Risk and prevalence of oral cancer in patients with different types of lupus erythematosus: a systematic review and meta-analysis.

OBJECTIVE: The objective of this study was to assess the risk and prevalence of oral cancer in patients with systemic lupus erythematosus (SLE) or discoid lupus erythematosus (DLE). STUDY DESIGN: The review included observational cohort and cross-sectional studies that investigated the incidence or prevalence of oral cancer in adults with confirmed diagnoses of SLE or DLE. Studies were selected based on predefined eligibility criteria, including the use of specific diagnostic criteria for SLE and DLE. After searches in PubMed/MEDLINE, EMBASE, Scopus, Web of Science, LILACS, and LIVIVO databases and gray literature for relevant studies, the selection process was conducted by independent reviewers. RESULTS: A total of 5,545 articles were identified. After screening, 8 studies met the inclusion criteria. The pooled risk estimate indicated a significantly increased risk of oral cancer in patients with SLE (risk ratio = 2.69; 95% confidence interval, 1.75 to 4.16; I2 = 0%; P = .78) compared with the general population. The pooled prevalence of oral cancer in patients with DLE was 10% (95% ci, 0.03 to 0.13; I2 = 59%; P = .12). CONCLUSIONS: This review provides evidence supporting an elevated risk for individuals with SLE or DLE developing oral cancer. The findings highlight the importance of monitoring oral mucosa in patients with these conditions.

Systemic lupus erythematosus presenting as lupus erythematosus tumidus and lupus nephritis: a case report.

BACKGROUND: Lupus nephritis and lupus erythematosus tumidus (LET) are uncommon manifestations of systemic lupus erythematosus (SLE), and their coexistence as the initial presentation of SLE is exceedingly rare. Here, we report such a case, emphasizing the diagnostic challenges and therapeutic implications of this unusual association. CASE REPORT: A 38-year-old North African woman presented in Nephrology department with a history of lower extremity edema, fatigue, and weight loss of 3 kg in 4 weeks. Physical examination revealed LET lesions on the chest and the Neck. Laboratory investigations showed lymphopenia, low C3 and C4 complement levels, positive antinuclear antibodies, anti-dsDNA antibodies, and anti-SSA/Ro antibodies. Renal function tests showed normal serum creatinine and nephrotic proteinuria. Renal biopsy revealed Class V lupus nephritis. Skin biopsy confirmed the diagnosis of LET, with the presence of lymphohistiocytic infiltrates and dermal mucin. The patient was diagnosed with SLE based on the 2019 EULAR/ACR criteria and treated with prednisone (1 mg/kg/day) and hydroxychloroquine. She showed significant improvement in her cutaneous and renal symptoms at 6 and 12 months follow-up. CONCLUSION: The rarity of the coexistence of LET and lupus nephritis as the initial manifestation of SLE, especially in the North African population, underscores the need for further research to elucidate the immunopathogenic mechanisms and prognostic factors associated with this association.

Comedonic lupus, a rare variant of chronic cutaneous lupus erythematosus (CCLE): case series and literature review.

BACKGROUND: Cutaneous lupus erythematosus (CLE) is an autoimmune disease with several clinical presentations. The chronic form predominantly presents as discoid rashes but may present with less common morphological findings that can sometimes make diagnosis difficult. Comedonic lupus is a rare and underdiagnosed variant, with unknown etiology and still poorly defined treatment. METHODS: The report illustrates a series of five cases of patients diagnosed with comedonic lupus, and it reviews 18 cases previously published in the literature. RESULTS: The clinical presentation is of comedonal lesions, mostly located on the face, making a differential diagnosis with other benign conditions such as acne vulgaris, Favre-Racouchot syndrome, and syringoma, emphasizing the importance of clinical practice and histopathology for diagnostic confirmation. CONCLUSIONS: There is scarcity in the literature regarding the condition and therapeutic possibilities for these cases of comedonic lupus.

A 30-Year-Old Woman with a History of Autoimmune Hyperthyroidism Presenting with Fever and Oral Ulcers, Diagnosed with Discoid Lupus Erythematosus.

BACKGROUND Lupus erythematosus (LE) is mainly clinically divided into cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) depending on the presence of multi-system manifestations. The most common subtype of CLE is discoid lupus erythematosus (DLE). Graves' disease (GD) is immunologically characterized by lymphocytic infiltration of the thyroid gland and the presence of thyroid-stimulating hormone (TSH) receptor antibodies (TSH-R-Ab), and is the most common autoimmune pathogenic cause of hyperthyroidism. Autoimmune thyroid dysfunction has been widely described in association with rheumatic diseases. A certain rate of coexistence of GD with LE, mainly SLE, has been reported in the literature. Herein, we present a rare case of Graves' hyperthyroidism complicated with DLE. CASE REPORT A 30-year-old female patient, with a history of hyperthyroidism and discontinued methimazole treatment, initially presented with symptoms of infection and oral ulcers. Thyroid hormone, thyroid-stimulating hormone receptor antibody, and immunological tests were consistent with a diagnosis of Graves' hyperthyroidism-associated DLE. Corticosteroids and radioactive iodine (RAI) were used to treat DLE and GD, respectively. Post-treatment evaluation suggested the remission of her hyperthyroidism and active DLE. CONCLUSIONS Autoimmune thyroid diseases have been previously described in association with rheumatic diseases. This association shows the importance of prompt awareness of the increased risk of DLE when evaluating autoimmune thyroid dysfunction, especially under certain conditions, such as after treatment with anti-thyroid drugs (ATDs), or in the absence of multiple organ damage manifestations of SLE.

Autoimmune Skin Conditions: Cutaneous Lupus Erythematosus.

Cutaneous lupus erythematosus (CLE) is a spectrum of autoimmune skin conditions associated with systemic lupus erythematosus (SLE). CLE and SLE may exist concurrently or independently. Accurate recognition of CLE is crucial because it may herald systemic disease onset. Lupus-specific skin conditions include acute cutaneous lupus erythematosus (ACLE) which manifests as a malar or butterfly rash; subacute cutaneous lupus erythematosus (SCLE); and chronic cutaneous lupus erythematosus, which includes discoid lupus erythematosus (DLE). All three types of CLE present as pink-violet macules or plaques with unique morphology, in areas of sun-exposed skin. Association with SLE differs: ACLE is most closely associated, with SCLE in the middle, and DLE the least so. All types of CLE are pruritic, sting, and burn, and DLE can result in disfiguring scarring. All CLE is exacerbated by UV light exposure and smoking. Diagnosis combines clinical evaluation with skin biopsy. Management focuses on mitigating modifiable risk factors and using pharmacotherapy. UV protection includes use of sun protective factor (SPF) 60 or higher sunscreens containing zinc oxide or titanium dioxide, avoidance of sun exposure, and use of physical barrier clothing. Topical therapies and antimalarial drugs are first-line, followed by systemic therapies (eg, disease-modifying antirheumatic drugs, biologic therapies [eg, anifrolumab, belimumab], or other advanced systemic drugs).

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.

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.

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.

Merkel cell number and distribution, and CD200 expression in patients with lichen planopilaris and discoid lupus erythematosus.

BACKGROUND: Immune mechanisms are considered to be responsible for the pathogenesis of cicatricial alopecia in lichen planopilaris (LPP) and discoid lupus erythematosus (DLE) diseases. CD200 has an immunomodulatory function in hair follicles. The functions of Merkel cells (MCs) in hair follicles remain to be fully understood. OBJECTIVE: This study aimed to determine the number and distribution of MCs as well as CD200 expression in patients with DLE and LPP. METHODS: Using immunohistochemistry, the number and distribution of MCs (staining with CK20) and CD200 expression in biopsy specimens of LPP and DLE patients were compared with control group patients. RESULTS: The number of follicular MCs, total MCs, mean follicular MCs, and CD200 expression were significantly lower in the case groups compared to the control group. In CD200- cases, the number of follicular MCs and mean follicular MCs were significantly lower than in CD200+ cases. Retrospective design, lack of data regarding the history of alopecia in the control group, and unknown stage of disease in patients were the limitations. CONCLUSION: MC loss might play a role in immune privilege collapse in hair follicles. This study is novel in terms of investigating MCs in DLE and LPP patients.

Imiquimod-induced hypertrophic lupus erythematosus-like reaction.

Imiquimod is a topical immunomodulator that acts as an inducer of interferon (IFN)-a expression through Toll-like receptor (TLR)7 signaling with indications for the treatment of non-hyperkeratotic actinic keratosis of the face or scalp, superficial basal cell carcinoma (BCC), and external genital and perianal warts. Imiquimod is also used off-label for nodular BCC, cutaneous T-cell lymphoma, pyogenic granuloma, and melanoma. Imiquimod-induced lupus-like reactions have been reported. However, hypertrophic lupus erythematosus (HLE) is a rare variant of cutaneous lupus and imiquimod-induced hypertrophic lupus has not been reported to date. We report a case of local induction of a plaque that resembled HLE clinically and histologically in an 82-year old woman following topical treatment with imiquimod.

Differential genotypes of TNF-α and IL-10 for immunological diagnosis in discoid lupus erythematosus and oral lichen planus: A narrative review.

Discoid lupus erythematosus and oral lichen planus are chronic systemic immune system-mediated diseases with unclear etiology and pathogenesis. The oral mucosa is the common primary site of pathogenesis in both, whereby innate and adaptive immunity and inflammation play crucial roles. The clinical manifestations of discoid lupus erythematosus on the oral mucosa are very similar to those of oral lichen planus; therefore, its oral lesion is classified under oral lichenoid lesions. In practice, the differential diagnosis of discoid lupus erythematosus and oral lichen planus has always relied on the clinical manifestations, with histopathological examination as an auxiliary diagnostic tool. However, the close resemblance of the clinical manifestations and histopathology proves challenging for accurate differential diagnosis and further treatment. In most cases, dentists and pathologists fail to distinguish between the conditions during the early stages of the lesions. It should be noted that both are considered to be precancerous conditions, highlighting the significance of early diagnosis and treatment. In the context of unknown etiology and pathogenesis, we suggest a serological and genetic diagnostic method based on TNF-α and IL-10. These are the two most common cytokines produced by the innate and adaptive immune systems and they play a fundamental role in maintaining immune homeostasis and modulating inflammation. The prominent variability in their expression levels and gene polymorphism typing in different lesions compensates for the low specificity of current conventional diagnostic protocols. This new diagnostic scheme, starting from the immunity and inflammation of the oral mucosa, enables simultaneous comparison of discoid lupus erythematosus and oral lichen planus. With relevant supportive evidence, this information can enhance physicians' understanding of the two diseases, contribute to precision medicine, and aid in prevention of precancerous conditions.

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.

Cutaneous sarcoidosis: Lupus pernio and more.

Sarcoidosis is a multiorgan disease commonly evident with skin involvement. Cutaneous manifestations occur in about 25% of sarcoid patients and are of two types: histologically specific sarcoidal infiltrations and a cutaneous reaction pattern not containing sarcoidal changes, usually erythema nodosum. Cutaneous plaques, nodules, and tumors, sometimes with disfiguring facial features are associated with pain and paresthesia. The disease itself may produce substantial morbidity due to visceral involvement. Advances in therapeutic options include tocilizumab, an IL-6 inhibitor, and tofacitinib - a Janus kinase inhibitor. This review discusses sarcoidosis etiology and pathogenesis, its clinical features, differential diagnosis, and management.

Skin CD4+ Trm cells distinguish acute cutaneous lupus erythematosus from localized discoid lupus erythematosus/subacute cutaneous lupus erythematosus and other skin diseases.

BACKGROUND: Although the contribution of aberrant CD4+ T cell signaling to systemic lupus erythematosus (SLE) is well established, its role in cutaneous lupus erythematosus (CLE) skin is largely unknown. Because the rate of systemic manifestations varies in each subtype, resident memory CD4+ T cells in lesions that are responsible for only skin-associated tissue responses may vary in each subtype. However, the role of CD4+ tissue-resident memory T (CD4+ Trm) cells in each CLE subtype remains unclear. OBJECTIVES: To analyze and compare CD4+ Trm cells and absent in melanoma 2 (AIM2) identified by smart RNA sequencing (Smart-seq) in CD4+ Trm cells from patients with acute CLE (ACLE), subacute CLE (SCLE), and localized discoid lupus erythematosus (localized DLE) lesions. METHODS: We performed Smart-seq to investigate differences in dermal CD4+ Trm cells between patients with ACLE and normal controls (NCs). Multicolor immunohistochemistry was utilized to measure the levels of AIM2 in CD4+ Trm cells present in the skin of 134 clinical patients, which included patients with localized DLE (n = 19), ACLE (n = 19), SCLE (n = 16), psoriasis (n = 12), rosacea (n = 17), lichen planus (n = 18), and annular granuloma (n = 15), as well as NCs (n = 18). RESULTS: The Smart-seq data showed higher AIM2 expression in skin CD4+ Trm cells from ACLE lesions than NCs (fold change >10, adjusted P < 0.05). AIM2 expression in CD4+ Trm cells did not vary according to age or sex. AIM2 expression in CD4+ Trm cells was significantly lower in patients with ACLE (6.38 ± 5.22) than localized DLE (179.41 ± 160.98, P < 0.0001) and SCLE (63.43 ± 62.27, P < 0.05). In an overall comparison of ACLE with localized DLE and SCLE, the receiver operating characteristic curve for AIM2 expression in CD4+ Trm cells had a sensitivity of 100.00% and a specificity of 82.86% at a cutoff value of 18.26. In a comparison of ACLE with localized DLE, the sensitivity was 89.47%, and the specificity was 100.00% at a cutoff value of 12.26. In a comparison of ACLE with SCLE, the sensitivity was 100.00%, and the specificity was 75.00% at a cutoff value of 18.26. CONCLUSIONS: The number of CD4+ Trm cells is increased in lesions of SCLE and localized DLE compared to ACLE, suggesting that CD4+ Trm cells may have a more crucial role in persistent lesions of SCLE and localized DLE. In addition, AIM2 expression in CD4+ Trm cells discriminates patients with ACLE from those with localized DLE and SCLE.

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.

Clinicohistological and immunopathological features of patients with cutaneous lupus erythematosus at tertiary dermatology centre in Malaysia.

BACKGROUND: Cutaneous lupus erythematosus (CLE) is a chronic, autoimmune skin disease with a wide spectrum of clinical presentations in different populations. AIM: To study the clinicohistological and immunological features of CLE in a multiethnic population and to identify the predictive factors of disease severity based on the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). METHODS: This was a cross-sectional study of CLE conducted from March 2019 to February 2020. RESULTS: In total, 111 patients were recruited with a female/male ratio of 4.9 : 1. Acute CLE contributed 47.7%, followed by chronic CLE at 46.9% and subacute CLE at 5.4%. A large majority (84%) of patients had systemic lupus erythematosus. Of patients with chronic CLE, about 67.3% developed systemic involvement. Antinuclear antibody (ANA) was detected in 90.0%. Skin biopsy was taken from 42 patients and showed perivascular lymphocytic infiltration (95.2%), epidermal atrophy (47.6%) and hydropic degeneration of the basal layer (47.6%). Immunoglobulin deposition at the dermoepidermal junction was seen in > 40% of patients, predominantly in a granular pattern. Mean CLASI Total was 6.44 ± 7.70, while CLASI Activity (CLASI-A) was 2.75 ± 4.10 and CLASI Damage (CLASI-D) was 3.71 ± 4.76. Involved body surface area (BSA) was found to be an independent predictive factor for CLASI-A (OR = 1.34, P < 0.02). For CLASI-D, positive predictive factors were involved BSA (OR = 4.14, P < 0.001), discoid lupus erythematosus subtype (OR = 13.10, P = 0.001), cutaneous vascular disease (OR = 26.59; P = 0.014), scalp involvement (OR = 8.7, P < 0.01) and hypocomplementaemia (OR = 5.71, P < 0.5). Mean Dermatology Life Quality Index was 5.91 ± 5.34 and correlated significantly with disease severity. CONCLUSIONS: We observed a high percentage of patients with CLE with systemic manifestations and positive ANA result. More aggressive treatment of patients with positive predictive factors for severe disease combined with significant clinical activity may be warranted.

Platelet Rich Plasma for the Treatment of Scarring Alopecia Due to Discoid Lupus Erythematosus.

Platelet-rich plasma (PRP) is an autologous concentration of plasma from a patient’s blood containing platelets up to 7 times higher than normal plasma. Originally indicated to improve connective tissue regeneration in orthopedic surgery, PRP has also proven to be advantageous in the treatment of androgenic alopecia (AGA), alopecia areata (AA), and other forms of non-scarring alopecia.