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Rheumatology AND Discoid lupus erythematosus [keywords]
- Invariant natural killer T cells are enriched at the site of cutaneous inflammation in lupus erythematosus. [JOURNAL ARTICLE]
- J Dermatol Sci 2013 Apr 19.
BACKGROUND:Systemic lupus erythematosus (SLE) is associated with a numerical and functional reduction of peripheral blood (PB) invariant natural killer T (iNKT) cells. Limited information exists on the role of iNKT cells in the pathogenesis of lupus erythematosus.
OBJECTIVE:To investigate the frequency and phenotype of iNKT cells in PB and dermal infiltrates from patients with SLE, subacute-cutaneous lupus erythematosus (SCLE) and discoid lupus erythematosus (DLE).
METHODS:PB was obtained from 23 SLE, 6 SCLE, and 11 DLE patients, and from 30 healthy controls. iNKT cell frequency and CCR4/CCR6 surface expression were assessed by flow cytometry. The frequency and phenotype of skin infiltrating Vα24(+)Vβ11(+) iNKT cells were investigated by immunofluorescence in lesional biopsies from 20 patients, unaffected skin from 3 patients, and from 6 healthy controls.
RESULTS:Lupus erythematosus patients displayed significantly lower percentages of circulating CD3(+)6B11(+) iNKT cells compared to healthy controls. Whereas CCR6 expression on iNKT cells was enhanced in active SLE patients regardless of cutaneous involvement compared to healthy controls, CCR4 was exclusively increased in patients with active cutaneous lesions. Furthermore, iNKT cells were significantly enriched in lesional skin of SLE and DLE patients, but not in unaffected skin of lupus patients. The majority of lesional iNKT cells expressed IFN-γ and CCR4.
CONCLUSION:The deficiency in circulating iNKT cells in cutaneous lupus erythematosus is associated with an increase of iNKT cells at the site of cutaneous inflammation. These data underscore the importance of analyzing iNKT cells not only in PB, but also in the target tissues.
- Association of discoid lupus erythematosus with other clinical manifestations among patients with systemic lupus erythematosus. [JOURNAL ARTICLE]
- J Am Acad Dermatol 2013 Mar 27.
BACKGROUND:Cutaneous discoid lupus erythematosus (DLE) among patients with systemic lupus erythematosus (SLE) may be associated with less severe disease and with low frequency of nephritis and end-stage renal disease (ESRD).
OBJECTIVE:We sought to investigate associations between confirmed DLE and other SLE manifestations, adjusting for confounders.
METHODS:We identified patients with rheumatologist confirmation, according to 1997 American College of Rheumatology (ACR) SLE classification criteria, more than 2 visits, longer than 3 months of follow-up, and documented year of SLE diagnosis. DLE was confirmed by a dermatologist, supported by histopathology and images. SLE manifestations, medications, and serologies were collected. Multivariable-adjusted logistic regression analyses tested for associations between DLE and each of the ACR SLE criteria, and ESRD.
RESULTS:A total of 1043 patients with SLE (117 with DLE and 926 without DLE) were included in the study. After multivariable adjustment, DLE in SLE was significantly associated with photosensitivity (odds ratio [OR] 1.63), leukopenia (OR 1.55), and anti-Smith antibodies (OR 2.41). DLE was significantly associated with reduced risks of arthritis (OR 0.49) and pleuritis (OR 0.56). We found no significant associations between DLE and nephritis or ESRD.
LIMITATIONS:Cross-sectional data collection with risk of data not captured from visits outside system was a limitation.
CONCLUSIONS:In our SLE cohort, DLE was confirmed by a dermatologist and we adjusted for possible confounding by medication use, in particular hydroxychloroquine. We found increased risks of photosensitivity, leukopenia, and anti-Smith antibodies and decreased risks of pleuritis and arthritis in patients with SLE and DLE. DLE was not related to anti-double-stranded DNA antibodies, lupus nephritis, or ESRD. These findings have implications for prognosis among patients with SLE.
- Smoking is associated with cutaneous manifestations in systemic lupus erythematosus. [JOURNAL ARTICLE]
- Arthritis Care Res (Hoboken) 2013 Feb 11.
OBJECTIVE:To examine the association between smoking and cutaneous involvement in SLE.
METHODS:We analyzed data from a multicenter Canadian SLE cohort. Muco-cutaneous involvement was recorded at most recent visit, using the SLEDAI-2K (rash, alopecia, oral ulcers), the SLICC/ACR Damage Index (SDI; alopecia, extensive scarring and skin ulceration) and the ACR criteria (malar rash, discoïd rash, photosensitivity, mucosal involvement). Multivariate logistic regression models were used to estimate independent association between muco-cutaneous involvement and cigarette smoking, age, sex, lupus duration, medications, and laboratory data.
RESULTS:In our cohort of 1346 patients, 91.0% were female, with mean age 47.1 years (standard deviation, SD 14.3) and mean disease duration of 13.2 years (SD 10.0). A total of 41.2% reported ever smoking, 14.0% were current smokers and 27.1% were past smokers. Active cutaneous manifestations occurred in 28.4%; cutaneous damage occurred in 15.4%. Regarding ACR criteria, malar rash was noted in 59.5%, discoid rash in 16.9%, and photosensitivity in 55.7%. In multivariate analysis, current smoking was associated with active SLE rash (OR 1.63; 95% CI 1.07-2.48). Having ever smoked was associated with the ACR criteria discoid rash (2.36; 1.69-3.29) and photosensitivity (1.47; 1.11-1.95), and with the total cutaneous ACR score (1.50; 1.22-1.85). We did not detect associations between previous smoking and active cutaneous manifestations. No association was found between smoking and cutaneous damage or mucosal ulcers. No interaction was seen between smoking and antimalarials.
CONCLUSION:Current smoking is associated with active SLE rash, and ever smoking with cutaneous ACR criteria. This provides additional motivation for smoking cessation in SLE. © 2013 by the American College of Rheumatology.
- Increased neutrophil oxidative burst metabolism in systemic lupus erythematosus. [Journal Article, Research Support, Non-U.S. Gov't]
- Lupus 2012 Dec; 21(14):1543-51.
There is increased frequency of discoid lesions (2.7%) and SLE (0.5%) in patients with chronic granulomatosus disease, but the literature is still controversial about phagocyte oxidative burst in SLE patients.300 SLE patients and 301 blood donors were evaluated for quantitation of the oxidative burst in phagocytes by flow cytometry based on the oxidation of 2,7-dichlorofluorescein-diacetate after stimuli with Staphylococcus aureus and Pseudomonas aeruginosa.Neutrophils from SLE patients displayed higher basal reactive oxygen species (ROS) production than healthy controls [Mean of fluorescence intensity (MFI) = 53.77 ± 11.38 vs 15.08 ± 2.63, p < 0.001] and after stimulation with S. aureus (MFI = 355.46 ± 58.55 vs 151.92 ± 28.25, p < 0.001) or P. aeruginosa (MFI = 82.53 ± 10.1 vs 48.99 ± 6.74, p < 0.001). There was stronger neutrophil response after bacterial stimuli (ΔMFI) in SLE patients than in healthy controls (S. aureus = 301.69 ± 54.42 vs 118.38 ± 26.03, p < 0.001; P. aeruginosa = 28.76 ± 12.3 vs 15.45 ± 5.15, p < 0.001), but no difference with respect to the oxidative burst profile according to disease activity (SLEDAI ≥ 6) or severity (SLICC-DI ≥2). Patients with kidney involvement presented higher basal and stimulated ROS production in neutrophils.The present findings corroborate the important role of innate immunity in SLE and implicate neutrophils in the pathophysiology of the disease.
- Cutaneous manifestations of systemic lupus erythematosus. [Journal Article]
- Autoimmune Dis 2012.:834291.
Systemic lupus erythematosus (SLE) is a multiorgan autoimmune disease of unknown etiology with many clinical manifestations. The skin is one of the target organs most variably affected by the disease. The American College of Rheumatology (ACR) established 11 criteria as a classificatory instrument to operationalise the definition of SLE in clinical trials. They were not intended to be used to diagnose individuals and do not do well in that capacity. Cutaneous lesions account for four of these 11 revised criteria of SLE. Skin lesions in patients with lupus may be specific or nonspecific. This paper covers the SLE-specific cutaneous changes: malar rash, discoid rash, photosensitivity, and oral mucosal lesions as well as SLE nonspecific skin manifestations, their pathophysiology, and management. A deeper thorough understanding of the cutaneous manifestations of SLE is essential for diagnosis, prognosis, and efficient management. Thus, dermatologists should cooperate with other specialties to provide optimal care of SLE patient.
- Systemic lupus erythematosus in an African Caribbean population: incidence, clinical manifestations, and survival in the Barbados National Lupus Registry. [Journal Article, Research Support, Non-U.S. Gov't]
- Arthritis Care Res (Hoboken) 2012 Aug; 64(8):1151-8.
To assess the epidemiology, clinical features, and outcomes of systemic lupus erythematosus (SLE) in the predominantly African Caribbean population of Barbados.A national registry of all patients diagnosed with SLE was established in 2007. Complete case ascertainment was facilitated by collaboration with the island's sole rheumatology service, medical practitioners, and the lupus advocacy group. Informed consent was required for inclusion.Between January 1, 2000 and December 31, 2009, there were 183 new cases of SLE (98% African Caribbean) affecting 172 women and 11 men for unadjusted annual incidence rates of 12.21 (95% confidence interval [95% CI] 10.46-14.18) and 0.84 (95% CI 0.42-1.51) per 100,000 person-years, respectively. Excluding pediatric cases (ages <18 years), the unadjusted incidence rate among women was 15.14 per 100,000 person-years. The principal presenting manifestations were arthritis (84%), nephritis (47%), pleuritis (41.5%), malar rash (36.4%), and discoid lesions (33.1%). Antinuclear antibody positivity was 95%. The overall 5-year survival rate was 79.9% (95% CI 69.6-87.1), decreasing to 68% in patients with nephritis. A total of 226 persons with SLE were alive at the end of the study for point prevalences of 152.6 (95% CI 132.8-174.5) and 10.1 (95% CI 5.4-17.2) per 100,000 among women and men, respectively.Rates of SLE in Barbadian women are among the highest reported to date, with clinical manifestations similar to African American women and high mortality. Further study of this population and similar populations of West African descent might assist our understanding of environmental, genetic, and health care issues underpinning disparities in SLE.
- Association of discoid lupus erythematosus with clinical manifestations and damage accrual in a multiethnic lupus cohort. [Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't]
- Arthritis Care Res (Hoboken) 2012 May; 64(5):704-12.
To determine the clinical manifestations and disease damage associated with discoid rash in a large multiethnic systemic lupus erythematosus (SLE) cohort.SLE patients (per American College of Rheumatology [ACR] criteria) ages ≥16 years with a disease duration of ≤10 years at enrollment and defined ethnicity (African American, Hispanic, or white) from a longitudinal cohort were studied. Socioeconomic-demographic features, clinical manifestations, and disease damage (per the Systemic Lupus International Collaborating Clinics/ACR Damage Index) were determined. The association of discoid lupus erythematosus (DLE) with clinical manifestations and disease damage was examined using multivariable logistic regression.A total of 2,228 SLE patients were studied. The mean ± SD age at diagnosis was 34.3 ± 12.8 years and the mean ± SD disease duration was 7.9 ± 6.0 years; 91.8% were women. DLE was observed in 393 patients with SLE (17.6%). In the multivariable analysis, patients with DLE were more likely to be smokers and of African American ethnicity and to have malar rash, photosensitivity, oral ulcers, leukopenia, and vasculitis. DLE patients were less likely to be of Hispanic (from Texas) ethnicity and to have arthritis, end-stage renal disease, and antinuclear, anti-double-stranded DNA, and antiphospholipid antibodies. Patients with DLE had more damage accrual, particularly chronic seizures, scarring alopecia, scarring of the skin, and skin ulcers.In this cohort of SLE patients, DLE was associated with several clinical features, including serious manifestations such as vasculitis and chronic seizures.
- Mycophenolate mofetil inducing remission of lupus enteritis. [Case Reports, Journal Article]
- Lupus 2012 Apr; 21(5):556-8.
We report the case of a young woman with a background history of discoid lupus who presented with abdominal pain, vomiting and intermittent diarrhoea. Physical examination revealed tenderness in the right upper quadrant with a palpable right inguinal lymph node without any other clinical signs of active lupus. Laboratory investigations showed normal inflammatory markers, positive ANA and Anti-Ro antibodies, persistent hypocomplementemia and lymphopenia, CT showed marked bowel oedema involving the small and large bowel (halo sign) with massive ascites and moderate right-sided pleural effusion. Mantoux test, AFB and TB cultures were negative. A diagnosis of lupus enteritis was made and treatment with high-dose steroids was commenced with little improvement. Treatment with cyclophosphamide was discussed but declined by the patient. Mycophenolate mofetil was commenced and resulted in significant clinical and radiological resolution. To the best of the authors' knowledge this is the first report of the successful use of mycophenolate mofetil in inducing and maintaining remission in lupus enteritis.
- Hydroxychloroquine in systemic lupus erythematosus and rheumatoid arthritis and its safety in pregnancy. [Journal Article, Review]
- Expert Opin Drug Saf 2011 Sep; 10(5):705-14.
INTRODUCTION:The antimalarial drug hydroxychloroquine (HCQ) is widely used to treat various rheumatic diseases. Many autoimmune diseases occur in women of child-bearing age who may become pregnant while on therapy, which raises concerns regarding the teratogenicity of HCQ and its effect on the outcome of the pregnancy. There is a lack of data regarding the safety of HCQ during pregnancy. AREAS COVERED: In this review, the authors attempt to identify relevant publications by searching MEDLINE, Cochrane database, Ovid-Currents Clinical Medicine, Ovid-Embase:Drugs and Pharmacology, EBSCO, Web of Science and SCOPUS using the search terms HCQ and/or pregnancy. A basis for the mechanism of action of HCQ is provided. EXPERT OPINION: HCQ has been shown by numerous studies over the past 15 years to be efficacious in the treatment of autoimmune diseases, including systemic lupus erythematosus, discoid lupus erythematosus and rheumatoid arthritis. HCQ does not appear to be associated with any increased risk of congenital defects, spontaneous abortions, fetal death, prematurity or decreased numbers of live births in patients with autoimmune diseases. Therefore, in the author's opinion, HCQ is safe for the treatment of autoimmune diseases during pregnancy.
- Successful treatment of cyclosporine-A-resistant cytophagic histiocytic panniculitis with tacrolimus. [Case Reports, Journal Article]
- Mod Rheumatol 2011 Oct; 21(5):553-6.
A 34-year-old woman with discoid lupus erythematosus and lupus profundus was admitted to our hospital showing signs of a fever, malaise, and abdominal swelling. Diagnosis of cytophagic histiocytic panniculitis (CHP) was made based on lobular panniculitis with a hemophagocytosis. Treatment with high doses of prednisolone combined with cyclosporine A (CsA) was not effective enough. However, after changing CsA to tacrolimus (TAC), CHP improved. Our case demonstrates that TAC may be a novel therapy for CHP.