Rosacea

Spread of the disease

According to the National Rosacea Society, as of 2018, 415 million people worldwide suffer from this disease, characterized by redness and vasodilation on the skin of the face^[1] in the^[1]. Rosacea affects up to 15% of certain populations, especially in the light-skinned Caucasian^[2].

For example, according to data for 2018, in Estonia rosacea is diagnosed in 22% of the population, in Sweden - in about 10% of the population. In the U.S., among all dermatoses, pink eels account for about 10%^[3].

According to The Acne and Rosacea Society of Canada for 2021, more than three million Canadians live with rosacea. According to NRS in the United States, the number of such people is approximately 16 million people.

Most often, rosacea is diagnosed in people with light and sensitive skin. As of 2022, only 4% of rosacea patients are of African, Hispanic or Asian descent.

In women, it occurs on average by a third more than men.

More often, rosacea is affected by people of the 1st and 2nd phototypes with sensitive skin. At the same time, the clinical picture of the disease in most cases manifests itself in the third or fourth decade of life.

Rosacea usually occurs in patients aged 30-50 years, but can occur in children with a family history of rosacea, persisting and progressing into adulthood.

At the same time, most people do not even suspect this disease.

Rosacea, cuperosis and acne

For the first time, the French doctor Guy de Chaliac studied and described this disease back in the XIV century. He also introduced the term "cuperosis" into medical use. But in parallel, this disease was called "Pustule de vin," which translates as "acne from wine." It was believed that it was the use of alcohol that led to the formation of pink eels. 

In 1812, the English dermatologist Thomas Bateman proposed renaming the disease rosacea (rosaceus), since in Latin rosaceus it is translated as pink (meaning color) or made of roses. Thus, this term most accurately characterizes the symptomatic manifestation of the disease. Today, all three names are actively used, cuperosis is predominantly in cosmetology, and rosacea or pink acne is in medical practice^[3].

There are two points of view. According to one of them, cuperosis and rosacea are different diseases. This approach is argued by dissimilar symptoms and the fact that cuperosis is allegedly associated precisely with vasodilation, and rosacea - with skin changes, that is, the appearance of inflammatory elements. In this case, it is said that cuperosis is not a dermatological, but a generally accepted cosmetological term that promotes sales of cosmetology products. He describes a condition characterized by persistent redness of the skin of the face and the appearance of a capillary mesh (telangiectasias) on it mainly in the nose, cheekbones and cheeks.

Other doctors believe that this is one disease that can combine these two conditions - both the primary vascular disorder of the skin and the disease of the epidermis, which is accompanied by a malfunction of the sebaceous glands.

Others believe that the main difference between acne and rosacea is the presence of open and closed comedones. Black dots, "favorite" places of accumulation of which on the nose, cheeks, chin and T-zone - an open form of the disease. If the face is dominated by white greasy corks under the skin, this is a closed form of comedones. And this pathology is undoubtedly acne. Such a clinical picture is not at all characteristic of rosacea^[4]

Symptoms and 4 forms of rosacea

The author of the book "Acne" Wiliam Danny in the early 2020s gave the following definition: "Rosacea is simultaneously four processes:

• damage to collagen by ultraviolet light,
• blood accumulation in dilated capillaries,
• fibrosis and
• inflammation in the pustules. "

It often happens that an animal - demodex lives in pustules.

Rosacea is characterized by repeated episodes of redness along with other skin manifestations, usually capturing the center of the face. In the early stages of rosacea development, patients may experience only episodes of facial redness. In later stages, persistent erythema (Greek ἐρυθρός - red, limited intense redness of the skin due to dilation of the dermal vessels), telangioectasia (persistent dilation of small vessels of the skin) and/or intermittent papules (nodules located above the level of the skin) and pustules (blisters with pus) may appear.

In men, the nose noticeably turns red and inflamed. This symptom occurs because sebaceous glands become inflamed on the nose and old skin cells accumulate, which entails a clear change in color.

Long-term disease is characterized by hypertrophy of the middle layer of the skin with increased production of elastin fibers - over time, these fibers are replaced by connective tissue and fibrosis (lat. Fibrosis) begins to form - growth of connective tissue with the appearance of scar changes, which occurs, as a rule, as a result of chronic inflammation. It is considered as a reaction of the body aimed at isolating the focus of inflammation from surrounding tissues and systemic blood flow.

Externally, this is a tuberous skin structure with persistently dilated pores and vessels^[5]. Sebaceous glands are activated, resulting in acne (Acne rosacea) and hyperkeratosis (thickening of the skin)

There are three stages of development of pink eels^[3].

At the first stage, the skin acquires an unstable red tint, which periodically occurs, as a rule, in the cheek area, and then disappears without a trace. However, over time, closer to the beginning of the second stage of rosacea development, the situation worsens - "vascular stars" appear on the epidermis, which signal persistent vasodilation.

This suggests that they no longer narrow, as a result of which the blood does not move at the desired speed, the tissues do not receive enough nutrients, and the old products of decay and metabolism are not properly excreted. If you seek help from a dermatologist at the stage of temporary redness of the skin, you can avoid the appearance of "stars" and restore the nutrition of the vessels.

At the second stage, the patient develops rashes, swelling of the face, nodules, inflammatory elements, small pustules begin to form. This is due to decreased skin immunity. Also, painful sensations may appear in the eye area, in particular - burning, redness of the eyelids, tear, etc. In this case, only a complex treatment involving the administration of drugs can improve the situation.

At the third stage of development, which is quite rare, tumor neoplasms (rhinophyma) appear in the forehead, nose, chin, eyelids, as well as in the auricles.

In the painting "Portrait of an Old Man with a Grandson," Ghirlandayo painted the most frequent complication of rosacea - nasal tissue overgrowth - rhinophyma.

The following forms are distinguished:

• rhinophyma - nose, as in the picture;
• metophyma - thickening of the forehead skin;
• blepharophyma - thickening of the eyelids;
• otophyma - growth of the earlobe;
• gnatophyma - thickening of the chin skin.

The skin of the face acquires a persistent pink color, can annoy burning (as in the second stage).

According to these clinical characteristics, rosacea is divided into four main forms:

• erythematous-telangioectatic (the most common species characterized by dilated blood vessels, redness and inflammation). Tidal erythema, the duration of which ranges from several minutes to several hours. Accompanied by a feeling of heat or heat, disappears without a trace. Located in the central part of the face and nasolabial folds. In the future, against the background of persistent erythema, capillary telangioectasias are formed - branching, intertwining vessels of bright or dark red color.

• papular-pustular (acne on the face, which can cause swelling and formation of pustules with white heads). Against the background of erythema and diffuse infiltration, pink-red papules with a diameter of 3-5 mm appear. With further progression of the disease, many nodules undergo suppuration, resulting in pustules 1-5 mm in diameter with yellow or greenish-yellow content, which are prone to grouping, especially in the nose, nasolabial folds and chin. There is a pronounced swelling of the face, especially in the eyelid area, narrowing of the eye gaps. Rashes can pass to the front surface of the neck and even the chest.

• phimatous (skin compaction, sometimes on the nose. Some people with this type of rosacea may also develop rhinophyma. This is a very rare occurrence - usually found in men after the age of 60). In chronic course, it is possible to form inflammatory nodes, infiltrates, tumor-like growths due to hyperplasia of sebaceous glands of connective tissue and an abundance of persistently dilated vessels. Further development of the disease in men in about 10% of cases is transformed into rhinophyma (thickening of the nasal tissues with sebaceous gland hypertrophy, vascular neoplasm and enlargement of the organ).

Rhinophyma

It is possible to develop otophyma (damage to the earlobe), gnatophyma (damage to the chin skin), metophyma (pillow-like thickening of the forehead skin^[6].

Ocular rosacea

ophthalmorosacea, ocular rosacea (the area around the eyes becomes inflamed^[7].

The pathophysiology of eye damage in 2024 is not yet completely clear. It is known that the inflammatory and immune responses of the body to the effects of various triggers play a key role. This is confirmed by research - scientists have identified an increase in the concentration of tear fluid IL-1α, collagenase-2, an increase in the activity of matrix metalloproteinase-9 in patients with ophthalmorozacea. Inflammatory cytokines destroy the corneal epithelium, dissolve collagen and other stroma substances, contributing to a change in the biomechanics of the cornea^[8].

Ophthalmorosacea may occur in isolation as an independent disorder or in combination with skin manifestations. The process is most often bilateral - both eyes are affected at the same time. Common nonspecific symptoms associated with damage to the corneal epithelium and conjunctiva are burning, tingling, photosensitivity, foreign body sensation.

For an objective assessment of dry eye syndrome, perform a Schirmer test or use questionnaires such as OSDI (Ocular Surface Disease Index). Another disorder characteristic of ocular rosacea is dysfunction of the meibomian glands, or "posterior" blepharitis. It occurs in 92% of cases due to keratinization and sealing of the terminal ducts. Its signs: chalazion - "inner" barley, conjunctivitis, crusts and scales of the ciliary edge of the eyelid with the formation of couplings around the eyelashes, uneven edge of the eyelid, telangioectasia.

During examination, you can gently press on the eyelid - a thick secret will be released during the pathology of the meibomian glands. Eyelid involvement results in accelerated tear film rupture time and dry eye syndrome.

Also, in some patients, visual acuity may decrease. Causes - spot and marginal keratitis, infiltrate or corneal ulcer. The clinical picture depends on the severity of the disease. Signs of different severity of ophthalmorozacea:

• Mild - blepharitis
• Mild to moderate blepharitis and conjunctival injection
• Moderate to severe - corneal lesion with spot keratitis, infiltration, ulcers and vascularization
• Severe - keratitis with the threat of perforation or scleritis.

Patients may simultaneously have symptoms of several forms of the disease or individual signs that are not characteristic of a certain form of rosacea. The severity of symptoms often varies between exacerbations and periods of remission.

Pathogenesis: mechanisms of occurrence and course of rosacea

Dysregulation of the immune system and increased expression of catelicidin

For 2017, the exact pathogenesis of rosacea was unknown. Given the higher incidence of individuals of northern European origin, a hypothesis has been put forward about the genetic etiology of the disease, although a specific gene has not yet been found. For 2017, it is believed that rosacea is the result of dysregulation of the immune system, abnormal conduction of nerve impulses from the vasculature and dysbiosis, the combination of which ultimately leads to hypersensitivity and inflammation of the skin.

Possible molecular mechanism of rosacea development, Kenshi Yamasaki et al. J Dermatol Sci. 2009 Aug.

In patients with rosacea, innate immunity is impaired. These disorders result in abnormal release of inflammatory cytokines and antimicrobial peptide (AMP) response. Skin affected by rosacea is characterized by significantly more pronounced expression of catelicidin compared to healthy skin^[9]. Catelicidin is an AMP expressed by white blood cells and epithelial cells, and it plays an important role in antibacterial protection of the skin.

With rosacea, the activity of antimicrobial peptides of cathelicidins increases 10 times, and the level of peptidase - 10 thousand times! - said in 2021 Elena Arabiyskaya, dermatologist, cosmetologist, doctor of medical sciences^[10]

The active form of catelicidin, LL-37 is the cleavage product of the molecule by the serine protease kallikrein-5 (KLK5)^[11]. In rosacea patients, the LL-37 and KLK5 molecules are different from healthy skin molecules. These differences lead to pathological changes, including enhanced leukocyte chemotaxis, vasodilation, angiogenesis, and extracellular matrix deposition.

The peptide is LL-37 active in cells of the middle layer of the epidermis - keratinocytes, as well as in salivary and sweat glands. The main function of LL-37 is protective: cathelicidin exhibits an antibacterial, antiviral and antifungal effect. He is also involved in the processes of rapitalization (wound healing).

However, despite the positive nature of catelicidin, which protects our skin from infectious agents and damage, its excessive activity can harm. The fact is that catelicidin is involved in processes that are very undesirable in the context of the described problem:

• development of chronic inflammation,
• angiogenesis - the process of formation ("germination") of new vessels,
• reconstruction and transformation of skin cells^[12].

Showing excessive activity, catelicidin no longer helps to protect and heal the skin, but causes harm to it - after all, it acts as a factor of constant irritation.

Increased number of TRP receptors in the skin

Abnormal nerve impulses also play a role in the pathogenesis of rosacea. The skin and nervous system are not only connected, but also interconnected. In the case of rosacea, there are certain features of their interaction.

There are so-called transient receptor potential (TRP) cationic channels in the body - an important system that plays a role in the pathogenesis of rosacea. They are involved in vascular regulation, pain perception, and inflammation.

Activation of TRP channels leads to the release of mediators of neurogenic inflammation and pain - substance P and peptide. These vasoregulatory neuropeptides are the most important mediators that cause prolonged redness on the skin, characteristic of rosacea.

The receptors that are located on these channels are formed by special nerve fibers and due to activation by heat, cold, ethanol, inflammatory conditions (for example, the addition of infection or the development of allergic reactions) transmit an impulse to keratinocytes. In people with rosacea, the response of these receptors explains the particular sensitivity of the skin. Scientists have found that in skin affected by rosacea, these receptors are present in greater numbers compared to healthy skin^[13].

Heat and other factors, including nutritional factors, stimulate the cationic channels of the transient receptor potential^[14]. Stimulation of these channels initiates a pro-inflammatory cascade of responses. TRP receptors are expressed by both sensory nerve fibers and keratinocytes.

Glazko Irina Ivanovna, Head of the Department of Aesthetic Rehabilitation, FSBI SSC FMBC named after A.I. Burnazyan FMBA of Russia, 2023

Neurotransmitters released in response to triggers stimulate the synthesis of proinflammatory cytokines by immune system cells, which trigger the process of inflammation manifested as characteristic symptoms of rosacea - erythema, telangiectasias, papules and pustulesNEUROGENIC INFLAMMATION AS A CAUSE OF ROSACEA DEVELOPMENT AND THERAPEUTIC TARGET.

Demodex ticks

Main article: Demodex folliculorum

In addition, it is believed that microorganisms play an etiopathogenetic role in rosacea, although their significance has yet to be determined. A number of studies have recorded differences in the microbial composition of the skin of patients with rosacea and healthy people. In particular, patients with rosacea have a high concentration of Demodex folliculorum, the saprophytic mites that pierce the cells lining the hair follicle and absorb the contents and sebum.

The cell membrane components of Demodex mites are believed to activate toll-like receptors-2 (TLR2), which enhance the expression and activity of KLK5^[15]. However, this tick is not considered the only likely causative agent, as one of the studies showed that a decrease in colonization of D. folliculorum by topical antibiotics did not lead to a corresponding decrease in^[16].

Demodex folliculorum tick

In a number of rosacea patients, demodex destruction alleviates rosacea symptoms, probably preventing the formation of pro-inflammatory cytokines^[17].

Bacteria: Bacillus oleronius, Staphylococcus epidermidis

Since antibiotics were used in the treatment of rosacea, the researchers suggested that bacteria could be an etiological factor. Bacillus oleronius, a stationary Gram-negative bacterium isolated from Demodex mites, has been shown to induce antigenic proteins in patients with some forms of rosacea^[18][19]. Under the action of B. oleronius, neutrophils strongly produced matrix metalloproteinase (MMP) -9, tumor necrosis factor and IL-8, stimulating a sustained inflammatory response even in people without rosacea^[13][20][21].

Other studies have looked at the role of Staphylococcus epidermidis (Epidermal staphylococcus), a commensal bacterium. In healthy skin, S. epidermidis produces AMPs that help prevent diseases caused by pathogenic bacteria. However, studies have shown that when placed on skin with rosacea, S. epidermidis produces specific virulence factors leading to activation of the TLR2 and inflammatory cascade of katelicidin-KLK5#^[13]

In a 2019 publication^[22] cited a possible association of rosacea with chlamydia pneumonia - an infectious-inflammatory process in the lungs caused by obligate intracellular bacteria of the genus Chlamydia and Chlamydophila. Chlamydia pneumonia is characterized by respiratory manifestations (rhinitis, tracheobronchitis), unproductive cough, subfebrile and febrile fever, extrapulmonary symptoms (arthralgia, myalgia).

Bacillus olenorium and Escherichia coli were mentioned in the same series. Undiagnosed and advanced GI diseases can lead to microorganism dysbiosis.

Endocrine disorders, genital dysfunction, stomach and intestinal diseases, hypovitaminosis, meteorological effects

According to other sources (Dr. Serrano, developer of the method of pilling with azelaic acid, see below, 2018^[23], the development of rosacea is based on an increased sensitivity of the facial vessels to various influences. The development of this angiopathy is facilitated by endocrine disorders, genital dysfunction, chronic diseases of the stomach and intestines, vegetative vascular dystonia, hypovitaminoses (A, E, B), meteorological effects.

Due to constant venous stagnation and hypoxia, protein-synthetic processes in connective tissue are activated. Dermal hypertrophy occurs, and with it the function of the sebaceous glands increases. The skin acquires a bluish color, nodularities of different magnitude, separated by furrows, marked by gaping mouths of sebaceous glands with comedones (novolat. acne comedonica - a type of cyst formed during blockage of the mouth of the hair follicle with horny masses (collapsed epithelium in a mixture with thick lard) in hyperkeratosis) and telangiectasias (nodules located above the skin level).

Other experts^[24]indicate possible causative agents of the disease - enhancement of the taste of sodium glutamate, food and liquid over 60 ˚S and even the use of halogens (for example, fluoride in toothpaste) - all this contributes to vasodilation and can lead to disease or exacerbate it.

In addition, a different role is assigned to biologically active substances (hereinafter referred to as BAVs), which are synthesized in immunocompetent cells (macrophages, mast cells) - such cells synthesize a huge number of inflammatory mediators. For example, bradykinin and histamine. Bradykinin is a mediator of inflammation, which is precisely responsible for redness of the skin. The excess amount of this mediator in the tissues leads to persistent dilation of small vessels, swelling and the formation of red skin color. But why an excessive amount of bradykinin is formed in this zone, medicine does not know to this day. It can be assumed that the release of an increased number of BAVs occurs under the influence of stimuli that come from the central nervous system (hereinafter - the CNS), but which ones and why this happens is also unclear. One thing is clear - having received stagnation, we get the formation of inflammation and small nodules with vesicles. If the inflammation in the tissues is long, then their partial sclerosis occurs - the same hyperproduction of elastin fibers. As a result, the case ends with^[25] fibrosis^[25].

Some of the possible causes of the disease are diseases of the gastrointestinal tract, especially the hepatobiliary system^[26].

"All foods that irritate the gastrointestinal mucosa cause the vagus and then trigeminal nerve to agitate. It, in turn, extends irritation to the central face zone and gives a signal to expansion of vessels", - the dermatovenerologist and the beautician Natalya Koltunova, the doctor of higher category said in 2021^[27].

In 2021, it was mentioned that in the overwhelming majority of cases, the cause of rosacea is hypoacidity (low acidity of gastric juice)^[28].

In 2024 , it was mentioned that the presence of intestinal diseases (gastritis, ulcer, etc.) often affects the manifestation of vessels on the face.

Fatty liver disease

The link between rosacea and fatty liver disease was discovered in a 2017 study published in the Journal of the American Academy of Dermatology.

Helicobacter

Another theory linking rosacea to gastritis explains the development of the disease under the influence of a bacterium considered by some to be the culprit of gastritis - helicobacter.

Trigeminal nerve dysregulation

Ветви тройничного нерва показаны жёлтым

By 2021, some scientists in their scientific works pay attention to the question of the dependence of the skin condition on the nervous regulation of the trigeminal nerve. Abnormalities in this regulation can occur either without neoplasms and without lesions of the trigeminal nerve in the region, brain or have lesions in the frontal, maxillary and mandibular branches. In the context of the skin condition, the maxillary branch plays a large role, as it has a branch that performs innervation (supply of organs and tissues with nerves) of the skin of the face.

Why dysfunction occurs in the trigeminal nerve structure:

• herpes nerve lesion,
• the manifestation of old injuries, damage to the skin,
• impaired facial soft tissue mobility,
• operational intervention,
• infectious disease.

Carefully repaired facial arteries

Similarly, the condition of the skin is affected by disorders in the cervical spine, because the first four vertebrae of this segment provide innervation of the skin and muscles.

You can get rid of an unpleasant condition by osteopathic practices applicable to the cervical spine and the places where the trigeminal nerve exits. Working with such patients is not easy, since maintaining a stable result is quite difficult due to many reasons. Some foods, such as cottage cheese, cheese, milk, confectionery, chocolate, can affect the treatment process.

Another important point in cervical spine repair is the combination of recovery processes with exercise therapy or gymnastics, which can be developed by both an experienced exercise therapy doctor and an experienced osteopathic doctor or therapist.

Osteopathic, as well as manual therapy, are inherent in "soft" techniques for working with the cervical spine, improving tissue function, trophia and restoring the functions of nerve endings, which leads to an improvement in the condition of the skin.

It is argued that osteopathy can have an effect on the skin, as it has similar experience in working with rosacea and gives good results^[29] to^[30].

Other possible causes

The development of the disease is associated with the influence of other factors:

• angioneurosis due to dysfunction of the autonomic, central nervous and endocrine systems, functional insufficiency of the facial vein;
• dysregulation of the cerebral influence on the blood vessels of the skin of the face and weakness in the drainage of the blood and lymphatic vessels of the skin of the face;
• pathology of the endocrine system (exacerbation of the disease during menopause, pregnancy, before menstruation).

Trigger factors that increase symptoms

Individual facts say that there are many trigger factors that can exacerbate the symptoms of rosacea. These include:

• high temperature,
• direct sunlight,
• spicy food (contains capsaicin, which enhances the effect of vasodilation),
• alcohol consumption,
• exercise,
• as well as emotions such as anger and embarrassment.

Some of these triggers, such as high temperature, act directly to cause vasodilation. Other factors activate various mechanisms that eventually lead to inflammation of the skin.

Ultraviolet radiation and vitamin D excess

Exposure to direct sunlight is one of the most commonly mentioned triggers of skin redness and worsening rosacea symptoms. It is assumed that exacerbation under the influence of ultraviolet (UV) radiation develops as a result of three processes. First, vitamin D induces overexpression of catelicidin by keratinocytes, which then initiates a pro-inflammatory cascade. Second, UVB enhances vascular proliferation due to fibroblast growth factor-2 (FGF2) and vascular endothelial growth factor-2 (VEGF2)^[31]. Finally, skin exposed to excessive UV radiation contains more reactive oxygen species (ROS) further activating the KLK5-catelicidin inflammatory cascade^[31].

Ultraviolet radiation destroys collagen - a structural protein that maintains in tone not only the skin, but also the walls of blood vessels. As soon as the collagen fibers begin to break down under the influence of ultraviolet light, the tissue becomes weaker, loses elasticity, begins to stretch and "sag." Returning to its original state after serious damage is not so easy. Reducing collagen support also entails another problem - reduced pressure from the tissues surrounding the vessels, and this makes them more noticeable, they clearly shine through the skin. In most cases, the situation is aggravated by the wrong cosmetic care (and the harmful effect of the ubiquitous free radicals)^[32].

The tendency of rosacea to affect the central part of the face can be influenced by the preferential effect of ultraviolet radiation on the bulges of this part of the body.

In 2024, a popular publication mentioned that excess vitamin D may be one of the reasons for the development of rosacea^[33].

The choice of sunscreen is very important. There are two types of sun-damaging rays: UVA rays age the skin, and UVB rays burn it. Not all sunscreens protect against both types of harmful rays. Look for non-chemical sunscreens that contain zinc or titanium dioxide and offer protection against UVA/UVB with SPF30 factor or higher.

Some foods

Patients also often mention trigger foods, but the field had not seen enough research by 2017. According to one survey by the National Society for the Treatment of Rosacea, 78% of more than 400 patients changed their diet due to rosacea. 95% of patients in this group had a decreased relapse rate^[34].

Triggers of this group can be subdivided into:

• related to heat,
• alcohol-related,
• associated with capsaicin and
• bound to cinnamaldehyde.

In particular, hot drinks served as triggers: hot coffee (33% of patients called it a trigger) and hot tea (30%). Another common trigger factor was alcohol, including wine (52%) and strong alcohol (42%).

The negative consequence of alcohol is that it causes redness. Moreover, this property is noticed for all its types, including wine, beer and strong drinks. Scientists have found that the risk of developing rosacea increases with the amount of alcohol drunk. Its most dangerous species for women in terms of skin health was called white wine and strong drinks^[35]

If earlier, with a tendency to cuperose and rosacea, they advised to abandon red wine, then by 2021 new research has proven that white wine and strong alcohol are more dangerous for blood vessels. Dermatologists have found that the disease worsens liquor and white varieties of wines, but red wine does not affect the manifestation of the disease^[36]. The reason is that red wine contains biologically active substances - antioxidants that neutralize the effect of inflammatory mediators, but they are not in white wine.

Capsaicin is found in some spices and peppers. Respondents often reported that spices (75%) served as the trigger, as well as hot sauce (54%), cayenne pepper (47%) and red pepper (37%).

Finally, cinnamaldehyde is found in some seemingly unrelated foods, including tomatoes, citrus, cinnamon and chocolate^[13]. Respondents often referred to products containing cinnamaldehyde as a trigger, including tomatoes (30%), chocolate (23%) and citrus fruits (22%).

Ginger, cumin, cloves, eggplant, onions, radishes, spinach, tea and coffee also provoke inflammation and irritation^[13].

As noted in the previous section, transient receptor potential (TRP) channels are considered one of the possible mechanisms of rosacea pathogenesis. Various stimuli can activate TRP channels and cause increased skin blood flow by neurogenic vasodilation leading to symptoms such as redness and burning^[37]. Sulk et al. found that some vanilloid channels (TRPV1-6^[38] were active in rosacea patients. Located in keratinocytes, neurons, endothelial and immune^[39], vanilloid receptors are activated by high temperatures^[40], resulting in vasodilation and inflammatory^[41][42]. Similarly, TRPA1 is an ankyrin receptor primarily found in sensory neurons. TRPA1 activated with mustard oil and cinnamaldehyde affects vasodilation and can lead^[15][43].

Treatment and reduction of rosacea symptoms

Main article: Rosacea treatment

Rosacea is a consequence of problems in the gastrointestinal tract and refers to diseases dealt with by gastroenterology.

For 2018, if topical drugs are ineffective, oral antibiotics, especially tetracyclines, become the basis for treatment.

For 2018, according to international recommendations, the gold standard of therapy for this dermatosis is metronidazole derivatives, antibiotics and retinoids. Domestic recommendations regarding systemic therapy of rosacea are generally similar to international ones, somewhat differing in dosage and/or frequency of drug administration:

• tetracyclines - doxycycline 100-200 mg, 1 times a day;
• erythromycin - 250 mg, 4 times a day;
• clarithromycin - 500 mg per day;
• metronidazole - 1.0-1.5 gr per day^[44]).

However, long-term antibiotic therapy cannot be considered as an ideal treatment option due to possible side effects and the potential development of antibiotic resistance. Therefore, the focus was again on the role of modifiable lifestyle factors, including nutrition.

It is well known that certain foods can act as triggers for the development of rosacea. Research has even suggested certain mechanisms by which other foods may be useful in this disease. Dietary change can become an important component of rosacea therapy through the study of the pathogenesis of the disease.

Diseases associated with rosacea

High risk of liver, skin and breast cancer. Low risk of lung cancer

In 2017, a Danish study found that people with rosacea had a higher risk of developing liver cancer, skin cancer and breast cancer. The results failed to prove a causal relationship, meaning more research is needed before any such conclusions can be drawn.

The study aimed to investigate the likelihood that rosacea patients would be diagnosed with 13 different forms of cancer. The authors analyzed a five-year medical history of more than 50,000 patients and more than 4,000,000 control subjects.

The results showed no increased risk of certain cancers, including cancers of the esophagus, kidneys, thyroid, pancreas and ovaries.

"However, the researchers found that rosacea patients had a 42% higher risk of developing liver cancer."

Moreover, the risk of non-melanoma skin cancer and breast cancer was 36% and 25% higher, respectively, among patients with rosacea. Interestingly, evidence suggests that rosacea patients may have a 22% lower risk of developing lung cancer than the general population.

Increased risk of developing Alzheimer's disease

In 2016, scientists found that people with rosacea had an increased risk of developing dementia - Alzheimer's disease in particular. Researchers from Denmark, who came to this conclusion, also emphasize that the risk is highest in elderly patients. The results of the study are published in the scientific journal ^[45]

There is evidence that rosacea is associated with high levels of some proteins that are also involved in various disorders, brain such as Alzheimer's disease and other forms of dementia. These proteins include matrix metalloproteinases and antimicrobial peptides.

The researchers used patient data from the period 1997-2012, including looking at the medical histories of 83,500 people with rosacea. When the scientists analyzed this data, they found that rosacea patients had a 7% higher risk of dementia and a 25% higher risk of developing Alzheimer's disease, with older people having the highest risk. For women, the risk of developing Alzheimer's disease associated with rosacea was 28% higher, while for men it was 16% higher.

Alexander Egeberg of the University of Copenhagen said:

"Rosacea patients have notable neurological symptoms such as burning and skin pain, migraines and neuropsychiatric symptoms, indicating a link between rosacea and neurological diseases."[46].

Now, evidence has emerged that suggests rosacea is not only associated with neurological disorders, including Parkinson's, but also Alzheimer's.

The researchers explain that there are certain basic mechanisms linking rosacea and Alzheimer's disease, but we don't know if they affect each other.

Scientists believe doctors should be mindful of symptoms of cognitive dysfunction in older rosacea patients. Only further research will help identify whether rosacea treatment can change patients "risk of dementia.

Association with multiple sclerosis, diabetes, celiac disease and rheumatism

In 2021, it was reported that there is a medical link between rosacea and autoimmune diseases such as multiple sclerosis^[47]type 1 diabetes mellitus, celiac disease (gluten intolerance) and rheumatoid arthritis^[48].

Increased risk of migraine in rosacea patients

In a study published in the British Journal of Dermatology in 2021, scientists from the University Hospital of Oulu found that migraines are more common in people with rosacea.

Scientists studied the association between rosacea and migraine using data from a 1966 Northern Finland cohort study (1932 participants; 53.7% of women).

The researchers found that the prevalence of rosacea was 15.1% overall. Self-reported migraine was more common among people with rosacea than among those who did not (21.5 versus 18.5%).

Patients with rosacea and migraine were more likely to report unilateral (25.3% versus 18.4% without rosacea) and pulsating headache (33.9% versus 24.6% without rosacea). Scientists have found that male patients with rosacea have twice the risk of migraine, a unilateral throbbing headache, a headache that interferes with daily activities, and a headache that is irritated by bright light and loud voices. No similar risk was observed in female patients.

In addition to genetic predisposition, impaired epidermal barrier and dysregulation of the immune system, rosacea is characterized by neurovascular dysregulation and neurogenic inflammation, thus sharing pathomechanisms with migraine. Based on the study's findings, scientists recommend that doctors meeting rosacea patients, especially men, ask about migraine symptoms^[49].

Cardiovascular risk not confirmed

Although the association of cardiovascular (CVD) and chronic inflammatory diseases such as rheumatoid arthritis and psoriasis has long been established, the risk of developing cardiovascular disease in rosacea is unclear. For 2017, given the increased risk of CVD as well as metabolic diseases such as diabetes mellitus and hypertension, dietary changes in psoriasis to reduce the risk of their development is considered an important aspect of therapy.

A number of studies have examined the risk of developing these diseases in patients with rosacea. In one case-control study, patients with rosacea had an increased risk of CVD. The authors suggested that cathelicidin peptides and serine proteases act as common etiopathogens to rosacea and atherosclerosis. However, a Danish case-control study of about 5,000 rosacea patients found no increased risk of adverse cardiovascular events. With these data, further studies of CVD risk in rosacea patients should be conducted. When confirming such a risk, making changes to the nutrition of patients to reduce it will be absolutely justified.

Risk of loss of eyebrows and baldness

In 2023, it was mentioned that rosacea could be the cause of loss of eyebrows and baldness^[50].

The largest companies in the rosacea treatment market

As of 2019, the following companies receive the largest revenues in the rosacea treatment market:

• Galderma Laboratories
• Allergan
• Topix
• Barrier Therapeutics, Inc
• Bayer AG
• PharmaDerm Pharmaceuticals, Inc
• Bristol-Myers Squibb
• Genentech, Inc.
• GlaxoSmithKline

Forums

• "Rosacea Support Group."
• Woman.ru: Who cured ROSACEA?

Notes