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Development of a Core Set Questionnaire by the European Society of Cutaneous Lupus Erythematosus (EUSCLE)
Abstract
A study group of the European Society of Cutaneous Lupus Erythematosus (EUSCLE) developed a Core Set Questionnaire for the evaluation of patients with cutaneous lupus erythematosus (CLE). The aim of the EUSCLE Core Set Questionnaire is to gain a broad and comparable data collection of patients with CLE from different European centers, to achieve consensus concerning evidence-based clinical standards for disease assessment, and to develop diagnostic and therapeutic guidelines. The authors designed the EUSCLE Core Set Questionnaire by including parameters considered most relevant for the evaluation of CLE and compiled from international literature, clinical praxis, and long-term experience with this disease. The compilation of the different parameters for the evaluation of CLE resulted in the 4-sided EUSCLE Core Set Questionnaire with six sections on patient data, diagnosis, skin involvement, activity and damage of disease, laboratory analysis, and treatment. Thus, the EUSCLE Core Set Questionnaire for CLE constitutes a useful tool for the collection and evaluation of epidemiological data from patients with this disease. It enables consistent statistical evaluation, exchange, and comparison of patient's data within several European countries and provides a set of guidelines for standardized diagnostic and therapeutic strategies in CLE.
... 2 The Core Set Questionnaire developed by the European Society of Cutaneous Lupus Erythematosus (EUSCLE) provides a comprehensive assessment method of mucocutaneous involvement in lupus. 3 According to the Duesseldorf Classification, CLE is classified into four major categories: acute cutaneous lupus erythematosus (ACLE), subacute cutaneous lupus erythematosus (SCLE), chronic cutaneous lupus erythematosus (CCLE) and intermittent CLE (ICLE). [3][4][5] The major categories of CLE can also be further grouped into several secondary subtypes: ACLE consists of localised and generalised forms; SCLE, annular and papulosquamous types; CCLE, discoid lupus erythematosus (DLE); lupus erythematosus profundus (LEP); and chilblain lupus erythematosus (CHLE). ...
... 3 According to the Duesseldorf Classification, CLE is classified into four major categories: acute cutaneous lupus erythematosus (ACLE), subacute cutaneous lupus erythematosus (SCLE), chronic cutaneous lupus erythematosus (CCLE) and intermittent CLE (ICLE). [3][4][5] The major categories of CLE can also be further grouped into several secondary subtypes: ACLE consists of localised and generalised forms; SCLE, annular and papulosquamous types; CCLE, discoid lupus erythematosus (DLE); lupus erythematosus profundus (LEP); and chilblain lupus erythematosus (CHLE). 4 6 LE-non-specific cutaneous manifestations include photosensitivity, oral ulcers, non-cicatricial alopecia, Raynaud's phenomenon, vasculitis, etc. 3 4 7 In the EUSCLE Core Set Questionnaire, photosensitivity is self-reported by the patient based on history, whereas other skin lesions are objectively present. ...
... [3][4][5] The major categories of CLE can also be further grouped into several secondary subtypes: ACLE consists of localised and generalised forms; SCLE, annular and papulosquamous types; CCLE, discoid lupus erythematosus (DLE); lupus erythematosus profundus (LEP); and chilblain lupus erythematosus (CHLE). 4 6 LE-non-specific cutaneous manifestations include photosensitivity, oral ulcers, non-cicatricial alopecia, Raynaud's phenomenon, vasculitis, etc. 3 4 7 In the EUSCLE Core Set Questionnaire, photosensitivity is self-reported by the patient based on history, whereas other skin lesions are objectively present. 3 Therefore, we define LE-nonspecific cutaneous manifestations other than photosensitivity as LE-non-specific cutaneous lesions to distinguish them from photosensitivity. ...
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%).
... A lack of formalised consensus for the classification criteria of SCLE [11][12][13] required the development of inclusion criteria by a multinational panel of dermatologists, rheumatologists and a dermatohistopathologist ( Table 1). The agreed criteria incorporated morphological features specified by the European Society of Cutaneous Lupus Erythematosus (EUS-CLE) [18] and previously published features of the disease [14,19,20]. To avoid ambiguity, the presence of lesions in sun-exposed regions was used to define 'photosensitivity'. ...
... The devised scoring criteria combined multiple clinical factors to reflect the diagnostic approach to SCLE [18,19,36]. (8)(9)(10)(11)(12)(13)(14) In isolation, the specificity of many criteria is limited [12,37,38]. ...
... Some lesion types have been rarely considered as forms of SCLE, for example with gyrate, bullous or nodular appearances [40,41]. In keeping with the EUSCLE categories [18], these lesion types were considered to be non-specific LE forms and were not included in our morphological criteria of SCLE. We opted for a specific set of phenotypes to promote clear and comparable use of diagnostic terms, aiming to assist in research and clinical management. ...
Background:
Subacute cutaneous lupus erythematosus (SCLE) lacks consensus diagnostic criteria and the pathogenesis is poorly understood. There are increasing reports of SCLE induced by monoclonal antibodies (mAbs), but there are limited data on the aetiology, clinical characteristics and natural course of this disease.
Methods:
We devised a set of diagnostic criteria for SCLE in collaboration with a multinational, multispecialty panel. This systematic review employed a two-layered search strategy of five databases for cases of mAb-induced SCLE (PROSPERO registered protocol CRD42019116521). To explore the relationship between relative mAb use and the number of SCLE cases reported, the estimated number of mAb users was modelled from 2013 to 2018 global commercial data and estimated annual therapy costs.
Results:
From 40 papers, we identified 52 cases of mAb-induced SCLE, occurring in a cohort that was 73% female and with a median age of 61 years. Fifty percent of cases were induced by anti-tumour necrosis factor (TNF)-ɑ agents. A median of three drug doses preceded SCLE onset and the lesions lasted a median of 7 weeks after drug cessation. Oral and topical corticosteroids were most frequently used. Of the licensed mAbs, adalimumab, denosumab, rituximab, etanercept and infliximab were calculated to have the highest relative number of yearly users based on global sales data. Comparing the number of mAb-induced SCLE cases with estimated yearly users, the checkpoint inhibitors pembrolizumab and nivolumab showed strikingly high rates of SCLE relative to their global use, but ipilimumab did not.
Conclusion:
We present the first systematic review characterising mAb-induced SCLE with respect to triggers, clinical signs, laboratory findings, prognosis and treatment approaches. We identify elevated rates associated with the use of checkpoint inhibitors and anti-TNFɑ agents.
... In 2009, the European Society of Cutaneous Lupus Erythematosus (EUSCLE) developed a Core Set Questionnaire to gain a broad and comparable data set for patients with CLE from different European centres. 1,2 The EUSCLE Core Set Questionnaire was designed to include parameters that are considered the most relevant for evaluation of the different CLE subtypes and which were compiled from the international literature, clinical praxis, and long-term experience with the disease. The compilation of these different parameters resulted in the four-page EUSCLE Core Set Questionnaire with six sections: (A) patient data, (B) diagnosis, (C) skin involvement, (D) Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), (E) laboratory analysis and (F) treatment. ...
... The group's aim is to improve clinical research and to define diagnostic and therapeutic guidelines of the disease. 1 The structure of the EUSCLE Core Set Questionnaire and the included CLASI disease severity scoring system have been described previously. 2,3 According to Klein et al., 16 the CLASI activity scores of 0-9, 10-20 and 21-70 correspond to mild, moderate and severe disease, respectively. ...
... The parameters included in the EUSCLE Core Set Questionnaire were precisely defined in an associated glossary that was distributed to the participating centres. 1 The EUSCLE Core Set Questionnaire was completed for each patient at one time point by all participating centres. In the present analysis, we focused on sections D and F of the EUSCLE Core Set Questionnaire, which address the activity and damage of the disease using the CLASI scoring system, the treatment with antimalarials (at present, ever in the past), and the smoking behaviour (ever smoked: yes, no; smoked at the date of the first diagnosis: yes, no). ...
Background
In the last years, it has been controversially discussed in the literature if smoking is associated with the activity of cutaneous lupus erythematosus (CLE) and the efficacy of antimalarial agents.Objectives
To investigate the influence of smoking on disease severity and antimalarial treatment in patients with CLE using the Core Set Questionnaire of the European Society of Cutaneous Lupus Erythematosus (EUSCLE).MethodsA total of 1002 patients (768 female, 234 male) with different CLE subtypes were included in this cross-sectional study, which was performed in 14 different countries. Smoking behaviour was assessed by the EUSCLE Core Set Questionnaire and statistically analysed using an SPSS database. The results were correlated with the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the efficacy of antimalarial treatment.ResultsA high percentage (87.2%) of the 499 CLE patients, who have ever smoked, had already smoked by the date of their first diagnosis. Patients with intermittent CLE smoked significantly more often than patients with subacute CLE (p<0.05) and chronic CLE (p<0.05). The total CLASI activity and damage score of CLE patients was 6.6 ± 7.1 and 2.6 ± 4.3, respectively, and was higher in patients who have ever smoked than in non-smokers. Antimalarial treatment was successful in 84.3% of cases, with a significantly higher efficacy in non-smokers than in patients who have ever smoked (p<0.05). The total CLASI activity score was lower in CLE patients treated with antimalarials at the time point of the evaluation compared to untreated patients.Conclusion
This multicentre analysis of 1002 CLE patients assessed by the EUSCLE Core Set Questionnaire statistically confirms that smoking influences CLE disease severity and the efficacy of antimalarial treatment.This article is protected by copyright. All rights reserved.
... Patients were fully examined and skin samples were taken in the Department of Dermatology and Venereology of the Alexandrovska University Hospital -Sofia for a 4-year period (from 2017 till 2020). The diagnosis of CLE was based on the EUSCLE questionnaire [3] and according to the ACR 1997 and SLICC 2012 criteria [4]. The youngest investigated patient was 17 year-old, while the eldest one -80 year-old (mean patients' age of 48 years). ...
... Based on the Gilliam clinical/histologic classification [5], later revised by Werth [6] and Ting [7], the cutaneous lupus erythematosus lesions can be divided into LE-specific and LE-nonspecific ones. LE non-specific manifestations had been observed in about 30% of SLE patients and included Raynaud's phenomenon, urticaria vasculitis, alopecia, lupus pernio, palpable purpura, livedo reticularis, periungual telangiectasia, anetoderma, erythema multiforme, papulo-nodular mucinosis and others [3,6]. ...
Lupus erythematosus is an autoimmune connective tissue disorder showing a broad spectrum of clinical manifestations.
The aim of this study was to assess the correlation of skin histology and different types of lupus erythematosus.
Materials and methods: Fifty-one skin specimens were assessed from 39 female and 12 male patients with acute, subcutaneous and chronic lupus erythematosus, diagnosed and treated in the Department of Dermatology and Venereology, Alexandrovska University Hospital for a 4-year period.
Results: Follicular hyperkeratosis, epidermal atrophy, vacuolar degeneration and interface dermatitis were the most frequently observed lesions in chronic cutaneous lupus erythematosus while diffuse hyperkeratosis, epidermal atrophy and indistinct interface dermatitis in the dermis were predominant in subacute cutaneous lupus erythematosus. Lupus tumidus, a rare intermittent variant of cutaneous lupus erythematosus, showed almost no epidermal involvement and mucin deposition in the dermis. However, in one of our lupus tumidus patients the disease progressed to a systemic form with histological changes of acute cutaneous lupus erythematosus including atrophy, dermal-epidermal smoothing and lymphocytic infiltration in the dermis. Of note, a few patients showed histological changes of urticarial vasculitis-like and rheumatic-like patterns.
Conclusion: The correlation of clinical course, histopathological findings and immunological tests are of vital importance for the correct diagnosis and follow up of patients with lupus erythematodes, thus preventing complications and improving their quality of life.
... As a result, varying diagnostic and therapeutic strategies exist in different European centers, impeding the standardized comparison of patient data. Therefore , a study group of the European Society of Cutaneous Lupus Erythematosus (EUSCLE) defined a core set of variables for the evaluation of the characteristic features of the disease, resulting in development of the four-page EUSCLE Core Set Questionnaire [8]. By collecting data from CLE patients all over Europe, the non-profit working group EUSCLE aims to achieve a general consensus concerning evidencebased clinical standards for disease assessment and to develop diagnostic and therapeutic guidelines. ...
... The EUSCLE Core Set Questionnaire consists of four pages and is subdivided into six sections. The sections include (A) patient's data, (B) diagnosis, (C) skin involvement, (D) activity and damage of disease , (E) laboratory analysis, and (F) treatment [8]. All parameters were precisely defined by the EUSCLE study group, which developed the Core Set Questionnaire, and were communicated with every participating center. ...
In this prospective, cross-sectional, multicenter study, we assessed clinical and laboratory characteristics from patients with cutaneous lupus erythematosus (CLE) using the Core Set Questionnaire of the European Society of Cutaneous Lupus Erythematosus (EUSCLE). 1002 (768 females, 234 males) patients with different subtypes of CLE, such as acute CLE (ACLE, 304 patients), subacute CLE (SCLE, 236 patients), chronic CLE (CCLE, 397 patients), and intermittent CLE (ICLE, 65 patients), from 13 European countries were collected and statistically analyzed by an SPSS database. The main outcome measures included gender, age at onset of disease, LE-specific and LE-nonspecific skin lesions, photosensitivity, laboratory features, and the criteria of the American College of Rheumatology (ACR) for the classification of systemic lupus erythematosus. The mean age at onset of disease was 43.0 ± 15.7 years and differed significantly between the CLE subtypes. In 347 (34.6%) of the 1002 patients, two or more CLE subtypes were diagnosed during the course of the disease and 453 (45.2%) presented with LE-nonspecific manifestations. Drug-induced CLE and Sjögren´s Syndrome had the highest prevalence in SCLE patients (13.1% and 14.0%, respectively). Photosensitivity was significantly more frequent in patients with ACLE, SCLE, and ICLE compared with those with CCLE. The detection of antinuclear antibodies such as anti-Ro/SSA and anti-La/SSB antibodies revealed further significant differences between the CLE subtypes. In summary, the EUSCLE Core Set Questionnaire and its database facilitate the analysis of clinical and laboratory features in a high number of patients with CLE and will contribute to standardized assessment and monitoring of the disease in Europe.
... A study group of the European Society of Cutaneous Lupus Erythematosus (EUSCLE) defined a core set of variables for the evaluation of the characteristic features of the disease, resulting in the development of the four-page EUSCLE Core Set Questionnaire [20]. In a recent study, data of 1002 CLE patients from 30 centres were collected using the EUSCLE Core Set Questionnaire, and a statistical analysis of clinical and laboratory features was performed [21]. ...
... The EUSCLE Core Set Questionnaire was applied in 1002 patients with CLE [20,21]. In the present analysis, the efficacy of the therapeutic agents was assessed in section F of the EUSCLE Core Set Questionnaire (applying at present, applied ever in the past, ever successful: yes, no, unclear). ...
The aim of this prospective, cross-sectional, multicentre study performed by the European Society of Cutaneous Lupus Erythematosus (EUSCLE) was to investigate different therapeutic strategies and their efficacies in cutaneous lupus erythematosus (CLE) throughout Europe. Using the EUSCLE Core Set Questionnaire, topical and systemic treatment options were analysed in a total of 1002 patients (768 female and 234 male) with different CLE subtypes. The data were correlated with the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the criteria of the American College of Rheumatology for the classification of systemic lupus erythematosus. Sunscreens were applied by 84.0% of the study cohort and showed a high efficacy in preventing skin lesions in all disease subtypes, correlating with a lower CLASI activity score. Topical steroids were used in 81.5% of the patients, with an efficacy of 88.4%, whereas calcineurin inhibitors were only applied in 16.4% of the study population and showed an efficacy of 61.7%. Systemic agents including antimalarials and several immunomodulating drugs, such as systemic steroids and methotrexate, were used in 84.4% of the 1002 patients, particularly in cases of acute CLE. The CLASI activity and damage score was higher in treated CLE patients as compared to untreated patients, regardless of therapy with topical or systemic agents. In summary, preventive and therapeutic strategies of 1002 patients with different subtypes of CLE were analysed in this prospective, multicentre, Europe-wide study. Sunscreens were confirmed to be successful as preventive agents, and topical steroids showed a high efficacy, whereas antimalarials were used as first-line systemic treatment.
... The increase in sensitivity of SLICC-2012 compared with ACR-1997 seems to be predominantly attributed to the addition of considering positive renal histological examination as a sufficient condition as well as of subacute cutaneous lupus (38) and hypocomplementemia (5). As such, these three items that facilitate increasing sensitivity are still used in EULAR/ACR-2019. ...
Aim
To evaluate the diagnostic performance of the American College of Rheumatology (ACR)-1997, the Systemic Lupus International Collaborating Clinics (SLICC)-2012, and the European League against Rheumatism (EULAR)/ACR-2019 classification criteria in adult patients with systemic lupus erythematosus (SLE).
Methods
PubMed, Embase, Web of Science and Cochrane Library databases were searched for literature comparing the three classification criteria of ACR-1997, SLICC-2012 and EULAR/ACR-2019, which took clinical diagnosis as reference. Meta-analysis was used to evaluate and compare the sensitivity, specificity and diagnostic odds ratio of ACR-1997, SLICC-2012 and EULAR/ACR-2019. To assess the early diagnosis capability of the classification criteria, subgroups of patients with disease duration < 3 years and < 1 year were selected for comparison of sensitivity and specificity based on the inclusion of the original study. The sensitivity and specificity of each item in three sets of classification criteria were evaluated. In addition, the clinical and immunological characteristics of patients who did not meet the three classification criteria were compared.
Results
Nine original studies were included in the analysis, including 6404 SLE patients and 3996 controls. Results showed that the diagnostic odds ratios (95% confidence interval) of the SLICC-2012 [136.35 (114.94, 161.75)] and EULAR/ACR-2019 [187.47 (158.00, 222.42)] were higher than those of the ACR-1997 [67.53 (58.75, 77.63)]. Compared with ACR-1997[(0.86 (0.82, 0.89)], SLICC-2012[(0.96 (0.93, 0.97)] and EULAR/ACR-2019[(0.95 (0.92, 0.97)] had higher sensitivity. The specificity of the three classification criteria was similar: ACR-1997, SLICC-2012, and EULAR/ACR-2019 were 0.93 (0.89, 0.95), 0.86 (0.79, 0.91), and 0.91 (0.85, 0.95), respectively. The sensitivity of SLICC-2012 and EULAR/ACR-2019 were higher than that of ACR-1997 in early-course subgroups. Patients who did not meet ACR-1997 had more hypocomplementemia, patients who did not meet SLICC-2012 had more cutaneous lupus and photosensitivity, and patients who did not meet EULAR/ACR-2019 had more cutaneous lupus and leucopenia.
Conclusions
SLICC-2012 and EULAR/ACR-2019 have better diagnostic ability than the ACR-1997, and the sensitivity of the former two criteria is also higher than that of the latter; Moreover, the SLICC-2012 and EULAR/ACR-2019 for patients in the early stages of disease performed equally excellent.
... A secukinumabbal, JAK-gátlókkal és tirozin kináz gátlókkal kapcsolatos vizsgálatok jelenleg 2-es fázisban tartanak, melyek esetében terápiás robbanás várható(37).(35). Az EUSCLE egy meghatározott kérdőív használatát javasolja a klinikai tünetek felmérésére az epidemiológiai adatgyűjtésre és a terápiás guidelinok kifejlesztésére(36). A pathomechanizmus jobb megértése új terápiás alternatívák előtt nyitott utat. ...
The authors present the different clinical forms of cutaneous lupus erythematosus and their prognostic relevance, along with discusson of the uncommon subtypes of the disease. Furthermore, in addition to the lupus specific cutaneous symptoms, the nonspecific cutaneous manifestations are also reviewed. The newest diagnostic criterias and the EDF therapeutic guideline are summarized.
... The incidence of CLE was found to be "Duesseldorf Classification", which was published in the context of the first ICCLE 2004 in Duesseldorf, Germany, including LET as the intermittent subtype of CLE (ICLE) (Kuhn and Lehmann, 2004). In addition, Dr. Annegret Kuhn delivered an update on the European Society of Cutaneous Lupus Erythematosus (EUSCLE) and the core set questionnaire, which was originally published in 2009 with the aim to contribute to standardized assessment and monitoring of CLE and to develop diagnostic and therapeutic guidelines (Kuhn et al., 2009). Since then, 1002 patients from 30 centers in 14 countries were included in the database, documenting the clinical subtypes of this disease (ACLE 30.3%, SCLE 23.6%, CCLE 39.6%, and ICLE 6.5%) . ...
The Journal of Investigative Dermatology publishes basic and clinical research in cutaneous biology and skin disease.
... Der LE (CLE und SLE) gilt grundsätzlich als seltene Erkrankung. Zur Epidemiologie des CLE sind einige Untersuchungen erschienen [1,4,5]. Die Inzidenz des CLE liegt basierend auf einer schwedischen Studie an über 1 000 Patienten bei 4,0 pro 100 000 Einwohner und Jahr [6]. ...
... Incidence LE (CLE and SLE) is not a common disorder. Several studies have been published on the epidemiology of CLE [1,4,5]. The incidence of CLE is around 4.0 per 100,000 population and year, based on a Swedish study of over 1,000 patients [6]. ...
Lupus erythematosus (LE) is an important dermatologic autoimmune disease and in many aspects, including epidemiology, genetics, immunology, diagnostics and treatment, may be regarded as model for many other autoimmune diseases. Constant efforts in the past years have unraveled important new aspects of LE pathogenesis. Among these are the genetic associations with immunoregulatory signaling pathways such as TNF-, NF-κB-, IL23/IL17- and interferon pathway as well as new insights into the relevance of the innate immune system. Here Toll-like receptors and neutrophils play a central role. The knowledge about immune and autoimmune interactions in LE pathogenesis and the contributing cell types is steadily increasing and has led to new therapeutic approaches using antibodies directed against the B-cell activating factor BLyS. In the first part of this review article, the current knowledge about epidemiology, genetics and immunology is summarized. A second article will deal with diagnostics, clinical picture and different treatment modalities.
... Since its development, the CLASI has been used in several prospective studies involving the most common subsets of CLE [19,37]. The CLASI, favored by international consensus, is a useful clinical instrument to evaluate response of patients to therapies [48,49]. Recent studies have determined the minimal change in CLASI activity score that correlates with clinically significant improvement [48]. ...
Cutaneous lupus erythematosus (CLE) is an autoimmune inflammatory skin disease seen in patients with or without systemic lupus erythematosus. The management of CLE includes treatment and prevention of lesions as well as routine assessment for systemic disease. Treatment options include topical and systemic therapies. Topical therapies include corticosteroids and calcineurin inhibitors. Systemic therapies generally fall under one of three categories: antimalarials, immunomodulators (eg, dapsone and thalidomide), and immunosuppressives (eg, methotrexate and mycophenolate). Evidence for the treatment of CLE has been limited by few prospective studies and the lack of a validated outcome measure (until recently). There is good evidence to support the use of topical steroids and calcineurin inhibitors, although most of these trials have not used placebo or vehicle controls. There have been no randomized, placebo-controlled trials evaluating systemic therapies in the treatment of CLE.
... 24 However, they evaluate laboratory parameters and organ involvements that are not very representative of CLE. Recently, a standardized set of clinical core data has been suggested by the European Society for Cutaneous LE. 27 Early diagnosis and treatment are mandatory for CLE, especially in cases with scarring disease, to prevent any residual and irreversible disfiguration. Furthermore, the risk of neoplastic transformation in long-standing hypertrophic and scarring disease has to be minimized. ...
Cutaneous manifestations of lupus erythematosus (CLE) are manifold, presenting with unspecific skin manifestations or well-defined clinical dermatological entities. Their relation to each other as well as to systemic lupus erythematosus is variable, yet diagnostically and therapeutically challenging. Therapeutic decisions have to be based on the activity and distribution as well as the type of skin lesions and the extent of systemic disease. Limited skin manifestations may be amply tackled by topical therapy, so far, mainly relying on corticosteroids. In many cases, however, internal treatment has to be combined by using antimalarials, in addition to strict UV-protection. The advent of topical calcineurin inhibitors has contributed substantially to the armamentarium of external treatment options. By specifically interfering with intracytoplasmic signal transduction to activate the nuclear factor of activated T-cells (NF-AT), they are able to modulate various inflammatory mechanisms. The two available compounds, pimecrolimus and tacrolimus, do not induce the skin atrophy characteristic of corticosteroids. They have been studied in a number of case reports, but only in a few randomized, comparative studies. Both are well-tolerated, but differentially effective in the various subsets of CLE. Further studies are needed to directly compare the two compounds to each other, as well as to topical corticosteroids, before final recommendations can be made.
... All subjects were Caucasian, and the diagnosis and classification of CLE were performed according to the Düsseldorf Classification 2004 (11). Clinical data were evaluated by the recently developed and published Core Set Questionnaire of the 'European Society of Cutaneous Lupus Erythematosus' (12). It includes the 11 revised clinical and laboratory criteria of the American College of Rheumatology (ACR) for the classification of SLE (13). ...
Annexin 1 is an anti-inflammatory molecule and has also been described to be a common target of autoantibodies. In this study, we determined whether antibodies against annexin 1 can be detected in sera of patients with cutaneous lupus erythematosus (CLE). Levels of anti-annexin 1 antibodies were evaluated by a new established enzyme-linked immunosorbent assay and found to be significantly higher in sera of patients with CLE when compared to normal healthy donors (NHD). Moreover, the percentage of sera positively tested for anti-annexin 1 antibodies was elevated in patients with CLE when compared to NHD. In particular, the percentage of positive sera for anti-annexin 1 antibodies was significantly higher in patients with discoid lupus erythematosus (DLE); however, disease activity did not correlate with the antibody levels. The results of this study indicate that anti-annexin 1 antibodies in sera of patients with DLE might be a valuable aid in the diagnosis of this subtype.
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.ResultsA 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.ConclusionsA 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 registrationThis 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.
Background
Cutaneous lupus erythematosus is a chronic autoimmune disease that can leave important sequelae.
Objective
To determine the factors that predict the activity and damage of the skin disease, and the impact of tobacco on the efficacy of antimalarials using the Cutaneous Lupus Erythematosus Disease Area and Severity Index.
Materials and Methods
A consecutive case series was performed on 260 patients with cutaneous lupus erythematosus (α = 0.05; precision ± 6.5%). We carried out a descriptive analysis of the variables included, with a multivariate analysis to measure the association of variables with the Cutaneous Lupus Erythematosus Disease Area and Severity Index activity and damage ( p value < 0.05).
Results
The Cutaneous Lupus Erythematosus Disease Area and Severity Index activity was greater in smokers than non-smokers (4.0 ±5.3 vs 1.2 ±3.4, p = 0.006). No significant differences were observed in the Cutaneous Lupus Erythematosus Disease Area and Severity Index activity when the efficacy of antimalarials was analyzed between smokers and non-smokers. Cutaneous Lupus Erythematosus Disease Area and Severity Index damage was higher in smokers than in non-smokers (2.0 ± 3.6 vs 1.2 ± 2.6, p = 0.029). Cutaneous Lupus Erythematosus Disease Area and Severity Index activity was associated with: (a) being an active smoker (odds ratio 3.04, 95% confidence interval 1.68–5.51, p < 0.001; regression coefficient 2.05, 95% confidence interval 0.69–3.42, p = 0.003); (b) the chronic cutaneous lupus erythematosus subtype (odds ratio 1.98, 95% confidence interval 1.02–3.84, p = 0.044); and (c) C-reactive protein increase (≥0.5 mg/dL) (regression coefficient 2.56, 95% confidence interval 0.40–4.71, p = 0.020). Cutaneous Lupus Erythematosus Disease Area and Severity Index damage was associated with: (a) the activity (regression coefficient 0.11, 95% confidence interval 0.01–0.20, p = 0.024); (b) the chronic cutaneous lupus erythematosus subtype (regression coefficient 2.46, 95% confidence interval 1.37–3.56, p < 0.001); (c) the use of topical treatment (regression coefficient 1.31, 95% confidence interval 0.01–2.61, p = 0.049); and (d) systemic treatment (regression coefficient 1.44, 95% confidence interval 0.35–2.53, p < 0.010).
Conclusion
Smoking is related to an increase risk and a greater activity of cutaneous lupus erythematosus. The chronic cutaneous lupus erythematosus subtype and an increased C-reactive protein level were also associated with a higher disease activity. The sequelae were related to the activity, the chronic cutaneous lupus erythematosus subtype, and the use of topical and systemic treatment. The impact of tobacco on the efficacy of antimalarials may be caused by an increase in the severity of the disease more than by resistance in smokers.
Lupus erythematosus (LE) is an inflammatory autoimmune disease, characterized by a heterogeneous clinical presentation. The skin lesions are one of the most frequent symptoms of the disease and present with a broad spectrum of LE-nonspecific and LE-specific cutaneous manifestations. Therefore, the development of a classification for skin lesions in the disease has proven difficult. For example, the LE-nonspecific cutaneous manifestations include livedo racemosa, thrombophlebitis, and leukocytoclastic vasculitis and can be associated with high disease activity and systemic organ involvement. The LE-specific cutaneous manifestations encompass the subtypes of cutaneous lupus erythematosus (CLE): acute CLE, subacute CLE, and chronic CLE, such as discoid LE, chilblain LE, and LE profundus/panniculitis. In the “Duesseldorf Classification,” LE tumidus is included as a separate entity, named intermittent CLE. In this chapter, we describe the characteristic features of the various cutaneous manifestations of the disease.
Dermatological disease has a significant impact on quality of life (QoL). However, information is scarce for cutaneous lupus erythematosus (CLE) in this regard. Thus, the manifestation of and co-morbidities associated with CLE were assessed in the current study to determine factors predictive of QoL impairment. A descriptive cross-sectional study was performed on predominantly Caucasian patients with CLE, recruited at our institution between April 2013 and August 2016 (α = 0.050; precision ± 6.5%). This article is protected by copyright. All rights reserved.
SLE presents many challenges for clinicians. The onset of disease may be insidious, with many different symptoms and signs, making early and accurate diagnosis challenging. Tests for SLE in the early stages lack specificity; those that are useful later often appear only after organ damage is manifest. Disease patterns are highly variable; flares are not predictable and not always associated with biomarkers. Children with SLE may have severe disease and present special management issues. Older SLE patients have complicating co-morbid conditions. Therapeutic interventions have improved over recent decades, but available drugs do not adequately control disease in many patients, and successful outcomes are limited by off-target effects; some of these become manifest with longer duration of treatment, now in part revealed by improved rates of survival. Despite all of these challenges, advances in understanding the biological basis of SLE have translated into more effective approaches to patient care. This review considers the current state of SLE diagnosis and management, with a focus on new approaches and anticipated advances.
Lupus erythematosus (LE) is an inflammatory autoimmune disease, characterized by a heterogeneous clinical presentation. The skin lesions are one of the most frequent symptoms of the disease and present with a broad spectrum of LE-nonspecific and LE-specific cutaneous manifestations. Therefore, the development of a classification for skin lesions in the disease has proven difficult. For example, the LE-nonspecific cutaneous manifestations include livedo racemosa, thrombophlebitis, and leukocytoclastic vasculitis and can be associated with high disease activity and systemic organ involvement. The LE-specific cutaneous manifestations encompass the subtypes of cutaneous lupus erythematosus (CLE): acute CLE, subacute CLE, and chronic CLE, such as discoid LE, chilblain LE, and LE profundus/panniculitis. In the “Duesseldorf Classification”, LE tumidus is included as a separate entity, named intermittent CLE. In this chapter, we describe the characteristic features of the various cutaneous manifestations of the disease.
En este capitulo se revisan las manifestaciones cutáneas específicas y no especificas en el lupus eritematoso sistémico.
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.
Antimalarial agents ameliorate disease in more than half of patients with cutaneous lupus erythematosus (CLE), regardless of smoking status. The major determinant of responsiveness appears to be severity: more extensive CLE and CLE in the setting of systemic lupus erythematosus (SLE) respond less well to antimalarial therapy. Prospective studies are needed to determine whether antimalarials are more likely to benefit patients--smokers and nonsmokers--who have milder cutaneous lupus. Agreement on a single, validated disease severity measure for CLE would permit comparisons among studies and thereby foster progress in the field.
The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) is a scoring system for patients with cutaneous lupus erythematosus (CLE) to assess disease activity and damage. Objective The aim of this study was to evaluate whether the CLASI is a useful instrument which reflects the different subtypes of CLE comparably well in each parameter.
A total of 50 patients (42 female, 8 male) with different subtypes of CLE, including acute CLE (ACLE), subacute CLE (SCLE), chronic CLE (CCLE) and LE tumidus (LET), from the Departments of Dermatology, University of Düsseldorf, Germany, and Danderyd Hospital, Stockholm, Sweden, were evaluated using the CLASI at one time point.
The total CLASI activity score was significantly lower in patients with LET compared with ACLE (P<0.05) and CCLE (P<0.001), and the total CLASI damage score was significantly lower in patients with LET than with ACLE (P<0.05), SCLE (P<0.001) and CCLE (P<0.001). The erythema score and the scale/hypertrophy score were significantly lower in LET than in ACLE (P<0.05, both) and CCLE (P<0.05 and P < 0.001, respectively). The dyspigmentation score was lowest in patients with LET, differing significantly from ACLE (P<0.05), SCLE (P<0.05) and CCLE (P<0.001). The scarring/atrophy/panniculitis score was significantly higher in patients with CCLE in contrast to SCLE and LET (P<0.05 and P<0.001, respectively).
These data characterize the CLASI as an overall useful instrument to analyse disease activity and damage in CLE. However, the CLASI does not give an accurate assessment of all disease subtypes; therefore, a revision of the CLASI with critical analysis of all parameters is recommended.
The number of 2009 publications in indexed journals dealing with 'autoimmunity' has maintained its increasing trend compared to the previous five years. Numerous developments have been proposed in our understanding of systemic and organ-specific autoimmune diseases (particularly multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis) and of basic autoimmunity mechanisms (particularly Th17, T regulatory cells, and autoantibodies). Both these lines of evidence share a significant potential to be translated into new therapeutic options to impact clinical practice. This article will discuss selected publications from prominent scientific journals dedicated to immunology and autoimmunity and ultimately include some expectations in branches of autoimmunity that appear promising for future developments.
Epidemiological data and standard European guidelines for the diagnosis and treatment of cutaneous lupus erythematosus (CLE) are lacking in the current literature. In order to provide a standardized tool for an extensive consistent data collection, a study group of the European Society of Cutaneous Lupus Erythematosus (EUSCLE) recently developed a Core Set Questionnaire for the assessment of patients with different subtypes of CLE. The EUSCLE Core Set Questionnaire includes six sections on patient data, diagnosis, skin involvement, activity and damage of disease, laboratory analysis, and treatment. An instrument like the EUSCLE Core Set Questionnaire is essential to gain a broad and comparable data collection of patients with CLE from different European centres and to achieve consensus concerning clinical standards for the disease. The data will also be important for further characterization of the different CLE subtypes and the evaluation of therapeutic strategies; moreover, the EUSCLE Core Set Questionnaire might also be useful for the comparison of data in clinical trials. In this review, the impact of the EUSCLE Core Set Questionnaire is discussed in detail with regard to clinical and serological features as well as therapeutic modalities in CLE.
The aim of this study was to determine whether the Core Set Questionnaire developed recently by the European Society of Cutaneous Lupus Erythematosus (EUSCLE) is a useful tool to evaluate clinical features and therapeutic strategies in cutaneous lupus erythematosus. Disease characteristics were analysed in 50 patients with different subtypes of cutaneous lupus erythematosus from two European centres (Germany and Sweden). Mean age at onset of disease was 42.0 +/- 13.3 years (range: 7-69 years) and this differed significantly between the cutaneous lupus erythematosus subtypes. Moreover, 22 (44.0%) of the patients with cutaneous lupus erythematosus fulfilled four or more of the American College of Rheumatology (ACR) criteria; however, only 7 (14.0%) had severe systemic organ manifestations, such as kidney involvement. The analysis of serological features, such as antinuclear antibodies, revealed further significant differences between the cutaneous lupus erythematosus subtypes. In conclusion, the EUSCLE Core Set Questionnaire provides a useful tool for standardized collection and statistical analysis of data on cutaneous lupus erythematosus in clinical practice.
There is an increasing interest in improving the understanding of pathophysiology, outcome measures, and therapies of rheumatic skin disease. Increasingly, studies are using the skin as a primary endpoint for evaluating therapies. This will review the current state of the art for the most common rheumatic skin diseases.
A number of medications, including biologics such as tumor necrosis factor alpha and interferon, have been associated with onset of cutaneous lupus. The cutaneous lupus erythematosus area and severity index has been further validated and utilized in a number of studies. Smoking continues to be associated both with presence and refractoriness of cutaneous lupus erythematosus to therapy. There are several tools now available for evaluating the skin disease of dermatomyositis, but there is a need for new effective therapies. Measurement of skin disease in scleroderma continues to be a challenge, and there is a need for more effective therapies. Several studies show efficacy of intravenous iloprost for severe Raynaud's and skin ulcers, and of bosentan for digital ulcers.
The present review covers new outcome measures, treatments, and unusual manifestations of cutaneous lupus, dermatomyositis, scleroderma, and rheumatoid arthritis. There have been a number of new studies related to validation of disease activity measures, as well as their use in evaluation of new therapies for these conditions. Validated outcome measures are required to perform meaningful studies, and will facilitate organized epidemiologic, quality of life, and therapeutic studies.
Nonspecific cutaneous lesions in systemic lupus erythematosus (SLE) are morphologically varied (Table 7.1). Some lesions, such as urticarial-like vasculitis and livedo reticularis, are reflective of potentially serious complications. Others, however, such as hypopigmentation and hyperpigmentation and dermal mucinosis, have no prognostic significance.
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.
We developed and validated a measurement instrument (CLASI—Cutaneous Lupus Erythematosus Disease Area and Severity Index) for lupus erythematosus that could be used in clinical trials. The instrument has separate scores for damage and activity. A group of seven American Dermato-Rheumatologists and the "American College of Rheumatology Response Criteria Committee on SLE (systemic lupus erythematosus)" assessed content validity. After a preliminary session, we conducted standardized interviews with the raters and made slight changes to the instrument. The final instrument was evaluated by five dermatologists and six residents who scored nine patients to estimate inter- and intra-rater reliability in two sessions. Consultation with experts has established content validity of the instrument. Reliability studies demonstrated an intra-class correlation coefficient (ICC) for inter-rater reliability of 0.86 for the activity score (95% confidence interval (CI)=0.73–0.99) and of 0.92 for the damage score (95% CI=0.85–1.00). The Spearman's (Sp) for intra-rater reliability for the activity score was 0.96 (95% CI=0.89 to 1.00) and for the damage score Sp was 0.99 (95% CI=0.97–1.00). Clinical responsiveness needs to be evaluated in a prospective clinical trial, which is ongoing.Keywords: clinical trial, cutaneous lupus erythematosus, discoid lupus erythematosus, outcome instrument, subacute lupus erythematosus
The two dimensional classification system for lupus erythematosus (LE) is proposed. The terms for diagnoses and those for eruptions should be used separately. The terms for diagnoses are cutaneous-limited LE (CLE), intermediate LE (ILE) and systemic LE (SLE). CLE is an entity which has only cutaneous manifestations, and ILE has mild systemic manifestations. On the other hand, the terms for skin manifestations are chronic cutaneous LE (CCLE), subacute cutaneous LE (SCLE) and acute cutaneous LE (ACLE). CCLE includes discoid LE (DLE), chilblain LE and LE profundus. SCLE includes annular SCLE and papulosquamous SCLE. In this classification system, the condition of each LE patient is estimated integratedly both in systemic and cutaneous standpoints. Analyzing Japanese LE patients by this classification system, the usefulness of this system and the features of Japanese LE patients are discussed.
We reviewed the clinical and histological characteristics of the 44 cases of lupus erythematosus profundus (LEP) that have been encountered in our department. The female to male ratio was 4.5:1. The mean age of the females was 36 years, and the mean age of the males was 34 years. The most common sites were the face (38.4%) and upper limbs (26.0%). Even among the patients with LEP alone many of the positive patients had low antibody titers of 1:40 or 1:80. In 18 of the 44 cases SLE was complicated by LEP, and in those cases there was a tendency for LEP to develop during the course of SLE (11 cases). The important histological findings were lobular panniculitis associated with mucin deposition (32 cases) and a tendency to be associated with damage to the basal cell layer. In addition, the direct immunofluorescence test was positive in both the basement membrane (90.5%) and blood vessels (85.7%) in a high percentage of even the cases of LEP alone. Based on the above findings, LEP is a cutaneous variant of erythematosus, and the importance of the histological findings when making the diagnosis of LEP was reconfirmed.
In 1909, the term "lupus erythematodes tumidus" was first introduced by the German Dermatologist E. Hoffmann. The next case reports of lupus erythematosus tumidus (LET) were not described until 1930, and in the following years, only a few further cases were reported. This might have been due to the fact that authors have not considered LET as a separate entity different from other variants of cutaneous lupus erythematosus (CLE), and it is likely that skin lesions described under different designations represent the same disease entity. Therefore, LET has been underestimated and neglected in the literature and has been characterized by clinical, histopathological, and immunohistochemical features only in recent years. In particular, phototesting has been crucial in defining LET as a very photosensitive entity of CLE. Up to now, more than 40 reports of LET have been published demonstrating that the course and prognosis of LET are generally more favorable than in other subtypes of CLE. A new classification system, including LET as the intermittent subtype of CLE (ICLE) has been suggested. On the occasion of the 100th anniversary of the first description of LET, we have reviewed the literature and provide here an overview on the different aspects of the disease.
Histologic examination of lesions plays a key role in the diagnostics of cutaneous lupus erythematosus (LE). LE has a broad spectrum of histopathological signs, which are related to the stages of the lesions. In addition to the main subtypes of LE, we report on special manifestations like Rowell's-syndrome and Chilblain LE, and give an account of Kikuchi-Fujimoto disease (histiocytic necrotizing lymphadenitis), which may be associated with systemic LE. Furthermore the most considerable histopathologic differential diagnoses are discussed.
The 1971 preliminary criteria for the classification of systemic lupus erythematosus (SLE) were revised and updated to incorporate new immunologic knowledge and improve disease classification. The 1982 revised criteria include fluorescence antinuclear antibody and antibody to native DNA and Sm antigen. Some criteria involving the same organ systems were aggregated into single criteria. Raynaud's phenomenon and alopecia were not included in the 1982 revised criteria because of low sensitivity and specificity. The new criteria were 96% sensitive and 96% specific when tested with SLE and control patient data gathered from 18 participating clinics. When compared with the 1971 criteria, the 1982 revised criteria showed gains in sensitivity and specificity.
A review is presented of the clinical, histological, and immunological aspects of the several subsets of 'cutaneous' LE.
The prevalence rates of systemic lupus erythematosus (SLE) may vary within 17-48/100 000 population worldwide. Although population-based epidemiological studies are still missing, the cutaneous variants of lupus erythematosus (LE) are 2-3 times more frequent than SLE itself. The most common age of onset is 20-40 y. Overall, cutaneous LE is regarded as a variant with less severe course and better prognosis. However, CDLE and SCLE last for many years and may lead, like SLE, to severe disability for work and limited life quality; also, a small proportion of patients with cutaneous LE develops SLE during the course of their disease. This implies considerable amount of medical management and costs for the community. Early recognition of cutaneous LE patients at risk to develop SLE and preventive measures against disease triggering factors are important tasks for physicians attending with cutaneous LE patients. It seems that signs of nephropathy, elevated ANA-titers and arthralgias may serve as prognostic predictors for transition into SLE.
Characteristic features of cutaneous LE are photosensitivity and female predominance. UV light is a major environmental triggering factor in cutaneous LE. Skin lesions may be induced or preexistent lesions may exacerbate due to UV light in up to 80-90% of all patients. Therefore, socioeconomic counseling of the young patients, for example choice of occupation and sun protection, are essentials in compliant patients. Also, since females are 3—6 times more frequently affected than males, the possibility of hormonal influences including pregnancy and estrogen- containing drugs should be discussed. Risk considerations for females wishing to become pregnant are required, and avoidance of estrogen-containing contraceptives should be recommended.
It has long been observed that sun exposure can induce or exacerbate skin lesions in patients with certain forms of lupus erythematosus. Despite the frequency of photosensitivity in these patients, the mechanism by which ultraviolet radiation alters the pathogenic course of this disease remains poorly understood. After development of standardized test methods, our group demonstrated in 1986 that skin lesions in patients with lupus erythematosus can be experimentally reproduced by UVA and UVB irradiation. In the following years, phototesting has received much attention as a valid model to study photosensitivity of different forms of lupus erythematosus and the pathogenetic mechanism of this disease. Further investigations have also made it possible to find genetic and immunologic factors associated with photosensitivity and have helped to identify the pathophysiologic steps involved in the induction of such skin lesions. We present phototesting results and clinical correlations of more than 400 patients with different forms of lupus erythematosus and discuss the recent advances in provocative phototesting.
The skin findings seen in lupus erythematosus can present with either lupus-specific or lupus-nonspecific findings, with lupus-specific skin disease showing findings histopathologically distinct for cutaneous lupus erythematosus. Lupus-specific skin diseases include chronic cutaneous, subacute cutaneous, and acute cutaneous lupus erythematosus. The types of skin lesions in each group are clinically distinct and recognizing the specific subsets helps in prognosticating the likelihood of underlying systemic lupus. A number of medications are associated with cutaneous lupus, in particular with subacute cutaneous lupus erythematosus. Lupus nonspecific skin lesions are not histopathologically distinct for cutaneous lupus and/or may be seen as a feature of another disease process. Nonspecific disease-related skin lesions are frequently seen in patients with SLE, usually in the active phase of the disease. The current ACR classification criteria for SLE include four somewhat overlapping dermatologic criteria, butterfly rash, discoid lupus, photosensitivity, and oral ulcers and thus patients can be classified as having SLE with only skin manifestations.
Lupus erythematosus (LE) is an autoimmune disease which can be triggered by environmental factors such as solar irradiation. It has long been observed that especially ultraviolet (UV) exposure can induce and exacerbate skin lesions in patients with this disease. However, despite the frequency of photosensitivity in LE, the mechanisms by which UV irradiation activates autoimmune responses is only now becoming increasingly unfolded by advanced molecular and cellular biological investigations. Phototesting, according to a standardized protocol with UVA and UVB irradiation has proven to be a valid model to study photosensitivity in various subtypes of LE and to evaluate the underlying pathomechanisms of this disease. Detailed analysis of the molecular events that govern lesion formation in experimentally photoprovoced LE showed increased accumulation of apoptotic keratinocytes and impaired expression of the inducible nitric oxide synthase (iNOS). In the near future, gene expression profiling and proteomics will further increase our knowledge on the complexity of the "UV response" in LE. This review summarizes the current understanding of the clinical and molecular mechanisms that initiate photosensitivity in this disease.
To estimate the incidence and prevalence of Ro/SSA-positive subacute cutaneous lupus erythematosus (SCLE) in Stockholm County, Sweden (1.8 million inhabitants) and to investigate the frequency of photosensitivity and other clinical manifestations associated with Ro/SSA autoantibodies.
Ro/SSA-positive patients in Stockholm were identified via registry-based searches. All patients who tested positive for the presence of Ro/SSA autoantibodies during 1996-2002 (n = 1,323; 85% women) were identified. A questionnaire was sent to all patients still living in Stockholm in 2003 (n = 1,048). Patients who reported having skin symptoms and photosensitivity (n = 125) underwent a clinical examination.
Of the 741 (71%) of 1,048 Ro/SSA-positive patients who responded to the questionnaire, 400 (54%) reported having photosensitivity, and of these patients, 125 agreed to be clinically examined. A diagnosis of LE was confirmed in 59 of the 125 patients (SCLE in 20, systemic LE [SLE] in 33, and chronic CLE in 6). Eighty-six patients reported experiencing symptoms consistent with polymorphous light eruption (PLE). Comorbidities such as cardiovascular disease, autoimmune disease, and other skin diseases were common. The incidence of Ro/SSA-positive SCLE during the study period was estimated to be 0.7 cases per 100,000 persons per year and the prevalence was approximately 6.2-14 in 100,000 persons.
The incidence of Ro/SSA-positive SCLE in Stockholm County, Sweden is estimated to be 0.7 per 100,000 persons per year as compared with an incidence of SLE in Sweden of 4.8 per 100,000 persons per year. The prevalence is estimated to be 6.2-14 in 100,000 persons. Self-reported photosensitivity commonly corresponds to a history of PLE in Ro/SSA-positive patients, even when the clinical profile of SCLE is absent. Photoprotection should therefore be included in the treatment recommendations for these patients.
Skin involvement is a frequent presenting manifestation of systemic lupus erythematosus (SLE). Cutaneous lupus erythematosus (CLE), frequently occurring without SLE, may be even more common than SLE. Until recently, clinical instruments to measure skin involvement in CLE did not exist, hampering clinical research in this field. In this paper the present authors describe outcome instruments for SLE and outline the considerations underlying the design and validation of an outcome instrument for CLE, the cutaneous lupus disease area and severity index. These studies serve as a model for development and validation of standardized instruments that can be applied to other cutaneous diseases, particularly autoimmune diseases, in order to facilitate epidemiologic studies and clinical trials.
Spain); Dusan Skiljevic (Clinical Center of Serbia, Serbia)
- Julia Sanchez
Julia Sanchez (Hospital del Mar, Spain); Dusan Skiljevic (Clinical Center of Serbia, Serbia);
Distinctive cutaneous subsets in the spectrum of lupus erythematosus
- Gilliam