The antimalarial hydroxychloroquine (HCQ) has demonstrated several crucial properties for the treatment of systemic lupus erythematosus (SLE). Herein, we reviewed the main HCQ pharmacologic features, ...detailed its mechanism of action, and summarized the existing guidelines and recommendations for HCQ use in rheumatology with a systematic literature search for the randomized controlled trials focused on lupus. HCQ has been shown to decrease SLE activity, especially in mild and moderate disease, to prevent disease flare and to lower the long-term glucocorticoid need. The numerous benefits of HCQ are extended to pregnancy and breastfeeding period. Based on cohort studies, antithrombotic and metabolic HCQ’s effects were shown, including lipid-lowering properties, which might contribute to an improved cardiovascular risk. Moreover, early HCQ use in antinuclear antibodies positive individuals might delay the progression to SLE. Finally, HCQ has a significant favorable impact on long-term outcomes such as damage accrual and mortality in SLE. Based on these multiple benefits, HCQ is now the mainstay long-term treatment in SLE, recommended by current guidelines in all patients unless contraindications or side effects. The daily dose associated with the best compromise between efficacy and safety is matter of debate. The concern regarding retinal toxicity rather than proper efficacy data is the one that dictated the daily dosage of ⩽5 mg/kg/day actual body weight currently agreed upon.
Background Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis with possible cutaneous-specific involvement. Objectives We sought to describe the clinical, pathological, ...and molecular features of the cutaneous manifestations of 40 patients with ECD identified from a cohort of 123 patients. Methods Confirmed cases of patients with ECD were included in a single-center retrospective observational study. Clinical and pathological cutaneous features were analyzed and BRAF V600E mutation was determined. Results The most frequent ECD cutaneous manifestations were xanthelasma-like lesions (XLL), which occurred in 31 (25%) patients. Other ECD cutaneous lesions were patches or papulonodular lesions. Mixed form of ECD and cutaneous Langerhans cell histiocytosis presented with crusty papules of the folds in some patients. Compared with classic xanthelasma palpebrarum, ECD XLL pathology more frequently involved the reticular dermis, displayed more multinucleated or Touton cells, and showed less extensive fibrosis. BRAF V600E mutation was more frequently detected in patients with cutaneous involvement than in those without (76% vs 52%; P = .005) and constantly found in 10 XLL. Limitations Some clinical data were not available because of the retrospective design of the study. Conclusions XLL are the most frequent cutaneous ECD manifestations and might be targeted both for pathology and determination of BRAF mutational status.
Transmission of dermatophytes, especially Trichophyton mentagrophytes genotype VII, during sexual intercourse has been recently reported. We report 13 such cases in France. All patients were male; 12 ...were men who have sex with men. Our findings suggest sexual transmission of this pathogen within a specific population, men who have sex with men.
Background Interaction between smoking and efficacy of antimalarials, the mainstay of treatment for cutaneous lupus erythematosus (CLE), remains controversial. Objectives We systematically reviewed ...the evidence for such an interaction and performed a meta-analysis to compare the efficacy of antimalarials among smoker versus nonsmoker patients with CLE. Methods Observational studies published up to March 2014 in the MEDLINE, Embase, and Cochrane databases were selected if they reported on the efficacy of antimalarials for treatment of CLE, according to smoking status. The strength of association between smoking and cutaneous response rate was expressed using the odds ratio. Individual study odds ratios were combined in the meta-analysis using a random effects model. Results Of 240 citations retrieved, 10 studies met inclusion criteria, for a total of 1398 patients. The pooled odds ratio for the response to antimalarials in smoker patients with CLE (n = 797) was 0.53 (95% confidence interval 0.29-0.98) compared with nonsmokers (n = 601). Limitations Subgroup analyses for the response to antimalarials considering CLE subtypes, type, and dosage of antimalarials could not be performed because of the lack of available data. Conclusions Smoking is associated with a 2-fold decrease in the proportion of patients with CLE achieving cutaneous improvement with antimalarials. Smoking cessation should be considered in patients with CLE and refractory cutaneous involvement.
Background Up to 30% of patients with cutaneous lupus erythematosus (CLE) fail to respond to hydroxychloroquine (HCQ). Objectives We sought to evaluate the efficacy of increased daily doses of HCQ on ...cutaneous response in refractory CLE. Methods We conducted an open-label prospective study between 2010 and 2014. Patients with CLE and HCQ blood level less than or equal to 750 ng/mL were included. The daily dose of HCQ was increased to reach blood concentrations greater than 750 ng/mL. The primary end point was the number of responders defined by an improvement of CLE Disease Area and Severity Index score (4 points or 20% decrease) in patients with HCQ blood concentration greater than 750 ng/mL. Results We included 34 patients (26 women; median age 45 range 28-72 years). Two nonadherent patients were excluded. The median CLE Disease Area and Severity Index score before treatment was significantly improved after treatment (8 range 2-30 vs 1.5 range 0-30), P < .001). The primary response criterion was reached in 26 (81%) of the 32 patients analyzed. A decrease in HCQ doses without further CLE flare (median follow-up 15.8 range 3.06-77.4 months) was achieved in 15 of the 26 responders. Limitations The main limitations of the study are its open-label design and the limited number of patients included. Conclusions Increasing HCQ doses to reach blood concentrations greater than 750 ng/mL should be considered before addition of other treatments in refractory CLE.
Significant advances in the understanding of the molecular basis of innate immunity have led to the identification of interferons (IFNs), particularly IFN-α, as central mediators in the pathogenesis ...of Systemic Lupus Erythematosus. Therefore, targeting of IFNs and of their downstream pathways has emerged as important developments for novel drug research in SLE. Based on this, several specific interferon blocking strategies using anti-IFN-α antibodies, anti-type I interferon receptor antibodies, Interferon-α-kinoid, or anti-IFN-γ antibodies have all been assessed in recent clinical trials. Alternative strategies targeting the plasmacytoid dendritic cells (pDCs), Toll-Like Receptors (TLRs)-7/9 or their downstream pathways such as the myeloid differentiation primary-response protein 88 (MYD88), spleen tyrosine kinase (Syk), Janus-kinases (JAKs), interleukin-1 receptor-associated kinase 4 (IRAK4), or the Tyrosine Kinase 2 (TYK2) are also investigated actively in SLE, at more preliminary clinical development stages, except for JAK inhibitors which have reached phase 2 studies. In a near future, in-depth and personalized functional characterization of IFN pathways may provide further guidance for the selection of the most relevant therapeutic strategy in SLE, tailored at the patient-level.
•Interferons (IFNs), particularly IFN-α, are central mediators in the pathogenesis of Systemic Lupus Erythematosus.•The main IFN-α blocking strategies currently developed include anti-IFN-α antibodies, anti-type I interferon receptor antibodies, interferon-α-kinoid.•Alternative targets under current development include the pDCs, TLR-7/9 or their downstream pathways such MYD88, Syk, JAKs, IRAK4, and TYK2.•Personalized characterization of IFN pathways may provide further guidance for the selection of the most relevant therapeutic strategy in SLE.
Abstract
Calcific uremic arteriolopathy (CUA) is a severely morbid disease, affecting mostly dialyzed end-stage renal disease (ESRD) patients, associated with calcium deposits in the skin. ...Calcifications have been identified in ESRD patients without CUA, indicating that their presence is not specific to the disease. The objective of this retrospective multicenter study was to compare elastic fiber structure and skin calcifications in ESRD patients with CUA to those without CUA using innovative structural techniques. Fourteen ESRD patients with CUA were compared to 12 ESRD patients without CUA. Analyses of elastic fiber structure and skin calcifications using multiphoton microscopy followed by machine-learning analysis and field-emission scanning electron microscopy coupled with energy dispersive X-ray were performed. Elastic fibers specifically appeared fragmented in CUA. Quantitative analyses of multiphoton images showed that they were significantly straighter in ESRD patients with CUA than without CUA. Interstitial and vascular calcifications were observed in both groups of ESRD patients, but vascular calcifications specifically appeared massive and circumferential in CUA. Unlike interstitial calcifications, massive circumferential vascular calcifications and elastic fibers straightening appeared specific to CUA. The origins of such specific elastic fiber’s alteration are still to be explored and may involve relationships with ischemic vascular or inflammatory processes.
Objective
Pruritus is an important symptom frequently accompanying various inflammatory skin conditions and some recent data indicated that it may be associated with autoimmune connective tissue ...diseases. The aim of this study was to assess the frequency and clinical presentation of itch in CLE.
Methods
A multinational, prospective, cross-sectional study was performed to assess the prevalence, intensity and clinical characteristic of pruritus in various subtypes of CLE. A total of 153 patients with active CLE lesions were included. Their age ranged between 17 and 82 years (mean 49.8 ± 15.4 years), and 115 patients (75.2%) were women. The disease activity and damage were assessed according to the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). Pruritus severity was assessed with Numeric Rating Scale (NRS) and the 12-Item Pruritus Severity Scale. Dermatology Life Quality Index and EQ-5D questionnaire were used to measure quality of life.
Results
Pruritus was present in 116 (76.8%) of patients of whom half had NRS scoring equal or above 4 points indicating moderate or severe pruritus. Most commonly itch was localized on the scalp, face (excluding ears and nose) and arms (40.5%, 36.2%, 31.9%, respectively). Sensations connected with pruritus were most frequently described as burning, tingling and like ants crawling feeling, but 31.9% patients described it as “pure itch”. More than half of patients reported that pruritus was present every day, and it was most frequent during the evenings. The pruritus scoring and the CLASI activity score were significantly correlated (r = 0.42, p = 0.0001), while no correlation was found with the CLASI damage score (p = 0.16). Both the maximum and average itch intensity were correlated with systemic lupus erythematosus (SLE) activity measured with the Systemic Lupus Erythematosus Disease Activity Index.
Conclusions
Pruritus is a common, but frequently overlooked symptom of CLE. Its intensity correlates with the activity of CLE, but not with the skin damage. In more than a half of patients it occurs on a daily basis. The correlation between the intensity of pruritus and the activity of the skin lesions and the systemic involvement indicate that pruritus could be an individual indicator of both SLE and CLE activity.
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