Validation and reliability of a disease-specific quality-of-life measure in patients with cutaneous lupus erythematosus

The term ‘lupus erythematosus’ refers to a range of related disorders, and types of lupus affecting the skin are collectively known as cutaneous lupus erythematosus (CLE). CLE can cause several different types of rashes. Many of these are often seen in areas of the body that are exposed to the sun. CLE patients can suffer from fatigue, pain, scarring, hair loss, and even sensitivity to the sun, all of which have been shown to negatively affect quality of life (QoL). Because of how subjective most of these symptoms are, it is important to use appropriate measures that can adequately examine the QoL in patients. Therefore, this study, from the U.S.A., aimed to demonstrate the ‘reliability’ and ‘validity’ of the cutaneous lupus erythematosus quality of life (CLEQoL) measure, which is a tool that allows patients to describe how CLE affects their QoL. Reliability means that if you take the same test multiple times, you should get roughly the same results every time, while validity broadly means that the test measures what it's supposed to. The CLEQoL was found to have sufficient reliability and validity in assessing the QoL in patients with CLE. Our findings show that CLEQoL is a practical and useful tool in examining QoL in CLE patients and could be considered for use in future drug development and clinical trials, as well as in clinical practice for routine monitoring of patients’ well-being.     

A multicentre,cross‐sectional study on quality of life in patients with cutaneous lupus erythematosus

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.     

Development of the CLASI as an outcome instrument for cutaneous lupus erythematosus

Skin involvement is a frequent presenting manifestation of systemic lupus erythematosus (SLE). Cutaneous lupus erythematosus (CLE), frequently occurring without SLE, may be even more common than SLE. Until recently, clinical instruments to measure skin involvement in CLE did not exist, hampering clinical research in this field. In this paper the present authors describe outcome instruments for SLE and outline the considerations underlying the design and validation of an outcome instrument for CLE, the cutaneous lupus disease area and severity index. These studies serve as a model for development and validation of standardized instruments that can be applied to other cutaneous diseases, particularly autoimmune diseases, in order to facilitate epidemiologic studies and clinical trials.     

Medidas de los resultados percibidos por el paciente en estudios de vida real en dermatitis atópica en España: revisión sistemática de la literatura

Atopic dermatitis (AD) is a chronic inflammatory skin disease with symptoms such as pruritus that can be a major burden for patients. Patient-reported outcomes (PRO) complement clinician-reported outcomes in AD. This systematic review aims to identify and describe patient-reported outcome measures (PROM) used in observational studies of AD over the last decade in Spain. Eighteen PROM were identified to measure 13 different PRO that assess multiple aspects of the disease, including symptoms and disease severity, impact on daily activities and on work productivity/functioning, psychosocial impact, patient empowerment, and health-related quality of life (HRQoL). HRQoL, symptoms (particularly pruritus), and anxiety/depression were the most frequently assessed PRO, and the Dermatology Quality of Life Index, the Visual Analogue Pruritus Scale, and the Hospital Anxiety and Depression Scale were the most frequently used PROM, respectively. The growing number of observational studies on AD including PROM in Spain suggests that PRO are becoming increasingly important in the management of AD.     

Estudio de calidad de vida en pacientes con lupus eritematoso cutáneo

Background and objectivesThe study of quality of life in patients with skin disorders has become more important in recent decades. In the case of lupus erythematosus, most quality-of-life studies have focused on the systemic form of the disease, with less attention being paid to the cutaneous form. The main objective of this study was to evaluate quality of life in patients with cutaneous lupus erythematosus (CLE) using a dermatology-specific questionnaire: the Dermatology Life Quality Index (DLQI). Our secondary objective was to investigate associations between DLQI scores and other aspects of the disease.Material and methodsThirty-six patients with CLE completed the DLQI questionnaire. Other factors assessed were disease severity (measured using the Cutaneous Lupus Erythematosus Disease Area and Severity Index), time since diagnosis, body surface area affected, previous and current treatments, and the presence of criteria for systemic lupus erythematosus (SLE).ResultsAccording to the DLQI, CLE had a moderate, very large, or extremely large effect on quality of life in 50% of the patients analyzed (18/36). No significant associations were found between DLQI scores and disease severity, time since diagnosis, body surface area affected, number, type, or duration of pharmacologic treatments, or the presence or absence of SLE criteria.ConclusionCLE has a significant and lasting effect on patient quality of life. This effect is probably primarily due to multiple factors, including the chronic nature of the disease, the visibility of the lesions, and the fact that they can cause disfigurement.     

[Translated article] Patient-Reported Outcome Measures in Real-World Atopic Dermatitis Studies in Spain: A Systematic Review

Atopic dermatitis (AD) is a chronic inflammatory skin disease with symptoms such as pruritus that can be a major burden for patients. Patient-reported outcomes (PRO) complement clinician-reported outcomes in AD. This systematic review aims to identify and describe patient-reported outcome measures (PROM) used in observational studies of AD over the last decade in Spain. Eighteen PROM were identified to measure 13 different PRO that assess multiple aspects of the disease, including symptoms and disease severity, impact on daily activities and on work productivity/functioning, psychosocial impact, patient empowerment, and health-related quality of life (HRQoL). HRQoL, symptoms (particularly pruritus), and anxiety/depression were the most frequently assessed PRO, and the Dermatology Quality of Life Index, the Visual Analogue Pruritus Scale, and the Hospital Anxiety and Depression Scale were the most frequently used PROM, respectively. The growing number of observational studies on AD including PROM in Spain suggests that PRO are becoming increasingly important in the management of AD.     

Varied responses to and efficacies of hydroxychloroquine treatment according to cutaneous lupus erythematosus subtypes in Japanese patients

Hydroxychloroquine is recommended as the first‐line systemic treatment for cutaneous lupus erythematosus (CLE) in Western countries, and it was approved in Japan in 2016. However, the efficacy of hydroxychloroquine in various cutaneous lupus erythematosus subtypes in Japanese patients has not been elucidated to date. Therefore, we investigated the efficacy of hydroxychloroquine for the treatment of cutaneous manifestations according to CLE subtypes in Japanese patients. We enrolled 35 patients (29 diagnosed with systemic lupus erythematosus and six with CLE) in this retrospective study. We analyzed the efficacy of hydroxychloroquine for the treatment of cutaneous manifestations according to cutaneous lupus erythematosus subtypes, time to the first skin improvement, as well as effects on laboratory data and reduction of concomitant immunosuppressive drug administration at 16 and 32 weeks of therapy. Complete improvement was observed at high rates for acute CLE (ACLE); however, partial or non‐improvement rates were higher for chronic CLE (CCLE) at 16 weeks. Several patients with alopecia without scarring achieved complete improvement at 32 weeks. CCLE tended to take more time to improve than ACLE. Overall, hydroxychloroquine was highly effective for skin: 87% of patients had at least some beneficial response at 16 weeks. Nevertheless, there were wide variations in complete improvement rates and duration for improvement among CLE subtypes. Our findings suggest that a therapeutic approach considering the subtypes of CLE will improve its management.     

Cigarette smoking and response to antimalarials in cutaneous lupus erythematosus patients: evolution of a dogma

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.     

Evaluation of the reliability and validity of the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) in paediatric cutaneous lupus among paediatric dermatologists and rheumatologists

The term ‘lupus erythematosus’ refers to a range of related disorders. As many as 70–80% of lupus patients will develop skin lesions (abnormal patches) at some point during the course of their disease. Types of lupus affecting the skin are collectively known as cutaneous lupus erythematosus (CLE). The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) is a tool for classifying how severe the skin symptoms are in people with CLE. Being able to accurately and reliably measure skin lesions is an important way to monitor any improvement or worsening of the disease, which is useful in clinical trials to see if a treatment is working. It is already known that the CLASI is a reliable (accurate) measure in adults, but researchers based in the USA conducted this study to validate the reliability of the CLASI in the pediatric (child) population, where CLE can appear differently than in adults. This validation will allow clinical trials to reliably assess treatment efficacy in CLE. The researchers recruited 11 pediatric patients with active CLE, 6 dermatologists, and 6 rheumatologists to attend a one-day event at the University of Pennsylvania. Physicians were trained to use the CLASI as well as another scoring system called the Physician Global Assessment (PGA) to allow for comparison. Physicians (doctors) individually rated all patients using both tools. Each physician reassessed two randomly selected patients. CLASI proved to be a reliable and valid measurement tool and superior to the PGA for pediatric CLE, and the researchers conclude that it can be used in future clinical trials.     

The interferon-regulated gene signature is elevated in subacute cutaneous lupus erythematosus and discoid lupus erythematosus and correlates with the cutaneous lupus area and severity index score

Background There is increased expression of type I interferon (IFN)‐regulated proteins in the blood and target tissues of patients with cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE). Patients with SLE have increased IFN‐regulated gene expression pointing towards a possible underlying genetic defect. Objectives To determine expression levels of five type I IFN‐regulated genes that are highly expressed in SLE in the peripheral blood of patients with CLE and to correlate the expression levels with cutaneous disease activity. Methods Peripheral blood was obtained from 10 healthy controls and 30 patients with CLE, including eight with concomitant SLE. Total RNA was extracted and reverse transcribed into complementary DNA. Gene expression levels were measured by real‐time polymerase chain reaction. Gene expression was normalized to GAPDH, standardized to healthy controls and then summed to calculate an IFN score for each patient. Disease activity was assessed with the Cutaneous Lupus Area and Severity Index (CLASI). Results Patients with subacute CLE (SCLE) and discoid lupus erythematosus (DLE) had elevated IFN scores compared with healthy controls regardless of concomitant SLE (P < 0·01 with SLE and P < 0·05 without SLE). There was no difference between patients with tumid lupus erythematosus (TLE) and healthy controls. The IFN score correlated with CLASI scores (Spearman’s rho = 0·55, P = 0·0017). Conclusions Patients with SCLE and DLE have an IFN signature, as seen in SLE. The level of gene expression correlates with cutaneous disease activity. These findings support a shared pathogenesis between SLE and some subtypes of CLE.     

S2k guideline for treatment of cutaneous lupus erythematosus – guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV)

Cutaneous lupus erythematosus (CLE) is a rare inflammatory autoimmune disease with heterogeneous clinical manifestations. To date, no therapeutic agents have been licensed specifically for patients with this disease entity, and topical and systemic drugs are mostly used ‘off‐label’. The aim of the present guideline was to achieve a broad consensus on treatment strategies for patients with CLE by a European subcommittee, guided by the European Dermatology Forum (EDF) and supported by the European Academy of Dermatology and Venereology (EADV). In total, 16 European participants were included in this project and agreed on all recommendations. Topical corticosteroids remain the mainstay of treatment for localized CLE, and further topical agents, such as calcineurin inhibitors, are listed as alternative first‐line or second‐line topical therapeutic option. Antimalarials are recommended as first‐line and long‐term systemic treatment in all CLE patients with severe and/or widespread skin lesions, particularly in patients with a high risk of scarring and/or the development of systemic disease. In addition to antimalarials, systemic corticosteroids are recommended as first‐line treatment in highly active and/or severe CLE. Second‐ and third‐line systemic treatments include methotrexate, retinoids, dapsone and mycophenolate mofetil or mycophenolate acid, respectively. Thalidomide should only be used in selected therapy‐refractory CLE patients, preferably in addition to antimalarials. Several new therapeutic options, such as B‐cell‐ or interferon α‐targeted agents, need to be further evaluated in clinical trials to assess their efficacy and safety in the treatment of patients with CLE.     

Anti‐annexin 1 antibodies: A new diagnostic marker in the serum of patients with discoid lupus erythematosus

Abstract: Annexin 1 is an anti‐inflammatory molecule and has also been described to be a common target of autoantibodies. In this study, we determined whether antibodies against annexin 1 can be detected in sera of patients with cutaneous lupus erythematosus (CLE). Levels of anti‐annexin 1 antibodies were evaluated by a new established enzyme‐linked immunosorbent assay and found to be significantly higher in sera of patients with CLE when compared to normal healthy donors (NHD). Moreover, the percentage of sera positively tested for anti‐annexin 1 antibodies was elevated in patients with CLE when compared to NHD. In particular, the percentage of positive sera for anti‐annexin 1 antibodies was significantly higher in patients with discoid lupus erythematosus (DLE); however, disease activity did not correlate with the antibody levels. The results of this study indicate that anti‐annexin 1 antibodies in sera of patients with DLE might be a valuable aid in the diagnosis of this subtype.     

Ten‐year retrospective clinicohistological study of cutaneous lupus erythematosus in Korea

An understanding of the differences in clinical manifestations and laboratory abnormalities between subtypes of cutaneous lupus erythematosus (CLE) is still lacking. The purpose of this study was to analyze demographic, clinical and histological features of CLE according to three main presentation subsets: acute (ACLE), subacute (SCLE) and chronic (CCLE). A 10‐year retrospective analysis was performed on data from patients who were diagnosed with CLE between March 2005 and September 2015 in a Korean tertiary referral dermatology clinic. We compared demographic data and clinical and histological findings between three different CLE groups. An overall sample of 220 patients with CLE consisted of 67 patients with ACLE, 25 patients with SCLE and 135 patients with CCLE. Patients with CCLE regardless of systemic lupus erythematosus (SLE) presence had lower prevalence of anemia, urinary abnormalities and elevated erythrocyte sedimentation rate. Furthermore, CCLE patients who only had skin lesions showed lower female predominance, lower extracutaneous manifestation, fewer laboratory and immunological abnormalities including low antinuclear antibody titers and the lowest positivity for C3, C4 and anti‐dsDNA, anti‐Ro, anti‐Sm and anti‐RNP antibodies, and more prominent perieccrine inflammation and dermal fibrosis in histological findings. Considering distinct cutaneous manifestations of LE, a comprehensive awareness of each CLE subtype is important for achieving a favorable prognosis through appropriate diagnosis and management. This study provides comparative clinical and histological profiles of patients with different CLE subtypes in Korea.     

Relevant new insights into the effects of photoprotection in cutaneous lupus erythematosus

Cutaneous lupus erythematosus (CLE) denotes a heterogeneous spectrum of autoimmune diseases that primarily affect the skin. Ultraviolet irradiation (UV) is one of the most important environmental factors that can trigger skin lesions in CLE or even induce systemic organ manifestation. It has been shown that broad‐spectrum sunscreen with high sun protection factors can effectively prevent UV‐induced skin lesions in patients with different subtypes of CLE. In a recent issue of Experimental Dermatology, Zahn and colleagues demonstrate that potent photoprotection blocks disease‐specific skin lesions in CLE patients by reducing lesional tissue damage and interferon‐driven inflammation.     

Cutaneous lupus erythematosus and the association with systemic lupus erythematosus: a population-based cohort of 1088 patients in Sweden

Background Studies reporting the incidence of isolated cutaneous lupus erythematosus (CLE) are rare. Objectives 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. Methods 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. Results 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. Conclusions 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.     

High expression of B lymphocyte stimulator in lesional keratinocytes of patients with cutaneous lupus erythematosus

Belimumab, an anti‐B lymphocyte stimulator (BLyS) monoclonal antibody, is approved for systemic lupus erythematosus; however, it is unclear if it can be used to treat specific skin lesions in this disease. In this analysis, we investigated the expression of BLyS and its receptors in skin lesions of different subtypes of cutaneous lupus erythematosus (CLE) using immunohistochemistry and gene expression analyses. Compared to healthy controls, the expression of BLyS was significantly higher in skin lesions of all included CLE subtypes. Similar results were seen for the BLyS receptors BAFF‐R and BCMA. Moreover, CLE‐typical pro‐inflammatory mediators (immunostimulatory DNAs) significantly enhanced the BLyS expression of keratinocytes in vitro. This study suggests a potential role for BLyS as therapeutic target in the treatment of CLE skin lesions.     

Psoriasis: is it the tip of the iceberg for the quality of life of patients and their families?

Objective To evaluate the impact of psoriasis on patients’ and their relatives’ quality of life (QoL). Methods Eighty patients with their accompanying family members were included in the study. For measuring health related QoL (HRQoL) of patients with psoriasis, two questionnaires were used: Short Form 36 Health Survey (SF‐36) and EuroQol (EQ‐5D). Disease‐specific HRQoL was assessed by the Dermatology Life Quality Index. For measuring the quality of life of patients’ relatives, a specific questionnaire for dermatological diseases was used (Family Dermatology Life Quality Index, FDLQI). Results Of our patients, 88.3% reported that their disease affects in many and different ways their QoL whereas only 11.2% reported that psoriasis does not influence at all their life. Regarding FDLQI, 90% of the participating family members, responded that their relative’s psoriasis affected their own QoL. Conclusions Psoriasis is a chronic disease that affects in a cumulative way the quality of life of both patients and their close relatives.     

Instrumentos para la valoración de los resultados percibidos por el paciente con psoriasis en España: revisión sistemática de la literatura

ObjectivesTo review the literature on validated tools for measuring patient-reported outcomes (PROs) in psoriasis in Spain. To evaluate the psychometric properties of the tools and describe the results of their practical application.Material and methodsSystematic review of studies validating or using instruments for assessing PROs in Spanish patients with psoriasis. Literature searches were performed in international (PubMed/Medline) and Spanish (Medes, Ibecs) databases. We also searched databases of instruments for measuring PROs (BiblioPRO, PROQOLID). The review included studies published in English or Spanish up to January 9, 2017. We also checked the reference lists of the key publications identified. The quality of the questionnaires was evaluated based on their psychometric properties (construct, transcultural adaptation, reliability, validity, feasibility, and sensitivity to change).ResultsEighteen publications were included. Six articles described the validation of Spanish versions of 5 PROs tools: 4 health-related quality of life (HRQoL) questionnaires specific to psoriasis and dermatologic diseases and 1 questionnaire specific to satisfaction with treatment. Our assessment of the HRQoL tools’ psychometric properties showed that the PSO-LIFE questionnaire received the highest scores, although specific properties varied from instrument to instrument. The 12 remaining articles were observational studies that used the validated instruments. In use, these tools detected the high impact of psoriasis on HRQoL, especially in young female patients with severe disease.ConclusionsWe identified 5 specific instruments validated in Spain for scoring PROs in patients with psoriasis. The tools’ psychometric properties vary, and it is essential to understand their strengths and weaknesses when selecting the right one for each situation. In use, these questionnaires are able to detect the high impact of psoriasis on patients’ HRQoL. PROs provide useful information to complement routine clinical findings in psoriasis and may contribute to improving disease management.     

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

Background 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. Objectives To evaluate prospectively the clinical efficacy and safety of low‐dose thalidomide in an observational study and to establish prognostic factors of clinical outcome. Methods 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. Results 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. Conclusions 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.