Presence of immunoglobulin E-expressing antibody-secreting cells in the dermis close to bullous pemphigoid lesions.

Antibody-secreting cells (ASCs) produce immunoglobulin (Ig) G and IgE autoantibodies in secondary lymphoid organs. Evidence also suggests their existence in the skin in various chronic inflammatory conditions, and in association with CXCL12 and CXCL13, they regulate the recruitment/survival of ASCs and germinal center formation to generate ASCs, respectively. However, the presence of IgG and IgE in bullous pemphigoid (BP) lesions needs to be addressed. Here, we aimed to analyse BP skin for the presence of IgG and IgE and the factors contributing to their generation, recruitment, and persistence. Skin samples from 30 patients with BP were stained to identify ASCs and the immunoglobulin type they expressed. The presence of tertiary lymphoid organ (TLO) elements, which generate ASCs in non-lymphoid tissues, and the chemokines CXCL12 and CXCL13, which regulate the migration/persistence of ASCs in lymphoid tissues and formation of TLOs, respectively, were evaluated in BP skin. BP skin harboured ASCs expressing the two types of antibodies IgG and IgE. ASCs were found in high-grade cellular aggregates containing TLO elements: T cells, B cells, CXCL12+ cells, CXCL13+ cells and high endothelial venules. IgG+ ASCs were detected among these aggregates, whereas IgE+ ASCs were dispersed throughout the dermis. CXCL12+ fibroblast-like cells were located close to ASCs. The inflammatory microenvironment of BP lesions may contribute to the antibody load characteristic of the skin of patients with BP by providing a site for the presence of ASCs. CXCL13 and CXCL12 expression may contribute to the generation and recruitment/survival of ASCs, respectively.

Stratum corneum as polymer sheet: concept and cornification processes.

The skin barrier protects our body from external insults and water loss through a specialized layer, the stratum corneum. The stratum corneum, an accumulation of dead keratinocytes (corneocytes), comprises lipids and supporting cell bodies. We propose a framework of lipid-filled polymer sheet of corneocytes, a unique structure that achieves flexibility and robustness, updating the rigid image of the historical bricks-and-mortar model. The polymerization of polymer sheet (cornification) by cell death of keratinocytes (corneoptosis) is delicately and dynamically controlled by cytoplasmic calcium ion and pH. Understanding the structure and formation of the stratum corneum can lead to better treatments for skin diseases and a better understanding of the evolution of the stratum corneum.

Secukinumab retreatment associated psoriasis flare with pustules.

This case report describes a patient with plaque psoriasis and psoriatic arthritis who experienced IL-17A blocking antibody secukinumab treatment-interruption followed by re-treatment. The patient showed heterogeneous responses; significant improvement at initial introduction of secukinumab with rapid deterioration after discontinuation, followed by worsening symptoms and pustular eruption with reintroduction, and skin clearance after dose escalation.

Assessment of Quality of Life of Patients with Inflammatory Skin Diseases Using Skindex-16: A Cross-Sectional Multicenter Study.

Inflammatory skin diseases are highly prevalent, yet their impacts on patients' quality of life (QoL) are not addressed. In this cross-sectional study, the Arabic version of Skindex-16 was used to evaluate the symptomatic, emotional, and functional distress of patients with inflammatory skin disorders attending several outpatient dermatology clinics in Egypt and Saudi Arabia. Patients with ≥50% of the symptoms score, ≥50% of the emotions score, and ≥33% of the functioning score were considered having poor QoL. A total of 1,310 patients aged 30 ± 13 years (70.6% from Egypt and 29.4% from Saudi Arabia) were included in this study. Of them, 1,192 patients had inflammatory skin diseases, and 118 had facial nevi, who served as controls. Patients with inflammatory skin diseases had significantly worse QoL than those with nevi. Autoimmune bullous disease group showed the highest prevalence poor symptoms (56.8%), poor emotions (75.7%), and poor functioning (83.8%) of QoL. Women with acne and psoriasis were more likely to have poor symptoms than men (16.3% vs. 4.7% and 52.7% vs. 25.3%, respectively). In conclusion, inflammatory skin diseases had profound negative effects on patients' QoL. Age, sex, education, and marital status of patients can affect their perception of QoL.

Teledermatology in the time of COVID-19.

AIMS: The enormous spread of the novel Corona virus disease (COVID-19) represents a challenge to dermatological practice. Accumulating evidence has suggested a possible role of teledermatology in facing this challenge. In this article, we aimed to give a general overview of teledermatology in terms of models of practice, modes of delivery, advantages, limitations, ethical considerations and legislative challenges as well as discussing, using examples from literature, how dermatological practice can benefit from teledermatology during the time of the COVID-19 pandemic. DISCUSSION AND CONCLUSION: Teledermatology could be an accessible, accurate and cost-effective substitute for conventional face-to-face dermatological consultations during the COVID-19 pandemic. However, teledermatology practice needs updated legislation and guidelines. More efforts should be done to encourage dermatologists, especially in underserved communities, to provide teledermatology services. Ethical issues and data security related to teledermatology have to be considered.

The association of acne and menstrual symptoms among young women (18-25 years) in Egypt: a population-based cross-sectional study.

BACKGROUND: Acne and menstrual symptoms are highly prevalent among young women. Since both acne and menstrual symptoms have similar hormonal pathogenesis, it is highly suggested that the two conditions are associated. Herein, we conducted this study to assess the relationship between acne and menstrual symptoms among young women. SUBJECTS AND METHODS: In this population-based cross-sectional study, a multi-stage random sampling approach was used to include 3065 young women (18-25 years) from Egypt. Women were interviewed for their socio-demographic characteristics, gynecological history, premenstrual and menstrual symptoms, and history of acne and perimenstrual acne flare during the past 6 months. RESULTS: The mean age of women was 21.5 ± 2.2 and their age of menarche was 13.1 ± 1.5 years. During the previous 6 months, 44.8% of participants had acne. After adjusting for socio-demographic and gynecological characteristics, acne was associated with most menstrual symptoms with odds ratios (ORs) and 95% confidence intervals (CIs) as follows: [premenstrual symptoms: 1.23 (1.05-1.44) for irritation or nervousness, 1.45 (1.24-1.68) for fatigue, 1.37 (1.15-1.62) for breast tenderness, 1.48 (1.21-1.80) for abdominal bloating, and 1.36 (1.11-1.66) for nausea or vomiting], [menstrual symptoms: 1.63 (1.19-2.23) for dysmenorrhea and 1.24 (1.06-1.45) for dysmenorrhea requiring drugs], and [symptoms severity: 1.44 (1.24-1.68) for missing events and 1.38 (1.16-1.64) for medical consultation]. Of acne patients, 56.7% reported perimenstrual acne flare: 58.5% before menses, 35% during menses, and 6.5% after menses. CONCLUSION: This study supports the concept that acne is associated with menstrual symptoms. Physicians should consider screening for menstrual symptoms among young women with acne.

The association between smoking and risk of skin cancer: a meta-analysis of cohort studies.

PURPOSE: The association between smoking and the risk of skin cancers has been studied without reaching consistent findings. This study aims to assess this association through an updated meta-analysis of cohort studies. METHODS: We retrieved cohort studies that investigated the temporal association between smoking and the risk of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and malignant melanoma (MM). Pooled relative risks (RRs) and confidence intervals (CIs) of the included articles were calculated for current, former, and heavy smoking compared with never smoking. Publication bias was detected using the Egger's regression. RESULTS: A total of 15 studies, published between 1990 and 2018, were included. Current smoking was associated with a higher risk of SCC (pooled RR = 1.32, 95% CI 1.15, 1.52) but with a lower risk of BCC (pooled RR = 0.85, 95% CI 0.75, 0.96) and MM (pooled RR = 0.72, 95% CI 0.64, 0.82). No publication bias was detected, and no single study had a substantial impact on the pooled results. Similar results were detected for heavy smoking, while former smoking was not associated with the risk of skin cancer. CONCLUSION: Current smoking and heavy smoking were associated with a higher risk of SCC but a decreased risk of BCC and MM, while former smoking was not associated with skin cancer risk.

Immune Control by TRAF6-Mediated Pathways of Epithelial Cells in the EIME (Epithelial Immune Microenvironment).

In the protective responses of epithelial tissues, not only immune cells but also non-immune cells directly respond to external agents. Epithelial cells can be involved in the organization of immune responses through two phases. First, the exogenous harmful agents trigger the primary responses of the epithelial cells leading to various types of immune cell activation. Second, cytokines produced by the immune cells that are activated directly by the external agents and indirectly by the epithelial cell products elicit the secondary responses giving rise to further propagation of immune responses. TRAF6 is a ubiquitin E3 ligase, which intermediates between various types of receptors for exogenous agents or endogenous mediators and activation of subsequent transcriptional responses via NF-kappaB and MAPK pathways. TRAF6 ubiquitously participates in many protective responses in immune and non-immune cells. Particularly, epithelial TRAF6 has an essential role in the primary and secondary responses via driving type 17 response in psoriatic inflammation of the skin. Consistently, many psoriasis susceptibility genes encode the TRAF6 signaling players, such as ACT1 (TRAF3IP2), A20 (TNFAIP3), ABIN1 (TNIP1), IL-36Ra (IL36RN), IkappaBzeta (NFKBIZ), and CARD14. Herein, we describe the principal functions of TRAF6, especially in terms of positive and regulatory immune controls by interaction between immune cells and epithelial cells. In addition, we discuss how TRAF6 in the epithelial cells can organize the differentiation of immune responses and drive inflammatory loops in the epithelial immune microenvironment, which is termed EIME.

Clinical and genetic differences between pustular psoriasis subtypes.

BACKGROUND: The term pustular psoriasis indicates a group of severe skin disorders characterized by eruptions of neutrophil-filled pustules. The disease, which often manifests with concurrent psoriasis vulgaris, can have an acute systemic (generalized pustular psoriasis [GPP]) or chronic localized (palmoplantar pustulosis [PPP] and acrodermatitis continua of Hallopeau [ACH]) presentation. Although mutations have been uncovered in IL36RN and AP1S3, the rarity of the disease has hindered the study of genotype-phenotype correlations. OBJECTIVE: We sought to characterize the clinical and genetic features of pustular psoriasis through the analysis of an extended patient cohort. METHODS: We ascertained a data set of unprecedented size, including 863 unrelated patients (251 with GPP, 560 with PPP, 28 with ACH, and 24 with multiple diagnoses). We undertook mutation screening in 473 cases. RESULTS: Psoriasis vulgaris concurrence was lowest in PPP (15.8% vs 54.4% in GPP and 46.2% in ACH, P < .0005 for both), whereas the mean age of onset was earliest in GPP (31.0 vs 43.7 years in PPP and 51.8 years in ACH, P < .0001 for both). The percentage of female patients was greater in PPP (77.0%) than in GPP (62.5%; P = 5.8 × 10-5). The same applied to the prevalence of smokers (79.8% vs 28.3%, P < 10-15). Although AP1S3 alleles had similar frequency (0.03-0.05) across disease subtypes, IL36RN mutations were less common in patients with PPP (0.03) than in those with GPP (0.19) and ACH (0.16; P = 1.9 × 10-14 and .002, respectively). Importantly, IL36RN disease alleles had a dose-dependent effect on age of onset in all forms of pustular psoriasis (P = .003). CONCLUSIONS: The analysis of an unparalleled resource revealed key clinical and genetic differences between patients with PPP and those with GPP.

Lower Extremity Desmoplastic Malignant Melanoma in Egypt.

Desmoplastic melanoma (DM) is a type of spindle cell melanoma characterized by the absence of pigment. The clinical diagnosis of DM represents a challenge for the practitioner and the pathologists because it can mimic benign or malignant skin tumors and even inflammatory skin disorders. We here discuss a case of a patient presented with multiple nodular lesions of the lower extremity following electrocautary to a lesion in her sole which was misdiagnosed as planter wart. Our clinical diagnosis was Kaposi sarcoma, hypertrophic lichen, or extensive verruca vulgaris. However, histopathological examination showed spindle-shaped cells positive for Melan-A and S100 revealing the diagnosis of DM.