Article

Cutaneous Lupus and the Cutaneous Lupus Erythematosus Disease Area and Severity Index Instrument

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Abstract

This article provides an overview of cutaneous lupus erythematosus, including classification schemes, disease subtypes, and therapy. It also describes the Cutaneous Lupus Erythematosus Disease Area and Severity Index, a novel clinical outcome instrument that quantifies cutaneous activity and damage in cutaneous lupus erythematosus.

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... A recent review reports that the risk of SLE is highest in Acute Cutaneous Lupus Erythematosus (ACLE), followed by Subacute Cutaneous Lupus Erythematosus (SCLE), and lowest in Chronic Cutaneous Lupus Erythematosus (CCLE) [4]. One recent Swedish study demonstrated that the probability of being diagnosed with SLE during the first 3 years after SCLE diagnosis was 24.7 %, and for Discoid Lupus Erythematosus (DLE) the probability was 16.7 % [1@BULLET@BULLET]. ...
... One recent Swedish study demonstrated that the probability of being diagnosed with SLE during the first 3 years after SCLE diagnosis was 24.7 %, and for Discoid Lupus Erythematosus (DLE) the probability was 16.7 % [1@BULLET@BULLET]. Older studies, however, have shown a higher progression of DLE to SLE [4] than in this study [1@BULLET@BULLET] , but the discrepancy could be explained by differences in follow-up. In DLE patients, generalized in contrast to localized DLE may be a prognostic sign for SLE development4567 . ...
... Older studies, however, have shown a higher progression of DLE to SLE [4] than in this study [1@BULLET@BULLET] , but the discrepancy could be explained by differences in follow-up. In DLE patients, generalized in contrast to localized DLE may be a prognostic sign for SLE development4567 . SLE development was demonstrated in 13 % of generalized DLE patients compared with 1 % of localized DLE patients in Barcelona, Spain (p=0.003) ...
Article
Cutaneous Lupus Erythematosus (CLE) and Dermatomyositis (DM) are cutaneous autoimmune diseases that have been among the least systematically studied, due in part to the lack of validated outcome instruments in the past. More recent epidemiologic studies have elucidated the incidence and prevalence of these diseases and their subtypes. In addition, the advent of validated clinical outcome measures, including the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), has led to an objective means of measuring activity and damage of the disease. These outcome measures have established the framework for evaluating responsiveness and therapeutic efficacy in clinical trials as well as longitudinal studies to study disease course.
... 2,3 LE-nonspecific cutaneous findings, such as vasculitis or alopecia, occur frequently in patients with LE but may also be seen outside LE and do not show histological features characteristic for LE. [2][3][4] There are known differences in demographics and disease patterns between childhood-onset and adult-onset systemic lupus erythematosus (SLE). 5 Demographic and clinical characteristics for CLE in adults are also described in the literature; however, similar information specific to paediatric CLE is lacking. ...
... Modified Gilliam criteria were used to classify the subtypes (Table 1). 1,2,6 Puberty status was assigned by an age cut-off of 12 years based on U.S. national averages. 7 This study was conducted in Milwaukee, WI, U.S.A. ...
... Lupus erythematosus (LE) skin lesions, based on the modified Gilliam and vesiculobullous classification1,2,6 I. LE-specific skin disease (characterized by interface dermatitis) ...
Article
Background: Paediatric cutaneous lupus erythematosus (CLE) is uncommon and inadequately described in the literature. Similar to adults, children with CLE develop LE-specific and/or LE-nonspecific skin findings. Similarities and differences in demographics and clinical course between paediatric and adult CLE have not been sufficiently described. Objectives: To detail the demographic and clinical features of paediatric CLE and compare these findings with those reported in the adult literature. Methods: A retrospective chart review was performed of 53 children seen in a paediatric dermatology clinic with cutaneous manifestations of LE. Results: Patients presented with all five major subtypes of CLE, with some notable differences from adult CLE and previously published reports of paediatric CLE. Progression from discoid LE to systemic LE (SLE) did not occur in our cohort. Patients with subacute CLE were more likely than adults to have lesions below the waist as well as concomitant SLE. Sex distribution for CLE in our study was equal prior to puberty and female predominant in post-pubertal patients. Conclusions: Children with CLE have variable clinical presentations and progression to SLE that may be different from adult disease. Specifically, children with acute and subacute CLE may be more likely than adults to have systemic disease; therefore, patients with these subtypes should be monitored closely for evidence of SLE. Study limitations included small patient numbers that may limit the ability to generalize these data and relatively short follow-up intervals.
... Typically, it is localised to the head or neck (%70% of cases), with a high prevalence of photosensitivity. 2 Generalised discoid lupus erythematosus, affecting the limbs and trunk, has been associated with a greater incidence of systemic symptoms. 1,2 Presentations with scalp lesions and follicular plugging tend to progress to scarring alopecia. ...
... Typically, it is localised to the head or neck (%70% of cases), with a high prevalence of photosensitivity. 2 Generalised discoid lupus erythematosus, affecting the limbs and trunk, has been associated with a greater incidence of systemic symptoms. 1,2 Presentations with scalp lesions and follicular plugging tend to progress to scarring alopecia. 1,3 Accurate epidemiology of discoid lupus erythematosus is hampered by the retrospective nature of existing studies. ...
... Bu çalışmada, dermatolog ve romatologlar başta olmak üzere, lupuslu hastaları değerlendirmede pratik şekilde kullanabilecek bir ölçeğin Türkçe'ye kazandırılması ve bu ölçeğin bir grup lupus hastasına uygulanarak, hastaların sosyo-demografik ve klinik özelliklerinden etkilenip etkilenmeyeceğinin ortaya konulması amaçlanmıştır. 14 . Literatürde daha yüksek skorlara rastlanmakla birlikte, çalışmamızda hastaların çoğunun SLE hastası olması ve bunların yeterli tedavi almakta olan takipteki hastalar olmaları nedeniyle, aktivite ve hasar skoru daha düşük bulunmuştur ve bu da çalışmamızı kısıtlamıştır. ...
... Hastalığın monitorizasyonu için birçok protokol belirlenmiştir. Bunlar arasında İngiliz adalar lupus değerlendirme grubu skala indeksi (BILAG), SLE hastalık aktivite indeksi (SLEDAI), sistemik lupus aktivite hesaplaması (SLAM) ve lupus aktivite indeksi (LAI) yer alır14 . Bu skorlama sistemleri daha çok hastalığın sistemik organ tutulumlarına yöneliktir. ...
Article
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Background and Design: The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) is used to evaluate the cutaneous manifestations in patients with lupus erythematosus (LE). In recent years, the Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (RCLASI) which provides more objective assessment has been developed, but the number of studies utilizing RCLASI are limited. The aim of this study was to increase the clinical use of the RCLASI by translating this scale into Turkish and to evaluate the effects of factors, which affect CLASI, on RCLASI. Materials and Methods: The scale was translated into Turkish by using proper international translation steps. Ninety-three LE patients who were admitted to Trakya University Faculty of Medicine were included in this study. Socio-demographic and clinical characteristics of the patients were recorded. Cutaneous manifestations were calculated using RCLASI. Two scores were obtained: activity and damage scores. The relationship of the scores with patient age, gender, duration of illness, facial involvement, subtypes of LE, and antinuclear antibody, Anti-Ro/ SS-A antibody and Anti-La/SS-B antibody positivities were evaluated. Results: The mean activity and damage scores were 2.59±2.88 and 0.81±1.88, respectively. When activity and damage scores were compared between the age groups, there was no statistically significant difference. The damage scores were significantly higher in male patients than in female patients. The activity scores were statistically significantly higher in patients with disease duration of more than three years and facial involvement. There was no statistically significant difference between the subtypes of LE and the activity and damage scores. RCLASI damage scores were statistically significantly higher in Anti-La/SS-B antibody positive patients. Conclusion: RCLASI is an appropriate scoring system to evaluate the cutaneous manifestations in patients with LE. The scores obtained from this scale may vary depending on gender, disease duration and presence of facial involvement.
... Four major subtypes are defined according to the modified Gilliam grouping system. 3 Many clinical phenotypes can present within each of these major subtypes. Discoid LE (DLE) is the most common form of chronic CLE (CCLE), and as many as 25% of those with SLE have discoid lesions. ...
... [6][7][8][9][10][11] Clinically, less autoantibody production (20% in DLE) and a weaker association of CCLE with SLE (6%-28%) also support the notion of variable underlying pathogenic pathways in different clinical scenarios. 3,14,15 Treatment of CLE commonly focuses on strict photoprotection, topical therapies, systemic corticosteroids, antimalarials, or broadly immunosuppressive corticosteroid-sparing agents. More recently, treatment with biologic agents targeting B cells, such as rituximab, have shown efficacy in many inflammatory conditions, including SLE. ...
Article
Importance Cutaneous lupus erythematosus (CLE) can be severe and treatment resistant. B-cell depletion therapy (BCDT) with rituximab is well recognized in organ involvement in systemic lupus erythematosus (SLE), but its efficacy in cutaneous manifestations is less well established. Objective To evaluate the outcomes of BCDT in CLE and its clinical subtypes in the setting of associated SLE. Design, Setting, and Participants This single-center, retrospective, cohort study was performed at the adult tertiary referral Rheumatology Department of University College London Hospital, London, United Kingdom, from January 1, 2000, through March 31, 2016, with 12-month follow-up completed on March 31, 2017. Adult patients with carefully classified CLE and mucocutaneous British Isles Lupus Assessment Group (BILAG) grade A or B who were treated with rituximab BCDT were selected from a prospective database of 709 patients with SLE. Data were analyzed from April through December 2017. Main Outcomes and Measures Clinical response was examined at 6 and 12 months after treatment for CLE and its subtypes acute CLE (ACLE), subacute CLE (SCLE), chronic CLE (CCLE), and nonspecific LE (NSLE). A complete response was defined as achieving BILAG grade D; partial response, BILAG grade C; stable disease, no change; and disease flare, change from BILAG grade C or D to grade A or B. Results A total of 50 patients with SLE were eligible for inclusion; mean (SD) age at diagnosis was 26.9 (12.1) years, and 49 (98%) were women. Twenty-one patients had ACLE; 6, SCLE; 10, CCLE; and 11, NSLE (including 2 with concurrent ACLE and CCLE). Overall, at 6 months, 38 patients (76%) improved their mucocutaneous BILAG grade A or B status, including 20 (40%) with a complete response. At 12 months, 28 of 46 patients (61%) maintained this response, including 24 (52%) with a complete response. Two of 6 patients (33%) with SCLE showed a complete response at 6 and 12 months. Five of 12 patients (42%) with CCLE showed a complete response at 6 months, and 5 of 11 (45%), at 12 months. Fifteen patients (30%) required further rituximab therapy within 12 months for cutaneous involvement. Conclusions and Relevance B-cell depletion therapy using rituximab appears effective in patients with SLE and severe active CLE; however, outcomes are variable in those with SCLE and CCLE subtypes.
... Biazar et al. [20] reported that 408 of the 1002 (40.7%) patients with CLE fulfilled four or more ACR criteria for SLE. Recent review reports that the risk of SLE is highest in ACLE, followed by SCLE and lowest in CCLE [30]. In our series, patients with ACLE fulfilled criteria for SLE more frequently than patients with SCLE (71.1% vs 41.1%, p=0.001) as well as than those with CCLE (71.1% vs 6.3%, p<0.001). ...
Article
Full-text available
Abstract Background: Patients with acute cutaneous lupus erythematosus (ACLE) usually have systemic manifestations and there is a strong association between ACLE and systemic lupus erythematosus (SLE) involvement. However, there is scarce information on the differences in the systemic manifestations when compared with subacute cutaneous lupus erythematosus (SCLE) and chronic cutaneous lupus erythematosus (CCLE). Objective: To analyse and compare the prevalence and characteristics of the main clinical and immunological manifestations of patients with ACLE, who were initially attending a Department of Dermatology, with respect to those with SCLE and CCLE. Methods: A total of 38 patients with ACLE were studied. The clinical and serological characteristics of all the patients were collected in a chart review. These patients were compared to 112 patients with SCLE and 158 with CCLE that were previously reported. Results: Patients with ACLE had a higher prevalence of mucous membrane ulcers (p=0.012), livedo reticularis (p=0.036), vasculitis (p=0.030), nephropathy (p=0.025) and serositis (p=0.036) compared with patients with SCLE. Patients with ACLE also had a higher frequency of livedo reticularis (P=0.001), mucous membrane ulcers (P<0.001), vasculitis (P<0.001), arthralgias (P<0.001), arthritis (P<0.001), nephropathy (P<0.001) and serositis (P=0.005) compared with patients with CCLE. Furthermore, we detected that patients with ACLE had a higher prevalence of decreased C4 and CH50 levels than SCLE, and a higher frequency of decreased C3, C4 and CH50 levels than CCLE. Conclusions: In our series, differences in the expression of ACLE, CCLE and SCLE were found with respect to the distribution and type of lesions, the systemic features and the immunological findings.
... The clinical heterogeneity of CLE is well recognized. Four major subtypes are defined according to the modified Gilliam grouping system [9]; among them, the discoid LE (DLE) is the most common form of chronic CLE. In a previous study, we evaluated the prevalence of HBV and HCV infection, together with the possible associations with clinical, epidemiological characteristics in a large cohort including patients affected by SLE and CLE attending the Lupus Clinic of the Rheumatology Unit, Sapienza University of Rome (Italy) [10]. ...
Article
Full-text available
Hepatitis B virus (HBV) infection is a serious global health problem. Patients with autoimmune diseases, such as Lupus Erythematosus, are exposed to a higher risk of acquiring infections. In this study, a molecular characterization, genomic investigation of the Hepatitis B virus, polymerase (P) and surface (S) genes, from a patient affected by Cutaneous Lupus Erythematosus (CLE), was presented. Viral DNA was extracted from 200 μL of serum, and the HBV-DNA was amplified by real-time polymerase chain reaction (PCR) with the Platinum Taq DNA Polymerase. The PCR products were purified and sequencing reactions were performed. A phylogenetic analysis was performed through maximum likelihood and Bayesian approaches. The HBV CLE isolate was classified as sub-genotype D3 and related to other Italian HBV D3 genomes, and some from foreign countries. No drug resistant mutations were identified. One mutation (a.a. 168 M) was located in the last part of the major hydrophilic region (MHR) of the surface antigen (HBsAg). Moreover, three sites (351G, 526Y, 578C) in the polymerase were exclusively present in the CLE patient. The mutations identified exclusively in the HBsAg of our CLE patient may have been selected because of the Lupus autoantibodies, which are characteristic in the Lupus autoimmune disease, using a possible molecular mimicry mechanism.
... The first line management of all LE-specific skin diseases include photoprotection from sunlight and artificial sources of UV light [7]. The use of high-potency sunscreens especially for parts of the body that cannot effectively be covered by clothing is very important [8]. The used sunscreens must be photostable, and they must get rid of the absorbed energy through photophysical or photochemical pathway that rule out the formation of harmful oxygen species which can cause deleterious damage to DNA if they are transported to human cells [9]. ...
Article
Discoid lupus erythematosus is a condition of chronic inflammation of the skin which requires protection from ultraviolet radiations and prolonged treatment with topical corticosteroids. The aim of this study was to prepare semisolid nanostructured lipid carrier (NLC) formulations containing diflucortolone valerate (DFV) as a model corticosteroid drug and titanium dioxide (TiO2) as an inorganic UV-filter in the same formulation. The NLC formulations were prepared by applying high shear homogenization and ultrasonication techniques using Precriol®ATO5 or Tristearin® as the solid lipids, Capryol™ or isopropyl myristate as the liquid lipids, Poloxamer® 407 as a surfactant and Labrafil® M1944CS as a lipid based surfactant. The incorporation of TiO2 in the NLCs in concentration of 5% w/w was found to be the optimum concentration which enhances the intrinsic sun protection factor (SPF) of this carrier system and resulted in suitable sun protection values ranged from 4.94 to 21.27 with an acceptable spreadable consistency for the NLC formulation. Semi-solid NLC formulations were characterized by small particle size ranged from 180.8 to 255.1 nm before the addition of TiO2 and the particle size reached 540.1 nm after addition of 5% TiO2. Incorporation of TiO2 in NLC formulations leads to a synergistic photoprotection and increase patient compliance.
... The CLASI scoring system provides a validated measure of cutaneous involvement that has been shown to be responsive to treatment-induced reductions in lupus skin lesions. 26 Both CLASI and the Tender and Swollen Joint Count assess cutaneous and musculoskeletal manifestations of SLE at a specific point in time, and have been used in other investigational SLE trials to verify measures of disease activity in these organ systems captured by SLEDAI and BILAG. 19 Significant response to RCI was not reflected by the PGA, a subjective assessment describing global disease activity at a single point in time. ...
Article
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Objective To evaluate the efficacy of a prolonged-release formulation of a porcine adrenocorticotropic hormone analogue (repository corticotropin injection (RCI)) added to standard of care in patients requiring moderate-dose corticosteroids for symptomatic SLE. Methods This prospective, randomised, double-blind, phase 4, pilot study (NCT01753401) enrolled 38 patients with persistently active SLE involving skin and/or joints. Enrolled patients received RCI, 40 U daily or 80 U every other day, or volume-matched placebo gel, for 8 weeks, with dose tapering to twice weekly during weeks 5–8. Efficacy endpoints included proportion of responders at week 4 based on a novel composite measure that included resolution of rash or arthritis measured using the hybrid SLE Disease Activity Index (hSLEDAI) without worsening British Isles Lupus Assessment Group (BILAG) scores in other organ systems at week 4 (primary), as well as improvements in total hSLEDAI and BILAG scores and other measures of skin and joint disease activity over the 8-week treatment period. Results Response, as defined for the primary endpoint, did not differ significantly between the combined placebo and RCI-treated groups at week 4. At week 8, the proportion of responders was higher in RCI-treated patients but did not statistically differ between groups (RCI 40 U (53.8%), RCI 80 U (33.3%), combined placebo (27.3%)). However, RCI treatment was associated with statistically significant improvements in several secondary endpoints, including total hSLEDAI, total BILAG and Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity scores within 8 weeks. Treatment was well tolerated. Conclusions Although the primary endpoint was not met in this pilot study, secondary and post hoc analyses suggested that RCI was associated with improvements in SLE disease activity in a select patient population with steroid-dependent persistent disease. Trial registration number NCT01753401; results.
... [73] CLASI is a clinical tool to follow disease progression in an individual patient, classify patients into severity groups, determine responsiveness after treatment, and compare new therapies. [21,74,75] A revised version of CLASI (RCLASI) has also been developed as an alternative instrument to assess disease severity. [76] Newer epidemiological studies based on population-based registries and ongoing CLE quality registers as well will improve the knowledge and treatment of CLE. ...
Article
Full-text available
Lupus erythematosus (LE) is a chronic, autoimmune, multisystem disease that displays many diverse symptoms in which localized cutaneous LE (CLE) is on one end of the spectrum and severe systemic LE (SLE) on the other end. The underlying cause of LE is unknown but the etiology is thought to be multifactorial and polygenic. CLE is a disfiguring, chronic skin disease, with a significant impact on the patients' everyday life. CLE are further divided into three main subsets: Acute CLE (ACLE), subacute CLE (SCLE) and chronic CLE (CCLE), where classic discoid LE (DLE) is the most common form. These subsets are defined by clinical symptoms, average duration of symptoms and histological and serological findings, although, the three subtypes can have overlapping clinical features. CLE patients display well-defined skin lesions, often in sun-exposed areas. The disease often has a chronic and relapsing course that can be induced or aggravated by UV light. It is important to confirm a CLE diagnosis histopathologically by a biopsy and in that there are several differential diagnoses and because CLE is a chronic disease in which regular follow-up is important and systemic treatment is sometimes indicated.
... In most cases, the disease is localized and limited to the skin area, without multisystemic involvement characteristic of SLE. While approximately 10%–40% of CLE—depending on the clinical subset of CLE—may transit to systemic disease, skin lesions in the setting of SLE can occur in up to 70% of patients during the disease course [74, 75]. While the pathogenesis of the CLE remains still unclear, a number of contributors—among them type I IFNs— have been proposed. ...
Article
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Growing evidence over the last few years suggests a central role of type I IFN pathway in the pathogenesis of systemic autoimmune disorders. Data from clinical and genetic studies in patients with systemic lupus erythematosus (SLE) and lupus-prone mouse models, indicates that the type I interferon system may play a pivotal role in the pathogenesis of several lupus and associated clinical features, such as nephritis, neuropsychiatric and cutaneous lupus, premature atherosclerosis as well as lupus-specific autoantibodies particularly against ribonucleoproteins. In the current paper, our aim is to summarize the latest findings supporting the association of type I IFN pathway with specific clinical manifestations in the setting of SLE providing insights on the potential use of type I IFN as a therapeutic target.
... The most commonly used scoring system for CLE is the Cutaneous Lupus Activity and Severity Index (CLASI), which independently grades manifestations of CLE disease activity (CLASI-A), such as erythema and scaling, and skin damage (CLASI-D), such as dyspigmentation and scarring. [9][10][11] In validation studies, CLASI demonstrates high inter-rater and intrarater reliability and correlates well with subjective physician and patient global assessments of disease burden. 9 12 However, there is little consensus on how changes in CLASI scores should be used to classify treatment response. ...
Article
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Objective The severity and disease course of cutaneous lupus erythematosus (CLE) are highly variable. Consequently, outcome measures for CLE clinical improvement are heterogeneous, complicating treatment decisions and therapeutic development. This study characterises CLE outcome measures and identifies the influence of clinical improvement thresholds on strengths of associations with patient demographic and clinical factors. Methods In this pilot cohort study, multivariable models identified factors associated with CLE activity and skin damage improvement, defined as relative decreases in Cutaneous Lupus Activity and Severity Index (CLASI) activity (CLASI-A) and damage (CLASI-D) scores, over ranges of response thresholds. Results 66 patients with 119 visit-pairs were included in the CLASI-A analysis. 74 patients with 177 visit-pairs were included in the CLASI-D analysis. Factors associated with CLE activity and damage improvement depended on the response threshold. Some associations were stronger at more stringent thresholds, including subacute CLE predominance with increased likelihood of CLASI-A improvement ( R² =0.73; 50% reduction: OR 1.724 (95% CI 0.537 to 5.536); 75%: 5.67 (95% CI 1.56 to 20.5)) and African-American race with decreased likelihood of CLASI-D improvement ( R² =0.80; 20%: 0.40 (95% CI 0.17 to 0.93); 40%: 0.25 (95% CI 0.08 to 0.82)). Other associations were stable across multiple thresholds, including older age of CLE development with increased likelihood of CLASI-A improvement ( R² =0.25; 50%: 1.05 (95% CI 1.01 to 1.09]; 75%: 1.05 (95% CI 1.00 to 1.10)) and higher initial disease activity with decreased likelihood of CLASI-D improvement ( R² =0.55; 20%: 0.91 (95% CI 0.84 to 0.98); 40%: 0.88 (95% CI 0.79 to 0.97)). Conclusions Examining a range of CLASI threshold outcomes can comprehensively characterise changes in disease course in patients with CLE. Insufficiently stringent thresholds may fail to distinguish meaningful clinical change from natural fluctuation in disease activity.
... Doses of all other background antimalarials, NSAIDs, and immunosuppressants remained stable throughout the study. The following assessments were performed through study week 24: BILAG-2004; Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)-Activity [17]; Physician Global Assessment (PGA) [18]; Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) Flare Index [19]; SLEDAI-2K; and 28 Swollen Joint Count/Tender Joint Count (28 SJC/TJC). The BILAG-2004 Index was assessed over a 4-week period, and total scores were the sum of scores from all nine organ systems in the BILAG questionnaire using the coding scheme of A = 12, B = 8, C = 1, and D/E = 0 [20]. ...
Article
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Introduction: We assessed the efficacy and safety of repository corticotropin injection (RCI; Acthar® Gel) for persistently active systemic lupus erythematosus (SLE) despite use of moderate-dose glucocorticoids. Methods: This multicenter, double-blind, randomized, placebo-controlled study enrolled patients ≥ 18 years with active SLE and moderate to severe rash and/or arthritis despite stable glucocorticoid doses (7.5-30 mg/day prednisone equivalent) and antimalarials for ≥ 4 weeks and/or immunosuppressants for ≥ 8 weeks before screening. Stable glucocorticoid doses were required through week 16 with optional taper from weeks 16 to 24. Patients were randomized (1:1) to 80 U RCI subcutaneously or placebo every other day to week 4, then twice weekly to week 24. Endpoints included the proportion of SLE Responder Index (SRI)-4 responders at week 16; changes from baseline to week 16 in 28 Swollen Joint Count/Tender Joint Count (28 SJC/TJC) and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)-Activity score; and changes from baseline to week 24 in inflammatory cytokines. Safety was assessed by adverse events. Results: In the modified intention-to-treat population (RCI, n = 84; placebo, n = 85), the proportion of SRI-4 responders at week 16 was not significantly different between groups (RCI, 47.6%; placebo, 43.5%; OR [95% CI] 1.2 [0.6 to 2.2]; p = 0.5762). RCI treatment resulted in a reduction from baseline to week 16 in 28 SJC/TJC and CLASI-Activity score and from baseline to week 8 in a proliferation-inducing ligand cytokine. Post hoc analyses demonstrated a greater proportion of BILAG-based Combined Lupus Assessment responders for RCI than placebo at weeks 4, 12, and 20 and greater SRI-4 response in RCI-treated patients with baseline SLE Disease Activity Index-2000 ≥ 10 and CLASI-Activity ≥ 11. No new safety signals were identified. Conclusions: Despite failure to achieve the primary endpoint, these results support the utility of RCI for treating persistently active SLE. Trial registration: ClinicalTrials.gov identifier NCT02953821.
... Использование индекса cLASI позволяет выполнить количественную оценку проявлений кожных форм КВ, Рис. 10. Эритема Биетта измерить площадь и тяжесть поражений, оценить эффективность проводимой терапии и сравнить данные различных исследований [40]. ...
Article
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This article contains the latest information about the mechanisms of development of lupus erythematosus based on the literature review. The modern classification of specific and non-specific skin lesions in lupus erythematosus is shown.The authors described the clinical pattern of cutaneous forms of lupus erythematosus very detailed. the data about pathological and immunological criteria for the disease diagnostics, modern methods of pharmacotherapy lupus erythematosus was classified.
... Subsequent studies extended the validation of the CLASI to rheumatologic practitioners and their patients, examined responsiveness in the context of therapeutic interventions, determined the minimal clinically significant change in the score, and demonstrated a strong correlation between disease severity, as determined by the CLASI, and external measures of disease severity and quality of life (Albrecht and Werth, 2010; Klein et al., 2011). Several published studies have demonstrated that, with appropriate training, the CLASI allows rapid and consistent capture of disease severity in cutaneous lupus disease activity for all but the most rare subsets of CLE patients, and that it is responsive to change (Albrecht and Werth, 2010; Klein et al., 2010). Currently, at least five multicenter international trials are relying on the CLASI to evaluate skin disease in CLE and SLE patients, either as a primary or secondary outcome (ClinicalTrials.gov ...
Article
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.
... Validated outcome measures to document disease activity and to differentiate it from damage have proved to be extremely valuable to help guide clinical practice in autoimmune diseases. In 2005, an index was developed to specifically follow cutaneous disease in patients with SLE [13]. CLASI provides a quantitative measure of the skin-specific burden of disease. ...
... A scores of 0-9, 10-20, and >20-70 represent mild, moderate, and severe disease activity, respectively. 2 In the current trial, all CLASI assessments were conducted by a trained evaluator. ...
Article
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Blood dendritic cell antigen 2 (BDCA2) is a receptor that is exclusively expressed on plasmacytoid dendritic cells, which are implicated in the pathogenesis of lupus erythematosus. Whether treatment with litifilimab, a humanized monoclonal antibody against BDCA2, would be efficacious in reducing disease activity in patients with cutaneous lupus erythematosus has not been extensively studied. METHODS In this phase 2 trial, we randomly assigned adults with histologically confirmed cutaneous lupus erythematosus with or without systemic manifestations in a 1:1:1:1 ratio to receive subcutaneous litifilimab (at a dose of 50, 150, or 450 mg) or placebo at weeks 0, 2, 4, 8, and 12. We used a dose–response model to assess whether there was a response across the four groups on the basis of the primary end point, which was the percent change from baseline to 16 weeks in the Cutaneous Lupus Erythematosus Disease Area and Severity Index–Activity score (CLASI-A; scores range from 0 to 70, with higher scores indicating more widespread or severe skin involvement). Safety was also assessed. RESULTS A total of 132 participants were enrolled; 26 were assigned to the 50-mg litifilimab group, 25 to the 150-mg litifilimab group, 48 to the 450-mg litifilimab group, and 33 to the placebo group. Mean CLASI-A scores for the groups at baseline were 15.2, 18.4, 16.5, and 16.5, respectively. The difference from placebo in the change from baseline in CLASI-A score at week 16 was −24.3 percentage points (95% confidence interval [CI] −43.7 to −4.9) in the 50-mg litifilimab group, −33.4 percentage points (95% CI, −52.7 to −14.1) in the 150-mg group, and −28.0 percentage points (95% CI, −44.6 to −11.4) in the 450-mg group. The least squares mean changes were used in the primary analysis of a best-fitting dose–response model across the three drugdose levels and placebo, which showed a significant effect. Most of the secondary end points did not support the results of the primary analysis. Litifilimab was associated with three cases each of hypersensitivity and oral herpes infection and one case of herpes zoster infection. One case of herpes zoster meningitis occurred 4 months after the participant received the last dose of litifilimab. CONCLUSIONS In a phase 2 trial involving participants with cutaneous lupus erythematosus, treatment with litifilimab was superior to placebo with regard to a measure of skin disease activity over a period of 16 weeks. Larger and longer trials are needed to determine the effect and safety of litifilimab for the treatment of cutaneous lupus erythematosus
... The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) was developed in 2005 as a tool to more accurately track skin disease in these patients. 30,31 While often used for clinical trials, CLASI can also be a meaningful tool for assessing clinical progress in practice. ...
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Nathaniel Goldman,1,2 Joseph Han,3 Avery LaChance1 1Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; 2New York Medical College, School of Medicine, Valhalla, NY, USA; 3Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USACorrespondence: Avery LaChance, Connective Tissue Diseases Clinic, Health Policy and Advocacy, Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA, 02215, USA, Tel +1 617-582-6060, Fax +1 617-532-6060, Email alachance@bwh.harvard.eduAbstract: The cutaneous features of autoimmune connective tissue disease pose a unique challenge to patients and clinicians managing these conditions. In this review, we outline the key elements of diagnosis and treatment of cutaneous lupus erythematosus, dermatomyositis, systemic sclerosis, and morphea. This article also aims to present an update on gold standard as well as new and emerging therapies for these conditions. Overall, dermatologists can play a key role in diagnosing and treating autoimmune connective tissue diseases and this review intends to provide an up-to-date toolkit to guide clinical dermatologists in this endeavor.Keywords: cutaneous lupus erythematosus, dermatomyositis, systemic sclerosis, morphea, eosinophilic fasciitis
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The aim was to assess the level of systemic involvement and character of renal disease in patients with chronic cutaneous lupus erythematosus of the discoid lupus variety (hereafter referred to as 'discoid lupus') and features of systemic lupus erythematosus (SLE). Clinical confusion with other types of cutaneous lupus erythematosus complicates interpretation of some previously reported studies. Over three years, sixteen patients met the diagnostic criteria of discoid lupus, positive anti-nuclear-antibody, and at least one extracutaneous manifestation. Most patients (14/16) were female, between 26 to 66 years old. Arthritis was the most common extracutaneous manifestation followed by Raynaud's phenomenon. The anti-nuclear-antibody was speckled in ten patients with titers ranging from 1:40 to 1:1280 IU/mL. Elevated levels of double-stranded-DNA in low titers were found in four patients, anti-Smith-antibody in four; anti-Sjogren-syndrome-A-antibody in seven, and anti-ribonucleoprotein-antibody in seven. Renal function markers were transiently high in some patients but normalized over time. Hematuria and/or proteinuria were present at some time in seven patients. The highest BUN and creatinine levels were 42 mg/dL and 1.5 mg/dL, respectively. One patient had membranous glomerulonephropathy class 5; however, discoid lupus developed well after the onset of renal disease during a time when renal function had returned to normal. Our observational data supports previous reports suggesting that patients with active discoid lupus rarely have progressive renal insufficiency. The mechanism for the development of discoid lupus may involve an immunologic mechanism that differs from that which produces severe organ involvement, especially advanced immune-complex-mediated renal disease. Patients with discoid lupus rarely have sustained high levels of antibodies to double-stranded-DNA. Discoid lupus appears to be a marker for a more benign lupus course. This clinical observation lays the groundwork for a larger prospective, longitudinal cohort study for further validation.
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Major scientific advances in basic science, pharmacology, and translational medicine have allowed the discovery of new molecular targets whose manipulation by new chemical entities has led to treatments for inflammatory diseases, including rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease. Development of new agents for systemic lupus erythematosus (SLE) has lagged, however, because the protean manifestations of SLE present challenges for measuring therapeutic effects in a consistent manner. Composite end points combining several Disease Activity Indices (DAIs) are being used in ongoing global studies, but the uniform application of these complex DAIs across large numbers of clinical sites has proven difficult. We describe herein approaches that are being utilized to facilitate collection, review, and analysis of the clinical measures utilizing independent central adjudication committees.
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Background: A study at the University of Pennsylvania (UPenn) Medical Center demonstrated that quality of life in patients with cutaneous lupus erythematosus (CLE) is negatively impacted. Whether patients with CLE in other geographic locations have similar quality of life is unknown. Objectives: We sought to compare quality of life indicators between patients with CLE at the University of Texas Southwestern (UTSW) Medical Center at Dallas and those at UPenn. Methods: Patients with CLE (total n=248) at UTSW (n=91) and UPenn (n=157) completed the Skindex-29 +3 and Short Form-36 (SF-36) surveys related to quality of life. Additional information, including demographics, presence of systemic lupus erythematosus (SLE) and disease severity, was collected from UTSW patients with CLE. Results: Most Skindex-29 + 3 and SF-36 subdomain scores between UTSW and UPenn patients with CLE were similar. However, UTSW patients with CLE were significantly more affected in the functioning and lupus-specific Skindex-29 + 3 domains, and physical functioning, role-physical and general health SF-36 subscales than UPenn patients with CLE (P<0·05). Factors related to poor quality of life in UTSW patients with CLE include sex, income, education, presence of SLE, and skin disease activity. Conclusions: Most quality of life indicators were similar between the two CLE populations. Differences in psychosocial behaviour, and a larger proportion of patients with SLE and females in the UTSW group likely attributed to differences in a minority of Skindex-29+3 and SF-36 subdomains. Capturing data from CLE populations in different locations provides a more thorough picture of the quality of life that patients with CLE experience on a daily basis with special attention to quality of life issues in select patients with CLE.
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Skin manifestations are frequently observed in lupus erythematosus (LE) and are manifold. Nonspecific and specific symptoms can be differentiated with the latter belonging to the dermatologically well-characterized clinical entities of acute cutaneous, subacute cutaneous, chronic cutaneous as well as intermittent cutaneous LE. These forms are differentially related to systemic LE. Patient history and clinical examinations, laboratory and immunoserological findings as well as organ imaging results determine the time point as well as the intensity of therapy. Apart from cessation of smoking and alcohol consumption as well as stringent UV protection, topical therapy with corticosteroids or calcineurin inhibitors may suffice with limited forms of the disease. In many cases, however, systemic treatment with antimalarial drugs as a basic treatment is mandatory. Several immunosuppressive agents can alternatively be used in conjunction with systemic corticosteroids. Early and effective therapy is important to prevent irreversible scarring of the skin and to avoid internal organ damage.
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Studies reporting the incidence of isolated cutaneous lupus erythematosus (CLE) are rare. To examine in a population-based cohort study the incidence of CLE and its subsets in Sweden. The short-term probability of receiving an additional diagnosis of systemic lupus erythematosus (SLE) is also assessed. A population-based open cohort study including all patients with CLE [International Classification of Diseases (ICD) code, ICD-10: L93] in Sweden, 2005-2007. Patients (n=1088) were identified in the Swedish National Patient Register. The incidence of CLE was 4·0/100,000; the female/male ratio was 3:1. Mean age at disease onset was 54 years. The most common subset was discoid lupus erythematosus (DLE) (80%, n = 868). A quarter of the patients (24%, n=260) were already diagnosed with SLE at the time they were diagnosed with CLE. During the whole observation period (2005-2007), an additional 18% (n = 107) were diagnosed with SLE, the probability of receiving an additional SLE diagnosis being highest for the subacute CLE (SCLE) subset. This is the first nationwide epidemiological study on CLE. We found the incidence of CLE to be about equal to that of SLE, and found a higher short-term probability for receiving an additional diagnosis with SLE than previously described for CLE. Subsets other than DLE and SCLE were rarely reported in our system; an update of the ICD codes for this diagnostic group could increase reporting of these more unusual cases. Our study clarifies that monitoring and follow-up are called for in this patient group due to the risk for SLE, and underscores the need for clear criteria for risk assessment in the large group of patients with CLE who also fulfil criteria for SLE.
Article
Importance Patients with cutaneous lupus erythematosus (CLE) who develop systemic lupus erythematosus (SLE) may have few and mild systemic symptoms.Objective To characterize the types and severity of systemic symptoms in a longitudinal cohort of patients with CLE.Design, Setting, and Participants Prospective, longitudinal cohort study of 77 patients with CLE who presented between January 2007 and April 2011 at a university autoimmune skin disease clinic.Main Outcomes and Measures Systemic symptoms and severity were determined from data recorded at each study visit and from medical records.Results Of 77 patients with CLE, 13 (17%) went on to meet criteria for SLE, with a mean (SD) time from CLE diagnosis to SLE of 8.03 (6.20) years. Of the 13 patients, 1 (8%) solely met the mucocutaneous American College of Rheumatology (ACR) criteria of malar rash, discoid rash, photosensitivity, and oral ulcers, and 3 (23%) met the mucocutaneous ACR criteria plus positive antinuclear and other antibody titers. After a mean (SD) follow-up time of 2.81 (1.34) years, only 5 of the 13 patients with CLE (38%) who progressed to meet SLE criteria developed moderate to severe additional systemic disease.Conclusions and Relevance Patients with CLE who developed SLE during our study did so mostly by meeting the mucocutaneous ACR criteria, and the majority developed none to mild additional systemic disease during the study period. Thus, our study suggests that a small percentage of patients with CLE eventually develop SLE and that even if they do, most patients will have mild systemic disease.
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O lúpus eritematoso cutâneo pode ocorrer como um distúrbio independente ou associado ao lúpus eritematoso sistêmico. O lúpus eritematoso cutâneo inclui três categorias de doenças de pele específicas do LE: lúpus eritematoso cutâneo agudo, lúpus eritematoso cutâneo subagudo e lúpus eritematoso cutâneo crônico. A característica chave que une as dermatoses específicas do lúpus eritematoso é a histopatologia, as características histopatológicas comuns compartilhadas incluem uma dermatite de interface vacuolar (degeneração liquefativa da camada basal da epiderme); hiperqueratose; atrofia epidérmica; infiltrado inflamatório de células mononucleares superficiais, perivasculares e perifoliculares; espessamento da membrana basal; e incontinência pigmentar. Em particular, a dermatite de interface é uma característica histopatológica consistente de lúpus eritematoso cutâneo agudo, lúpus eritematoso cutâneo subagudo e lúpus eritematoso discóide (a forma mais comum de lúpus eritematoso cutâneo crônico), mas não é uma característica típica de lúpus eritematoso túmido ou lúpus profundo. A dermatite de interface também pode ser observada em distúrbios não relacionados ao lúpus eritematoso, como a dermatomiosite. Além disso, a maioria das dermatoses específicas do lúpus eritematoso pode ocorrer em associação com o lúpus eritematoso sistêmico, com exceção do lúpus eritematoso tumidus, para o qual o lúpus eritematoso sistêmico associado é raro. As doenças específicas de lúpus eritematoso também podem ocorrer em conjunto com outras doenças de pele específicas de lúpus eritematoso e têm uma abordagem semelhante ao tratamento.
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Hautmanifestationen finden sich beim Lupus erythematodes (LE) häufig und in vielfältiger Weise. Es lassen sich unspezifische und spezifische Symptome unterscheiden, wobei Letztere dem akut kutanen LE, dem subakut kutanen LE, dem chronisch kutanen und dem intermittierenden LE zuzuordnen sind und in unterschiedlichem Zusammenhang zu einem systemischen LE stehen. Anamnestische und klinische Untersuchungen, klinisch-chemische, immunserologische sowie je nach verdächtigtem Organbefall apparative Untersuchungen belegen die Krankheitsaktivität und bestimmen Zeitpunkt und Ausmaß einer Therapie. Neben Einstellen von Zigarettenrauchen und Alkoholgenuss sowie konsequentem UV-Schutz ist dabei eine topische Therapie mit Glukokortikosteroiden, ggf. Calcineurininhibitoren bei umschriebenen Formen möglich. Vielfach wird jedoch eine systemische Therapie, allen voran mit Antimalariamitteln als Basistherapie erforderlich sein. Verschiedene Immunsuppressiva sind je nach Krankheitsaktivität, ggf. in Kombination mit systemischen Kortikosteroiden Alternativen. Wichtig ist eine frühzeitige und effektive Therapie, um eine irreversible Vernarbung der Haut oder eine innere Organschädigung zu vermeiden.
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Objective: The specific autoantibodies and antigens which mediate systemic lupus erythematosus (SLE)-related organ injuries remain largely unknown. This study aimed to investigate the antibody-mediated immune response that leads to SLE skin lesions.Methods: The study involved 85 SLE patients with specific lupus skin lesions and 31 without skin lesions. The reactivity of serum antibody to skin antigens was determined by immunoblot using human foreskin as the substrate. Skin antigens were identified using mass spectrometry. Serum antibody was isolated by affinity purification and was injected intracutaneously into mouse skin to determine pathogenicity. The antibody serum levels were monitored by enzyme-linked immunoabsorbent assay.Results: We determined that 78% of patients with skin lesions presented serum antibodies reactive to 35kD and/or 25kD skin antigens, which was significantly higher than patients without skin lesions (p < 0.0001), suggesting a correlation between immune response and skin lesions. Acidic ribosomal P protein 0 (RPLP0) and galectin-3 were two target antigens identified from 35kD and 25kD proteins, respectively. Purified serum anti-RPLP0 and anti-galectin-3 antibodies induced lupus-like histological changes after intracutaneous injection. Anti-RPLP0 and anti-galectin-3 antibodies were significantly higher in SLE patients than in healthy controls and decreased with skin recovery. Anti-galectin-3 antibody was also significantly higher in SLE patients than in patients with dermatomyositis and systemic scleroderma, and strongly related to lupus cutaneous vasculitis. Additionally, the two antibodies were positively correlated with leucopenia and C3 deficiency, and anti-RPLP0 antibody was also positively correlated with arthritis and SLE disease activity.Conclusion: The immune response mediated by serum anti-RPLP0 and anti-galectin-3 antibodies play a key role in the pathogenesis of SLE skin lesions. These findings provide new insights into the mechanism of SLE-related organ disorders. © 2014 American College of Rheumatology.
Article
Lupus erythematosus (LE) is a chronic inflammatory autoimmune disease characterized by diverse clinical features and autoantibodies. Lupus erythematosus includes both systemic disease (SLE), which may affect multiple organ systems, and cutaneous disease (CLE) involving the skin and mucous membranes. Cutaneous disease has been estimated to occur as the initial manifestation in 25 % of patients diagnosed with systemic lupus erythematosus and in 70–80 % of patients at some point during their disease course. The skin manifestations of LE are generally classified as either LE specific or LE nonspecific. The diagnosis of the subtype of CLE is based on the patient’s history, clinical findings, skin biopsy histology, and laboratory results. Treatment of CLE is multifaceted and includes photoprotection, topical therapies, and systemic medications. Antimalarials are first-line systemic therapy for CLE. Additional systemic therapies include antimetabolite immunosuppressants, thalidomide, dapsone, retinoids, intravenous immunoglobulin, and biologics. The increasing standardization of CLE assessment will potentially lead to more rigorous clinical trials investigating potential therapies for cutaneous lupus.
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Rowell's syndrome is defined as the rare association of lupus erythematosus and erythema multiforme-like lesions, with immunological markers including antinuclear antibodies in speckled pattern, anti-Ro/SSA and/or anti-La/SSB. This is a case report confirmed by histological and immunological criteria.
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Introduction Due to a wide array of dermatologic manifestations, assessment of disease severity in cutaneous lupus erythematosus (CLE) remains challenging. Given a need for some standardization in this field, we conducted a worldwide questionnaire-based study among physicians experienced in CLE management. Aim We asked about CLE assessment, their prophylactic measures advised to patients, and treatment recommendations. Material and methods A total of 83 completed questionnaires were received. Participating physicians recommended assessing disease severity at each patient’s visit (39.1%), monthly (4.9%) or at least every third month (17.3%). Almost half of the responding physicians (47.0%) waited 2–3 months before identifying a specific treatment option as not effective. Results The vast part of the participants informed their patients about of the risks of sun exposure and advised adequate preventive measures. Smoking was less frequently a matter of discussion between physicians and their patients. Recommendations for the timing of CLE severity assessment likely depends on disease severity and the type of therapeutic intervention. Conclusions Proper patient education about effective prophylactic measures should be included during routine CLE patient consultations.
Article
A 53‐year‐old lady presented with a 5cm by 4cm erythematous, annular skin lesion with central clearance on the posterior aspect of her right arm (Figure 1). The patient was known to suffer from systemic lupus erythematosus (SLE), controlled by a stable regimen of hydroxychloroquine 200mg twice daily, mycophenolic acid 360mg twice daily and prednisolone 5mg daily. The only cutaneous manifestation of her disease had been a malar rash at diagnosis nineteen years previously. The lesion started as a pruritic, erythematous papule on the posterior aspect of her right arm, coinciding with the exact location at which an influenza vaccine had been administered three days previously.
Chapter
Systemic lupus erythematosus (SLE) clinical trials have employed a variety of outcome measures, which are elucidated in this chapter. Composite outcome measures such as the SRI (Systemic Lupus Erythematosus Responder Index) and BICLA (BILAG-Based Composite Lupus Assessment), which comprise several measures of disease activity such as the SLEDAI (SLE Disease Activity Index), BILAG (British Isles Lupus Assessment Group Index) and PGA (Physician Global Assessment), have been favoured as primary endpoints in recent clinical trials. These composite measures have the advantage of being able to comprehensively capture both organ-specific and global disease activity, although they are therefore more complex and time-consuming to score. Global disease activity indices such as the SLEDAI and BILAG, organ-specific disease activity measures such as the CLASI, other measures such as steroid-sparing ability and patient-reported outcome measures are usually evaluated as secondary outcome measures in clinical trials. These specific measures may indicate subpopulations of patients who may benefit from specific therapies. Given the relative paucity of successful late phase SLE clinical trials and that the choice of primary endpoint for a trial can be critical to its success or failure, formulating a consensus on the use of outcome measures in SLE clinical trials is paramount.
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Background: Iberdomide, a cereblon modulator promoting degradation of the transcription factors Ikaros and Aiolos, which affect leukocyte development and autoimmunity, is being evaluated for the treatment of systemic lupus erythematosus (SLE). Methods: In this phase 2 trial, we randomly assigned patients in a 2:2:1:2 ratio to receive oral iberdomide (at a dose of 0.45, 0.30, or 0.15 mg) or placebo once daily for 24 weeks, in addition to standard medications. The primary end point at week 24 was a response on the SLE Responder Index (SRI-4), which was defined as a reduction of at least 4 points in the Systemic Lupus Erythematosus Disease Activity Index 2000 score (a 24-item weighted score of lupus activity that ranges from 0 to 105, with higher scores indicating greater disease activity), no new disease activity as measured on the British Isles Lupus Assessment Group 2004 index, and no increase of 0.3 points or more in the Physician's Global Assessment score (on a visual-analogue scale ranging from 0 [no disease activity] to 3 [maximal disease]). Results: A total of 288 patients received the assigned intervention: 81 received iberdomide at a dose of 0.45 mg, 82 received iberdomide at a dose of 0.30 mg, 42 received iberdomide at a dose of 0.15 mg, and 83 received placebo. At week 24, the percentages of patients with an SRI-4 response were 54% in the iberdomide 0.45-mg group, 40% in the iberdomide 0.30-mg group, 48% in the iberdomide 0.15-mg group, and 35% in the placebo group (adjusted difference between the iberdomide 0.45-mg group and the placebo group, 19.4 percentage points; 95% confidence interval, 4.1 to 33.4; P = 0.01), with no significant differences between the groups that received the lower doses of iberdomide and the group that received placebo. Iberdomide-associated adverse events included urinary tract and upper respiratory tract infections and neutropenia. Conclusions: In this 24-week, phase 2 trial involving patients with SLE, iberdomide at a dose of 0.45 mg resulted in a higher percentage of patients with an SRI-4 response than did placebo. Data from larger, longer trials are needed to determine the efficacy and safety of iberdomide in SLE. (Funded by Bristol Myers Squibb; ClinicalTrials.gov number, NCT03161483; EudraCT number, 2016-004574-17.).
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Cutaneous lupus erythematosus (CLE) is a disfiguring and poorly understood condition frequently associated with systemic lupus. Previous studies suggest that nonlesional keratinocytes play a role in disease predisposition, but this has not been investigated in a comprehensive manner or in the context of other cell populations. To investigate CLE immunopathogenesis, normal-appearing skin, lesional skin, and circulating immune cells from lupus patients were analyzed via integrated single-cell RNA sequencing and spatial RNA sequencing. We demonstrate that normal-appearing skin of patients with lupus represents a type I interferon-rich, prelesional environment that skews gene transcription in all major skin cell types and markedly distorts predicted cell-cell communication networks. We also show that lupus-enriched CD16+ dendritic cells undergo robust interferon education in the skin, thereby gaining proinflammatory phenotypes. Together, our data provide a comprehensive characterization of lesional and nonlesional skin in lupus and suggest a role for skin education of CD16+ dendritic cells in CLE pathogenesis.
Article
Objective: To assess the efficacy and safety of deucravacitinib, an oral, selective, allosteric inhibitor of TYK2, in a phase II trial in adult patients with active systemic lupus erythematosus (SLE). Methods: Adults with active SLE were enrolled from 162 sites in 17 countries. Patients (n = 363) were randomized 1:1:1:1 to receive deucravacitinib 3 mg twice daily, 6 mg twice daily, 12 mg once daily, or placebo. The primary end point was SLE Responder Index 4 (SRI-4) response at week 32. Secondary outcomes assessed at week 48 included SRI-4, British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response, Cutaneous Lupus Erythematosus Disease Area and Severity Index 50 (CLASI-50), Lupus Low Disease Activity State (LLDAS), and improvements in active (swollen plus tender), swollen, and tender joint counts. Results: At week 32, the percentage of patients achieving SRI-4 response was 34% with placebo compared to 58% with deucravacitinib 3 mg twice daily (odds ratio [OR] 2.8 [95% confidence interval (95% CI) 1.5, 5.1]; P < 0.001 versus placebo), 50% with 6 mg twice daily (OR 1.9 [95% CI 1.0, 3.4]; P = 0.02 versus placebo), and 45% with 12 mg once daily (OR 1.6 [95% CI 0.8, 2.9]; nominal P = 0.08 versus placebo). Response rates were higher with deucravacitinib treatment for BICLA, CLASI-50, LLDAS, and joint counts compared to placebo. Rates of adverse events were similar across groups, except higher rates of infections and cutaneous events, including rash and acne, with deucravacitinib treatment. Rates of serious adverse events were comparable, with no deaths, opportunistic infections, tuberculosis infections, major adverse cardiovascular events, or thrombotic events reported. Conclusion: Deucravacitinib treatment elicited higher response rates for SRI-4 and other end points compared with placebo, with an acceptable safety profile, in adult patients with active SLE.
Article
Acne vulgaris is a chronic and frequently recurring disease. A fixed-dose adapalene-benzoyl peroxide (adapalene-BPO) gel is an efficacious and safe acne treatment. To assess the long-term effect of adapalene-BPO on relapse prevention among patients with severe acne after successful initial treatments. This is a multicentre, double-blind, randomized and controlled study. In total, 243 subjects who had severe acne vulgaris and at least 50% global improvement after a previous 12-week treatment were randomized into the present study to receive adapalene-BPO gel or its vehicle once daily for 24 weeks. At week 24, compared with vehicle, adapalene-BPO resulted in significantly higher lesion maintenance success rate (defined as having at least 50% improvement in lesion counts achieved in initial treatment) for all types of lesions (total lesions: 78·9% vs. 45·8%; inflammatory lesions: 78·0% vs. 48·3%; noninflammatory lesions: 78·0% vs. 43·3%; all P < 0·001). Significantly more subjects with adapalene-BPO than with vehicle had the same or better Investigator's Global Assessment score at week 24 than at baseline (70·7% vs. 34·2%; P < 0·001). The time when 25% of subjects relapsed was 175 days with adapalene-BPO and 56 days with vehicle (17 weeks earlier; P < 0·0001). Adapalene-BPO led to further decrease of lesion counts during the study and 45·7% of subjects were 'clear' or 'almost clear' at week 24. It was also safe and well tolerated in the study. Adapalene-BPO not only prevents the occurrence of relapse among patients with severe acne, but also continues to reduce disease symptoms during 6 months.
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Lupus erythematosus tumidus (LET) is characterized clinically by erythematous, succulent, edematous, nonscarring plaques in sun-exposed areas. Results of histological examination show perivascular and periadnexal lymphocytic infiltration and interstitial mucin deposition. The main differential diagnoses are polymorphous light eruption, Jessner's lymphocytic infiltration of the skin, reticular erythematous mucinosis, and pseudolymphoma. Since its first description in 1930, LET has been documented rarely in the literature, and its clinical importance has not been fully appreciated. We characterized 40 patients with clinical and histological features of LET observed at our department from 1984 through 1998. The onset of the disease clustered in summer because of sun exposure, and 28 (70%) of the patients showed a remarkable photosensitivity confirmed by results of provocative phototesting. A complete resolution of the skin lesions was seen after systemic therapy with antimalarials and, in some cases, with local corticosteroids or spontaneously without any treatment. In 4 (10%) of the patients, antinuclear antibodies were detected; however, there was no evidence of underlying systemic involvement in any of the patients. Our data constitute the largest number of patients with LET collected until now. The clinical picture, extreme photosensitivity, histological findings, and effective treatment with antimalarials are so characteristic that LET should be considered as a separate entity and differentiated from other variants of cutaneous LE. Arch Dermatol. 2000;136:1033-1041
Article
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To determine how to use the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) to classify patients according to disease severity (mild, moderate, and severe) and to identify which patients respond to therapy. Cohort. The connective-tissue disease clinic at the Hospital of the University of Pennsylvania, Philadelphia. Seventy-five patients with clinical or histopathologic evidence of cutaneous lupus erythematosus or systemic lupus erythematosus were included in the study. The CLASI, Skindex-29, and the physician's subjective assessment of severity and improvement were completed at every visit. Disease severity was assessed with 45 patient visits. Mild, moderate, and severe disease corresponded with CLASI activity score ranges of 0 to 9, 10 to 20, and 21 to 70, respectively. Improvement in disease activity was assessed in 74 patients. A clinical improvement was associated with a mean 3-point or 18% decrease in the CLASI activity score. However, receiver operating characteristic analysis demonstrated an increased percentage of patients correctly classified when a 4-point (sensitivity, 39%; specificity, 93%; correctly classified, 76%) or 20% (sensitivity, 46%; specificity, 78%; correctly classified, 67%) decrease in the CLASI activity score was used instead to identify improvement. The CLASI can be used to classify patients into groups according to disease severity and to identify clinically significant improvements in disease activity.
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At least 71 patients have been reported in which their otherwise typical subacute cutaneous lupus erythematosus (SCLE) skin lesions were felt to have been temporally associated with the systemic administration of a drug. The mean age of this cohort of drug-induced SCLE (DI-SCLE) patients was 59 years of age which is somewhat older than the mean age of previously reported idiopathic SCLE patient cohorts. Patients had been taking the suspected triggering drug for weeks to years before the onset of SCLE skin lesions. In addition, it was not unusual for 2-3 months to be required for resolution of the SCLE skin lesions following discontinuation of the triggering drug. A relatively large number of drugs representing different pharmacological classes have been implicated in the induction of SCLE. The drug classes that were more frequently encountered were those used for the treatment of cardiovascular disease, especially hypertension. Calcium channel blockers were especially common in this regard. Elderly individuals being treated for hypertension are often taking multiple classes of drugs that have been implicated in triggering SCLE (thiazide diuretics, calcium channel blockers, angiotensin converting enzyme (ACE) inhibitors, beta-blockers). An approach to the management of DI-SCLE is presented. Ro/SS-A autoantibodies tended to remain present in the blood after resolution of drug-induced SCLE skin lesions. A common link between the disparate group of drug structures implicated in triggering SCLE is their tendencies to produce photosensitivity and lichenoid drug reactions. This leads to the speculation that DI-SCLE could represent a photo-induced isomorphic/Köebner response in an immunogenetically predisposed host.
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Chronic vesiculobullous eruptions are relatively uncommon in systemic lupus erythematosus (SLE). Their incidence among patients with skin lesions has been estimated at less than 5% [1–3]. Blistering eruptions in SLE can be divided into three categories. The first includes a number of primary blistering diseases that have been reported in association with SLE. These include bullous pemphigoid (BP) [4–9], dermatitis herpetiformis (DH) [10–14], pemphigus vulgaris/foliaceous [15–20], epidermolysis bullosa acquisita (EBA) [21, 22], erythema multiforme [23, 24], porphyria cutanea tarda [25], toxic epidermal necrolysis [26] and dystrophic epidermolysis bullosa [27]. Each of these diseases has its own diagnostic features and the association with SLE is generally regarded as fortuitous and not a specific manifestation of SLE. Many of the primary blistering diseases are associated with autoimmune features that may be difficult to distinguish from the cutaneous immunological features of SLE.
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The importance of direct immunofluorescence in the diagnosis of bullous skin lesions is illustrated by the following report of bullous systemic lupus erythematosus (SLE). Direct immunofluorescence of the bullous lesions of SLE demonstrated the lupus band six months before the lupus erythematosus cell phenomenon became positive. Direct immunofluorescent studies may provide an important tool for the early diagnosis of SLE particularly when other tests are not helpful.
Article
We investigated 33 patients affected with chilblain lesions following a persisting course of more than 1 month. We focused on the incidence of an underlying connective tissue disease, mostly lupus erythematosus (LE), and we analyzed features of idiopathic chilblains compared with those of chilblain lesions associated with connective tissue disease. We also carried out a prospective follow-up of patients. Eleven patients included in the study were free of any clinical and/or laboratory abnormality suggestive of connective tissue disease, while 22 of 33 patients showed 1 or several abnormalities raising suspicion for connective tissue disease, and among them 8 had a diagnosis of systemic lupus erythematosus (SLE) established at initial evaluation based on the American College of Rheumatology revised criteria. The comparative analysis of patients with idiopathic chilblains and patients with chilblains associated with LE showed that female sex and persistence of lesions beyond cold seasons were significantly associated with chilblain LE. Histopathologic studies of chilblain lesions did not reveal features typical of LE in any case, but revealed a higher incidence of a deep perisudoral infiltrate in idiopathic chilblains. In patients showing signs of connective tissue disease, positive cutaneous immunofluorescence was correlated with the presence of circulating antinuclear antibodies. Two patients had an ascertained diagnosis of SLE with severe manifestations during prospective follow-up, requiring treatment with oral steroids in both cases. Chilblains following a chronic course may reveal connective tissue disease, and patients affected with chilblains associated with autoimmune abnormalities may develop severe SLE. Accordingly, long-term follow-up of these patients is warranted.
Article
We studied the autoimmune serologic features and histocompatibility antigen associations of 27 patients who had a widespread, nonscarring and often photosensitive form of histologically specific cutaneous lupus erythematosus. We designated this disorder as subacute cutaneous lupus erythematosus. Skin lesions from this disorder can be distinguished from scarring discoid lupus erythematosus lesions both on a morphologic and histopathologic basis. Antinuclear and anticytoplasmic antibodies (Ro or Ro and La) and circulating immune complexes were frequently present in patients with subacute cutaneous lupus erythematosus, whereas rheumatoid factor and anti-lymphocyte, anti-DNA, anti-nRNP, and anti-Sm antibodies were found less frequently. Patients having annular skin lesions represented a particularly homogeneous subgroup in which there was a striking concordance of anti-Ro antibodies and the HLA-DR3 phenotype. These studies clearly establish that the presence of these lesions can serve as a cutaneous marker for a distinct subset of patients with lupus erythematosus who share similar clinical, serologic, and genetic features.
Article
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
Article
Background: Lupus erythematosus (LE) is a multi-organ-system disease, the characteristics of which are reflected in the 1982 American Rheumatism Association (ARA) criteria for systemic lupus erythematosus (SLE). From a dermatological point of view, only the presence of LE-specific histopathology is necessary and sufficient for the diagnosis of LE. The association between the type of LE-specific skin lesion and the severity of extracutaneous manifestations of LE has not yet been investigated systematically. Objective: The aim of this study was to evaluate, according to the type of LE skin lesions, the prevalence of the 1982 criteria for SLE. Methods: We selected 191 patients whose skin lesions were histologically diagnosed as LE specific. Patients were classified on the basis of skin disease, and their clinical and laboratory data were analyzed. Results: Of 191 patients, 130 (68%) exhibited only one type of LE-specific skin lesion (monomorphic), 55 (29%) had two types (bimorphic) and the remaining 6 (3%) displayed three types (trimorphic). Nineteen of 22 (86%) patients who presented discoid lupus skin lesions above the neck without other eruptions were classified in the cutaneous-limited LE spectrum. Of 116 patients with acute lupus skin lesions (malar rash), 83 (72%) clearly fulfilled the 1982 ARA criteria for SLE. In skin lesions of LE profundus, chilblain lupus, subacute lupus (annular-polycyclic erythema and the papulosquamous variant), there were no significant correlations between the type of eruption and the severity of extracutaneous manifestations. Conclusion: Patients with acute lupus skin lesions could usually be classified as suffering from SLE, whereas monomorphic patients with localized discoid lesions rarely exhibited extracutaneous manifestations. This tendency was less distinct in bimorphic patients. Almost all patients with subacute skin lesions were bimorphic or trimorphic, which might be due to genetic or racial differences between Japanese and other populations.
Article
Background. Assessment methods for atopic dermatitis (AD) are not standardized, and therapeutic studies are difficult to interpret. Aims. To obtain a consensus on assessment methods in AD and to use a statistical method to develop a composite severity index.Methods. Consensus definitions were given for items used in the scoring system (extent, intensity, subjective) and illustrated for intensity items. Slides were reviewed to address within and between-observer variability by a group of 10 trained clinicians, and data were statistically evaluated with a two way analysis of variance. Two variants of an assessment system were compared in 88 patients at 5 different institutions. Data were analyzed using principal-component analysis. Results. For 5 intensity items studied (erythema, edema/papulation, oozing/crusts, excoriations, lichenification), within- and between-observer variability was good overall, except for edema/papulation which was difficult to assess with slides. In the series of 88 patients, principal-component analysis allowed to extract two unrelated components: the first one accounting for 33% of total variance was interpreted as a ‘severity’ component; the second one, accounting for 18% of variance, was interpreted as a ‘profile’ component distinguishing patients with mostly erythema and subjective symptoms and those with mostly lichenification and dryness and lower subjective symptoms. Of the two evaluation systems used, the one using the rule of nine to assess extent was found more workable than the one using a distribution × intensity product. A scoring index (SCORAD) combining extent, severity and subjective symptoms was mathematically derived from the first system and showed a normal distribution of the population studied. Conclusion. The final choice for the evaluation system was mostly made based on simplicity and easy routine use in outpatient clinics. Based on mathematical appreciation of weights of the items used in the assessment of AD, extent and subjective symptoms account for around 20% each of the total score, intensity items representing 60%. The so-designed composite index SCORAD needs to be further tested in clinical trials.
Article
Objective To evaluate the validity of the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) for use by rheumatologists via reliability testing, and to extend the validation for dermatologists.Methods Fourteen subjects with cutaneous lupus erythematosus (CLE; n = 10), a mimicker skin disease only (a cutaneous lesion that may appear clinically similar to CLE; n = 1), or both (n = 3) were rated with the CLASI by academic-based dermatologists (n = 5) and rheumatologists (n = 5).ResultsThe dermatology intraclass correlation coefficient (ICC) was 0.92 for activity and 0.82 for damage; for rheumatology the ICC was 0.83 for activity and 0.86 for damage. For intrarater reliability, the dermatology Spearman's rho was 0.94 for activity and 0.97 for damage; for rheumatology the Spearman's rho was 0.91 for activity and 0.99 for damage.Conclusion Our data confirm the reliability of the CLASI when used by dermatologists and support the CLASI as a reliable instrument for use by rheumatologists.
Article
To evaluate the efficacy of hydroxychloroquine (HCQ) and quinacrine (Qn) association, at two different dosages, in treatment of lupus skin lesions not responding to HCQ alone. Thirty-four patients, affected by cutaneous and systemic lupus erythematosus, were retrospectively analysed. They were treated by HCQ (5 mg/Kg/qd) and Qn with two regimens: 100 mg/qd (29 cases) and 50 mg/qd (5 cases). Discoid lupus erythematosus (19 cases), acute malar rash (6 cases), chilblain lupus (4 cases) showed a significant improvement with combination therapy (P = 0.009, P = 0.019, and P = 0.04, respectively). Ten patients with subacute cutaneous lupus showed a partial response, whereas lupus profundus didn't improve. The same overall response rate was recorded comparing two Qn regimens, but subjects taking 100 mg/qd improved more rapidly than the others (P = 0.001). Ten patients developed side effects, mainly represented by skin yellowish discolouration. Depression and severe headache with nausea, which were globally recorded in two cases, led to drug withdrawal. One additional case of hepatitis was recorded in a patient with preexisting Hepatitis C virus (HCV) infection. Combination of HCQ and Qn is rapidly effective at 100 mg/qd and well tolerated in the treatment of lupus skin lesions unresponsive to HCQ alone.
Article
Treatment of chronic discoid lupus erythematosus (CDLE) with a pulsed dye laser (PDL) has shown promising results, although outcomes in previous studies were not validated and laser parameters were inconsistent. We conducted an open prospective study to assess the efficacy and safety of PDL for the treatment of recalcitrant CDLE, using a validated scoring method and a fixed treatment schedule. Twelve patients with active CDLE lesions were treated with PDL (585 nm, fluence 5.5 J/cm(2), spot size 7 mm) 3 times with an interval of 6 weeks followed by a 6-week follow-up period. Treatment outcomes were evaluated by 3 observers using the validated Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). Cosmetic results and adverse events were recorded. A significant decline in "active" CLASI was observed after 6 weeks, after 12 weeks, and at follow-up. Baseline active CLASI was 4.4 +/- 0.2 (mean +/- SEM), reaching 1.3 +/- 0.3 after follow-up (P < .0001). Individual scores for erythema and scaling/hypertrophy significantly declined 6 weeks after treatment. The "damage" CLASI (dyspigmentation, scarring, and atrophy) did not show any significant change during or after therapy. The observed clinical improvement was confirmed by two independent observers by clinical assessment of photographs (r = 0.87 and r = 0.89; both P < .05). The treatment was well tolerated, only minimal pain was reported, and the cosmetic result was fair. Small sample size and short follow-up duration were limitations. PDL treatment is an effective and safe therapy for patients with refractory CDLE.
Article
In this issue of the Archives there are 6 articles on the subject of cutaneous lupus erythematosus (CLE) that provide dermatologists with new insights and offer us practical advice about the manner in which we might care for patients who present to our clinics and offices with cutaneous lesions of lupus erythematosus (LE). I reached out to several of the authors for answers to some of the questions that developed as I reviewed this group of articles systemically rather than individually. The answers that I received to some of my questions are within this editorial. As part of the process of preparing this editorial, I have included some practical information about how I evaluate and treat patients with CLE in my clinical practice and conclude with what I see are unanswered questions that remain for future study.
Article
To determine the efficacy of antimalarial drug use in patients with lupus erythematosus tumidus. Retrospective single-center study. Dermatologic clinic at a university hospital. Thirty-six patients with multifocal lupus erythematosus tumidus. Intervention Treatment with either chloroquine phosphate or hydroxychloroquine sulfate. Cutaneous Lupus Erythematosus Disease Area and Severity Index score. Treatment with antimalarial drugs resulted in a significant reduction in the Cutaneous Lupus Erythematosus Disease Area and Severity Index score, from 4 (range, 2-8) at baseline to 1 (range, 0-6) after 3 months of therapy (P < .001). Twenty-two patients (61%) exhibited complete or almost complete clearance of skin lesions, consistent with a clinical score of 0 or 1. No difference in efficacy was noted between the chloroquine-treated group and the hydroxychloroquine-treated group (P = .40). Adverse effects (nausea, dizziness, and headache) occurred only in patients treated with chloroquine. Twenty-eight patients (78%) were smokers, and smokers had a significantly higher mean (SD) clinical score than nonsmokers (5.1 [1.8] vs 3.3 [1.6]; P = .03). Moreover, smokers had a significantly lower reduction in clinical score with antimalarial treatment compared with nonsmokers (r = 0.30; P = .03; 95% confidence interval, -0.05 to 0.57). Eighty-eight percent of nonsmokers (7 of 8 patients) but only 57% of smokers (16 of 28 patients) had a clinical score of 1 or 0 after 3 months of treatment with antimalarial drugs. These retrospective study findings demonstrate that antimalarial treatment is highly effective in multifocal lupus erythematosus tumidus. Lower incidence of adverse effects and equal efficacy might favor the use of hydroxychloroquine. Patients who smoke should be encouraged to join smoking cessation programs because they will respond better to antimalarial treatment.
Article
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.
Article
Drug-induced lupus erythematosus (DILE) is defined as a lupus-like syndrome temporally related to continuous drug exposure which resolves after discontinuation of the offending drug. There are currently no standard diagnostic criteria for DILE and the pathomechanisms are still unclear. Similarly to idiopathic lupus, DILE can be diveded into systemic (SLE), subacute cutaneous (SCLE) and chronic cutaneous lupus (CCLE). Systemic DILE is characterized by typical lupus-like symptoms including skin signs, usually mild systemic involvement and a typical laboratory profile with positive antinuclear and anti-histone antibodies, while anti-double strand (ds) DNA and anti-extractable nuclear antigens antibodies are rare. High risk drugs include hydralazine, procainamide and isoniazid. Drug-induced SCLE is very similar to idiopathic SCLE in terms of clinical and serologic characteristic, and it is more common than the systemic form of DILE. Drugs associated with SCLE include calcium channel blockers, angiotensin-converting enzyme inhibitors, interferons, thiazide diuretics and terbinafine. Drug-induced CCLE is very rarely reported in the literature and usually refers to fluorouracile agents or non steroidal anti-inflammatory drugs. Recently, cases of DILE have been reported with anti-TNFalpha agents. These cases present with disparate clinical features including arthritis/arthralgia, skin rash, serositis, cytopenia and variable laboratory abnormalities. DILE to anti-TNFalpha agents differs in several ways to classic DILE. The incidence of rashes is higher compared to classical systemic DILE. In most cases of classic DILE visceral involvement is rare, whereas several cases of anti-TNFalpha DILE with evidence of renal disease have been reported. Low serum complement levels as well as anti-extractable nuclear antigen antibodies and anti-dsDNA antibodies are rarely present in classic DILE, whereas they are reported in half the cases of anti-TNFalpha DILE; in contrast, anti-histone antibodies are described in classic DILE more often than in anti-TNFalpha DILE. Recognition of DILE in patients receiving anti-TNFalpha therapy can be difficult due to the symptoms of their underlying disease. A temporal association (months to years) of the offending drug with characteristic or suggestive symptoms, and resolution of symptoms on drug withdrawal is the best evidence for this diagnosis of DILE.
Article
Lupus erythematosus panniculitis is an uncommon variant of lupus erythematosus characterized by a specific involvement of the subcutaneous fat. It is a panniculitis with peculiar clinical features and histopathologically characterized by a mostly lobular panniculitis. It may appear in patients with discoid lupus erythematosus and systemic lupus erythematosus, but also as the unique manifestation of lupus erythematosus, and in the latter cases the diagnosis may be problematic. Histopathologic differential diagnosis with subcutaneous panniculitis-like T-cell lymphoma may also be extremely difficult. This article reviews the salient clinicopathologic features and treatment of lupus erythematosus panniculitis, with special emphasis on the histopathologic features.
Article
We have characterized the clinical and laboratory features of 27 patients who had in common a recurring, superficial, nonscarring type of cutaneous lupus erythematosus (LE) that occurred in a characteristic distribution (subacute cutaneous lupus erythematosus [SCLE]). This clinically distinct form of cutaneous LE has not previously been analyzed as a separate entity and thus, its clinical importance has not been fully appreciated. We found that these patients frequently had a mild systemic illness marked by musculoskeletal complaints and serologic abnormalities. Forty-eight percent had systemic LE by American Rheumatism Association criteria; however, none had serious CNS or renal disease. Thus, those with SCLE are a subset of patients with LE who generally have an illness intermediate in severity between discoid LE and severe systemic LE.
Article
A small percentage of patients with alopecia areata have connective diseases such as systemic lupus erythematosus, discoid lupus erythematosus, rheumatoid arthritis, and scleroderma. Lupus erythematosus is associated with a number of different types of alopecia, but the incidence of alopecia areata in lupus erythematosus has not been examined. Of our cohort of 39 patients with lupus erythematosus, alopecia areata developed in 10% (four patients), in contrast to 0.42% of general dermatologic patients. Biopsy specimens of alopecia areata lesions in each of our patients showed continuous granular deposition of IgG at the dermoepidermal junction, a finding usually found in only a minority of alopecia areata cases. Intralesional injections of corticosteroids were effective treatment. The incidence of alopecia areata in patients with lupus erythematosus is increased. Recognition of this form of alopecia allows for specific therapy with intralesional corticosteroids.
Article
In this retrospective study, the authors describe the clinical, histologic and laboratory features of 15 cases of chilblain or perniotic lupus. In winter, the patients (14 women, 1 man) develop chilblain-like lesions, chiefly in the toes (8 times) and fingers (11 times). Histologic features are identical to those of discoid lupus erythematosus. The damaged skin gives a positive fluorescent band test. Usually, these lesions occur in association with discoid lupus of the face. However, in 8 patients, they were the only cutaneous sign of lupus. This form of lupus can evolve to a systemic form, as was the case with 3 patients.
Article
Three methods of measuring the surface area of the involved skin were compared in 10 patients with psoriasis. Using the rule of nines, four untrained observers estimated the average extent of psoriasis as 20, 14, 23 and 33% of the body surface area. Measuring the area of tracings of plaque outlines using image analysis gave a mean involved surface area of 9% and image analysis of whole body photographs gave a mean value of 7%. We conclude that untrained observers using the rule of nines will overestimate the extent of psoriasis and that image analysis of whole body photographs is comparable to that of traced outlines.
Article
The prevalence and pattern of mucosal involvement in 121 patients with lupus erythematosus (LE) was investigated. Fifty-three patients had systemic LE (SLE) and 68 patients had chronic cutaneous LE (CCLE). Twenty-one per cent (11/53) of patients with SLE and 24% (16/68) of patients with CCLE had signs of mucosal involvement, but the pattern of involvement differed in the two groups. Nasal mucosal lesions were a feature in 2% (I/53) of patients with SLE and 9% (6/68) of patients with CCLE. Hyperkeratotic lichen planus-like plaques on buccal mucosa and the palate occurred in 9% (6/68) of patients with CCLE and 4% (2/53) of patients with SLE. Episcleritis occurred in 9% (5/53) of patients with SLE and not seen in CCLE. Erythematous plaques on the lower eyelids were present in 6% (4/68) of patients with CCLE and these were associated with conjunctival scarring in two patients. Vulval lesions were present in 5% (2/42) of female patients with CCLE. Oral plaques may occur when the disease is relatively quiescent elsewhere. The prevalence of mucosal involvement in lupus is underestimated as the lesions may be asymptomatic.
Article
Serologic and clinical data were obtained from forty patients with discoid lupus erythematosus in 1982. Clinical disease was characterized by quality, extent, severity, activity, photosensitivity, and systemic manifestations. The patient's sera were examined for the presence of antinuclear, anti-Ro and anti-La, anti-ribonucleoprotein and anti-Sm, anti-single-stranded deoxyribonucleic acid (ssDNA), and antinative DNA antibodies. In late 1984, thirty-three patients had follow-up clinical examinations. On the initial evaluation the patients with positive antinuclear antibody (ANA) findings were clinically characterized by a significantly higher incidence of photosensitivity and arthritis, an elevated erythrocyte sedimentation rate, and cutaneous lesions of subacute cutaneous lupus erythematosus. The activity and extent of disease in 1982 did not correlate with the presence of ANA. Elevated levels of ssDNA antibodies were present in seven of the forty patients (significantly greater than control subjects; (p less than 0.005) and correlated with widespread, active discoid lupus erythematosus, an elevated erythrocyte sedimentation rate, and a slightly greater risk of systemic lupus erythematosus in 1982. At the 2-year follow-up examination, thirteen of the seventeen patients with a positive ANA had active clinical cutaneous disease, and ten of the sixteen patients with negative ANA findings had continued activity (not statistically significant). However, all seven patients with elevated ssDNA antibody levels had continued activity, and disease progression had occurred in three. Thus the presence of ssDNA seems to correlate strongly with active, progressive lupus erythematosus. The presence of antibody abnormalities in patients with discoid lupus erythematosus correlates with clinical disease and provides more support for the theory linking discoid lupus erythematosus to systemic lupus erythematosus as part of a continuum.
Article
Circulating and tissue-deposited IgG antibodies to the cutaneous basement membrane zone (BMZ) were detected in 3 patients with the clinical, pathologic, and immunologic features of bullous eruption of systemic lupus erythematosus (SLE). The antibodies were present in sera and IgG fractions in all cases and in eluates of cutaneous immune deposits from one of the cases. The antibodies were easily detected in sera by indirect immunofluorescence on adult human thigh skin separated through the lamina lucida by incubation in 1.0 M NaCl but were less easily detected on intact neonatal foreskin. The antibodies had features of epidermolysis bullosa acquisita (EBA) anti-BMZ antibodies including binding to the dermal side of the BMZ in separated skin, binding to the cutaneous but not vascular or glomerular basement membranes, binding to and just below the lamina densa, and binding to 290 or 290 and 145 kD dermal proteins previously identified as components of the EBA autoantigen. The antibodies were relatively specific for SLE patients with features of bullous eruption of SLE since they were detected in 3 of 4 of those cases and in only 1 of 20 SLE patients without blisters. These results show anti-BMZ antibodies with features of EBA antibodies are present in patients with bullous eruption of SLE and suggest there may be a close relationship between that disease and EBA. The results also suggest that EBA antibodies may be part of the autoantibody spectrum of SLE and that separated skin is more sensitive than intact skin for their detection.
Article
colon; Alopecia is a well recognized manifestation of systemic lupus erythematosus (SLE) and it was found to occur in 58.5 per cent of 176 SLE patients prospectively studied. More characteristic although less frequent was shortening of the frontal hair which was described and termed "lupus hair" by Armas-Cruz and his coworkers. Although confirmed by others, this sign has been little recognized. Inasmuch as it was found in 30 per cent of our 176 patients, when present it may be an important clue to the diagnosis of SLE.
Article
Vesicles and bullae complicating systemic lupus erythematosus (SLE) are relatively uncommon. Two young women with SLE presented with vesiculobullous eruptions on sun-exposed areas that resembled dermatitis herpetiformis (DH) histologically. There were active visceral manifestations of SLE in both patients, including mesangioproliferative glomerulonephritis. Granular deposits of IgG and/or IgM, along with IgA, were demonstrated along the basement membrane of skin by direct immunofluorescence microscopy. Review of fifteen additional cases of vesiculobullous SLE reported in the literature suggests that this cutaneous manifestation of SLE is associated with a high incidence of IgA deposits in skin and glomerulonephritis. The following criteria for the diagnosis of a distinct subset of vesiculobullous skin lesions occurring in patients with SLE are proposed: (1) a diagnosis of SLE based upon American Rheumatism Association (ARA) criteria; (2) vesicles and bullae arising upon but not limited to sun-exposed skin; (3) histopathology compatible with DH; (4) negative indirect immunofluorescence for circulating basement membrane zone (BMZ) antibodies; (5) direct immunofluorescence reveals IgG and/or IgM and often IgA at the BMZ.
Article
Two patients with established systemic lupus erythematosus developed bullous dermatoses clinically suggestive of bullous pemphigoid (BP). Direct immunofluorescence demonstrated linear staining at the dermoepidermal junction for IgG and C3 in a pattern typical for BP. However, immunoelectron microscopy demonstrated deposits of IgG largely below the basal lamina, with little if any deposit present within the lamina lucida. These findings are consistent with systemic lupus erythematosus (SLE) and effectively rule out BP. In addition, the leukocyte attachment assay, an in vitro assay of the functional activity of tissue-deposited immune complexes, demonstrated strong attachment of leukocytes to the dermoepidermal junction of patients' skin, suggesting that the immune reactants were functional immune complexes of possible importance to the pathogenesis of the bullous lesions. To our knowledge, this is the first time that immunoelectron microscopy has been performed on skin from patients suspected of manifesting concurrent SLE and BP. Our findings cast doubt on previous such reports by demonstrating the existence of a bullous form of SLE resembling BP both clinically and by direct immunofluorescence.
Article
The 30-item General Health Questionnaire (GHQ) (Goldberg, 1972) was administered to 196 consecutive new dermatology out-patients and 40 consecutive admissions to dermatology beds. Thirty per cent of the outpatients and 60 per cent of the in-patients obtained high scores, while half the high scorers in each group scored high on the Wakefield Self-Assessment Depression Scale (Snaith et al , 1971). These findings suggest that dermatology out-patients have a higher prevalence of psychiatric disorder than the general population, and dermatology in-patients a higher prevalence than general medical in-patients. High GHQ scores were associated with (a) diagnoses of acne, eczema, psoriasis or alopecia; with (b) extensive lesions on exposed parts of the body; and with (c) the use of high potency topical steroid. We indicate other areas that might be profitably explored in a full-scale study.
Article
We studied the autoimmune serologic features and histocompatibility antigen associations of 27 patients who had a widespread, nonscarring and often photosensitive form of histologically specific cutaneous lupus erythematosus. We designated this disorder as subacute cutaneous lupus erythematosus. Skin lesions from this disorder can be distinguished from scarring discoid lupus erythematosus lesions both on a morphologic and histopathologic basis. Antinuclear and anticytoplasmic antibodies (Ro or Ro and La) and circulating immune complexes were frequently present in patients with subacute cutaneous lupus erythematosus, whereas rheumatoid factor and anti-lymphocyte, anti-DNA, anti-nRNP, and anti-Sm antibodies were found less frequently. Patients having annular skin lesions represented a particularly homogeneous subgroup in which there was a striking concordance of anti-Ro antibodies and the HLA-DR3 phenotype. These studies clearly establish that the presence of these lesions can serve as a cutaneous marker for a distinct subset of patients with lupus erythematosus who share similar clinical, serologic, and genetic features.
Article
• Chronic discoid lupus erythematosus (DLE) is a common condition. Sixty-two patients with biopsy-proved, active DLE were observed and their conditions were analyzed for clinical, laboratory, and therapeutic data. Fifty-six patients had disease limited to the skin—2 localized and 30 widespread (above and below the neck). At the time of follow-up examination, active disease was present in 32 patients, 28 of whom had widespread DLE. Six patients had DLE as a manifestation of systemic LE (SLE). In four patients, the DLE preceded the development of SLE. Laboratory abnormalities were substantially more common in patients with widespread DLE than in patients with localized DLE. An analysis of therapeutic results in this series confirmed the beneficial effects of intralesional corticosteroids and antimalarial agents and demonstrated relatively poor responsiveness to topical or oral corticosteroids. (Arch Dermatol 1982;118:412-416)
Article
Epidermolysis bullosa acquisita may be associated with various systemic diseases, including systemic lupus erythematosus. We describe the clinical and immunological findings in a 38-year-old women with epidermolysis bullosa acquisita and systemic lupus erythematosus. The epidermolysis bullosa acquisita preceded a dramatic flare of systemic lupus erythematosus and fatal cerebral vasculitis. If serologic evidence of lupus erythematosus develops during the course of epidermolysis bullosa acquisita, a thorough investigation is warranted to rule out potentially life-threatening systemic lupus erythematosus.
Article
Lupus erythematosus (LE) is a multi-organ-system disease, the characteristics of which are reflected in the 1982 American Rheumatism Association (ARA) criteria for systemic lupus erythematosus (SLE). From a dermatological point of view, only the presence of LE-specific histopathology is necessary and sufficient for the diagnosis of LE. The association between the type of LE-specific skin lesion and the severity of extracutaneous manifestations of LE has not yet been investigated systematically. The aim of this study was to evaluate, according to the type of LE skin lesions, the prevalence of the 1982 criteria for SLE. We selected 191 patients whose skin lesions were histologically diagnosed as LE specific. Patients were classified on the basis of skin disease, and their clinical and laboratory data were analyzed. Of 191 patients, 130 (68%) exhibited only one type of LE-specific skin lesion (monomorphic), 55 (29%) had two types (bimorphic) and the remaining 6 (3%) displayed three types (trimorphic). Nineteen of 22 (86%) patients who presented discoid lupus skin lesions above the neck without other eruptions were classified in the cutaneous-limited LE spectrum. Of 116 patients with acute lupus skin lesions (malar rash), 83 (72%) clearly fulfilled the 1982 ARA criteria for SLE. In skin lesions of LE profundus, chilblain lupus, subacute lupus (annular-polycyclic erythema and the papulosquamous variant), there were no significant correlations between the type of eruption and the severity of extracutaneous manifestations. Patients with acute lupus skin lesions could usually be classified as suffering from SLE, whereas monomorphic patients with localized discoid lesions rarely exhibited extracutaneous manifestations. This tendency was less distinct in bimorphic patients. Almost all patients with subacute skin lesions were bimorphic or trimorphic, which might be due to genetic or racial differences between Japanese and other populations.
Article
Blistering in systemic lupus erythematosus has been divided into three groups. A specific subgroup of 'bullous systemic lupus erythematosus' has been defined by Gammon et al. on the basis of a number of criteria. From our experience of seven patients with bullous systemic lupus erythematosus, and after reviewing the literature, we suggest that the current classification is too narrow. Our patients displayed clinical and immunohistological (based on direct and indirect immunofluorescence and Western immunoblotting) heterogeneity. Sera from two patients bound to epidermal epitopes in sodium chloride-split skin, but immunoblotting was negative. In neither of these patients could the target antigen be type VII collagen, the only antigen identified as pathogenic in this disease. Patients with epidermal binding should not be excluded from a diagnosis of bullous systemic lupus erythematosus. SLE is a disease in which there is a genetic predisposition to form antibodies to type VII collagen, along with other autoantibodies, many of which may be implicated in blistering. We suggest that the criteria for the diagnosis of BSLE should be revised. We define this disease as an acquired subepidermal blistering disease in a patient with SLE, in which immune reactants are present at the basement membrane zone on either direct or indirect immunofluorescence.
Article
Hypertrophic discoid lupus erythematosus (HDLE) may resemble cutaneous squamous cell carcinoma (SCC) histologically. The histologic features that help to differentiate HDLE from SCC are reviewed. Two patients are described with HDLE. Both patients were treated initially with Mohs surgery for "biopsy-proven" SCC. Subsequent biopsies confirmed the diagnosis of HDLE and the patients responded well to appropriate therapy. No significant complications occurred in either patient. Lesions of HDLE may imitate SCC. Strategies are suggested to avoid surgical procedures based on an incorrect biopsy report.
Article
Responses to a range of doses of common contact dermatitis-producing allergens were measured using a novel scanning laser Doppler velocimeter and three commonly used conventional measurement techniques. The techniques were compared in terms of sensitivity, measurement error, range of the linear portion of the dose-response curve and ease of use. The detection thresholds of the objective methods did not differ significantly and did not detect responses at concentrations less than those required to produce a visible response. Of the objective methods the range of linearity was greatest when reactions were measured using change in skin fold thickness, erythema or area of inflammation. Measurement error was greatest with measurements made using the conventional laser Doppler velocimeter. Present instrumental methods are no more sensitive than visual assessment in the reading of patch test reactions. The conventional laser Doppler velocimeter was least suited for measurement of allergic contact hypersensitivity reactions as readings are time-consuming, show detectable changes over a more limited range of allergen concentration, and have a larger measurement error than the other methods. There is no single best method for measuring allergic contact hypersensitivity reactions. Useful data over a wide range of allergen concentrations can best be obtained by measurement of skin fold thickness, erythema or area of reaction using the scanning laser Doppler velocimeter. The scanning laser Doppler velocimeter has the added advantages of being able to measure area of reaction without contact with the skin surface and to measure reactions at all skin sites.
Article
Visual grading, a laser Doppler flowmeter, a spectroradiometer, a two-channel erythema meter and a Minolta chroma meter were compared in the measurement of erythemas arising from immediate contact reactions produced either by 250 mM benzoic acid or 10 mM methyl nicotinate in petrolatum in an open application test or by ultraviolet irradiation. A good correlation between visual grading and objectively measured values was found for all the instruments, but the laser Doppler flowmeter gave proportionally lower values for the ultraviolet erythemas than the skin reflectance meters, suggesting that these differ from erythemas induced by benzoic acid or methyl nicotinate. The laser Doppler flowmeter gave less repeatable results than other meters when measuring moderate and pronounced erythemas produced by ultraviolet irradiation. Measuring both the blood flow and the actual erythema may give more information about the reaction than either measurement system alone.
Article
Bullous systemic lupus erythematosus (SLE) is a rare blistering disease with a distinctive combination of clinical, histologic and immunopathologic features that together constitute a unique bullous disease phenotype. There appear to be at least two immunologically distinct subtypes of bullous SLE characterized by the presence or absence of circulating and/or tissue-bound basement membrane zone autoantibodies that recognize type VII collagen. The two subtypes are not clearly distinguishable except by indirect immunofluorescence and/or direct immunoelectron microscopy. In patients without circulating antibodies, immunoelectron microscopy is required to distinguish between the two subtypes. Patients with autoantibodies to type VII collagen are similar but not identical to patients with epidermolysis bullosa acquisita--another bullous disease associated with autoantibodies to type VII collagen. Autoantibodies to type VII collagen in patients with bullous SLE is only one of several lines of evidence that indicate autoimmunity to that protein and susceptibility to SLE are associated phenomena. In addition, there is emerging evidence for an association between epidermolysis bullous acquisita and SLE. There is also evidence that autoantibodies to type VII collagen are pathogenic in bullous SLE (and epidermolysis bullosa acquisita) and that their production is regulated by the class II major histocompatibility complex DR beta 1 allele, 1501 and possibly other DR beta 1 alleles that share a similar sequence of amino acids in the second hyper-variable region.
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The ability to assess the severity of dermatoses by measurement of area of involvement is important in both clinical practice and research. Using schematic figure outlines we have shown that physicians, nurses and other groups are unable to assess area accurately, and that the degree of error is partially dependent on absolute area, but also on other factors. The pattern and magnitude of the errors varied between the groups examined, but overall was such that it calls in question the use of area indices such as the PASI (psoriasis area and severity index) score in the assessment of inflammatory dermatoses.
Article
Despite widespread use of acne lesion counting, little has been published on its reliability, particularly for multiple raters. Our purpose was to assess reliability of acne lesion counting with the use of a five-segment facial template. After training, 12 raters each evaluated 12 patients in randomized order, in the morning and again in the afternoon, and recorded counts for different types of lesions on a five-segment facial template. Individual raters could reproduce their total lesion counts (reliability estimates, 0.81 to 0.97). Variability between raters was high, and overall reliability estimated across raters was 0.61. For a subgroup of commonly trained raters, overall reliability was higher (0.80). The reliability of acne lesion counting is excellent when performed by the same trained rater over time. The high variability between raters appears to be reduced by standardized training. Because fewer lesions are counted with less variation, use of a template may have contributed to the high within-rater reliability.
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Many different systems have been proposed for the recording and measurement of disease activity in atopic dermatitis (AD). This review describes the techniques that have been used and published in recent years for clinical evaluation and for objective measurement of AD, as well as for recording its effects on quality of life. Recommendations are made concerning which methods should be used.