Oral lichen planus-like lesions in skin of color: a review.

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.

Comedogenic lupus: a rare variant of chronic cutaneous lupus erythematosus - case series.

BACKGROUND: Comedogenic lupus is an uncommon variant of cutaneous lupus, clinically characterized by the presence of comedones, papules and erythematous-infiltrated plaques, cysts and scars in photo-exposed areas, mimicking acne vulgaris and acneiform eruptions. OBJECTIVES: To report clinicopathological characteristics of patients with comedogenic lupus in a tertiary dermatology service over a 15-year period and review cases described in the literature. METHODS: Retrospective study of patients with clinical and histopathological diagnoses of comedogenic lupus between the years 2006 and 2021. The literature search was carried out in the PubMed and VHL Regional Portal databases, using the terms: "comedogenic lupus" and "acneiform lupus" in Portuguese and English. RESULTS: Five patients were diagnosed during the described period, all female, with a mean age of 56.6 years. Smoking was observed in three cases, as well as pruritus. The most affected site was the face, especially the pre-auricular, malar and chin regions. Follicular plugs, epidermal thinning and liquefaction degeneration of the basal layer were predominant histopathological findings. Hydroxychloroquine was used as the first-line treatment; however, other medications were used, such as dapsone, methotrexate, tretinoin cream, and topical corticosteroids. The literature search identified 17 cases, with a mean age of 38.9 years, 82% of which were women. Only 23% had a diagnosis of systemic lupus erythematosus. Hydroxychloroquine was the most recommended systemic medication. STUDY LIMITATIONS: Retrospective, single-center study. The literature search was carried out in two databases. CONCLUSIONS: Dermatologists should be aware of acneiform conditions with poor response to the usual treatment. Early diagnosis and treatment reduce the risk of unaesthetic scars.

Unilateral lupus mastitis.

Lupus mastitis is a rare clinical manifestation associated with systemic lupus erythematosus or discoid lupus erythematosus. It is necessary to make a correct diagnosis to differentiate it from inflammatory breast cancer. The histological study shows involvement of the adipose tissue of the breast with histopathological findings of cutaneous lupus erythematosus. Direct immunofluorescence detects the lupus band at the dermal-epidermal junction. The treatment of choice is hydroxychloroquine. We present a case of unilateral lupus mastitis in a patient with no previous diagnosis of lupus with complete remission after the use of hydroxychloroquine and topical corticosteroids.

Development of squamous cell carcinoma in the setting of chronic discoid lupus erythematosus may be associated with plasmacytoid dendritic cell inflammation.

Discoid lupus erythematosus (DLE) is the most common type of cutaneous lupus and is clinically characterized by alopecia, depigmentation, and scars on sun-exposed skin. Squamous cell carcinoma is a potential long-term complication. The most important risk factor for squamous cell carcinoma development in people with dark skin is chronic scarring and inflammation, such as those seen in long-standing discoid plaques. African Americans who develop squamous cell carcinoma in the setting of chronic scarring and inflammation have a greater risk of metastasis and recurrence compared to sun-induced squamous cell carcinoma seen in whites. Despite this, the pathogenesis of squamous cell carcinoma development in chronic DLE is not fully understood. Herein, we describe a case of an African American patient who developed squamous cell carcinoma on a long-standing discoid plaque. Analysis of the lesion revealed a null type pattern of p53 protein expression and abundant CD123+ plasmacytoid dendritic cells, as potential drivers of oncogenesis and inflammation, respectively. Dermatologists should be aware of the increased risk of squamous cell carcinoma development within long-standing discoid plaques for a prompt early diagnosis and active long-term surveillance.

Linear discoid lupus erythematous simulating en coup de sabre morphea in a female chronic granulomatous disease carrier.

Discoid lupus erythematosus (DLE), a subtype of chronic cutaneous lupus may be observed in a linear pattern. A 21-year-old woman with history of chronic granulomatous disease state presented to our clinic for a chronic six-year skin eruption on her left eyebrow, left cheek, and left forehead. A punch biopsy of involved left forehead skin was performed and revealed perivascular and periadnexal lymphohistiocytic infiltrate without features of morphea or panniculitis, confirming the histopathologic changes of cutaneous lupus erythematous. The patient was diagnosed with linear DLE, mimicking en coup de sabre, within Blaschko lines. The pathogenesis for DLE in association with chronic granulomatous disease is ambiguous; however, X-linked lyonization is crucial for both conditions and may explain cooccurrence of disease states.

Immunohistochemical Study of the PD-1/PD-L1 Pathway in Cutaneous Lupus Erythematosus.

The pathomechanism of various autoimmune diseases is known to be associated with the altered function of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) axis. We aimed to investigate the role of this pathway and inflammatory cell markers in subtypes of cutaneous lupus erythematosus (CLE): discoid lupus erythematosus (DLE), subacute CLE (SCLE) and toxic epidermal necrolysis (TEN)-like lupus, a hyperacute form of acute CLE (ACLE). Ten skin biopsy samples from 9 patients were analyzed with immunohistochemistry regarding the following markers: CD3, CD4, CD8, Granzyme B, CD123, CD163, PD-1, PD-L1. Our group consisted of 4 SCLE (2 idiopathic (I-SCLE) and 2 PD-1 inhibitor-induced (DI-SCLE)), 4 DLE and 1 TEN-like lupus cases. From the latter patient two consecutive biopsies were obtained 1 week apart. Marker expression patterns were compared through descriptive analysis. Higher median keratinocyte (KC) PD-L1 expression was observed in the SCLE group compared to the DLE group (65% and 5%, respectively). Medians of dermal CD4, Granzyme B (GB), PD-1 positive cell numbers and GB+/CD8+ ratio were higher in the DLE group than in the SCLE group. The I-SCLE and DI-SCLE cases showed many similarities, however KC PD-L1 expression and dermal GB positive cell number was higher in the former. The consecutive samples of the TEN-like lupus patient showed an increase by time within the number of infiltrating GB+ cytotoxic T-cells and KC PD-L1 expression (from 22 to 43 and 30%-70%, respectively). Alterations of the PD-1/PD-L1 axis seems to play a role in the pathogenesis of CLE.

Lupus Erythematosus Tumidus Associated With Hemophagocytosis.

ABSTRACT: A case of lupus erythematosus tumidus (LET), a subtype of chronic cutaneous lupus erythematosus, in an 85-year-old woman who presented with discrete indurated erythematous plaques over the face and upper chest is described. A skin biopsy showed features in keeping with a diagnosis of LET. Unusually however, the lymphocytic infiltrate contained frequent macrophages that demonstrated hemophagocytosis. Most of the phagocytosed cells were lymphocytes, but there was also evidence of erythrophagocytosis. The presence of conspicuous hemophagocytosis has only rarely been reported in skin biopsies of patients with autoimmune conditions. These include systemic lupus, neonatal lupus and dermatomyositis, and on 2 occasions in cases of nonspecified cutaneous lupus erythematosus. To the best of our knowledge, hemophagocytosis as a feature of LET has not been previously described in the literature.

Assessing the quality of acne and rosacea treatment information on YouTube.

Cutaneous lupus erythematosus has different manifestation depending on the type. In this study, discoid lupus, extensive skin lesions, fairer skin types and scalp involvement were found to be positive predictive factors for more severe disease.

Ultraviolet light induces HERV expression to activate RIG-I signalling pathway in keratinocytes.

Skin inflammation and photosensitivity are common in lupus erythematosus (LE) patients, and ultraviolet (UV) light is a known trigger of skin and possibly systemic inflammation in systemic lupus erythematosus (SLE) and discoid lupus erythematosus (DLE) patients. Type I interferons (IFN) are upregulated in LE skin after UV exposure; however, the mechanisms to explain UVB-induced inflammation remain unclear. Here, we demonstrated that UVB irradiation-induced activation of human endogenous retroviruses (HERVs) plays a major role in the immune response. UVB-induced HERV-associated dsRNA transcription and subsequent activation of the innate antiviral RIG-I/MDA5/IRF7 pathway led to downstream transcription of interferon-stimulated genes, which promotes UVB-induced apoptosis and proliferation inhibition in keratinocytes through RIG-I and MDA5 pathways. Our findings indicate that UVB irradiation induces HERV-dsRNA overexpression, and the dsRNA-sensing innate immunity pathway promotes type I IFN production, which may be a potential mechanism of skin inflammatory response and skin lesion of SLE/DLE.

Systemic lupus erythematosus/ANCA-associated vasculitis overlap: An explanation for atypical lupus manifestation.

The coexistence of systemic lupus erythematosus (SLE) and ANCA-associated vasculitis (AAV) as an overlapping syndrome is not common. Here, we report a case of a 33-year-old woman, with recent SLE diagnosis due to skin, kidney, articular, and immunologic compromise, in whom a chest CT scan showed bilateral nodules, consolidations, and tree-in-bud pattern; thoracoscopic lung biopsy revealed diffuse non-caseating granulomas, without other features of sarcoid, organizing pneumonia, or hypersensitivity pneumonitis with high positive p-ANCA titers. Overlap between SLE and AAV was a possible explanation for lupus granulomatous pneumonitis, and for this reason, a multidisciplinary meeting was held to evaluate complex patients with interstitial lung diseases patients.

Biopsy-proven PML in an HIV-negative patient with discoid lupus: Failure to detect JC virus in CSF.

We present a case of a 58-year-old man with a history of severe discoid lupus erythematosus and acute encephalopathy and incoordination. Antinuclear antibody testing was weakly positive but all other laboratory tests for systemic lupus erythematosus were negative and serum quantitative immunoglobulins and lymphocytes were normal. MRI brain showed T2/FLAIR hyperintensities within the bilateral parietal and temporal lobes with involvement of subcortical U fibers. CSF PCR was negative for varicella-zoster virus, herpes simplex, JCV and BK virus. However, JCV antibody index was elevated (3.88; reference: < 0.2). Right parietal brain biopsy was consistent with JCV infection and diagnostic of progressive multifocal leukoencephalopathy (PML). To the best of our knowledge, this is the first reported case of PML in a patient with discoid lupus without other traditional risk factors for the disease and highlights the need for clinical vigilance in this patient population.

Identification of key genes and pathways in discoid lupus skin via bioinformatics analysis.

ABSTRACT: Discoid lupus erythematosus (DLE) is the most common skin manifestation of lupus; however, the molecular mechanisms underlying DLE remain unknown. Therefore, we aimed to identify key differentially expressed genes (DEGs) in discoid lupus skin and investigate their potential pathways.To identify candidate genes involved in the occurrence and development of the disease, we downloaded the microarray datasets GSE52471 and GSE72535 from the Gene Expression Database (GEO). DEGs between discoid lupus skin and normal controls were selected using the GEO2R tool and Venn diagram software (http://bioinformatics.psb.ugent.be/webtools/Venn/). The Database for Annotation, Visualization, and Integrated Discovery (DAVID), Enrichr, and Cytoscape ClueGo were used to analyze the Kyoto Encyclopedia of Gene and Genome pathways and gene ontology. Protein-protein interactions (PPIs) of these DEGs were further assessed using the Search Tool for the Retrieval Interacting Genes version 10.0.Seventy three DEGs were co-expressed in both datasets. DEGs were predominantly upregulated in receptor signaling pathways of the immune response. In the PPI network, 69 upregulated genes were selected. Furthermore, 4 genes (CXCL10, ISG15, IFIH1, and IRF7) were found to be significantly upregulated in the RIG-I-like receptor signaling pathway, from analysis of Enrichr and Cytoscape ClueGo.The results of this study may provide new insights into the potential molecular mechanisms of DLE. However, further experimentation is required to confirm these findings.

Bioinformatic analysis of key biomarkers and immune filtration of skin biopsy in discoid lupus erythematosus.

OBJECTIVE: Discoid lupus erythematosus (DLE) is the most common category of chronic cutaneous lupus erythematosus, where the pathological process is proved to be closely associated with immunity. This bioinformatic analysis sought to identify key biomarkers and to perform immune infiltration analysis in the skin biopsy samples of DLE. METHODS: GSE120809, GSE100093, GSE72535, GSE81071 were used as the data source of gene expression profiles, altogether containing 79 DLE samples and 47 normal controls (NC). Limma package was applied to identify differentially expressed genes (DEGs) and additional Gene Ontology (GO) together with The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were done. Protein-protein interaction network (PPI) was constructed using STRING and Cytoscape. Hub genes were selected by CytoHubba. Finally, immune filtration analysis was finished by the CIBERSORT algorithm, and comparisons between the two groups were accomplished. RESULTS: A total of 391 DEGs were identified, which were composed of 57 up-regulated genes and 334 down-regulated genes. GO and KEGG enrichment analyses revealed that DEGs were closely related with different steps in the immune response. Top 10 hub genes included GBP2, HLA-F, IFIT2, RSAD2, ISG15, IFIT1, IFIT3, MX1, XAF1 and IFI6. Immune filtration analysis from CIBERSORT had found that compared with NC, DLE samples had higher percentages of CD8+ T cells, T cells CD4 memory activated, T cells gamma delta, macrophages M1 and lower percentages of T cells regulatory, macrophages M2, dendritic cells resting, mast cells resting, mast cells activated. CONCLUSION: This bioinformatic study selected key biomarkers from the contrast between DLE and NC skin samples and is the first research to analyze immune cell filtration in DLE.

Macrophage Migration Inhibitory Factor (MIF) and Its Homologue d-Dopachrome Tautomerase (DDT) Inversely Correlate with Inflammation in Discoid Lupus Erythematosus.

Discoid Lupus Erythematosus (DLE) is a chronic cutaneous disease of unknown etiology and of immunoinflammatory origin that is characterized by inflammatory plaques and may lead to disfiguring scarring and skin atrophy. Current treatments are limited, with a large proportion of patients either poorly or not responsive, which makes DLE an unmet medical need. Macrophage migration inhibitory factor (MIF) is the prototype of a pleiotropic family of cytokine that also includes the recently discovered homologue D-dopachrome tautomerase (DDT) or MIF2. MIF and DDT/MIF-2 exert several biological properties, primarily, but not exclusively of a proinflammatory nature. MIF and DDT have been suggested to play a key role in the pathogenesis of several autoimmune diseases, such as multiple sclerosis and type 1 diabetes, as well as in the development and progression of certain forms of cancers. In the present study, we have performed an immunohistochemistry analysis for the evaluation of MIF in DLE lesions and normal skin. We found high levels of MIF in the basal layer of the epidermis as well as in the cutaneous appendage (eccrine glands and sebocytes) of normal skin. In DLE lesions, we observed a significant negative correlation between the expression of MIF and the severity of inflammation. In addition, we performed an analysis of MIF and DDT expression levels in the skin of DLE patients in a publicly available microarray dataset. Interestingly, while these in silico data only evidenced a trend toward reduced levels of MIF, they demonstrated a significant pattern of expression and correlation of DDT with inflammatory infiltrates in DLE skins. Overall, our data support a protective role for endogenous MIF and possibly DDT in the regulation of homeostasis and inflammation in the skin and open up novel avenues for the treatment of DLE.

The combined role of clinical, reflectance confocal microscopy and dermoscopy applied to chronic discoid cutaneous lupus and subacutus lupus erythematosus: A case series and literature review.

Main subtypes of cutaneous lupus erythematosus are represented by acute, subacute cutaneous, intermittent and chronic cutaneous lupus erythematosus. Discoid lupus erythematosus represents the most common phenotype of chronic cutaneous lupus erythematosus. The spectrum of clinical manifestations mirrors that of several and distinct histopathological features. Such variability among different CLE subtypes is also observed at dermoscopy. Dermoscopy is nowadays considered an additional valuable method for skin lesions assessment in general dermatology, following and completing the well-known clinical diagnostic steps, such as medical history and clinical examination. In vivo reflectance confocal microscopy (RCM) is a non-invasive imaging tool able to assess the epidermis and upper dermis producing high resolution (horizontal ∼1.25 µm, vertical ∼5 µm), en face tissue sections used for melanocytic and inflammatory evaluation. In this study, we reported dermoscopic and RCM features about 9 patients affected by subacute and chronic lupus erythematosus retrospectively analyzed.