Explore the vast range of titles available.

A nested case-control study using the National Institutes of Health All of Us database was conducted, with patients ≥ 18 years with AA diagnosis matched with controls 1:4 by age, sex at birth, and race/ethnicity. Demographic characteristics of alopecia areata and control patients matched by age and self-reported race/ethnicity Controls (n = 3,828) Alopecia areata (n = 957) P value Age, mean (std) 55.8 (15.2) 55.8 (15.2) 1 Sex at birth  Male 892 (23.3) 223 (23.3) 1  Female 2,836 (74.1) 709 (74.1)  Other 100 (2.6) 25 (2.6) Self-reported race/ethnicity count (%)  White 1,560 (40.8) 390 (40.8) 1  Hispanic or Latino 956 (24.9) 239 (24.9)  Black or African American 816 (21.3) 204 (21.3)  Asian 168 (4.4) 42 (4.4)  Other 328 (8.6) 82 (8.6) Table 2. [5] Based on our findings, we recommend conducting a history and review of systems with special attention to thyroid (e.g., cold/heat sensitivity), gastrointestinal (e.g., diarrhea or weight loss suggestive of celiac disease), respiratory (e.g., wheezing suggestive of asthma), and dermatologic (e.g., pruritus) symptoms, and physical examination of wrists and oral cavity for LP, anogenital region for LSA, extensor regions, nails, and scalp for psoriasis, and face and hands for vitiligo. Funding The All of Us Research Program is supported by the National Institutes of Health, Office of the Director: Regional Medical Centers: 1 OT2 OD026549; 1 OT2 OD026554; 1 OT2 OD026557; 1 OT2 OD026556; 1 OT2 OD026550; 1 OT2 OD 026552; 1 OT2 OD026553; 1 OT2 OD026548; 1 OT2 OD026551; 1 OT2 OD026555; IAA #: AOD 16037; Federally Qualified Health Centers: HHSN 263201600085U; Data and Research Center: 5 U2C OD023196; Biobank: 1 U24 OD023121; The Participant Center: U24 OD023176; Participant Technology Systems Center: 1 U24 OD023163; Communications and Engagement: 3 OT2 OD023205; 3 OT2 OD023206; and Community Partners: 1 OT2 OD025277; 3 OT2 OD025315; 1 OT2 OD025337; 1 OT2 OD025276.

Vulvar lichen sclerosus and lichen planus are T-cell–mediated chronic skin disorders. Although autoimmunity has been suggested, the exact pathogenesis of these disorders is still unknown. Therefore, the aim of the current study was to investigate the molecular and immunological mechanisms critical to the pathogenesis of vulvar lichen sclerosus and lichen planus. By using gene expression profiling and real-time RT-PCR experiments, we demonstrated a significantly increased expression of the pro-inflammatory cytokines (IFNγ, CXCR3, CXCL9, CXCL10, CXCL11, CCR5, CCL4, and CCL5) specific for a Th1 IFNγ-induced immune response. In addition, BIC/microRNA-155 (miR-155)—a microRNA involved in regulation of the immune response—was significantly upregulated in lichen sclerosus and lichen planus (9.5- and 17.7-fold change, respectively). Immunohistochemistry showed a significant T-cell response, with pronounced dermal infiltrates of CD4+, CD8+, and FOXP3+ cells. In conclusion, these data demonstrate an autoimmune phenotype in vulvar lichen sclerosus and lichen planus, characterized by increased levels of Th1-specific cytokines, a dense T-cell infiltrate, and enhanced BIC/miR-155 expression.

Lichen sclerosus (LS) is a chronic, inflammatory, mucocutaneous disorder of genital and extragenital skin. LS is a debilitating disease, causing itch, pain, dysuria and restriction of micturition, dyspareunia, and significant sexual dysfunction in women and men. Many findings obtained in recent years point more and more towards an autoimmune-induced disease in genetically predisposed patients and further away from an important impact of hormonal factors. Preceding infections may play a provocative part. The role for Borrelia is still controversial. Trauma and an occlusive moist environment may act as precipitating factors. Potent and ultrapotent topical corticosteroids still head the therapeutic armamentarium. Topical calcineurin inhibitors are discussed as alternatives in the treatment of LS in patients who have failed therapy with ultrapotent corticosteroids, or who have a contraindication for the use of corticosteroids. Topical and systemic retinoids may be useful in selected cases. Phototherapy for extragenital LS and photodynamic therapy for genital LS may be therapeutic options in rare cases refractory to the already mentioned treatment. Surgery is restricted to scarring processes leading to functional impairment. In men, circumcision is effective in the majority of cases, but recurrences are well described. Anogenital LS is associated with an increased risk for squamous cell carcinoma of the vulva or penis. This review updates the epidemiology, clinical presentation, histopathology, pathogenesis, and management of LS of the female and male genitals and extragenital LS in adults and children.

Isousnic acid (isoUA) has been detected in a few usnic acid (UA)-producing lichens with chemotaxonomic values. IsoUA was first isolated from a specimen belonging to Cladonia arbuscula s.l. (referred to as C. mitis in the publication). However, the isolation and detection of isoUA in this Cladonia species have not been reproduced and confirmed with clear evidence. This study focused on C. arbuscula s.l. collected in Iceland and aimed to (1) identify the lichen specimen using DNA barcoding and (2) investigate whether isoUA is produced using a series of chromatographic methods. The fungal nuclear ribosomal internal transcribed spacer (nrITS) barcode was sequenced, and the specimen was identified as C. arbuscula, following recent circumscription recommendations. Routine metabolite profiling did not detect isoUA, and it could only be identified after vigorous chromatographic purification and concentration steps using flash chromatography and preparative high-performance liquid chromatography. IsoUA was found in trace quantities (~24 µg/g dry weight), which likely explains its absence in routine metabolite profiling. A rapid ultra-high-performance liquid chromatography (UHPLC) method using a pentafluorophenyl column was developed to separate UA and isoUA. Our study highlights the importance of an integrative approach combining DNA barcoding and detailed chromatographic analyses for lichen chemistry research.

Lichens play significant roles in ecosystem function and comprise about 20% of all known fungi. Polyketide-derived natural products accumulate in the cortical and medullary layers of lichen thalli, some of which play key roles in protection from biotic and abiotic stresses (e.g., herbivore attacks and UV irradiation). The depside and depsidone series compounds of polyketide origin accumulate in the cortical or medullary layers of lichen thalli. Despite the taxonomic and ecological significance of lichen chemistry and its pharmaceutical potentials, there has been no single piece of genetic evidence linking biosynthetic genes to lichen substances. Thus, we systematically analyzed lichen polyketide synthases (PKSs) for categorization and identification of the biosynthetic gene cluster (BGC) involved in depside/depsidone production. Our in-depth analysis of the interspecies PKS diversity in the genus Cladonia and a related Antarctic lichen, Stereocaulon alpinum , identified 45 BGC families, linking lichen PKSs to 15 previously characterized PKSs in nonlichenized fungi. Among these, we identified highly syntenic BGCs found exclusively in lichens producing atranorin (a depside). Heterologous expression of the putative atranorin PKS gene (coined atr1 ) yielded 4- O -demethylbarbatic acid, found in many lichens as a precursor compound, indicating an intermolecular cross-linking activity of Atr1 for depside formation. Subsequent introductions of tailoring enzymes into the heterologous host yielded atranorin, one of the most common cortical substances of macrolichens. Phylogenetic analysis of fungal PKS revealed that the Atr1 is in a novel PKS clade that included two conserved lichen-specific PKS families likely involved in biosynthesis of depsides and depsidones. Here, we provide a comprehensive catalog of PKS families of the genus Cladonia and functionally characterize a biosynthetic gene cluster from lichens, establishing a cornerstone for studying the genetics and chemical evolution of diverse lichen substances. IMPORTANCE Lichens play significant roles in ecosystem function and comprise about 20% of all known fungi. Polyketide-derived natural products accumulate in the cortical and medullary layers of lichen thalli, some of which play key roles in protection from biotic and abiotic stresses (e.g., herbivore attacks and UV irradiation). To date, however, no single lichen product has been linked to respective biosynthetic genes with genetic evidence. Here, we identified a gene cluster family responsible for biosynthesis of atranorin, a cortical substance found in diverse lichen species, by categorizing lichen polyketide synthase and reconstructing the atranorin biosynthetic pathway in a heterologous host. This study will help elucidate lichen secondary metabolism, harnessing the lichen’s chemical diversity, hitherto obscured due to limited genetic information on lichens.

Lichen sclerosus is a chronic skin disease, mainly localised at the introitus and perineum. When the condition remains untreated, gradual atrophy of skin structures leads to permanent scarring, making early diagnosis and treatment crucial. We reviewed all patients diagnosed with lichen sclerosus presenting to a tertiary referral centre for paediatric and adolescent gynaecology between January 2011 and December 2015 to assess disease presentation and response to treatment. We identified 15 cases, with a mean age at diagnosis of 8.8 years. Their main presenting symptoms were vulvar pruritus and vulvar soreness. Seven girls had already atrophic changes, and in four girls, this amounted to clitoral phimosis, labial resorption or labial adhesion formation. The median delay in diagnosis was 7 months. Thirteen patients received local treatment with potent corticosteroids, responding well to treatment. However, 4 girls relapsed within 2 to 36 months. Two adolescents required surgical treatment, one because of urinary retention and the second because of dyspareunia caused by clitoral entrapment. Conclusions : There was a delay in diagnosis in most patients and this resulted in irreversible genital skin changes, which would have been preventable, had treatment been instituted promptly. The response to treatment with local corticosteroids was usually effective, leading to both symptom alleviation and prevention of disease progression. Atrophic changes and skin complications however were not reversed. What is Known: • Lichen sclerosus affects women of all ages, including girls, particularly prior to adolescence. • Lichen sclerosus responds well to local corticosteroid treatment . What is New: • In the majority of patients with lichen sclerosus there was a long delay between onset of symptoms and diagnosis . • Nearly half of the children diagnosed with lichen sclerosus had irreversible atrophic genital skin changes at the time of first presentation. These changes may have been prevented by a timely diagnosis and intervention .

Lichen planus (LP) is a common chronic inflammatory condition that can affect skin and mucous membranes, including the oral mucosa. Because of the anatomic, physiologic and functional peculiarities of the oral cavity, the oral variant of LP (OLP) requires specific evaluations in terms of diagnosis and management. In this comprehensive review, we discuss the current developments in the understanding of the etiopathogenesis, clinical-pathologic presentation, and treatment of OLP, and provide follow-up recommendations informed by recent data on the malignant potential of the disease as well as health economics evaluations.

Lichen planus pemphigoides (LPP) is a very rare autoimmune sub-epidermal blistering disease associated with lichenoid skin changes. Initially thought to be a mere variant of more common inflammatory dermatoses, particularly Bullous Pemphigoid (BP) or Lichen Planus (LP), a growing body of evidence suggests that it is a disease entity in its own right. In common with a range of autoimmune blistering diseases, including BP, pemphigoid gestationis (PG), mucous membrane pemphigoid (MMP) and linear IgA dermatosis (LAD), a key feature of the disease is the development of autoantibodies against type XVII collagen (COL17). However, accurately establishing the diagnosis is dependent on a careful correlation between the clinical, histological and immunological features of the disease. Therefore, we present an up to date summary of the epidemiology and etiopathogenesis of LPP, before illustrating the predisposing and precipitating factors implicated in the development of the disease. In addition to a selective literature search, we compare reports of potential drug-induced cases of LPP with pharmacovigilance data available via OpenVigil. We subsequently outline the cardinal clinical features, important differential diagnoses and current treatment options. We conclude by demonstrating that an improved understanding of LPP may not only lead to the development of novel treatment strategies for the disease itself, but may also shed new light on the pathophysiology of more common and treatment-refractory autoimmune blistering diseases.