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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’s. J Drugs Dermatol. 2021;20(1):98-100. doi:10.36849/JDD.5678.

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.

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.)

Chronic granulomatous disease (CGD) is a primaryimmunodeficiency disorder that affects the phagocyticcells of the innate immune system. It is characterizedby recurrent or persistent infections with granulomaformation. Lupus-like lesions have been reported incarriers of CGD and less frequently, in patients withCGD. Immunological study in these patients areusually negative. We describe the case of an 8-yearoldboy with CGD who developed chronic and acutecutaneous lupus erythematous with angular cheilitis,oral ulcers, Raynaud phenomenon, and positiveserologies for antinuclear, anticentromere, and anti-Saccharomyces cerevisiae antibodies.

Background: Differences in immune profile between actinic cheilitis (AC), a precursor of lip squamous cell carcinoma, and normal lip vermillion (NL) have not been elucidated., Objectives: To compare density, distribution, and ratios of CD8+ and FoxP3+ cells between AC and NL and assess their associations with clinicopathologic variables., Methods: Samples of AC and NL obtained between 2001 and 2013 at the College of Dentistry of the University of Concepcion, Chile, were retrospectively analyzed for immunohistochemical detection of CD8+ and FoxP3+ cells. Differences between groups were tested by Mann-Whitney U and Fisher's exact tests. Independent effects of cell densities and CD8/FoxP3 ratio with AC were assessed by multiple logistic regression analysis after adjustment for potential confounding., Results: A total of 62 AC and 24 NL biopsies were included. Densities of CD8+ and FoxP3+ cells in AC were significantly higher than in NL. Conversely, the CD8+/FoxP3+ ratio was significantly lower in AC as compared to NL. After adjustment for sun exposure, age, gender, and smoking status, a stromal FoxP3+ cell density higher than 0.35 cells/field was significantly associated with increased odds of AC (odds ratio [OR] = 5.01, 95% confidence interval [CI]: 1.18-21.31), while a stromal CD8+/FoxP3+ ratio higher than 5.91 was associated with decreased odds of AC (OR = 0.29, 95% CI: 0.08-1.08)., Conclusions: AC is characterized by increased FoxP3+ cell infiltration and a reduced CD8/FoxP3 ratio as compared to NL. Therefore, increased infiltration of FoxP3+ cells relative to CD8+ cells may contribute to the transition from normal to preneoplastic stages in lip carcinogenesis., (© 2016 The International Society of Dermatology.)

Background: Epigenetic modifications, including DNA methylation of tumor suppressor genes carried out by DNA methyltransferases (DNMTs), are important events in carcinogenesis. Although there are studies concerning to its expression in several cancer types, DNMTs expression pattern is not known in photoinduced lip carcinogenesis. The aim of this study was to investigate the immunoexpression of DNMTs 1, 3a, and 3b in lip precancerous lesion (actinic cheilitis) and cancer., Methods: Thirty cases of actinic cheilitis (AC), thirty cases of lip squamous cell carcinoma (LSCC), and twenty cases of non-neoplastic tissue (NNT) were selected for immunohistochemical investigation of DNMTs 1, 3a, and 3b., Results: Nuclear DNMT 1 immunoreactivity was significantly higher in the LSCC group (68.6%) compared with NNT (47%), and nuclear DNMT 3b was higher in LSCC (70.9%) than in NNT (37.9%) and in AC (44%). Only DNMT 3a showed both higher nuclear and cytoplasmic expression in AC (35.9% and 35.5%, respectively) than in NNT (4.4% and 16.1%, respectively) and LSCC (8.8% and 13.2%, respectively) (P < 0.05)., Conclusions: The results suggested that DNMT 3a could play a key role in the methylation process of initial steps of UV carcinogenesis present in AC while DNMT 3b could be responsible for de novo methylation in already established lip cancer., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Actinic cheilitis (AC) is a potentially malignant lesion diagnosed in the lip of patients chronically exposed to the sun that may give rise to a fully invasive lower lip squamous cell carcinoma (LLSCC). It is known that ultraviolet radiation causes dendritic cells (DCs) depletion in the epidermis, but the role of this cellular population in lip cancer progression remains uncertain. Therefore, this study investigated the distribution of DCs in normal, dysplastic and neoplastic tissues of the lower lip., Methods: Thirteen cases of lower lip mucocele, 42 of ACs and 21 of LLSCC were retrieved and original diagnoses confirmed by two oral pathologists, who further classified ACs as low- and high-risk lesions. Immunoreactions against CD1a and CD83 identified immature and mature DCs, respectively., Results: Immature CD1a+ Langerhans cells (LCs) were significantly decreased in LLSCC when compared to morphologically normal (P < 0.009) and dysplastic epitheliums (P < 0.003), whereas mature CD83+ LCs were significantly decreased in LLSCC when compared to normal epithelium (P = 0.038). There was no significant difference between low- and high-risk ACs regarding CD1a+ and CD83+ LCs (P > 0.05), but ACs demonstrated a lower concentration of CD1a+ LCs than normal epithelium (P < 0.009). There was no significant difference in the distribution of CD1a+ and CD83+ interstitial dendritic cells (IDCs) in the connective tissue among the studied groups (P > 0.05)., Conclusion: These results suggest that depletion of epithelial LCs, but not IDCs in the connective tissue, would represent an important step for lip cancer development., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Pediatric HIV is growing at an alarming rate in developing countries. Due to their compromised immune status, children infected with HIV are prone to a number of opportunistic infections. Oral manifestations are the first signs of the disease in many of them. To assess the oral mucosal status of Indian children with HIV, based on their CD4 cell counts., Methodology: Two hundred and twenty one HIV infected children aged 6-18 years from various HIV centers, were divided into three groups, based on their CD4 cell counts; Group 1: ≥500, Group 2: 201-499 and Group 3: ≤200 cells. The children in each group were further considered as 'prior to antiretroviral treatment (ART)' and 'on ART'. Oral mucosal examination was done based on presumptive criteria given by Ramos-Gomez for diagnosis of oro-facial lesions commonly associated with HIV infection in children. Data obtained was subjected to statistical analysis., Results: Angular cheilitis and pseudomembranous candidiasis were the frequently seen oral lesions. Children with CD4 cell count ≥500 had significantly fewer oral lesions each., Conclusion: A high percentage of HIV-infected children were affected with oral mucosal lesions. There was a significant association between immune status and frequency of oral lesions., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Actinic cheilitis (AC) is an oral potentially malignant lesion which is the counterpart of actinic keratosis of the skin and has potential to develop into squamous cell carcinoma. Regulatory T cells (Tregs) have a critical role in modulating the antitumor immune responses. The presence of regulatory T cells in potentially malignant lesions has not been described. We chose investigate the involvement of regulatory T cells in potentially malignant lesions., Methods: The frequency, phenotype, and activity of CD4+CD25+ T cells isolated from blood and lesion of AC patients were analyzed by flow cytometry. Cytokines were quantified by ELISA. Data were compared with samples from healthy subjects., Results: The frequency and suppressor activity of circulating CD4+CD25+ T cells was similar in AC patients and control subjects. However, the frequencies of IL-10-positive Tregs were higher in AC patients, and these cells inhibited interferon-gamma (IFN-γ) and increased interleukin (IL)-10 productions in co-cultures. Furthermore, CD4+CD25+ T cells accumulate in AC lesions. Lesions-derived regulatory T cells suppressed lymphocyte proliferation and pro-inflammatory cytokine production. Moreover, high levels of IL-10 and transforming growth factor-β (TGF-β), and low IFN-γ were detected in the potentially malignant lesions., Conclusion: Therefore, our data show that Tregs accumulate in AC lesions, and these cells could be suppressing immune responses in a potentially malignant microenvironment., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Plasma cell cheilitis is a chronic inflammatory disease that presents with erythema, erosions, ulcers and occasional nodules within the mucosa, including the lips. It is histopathologically characterized by dense plasma cell infiltration in the lamina propria of the mucous membranes. Several treatments for plasma cell cheilitis have been reported, including topical steroids, topical antibiotics or topical tacrolimus. However, 308-nm monochromatic excimer light (MEL) has never been reported as a treatment option, while it was reported to be very effective in treating erosive oral lichen planus. We report a 62-year-old man who had chronic plasma cell cheilitis on the lower lip, which was refractory to topical and systemic corticosteroid. The lesion and severe pain were significantly improved by the treatment with nine sessions of 308-nm MEL twice per week with a total dose of 1120 mJ/cm(2). However, the lesion gradually worsened after treatment frequency was reduced to once per month. Subsequent tacrolimus 0.03% ointment cleared the lesion completely in a month and no recurrence was observed a year later. Refractory plasma cell cheilitis and concomitant severe pain quickly responded to 308-nm MEL when administrated twice per week. Because the long interval between each MEL treatment seemed ineffective to improve the lesion, appropriate frequency and adequate total dose of MEL treatment may be necessary for a successful treatment., (© 2013 Japanese Dermatological Association.)

Lip abscesses are a potentially serious condition rarely reported in the medical literature. This disease requires prompt diagnosis and treatment with hospitalization, intravenous antibiotics, and urgent surgical drainage. Clinical knowledge of this condition is essential to guide the differential diagnosis and correctly adapt the etiological treatment. The presence of necrotic and cavitated lesions requires ruling out immunosupression or methicillin-resistant agent. We report a necrotic and cavitated bacterial lip abscess caused by methicillin-sensitive Staphylococcus aureus in an immunocompetent male.

Background: CD8+ and natural killer (NK) cells have been considered the most effective cells in the combat of cancer, contributing to better prognosis and longer survival., Methods: The aim of this study was to evaluate the population of CD8+ and NK cells, by immunohistochemistry, in samples of oral cavity squamous cell carcinoma (OCSCC) and lip squamous cell carcinoma (LSCC), leukoplakia, actinic cheilitis, and healthy oral mucosa (control). The relationship of CD8+ and NK cells with survival data, lymph node metastasis, tumor size, and proliferative index was also evaluated., Results: The number of peritumoral and intratumoral CD8+ and NK cells was significantly higher in LSCC, when compared with control, pre-malignant lesions, and OCSCC. A higher proportion of peritumoral CD8+ cells demonstrated correlation with a lower neoplastic proliferative index. Moreover, patients with OCSCC with a high density of peritumoral CD8+ cells showed a tendency towards a longer survival time., Conclusions: The differential CD8+ and NK cells infiltration in oral SCC might reflect a distinctive tumor microenvironment with a favorable local cytotoxic immune response against neoplastic cells.

Background: Allergic contact cheilitis may appear after exposure to different substances, including dental materials, toothpastes, cosmetics, foods and medications., Objective: To compare the rate of toothpaste allergy between patients with and without cheilitis and to examine the yield of our proposed toothpaste patch test kit for use in patients with cheilitis., Methods: A patch test kit containing 11 substances used in toothpastes was formed. The study sample consisted of 44 patients, 24 with cheilitis (study group) and 20 with contact dermatitis but without cheilitis (control group)., Results: Eleven patients in the study group (45%) were found to be allergic to toothpaste, compared to only one patient (5%) in the control group (p < .05)., Conclusion: The rate of toothpaste allergy among patients with cheilitis might be higher than previously reported. Patch-testing with our toothpaste series is recommended in the evaluation of cheilitis.

During recent years demands for permanent make up and especially permanent lip liner is increasing not only in the USA but also in Germany. Adverse reactions to these products are almost unknown and not documented in literature. Declaration of contents and side effects are not required for tattoo colors, in contrast to the rules for medical treatments. Our patient developed inflammation and vesiculation within the area of tattooing three days after injection of a permanent lip liner. Treatment with steroids induced complete resolution of the lip liner-associated dermatitis. However, not only the effect of the lip liner was lost but also the natural color of her lip was partly destroyed by inflammation. Diagnostic allergy testing revealed strong delayed hypersensitivity to nickel and a mild patch test reaction to the permanent lip liner. Examination of the permanent make-up by mass spectrometry detected nickel in a concentration of 1.8 ppm. No allergic reaction could be seen when the purified red dye itself was tested. This patient with pre-existing nickel allergy developed an allergic contact dermatitis from the injection of a permanent lip liner contaminated with nickel.

Objective: The objective of this study was to define the oro-facial lesions associated with Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS) in an adult population in Oyo state, Nigeria and to relate these with the level of immune suppression as measured by the CD4 counts., Materials and Method: The study population consisted of 679 consecutive subjects who were seen at the state-owned blood bank. Information on demography, medical and medication histories were obtained. Oro-facial examinations were carried out according to Greenspan et al [Oral Surg Oral Med Oral Pathol (1992)73:142-144]. HIV sero-prevalence status was determined for all patients. CD4+ T-lymphocyte count was carried out for those sero-positive for HIV and 31 randomly selected HIV-negative subjects. Data were analyzed using the chi-square test, Fisher's exact test, Student's t-test and odds ratio where appropriate., Results: Eighty-one (11.9%) of the entire study sample were confirmed HIV positive. The prevalence of specific oral lesions by HIV sero-status revealed that pseudomembranous oral candidiasis and angular cheilitis occurred significantly and more frequently in HIV-positive subjects (33.3 and 21% respectively) than those who were HIV negative (4.3 and 1.8% respectively, P < 0.05). The mean CD4 count of the HIV-positive subjects was 452 cells mm(-3), s.d. 137, while it was 602 cells mm(-3), s.d. 251, for the HIV negatives. The difference was statistically significant (P = 0.000). Forty-four (66.7%) subjects with CD4 counts <500 cells mm(-3) had oro-facial lesions whereas among those with CD4 counts >500 cells mm(-3) only 22 (33.3%) had oro-facial lesions (OR = 4.57)., Conclusion: The type of oro-facial lesions most commonly associated with HIV/AIDS in Oyo state, Nigeria, has been shown to be pseudomembranous oral candidiasis. This was followed by angular cheilitis. These lesions, although found in HIV-negative subjects, were in a lower proportion as compared with HIV-positive subjects. Mean CD4 counts were lower in HIV-positive subjects and this was associated with greater prevalence of oro-facial candidiasis and angular cheilitis.

The present work reports the results of a multicentre study of toothpaste allergic contact cheilitis (TACC) conducted by GIRDCA (Gruppo Italiano Ricerca Dermatiti da Contatto e Ambientali). The study examined 54 patients with eczematous lesions on the lips, the possible cause of which was suspected to be the use of toothpastes. Patch tests were conducted with a standard series, a specially-targeted series (toothpaste cheilitis series, TCS), and with suspected toothpaste(s). A stop-restart test (SRT) was carried out with these, together with a use test to identify possible alternative products. The TCS produced 17 positive reactions in 13 patients, the most frequent being to spearmint oil. Of the 54 patients, 5 displayed positive reactions only to the TCS. The patch tests with toothpaste produced positive reactions in 11/32 patients, the SRT a positive response in 10/12 cases. The diagnosis of TACC was confirmed in 15/54 patients. Alternative products were identified for 5 patients. In conclusion, the allergens most frequently responsible for TACC were the flavourings, and the additional series proved to be useful in many cases (together with patch tests with toothpastes and the SRT) for correct diagnosis and to initiate effective prevention.

Allergic contact cheilitis describes a not uncommon inflammatory reaction of the lips. We reviewed its allergic causes, and suspect that the literature does not adequately document the frequency and etiologic factors involved.

In the present study we characterized the phenotypes of infiltrating mononuclear cells in angular cheilitis lesions to further explore the pathogenesis of this disorder. Frozen sections from lesions infected by Candida albicans and/or Staphylococcus aureus were subjected to immunohistochemical analysis utilizing monoclonal antibodies directed to subsets of T-lymphocytes, B-lymphocytes, and macrophages. In addition, the expression of Class II antigens (HLA-DP, -DQ, -DR), the interleukin 2- and transferrin-receptors was studied on resident and infiltrating cells. An intense infiltration of T-lymphocytes was accompanied by expression of Class II antigens on the epidermal keratinocytes in lesion infected by Candida albicans. The Staphylococcus aureus infected lesions displayed a diffuse infiltration of T-lymphocytes but virtually no expression of Class II antigen by epidermal keratinocytes. These observations suggest that the cell-mediated arm of the immune system is involved in the inflammatory reaction of lesions infected by Candida albicans. In addition, the present study confirms that epidermal expression of Class II antigens is closely related to the type and magnitude of the infiltrating T-lymphocyte. Finally, these findings indicate that the type of inflammatory reaction in angular cheilitis is primarily dependent on the isolated microorganism, although the clinical pictures of the disorder are virtually identical.

Cheilitis was observed in a 74-year-old patient after use of a new toothpaste which occurred after several weeks despite withdrawal of the paste. Positive patch testing with the toothpaste confirmed suspect contact sensitization. The cause was the main component of the flavour additive i. e. the terpene ketone L-carvone. Due to the characteristic flavour it is contained in many mint and peppermint oils. In this case it also caused the recurrences by sucking of refreshment lozenges. L-Carvone is also contained in most chewing gums and should thus be considered aetiologically in cases of cheilitis and stomatitis.

Plasma cell orificial mucositis is a benign idiopathic condition of orificial mucous membranes characterized histologically by a dense band-like plasmacytic infiltrate. We studied 8 cases of this disease by immunohistochemical methods for subsets of immunoglobulin-producing cells. The infiltrating plasma cells were found to produce mostly IgG and IgA with the predominance of kappa chain-producing cells over lambda chain-producing cells. This polyclonal plasma cell infiltrate composed of IgG- and IgA-producing cells is in accordance with the pattern observed in the inflammatory infiltrate around certain epidermal neoplasms accompanied by the plasmacytic infiltrate, such as actinic keratosis, Bowen's disease, squamous cell carcinoma, and syringocystadenoma papilliferum.