Treatment of ocular rosacea with 40 mg doxycycline in a slow release form

Background: About 30–50 % of rosacea patients have ocular involvement. The symptoms range from a foreign‐body sensation to conjunctivitis or blepharitis and may even include severe corneal ulcerations. Systemic treatment is generally with tetracycline. Side effects can occur with the usual antimicrobial dose. Patients and Methods: In a retrospective study, seven patients were evaluated who had been treated for ocular rosacea with a sub‐antimicrobial dose of doxycycline 40 mg in a slow‐release form (Oraycea^®). The responses were evaluated on the basis of clinical findings. Results: Seven patients with an average age of 63 took slow release doxycycline 40 mg every day for at least two months. In five patients, other systemic drugs had already failed. All patients experienced a clear improvement in their ocular rosacea after an average of 2.29 months of treatment. One patient had complete clearance and another had almost complete clearance. None of the patients experienced side effects. Conclusions: A sub‐antimicrobial dose of slow release doxycycline 40 mg daily is an effective long‐term therapy for ocular rosacea. It is not associated with the side effects of long‐term antibiotic therapy or the risk of resistance.     

Clinical and laboratory study of ocular rosacea in northern Greece

Background The prevalence of ophthalmic involvement in rosacea is probably higher than previously presumed and varies considerably among several studies. Objective This study aimed to determine the incidence of ocular disease among a population of rosacea patients in Northern Greece, to objectively determine the presence of eye dryness in rosacea patients with and without clinical ophthalmic involvement and correlate the severity of ocular disease with the severity of cutaneous rosacea. Methods One hundred patients with rosacea were assessed for the stage of their disease and examined for ocular symptoms and signs. In 24 of them the tear break up time (TBUT) and Schirmer test were performed in each eye, along with 24 controls. Results A total of 33 patients (33%) were positive for ophthalmic findings. The most frequent symptoms and signs were burning sensation and tearing, and conjunctivitis and blepharitis, respectively. Eleven patients with ophthalmic manifestations had mild to moderate erythematotelangiectatic rosacea, 17 had moderate papulopustular rosacea and four exhibited findings of phymatous rosacea. The total mean value of patients’ Schirmer tests was significantly lower compared with the healthy controls (P < 0.0001). Mean TBUT was shorter in the rosacea group than that in the age‐matched controls (P < 0.0001). Conclusion Ocular involvement in rosacea is a common phenomenon with eye dryness being an early sign. Tear function tests, like Schirmer test and TBUT, although not specific, could contribute to the screening and early diagnosis of the disease, to prevent the potential development of sight‐threatening conditions.     

Interventions for rosacea: abridged updated Cochrane systematic review including GRADE assessments

Rosacea is a common chronic facial dermatosis. This update of our Cochrane review on interventions for rosacea summarizes the evidence, including Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group assessments, of the effects of the currently available treatments. Searches included the following: Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE, EMBASE, LILACS and the Science Citation Index, and ongoing trials registries (July 2014). We included 106 randomized controlled trials (RCTs) with 13 631 participants, a more than 80% increase since the last update in 2011. Pooling of data was feasible for a few outcomes, for topical metronidazole and azelaic acid and both appeared to be more effective than placebo (moderate and high‐quality evidence, respectively). Topical ivermectin was more effective than placebo based on two studies (high‐quality evidence), and slightly more effective than metronidazole in one study. Brimonidine was more effective than vehicle in reducing erythema in rosacea (high‐quality evidence). Ciclosporin ophthalmic emulsion was effective for ocular rosacea (low‐quality evidence). For oral treatments there was moderate‐quality evidence for the effectiveness of tetracycline based on two old studies, and high‐quality evidence for doxycycline 40 mg compared with placebo according to physician assessments. One study at high risk of bias demonstrated equivalent effectiveness for azithromycin and doxycycline 100 mg. Minocycline 45 mg may be effective for papulopustular rosacea (low‐quality evidence). Low‐dose isotretinoin appeared to be slightly more effective than doxycycline 50–100 mg (high‐quality evidence). Laser and light‐based therapies for erythema in rosacea were effective (low‐quality evidence). Further RCTs are required for ocular rosacea.     

Ophthalmorosazea

Half of patients with rosacea develop ocular involvement. The complaints are often nonspecific. The most common ocular manifestation is blepharoconjunctivitis with dry eye, while on rare occasion rosacea keratitis can lead to corneal ulcer, which then requires urgent ophthalmologic consultation. Topical therapy with preservative-free artificial lubricants and lid hygiene is recommended for the primary treatment of ocular rosacea. Secondarily, systemic medications are indicated depending on severity of the ocular and skin findings.     

Pediatric ocular rosacea,a misdiagnosed disease with high morbidity: Proposed diagnostic criteria

Ocular rosacea is an important and underdiagnosed chronic inflammatory disorder observed in children. A clinical spectrum ranging from chronic eyelid inflammation, recurrent ocular redness, photophobia and/or hordeola/chalazions and conjunctival/corneal phlyctenules evolving to neovascularization and scarring may occur. Visual impairment and consequent amblyopia are frequent and corneal perforation although rare is the most feared complication. Ocular manifestations usually precede cutaneous lesions. Although few cases of pediatric ocular rosacea (POR) have been reported in the literature, many cases must have been underdiagnosed or misdiagnosed. The delay in diagnosis is greater than one year in the large majority of cases and may lead to serious ocular sequelae. This review aims to highlight the clinical features of POR, its epidemiology, easy diagnosis and effective treatment. We also propose new diagnostic criteria, in which at least three of the five clinical criteria must be present: (1) Chronic or recurrent keratoconjunctivitis and/or red eye and/or photophobia; (2) Chronic or recurrent blepharitis and/or chalazia/hordeola; (3) Eyelid telangiectasia documented by an ophthalmologist; (4) Primary periorificial dermatitis and/or primary features of rosacea; and (5) Positive familial history of cutaneous and/or ocular rosacea.     

Seborrheic dermatitis

Seborrheic dermatitis is present in 1% to 3% of immunocompetent adults, and is more prevalent in men than in women. Seborrheic dermatitis may be seen in conjunction with other skin diseases, such as rosacea, blepharitis or ocular rosacea, and acne vulgaris. Malassezia yeasts have been associated with seborrheic dermatitis. Abnormal or inflammatory immune system reactions to these yeasts may be related to development of seborrheic dermatitis. Treatment modalities for seborrheic dermatitis include keratolytic agents, corticosteroids, and more recently, antifungal agents. Antifungal agents do not carry a risk of skin atrophy or telangiectasia with prolonged use, and it is more prudent to consider antifungals than corticosteroid preparations. The wide range of antifungal formulations available (creams, shampoos, or oral) provides safe, effective, and flexible treatment options for seborrheic dermatitis.     

Pathogenese,Klinik und aktuelle Therapie der Rosazea

Rosacea is a common chronic inflammatory disease, especially in patients with fair skin and positive family history. Typical locations are forehead, nose, cheeks and chin; the periorbital region is usually not involved. Clinical features can be very heterogeneous. Besides different subtypes (erythematotelangiectatic rosacea, papulopustular rosacea, phymatous rosacea), which often overlap, various special forms of rosacea exist. Up to 60?% of patients with cutaneous rosacea suffer from ocular rosacea. In Germany, brimonidine, metronidazol, azelaic acid, and ivermectin are approved for topical therapy of rosacea; for systemic therapy, doxycycline at a subantimicrobial dose (40 mg/day) is the only approved substance. In case of resistance to this therapy, contraindications or side effects, various alternative therapies are available, however off-label.     

Quantification of Demodex folliculorum by PCR in rosacea and its relationship to skin innate immune activation

The aim of this study is to quantify D. folliculorum colonisation in rosacea subtypes and age‐matched controls and to determine the relationship between D. folliculorum load, rosacea subtype and skin innate immune system activation markers. We set up a multicentre, cross‐sectional, prospective study in which 98 adults were included: 50 with facial rosacea, including 18 with erythematotelangiectatic rosacea (ETR), and 32 with papulopustular rosacea (PPR) and 48 age‐ and sex‐matched healthy volunteers. Non‐invasive facial samples were taken to quantify D. folliculorum infestation by quantitative PCR and evaluate inflammatory and immune markers. Analysis of the skin samples show that D. folliculorum was detected more frequently in rosacea patients than age‐matched controls (96% vs 74%, P < 0.01). D. folliculorum density was 5.7 times higher in rosacea patients than in healthy volunteers. Skin sample analysis showed a higher expression of genes encoding pro‐inflammatory cytokines (Il‐8, Il‐1b, TNF‐a) and inflammasome‐related genes (NALP‐3 and CASP‐1) in rosacea, especially PPR. Overexpression of LL‐37 and VEGF, as well as CD45RO, MPO and CD163, was observed, indicating broad immune system activation in patients with rosacea. In conclusion, D. folliculorum density is highly increased in patients with rosacea, irrespective of rosacea subtype. There appears to be an inverse relationship between D. folliculorum density and inflammation markers in the skin of rosacea patients, with clear differences between rosacea subtypes.     

A case of Scalp Rosacea treated with low dose doxycycline and probiotic therapy and literature review on therapeutic options

Rosacea is a common chronic inflammatory disorder showing a wide range of clinical features such as telangiectasia, erythema, papules, and pustules primarily involving the central part of face (forehead, cheeks and nose) although extra facial manifestation have been described. We describe a case of rosacea with predominant scalp involvement successfully treated with a 8‐week‐course of doxycycline 40 mg once a day and probiotic therapy twice a day (Bifidobacterium breve BR03, Lactobacillus salivarius LS01 1 × 10⁹ UFC/dose).     

Ocular changes in patients with psoriasis

Eye involvement in psoriasis is little known to many dermatologists, although psoriasis has been acknowledged as a systemic disease for decades. The ophthalmic complications of psoriasis are numerous and can affect almost any part of the eye. The most common ocular changes in patients with psoriasis, including blepharitis, conjunctivitis, keratitis, iridocyclitis, UV-induced cataracts, uveitis, and birdshot chorioretinitis, have been described in the literature. Recognition of the ocular complications of psoriasis is of significant clinical importance, because various pathogenic mechanisms may contribute to the development of ocular manifestations, including direct eye involvement with psoriatic plaques, psoriasis-related immune-mediated inflammatory processes, and complications of psoriasis treatments.     

Carotid intima‐media thickness and serum proinflammatory cytokine levels in rosacea patients without cardiovascular risk factors

There is a growing body of evidence linking rosacea to various systemic disorders, even though data regarding the association between rosacea and cardiovascular diseases are presently controversial. We sought to investigate the potential association of rosacea with subclinical atherosclerosis and serum proinflammatory/proatherogenic markers. This study included 44 patients with rosacea and 44 age‐matched and sex‐matched healthy control subjects. Patients with traditional cardiovascular risk factors or a history of cardiovascular events were excluded. Demographic, clinical, and laboratory data, including serum interleukin‐1 beta (IL‐1β), interleukin‐6 (IL‐6), tumor necrosis factor‐alpha (TNF‐α), and high‐sensitivity C‐reactive protein (hs‐CRP) levels were assessed. Carotid intima‐media thickness (CIMT) and carotid plaques were measured by carotid ultrasonography. Serum IL‐1β (P < .001), IL‐6 (P < .001), TNF‐α (P < .001), and hs‐CRP (P < .001) levels were significantly higher in the patient group compared with the control group. Mean CIMT values did not differ significantly between the patient group and control group (P > .05). Patients with moderate to severe rosacea had a significantly greater CIMT than those with mild rosacea (P = .047). Rosacea patients with eye involvement had a significantly greater CIMT than those without eye involvement (P = .008). There was no significant correlation between CIMT values and inflammation parameters. As conclusion, in the absence of other traditional cardiovascular risk factors, rosacea does not seem to affect mean CIMT value. However, specific subgroups such as patients with moderate to severe disease or with eye involvement are associated with increased subclinical atherosclerosis and may require additional attention for cardiovascular disease prevention.     

Childhood ocular rosacea: Considerations for diagnosis and treatment

Rosacea in children is not as well described as it is in adults. Ocular signs may be a dominant feature and some children with what has previously been called periorificial dermatitis may in fact have rosacea. We report three cases of paediatric ocular rosacea responding to prolonged treatment with oral erythromycin. Our cases demonstrate the close association of periorificial dermatitis with childhood rosacea, and highlight the importance of eye signs in its diagnostic criteria.     

Comparison of efficacy of azithromycin vs. doxycycline in the treatment of rosacea: a randomized open clinical trial

Background Rosacea is a common inflammatory disorder of the skin. Systemic antibiotics currently used in the treatment of rosacea are sometimes associated with uncomfortable side effects. Therefore, a need for an effective agent with few side effects and good patient compliance exists. Azithromycin, a macrolide antibiotic with prolonged mode of action, has recently been found to be an effective alternative in the treatment of inflammatory acne. Methods For evaluation of the efficacy of azithromycin in the treatment of rosacea, we planned a randomized, open, clinical trial study to compare the efficacy of azithromycin with doxycycline in the treatment of this disease. Sixty‐seven patients were randomized to receive either azithromycin 500 mg thrice weekly (on Monday, Wednesday, and Saturday) in the first, 250 mg thrice weekly (on Monday, Wednesday, and Saturday) in the second, and 250 mg twice weekly (on Tuesday, and Saturday) in the third month. The other group was given doxycycline 100 mg/day for the three months. Clinical assessment was made at baseline, at the end of first, second, third, and 2 months after treatment. Side affects were recorded. The limitation of this study is that there was no blindness. Results Statistically significant improvement was obtained with both drugs. Neither drug was shown to be more effective than the other. In the azithromycin group four patients had diarrhea, while epigastric burning was seen in two patients using doxycycline. Conclusion This study indicates that azithromycin is at least as effective as doxycycline in the treatment of rosacea.     

Rosacea and its management: an overview

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.     

Efficacy of oregonin investigated by non‐invasive evaluation in a B16 mouse melanoma model

Oregonin has been reported to act as a mediator of antibiosis, a liver‐protective agent, an antioxidant, an anti‐inflammatory agent, and to prevent cancer outbreaks. B16 melanoma cells were separated with trypsin‐ethylenediaminetetraacetic acid, resuspended in 50 μl of phosphate‐buffered saline and transplanted into the backs of 6‐ to 8‐week‐old male Balb/c nude mice through subcutaneous injection. Treatment doses of oregonin were administered three times weekly, for 30 days from the 11th day after transplantation of the melanoma cells, in each group. The study consisted of a control group, a dacarbazine group, an oregonin group and a dacarbazine + oregonin group. Measurements were taken before treatment and on the 5th, 7th, 10th and 15th days after treatment for each group. Based on survival rates after transplantation, the control group showed less than 50% survival after 20 days, while the treatment groups showed at least 50% survival up to the 41st day.     

Rosacea treatment with intermediate-dose isotretinoin: follow-up with erythema and sebum measurements

Isotretinoin is one of the therapeutic options for rosacea. However, the response of erythema to treatment with isotretinoin is usually slow and incomplete with common (0.5-1 mg/kg/day) or low (10 mg/day) doses. This study investigated the efficacy of, and relapse on, 20 mg/day isotretinoin treatment in rosacea, with the aid of instrumental measurement of facial erythema and sebum levels. A 20 mg/day dose of isotretinoin was given for 4 months, and then the dose was tapered off within the following 6 months. A total of 25 patients were included in the study. Papule and pustule counts, erythema index, sebum level, dermatologist's and patient's erythema scores, and dermatologist's sebum scores were significantly lower in the first month of therapy compared with pre-treatment values (p < 0.05). Within a median follow-up of 11 months (95% confidence interval: 8.4-13.5 months) 45% of patients had a relapse. In conclusion, 20 mg/day isotretinoin was rapidly efficient for reducing both inflammatory lesions and erythema in rosacea.     

Nail improvement during alitretinoin treatment: three case reports and review of the literature

Alitretinoin is an endogenous vitamin A derivative, 9‐cis‐retinoic acid. Its anti‐inflammatory and immunomodulatory efficacy results from controlling leukocyte activity and cytokine production in keratinocytes. We describe three patients with severe chronic hand eczema accompanied by nail dystrophy, which was treated with alitretinoin 30 mg. Clinical evaluation at 6 months showed complete or almost complete clearing of the nail lesions. We also briefly review the literature reporting on nail dystrophy and alitretinoin treatment. There is some evidence of the clinical effect of retinoids on nail formation, owing to the presence of retinoid receptors on the nail matrix. Further studies are required to better understand the impact of alitretinoin in nail diseases. Our observation supports alitretinoin as a treatment option in retinoid‐responsive dermatoses associated with nail involvement.     

Positive correlation between serum immunoreactivity to Demodex‐associated Bacillus proteins and erythematotelangiectatic rosacea

Background Rosacea is a chronic inflammatory condition that affects the skin of the face and the eyes. Erythematotelangiectatic rosacea is characterized by flushing, oedema and telangiectasia. Patients with rosacea demonstrate elevated densities of Demodex mites in their skin compared with controls. A bacterium (Bacillus oleronius) isolated from Demodex mites from a patient with papulopustular rosacea has been demonstrated to produce antigenic proteins that may play a role in papulopustular and ocular rosacea. Objectives To establish whether there was a correlation between the reactivity of sera from patients with erythematotelangiectatic rosacea to Bacillus antigens, and to characterize the proteins to which these patients showed reactivity. Methods Serum samples from patients with erythematotelangiectatic rosacea and controls were examined for reactivity to Bacillus proteins by Western blot analysis. Proteins to which the sera reacted were excised from gels, trypsin digested, and putative identities were assigned following liquid chromatography‐mass spectrometry (LC‐MS) analysis. Results Eighty per cent (21/26) of patients with erythematotelangiectatic rosacea showed serum reactivity to the 62‐ and 83‐kDa proteins of B. oleronius, compared with 40% (9/22) of controls (P = 0·004). The 62‐kDa protein was characterized by LC‐MS and showed homology to groEL chaperonin, which provokes a strong immune response in mammals. The 83‐kDa protein showed homology to aconitate hydratase, of which expression is increased in bacteria under oxidative stress, and which is highly immunogenic. Conclusions The majority of patients with erythematotelangiectatic rosacea show serum reactivity to two proteins from B. oleronius, suggesting that this bacterium may play a role in the induction of this condition. The two proteins to which patient sera reacted were found to be similar to a heat shock protein and an enzyme involved in regulating the stress response of the bacterium.     

Ocular findings in alopecia areata

Alopecia areata is a T cell mediated disease with which many disorders may be associated. There are few studies reporting ocular findings in alopecia areata. The aim of the study is to assess tear function and ocular surface pathologies in alopecia areata. Thirty‐two patients with alopecia areata and 20 age‐ and sex‐matched healthy controls were enrolled in the study. Ocular surface disease index questionnaire, Schirmer, tear break‐up time, and corneal staining stage tests were done. The data was analyzed using SPSS 10.0 software. One‐way variance analysis and Chi‐square tests were used as tests of significance. The patient group had significantly higher ocular surface disease index questionnaire and corneal staining stage test scores and lower tear break‐up time test scores compared with the control group (P < 0.05). Dry eye disease (DED) was diagnosed in 27 (84%) of 32 alopecia areata patients and in only 3 (15%) of 20 controls, and there was a significant difference between the groups (P < 0.01). T cell mediated autoimmunity has a prominent role in the etiopathogenesis of alopecia areata and dry eye disease. We think that inflammatory mechanisms causing alopecia areata may trigger dry eye disease or vice versa. All patients with AA should be referred to an ophthalmologist for the evaluation of DED and other possible eye pathologies.     

Four mild but refractory cases of pemphigus foliaceus successfully treated with intravenous immunoglobulin

Intravenous immunoglobulin (IVIG) is a potential second line of therapy for pemphigus, with increasing evidence of its effectiveness and safety, although oral corticosteroids remain the first treatment for pemphigus. IVIG is usually applied in severe cases of pemphigus, particularly pemphigus vulgaris (PV). Pemphigus foliaceus (PF) caused by immunoglobulin PF autoantibodies to desmoglein 1 (Dsg1) is usually milder than PV. However, PF cases are occasionally resistant to corticosteroids and require long‐term treatment to control the disease, leading to various adverse effects. IVIG was used in patients with relatively mild PF, who were resistant to therapies with corticosteroids and dapsone. We assessed the disease severity by Pemphigus Disease Area Index (PDAI) and measured anti‐Dsg1 antibody indices by enzyme‐linked immunosorbent assay, before and 4 months after IVIG. Four Japanese female PF patients (57.3 ± 8.6 years) were treated with a single cycle of IVIG (400 mg/kg per day for five consecutive days) in combination with the previous therapies. Within 1–2 months of addition of IVIG, all PF cases showed remarkable improvement of skin lesions, and PDAI also markedly decreased. For 2 years after IVIG, no apparent exacerbation was observed. Anti‐Dsg1 antibody indices decreased in all cases during the 2 years. IVIG could be a potential treatment for not only severe cases of PV but also mild and refractory cases of PF. IVIG may trigger the shift from intractable condition to remission via non‐pathogenic anti‐Dsg1 antibodies or some mechanisms excluding anti‐Dsg1 antibody.