Management of cutaneous manifestations of lupus erythematosus: A systematic review.

BACKGROUND: Cutaneous lupus erythematosus (CLE), occurring with or without systemic lupus erythematosus (SLE), is a group of inflammatory skin diseases that can be very debilitating, causing significant psychological distress, and sometimes scarring. OBJECTIVES: We sought to comprehensively present the evidence for different treatment modalities in patients with cutaneous manifestations of lupus erythematosus (LE). METHODS: Medline, Embase, Scopus and Cochrane CENTRAL were searched electronically from 1990 to March 2019, using keywords related to cutaneous lupus and synonyms and treatment. Articles retrieved were screened for relevance, including reference lists of retrieved reviews. We included clinical trials, observational studies or case series with ≥5 patients focussing on treatment of CLE, with or without SLE. RESULTS: The search identified 6637 studies, of which 107 were included. Each study commonly included a heterogeneous mixture of CLE subtypes, with or without SLE. The 107 included studies investigated 11 different categories of treatment in 7343 patients. Treatments included topical calcineurin inhibitors (13 studies), sun protection (5 studies), R-salbutamol cream (2 studies), antimalarials (22 studies), synthetic DMARDs (10 studies), retinoids (2 studies), thalidomide/lenalidomide (22 studies), biologic therapies (15 studies), intravenous immune globulin (3 studies), laser (6 studies) and other therapies (7 studies). General measures to be considered include smoking cessation, sun protection measures and optimisation of vitamin D levels. Moderate evidence exists for benefit with topical CNIs, particularly as a steroid sparing agent in areas at high risk of steroid complications (e.g. facial skin). There is moderate evidence for hydroxychloroquine, which is first-line in SLE patients, limited evidence to support other synthetic DMARDs, and moderate evidence supporting thalidomide but with significant risk of toxicity. Of biologic therapies, there are moderate data to support belimumab. Limited evidence exists for other therapies. CONCLUSION: Many management options are available for CLE, including topical, systemic and biologic therapies, with a variable balance of efficacy and toxicity. There is a paucity of high-quality clinical trial data. Further trials are required to better understand optimal management of CLE, particularly in specific subgroups.

The molecular pathogenesis of morphoea: from genetics to future treatment targets.

A number of immunoinflammatory and profibrotic mechanisms are recognized in the pathogenesis of broad sclerotic skin processes and, more specifically, morphoea. However, the precise aetiopathogenesis is complex and remains unclear. Morphoea is clinically heterogeneous, with variable anatomical patterning, depth of tissue involvement and sclerotic, inflammatory, atrophic and dyspigmented morphology. Underlying mechanisms determining these reproducible clinical subsets are poorly understood but of great clinical and therapeutic relevance. Regional susceptibility mechanisms (e.g. environmental triggers, mosaicism and positional identity) together with distinct pathogenic determinants (including innate, adaptive and imbalanced pro- and antifibrotic signalling pathways) are likely implicated. In the age of genetic profiling and personalized medicine, improved characterization of the environmental, systemic, local, genetic and immunopathological factors underpinning morphoea pathogenesis may open the door to novel targeted therapeutic approaches.

Severe recalcitrant cutaneous manifestations in systemic lupus erythematosus successfully treated with fumaric acid esters.

Fumaric acid esters (FAEs) have proven efficacy in the treatment of psoriasis and have been in use for decades. More recently, as their mechanism of action and abundant immunomodulatory effects become clearer, the potential benefits of treating other inflammatory skin conditions using FAEs are increasingly being recognized. The use of FAEs as combination systemic therapy has not been well studied and data are lacking regarding the safety and efficacy of this type of therapy. In this case report, three patients with severe, extensive and recalcitrant cutaneous manifestations of systemic lupus erythematosus (SLE) (one case of disseminated discoid lesions and two with severe chilblain lesions) were treated with Fumaderm® (containing the FAE dimethylfumarate and monoethylhydrogen fumarate salts), after failing to respond to a multitude of other monotherapies and combination therapies. All patients showed a substantial clinical response when FAEs were added to their treatment, with concurrent improvements in quality-of-life instrument scores. The treatment was well tolerated in the context of systemic organ involvement and as combination therapy with other agents, such as hydroxychloroquine and mycophenolate mofetil. These cases of SLE illustrate the potential use of FAEs in severe, disfiguring and otherwise therapy-resistant skin lesions, including, to our knowledge, the first two reported cases of FAE-treated chilblain lupus erythematosus.