Guideline for the diagnosis, treatment and long-term management of cutaneous lupus erythematosus.

Cutaneous lupus erythematosus (CLE) is an inflammatory, autoimmune disease encompassing a broad spectrum of subtypes including acute, subacute, chronic and intermittent CLE. Among these, chronic CLE can be further classified into several subclasses of lupus erythematosus (LE) such as discoid LE, verrucous LE, LE profundus, chilblain LE and Blaschko linear LE. To provide all dermatologists and rheumatologists with a practical guideline for the diagnosis, treatment and long-term management of CLE, this evidence- and consensus-based guideline was developed following the checklist established by the international Reporting Items for Practice Guidelines in Healthcare (RIGHT) Working Group and was registered at the International Practice Guideline Registry Platform. With the joint efforts of the Asian Dermatological Association (ADA), the Asian Academy of Dermatology and Venereology (AADV) and the Lupus Erythematosus Research Center of Chinese Society of Dermatology (CSD), a total of 25 dermatologists, 7 rheumatologists, one research scientist on lupus and 2 methodologists, from 16 countries/regions in Asia, America and Europe, participated in the development of this guideline. All recommendations were agreed on by at least 80% of the 32 voting physicians. As a consensus, diagnosis of CLE is mainly based on the evaluation of clinical and histopathological manifestations, with an exclusion of SLE by assessment of systemic involvement. For localized CLE lesions, topical corticosteroids and topical calcineurin inhibitors are first-line treatment. For widespread or severe CLE lesions and (or) cases resistant to topical treatment, systemic treatment including antimalarials and (or) short-term corticosteroids can be added. Notably, antimalarials are the first-line systemic treatment for all types of CLE, and can also be used in pregnant patients and pediatric patients. Second-line choices include thalidomide, retinoids, dapsone and MTX, whereas MMF is third-line treatment. Finally, pulsed-dye laser or surgery can be added as fourth-line treatment for localized, refractory lesions of CCLE in cosmetically unacceptable areas, whereas belimumab may be used as fourth-line treatment for widespread CLE lesions in patients with active SLE, or recurrence of ACLE during tapering of corticosteroids. As for management of the disease, patient education and a long-term follow-up are necessary. Disease activity, damage of skin and other organs, quality of life, comorbidities and possible adverse events are suggested to be assessed in every follow-up visit, when appropriate.

Interventions for cutaneous disease in systemic lupus erythematosus.

BACKGROUND: Lupus erythematosus is an autoimmune disease with significant morbidity and mortality. Cutaneous disease in systemic lupus erythematosus (SLE) is common. Many interventions are used to treat SLE with varying efficacy, risks, and benefits. OBJECTIVES: To assess the effects of interventions for cutaneous disease in SLE. SEARCH METHODS: We searched the following databases up to June 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, Wiley Interscience Online Library, and Biblioteca Virtual em Saude (Virtual Health Library). We updated our search in September 2020, but these results have not yet been fully incorporated. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of interventions for cutaneous disease in SLE compared with placebo, another intervention, no treatment, or different doses of the same intervention. We did not evaluate trials of cutaneous lupus in people without a diagnosis of SLE. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Primary outcomes were complete and partial clinical response. Secondary outcomes included reduction (or change) in number of clinical flares; and severe and minor adverse events. We used GRADE to assess the quality of evidence. MAIN RESULTS: Sixty-one RCTs, involving 11,232 participants, reported 43 different interventions. Trials predominantly included women from outpatient clinics; the mean age range of participants was 20 to 40 years. Twenty-five studies reported baseline severity, and 22 studies included participants with moderate to severe cutaneous lupus erythematosus (CLE); duration of CLE was not well reported. Studies were conducted mainly in multi-centre settings. Most often treatment duration was 12 months. Risk of bias was highest for the domain of reporting bias, followed by performance/detection bias. We identified too few studies for meta-analysis for most comparisons. We limited this abstract to main comparisons (all administered orally) and outcomes. We did not identify clinical trials of other commonly used treatments, such as topical corticosteroids, that reported complete or partial clinical response or numbers of clinical flares. Complete clinical response Studies comparing oral hydroxychloroquine against placebo did not report complete clinical response. Chloroquine may increase complete clinical response at 12 months' follow-up compared with placebo (absence of skin lesions) (risk ratio (RR) 1.57, 95% confidence interval (CI) 0.95 to 2.61; 1 study, 24 participants; low-quality evidence). There may be little to no difference between methotrexate and chloroquine in complete clinical response (skin rash resolution) at 6 months' follow-up (RR 1.13, 95% CI 0.84 to 1.50; 1 study, 25 participants; low-quality evidence). Methotrexate may be superior to placebo with regard to complete clinical response (absence of malar/discoid rash) at 6 months' follow-up (RR 3.57, 95% CI 1.63 to 7.84; 1 study, 41 participants; low-quality evidence). At 12 months' follow-up, there may be little to no difference between azathioprine and ciclosporin in complete clinical response (malar rash resolution) (RR 0.83, 95% CI 0.46 to 1.52; 1 study, 89 participants; low-quality evidence). Partial clinical response Partial clinical response was reported for only one key comparison: hydroxychloroquine may increase partial clinical response at 12 months compared to placebo, but the 95% CI indicates that hydroxychloroquine may make no difference or may decrease response (RR 7.00, 95% CI 0.41 to 120.16; 20 pregnant participants, 1 trial; low-quality evidence). Clinical flares Clinical flares were reported for only two key comparisons: hydroxychloroquine is probably superior to placebo at 6 months' follow-up for reducing clinical flares (RR 0.49, 95% CI 0.28 to 0.89; 1 study, 47 participants; moderate-quality evidence). At 12 months' follow-up, there may be no difference between methotrexate and placebo, but the 95% CI indicates there may be more or fewer flares with methotrexate (RR 0.77, 95% CI 0.32 to 1.83; 1 study, 86 participants; moderate-quality evidence). Adverse events Data for adverse events were limited and were inconsistently reported, but hydroxychloroquine, chloroquine, and methotrexate have well-documented adverse effects including gastrointestinal symptoms, liver problems, and retinopathy for hydroxychloroquine and chloroquine and teratogenicity during pregnancy for methotrexate. AUTHORS' CONCLUSIONS: Evidence supports the commonly-used treatment hydroxychloroquine, and there is also evidence supporting chloroquine and methotrexate for treating cutaneous disease in SLE. Evidence is limited due to the small number of studies reporting key outcomes. Evidence for most key outcomes was low or moderate quality, meaning findings should be interpreted with caution. Head-to-head intervention trials designed to detect differences in efficacy between treatments for specific CLE subtypes are needed. Thirteen further trials are awaiting classification and have not yet been incorporated in this review; they may alter the review conclusions.

A Case of Linear Cutaneous Lupus Erythematosus in a 55-Year-Old Woman.

BACKGROUND Linear cutaneous lupus erythematosus (LCLE) is uncommon and occurs mainly in children and young adults. To our knowledge, only ten cases of LCLE in adults have been previously reported. A case is presented of LCLE of the left arm in a 55-year-old woman. CASE REPORT A 55-year-old Caucasian woman from the Midwestern United States presented with a three-month history of a pruritic linear eruption on the left arm. She had a previous history of methicillin-resistant Staphylococcus aureus (MRSA) infection of the left forearm. She had previously been treated with topical triamcinolone, hydrocortisone cream, hydroxyzine, and two courses of prednisone. Physical examination showed a unilateral and linear erythematous skin lesion of the left arm that contained papules and followed the embryonal developmental epidermal lines of Blaschko. Histopathology of a 4 mm skin punch biopsy showed an interface dermatitis with keratinocyte necrosis and increased dermal mucin. Immunofluorescence of the skin biopsy, including for antinuclear antigen (ANA), was negative. Prednisone treatment reduced the symptoms of pruritis but did not resolve the rash. However, following topical treatment with betamethasone dipropionate cream for between two and three weeks, and the use of sunblock, the skin lesions resolved. CONCLUSIONS This rare case of LCLE in an older adult showed a similar response to treatment as other forms of cutaneous lupus erythematosus, with treatment that included topical steroids and sun protection. Also, this case supports that environmental trigger factors, such as prior infections, might provide insights into the etiology of LCLE.

Lupus eritematoso cutáneo y lupus eritematoso sistémico: revisión de una historia sin fin / Cutaneous lupus erythematosus and systemic lupus erythematosus: endless story review

l lupus eritematoso es una afección que se conoce desde antiguo, referida en especial al compromiso cutáneo, pero ha sido mejor definida desde principios del siglo XIX, constituyéndose como una enfermedad sistémica con una base autoinmune. Mecanismos patogénicos inmunogenéticos desempeñan un papel en la susceptibilidad a la enfermedad, sobre la que actuarían variaciones hormonales y factores ambientales. De esta interacción deriva la producción de múltiples anormalidades inmunológicas, cuya acción sobre los tejidos da origen a la expresión clínica de la enfermedad. La relación entre el compromiso cutáneo, en especial crónico discoide, y sistémico, ha sido un factor de polémica, importante de dilucidar por el significado terapéutico y de pronóstico para el enfermo. De esta revisión se puede concluir que las diferentes manifestaciones del lupus constituyen una misma enfermedad, pero probablemente factores etiopatogénicos genéticos, hormonales y ambientales marcan la diferencia.

Lupus erythematosus is a condition that has been known since ancient times, especially referring to skin involvement, but has been better defined since the beginning of the 19th century, constituting itself as a systemic disease with an autoimmune basis. Immunogenetic pathogenic mechanisms play a role in disease susceptibility, on which hormonal variations and environmental factors would act. From this interaction derives the production of multiple immunological abnormalities, whose action on the tissues gives rise to the clinical expression of the disease. The relationship between cutaneous involvement, especially chronic discoid, and systemic, has been a controversial factor, important to elucidate due to its therapeutic and prognostic significance for the patient. From this review it can be concluded that the different manifestations of lupus constitute the same disease, but genetics, hormonal and environmental etiopathogenic factors probably make the difference.

Current Concepts and Future Approaches in the Treatment of Cutaneous Lupus Erythematosus: A Comprehensive Review.

Standard treatment of cutaneous lupus erythematosus (CLE) includes preventive measures such as smoking cessation and photoprotection associated with topical therapies and antimalarial agents, which are recommended as first-line systemic treatment. In more severe disease, alternative therapeutic options include immunosuppressive and immunomodulatory drugs. Recently, the development of specific tools to assess CLE activity and the publication of European CLE guidelines have improved the management of CLE. Moreover, several biologic agents are currently being studied specifically in CLE or in systemic lupus erythematosus with assessment of skin involvement and may be promising therapies. However, improvement of the management of CLE remains a major unmet need. In this review, we summarize current concepts in the management of CLE as well as future approaches for more targeted treatments.

Cutaneous lupus erythematosus: Reflecting on practice-changing observations over the past 50 years.

Several historical observations have led to the current understanding of the diagnosis, evaluation, and management of patients with cutaneous lupus erythematosus. Seminal advances in the management of this disease include the development of a classification system for cutaneous lupus, the use of a validated scoring system to assess patient disease activity, and expansion of knowledge of the action spectrum of this disease; further, observations regarding certain medications as potential causes of subacute cutaneous lupus erythematosus, the risk of progression from "pure" cutaneous disease to systemic disease, and traditional versus newer therapies are reviewed with closer inspection.

Cutaneous lupus erythematosus in dogs: a comprehensive review.

Since the first description of discoid lupus erythematosus (LE) in two dogs in 1979, the spectrum of canine cutaneous lupus erythematosus (CLE) variants has expanded markedly.In this review, we first propose an adaptation of the Gilliam-Sontheimer classification of CLE for dogs. We then review the signalment, clinical signs, laboratory and histopathology and treatment outcome of the currently recognized variants of canine CLE, which are vesicular CLE, exfoliative CLE, mucocutaneous LE and facial or generalized discoid LE. We end with a short description of the rare cutaneous manifestations of systemic LE in dogs.Canine CLE variants are heterogeneous, some of them mirror their human counterparts while others appear-thus far-unique to the dog. As most CLE subtypes seem to have a good prognosis after diagnosis, veterinarians are encouraged to become familiar with the spectrum of often-characteristic and unique clinical signs that would permit an early diagnosis and the rapid implementation of an effective treatment.

The use of SLICC and ACR criteria to correctly label patients with cutaneous lupus and systemic lupus erythematosus.

The American College of Rheumatology (ACR) classification criteria for lupus and Systemic Lupus International Collaborating Clinics (SLICC) criteria are designed to classify disease. However, they have become widely used as diagnostic criteria in clinical situations. Patients may be labelled as systemic lupus erythematosus (SLE) in their medical records, when in fact they have cutaneous lupus erythematosus (CLE) without systemic symptoms. We sought to investigate how many of our cutaneous lupus patients attending a dermatology lupus clinic were mislabelled as either CLE or SLE using the ACR and SLICC criteria. Thirty-six patients with biopsy-proven cutaneous lupus were identified. Fourteen (39%) of the patients were labelled as 'SLE' in their medical notes, either by dermatology or another medical team. Of these 14 patients, 12 (86%) fulfilled the ACR and SLICC criteria; however, two (14%) did not meet the criteria for SLE. Of the remaining 22 patients who were not labelled as having SLE, four (18%) met both the SLICC and ACR criteria, one (5%) met the ACR criteria and one (5%) met the SLICC criteria. These patients had a history of discoid or subacute lupus, with very few systemic symptoms. They met the criteria for SLE primarily on their cutaneous signs and positive serology. It is important to screen patients with CLE routinely for SLE. Although the ACR and SLICC criteria can be helpful as they have a high sensitivity for systemic lupus, their use needs to be paired with the clinical context and patient evolution. We found patients were labelled as SLE when in fact they had no evidence of systemic involvement, as well as patients labelled as cutaneous lupus who fulfilled the criteria for SLE, although unlikely having any systemic involvement. It is important to correctly identify patients as 'cutaneous lupus' or 'systemic lupus erythematosus' and documentation in clinical notes should be accurate to avoid confusion and allow appropriate treatment.

[Cell-mediated immunity: Lupus and connective tissue diseases]. / Auto-immunité à médiation cellulaire : lupus et connectivités.

Lupus can present itself in a multitude of clinical and histopathological manifestations. Cutaneous lesions can be very variable either from the clinical point of view or at the microscopic scale. Signs can be specific, concerning the dermo-epidermal stage, the dermal stage or the hypodermal stage. Conversely, some manifestations can be not specific but associated to the lupus. Finally, the question of the differential diagnosis can be tricky and often requires a beam of clinical, biological and histopathological arguments.

Using the American College of Rheumatology (ACR) and Systemic Lupus International Collaborating Clinics (SLICC) criteria to determine the diagnosis of systemic lupus erythematosus (SLE) in patients with subacute cutaneous lupus erythematosus (SCLE).

BACKGROUND: Approximately 50% of patients with subacute cutaneous lupus erythematosus (SCLE) meet criteria for systemic lupus erythematosus (SLE). The Systemic Lupus International Collaborating Clinics (SLICC) developed new SLE criteria to improve the American College of Rheumatology (ACR) criteria but the SLICC criteria have not been evaluated in patients with SCLE. OBJECTIVE: We sought to determine how patients with SCLE/SLE meet the ACR and SLICC criteria to compare the 2 sets of criteria. METHODS: This was a retrospective analysis of 107 patients with SCLE enrolled in a database at the University of Pennsylvania. RESULTS: Patients with SCLE/SLE were more likely than those with only SCLE to have oral ulcers, positive anti-double-stranded DNA antibodies, and positive antinuclear antibody test findings using both sets of criteria. Patients with SCLE/SLE were also more likely to have low complement using the SLICC criteria. There was a statistically insignificant increase in individuals meeting the SLICC criteria. LIMITATIONS: Not all patients received comprehensive laboratory testing. CONCLUSIONS: Most patients with SCLE who formally meet criteria for SLE do so based on the laboratory and mucocutaneous criteria. Neither the ACR nor SLICC criteria distinguish patients with SCLE and major internal disease from patients with SCLE without major internal disease.

Cutaneous lupus erythematosus in skin of color.

Cutaneous Lupus Erythematosus (CLE) is a common manifestation in patients with Systemic Lupus Erythematosus. In a significant population of patients, CLE is the predominant feature and, in some cases, patients suffer from cutaneous disease alone. Chronic Cutaneous Lupus Erythematosus (CCLE) is a scarring subtype, more prevalent in blacks. Patients with skin of color may pose a challenge to physicians due to exaggerated cutaneous findings and increased risk of post-inflammatory hyperpigmentation and hypertrophic scarring. With the demographics of the United States rapidly shifting towards a greater population of non-Caucasian racial and ethnic groups, it is imperative that we expand on the limited research into molecular variation, clinical presentation, and therapeutic efficacy in CLE. The purpose of this review is to bring attention to the unique and severe aspects of CLE in persons of color, which calls for early and aggressive treatment.

Lupus erythematosus tumidus: a unique disease entity.

Lupus erythematosus tumidus (LET) is a photosensitive skin disease characterized by succulent, edematous, and non-scarring plaques. Histologic features include perivascular and periadnexal lymphocytic infiltration and interstitial mucin deposition. Despite being first described in 1909, there are few case reports in the current literature describing this disease and even fewer that discuss treatment. We describe a case of a 22-year-old woman with systemic lupus erythematosus (SLE) and secondary class V lupus nephritis. She was referred to Dermatology for an intermittent pruritic facial eruption that was clinically and histologically consistent with LET. There is much controversy in literature as to whether or not LET is a unique variant of cutaneous lupus erythematosus. Interestingly, the mainstay of treatment for LET, in the limited case reports and series that exist, is with antimalarial drugs, which our patient had already been taking for SLE. This case exemplifies the need for complete disease characterization, evidence-based treatment, and a multidisciplinary approach.

The classification and diagnosis of cutaneous lupus erythematosus.

Lupus erythematosus (LE) is an inflammatory connective tissue disease of generalized autoimmunity characterized by pathogenic autoantibodies and immune complexes, attributed to loss of immune tolerance. Cutaneous involvement, which appears in the majority of patients with the disease, can present as LE-specific or LE-nonspecific manifestations. The LE-nonspecific manifestations include e.g. vascular skin changes and may be associated with systemic organ manifestations or other autoimmune diseases. In contrast, the LE-specific manifestations encompass the various subtypes of cutaneous lupus erythematosus (CLE), which are classified as separate entities without or with less severe systemic organ involvement. In the "Duesseldorf Classification", CLE is subdivided into four different categories: acute CLE (ACLE), subacute CLE (SCLE), chronic CLE (CCLE), and intermittent CLE (ICLE). Differentiation between these subtypes is based on clinical features and average duration of the cutaneous lesions, but can also consider histological changes of skin biopsy specimens and laboratory abnormalities. In addition, direct immunofluorescence and photoprovocation may be applied to confirm the diagnosis in specific cases. Further investigations should be considered dependent on the clinical symptoms of the CLE patient and the results of the laboratory tests. A revised scoring system, the Cutaneous Lupus Erythematosus Disease Area and Severity Index (RCLASI) has recently been validated to assess disease activity and damage in CLE. In this review, we focus on the classification of CLE and the diagnostic procedures to identify and confirm the different subtypes of the disease.

Cutaneous lupus erythematosus: diagnosis and treatment.

Cutaneous lupus erythematosus (CLE) encompasses a wide range of dermatologic manifestations, which may or may not be associated with the development of systemic disease. Cutaneous lupus is divided into several sub-types, including acute CLE (ACLE), sub-acute CLE (SCLE) and chronic CLE (CCLE). CCLE includes discoid lupus erythematosus (DLE), LE profundus (LEP), chilblain cutaneous lupus and lupus tumidus. The diagnosis of these diseases requires proper classification of the sub-type, through a combination of physical examination, laboratory studies, histology, antibody serology and occasionally direct immunofluorescence, while ensuring to exclude systemic disease. The treatment of cutaneous lupus consists of patient education on proper sun protection along with appropriate topical and systemic agents. Systemic agents are indicated in cases of widespread, scarring or treatment-refractory disease. In this chapter, we discuss issues in classification and diagnosis of the various sub-types of CLE, as well as provide an update on therapeutic management.

Impact of smoking in cutaneous lupus erythematosus.

OBJECTIVE: To investigate cigarette smoking in cutaneous lupus erythematosus (CLE). DESIGN: Prospective longitudinal cohort study. SETTING: Urban cutaneous autoimmune disease clinic. PARTICIPANTS: A total of 218 individuals with CLE or systemic lupus erythematosus and lupus nonspecific skin disease seen between January 5, 2007, and July 30, 2010. MAIN OUTCOME MEASURES: Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) scores to assess disease severity and response to treatment and Skindex 29+3 scores to assess patient quality of life. RESULTS: Current smokers with lupus erythematosus had higher median CLASI scores (9.5) than did never (7.0) and past (6.0) smokers with CLE (P = .02). Current smokers had higher median scores on all the Skindex 29+3 subsets. Current smokers taking hydroxychloroquine sulfate had higher quinacrine hydrochloride use than did nonsmokers (P = .04). Two to 7 months after enrollment, current smokers (median CLASI change, -3) treated with only antimalarial agents improved more than never (1) and past (0) smokers (P = .02). Eight months or more after enrollment, current smokers (CLASI change, 3.5) treated with antimalarial drugs plus at least 1 additional immunomodulator improved less than never (-1.5) and past (0) smokers (P = .04). CONCLUSIONS: Current smokers with lupus erythematosus had worse disease, had worse quality of life, and were more often treated with a combination of hydroxychloroquine and quinacrine than were nonsmokers. Never and past smokers showed greater improvement when treated with antimalarial agents plus at least 1 additional immunomodulator. Current smokers had greater improvement when treated with antimalarial drugs only.

Lupus eritematoso túmido, una entidad en proceso de definición / Lupus Erythematosus Tumidus: A Clinical Entity Still Being Defined

El lupus eritematoso túmido (LET) es una forma de lupus eritematoso cutáneo (LEC) ya descrita en la literatura hace años. Sin embargo, no ha sido hasta la última década en que esta entidad ha generado un mayor interés, dando lugar a la publicación de numerosos trabajos que han permitido caracterizarlo como un subtipo de LEC con unos rasgos particulares. Dichos rasgos son, desde el punto de vista clínico, la ausencia de alteraciones en la superficie epidérmica (erosión, atrofia, descamación y taponamiento folicular) y la curación sin dejar cicatriz. Las lesiones son, por otra parte, fácilmente inducibles por la fotoexposición, por lo que suelen cursar a brotes. Sin embargo, algunas cuestiones acerca del LET, como son su clasificación, ciertas características microscópicas y el diagnóstico diferencial con otras entidades, como la erupción polimorfa lumínica o la infiltración linfocitaria de Jessner, siguen siendo objeto de controversia a día de hoy y dificultan el diagnóstico de estos pacientes (AU)

Lupus erythematosus tumidus (LET), a form of cutaneous lupus erythematosus that was described some years ago, has begun to receive more attention in the past decade as many published studies have helped to define the particularities of this subtype. The clinical features of LET include the absence of changes on the surface of the epidermis (such as erosion, atrophy, scaling, or follicular plugging) and the lack of scarring on resolution. Because flares are easily induced on exposure to sunlight, eruptions tend to occur in episodes. The diagnosis of LET remains difficult, however, as we continue to debate such issues as the classification of this disease, certain of its microscopic features, and the differential diagnosis of LET in relation to such entities as polymorphic light eruption or Jessner lymphocytic infiltration (AU)