Rosacea and rosacea-like demodicidosis.
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BACKGROUND: Rosacea is a chronic inflammatory disorder that affects 10% of the population. The prevalence of rosacea is highest among fair-skinned individuals, particularly those of Celtic and northern European descent. Since a cure for rosacea does not yet exist, management and treatment regimens are designed to suppress the inflammatory lesions, erythema, and to a lesser extent, the telangiectasia involved with rosacea. OBJECTIVES: This review outlines the treatment options that are available to patients with rosacea. METHODS: Published literature involving the treatment or management of rosacea was examined and summarized. RESULTS: Patients who find that they blush and flush frequently, or have a family history of rosacea are advised to avoid the physiological and environmental stimuli that can cause increased facial redness. Topical agents such as metronidazole, azelaic acid cream or sulfur preparations are effective in managing rosacea. Patients who have progressed to erythematotelangiectatic and papulopustular rosacea may benefit from the use of an oral antibiotic, such as tetracycline, and in severe or recalcitrant cases, isotretinoin to bring the rosacea flare-up under control. Treatment with a topical agent, such as metronidazole, may help maintain remission. Patients with ocular involvement may benefit from a long-term course of an antibiotic and the use of metronidazole gel. A surgical alternative, laser therapy, is recommended for the treatment of telangiectasias and rhinophyma. Patients with distraught feelings due to their rosacea may consider cosmetic camouflage to cover the signs of rosacea. CONCLUSIONS: With the wide variety of oral and topical agents available for the effective management of rosacea, patients no longer need to feel self-conscious because of their disorder.
Rosacea is a common condition of unknown etiology usually accompanied by gastrointestinal symptoms and favorably responding to the treatment with antibiotics. This study was designed to examine the prevalence of gastric Helicobacter pylori (Hp) infection verified by 13C-UTB-test, CLO, Hp culture and serology (IgG) in patients with rosacea. Gastroduodenoscopy was combined with pentagastrin secretory test and antral and fundic biopsy samples were taken for histological evaluation (the Sydney system). Blood samples were also taken for the determination of plasma gastrin using RIA and plasma interleukin (IL)-8 and tumor necrosis factor alpha (TNFalpha) using ELISA. This study was performed in 60 patients, 31-72 year old, with visible papules and pustules associated with erythema and flushing on the face and on 60 age- and gender-matched patients without any skin diseases but with similar as in rosacea gastrointestinal symptoms but without endoscopic changes in gastroduodenal mucosa (non-ulcer dyspepsia - NUD). The Hp prevalence in rosacea patients was about 88 % as compared to 65% in control NUD patients. Among rosacea patients, 67% were cytotoxin associated gene A (CagA) positive, while in NUD patients only 32% were CagA positive. Rosacea patients showed gastritis with activity of about 2.1 in antrum and 0.9 in the corpus of the stomach while those with NUD only mild gastritis with activity of approximately 1.0) confined to the antrum only. Following initial examination, typical 1 wk anti-Hp therapy including omeprazole (20 mg bd.), clarithromycin (500 mg bd.) and metronidazol (500 mg bd.) was carried out. After eradication, 51 out of 53 treated rosacea patients became Hp negative. Within 2-4 weeks, the symptoms of rosacea disappeared in 51 patients, markedly declined in 1 and remained unchanged in 1 other subject. A dramatic reduction in activity of gastritis (to 0.3 in antrum and to 0.1 in corpus) was observed. Basal plasma gastrin decreased from 48 +/- 5 pM before to 17+/-3 pM after eradication, while pentagastrin-induced maximal (MAO) declined, respectively, from about 16.6 +/- 4.2 to 8.5 +/- 1.8 mmol/h. Plasma TNFalpha and IL-8 were reduced after the therapy by 72% and 65%, respectively. We conclude that: 1) Rosacea is a disorder with various gastrointestinal symptoms closely related to gastritis, especially involving the antrum mucosa, with Hp expressing cagA in the majority of cases and elevated plasma levels of TNFalpha and IL-8; 2) The eradication of Hp leads to a dramatic improvement of symptoms of rosacea and reduction in related gastrointestinal symptoms, gastritis, hypergastrinemia and gastric acid secretion; and 3) Rosacea could be considered as one of the major extragastric symptoms of Hp infection probably mediated by Hp-related cytotoxins and cytokines.
PURPOSE OF REVIEW: Ocular rosacea is a common and potentially blinding eye disorder with an uncertain etiology. Therapies currently in vogue for ocular rosacea have not been rigorously studied with regards to specific indications, optimal dosing regimens, or treatment efficacy. This review will summarize the recent literature with regards to etiology and therapy of ocular rosacea, and will also examine current thinking about the parent disorder, acne rosacea. RECENT FINDINGS: Comparatively few papers on ocular rosacea were published in the past year. Recent articles on the prevalence of ocular rosacea in patients with acne rosacea suggested that between 6 and 18% of acne rosacea patients have signs or symptoms of ocular rosacea, but few cases were confirmed by an ophthalmologist. Recent articles on the pathogenesis of ocular rosacea have focused on the role of bacterial lipases, and interleukin-1alpha and matrix metalloproteinases in the blepharitis and corneal epitheliopathy, respectively. Other reports highlighted the presence of the disorder in children, and the lack of masked, placebo-controlled studies for those therapies currently in common use. SUMMARY: The epidemiology, etiology, and optimal therapy of ocular rosacea remain to be determined, and will require a more concerted effort to delineate.
BACKGROUND: Rosacea is a common condition of unknown aetiology that is usually accompanied by gastrointestinal symptoms and responds favourably to treatment with antibiotics. AIMS/METHODS: This study was designed to examine the prevalence of gastric Helicobacter pylori (Hp) infection verified by 13C-UBT, CLO-test, Hp culture and serology (IgG and IgA) and the presence of Hp in the oral cavity evidenced by CLO-test, Hp culture and saliva anti-Hp antibodies (IgG and IgA). During gastroduodenoscopy antral and fundic biopsy samples were taken for histological evaluation (the Sydney system). This study was performed on 60 subjects 30-70 years old with visible cutaneous rosacea symptoms and 60 age- and gender-matched controls without skin diseases but with dyspeptic symptoms similar to those of rosacea and without endoscopic changes in gastroduodenal mucosa (non-ulcer dyspepsia--NUD). RESULTS: The Hp prevalence in rosacea patients was about 88%, compared to 65% in the NUD controls. A noticeable number of rosacea patients showed chronic active gastritis predominantly in antrum but also in the corpus while those with NUD showed only mild gastritis confined to the antrum only. Following the initial examination, a typical 1 week systemic anti-Hp therapy, induding omeprazole (2 x 30 mg), clarithromycin (2 x 500 mg) and metronidazole (2 x 500 mg), plus gargling and application of metronidazole paste in the case of Hp oral cavity infection. After the application of the systemic and local therapy in the oral cavity, Hp was eradicated from the stomach in 97% and from the oral cavity in 73% of treated patients. Within 2-4 weeks, the symptoms of rosacea disappeared or decreased markedly in 51 subjects. SUMMARY: We conclude that: (1) rosacea is a disorder with various gastrointestinal symptoms closely related to gastritis, especially involving the antrum mucosa; (2) the eradication of Hp leads to improvement of symptoms of rosacea and reduction in related gastrointestinal symptoms; (3) the lack of improvement of cutaneous symptoms in rosacea after eradication of Hp from the gastric mucosa could depend on bacteria in the oral cavity; and (4) rosacea could be considered as one of the extragastric symptoms of Hp infection probably mediated by Hp-related cytotoxins and cytokines.
OBJECTIVE: To examine clinical associations, family history of rosacea, and response to treatment in prepubertal children with steroid rosacea. DESIGN: Retrospective case-series evaluation of children younger than 13 years with steroid rosacea seen over an 8-year period (1991-1998). SETTING: Ambulatory care university hospital. PATIENTS: Referral patients from pediatricians serving a population of 3.4 million. INTERVENTIONS: Abrupt cessation of topical corticosteroid use and initiation of treatment with oral erythromycin stearate for 4 weeks. MAIN OUTCOME MEASURES: Age at onset, class of topical corticosteroid used, family history of rosacea, location of lesions, treatment, and weeks to clearing. RESULTS: We evaluated 106 (46 boys and 60 girls) who developed steroid rosacea. Preceding steroids used were predominantly (54% of children) class 7 agents including 1% hydrocortisone and over-the-counter hydrocortisone preparations. Only 3% of children had used superpotent (class 1) topical corticosteroids. The mean age at onset was 7.04 years (range, 6 months to 13 years). Twenty-nine children were younger than 3 years. A family history of rosacea was found for 20% of the children. After abruptly stopping topical steroid use and starting treatment with oral erythromycin, 86% of children had complete clearing within 4 weeks and 100% by 8 weeks. Clearing within 3 weeks was observed in 22% of children. CONCLUSIONS: Abrupt discontinuation of topical corticosteroids and institution of oral antibiotics resulted in clearing within 4 weeks. This finding does not support the concept that prepubertal children with steroid rosacea need to continue low-strength steroids in a gradual withdrawal strategy. This conclusion is supported by the finding that 54% developed the steroid rosacea while being treated with the lowest-strength (class 7) topical corticosteroids. Even over-the-counter hydrocortisone preparations induced steroid rosacea in susceptible children. Susceptibility may be genetic as 20% of children had a first-degree relative with rosacea.
The examination was carried out in 50 rosacea patients (30 females and 20 males) in order to establish the connexion between skin surface lipids, infestation with Demodex folliculorum and previous local corticosteroid treatment with the appearance of epitheloid granulomas. Our analysis showed three types of histological conditions: 1) chronic dermatitis of the rosacea type was noted in 15 patients (30%); 2) granulomas composed of epitheloid cells was found in 16 patients (32%). In three female patients of this group presence of caseous necrosis associated with epitheloid granuloma was noted, too; 3) prevalence of perifollicular absceses was found in 19 patients (38%). Demodex folliculorum was detected in 43 rosacea patients (86%), considerably more then in the control group. The normal value of the skin surface lipids was found in 9 female rosacea patients (30%) and in 9 female controls (43%), in 8 male rosacea patients (40%) and in 5 males controls (33%). Lower amounts of skin surface lipids were found in 19 female rosacea patients (63%) and in 9 female controls (43%), in 4 male rosacea patients (20%) and in 1 male control (7%). Higher amounts of skin surface lipids were found in 2 female rosacea patients (7%) and in 3 female controls (14%), in 8 male rosacea patients (40%) and in 9 male controls (60%). Lower quantities of lipids determined a higher incidence of Demodex folliculorum in rosacea patients. Demodex folliculorum were also more frequently detected in patients who had previously been treated with topical corticosteroids (even in 91.9%), what was often followed by epitheloid granulomas. The treatment with tetracycline yielded good or excellent results in 90% of all the patients.
OBJECTIVE: To examine ocular signs, symptoms, and results of tear analysis in patients with cutaneous rosacea before, during, and after doxycycline therapy. DESIGN: Before-after trial. SETTING: General community. PATIENTS OR OTHER PARTICIPANTS: Thirty-nine patients with cutaneous rosacea underwent dermatologic and ocular examinations, testing of tear break-up time, and Schirmer testing at baseline and 4, 8, and 12 weeks. Six patients did not complete the study. Baseline tear break-up time and results of Schirmer test were compared with those of 13 patients without rosacea who were matched for age and sex. INTERVENTION: Patients with rosacea were given doxycycline, 100 mg daily for 12 weeks. MAIN OUTCOME MEASURE: Statistically significant (P, .05) improvement in tear break-up time. RESULT: The most frequent ocular symptoms were dryness, itching, blurred vision, and photosensitivity, all of which improved significantly with treatment. All patients had signs of ocular disease, most commonly erythema and telangiectasia, meibomian gland dysfunction, and ciliary base injection. Significant improvement (P,.05) for scales, erythema and telangiectasia, ciliary base injection, bulbar injection, papillary hypertrophy, and punctate epithelial erosions was seen. Average tear break-up time for the patients with rosacea was 5.7 seconds, which improved to 10.8 seconds after 12 weeks of treatment (P = .007). Baseline tear break-up time was significantly lower than for the comparison group of normal subjects (P = .001). There was no correlation between severity of cutaneous disease and ocular disease. CONCLUSIONS: All patients with cutaneous rosacea had some degree of ocular involvement. Tear break-up time is abnormal in patients with rosacea. Ocular erythema and telangiectasia, meibomian gland dysfunction, and short tear break-up time in patients with cutaneous rosacea are indicators of ocular rosacea. Doxycycline, 100 mg daily, will improve ocular disease and increase the tear break-up time.
OBJECTIVE: To evaluate the clearing and intensity of symptoms of rosacea 60 days after the treatment of Helicobacter pylori infection. DESIGN: Randomized, double-blind, placebo-controlled clinical trial. SETTING: The dermatology section of a large multispecialty clinic in the North Central United States. PARTICIPANTS: Men and women older than 25 years with active signs of rosacea who tested positive for H pylori with both the rapid whole blood test and the urea breath test. INTERVENTION: Treatment of H pylori infection with 14-day therapy using clarithromycin. 500 mg orally 3 times a day, and omeprazole, 40 mg orally once a day. MAIN OUTCOME VARIABLES: The extent and intensity of rosacea as measured by the number of papules and pustules and the extent and intensity of erythema and telangiectasia. RESULTS: Three hundred twenty patients presented with rosacea. For 50 patients, the results of a urea breath test were positive for H pylori, and 44 patients were enrolled in the study. Rosacea abated in almost all patients, but none were cured. Notably, lessening of rosacea for patients treated for H pylori was not significantly better than for the control cohort. CONCLUSIONS: Rosacea abated in most participants in this study, whether they were in the treatment or the control cohort. There was no statistical difference when the results of active treatment were compared with those of placebo. Treating H pylori infection has no short-term beneficial effect on the symptoms of rosacea to support the suggested causal association between H pylori infection and rosacea.
Acne rosacea is an idiopathic dermatologic disease that frequently produces conjunctival inflammation. The authors studied the histology and immunopathology of epibulbar conjunctival biopsy specimens from eight patients with ocular rosacea and compared the findings with those from conjunctiva from 13 normal individuals. The conjunctival epithelium in ocular rosacea was attenuated and infiltrated by inflammatory cells, mainly T-helper/inducer (CD4) cells, phagocytic cells, and antigen-presenting (CD14, Mac-1) cells. The difference between the normal control group and the rosacea group in the number of mononuclear cells forming these populations was statistically significant (P less than 0.01). The substantia propria of the rosacea specimens contained large subepithelial infiltrates of chronic inflammatory cells, and in some cases frank granuloma formation was evident. There was an overall mean increase of nearly all cell types, but especially of T-helper cells in the rosacea specimens compared with the controls. Interestingly, T-helper/inducer (CD4) cells, which were outnumbered by the T-suppressor (CD8) cells in the normal conjunctival epithelium (CD4/CD8 = 0.85), outnumbered the CD8-positive cells in the rosacea specimens (CD4/CD8 = 1.6). There also was a 3.5-fold increase of the CD4/CD8 ratio in the rosacea conjunctival stroma compared with the normal specimens. The mechanism involved in rosacea conjunctival inflammation resembles a type IV hypersensitivity reaction.
A Glycomics approach to detect disease is illustrated in the analyses of human tear fluid for rosacea. The diagnosis of ocular rosacea is particularly challenging in a subgroup of patients that do not present with typical facial skin findings but have ocular signs and symptoms. Indeed, up to 90% of patients with ocular rosacea may have neither obvious roseatic skin changes nor a previous diagnosis of rosacea. Tear fluid was collected from 37 subjects (21 controls and 16 patients with ocular rosacea) after conjunctival stimulation with filter (Schirmer) paper. O-linked oligosaccharides were released from tear fluid by beta-elimination and then purified using solid-phase extraction. Mass spectra were recorded on an external source HiResMALDI with a 7.0 T magnet. Mass spectra were obtained in both the positive and negative modes. However, signals were stronger in the negative mode. Tear fluid samples from rosacea patients yielded distinctive clusters of peaks that extend to higher masses. Patients with rosacea presented several oligomeric series that were not found in the controls. To discriminate the ocular rosacea cases from the normal controls, the sum of absolute intensities of 13 series corresponding to nearly 50 identified mass spectrum peaks was used. Thirty-six out of the 37 samples were correctly classified. This yields a sensitivity of 100% (95% CI 79.5-100) and specificity of 95.2% (95% CI 76.2-99.9). The high abundance of oligosaccharides in the tear fluid of patients with rosacea may lead to an objective diagnostic marker for the disease.
BACKGROUND: Demodex folliculorum has been reported in rosacea in a number of clinical studies. As the Demodex mite is also present in many healthy individuals, it has been suggested that the mite may have a pathogenic role only when it is present in high densities. Moreover, some authors have proposed that a mite density above 5/cm2 may be a criterion for the diagnosis of inflammatory rosacea. In this study, the possible role of D. folliculorum and the importance of mite density in rosacea were investigated using a skin surface biopsy technique. METHODS: Thirty-eight patients with rosacea and 38 age-and-sex-matched healthy subjects entered the study. With the skin surface biopsy technique, we obtained samples from three facial sites. We then determined the mite positivities, the mean mite counts in both study groups, the mean mite densities at each facial site and in the rosacea subgroups, and the mite densities above 5/cm2. RESULTS: The mean mite count in the rosacea group (6,684) was significantly higher than that in controls (2,868; p < 0.05). The cheek was the most frequently and heavily infested facial region. Ten rosacea patients and five normal subjects had mite densities over 5/cm2; the difference was not statistically significant (p > 0.05). CONCLUSIONS: Rosacea is a disease of multifactorial origin, and individual properties may modify the severity of the inflammatory response to Demodex. We suggest that a certain mite density is not an appropriate criterion in the diagnosis of the disease; nevertheless, large numbers of D. folliculorum may have an important role in the pathogenesis of rosacea, together with other triggering factors.
BACKGROUND: Psychogenic factors have been considered to be important in the exacerbation and possibly the onset of rosacea. However, there are very few studies that have reported conclusive findings. OBJECTIVES: To examine the association between rosacea and major depressive disease, a common and usually treatable psychiatric disorder. METHODS: Data from 1995 to 2002, collected by the National Ambulatory Medical Care Survey and the outpatient component of the National Hospital Ambulatory Care Survey, which are both nationally representative surveys of healthcare visits in the U.S.A., were studied. The basic sampling unit in both surveys is the patient visit or encounter. A "Rosacea" variable was created by grouping all rosacea (ICD-9-CM code 695.3) visits and a "Depression" variable was created by grouping the patient visits related to major depressive disorder (ICD-9-CM codes 296.2, 296.3 and 311). As alcohol abuse has been implicated in rosacea, and alcohol can confound symptoms of depression, an "Alcohol" variable was created by grouping all ICD-9-CM codes related to alcohol dependence and abuse (codes 303, 303.0, 303.9 and 305.0). All analyses were conducted using the Complex Samples module of SPSS version 13, to account for the multistage probability sampling design used to collect the data. RESULTS: The weighted data were representative of over 608 million dermatology visits between 1995 and 2002. Logistic regression analysis using "Rosacea" as the dependent variable and age, sex, "Alcohol" and "Depression" as independent variables revealed that the odds ratio for depressive disease in the rosacea group was 4.81 (95% confidence interval 1.39-16.62). The association between "Alcohol" and "Rosacea" was not significant. CONCLUSIONS: The comorbidity between major depressive disease and rosacea may have important clinical implications. Alcohol abuse does not appear to play a significant role in this association.
A good skin care regimen is a critical part of rosacea treatment; however, care must be taken to choose nonirritating products because individuals with rosacea tend to have sensitive skin, and irritants can trigger a worsening of symptoms. This study examines the use of Cetaphil Gentle Skin Cleanser (a nonalkaline nonirritating cleanser) in patients with rosacea. To eliminate the confounding effects of various treatments, the cleanser was studied for a 2-week period in the absence of rosacea therapy following a 2-week washout period in patients with mild to moderate rosacea. During the washout period, patients were asked to cleanse twice daily with Dove Sensitive Skin Bar. During the 2-week study period, patients were monitored for skin barrier function through transepidermal water loss (TEWL) and corneometry; patients also were monitored for rosacea severity. Thirty patients were enrolled. No significant increase in TEWL was demonstrated at any point during the study, indicating that the gentle skin cleanser did not damage the skin barrier. Additionally, the cleanser was shown to maintain skin hydration. Furthermore, a post hoc statistical analysis suggests there was a significant reduction (P<.05) in investigator-assessed rosacea severity on the cheeks, forehead, and nose at the end of week 1 and on the cheeks, forehead, and chin at the end of week 2 compared with the end of the washout period (after 2 weeks of cleansing with Dove Sensitive Skin Bar). The mild nonirritating action of the gentle skin cleanser was supported by the lack of adverse events and the tolerability shown in the study. There were no increases in erythema, scaling, dryness, stinging, burning, or lack of smoothness in the skin during the 2-week study period, despite the fact that patients were not being treated for their rosacea during the study. These results indicate that Cetaphil Gentle Skin Cleanser may be a good choice for the cleansing part of a total rosacea skin care regimen.