Acute Cutaneous Lupus Research Articles

Cutaneous lupus erythematosus: An update

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.

Demographic and clinical characteristics of cutaneous lupus erythematosus at a paediatric dermatology referral centre

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. To detail the demographic and clinical features of paediatric CLE and compare these findings with those reported in the adult literature. A retrospective chart review was performed of 53 children seen in a paediatric dermatology clinic with cutaneous manifestations of LE. 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. 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.

Cutaneous lupus erythematosus: Diagnosis and treatment

Cutaneous lupus erythematosus (CLE) encompasses a wide range of dermatologic manifestations, which may or may not be associated with the development of systemic disease. Cutaneous lupus is divided into several sub-types, including acute CLE (ACLE), sub-acute CLE (SCLE) and chronic CLE (CCLE). CCLE includes discoid lupus erythematosus (DLE), LE profundus (LEP), chilblain cutaneous lupus and lupus tumidus. The diagnosis of these diseases requires proper classification of the sub-type, through a combination of physical examination, laboratory studies, histology, antibody serology and occasionally direct immunofluorescence, while ensuring to exclude systemic disease. The treatment of cutaneous lupus consists of patient education on proper sun protection along with appropriate topical and systemic agents. Systemic agents are indicated in cases of widespread, scarring or treatment-refractory disease. In this chapter, we discuss issues in classification and diagnosis of the various sub-types of CLE, as well as provide an update on therapeutic management.

Hypertrophic (Verrucous) Cutaneous Lupus Erythematosus of the Lip and Oral Cavity: A Series of 4 Cases

So-called “hypertrophic cutaneous lupus erythematosus (LE)” (also termed “verrucous cutaneous LE”) is a dis-tinct and rare clinical variant of chronic cutaneous LE that is characterized by intense tissue hyperplasia and hyperkeratosis. Hypertrophic LE causes marked disfigu-rement and is usually resistant to therapy (1, 2). Lesions occur more commonly on the face and upper limbs, with no specific mention in the literature of lesions occurring on the lips or oral mucosa. We describe here a series of 4 cases with a diagnosis of LE who presented with hypertrophic lesions on the skin and oral mucosa. Clinical and laboratory data are presented, together with detailed characterization of the mucosal involvement.CaSE REpoRtSClinical data for the 4 patients are shown in table SI (available from http://www.medicaljournals.se/acta/content/?doi=10.2340/00015555-1433). all patients presented hypertrophic cutaneous LE of longstanding duration. only patient 1 had multiple active cutaneous LE lesions at the time of examination (Fig. 1A, B). Skin lesions in patients 2 and 4 were mainly residual, with intense scarring. The lesion in patent 3 was confined to the lip area (Fig. 1C–F). Histopathology of biopsied oral lesions revealed marked hyperkeratosis, presence of a granular layer, focal hydropic degeneration of the basal layer, necro-tic basal keratinocytes, and melanophages of variable intensity (Fig. 1G, H). There were no signs of kerati-nocytic atypia. Dermal components included dilated papillary vessels, mucin, and scarce inflammatory in-filtrate, except for case 2, in which inflammatory cells were abundant in a superficial and deep pattern. Direct immunofluorescence findings were non-diagnostic.In patients 1, 2 and 3, LE activity was more pronoun -ced on the tegument. In addition to skin lesions, patient 4 had a several year history of lupus arthritis.DISCuSSIonthere are few published case series of oral compromise in LE. of these, some uniformity can be observed in the clinical picture, despite the great variety of descriptive terms employed (“oral discoid lesion”, “chronic pla-que”, “lupus cheilitis”, “acute ulcer”, “erythematous ulcer”, “ulcerated plaque”, “pebbly red areas”, “ho-neycomb lesions”, “keratotic white lesion”, “purpuric lesion”, and “diffuse palatal petechial erythema”, among others); a clinical characterization based on established dermatological criteria would be useful. Our group has proposed a method that simply compares mucosal LE lesions with their cutaneous counterparts (acute, subacute and chronic mucosal LE in analogy to acute, subacute and chronic cutaneous LE) in order to better understand those lesions (3).We describe here 4 patients with what is known as hypertrophic/verrucous LE (a subtype of chronic cuta -

Detection of Ro/SS-A antibodies in lupus erythematosus: What does it mean for the dermatologist?

Lupus erythematosus (LE) is a systemic autoimmune disease. However, some patients have only cutaneous LE (CLE), whereas others develop internal organ involvement. Ro/SS-A antibodies are frequently detected in photosensitive variants of LE. The prevalence of LE-specific and LE-nonspecific cutaneous manifestations and their relation to internal organ involvement in Ro/SS-A antibody-positive patients were investigated. All Ro/SS-A-positive patients between January 2000 and December 2011 were reviewed. Only patients with Ro/SS-A antibodies and LE were enrolled and retrospectively analyzed. In all, 215 Ro/SS-A antibody-positive patients were given the diagnosis of LE. Older patients (>50 years old) presenting with subacute CLE or chronic CLE and negative antinuclear antibody usually only experienced skin involvement. In contrast, internal organ involvement was observed in younger patients (<50 years old) with subacute CLE or chronic CLE presenting with the clinical and laboratory markers: fatigue, positive antinuclear antibody, and additional extractable nuclear antigen. Young female patients with acute CLE should be recognized as a separate subset of Ro/SS-A antibody-positive patients because almost a third was given the diagnosis of kidney involvement. Logistic regression analysis revealed that internal organ involvement was observed in patients with LE presenting with LE-nonspecific cutaneous manifestations, arthralgia, leukopenia, positive antinuclear antibody, and fatigue. This was a retrospective study from a single referral center specializing in dermatologic diseases. The particular cutaneous variant of LE and age at Ro/SS-A detection predict different risks for internal organ involvement in Ro/SS-A antibody-positive patients with LE.

Dermatopathology of rheumatologic diseases

Rheumatologic diseases are multisystem disorders that may initially manifest in the skin and accurate dermatopathologic diagnosis can lead to the identification of a systemic disorder. We review the clinical presentation and histopathologic findings in rheumatologic disease. This includes the variants of lupus: acute, subacute and chronic cutaneous lupus erythematosus, tumid lupus, discoid lupus, lupus panniculitis, nonbullous lupus, and depigmented lesions in lupus. Also discussed are dermatomyositis, systemic sclerosis and vasculitides, including leukocytoclastic vasculitis, lymphocytic vasculitis, neutrophilic vasculitis, polyarteritis nodosa, nodular vasculitis, eosinophilic vasculitis, granulomatous vasculitis, Henoch–Schonlein purpura and cryoglobulinemia.

Toxic epidermal necrolysis–like acute cutaneous lupus erythematosus (TEN-like ACLE) in SLE patients: A report of two cases

Acute cutaneous lupus erythematosus (ACLE) is a specific lesion in systemic lupus erythematosus (SLE) patients. ACLE can be categorized into localized ACLE, generalized ACLE and toxic epidermal necrolysis-like ACLE. Toxic epidermal necrolysis (TEN) that occurs in SLE patients has been infrequently reviewed. This condition is complicated to diagnose because medication can produce a blistering eruption that resembles vesiculobullous disease in SLE.To describe two cases of newly diagnosed SLE that had a cutaneous presentation compatible with TEN-like ACLE.Characteristics of two patients presenting with TEN-like ACLE and SLE are presented.The authors have described two cases of TEN-like ACLE which occurred in the context of systemic involvement of SLE. The cutaneous lesion was gradually progressed, with less mucosal involvement and mainly photodistributed. The authors suggest that the complexity and rarity of this condition could be related to systemic severity of SLE.

Expression and significance of skin aspartic protease in lesions of cutaneous lupus erythematosus

Objective To study the expression of skin aspartic protease (SASPase) in lesions of cutaneous lupus erythematosus (CLE) and its role in the pathogenesis of CLE.Methods Skin samples were resected from the lesions and normal skin of 9 patients with CLE,including 3 cases of subacute cutaneous lupus erythematosus (SCLE),4 cases of discoid lupus erythematosus (DLE) and 2 cases of acute cutaneous lupus erythematosus (ACLE).Keratinocytes were isolated from the tissue samples and cultured in serum-free medium.Total proteins were extracted from the keratinocytes and separated by two-dimensional gel electrophoresis.ImageMaster 2D analysis software was used to assess differentially expressed proteins in keratinocytes between the lesional and normal skin,which were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS).The expression levels of SASPase were further determined by Western blot.The data were analyzed statistically by Student's t test.Results Keratinocytes were isolated from the tissue samples and successfully cultured in vitro.Two-dimensional electrophoresis profiles of proteins from the keratinocytes were obtained with high resolution and reproducibility,and the average matching protein spots were about 1200 with the matching rate higher than 80％.As Western blot showed,the relative expression level of SASPase was 0.463 ± 0.018 in keratinocytes from the lesional skin,and 0.145 ± 0.011 in those from the normal skin (P ＜ 0.05).The Western blot results were consistent with those of two-dimensional electrophoresis.Conclusion The initiation and progression of CLE seem to be associated with the abnormal activation and overexpression of SASPase. Key words: Lupus erythematosus, cutaneous; SASPase; Keratinocytes

Erythema multiforme and Stevens-Johnson syndrome/toxic epidermal necrolysis associated with lupus erythematosus

The occurrence of erythema multiforme (EM)-like lesions in association with lupus erythematosus (LE) is often referred to as "Rowell syndrome" (RS). However, the existence of RS, or at least its nosographic independence from LE, is questioned. The association of Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) with LE is also controversial. We sought to define the features of EM and SJS/TEN in the setting of LE. The worldwide literature on the topic was systematically collected and reviewed. A total of 132 citations were found, from which 95 cases of EM-like lesions and 47 of SJS/TEN associated with LE were retrieved. Our analysis identified a subgroup defined as "subacute cutaneous LE (CLE)/acute CLE with EM-like lesions" and highlighted that this and subacute CLE/acute CLE with TEN-like lesions are variants of already known CLE subpatterns. On the other hand, RS can be considered an independent chronic CLE subtype characterized by the distinctive co-occurrence of chronic CLE and EM-like lesions and frequent, albeit mild, systemic involvement. The study was based on retrospective data and the number of reported cases identified was relatively small. RS might be included as a chronic CLE subtype within the spectrum of LE-specific skin disease.

Cutaneous lupus erythematosus on the elbows: a peculiar localization

The presence of lesions limited to the elbows as expression of a cutaneous lupus erythematosus (CLE) is very unusual. To describe the clinical and microscopic characteristics of these lesions, as well as their relationship with the different cutaneous lupus erythematosus subsets. Seven cases of CLE with lesions on the elbows, collected from 1998 to 2009, were retrospectively analysed. All patients had a previous or concomitant diagnosis of lupus erythematosus based on other typical skin lesions for each subtype of lupus erythematosus, and they all met clinical and microscopic criteria. Six patients were women with a mean age of 33.8 years. Five cases had been previously diagnosed with CLE (three lupus erythematosus [LE] tumidus, one subacute CLE and one acute CLE). In the other two cases, these lesions were the first manifestation of the disease. The lesions consisted of pruriginous, erythematous papules and plaques with a slightly scaly surface, located on both elbows. Microscopically, in addition to the typical features of CLE, other changes were observed, including alterations in the texture and the staining properties of collagen fibres (five cases), an interstitial histiocytic infiltrate (four cases), eosinophils (one case) and a Churg-Strauss granuloma (one case). These peculiar lesions located on the elbows should be included in the spectrum of cutaneous manifestations of LE. Their histopathology combines changes of both LE and interstitial granulomatous dermatitis.

The study of Cutaneous Lupus Erythematosus Disease Area and Severity Index in Indian patients with systemic lupus erythematosus

The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) is a newly described tool used to assess the activity of and damage caused by cutaneous lupus erythematosus (CLE). There is a paucity of data on CLASI from the Indian subcontinent. We sought to determine the applicability of CLASI in specific lesions of CLE in patients with systemic lupus erythematosus (SLE) attending a tertiary care hospital in India. In this prospective, cross-sectional study, 93 patients of SLE with cutaneous lesions were recruited. CLASI activity and damage scores of lupus erythematosus (LE)-specific skin lesions were done in 75 patients with SLE. The mean CLASI activity score was 15.4 ± 9.4 (range 0-39) and the mean damage score was 6.87 ± 7.75 (range 0-30). Higher mean CLASI activity scores were seen in patients with a combination of acute, subacute and chronic CLE and in those with widespread lesions. Patients with longstanding disease and long duration of skin lesions had higher damage scores. This study shows that CLASI is an effective tool to assess cutaneous activity of LE-specific lesions, and the damage caused by them, in Indian patients.

Expression of interleukin-17 is correlated with interferon-α expression in cutaneous lesions of lupus erythematosus

Type I interferon (IFN) has been reported to have an important role in the development of cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE). A new subset of CD4+ T cells, T helper (Th)17 cells, also plays a role in the development of autoimmunity. To investigate expression of interleukin (IL)-17 and IFN-α in different CLE subsets, and their associations with the pathogenesis of LE. Skin tissue samples from 33 cases, including chronic discoid LE (n = 24), acute (A)CLE (n = 4), subacute CLE (n = 1) and lupus panniculitis (n = 4) were collected for immunohistochemistry. Expression of IL-6, IL-17A, IFN-α, IFN-γ, myxovirus protein (Mx)A and transforming growth factor (TGF)-β was assessed in these samples. All LE specimens had staining for IL-6 and TGF-β in the infiltrated inflammatory cells. IL-17A staining was seen in 84.8% of specimens, and IFN-α or MxA was seen in 93.9%. TGF-β expression in ACLE was significantly greater than that in both chronic cutaneous (CC)LE and in lupus panniculitis (P = 0.02 for both). Expression of IL-17A was positively associated with expression of IFN-α and MxA (Spearman's ρ = 0.56 and 0.39, respectively). In addition, the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) correlated positively with expression of IFN-α and MxA (ρ = 0.40 for both), whereas there was no correlation with IL-17A expression. Two major cytokines, IL-17A and IFN-α, may play roles in the pathogenesis of CLE. Their patterns of expression positively correlated with each other.

Remission of Incapacitating Acute Cutaneous Lupus Erythematosus in a Patient With Systemic Lupus Erythematosus by B Cell-Depletive Therapy

Remission of Incapacitating Acute Cutaneous Lupus Erythematosus in a Patient With Systemic Lupus Erythematosus by B Cell-Depletive Therapy

Evaluation of disease activity and damage in different subtypes of cutaneous lupus erythematosus using the CLASI

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. Objective The aim of this study was to evaluate whether the CLASI is a useful instrument which reflects the different subtypes of CLE comparably well in each parameter. A total of 50 patients (42 female, 8 male) with different subtypes of CLE, including acute CLE (ACLE), subacute CLE (SCLE), chronic CLE (CCLE) and LE tumidus (LET), from the Departments of Dermatology, University of Düsseldorf, Germany, and Danderyd Hospital, Stockholm, Sweden, were evaluated using the CLASI at one time point. The total CLASI activity score was significantly lower in patients with LET compared with ACLE (P<0.05) and CCLE (P<0.001), and the total CLASI damage score was significantly lower in patients with LET than with ACLE (P<0.05), SCLE (P<0.001) and CCLE (P<0.001). The erythema score and the scale/hypertrophy score were significantly lower in LET than in ACLE (P<0.05, both) and CCLE (P<0.05 and P < 0.001, respectively). The dyspigmentation score was lowest in patients with LET, differing significantly from ACLE (P<0.05), SCLE (P<0.05) and CCLE (P<0.001). The scarring/atrophy/panniculitis score was significantly higher in patients with CCLE in contrast to SCLE and LET (P<0.05 and P<0.001, respectively). These data characterize the CLASI as an overall useful instrument to analyse disease activity and damage in CLE. However, the CLASI does not give an accurate assessment of all disease subtypes; therefore, a revision of the CLASI with critical analysis of all parameters is recommended.

Photosensitivity, phototesting, and photoprotection in cutaneous lupus erythematosus

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.

Overview of common, rare and atypical manifestations of cutaneous lupus erythematosus and histopathological correlates

The skin is the second most frequently affected organ system in lupus erythematosus. Although only very rarely life threatening--an example is lupus erythematosus-associated toxic epidermal necrolysis--skin disease contributes disproportionally to disease burden in terms of personal and psychosocial wellbeing, vocational disability, and hence in medical and social costs. Since several manifestations are closely associated with the presence and activity of systemic lupus erythematosus, prompt and accurate diagnosis of cutaneous lupus erythematosus is essential. This review aims to cover common, rare, and atypical manifestations of lupus erythematosus-associated skin disease with a detailed discussion of histopathological correlates. Cutaneous lupus erythematosus covers a wide morphological spectrum well beyond acute, subacute and chronic cutaneous lupus erythematosus, which are commonly classified as lupus-specific skin disease. Other uncommon or less well-known manifestations include lupus erythematosus tumidus, lupus profundus, chilblain lupus, mucosal lupus erythematosus, and bullous lupus erythematosus. Vascular manifestations include leukocytoclastic and urticarial vasculitis, livedoid vasculopathy and livedo reticularis/ racemosa. Finally, we discuss rare presentations such as lupus erythematosus-related erythema exsudativum multiforme (Rowell syndrome), Kikuchi-Fujimoto disease, extravascular necrotizing palisaded granulomatous dermatitis (Winkelmann granuloma), and neutrophilic urticarial dermatosis.

Lupus erythematodes

The typical clinical forms of cutaneous lupus erythematosus (LE) are the butterfly rash, acute, subacute and chronic cutaneous lupus, intermediate lupus (lupus tumidus), chilblain- and bullous lupus, lupus profundus, and ulcerating lesions on the mucous membrane. Besides the typical lupus forms, nonspecific skin lesions are also observed such as dermal mucinosis, acneiform skin lesions, different variants of livedo, necrotizing vasculitis with ulcers, purpura, urticaria vasculitis, neutrophilic dermatosis, hyperpigmentation, hair and nail changes as well as overlap syndromes with erythema multiforme, scleroderma, Sjögren syndrome, Raynaud phenomenon, lichen planus, bullous pemphigoid und psoriasis. There are lupus imitators which create differential diagnostic challenges, such as infections with atypical mycobacteria or subcutaneous T-cell lymphoma both of which are similar to lupus profundus. All these skin lesions can present as maximal pathological findings seen in lupus or be caused by a variety of pathological laboratory findings such as the anti-phospholipid antibodies or a deficiency of complement factors. In the latter situation severe lupus often with complications can be expected.

Marked papillary dermal edema - an unreliable discriminator between polymorphous light eruption and lupus erythematosus or dermatomyositis

The clinical differential diagnosis of photo-distributed papules and plaques includes polymorphous light eruption (PMLE) and lupus erythematosus (LE). These entities share many histopathological features. However, in most contemporary textbooks, a broad band of papillary dermal edema is reported to be characteristic of PMLE and not seen in LE. Nonetheless, older reports describe papillary dermal edema in LE, including acute cutaneous LE (ACLE) in patients with systemic LE (SLE) and early lesions of discoid lupus erythematosus (DLE). Older reports also describe papillary dermal edema in microscopic sections of dermatomyositis (DM). Retrospective review. Nine cases of LE (including two patients with acute lesions of SLE, six with DLE and one unclassifiable) and three cases of DM were identified in which sections showed striking papillary dermal edema. Attributes of chronicity, such as epidermal atrophy, follicular plugging and basement membrane thickening, were present concurrently in many sections. Marked papillary dermal edema does not reliably distinguish PMLE from LE as it can be seen in ACLE, early and late lesions of DLE and DM. This phenomenon has been underemphasized in recent reports and textbooks. Furthermore, papillary dermal edema in chronic lesions of DLE has not been previously reported.

Tyrosine kinase 2 and interferon regulatory factor 5 polymorphisms are associated with discoid and subacute cutaneous lupus erythematosus

Lupus erythematosus (LE) is a heterogeneous disease ranging from skin-restricted manifestations to a progressive multisystem disease. The specific skin lesions include chronic cutaneous, subacute cutaneous and acute cutaneous LE. Both genetic and environmental factors are involved in the development of LE. However, reports on the genetic background of cutaneous lupus erythematosus (CLE) forms, namely discoid (DLE) and subacute cutaneous lupus erythematosus (SCLE), are sparse. We investigated whether the known systemic LE (SLE) susceptibility genes also predispose to CLE. Altogether, 219 Finnish patients with DLE or SCLE and 356 healthy controls were recruited. Single nucleotide polymorphisms tagging reported risk genes were genotyped. Tyrosine kinase 2 (TYK2) rs2304256 was associated with increased risk of DLE (P = 0.012, OR = 1.47, 95% CI = 1.01-1.98). Expression of TYK2 was demonstrated by immunohistochemistry in macrophage-like cells and neutrophils and interferon regulatory factor 5 (IRF5) in macrophage- and fibroblast-like cells of DLE, SCLE and SLE skin. IRF5 rs10954213 showed association with DLE (P = 0.017, OR = 1.40, 95% CI = 1.06-1.86) and SCLE (P = 0.022, OR = 1.87, 95% CI = 1.09-3.21). A haplotype of cytotoxic T-lymphocyte-associated protein 4 (CTLA4) showed association with DLE (P = 0.0065, OR = 2.51, 95% CI = 1.25-5.04). Our results show that the TYK2, IRF5 and CTLA4 genes previously associated with SLE also confer risk for DLE and SCLE, suggesting that different LE subphenotypes may share pathogenetic pathways.

Cutaneous Lupus Erythematosus

Cutaneous lupus erythematosus (LE) may present in a variety of clinical forms. Three recognized subtypes of cutaneous LE are acute cutaneous LE (ACLE), subacute cutaneous LE (SCLE), and chronic cutaneous LE (CCLE). ACLE may be localized (most often as a malar or 'butterfly' rash) or generalized. Multisystem involvement as a component of systemic LE (SLE) is common, with prominent musculoskeletal symptoms. SCLE is highly photosensitive, with predominant distribution on the upper back, shoulders, neck, and anterior chest. SCLE is frequently associated with positive anti-Ro antibodies and may be induced by a variety of medications. Classic discoid LE is the most common form of CCLE, with indurated scaly plaques on the scalp, face, and ears, with characteristic scarring and pigmentary change. Less common forms of CCLE include hyperkeratotic LE, lupus tumidus, lupus profundus, and chilblain lupus. Common cutaneous disease associated with, but not specific for, LE includes vasculitis, livedo reticularis, alopecia, digital manifestations such as periungual telangiectasia and Raynaud phenomenon, photosensitivity, and bullous lesions. The clinical presentation of each of these forms, their diagnosis, and the inter-relationships between cutaneous LE and SLE are discussed. Common systemic findings in SLE are reviewed, as are diagnostic strategies, including histopathology, immunopathology, serology, and other laboratory findings. Treatments for cutaneous LE initially include preventive (e.g. photoprotective) strategies and topical therapies (corticosteroids and topical calcineurin inhibitors). For skin disease not controlled with these interventions, oral antimalarial agents (most commonly hydroxychloroquine) are often beneficial. Additional systemic therapies may be subdivided into conventional treatments (including corticosteroids, methotrexate, thalidomide, retinoids, dapsone, and azathioprine) and newer immunomodulatory therapies (including efalizumab, anti-tumor necrosis factor agents, intravenous immunoglobulin, and rituximab). We review evidence for the use of these medications in the treatment of cutaneous LE.