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.

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.

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.