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Use of cyclosporine in the treatment of patients with possible neurogenic rosacea presenting as persistent facial edema with burning sensation: A case series
The goal of this systematic review was to explore emerging perspectives on the role of skin microbiota in acne vulgaris, skin aging, and rosacea. We searched the literature for published clinical trials, randomized controlled trials, cross-sectional studies, and cohort studies, both experimental and observational, whose primary main purpose was to ascertain the associations between the skin microbiome and chronic skin disease, acne vulgaris, rosacea, and skin aging, using the Embase and PubMed databases. Fifty-one relevant published articles were identified for systematic review (up to December 2021). The possible roles of the skin microbiome in these skin diseases were explored to shed light on its development and to identify potential therapeutic targets for treatment. However, the mechanisms of microbial interaction in these diseases are still under-studied. The results of this evidence-based review suggest that it may be possible to develop individualized therapies targeting the pathogenic strains within the skin microbiome involved in these diseases. This alternative therapeutic approach, involving modifications of the microbiome, may form the basis of the next generation of treatment, known collectively as “ecobiological” anti-inflammatory therapies.
Rosacea with severe neurological symptoms such as burning and stinging is often not treated effectively by conventional therapies. The aim of this study was to investigate the clinical characteristics of Korean rosacea patients with prominent neurological symptoms. The demographic features, medical history, clinical manifestations and treatment modalities of 17 neurogenic rosacea patients who had prominent neurological symptoms and 106 erythematotelangiectatic rosacea (ETR) patients as a control group were investigated. All 17 neurogenic rosacea patients had severe persistent erythema with burning/stinging sensation limited to both cheeks. Among these patients, 94.1% were female (16/17). Heat stimuli (58.8%, 10/17) and stress (52.9%, 9/17) were major aggravating factors. Fourteen of 17 patients (82.3%) improved after receiving anticonvulsants and antidepressants. In conclusion, rosacea patients with severe neurological symptoms show distinct clinical manifestations and should be classified separately, and a different therapeutic approach is necessary for them.
Background A transition from a subtyping to a phenotyping approach in rosacea is
underway, allowing individual patient management according to presenting fea-
tures instead of categorization by predefined subtypes. The ROSacea COnsensus
(ROSCO) 2017 recommendations further support this transition and align with
guidance from other working groups.
Objectives To update and extend previous global ROSCO recommendations in line
with the latest research and continue supporting uptake of the phenotype
approach in rosacea through clinical tool development.
Methods Nineteen dermatologists and two ophthalmologists used a modified Delphi
approach to reach consensus on statements pe rtaining to critical aspects of rosacea
diagnosis, classification and man agement. Voting was electronic and blinded.
Results Delphi statement s on which the panel achieved consensus of ≥ 75% voting
‘Agree’ or ‘Strongly agree’ are presented. The panel recommends discussing disease
burden with patients during consultations, using four questions to assist conversa-
tions. The primary treatment objective should be achievement of complete clear-
ance, owing to previously established clinical benefits for patients. Cutaneous and
ocular feat ures are defined. Treatments have been reassessed in line with recent
evidence and the prior treatment algorithm updated. Combination therapy is rec-
ommended to benefit patients with multiple features. Ongoing monitoring and dia-
logue should take place between physician and patients, covering defined factors to
maximize outcomes. A prototype clinical tool (Rosacea Tracker) and patient case
studies have been developed from consensus statements.
Conclusions The current survey updates previous recommendations as a basis for
local guideline development and provides clinical too ls to facilitate a phenotype
approach in practice and improve rosacea patient management.
Rosacea is a chronic inflammatory condition with predominant facial involvement. Because of that, many patients sense that rosacea affects quality of life. The etiology of rosacea remains unknown. Recent studies have suggested that aberrant innate immunity is central to this disease. The aim of this study was to examine the presence of Langerhans cells, plasmacytoid dentritic cells (PDC), the expression of Toll-like receptors (TLR) and inducible oxide nitric synthase (iNOS) in skin of patients with rosacea, to highlight the participation of innate immunity in its pathogenesis. 28 biopsy specimens were taken from patients with clinical and histopathological findings of rosacea. Immunohistochemical demonstration of Langerhans cells (anti-CD1a antibody), PDC (anti-CD 123 antibody), TLR2, TLR4 and iNOS was performed in skin samples and compared with normal skin controls. The expression of Langerhans cells was lower in rosacea group than in control group. PDC were found in skin samples of rosacea as isolated cells and forming small clusters. Expression of TLR2, TLR4 and iNOS was higher in rosacea samples than in normal skin controls. This research demonstrates early and late stage components of innate immunity in specimens of rosacea ratifying the existence of an altered innate immunity in its pathogenesis.
Author Contributions: Drs Scharschmidt, Wang, and Berger had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Scharschmidt and Yost contributed equally to this work. Study concept and design: Scharschmidt, Yost, Wang, and Berger. Acquisition of data: Scharschmidt, Yost, Truong, and Steinhoff. Analysis and interpretation of data: Scharschmidt, Yost, Steinhoff, and Wang. Drafting of the manuscript: Scharschmidt, Truong, and Steinhoff. Critical revision of the manuscript for important intellectual content: Steinhoff, Wang, and Berger. Statistical analysis: Yost. Administrative, technical, and material support: Scharschmidt, Truong, and Steinhoff. Study supervision: Scharschmidt, Steinhoff, Wang, and Berger.
Background:
Expression of inducible nitric oxide synthase (NOS) is higher in rosacea skin samples than in normal skin controls. Hydroxocobalamin is a potent inhibitor of all isoforms of NOS, capable of reducing the vasodilatations induced by nitric oxide.
Objective:
We aimed to evaluate the role of hydroxocobalamin in treating facial flushing and persistent erythema of rosacea.
Methods:
Thirteen patients with rosacea who displayed facial flushing and persistent erythema received 1 to 4 weekly intramuscular injections of hydroxocobalamin 1 to 2 mg. The outcomes were measured using the Clinician's Erythema Assessment (CEA) by photography and an infrared thermometer to evaluate the difference in skin surface temperature (SST) of the cheeks before and after treatment.
Results:
Thirty minutes after the first dose of intramuscular injection of hydroxocobalamin, the mean CEA significantly reduced from 2.2± 0.6 to 1.2±0.4 (p<0.001), and average SST also significantly reduced from 36.7±0.70°C to 36.2±0.61°C (p<0.001) on the cheeks.
Conclusion:
In our patient sample, intramuscular administration of hydroxocobalamin was effective for immediate reduction of facial erythema associated with rosacea.
Rosacea is a common chronic inflammatory skin disease of unknown etiology. Our knowledge about an involvement of the adaptive immune system is very limited. We performed detailed transcriptome analysis, qRT-PCR, and quantitative immunohistochemistry on facial biopsies of rosacea patients, classified according to their clinical subtype. As controls, we used samples from patients with facial lupus erythematosus and healthy controls. Our study shows significant activation of the immune system in all subtypes of rosacea, characterizing erythematotelangiectatic rosacea (ETR) already as a disease with significant influx of proinflammatory cells. The T cell response is dominated by Th1/Th17-polarized immune cells, as demonstrated by significant upregulation of IFNγ or IL-17, for example. Chemokine expression patterns support a Th1/Th17 polarization profile of the T cell response. Macrophages and mast cells are increased in all three subtypes of rosacea, while neutrophils reach a maximum in papulopustular rosacea. Our studies also provide evidence for activation of plasma cells with significant antibody production already in ETR, followed by a crescendo pattern towards phymatous rosacea. In sum, Th1/Th17 polarized inflammation and macrophage infiltration is an underestimated hallmark in all subtypes of rosacea. Therapies directly targeting the Th1/Th17 pathway are promising candidates in the future treatment of this skin disease.Journal of Investigative Dermatology accepted article preview online, 07 April 2015. doi:10.1038/jid.2015.141.
In inflammation, bacterial products and pro-inflammatory cytokines induce the expression of inducible nitric oxide synthase (iNOS) and formation of high amounts of nitric oxide (NO). In a number of inflammatory diseases NO has pro-inflammatory and cytotoxic effects. The aim of the present study was to investigate the effects of immunosuppressive drugs cyclosporin A (CsA), tacrolimus (FK-506) and pimecrolimus on NO production through iNOS pathway in activated macrophages and fibroblasts. Calcineurin inhibitors (CsA, FK-506 and pimecrolimus) inhibited NO production and iNOS expression in a concentration-dependent manner, CsA being more potent than FK-506 and pimecrolimus. No effect on the activation or activity of the transcription factors nuclear factor-kappaB (NF-kappaB) and signal transducer and activator of transcription 1 (STAT-1) was found. CsA, FK-506 and pimecrolimus did not reduce iNOS mRNA levels when measured 6-8 h after the inflammatory stimulus, but significantly lower levels of iNOS mRNA were found after 24 h incubation. Also, in cells transfected with a luciferase gene under the control of 3' untranslated region (3'UTR) of iNOS, CsA reduced luciferase activity. In conclusion, the results suggest that calcineurin inhibitors cyclosporin A, tacrolimus (FK-506) and pimecrolimus inhibit iNOS expression and NO production in response to inflammatory stimuli by enhancing the decay of iNOS mRNA by a 3'UTR-dependent manner. The findings add our knowledge on the anti-inflammatory effects of CsA, FK-506 and pimecrolimus, and suggest that calcineurin may have a role in the regulation of iNOS expression.