicated in the pathogenesis and progression of nonsegmental vitiligo. Furthermore, they may serve as potential therapeutic targets for vitiligo. 

Serum calprotectin as a predictive biomarker in the treatment of psoriasis vulgaris with methotrexate
Ashraf M Hamza, Eman M Hassan, Hanaa M Donia, Yasmin M Maamon

Journal of the Egyptian Women�s Dermatologic Society 2019 16(2):112-118

Background Psoriasis is a chronic inflammatory disease that poses a challenge in its pathogenesis and treatment. Calprotectin is upregulated in psoriatic epidermis and is supposed to have a role in the inflammatory process of psoriasis. Calprotectin was suggested as a biomarker to detect responders to methotrexate in juvenile idiopathic arthritis. Objective To evaluate the relation of calprotectin serum level and psoriasis severity and to assess if it can predict response to methotrexate and disease relapse after stoppage of the treatment. Patients and methods Thirty patients with psoriasis vulgaris and 30 controls were included. Serum calprotectin was measured in controls and in patients before and after methotrexate therapy for 3 months. The patients were followed up for 6 months to detect disease stability or relapse and its relation to calprotectin level at the end of therapy. Results Higher calprotectin level in psoriatic patients was detected before methotrexate treatment than after treatment. Significant positive correlation was found between serum calprotectin and psoriasis area and severity index score. Calprotectin was higher in patients before starting methotrexate in those defined as responders than nonresponders (P=0.015) and can predict response to treatment with a cutoff value of 60 ng/ml (sensitivity 82.35% and specificity 69.23%). The level of calprotectin was higher in patients during their clinical remission who relapsed after stoppage of methotrexate than the nonrelapsed cases (P=0.021) and can predict the relapse with a cutoff value of 56.5 ng/ml (sensitivity 66.67% and specificity 100%). Conclusion Calprotectin can be a marker of psoriasis severity. Higher level of baseline serum calprotectin can predict psoriatic patients who will improve on methotrexate therapy. In addition, higher calprotectin levels were associated with relapse risk after stoppage of methotrexate. 

Assessment of cardiovascular risk in patients with androgenetic alopecia using high-sensitivity C-reactive protein and lipoprotein a
Magdy A Ragab, Eman M Hassan, Eman T El Sayed, Salwa A Abdaljawad

Journal of the Egyptian Women�s Dermatologic Society 2019 16(2):119-125

Background The association between androgenetic alopecia (AGA) and cardiovascular risk is still controversial. Objective To evaluate the association between AGA and the risk of cardiovascular diseases (CVDs) using lipoprotein a [Lp (a)] and high-sensitivity C-reactive protein (hs-CRP) as biomarkers of cardiovascular risk. Patients and methods A case–control study was done on 30 patients with AGA and 25 healthy controls with normal hair status. Both patients and their controls were examined generally and locally. Classification of AGA was done according to Hamilton–Norwood scale for male patients and Ludwig’s classification for women. Hair examination was confirmed using dermoscopy for the assessment of signs of AGA. All participants were investigated for serum lipids including cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, and Lp (a), in addition to hs-CRP. Results After exclusion of the well-known risk factors for CVD, AGA patients showed higher positive family history of CVD in first-degree relatives than the controls. Serum lipids including serum Lp (a) and hs-CRP were significantly higher in AGA patients. Lp (a) was positively correlated with hs-CRP in AGA patients. Both Lp (a) and hs-CRP were positively correlated with the severity of AGA in both men and women. Both markers did not correlate significantly with lipid parameters including cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein. There was no significant difference between men and women with AGA as regards the studied parameters. Both hs-CRP and Lp (a) showed significant discrimination using area under the receiver operating characteristic curve where Lp (a) showed area under the curve=0.928 with 95% confidence interval, 0.863–0.993 and P=0.001 while hs-CRP showed area under the curve=0.963 with 95% confidence interval 0.921–1.0, and P value less than 0.001. Multivariate logistic regression analysis showed that hs-CRP was the only significant independent factor affecting cardiac risk in AGA cases. Conclusion AGA patients showed higher risk for CVD. Both Lp (a) and hs-CRP can be used as a predictor for cardiovascular risk in such patients; however, hs-CRP is still considered an independent risk factor for cardiovascular insults in AGA patients. 

Serum galectin-9 levels in some inflammatory skin diseases: a pilot study
Eman Nofal, Fatma Eldesoky, Ahmed S Abdelshafy, Reham Elkot, Amal Zedan

Journal of the Egyptian Women�s Dermatologic Society 2019 16(2):126-132

Background Galectin-9 (Gal-9) is a tandem-repeat galectin family member. It is a physiological ligand for T-cell immunoglobulin and mucin-domain containing molecule-3. The interaction of T-cell immunoglobulin and mucin-domain containing molecule-3 and Gal-9 induces apoptosis in T helper 1 cells and T helper 17 cells. Atopic dermatitis (AD), psoriasis, and allergic contact dermatitis (ACD) are common, chronic, and relapsing inflammatory skin diseases associated with various immunologic abnormalities. Objective To investigate a potential role of Gal-9 in the pathogenesis of AD, psoriasis, and ACD and to assess its relation to the disease severity. Patients and methods Fifty-four patients (18 AD, 18 psoriasis, and 18 ACD) with different grades of severity and 18 healthy participants were included in the study. The severity of the diseases was determined by scoring of atopic dermatitis in AD cases, by psoriasis area and severity index score in psoriasis cases, and by staging of ACD. Serum Gal-9 levels were measured in all patients and controls by enzyme-linked immunosorbent assay. Results A statistically significant elevation in serum levels of Gal-9 in patients with AD was detected and was positively correlated with the disease severity. No statistical significant differences were detected between the serum levels of Gal-9 in psoriasis and ACD groups and control group. Limitations The small sample size and the inability to study Gal-9 in the skin were the main limitations. Conclusion It could be concluded that Gal-9 may be implicated in the pathogenesis of AD and is correlated with the disease severity. Its role in psoriasis and ACD could not be verified by this study. Restoration of immune equilibrium lost in AD, psoriasis, and ACD by galectins requires more and more recognition of these immunoregulatory molecules, which might be considered as a new therapeutic tool. 

YKL-40, fetuin-A plasma levels, and carotid intima-media thickness: do they have relations with subclinical atherosclerosis associated with psoriasis and the disease severity?
Naglaa F Agamia, Aly El-Ariny AF, Abeer El-Hadidy, Amr El-Abd AM, Doha Gaber

Journal of the Egyptian Women�s Dermatologic Society 2019 16(2):133-141

Background Despite the risk of cardiovascular incidents being high among patients with psoriasis, the mechanism of such association has not been established yet. YKL-40 is an active biological compound that could be related to subclinical atherosclerosis. Fetuin-A is a glycoprotein that inhibits vascular calcification, and its serum level is low in patients with atherosclerosis. Objective To find out if there is a relation between fetuin-A, YKL-40, and carotid intima-media thickness (CIMT) and subclinical atherosclerosis associated with psoriasis. Patients and methods The current study was carried out on 30 patients admitted to Alexandria Main University Hospital with chronic generalized psoriasis. Enzyme-linked immunosorbent assay was used to evaluate serum YKL-40 and fetuin-A. Carotid artery intima-media thickness was evaluated by B-mode ultrasonography. Psoriasis area and severity index was calculated in all psoriatic patients. Patients with BMI more than 30, waist circumference, fasting blood sugar, and lipid profile levels were excluded. Results Patients with psoriasis demonstrated a significantly higher YKL-40 serum levels, significantly lower fetuin-A, and significantly higher carotid artery intima-media thickness than controls. Psoriasis area and severity index score showed a significant positive correlation with YKL-40 and CIMT and no correlation with fetuin-A levels. YKL-40 is significantly correlated with abnormal CIMT. Fetuin-A is significantly correlated with normal and abnormal CIMT. Conclusion The increased plasma YKL-40 and the decreased plasma fetuin-A levels reported in patients with psoriasis might play a role in the increased risk of cardiovascular risk disorders in these patients. Carotid ultrasonography is a noninvasive, simple tool that detects subclinical atherosclerosis in patients with psoriasis. 

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