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.

Cutaneous lupus erythematosus is associated with an increased risk of cardiac and vascular diseases: a large-scale, propensity-matched global retrospective cohort study.

BACKGROUND: Autoimmune skin diseases can expedite various systemic sequelae involving other organs. Although limited to the skin, cutaneous lupus erythematosus (CLE) was noted to be associated with thromboembolic diseases. However, small cohort sizes, partially discrepant outcomes, missing data on CLE subtypes, and incomplete risk assessment limits these findings. METHODS: The Global Collaborative Network of TriNetX provides access to medical records of more than 120 million patients worldwide. We used TriNetX to elucidate the risk for cardiac and vascular diseases after diagnosis of CLE, and its subtypes chronic discoid (DLE) and subacute cutaneous lupus erythematosus (SCLE). We included 30,315 CLE, 27,427 DLE, and 1613 SCLE patients. We performed propensity-matched cohort studies determining the risk to develop cardiac and vascular diseases (ICD10CM:I00-99) following diagnosis of CLE, DLE, or SCLE. Patients with systemic lupus erythematosus were excluded. FINDINGS: We document that CLE and its subtype DLE but less so SCLE are associated with a higher risk for various cardiac and vascular diseases. This included predominantly thromboembolic events such as pulmonary embolism, cerebral infarction, and acute myocardial infarction, but also peripheral vascular disease and pericarditis. For example, the hazard ratio of arterial embolism and thrombosis was 1.399 (confidence interval: 1.230-1.591, p < 0.0001) following CLE diagnosis. The study is limited by retrospective data collection and reliance on ICD10-disease classification. INTERPRETATION: CLE and its major subtype DLE are associated with an increased risk for the development of a wide range of cardiac and vascular diseases. FUNDING: This research was funded by Deutsche Forschungsgemeinschaft (EXC 2167, CSSL/CS01-2022) and the Excellence-Chair Program of the State of Schleswig-Holstein.

The differential panorama of clinical features of lupus erythematosus patients with different onset ages: a cross-sectional multicenter study from China.

OBJECTIVES: This study aims to compare the differences among patients of different onset ages in various subtypes of lupus erythematosus (LE) and to draw a panorama of the clinical characteristics of patients with different onset ages. METHOD: Subjects were recruited from the Lupus Erythematosus Multicenter Case-control Study in Chinese populations (LEMCSC), grouped by the age of onset (childhood-onset: onset < 18 years, adult-onset: onset 18-50 years, late-onset: onset > 50 years). The data collected included demographic characteristics, LE-related systemic involvement, LE-related mucocutaneous manifestations, and laboratory results. All included patients were assigned into three groups: systemic LE (SLE) group (with systemic involvement, with or without mucocutaneous lesions), cutaneous LE (CLE) group (patients who were accompanied by any type of LE-specific cutaneous manifestations), and isolated cutaneous LE (iCLE) group (patients who were in CLE group without systemic involvements). Data were analyzed using R version 4.0.3. RESULTS: A total of 2097 patients were involved, including 1865 with SLE and 232 with iCLE. We also identified 1648 patients with CLE among them, as there was some overlap between the SLE population and CLE population (patients with SLE and LE-specific cutaneous manifestations). Later-onset lupus patients seemed to be less female predominance (p < 0.001) and have less systemic involvement (except arthritis), lower positive rates of autoimmune antibodies, less ACLE, and more DLE. Moreover, childhood-onset SLE patients presented a higher risk of LE family history (p = 0.002, vs adult-onset SLE). In contrast to other LE-nonspecific manifestations, the self-reported photosensitivity history decreased with the age of onset in SLE patients (51.8%, 43.4%, and 39.1%, respectively) but increased in iCLE patients (42.4%, 64.9%, and 89.2%, respectively). There was also a gradual increase in self-reported photosensitivity from SLE, CLE, to iCLE in both adult-onset and late-onset lupus patients. CONCLUSIONS: A negative correlation was suggested between the age of onset and the likelihood of systemic involvement, except for arthritis. As the age of onset increases, patients have a greater propensity to exhibit DLE compared to ACLE. Moreover, the presence of rapid response photodermatitis (i.e., self-reported photosensitivity) was associated with a lower rate of systemic involvement. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR2100048939) on July 19, 2021, retrospectively registered. Key Points • We confirmed some phenomena that have been found in patients with SLE, such as the highest proportion of females of reproductive age, the higher risk of LE family history in childhood-onset SLE patients, and the less self-reported photosensitivity in the late-onset SLE group. We also compared the similarities and differences of these phenomena in patients with CLE or iCLE for the first time. • In patients with SLE, the proportion of females peaked in adult-onset patients, but this phenomenon disappeared in iCLE patients: the female-male ratio tends to decrease from childhood-onset iCLE, adult-onset iCLE, to late-onset iCLE. • Patients with early-onset lupus are more likely to have acute cutaneous lupus erythematosus (ACLE), and patients with late-onset lupus are more likely to have discoid lupus erythematosus (DLE). • In contrast to other LE-nonspecific manifestations, the incidence of rapid response photodermatitis (i.e., self-reported photosensitivity) decreased with the age of onset in SLE patients but increased with the age of onset in iCLE patients.

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.

Scarring Alopecia.

African hair shaft and pigmented scalp have unique features that challenge diagnosis in scarring alopecia. In addition, Black patients may associate 2 or more types of hair disorders. Therefore, it is imperative to understand their findings thoroughly to establish a good diagnosis. Differential diagnosis on the frontal scalp includes traction alopecia and frontal fibrosing alopecia. Disorders such as central centrifugal cicatricial alopecia, fibrosing alopecia in a pattern distribution, discoid lupus erythematosus, and lichen planopilaris usually affect the middle scalp. Folliculitis decalvans, dissecting cellulitis, and acne keloidalis nuchae are the main differential diagnosis of the posterior scalp.

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.

Panoramic view of clinical features of lupus erythematosus: a cross-sectional multicentre study from China.

OBJECTIVE: Lupus erythematosus (LE) is a complicated disease with highly heterogeneous clinical manifestations. Previous studies have rarely included all subgroups of patients with lupus and have overlooked the importance of the cutaneous manifestations thereof. We aimed to compare the demographic and clinical differences among patients with different subtypes of lupus. METHODS: This is the first real-world study with a relatively large sample size that simultaneously includes patients with isolated cutaneous lupus erythematosus (iCLE) and SLE. All samples were obtained from the Lupus Erythematosus Multicenter Case-control Study in Chinese populations (LEMCSC) (registration number: ChiCTR2100048939). Comparative analyses between different LE subgroups were performed. RESULTS: A total of 2097 patients with lupus were included, with 1865 patients with SLE, 1648 with cutaneous lupus erythematosus (CLE), and 232 with iCLE. Among the patients with CLE, 1330 had acute cutaneous lupus erythematosus (ACLE); 160 had subacute cutaneous lupus erythematosus (SCLE); and 546 had chronic cutaneous lupus erythematosus (CCLE). The study included a relatively large number of patients with CCLE subtypes, including 311 with discoid lupus erythematosus (DLE), 262 with chilblain lupus erythematosus (CHLE) and 45 with lupus erythematosus profundus (LEP). Demographic characteristics, systemic involvement, mucocutaneous manifestations and autoantibodies were significantly different among the groups. CONCLUSIONS: CLE and iCLE are two distinct disease states, and the selection of broad or narrow CLE definitions should be emphasised in scientific reports. LE-non-specific cutaneous lesions imply more severity, while self-reported photosensitivity and LE-specific cutaneous manifestations imply milder severity. Generalised ACLE appears to be a more severe state than localised ACLE, and CHLE appears to be more severe than DLE. Anti-Sjögren's syndrome-related antigen B (SSB) antibodies have higher specific directivity than anti-Sjögren's syndrome-related antigen A (SSA) antibodies for SCLE lesions. Anti-double-stranded DNA antibodies have a higher co-occurrence with ACLE and a lower co-occurrence with SCLE and CCLE. Compared with DLE, CHLE has significantly higher positive rates of anti-SSA/Ro60 (71%) and anti-SSA/Ro52 (42.4%) antibodies, whereas LEP is associated with a higher positive rate of antinucleosome antibodies (31.1%).

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.

Orbital myositis in systemic lupus erythematosus: a case-based review.

Ocular complications occur in up to one-third of patients with systemic lupus erythematosus (SLE). Among them, orbital myositis (OM) is considered a rare manifestation that affects the extraocular muscles and causes pain and restriction with eye movement. We report a case of OM in a 48-year-old female with SLE and secondary Sjogren's Syndrome, who presented headache, periorbital edema, and painful ocular movements in both eyes, with no other systemic manifestations. An orbital magnetic resonance image revealed thickening of the right medial rectus and left lateral rectus muscles. Laboratory tests were normal and there was no further disease activity. The patient was treated with prednisone 1 mg/Kg/day with a resolution of symptoms. We found 13 additional cases of OM from our literature review (11 SLE patients and 2 with discoid lupus erythematosus). There was a female predominance in these cases with a mean age of 43.6 years (SD ± 16.9). Their main clinical features included eye pain, swelling, proptosis, diplopia, and limitations in extraocular muscles, while in most of them, there was no other active systemic manifestation. Treatment with steroids led to the complete resolution of symptoms in most of these patients. The available evidence suggests that it is essential to have a high index of suspicion for OM in SLE patients even when there is no systemic disease activity so that proper treatment is initiated early.

Chilblains in immune-mediated inflammatory diseases: a review.

Chilblains were first described over a hundred years ago as cutaneous inflammatory lesions, typically on the digits, occurring on cold exposure. Chilblains can be primary, or secondary to a number of conditions such as infections, including COVID-19, and immune-mediated inflammatory disorders (IMIDs) with SLE being the commonest. Chilblain lupus erythematosus (CHLE) was first described in 1888 as cold-induced erythematous lesions before the terms 'chilblains' or 'perniosis' were coined. Diagnostic criteria exist for both chilblains and CHLE. Histopathologically, CHLE lesions show interface dermatitis with perivascular lymphocytic infiltrate. Immunofluorescence demonstrates linear deposits of immunoglobulins and complement in the dermo-epidermal junction. This narrative review focuses on chilblains secondary to immune-mediated inflammatory disorders, primarily the epidemiology, pathogenesis and treatment of CHLE.

Jaccoud-type lupus arthropathy.

BACKGROUND: Jaccoud's arthropathy (JA) is a condition characterized by joint deformities that have a "reducible" pattern, that is, they return to the normal appearance with a passive manoeuvre. JA was described in patients with rheumatic fever (RF) more than a century ago, and presently, the majority of the patients have systemic lupus erythematosus (SLE). PURPOSE: The aim of this review is to draw one attention to the epidemiology, pathogenesis, histopathology, clinical features, imaging, and management of JA in patients with SLE (Jaccoud-type lupus arthropathy). DATA COLLECTION: The search strategy included articles retrieved from PubMed utilizing the terms "lupus arthropathy", "lupus deforming arthropathy", "lupus hand", "lupus foot", "chronic postrheumatic arthropathy", "Jaccoud's" and "Jaccoud" from 1950 until March 2021, with no language restriction. RESULTS: The prevalence of Jaccoud-type arthropathy in SLE is approximately 5%. The aetiopathogenic mechanisms of JA are not yet known. The most common joint deformities of JA, are ulnar deviation, swan neck, and the "z" of the thumb. Unfortunately, none of the proposed classification criteria for JA have been validated so far. Characteristically, there is no bone erosion on plain radiographs of the joints, but more sensitive imaging methods, magnetic resonance imaging or high-performance ultrasound may reveal small bone erosions. There is no preventive measure against JA development, specific clinical treatment or convincing surgical approach for correcting the deformities. CONCLUSION: As daily activities and quality of life are compromised in patients with JA, other studies are urgently needed in this area.

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.

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.

Clinical Significance of Raynaud Phenomenon in Systemic Lupus Erythematosus.

OBJECTIVE: There are limited reports of the clinical significance of Raynaud phenomenon (RP) in systemic lupus erythematosus (SLE), with some suggesting RP is associated with less severe lupus. Since most prior studies were small and/or focused on a specific race/ethnic demographic, it is unclear if those results are generalizable. We evaluated whether RP was associated with demographic and clinical factors in a large multiethnic SLE cohort. METHODS: We studied Montreal General Hospital SLE cohort patients who are followed with standardized annual assessments. We included patients with at least 1 visit across 2011-2018 and assessed demographic and clinical variables (using the 1997 American College of Rheumatology criteria and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index) at their first visit. We present multivariate logistics regression analyses of cross-sectional associations between these variables and RP in SLE. RESULTS: Of 489 SLE patients, most were female (n = 445, 91%). Mean age at SLE diagnosis was 31.5 (standard deviation, 13.5) years, and 169 (34.6%) had RP. In our fully adjusted model, female sex (odds ratio [OR], 2.43; 95% confidence interval [CI], 1.07-6.03), White race/ethnicity (OR, 1.85; 95% CI, 1.10-3.17), neurological/neuropsychiatric manifestations (OR, 1.98; 95% CI, 1.10-3.56), and anti-RNP antibodies (OR, 3.03; 95% CI, 1.73-5.38) were positively associated with RP, whereas hemolytic anemia and cellular casts were negatively associated. CONCLUSIONS/DISCUSSION: Over one third of our large multiethnic North American SLE cohort had RP. This study confirmed associations between RP and a specific SLE phenotype.

Discoid lupus in antiphospholipid syndrome: case description and literature review.

OBJECTIVE: The aim of the study was to report about a patient with discoid lupus erythematosus (DLE) who developed antiphospholipid syndrome (APS) 12 years after DLE diagnosis and review related literature. PATIENTS AND METHODS: This is a case report of a 34-year-old woman with DLE who developed APS. A review of articles published in the PubMed/MEDLINE, LILACS, and SciELO databases from 1966 to October 2020 was conducted using the following search terms: "antiphospholipid syndrome," "antiphospholipid antibodies," and "discoid lupus erythematosus" No language limitation was applied. RESULTS: Besides the present case, 5 case reports were identified. One case-control and two cross-sectional studies on antiphospholipid antibodies with or without APS in DLE were also reviewed. These studies revealed that APS can develop even 37 years after DLE was diagnosed. The case-control study found that patients with DLE have more anticardiolipin antibodies than controls. In contrast, one cross-sectional study showed a low prevalence of antiphospholipid antibodies in their group of patients, which was similar to findings in the general population. CONCLUSIONS: This study reviewed previous articles on DLE cases associated with antiphospholipid antibodies and/or APS, adding a new case description.

The role of interleukin-17 (IL-17) in the pathogenesis of discoid lupus erythematosus and lichen planopilaris: is immunohistochemistry for IL-17 a promising way to differentiate these entities?

BACKGROUND: Interleukin-17 (IL-17) is a pro-inflammatory mediator which its excess secretion by immune cells is found in many chronic autoimmune diseases. This survey is aimed to compare the amount and pattern of distribution of IL-17 positive cells in lichen planopilaris (LPP) and discoid lupus erythematosus (DLE) which are of the most frequent causes of primary cicatricial alopecia (CA). METHODS: Biopsies of lesional scalp skin from adult LPP (n = 30), DLE patients (n = 19), and control scalp skin (n = 18) were analyzed by immunohistochemistry (IHC) method using rabbit polyclonal antibody against IL-17. Cells stained positive for IL-17 and their pattern of distribution were assessed and compared between these groups. RESULTS: The mean of IL-17 positive cell counts per high power field (HPF) in both LPP and DLE groups was significantly higher in comparison with the control group (both p < .0001). The LPP group had higher values of IL-17 positive cell counts per HPF (47.56 ± 13.37) compared to the DLE group (22.21 ± 11.06) (p < .0001). More than 30 IL-17 positive cell counts in IHC have a sensitivity of 90% and a specificity of 78% for differentiating LPP from DLE. CONCLUSIONS: Our findings suggest that IL-17 is effective in the pathogenesis of DLE and LPP and its role is more prominent in LPP. IL-17 positive cells in IHC can distinguish DLE from LPP with satisfactory sensitivity and specificity.