Rosacea is a chronic inflammatory skin disease affecting the central part of face and characterized by erythema, teleangiectasia, papules, pustules and edema. The condition usually occurs in adults, although very rarely children may also be affected (1-4).

Epidemiological data coming from the American and European studies are divergent. Some data report the incidence of rosacea as 1% of the disorders diagnosed by dermatologists, or as 4000-5000 new patients cases per year (1, 2, 5, 6). The disease occurs in both men and women, but according to some authors affects both sexes equally, or much more frequently is observed in women (1, 2). It is worth to stress, that the extremely severe forms of rosacea are seen much more frequently in the male patients (1, 4, 5). Generally, the prevalence of rosacea reported to be 1-10% seems to be the highest among Caucasians of Celtic and northern European origin, occuring more frequently in women of 30-50 years of age (1, 2, 3, 6).

Although the disorder is common in adult population its etiopathogenesis as well as pathophysiology is not entirely elucidated yet. Possible pathogenic roles have been suggested for vascular abnormalities, neurogenic inflammation and altered innate immune response to heterogenous stimuli (2, 3, 7, 8). Genetic and environmental factors are believed to influence the onset and clinical development of rosacea, including immunological, infectious, endocrine, pharmacological, climatic, thermal and dietary triggers (3, 4, 9).

There are numerous triggering factors known, but their exact role remain to be elucidated yet. Among them, dietary factors, such as spicy foods, cheese, nuts, alcohol and hot beverages can exacerbate symptoms of rosacea, but are not considered as the primary causes (1, 3, 4, 7, 10). Apart from these, sun exposure, hot and cold weather, heat, humidity, cosmetics, medications, physical exercises, and emotional stress are recognized as the predisposing factors (1, 3, 9-11). Estonian authors have found that positive family history can be regarded the strongest risk factor for rosacea (9).

Helicobacter pylori is believed to be connected with the development or aggravation of rosacea by the release of inflammatory vasoactive mediators (histamine, leucotrienes, prostaglandines, cytokines, nitrous oxide), but its role remains still controvertial (1, 6).

Demodex folliculorum mites are suggested as another possible trigger of the skin inflammation in rosacea (1, 2, 4). Considerably increased number of mites in the skin and what is more, specific IgG antibodies against Demodex have been shown in rosacea patients (5, 12, 13). Additionally, Demodex mites are found to be a vector for bacteria Bacillus oleronius and its proteins can induce the immune response leading to development of papules and pustules (1, 8). Lately, the results of Whitfeld et al. suggest that in the altered milieu of the rosacea skin the commensal Staphylococcus epidermidis may act as a pathogenic agent and contribute to development of pustular and ocular rosacea (14). Therefore, up till now, actual role of microorganisms in the pathophysiology of rosacea has not been clearly defined. The available data suggest that they may possibly have a rather synergistic role additional to other triggering factors (6).

Although the numerous endogenous and environmental factors seem to be implicated, the exact pathogenic pathways in which these possible triggers are engaged are not entirely recognized. Pathological mechanisms of rosacea are connected with abnormalities of innative immunity, vascular changes, reactive oxygen species released by neutrophiles, inflammatory mediators, ultraviolet radiation and microorganisms (1-3, 15). Abnormal vascular reactivity seems to be the basical phenomenon in pathogenesis and vasodilatation is associated with increased levels of inflammatory mediators, including histamine, prostaglandins and reactive oxygen species (1-3, 15). Dermal extracellular matrix degeneration caused by degradative proteases released by neutrophils can additionally damage the connective tissue around the skin vessels (3). Recent data indicate that dysfunction of the innate immune system may play a central role in the development of vascular abnormalities and skin inflammation in patients with rosacea (2, 3, 10, 16). It is found that rosacea is associated with an exacerbated response by the innate immune system to environmental stimuli by releasing the elevated levels of abnormally processed cathelicidin antimicrobial peptides (1-3, 6, 15-17). It should be stressed that 10-fold higher level of cathelicidin than normal can be found in the facial skin of rosacea patients and almost 1000 times higher levels of kallikrein-5, a protease that activates epidermal cathelicidin (2, 3, 18). It seems that due to its proinflammatory and angiogenic properties cathelicidin LL-37 dysfunction may be considered as the pivotal factor in the pathogenesis of rosacea (4, 17). It is speculated wheather Toll-like Receptor-2 (TLR-2) may be involved in the patophysiological events in rosacea, because its activation can induce production of the kallikrein 5 in keratinocytes (2, 8). A suggested ligand for TLR-2 in the rosacea skin is chitin from the Demodex mites (2, 19).

Neurogenic inflammatory reaction is also being discussed. Some authors believe that rosacea patients are hypersensitive to physiological stimuli causing recurrent flushing of the facial skin (2, 20). In normal dermis the blood vessels, mast cells and sensory nerves are found close together, but a significantly higher number of mast cells have been reported in the skin of rosacea patients (2). So, it is speculated that the mast cells may play a role in regulation of neuroimmunological and neurovascular communication mechanisms in initial stages of rosacea (2).

Clinical manifestation of rosacea is heterogenous with polymorphic lesions and various disease severity observed. The disease usually affects the central part of the face, the forehead, nose, chin and cheeks (1, 2, 4, 21). It is worth to stress that the extrafacial location has been very rarely reported, involving neck, scalp or the chest skin (2, 22). During the chronic course the development of lesions can be observed from early transient flushing, persistent facial redness, teleangiectasia to inflammatory papules and pustules (10, 21, 23). Intermittent or chronic facial edema may also occur resulting occasionally in thickening of skin (1, 2).

There are 3 stages of clinical severity differing morphologically (1-3, 8, 21).

Stage I is characterized by recurrent epizodes of flushing easily triggered by various endogenous or exogenous stimuli. Futher, transient erythema becomes more persistent and teleangiectasia of varying severity develop (2). The patients complain of intense subjective sensations – burning, stinging, itching or dryness of the affected skin (1, 2, 20, 23).

In stage II, the persistent erythema and teleangiectasia on the center of the face with solitary or numerous red papules and pustules can be observed (1, 2). These lesions may be accompanied by lymphedema affecting the entire face as well as the involvement of adjacent skin of scalp, neck and chest (2).

In stage III, additionally to persistent erythema, papules and pustules large inflammatory nodules and hyperplasia of the connective tissue and the sebaceous glands develop (1, 2). That can manifest as diffuse skin thickening and development of inflammatory nodules, especially prominent in phymatous clinical variant of rosacea (1, 2). Involvement of the eyes as well as the psychological complications are common (1, 3, 24).

Taking into consideration the broad diversity in clinical presentation, differences in severity and type of dominating cutaneous lesions, four clinical subtypes of rosacea are proposed: erythematoteleangiectatic, papulopustular, phymatous and ocular with one variant, granulomatous rosacea (25, 26).

Erythematoteleangiectatic type is the frequently observed with its typical symptoms such as flushing, persistent central facial erythema and teleangiectasia developing on the cheeks and nose, becoming more prominent in stages II or III of rosacea (1, 24). Patients may complain of stinging or burning of the face (1, 8). What is more, patients often report that their facial skin is very sensitive to cosmetics and other topical substances (1, 24).

Papulopustular rosacea is characterized by the presence of many erythematous papules and pustules on the skin of the central face based upon the persistent erythema (1, 8, 24). Teleangiectasia, ocular involvement, facial edema can also be seen and men are usually much more affected (1). Ocular involvement is found in more than 50% of patients (1-3, 24).

What is interesting, it may precede the development of facial lesions in about 20% of rosacea patients and in primary ophthalmic rosacea, the skin lesions may be quite discrete (1, 2, 24). Among the ocular symptoms, blepharitis and conjuctivitis are the most frequently seen (1, 2, 5). Blepharitis of various severity manifests as the eyelid margin erythema, with teleangiectasia, scale, crusting, occasionally with secondary streptococcal infections (1). More severe ocular involvement with keratitis, scleritis iritis and hypopyon can also be observed (1, 6). Among them, keratitis is serious condition which may result in corneal ulceration, neovascularization, scarring and permanent damage of eyesight (1, 3). Ocular involvement is usually connected with intense subjective symptoms, such as dryness, burning, itching, foreign-body sensation, sensitivity to light (1, 2). However, there is no correlation between the severity of cutaneous and ocular symptoms (1, 2).

Phymatous rosacea is rare ultimate clinical subtype observed predominantly in men with its onset between 40 and 60 years (1, 24). The most frequently the nose is affected (rhinophyma), occasionally other areas of face, such as chin, forehead, ear or eyelid (1, 2). Patient presents thickened skin with prominent pores and irregular disturbed surface contours based patophysiologicaly on chronic edema and progressive hypertrophy of the sebaceous glands and connective tissue (1, 8). Disfiguring large nodular lesions may cause the nasal passage narrowing resulting in sleep disturbances or apnea (1).

Granulomatous (lupoid) rosacea is a rare variant characterized by disseminated dense, brown red or yellow papules and nodules located on the cheeks, upper and lower lids and periorificial facial skin (1, 4, 24). What is important, upon diascopy, these lesions reveal a yelowish change in colour („apple-jelly”) similar to seen in lupus vulgaris and sarcoidosis (1). This condition has also typical lesions of rosacea, such as persistent erythema, teleangiectases and some more usual papules (2, 4).

Rosacea fulminans (pyoderma faciale) is dramatic variant of rosacea affecting young women (1, 2, 4). The pathogenesis is unclear, but it is suggested that rosacea fulminans may be connected with pregnancy, oral contraceptives, inflammatory bowel disease or some medications (1, 2, 8). Onset of lesions is always sudden, clinical presentation may resemble acne fulminans with large, elevated, firm, sometimes fluctuating nodules and numerous pustules. Lack of comedones and presence of erythema and teleangiectasia are typical features of rosacea and differentiate this condition from acne fulminans (1, 2).