Living With Rosacea
What is Rosacea?
Rosacea affects approximately 10% of the total UK population (1). It represents a chronic inflammatory skin disease that predominantly involves the central face and tends to progress with time. It can also affect the neck, scalp, and eyes (2) and is characterized by flushing, erythema (redness), papules and pustules (raised red or pus filled spots) and dilated (open) blood vessels in the skin known as telangiectasias. In some cases it can result in thickening of the skin leading to disfigurements e.g. a bulbous nose (phymatous hyperplasia) (3).
Incidence and distribution of rosacea
Rosacea is more common in women than men, by a ratio of 3:1, although men seem to suffer more severe disease (1). There is a genetic tendancy as rosacea can run through families and although it is seen more commonly in fair-skinned people and is sometimes referred to as the “Curse of the Celts” it is recognised in Asian skin.
Rosacea peaks at the age of 40-60 years, but may occur in teenagers and early 20s. The condition may coincide with acne and a form of eczema called seborrhoeic dermatitis. It is important for a doctor to distinguish these conditions so that the best treatment can be offered.
Diagnosing Rosacea
There are no specific tests for rosacea. Diagnosis relies largely on the clinical assessment based on a thorough history and a visual inspection of the skin. Until fairly recently, rosacea was seen as a progressive disease, beginning with flushing, followed by erythema (redness) and dilated blood vessels (telangiectasia), red inflamed and pus filled spots, as well as skin thickening especially on the nose which is called rhinophyma. This progression is now not considered inevitable and four individual subtypes of rosacea are now recognised (4).
Erythematotelangiectatic Rosacea
This is characterised by symptoms of flushing and persistent erythema (redness) of the central face with or without the dilation of superficial blood vessels (telangiectasia). Patients frequently report a burning or stinging sensation in the affected area. Ocular (eye) involvement may also be present and, occasionally, the thickening of the skin of the nose (rhinophyma).
Papulopustular Rosacea
This affects the central face causing erythema (redness) which is also accompanied by transient pustules (pus filled spots) and/or dome-shaped papules (raised red spots). Stinging or burning sensations are frequently reported, and patients are frequently very intolerant of creams, lotions, potions applied to the skin (topical therapies). Other areas of the body can be affected, such as the chest, ears and, in bald men, the scalp. If these areas are affected, response to treatment is usually very slow.
Phymatous Rosacea
This is caused by thickening / enlargement of the connective tissue in the skin and the grease glands (sebaceous) and can result in a disfiguring appearance. Typically, thickening of the skin occurs on the nose, with skin pores becoming prominent. Other areas of the face can also be involved, such as the chin (gnathophyma), forehead (metophyma), ears (otophyma) and eyelids (blepharophyma). There may be no other features of rosacea present. Phymatous rosacea is much more common in males in a ratio of 10:1.
Ocular Rosacea
Both eyes are usually affected and in 50% of affected cases there is a strong link to flushing, although occasionally the ocular symptoms can precede any skin problems by a considerable period of time. The condition can manifest itself in many ways, including watery or bloodshot conjunctivae, foreign body sensation, irritation, sensitivity to light and blurred vision. Blepharo-conjunctivitis (crusty sore red eyelids), with telangiectasia and conjunctival infection and inflammation of the lid margin, may occur. In 5% of cases, keratitis can arise, causing severe pain and aversion to light, with blurring of vision. This condition is more common in males and may lead to damage of the cornea. Episcleritis, scleritis and iritis may occur rarely, as may Sicca syndrome where the eyes become very dry.
A separate and unusual condition is “granulomatous” rosacea, characterised by the appearance of firm red, brown and yellowish spots on the cheeks. The condition has been linked to ulcerative colitis.
Persistent oedema (swelling) can occur in up to 25% of rosacea patients: technically speaking, this is not true oedema, but rather is an increase in connective tissue. Commonly, the central portion of the cheeks and eyelids are affected. The condition is twice as common in males as in females.
Underlying causes of rosacea
Underlying causes are a mixture of genetic predisposition and environmental/behavioural influences. The underlying pathophysiology is not clearly understood currently. Rosacea can run in families and many sufferers think that they have simply inherited “rosy cheeks” not appreciating that there may be some therapy to help modify this appearance. In addition a flushed complexion is also associated in people’s minds with high alcohol intake: this stigma can be unfairly applied to rosacea sufferers, although alcohol is one of the recognised trigger factors for flushing and an attack of rosacea. In 70% of cases, sun exposure will aggravate the condition and can lead to degeneration of the elastic tissue in the skin. There are a number of trigger factors for flushing which may also aggravate the disease. Because these factors can vary from person to person, it is a good idea for the patient to keep a detailed daily diary to help establish links between flushing episodes and possible triggers.
Triggers for flushing:
Environmental: temperature extremes, wind, UVL
Diet: hot, spicy food, alcohol, hot drinks
Drugs: vasodilators
Emotional factors
Physical exertion
Hormonal factors
Skin care products
It has been suggested that sunlight and other environmental factors provoke damage to the elastic tissue in the skin and blood vessels over time leading to dilatation of blood vessels and leaky vessel walls resulting in fluid leakage from the blood vessels which subsequently leads to inflammation and swelling. An association between rosacea and migraine has been noted in some patients.
Other studies have looked for an immunological cause for rosacea with some evidence suggesting there may be an allergic component possibly to light-altered collagen or the presence of a mite called Demodex folliculorum in the skin follicles. Intriguingly, increased numbers of Demodex mites have been reported in cases of papulopustular rosacea, but not in erythematotelangiectatic rosacea. Patients wit reduced immunity show an increased mite population, so the immunological status of the patient may be important. Other theories include mechanical obstruction of the follicles by the mite, host reaction to the mite, physical irritation by mite exoskeleton particles or the possibility that the mites act as vectors for bacterial invasion/infection.
Historically, it has been suggested that there is an association between rosacea and gastrointestinal disease, leading to the idea that Helicobacter pylori may be involved. However, there is no clear evidence of increased incidence of H. pylori in rosacea patients, and treatment of H. pylori doesn’t always lead to resolution of rosacea.
Bacteria isolated from rosacea patients have been shown to secrete different proteins and variable amounts at different temperatures, although the significance of this observation is as yet unclear. Similarly, it is known that cathelicidins (antimicrobial peptides that are produced in response to inflammation or injury) are over-expressed in rosacea patients, although whether this is directly due to a bacterial invasion or simply a result of having rosacea has not yet been clarified.
New theories of the pathogenesis of rosacea involve the role of endothelin 1 and its converting enzyme (ECE-1) in the regulation of vascular tone and infiltration of the skin by inflammatory cells.
Treatment Options
A recently published review examining treatments for rosacea (5) concluded that there was good evidence for the use of the topical treatments, ie.e treatments that are directly applied to the skin in the form of metronidazole and azelaic acid, and some evidence for the use of the oral antibiotics oxytetracycline and metronidazole. There was no good evidence to support the use of minocycline, lymecycline, erythomycin, trimethoprim, oral isotretinoin, topical retinoids, dapsone or laser therapy.
Metronidazole
Since its introduction in 1983, there has been some debate about the optimum dosing of topical metronidazole. However, no significant differences have been found between formulations containing 0.75% and 1% metronidazole, or between once daily and twice daily application (6). In comparative studies, topical metronidazole was considered to have similar action and effect to oral oxytetracycline (7-8). The mechanism of action of metronidazole is thought to be more anti-inflammatory than antibacterial. Nevertheless, metronidazole is used worldwide primarily as an antimicrobial agent, so its use in a non-antibacterial role is not ideal. Although there are no reports of antimicrobial resistance with the use of topical metronidazole administration, there are several reports of metronidazole resistance in Bacteroides spp and Helicobacter spp, and a single report of resistance in Clostridium difficile (9).
Azelaic Acid
Azelaic acid is a naturally occurring dicarboxylic acid, found in wheat, barley and some animals its use in rosacea dates from 1993. Trials comparing this new agent against a placebo in rosacea (10, 11) showed a reduction in inflammatory lesions, and a comparative trial against metronidazole showed equivalent effects (12).
Finacea is a recently developed formulation of azelaic acid, consisting of 15% azelaic acid (as micronised particles of 1-10nm) in a hydrogel matrix. This increases skin penetration in comparison to the 20% azelaic acid cream formulation.
Finacea has been shown to be effective in 2 large randomised controlled trials against a placebo (13). Against metronidazole, Finacea has demonstrated equivalence out to 8 weeks after start of therapy, and thereafter a significant continuation in reduction of lesions over metronidazole (14).
Side-effects, largely consisting of facial signs and symptoms, were higher in the Finacea group, but only 4 patients (3%) had to discontinue treatment. It is important to warn patients beforehand about side-effects, but they are generally tolerable or treatable with dose reduction.
Systemic Therapy
Oral tetracycline therapy (250mg bd) has been shown to be far more effective than placebo, and a recent trial (15) showed that a sub-antimicrobial dose of controlled release doxycycline was significantly effective in reducing rosacea inflammatory lesions without raising doxycycline serum levels to a point where selective pressure might come to bear on commensal flora or pathogenic bacteria. Although apparently ineffective in most instances of rosacea, oral isotretinoin has a role in the treatment of phymatous rosacea, by decreasing the nasal volume and number/size of sebaceous glands. This treatment is best used in younger patients and mild disease. Although there are anecdotal reports of the benefit of a number of agents in controlling flushing in rosacea, no formal controlled trials have been performed.
Surgery
Surgery, either by conventional surgical dermobrasion or laser ablation, has a role in reduction of rhinophyma. Lasers may also be used in the treatment of persistent erythema: however, the patient must be warned about their immediate post-treatment appearance as disfiguring red raw areas and bruising may occur. Intense pulsed light therapy offers a good alternative treatment option for persistent redness with impressive results and minimal post-treatment bruising, compared to pulsed dye lasers. Patient management should be based upon the individual subtype of rosacea in order to optimise outcome.
Evidence-Based Treatment for Rosacea according to sub-type
• Erythematotelangiectatic rosacea
Intense pulsed light
Vascular lasers
• Papulopustular rosacea
Topical 15% azelaic acid
Topical metronidazole
Oral tetracyclines/low-dose doxycycline
• Phymatous rosacea
Oral isotretinoin
Physical ablation
• Ocular rosacea
Oral tetracyclines
Psychosocial impact of rosacea
A link between depression and rosacea has been highlighted in a controlled trial (16) and other studies have supported this connection (17). Not surprisingly, successful treatment of rosacea has a positive effect on patient mood. A trial of azelaic acid and/or systemic treatment in patients with mild to moderate rosacea (18) reported significant improvements in patient quality of life (QOL) scores. The use of pulsed dye laser therapy was shown to improve rosacea erythema and symptomology, but also to improve the QOL scores of treated patients (19). Clinicians need to be aware of these QOL issues and appreciate that patients may be highly susceptible to psychological upset. Patients need to receive comprehensive information explaining the condition: this can be through a variety of methods, such as leaflets, websites, patient help groups, etc. Trigger factors should be highlighted and lifestyle adjustments suggested where possible. Advice on camouflage should not be underestimated: patients find it very beneficial and it can aid them to function more normally during periods of flare-up, again improving their QOL.
Patients could be put in touch with support groups, who can provide additional information and help, such as the teaching of cognitive behavioural therapy techniques, which aim to make patients more socially confident. Examples of patient support groups include:
Outlook (http://www.nbt.nhs.uk/services/surgery/outlook/); and
Changing Faces (http://www.changingfaces.org.uk/Home).
Advice on how to remain in remission from flare-ups (20) is helpful.
Maintaining Remission.
• Wash with body temperature water
• Use very gentle non-alcohol-based cleansers
• Use fingertips and not a flannel to wash
• Blot dry, don’t rub
• Apply topical agents 30 minutes after cleansing
• Try to avoid anything known to cause stinging, flushing or redness
Summary
Rosacea represents an enigmatic disease of uncertain pathophysiology. Although rosacea cannot yet be prevented or cured, it is now recognized as a common and distinct medical condition that can be successfully managed with specific medical therapies and lifestyle modifications. Patient management should be appropriate to the particular clinical subtype of the patient.
It should not be forgotten that, as well as the physical aspects, there is a significant impact on the psychosocial status of the patient. The diverse spectrum of symptoms seen can be confused with a range of other conditions, so careful attention should be paid to differential diagnosis.
References
1. Berg M, Linden S 1989 Acta Derm Venereol 69 419-423
2.Gupta AK, Chaudhry MM. J Eur Acad Dermatol Venereol. 2005;19:273-285
3. Millikan L, Postgrad Med 1999; 105: 149-158
4. Wilkin J, Dahl M, Detmar M, et al. J Am Acad Dermatol. 2002;46:584-587.
5. Van Zuuren E et al 2007 J Am Acad Dermatol 56 107-115
6. Dahl M et al 2001 J Am Acad Dermatol 45 723-730
7. Neilsen P 1983 Brit J Dermatol 109 63-65
8. Veien N et al 1986 Cutis 38 209-210
9. Nazarro-Porro M, Passi S 1978 J Invest Dermatol 71 205-208
10. Carmichael A et al 1993 J Dermatol 4 (suppl 1) S19-S22
11. Bierke R et al 1999 Acta Derm Venereol 79 456-459
12. Maddin S 1999 J Am Acad Dermatol 40 961-965
13. Thiboutot D 2003 J Am Acad Dermatol 48 836-845
14. Elewski B et al 2003 Arch Dermatol 139 1444-14450
15. Del Rosso J et al 2007 J Am Acad Dermatol 56 791-802
16. Marks R 1968 Brit J Dermatol 80 170-177
17.National Rosacea Society. 2008. available at:
http://www.rosacea.org/index.php
18. Fleischer A, Chen S 2005 J Drugs Dermatol 4 585-590
19. Tope W 2004 J Am Acad Dermatol 51 592-599
20. Wilkin J 1999 Arch Dermatol 135 79-80