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Rosacea: Pathogenesis, clinical features, and diagnosis

Rosacea: Pathogenesis, clinical features, and diagnosis
Authors:
Lisa E Maier, MD
Yolanda R Helfrich, MD
Section Editors:
Robert P Dellavalle, MD, PhD, MSPH
Cindy Owen, MD
Deputy Editor:
Abena O Ofori, MD
Literature review current through: Sep 2022. | This topic last updated: Mar 17, 2022.

INTRODUCTION — Rosacea is a common, chronic disorder that can present with a variety of cutaneous or ocular manifestations. Cutaneous involvement primarily affects the central face, with findings such as persistent centrofacial redness (picture 1A-C), papules, pustules (picture 1B, 1D-F), flushing, telangiectasia, and phymatous skin changes (eg, rhinophyma (picture 2A-B)). Ocular involvement may manifest with lid margin telangiectases, conjunctival injection, ocular irritation, or other signs and symptoms (picture 3A-B).

The pathogenesis, clinical manifestations, and diagnosis of rosacea will be reviewed here. The treatment of rosacea is discussed separately. (See "Management of rosacea".)

General approaches to the diagnosis of facial erythema, pustular skin lesions, and flushing are also reviewed separately.

(See "Approach to the patient with facial erythema".)

(See "Approach to the patient with pustular skin lesions".)

(See "Approach to flushing in adults".)

EPIDEMIOLOGY — Although generally considered common, assessment of the true prevalence of rosacea is challenging because of the variable clinical manifestations, the existence of other skin disorders with overlapping features, and underdiagnosis [1,2]. A systematic review and meta-analysis of population-based studies from Europe, North America, Asia, Africa, and South America found an estimated prevalence of 5 percent of adults [3]. The majority of studies in the systemic review were from Europe and North America.

Certain demographic factors may influence the likelihood of a diagnosis of rosacea:

Age and sex – Rosacea primarily occurs in adults over the age of 30 years, and the disorder occurs more frequently in females than in males [2-5]. Phymatous skin changes of rosacea are an exception; adult males comprise the vast majority of affected patients (picture 3A-B). (See 'Phenotypes' below.)

Rosacea occasionally occurs in adolescents, a population in which rosacea is often mistaken for acne vulgaris. Rarely, rosacea occurs in children. Children may exhibit all subtypes except phymatous changes, and symptoms may persist into adulthood [6-8].

Impact of skin pigmentation – Although rosacea occurs in all populations, it is often considered to be most common in people with skin types most susceptible to sunburn (eg, individuals with lightly pigmented skin or skin phototypes I or II (table 1)). However, whether this is related to true differences in prevalence or disparities in diagnosis is unclear. Skin pigmentation may mask some of the characteristic manifestations of rosacea, impacting recognition of the diagnosis in patients with moderately to highly pigmented skin [1]. (See 'Skin of color' below.)

PATHOGENESIS — The pathways that lead to the development of rosacea are not well understood [9,10]. Proposed contributing factors include abnormalities in immunity, inflammatory reactions to cutaneous microorganisms, vascular dysfunction, ultraviolet light exposure, and genetic factors.

Immune dysfunction — Abnormalities in both the innate and adaptive immune systems have been proposed to contribute to rosacea:

Innate immune system – The innate immune system plays a key role in the cutaneous immune response to microorganisms and to insults, such as ultraviolet radiation and physical or chemical trauma [11]. Dysfunction of the innate immune system may contribute to the development of chronic inflammation and vascular abnormalities in rosacea. (See "An overview of the innate immune system".)

The process through which aberrations of the innate immune system may contribute to rosacea involves the excessive production of cathelicidin peptides, peptides that have been associated with vasoactive and inflammatory properties [12]. Abnormally high levels of cathelicidin and abnormal forms of cathelicidin peptides have been detected in the facial skin of patients with rosacea [12]:

LL-37 – LL-37 is a cathelicidin-derived antimicrobial peptide generated through kallikrein 5-mediated cleavage of the cathelicidin human cationic antimicrobial protein [13]. Compared with normal skin, LL-37 is more abundant on rosacea-affected skin [12]. LL-37 is proposed to contribute to skin inflammation through activation of the NLRP3 inflammasome [13].

Toll-like receptor 2 – Toll-like receptor 2, a component of the innate immune system that interacts with environmental stimuli, can stimulate release of kallikrein 5 from epidermal keratinocytes. This observation offers a potential explanation for a link between environmental insults and cathelicidin-mediated abnormalities in rosacea [14]. (See "Toll-like receptors: Roles in disease and therapy".)

Mast cells – Mast cells have been found in increased numbers in rosacea-affected skin and are proposed to contribute to cathelicidin-induced inflammation in rosacea [15,16]. Mast cells are a source of cathelicidin and can be activated to produce inflammatory mediators and proteases in response to the active LL-37 form of cathelicidin [16]. Mast cell activation also contributes to the production of mediators that result in angiogenesis and fibrosis [15].

Adaptive immune system – An aberrant adaptive immune response may also play a role in rosacea. In a study that evaluated the inflammatory infiltrate within facial biopsies from patients with rosacea, T cells within the inflammatory infiltrates exhibited a Th1/Th17 T cell polarization profile [17]. Plasma cells were also increased in specimens from patients with rosacea.

Microorganisms — Demodex mites and various bacteria are proposed stimulators for cutaneous inflammation in rosacea. However, the role of these organisms in the pathogenesis of rosacea remains uncertain:

Demodex mitesDemodex folliculorum is a saprophytic mite that resides in sebaceous follicles (picture 4).

Demodex mites can be found on normal skin in almost all adults; however, increased density of Demodex mites in patients with rosacea has been reported in multiple studies [18-21]. A meta-analysis of case-control studies found an association between Demodex infestation and rosacea, with the degree of infestation being more important than the rate of infestation [18].

Demodex mites are also proposed to play a role in ocular manifestations of rosacea; the mites have been found in eyelash follicles and meibomian glands [22].

Helicobacter pylori – Data conflict on whether the prevalence of H. pylori infection is increased in patients with rosacea. A meta-analysis of 14 observational studies did not find a significant association between H. pylori infection and rosacea (odds ratio 1.68, 95% CI 1.00-2.84) nor an effect of H. pylori eradication therapy on rosacea symptomatic improvement (relative risk 1.28, 95% CI 0.98-1.67) [23]. Improvement in rosacea following antibiotic therapy for H. pylori infection may be attributable to anti-inflammatory effects of the antibiotics used for treatment [24].

Small intestinal bacterial overgrowth – The relationship between small intestinal bacterial overgrowth (SIBO) and rosacea is unclear. Increased prevalence of SIBO in patients with rosacea and resolution or improvement of rosacea following rifaximin treatment for SIBO have been reported in small studies [25,26]. In contrast, a population-based study in Denmark did not find an association between SIBO and rosacea [27]. (See "Small intestinal bacterial overgrowth: Etiology and pathogenesis" and "Small intestinal bacterial overgrowth: Clinical manifestations and diagnosis".)

Other bacteriaStaphylococcus epidermidis [28,29], Bacillus oleronius [30], and Chlamydia pneumoniae [31] have been linked to rosacea in a few studies. Other studies suggest that rather than a single pathogenic organism, a disturbance of the microbiome as a whole may contribute to rosacea [32].

Vascular hyperreactivity — Frequent and prolonged flushing is a common feature in rosacea.

The pathways that may lead to neurovascular dysregulation in rosacea are not well understood. One theory proposes that activation of transient receptor potential vanilloids 1 and 4 and transient receptor potential ankyrin 1 (receptors found on primary sensory neuron endings as well as keratinocytes) by triggers of rosacea (eg, extremes of temperature, spices, etc) may stimulate the release of vasoactive peptides that exacerbate rosacea [33,34].

Data conflict on whether rosacea is more common among people with migraines (another disorder proposed to involve vascular dysregulation) [35-39]. (See 'Associated disorders' below.)

Ultraviolet light — Although ultraviolet light has been proposed as a contributor to rosacea through mechanisms such as the promotion of angiogenesis and reactive oxygen species-mediated activation of the innate immune system, the role of ultraviolet light exposure in the pathogenesis of the disorder is unclear [11,40-42]. (See 'Potential exacerbating factors' below.)

Genetics — Individuals with a family history of rosacea may be more likely to develop the disorder [4]. Genetic variations in antigen presentation may contribute to an increased risk of rosacea:

Human leukocyte antigen (HLA) alleles involved in extracellular antigen presentation (HLA-DRB1*03:01, HLA-DQB1*02:01, HLA-DQA1*05:01) have been associated with rosacea [43]. These alleles have also been associated with other autoimmune conditions, such as diabetes and celiac disease.

Rosacea has been associated with a single nucleotide polymorphism (SNP) in an intergenic location on chromosome 6 [43]. This is located near HLA-DRA (HLA class II histocompatibility antigen, DR alpha chain) and downstream of BTNL2 (butyrophilin-like 2). Further studies are needed to understand the role of this SNP in rosacea.

Another proposed risk factor is a polymorphism of the VEGF (vascular endothelial growth factor) gene (+405C/G) [44]. VEGF is involved in vascular permeability, vasodilatation, and angiogenesis.

Others have hypothesized that an inherited variation in the endoplasmic reticulum (ER) stress signaling pathway (one that is more responsive to stimuli such as ultraviolet radiation, heat, and microbes) is contributory. This results in exaggerated vitamin D-independent CAMP (cathelicidin antimicrobial peptide) expression [45]. A specific responsible mutation has not yet been identified.

Further studies are necessary to explore the impact of family history and genetic background on risk for rosacea.

CLINICAL FEATURES — Rosacea is a disorder with multiple clinical manifestations.

Classification — The classification of rosacea has evolved over time. A 2002 report from an expert committee from the National Rosacea Society outlined four distinct subtypes of rosacea: erythematotelangiectatic, papulopustular, phymatous, and ocular rosacea [46]. Since then, increasing knowledge of the pathophysiology of rosacea has favored a view of rosacea as a consistent multivariate disease process with multiple clinical manifestations rather than a disease with distinct subtypes [47,48].

Following recommendations from the global ROSacea COnsensus (ROSCO) panel supporting use of a phenotype-based, rather than a subtype-based, approach to the diagnosis and classification of rosacea, the National Rosacea Society expert committee released an update supporting a similar approach [47,49].

Phenotypes — The phenotype-based approach divides clinical features of rosacea into diagnostic, major, and secondary (or minor) features/phenotypes (see 'Diagnosis' below):

Diagnostic phenotypes:

Centrofacial erythema – Centrofacial erythema manifests as chronic erythema of the nose and medial cheeks (picture 1A-C). Similar involvement of other sites, such as the ears, lateral face, neck, scalp, or chest, occurs occasionally [50]. Centrofacial erythema may be subtle in some patients with moderately to highly pigmented skin [1]. (See 'Skin of color' below.)

Phymatous changes – Phymatous change is characterized by tissue hypertrophy manifesting as thickened skin with irregular contours (picture 2A-B). The nose (rhinophyma) is the most common site of involvement. Less frequently involved sites include the chin (gnathophyma), forehead (metophyma or glabellophyma), and cheeks. Common associated features include prominent sebaceous hyperplasia and oily skin.

Major phenotypes:

Papules and pustules – Inflammatory papules and pustules of rosacea primarily localize to the central face (picture 1B, 1D-F). Inflammation may extend outward beyond the follicular unit to form plaques.

Flushing – Prolonged episodes of flushing, the involuntary occurrence of increased blood flow to the skin, may occur in rosacea. Patients experience a sensation of warmth in the skin that may be accompanied by facial reddening; sweating; or subtle, transient, facial swelling. Certain factors may trigger flushing. (See 'Potential exacerbating factors' below.)

Telangiectasia – Telangiectasias are visible, enlarged, cutaneous blood vessels (picture 5). Telangiectasias are predominantly located on the central face, especially on the cheeks, and may be challenging to visualize in patients with highly pigmented skin. (See 'Skin of color' below.)

Ocular features – Ocular involvement is common in rosacea and may follow, precede, or occur concurrently with cutaneous disease [46]. Prevalence estimates in patients with rosacea range from 6 to 72 percent [22,51]. Ocular features occur in both adults and children and do not appear to have a sex predilection [6,52].

Associated symptoms include tearing, redness, foreign body sensation, burning, itching, photophobia, and blurred vision. Readily apparent physical findings may include eyelid edema and/or erythema, recurrent hordeolum or chalazion, and crusting along the lash line.

Physical examination may reveal telangiectasia of the lid margin and interpalpebral conjunctival injection, redness, and telangiectasia (picture 3A-B). Spade-shaped infiltrates on the cornea, scleritis, and sclerokeratitis may be appreciated on slit lamp examination [22,47]. As many as one-third of patients with ocular involvement may develop corneal involvement; this can range from mild to severe.

Secondary features:

Burning or stinging – Stinging or burning sensations in affected areas are common in rosacea. Skin care products may irritate the skin and aggravate symptoms.

Edema – Facial edema may occur during or after an episode of prolonged erythema or flushing and may persist for days [47]. (See "Pathogenesis, clinical manifestations, and diagnosis of acne vulgaris", section on 'Solid facial edema'.)

Dry appearance of skin – A dry quality to the skin, manifesting as roughness and scaling, is often present.

Potential exacerbating factors — Multiple factors have been anecdotally associated with exacerbations of cutaneous signs and symptoms of rosacea, including:

Exposure to extremes of temperature

Sun exposure

Hot beverages

Spicy foods

Alcohol

Exercise

Irritation from topical products

Psychologic feelings, especially anger, rage, and embarrassment

Certain drugs, such as nicotinic acid and vasodilators

Skin barrier disruption

The relationships between rosacea and some of the factors have been evaluated in clinical studies. Examples include:

Alcohol – An analysis of data reported by over 82,000 adult females in the Nurses' Health Study II found a slight increase in risk for a history of clinician-diagnosed rosacea among participants with alcohol intake compared with participants who denied use of alcohol [53]. Although historically thought to be associated with heavy alcohol consumption, definitive evidence in support of an association between alcohol and the development of phymatous skin changes is lacking [50].

Ultraviolet light – Sun exposure is often cited as an exacerbating factor for rosacea based upon the distribution of lesions on chronically sun-exposed skin; the detection of signs of solar elastosis on skin biopsy specimens; the perceived higher prevalence of the disorder in individuals with skin types most susceptible to sunburn (skin phototypes I and II (table 1)); and associations of ultraviolet exposure with angiogenesis, the production of reactive oxygen species, and activation of the innate immune system related to keratinocyte damage [11,40-42,54].

However, study data confirming an association between all phenotypes of rosacea and ultraviolet radiation are lacking [50]. Less than one-third of patients with rosacea report exacerbations of symptoms with sunlight [50], and a retrospective study in Korea of 168 patients with rosacea found that although high daily sun exposure correlated with increased severity of erythematotelangiectatic disease, it did not appear to have a significant effect on papulopustular, phymatous, or ocular rosacea [55]. In addition, a study of 1000 adults in Ireland found no difference in the prevalence of papulopustular rosacea in subjects with high sun exposure versus those with lower sun exposure [56].

Coffee consumption – Although consumption of hot beverages has been considered an exacerbating factor for rosacea, consumption of coffee may not increase risk for rosacea. Caffeine has vasoconstrictive and immunosuppressive properties that could, theoretically, inhibit rosacea.

An analysis of data from a cohort of over 80,000 adult females in the Nurses' Health Study II supports the theory that consumption of caffeinated coffee does not increase risk for rosacea [57]. The study found 4945 incident cases of rosacea and detected an inverse relationship between increased caffeine intake and risk of incident rosacea (hazard ratio [HR] for highest quintile of caffeine intake versus the lowest quintile of 0.76, 95% CI 0.69-0.84). Moreover, participants who consumed at least four servings of caffeinated coffee per day had a lower risk of rosacea than those who consumed less than one serving per month (HR 0.77, 95% CI 0.69-0.87). There was not a relationship between intake of decaffeinated coffee and rosacea, suggesting an effect of caffeine rather than other components of coffee. There was not a significant relationship between increased caffeine intake from tea or soda and risk for rosacea, which the authors postulated to be related to low consumption of caffeine from these sources.

Smoking – Data from the Nurses' Health Study II suggest that a past smoking history may be a risk factor for rosacea in females [58].

ASSOCIATED DISORDERS — Rosacea may be associated with increased risk for other diseases [59-61]. Further study is necessary to confirm these associations and to determine whether patients with rosacea require increased screening for systemic diseases.

The reasons for observed associations between rosacea and other diseases are unclear. A shared role for systemic inflammation is postulated for the association between rosacea and cardiovascular disease. In addition, dysregulation of the microbiome or abnormal neurovascular and immune responses are common pathways that may lead to rosacea and gastrointestinal, cardiovascular, and neurologic disorders [61-64].

Examples of reported associations include:

Gastrointestinal disease – The strongest link is between rosacea and inflammatory bowel disease [61,65,66]. Modest associations between rosacea and celiac disease and irritable bowel syndrome have also been noted [27].

Components of the metabolic syndrome – Some studies have shown that rosacea can be associated with modest increases in dyslipidemia, coronary artery disease, and hypertension [62,67]. However, several studies, including a large claims database analysis of rosacea patients, did not support an association between rosacea and cardiovascular disease [68,69].

Data from the Nurses' Health Study II suggest that obesity may be a risk factor for rosacea in females [70].

Malignancy – Rosacea has been associated with mild increased risk for thyroid cancer, basal cell carcinoma, and glioma [71,72]. No increased screening for these malignancies is recommended.

Autoimmune disorders – A large, case-control study found an increased risk of autoimmune disorders, including type 1 diabetes mellitus, celiac disease, multiple sclerosis, and rheumatoid arthritis [73].

Psychiatric disorders – Some studies have noted an increased association between rosacea and depression [74].

Neurologic disorders – Rosacea may be associated with an increased incidence of migraine, especially in females over age 50 [35,75]. One large, cohort study noted increased risk for dementia or Alzheimer disease in patients with rosacea [76].

HISTOPATHOLOGY — Specimens from erythematous facial skin exhibiting centrofacial erythema and telangiectasias usually show dilation of superficial blood vessels and a low-grade, perivascular, lymphohistiocytic, inflammatory infiltrate with occasional plasma cells. Solar elastosis is often present.

Histopathologic examination of papular lesions usually reveals prominent perivascular and perifollicular inflammatory infiltrates in the superficial and mid-dermis composed of lymphocytes, neutrophils, and plasma cells. Superficial accumulations of neutrophils are present in pustules. In contrast to acne vulgaris, inflammation is often more perivascular and extends well beyond the follicle [77]. Demodex mites are often detected in follicular orifices.

The histopathologic findings in skin exhibiting phymatous changes include sebaceous gland hyperplasia, follicular plugging, telangiectasias, pronounced dermal thickening and fibrosis, and large amounts of dermal mucin. Increased numbers of factor XIIIa-positive cells may be present in the dermis [78,79].

DIAGNOSIS — Clinical assessment of the patient is usually sufficient for the diagnosis of rosacea. Skin biopsies are not typically necessary. (See 'Skin biopsy' below.)

History and physical examination — The diagnosis can be made based upon an assessment for diagnostic, major, and minor phenotypes with a history and skin examination. In sum, physical changes of the skin (erythema, phymatous change, papules, pustules, edema, and skin dryness) and conjunctiva should be noted, and patients should be asked about symptoms of skin discomfort (eg, burning, stinging), eye discomfort (foreign body sensation, burning, itching, photophobia, and blurred vision), and flushing. (See 'Referral to ophthalmology' below.)

At least one diagnostic phenotype or two major phenotypes are required for diagnosis:

Diagnostic phenotypes:

Fixed centrofacial erythema in a characteristic pattern that may periodically intensify

Phymatous changes

Major phenotypes:

Papules and pustules

Flushing

Telangiectasia

Ocular manifestations (eg, lid margin telangiectases, interpalpebral conjunctival injection, spade-shaped infiltrates in the cornea, scleritis, sclerokeratitis)

Secondary phenotypes:

Burning or stinging

Edema

Dry appearance

Skin of color — The risk of misdiagnosis may increase with increasing skin pigmentation, as melanin may mask features such as erythema and telangiectasias (picture 1B). Careful attention to other features of rosacea, such as facial stinging or burning sensations, flushing, edema, dry-appearing skin, and papules and pustules, can aid with diagnosis of rosacea in patients with highly pigmented skin [1].

Additionally, diagnostic techniques such as dermoscopy and diascopy may be of benefit [1]. Dermoscopy may enable visualization of telangiectasia. Subtle erythema may be identified with diascopy (pressing a glass microscope slide against the skin to assess for blanching), as the skin will blanch if erythema is present. Photographing patients on a dark blue background may also make erythema more apparent [1].

Skin biopsy — The cutaneous histopathologic findings in rosacea are nonspecific, and skin biopsies are rarely indicated. When the diagnosis is uncertain, biopsies may be performed to rule out other disorders or to provide support for a diagnosis of granulomatous rosacea.

REFERRAL TO OPHTHALMOLOGY — Patients who have ocular symptoms or who are found to have visible signs suggestive of ocular involvement should be referred to ophthalmology for further evaluation. (See 'Phenotypes' above.)

DIFFERENTIAL DIAGNOSIS — Multiple skin conditions have clinical features that resemble features of rosacea.

Centrofacial erythema — Facial erythema can occur in a wide variety of disorders. (See "Approach to the patient with facial erythema".)

Examples of conditions exhibiting centrofacial erythema include:

Sun-damaged skin – Telangiectasia may occur as a manifestation of sun-damaged skin. Common associated features include dyspigmentation and skin wrinkling. In contrast to rosacea, which primarily affects the central face, sun damage is often most evident on the lateral face and neck (picture 6). The presence of other characteristics of rosacea, such as persistent facial erythema and frequent flushing, also support a diagnosis of rosacea. (See "Photoaging".)

Seborrheic dermatitis Macular erythema and scale involving the perinasal area is a common finding in seborrheic dermatitis (picture 7A-B). A greasy quality to the scale and involvement of other sites, such as the scalp, retroauricular skin, and brow, suggest this diagnosis. Coexistence of seborrheic dermatitis and rosacea is not uncommon. (See "Seborrheic dermatitis in adolescents and adults".)

Acute cutaneous lupus erythematosus – The centrofacial redness in rosacea may be confused with malar erythema of systemic lupus erythematosus, particularly in patients who lack papulopustular lesions (picture 8A-B). In acute cutaneous lupus erythematosus, the color of the skin often has a violaceous quality and may show a more abrupt cutoff, especially at the lateral margins (resembling a butterfly wing). (See "Overview of cutaneous lupus erythematosus", section on 'Acute cutaneous lupus erythematosus'.)

Serologic testing for antinuclear antibodies in all patients with centrofacial erythema is not indicated. Patients should be clinically assessed for signs or symptoms of systemic lupus erythematosus; the need for laboratory work-up should be based upon the presence of mucocutaneous or systemic findings suggestive of this disorder. (See "Clinical manifestations and diagnosis of systemic lupus erythematosus in adults".)

Skin biopsies of acute cutaneous lupus erythematosus usually demonstrate interface dermatitis characterized by necrotic keratinocytes, intraepidermal lymphocytes, basal vacuolar degeneration, colloid bodies, and melanin incontinence. Although biopsies of rosacea may exhibit occasional intraepidermal lymphocytes and pyknotic keratinocytes, true interface dermatitis does not occur in rosacea [80]. Differences in the likelihood of other pathologic findings have also been reported [80].

Dermatomyositis – Dermatomyositis is an idiopathic, inflammatory disorder that can affect skin and muscle tissue. Violaceous erythema involving the periorbital skin and central face can occur (picture 9A-B). Examination for muscle weakness and other cutaneous signs of dermatomyositis is useful for diagnosis. Like acute cutaneous lupus erythematosus, skin biopsies reveal features of an interface dermatitis. (See "Cutaneous dermatomyositis in adults: Overview and initial management", section on 'Overview of clinical features' and "Clinical manifestations of dermatomyositis and polymyositis in adults", section on 'Skin findings in dermatomyositis'.)

Other flushing disorders – In addition to rosacea, facial flushing may occur in a wide variety of disorders. Examples include medication reactions, menopausal hot flashes, neurologic disorders, carcinoid syndrome, mastocytosis, pheochromocytoma, medullary thyroid carcinoma, and serotonin syndrome. The possibility of such disorders should be considered in patients who present with flushing. (See "Approach to flushing in adults".)

Papules and pustules — The following papular and pustular disorders share features with rosacea:

Acne vulgaris – Acne vulgaris is the most common skin disorder in the differential diagnosis of papulopustular rosacea (figure 1). Individual inflammatory lesions of the two disorders may appear clinically identical. A key distinguishing feature between acne vulgaris and rosacea is the absence of comedones in rosacea (picture 10). A prominent centrofacial distribution also suggests a diagnosis of rosacea. Acne vulgaris and rosacea coexist in some patients. (See "Pathogenesis, clinical manifestations, and diagnosis of acne vulgaris".)

Topical corticosteroid-induced acneiform eruptions – Topical corticosteroid use can result in the appearance of monomorphic, inflammatory papules on facial skin (picture 11). The patient history is valuable for diagnosis. Topical corticosteroids can also cause redness and burning skin sensations as a consequence of overuse. (See "Topical corticosteroids: Use and adverse effects", section on 'Cutaneous'.)

Periorificial dermatitis – Periorificial dermatitis commonly presents with numerous small papules with fine scale in the perioral area (picture 12). Sparing of the skin adjacent to the vermillion border of the lip is characteristic. Lesions may also occur in periorbital and perinasal distributions (picture 13). In patients who have erroneously attempted to treat the eruption with topical corticosteroids, acneiform eruptions may also be present.

Keratosis pilaris rubra faciei – Persistent, rough, 1 to 2 mm, follicularly based papules on the face can occur as a manifestation of keratosis pilaris in children, adolescents, and young adults (picture 14). The condition presents with a rough, red, symmetrical, triangular patch of skin on each cheek that lacks papules or pustules. Typical keratosis pilaris may also be present on the backs of the arms and fronts of the thighs (picture 15A-B).

Demodicosis (Demodex folliculitis) Demodicosis can present with numerous inflammatory papules on the face and is difficult to distinguish from papulopustular rosacea on clinical examination (picture 16) [81]. Potassium hydroxide (KOH) preparation, skin surface sampling with cyanoacrylate adhesive (superglue) [20], or skin punch biopsy may demonstrate numerous Demodex mites (picture 4). However, Demodex mites are also commonly detected in rosacea and in normal skin. Therefore, finding Demodex mites in a skin surface sample or skin biopsy specimen does not necessarily indicate demodicosis. (See "Infectious folliculitis", section on 'Demodex folliculitis'.)

Immunocompromised patients are at increased risk for this disorder. Multiple therapies have been reported to be effective for demodicosis in individual patients. Examples include topical permethrin, topical crotamiton, oral ivermectin, and topical or oral metronidazole [81-85]. (See "Office-based dermatologic diagnostic procedures", section on 'Potassium hydroxide preparation'.)

RELATED DISORDERS

Granulomatous rosacea — The relationship of granulomatous rosacea to other presentations of rosacea has been debated. Although previously recognized by the National Rosacea Society as a possible variant of rosacea [46], granulomatous rosacea was not mentioned in a 2017 update [47].

Granulomatous rosacea presents with yellow-brown or pink, persistent papules that are usually distributed on the cheeks and periorbital or perioral skin; background facial erythema and flushing are often absent. A granulomatous infiltrate is characteristically present on biopsy [50]. Granulomatous rosacea is characterized by the presence of epithelioid granulomas adjacent to hair follicles. Caseation is present in approximately 10 percent of cases [86].

The features of granulomatous rosacea overlap with other disorders described in the literature that present with numerous small, monomorphic facial papules and granulomatous infiltrates on biopsy. In adults, lupus miliaris disseminatus faciei, which presents with multiple red-brown 2 to 5 mm papules on the face and caseating granulomas on biopsy, has been reported [87-89]. Rarely, B cell lymphomas and chronic lymphocytic leukemia present with facial cutaneous lesions that resemble granulomatous rosacea or phymatous skin changes of rosacea [90].

In addition, granulomatous facial dermatoses identified as childhood granulomatous periorificial dermatitis [91-93] and facial Afro-Caribbean childhood eruption [94,95] have been described in children. The status of these disorders as independent entities or forms of rosacea is unclear.

Pyoderma faciale (rosacea fulminans) — The relationship of pyoderma faciale (also known as rosacea fulminans or rosacea conglobata) to rosacea is also uncertain [46]. Patients present with intensely inflammatory, purulent facial plaques and nodules with draining sinuses on a background of erythema (picture 17) [96,97]. A history of rosacea may or may not be present. Young females are most commonly affected.

Solid facial edema (Morbihan disease) — Solid facial edema is a poorly understood entity that has been linked to rosacea and acne vulgaris but also can arise in patients with no prior or concurrent history of either condition [98]. It is characterized by persistent erythema and firm, nonpitting edema, primarily affecting the upper two-thirds of the face.

It is thought to be associated with fibrotic induration of the lymphatic vessels of the face, and skin biopsies, while not diagnostic, have exhibited variable findings, including dilated blood vessels and lymphatic vessels, perifollicular fibrosis, perivascular and perifollicular infiltration of lymphocytes, and increased number of mast cells [99]. One hypothesis is that recurrent episodes of vascular dilation and inflammation associated with rosacea can lead to eventual fibrosis and damage of blood and lymphatic vessels [98]. However, it should be noted that some patients with solid facial edema have no prior history of rosacea or other facial skin disease.

Neurogenic rosacea — A small subset of patients with typical skin findings of rosacea may experience prominent neurologic symptoms, especially burning or stinging pain [100,101]. Typically, the dysesthesia is out of proportion to the inflammation visible on examination. Rosacea findings are primarily erythema and flushing, but facial edema and papules or pustules can be seen as well.

Common triggers include heat and sunlight [100,101]. Patients often report improvement with cooling, elicited by fans or with cold water or ice applied to the skin or by holding ice cubes in the mouth [100].

Concomitant neurologic or neuropsychiatric conditions may be common. In a case series of 14 patients with neurogenic rosacea, neurologic or neuropsychiatric conditions were present in 43 and 50 percent, respectively [100]. Associated conditions included complex regional pain syndrome, essential tremor, depression, and obsessive-compulsive disorder. A history of headaches was also common, occurring in 71 percent of patients.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Rosacea".)

SUMMARY AND RECOMMENDATIONS

Epidemiology – Rosacea is a common skin disorder that typically occurs in adults. Rarely, rosacea occurs in children. (See 'Epidemiology' above.)

Pathogenesis – The pathogenesis of rosacea is poorly understood. Factors such as abnormalities in the innate immune system, inflammatory reactions to cutaneous microorganisms, ultraviolet radiation exposure, vascular hyperreactivity, and genetics have been identified as potential contributing factors. (See 'Pathogenesis' above.)

Clinical features – Persistent centrofacial redness, phymatous skin changes, papules, pustules, flushing, telangiectasia, burning or stinging sensations, cutaneous edema, and dryness are potential cutaneous manifestations of rosacea. Ocular abnormalities may also occur. (See 'Clinical features' above.)

Diagnosis – In most patients, clinical assessment is sufficient for diagnosing rosacea and excluding other disorders that may resemble rosacea (figure 1). Skin biopsies are rarely indicated but can be useful in cases in which another disorder with specific histopathologic findings is suspected or for supporting a diagnosis of granulomatous rosacea. (See 'Diagnosis' above and 'Differential diagnosis' above.)

The appearance of centrofacial erythema and telangiectasias may be subtle in patients with highly pigmented skin. Careful attention to other features of rosacea and techniques such as dermoscopy and diascopy may aid with diagnosis of rosacea in patients with highly pigmented skin. (See 'Skin of color' above.)

Ocular involvement – Ocular involvement may present independently or in association with cutaneous manifestations of rosacea. Patients may exhibit features such as lid margin telangiectases, conjunctival injection, and ocular irritation. Patients with signs or symptoms of ocular rosacea should be referred to an ophthalmologist for further evaluation. (See 'Referral to ophthalmology' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Mark V Dahl, MD, who contributed to an earlier version of this topic review.

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References