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Infection with the human papillomaviruses (HPV) often involves the epigenetic modification of the host genome. Despite its prevalence among the population, host genome methylation in HPV-induced warts is not clearly understood. In this study, genome-wide methylation profiling was carried out on paired healthy skin and wart samples in order to investigate the effects that benign HPV infection has on gene methylation status. To overcome this gap in knowledge, paired wart (n = 12) and normal skin (n = 12) samples were obtained from Arab males in order to perform DNA extraction and subsequent genome-wide methylation profiling on the Infinium Methylation EPIC Bead Chip microarray. Analysis of differential methylation revealed a clear pattern of discrimination between the wart and normal skin samples. In warts, the most differentially methylated (DM) genes included long non-coding RNAs (AC005884, AL049646.2, AC126121.2, AP001790.1, and AC107959.3), microRNAs (MIR374B, MIR596, MIR1255B1, MIR26B, and MIR196A2),snoRNAs (SNORD114-22, SNORD70, and SNORD114-31), pseudogenes (AC069366.1, RNU4ATAC11P, AC120057.1, NANOGP3, AC106038.2, TPT1P2, SDC4P, PKMP3, and VN2R3P), and protein-coding genes (AREG, GJB2, C12orf71, AC020909.2, S100A8, ZBED2, FABP7, and CYSLTR1). In addition, pathway analysis revealed that, among the most differentially methylated genes, STAT5A, RARA, MEF2D, MAP3K8, and THRA were the common regulators. It can be observed that HPV-induced warts involve a clear and unique epigenetic alteration to the host genome.

Background The world has changed dramatically since the COVID-19 pandemic began. Jordan was among countries which enforced early lock-down for most non-vital services. Health care was mainly directed to cope with COVID-19 cases. The pandemic posed challenges for all patients, including dermatology patients especially those on systemic treatments. This resulted in interruption of medical care and exacerbation of pre-existing skin diseases for many patients. Material and methods A cross-sectional, questionnaire-based study of dermatology patients on systemic treatment prior to corona pandemic. After lockdown was lifted, patients taking systemic treatments were evaluated for continuity of care during lockdown period and how that affected their skin condition. Demographic data, details of skin condition, continuity of care and impact on skin condition data were collected and analyzed. Results 154 patients (120 males, 34 females) were included. The majority (around 80%) of patients were unable to attend to dermatology clinics or do the needed lab monitoring. Around one fifth of patients had drug interruption mostly due to no access to hospital pharmacy. Most patients were using oral isotretinoin for acne, others include methotrexate and other immune suppressive agents. Patients with acne and oral isotretinoin treatment were more likely to continue their treatment during lockdown period. Amongst those who stopped treatment, around 42% had flare up of their disease. Conclusion COVID-19 pandemic had an important impact on various aspects of care for dermatology patients especially those on systemic therapy. This study demonstrated limited access to specialist care, inability to do lab tests and discontinuation of treatment during lockdown. Some patients (42%) had flare up of their skin condition as a result., Highlights • COVID-19 pandemic had dramatic impact on the continuity of care for dermatologic patients especially those on systemic therapy. • Health authorities should ensure proper access to medical care for especially patients with severe skin disease treated with systemic drugs during periods of lockdown to minimize complications for these patients.

Jihan M Muhaidat,1 Firas Al-Qarqaz,1 Yousef Khader,2 Diala M Alshiyab,1 Hadeel Alkofahi,1 Mohanad Almalekh1 1Department of Dermatology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 2Department of Public Health, Community Medicine, Jordan University of Science and Technology, Irbid, JordanCorrespondence: Jihan M MuhaidatDepartment of Dermatology, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, JordanTel +96227200600Fax +96227200624Email jmmuhaidat@just.edu.joBackground: Alopecia areata (AA) usually manifests as patches of non-scarring hair loss due to immune dysregulation. Intradermal injection of steroids is considered a first-line treatment of patchy AA.Purpose: To compare the efficacy and safety of two commonly used concentrations of intralesional triamcinolone acetonide (ILT) (5 mg/mL vs 10 mg/mL) in the treatment of patchy AA on the scalp.Patients and Methods: A retrospective comparative study that included 85 patients diagnosed with patchy AA on the scalp, who were treated with monthly injections of ILT. Patients were divided into Group 1 that received 5 mg/mL and Group 2 that received 10 mg/mL. The response rate (defined as the percentage of patients who achieved complete hair regrowth) and the side effects were compared between the two groups after completion of three treatment sessions, and recurrence was assessed after 1− 3 years.Results: Demographic composition of the two groups was comparable. The difference in response rate and the side-effects between the two groups were not statistically significant. Complete hair regrowth was noted in 43.5% of patients in Group 1 and 53.8% of those in Group 2 (P=0.340). About 17% and 25% of patients in Group 1 and Group 2, respectively, developed minor local side-effects (P=0.354), and almost 45% of patients from both groups had recurrence after 1− 3 years. Disease duration exceeding 6 months correlated with poor treatment response.Conclusion: Intralesional injection of triamcinolone acetonide 5 mg/mL is equally effective and safe compared to 10 mg/mL in the treatment of patchy alopecia areata.Keywords: alopecia areata, intralesional steroids, triamcinolone acetonide

Background Pruritus is the most common symptom in patients with skin disease. Psoriasis and atopic dermatitis are clinically distinct inflammatory diseases. Interleukins are cytokines which play key roles in inflammatory signaling pathways. Materials and methods Cross-sectional study was conducted among patients with psoriasis and atopic dermatitis: 59 psoriatic patients, 56 AD patients, and 49 matched healthy controls. Interleukins 4, 13, 31, 33 serum levels were assayed by ELISA and results were compared using SPSS. Itch severity and disease severity were measured and correlation with interleukin levels was determined using SPSS. Results The serum levels of IL-4, -13, -31, -33 were elevated in atopic dermatitis patients compared to controls. Itch and disease severity were not correlated with elevated serum levels of these interleukins. In psoriasis, the levels of IL-4 and -31 were elevated compared to controls, whereas the levels of IL-13 and -33 were lower than controls. The levels of measured interleukins in psoriasis did not correlate with itch and disease severity. Conclusion IL-31 is the key mediator for pruritus in both AD and Ps patients. IL-4/31 axis and IL-33/13 axis play distinct roles in the pathogenesis of Atopic dermatitis and Psoriasis. Interleukin serum levels were not correlated with itch and disease severity in both conditions.

Epigenetic alteration of host DNA is a common occurrence in both low- and high-risk human papillomavirus (HPV) infection. Although changes in promoter methylation have been widely studied in HPV-associated cancers, they have not been the subject of much investigation in HPV-induced warts, which are a temporary manifestation of HPV infection. The present study sought to examine the differences in promoter methylation between warts and normal skin. To achieve this, DNA was extracted from 24 paired wart and normal skin samples and inputted into the Infinium MethylationEPIC BeadChip microarray. Differential methylation analysis revealed a clear pattern of hyper- and hypomethylation in warts compared to normal skin, and the most differentially methylated promoters were found within the EIF3EP2, CYSLTR1, C10orf99, KRT6B, LAMA4, and H3F3B genes as well as the C9orf30 pseudogene. Moreover, pathway analysis showed that the H3F3A, CDKN1A, and MAPK13 genes were the most common regulators among the most differentially methylated promoters. Since the tissue samples were excised from active warts, however, this differential methylation could either be a cellular response to HPV infection or an HPV-driven process to establish the wart and/or promote disease progression. Conclusively, it is apparent that HPV infection alters the methylation status of certain genes to possibly initiate the formation of a wart and maintain its presence.

Background: Acne is common among young individuals. People with dark skin have a higher risk for developing pigmentary complications. Inflammation is an important factor in post-acne hyperpigmentation however other factors are also involved in developing this complication however these factors are not well studied. Objective: The aim of this study is to identify risk factors involved in post-acne hyperpigmentation. Materials and Methods: Clinical data related to acne, acne- related hyperpigmentation were collected. Data was analyzed for risk factors associated with acne pigmentation. Artificial neural network was used as predictive disease classifier for the outcome of pigmentation. Results: Majority of patients in this study (339 patients) had dark skin phototypes (3 and 4). Post- acne hyperpigmentation was seen in more than 80% of patients. Females, darker skin color, severe acne, facial sites, and excessive sunlight exposure, squeezing or scratching lesions are important risk factors for post-acne hyperpigmentation. Conclusion: Post-acne hyperpigmentation is multifactorial. Several factors implicated in PAH are modifiable by adequate patient education (lesion trauma, excessive sunlight exposure). The use of ANN was helpful in predicting appearance of post-acne hyperpigmentation based on identified risk factors.

Background Alopecia areata (AA) is a non-cicatricial patchy hair loss on the scalp, face or other parts of the body. AA was found to be responsive to immunosuppressive therapies, a finding that supports an autoimmune basis for the disease. Several genetic studies have shown the significance of immunological factors as key genetic components in AA. Objective In this study, we aimed to investigate the genetic association of 7 single-nucleotide polymorphisms (SNPs) within five candidate genes including TAP1, CXCL1, CXCL2, HSPA1B, and TNFα with AA susceptibility in the Jordanian Arab population. Methods A case-control genetic association study conducted in 152 patients and 150 healthy individuals was performed using the sequenom MassARRAY system (iPLEX GOLD) to genotype the selected SNPs. Results rs1800629 SNP of the TNFα gene was significantly associated with AA in the heterozygous and rare homozygous genotypes (P=0.022 and P=0.0079, respectively) with no linkage of the TAP1, CXCL1, CXCL2 and HSPA1B variants. Conclusion This is the first study of its kind among the Jordanian population providing evidence of genetic association of the TNFα with AA susceptibility. Further genetic studies on Arab descent including other variants are required to clarify and strengthen the association of these genes with susceptibility to develop AA.

Objective: Basal cell carcinoma (BCC) is the most common malignancy in humans and represents a growing public health care problem. The major etiological factors contributing to BCC development are exposure to ultraviolet radiation and genetic alterations. BCC is primarily caused by dysregulation of sonic Hedgehog (HH) signaling pathway in basal cells of the skin. BCC can be classified into low risk non-aggressive and high risk aggressive subtypes. BCC subtypes differentiation is essential for prognosis and for better disease management and treatment strategies. The aim of this study was to assess the correlation between PTCH1 protein expression level and the aggressiveness of BCC histopathology. Methods: Archival paraffin embedded blocks containing BCC were retrieved from a cohort of 101 patients. Immunohistochemistry staining was performed to assess the expression level of PTCH1 which is a key component of Hedgehog pathway. Results: 101 paraffin embedded samples were evaluated and classified as high risk and low risk BCC subtypes by histopathological finding. High risk BCC subtypes were found in 40 samples (39.6%) and low risk subtypes were identified in 61 samples (60.4%). Nodular was the most frequent subtype which was found in (56/ 101), followed by infiltrative (22/101) and micronodular (14/ 101) subtypes. Positive PTCH1 expression was found highest in nodular subtypes (46.5%). Conclusion: In this study, the correlation between low risk or high risk BCC subtypes and PTCH1 expression level was not statistically significant (p>0.05), but the frequency of positive PTCH1 expression was found to be higher in low risk subtypes than high risk BCC subtypes.

Introduction The use of sunscreen is an important preventive measure against skin cancer and treatment for other skin conditions. There is evidence pointing to lack awareness and misconceptions regarding use of Sunscreen. This is especially evident in populations with skin of color (POC). Methods This is a cross-sectional study of 2000 individuals. A structured questionnaire was designed to collect data on general knowledge and use of sunscreen as well as reasons for stopping use of sunscreen. Results The results of this study indicate a clear deficiency in the use and knowledge about sunscreen among Jordanians. Females are using sunscreen more than males. However, the use of sunscreen is inadequate in many aspects including timing of application, frequency of use, and amount used among other things. There is an obvious lack of knowledge about sunscreen as shown by lack of awareness about benefits of use in various times of the year, use in children, use for all skin types, and several misconceptions among other knowledge gaps. Main reasons for stopping sunscreen include side effects, cost, and being not suitable for skin. Awareness about sunscreen can be improved by proper counseling by healthcare professionals and utilization of various media platforms. Conclusions The use of sunscreen is inadequate in this population of color (POC). Lack of proper counseling, failure to read use instructions can contibute to inadequate use of sunscreen. Risks and benefits of sunscreen should be explained by medical professionals. The media should be more utilized to disseminate such knowledge.

Introduction: Uremic pruritus is a multifactorial devastating complication of renal failure, which has a significant negative impact on patients’ quality of life including medical, psychological, as well as social aspects. It is also associated with an increased mortality in dialysis patients. Methods: A cross sectional study evaluating the traditional risk factors for uremic pruritus (UP) – using pruritus grading system (PGS) and visual analogue scale (VAS) - as well as measuring the serum levels of different inflammatory cytokines (ILs 13, 31 and 33) in chronic hemodialysis and healthy controls, in a tertiary referral hospital. Results: 65 hemodialysis (HD) patients and 49 heathy controls were enrolled in the study. The mean age for the HD patients was 43.4 years (SD ± 21.3), and 31.5 years (SD ± 11.1) for the control group. The most common cause for End Stage Renal Disease (ESRD) was diabetes mellitus (DM) 27.7%. The mean PGS score in HD patients was 5.92 (SD ± 2.9); 50% had mild itch, 43.8% moderate itch and 6.2% had severe itch. The mean serum levels for IL-13 was 8674.3 pg/ml (SD ± 4353.9), serum levels of IL-31 were 150.7 pg/ml (SD ± 178.2) and for IL-33 it was 42850.5 pg/ml (SD ± 11370.7) in hemodialysis patients; in comparison to serum levels of 7913.4 pg/ml (SD ± 3454.1), 67.1 pg/ml (SD ± 71.9) and 44875.9 pg/ml (SD ± 12114.6), respectively in the control group. IL-31 level was significantly higher in HD patients than in the control group (P = 0.0001), while the difference in the levels of IL-13 and IL-33 between the two groups were not statistically significant (P = 0.41 and 0.18, respectively). IL-13 had a statistically significant relationship with the itch score (P = 0.014) and the severity of itch (P = 0.03), while IL-31 and IL-33 were not statistically significant. Conclusion: UP is a complex and multifactorial problem. In patients with UP the high levels of IL-31 indicates a possible role in pathogenesis. IL-13 serum level on the other hand may be related to the severity of itch in these patients. Optimizing dialysis and targeting these cytokines may provide a potential therapeutic option especially in refractory UP. Further studies addressing these cytokines and their levels in response to various treatments may provide additional information on UP.

Background The human papillomaviruses (HPV) are a group of viruses that, depending on the strain, can cause cancer or the formation of benign growths known as warts. Scarce information exists with regard to the genetic nature of non-genital cutaneous warts induced by the human papillomavirus (HPV). Methods The main purpose of this study is to investigate the differences between the gene expression profiles of common warts and healthy skin in HPV-positive individuals by RNA sequencing on the Illumina HiSeq 2500. After obtaining shave biopsies of common warts and healthy skin from twelve Arab males, we were able to analyze the transcriptomes of 24 paired cases and controls. Results Common warts were found to possess a highly significant and unique molecular signature. Many of the most up-regulated (KRT16, EPGN, and ABCG4) and down-regulated genes (C15orf59, CYB561A3, and FCGRT) in warts were the subject of little investigation in the published literature. Moreover, the top 500 differentially expressed genes were found to be associated with immune and autoimmune pathways, such as the neutrophil degranulation, toll-like receptor 7/8 (TLR 7/8) cascade, toll-like receptor 9 (TLR9) cascade, and toll-like receptor 10 (TLR10) pathways, among others. Conclusions Our findings are particularly important because they serve as the most comprehensive to date with regard to the modulation of human skin gene expression by HPV infection.

The pathogenesis of vitiligo is complex and multifactorial, accumulating evidence of increased oxidative stress and reduction in catalase levels in vitiligo patients has been shown, hence, pseudocatalase/superoxide dismutase (PSD) gel has been used as treatment option for vitiligo.To assesses the synergic effect of PSD when combines with Tacrolimus 0.1% ointmentA randomized controlled trial that included 49 children with vitiligo with limited area (10% or less). Patients were randomized into two groups: Group 1 (24 patients) were treated only with Tacrolimus 0.1% ointment whereas Group 2 (25 patients) were treated with Tacrolimus 0.1% ointment plus PSD. Degree of repigmentation compared to baseline was assessed at 3, 6, and 9 months.The median age was 10.05 years (range 2-18). The percentages of pigmentation on 3, 6, and 9 months for Group 1 were 23.9%, 40.4%, and 60%, respectively and for Group 2 were 23.2%, 40.7%, and 62.4%, respectively. There was no significant difference according to repigmentation percentages between the two groups (The results showed that the addition of PSD to Tacrolimus ointment in children with limited vitiligo was not associated with any therapeutic benefit.

Background. Acne is a common condition of pilosebaceous follicle especially among young. Clinically, the most used medication in the treatment of moderate to severe acne is oral isotretinoin. However, interindividual variability in therapeutic response to isotretinoin and many side effects such as musculoskeletal pain, headache, and alteration in lipid profile can be seen with this treatment. Aim. In this study, the effect of genetic polymorphisms, rs2241766 and rs1501299, of the adiponectin gene was investigated in relation to the side effects of isotretinoin-treated young adult acne patients (n = 230). Methods. Several biochemical parameters were measured at baseline and after treatments with isotretinoin. The ADIPOQ gene SNPs, rs2241766 and rs1501299, were genotyped in 230 patients. Results. Alterations in lipid profile with a significant increase of ALT (P=0.007) were detected after isotretinoin treatment. Moreover, percentage change in HDL following isotretinoin treatment was significantly associated with rs1501299 (P=0.008). On the other hand, no associations between examined SNPs and side effects of isotretinoin and other lipid parameters (total cholesterol, LDL, and triglycerides) or liver function enzymes (ALT and AST) were detected. Conclusions. Current findings showed that rs1501299 of the ADIPOQ gene might be associated with changes in HDL level in acne patients following treatment with isotretinoin.

The human papillomaviruses (HPV) are a group of double-stranded DNA viruses that exhibit an exclusive tropism for squamous epithelia. HPV can either be low- or high-risk depending on its ability to cause benign lesions or cancer, respectively. Unsurprisingly, the majority of epigenetic research has focused on the high-risk HPV types, neglecting the low-risk types in the process. Therefore, the main objective of this study is to better understand the epigenetics of wart formation by investigating the differences in methylation between HPV-induced cutaneous warts and normal skin. A number of clear and very significant differences in methylation patterns were found between cutaneous warts and normal skin. Around 55% of the top-ranking 100 differentially methylated genes in warts were protein coding, including the EXOC4, KCNU, RTN1, LGI1, IRF2, and NRG1 genes. Additionally, non-coding RNA genes, such as the AZIN1-AS1, LINC02008, and MGC27382 genes, constituted 11% of the top-ranking 100 differentially methylated genes. Warts exhibited a unique pattern of methylation that is a possible explanation for their transient nature. Since the genetics of cutaneous wart formation are not completely known, the findings of the present study could contribute to a better understanding of how HPV infection modulates host methylation to give rise to warts in the skin.

HPV infection is one of the most commonly transmitted diseases among the global population. While it can be asymptomatic, non-genital HPV infection often gives rise to cutaneous warts, which are benign growths arising from the epidermal layer of the skin. This study aimed to produce a global analysis of the ways in which cutaneous wart formation affected the CpG island methylome. The Infinium MethylationEPIC BeadChip microarray was utilized in order to quantitatively interrogate CpG island methylation in genomic DNA extracted from 24 paired wart and normal skin samples. Differential methylation analysis was carried out by means of assigning a combined rank score using RnBeads. The 1000 top-ranking CpG islands were then subject to Locus Overlap Analysis (LOLA) for enrichment of genomic ranges, while signaling pathway analysis was carried out on the top 100 differentially methylated CpG islands. Differential methylation analysis illustrated that the most differentially methylated CpG islands in warts lay within the ITGB5, DTNB, RBFOX3, SLC6A9, and C2orf27A genes. In addition, the most enriched genomic region sets in warts were Sheffield&rsquo, s tissue-clustered DNase hypersensitive sites, ENCODE&rsquo, s segmentation and transcription factor binding sites, codex sites, and the epigenome sites from cistrome. Lastly, signaling pathway analysis showed that the GRB2, GNB1, NTRK1, AXIN1, and SKI genes were the most common regulators of the genes associated with the top 100 most differentially methylated CpG islands in warts. Our study shows that HPV-induced cutaneous warts have a clear CpG island methylation profile that sets them apart from normal skin. Such a finding could account for the temporary nature of warts and the capacity for individuals to undergo clinical remission.

BackgroundLow-risk HPV infection has not been the subject of epigenetic investigation. The present study was carried out in order to investigate the methylation status of CpG sites in non-genital cutaneous warts.MethodsGenomic DNA was extracted from 24 paired epidermal samples of warts and normal skin. DNA samples were bisulfite converted and underwent genome-wide methylation profiling using the Infinium MethylationEPIC BeadChip Kit.ResultsFrom a total of 844,234 CpG sites, 56,960 and 43,040 CpG sites were found to be hypo- and hypermethylated, respectively, in non-genital cutaneous warts. The most differentially methylated CpG sites in warts were located within theC10orf26,FAM83H-AS1,ZNF644,LINC00702,GSAP,STAT5A,HDAC4,NCALD, andEXOC4genes.ConclusionNon-genital cutaneous warts exhibit a unique CpG methylation signature.

Background. Low vitamin D serum levels have been associated with many autoimmune disorders and several other skin diseases. Vitiligo is an autoimmune disease characterized by destruction of melanocytes by immune mechanisms. Melanocytes express vitamin D receptors, and their function can be affected by vitamin D status. Objectives. The main objective of this study is to compare vitamin D levels in patients with vitiligo vs normal population and whether vitamin D deficiency is associated with vitiligo. Methods. A case-control study was conducted. 100 vitiligo patients and 100 as controls were included in this study. Serum vitamin D level was measured for both vitiligo patients and controls, results were compared, and statistical analysis was done to compare the results. Results. The median age of vitiligo cases was 23 years (ranges, 2–80). 58% of vitiligo patients were females. The median vitamin D level was not significantly different between the two groups (vitiligo = 14.1 (IQR 9.9–20.4) vs control = 16.5 (IQR 10.3–25.3) (P=0.28)). Most vitiligo cases and controls were found to have low levels of vitamin D (either insufficient 20–30 ng/mL or low Conclusions. There was no significant difference in vitamin D levels in vitiligo patients compared to controls. However, vitamin D levels were generally low in both groups.

Basal cell carcinoma (BCC) is the most common cancer affecting humans. It almost has no tendency for metastasis; however it can be destructive to surrounding tissue. Patients with darker skin colors have lower risk of developing skin cancers and the clinical characteristics may differ from populations with lighter skin colors.Methods. This is a retrospective clinical study (2003–2017). Data on age, gender, and location of tumor were collected and analyzed.Results. 335 cases were identified. Males tend to get BCC at a younger age than females. Face was the most common site in both males and females. Cheeks and nose were the most likely areas of the face to be involved. Scalp was the most common extrafacial site to be involved in males; however in females scalp was much less likely to be involved.Conclusion. BCC is less common in populations with darker skin. Males were more affected and at an earlier age compared to females. Facial skin followed by scalp was the most common site affected. Skin phototype, cultural and religious dress type, and different sun exposure behavior may explain many of the clinical and demographic findings related to BCC in patients with darker skin tones.

Infection with the human papillomavirus (HPV) is a common occurrence among the global population, with millions of new cases emerging on an annual basis. Dysregulated microRNA (miRNA) expression is increasingly being identified to play a role in a number of different diseases, especially in the context of high-risk HPV infection. The present study investigated the miRNA expression profiles of warts induced by low-risk HPV. In warts, miR-27b, miR-24-1, miR-3654, miR-647, and miR-1914 were downregulated while miR-612 was upregulated compared to normal skin. Using miRTargetLink Human, experimentally supported evidence was obtained showing that miR-27b targeted the vascular endothelial growth factor C (VEGFC) and CAMP-responsive element binding protein 1 (CREB1) genes. The VEGFC and CREB1 genes have been reported to be involved in tumorigenesis and wart formation, respectively. Similarly, the oxidized low-density lipoprotein receptor 1 (OLR1) gene, which plays an important role in the humoral immunity of the skin, and the plexin D1 (PLXND1) gene, which is highly expressed in tumor vasculature, were both found to be common targets of miR-27b, miR-1914, and miR-612.