Circulating and/or cutaneous irisin resistance: A novel link among androgenetic alopecia, comorbid metabolic syndrome and cardiovascular risks.

BACKGROUND: Androgenetic alopecia (AGA) is a common cause of hair loss in both genders that may be associated with disturbed systemic metabolism. Irisin is a hormone-like myokine that greatly influences systemic metabolism and is linked to cardiovascular diseases. AIM: To detect irisin role in AGA and its associated metabolic syndrome (MetS) and cardiovascular risk. PATIENTS/METHODS: This case-control study included 44 AGA patients of both genders and 22 healthy individuals. Serum irisin level was measured using ELISA and scalp biopsy was taken to detect irisin immunohistochemically. Carotid Doppler ultrasonography was performed to measure carotid intima media thickness (CIMT). RESULTS: Higher serum irisin was significantly detected in AGA patients (p ˂ 0.001), and in males (p = 0.01) particularly severe cases (p ˂ 0.001). It was significantly higher in AGA patients presenting with MetS and those suffering from dyslipidemia (p ˂ 0.001 for both). Multivariate regression analysis proved BMI (p = 0.01) and serum irisin (p = 0.02) as independent predictors of CIMT abnormality among AGA patients. Regarding cutaneous irisin expression, the epidermal H-score was significantly higher in AGA patients with MetS compared to those without (p = 0.04). Epidermal H-score ˃100 was significantly associated with male gender (p = 0.05), severe AGA (p = 0.02), MetS (p = 0.03), dyslipidemia (p = 0.03), and abnormal CIMT (p = 0.03). CONCLUSION: High serum irisin and upregulated epidermal irisin expression are associated with the incidence of MetS, dyslipidemia, and CIMT abnormality among AGA patients. This may indicate resistance to irisin, which hinders its favorable cardiometabolic actions. Further studies are warranted to investigate the concept of irisin resistance in AGA patients, which was uniquely discussed in the present study.

Basal Cell Carcinoma in Xeroderma Pigmentosa: Reduced CD1a Expression as a Sensitive Predictor of Recurrence.

Xeroderma pigmentosa (XP) is a rare genetic disorder that is characterized by defective DNA repair after ultraviolet induced damage with a great tendency for recurrent cutaneous malignancies including basal cell carcinoma (BCC). BCC is frequently linked to impaired local immune response with a major role played by Langerhans cells (LCs). The current study aims at investigating LCs in BCC specimens of XP and non-XP patients, in a trial to study its possible impact on tumor recurrence. It included 48 retrospective cases of primary facial BCC (18 for XP patients and 30 for non-XP controls). Each group was subdivided, based on the 5 years follow-up data, into recurrent and non-recurrent BCC groups. LCs were assessed immunohistochemically using the sensitive marker; CD1a. Results showed significantly reduced LCs count (intratumoral, peritumoral, and in perilesional epidermis) in XP patients compared with non-XP controls ( P ˂0.001 for all). Intratumoral ( P =0.008), peritumoral ( P =0.005), and perilesional epidermal ( P =0.02) LCs mean values were significantly lower in recurrent versus non-recurrent BCC specimens. Also, within each group (XP and controls), LCs were of significantly lower means in recurrent versus non-recurrent cases ( P ≤0.001 for all). Regarding recurrent BCC cases, peritumoral LCs showed a significant positive correlation with 1ry BCC duration ( P =0.05). Also, intratumoral and peritumoral LCs correlated positively with BCC relapse interval ( P =0.04 for both). Among non-XP controls, periocular tumors had the least LCs count (22.00±3.56), whereas tumors located in the rest of the face had the greatest count (29.00±0.00) ( P =0.02). Sensitivity and specificity of LCs to predict BCC recurrence in XP patients reached 100% in intartumoral area and perilesional epidermis when cutoff points were less than 9.5 and 20.5, respectively. In conclusion; reduced LC count in primary BCC specimens of XP patients and also in normal subjects could help to predict its recurrence. Thus, it might be identified as a risk factor for relapse to apply new strict therapeutic and preventive measures. This presents new avenue for the immunosurveillance against skin cancer relapse. However, being the first study to investigate that link in XP patients recommends further research to confirm.

Translation, cultural adaptation and psychometric validation of the SF-6D measure of health-related quality of life for use in Arabic-Speaking countries.

BACKGROUND: The SF-6D is a generic, six-dimensional health-related quality of life (HRQoL) measure derived from a selection of items from the SF-36. OBJECTIVES: To translate, culturally adapt and validate the SF-6D for use in Arabic-speaking countries. METHODS: The International Quality of Life Assessment (IQOLA) methodology was followed. Two forward translations, one consensus and one backward translation were undertaken. Difficulties encountered were categorized as grammatical, idiomatic, semantic/conceptual, and cultural. The content validity of the final version was tested and Cronbach's alpha test of internal consistency was used for assessing reliability. Confirmatory factor analysis (CFA), was also used to assess construct validity and to test a pre-specified relationship of observed measures. RESULTS: Minor changes were made to the forward translation to improve cultural appropriateness. The Backward translation did not reveal major problems and equivalence to the original was confirmed following committee review. A total of 470 participants from Jordan, Egypt, UAE, Qatar and Palestine completed the translated SF-6D. All the incremental indices values are ≥0.90 and close to 1. Item loading values ranged from 0.52 to 0.87. The measurement model weight for those with chronic health conditions ranged from 0.68 to 0.91, and from 0.42 to 0.73 for those without. The percentage of variation in self-reported health state was about 55%. The measurement weight of SF-6D on self-reported health state among chronic responders was 0.87 while among responders reporting no chronic disease was 0.61. The t-value for the difference in measurement weight was -8.93 (p ≤ 0.01). CONCLUSION: Arabic translation and cultural adaptation of SF-6D has resulted in an acceptable and culturally-adapted version that can be used in Arabic-speaking countries. Reliability and validity have been confirmed as well as ability to assess the difference in quality of life between patients with chronic health conditions and healthy individuals.

New onset of axial spondyloarthropathy in patients treated with isotretinoin for acne vulgaris: incidence, follow-up, and MRI findings.

INTRODUCTION: Oral isotretinoin is commonly prescribed for acne vulgaris. Several case reports and observational studies have reported serious musculoskeletal side effects; however, the incidence, imaging findings, and longitudinal follow-up data are limited for patients who develop inflammatory back pain (IBP). OBJECTIVE: To assess the incidence of isotretinoin-triggered axial spondyloarthropathy (SpA) in acne vulgaris patients based on clinical features and MRI findings and to examine clinical and radiological outcomes following drug withdrawal. METHODS: Five hundred thirteen acne patients receiving isotretinoin were screened for IBP; IBP patients were assessed for CRP, plain radiographs, and MRI of the sacroiliac joint. MRI-proven sacroiliitis was scored semi-quantitatively. Patients were followed longitudinally to assess SpA clinical course and longitudinal MRI sacroiliac joints, and CRP levels were reassessed 3 weeks after patients were symptom-free, following isotretinoin discontinuation. RESULTS: Of the 513 patients, 23.98% developed IBP. MRI-proven sacroiliitis was detected in 42.3% of the symptomatic patients or 10.1% of the cohort. Among MRI-proven sacroiliitis cases, 51.9% fulfilled the Assessment of Spondyloarthritis International Society criteria for axial SpA. Mean CRP level was 32.05 ± 17.23 mg/L at pain onset and 3.4 ± 2.7 mg/L after symptom resolution. MRI findings completely resolved within 9 months (mean 6.27 ± 1.7) after isotretinoin discontinuation. MRI scores positively correlated with baseline CRP levels and global acne grading system score, pain, and the Ankylosing Spondylitis Disease Activity Score. CONCLUSION: Isotretinoin-induced axial SpA is a prevalent side effect in acne vulgaris patients. Early detection and follow-up of isotretinoin-induced sacroiliitis can be facilitated by MRI. Cessation of isotretinoin resulted in complete resolution in all affected patients.Key Points• Detection of underdiagnosed isotretinoin side effects which are common but not always correctly diagnosed and managed.• Incidence, diagnosis, and management of these side effects in a real-world setting.• This is the first large prospective longitudinal cohort study to report on axial manifestations in patients treated with isotretinoin as well as the effect of drug cessation upon the clinical, laboratory, and radiological findings.

Subclinical synovitis and enthesitis in psoriasis patients and controls by ultrasonography in Saudi Arabia; incidence of psoriatic arthritis during two years.

OBJECTIVE: To evaluate ultrasonographic subclinical inflammatory synovitis and enthesitis in psoriasis patients, without clinical arthritis or enthesitis compared with healthy controls, with a 2-year follow-up to study the associated incidence of psoriatic arthritis (PsA). METHODS: A total of 109 consecutive psoriasis vulgaris patients without clinical signs of PsA and 90 healthy controls were included from two tertiary medical centers. Subjects underwent dermatological examination, PASI score evaluation for severity of psoriasis, musculoskeletal examination using 68/66 joints count for tenderness and swollen joints. Patients were assessed for CRP, musculoskeletal ultrasound (MSUS) in the form of grayscale ultrasound (GSUS), and power Doppler ultrasound (PDUS) for eight entheses and 34 joints to detect MSUS subclinical enthesitis and synovitis. All patients were followed-up for 2 years to detect evolving PsA. RESULTS: Subclinical enthesitis and synovitis were detected in 39.5% of psoriasis patients and 10% of controls (P < 0.001). CRP was significantly higher in psoriasis patients with MSUS manifestations (P < 0.01). PDUS and GSUS subclinical synovitis and/or enthesitis were detected at least in one site in psoriatic patients more than in controls (P < 0.05). During a 2-year follow-up of patients, the annual PsA incidence was 4.3%. Psoriasis patients who developed PsA showed a higher prevalence of baseline enthesitis, higher PDUS and GSUS synovitis scores, and higher baseline CRP level than those who did not develop PsA. CONCLUSIONS: MSUS subclinical synovitis and enthesitis are quite common in psoriasis patients. The incidence of PsA in Saudi's psoriasis patients was slightly higher than worldwide reports. Subclinical enthesitis, PDUS, and GSUS synovitis could predict PsA development.

Narrow-band UVB effects on cutaneous vitamin D receptor expression and serum 25-hydroxyvitamin D in generalized vitiligo.

BACKGROUND/PURPOSE: Vitamin D has a role in variety of autoimmune diseases including vitiligo. Narrow-band UVB (NB-UVB) treatment of vitiligo might act through its effects on vitamin D and its receptor.This study is the first to elucidate NB-UVB effects on immunohistochemical vitamin D receptor (VDR) expression in generalized vitiligo and correlate it with serum vitamin D and repigmentation response. METHODS: Using immunohistochemistry, VDR expression was estimated in skin biopsies of 30 controls and 30 vitiligo patients; from vitiligo lesion, perilesional skin at baseline and from repigmented and nonresponding skin after 24 NB-UVB sessions. Baseline serum 25-hydroxyvitamin D [25(OH)D] was investigated and repeated after 24 NB-UVB sessions. RESULTS: Vitamin D receptor expression and serum 25(OH)D in controls were significantly higher compared to vitiligo patients. After NB-UVB therapy, there was a significant rise in VDR expression and serum 25(OH)D. VDR expression was significantly higher in repigmented skin compared to nonresponding lesion. Improvement in the clinical outcome score was associated with higher baseline VDR expression and higher serum 25(OH)D. CONCLUSIONS: NB-UVB phototherapy is associated with improved cutaneous VDR expression and vitamin D synthesis. Better repigmentation response to NB-UVB may be related to higher baseline VDR expression and its upregulation after phototherapy.

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.

Homozygous Familial Hypercholesterolemia Associated with Symmetric Subcutaneous Lipomatosis.

Homozygous familial hypercholesterolemia is an autosomal dominant disorder of lipid metabolism, characterized by reduced clearance of low-density lipoprotein-cholesterol and a high risk of rapid development of cardiovascular diseases. Its incidence is relatively rare and estimated to be one in one million in general populations. Here, we report homozygous familial hypercholesterolemia in two Egyptian young siblings, presented with cutaneous, tendinous xanthomas, and corneal arcus. One of them has symmetric subcutaneous lipomatosis, which has not been reported before in association with familial hypercholesterolemia.

Immunohistochemical expression of aberrant Notch-1 signaling in vitiligo: an implication for pathogenesis.

The etiopathogenetic mechanisms leading to pigment loss in vitiligo are not fully understood. Notch signaling is required for development and maintenance of melanocyte lineage and acts as a key component among keratinocyte-melanocyte interactions. The current study aimed to investigate the possible role of Notch signaling and its effect on the whole melanocyte lineage in vitiligo and correlating it with the different clinicopathologic parameters. Using immunohistochemical technique, Notch-1 expression was evaluated in 50 lesional and 20 perilesional biopsies of patients with vitiligo in comparison with 20 normal skin biopsies as a control group. Lesional biopsies were stained with human melanoma black-45 and tyrosinase-related protein-2 to demonstrate the melanocyte lineage. Membranous and/or nuclear expression of Notch-1 was in favor of control and perilesional skin, whereas cytoplasmic expression appeared only in vitiliginous lesions (P < .05). Membranous and/or nuclear expression of Notch-1 was significantly associated with epidermal human melanoma black-45 positivity (P = .01) and percentage of expression in both epidermis (P = .02) and hair follicles (P = .03) of lesional skin. Cytoplasmic pattern of Notch-1 expression in epidermis was significantly found in lesions with white hair (P = .04) and in cases with marked keratinocyte vacuolization (P = .03). Segmental and acrofacial vitiligo were associated with mild to moderate Notch-1 intensity, whereas generalized vitiligo was associated with strong intensity of expression (P = .02). In conclusion, Notch-1 signaling is inactivated in vitiligo with consequent loss of epidermal and/or follicular active melanocytes. Aberrant Notch signaling in vitiliginous white hair and acral and segmental vitiligo may be the cause of their treatment resistance.

Immunohistochemical study of melanocyte-melanocyte stem cell lineage in vitiligo; a clue to interfollicular melanocyte stem cell reservoir.

There has been a long lasting controversy over whether melanocytes (MCs) in vitiligo are actually lost or still present but functionally inactive. We aimed to evaluate the MC cell lineage in follicular and interfollicular vitiliginous epidermis through immunohistochemical localization of Human Melanoma Black-45 (HMB-45) and Tyrosinase Related Protein 2 (TRP2) and to correlate it with clinicopathologic parameters. Using immunohistochemical techniques, skin biopsies from 50 vitiligo patients and 20 age- and gender-matched healthy subjects were examined. Differentiated active MCs were detected in 44% of interfollicular epidermis (IFE) and 46.7% of follicular epidermis (FE) in lesional skin. Melanocyte precursors/stem cells were detected in 54% of IFE and 63.3% of FE in lesional skin. Melanocyte precursors/stem cells of IFE were significantly associated with residual melanin pigment (p = 0.007) and with absence of angiogenesis (p = 0.05). HMB-45 percentage of expression in IFE was positively correlated with MC precursors/stem cells percentage in FE (r = +0.65, p < 0.001) and IFE (r = +0.33, p = 0.01). Melanocyte precursors/stem cells positivity (p < 0.001) was progressively decreasing with advanced histopathologic grading. There was no significant association between interfollicular or follicular expression of HMB-45, TRP2 or MC precursors/stem cells and the clinical type of vitiligo or its duration. In conclusion, functioning MCs may exist in vitiligo. The presence of MC precursors/stem cells in IFE may provide an additional reservoir needed for repigmentation.