Rosacea: the battle goes on.
Journal: Compr Ther. 2005 Summer;31(2):145-58.
Landow K.  

Rosacea presents an enigma to patients and physicians alike. Although new insights and a plethora of therapies provide hope, the underlying etiology remains unknown. This assures a certain amount of frustration as available treatments temporize rather than cure the disease. This article examines the current state of knowledge regarding this fascinating entity.  

Rosacea. Clinical features, pathogenesis and therapy
Journal: Hautarzt. 2005 Sep;56(9):871-85; quiz 886-7.
Lehmann P.  

Rosacea is a common facial dermatosis, which may have detrimental effects on the patient's psychological and social interactions. It is a disease of the middle aged, skin types I and II are more often affected than darker skin types. Clinically, pre-rosacea, and rosacea grade I-III may be distinguished. Pre-rosacea is characterized by flushing and blushing, grade I to III by erythemato-teleangiectasies, papulopustules, and inflammatory nodules. Especially severe subtypes include rosacea conglobata and rosacea fulminans. Hyperglandular subtypes lead to different forms of phyma, of which Rhinophyma is the most frequent. Pathogenetically destruction of the dermal vessels and connective tissue seems to be decisive for the development of a chronic inflammation, which leads to the phenotype of the various forms of rosacea. Mild forms can be treated exclusively by topical medication. Antibiotics (erythromycin, clindamycin, tetracyclin), metronidazol, azelaic acid, and the retinoid adapalene have been shown to be effective in well controlled randomized studies. The best evaluated topical medication is metronidazol. In severe forms systemic therapy must be applied. Systemic antibiotics are effective and especially isotretinoin has shown a very good response even in low dose regimens. Rhinophyma must be treated surgically.    

Interventions for rosacea.
Journal: Cochrane Database Syst Rev. 2005 Jul 20;(3):CD003262.
van Zuuren EJ et al   

BACKGROUND: Rosacea is a common chronic skin condition affecting the face, characterised by flushing, redness, pimples, pustules, and dilated blood vessels. The eyes are often involved. Frequently it can be controlled, but it is not clear which treatments are most effective. OBJECTIVES: To assess the evidence for the efficacy and safety of treatments for rosacea. SEARCH STRATEGY: We searched the Skin Group Specialised Register (February 2005), Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to February 2005), EMBASE (1980 to February 2005), BIOSIS (1970 to March 2002) and the Science Citation Index (1988 to February 2005). Reference lists of trials and key review articles were searched. Relevant manufacturers and experts were contacted. SELECTION CRITERIA: Randomised controlled trials in people with moderate to severe rosacea were included. Studies judged by the authors to have seriously flawed methodology were excluded. DATA COLLECTION AND ANALYSIS: Study selection, assessment of methodological quality, data extraction and analysis were carried out by two independent authors. Disagreements were resolved by discussion and consensus. MAIN RESULTS: The evidence provided by twenty-nine included studies was generally weak because of poor methodology and reporting. One of our primary outcome measures, 'quality of life', was not assessed in any of the studies. Only two studies of ocular rosacea were included.Pooled data from two trials involving 174 participants indicated that according to the participants, topical metronidazole is more effective than placebo (odds ratio (OR) 5.96, 95% confidence interval (CI) 2.95 to 12.06). Data pooled from three between-patient trials showed a clear improvement in the azelaic acid group; the rates of treatment success were approximately 70 to 80% versus 50% to 55% (OR 2.45, 95% CI 1.82 to 3.28). A within-patient trial of azelaic cream versus placebo could not be pooled with the other three studies, but also showed good evidence of efficacy. Data pooled from three studies of oral tetracycline versus placebo involving 152 participants showed that, according to physicians, tetracycline was effective (OR 6.06, 95% CI 2.96 to 12.42). Some evidence of efficacy of oral metronidazole was provided by one small study. AUTHORS' CONCLUSIONS: The quality of studies evaluating rosacea treatments was generally poor. There is evidence that topical metronidazole and azelaic acid are effective. There is some evidence that oral metronidazole and tetracycline are effective.There is insufficient evidence concerning the effectiveness of other treatments. Good RCTs looking at these treatments are urgently needed.    

Topical metronidazole combination therapy in the clinical management of rosacea.
Journal: J Drugs Dermatol. 2005 Jul-Aug;4(4):473-80.
Del Rosso JQ and Bikowski J.  

Metronidazole was the first topical agent approved by the U.S. Food and Drug Administration for the treatment of rosacea. Several controlled studies have confirmed the efficacy and safety of topical metronidazole 0.75% gel, lotion and cream and 1% cream for rosacea. At present, little data exists regarding the use of combination topical therapy in rosacea management, although anecdotal evidence and preliminary studies suggest at least some additive benefit when topical metronidazole is used in combination with sulfacetamide 10% /sulfur 5%. In this paper, the results of observational experience evaluating topical metronidazole 0.75% gel used in combination with other topical rosacea therapies and/or subantimicrobial dose doxycycline are reported.    

Rosacea, light, and phototherapy.
Journal: J Drugs Dermatol. 2005 May-Jun;4(3):326-9.
Lee M and Koo J.  

The long-established notion that rosacea is worsened by light is of particular concern in the phototherapy of diseases such as psoriasis, eczema, or vitiligo, which often can be coexistent with rosacea. A literature search was conducted and much evidence was found to challenge this belief that light adversely affects rosacea. In fact, more patients actually improved with sunlight in a more recent published survey. Several other studies have also shown that rosacea patients were similar to control subjects in sun exposure, solar skin damage, and sun sensitivity. Additionally, all clinical trials to date have failed to find a difference between rosacea patients and control subjects when challenged with ultraviolet light. Thus, phototherapy with rosacea may be safer than is commonly believed.  

Rosacea and its management: an overview.
Journal: J Eur Acad Dermatol Venereol. 2005 May;19(3):273-85.
Gupta AK, Chaudhry MM 

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.    

The pharmacologic therapy of rosacea: a paradigm shift in progress.
Journal: Cutis. 2005 Mar;75(3 Suppl):27-32; discussion 33-6.
Bikowski JB 

A number of topical and systemic pharmacologic therapies, some of which remain investigational, have been used to treat rosacea. The pathophysiology of rosacea appears to be inflammatory, and most of the interventions modulate the inflammatory process in some way. Topical agents include various formulations of sodium sulfacetamide and sulfur, metronidazole, azelaic acid, and benzoyl peroxide/clindamycin. Oral agents include antibiotics in conventional and subantimicrobial doses. A paradigm shift in progress in the management of rosacea encompasses the use of these and other agents either alone or, increasingly, in different combinations, based on the subtype of rosacea.    

Lasers and light sources for rosacea.
Journal: Cutis. 2005 Mar;75(3 Suppl):22-6; discussion 33-6.
Goldberg DJ 

Pharmacologic agents remain the mainstay for initial and maintenance treatment of rosacea. However, monochromatic (i.e., laser) and polychromatic light-based therapies are increasingly being used for the treatment of certain signs of rosacea. Despite the increased use of lasers and other light-based therapies, few well-controlled studies have been conducted on their use for the treatment of rosacea. The studies that do exist suggest that these modalities have value in treating erythematotelangiectatic rosacea, including persistent erythema and phymatous rosacea. Light-based therapies should be strongly considered in cases of serious erythema, flushing, and telangiectasia because these signs are not optimally addressed by pharmacologic interventions.    

Adjunctive skin care in the management of rosacea: cleansers, moisturizers, and photoprotectants.
Journal: Cutis. 2005 Mar;75(3 Suppl):17-21; discussion 33-6.
Del Rosso JQ 

Certain skin characteristics, such as altered vascular reactivity, appear to be common among patients with rosacea. This may partly explain the observation that these patients appear to have increased sensitivity to certain components of commonly used topical agents. Accordingly, patients with rosacea should be educated regarding which general skin care products to use and to avoid. This review summarizes information regarding 3 classes of these products--cleansers, moisturizers, and photoprotectants--with emphasis on barrier function and skin irritation.    

The rigor of trials evaluating Rosacea treatments.
Journal: Cutis. 2005 Mar;75(3 Suppl):13-6; discussion 33-6.
van Zuuren EJ and Graber MA 

The Cochrane Collaboration is an international nonprofit organization that conducts systematic reviews of healthcare interventions. The organization has recently reviewed all studies meeting designated criteria on interventions for rosacea. To be included in the review, trials had to be randomized controlled trials (RCTs) that met the methodological criteria of the reviewers and that were conducted in an adult patient population with moderate to severe rosacea. The electronic databases searched included The Cochrane Skin Group Specialised Trials Register, The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, BIOSIS, and Science Citation Index. The reviewers tried to obtain details of unpublished and ongoing RCTs through correspondence with authors and pharmaceutical companies. After evaluating the included studies, the reviewers concluded there is evidence that topical metronidazole in 1% cream and 0.75% gel formulations and azelaic acid in 20% cream formulation are effective and safe. Furthermore, there is some evidence that oral metronidazole and tetracycline are effective. The reviewers also made suggestions about future rosacea research.    

Present and future rosacea therapy.
Journal: Cutis. 2005 Mar;75(3 Suppl):4-7; discussion 33-6 .
Wolf JE Jr 

Despite its prevalence, rosacea has not received the same attention of researchers as other dermatologic disorders. Nevertheless, new pharmacologic and nonpharmacologic therapies for the condition continue to be developed. The future of rosacea treatment will probably involve a combination of drugs and devices. Certain core therapies (i.e., topical metronidazole, topical azelaic acid, oral tetracyclines, and topical sulfur/sodium sulfacetamide) are validated by the greatest amount of high-order clinical evidence and will undoubtedly remain first-line therapeutic choices. However, more research is necessary to validate the efficacy and safety of newer pharmacologic agents and light-based therapy. Because rosacea is a chronic condition, pharmacologic maintenance therapy is necessary to maintain remission.    

Rosacea: an update.
Journal: Dermatology. 2005;210(2):100-8.
Buechner SA 

Rosacea is a common chronic cutaneous disorder of unknown etiology which occurs most commonly in middle-aged individuals. Cutaneous manifestations include transient or persistent facial erythema, telangiectasia, edema, papules and pustules that are usually confined to the central portion of the face. The National Rosacea Society's Expert Committee on the Classification and Staging of Rosacea identified four subtypes of rosacea: erythematotelangiectatic, papulopustular, phymatous and ocular. Recently, a standard grading system for assessing gradations of the severity of rosacea has been reported. Little is known about the cause of rosacea. Genetic, environmental, vascular, inflammatory factors and microorganisms such as Demodex folliculorum and Helicobacter pylori have been considered. Topical metronidazole and azelaic acid have been demonstrated to be effective treatments for rosacea. Severer or persistent cases may be treated with oral metronidazole, tetracyclines or isotretinoin.    

Rosacea: II. Therapy.
Journal: J Am Acad Dermatol. 2004 Oct;51(4):499-512; quiz 513-4.
Pelle MT et al 

Despite an incomplete understanding of the pathogenesis of rosacea, therapeutic modalities continue to expand. The principal subtypes of rosacea include erythematotelangiectatic rosacea, papulopustular rosacea, phymatous rosacea, and ocular rosacea. These phenotypic expressions are probably caused by divergent pathogenic factors and consequently respond to different therapeutic regimens. A subtype-directed approach to therapy is discussed in part II of this review. We provide an overview of the available topical, oral, laser, and light therapies in the context of these cutaneous subtypes, review the evidence that supports their use, and outline their therapeutic approach. Suggestions for future areas of study also are provided.Learning objective At the completion of this learning activity, participants should be familiar with the subtype-directed approach to therapy for rosacea including available topical, oral, laser, and light therapies.  

Treating beyond the histology of rosacea.
Journal: Cutis. 2004 Sep;74(3 Suppl):28-31, 32-4.
Draelos ZD   

Current treatment paradigms for rosacea focus on inflammatory lesions and other signs and symptoms of rosacea that appear on the skin surface. However, it is important to recognize the effects of the disease and its various treatments not only on the stratum corneum barrier but also on the biofilm. The effects of skin care products, cosmetics, and medications on the stratum corneum and biofilm must be carefully assessed, and nonirritating formulations should be used whenever possible.    

Rosacea subtypes: a treatment algorithm.
Journal: Cutis. 2004 Sep;74(3 Suppl):21-7, 32-4.
Dahl MV 

Based on various signs and symptoms, the National Rosacea Society (NRS) Expert Committee has divided the syndrome of rosacea into 4 major subtypes: erythematotelangiectatic, papulopustular (inflammatory), phymatous, and ocular. Each of the subtypes can be divided further into more specific subgroups. For example, sensory rosacea is an additional subtype that can be recognized and treated. Signs and symptoms may direct therapy. This article proposes an overview of common treatments based on subtypes. Treatments that have been validated by randomized controlled trials are reviewed. However, many excellent treatments have not been validated by double-blind randomized trials.    

Reactive oxygen species and rosacea.
Journal: Cutis. 2004 Sep;74(3 Suppl):17-20, 32-4.
Jones D.  

Although the fundamental pathogenesis of rosacea remains unknown, inflammation is a central process in this disorder. Recent evidence suggests that this inflammation is associated with the generation of reactive oxygen species (ROS) that are released by inflammatory cells such as neutrophils. In vitro studies suggest that certain core therapies for rosacea, including metronidazole and the tetracyclines, show antioxidant effects, and this may be one aspect of their mechanism of action.    

Ultraviolet light and rosacea.
Journal: Cutis. 2004 Sep;74(3 Suppl):13-6, 32-4.
Murphy G.  

The general consensus among clinicians is that rosacea is a photoaggravated disorder. Pathophysiologic processes induced by UV radiation, which are processes similar to those seen in photoaging, contribute to the signs and symptoms of rosacea. Because of the purported role of solar radiation, clinicians may want to use photosensitizing antibiotics with discretion in patients with rosacea. In addition to topical and oral therapy for rosacea, clinicians should recommend that patients use sunscreens or sunblocks (inorganic chemicals such as zinc oxide or titanium dioxide).    

Rosacea and the pilosebaceous follicle.
Journal: Cutis. 2004 Sep;74(3 Suppl):9-12, 32-4.
Powell FC 

The pathophysiology of rosacea remains unknown. A leading theory suggests a vascular basis; however, clinical observations and histopathologic studies suggest that inflammation of the pilosebaceous follicle may be central to the pathogenesis of rosacea. Demodex folliculorum is a frequently seen commensal in the follicles of facial skin. According to evidence from biopsies of the skin surface, individuals with rosacea have a higher density of this parasite. This increased mite density may play a role in the pathophysiology of rosacea by triggering inflammatory or specific immune reactions, mechanically blocking the follicles, or acting as a vector for bacteria. Ongoing research has shown that bacteria from patients with rosacea may behave differently at the higher skin temperature that may be present in patients with rosacea. Another group has isolated bacteria from the Demodex mites; these bacteria may play a pathogenic role in papulopustular rosacea by facilitating follicular-based inflammatory changes.    

The nosology of rosacea.
Journal: Cutis. 2004 Sep;74(3 Suppl):5-8, 32-4.
Odom R.  

The National Rosacea Society (NRS) convened a committee of dermatology thought leaders to develop a standard classification system for rosacea. Based on the primary and secondary characteristics of this disorder, the NRS Expert Committee identified 4 types of rosacea: erythematotelangiectatic, papulopustular, phymatous, and ocular; one variant, granulomatous, also was recognized. The NRS Expert Committee also developed a grading system for rosacea signs and symptoms that will complement this classification system. The classification system and forthcoming grading system will help practitioners refine their diagnosis and treatment of rosacea to ensure better outcomes for patients.  

Rosacea: I. Etiology, pathogenesis, and subtype classification.
Journal: J Am Acad Dermatol. 2004 Sep;51(3):327-41; quiz 342-4.
Crawford GH et al 

Rosacea is one of the most common conditions dermatologists treat. Rosacea is most often characterized by transient or persistent central facial erythema, visible blood vessels, and often papules and pustules. Based on patterns of physical findings, rosacea can be classified into 4 broad subtypes: erythematotelangiectatic, papulopustular, phymatous, and ocular. The cause of rosacea remains somewhat of a mystery. Several hypotheses have been documented in the literature and include potential roles for vascular abnormalities, dermal matrix degeneration, environmental factors, and microorganisms such as Demodex folliculorum and Helicobacter pylori. This article reviews the current literature on rosacea with emphasis placed on the new classification system and the main pathogenic theories.Learning objective At the conclusion of this learning activity, participants should be acquainted with rosacea's defining characteristics, the new subtype classification system, and the main theories on pathogenesis.    

Advances in the topical treatment of acne and rosacea.
Journal: J Drugs Dermatol. 2004 Sep-Oct;3(5 Suppl):S12-22.
Ceilley RI 

Acne and rosacea are common skin diseases which may present similarly and both involve inflammation. Both can result in significant cosmetic impairment and lead to quality of life decrements if not optimally treated. The conventional approach for both diseases involves the use of topical therapy to treat inflammatory lesions in combination, when needed, with a systemic or topical antibiotic. An important issue in the management of both diseases at present is the need to reduce antibiotic usage due to the increasing problem of bacterial resistance. One of the emerging treatment paradigms that is becoming increasingly useful as an antibiotic-sparing strategy is the use of procedural therapies in combination with medical management. Such procedural modalities include lasers, intense pulsed light (IPL), and photodynamic therapies (PDT). Topical regimens are used pre-treatment and following physical modalities for maintenance of remission.    

Rosacea in the pediatric population.
Journal: Cutis. 2004 Aug;74(2):99-103.
Lacz NL and Schwartz RA 

Rosacea is a condition of vasomotor instability characterized by facial erythema most notable in the central convex areas of the face, including the forehead, cheek, nose, and perioral and periocular skin. Rosacea tends to begin in childhood as common facial flushing, often in response to stress. A diagnosis beyond this initial stage of rosacea is unusual in the pediatric population. If a child is identified with the intermediate stage of rosacea, consisting of papules and pustules, an eye examination should be performed to rule out ocular manifestations. It may be beneficial to recognize children in the early stage of rosacea; however, it is uncertain if prophylactic treatment is necessary.  

Rosacea: where are we now?
Journal: J Drugs Dermatol. 2004 May-Jun;3(3):251-61.
Bikowski JB and Goldman MP 

Advances continue to be made in the classification and treatment of rosacea, a chronic dermatologic syndrome. A new empiric classification system identifies 4 rosacea subtypes (erythematotelangiectatic, papulopustular, phymatous, and ocular) that may aid in more precise diagnosis. Several new therapies have recently been approved for treatment of rosacea. Azelaic acid 15% gel is a new first-tier topical agent proven effective in reducing inflammatory lesions and erythema. New formulations of metronidazole and sulfacetamide 10%/sulfur 5% that offer cosmetic or tolerability advantages are now available. Intense pulsed light therapy has demonstrated effectiveness in reducing flushing, erythema, and telangiectases, with greater tolerability than existing laser systems. Other treatments under investigation include low-dose doxycycline hyclate (which may provide greater safety than existing oral antibiotics), benzoyl peroxide/clindamycin gel, and tacrolimus ointment (for steroid-induced rosacea). With this expanded armamentarium of medical and light-based therapies, clinicians can now implement a multifaceted approach to treatment, crafting new treatment combinations to address the unique and evolving features of rosacea in each individual patient.  

Facial hygiene and comprehensive management of rosacea.
Journal: Cutis. 2004 Mar;73(3):183-7.
Draelos ZD 

The skin of patients with rosacea is exquisitely sensitive to various dietary, environmental, and topical factors that initiate the facial erythema characteristic of this sensitive skin condition. This sensitivity is probably due to epidermal barrier dysfunction. Overall management of rosacea involves the avoidance of dietary and environmental triggers, concurrent with the use of prescription therapies. The appropriate selection of over-the-counter and prescription skin care products is equally important. This article reviews the use of therapeutic skin cleansers, including the newest category of prescription antimicrobial cleansers, which can enhance the overall management of this inflammatory dermatologic disorder.    

Skin diseases in alcoholics.
Journal: Acta Dermatovenerol Croat. 2004;12(3):181-90.
Kostovic K and Lipozencic J.  

Alcohol abuse is associated with many health problems, especially skin changes. As a small, water- and lipid-soluble molecule, alcohol reaches all tissues of the body and affects most vital functions. Cutaneous diseases are now emerging as useful markers of alcoholism detectable at an early and possibly reversible stage of the disease, thus being of substantial importance to dermatologists and general practitioners. The most common skin manifestations of alcoholism presented in this review article are urticarial reactions, porphyria cutanea tarda, flushing, cutaneous stigmata of cirrhosis, psoriasis, pruritus, seborrheic dermatitis, and rosacea.    

Interventions for rosacea.
Journal: Cochrane Database Syst Rev. 2004;(1):CD003262.
van Zuuren EJ et al 

BACKGROUND: Rosacea is a common skin condition affecting the face, characterised by flushing, redness, pimples, pustules and dilated blood vessels. The eyes are often also involved. The cause of rosacea is unclear. It is a chronic disease, which can be controlled in most cases with appropriate treatment. Numerous treatments are in use although it is unclear which are best, and which are most appropriate for the different types of rosacea. OBJECTIVES: To assess and summarise current evidence for the efficacy and safety of treatments for rosacea. SEARCH STRATEGY: We searched the Skin Group Specialised Trials Register (March 2002), Cochrane Central Register of Controlled Trials (CENTRAL, March 2002), MEDLINE (from 1966 to March 2002), EMBASE (from 1980 to March 2002), Biosis (from 1970 to March 2002) and the Science Citation Index (from 1988 to March 2002). Reference lists of trials and key review articles were also searched. Relevant manufacturers and experts were contacted. SELECTION CRITERIA: Randomised controlled trials in people with moderate to severe rosacea were included. Studies judged by the reviewers to have seriously flawed methodology were excluded. DATA COLLECTION AND ANALYSIS: Study selection, assessment of methodological quality, data extraction and analysis were carried out by two independent reviewers. MAIN RESULTS: The evidence provided by twenty-two included studies was generally weak because of poor methodology and reporting. One of our primary outcome measures, 'quality of life', was not assessed in any of the studies. Only two studies of ocular rosacea could be included.Pooled data from two trials involving 174 participants indicated that topical metronidazole is more effective than placebo (odds ratio 5.96, 95% confidence interval 2.95 to 12.06). Data from a between-patient trial (114 patients) and a within-patient trial (33 patients) of azelaic cream versus placebo were not pooled, but both showed good evidence of efficacy. Data pooled from three studies of oral tetracycline versus placebo involving 152 participants showed that, according to physicians' ratings, tetracycline was effective (odds ratio 6.06, 95% confidence interval 2.96 to 12.42). Some evidence of efficacy of oral metronidazole was provided by one small study. REVIEWER'S CONCLUSIONS: The quality of studies evaluating rosacea treatments was generally poor. There is evidence that topical metronidazole and azelaic acid cream have a therapeutic effect. There is some evidence that oral metronidazole and tetracycline are effective.There is insufficient evidence concerning the effectiveness of other treatments. As many of these treatments are used for rosacea, good RCTs are urgently needed.    

Evaluating the role of topical therapies in the management of rosacea: focus on combination sodium sulfacetamide and sulfur formulations.
Journal: Cutis. 2004 Jan;73(1 Suppl):29-33.
Del Rosso JQ 

The combination of sodium sulfacetamide and sulfur is unique in the rosacea armamentarium because of its dual use as topical therapy and therapeutic cleanser. Several formulations of sulfacetamide 10% and sulfur 5% are now available as topical lotions and cleansers. The sulfacetamide/sulfur cleansers serve as adjunctive therapy by providing additive effects to other topical and oral therapies for rosacea with favorable tolerability and cosmetic appeal.    

The role of topical metronidazole in the treatment of rosacea.
Journal: Cutis. 2004 Jan;73(1 Suppl):19-28.
Wolf JE Jr.  

Many topical and oral pharmacologic agents have shown well-tolerated efficacy for the treatment of rosacea. Metronidazole was the first topical therapy approved for rosacea and is still considered the foundation therapy by many researchers and dermatologists. The efficacy and tolerability of topical metronidazole in combination with an oral antibiotic or as monotherapy to maintain remissions have been shown in multiple well-controlled trials.    

Mechanism-based selection of pharmacologic agents for rosacea.
Journal: Cutis. 2004 Jan;73(1 Suppl):15-8.
Shalita A and Leyden J.  

All effective agents used to treat rosacea have a common mechanism of action: anti-inflammatory effects. Concomitant with this, many of these agents also show antioxidant effects. Both anti-inflammatory and antioxidant effects may address the proposed underlying pathophysiology of rosacea. Future topical formulations may involve the combination of active pharmacologic agents and sunscreens or sun blocks to address the proposed etiologic role played by UV radiation in the pathophysiology of rosacea.    

The subtypes of rosacea: implications for treatment.
Journal: Cutis. 2004 Jan;73(1 Suppl):9-14. Odom RB.  

Lack of standardized rosacea nosology was the rationale for the National Rosacea Society to convene a committee of dermatology thought leaders to develop a standard classification system. Standardization of rosacea classification should be followed by standardization of treatment. Many pharmacologic and nonpharmacologic interventions for rosacea are being used based on clinical observation alone. Many oral and topical pharmacologic agents, however, are validated by randomized controlled trials (RCTs). Topical therapies (eg, metronidazole or an alternative agent such as azelaic acid) and oral antibiotics (eg, the tetracycline family) should remain as foundation therapies for subtypes 1 and 2 rosacea, based on the strength of the evidence.    

Rosacea as an inflammatory disorder: a unifying theory?
Journal: Cutis. 2004 Jan;73(1 Suppl):5-8.

Millikan LE.   Rosacea is increasingly being viewed as an immune-based disorder. Various immune factors, such as eicosanoids, proinflammatory cytokines, and polymorphonuclear leukocytes, appear to be involved in the vascular, inflammatory, and proliferative subtypes of this disorder. Many pharmacologic agents that effectively treat the symptoms of rosacea show anti-inflammatory and/or immunomodulating effects, providing further evidence that rosacea is an inflammatory disorder.    

Medical treatment of rosacea with emphasis on topical therapies.
Journal: Expert Opin Pharmacother. 2004 Jan;5(1):5-13.
Del Rosso JQ 

Due to the development and release of newer topical formulations, the diagnosis and treatment of rosacea has received renewed attention over the past 3-5 years both in the literature and at medical symposia. Rosacea is a very common facial dermatosis. In the US , rosacea is estimated to affect > 14 million people, predominantly adults with approximately 60% of cases diagnosed before the age of 50. A frustrating aspect of the disease is its inherent chronicity punctuated with periods of exacerbation and relative remission. A variety of subtypes have been identified which correlate with clinical presentation. Although the pathogenesis of rosacea is poorly understood, multiple topical agents are available. The efficacy of topical therapy for rosacea relates primarily to reduction in inflammatory lesions (papules, pustules), decreased intensity of erythema, a reduction in the number and intensity of flares and amelioration of symptoms, which may include stinging, pruritus and burning. The list of main topical agents utilised for the treatment of rosacea include metronidazole, sulfacetamide-sulfur, azelaic acid and topical antibiotics (clindamycin, erythromycin). Depending on the severity at initial presentation, topical therapy may be combined with systemic antibiotic therapy (e.g., oral tetracycline derivative). Newer therapeutic choices primarily involve improved vehicle formulations, which demonstrate favourable skin tolerability and cosmetic elegance.    

Etiopathogenesis, classification, and current trends in treatment of rosacea.
Journal: Acta Dermatovenerol Croat. 2003 Dec;11(4):236-46.
Tisma VS et al 

Rosacea is a common chronic dermatosis characterized by varying degrees of flushing, erythema, telangiectasia, edema, papules, pustules, ocular lesions, and phymas. Etiology and pathogenesis of rosacea are still unknown. Many possible causes have been described as inducing the disease or contributing to its manifestation, such as genetic predisposition, abnormal vascular reactivity, changes in vascular mediating mechanisms, Helicobacter pylori infection, Demodex folliculorum infestation, seborrhea, sunlight, hypertension, and psychogenic factors. However, none of these factors has been proved. Rosacea shows a wide spectrum of clinical presentations, which vary over time and with age. Successful management of rosacea requires careful patient evaluation and individualized therapy with appropriate variations and modifications, as the severity of the disorder fluctuates. In mild cases of rosacea, patients are instructed to avoid sun, to apply sun-protective creams, and to avoid facial irritants and other triggers that provoke symptoms. At later stage, drug therapy is often necessary. The disease commonly requires long-term treatment with topical or oral medicaments. Surgical correction may be required for rhinophyma and telangiectasia. We reviewed the current literature on the aspects of the pathogenesis, diagnostic criteria, and treatment options for rosacea.    

Critical review of the manner in which the efficacy of therapies for rosacea are evaluated.
Journal: Int J Dermatol. 2003 Nov;42(11):909-16.
Gupta AK and Chaudhry MM   

BACKGROUND: Rosacea is a relatively common disorder that may affect individuals of all races, particularly those of northern European decent. Its onset generally occurs in individuals between the ages of 20 and 50 years. Rosacea may be classified into four subtypes and one variant. Although individuals with rosacea may not pass through all of the stages, the primary features of the disorder include frequent flushing and blushing, nontransient erythema, the presence of papules and pustules, and telangiectasia. Many agents have been used to treat rosacea stigmata, especially because none of these is uniformly effective. AIM: To identify the parameters that are used to evaluate the response to therapy when different agents are used to treat rosacea. For a given parameter, to determine whether the different trials are consistent in the manner in which this variable is measured. METHODS: The reports on the efficacy and safety of the different drug therapies used to treat rosacea were identified. We searched MEDLINE (1966 to June 2002) for studies where rosacea was treated. The parameters used to evaluate the efficacy of therapy were determined. For each parameter, the ways in which it has been measured were identified. RESULTS: Efficacy of treatment is generally judged by evaluating the effect of the intervention on papules and pustules, erythema, and telangiectasia. Manual lesional counts of papules and pustules are usually performed. There is, however, substantial variation in the methodology chosen for comparison of erythema and telangiectasias. Color scales are popular for erythema and telangiectasia, while grading scales are most commonly used for physician and patient evaluations. CONCLUSIONS: For each of the parameters that are commonly used to measure the efficacy of treatments for rosacea, the different approaches by which it has been measured in the various trials have been highlighted; these dissimilarities can make it problematic to compare between clinical trials. A greater degree of uniformity in the manner in which the various parameters are evaluated would enable a more objective comparison between the studies.     Use of topical metronidazole in moderate to severe rosacea. Journal: Adv Ther. 2003 Jul-Aug;20(4):177-90. Lowe NJ .   Rosacea is a chronic condition requiring long-term therapy for control and maintenance. Numerous controlled studies have shown that metronidazole 0.75% in combination with oral antibiotics significantly reduces the number of papules and pustules and erythema severity scores in patients with severe disease. Topical metronidazole 0.75% also maintains long-term remissions after oral tetracycline has been discontinued. Although original studies involving topical metronidazole 0.75% used a twice-daily regimen, subsequent work has shown that this formulation used once daily is as effective as 1% metronidazole.  

Measuring the severity of rosacea: a review.
Journal: Int J Dermatol. 2003 Jun;42(6):444-8.
Gessert CE and Bamford JT 

BACKGROUND: Assessment of severity is essential in the clinical care of rosacea patients and in the research on rosacea. OBJECTIVE: To determine the range of methods used to assess rosacea severity in clinical trials. METHODS: The medical literature from 1965 through 2001 was searched for rosacea clinical trials using MEDLINE and published citations. Forty-seven articles were reviewed. RESULTS: The most frequently assessed signs of rosacea were papules/pustules (43 studies), erythema (35), and telangiectasia (24). Other signs and symptoms of rosacea and adverse reactions to therapies were assessed in 27 studies. Counts of papules/pustules were conducted in 34 studies. Four-point scales were the most frequently used assessment tools for erythema (17) and telangiectasia (11). Other frequently used techniques included global assessment by clinicians (29) and by patients (21), and photography (13). CONCLUSIONS: At present, there are no standard validated tools for assessing the severity of rosacea or its signs or symptoms.    

Rosacea: a common, yet commonly overlooked, condition.
Journal: Am Fam Physician. 2002 Aug 1;66(3):435-40.
Blount BW, Pelletier AL 

Rosacea is a common, but often overlooked, skin condition of uncertain etiology that can lead to significant facial disfigurement, ocular complications, and severe emotional distress. The progression of rosacea is variable; however, typical stages include: (1) facial flushing, (2) erythema and/or edema and ocular symptoms, (3) papules and pustules, and (4) rhinophyma. A history of exacerbation by sun exposure, stress, cold weather, hot beverages, alcohol consumption, or certain foods helps determine the diagnosis; the first line of treatment is avoidance of these triggering or exacerbating factors. Most patients respond well to long-term topical antibiotic treatment. Oral or topical retinoid therapy may also be effective. Laser treatment is an option for progressive telangiectasis or rhinophyma. Family physicians should be able to identify and effectively treat the majority of patients with rosacea. Consultation with subspecialists may be required for the management of rhinophyma, ocular complications, or severe disease. (Am Fam Physician 2002;66:442.)  

Diagnosis and treatment of rosacea.
Journal: J Am Board Fam Pract. 2002 May-Jun;15(3):214-7
Cohen AF and Tiemstra JD 

BACKGROUND: Rosacea is a common skin disorder affecting middle-aged and older adults. Many patients mistakenly assume that early rosacea is normally aging skin and are not aware that effective treatments exist to prevent progression to permanent disfiguring skin changes. METHODS: The medical literature was reviewed on the pathophysiology, diagnosis, and treatment of rosacea. MEDLINE was searched using the key search terms "rosacea," "rhinophyma," "metronidazole," "Helicobacter pylori," and "facial redness." RESULTS AND CONCLUSIONS: Rosacea is easily diagnosed by physician observation, and physicians should initiate discussion of rosacea treatment with patients. Effective treatment of rosacea includes avoidance of triggers, topical and oral antibiotic therapy, both topical and oral retinoid therapy, topical vitamin C therapy, and cosmetic surgery.  

The management of rosacea.
Journal: Am J Clin Dermatol. 2002;3(7):489-96 .
Rebora A.  

Rosacea is a multiphasic disease which is associated with flushing, erythrosis, papulopustular rosacea and phymas; each phase is likely to have its own treatment. Flushing is better prevented rather than treated, and its etiology investigated. Beta-blockers, atenolol in particular, are worthy of prophylactic trials examining their efficacy in treating the flushing associated with rosacea. Currently, clonidine is the only drug available for the treatment of flushing. Treatment for erythrosis includes topical and systemic therapies. Metronidazole 1% cream and azelaic acid 20% cream have been reported to reduce the severity score of erythema. The systemic treatment of erythrosis is based on the association of Helicobacter pylori with rosacea. However, this role is still being debated. Eradication of H. pylori can be achieved using a triple therapy regimen lasting 1 to 2 weeks [omeprazole and a combination of two antibacterials (a choice from clarithromycin, metronidazole or amoxicillin)]. Both the flashlamp-pumped long-pulse dye laser and the potassium-titanyl-phosphate laser may be used in the treatment of facial telangiectases. Both systemic and topical remedies may be used to treat the papulopustules of rosacea. Systemic treatment includes metronidazole, doxycycline, minocycline, clarithromycin and isotretinoin, while topical treatment is based on metronidazole cream and gel. The presence of Demodex folliculorum is important in the inflammatory reaction, whether it is pathogenetic or not. Crotamiton 10% cream or permethrin 5% cream may be useful medications for papulopustular rosacea, although they are rarely successful in eradicating D. folliculorum. Oral or topical ivermectin may also be useful in such cases. Ocular involvement is common in patients with cutaneous rosacea and can be treated with orally administered or topical antibacterials. Once rhinophyma starts to be evident, the only way to correct it is by aggressive dermatosurgical procedures. Decortication and various types of lasers can also be used. Associated conditions, such as seborrheic dermatitis and possible contact sensitizations, deserve attention.    

Topical metronidazole for rosacea.
Journal: Skin Therapy Lett. 2002 Jan;7(1):1-3, 6.  
Gupta AK and Chaudhry M.  

Rosacea is relatively common, typically occurring in individuals of Northern European and Celtic origin between 30 and 50 years of age. It is more common in women, but may be more severe in men. Currently there is no cure available for rosacea, but it can be controlled with topical and oral drug therapy. Topical metronidazole 1% cream is approved by the US FDA for the treatment of inflammatory lesions (papules and pustules) and erythema associated with rosacea. This treatment option is effective, safe and well tolerated.  

Medication adherence: a key factor in effective management of rosacea.
Journal: Adv Ther. 2001 Nov-Dec;18(6):272-81.
Wolf JE Jr 

Rosacea is a chronic condition associated with relapses. Unsuccessful treatment is predicated, in part, on suboptimal adherence with the medication regimen. Motivating long-term compliance remains a challenge. The literature on adherence with rosacea medication is scant, but data from other diseases suggest that a multifactorial approach combining nonpharmacologic and adherence-enhancing pharmacologic interventions appears to offer the greatest success. The variety of topical metronidazole formulations that are relatively well tolerated and convenient to administer has been a notable advance in rosacea management. The dermatologist, by emphasizing the importance of adherence with therapy, can do much to facilitate this most critical behavior.  

Rosacea: current thoughts on origin.
Journal: Semin Cutan Med Surg. 2001 Sep;20(3):199-206.
Bamford JT 

Rosacea is a clinical pattern beginning and evolving in the genetically susceptible individual in response to a host of exposures. It produces a variety of clinical presentations, which vary over time and with age. Recently, many specific mediators of rosacea development have been described. A primary genetic cause for rosacea is suggested as single genes often control such mediators: enzymes, neuroendocrine transmitters, and cytokines are found in pathways to rosacea signs and symptoms. Currently, neither a specific cause nor a laboratory indicator of rosacea has been suggested. However, broadening interest in rosacea portends future increase in knowledge.

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