Krox20 expression in abnormal scars: An immunohistochemical study.

BACKGROUND: Scars are the end outcome of healing. They are grouped into several types, the common of which are keloids, hypertrophic, and atrophic scars. The role of Krox20 in skin and hair physiology and pathology had emerged. Overexpression of Krox20 was sufficient to stimulate collagen gene expression and myofibroblast differentiation and is necessary for transforming growth factor-ß (TGF-ß) induced profibrotic responses. OBJECTIVE: To investigate the role of Krox20 in abnormal scar pathogenesis. Hopefully, this insight can set the route for newer therapeutic approaches. MATERIALS AND METHOD: This study was carried out on 30 cases (10 cases of keloids, 10 cases of atrophic scars, and 10 cases with hypertrophic scars [HTS]) and 10 age and gender-matched apparently healthy subjects as a control group. Thirty biopsies were taken from perilesional areas. Evaluation of Krox20 expression was done using standard immunohistochemical technique. RESULTS: Krox20 was downregulated in epidermis of scar biopsies compared with perilesional and normal skin (p = 0.02) while it was overexpressed in fibroblasts in lesional scar biopsies compared with perilesional and normal skin (p < 0.001). Keloid cases have significantly higher Krox20 expression in fibroblasts compared with HTS cases (p < 0.001). Krox20 had significantly nucleocytoplasmic pattern of staining in scar cases compared with normal skin (p < 0.001). CONCLUSION: Krox20 overexpression may have a role in scar pathogenesis through upregulation of multiple genes associated with tissue remodeling and wound healing. This may open an avenue for research for new therapies based on Krox20 inhibition.

Serum nuclear factor E-2-related factor 2 in female pattern hair loss.

BACKGROUND: Female pattern hair loss (FPHL) is a common dermatological complaint with multifactorial etiology. Nuclear factor erythroid-2-related factor 2 (NRF2) is a transcription factor that has a major role in protection from ROS-induced apoptosis. AIM: To investigate the relationship between Nrf2 and systemic oxidative stress in FPHL patients. PATIENTS AND METHODS: This case-control study included 30 patients with FPHL and 30 age- and sex-matched healthy volunteers as a control group. Serum NRF2, total antioxidant capacity (TAC), and total oxidant capacity (TOC) were measured by ELISA, and oxidative stress index (OSI) was calculated. RESULTS: The serum level of TOC and OSI was found to be significantly higher (p ≤ 0.001 for both) while serum level of NRF2 and TAC was found to be significantly lower in cases than controls (p < 0.001 for both). There were a significant negative correlation between TAC and BMI (p = 0.03, r = -0.391) and a significant positive correlation between OSI and BMI (p = 0.04, r = 0.365). There were a significant positive correlation between serum level of NRF2 and TAC (p = 0.003, r = 0.532) and a significant negative correlation between serum the level of NRF2 and TOC (p = 0.02, r = -0.418) and OSI (p = 0.003, r = -0.395). CONCLUSION: Systemic oxidative stress in FPHL may be, at least in part, due to NRF2 deficiency. NRF2 activators may help in treatment of this disease. NRF2 deficiency has no role in disease severity. Healthy diet and body weight reduction may help in improving oxidative stress and subsequently improving FPHL.

Vitamin D Receptor Gene Polymorphism In Chronic Telogen Effluvium; A Case-Control Study.

BACKGROUND: Telogen effluvium (TE) is a form of alopecia characterized by diffuse hair shedding. Vitamin D receptor (VDR) plays a role in hair cycle regulation as it is expressed in follicular keratinocytes and dermal papilla cells. PURPOSE: To investigate the association between Cdx1 and Taq1 VDR gene polymorphisms and chronic TE. METHODS: Thirty female patients with chronic TE were selected and 30 healthy, age- and sex-matched volunteers were included as a control group. Detection of VDR gene polymorphisms Taq1 and Cdx1 was done by real-time polymerase chain reaction. RESULTS: Regarding Taq 1, CC genotype was present in 30% of cases versus 3.3% of controls. TC genotype was present in 33.3% of cases and 36.7% of controls. CC genotype was significantly associated with cases (P=0.01). It increases the risk of chronic TE by 14.7 folds. C allele was significantly associated with patient group (P=0.004). It increases the risk of disease occurrence by 3.1 folds. Regarding Cdx1, AA genotype was present in 6.7% of cases versus 3.3% of controls. GA genotype was present in approximately 30% of cases and 6.7% of controls. GA genotype was significantly associated with cases (P=0.03). It increases the risk of chronic TE by 6.3 folds. A allele was significantly associated with patient group (P=0.007). It increases the risk of disease occurrence by 3.8 folds. LIMITATIONS: The main limitation is the small number of cases due to the time and financial constraints. Only chronic TE was analyzed, therefore, other types should be investigated in the following studies. CONCLUSION: After exposure to primary physical or mental stressor, hair follicles are stimulated to enter prematurely into telogen and shed out. In individuals with Taq1 and Cdx1 polymorphisms, the disease persists as a result of prevention of new anagen growth and inhibition of hair follicle stem cell proliferation.

Is Aquaporin-3 a Determinant Factor of Intrinsic and Extrinsic Aging? An Immunohistochemical and Morphometric Study.

Aquaporin-3 (AQP3) is an aquaglyceroporin that plays a role in skin hydration, cell proliferation, and migration. The aim of this work was to investigate the expression of AQP3 in sun-exposed and sun-protected human skin from different age groups to understand the relationship between AQP3 and skin aging. Using standard immunohistochemical techniques, sun-exposed and sun-protected skin biopsies were taken from 60 normal individuals. AQP3 was expressed in the basal and the suprabasal layers, sparing the stratum corneum, in all specimens. Dermal expression was detected in fibroblasts, endothelial cells, and adnexa. Sun-protected skin showed a significantly higher epidermal H-score and percentage of expression (P=0.002 and <0.001, respectively) compared with sun-exposed skin. The AQP3 expression intensity showed a gradual decrease from the 20 to 35-year-old group to the 35 to 50-year-old group, with the least immunoreactivity in the above 50-year-old group. A significant difference was detected in the H-score in favor of the 20 to 35-year-old group in sun-exposed and sun-protected skin (P<0.001 for both). A significant negative correlation was noted between the AQP3 expression percentage and the age in sun-exposed (r=-0.64, P<0.001) and sun-protected skin (r=-0.53, P<0.001). In conclusion, the skin dryness observed in intrinsic and extrinsic aged skin may be explained, at least in part, by AQP3 downregulation. This may open new avenues sufficient to control skin texture and beauty. Its interaction in skin protein organization and gene polymorphism can also be tackled in future research. In addition, clinical trials using AQP3 topical applications should be carried out to evaluate its effectiveness in the reversal of age-related skin changes.

Serum Vitamin D and Facial Aging: Is There a Link?

BACKGROUND: The vitamin D endocrine system, besides multiple other functions, regulates aging in many tissues, including the skin. It protects the skin against the hazardous effects of many skin age-inducing agents, including ultraviolet radiation. Thus, in the present study we aimed to investigate the relationship between facial skin aging and 25-hydroxyvitamin D [25(OH)D] serum levels in healthy Egyptian adults. METHODS: Sixty-one healthy adult subjects were included. Photodamage scores (erythema/telangiectasias, lentigines, hyperpigmentation and coarse wrinkling) were assessed and graded. Serum vitamin D was measured using enzyme immunoassay and subjects were classified as sufficient, insufficient or deficient according to the vitamin level. RESULTS: The mean 25(OH)D serum level was 43.90 nmol/l. A high prevalence of vitamin D deficiency was detected in the studied subjects regardless of their age or gender. Also, vitamin D levels were not correlated with photodamage scores and were not affected by the Fitzpatrick skin phototype, duration of sun exposure per day or the use of sunscreens (p > 0.05 for all). CONCLUSIONS: Aging is a complex process that is influenced by many genetic and environmental factors. Facial aging is not correlated with serum vitamin D level, and clinical trials using oral or topical vitamin D to combat aging are better predictors of its effects rather than in vivo studies.

Immunohistochemical Evaluation of Leptin Expression in Wound Healing: A Clue to Exuberant Scar Formation.

Leptin has been recognized as an important factor for promoting normal cutaneous wound healing. The aim of this work was to explore leptin expression in keloid and hypertrophic scars (HS) compared with surgical scars and normal skin. The relationship of this expression with clinicopathologic parameters of studied cases was also evaluated. Using immunohistochemical techniques, leptin was analyzed in skin biopsies of 60 nonobese subjects without metabolic syndrome who presented with keloids (20), HS (20), and surgical scars (20). Twenty normal skin samples, from age-matched, sex-matched, and body mass index-matched subjects, were enrolled as a control group. Leptin showed positive immunoreactivity in epidermis in all cases of surgical scars and keloids and in 75% of HS cases. Dermal expression in fibroblasts, inflammatory cells, and endothelial cells was positive in all cases of surgical scars and keloids and in 70% of HS cases. Leptin was overexpressed in keloids and HS compared with normal skin in epidermis (P<0.001 for both) and dermis (P<0.001 for both) and to surgical scars both in epidermis (P=0.0006, P=0.01, respectively) and dermis (P=0.0001, P=0.001, respectively). Higher leptin H score was significantly associated with older age (P=0.02) and positive family history (P=0.002) in keloid cases and with axial site in keloid and HS cases (P=0.001, P=0.02, respectively). Significant positive correlation was noted between epidermal and dermal leptin H scores in keloids (r=+0.37, P=0.04) and HS (r=+0.39, P=0.02). This may be due to epithelial-mesenchymal interactions in scar pathogenesis. In conclusion, in situ leptin overexpression may increase the possibility of keloid and HS occurrence through altered cytokine production and prolonged healing phases with excessive deposition and delayed collagen degradation. This may open an avenue for research for new therapeutic modalities based on its inhibition.

Atherogenic index of plasma in non-obese women with androgenetic alopecia.

BACKGROUND: Androgenetic alopecia (AGA) is characterized by the local and gradual transformation of terminal scalp hair into vellus hair, which has a shorter and thinner shaft. Several studies have analyzed the relationship between AGA and cardiovascular disease in males, and few were conducted in females. The current study aimed to investigate lipid profile and atherogenic index of plasma in non-obese females with AGA. METHODS: Forty non-obese females with early-onset AGA were selected with 40 age- and gender-matched healthy subjects as a control group. Total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides were measured, and the atherogenic index of plasma was calculated for all cases and control subjects. RESULTS: Mean values of total cholesterol (P < 0.001), low-density lipoprotein cholesterol (P = 0.03), and triglycerides (P = 0.001) were significantly higher in cases than controls. Mean value of high-density lipoprotein cholesterol was significantly lower in cases than controls (P = 0.008). The atherogenic index of plasma was significantly higher in cases than controls (P < 0.001). CONCLUSION: Current findings support the relationship between early-onset AGA and unfavorable lipid profile and cardiovascular risk in affected females. Assessment and follow-up of these cases will allow early intervention to avoid cardiovascular complications.

Thyroid disorders associated with alopecia areata in egyptian patients.

CONTEXT: Alopecia areata (AA) is a common form of localized, non-scarring hair loss. The etiopathogenesis of the disease is still unclear, but the role of autoimmunity is strongly suggested. AA is commonly associated with various autoimmune disorders; the most frequent among them is autoimmune thyroid disorders. AIM: To determine whether AA is associated with thyroid autoimmunity or thyroid function abnormalities in Egyptian patients. MATERIALS AND METHODS: Fifty subjects with AA (37 males and 13 females) without clinical evidence of thyroid disorders were selected from Dermatology Outpatient Clinic, Menoufiya University Hospital, Menoufiya Governorate, Egypt, during the period from June 2009 to February 2010. They were divided into 3 groups according to severity of AA. Fifty age and sex-matched healthy volunteers (35 males and 15 females) were selected as a control group. Every case and control were subjected to history taking, complete general and dermatological examination. Venous blood samples were taken from cases and controls after taking their consents for measurement of thyroid stimulating hormone (TSH), free T3, freeT4 and detection of Anti-thyroglobulin Antibody (Tg-Ab) and Anti-thyroid Peroxidase Antibody (TPO-Ab). RESULTS: Subclinical hypothyroidism was detected in 16% of cases. There were statistically significant differences between cases and controls regarding levels of TSH, free T3 and free T4. There were significant differences between cases and controls regarding the presence of Tg-Ab and TPO-Ab. CONCLUSIONS: Every patient with AA should be screened for thyroid functions and presence of thyroid autoantibodies even in absence of clinical manifestations suggestive of thyroid affection.

Multiple familial trichoepithelioma with malignant transformation.

Trichoepithelioma (TE) is a benign tumor of follicular origin that presents as small, skin-colored papules predominantly on the face. When more than one family member is affected, the disease is known as multiple familial trichoepithelioma (MFT). It is a rare autosomal dominant (AD) skin disease. Malignant transformation is very rare. We present a case of MFT in a female patient and her father with malignant transformation to basal cell carcinoma (BCC) in the father. We summarized the main histological differential parameters between TE and BCC and applied immunophenotyping for both by administration of Bcl2, CD34, CD10 and androgen receptor (AR) antibodies.

Olmsted syndrome.

BACKGROUND: Olmsted syndrome is a rare keratinization disorder characterized by a combination of periorificial keratotic plaques and bilateral palmoplantar transgredient keratoderma. Other clinical manifestations include diffuse alopecia, leukokeratosis of the oral mucosa, onychodystrophy, hyperkeratotic linear streaks, follicular hyperkeratosis and constriction of digits. MAIN OBSERVATIONS: We report a case of Olmsted syndrome in a 5-year-old male presented by mutilating palmoplantar keratoderma, perioral keratoses and linear hyperkeratotic lower limb plaques. CONCLUSIONS: Olmsted syndrome is a rare genodermatosis with only 43 cases reported so far. We present another case of the disease.

Indeterminate cell histiocytosis with naïve cells.

Histiocytoses are a heterogeneous group of disorders characterized by proliferation and accumulation of cells of mononuclear-macrophage system and dendritic cells. Histiocytoses are categorized according to the cell of origin into Langerhans cell histiocytosis (LCH), Non Langerhans cell histiocytoses and indeterminate cell histiocytosis (ICH). ICH is an extraordinary rare neoplastic dendritic cell disorder that has poorly understood histogenesis and pathogenesis. It is characterized by a proliferation of dendritic cells, which mimic Langerhans cells immunophenotypically (positive for CD1a and S-100 protein), but lack Birbeck granules characteristic of Langerhans cells. Twenty-four year-old Egyptian male was presented with reddish brown chest wall nodule. Clinical, histopathological, immunohistochemical and ultrastructure features are typical for ICH. He was in a good state without any evidence of recurrence or metastasis after 24 months follow up. Peculiar histopathological features were detected in the present case. Many unidentified cells with Hematoxylin & Eosin Langerhans like features showed negative staining for S-100, CD1a, Langerin and CD68. In absence of cellular atypia and mitosis, the infiltrating cells showed epidermotropism that was reported once in ICH as well as neural and perineural invasion that were not previously reported. Therefore we prefer using a tentatively designated diagnosis; dendritic cell tumor, not otherwise specified or newly proposed diagnosis (Indeterminate cell histocytosis with naïve cells) for the present case.

Immunohistochemical detection of P53 and Mdm2 in vitiligo.

BACKGROUND: Vitiligo is a common depigmented skin disorder that is caused by selective destruction of melanocytes. It is generally accepted that the main function of melanin resides in the protection of skin cells against the deleterious effect of ultraviolet rays (UVRs). Association of vitiligo and skin cancer has been a subject of controversy. Occurrence of skin cancer in long-lasting vitiligo is rare despite multiple evidences of DNA damage in vitiliginous skin. AIM: To detect the expression of P53 and Mdm2 proteins in both depigmented and normally pigmented skin of vitiligo patients and to compare it to control subjects suffering from nonmelanoma skin cancer (NMSC). MATERIALS AND METHODS: Thirty-four patients with vitiligo and 30 age and sex-matched patients with nodulo-ulcerative basal cell carcinoma (BCC) as a control group were selected. Both patients and control subjects had outdoor occupations. Skin biopsies were taken from each case and control subjects. Histopathological examination of Hematoxylin and eosin-stained sections was done. Expression of P53 and Mdm2 proteins were examined immunohistochemically. RESULTS: Both P53 and Mdm2 were strongly expressed in depigmented as well as normally pigmented skin of vitiligo patients. This expression involved the epidermis, skin adnexa and blood vessels with significant differences between cases and controls. CONCLUSIONS: The overexpression of P53 and Mdm2 proteins in both normally pigmented and depigmented skin of patients with vitiligo could contribute to the decreased occurrence of actinic damage and NMSC in these patients.

Photoletter to the editor: Pityriasis Rotunda.

Pityriasis rotunda is described as persistent, large, sharply defined circular patches of dry ichthyosiform scaling with no inflammatory changes. Pityriasis rotunda may be associated with systemic diseases (eg. hepatocellular carcinoma). We report a case of pityriasis rotunda in a 19-year-old, otherwise healthy male. The condition started one year prior to his referral. Lesions were distributed over the trunk and upper extremities. Histopathological examination revealed hyperkeratosis, absent granular layer, pigmented basal layer, pigmentary incontinence and perivascular lymphocytic infiltrate. PAS staining for fungi was negative. Treatment of pityriasis rotunda in this case was challenging. When there's an underlying disease, successful treatment of the original disease leads to clearance of pityriasis rotunda lesions.