Cutaneous Lupus Erythematosus Disease Research Articles

Dermoscopic Characteristics of Cutaneous Lupus Erythematosus According to Subtype, Lesion Location, Lesion Duration, and CLASI Score.

Dermoscopic findings are used to diagnose and evaluate disease activity in patients with cutaneous lupus erythematosus (CLE). This study aimed to characterize the dermoscopic features of discoid LE (DLE) and LE tumidus (LET) by lesion duration and CLE Disease Area and Severity Index (CLASI) scores and to examine the dermoscopic findings of lesions in different locations in DLE patients. Dermoscopic findings (follicular features, perifollicular surface, interfollicular features, and vessel pattern) were assessed and lesion duration (≤12 and >12 months) and CLASI scores (grouped as mild or moderate) were calculated. DLE lesion locations were categorized as, non-scalp, scalp and lip. Forty-eight dermoscopic images from 35 DLE and 4 LET patients were analyzed. The most common dermoscopic findings in non-scalp DLE were follicular keratotic plugs (82.8%) and white scales (69%). In scalp DLE (n=9), the most common findings were absent follicular openings (77.8%), white structureless areas (77.8%), and perifollicular scaling (66.7%). All LET patients had pink-white background and linear vessels. Follicular plugs, peripheral pigmentation, and polymorphous vessels were lower in patients with mild CLASI activity than moderate activity (P = 0.036, 0.039, and 0.019, respectively). Fibrotic white dots, honeycomb pigment pattern, and blue-gray dots/globules were lower in those with mild CLASI damage scores than moderate damage (P = 0.010, 0.010, and 0.020, respectively). Peripheral pigmentation was more common in patients with lesion duration ≤12 months, while blue-gray dots/globules were more common with lesion durations >12 months. Certain dermoscopic features may facilitate the differential diagnosis of DLE and LET.

Rapid efficacy of anifrolumab across multiple subtypes of recalcitrant cutaneous lupus erythematosus parallels changes in discrete subsets of blood transcriptomic and cellular biomarkers.

Observations with rituximab suggest B-cell independent mechanisms of cutaneous lupus erythematosus (CLE) in systemic lupus erythematosus (SLE), especially discoid lupus erythematosus (DLE). Type-I interferon receptor blockade with anifrolumab shows efficacy in SLE, but efficacy for cutaneous disease of specific morphologies has not been studied. Interferon has pleotropic immune effects and it is unknown which of these are critical to therapeutic response. We evaluated clinical efficacy and quality-of-life impact of type-I interferon-blockade in: (i) rituximab-refractory CLE; (ii) DLE and other morphologies and (iii) transcriptomic and flow cytometric biomarkers. We conducted a prospective single-centre study of anifrolumab in refractory mucocutaneous SLE. CLE Disease Area and Severity Index (CLASI) activity score, health-related quality of life, 96-probe TaqMan® gene expression analysis capturing key SLE blood transcriptome signatures, and eight-colour flow cytometry were undertaken at baseline, 1, 3 and 6 months. Seven patients [DLE (n = 5), chilblain lupus erythematosus (n = 1), subacute CLE (n = 1)] were evaluated. The median number of prior therapies was six (range 3-15), including rituximab in six of seven patients. Median CLASI-A showed rapid and sustained improvement from 17 at baseline to 6 (P = 0.016) at 1 month and 0 (P < 0.001) by 3 months. The median percentage reduction in CLASI-A at 3 months was 60%. Significant improvements were observed in Dermatology Life Quality Index scores (P < 0.001), EuroQol 5D visual analogue scale (P = 0.002) and LupusQoL fatigue, image and planning domains (P ≤ 0.05). One patient discontinued treatment owing to severe herpes zoster. Clinical responses paralleled discrete suppression of interferon-stimulated genes (ISGs) from SLE blood transcriptome module M1.2 with more varied downregulation in other interferon modules. Myeloid and inflammation-annotated genes remained upregulated throughout treatment. Intermediate monocytes (CD14++CD16+) reduced to normal levels during therapy (P = 0.014), while other flow subsets showed no substantive changes. These data indicate rapid efficacy of anifrolumab in DLE and rituximab-resistant CLE. Response is associated with suppression of a subset of ISGs and decline in intermediate monocytes. Suppression of all ISGs or the wider SLE blood transcriptome is not required for response.

Discoid lesions and smoking history are negative predictors of disease activity remission in cutaneous lupus erythematosus

To the Editor: Cutaneous lupus erythematosus (CLE) is a photosensitive skin disorder with a heterogeneous clinical course.1 While it is known that long-term stabilization of disease activity can be achieved on standard therapies, frequencies of remission and recurrence of CLE disease activity are not well studied.2 In this retrospective study, we assessed the rates of disease activity remission and recurrence in a cohort of CLE patients and identified the factors associated with each outcome.

Correlation of whole blood hydroxychloroquine concentration with cutaneous lupus erythematosus and factors associated with it: First multicenter, cross-sectional analysis in Malaysia.

Hydroxychloroquine (HCQ) is the first-line systemic treatment for cutaneous lupus erythematosus (CLE). Whole blood HCQ concentration (WBHCQ) was found to correlate with CLE severity among Caucasians. However, studies on Asians are scarce. We aim to explore the relationship of WBHCQ with CLE disease activity among multi-racial Malaysians and the factors associated with WBHCQ. A cross-sectional study targeting patients with CLE was conducted from 1 June till 30 November 2019. Disease activity was assessed using Cutaneous Lupus Erythematosus Disease Area and Severity Index - Activity Score (CLASI-AS). Blood was analyzed for WBHCQ concentration using a high-performance liquid chromatography technique. Statistical analysis was done using R studio version 1.2.1335. A total of 88 subjects (male:female, 4.5:1) with a median age of 41years old were recruited. The median duration CLE was 5years. The majority had acute cutaneous lupus (n=45, 51.1%). The median WBHCQ was 946.8ng/mL. Indians were found to have the highest WBHCQ (median±interquartile range [IQR], 1515.4±1494.8ng/mL). Males had a lower WBHCQ (median±IQR, 733.5±573.8ng/mL) than females (995.5±925.1ng/mL). However, no statistically significant association between race and sex with WBHCQ was demonstrable (p=0.247, p=0.066). No correlation was demonstrated between WBHCQ and CLASI-AS (r=-0.02, p=0.851). A positive correlation was found between HCQ dosage (ideal bodyweight) and WBHCQ (r=0.24, p=0.027). No other factors were found associated with WBHCQ. Indians and females were observed to have higher WBCHQ; however, no significant correlation was identified. Further study is required to confirm the finding.

Senescent Progenitor Cells in the Skin of Patients with Cutaneous Lupus Erythematosus

Senescent Progenitor Cells in the Skin of Patients with Cutaneous Lupus Erythematosus

Treatments for disease damage in cutaneous lupus erythematosus: A narrative review.

Cutaneous lupus erythematosus (CLE) is an autoimmune photosensitive disorder that affects the skin. CLE lesions can have signs of skin damage including dyspigmentation, scarring, atrophy and/or alopecia. Disease damage secondary to CLE can be cosmetically disfiguring and causes patients significant distress. While many current treatments for CLE focus primarily on reducing inflammation, there are few options for managing disease damage. Providers currently lack strong guidance on managing CLE damage due to the paucity of literature on this topic. Because of this knowledge gap, we aim to provide an overview of what is currently known about the pathogenesis and management of signs of disease damage in CLE. In this narrative review, Pubmed, Ovid Medline, and Google scholar were searched for relevant articles assessing pathogenesis and treatment of disease damage. Therapeutic options for CLE damage, including hyperpigmentation (laser and camouflage), hypopigmentation (melanocyte grafting and camouflage), scarring (laser, dermabrasion, and camouflage), atrophy (filler, fat transplantation, and flap procedures), and scarring alopecia (hair transplantation and camouflage) were identified. We found that investigations of therapeutics for CLE disease damage primarily consist of case reports and small case series. Reported adverse events due to treatment for CLE disease damage range from temporary erythema and discomfort to disease reactivation and pigmentary defects. There are various treatments for disease damage for each sign of disease damage. However, more robust investigations are needed to assess disease pathogenesis and improve treatments of disease damage due to CLE.

Expression pattern of tissue-resident memory T cells in cutaneous lupus erythematosus.

Tissue resident memory T cells (TRMs) persist long-term in peripheral tissues without recirculation, triggering an immediate protective inflammatory state upon the re-recognition of the antigen. Despite evidence incriminating the dysregulation of TRMs in autoimmune diseases, few studies have examined their expression in cutaneous lupus erythematosus (CLE). We aimed to examine whether there are differences among TRM populations in CLE depending on different clinical conditions, such as the CLE subtype or association with systemic lupus erythematosus, and to determine the effect of type I interferon (IFN) on the development of TRMs in CLE. CLE disease activity was evaluated using the Cutaneous Lupus Erythematosus Disease Area and Severity Index. The expression of the TRM markers CD69 and CD103 in CLE lesions was evaluated by immunofluorescence. Flow cytometry was performed on peripheral blood mononuclear cells after IFNα treatment. The number of TRMs expressing either CD69 or CD103 was significantly higher in CLE lesions than in control skin; however, it was not significantly different between discoid lupus erythematosus and subacute CLE, or dependent on the presence of concomitant systemic lupus. Lesional severity was not correlated with an increase in TRMs in CLE. IFNα treatment induced a conspicuous increase in CD69 expression in skin-homing T cells, more profoundly in CD4+ T cells than in CD8+ T cells. Skin TRMs, either CD69 or CD103-positive cells, showed increased levels in the lesional skin of CLE, and IFNα increased the expression of CD69 in T cells.

Belimumab for refractory manifestations of cutaneous lupus: A multicenter, retrospective observational study of 16 patients

Belimumab for refractory manifestations of cutaneous lupus: A multicenter, retrospective observational study of 16 patients

Natural history of disease activity and damage in patients with cutaneous lupus erythematosus

Long-term studies characterizing disease course of cutaneous lupus erythematosus (CLE) patients on standard-of-care treatments are lacking. We characterized and compared disease course of CLE patients using Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). In total, 83 CLE patients with CLASI scores collected from ≥3 study visits within 2years had disease activity and damage trends calculated by average change scores (ACS). Trends were classified as improved (ACS ≤-3), worsened (ACS ≥3), or stable (-3<ACS<3). Linear regression models compared CLASI trends between groups. Most patients (72.73%) with initial CLASI activity (CLASI-A) scores >9 (N=33) had improved disease activity versus 14.00% of those with initial CLASI-A scores ≤9 (N=50). Linear regression analyses showed significant improvement in CLASI-A scores in patients of minority races (P<.05), with baseline CLASI-A scores >9 (P<.0001), baseline CLASI damage (CLASI-D) scores ≥10 (P=.0001), and CLE disease duration ≤1year (P=.01). Of 28 patients with baseline CLASI-D scores ≥10, 35.71% had improvements in damage, while 5.26% of patients with initial CLASI-D scores of 5-9 (N=19) and 0% with initial CLASI-D scores <5 (N=36) (P=.0005) had improvements. Limitations include small sample size. Baseline CLASI-A score >9, minority race, and short disease duration predict CLE diseaseactivity improvement. A baseline CLASI-D score ≥10 is associated with disease damage improvement.

The effect of increasing the dose of hydroxychloroquine (HCQ) in patients with refractory cutaneous lupus erythematosus (CLE): An open-label prospective pilot study

Up to 30% of patients with cutaneous lupus erythematosus (CLE) fail to respond to hydroxychloroquine (HCQ). We sought to evaluate the efficacy of increased daily doses of HCQ on cutaneous response in refractory CLE. We conducted an open-label prospective study between 2010 and 2014. Patients with CLE and HCQ blood level less than or equal to 750 ng/mL were included. The daily dose of HCQ was increased to reach blood concentrations greater than 750 ng/mL. The primary end point was the number of responders defined by an improvement of CLE Disease Area and Severity Index score (4 points or 20% decrease) in patients with HCQ blood concentration greater than 750 ng/mL. We included 34 patients (26 women; median age 45 [range 28-72] years). Two nonadherent patients were excluded. The median CLE Disease Area and Severity Index score before treatment was significantly improved after treatment (8 [range 2-30] vs 1.5 [range 0-30]), P < .001). The primary response criterion was reached in 26 (81%) of the 32 patients analyzed. A decrease in HCQ doses without further CLE flare (median follow-up 15.8 [range 3.06-77.4] months) was achieved in 15 of the 26 responders. The main limitations of the study are its open-label design and the limited number of patients included. Increasing HCQ doses to reach blood concentrations greater than 750 ng/mL should be considered before addition of other treatments in refractory CLE.

Influence of smoking on disease severity and antimalarial therapy in cutaneous lupus erythematosus: analysis of 1002 patients from the EUSCLE database

In recent years it has been controversially discussed in the literature if smoking is associated with the activity of cutaneous lupus erythematosus (CLE) and the efficacy of antimalarial agents. To investigate the influence of smoking on disease severity and antimalarial treatment in patients with CLE using the Core Set Questionnaire of the European Society of Cutaneous Lupus Erythematosus (EUSCLE). A total of 1002 patients (768 female, 234 male) with different CLE subtypes were included in this cross-sectional study, which was performed in 14 different countries. Smoking behaviour was assessed by the EUSCLE Core Set Questionnaire in 838 patients and statistically analysed using an SPSS database. The results were correlated with the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the efficacy of antimalarial treatment. A high percentage (87·2%) of the 499 patients with CLE, who have ever smoked, had already smoked at the date of their first diagnosis. Patients with intermittent CLE have ever smoked significantly more often than patients with subacute CLE (P < 0·05) and chronic CLE (P < 0·05). The total CLASI activity and damage score of patients with CLE was 6·6 ± 7·1 and 2·6 ± 4·3, respectively, and was higher in patients who have ever smoked than in nonsmokers. Antimalarial treatment was successful in 84·3% of cases, with a significantly higher efficacy in nonsmokers than in patients with CLE who have ever smoked (P < 0·05). This analysis of a multicentre study population of 838 patients with CLE assessed by the EUSCLE Core Set Questionnaire confirms that smoking negatively influences CLE disease severity and the efficacy of antimalarial treatment.

Characterization of clinical photosensitivity in cutaneous lupus erythematosus

Photosensitivity (PS) in lupus erythematosus (LE) is frequently determined by patient report. We sought to characterize self-reported PS in cutaneous LE (CLE). The PS survey was used to classify subject responses into 5 phenotypes: direct sun-induced CLE flare (directCLE); general exacerbation of CLE (genCLE); polymorphic light eruption-like reactions (genSkin); general pruritus/paresthesias (genRxn); and sun-induced systemic symptoms (genSys). In all, 91 subjects with CLE alone or with CLE and systemic LE were interviewed. In all, 81% ascribed to 1 or more PS phenotypes. CLE-specific reactions (direct sun-induced CLE flare or general exacerbation of CLE) were reported by 86% of photosensitive subjects. Higher CLE disease activity (measured by CLE Disease Area and Severity Index activity scores) was suggestive of direct sun-induced CLE flare reactions (P = .09). In all, 60% of photosensitive subjects described CLE-nonspecific reactions: polymorphic light eruption-like rash and general pruritus/paresthesias. These phenotypes often co-occurred with CLE-specific reactions and were predicted by more systemic disease activity as measured by Physicians Global Assessment (PGA) scores in regression analyses (genSkin, P = .02) and (genRxn, P = .05). In all, 36% of subjects reported systemic reactions and higher PGA scores were predictive of the sun-induced systemic symptoms phenotype (P = .02); a diagnosis of systemic LE was not (P = .14). PS was inferred from patient report and not directly observed. Characterization of self-reported PS in LE reveals that patients experience combinations of CLE-specific, CLE-nonspecific, and systemic reactions to sunlight. Sun-induced CLE flares are associated with more active CLE disease. Polymorphic light eruption-like, generalized pruritus/paresthesias, and systemic reactions are associated with more active systemic disease. Recognition of PS phenotypes will permit improved definitions of clinical PS and allow for more precise investigation into its pathophysiology.

Thalidomide in the treatment of refractory cutaneous lupus erythematosus: prognostic factors of clinical outcome

Although thalidomide has been shown to be effective in patients with refractory cutaneous lupus erythematosus (CLE), its use is still hampered by its potential severe side-effects and the current restricted availability. To evaluate prospectively the clinical efficacy and safety of low-dose thalidomide in an observational study and to establish prognostic factors of clinical outcome. Sixty consecutive patients with refractory CLE were treated with thalidomide (100 mg daily). Clinical response was assessed by the CLE Disease Area and Severity Index (CLASI). Clinical and immunological parameters were evaluated during treatment. Patients were followed for up to 8 years (range 2-18). One patient discontinued treatment because of side-effects. Of the 59 remaining patients, 58 (98%) achieved clinical response, already noticeable at 2 weeks following treatment. Complete response occurred in 50 patients (85%). Clinical relapse was frequent (70%) and usually occurred 5 months after withdrawal or reduction of thalidomide. Subacute CLE (SCLE) was the predicting factor of long-term remission after therapy discontinuation [odds ratio (OR) 30, 95% confidence interval (CI) 5·82-154·63], whereas discoid lupus erythematosus (DLE) was predictive of relapse (OR 5·71, 95% CI 1·36-24·06). Eleven patients (18%) reported paraesthesia; in five of the 11, nerve conduction studies confirmed a sensory polyneuropathy. Neurological symptoms resolved in 12 months (range 6-18) after thalidomide withdrawal. Two patients, heavy smokers and without antiphospholipid antibodies, had a cerebral ischaemic event. Low-dose thalidomide is an effective treatment for refractory CLE, but its benefits need to be balanced against the potential adverse effects. Whereas DLE forms tended to relapse and required a long-term maintenance dose of thalidomide, SCLE forms showed a sustained remission after withdrawal.

Cross-sectional Analysis of a Collaborative Web-Based Database for Lupus Erythematosus–Associated Skin Lesions

To assess disease severity in subsets of patients with cutaneous lupus erythematosus (CLE) by using outcome and quality-of-life measures, and to determine treatment responsiveness by establishing a Web-based database of patients with skin manifestations of lupus. Prospective, cross-sectional study. University hospital cutaneous autoimmunity outpatient clinic. One hundred fourteen patients who presented from January 15, 2007, to November 8, 2007, and met the criteria for having CLE or lupus-nonspecific skin disease. Scores on the CLE Disease Activity and Severity Index and the modified Skindex-29 (a quality-of-life measure) completed at each visit. Seven patients (6.1%) presented with acute CLE, 21 (18.4%) with subacute CLE, 77 (67.5%) with chronic CLE, 7 (6.1%) with systemic lupus erythematosus and LE-nonspecific skin lesions, and 1 (0.9%) with LE-nonspecific skin disease only. The mean baseline CLE Disease Activity and Severity Index activity/damage scores in patients with acute, subacute, and chronic CLE were 6.4/5.1, 11.1/1.6, and 7.5/10.2, respectively. The mean baseline modified Skindex-29 scores were 76.3, 79.4, and 82.7, respectively (P = .80). The disease in 11 of the patients (9.6%) was considered refractory to conventional therapies. Significantly more patients in the refractory group than the nonrefractory group were current smokers (P = .006). This Web-based database should allow collection of data related to disease activity, quality of life, and response to therapy at multiple centers.