Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied in vitro spontaneous and ultraviolet light (UV)-induced lymphocyte apoptosis in patients with systemic lupus erythematosus (SLE, n = 11), cutaneous lupus erythematosus (CLE, n = 8), and other collagen diseases (n = 6), as well as normal individuals (n = 6). Apoptosis was confirmed by the presence of a 180 bp DNA ladder on gel electrophoresis. UVB-induced apoptosis was observed in 4 of 11 patients with SLE (36.3%), 3 of 8 patients with CLE (37.5%) and 2 of 6 patients (33.3%) with other collagen diseases. There was no clinical correlation between clinical photosensitivity and UV-induced apoptosis. Similarly, spontaneous apoptosis was also found in lymphocytes from patients with diseases other than SLE. No apoptosis was found in normal subjects with or without UVB irradiation (25 mJ/cm2). These data suggest that UV-induced lymphocyte apoptosis may not be specific to SLE but may be common in collagen diseases.
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PMID:In vitro spontaneous and UVB-induced lymphocyte apoptosis are not specific to SLE. 954 60

Keratinocyte apoptosis may be induced by ultraviolet-B radiation and represents a potential source of fragmented autoantigens in autoimmune diseases. This study investigates whether excessive keratinocyte apoptosis occurs in the skin lesions of cutaneous lupus (CLE) and dermatomyositis (DM) and the potential mechanisms responsible for this phenomenon. Skin biopsies have been studied from 19 patients with CLE and DM, eight with scleroderma, and five healthy controls. Apoptosis was detected by in situ end-labelling of fragmented DNA. The expression of Bcl-2, PCNA, p53, and Ki-67 proteins was studied by immunohistochemistry. In DM and CLE skin, the number of apoptotic keratinocytes was significantly increased (p=0.008) compared with normal skin. In both diseases, a large accumulation of apoptotic keratinocytes and apoptotic bodies was present in the disrupted basal zone. Unlike normal skin, a large number of keratinocytes, particularly those morphologically apoptotic, expressed p53 protein. A significant increase in the number of proliferating Ki-67 positive (p=0.0007) and PCNA-positive (p=0.0008) nuclei was also observed. In both CLE and DM, exaggerated and inappropriate keratinocyte apoptosis occurs. It is associated with increased expression of p53 and PCNA. This suggests that normal solar radiation alone or in combination with additional local factors induces DNA damage and excessive keratinocyte apoptosis in these autoimmune diseases of the skin. Apoptosis can mediate the severe epidermal lesions observed in both diseases and the release of fragmented autoantigens into the dermis.
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PMID:Keratinocyte apoptosis and p53 expression in cutaneous lupus and dermatomyositis. 1039 42

This article will review and update information about the pathogenesis, clinical presentation, diagnosis, and treatment of cutaneous lupus erythematosus. Lupus erythematosus (LE) can present as a skin eruption, with or without systemic disease. Cutaneous LE is subdivided into chronic cutaneous LE, subacute cutaneous LE and acute LE. The prevalence of systemic lupus erythematosus (SLE) is 17-48/100,000 population worldwide. Skin disease is one of the most frequent clinical complaints of patients suffering from SLE. It has been found to occur in up to 70% of patients during the course of the disease. The most frequent mucocutaneous manifestations of SLE are malar rash (40%), alopecia (24%), and oral ulcers (19%). It has been suggested that risk factors that are more likely to signal transition of cutaneous into systemic LE are high ANA titers (> 1:320) and the presence of arthralgias. CLE patients who exhibit these symptoms should be monitored closely, since they may be at increased risk to develop SLE.
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PMID:Cutaneous lupus erythematosus: a review. 1217 Aug 73

HMGB1 is a pro-inflammatory cytokine that together with TNF-alpha and IL-1beta is involved in the pathogenesis of spontaneously occurring skin lesions in lupus erythematosus. The purpose of the present study was to explore the sequence of events in HMGB1, TNF-alpha and IL-1beta expression under development and resolution of experimentally induced CLE lesions. The study involved investigation of 38 serial skin biopsies acquired from photoprovoked skin lesions of nine CLE patients, using immunohistochemical staining of tissue sections. In biopsies from the clinically most active phase of skin involvement extracellular, secreted HMGB1 and increased cytoplasmic HMGB1 were found, as compared with the late and fading lesions or non-lesional skin. Besides HMGB1, increased expression of TNF-alpha and IL-1beta was observed in dermal infiltrates of the induced CLE lesions. These cytokines were however not upregulated in all lesions, and increased expression of IL-1beta was seen predominantly in late biopsies.In conclusion, extracellular and cytoplasmic HMGB1 coincides with the clinically most active phase of photoinduced lesions of cutaneous lupus, and suggests that HMGB1 is an important factor in the inflammatory autoimmune process of CLE. HMGB1 can induce expression of TNF-alpha and IL-1beta, and formation of a pro-inflammatory loop between HMGB1, TNF-alpha, and IL-1beta may be responsible for the prolonged and sustained inflammation in CLE.
Lupus 2007
PMID:Translocation of the novel cytokine HMGB1 to the cytoplasm and extracellular space coincides with the peak of clinical activity in experimentally UV-induced lesions of cutaneous lupus erythematosus. 1789 2

Lupus erythematosus (LE) is an autoimmune disease that can affect one or more internal organs (systemic LE [SLE]) as well as the skin (CLE). Common cutaneous subtypes of CLE are chronic CLE (CCLE) and subacute CLE (SCLE). CCLE is the only type of CLE which heals with scarring and this may affect any site in the body. The fact that inflammation in CCLE generally involves the bulge area of the follicles (where the stem cells reside) raises the possibility that damage to the stem cells may be one process leading to permanent loss of follicles. One of the most useful distinctive markers of the stem cells is cytokeratin 15 (CK15) and this has been used in some studies to demonstrate the involvement of the bulge region in the scarring process in primary cicatricial alopecia and DLE. The bulge region appears to be involved in the scarring process in CLE and other types of cicatricial alopecia as part of broader involvement of the hair follicles; it is secondarily affected by the surrounding inflammatory cell infiltrate. Expression of the stem cell marker CK15 diminished and was then absent indicating either damage to stem cells or differentiation to help in the repair process.
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PMID:Hair follicle stem cells in the pathogenesis of the scarring process in cutaneous lupus erythematosus. 1916 47

Lupus erythematosus is a chronic and inflammatory multiorgan disease with variable clinical appearance and variable course. Most patients with systemic lupus erythematosus show cutaneous manifestations and conversely, all forms of cutaneous LE may change into a systemic involvement. Specific lesions of cutaneous LE are classified in different subtypes of acute cutaneous lupus erythematosus (ACLE), subacute cutaneous lupus erythematosus (SCLE), chronic cutaneous lupus erythematosus (CDLE) and intermittent cutaneous lupus erythematosus (ICLE) according to clinical, histological and immunoserological parameters. Regular laboratory tests are important to monitor the activity and course of the disease or side effects of the therapy. In case of clinical or laboratory dysfunctions of internal organs, additional technical investigations are necessary. Histology is needed to support clinical diagnosis. A large number of drugs are able to induce SCLE, e.g. hydrochlorothiazide, terbinafine, or angiotensin-converting enzyme inhibitors. Drug-induced SCLE can be differentiated by possible complementary immunoserological parameters. Neonatal lupus can be induced by transplacental transmission of maternal anti-Ro(SS-A) and anti-La(SS-B)-antibodies. Children with neonatal lupus might suffer from congenital atrioventricular block. Their mothers may suffer from active LE, but can be clinically healthy as well. As a consequence, pregnancies at risk should be monitored in short intervals by serial echocardiographic interventions. Protection against UV light is recommended for all types of CLE. There are some topical and many systemic treatment options e.g. topical and systemic glucocorticosteroids, antimalarial drugs, dapsone, azathioprine, or mycophenolate mofetil with different response to skin or organ involvement.
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PMID:The different faces of cutaneous lupus erythematosus. 1935 21

In the first part of the review, topical agents and first-line systemic treatment options for cutaneous lupus erythematosus were discussed whereas in the second part, recent information on efficacy, dosage, and side effects for further systemic treatment options are described in detail. In contrast to other immunosuppressive agents, such as azathioprine, cyclophosphamide, and cyclosporine, methotrexate has recently received more attention in the treatment of the disease. Further second-line treatment includes retinoids, dapsone, and mycophenolate mofetil. Because of severe side effects or high costs, other agents, such as thalidomide or high-dose intravenous immunoglobulins, are reserved for severe recalcitrant CLE. Biologics, ie, rituximab, have been used to treat systemic lupus erythematosus; however, in CLE, most biologics have only been applied in single cases. In addition to successful treatment, induction of CLE subtypes by biologics has been reported. In conclusion, many treatment options exist for CLE, but not many are supported by evidence from randomized controlled trials.
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PMID:Cutaneous lupus erythematosus: update of therapeutic options part II. 2080 Mar 19

To date, 71 patients having the so-called 'Rowell's syndrome' (RS) have been reported in the literature. However, most of them did not show all the clinical and serological features first described by Rowell and co-workers in 1963. Moreover, since then, subacute cutaneous lupus erythematosus (SCLE) has been identified and the diagnostic criteria as well as the clinical features of erythema multiforme (EM) defined. Accordingly several authors have questioned the existence of RS over the past years. In the present paper, the main clinical, histopathological and immunopathological features of both SCLE and EM are described and all of the cases of RS reported in the literature are also reviewed in depth. A real association between discoid LE and EM was present only in a minority of cases and could be considered a mere coincidence. As for other associations, e.g. those between CLE and lichen planus or psoriasis, the coexistence of CLE and EM does not justify the framing of a separate syndrome as suggested by Rowell et al.
Lupus 2012 May
PMID:The last word on the so-called 'Rowell's syndrome'? 2217 Jul 59

Lupus erythematosus (LE) is a multifactorial autoimmune disease with clinical manifestations of differing severity which may present with skin manifestations as primary sign of the disease (cutaneous lupus erythematosus, CLE) or as part of a disease spectrum (systemic lupus erythematosus, SLE). To date, no drugs are approved specifically for the treatment of CLE and only single agents have been applied in randomized controlled trials. Therefore, topical and systemic agents are used "off-label", primarily based on open-label studies, case series, retrospective analyses, and expert opinions. In contrast, several agents, such as hydroxychloroquine, chloroquine, cyclophosphamide, azathioprine, and belimumab, are approved for the treatment of SLE. Recent approaches in the understanding of the molecular pathogenesis of LE enabled the development of further new agents, which target molecules such as interleukin 6 (IL-6) and interferon (IFN). Only single trials, however, applied these new agents in patients with cutaneous involvement of the disease and/or included endpoints which evaluated the efficacy of these agents on skin manifestations. This article provides an updated review on new and recent approaches in the treatment of CLE.
Lupus 2016 Jul
PMID:Advances in the treatment of cutaneous lupus erythematosus. 2725 59

This study was stimulated by the clinical observation of a rapid response of a chilblain lupus patient to treatment with JAK1/2-kinase inhibitor ruxolitinib. We investigated the in vivo expression of phospho-JAK2 in CLE skin samples as well as the immunomodulatory in vitro effect of ruxolitinib in cultured immortalized keratinocytes and in a 3D human epidermis model (epiCS). Our results demonstrate that ruxolitinib significantly decreases the production of CLE-typical cytokines (CXCL10, CXCL9, MxA) and might be a promising drug for future clinical studies in patients with CLE and related autoimmune skin diseases.
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PMID:JAK inhibitor ruxolitinib inhibits the expression of cytokines characteristic of cutaneous lupus erythematosus. 2789 10


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