Judy Seraphine, Medical Editor, Maui Derm News
In this presentation, Dr Webster provides an update for the management of patients with rosacea.
There have been a number of theories about rosacea. In the past, clinicians believed that it had to do with blushing but that was never clear. Since then, newer observations have been made trying to explain the cause of rosacea.
Helicobacter pylori and Rosacea
Dermatologists should recognize that rosacea can improve during H. pylori therapy as H. pylori drugs may be active in rosacea independent of effects on the GI tract. It is important to understand that H. pylori is as common in rosacea as it is in normal controls and a blinded study showed no greater effect on the controls for H. pylori therapy. What was found that the therapy used to treat the GI effects of H. pylori, namely doxycycline, also tended to treat the rosacea.
Demodex in Rosacea
It is difficult to say what the role of Demodex is in rosacea. Demodex is present on both normal and rosacea skin, yet elevated demodex counts are seen in rosacea; however, demodex quantification is flawed, prone to error and difficult to do. Demodex is most increased in inflammatory rosacea. Follicles with demodex in normal skin tend to be inflamed. Dr Webster feels that an important study with regards to Demodex is that of it killing Lindane. The results were is ineffective.
B. oleronius in Rosacea
More recently, Dr Frank Powell and his colleagues discovered a Demodex-related bacteria that is more active in rosacea patients. They cultured mites and one mite grew a bacterium that was different from other skin flora, Bacillus oleronius. They found that ruptured activate mononuclear cells [16/23 (73%) rosacea patients versus 5/17 (29%) controls]. Rosacea patients seem to recognize a few antigens in western blots.
Dr Li and colleagues found an even greater reaction between B. oleronius and ocular rosacea. There are problems however, as in the first study only one mite out of 40 contained the bug. In addition to that and more importantly, PCR of many new Demodexs did not reveal the bug.. The cross-reactivity of the bug antigens with other more common bugs hasn’t been investigated. Many patients did not react and some normal patients did. As of now, this information is on hold.
Etiology of Rosacea
What do we know about the etiology of rosacea? We know that there is excessive vascular reactivity and those who have rosacea tend to be “blushers and flushers.” We know that the papules and postules, when cultured, are sterile and in some small genetic analyses, the skin does not show bacteria so we know that it is not some sort of infection. Rosacea does respond to anti-inflammatory drugs. It is becoming clearer and clearer that the nerves are involved in skin “things” that we don’t quite understand, for example the sebaceous gland. It is also pretty clear that there is a defect in control of the innate immune system. The inflammatory subunits are present in rosacea skin and if you purify them and inject them into mice, you can make rosacea-like inflammation in the back of the mouse.
Neuro-vascular Factors in Rosacea
The blush reflex to thermal stimuli is more easily triggered in rosacea patients than in normal patients. Also, plasma leakage from the blood vessels may incite inflammation. There are multiple flush/blush mechanisms, these include thermal, hormonal, nicotinamide, and autonomic and they are different among each patient.
Clinical Issues with Rosacea
The tried and true topical agents for the treatment of rosacea include:
- Metronidazole (FDA approved)
- 0.75 and 1%
- “overlap” rosacea (e.g. eczema and rosacea)
- Azeleic acid (FDA approved)
- Sodium sulfacetamide/sulfur
- Sun damage or rosacea? (data unclear)
Oral Flush Blockers
The flushing and the redness is the most difficult to treat.
- Blocks carcinoid and menopause flush
- No effect in chocolate, red wine, thermal flushing
- No effect in rosacea thermal blush
- Blocks Nicotinic acid flush
(Arch Derm 119:211, 1983; 118:109, 1983; Clin Pharm Ther 31:478, 1982; JAAD 20:202, 1989)
Topical Treatment of Erythema
Metronidazole and azelaic acid may diminish peri-lesional erythema. Oxymetazolone has also been shown to reduce erythema. A phase II study with topical brimonidine, which is an Alpha-2 inhibitor, has shown a clear benefit when reducing erythema. Its effect has been very dramatic and produces 4-8 hours of reduced erythema.
One of the questions when using vasoconstrictors is “Do you get a rebound?” In Dr Webster’s experience, he has only seen one rebound that lasted about one day.
Rosacea in Darker Skin
It is important to remember that rosacea is not a disease just of the fair skinned. Symptoms of rosacea in darker skinned patients include irritable skin, stinging, facial warmth, and a history of ocular rosacea. Darker skinned patients can be treated using the standard approaches.
When patients are applying steroids to their face, it becomes very irritable, There are lots of “homeopathic” products that have vasoconstrictor activity. Rosacea under the nares is a tip-off. Dermatologists should be aware that a “gentle withdrawal” does not work to treat this condition. TIMs and minocycline/doxycycline is the standard treatment.
Atopic/Seb Derm-Rosacea Overlap
Overlap is common among these patients and can also be very resistant to traditional rosacea treatment. It is important as dermatologists to remember to avoid irritants when managing these patients. Topical treatment includes tacrolimus/pimecrolimus and ciclopirox. Oral therapy includes the tetracyclines and cyclosporine followed by a topical treatment.
Defective Barrier in Rosacea
The fact that rosacea patients sting and burn is not just because they are blushy, but also because of the microscopic ruptures in their skin barrier, i.e., their stratum corneum is not in tact. There are areas that are extremely “leaky”. Sun damage can also affect the barrier. We also know that irritants can provoke rosacea by provoking inflammation and proteases. Moisturizing improves rosacea TEWL and the associated symptoms.
The graph below demonstrates barrier improvement as rosacea gets better with Metronidazole, which is designed to take the inflammation away.
What do we know about the pathogenesis and treatment of rosacea? We know that it is very complex. Improving the barrier, can improve rosacea and it is important to remember that rosacea skin is extremely sensitive, such as that of atopic skin.