telangiectasia, oedema, papules and pustules, as well as hyperplasia of nasal sebaceous glands. Patients may also complain of dry, burning and stinging sensations from the skin and eyes, and often suffer from migraines and gastrointestinal disorders. Rosacea is a common yet somewhat understudied disorder, and whether disease classification should be made according to subtypes or clinical features remains debated. However, rosacea is currently treated according to subtype, with therapeutic options ranging from topical agents to systemic antibiotics, laser treatments and even surgery. While off-label treatments may include drugs such as isotretinoin and topical calcineurin inhibitors, there have been reports of allergic contact dermatitis caused by approved rosacea treatments such as brimonidine tartrate gel and topical metronidazole. In the current issue of the BJD, an international group comprising 17 dermatologists and three ophthalmologists report their use of a modified Delphi process to formulate a consensus statement on the management of rosacea. Evidence was derived from a recent Cochrane review and a summarized literature search, which together with the participants’ clinical experience formed the basis for the treatment recommendations. Systematic Cochrane reviews are generally recognized as the highest standard in evidence-based health care. However, the sole inclusion of randomized clinical trials (RCTs) in Cochrane reviews may result in omission of large parts of available and valuable data. A particular strength of the present publication is therefore the panel’s addition to the Delphi process of a wider body of evidence in the form of a summarized literature review and clinical expertise. This allows for the recommendation of less common features such as phyma and ocular rosacea, of which RCTs are scarce. There is currently a wide range of approved and unapproved therapeutic options for rosacea, as well as emerging data suggesting that patients may also frequently suffer from certain other conditions at the same time. In light thereof, the present review, and its recommendations for shortand long-term disease management, is important as it may help clinicians to evaluate the relative merits and safety of the available therapies for their patients with rosacea.

Objective The aim of the study was to assess the efficacy and safety of fumaric acid esters (FAEs) in patients with cutaneous lupus erythematosus (CLE).Methods In this 24-week, prospective, open-label, phase II pilot study, 11 patients with CLE, refractory to topical corticosteroids, were included. The primary endpoint of the study was the evaluation of the efficacy of FAEs after 24 weeks of treatment as assessed by the Revised Cutaneous Lupus Disease Area and Severity Index (RCLASI).Results Compared to baseline, significant improvement in the mean total RCLASI activity score and the mean RCLASI activity score for skin lesions was observed in week 12 (p=0.002, p=0.002, respectively) and in week 24 (p=0.009, p=0.009, respectively). Most common adverse events included abdominal cramps and headache.Conclusions FAEs could be an alternative and safe treatment in patients with therapy-refractory CLE; however, randomized controlled trials are warranted to evaluate the efficacy and safety of FAEs in this disease.

Background Pemphigus vegetans is a rare variant of pemphigus vulgaris, accounting for 1-2% of all pemphigus diseases. Systemic corticosteroids are the therapy of first choice in combination with immunosuppressants as steroid-sparing agents. Objective To highlight the exceptional but successful use of minocycline/nicotinamide monotherapy in pemphigus vegetans. Methods A review of the literature to date about pemphigus vegetans with special emphasis on therapy was performed. Due to its rarity, multiple anecdotal reports without long-term follow-up are available and prospective controlled trials are lacking. Only one retrospective study from Tunisia includes 17 patients with pemphigus vegetans. Results We present a 76-year-old woman with pemphigus vegetans achieving complete response to a minocycline/nicotinamide monotherapy at onset and at relapse of the disease. Treatment has been discontinued after repeated direct immunofluorescence (DIF) of previously affected normal skin and anti-desmoglein 3 antibodies had become negative. In addition, DIF of previously involved oral mucosa was negative. During long-term follow-up clinical remission has been maintained for more than 5 years. Up to now, negative results of serial performed indirect immunofluorescence and desmoglein ELISA testing also predict immunological remission. Conclusion In our patient and in a case with oesophageal involvement, published more than 20 years ago, clearly the benefit of minocycline/nicotinamide monotherapy was demonstrated. We propose to consider minocycline/nicotinamide as first-line monotherapy in pemphigus vegetans, especially in elderly patients with comorbidities and contraindications to standard therapy, as it avoids the toxicities of systemic corticosteroids and immunosuppressants.

Treatment of skin manifestations in systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and dermatomyositis (DM) is based on the results of only few randomized controlled trials. The first-line treatment for disfiguring and widespread cutaneous involvement in SLE is antimalarials, but some patients are therapy resistant. Recently, the monoclonal antibody belimumab was approved for SLE as an adjunct therapy for patients with autoantibody-positive disease who despite standard therapy show high disease activity, intolerance of other treatments, or an unacceptably high need for corticosteroids. However, a validated skin score has not been used to confirm the efficacy of belimumab on mucocutaneous manifestations. In SSc, another multi-systemic progressive disease, involvement of the lung, kidney, and the heart is frequently treated with corticosteroids and immunosuppressives, but therapeutic modalities for cutaneous lesions, such as skin sclerosis and digital ulcers, are limited. In the past years, treatment with the endothelin-receptor antagonist bosentan has been proven to reduce the occurrence of new digital ulcers in SSc patients but has no or limited effect on healing of digital ulcers. DM is an idiopathic autoimmune disease characterized by inflammation of the muscles and skin, which is treated with immunosuppressives. Corticosteroids are the first-line treatment for muscle involvement in DM, but skin lesions often flare by reduction or discontinuation. In summary, there is a high unmet need for new therapeutic strategies focusing on skin involvement in systemic autoimmune diseases. Therefore, innovative designs of randomized controlled trials with validated skin scores are warranted to develop new therapeutic strategies for patients with cutaneous manifestations.

BACKGROUNDSystemic lupus erythematosus (SLE) is an autoimmune disease with a prevalence of 36.7/100 000 in Germany and a female/male ratio of 4:1. The clinical course is variable, with a broad spectrum of organ manifestations; lupus nephritis develops in about half of all patients.METHODSThis review is based on a selective search of PubMed and the Cochrane Library, including current guidelines and expert recommendations.RESULTSAssessment of clinical symptoms, laboratory findings, and optional biopsy results are the basis for early diagnosis of SLE. All patients should be treated with antimalarials as soon as the diagnosis is confirmed. In particular, hydroxychloroquine is associated with a higher rate of remission, fewer relapses, and reduced damage in the course of the disease, even in lupus nephritis. High-dose glucocorticoids should be given only when acutely indicated; immunosuppressives such as azathioprine, methotrexate, or mycophenolate mofetil may be administered to reduce glucocorticoids, according to the EULAR recommendations. Belimumab was recently approved as add-on therapy in autoantibody-positive SLE patients with high disease activity unresponsive to standard treatment. Short-term induction pulse therapy with low-dose intravenous cyclophosphamide, as well as continued mycophenolate mofetil treatment are advances in lupus nephritis.CONCLUSIONThe long-term prognosis for SLE has improved markedly in recent decades because of earlier diagnosis and optimized treatment. Further research and randomized controlled trials are needed for the development of specifically targeted therapies.

BACKGROUND: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.OBJECTIVES:To investigate the influence of smoking on disease severity and antimalarial treatment in patients with CLE using the Core Set Questionnaire of the European Society of Cutaneous Lupus Erythematosus (EUSCLE).METHODS: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.RESULTS: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).CONCLUSIONS: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.

Der Lupus erythematodes (LE) ist eine entzündliche Autoimmunerkrankung, die eine lebensbedrohliche Organmanifestation aufweisen kann. Die am häufigsten beteiligten Organe sind die Haut, Gelenke und Nieren, aber auch das kardiovaskuläre und zentralnervöse System können betroffen sein [1]. Da sich die klinische Symptomatik bei vielen Patienten allein auf die Haut beschränkt, kann der kutane LE (CLE) auch als eigenes Krankheitsbild definiert und somit vom systemischen LE (SLE) abgegrenzt werden [3]. Andererseits können aber auch alle Subtypen des CLE in unterschiedlicher Häufigkeit in Assoziation mit einem SLE auftreten. In der Literatur wird die Angabe über die Häufigkeit kutaner Manifestationen meistens nur in Assoziation mit dem Auftreten eines SLE erwähnt [2]. Im Verlauf der Erkrankung können sich bei 72–85% der SLE-Patienten Hautläsionen manifestieren, bei 25% sogar als erstes Symptom [3]. Die Inzidenz des CLE wird 2–3-mal höher eingeschätzt als diejenige des SLE [4]. Im Jahr 2007 bewertete die Europäische Arzneimittelagentur (European Medicines Agency, EMA) den CLE als schwerwiegende und seltene Erkrankung mit einer Prävalenz von <5 pro 10000 Einwohner in Europa (Astion Press Release 08/2007). Eine kürzlich in Schweden durchgeführte Studie, bei der 1088 Patienten aus Stockholm analysiert wurden, hat jedoch ergeben, dass der CLE etwa genauso häufig vorkommt wie der SLE [5]. Der mit 30–60% am häufigsten im Rahmen eines SLE auftretende Subtyp ist der akut kutane LE (ACLE), der lokalisiert als Schmetterlingserythem oder als generalisierte Variante in Form eines makulopapulösen Exanthems vorkommen kann. Auch zeigen 23–28% der Patienten mit SLE kutane Läsionen, die meist schon bei Erstmanifestation der Erkrankung vorhanden sind [6]. Die Angaben zur Häufigkeit des subakut kutanen LE (SCLE) innerhalb der verschiedenen Populationen schwanken in der ursprünglichen Publikation von Gilliam und Sontheimer zwischen 9% und 27% [7]. Im Jahr 2007 wurde die Prävalenz des antiRo/SSA-Antikörper-positiven SCLE in Stockholm, Schweden, mit 6,2–14 pro 100000 Einwohner beschrieben [3,8]. Die verschiedenen Subtypen des CLE können sich in jedemAltermanifestieren, zeigen aber eine Prädisposition zwischen dem 20. und 40. Lebensjahr. In einzelnen Studienwurde deutlich, dass der diskoide LE (DLE) vermehrt bei Afrikanern vorkommt, während der SCLE eher in der kaukasischen Bevölkerung anzutreffen ist [3,9]. Der Chilblain LE (CHLE) und der LE tumidus (LET)manifestieren sich nach Angaben der Literatur häufiger in Europa und seltener in den USA [10,11].Während der LET vermehrt bei Männern beschrieben wurde, überwiegen bei Frauen die anderen Subtypen [29,12]. In Bezug auf denVerlauf und die Prognose der Subtypen des CLE scheint jedoch ein Unterschied zwischen beiden Geschlechtern zu bestehen. Eine Studiemit 28männlichenund111weiblichen Patienten hat gezeigt, dass disseminierte Hautläsionen beim DLE signifikant häufiger bei Männern als bei Frauen vorkommen [13].

Journal Article Measuring disease activity and damage in cutaneous lupus erythematosus: reply from authors Get access A. Kuhn, A. Kuhn Department of Dermatology, University of Münster, Münster, Germany E‐mail: kuhnan@uni‐muenster.de Search for other works by this author on: Oxford Academic Google Scholar V. Ruland, V. Ruland Department of Dermatology, University of Münster, Münster, Germany E‐mail: kuhnan@uni‐muenster.de Search for other works by this author on: Oxford Academic Google Scholar G. Bonsmann G. Bonsmann Department of Dermatology, University of Münster, Münster, Germany E‐mail: kuhnan@uni‐muenster.de Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 164, Issue 1, 1 January 2011, Pages 222–224, https://doi.org/10.1111/j.1365-2133.2010.10073.x Published: 01 January 2011

Lupus erythematosus (LE) is an inflammatory autoimmune disorder, which is characterized by clinically heterogeneous manifestations of different organs. In systemic LE (SLE) the skin, the musculoskeletal system, the kidneys, the cardiovascular and central nervous systems can be involved. The skin lesions can be divided into LE-specific and LE-non-specific manifestations, the former represent the subtypes of cutaneous LE (CLE). The diagnosis is confirmed by clinical, histopathological, immunoserological and genetic features. The treatment is similar for the different subtypes of CLE; however, the therapeutic regimen should be individually defined in each patient. Antimalarials are still the first-line systemic therapy and in addition to sunscreens, glucocorticosteroids and calcineurin inhibitors have an important impact as topical agents in this disease.

In patients with cutaneous lupus erythematosus (CLE) and mild skin involvement, local therapy consisting of topically applied pharmacological agents, e.g., topical/intralesional steroids, may be sufficient. Recent reports have also shown efficacy of topical calcineurin inhibitors in patients with CLE, particularly on the face. Special attention receives consistent sun protection through photoresistant clothing and application of light-shielding substances with highly potent chemical or physical UVA- and UVB-protective filters. These substances should be applied in sufficient amount (ca. 2 mg/cm 2 ) at least 20—30 minutes before sun exposure in order to avoid induction and exacerbation of cutaneous lesions. The mainstay of treatment for disfiguring and widespread skin manifestations in patients with CLE, irrespective of the subtype of the disease, is antimalarial agents. Our understanding of the use of combinations of antimalarials and proper dosing according to the ideal bodyweight limits problems with toxicity. Further therapies, such as methotrexate, or retinoids, dapsone, mycophenolate mofetil, and thalidomide in selected cases, can be helpful for patients with resistant disease; however, side effects need to be taken into consideration. Recent advances in biotechnology resulted in the development of novel systemic agents, but randomized controlled trials are necessary for the approval of new therapeutic strategies in CLE. Lupus (2010) 19, 1125—1136.

Epidemiological data and standard European guidelines for the diagnosis and treatment of cutaneous lupus erythematosus (CLE) are lacking in the current literature. In order to provide a standardized tool for an extensive consistent data collection, a study group of the European Society of Cutaneous Lupus Erythematosus (EUSCLE) recently developed a Core Set Questionnaire for the assessment of patients with different subtypes of CLE. The EUSCLE Core Set Questionnaire includes six sections on patient data, diagnosis, skin involvement, activity and damage of disease, laboratory analysis, and treatment. An instrument like the EUSCLE Core Set Questionnaire is essential to gain a broad and comparable data collection of patients with CLE from different European centres and to achieve consensus concerning clinical standards for the disease. The data will also be important for further characterization of the different CLE subtypes and the evaluation of therapeutic strategies; moreover, the EUSCLE Core Set Questionnaire might also be useful for the comparison of data in clinical trials. In this review, the impact of the EUSCLE Core Set Questionnaire is discussed in detail with regard to clinical and serological features as well as therapeutic modalities in CLE. Lupus (2010) 19, 1144—1152.

Cutaneous lupus erythematosus (CLE) is a heterogeneous autoimmune disease involving well-defined skin lesions that can be categorized as acute CLE (ACLE), subacute CLE (SCLE), chronic CLE (CCLE), or intermittent CLE (ICLE). It is commonly accepted that ultraviolet (UV) exposure can induce and exacerbate skin lesions in patients with certain subtypes of CLE. Phototesting with UVA and UVB irradiation using a standardized protocol has proven to be a reliable model to study photosensitivity in CLE and to analyse the underlying pathomechanisms of the disease. In addition to UV-mediated induction of apoptosis, the molecular and cellular factors that may underlie the abnormal long-lasting photoreactivity in CLE include mediators of inflammation such as cytokines and chemokines, inducible nitric oxide (NO) synthase (iNOS), and cellular adhesion molecules. The photosensitivity associated with CLE requires education of the patient about avoidance of excessive sun exposure, continuous photoprotection through physical measures such as protective clothing, and daily application of broad-spectrum sunscreens. Novel approaches to UV-protection, such as alpha-MSH or thymidine dinucleotides, might also have an impact on photosensitivity in patients with CLE. In this review, we summarize the current knowledge about photosensitivity in patients with CLE, including an overview of standardized phototesting procedures, possible molecular pathomechanisms, and photoprotection. Lupus (2010) 19, 1036—1046.

Background  The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) is a scoring system for patients with cutaneous lupus erythematosus (CLE) to assess disease activity and damage.

BACKGROUND:In 2005, a scoring system (CLASI, Cutaneous Lupus Erythematosus Disease Area and Severity Index) was developed for patients with cutaneous lupus erythematosus (CLE) to assess disease 'activity' and 'damage'. However, the CLASI does not give an accurate assessment of the severity in all disease subtypes.OBJECTIVES:The main objective of this study was to analyse critically the included parameters of the CLASI and to revise the activity and damage score taking into account various clinical features of the different subtypes of CLE. The revised CLASI (RCLASI) was also validated for use in clinical trials. Patients and methods A RCLASI was designed with regard to the anatomical region (i.e. face, chest, arms) and morphological aspects (i.e. erythema, scaling/hyperkeratosis, oedema/infiltration, scarring/atrophy) of skin lesions and evaluated by nine dermatologists who scored 12 patients with different subtypes of CLE to estimate inter- and intrarater reliability.RESULTS:Reliability studies demonstrated an intraclass correlation coefficient (ICC) for an inter-rater reliability of 0.89 for the activity score [95% confidence interval (CI) 0.79-0.96] and of 0.79 for the damage score (95% CI 0.62-0.92). The ICC for intrarater reliability for the activity score was 0.92 (95% CI 0.89-0.95) and the ICC for the damage score was 0.95 (95% CI 0.92-0.98).CONCLUSIONS:In the present study, a RCLASI was developed by experts, and reliability studies supported the validity and applicability of the revised scoring instrument for CLE. Thus, the RCLASI is a valuable instrument in multicentre studies and for the clinical evaluation of activity and damage in different disease subtypes.

There exists no treatment of choice for follicular mucinosis (FM). Historically two distinct entities of FM have been proposed: FM of children and young adults not associated with other diseases ('idiopathic' FM), and FM in elderly patients associated with mycosis fungoides and Sézary syndrome ('lymphoma-associated' FM). Nowadays it is suggested that 'idiopathic' FM might represent a localized form of cutaneous T-cell lymphoma. Six patients with 'idiopathic' FM were treated with hydroxychloroquine (HCQ) at a dose of 200 mg three times daily for 10 days followed by a dose adjusted to the ideal body weight, usually 200 mg twice daily. All patients showed an improvement of 'idiopathic' FM already after 6 weeks and a complete remission with full hair regrowth after 2-5 months of HCQ therapy. In all patients no relapse occurred during follow up of between 3 and 23 years and no patient developed lymphoma. We conclude that HCQ is a highly effective therapy without significant side-effects in the treatment of so-called 'idiopathic' FM.

MADAM, We thank Dr Mutasim for his valuable comments and are grateful for the opportunity to clarify certain aspects of our study investigating lupus erythematosus tumidus (LET) as a separate subtype of cutaneous lupus erythematosus (CLE). Dr Mutasim remarks that the study ‘did not add anything new to what is already known about tumid lupus’, that it did not ‘accomplish a resolution to the objectives stated by the authors’, and that the objective of the paper, to evaluate ‘whether LET can be distinguished as a separate entity in the classification system of the disease, ... seems to be ill conceived’. He further notes that the ‘results could not have been otherwise as the authors have preselected patients whom they have identified as having LET prior to their entry into the study’. The of concern Dr Mutasim is comprehensible if our objective would have been to define LET as its own entity; however, this has already been shown by several groups. In our study, we sought to investigate if this existing entity of LET can be considered a separate subtype in the classification of CLE and be distinguished from other forms of CLE. Therefore, it was necessary to include patients with LET that had been diagnosed prior to inclusion in the study and to compare with other disease subtypes, such as subacute CLE (SCLE) and discoid lupus erythematosus (DLE) as the most common form of chronic CLE (CCLE). Until now, more than 40 studies including approximately 250 patients with LET have been published in the international literature. However, LET has been underestimated and neglected since the first description in 1909 and has been characterized by clinical, photobiological, histological, immunohistochemical and serological features only in more recent years. The lesions of LET are characterized by succulent, urticaria-like, single or multiple plaques with a bright reddish or violaceous, smooth surface on sun-exposed areas. This subtype, however, never leads to long-term sequelae, such as permanent scarring, hypoand hyperpigmentation, or lipatrophy, or vitilio-like hypopigmentation as seen in DLE, lupus erythematosus panniculitis (LEP) and SCLE, respectively. Also, provocative phototesting has been crucial in characterizing LET as a highly photosensitive variant of CLE. Moreover, the clinical characteristics of this subtype are an intermittent course with relapsing lesions after disease-free periods. The prognosis of LET is generally more favourable than in other forms of CLE and association with systemic disease seems to be very rare in patients with this disease subtype. The question applied to the data generated by our study is not whether LET is defined as its own entity, but rather where this disease should be placed as a separate subtype in the existing classification of CLE. LET has been listed among variants of the CCLE subtype by Gilliam in 1977, with several refinements thereafter. The other entities in this group include the chronic variants DLE, LEP and chilblain lupus erythematosus. However, in our opinion, LET is distinguishable from these chronic forms of the disease already on the basis of specific clinical criteria. Our study provides further evidence for the fact that LET is significantly distinct from DLE, and should not be considered a subtype of CCLE. Therefore, there is no doubt about LET being a separate entity in the classification of CLE due to the characteristic features described above, and our study provides further evidence to support the claim that LET should be attributed to a distinct subtype called ‘intermittent CLE’ (ICLE). Based on the nomenclature by Gilliam we modified the classification system in 2004 to include LET in ICLE (Table 1); however, there was a need to support this revised classification. In our study we evaluated several significant differences between LET and other subtypes of CLE with regard to clinical, histological and laboratory parameters. Therefore, these data strongly indicate that LET is a separate subtype in the classification of CLE and should not be classified as one of the forms of CCLE.