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In dermatology, lichenoid describes lesions with a violaceous hue that is a clinical reflection of basal cell damage in the epithelium and dense mononuclear infiltrate in the sub-epithelium. The violaceous color results from pigment incontinence due to basal cell damage and the Tyndall effect. Although classically described in lichen planus, a lichenoid hue is noted in the oral mucosa in several other disorders that often lead to diagnostic dilemmas. Early and accurate diagnosis is important for the appropriate management of the underlying condition and prognostication. Dermatologists play a central role in managing such patients since, apart from the oral mucosa findings, the cutaneous features also help to significantly differentiate various conditions. Mimickers of oral lichen planus include nicotine stomatitis, oral submucous fibrosis, oral lichenoid lesions, mucosal discoid lupus erythematosus, pemphigus vulgaris, paraneoplastic pemphigus, mucous membrane pemphigoid, fixed drug eruption, plasma cell cheilitis/gingivitis, and erythema multiforme. While a detailed history and clinical examination can help reach a diagnosis in most cases, histopathology, immunofluorescence, and other relevant investigations help establish the diagnosis., (© 2024 the International Society of Dermatology.)

Actinic cheilitis (AC) is a lip disorder, with no standard treatment. Imiquimod (IMIQ) is an immunomodulator that treat precancerous lesions; however, its commercial form causes severe adverse effects. This study aimed to assess IMQ release from a chitosan hydrogel containing 0.05 % nanoencapsulated (NANO) imiquimod (IMIQ-0.05 %-NANO) and its efficacy in AC treatment. The hydrogels were prepared by incorporating chitosan into polymeric nanocapsules (NCimiq) loaded with IMQ, produced using the interfacial deposition of preformed polymer method. IMQ release was evaluated using automated Franz Cells. A triple-blind randomized controlled trial (49 subjects) compared the efficacy of: IMIQ-0.05 %-NANO, 5 % free imiquimod (IMIQ-5 %), 0.05 % free imiquimod (IMIQ-0.05 %), and placebo hydrogel. The IMIQ-NANO-0.05 % and IMIQ-5 % groups exhibited significantly higher rates of clinical improvement (p < 0.05); however, the IMIQ-5 % group experienced more adverse effects (92.3 % of subjects) compared to other groups (p < 0.05). In conclusion, in the studied sample, IMIQ-NANO-0.05 % was a safe and effective option to treat AC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Evaluate the immunohistochemical expression of the ING3 in actinic cheilitis and squamous cell carcinoma of the lower lip., Methods: Forty-five specimens of actinic cheilitis and 48 specimens of squamous cell carcinoma of the lower lip were submitted to immunohistochemical detection of ING3. The protein expression in different cellular sublocations was compared between the two groups, and associations with the clinicopathological variables were analyzed. A significance level of 5% was adopted for all tests., Results: Deaths were significantly more frequent in tumors with a high histopathological risk score (p < 0.05). In actinic cheilitis, significant differences were found in the nucleus-cytoplasmic expression of ING3 and expression restricted to the cytoplasm with binary histopathological grading (p < 0.05). In squamous cell carcinoma of the lower lip, there was no statistically significant difference when comparing ING3 expressions with clinical and morphological parameters (p > 0.05). Nucleo-cytoplasmic ING3 expression was significantly lower in squamous cell carcinoma of the lower lip when compared to actinic cheilitis (p < 0.05) and the expression restricted to the cytoplasm was significantly higher in squamous cell carcinoma of the lower lip (p < 0.05)., Conclusion: The results of this study suggest that there is a marked decrease in the nuclear expression of ING3 as malignant progression occurs, indicating an impaired tumor suppressor function of this protein in actinic cheilitis and squamous cell carcinoma of the lower lip., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The aim of this study was to investigate oral mucosal changes in patients with confirmed moderate-scale severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection., Methods: We analyzed 85 COVID-19 patients (50 males, 35 females) with an average age of 53.6 years, treated at the prehospital infectious disease center and Aldent University Clinic in Tirana, Albania, from May 2021 to June 2022., Results: Elevated C-reactive protein levels were observed in 82 patients (±44.20), with 20 patients showing significant fibrinogen increase (mean ± 5.85 g/L), and 22 patients having elevated D-Dimer (mean ± 336.6 mg/mL). Despite the absence of anticoagulant history, 13 patients exhibited bleeding. Xerodermia, xerostomia, and angular cheilitis were noted, with 41 patients displaying angular cheilitis. In 82 patients, oral mucosal and tongue examinations revealed color changes from white to bright yellow, with brown edema. Pigmentation in the fixed gingiva of upper and lower front teeth was observed in 35 patients., Conclusions: Oral mucosal changes during COVID-19 appear more influenced by drug treatment and disease progression than the infection itself, suggesting that secondary factors play a significant role. Despite the oral cavity's potential for viral entry, these changes seem connected to other underlying causes.

Background: To evaluate the presence of myofibroblasts (MFs) in the development of lip carcinogenesis, through the correlation of clinical, histomorphometric and immunohistochemical parameters, in actinic cheilitis (ACs) and lower lip squamous cell carcinomas (LLSCCs)., Methods: Samples of ACs, LLSCCs, and control group (CG) were prepared by tissue microarray (TMA) for immunohistochemical TGF-β, α-SMA, and Ki-67 and histochemical hematoxylin and eosin, picrosirius red, and verhoeff van gieson reactions. Clinical and microscopic data were associated using the Mann-Whitney, Kruskal-Wallis/Dunn, and Spearman correlation tests (SPSS, p < 0.05)., Results: ACs showed higher number of α-SMA + MFs when compared to CG (p = 0.034), and these cells were associated with the vertical expansion of solar elastosis (SE) itself (p = 0.027). Areas of SE had lower deposits of collagen (p < 0.001), immunostaining for TGF-β (p < 0.001), and higher density of elastic fibers (p < 0.05) when compared to areas without SE. A positive correlation was observed between high-risk epithelial dysplasia (ED) and the proximity of SE to the dysplastic epithelium (p = 0.027). LLSCCs showed a higher number of α-SMA + MFs about CG (p = 0.034), as well as a reduction in the deposition of total collagen (p = 0.009) in relation to ACs and CG. There was also a negative correlation between the amount of α-SMA + cells and the accumulation of total collagen (p = 0.041). Collagen and elastic density loss was higher in larger tumors (p = 0.045) with nodal invasion (p = 0.047)., Conclusions: Our findings show the possible role of MFs, collagen fibers, and elastosis areas in the lip carcinogenesis process., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: The aim of the study. Improving the efficiency of diagnosis and detailing the features of the clinic of «potentially malignant» diseases of the oral mucosa., Materials and Methods: Clinical and laboratory examination of 124 patients of the department of oral mucosa diseases aged 35 to 80 years, among whom there were 75 women and 49 men, with diseases such as erythroplakia - 12 patients, verrucous leukoplakia - 52 patients, erosive form of leukoplakia - 35 patients, cheilitis Manganotti - 25 patients. Histological and immunohistochemical methods of investigation were used as diagnostics. To assess the proliferative activity of epithelial cells, the determination of the Ki-67 index was used. The synthesis of keratin 15 (K15) in epithelial layers was determined as a diagnostic criterion for the severity of neoplasia. The expression of human papillomavirus type 16 (HPV 16) antigens and p16INK4a protein in epithelial cells was studied, as well as the expression of p53 protein., Results: A high prevalence of p53 mutations was observed in patients with erythroplakia. In leukoplakia, the expression of the Ki-67 protein was detected in the cell nuclei in both the basal and parabasal layers of the multilayer squamous epithelium, in 77% of cases, the expression of the p16INK4a protein in the epithelial nuclei with varying degrees of dysplastic changes was noted, and a positive reaction to HPV16 was also observed in the cell nuclei and cytoplasm of epithelial cells in the basal, parabasal and spiny epithelial layers. The appearance of K15 in the cytoplasm of cells above the basal layer with abrasive precancerous cheilitis was found in 48% of cases., Conclusion: To diagnose early manifestations of neoplastic processes in «potentially malignant» diseases of the oral mucosa, it is necessary to use both classical histological and immunohistochemical methods of investigation with various markers.

Background: This systematic review aimed to conduct a complete investigation of the demographic aspects, clinicopathological features, degrees of epithelial dysplasia, and malignant transformation rate of actinic cheilitis., Methods: The study was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered in the International Prospective Register of Systematic Reviews (CRD42020201254). A search without year and language restrictions was performed using PubMed/MEDLINE, Embase, Virtual Health Library, Scopus, Web of Science, and gray literature. Studies that provided information on patients with actinic cheilitis were included, excluding those with general information on other diseases or other types of cheilitis. Risk of bias was explored using the Joanna Briggs Institute tool. Narrative and quantitative data syntheses were performed using meta-analyses and subgroup analyses. Association tests were also performed., Results: Thirteen studies (728 patients) were included. The most prevalent clinical signs were dryness (99%), blurred demarcation between the lip vermilion and skin (82%), scaling (69%), and atrophy (69%). Regarding epithelial dysplasia, a prevalence of mild dysplasia (34.2%), followed by moderate (27.5%), and severe (14.9%). The malignant transformation rate was 14%. Crusts, ulcerations, and erythematous areas were associated with lip carcinoma (p < 0.001), and scaling was associated with actinic cheilitis (p < 0.001)., Conclusions: This study revealed several features of actinic cheilitis, providing an overview of the disease. It is suggested that new studies help develop policy guides for the standardization of clinical criteria, enabling more rigorous and homogeneous analysis of actinic cheilitis., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Abstract: We describe a 20-year-old male with no significant medical history who presented with a 1-month history of painless upper and lower lip edema initially treated with antibiotics for suspected cellulitis before arriving to the clinic. After a failed response to that treatment, a lip biopsy was eventually performed and consistent with a diagnosis of granulomatous cheilitis. In addition to oral and topical corticosteroids and tacrolimus, the patient adopted the cinnamon- and benzoate-free diet with some improvement of his lip swelling. Persistent mild tachycardia led to a cardiology referral for further evaluation and sarcoidosis workup. A gastroenterology consult was placed to correlate his presentation with Crohn's disease. The cardiology workup was noncontributory, and the patient was ultimately diagnosed with Crohn's disease after evaluation with laboratory studies and colonoscopy. This case highlights the need to evaluate for Crohn's disease in patients who present with granulomatous cheilitis, even in the absence of gastrointestinal symptoms, and the potential benefit of incorporating a cinnamon- and benzoate-free diet in treatment., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Squamous cell carcinoma of the lip (LSCC) and oral cavity can be life-threatening if not diagnosed early. Precancerous lesions like actinic cheilitis (AC), can transform into LSCC. Laminin is a fundamental component for basement membrane (BM) and its integrity may prevent neoplastic invasion. Therefore, laminin immunostaining of BM may be useful in identifying early invasion in actinic cheilitis and thus in the differential diagnosis between AC and invasive LSCC or high-grade epithelial dysplasia (ED)., Materials and Methods: Biopsies from 46 patients with oral lesions were histologically analyzed and immunohistochemically stained for laminin-1., Results: AC was diagnosed in 34 patients and LSCC in 12 patients, including 3 patients with AC and concomitant high-grade ED/in situ carcinoma. Laminin-1 immunostaining revealed intense and linear expression of the BM in AC with low-grade ED. Loss of laminin expression was observed in LSCC. Intracellular laminin expression in parabasal cells was noted in AC with high-grade ED/in situ carcinoma., Conclusion: Laminin immunostaining could be useful in identifying AC cases suspected of early invasion. It could also contribute to the histopathological differential diagnosis between AC with low- and high-grade ED and between AC and invasive LSCC. The findings of this study provide new insights into the mechanism involved in the progression process of AC into LSCC, encouraging preclinical studies that may document the stochastic role of laminin in this process., (© 2022. The Author(s).)

Background: Atopic dermatitis (AD) is an inflammatory skin condition distinguished by an activated Th2 immune response. The local skin microbial dysbiosis is a contributing factor to the development of AD. The pathogenic coagulase-positive Staphylococcus aureus is the primary species responsible for the progression of AD. Even though Staphylococcus pseudintermedius is an animal-origin pathogen, it is increasingly becoming a source of concern in human diseases. As another coagulase-positive Staphylococci, it is crucial to pay more attention to S. pseudintermedius isolated from the lesion site., Results: In our investigation, we presented a case of cheilitis in a patient with atopic dermatitis (AD). We utilized culture and next-generation genomic sequencing (NGS) to identify the bacteria present on the skin swabs taken from the lip sites both prior to and following treatment. Our findings indicated that the predominant bacteria colonizing the lesion site of AD were S. pseudintermedius and S. aureus, both of which were eradicated after treatment. The Multi-locus sequence typing (MLST) of S. pseudintermedius and S. aureus demonstrated coordinated antibiotic susceptibility, with ST2384 and ST22 being the respective types. Although the skin abscess area resulting from S. pseudintermedius infection was significantly smaller than that caused by S. aureus in mice, the expression of cytokines interleukin-4 (IL-4) and interleukin-5 (IL-5) were significantly higher in the S. pseudintermedius-infected mice., Conclusions: The S. pseudintermedius strain isolated from the lesion site of the AD patient exhibited a higher expression of IL-4 and IL-5 when colonized on mouse skin, as compared to S. aureus. This observation confirms that S. pseudintermedius can effectively induce the Th2 response in vivo. Our findings suggest that animal-origin S. pseudintermedius may play a role in the development of AD when colonized on the skin, emphasizing the importance of taking preventive measures when in contact with animals., (© 2023. The Author(s).)

Objectives: Cheilitis Glandularis (CG) is an uncommon entity of obscure etiology. A cases series is presented with emphasis on etiopathogenesis., Materials and Methods: Fourteen CG cases were analyzed according to their demographic and clinicopathologic characteristics., Results: The mean age of the patients with CG was 68.1 years, while a male-to-female ratio of 1.8:1 was observed. One or more potential causative factors were identified for each patient, including long-term smoking (9 cases), xerostomia (4 cases), cosmetic filler injections (2 cases), and actinic cheilitis (1 case). The lesions were located on the lips, buccal mucosa, or both in 7, 2, and 5 cases, respectively. Multiple submucosal nodules with dilated ductal orifices and mucous or purulent discharge were observed in all cases. Histopathologically, ductal ectasia with metaplasia, intraductal mucin, and chronic or mixed inflammation were noted, as well as pools of hyaluronic acid in 2 cases with a history of cosmetic filler injections., Conclusions: CG etiopathogenesis is probably multifactorial. Reduced salivary flow rate and increased viscosity of saliva, potentially caused by long-term smoking, diabetes mellitus, and drug-induced xerostomia, may participate in the initial pathogenesis, while local irritants, for example, poor oral hygiene and local trauma, may further contribute to the development and aggravation of the condition., (© 2022 Wiley Periodicals LLC.)

Chronic cheilitis (CC) is a spectrum of inflammatory changes of unknown etiology that affect the vermilion of the lips. This study aimed to describe the epidemiology, clinical presentations and risk factors of CC. Patients with CC were recruited from the National Clinical Research Center for Oral Disease of China. A convenience sample of inhabitants who live in the same geographical region were recruited as the control group. The lip skin transepidermal water loss (TEWL) and capacitance of CC patients were compared with that of age- and gender-matched controls. Our results demonstrated that of the 109 patients with CC, 72 (66.1%; 95% CI: 57.0-75.1%) were female. The common clinical presentations of CC consisted of desquamation (n = 99; 90.8%), and/or chapping (n = 81; 74.3%), and/or pruritus (n = 64; 58.7%). Multivariable analysis showed that allergic dermatologic diseases (P < 0.001; OR: 4.5; 95% CI: 2.4-8.4), anemia (P = 0.001; OR: 3.3; 95% CI: 1.5-7.5), and indoor/outdoor alternate working environment (P < 0.001; OR: 2.1; 95% CI: 1.5-2.8) were the significant risk factors for CC. The mean lip skin TEWL was found to be significantly higher, while the capacitance was lower in CC patients compared to that of control individuals. This study provides insights into the etiopathogenesis of CC and may help clinicians to identify the most effective management strategies., (© 2022. The Author(s).)

Background: Actinic cheilitis is a potentially malignant lesion most commonly found in the lower lip of individuals with chronic exposure to ultraviolet radiation. The aim of this study was to develop and to test a clinical index that can be used to assess the severity of actinic cheilitis., Material and Methods: The clinical index of actinic cheilitis was applied to 36 patients. An incisional biopsy was obtained to grade oral epithelial dysplasias following the World Health Organization (WHO) and binary systems, and to evaluate their association with clinical characteristics by Fisher's exact test (P<0.05). The accuracy of the index was evaluated based on sensitivity, specificity, positive and negative predictive values, and receiver operating curve., Results: The blurring between the border of the lip and the skin was significantly associated with cases without dysplasia/mild epithelial dysplasia (P=0.041) and with low risk of malignancy (P=0.005). Ulcers and crusts were significantly associated with moderate/severe epithelial dysplasia (P=0.002 and P=0.012, respectively) and high risk of malignancy (P=0.005 and P=0.045, respectively). Erosion showed a significant association only with high-risk cases of malignancy (P=0.024). The cut-off values of the diagnostic test showing the best performance were 10 for the WHO grading system and 11 for the binary system., Conclusions: The index cut-offs with the highest accuracy were considered indicators for a biopsy. Erosion, ulceration and crusts were associated with more severe oral epithelial dysplasias.

Actinic cheilitis (AC) is a chronic inflammation of the lip considered an oral, potentially malignant disorder associated with an increased risk of lip squamous cell carcinoma (SCC) development. Controversies surrounding current therapeutic modalities of AC are under debate, and the implications of laser treatment have not been specifically investigated through a systematic review design. The present study aims to evaluate the degree of evidence of laser for the treatment of AC in terms of efficacy and safety. We searched for primary-level studies published before January 2022 through MEDLINE/PubMed, Embase, Web of Science, Scopus and CENTRAL, with no limitation in publication language or date. We evaluated the methodological quality and risk of bias of the studies included using the updated Cochrane Collaboration's tool for assessing risk of bias (RoB-2). Twenty studies (512 patients) met our eligibility criteria. Laser therapy showed a complete clearance of AC in 92.5% patients, with a maximum recurrence rate of 21.43%, and a very low frequency of malignant transformation to SCC (detected in only 3/20 studies analyzed). In addition, cosmetic outcomes and patient satisfaction were described as excellent. In conclusion, our findings indicate that laser therapy is a high efficacy approach to AC.

Objective: To investigate and compare the immunoexpression of E-cadherin, α-SMA, TGF-β and Snail proteins between cases of actinic cheilitis (AC) and squamous cell carcinoma of the lower lip (LLSCC)., Study Design: E-cadherin, α-SMA, TGF-β and Snail antibody immunostaining was analyzed semiquantitatively in 54 AC cases and in 49 LLSCCs. The cases were classified as low and high expression for analysis of the association with clinicopathological variables and overall survival (OS) and disease-free survival (DFS) rates., Results: High expression of E-cadherin (cytoplasmic) (p = 0.001) and α-SMA (p < 0.001) was identified in LLSCCs, as well as low expression of TGF-β in LLSCCs (p < 0.001) and high expression of Snail in AC cases (p = 0.006). Survival analysis revealed that high expression of α-SMA at the tumor invasion front, a network immunostaining pattern of this protein, and high expression of TGF-β in tumor buds were significantly associated with poor OS (p < 0.05). There was a higher risk of death among LLSCC cases with high expression of α-SMA (HR = 5.90, p = 0.03). High expression of TGF-β in tumor buds was significantly associated with poor DFS (p = 0.007) and with a higher risk of negative outcomes for DFS (HR = 4.44, p = 0.014)., Conclusions: The present results suggest the potential involvement of dysregulation of proteins associated with epithelial-mesenchymal transition in the modulation of lip carcinogenesis and greater aggressiveness of LLSCC., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Angular cheilitis, an infection mainly caused by Candida yeasts, is featured by the appearance of inflammatory lesions at the bilateral corners of the mouth, particularly in patients with poor oral hygiene, ill-fitting dentures and old age. The first isolation of an atypical yeast, Cystobasidium calyptogenae, from oral samples of a patient presenting with angular cheilitis is discussed in this study., Case Presentation: Angular cheilitis was diagnosed in a 60-year-old denture-wearing woman who presented with an irritation fibroma on her right lower buccal sulcus over the premolar region. Primary cultures of her oral swab and oral rinse samples grew a pure culture of an uncommon yeast strain resembling Rhodotorula sp. Sequence analysis of the yeast internal transcribed spacer (ITS) gene region and D1D2 domain showed highest similarity (99.6% and 100%, respectively) to C. calyptogenae CBS 9125 type strain. Following 2 weeks of treatment with miconazole/fusidic acid and mouthwash, the oral lesion showed improvement with less erythema. C. calyptogenae was not isolated from the patient's oral samples upon repeat sampling., Conclusion: This is the first report on the isolation of C. calyptogenae from human oral samples. The ability of C. calyptogenae to grow at 37 °C and the fact that it was the only yeast species isolated from the patient's oral samples suggests its pathogenic potential and possible involvement in angular cheilitis. The ubiquitous nature of the Cystobasidium yeast is believed to increase the likelihood of opportunistic infections among immunocompromised individuals. As Cystobasidium is phenotypically indistinguishable from Rhodotorula, an emerging opportunistic pathogen, surveillance using molecular identification in clinical settings is essential in providing accurate diagnosis and treatment of uncommon yeast infections., (© 2022. The Author(s).)

Abstract: Epidermal barrier disruption caused by atypical squamous proliferations of the lip (SOL) creates an ideal environment for fungal growth. Histologic features of SOL include parakeratosis overlying partial- or full-thickness keratinocyte atypia with or without invasion of the dermis, dermal solar elastosis, and scattered inflammatory cells which are predominantly lymphocytes. Histologic features of SOL with fungal superinfections overlap those seen in primary fungal cheilitis with reactive atypia, creating a diagnostic challenge. One-hundred seventy SOL cases were examined for the presence of fungal elements, and the histological features associated with superinfection were identified. Cases diagnosed as actinic cheilitis with fungal superinfection were carefully examined to rule out the possibility of misdiagnosed primary fungal cheilitis with reactive atypia. Histopathological characteristics commonly present with fungal hyphae included intraepidermal or intradermal neutrophils, bacterial colonies, and erosion or ulceration. Medical record review of those patients treated conservatively with topical antifungals revealed persistent clinical neoplasm and histological evidence of residual SOL on repeat biopsy. Thus, when biopsies exhibit histological overlap between these 2 entities, clinicians should keep a high index of suspicion for underlying SOL and carefully follow these patients if conservative antifungal therapy is initially trialed., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

To compare two grading systems of epithelial dysplasia-World Health Organization (WHO) and binary system (BS) -in actinic cheilitis (AC). Seventy cases diagnosed as AC in an Oral Pathology Laboratory from Brazil in the last 12 years were retrospectively retrieved, including the demographic data of each patient. All conventionally stained slides were reviewed, and epithelial dysplasia was evaluated by two independent observers using both WHO and BS grading systems. Data correlation was performed using kappa and chi-square tests (p < 0.05). Most patients were white men with a mean age of 57 years old and history of chronic exposure to sunlight. Most of the lesions were clinically described as whitish plaques with irregular surface located in the lower lip semi-mucosa. Most cases were microscopically graded as severe epithelial dysplasia and low-risk by both observers. The interobserver and intraobserver agreement between systems was slight. All reddish lesions were graded as severe epithelial dysplasia, showing an equal distribution between low and high-risk grading. Most ulcerated lesions showed severe epithelial dysplasia but was graded as low-risk of malignant transformation. Statistical significance was observed among the presence of "irregular stratification", severe epithelial dysplasia and high-risk lesions (p < 0.05) likewise among the presence of "loss of polarity of basal cells" and "drop-shaped ridges" (p < 0.05) with high-risk lesions. The absence of "increased mitotic figures", "dyskeratosis" and "keratin pearls" (p < 0.05) were strongly correlated to low-risk lesions. The presence of "hyperchromasia" was statistically significant with severe epithelial dysplasia (p < 0.05) as well the absence of "atypical mitotic figures" with low-risk lesions (p < 0.05). Although there was slight agreement between microscopic grading systems, microscopic analysis indicated that architectural epithelial changes individually may be the more reliable criteria to indicate the risk of malignant transformation in AC in both grading systems.

Objective: Lip skin dryness and chapping are major concerns related to lip skin care in many populations. The distinctive features of lip skin, such as the low water-holding capacity and weak skin barrier, are strongly associated with these problems; however, few studies have examined lip skin characteristics and the mechanisms underlying these issues. This study was conducted to identify the biophysical properties of dry lip skin and molecular targets affecting lip skin physiology., Methods: Skin hydration, transepidermal water loss and lip skin scaling were evaluated in 40 female subjects. Skin scaling was assessed as a percentage area divided into five categories (G0, G1, G2, G3 and G4) according to the thickness level of tape-stripped corneocytes. The activities and amounts of proteases, cathepsin D and bleomycin hydrolase were measured as markers for the desquamation process and skin hydration, respectively., Results: Skin hydration showed a significantly positive correlation with the percentage area of evenly thin corneocytes (G0) and negative correlations with the percentage areas of slightly thick to severely thick corneocytes (G1-G4). The corneocyte unevenness ratio (CUR) was calculated by dividing the sum of the G1, G2, G3 and G4 values with the G0 value. The CUR was significantly negatively correlated with skin hydration, suggesting that CUR is a new parameter representing the severity of lip scaling. Subjects with lower hydration and higher CUR had higher bleomycin hydrolase activity and lower cathepsin D activity, respectively, than subjects with higher hydration and lower CUR., Conclusion: Our study revealed a correlation between lip skin hydration and severity of lip scaling and verified the association of protease activity with the hydration and chapping state of lip skin. These observations provide a basis for further studies of the persistent problem of lip skin dryness and chapping., (© 2021 LG Household & Healthcare .International Journal of Cosmetic Science published by John Wiley & Sons Ltd on behalf of Society of Cosmetic Scientists and Societe Francaise de Cosmetologie.)

Broad spectrum tetracyclines are a well-known, widely used, and often successful treatment for use in inflammatory skin pathologies such as acne and rosacea. However, the steady rise of antibiotic resistance and gut dysbiosis associated with broad spectrum tetracyclines emphasizes the importance and responsibility of antibiotic stewardship. Narrow spectrum antibiotics have become increasingly important therapies to slow the progression of resistance as well as decrease negative side effect profiles, particularly those associated with broad spectrum tetracyclines. This case shows the successful treatment of periorificial dermatitis with a novel, narrow spectrum tetracycline, sarecycline, in a patient with underlying Crohn&rsquo;s. J Drugs Dermatol. 2021;20(1):98-100. doi:10.36849/JDD.5678.

Data on the occurrence and clinicopathological characteristics of actinic cheilitis (AC) and lip squamous cell carcinoma (LSCC) are well studied; however, they are based on studies limited to a single centre. Herein, we described the frequency of AC and LSCC submitted to microscopic examination from representative geographic regions of Brazil. A retrospective multicentre study was performed on biopsies obtained from 1953 to 2018 at 10 Brazilian oral and maxillofacial pathology centres. A total of 198,709 biopsy specimens were surveyed. Sociodemographic data and clinicopathologic characteristics were analysed. A total of 2017 cases of ACs (1.0%) and 850 cases of LSCCs (0.4%) were recorded. A strong fair-skinned (> 87%) male (> 70%) predilection was observed in both conditions. The mean age was 54.8 ± 18.7 for individuals with AC and 57.8 ± 19.0 for individuals with LSCC. The most commonly affected site was the lower lip (> 90%). This is a large multicentre study of AC and LSCC from Brazil. The frequency and clinicopathological features of AC and LSCC were similar to those described worldwide. This study provides robust and representative epidemiological data of these conditions for the scientific community.

Early identification and adequate treatment of actinic cheilitis (AC), which affects the lower lip vermillion and is considered a precursor of squamous cell carcinoma, is mandatory. Photodynamic therapy (PDT) has been successfully used in AC. PDT with the use of daylight (DLPDT) is equally effective and more convenient than the conventional PDT. Data on short and long-term efficacy of DLPDT in AC are limited. Our primary purpose was to assess efficacy of DLPDT in AC as well as safety and tolerance. Twenty-two individuals with histologically confirmed AC received 2 MAL (5-aminolevulinic acid)-DLPDT sessions 1 week apart. Patients were evaluated clinically 3, 6, and 12 months after treatment. Non-complete responders were biopsied and excluded from the study if histological alterations were indicative of AC. Adverse events were recorded from baseline to the end of the 12-month follow-up period. Twenty patients completed the study. Overall, complete clinical response 12 months after treatment was 80% (16/20), while an association between treatment response and grade of dysplasia was observed (p = 0.016). With respect to response by grade, complete clinical response achieved in grade I AC was 100% (12/12) and 50% (4/8) in grade II AC. Main adverse events included mild erythema, oedema, and scaling, with no pain associated with DLPDT. According to our results, DLPDT seems to be of significant benefit for the treatment of grade I AC. Combination with the other treatment modalities could improve the efficacy in grade II AC. Further studies are needed for the assessment of late recurrences.

Background: No large studies have defined the best treatment of actinic cheilitis., Methods: We conducted a systematic review to define the best therapies for actinic cheilitis in clinical response and recurrences., Results: We first identified 444 papers, and 49 were finally considered, including 789 patients and 843 treated areas. The following therapies were recorded in order of frequency: laser therapy, photodynamic therapy (PDT), 3% diclofenac in 2.5% hyaluronic acid, PDT + 5% imiquimod, aminolevulinic acid-laser or methyl-aminolevulinic acid-laser, 5% imiquimod, fluorouracil, partial surgery, 0.015% ingenol mebutate, 50% trichloroacetic acid, and laser + PDT. Concerning the primary outcome, complete clinical response was achieved in 76.5% of patients, and 10.2% had clinical recurrences. Partial surgery and laser therapy showed the highest complete response rates (14 of 14 [100%] and 244 of 260 [93.8%], respectively) with low recurrences. Only a limited number of patients were treated with other therapies, with the exception of PDT, with 68.9% complete responses and 12.6% of recurrences. Interestingly, when combined with 5% imiquimod, the efficacy of PDT was significantly enhanced., Limitations: Heterogeneity across studies., Conclusion: Laser therapy appears the best option among nonsurgical approaches for actinic cheilitis, and PDT showed higher efficacy when sequentially combined with 5% imiquimod. Larger studies are needed to confirm these data., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Actinic cheilitis is induced by chronic exposure to ultraviolet radiation and shows solar elastosis, a feature that has been associated with mast cell infiltrates. This study aimed to investigate the area of solar elastosis, collagen loss, and mast cell infiltrates in a series of actinic cheilitis., Methods: We evaluated the epithelial dysplasia in 52 cases of actinic cheilitis and the solar elastosis with Weigert's resorcin-fuchsin. Collagen loss was evaluated with Picrosirius red, analyzed under polarized microscopy, and scored from 1 to 3. Elastosis proportionate area (EPA) was calculated with image software. Mast cells were highlighted with toluidine blue stain., Results: EPA varied from 2% to 45%, with a mean of 17.1% in the cases, with no differences among epithelial dysplasia degrees. Most cases presented collagen loss scores of 2 or 3, and higher loss of type I collagen was associated with older age. Mast cell density was higher in severe epithelial dysplasia (P = 0.002) and in high-risk cases (P = 0.01)., Conclusion: Actinic cheilitis presented variable EPA and marked loss of type I collagen; however, these features were not associated with the degrees of epithelial dysplasia. Besides, mast cell density increased with epithelial dysplasia worsening and this was not associated with elastosis area or collagen loss., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Actinic cheilitis (AC) is a potentially malignant lesion caused by chronic sun exposure. This study aimed to evaluate the relationship between the degree of epithelial dysplasia and morphometric findings in AC. Sixty-eight slides of AC cases were selected and classified according to the grade of epithelial dysplasia, following morphologic criteria of World Health Organization. For morphometric analysis, the slides were scanned and images were analyzed using Pannoramic Viewer software. We obtained vertical measurements of the parameters: thicknesses of the keratin layer, lamina propria and zone of solar elastosis in three selected fields. Thirty-seven (54.4%) of the analyzed cases were classified as none/mild dysplasia and 31 (45.6%) as moderate/severe epithelial dysplasia. Cases with a moderate/severe dysplasia exhibited a thicker layer of keratin (median = 0.055 mm) than none/mild dysplasia (median = 0.045 mm) (p = 0.033). No significant differences in the thicknesses of lamina propria and zone of solar elastosis were observed according to the grade of epithelial dysplasia. A positive significant correlation between keratin layer and lamina propria thicknesses was found (p = 0.019). Based on our findings, rigorous clinical follow-up should be recommended for patients whose histopathological examination shows a greater thickness of the keratin layer., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

The aim of this study was to evaluate the immunoexpression of human leukocyte antigen-DR (HLA-DR) in actinic cheilitis (AC) and lower lip squamous cell carcinoma (LLSCC), and to correlate the findings with clinical (tumor size/extent, regional lymph node metastasis, and clinical stage) and histopathological (grade of epithelial dysplasia and inflammatory infiltrate for AC and histopathological grade of malignancy for LLSCC) parameters. Twenty-four AC and 48 LLSCC cases (24 with regional nodal metastasis and 24 without regional nodal metastasis) were selected. The scores of immunopositive cells for HLA-DR in the epithelial component of the lesions were assessed and the results were analyzed statistically using the nonparametric Mann-Whitney test. Epithelial expression of HLA-DR was observed in only five (20.8%) cases of AC (two low-grade and three high-grade lesions), with a very low median score of immunopositivity. By contrast, expression of HLA-DR was found in most LLSCC (97.9%), with a relatively high median score of positive cells. The score of HLA-DR-positive cells tended to be higher in tumors with regional lymph node metastasis, tumors in advanced clinical stages, and low-grade tumors, but the difference was not statistically significant (p > 0.05). In addition, there was a tendency towards higher expression of HLA-DR in highly/moderately keratinized tumors, and tumors with little/moderate nuclear pleomorphism (p > 0.05). The results suggest a potential role of HLA-DR in lip carcinogenesis, particularly in the development and progression of LLSCC. The expression of this protein can be related to the degree of cell differentiation in these tumors.

Background: Actinic cheilitis (AC) is a chronic condition that affects mainly the lower lip., Objectives: To investigate the use of lip photoprotection in patients with AC., Materials and Methods: A cross-sectional multicentre study of patients, ≥45 years of age, was performed in eight dermatology departments in the Galicia region over a period of one year. From 1,239 patients included in the study, 410 were diagnosed with AC and complete data were available for 408. An analysis of lip photoprotection habits and possible associations in patients with AC is reported., Results: Mean age of patients with AC was 71.9 years and 53.8% were women. More than 90% of AC patients (370/408) had never used lip photoprotection. In the group of patients who used it, 62.16% of them had only used a single stick within the previous year. The only variable significantly associated with the use of lip sun protection was low Fitzpatrick's skin types I and II (p=0.039). Study limitations include the inclusion of patients 45 years or older and the use of a semiquantitative scale for measuring the frequency of application of lip photoprotection., Conclusion: To our knowledge, this is the first European study focused on lip photoprotection in patients suffering from AC. Only a minority of AC patients protect their lips from UV radiation. Specific lip sun protection recommendations should be promoted, especially in high-risk populations.

Objective: The aim of this systematic review was to compare outcomes between surgical and non-surgical treatment of actinic cheilitis (AC)., Materials and Methods: A systematic review and meta-analysis based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses guideline were performed. A search of PubMed/MEDLINE, Web of Science, and Cochrane Library databases was conducted. Articles were selected based on the inclusion criteria: randomized clinical trials, prospective/retrospective studies, and case series with at least 10 patients, with a minimum follow-up period of 6 months. A weighted remission rate (RER) and recurrence rate (RR) with a 95% confidence interval was performed. Data analysis was performed using a comprehensive meta-analysis software., Results: A total of 283 ACs in 10 studies were included. About 2.5% surgically treated cases underwent malignant transformation. The weighted remission rate was higher for surgical (92.8%) compared to non-surgical treatment (65.9%). The recurrence rate was lower for surgical (8.4%) compared to non-surgical treatment (19.2%)., Conclusion: In this systematic review, the surgical treatment was more favorable than non-surgical for AC. Meanwhile, further studies are needed that should maximize methodological standardization and have greater rigor of the data collection process., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.)

Objectives: Programmed death ligand-1 (PD-L1) and human leukocyte antigen-G (HLA-G) are considered immune checkpoint molecules that inhibit T-cell effectiveness, contributing to tumor immune escape. This study investigated PD-L1, HLA-G, CD8, and granzyme B (GrB) expression at different stages of lip carcinogenesis., Design and Results: Forty cases of lip squamous cell carcinoma (LSCC), 55 actinic cheilitis (AC), and 10 healthy lip mucosa (HLM) were submitted to immunohistochemistry. Semiquantitative (PD-L1, HLA-G), and quantitative (CD8, GrB) analysis were performed. PD-L1 and HLA-G expression in neoplastic cells/keratinocytes and stroma/connective tissue was significantly higher in LSCC and AC, compared to HLM (p<0.05). PD-L1 was not associated with clinicopathological features of the lesions. HLA-G expression by malignant cells was significantly higher in LSCCs with distant metastasis (p = 0.041).CD8 + and GrB + cell numbers progressively increased from HLMs to LSCC, with AC exhibiting intermediate numbers (p<0.01). Most LSCCs showed coexistence of PD-L1 + and CD8 + cells (72.5%). PD-L1 was directly correlated to CD8 + and GrB + lymphocytic infiltration in LSCCs (p<0.05). Low cytotoxic immune response was associated with lymph node metastasis in LSCC (p<0.05)., Conclusions: PD-L1 and HLA-G-mediated immune evasion mechanisms are likely to occur from early pre-malignant to advanced malignant stages of lip carcinogenesis, which might provide a rationale for therapeutic blockade of these pathways. PD-L1 expression in LSCCs was correlated with the cytotoxic markers, suggesting that PD-L1 may appear as an escape mechanism in response to an active antitumor response., (Copyright © 2018. Published by Elsevier Ltd.)

The aim of the present systematic review was to determine the malignant transformation rate of actinic cheilitis (AC). A comprehensive literature search was conducted using Medline/PubMed, Cumulative Index of Nursing and Allied Health Literature, Scopus, OvidSP, and Google Scholar. The inclusion criteria comprised of observational human studies involving the malignant transformation of AC and publications in English. Studies included in this review were clinical follow-up, cohort, retrospective, or prospective investigations. The search yielded 1126 articles, and after exclusion, 34 full-text articles were eligible for full-text analysis. Only one article met the inclusion criteria. Based on the included article, it was determined that the malignant transformation rate of AC to squamous cell carcinoma (SCC) was 3.07%. Excluded articles focused on the clinicopathological characteristics and treatment efficacies of AC, and no malignant transformation rate was assessed. There is a need for more clinical studies on the malignant transformation of AC, as lip cancer is a public health concern. High-risk populations, including those living in tropical regions, have excessive exposure to UV radiation, and have older aged males, fair-skinned people, and smokers should be identified to prevent AC and its malignant change. Health practitioners should facilitate early intervention to prevent the progression of AC to SCC of the lip., (© 2018 John Wiley & Sons Australia, Ltd.)

Background: Oral Isotretinoin (13-cis-retinoic acid) is a gold standardtreatment for severe forms of acne with cheilitis as a most frequent complication. We designed this novel study to investigate the therapeutic effect of trichloroacetic acid (TCA) 33% as compared with placebo to treat cheilitis., Methods: In this pilot study, 90 acne vulgaris patients between 18 and 50 years, who referred dermatologic clinic with cheilitis, were assigned to either case (TCA) or control (Vaseline) group using permuted-block randomization from 2013 to 2015 with data analysis in 2016. Patients had follow-up visits after 2 and 6 weeks, at which their lesions were photographed. Two blinded expert dermatologists recorded physician International global score for each image., Results: Ninety eligible patients were randomly allocated into two groups. This included 45 patients in each group. At the end of follow-up, 44 patients in the intervention group and 37 patients in control group completed the final assessment. Compared to the control group, the TCA group had a greater reduction in the mean ICGS value from baseline to Week 6 (mean difference 2.59 points, p < .0001)., Conclusions: TCA can be considered as a good strategy in improvement of cheilitis to isotretinoin therapy.

Cancer stem cell (CSC) proteins have been observed in several lesions and are associated with tumor beginning, evolution, and resistance to treatment., Objectives: To investigate the presence of NANOG, NESTIN, and β-tubulin in lip squamous cell carcinoma (LSCC), actinic cheilitis (AC), and normal epithelium (NE)., Materials and Methods: Thirty cases of LSCC, thirty cases of AC (both analyzed according to the WHO classification and AC according to the binary classification), and twenty cases of NE were submitted to an immunohistochemical study., Results: NANOG was more expressed in the nuclei of AC compared to NE (p = 0.007), as well as in high-risk AC cases (p = 0.017) and well-differentiated LSCCs (no significance). There was an accumulation of nuclear NANOG from mild to moderate and severe ACs. NESTIN was significantly less present in NE compared to AC (p = 0.001) and LSCC (p = 0.003). There was a higher expression in severe dysplasia or high-risk AC and well-differentiated LSCC. These results indicate an upregulation of NANOG and NESTIN in the early stages of carcinogenesis. β-tubulin was intensely present in all lesions., Conclusion: The results suggest an upregulation of NANOG and NESTIN in the biological behavior these diseases, mainly in the transformation from AC to LSCC., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.)

Background: Actinic cheilitis (AC) is a potentially malignant disorder that can progress to squamous cell carcinoma (SCC), but this process is not fully understood. This study evaluated the immunoexpression of glucocorticoid receptor alpha (GRα) isoform and apoptotic proteins (Bcl-2 and Bax) in AC and lower lip SCC (LLSCC)., Methods: Twenty-two AC and 44 LLSCCs (22 with regional nodal metastasis and 22 without metastasis) were selected. The percentages of nuclear (GRα) and cytoplasmic (GRα, Bcl-2, and Bax) staining in epithelial cells were assessed and correlated with clinical (tumor size/extent and clinical stage) and histopathological parameters (risk of malignant transformation for AC and histopathological grade of malignancy for LLSCCs)., Results: Expression of GRα was observed in all cases studied, with relatively high median percentages of positive staining. When compared to AC, LLSCCs exhibited lower nuclear expression and higher cytoplasmic expression of GRα (P < 0.05). Regarding clinicopathological parameters, significant differences were only found for cytoplasmic expression of GRα according to the histopathological grade of LLSCCs (P = 0.036). Higher expression of Bax compared to Bcl-2 was observed in AC and LLSCCs (P < 0.05). In LLSCCs, there was a positive correlation between nuclear and cytoplasmic expressions of GRα (P = 0.006)., Conclusion: Reduced nuclear translocation and increased cytoplasmic expression of GRα may be important events in lip carcinogenesis but are not involved in the progression of LLSCC. The role of GRα in lip cancer development does not seem to be primarily related to modulations in the expression of Bcl-2 or Bax., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Actinic cheilitis (AC) can precede the development of squamous cell carcinoma (SCC) of the lip, a location with higher risk of invasiveness and metastasis. Herein, we reported the use of ingenol mebutate (IngMeb) 0.015% gel on three consecutive days to treat three patients suffering from AC. All the three patients achieved complete clearance of AC with rapid clinical effect, favorable safety profile, good patient's compliance related to short time of applications, and few local skin reactions. So IngMeb is an attractive new therapy for AC. Moreover, the present case report adds further evidence to the usefulness of dermoscopy and Reflectance confocal microscopy (RCM) in the assessment and monitoring of treatment outcome., (© 2018 Wiley Periodicals, Inc.)

Purpose: The aim of this work was to evaluate the expression of the cancer stem cell (CSC) markers CD44, ALDH1 and p75NTR in the ultraviolet-induced lesions actinic cheilitis (AC) and lip squamous cell carcinoma (LSCC), and to correlate it with p53 expression., Methods: Immunohistochemistry was performed in 4 cases of normal lip (NL), 43 of AC and 20 of LSCC., Results: All cases were positive for CD44, showing a membranous staining without differences between the groups. ALDH1 showed cytoplasmic staining and it was invariable amongst the grades of epithelial dysplasia and between AC and LSCC. p75NTR presented membranous/cytoplasmic staining in the basal and parabasal layer of NL and AC, while LSCC presented cytoplasmic staining in the peripheral layers of the tumor islands. p75NTR showed different expression amongst the dysplasia grades (p < 0.001) but no differences between AC and LSCC. p53 expression was similar amongst the dysplasia grades and between AC and LSCC. CD44, ALDH1 and p75NTR were unrelated amongst themselves and to p53 expression., Conclusions: CSC markers are expressed in potentially malignant and malignant lesions of the lip. Their expressions were invariable between AC and LSCC and unrelated to p53. p75NTR expression increased with the worsening of epithelial dysplasia grade.

Objective: Histones regulate chromatin density and therefore influence gene expression and cellular proliferation. These properties are modified by methylation, acetylation and phosphorylation of histones. The aim of this study was to investigate the variation of specific modified histones in actinic cheilitis (AC) and squamous cell carcinoma of the lip (SCCL)., Methods: Samples of non-neoplastic tissue of the lip (NNTL, n = 9), AC (n = 33), and SCCL (n = 27) were submitted to immunohistochemistry to detect the modified histones H3K36me3, H3K9ac, H4K12ac, and H3S10 ph., Results: Reactivity for all of the modified histones was significantly decreased from NNTL to AC, but not from AC to SCCL. Dysplasia in AC or histological grade in SCCL were not related to the reactivity of any modified histones., Conclusions: Histone modifications are related to initial actinic damage, but not to malignant transformation in the lip., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Oral potentially malignant disorders (OPMDs) are conditions that precede the onset of invasive cancers of the oral cavity. The term embraces precancerous lesions and conditions referred to in earlier World Health Organization (WHO) definitions. Leukoplakia is the most common OPMD; erythroplakia, although rare, is more serious. Several variants of leukoplakia are recognized, and clinical subtyping may help determine the prognosis to a limited extent. Biopsy is essential to confirm the provisional clinical diagnosis, and timely referral to a specialist is indicated. Certain OPMDs, such as oral submucous fibrosis, are encountered particularly in population groups from Asia with specific lifestyle habits. This review provides clinical descriptions of the wide range of potentially malignant disorders encountered in the oral cavity as a prelude to the topics discussed in this focus issue., (Copyright © 2018 Elsevier Inc. All rights reserved.)