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Background

Acne rosacea is another name for this common dermatitis of adults. There are four main clinical types with accompanying histopathologic changes.

Several associations have led to speculation about its cause. Vasodilator drugs may cause flushing and exacerbate the disease. Heavy local follicular infestations of Demodex folliculorum (mite) may lead to a response. Heavy topical application of potent fluorinated steroids may and HIV infection may also be associated.

OUTLINE

Epidemiology  
Disease Associations  
Pathogenesis  
Laboratory/Radiologic/
Other Diagnostic Testing
 
Gross Appearance and Clinical Variants  
Histopathological Features and Variants  
Special Stains/
Immunohistochemistry/
Electron Microscopy
 
Differential Diagnosis  
Prognosis  
Treatment  
Commonly Used Terms  
Internet Links  

 

EPIDEMIOLOGY CHARACTERIZATION
AGE  
Childhood stye and adult rosacea.

Department of Dermatology, St Mary's Duluth Clinic Health System, Duluth, Minnesota 55805-1983, USA.

 

J Am Acad Dermatol. 2006 Dec;55(6):951-5. Epub 2006 Sep 5. Abstract quote

BACKGROUND: Little is known about how individuals with a predisposition for rosacea appear in childhood. This retrospective, matched control, longitudinal study examined the relationship between childhood stye and adult rosacea.

METHODS: The records of the Rochester Epidemiology Project were examined to identify patients who received care for stye or blepharitis between ages 2 and 17 years, and received care for any cause at age 40 years or older. Patients were matched by group to control subjects (1:2).

RESULTS: Patients with stye during childhood (N = 201) had a higher prevalence of adult rosacea than did control subjects (5.5% vs 1.5%, P = .01). Patients who had other childhood eye conditions without stye (N = 504) were not at higher risk.

LIMITATIONS: The study population included few minority patients.

CONCLUSIONS: The association between childhood stye and adult rosacea appears to be significant and should be examined further. Rosacea prevalence in adults may be lower (2.1%) than previously reported.

PATHOGENESIS  
DEMODEX  
Demodicosis and rosacea: epidemiology and significance in daily dermatologic practice.

Forton F, Germaux MA, Brasseur T, De Liever A, Laporte M, Mathys C, Sass U, Stene JJ, Thibaut S, Tytgat M, Seys B.

J Am Acad Dermatol. 2005 Jan;52(1):74-87. Abstract quote

BACKGROUND: Demodicoses are thought to be rare, occurring mainly for patients with immunosuppression.

OBJECTIVE: We sought to demonstrate the high frequency of demodicoses and the overlapping with papulopustular rosacea (PPR) .

METHODS: We conducted a prospective epidemiologic study among 10 dermatologists. High Demodex density (Dd) was confirmed by standardized skin surface biopsy.

RESULTS: In all, 4372 diagnoses, in which 115 were demodicoses, were collected among 3213 patients. Demodicosis was the 9th most frequent diagnosis (13th new). Each dermatologist observed an average of 2.4 demodicoses a week (1.2 new). The proportion of demodicoses varied greatly according to the dermatologist. The general status was good in 110 patients; only 3 had known immunodeficiency. The most frequent symptoms were follicular scales (71%) and telangiectasia (63%). The mean Dd was higher in pityriasis folliculorum (m = 61 D/cm 2 ) than in PPR (m = 36 D/cm 2 ; P = .04); 42 patients with PPR had a high Dd, 6 had a low Dd.

CONCLUSION: Demodicoses are frequent and occur among patients who are immunocompetent. PPR with normal Dd are rare.
VASCULOGENESIS  
Lymphangiogenesis and angiogenesis in non-phymatous rosacea.

Dermatopathology Section, Boston University School of Medicine, Boston, MA, USA, and Department of Dermatology, Suez Canal University, Ismailia, Egypt.

 

J Cutan Pathol. 2007 Oct;34(10):748-53. Abstract quote

Background: Our study evaluated the expression of vascular endothelial growth factor (VEGF), CD31 and D2-40 in involved and uninvolved skin of 18 patients with rosacea.

Methods: Immunostaining of facial skin specimens with VEGF, CD31 and D2-40 was compared between the lesional and the non-lesional skin of patients with erythemotelangiectatic and papulopustular rosacea.

Results: Significantly increased dermal expression of VEGF in lesional vs. non-lesional skin (88.9% and 55.6%) was observed. Dermal expression of CD31 and D2-40 was also increased in lesional vs. non-lesional skin. There was no statistically significant difference in cutaneous expression of VEGF, CD31 and D2-40 between patients with papulopustular and erythemotelangiectatic rosacea, and no correlation was found between disease duration and immunoreactivity of VEGF, CD31or D2-40.

Conclusions: Our study showed marked immunostaining of lesional skin with VEGF, CD31 and D2-40 compared with non-lesional skin. Increased immunoreactivity of D2-40 in lesional skin is interesting, given that none of the patients had facial edema. There are no published data regarding the role of lymphangiogenesis in patients with non-phymatous rosacea; thus, our study represents a new understanding of its pathogenesis. Lack of correlation between D2-40 expression and disease duration suggests that lymphatics are involved early in the pathogenesis of rosacea and do not constitute a late event.

CLINICAL VARIANTS CHARACTERIZATION
DIAGNOSIS J Am Acad Dermatol 2002;46:584-587.
Presence of one or more of the following primary features Flushing (transient erythema)
Nontransient erythema
Papules and pustules
Telangiectasia
May include one or more of the following secondary features Burning or stinging
Plaque
Dry appearance
Edema
Ocular manifestations
Peripheral location
Phymatous changes
Rosacea: I. Etiology, pathogenesis, and subtype classification.

Crawford GH, Pelle MT, James WD.

Department of Dermatology, University of Pennsylvania Medical Center, USA.
J Am Acad Dermatol. 2004 Sep;51(3):327-41; quiz 342-4. Abstract quote  

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.

 

HISTOPATHO-LOGICAL VARIANTS CHARACTERIZATION
Erythematous telangiectatic Superficial telangiectasia with perivascular dermatitis
Papulopustular Pusutular folliculitis with perivascular dermatitis
Hyperplastic glandular
(Rhinophyma or Phymatous)
Sebaceous gland hypertrophy with follicular plugging, later cases may have fibrosis
Ocular Foreign body sensation in eye, burning or stinging, dryness, itching, ocular photosensitivity, blurred vision, telangiectasia of the sclera or other parts of the eye, or periorbital edema
VARIANTS  
GRANULOMATOUS Tuberculoid type granulomas usually periadnexal
Hard, brown, yellow, or red cutaneous papules or nodules of uniform size
Granulomatous rosacea.

Department of Dermatology, University of Puerto Rico, School of Medicine, San Juan, Puerto Rico.

Am J Dermatopathol. 2008 Feb;30(1):6-9. Abstract quote

Rosacea is classified into four clinical subtypes, namely erythematotelangiectatic, papulopustular, phymatous, and ocular. There is also a granulomatous variant, which is recognized in the rosacea spectrum.

The objective of this study is to take a closer look at the different histopathologic patterns and cellular compositions seen in granulomatous rosacea and their correlation to the clinical presentation. Facial biopsies from patients previously identified with a clinical diagnosis consistent with rosacea, and who demonstrated a granulomatous infiltrate upon histopathologic examination, were reviewed and the results were correlated to the clinical presentation.

Four distinct histopathologic granulomatous patterns were identified, namely nodular, perifollicular, diffuse, and a combined perifollicular and nodular patterns. The clinical presentation varied greatly among patients and failed to correlate to the microscopic findings. The varied clinical features seen in our study favors the theory that granulomatous rosacea is not a clinical subtype of rosacea per se, but a distinct histological variant, which can be found in most of its clinical spectrum.

 

PROGNOSIS AND TREATMENT CHARACTERIZATION
PROGNOSIS  
GRADING  
Standard grading system for rosacea: Report of the National Rosacea Society Expert Committee on the Classification and Staging of Rosacea.

Wilkin J, Dahl M, Detmar M, Drake L, Liang MH, Odom R, Powell F.
J Am Acad Dermatol. 2004 Jun;50(6):907-12. Abstract quote  
TREATMENT  
Rosacea: II. Therapy.

Pelle MT, Crawford GH, James WD.

Department of Dermatology, Boston University Medical Center, USA.
J Am Acad Dermatol. 2004 Oct;51(4):499-512; quiz 513-4. Abstract quote  

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.
AZELAIC ACID (15%)  


Efficacy and safety of azelaic acid (15%) gel as a new treatment for papulopustular rosacea: Results from two vehicle-controlled, randomized phase III studies.

Thiboutot D, Thieroff-Ekerdt R, Graupe K.

Pennsylvania State University College of Medicine, Hershey, Clinical Development, Berlex Laboratories, Montville, and Clinical Development, Dermatology, Schering AG, Berlin.

 

J Am Acad Dermatol. 2003 Jun;48(6):836-45 Abstract quote

BACKGROUND: Rosacea is a common, chronic dermatosis for which safe and effective new treatment options are needed. OBJECTIVE: The objective of these studies was to evaluate the efficacy, tolerability, and safety of a new formulation of 15% azelaic acid (15%) gel (AzA gel), for the topical treatment of moderate, papulopustular rosacea.

METHODS: Two multicenter, double-blind, randomized, parallel-group, vehicle-controlled studies were conducted using identical study designs, patient-selection criteria, and efficacy end points. Overall, 329 patients were enrolled in study 1 and 335 patients in study 2.

RESULTS: Both studies consistently demonstrated the superiority of AzA gel over vehicle in the topical treatment of moderate, papulopustular rosacea. AzA gel yielded statistically significantly higher reductions in mean inflammatory lesion count than vehicle: 58% versus 40%, study 1 (P =.0001); 51% versus 39%, study 2 (P =.0208). Significantly higher proportions of patients treated with AzA gel experienced improvement in erythema compared with vehicle gel: 44% versus 29%, study 1 (P =.0017); 46% versus 28%, study 2 (P =.0005). Using the investigator's global assessment, therapeutic success in terms of a clear, minimal, or mild final result was achieved in 61% and 62% of patients treated with AzA gel in studies 1 and 2, respectively, which was significantly superior to the result achieved with vehicle (40% and 48%, respectively) (P <.0001, study 1; P =.0127, study 2). No serious, treatment-related adverse events were reported.

CONCLUSION: The results of these 2 controlled studies demonstrate that AzA gel, used twice daily, is an efficacious, safe, and well-tolerated topical treatment for moderate, papulopustular rosacea.

LASER, PULSED DYE  
Pulsed dye laser treatment of rosacea improves erythema, symptomatology, and quality of life.

Tan SR, Tope WD.

Division of Dermatologic Surgery, Indiana University School of Medicine, University of Minnesota, USA
J Am Acad Dermatol. 2004 Oct;51(4):592-9. Abstract quote  

BACKGROUND: Persistent erythema and dysesthetic symptoms are typical manifestations of rosacea.

OBJECTIVE: We sought to assess improvement in erythema, symptoms, and quality of life after pulsed dye laser treatment.

METHODS: Sixteen patients with erythematotelangiectatic rosacea participated. Spectrophotometric erythema measurements were taken from the right and left malar prominence; chin; and nasal alae, dorsum, and tip. A questionnaire rating the Dermatology Life Quality Index and symptoms of flushing, burning, itching, dryness, swelling, and skin sensitivity was completed. Treatment was undertaken with the pulsed dye laser at purpuragenic fluences. Measurements and treatment were repeated at 8-week intervals for a total of two treatments.

RESULTS: A statistically significant improvement was observed in symptoms, quality-of-life score, and erythema in all areas with the exception of erythema of the left nasal ala.

CONCLUSIONS: Pulsed dye laser treatment at purpuragenic fluences is a safe and effective treatment for symptomatic rosacea, resulting in a significant improvement in erythema, symptoms, and quality of life.
METRONIDAZOLE  

Once-daily topical metronidazole cream formulations in the treatment of the papules and pustules of rosacea

Mark V. Dahl, MD
Michael Jarratt, MD
David Kaplan, MD
Michael R. Tuley, PhD
Michael D. Baker, BS

Scottsdale, Arizona; Minneapolis, Minnesota; Houston and Fort Worth, Texas; and Kansas City, Missouri

J Am Acad Dermatol 2001;45:723-30. Abstract quote

Background: The papules and pustules of rosacea can be effectively treated with topical metronidazole. The optimal concentrations of metronidazole and optimum frequencies of application are uncertain. Traditionally, twice-daily applications have been advised, based on the pharmacokinetic profile of metronidazole. Once-daily applications may be safer and less expensive, and they may enhance patient compliance.

Objective: We compared the efficacy and safety of 2 commercially available topical metronidazole formulations (0.75% metronidazole cream formulation and 1.0% metronidazole cream formulation) when both were used in a once-daily regimen.

Methods: A multicenter, randomized, investigator-blind, parallel group trial was conducted at 3 separate clinical sites located in 3 US cities. The study enrolled 72 rosacea patients with at least 8 to 50 inflammatory facial lesions (pustules and papules) and moderately severe facial erythema. Patients were randomly assigned to receive either 0.75% metronidazole cream or 1.0% metronidazole cream and instructed to apply the medication once daily for 12 weeks. Patients' lesions were evaluated at baseline and at weeks 3, 6, 9, and 12.

Results: There were no significant differences between treatment groups for any of the efficacy parameters evaluated. The overall median percentage change in lesion count at end point for patients in the 0.75% metronidazole cream treatment group was 62% compared with 60% for the 1.0% metronidazole cream treatment group. The overall percentage change in erythema scores at endpoint for patients in the 0.75% metronidazole cream treatment group was 26% compared with 30% for patients in the 1.0% metronidazole cream treatment group. Regarding physician assessment of global severity, 57% of subjects (20/35) in the 0.75% metronidazole cream group compared with 37% of subjects (13/35) in the 1.0% metronidazole cream group were rated as having a clear to mild condition at end point. Both drugs were well tolerated; there was no significant difference in the number of drug-related adverse events between the two agents.

Conclusion: This controlled trial demonstrates that both 0.75% metronidazole cream and 1.0% metronidazole cream, when used once daily, provide well-tolerated efficacy for moderate to severe rosacea.

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Last Updated January 28, 2008

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