Rosacea Bulletin Board; Latest news on rosacea treatments
2024 - A new drug is approved for the treatment of hot flashes. Veozah (fezolinetant) is a non-hormonal treatment in tablet form. A new study showed Veozah worked for six months toto decrease both the number and intensity of hot flashes among menopausal women who couldn’t take hormone therapy. It does so without serious side effects, according to new research presented this month at the European Congress of Endocrinology in Stockholm. It helps reducing hot flashes in women with moderate to severe hot flashes. The drug works via the brain, acting directly on the temperature-control pathway to alleviate hot flashes and night sweats. It works in your hypothalamus—the area of your brain that controls body temperature. It is designed to specifically block neurokinin B (NKB). NKB is a chemical that binds to a receptor in your brain, triggering hot flashes and night sweats due to menopause. Headaches are the most commonly reported side effect of Veozah. The prescribing information for the drug includes a warning for potential liver injury.
For some women, menopausal flushing can worsen or even start rosacea flushing. For women with existing rosacea, who enter menopause, this may be a med of interest. I myself am weary already for instance about HRT, since it adds progesterone to the mix, which I know from past use for fertility treatment, really did flare my rosacea quite a bit. I would be interested to try Veozah myself, as it has been approved in the Netherlands also by now. And as I am quite worried already about impending menopause and its effect on my severe flushing and rosacea. But it remains to be seen if Veozah is effective for rosacea flushing that isn't linked to menopause. It may, but there is a difference between hormone triggered hot flashes, and the complex flushing of rosacea skin. Because rosasea can of course have many causes and aggravating factors. Growing research suggests that environmental and psychological factors, including bacteria, UV radiation, diet, temperature extremes, skin barrier alteration, psychological stress, and hormonal fluctuations, may trigger rosacea. The theory that hyperreactivity or excessive activity of the skin blood vessels might play a role in causing rosacea is based on the fact that most individuals with rosacea experience flushing episodes.7 Excessive expression of CD31 (a marker of the lymphatic endothelium) and D2-40 (a marker of the lymphatic endothelium) have also been seen in individuals with rosacea. The loss of estrogen and progesterone, the female reproductive hormones, causes the transition into menopause. In addition to the sex hormones, androgens and estrogens, the ovaries also produce the asexual hormones, prostaglandins. These hormones are the strongest vasomodulators that can largely trigger a response of the hemodynamic centers of the main brain at different levels, resulting in symptoms like hot flushes and rosacea. Increased prostaglandin production by the uterus in response to fluctuating estrogen levels during perimenopause is a known risk factor for developing and worsening rosacea.
There is also a case to be made for hormonal therapy instead (HRT). Hormonal balance is an essential factor in reducing rosacea outbreaks. Similarly, the hot flashes that many women experience after menopause can be a precipitating factor in the development of rosacea. Hormone replacement therapy is useful for postmenopausal women because it can help balance hormones and reduce both the frequency and intensity of hot flashes and rosacea. The use of bioidentical hormones and other drugs can reduce inflammation, lessening the intensity of rosacea. Because of their anti-inflammatory properties, antihistamines may also help treat the condition. In addition, the emotional side effects of menopause can be treated with antidepressants, which may lessen the likelihood of stress-induced rosacea flare-ups.
More mainstream medication that is already prescribed for people suffering from (menopausal) hot flashes linked to rosacea, are oral medicines with vasoconstrictive effects such as adrenergic antagonists likemirtazapine (β-blocker), propranolol (β-blocker), or carvedilol (β-blocker) may be used to treat hot flushes and rosacea. Owing to their potential side effects, such as hypotension, insomnia, tiredness, and bronchospasm, they are often administered at very low dosages and should only be prescribed by medical professionals; moreover, patients taking them must be closely monitored. Clonidine, an oral α-2 agonist, can also be used to treat rosacea. While systemic α-2 agonists can be effective, topical formulations are usually recommended to prevent potential side effects. It has been shown that brimonidine, a topical α-2 agonist, can diminish rosacea for up to 12 hours by direct cutaneous vasoconstriction. (Nat: but be aware of the rebound risk!!) Antibiotics such as minocycline, doxycycline, erythromycin, clarithromycin, and clindamycin can also be taken orally to treat papulopustular rosacea. Moreover, oral isotretinoin can be used to treat papulopustular rosacea as well as phymatous rosacea.
The migraine drug Erenumab Reduces Persistent
Flushing and Erythema in Rosacea
A new study confirms the rosacea suppressing effects of SGRP (read more about this in the below post). A migraine drug could be offered to sufferers of facial flushing after a new study (also published here) found it significantly reduced symptoms. In the US study, 30 adults with severe rosacea were given the migraine drug erenumab, which is an injectable calcitonin gene-related peptide (CGRP) inhibitor. The jab blocks the effect of a protein which is linked to the debilitating headaches and nausea of migraine. The research found rosacea patients taking erenumab saw a significant reduction in their symptoms. Erenumab significantly reduced treatment-resistant flushing and erythema associated with rosacea. Those most affected by the condition saw an 80 per cent decline in severe to extreme flushing within days of beginning the treatment. Study author Dr John Barbieri, a consultant dermatologist at Brigham and Women’s Hospital in Boston, said the results showed ‘promising potential’ for rosacea patients. "The transient erythema of rosacea is one of the most challenging rosacea symptoms to treat," Emmy Graber, MD, MBA, who was not involved with the study, said in an interview. "As flushing can adversely impact quality of life in our rosacea patients, it is important to find therapeutic options for our patients. This study is exciting, not only because the treatment was successful for a notable number of patients, but also because it involved a drug with a novel mode of action in rosacea." Graber practices in Boston and is an affiliate clinical instructor at Northeastern University, Boston.
Conclusions and relevance: "These findings suggest that erenumab might be effective in reducing rosacea-associated flushing and chronic erythema (participants generally tolerated the treatment well, which was consistent with previous data), and that CGRP-receptor inhibition holds potential in the treatment of erythema and flushing associated with rosacea. Larger randomized clinical trials are needed to confirm this finding."
Rosacea's pathophysiology remains incompletely understood, wrote Nita K.F. Wienholtz, MD, PhD, Department of Dermatology, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Denmark, and coinvestigators. However, they added, mounting evidence suggests a possible role for CGRP. For example, a study published in JAMA Dermatology in 2015 revealed elevated CGRP levels in facial skin biopsies from patients with rosacea. For the present study, the investigators enrolled 30 adults (including 23 women) with rosacea who experienced at least 15 days of moderate to severe erythema or extreme flushing during a 4-week, treatment-free run-in period. Most participants (87%) had previously failed one or more rosacea treatments because of a lack of efficacy or adverse reactions, and 43% had failed three or more treatments. Investigators administered 3-monthly 140-mg doses of erenumab, which is approved by the US Food and Drug Administration for migraine prevention. Patients recorded scores on the Patient Self-Assessment (PSA) and item 2 of the Flushing Assessment Tool online daily and made a final follow-up visit 12 weeks after the third dose. Among the 27 patients who completed the study, the mean number of days with moderate to severe flushing from week 9 to week 12 fell by 6.9 from 23.6 days over 4 weeks at baseline (P < .001). Patients most severely affected by flushing at baseline experienced an 81% decline in days with severe to extreme flushing. Overall, 26% of patients experienced at least 50% reductions in moderate to extreme flushing days. The number of days with moderate to severe erythema as measured by PSA fell by 8.1 (mean) from baseline, and 56% of patients experienced at least 50% reductions in PSA scores. No unexpected safety signals emerged.
Questions Over QOL Data
"Although there were significant decreases in flushing and erythema," wrote John S. Barbieri, MD, MBA, in an accompanying Editor's Note, "the present study had relatively modest improvements in quality of life." He is director of the Advanced Acne Therapeutics Clinic, Brigham and Women's Hospital, Boston, and associate editor and evidence-based practice editor of JAMA Dermatology. Because the study was neither blinded nor controlled, Webster suggested considering it a tantalizing proof of concept. "If I were putting money into a CGRP inhibitor, I'd want at least a small, placebo-controlled, double-blinded study." Study authors and Barbieri recommended larger randomized studies involving different populations and erenumab doses. For now, Barbieri wrote, CGRP inhibition represents a promising potential strategy for patients who have rosacea with comorbid migraine or recalcitrant flushing and erythema.
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Anti-CGRP migraine drugs for rosacea treatmentI've read recently that several companies are busy with clinical trials for a new migraine treatment with anti CGRP drugs, with positive results. These drugs are geared for migraine, but the way in which they work (their aim is to constrict blood vessels), makes them also exciting and possible future treatment options for rosacea. From Science magazine:
"Four pharmaceutical companies are racing to complete advanced clinical trials of antibodies that either neutralize CGRP by binding to it, or block its receptor. So far, the data suggest the drugs work faster, for longer, and better than anything currently available. Most striking, is a subset of “superresponders,” whose attacks appear to cease entirely for 6 months after a single injection of a CGRP-blocking antibody."
CGRP is a 37–amino acid (neuro)peptide that is released by the nervous system and is a very potent blood vessel dilator. When released from the trigeminovascular nerves, CGRP is a powerful vasodilator of the blood vessels of the brain. Medication that was designed to block CGRP’s receptor turned out to have too many side effects. Then researchers focused on antibodies to block CGRP, because they can last a long time in the body and can be exceptionally specific, reducing the frequency with which people need injections. many colleagues didn't think it was worth a shot, because antibodies are generally too large to pass through the blood-brain barrier, and it was thought to be necessary for migraine meds to target migraines actually in the brain. However, to their surprise, the CGRP peptide-blocking antibody "TEV-48125" managed to just do this; treating migraines from outside the brain, by blocking CGRP only in the peripheral nervous system. Trials show significant reductions in number of headache days over placebo, even for the most severe cases. This type of drug also lowers the risk of the side effects often provoked by drugs that act in the brain. Although there are still worries too, because of CGRP’s natural role in dilating arteries and maintaining blood supply to the heart and brain. “Theoretically, if you block CGRP you could translate a minor stroke or cardiac ischemia … into a full blown stroke or heart attack.” So far, the companies say they haven’t seen that or other significant side effects in the several thousand people who have completed phase I and II trials, but the drugs have only been administered for up to 6 months—not long enough to judge long-term effects. CGRP-blocking drugs are also tested now for fibromyalgia, a condition that is somewhat overlapping in some symptoms with rosacea. And scientists have also discovered that CGRP plays a role in rosacea flushing and skin redness. Interestingly, migraine medication has so far been helping some people with rosacea. Drugs like propranolol, imitrex/sumatriptan and even botox have all been helpful for rosacea. Someone on the Rosacea Forum is successfully using the migraine med Maxalt/Rizatriptan for her severe type 1 rosacea/erythromelalgia.
Stress, rosacea flares and CGRPCGRP is also part of the puzzle as to why stress can make rosacea flare so badly. Apart from stress raising blood pressure and inflammatory substances, experiments in rats now showed that corticotropin-releasing hormone, which the body releases in response to stress, also increases neuronal production of CGRP. More CGRP means much more blood vessel dilation, which causes our rosacea flares (for those with burning, flushing and redness). Strikingly, many migraine medications also boost CGRP in animal models, possibly explaining why people who use drugs like triptans too frequently end up with more severe migraines.
CGRP antagonistic treatment options for Rosacea
I hope that we can soon benefit from injections of this CGRP peptide-blocking antibody "TEV-48125". Those medications are in the making now, from what I read, so it might take a bit more time before they come on the market. In the meantime, scientists are also working on a topical cream that works in a similar way, blocking CGRP. A patent is created for a special cream for rosacea patients to do just that. 'Therapeutic/cosmetic compositions comprising CGRP antagonists for treating skin redness/rosacea/discreet erythema.' But they are not just focusing on a CGRP blocker: "Skin redness, rosacea and/or discreet erythema afflicting a mammalian, notably human patient, are therapeutically treated by administrating to such patient a therapeutically/cosmetically effective amount of at least one CGRP antagonist, advantageously in combinatory immixture with at least one antagonist of a neuropeptide other than CGRP, e.g., a substance P antagonist, and/or at least one inflammation mediator antagonist."
So this patent for a new cream will focus on three things;
*blocking CGRP (and thus blocking one factor that leads to blood vessel dilation in our faces)
*blocking P antagonist
*blocking an inflammation mediator in the skin
CGRP is a polypeptide chemical species that is produced and released by nerve endings. CGRP dilates blood vessels and is involved in lung issues and inflammatory diseases, in allergic diseases and in certain skin diseases such as eczema and prurigo. It is a new concept to treat skin redness with a CGRP antagonist. But developers now think that CGRP blocking substances can not only treat skin redness, but also prevent it from occurring. Blocking CGRP in the skin of our faces, through a cream, should help combat skin redness and flushing. This will be tested on test persons with rosacea, by first inducing a flush (with a substance called capsaicin), and then applying the cream and seeing if the redness can be toned down by it. They will test if the levels of CGRP that is released (and that cause blood vessel dilation), will be reduced upon measuring. Secondly, P antagonist will have to be another type of antagonist of a neuropeptide used, reinforcing the CGRP antagonist. A third ingredient will have to reduce inflammation in the skin (and they will select it from a group consisting of histamine antagonists, interleukin 1 antagonists, and tumor necrosis factor alpha antagonists, and the inflammation mediator antagonist is supposed to be a diethylenediamine, aminopropane or phenothiazine compound, selected from a group consisting of cinnarizine, cyclizine, dexchlorpheniramine, triprolidine, alimemazine, promethazine, auranofin, lisophyline, A802715, sulfasalazine, cetirizine hydrochloride, loratadine, ebastine, and setastine hydrochloride).
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The patent described rosacea as follows: "Rosacea is a skin affliction characterized by erythema (redness) of the face, predominantly on the cheeks, the forehead and the nose, hyper seborrhoea (thickened skin) of the face on the forehead, the nose and the cheeks, and an infectious component manifesting acneiform pustules (skin outbreaks and bumps). Moreover, these indications are associated with a neurogenic component, namely, a cutaneous hyperreactivity of the skin of the face and of the neck (nerve burning), characterized by the appearance of redness and subjective sensations of the itching or pruritus type (skin itching), sensations of burning or of heating, sensations of stinging, tingling, discomfort, tightness, etc. These signs of hyperreactivity may be triggered by very varied factors such as the intake of food or of hot or alcoholic drinks, by rapid temperature variations, by heat and in particular exposure to ultraviolet or to infrared irradiation, by a low relative humidity (dry air), by exposure of the skin to strong winds or to currents of air (conditioned air, fans and blowing machines), by the application of surfactants (soaps, washing detergents), irritant dermatological topical agents (retinoids, benzoyl peroxide, alpha-hydroxy acids, etc.), or the use of certain cosmetics, even when these are themselves not recognized as being particularly irritating. - Hitherto, the mechanism for triggering these indications was very poorly understood and rosacea was treated with active agents such as anti-seborrhoeic agents and anti-infection agents, for example benzoyl peroxide, retinoic acid, metronidazole or cyclins, which act on infection and hyper seborrhoea but do not permit the neurogenic component of this affliction, and in particular hyperreactivity of the skin and redness, to be treated. Similarly, hitherto no treatment existed for the redness which develops in discreet erythema. This latter affliction occurs at times of emotion and is characterized by redness of the face and neckline, which possibly may be accompanied by pruritus (itching). This condition is very irritating for individuals suffering therefrom, and to date it could only be treated by beta-blockers, powerful drugs used for treating hypertension and exhibiting many contraindications. Thus, serious need continues to exist in this art for an effective treatment of skin redness and of the state of hyperreactivity of skin affected by rosacea or discreet erythema." The patent acknowledges that their invention does not necessarily have to be applied through a cream on top of the skin: it is also possible to inject the CGRP antagonist into the skin, or even to take pills to achieve the same effect. They aim for a acceptable cream carrier, but the problem with most creams is that they contain alcohols (they help the active ingredient to penetrate deeper into the skin) and preservatives (parabens for instance, which are skin irritants). And some companies even put propylene glycol and plastic elements into their creams, which make them pretty much unusable for those with hyper reactive, intolerant rosacea skin. In the examples for cream ingredients that are mentioned in the patent itself, the list seems fairly OK to be honest, the only ingredients I wouldn't tolerate myself (but my skin is sickly reactive) are sunflower oil (12%), stearic acid, fragrance (if they are smart they leave that one out!) and preservatives.
CGRP and Rosacea
Rosacea is a common skin disorder that is not yet fully understood. It has been suggested that it is linked to interactions between nerves and blood vessels, which release inflammatory substances, but also specific neuropeptides, which cause the blood vessels in our skin to dilate. This is probably especially the case in rosacea subtype 1, with flushing, redness of the skin and burning (and less in subtype 2 with pimples and skin outbreaks). These specific neurotransmitters are easily triggered to be released, for instance by stress, ultra-violet light or microbial antigens. And when they are released, they trigger flushing and redness for us. When you flush from heat or temperature changes, it are primary sensory neurons that stimulate the blood vessels to dilate and to release inflammatory neuropeptides. These neuropeptides play a very important role in rosacea. For example, flushing has been suggested to be controlled by two vasodilatory mechanisms including humoral substances and neuronal stimuli (Wilkin, 1988), but the exact mechanism of action is unknown. Although scientists learn increasingly more over time about how sensory nerve endings are activated to release vasoactive neuropeptides during flushing, which also triggers the inflammatory process in different stages of rosacea. Specific TRP Channels are involved in this.
Capsaicin receptor
This newly discovered TRP channel receptor family is currently composed of 28 channels with seven subfamilies. They sit on neuronal and non-neuronal tissues all over the body. One in particular is interesting for rosacea, as it is singe handedly capable to cause a lot of blood vessel dilation. It is called vanilloid 1 (TRPV1), also known as the “capsaicin receptor”. It has many functions, including as a censor in cells, signalling pain sensations and inflammation. This receptor responds to a lot of triggers, including heat, cold temperatures, touch and changes in the cell membrane. The image left shows the structure and activators "capsaicin receptor" (TRPV1), as well as ankyrin 1 (TRPA1) receptors in primary sensory neurons with a link to rosacea. Both receptors have a similar structure and can be activated by temperature increases or for instance by spicy food. TRPA1 can be activated by reactive oxygen species (ROS; they are chemically reactive chemical species containing oxygen. They are formed as a natural byproduct of the normal metabolism of oxygen and have important roles in cells. But during times of environmental stress, for instance when exposed to UV radiation or heat, ROS levels can increase dramatically). And when activated, TRPA1 will signal for signal blood vessel widening. When this happens, mediators, such as proteases, are released, and they create inflammation. It is thought that these two, TRPV1 and TRPA1, have an interaction with each other, that regulates their activity.
TRP Channels as Thermosensors in Rosacea?Both TRPA1 and TRPV1 channels are triggered by heat and temperature increase. It is no surprise probably that 53% of rosacea patients stated in polls that hot and cold weather are triggers for their rosacea. Very cold temperatures can also directly activate TRPA1 channels. Perhaps TRPA1 is a “cold sensor” channel. Another TRP channel (melastin) TRPM8 is also activated at temperatures below ∼23 °C. So when you are hypersensitive for the cold, it is most likely this TRPA1 channel deep in your body cells, that is responsible! (Just so you know how to blame haha). Anyway, the cold can also cause inflammation in rosacea skin. But heat is just as much a trigger for rosacea. Heat, sun, hot baths; they all dilate out blood vessels as our body temperature rises. And rosacea skin already is a little bit warmer than 'normal' skin temperature. When the temperature rises quickly, even in healthy people, our cells produce TRPV1. Therefore TRPV1 channels have an essential role in temperature hypersensitivity when it comes to inflammation. And on top of all this, rosacea facial skin has shown to have a significantly lower heat pain threshold compared to the rest of our skin. Our faces notice heat quicker and develop painful skin much quicker (tingling, burning, prickling, blushing, pain) when we are in a warm surrounding than the rest of our bodies skin. I think everyone had detected that for him or herself already anyway :) And again, our little friend TRPV1 seems to be involved in this. The same goes for flushing after eating spices TRPV1 is dubbed the "capsaicin receptor", because it is directly activated when someone eats capsaicin, which is the chemical that makes chilli peppers so hot. The same happened in trials with mice; capsaicin also stimulates an increase in mouse skin blood flow, which shows that this blood flow increase is triggered ultimately by TRPA1 stimulation. TRPA1 is triggered by cinnamaldehyde, the main ingredient of cinnamon, which also leads to intense and acute painful burning sensation. This is even the case by those who do not have rosacea, and the burning they can feel from this is probably similar to that observed in rosacea. These findings highlight that TRPA1 and TRPV1 may be activated by the triggers of rosacea, such as cold or hot temperatures and spices, to mediate flushing or burning sensation episodes of rosacea.
Another aspect that makes rosacea skin burn and flush, is blood flow. Flushing longer than 10 minutes is indicative for rosacea (and therefore 'not normal' for normal skin). The smallest systems of blood vessels in our body are dilated in rosacea patients. TRPA1 is also here a factor. It sits in the basal layer of the epidermis, in the dermis, and in the epithelium of the hair follicle, so basically all throughout our skin. And when this TRPA1 is activated (for instance through heat, cold, stress, spices), a substance called "proinflammatory cytokine IL-1" is released, which is a key contributor to skin inflammation. Our skin actually recovers from such a TRPA1 triggered rosacea attack, by exposing our skin to cold air. Apart from more blood flow in the skin, rosacea patients in studies also showed heightened sympathetic nerve activity compared to those without rosacea. The sympathetic nervous system is a part of the body’s autonomic nervous system that controls involuntary functions such as heart rate, digestion, breathing and perspiration. This portion of the autonomic nervous system functions largely below the level of consciousness and has been shown to respond to emotion.
Substance P and CGRP in Rosacea
So, studies have shown that activation of TRPV1 (by capsaicin) and TRPA1 (by mustard oil) caused the release of neuropeptides. Normal human skin that was rubbed in with a cream containing capsaicin, showed a big red flare. But, this flare could then controlled again by a specific TRPV1 antagonist, SB705498. And there is also a new oral CGRP antagonist, telcagepant, which also managed to bring down a capsaicin-induced flushed skin reaction. Ultimately, what makes our skin flare, is not TRPV1, but another chemical, that is triggered by TRPV1: called CGRP. CGRP is one of the strongest blood vessel dilators in the skin. And to make matters worse, it makes sure that your skin also has increased inflammatory substances as a result of all this extra blood flow going around. The Neuropeptide SP is elevated in rosacea skin. They linger around the dilated blood vessels. Research showed that laser treatment reduced facial sensitivity, sensory nerve marker, and SP-positive nerve fibers in the skin of 31 rosacea patients. And there is also evidence that SP can also induce skin redness. When rosacea patients have an inflammatory flare, and biopsies are taken from their skin, scientists tend to find widely dilated blood vessels in the skin. SP might play a role in all this, as SP can stimulate mast cells to release histamine and 5-hydroxy-tryptamine. These mediators bind to histamine H1 receptors and serotonin 5-hydroxy- tryptamine-1 receptors, and as such they cause blood vessel dilation through the nerves of the skin. CGRP can make matters worse then, by forming skin redness. It is therefore a whole cluster of substances that work together to fire up a flare for us: CGRP creates blood vessel dilation and SP triggers skin redness, histamine release and inflammation, and they even strengthen each others powers by blocking degradation of each other by the body.
Proteases in RosaceaIt is also known that protease activity is higher in the facial skin of rosacea patients, and that antibiotics such as tetracyclines can indirectly inhibit (control) these proteases. Proteases also degrade elastin and collagen, which means your skin becomes less firm and strong and is not beneficial for the lymphatic system in your skin. They also indirectly increase inflammation in the skin, by stimulating the release of SP and CGRP. And in the last place, there is Reactive Oxygen Species (ROS), which also seems to play a role in rosacea. Substance P can cause their release. There is evidence in the literature suggesting that inflammation in the early stage of rosacea may be linked with ROS such as superoxide anions, hydrogen peroxide, and hydroxyl radicals, which are released by inflammatory cells such as neutrophils. The level of ROS was significantly higher in the facial skin of patients with rosacea compared with healthy control subjects, OR of the same rosacea patients after being treated with the antibiotic azithromycin. ROS is involved in microbicidal activity.
Studies have shown that cathelicidin, a potent inflammatory peptide, is upregulated in rosacea.
Cathelicidin can stimulate ROS, which plays a role in inflammation. And ROS is in turn again linked to TRPV1 receptor activation, which dilates our blood vessels and increases blood flow in the skin. It is a rosacea avalanche, in other words, when all working and activating each other together. And this is another reason why rosacea should be treated as soon as possible and controlled.
So in summary
TRPV1 and TRPA1 may contribute to the development of rosacea. The high skin reactivity of rosacea skin can be blamed on TRPA1 and TRPV1 receptors. When they are activated, they create blood vessel dilating substances such as CGRP and SP, as well as inflammation, which may further aggravate the symptoms of rosacea. They work together and strengthen each others actions. All the more reason to be very excited about this new treatment option; blocking of the neuropeptide-driven inflammatory processes resulting from activation of TRPV1 and TRPA1 receptors. This could become a completely new therapeutic approach to treating rosacea.
October 22nd 2020, XOLAIRMy friend from Australia sent me some interesting information about a drug called Xolair (Omalizumab) for the treatment of allergy related skin issues such as Morbihan syndrome or urticaria. Morbihan syndrome is a rare condition that can be a late-stage complication of rosacea. People who have this syndrome suffer from bad swelling of the eyes and the upper cheeks (oedema), as well as redness (erythema) sometimes. They can also have visible blood vessels (telangiectasias) and occasionally papules, pustules and nodules. This issue is related to substances in the body which also play a role in allergies; an abundance of mast cells which make the blood vessels dilate as well as substances which increase inflammation; cathelicidins such as Cath-37, which also seem to play a role in rosacea. Scientists found that Omalizumab can not only help patients with allergy-related asthma and urticaria, but also can help suppress the symptoms of this Morbihan syndrome. It binds the circulating IgE antibodies and may stabilise mast cells. There are some similarities between rosacea subtype 1 and Morbihan syndrome and urticaria: the facial flushing which rosacea can give work through the same pathways as the temporary red swellings observed in urticaria and angioedema. Scientists believe that omalizumab helps stabilize mast cells and reduces the temporary swelling, but that it can also help rosacea subtype 1 by reducing blood vessel dilation and potentially also reducing inflammation. Another drug that is linked to suppressing mast cell activity, ketotifen, shows also beneficial outcome in the treatment of rosacea in studies.
CASE REPORT
"A 56-year-old woman, with moderate erythematous rosacea, developed persistent and prominent erythematous (red) oedema of the face, lasting for one year. Firm swelling of the eyelids, impairing vision, accompanied oedema of the cheeks and forehead. Neither itching nor scaling was observed. Pronounced swelling was seen after exposure to hot, cold and windy weather, and to a lesser extent to stress, sunlight and spicy food. The patient could not work or participate in the social events, due to her symptoms. She was diagnosed with Morbihan disease after excluding allergies, various connective tissue diseases such as dermatomyositis and superior vena cava syndrome. The patient was tested with a normal skin prick test, tryptase, antinuclear antibodies, thyroid function test, full blood count and X-ray of the lungs and mediastinum. Skin punch biopsy demonstrated non-specific inflammation consistent with rosacea. - MS was treated with lymecycline 300 mg twice daily for 3 months and later isotretinoin 10–20 mg daily for 4 months, but there was no effect on the swelling or erythema. Because of the temporary swelling caused by physical stimuli, in addition to the permanent oedema, we initiated a trial treatment with omalizumab 450 mg subcutaneously. A dramatic reduction in the swelling was seen 1–2 weeks post-treatment (Fig. 1B) and the patient subsequently became tolerant to the physical stimuli. The MS cleared completely after 5 months of monthly omalizumab injections, an initial dose of 450 mg and consecutive doses of 300 mg (Fig. 1C). Maintenance treatment was given for a further two months, every 4–6 weeks, and was then discontinued successfully without clinical relapse, 6 months later. The quality of life was markedly improved after omalizumab injections and the patient was able to resume working, instead of being on sick leave. Her photos show first a pre-treatment photo of prominent and persistent erythematous edema of the face. Firm swelling of the eyelids impairing vision. Then a photo showing the reduction of the edema as observed two weeks after the first subcutaneous injection with the monoclonal antibody - omalizumab 450 mg. The patient tolerated windy and cold weather and noticed less tenderness. Last photo: the patient is in her normal condition after monthly injections of omalizumab for five months. Her quality of life was substantially improved, and she was able resume normal life, including returning to work. A written permission from the patient to publish these photos was obtained." Source
A dermatology specialist wrote here: "We offer Xolair as an option to treat chronic hives which don’t respond well to antihistamines. Our office is one of only a handful of dermatologists in New Jersey who use Xolair. Xolair is an injectable prescription medicine used to treat patients with chronic hives that don’t have a known cause and are not controlled by H1 antihistamine treatment. Xolair is given in one or more injections under the skin for four weeks by our doctor."
More links:
On The Rosacea Forum, Lookout wrote on February 6th, 2009 about Xolair (=omalizumab): "Xolair..... is used for asthma (allergy based). I would want to try Xolair. I think the research for rosacea needs to include these types of meds since steroids make our condition worse or even brings it on! Xolair. From what I understand would be safe for long term use..... That's why I picked it as my "drug" of choice! LOL. I figured most of us here do have allergies but this med is only used for allergy induced asthma..... But in my mind why not try it on rosacea patients? If it is effective in reducing inflammation then it just may reduce rosacea symptoms...not cure but give us a pill that really address that inflammation! I would have to go back to my ENT.... and get tested and try to sell him on my theory to let me try it and see... I have to do more reading about it... I guess I am feeling frustrated that there is nothing coming out for rosacea and for some reason most still don't recognize that a flare is an inflammatory response IMO... Wish they would do clinical trials with this med for rosacea... Maybe I should write the company about it... like they would listen to me LOL!"Lamarr replied on February 7th, 2009: "Most anti inflammatories over time well help rosacea, IF they target the correct cytokines/inflammatory pathway. Cyclosporin works very well for rosacea, but like already said has some serious side effects. These drugs can be used in different ways though, Dr Chu has used cyclosporin for rosacea, you just take the drug every other day. Instead of everyday in RA/organ transplant etc. I am using the perfect anti inflammatory for rosacea, an anti milarial."
Lookout replied on February 6th, 2009: "They say you must first be tested to actually have allergies and then the person with asthma may be put on it......lot's of med's are effective for other conditions but it's almost an accident that we find this out many yrs later!"
Nansa replied on February 25th, 2019: "I have been on high dose fexofenadine for 2 - 2,5 years most of the time along with montolukast, tranexamic acid and Xolair (omalizumab) to control chronic urticaria (insanely itching and painful) and angiooedema. In it-self fexofenadine had little to no effect on itching, but... It might very well help others. It is a bit complicated as I have chronic idiopathic urticaria and angiooedema (and of course asthma and allergy) - I get xolair injections to modulate the immunesystem (at hospital at the immunology dept). The angiooedema is "different in nature" from time to time - (in the throat, on the jaw, around/on the ears, and at least two types of swelling around the eyes). The dermatologist consulted suggested that at least some of it was morbihans (also because I have suffered from rosacea, incl occular, for years). Whether morbihans is worse than the other angiooedema types I do not know... I do NOT like any of it :-)
And Laser_cat Nansa wrote on April 15th, 2019: "In the US - my experience is that most derms will not be able to offer much more than PCP. I began by asking PCP to trial medications mentioned here or in literature (clonidine, beta blockers). Eventually I landed on 2 derms who have an interest in neurovascular rosacea, but even they realize a large part comes down to trial and error per patient. My therapist had an "in" at my local teaching hospital and asked around for doctors who would specialize in flushing (how I found one of my derms). I found my other derm by looking up authors of rosacea publications. What I am able to get from these 2 derms I am not able to get from PCP or myself - how long to trial a given medication before I give up, why I wouldn't be a candidate for laser, how to titrate medications, medications that aren't typically "thought of" (calcium channel blockers, Xolair, birth control, IVIG, baclofen, ..), pathophysiology behind my symptoms and similar patients. There are derms who are very interested in neurovascular stuff and who realize that flushing conditions can be anywhere from mild to disabling, but these derms are far and few between I think, most derms will try to rx soolantra, antibiotics etc."
A patient with severe postural orthostatic tachycardia syndrome (POTS) and mast cell activation syndrome (MCAS) received immunotherapy with low-dose naltrexone (LDN) and intravenous immunoglobulin (IVIg) and antibiotic therapy for small intestinal bacterial overgrowth (SIBO). And this woman with crippling POTS that gave her face flushing as well, improved on ultra low dose naltrexone, ivig and sibo treatment. It pretty much reversed eighteen years of crippling pots, mcas, and sibo for this woman. She even had blue hands. Poor woman. Her facial flushing reduced quite quickly.
July 5th 2020, German TV-program about rosacea treatmentsThank you to Gunther, who sent me a link to this German program about a woman with rosacea, who gets tips on how diet can help her skin become less red and inflamed. I realize that diet is not a rosacea trigger for everyone. I read often about people who have not identified dietary skin triggers, despite all sorts of elimination diets. This video and info is therefore not necessarily for everybody with rosacea. But I think diet can play a role sometimes in finding improvement. Maybe more so in subtype 2 rosacea, with background redness and skin outbreaks and pimples. But from own experience I can say that even in subtype 1 rosacea, with skin flushing, burning and redness, diet changes can sometimes give some improvement (not a cure for me though, not even close...). I notice a pretty significant improvement in my skin as well, like the woman in this video - although she sees bigger results than me - when I stay clear of sugar, wheat, dairy and any spices. In my case there is also an issue with histamine rich foods, which does include quite a long list of food items. But, when I eat lots of vegetables (except tomatoes, eggplant and a couple of other vegetables high in histamine), and stick to carbs like potatoes, as well as eating organic beef or chicken and foods like olives, unions and fruit, my skin is really less red and less inflamed. It also takes more for me to flush then. Although I still flush very easily, even then. But my skin has a base colour which is a bit more pale then. It is much easier to stay cool. My weaknesses are chocolate, bread and pastries, as well as some sugary things pr pizza. I rarely give in to such foods, but when I do it's a good amount of sinning. Not just one square of chocolate :) The past weeks for instance, I stuck to the healthy diet and had nothing to sin with in the house; no chocolate, no bread, no sugary things. No crisps either. Then came that moment of boredom with the same safe foods day in and day out. I stuck it out some longer but by the time the new weekly shopping had to be done, I bought some chocolate, a chocolate pastry and some almonds covered in chocolate. I purposely bought small quantities, no large bars or anything, because I ate it all today. I guess it's supposed to be a reward for sticking to the low calorie, low carbohydrates, low on fun foods for as long as I did. But the 'reward' came in the shape of a flushed hot red face for most of the day and evening now. Damnit. And the effects are there right away, within half an hour. I always curse myself then and vow to never eat this crappy food again. Until the next time of course. Anyway, I just wanted to share this video with you, again thanks to Gunther for linking me to it. And I took the time to put English subtitles under the German video. To anyone German out there who may view it, please forgive me if I translated 1 or 2 muffled words incorrectly. I was poor at German in school..
March 1st 2020, Ted Talk about angiogenesisI watched this very interesting Ted Talk, from scientist and doctor William Li. He explains how certain foods can increase our chances or developing cancer in life, and others can reduce those chances. Now, he emphasizes that cancer can have different causes and some people have a genetic predisposition. But each and everyone of us endures gene mutations throughout our lives and especially once we are over the age of 40. William Li explains that these cell mutations can remain small clumps of cells and then be cleaned up by the body's immune system, or they can continue dividing and turn into cancerous tumors over time. Now scientists have discovered that certain foods can help speed up this process, or help undo this process. Dairy products for instance contain a substance which promotes it, whereas foods like specific mushrooms and soy beans can help reduce these chances. How? Through new blood vessel mechanisms; angiogenesis. Cancerous tumors can grow due to the body creating blood vessel systems for them. Without these blood vessels, the tumor cannot grow. And here a link with rosacea emerges. Because for us rosacea patients who have issues with red or flushed cheeks, the angiogenesis mechanisms have gone haywire too. The human body has a certain set of blood vessels, formed in the uterus, and we are set with those vessels through life. But the body can also create extra blood vessels during very specific circumstances, for instance during wound healing of a skin injury, or when a woman is pregnant and has to develop extra vessels in the uterus to form the placenta. After pregnancy, the body reabsorbs those extra blood vessels again and brings things back to the status quo through naturally occurring angiogenesis inhibitors in the body. Regulating the amount of blood vessels through a system of stimulators and inhibitors of blood vessel growth. Or so it should be. And there are other situations where this happens. Dr. Li even shares an image during his Ted Talk where he mentions rosacea as one of the possible medical conditions of which patients suffer due to angiogenesis going rife, and the body not cleaning up the excess blood vessels. Dr. Li then focuses on cancer and how trimming down the bodies ability to grow blood vessels for the tumor is a promising treatment mechanism for early stage tumors. He explains the mechanisms and interesting for us people with rosacea; he names potent angiogenesis foods and medication. Something we blushers and flushers may also benefit from. I cut the 20 minute long video up a bit to show you specifically what dr Li says about these blood vessels, I recommend it as it is extremely interesting I think. First the trimmed video in 2 parts (due to limited size options on blogger), then the full 20-minute video, also including info about cancerous tumors:
So, Dr. Li mentions a number of natural anti-angiogenesis foods, which help the body prune back excess blood vessels.
Taking some foods together can cause food synergy and enhance the anti-angiogenesis effects. He mentions:
-Soy products such as tofu and tempeh, (which contain the inhibitor "genistein")
-Agaricus subrufescens mushrooms (contain the inhibitors sodium pyroglutamate and ergosterol)
-Black raspberry (Rubus occidentalis) extract
-(Green) tea (catechins)
-Lingzhi mushrooms and Maitake mushrooms (via inhibition of VEGF and TGF-beta)
-Trametes versicolor mushrooms (Polysaccharide-K).
-Parsley
-Turmeric
-Lavender
-Citrus
-Red grapes
-Garlic
-Liquorice (glycyrrhizic acid)
-Red wine (resveratrol) -> -resveratrol 60% reduces unnatural angiogenesis!
-Royal Jelly (Queen bee acid)
-Berries
-Tomatoes (lycopene)
-Vitamin E
-Tranexamic acid
-Ellagic acid (strawberries)
-Bok choy
-olive oil
-Grape seed oil
-dark chocolate
In this NCBI research paper, you can read more about the potency of natural health products to reduce angiogenesis
It highlights several supplements which have a proven record for reducing angiogenesis: "The herbs that are traditionally used for anticancer treatment and that are anti-angiogenic through multiple interdependent processes (including effects on gene expression, signal processing, and enzyme activities) include Artemisia annua (Chinese wormwood), Viscum album (European mistletoe), Curcuma longa (curcumin), Scutellaria baicalensis (Chinese skullcap), resveratrol and proanthocyanidin (grape seed extract), Magnolia officinalis (Chinese magnolia tree), Camellia sinensis (green tea), Ginkgo biloba, quercetin, Poria cocos, Zingiber officinalis (ginger), Panax ginseng, Rabdosia rubescens hora (Rabdosia), and Chinese destagnation herbs." The article also mentions western medicine used to reduce angiogenesis, such as bevacizumab (Avastin) and heparin. Interestingly this research paper also mentions Vitamin D and bovine cartilage as scientifically proven anti-angiogenesis sources. There have been many rosacea patients who improved from increasing their (typically low) vitamin D levels, and drinking bone broth (containing bovine cartilage usually) has also been mentioned often as beneficial by rosaceans.
This is a study of the pathogenesis of rosacea: how angiogenesis and mast cells may participate in a complex multifactorial process
I myself have an issue with mast cells, and in thus study it was established that mast cells together with angiogenesis play a role in rosacea. When a biopsy sample was taken of the skin of rosacea patients, scientists found that the skin samples contained mast cells, as well as statistically important differences in angiogenesis: samples taken from skin with active rosacea (and high vascular density) showed more factors of angiogenesis than skin which clinically showed no rosacea symptoms. Researchers also found serum antibodies against H.pylori in the skin samples of rosacea patients. Also interesting: microvessels density (skin with a lot of extra blood vessels) and total vascular area showed no correlation with the degree of prolonged and excessive sun exposure the skin received, nor with inflammation or with the Demodex density. Which underlines once again that people with rosacea flushing and skin redness (without pimples) often do not suffer from demodex infections which cause the rosacea. The researchers concluded that "Angiogenesis seems to play an important role in the pathogenesis especially of the more severe clinical form of Rosacea. Mast cell numbers in the skin seem to participate in evolution to disease chronicity by contributing to inflammation, angiogenesis and tissue fibrosis."
This study proves that tranexamic acid ameliorates rosacea symptoms through regulating immune response and angiogenesis
The 2018 study confirms that rosacea is immune system influenced: "Rosacea is a chronic inflammatory cutaneous disease characterized by immune system anomalies and vascular hyperreactivity." Recently, therapy of rosacea has improved substantially with the approval of Tranexamic acid (TXA), an antifibrinolytic agent. Rosacea-like symptoms including skin erythema and histopathological alterations, as well as the elevated pro-inflammatory cytokines (IL-6 and TNFα) and MMP9 expression were significantly ameliorated by TXA treatment. In addition, TXA reduced the expression levels of innate immune gene (TLR2, KLK5 and Camp) and neutrophils relative gene in rosacea-like lesion. Furthermore, the anti-inflammatory effects of TXA were associated with the inhibition of TLR2, pro-inflammatory cytokines (IL-6 and TNFα) and chemokines (CCL10) expression in LL37-activated HaCaT cells. Finally, TXA repressed the angiogenesis by reducing the number of CD31+ cell and downregulating the expression levels of VEGF in rosacea. In conclusion, our finding defines a treatment mechanism by which TXA ameliorates rosacea symptoms by regulating the immune response and angiogenesis." - In other words: Tranexamic acid is a medication used to treat or prevent excessive blood loss. Side effects are rare and may include changes in color vision, blood clots, and allergic reactions. There is however a small risk that tranexamic acid may cause a clot in another part of the body. This research found that Tranexamic acid ameliorates rosacea symptoms through regulating immune response and angiogenesis.
The 2018 study confirms that rosacea is immune system influenced: "Rosacea is a chronic inflammatory cutaneous disease characterized by immune system anomalies and vascular hyperreactivity." Recently, therapy of rosacea has improved substantially with the approval of Tranexamic acid (TXA), an antifibrinolytic agent. Rosacea-like symptoms including skin erythema and histopathological alterations, as well as the elevated pro-inflammatory cytokines (IL-6 and TNFα) and MMP9 expression were significantly ameliorated by TXA treatment. In addition, TXA reduced the expression levels of innate immune gene (TLR2, KLK5 and Camp) and neutrophils relative gene in rosacea-like lesion. Furthermore, the anti-inflammatory effects of TXA were associated with the inhibition of TLR2, pro-inflammatory cytokines (IL-6 and TNFα) and chemokines (CCL10) expression in LL37-activated HaCaT cells. Finally, TXA repressed the angiogenesis by reducing the number of CD31+ cell and downregulating the expression levels of VEGF in rosacea. In conclusion, our finding defines a treatment mechanism by which TXA ameliorates rosacea symptoms by regulating the immune response and angiogenesis." - In other words: Tranexamic acid is a medication used to treat or prevent excessive blood loss. Side effects are rare and may include changes in color vision, blood clots, and allergic reactions. There is however a small risk that tranexamic acid may cause a clot in another part of the body. This research found that Tranexamic acid ameliorates rosacea symptoms through regulating immune response and angiogenesis.
This study proves that artemisinin is a potential option to inhibit inflammation and angiogenesis in rosacea
Artemisinin, an anti-malaria drug, was reported to have several effects including anti-inflammation and anti-angiogenesis activities. When this drug was tested on rosacea skin, the skin erythema (redness) improved. Elevated pro-inflammatory factors and inflammatory biomarkers were also significantly improved. Artemisinin also reduced rosacea-like inflammation and repressed angiogenesis. In conclusion, artemisinin improved rosacea-like dermatitis by regulating immune response and angiogenesis, indicating that it could represent an effective therapeutic option for patients with rosacea. Artemisinin derivatives are known for their ability to suppress immune reactions such as inflammation. One derivative, SM934, was approved in 2015 by the China Food and Drug Administration for clinical trial as a drug for systemic lupus erythematosus. Experiments in animal models have given good results. It can regulate T cell subsets, inhibit the activation of B cells, block the production of inflammatory cytokines and NF-κB signal transduction pathway.
Why women with neuropathic rosacea have a higher risk of developing migraine March 13, 2019
Scientific research has confirmed that people with rosacea, and especially neuropathic rosacea with facial flushing and burning, have a higher risk of developing types of headache such as migraine and cluster headaches. Our blood vessels are linked throughout our body and when the blood vessels in the facial skin do not function correctly, dilating too much, then this can also extend to the blood vessels going to our brain. Patients with cluster headaches for instance - which is a very severe type of headache that happens on one side of the head/face - deal with blood vessels in the head which dilate too much and are pressing on the nerve endings in your head, causing severe nerve pain; head aches. Often patients of cluster headaches notice some relief by walking in the cold air. Because just like with facial flushing, cold air makes the blood vessel constrict. And rosacea also involves inflammation of the skin and blood vessels and this inflammation in turn is also involved with migraine. So it is a twofold interaction and overlap thing. It is a two way street, science found that having rosacea increases the risk of developing migraines, and having migraines increases the risk of developing rosacea.
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In this research, scientists tracked more than 4.3 million individuals in the Danish National Patient Registry, of which roughly 50.000 were diagnosed with rosacea. The study found that rosacea patients were 31 percent more likely to experience migraines than patients who do not suffer from rosacea. Ocular rosacea patients even had a 69 percent increased risk of migraine, while patients with phymatous rosacea (subtype 3 of the nose) showed no increased risk. Female rosacea patients over the age of 50 had the highest increased risk of migraine. These percentages may even be on the low side, as the researchers determined them based on patients who took anti-migraine medication. And therefore all the rosacea patients with headaches who did not take specific medication for this, or who bought over the counter and freely available pain medication, have been overlooked. Which may be a significant amount, theoretically. Dr. Egeberg, who conducted the research, and his team believe that the vascular abnormalities that cause the rosacea symptoms we all know, are also to blame for the migraines. It is also interesting that both vascular rosacea and migraine have comparable triggers, for instance stress and alcohol consumption. Another study on this topic was done in the United Kingdom and it included more than 100,000 migraine patients. This study found that a smaller percentage of women with rosacea had also developed migraines: 22 percent. No association was found for rosacea and migraine in male patients. The association found between rosacea and migraine for female patients increased directly with age. Women over the age of 60 had a 66 percent increased risk of rosacea. The researchers also stated that it is possible that a specific medication group for migraines, triptans, can theoretically also help people with vascular and neuropathic rosacea, as they are both anti-inflammatory and vasoconstrictive (so they constrict the blood vessels, something we rosacea patients can benefit from). But that more research is needed for this.
This pubmed article also suggests some more treatment options for vascular and neuropathic rosacea: Conclusions and clinical implications: "Based on the findings linking rosacea to diseases involving dysregulation of the immune, vascular, and nervous systems, several new modalities for treating rosacea have been proposed. The success of neurologically focused drugs including gabapentin, duloxetine, pregabalin, and tricyclic antidepressants in a subset of rosacea patients suggests a neurological component of the disease. [..] The link between rosacea and autoimmune disease has prompted suggestion of probiotics as a potential therapy for both conditions, which may limit overactive innate immune responses to lipopolysaccharide (LPS). Specific targeting of both innate and adaptive immune responses is justified based on the above correlations, although finding the particular drug targets that will impart benefit in rosacea patients remains a challenge."Another treatment that can help both migraines and rosacea are botox treatments. They are administered differently here than for anti-wrinkle treatment (not in the nerves but in the skin). Some of the most common symptoms of a migraine include throbbing pain, sensitivity to light and sound, nausea and changes in vision. Migraine triggers include:
▪ Hormonal fluctuations.
▪ Certain foods and drinks, including alcohol and caffeine.
▪ Emotional stress.
▪ Changes in the weather.
▪ Some medications.
Triptans
Triptans are a class of medications that bind to serotonin receptors in the brain and diminish the swelling of blood vessels. They therefore constrict blood vessels and are also anti-inflammatory. Triptans are primarily used in the acute treatment of moderate to severe migraine and are fast acting, generally reducing head pain in about 2 hours. Some subtypes are called sumatriptan, naratriptan, rizatriptan, almotriptan and zolmitriptan. Because these drugs narrow the blood vessels, rosaceams who are also heart patients are not a good candidate. Also, from what I understand this class of medication is not meant to be taken long term.. And there is even mentioning of rebound flushing. After all, like Mirvaso, any medication that chemically constricts the blood vessels, comes with the risk of overcompensation by the body and rebound flaring once the medication is stopped... Yeh, not sounding all too great this, does it.
1. Stop vasomotion -- dilation and constriction ........ and place them into a semi-constricted state
2. An unidentified effect on vasodilator nerves up in the cerebral blood vessels (brain blood vessels).
Often times this has a positive action on facial blood vessels too. My general guesstimate is that 80% find relief while the others do not. This would give physicians working knowledge with a known medication."
Bethanne wrote on October 12th 2005: "I have suffered from migraines for over 20 years and have had Rosacea for more than ten years. I just took some Zomig (Zolmitriptan) this morning. In my case with this medication and those in its class (I took Imitrex years ago) my Rosacea flushing and redness either stays the same or, more frequently, ramps up. Part of this is often influenced by when I get the migraine and whether I am able to sleep it off after taking the meds. If I cannot continue to sleep after taking the medication, I am more likely to become flushy. I don't know if that is truly a mitigating factor or just stress-related. These meds are also known to have a rebound affect on migraines if used too frequently. I wonder if that means that they would also cause a rebound in Rosacea symptoms for those who are helped by them? Interesting post--thank you. Beth"
Irishgenes wrote on October 13th 2005: "I don't see how the triptan drugs could be used for rosacea. They are not supposed to be used over twice a week. Any effect on rosacea would be quite temporary."
G. Nase replied on 14th October 2005: "This would never be a long term treatment option for rosacea as you pointed out. It has significant constrictor actions and that is why some experience a rebound. The information that could be pulled out of this medication is how it affects vasodilatory nerves and not the second effect on blood vessels. One potential use down the road, is to use it after unusually bad flares that happen to rosacea sufferers. Sometimes, the one major flare can cause significant progression of the disorder -- so in very select cases, this may be an option for those that are caught in a horrific flare. Just anecdotal, but quite a few do notice transient improvement in rosacea symptoms with one or two shots. Of course there are many things that must be discussed with your doctor about these meds. Sometimes you can learn quite a lot about a disorder by how a medication affects its symptoms.
Bethanne replied on October 14th 2005: "Zomig now comes in a nasal spray dispenser. One dispenser administers 5 mg of the drug."
Laser_cat wrote on September 28th 2017: "Triptans for severe flushing - Hi, Just wanted to mention that if I ever take an imitrex (sumatriptan) when I feel a migraine coming on, it greatly helps with my flushing problems as well. You can read about the mechanism of action here. But basically it can help constriction of blood vessels and inhibit CGRP and substance P (which are implicated in sub 1 rosacea). A forum member (probably not here anymore) "Meg" I know used to take Maxalt (Rizatriptan) sometimes for her flushing/burning, but I am not sure how often she took it. My sense is your body will get used to it if you take it too often. For me any rebound isn't noticeable when the effects wore off. Just in case this helps someone! Lizzy" - Scroll down in this post to one of the earliest updates, which details this link between flushing and CGRP and Substance P.
January 31st 2019, Immune suppressing anti-inflammatoriesI am always on the lookout for ways to reduce inflammation, without wanting to take steroids of any type. I took diclofenac (NSAID) for several years but at some point developed heart cramps whenever I exercised and didn't want to keep taking them therefore. I also felt they stopped working and paradoxically might have made me more red eventually. I now heard about IVIG (Intravenous immunoglobin), which means that you get intravenously (IV) provided with extra antibodies, which stay in your body for several weeks and help your body fight off a large variety of infections. Unlike steroids, you can do this treatment long term. IVIG has proven to be effective in the treatment of various autoimmune and inflammatory disorders, lowering inflammation in the body. So, considering that rosacea is also an inflammatory disease (and some forms of rosacea quite possibly being an auto-immune related issue), you would think that it could improve rosacea in theory as well. However, apart from being anti-inflammatory, IVIG also boosts your immune system. Which paradoxically can worsen auto-immune related inflammation again. Anyway, the person who tried it for rosacea flushing found IVIG had absolutely no effect on the rosacea. Bummer.. I also read this account from a pregnant woman with rosacea who had a doctor suggest IVIG for her rosacea, and wrote:
"My rosacea started to blow up and Dr G did not want to take any risk. He is one of few who thinks the rosacea is an autoimmunological disease. After 16 weeks I got very awful reaction on my face and Dr G suggested me to try IVIg (just because of the facial condition). I did not take IVIg since 5 of the experts in Sweden refused to help me with that and I did not want to take a risk to fly to London in the worse flew-time in Sweden. However with help of a sulphur creme and the time my face become better."
This scientific article also states that: "High-dose intravenous immunoglobulins (IVIGs) are increasingly used to treat inflammatory and/or autoimmune disorders. In dermatology, they provide therapeutic benefit in Kawasaki disease and certain cases of dermatomyositis." But it goes on to warn for adverse reaction, such as 4 patients who developed severe eczema after IVIG treatment: "We report 4 cases of a characteristic severe extensive eczematous reaction that occurred approximately 10 days after IVIG infusion for polyradiculoneuritis." The scientists did not understand the exact mechanism behind it but were clear that its onset within days after the IVIG treatment, implied it was a direct reaction to it. Which goes to show that your immune system does get a boost.
However, there are more anti-inflammatory optionsI was suggesting a couple of other anti-inflammatories in addition to NSAID's and steroids (not suitable for rosacea, can make it worse). Methotrexate is one, which lowers the immune system. I have talked with Professor Tony Chu about this in the past. He recalled several patients with rosacea who had very severe cases and responded well to methotrexate. However, he warned, it is a very serious medication which lowers your immune defenses not only in favour of auto-immune diseases and immune related inflammation, but also makes you much more prone to complications from a simple flu or infection. Flu can turn easily into dangerous pneumonia for instance, infections might not heal properly and the immune system in the long term also helps us clear up cancerous cells, if all goes well. So there you have a heap of potentially very serious side-effects, and thus.. he wouldn't prescribe methotrexate to me. I understood. Some other meds that might be interesting for rosacea inflammation are CellCept, and azathioprine. These are non-steroidal medications that are broadly immunosuppressive and anti-inflammatory, BUT have the same downsides as methotrexate; by suppressing the immune system they also increase potential risks of infection and even certain cancers in the long run. But, they are definitely safer for rosacea itself than prednisone (a steroid), which can cause vasodilation, permanent blood vessel damage, flushing, thinning of the skin and worsening of symptoms.
"Never, never, never, ever prescribe steroids for rosacea" Dr.Kligman (Dermatology-University of Philadelphia) & Dr. Pleig (Dermatologische Klinik Und Poliklinik der Universitat Munchen, Germany) state in their 1973 book, entitled Acne & Rosacea, First edition. Likewise, their second edition in 1993 harshly criticizes dermatologists that prescribe steroids for rosacea".
The problem with steroids is that they can be super effective for certain other conditions, that can overlap in symptoms with rosacea, or can be misdiagnosed as rosacea. Think for instance of lupus, dermatitis, erythromelalgia and even seb derm and quite a few other conditions that can cause flushing. Some doctors can determine through the use of steroids that someone in fact has an autoimmune disease, as corticosteroids will lower the immune response and improve your symptoms, as well as inflammation. Doctors are often easily swayed to throw some steroids your way when your symptoms are inflammatory and vague. But one always needs to be cautious with them when it comes to rosacea. Even short term use of a steroid cream can trigger rosacea (as it did in my case). And existing rosacea can worsen due to steroid creams or pills. But some dermatologists prescribe steroids regardless, as they will help initially to make the skin less red and inflamed. I am of the opinions that steroids, both topical or in pill form, should never ever be used as a rosacea treatment.
Palmitoylethanolamide (PEA)I was also tipped on the supplement palmitoylethanolamide (PEA) for the treatment of pain, inflammation and even of mast cell instability. I ordered it this week and will give it a try as soon as it comes in. So far I have had bad reports with mostly all supplements however. Only Alpha Lipoic Acid seemed to help slightly, the rest either did nothing (a few) or made my flushing worse (most). But will try it anyway. So what is palmitoylethanolamide (PEA)? It is a fatty acid, produced in the body to combat pain and inflammation, by boosting your natural cannabinoids and protecting the nerves throughout your body. My rosacea is both vascular and neuropathic, meaning it shows itself through constant dilating of the blood vessels - flushing, redness - as well as giving me a lot of nerve pain in the face; my skin always feels tight, burned up and uncomfortable. And when I get massively flushed or more red than usual, it feels on fire, literally like someone threw something hot or acid-like on it. So the nerves in my facial skin have become hypersensitive after twenty years of rosacea flushing, inflammation and swelling. hence, this supplement sounds good so far :) What else? Palmitoylethanolamide (PEA) can also be found in soy lecithin, soybeans, egg yolk, peanuts, and alfalfa. However, most of these might not be a suitable option for people with food sensitivities (soy can be a trigger for rosacea as well as the high-histamine peanuts. Eggs can also be a trigger for some). As a supplement, PEA is available in tablet, capsule, and powder form and is considered a strong and safe natural painkiller and anti-inflammatory. More than 30 clinical trials so far have confirmed it can relieve complex pain (but also stated that more large-scale scientific research is needed). This scientific article concluded:
"PEA represents a promising addition to our therapeutic armamentarium for neuropathic pain, with potential for good tolerability and a low propensity for side effects."
It is also claimed that PEA can activate the cannabinoid receptors, protect the brain and heart, improve mood, reduce allergies, and may help fight the common cold. PEA also activates the energy-boosting, fat-burning, and anti-inflammatory PPAR alpha. This research paper states: "Palmitoylethanolamide (PEA), the naturally occurring amide of palmitic acid and ethanolamine, reduces pain and inflammation through an as-yet-uncharacterized mechanism. Here, we identify the nuclear receptor peroxisome proliferator-activated receptor-alpha (PPAR-alpha) as the molecular target responsible for the anti-inflammatory properties of PEA." In an analysis of 12 human studies, PEA supplements reduced chronic and neuropathic pain intensity without any serious adverse effects. It has to be used for at least 2 weeks to achieve pain relief. PEA was typically given over 3-8 weeks at dosages between 300 and 1200 mg/day. Taking it over a longer period of time strengthens its effects without causing tolerance. Normal dose is 300 or 600 mg/day, however: "At least 600 mg/day may be needed to relieve nerve pain, while doses of 1,2 g/day were used for diabetic nerve pain." You can read more favorable research outcomes in this article. One important benefit of it I like to name here is that PEA is said to reduce gut inflammation. I have a chronic low grade inflammatory condition of the gut (microscopic colitis) and it appears that many people with rosacea have in fact some issue or another with their gut and bowels (you can read my blog post about the link here). And depression! I'm of course not sure if this is really the wonder supplement that article makes it out to be :)
PEA Reduces Gut Inflammation"PEA was successfully used to relieve symptoms of inflammatory bowel disease (IBS) in animals. Mice with chronic gut inflammation have low PEA levels, while PEA supplements normalized bowel movement and prevented damage to the gut lining. In tissues taken by biopsy from people with ulcerative colitis, PEA lowered inflammatory cytokines and the buildup of neutrophils, immune cells that worsen symptoms and contribute to gut damage."
PEA Reduces Depression
"In a recent study of 58 people with depression, PEA (1,2 g/day) given over 6 weeks greatly and rapidly improved mood and overall symptoms. PEA was added to antidepressant treatment (citalopram) and lowered symptoms by an impressive 50%. This clinical study was a follow-up on numerous studies in which PEA improved symptoms of depression in animals."
PEA Reduces Histamine and Allergies
"PEA is a safe histamine-release blocker. People with allergies, histamine issues, and Th2-dominance will likely benefit from it. In animal and cell-based studies, PEA improved eczema and skin allergies by lowering mast cell activation and blocking the release of histamine. [..] In dogs with eczema, PEA helped soothe symptoms by reducing skin inflammation and itching. PEA reduced inflammatory substances (TNF alpha) and increased endocannabinoids in the skin (2-AG), which altogether strongly diminishes the allergic response." And there is more scientific info for now... Boring boring! But I want to share it anyway.
Peptide LL-37I was also told about research about a possible link between rosacea inflammation and the peptide LL-37. There is quite a bit of research online available on it, so I will write a bit more about it now. Know and realize here, that the true cause of rosacea has not been discovered yet. Doctors and scientists do not know what causes the different subtypes of rosacea (subtype 1: flushing and redness, Subtype 2: skin outbreaks and inflammation, Subtype 3: rosacea of the nose; rhinophyma, Subtype 4: ocular rosacea of the eyes and the recently added Subtype 5: neuropathic rosacea with nerve pain and burning). It is likely that these different subtypes may have some different underlying mechanisms. For instance; subtype 2 is often improving from topical ivermectin or Soolantra applications (see entire blog post about this here). Indicating that demodex mites can play a role in this subtype. However, for subtype 1 with flushing and burning these creams rarely work well. The flushing is also not improving when using textbook rosacea treatments, such as antibiotic pills or creams. In fact, flushing is one of the most difficult to treat symptoms of all, in rosacea patients. Topicals like Mirvaso (brimonidine) and Rhofade (oxymetazoline) have proven mostly disastrous for rosacea flushers. Large groups of people had their rosacea skin burned or deteriorated, had bad rebound flushing episodes that were often called "hellish" and long lasting. They chemically constrict the blood vessels, only for the body to compensate with abnormal blood vessel dilation rebound flushing) afterwards. It destabilizes the blood vessels in the long run and patients have mentioned their rosacea progressing to areas and severity they never had it before. of course another group states to have success with it, but it's a Russian Roulette drug, just like steroids. Better to reduce the flushing in my opinion are anti-flushing medication, or IPL or laser. (Read all about this here and here). And facial flushing goes by different pathways than the spots and outbreaks that subtype 2 patients tend to get. So, one big discovery, of one single cause, might be unlikely. Nevertheless, a (faulty) peptide called LL-37 may play a role in rosacea inflammation according to some research. In this scientific research, it is stated that:
"Chronic, common inflammatory skin diseases such as atopic dermatitis, psoriasis or rosacea are characterized by dysregulation of cutaneous innate immunity (aka; there is an issue in rosacea skin with the normal functioning of the immune system function). Cathelicidin LL-37 is an important effector molecule of innate immunity in the skin and atopic dermatitis, psoriasis or rosacea show defects in cathelicidin expression, function or processing. *In rosacea, cathelicidin processing is disturbed resulting in peptide fragments causing inflammation, erythema [skin redness] and telangiectasias [small dilated blood vessels at the surface of the skin]. *In atopic dermatitis, cathelicidin induction might be disturbed resulting in defective antimicrobial barrier function [causing infection]. *In contrast, psoriasis is characterized by overexpression of cathelicidin. However to date it is unclear whether pro- or anti-inflammatory functions of cathelicidin predominate in lesional skin in psoriasis. In this review, the current evidence on the role of cathelicidin LL-37 in the pathogenesis of inflammatory skin diseases will be outlined. As cathelicidin LL-37 might also serve as a future treatment target potential novel treatment strategies for those diseases will be discussed." - So the research article suggests that the skin of people with rosacea has a disturbed functioning of the LL-37 cathelicidin peptide. Does that mean that there are more of these peptides in rosacea skin? or less than normal? Or that there are normal numbers but that the peptides do not work as they should do in rosacea skin? And what is LL-37 peptide?
Cathelicidins in the human body play a crucial role in the bodies immune defenses against bacterial infections trying to infect from the outside. Wikipedia states that "Patients with rosacea have elevated levels of cathelicidin." And when wiki states that "Excessive production of LL-37 is suspected to be a contributing cause in all subtypes of Rosacea", it cites this research paper, which is the same as the earlier quoted research. Its authors, M. Reinholz, T. Ruzicka and J. Schauber published in 2012 their research, stating that normal skin has three ways to protect itself from bacteria's from the outside world, trying to get in. First you have the top layer of the skin, which forms a shield (if the skin barrier functions as it should do!). This outer layer of skin has special cells that work as part of the bodies immune system, signalling when substances enter the skin that do not belong to the body itself, for instance a bacteria. They signal to the other cells of the danger once a bacteria does try to invade the skin. If this happens, the bodies immune system sends specific cells to the surface that are causing inflammation, trying to work out or kill the invading bacteria. One of these specific cells are antimicrobial peptides (AMP's), of which there are to date several hundred different types found. They can kill bacteria by messing with their cell membranes (for instance in case of a skin injury), but also fungi and viruses. So they are part of our skins little army, so to say. Cathelicidins are part of this AMP system. The precise cathelicidin involved in AMP is called Cathelicidin antimicrobial peptide (CAMP). And Cathelicidin LL-37 belongs to the CAMP family. It can break up bacteria, fungi and viruses that land on the skin. But they can also give off an "alarm", which brings the skins army into action, causing inflammation to work out or kill the invading substances. They mainly get active and detectable in the skin once there is a skin injury. When all is normal and the skin functions as normal, they are hardly to be found in the upper skin. But Cathelicidin LL-37 can also trigger the immune system. Thus, it plays an important, dual, role in the immune function of the skin. And when this LL-37 peptide does not function as it should, it can in fact have the reverse effect on the skin, and cause skin inflammation. And also allow bacteria to infect the skin. The scientists found that in rosacea skin, cathelicidin LL-37 often does not function as it should, and what is worse, they found that rosacea skin has much higher levels of this LL-37:
"Indeed, cathelicidin is strongly increased lesional skin in rosacea compared to the skin of non-affected individuals."
Rosacea skin deals with different symptoms, but mostly from chronic inflammatory and vascular response [blood vessels dilating more than they should]. The "alarm" function of LL-37 is off in rosacea skin, meaning it calls for the help troops to come when there is, in fact, no real threat... No invading bacteria to fight off, no fungi and no viruses. And instead, it stimulates inflammation of the (rosacea) skin and dilation of the blood vessels (thanks to the help of nitric oxide and EDHF):
"In rosacea increased levels of the vasoactive and inflammatory host-defense peptide LL-37 and its proteolytic peptide fragments are found which can be explained by an abnormal cathelicidin production and pathologic protease activity."
The scientists got confirmation about all this, when they injected these specific cathelicidins in the normal skin of mice. They all developed rosacea-like skin symptoms then. The problem is now, that scientists do not understand yet WHY rosacea skin has these higher numbers of cathelicidins,a lthough they found 3 different 'portals' so to speak, through which the extra peptides were produced. They were retinoid-, vitamin D- and cytokine-activated. The vitamin D-pathway, for instance, could explain why rosacea is only present on the face normally, and not on the rest of the body: the body is usually covered up and it is the face that gets the most sun-exposure and therefore the most vitamin D. And therefore, the more vitamin D is made in the skin, the more Cathelicidin LL-37 (and thus the more disrupting inflammation and vasodilation). But this is only a small part of the puzzle, as many people with rosacea shun the sun and protect their faces from sunlight at all times. Also, many with rosacea have low levels of vitamin D (read more about that in this post). But scientists also found that cathelicidins could be triggered by keratinocytes (outer layers of skin cells), which have nothing to do with vitamin D. They found that the outer skin cells themselves can signal the making of more Cathelicidin LL-37 when they are injured, get exposed to UV radiation, or when the outer layer of the skin gets disrupted in any way. Skin Stress, one could call it. Ánd, interestingly: skin stress includes heat. "This again could explain why rosacea patients often report on unspecific triggers (e.g. heat) which would mediate their pro-inflammatory activities through ER stress and cathelicidin induction." So when our rosacea skin gets triggered by heat, for instance you enter a very warm room, then this heat touching the skin will cause stress in the outer layer of the skin, sending of "alarm signals", which stimulate the LL-37 and other peptides to come into action and create.... inflammation. Physical stress can trigger the same response by the way, as well as alcohol consumption: Inflammation.. Just like we see happening in our rosacea faces when dealing with triggers like heat. Demodex mite infection can also trigger the skin to make these inflammation alarm reactions, as demodex mites can cause increased protease activity in rosacea skin, which does the alarm bells of Cathelicidin LL-37 go off again. Which in turn trigger inflammation, redness and blood vessel dilation in the skin. This is probably why oral and topical antibiotics (tetracyclines for instance), azelaic acid and retinoids can work for rosacea: they directly interfere with this pro-inflammatory system and reduce the inflammation or stop it from being formed altogether. So antibiotics can work for rosacea not because of their ability to kill off bacteria, but instead of how they reduce inflammation. And the same goes for anti-demodex treatment. which can take away the prime trigger for LL-37-related skin inflammation IF you have a demodex mite infection.
And avoid sunlight on your face. Vitamin D from sun is a direct trigger for LL-37-mediated inflammation and blood vessel dilation of rosacea skin. You can bronze on the rest of your body, just not your face, if you want to calm down rosacea-inflammation. (And now that I am at it, could this perhaps explain why so many people flare up from vitamin D supplements?? I get beyond beet red from them and never understood why. Maybe here we have it, the explanation). Certain supplements and herbs can also act as anti-inflammatories. Check my (still not fully finished, sigh) blog post about them here. Think of supplements like turmeric/curcumin or boswellia for instance. If you want to know even more detailed, microscopic information about how exactly this mechanism works on cellular level, I advise you to go to this science article and scroll down to the section Rosacea. You can also read more in this scientific article. But that is not all, because these LL-37 cathelicidins are not only found in the skin. But also for instance in the bowels. In fact, LL-37 is linking to some other health issues (including many auto-immune diseases) that quite a few people with rosacea mention to suffer from, for instance: gut and bowel infections/inflammation, depression and anxiety and cardio vascular disease. Which could explain why this badly functioning, overabundance of LL-37 has different effects on the body, and perhaps (?) why many of us suffer from bowel issues, depression and anxiety on top of our skin problems. In other words: we REALLY need a treatment ASAP to bring these cathelicidins back under control! It might also be yet another way in which immune suppressing drugs, like the ones I discussed at the top of this blog entry, can work. When you suppress the immune function of the body, you also suppress the formation of LL-37 cathelicidin. And thus of inflammation, blood vessel dilation and redness. Wished those meds came with a better side-effect profile :)
January 26th 2019, H. pylori infection and rosaceaI have been tested for Helicobacter pylori IgG antistoffen. Seen my general practitioner about it some weeks ago and she sent me for a blood test. This because some people on rosacea forums and groups claimed to have "cured" their rosacea after getting treatment for H.Pylori. Now, that is often an antibiotic, and antibiotics are known to help some case of rosacea, regardless of H. Pylori. Also, the symptoms of H. Pylori in rosacea skin are often said to be skin outbreaks and p&p's, which I don't suffer from. (Only severe flushing, redness and burning for me). Research like this one concluded on this topic:
"Epidemiological investigations and experiments have confirmed that H. pylori infection is associated with the development of rosacea. The effect of anti-H. pylori therapy is better than the routine therapy for rosacea. H. pylori can stimulate the immune system to produce a large number of inflammatory mediators, leading to the occurrence and aggravation of rosacea inflammation.
It is suggested that rosacea patients should be tested for H. pylori infection, the H. pylori-positive rosacea patients should be treated with eradication of H. pylori, so as to enhance the therapeutic effect of rosacea." And this research paper states: "Many studies have been performed in order to evaluate the connection between H. pylori infection and rosacea, however there is still controversy around the matter. There is a lack of information regarding the genetic features and the biology of H. pylori. It is proposed that the bacterium produces specific cytotoxins which lead to the release of histamine, prostaglandins, leukotrienes, and cytokines. Inflammatory mediators from an altered innate immune response lead to higher levels of ROS, whereas in treated rosacea the aforementioned level is lower. However, there are no distinct histological features in rosacea patients positive for H. pylori infection." And it goes on to cite different research done on this matter, with different test outcomes. Some researchers did find a link between rosacea and active H.pylori infection, others failed to find such a link. Researchers agreed that H.pylori is more related to subtype 2 rosacea with skin outbreaks (papulopustular rosacea), than it is with subtype 1 rosacea with flushing and redness:
Abram et al evaluated the risk factors of the disease. H. pylori rate was lower in flushers and higher in the papulopustular subtype. [..] Patients with papulopustular rosacea had a better response [to H. pylori treatment] than those with erythematous (skin redness), which confirmed the results from previous studies.
This summary of various research papers came to a more ambiguous outcome. Some researchers found that anti-H. pylori antibody levels were higher in rosacea patients. Other research found that 67% of rosacea patients tested positive for H. Pylori, and that there was a higher prevalence of H. pylori in patients with rosacea. And some (but not all!) patients who have both rosacea and H. pylori infection can to see their rosacea calm down as well when they treat the H.pylori. Other researchers failed to establish a role of H. pylori in rosacea patients, and some researchers downright concluded that the relationship between rosacea and H. pylori may be a myth. The authors concluded: "Rosacea is a skin disease with an obscure and complicated pathogenesis. Many mechanisms have been described but its etiology remains an enigma. There is not sufficient evidence regarding how determinant the role of H. pylori is. According to some authors, rosacea is correlated with gastrointestinal disorders which justifies further clinical and laboratory examination. Based on the fact that the studies were not extensive, controlled studies are required. Additional research is mandatory in the field of the microbiology of H. pylori as there are subtypes with different levels of virulence. Further studies are warranted to delve into the multifactorial nature of rosacea in order to elucidate the role of each factor in the pathogenesis of the disease."But... no harm in testing it or myself! Well I got the results back today and they are negative. No H.Pylori infection.My blood level was 5. The doctor's assistant said that anything under value 50 is considered negative. I looked up the exact values:
From To Unit Comment
0 35 U/mL negatief
35 50 U/mL grenswaarde
50 U/mL positief
December 12th 2018, Neurovascular System involved in neurogenic and subtype 1 rosaceaThe National Rosacea Society reports that NRS-funded researcher (Dr. Martin Steinhoff, director of the Charles Institute of Dermatology at the University College Dublin School of Medicine, and colleagues at the University of California-San Francisco) have found that the nervous system is intimately linked with the vascular system in producing some typical signs and symptoms of rosacea; flushing of the face and inflammation of rosacea. Our bodies nervous system coordinates its actions by transmitting signals to and from different parts of its body. The article names several typical rosacea triggers for subtype 1 and neurogenic rosacea: exposure to ultraviolet radiation, changes in temperature, exposure to skin irritants, strong emotions, alcoholic beverages and spicy food. All of these triggers are linked to the sensory nervous system, the researchers said. (The sensory nervous system a part of the nervous system and responsible for processing information we get through our senses, for instance what we see, hear, smell, taste, touch etc. It sends this information from our senses to our brain, which interprets the information).
This type of research is not giving us any new treatment options unfortunately. But it does show how much mapping of all the underlying mechanisms to rosacea flushing there still is to do. The whole picture needs to be clear before satisfying medication to combat things can - hopefully - be developed. I hope this happens within my lifetime still, sigh..... Been only waiting twenty years for it, after all.
They also highlighted that there is another nervous system disorder, which is called neurogenic inflammation, that shows some similar symptoms to those of rosacea; redness and swelling, as well as activity of cells such as leukocytes at the site of inflammation. Dr. Steinhoff's team found that certain sensory nerves around blood vessels, which may be linked to the stinging and burning sensations that many of us suffer from, actually increase in numbers when rosacea develops and continues to cause trouble. They also discovered that there is an imbalance and a communication problem in rosacea skin between several neuropeptides — small protein-like molecules used by nerve cells to communicate with each other — and their corresponding receptors. Further research is under way to determine whether this imbalance contributes to the development of the flushing and inflammation of rosacea. The group observed that the lymphatic vessels also may be involved in the initial process of rosacea, which can result in swelling, of the skin of the face (that puffy look so many of us get, especially during a flare up) and noted that neuropeptides affect the function of lymph vessels as well. Dr. Steinhoff thinks that the face is a particularly complex region, with an interaction of both the sympathetic, the parasympathetic and the sensory nervous systems all playing a role and interacting and influencing each other. It is possible that these 3 systems together create a complex cycle of inflammation, which may explain why some cases of rosacea can be resistant to treatment.
Researchers have also discovered something else that is interesting. Adenosine triphosphate (ATP)a neurotransmitter and carrier of chemical energy throughout the body — and one of the most common and hard-working substances in the body, may be contributing to rosacea in a variety of ways, according to NRS-funded researchers Dr. Richard Granstein and colleagues at Weill Cornell Medical College. When ATP is released into the skin by the nerves, lots of complex biochemical processes may occur in rosacea sufferers that ultimately leads to the bumps and pimples of subtype 2 (papulopustular) rosacea. ATP has many functions in the body, but its role in the development of rosacea may involve its job as a messenger from the nerves. The nervous system regulates blood flow to the skin, using ATP to start the dilation of blood vessels following exposure to rosacea triggers such as sunlight, emotional stress or alcohol. This process may then result in the flushing and redness of subtype 1 (erythematotelangiectatic) rosacea. In addition, endothelial cells — cells that line the blood vessels — respond to ATP with changes in the expression of inflammatory cytokines, which are proteins that act to recruit the inflammatory cells of subtype 1 rosacea. Dr. Granstein’s group is also investigating whether production of Th17 cells, a newly discovered class of cells that appears to be involved in a number of inflammatory and immune disorders, may lead to inflammation during this process.
December 10th 2018,Heat triggers greater nerve blood flow and sweating response in rosacea patients than in those without rosacea
A study funded by the National Rosacea Society (by Dr. Thad Wilson and colleagues at Ohio University), found that heat, a well known rosacea trigger, produces greater nerve, blood flow and sweating responses in people with rosacea than in people without the disorder when exposed to increased heat or stress. This response takes place in the sympathetic nervous system, which for instance controls the “fight or flight” response and other key involuntary functions such as heart rate, digestion, breathing and perspiration. “Heat and stress have long been recognized as rosacea triggers, but it has not been clear what happens in the body to cause these flare-ups to occur, said Dr. Thad Wilson, associate professor of physiology at Ohio University. “That’s why we devised innovative ways to replicate these triggers in a controlled manner while studying their effects on facial nerves, skin blood flow and sweating.” "To increase body temperature, the researchers had 10 rosacea patients and 10 healthy control individuals wear a tight-fitting suit lined with tubes carrying water heated to 115°F until their body temperature increased by approximately 2°F. Each person was then precisely measured for supra-orbital nerve activity (a nerve just above the eyebrow that serves the forehead skin), forehead skin blood flow and forehead sweat rate.” The researchers found that rosacea patients had higher skin blood flow and sweating rates compared to normal subjects, both before and after the heating began, and their skin blood flow and sweating also began to increase more rapidly during heating." 12 rosacea patients and 12 healthy control subjects were also tested during mental and physical tasks, involving fast-paced mental subtraction exercises for two minutes, using hand gestures to indicate answers, and tightly squeezing a handgrip for two minutes. While heart rate and blood pressure were the same between the groups during the hand exercises, skin blood flow was higher during mental arithmetic in the rosacea patients. The rosacea patients also experienced heightened sympathetic nerve activity compared to those without rosacea during both the mental and physical portions of the test.
This can explain why during intense concentration (making exams for instance), so many of us end up with a hot flushed face.
“These results indicate that rosacea symptoms may be in part due to sympathetic nerve overactivity” Dr. Wilson said. “This is an important area that warrants further investigation, as it may lead to improvements in therapy and trigger prevention. [..] The sympathetic nervous system is a part of the body’s autonomic nervous system that controls involuntary functions such as heart rate, digestion, breathing and perspiration. This portion of the autonomic nervous system functions largely below the level of consciousness and has been shown to respond to emotion."
August 6th 2018,Anaesthetic injection could ease hot flushes and flushing
Injecting a local anaesthetic into the neck is associated with a 50% reduction in hot flushes among women with moderate to severe symptoms. They can also help curb facial flushing. A shot in the neck may curb extreme hot flushes associated with menopause, a small new study suggests. Injecting a local anaesthetic into an area of the neck that communicates with the brain's temperature regulation zone was associated with a 50% reduction in hot flushes among women with moderate to severe symptoms, the researchers reported. Since research over the last decade has suggested that taking hormone replacement therapy to control menopausal symptoms may be associated with increased risk for heart disease and cancer, many women have been searching for a safe and effective non-hormonal means of reducing hot flushes. The anesthetic treatment isn't designed for everyone with hot flushes. It's intended for those struggling with truly troubling hot flushes that occur regularly, affecting quality of life, said study author Dr David Walega, chief of the division of pain medicine at Northwestern University Feinberg School of Medicine in Chicago. "This is for people with multiple drenching sweats, women who can't function in the workplace, who have extreme anxiety preceding the hot flash. And when that happens several times a day, we also see anxiety and depression," explained Walega. Some breast cancer patients stop taking their medication – tamoxifen – because it causes hot flushes, he added. I have also read statements from bad flushers who have had this ganglion block recently and who noticed a reduction in facial flushing and nerve pain.
What are hot flushes?
Hot flushes are sudden feelings of heat or warmth starting in the face and extending to the neck and chest area, sometimes accompanied by sweating and flushing of the skin. They are associated with menopause, but can also occur in patients taking oestrogen-blocking medications, typically for breast or prostate cancer. Walega estimated that hot flushes affect more than 80% of menopausal women. To deliver the treatment, the physician uses guided imaging to inject a local anaesthetic into what is called the stellate ganglion, an area between the thyroid gland (around the "voice box") and the carotid artery. "The patient feels a sense of intense pressure from the physician's finger [guiding the needle], and the pain is moderate," said Walega. "In 30 seconds, we're done." The researchers got the idea of attacking extreme hot flushes by treating the stellate ganglion from unintended consequences of a pain study published in The Lancet in 2007. "Patients reported their pain was still there, but their hot flushes were gone."
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Anaesthetic injection
For this study, scheduled for presentation at the American Society of Anaesthesiologists' annual meeting in San Francisco, the researchers recruited 40 women between 35 and 65 years old. All were either in natural or surgically (when the ovaries are removed) induced menopause. Half of the women received a stellate ganglion blockade injection of bupivacaine hydrochloride, a local anaesthetic. The others were given a placebo, an injection of sterile saline. Participants kept track of their hot flushes for two weeks preceding the injection and six months afterward. The researchers found that stellate ganglion blockade reduces the incidence of hot flushes by half, especially in women with moderate or severe hot flushes, and the benefits appear to last for at least six months. Subjects also reported experiencing less depression after getting the bupivacaine injections, and they demonstrated improved verbal recall of spoken words. Walega said the treatment is safe when done by specially trained physicians using X-ray fluoroscopy to guide the injection. The stellate ganglion sits near the carotid artery, the vertebral artery and the spinal cord. "Injecting any of those arteries with anaesthetic could cause a seizure and loss of consciousness, and it could do damage to the spinal cord," he explained. As for the risk of radiation exposure from the fluoroscopy, it is equivalent to that of a chest X-ray, he added.
Resetting the thermostat
Why might these injections work? Walega said he thinks the ganglion may play a role in turning certain nerves on or off. "It's complex and there's so much else we don't know," Walega said. "We might be resetting the thermostat." Walega now plans to do a larger study with more than 200 participants, he noted. Dr Grace Forde, an attending physician and pain management specialist at Syosset Hospital in New York, noted that a large percentage of the patients receiving the placebo also reported an improvement in their hot flushes. "Invasive procedures often have a much stronger placebo effect," she noted. Walega estimated that the treatment, if proven effective in a larger study, would cost between $750 and $1000. Forde, who was not associated with the study, said she thinks the benefits of the treatment probably outweigh the risks. "You can't put a price on quality of life. I personally think it's worth it." Because this study was presented at a medical meeting, the data and conclusions should be viewed as preliminary until published in a peer-reviewed journal.
April 10th 2018,How does facial flushing happen exactly?
When my skin burns and flares and feels on fire, the most natural urge is to open all the windows and let in cold air. Or to put my head in a bucket of cold water. Or to sit right in front of a powerful air conditioning machine. The colder the better! But according to the Warm Room Theory, this is actually not the best thing to do when you have rosacea. Making your rosacea skin very cold, might cause rebound worsening in the long run. It is normal for anyone with rosacea to get a rush of warmth up the cheeks when entering a warm room. Every person that gets too hot, can rely on their body to deal with the overheating, usually by stimulating the body to sweat (a way to release excess heat from the body) but also by widening the blood vessels in the skin. The wider the vessels are, the more warm blood will be closely exposed to the skin and be able to lose some of its heat that way. When the body signals the blood vessels in our skin that the body is overheating, then the body activates nerves in the skin to dilate the blood vessels in the skin (vasodilation). The way in which the nerves do this, is by releasing certain chemicals, that message to the blood vessels to widen. And to make the effect even stronger; the more blood flows through the blood vessels, the more these blood vessels themselves release chemicals to keep this vasodilation going. This is a normal process; everyone alive experiences this, or else we humans wouldn't be able to regulate our temperature or fight off infections or have proper wound healing, for instance. The problem occurs when our skin has too many of these flushing events. When it becomes very frequent that the skin flares red and hot. This is the moment that the blood vessels are dilated for a longer period over time, and that the vessels give off a signal that make the body create new (and thus more!) blood vessels in the skin (angiogenesis). The bodies way to create more infrastructure for this extra blood flow. This principle is also normal, but in people with healthy skin it is a limited occurrence. For people with rosacea, it is however the mechanism in which our rosacea progresses, slowly over many years, from mild to moderate, to severe. Because when you have more blood vessels and more nerves in your skin, you will have more dilation of blood vessels and more facial flushing, especially when you are in a warm room and your body goes through its normal steps and paces to cool off the body.
ROSACEA INFRASTRUCTURE
So a person with rosacea will have more blood vessels and nerves in the skin than a person with healthy skin, and they have been made by the body to release heat. They will give a rosacea face often the distinctive red(der) cheeks and sometimes also nose and chin or forehead. The human face and head are special, in that they have more and different blood vessels and nerves than any other area of skin on the body. They have special nerves to dilate blood vessels and special blood vessels to release the heat carried in the blood. The nerves involved in these areas are sympathetic nerves. They can act to dilate special blood vessels (arteriovenous anastomoses), which open up and shunt blood into the blood vessels of your skin, creating the phenomenon we know as the flush. This also explains why many people have intense flushing confined to certain regions of the face. many people with rosacea flush on their cheeks, some (but far less) also flush in their neck and chest and it is very rare to find rosacea patients who flush on the rest of their body, unless they have other skin conditions that cause skin problems elsewhere. Rosacea, however, is mostly limited to the more densely vascularized face, where our skin is also thinnest, compared to other body parts. Showing the redness in our dilated blood vessels even more!
More on these nerves in the skin that are involved in skin flushing
Another important type of nerve involved in rosacea is the sensory nerve. Unlike sympathetic nerves that are triggered centrally in the brain, sensory nerves are locally handling the blood vessel dilation in the skin. When your face is exposed to sun for instance, or to a skin care product that has irritating ingredients, then it are the sensory nerves that can act immediately and signal to the blood vessels in the skin to dilate and give off a warning signal to us. They play a role in rosacea flushing, as such. When our blood vessels in the skin dilate, after being signaled to do so by the sensory nerves, they not only become wider and let more blood through, but they also create local inflammation, which in turn makes our nerves in the skin give off a burning pain feeling. For most people with rosacea, a deep flush is therefore painful, feeling hot, sore and like a burn almost. Due to rosacea, more nerves are created along with the new blood vessel infrastructure, but the existing nerves can also become hypersensitive. This can explain why early on, with mild rosacea, facial flushing can be fairly painless, but later on the flushing can create moderate to severe pain and hot burning sensations; the nerves in the skin have become super reactive and sensitive from the long history of being triggered by flushing attacks of the skin. As a result, some people with rosacea have such a sensitive and extensive nerve and blood vessel infrastructure, that even a small increase in blood flow will result in significant flushing episodes.
Chemicals involved in facial flushingThere are hundreds of known chemicals involved with nerves and blood vessels. But there are very specific chemicals released by our nerves and blood vessels, when we have rosacea and suffer from facial flushing, such as neurotransmitters, neuropeptides and growth factors. Neurotransmitters are chemicals that transmit a nerve signal to other nerves as well as other tissues, such as blood vessels. Neuropeptides do the same, but are stronger and act longer. Both can signal blood vessels to dilate or constrict, and nerves to feel pain or to go numb again. There is something special going on with these neuropeptides research showed. More on this soon. Growth factors, released by skin cells, help to maintain existing blood vessels and nerve structures, and also make it possible for both to grow. They also play a role in the process of our nerves becoming more sensitive and easily triggered to feel burning and pain. When the nerves in our skin are activated (for instance during a flush), this in turn stimulates more growth factor release, like a waterfall-construction. They are all in place to help the body deal with overheating, but with rosacea patients this system of blood vessels and nerves and chemicals are going in overdrive, causing our increasing facial flushing and red faces.
In most people facial blushing takes a minute or two for the blush to disappear. However, flushing is a different beast and can last much longer, and it usually is more severe than blushing too: more redness, deeper blood vessel dilation, hotter flushes and longer lasting. In some people severe and frequent blushing can become a real hindrance and affect both personal and professional life. Although the vascular –flushing- aspect is one of the most difficult aspects of rosacea to treat, there are several medications available that have proven to help treat facial flushing for a number of patients.
April 2nd 2018,
Rosacea patients are at increased risk of developing other health conditions
In this article from march 2018, specialists warn that people with rosacea are statistically at a higher risk to develop other health conditions. For instance, rosacea patients have 4 times more chance to develop cardiovascular disease than the average population. Rosacea patients also have a 4 times higher risk to develop gastroesophageal reflux disease (GERD), are 3 times more likely to develop Crohn's disease. Although it is not always clear how exactly rosacea is linked to a higher risk factor, the overlapping theme is inflammation. Rosacea is an inflammatory disease and inflammation is also thought to play a role in cardiovascular, gastrointestinal, neurological and autoimmune diseases. In their cases the inflammation is hidden inside the body, whereas with rosacea the inflammation is visible in and on the skin. Some scientists now say that this visible (rosacea) inflammation is a warning signal for more hidden inflammation inside the body.
*Cardiovascular disease – 4 times higher risk
*Gastroesophageal reflux disease (GERD) - 4 times higher
*Crohn's disease - almost 3 times
*Inflammatory bowel disease (IBD) - 2 times
*Celiac disease - 2 times
*Type 2 diabetes - 2.5 times
*Food allergies - 10 times higher risk
*Urogenital diseases (affecting the urinary tract or reproductive organs) - 7.5 times higher
*Respiratory diseases - 4 times higher risk
*Gastroesophageal reflux disease (GERD) - 4 times higher
*Crohn's disease - almost 3 times
*Inflammatory bowel disease (IBD) - 2 times
*Celiac disease - 2 times
*Type 2 diabetes - 2.5 times
*Food allergies - 10 times higher risk
*Urogenital diseases (affecting the urinary tract or reproductive organs) - 7.5 times higher
*Respiratory diseases - 4 times higher risk
The article mentions the following conditions:
Psychiatric conditions
Depression is among the most common comorbidities (means an additional health issue that goes with the original disease; in our case rosacea) identified in the research, followed closely by anxiety. Multiple studies have found a higher than average prevalence of depression and anxiety in patients with rosacea. Unfortunately, doctors tend to underestimate the psychological impact of having rosacea, and ignore the level of despair and mental suffering it can bring. Reversing this trend, at least one study found no greater risk for rosacea among those who already had clinical depression, but the association may be bidirectional given that stress can trigger rosacea flare-ups. A National Rosacea Society survey of more than 400 rosacea patients found that 75% of them feel low self-esteem, 70% feel embarrassed, and 69% feel frustrated. In those with severe symptoms, 88% cited the disorder as adversely affecting their professional interactions and 51% had missed work because of their condition. Prevalence of anxiety about the condition was present in 41%, and 25% reported having depression related to their disease.
Cardiovascular Disease
Patients with rosacea have a higher incidence of hypertension and dyslipidemia (an abnormal amount of lipids (e.g. triglycerides, cholesterol and/or fat phospholipids) in the blood), which increases with severity of rosacea symptoms, than the general population. Rosacea patients also have higher rates of peripheral artery disease, heart failure, diabetes mellitus, and coronary artery disease — the latter even after controlling for hypertension and dyslipidemia. Recent data have suggested the risk for vascular events increases with tetracycline treatment. People with rosacea were found in research to have four times the risk for cardiovascular disease and reflux. Although several cardiovascular-related conditions have been very clearly associated with rosacea, existing evidence does not suggest an increased risk for heart attack, stroke, or other cardiovascular events in patients with rosacea. It is a good idea to check if your family has a general history of heart disease and if so, to mention this to your doctor and have extra screening if suffering from any symptoms related to cardiovascular disease. Having a higher Body Mass Index (BMI - so a high weight) can increase the risk of such conditions. It is also wise to have your blood pressure checked routinely, and doctors also recommend for rosacea patients of 45 years and older to have their blood work done now and then to check fasting lipid panel, fasting glucose, or hemoglobin A1c levels. If you have 2 or more risk factors, doctors recommend taking 81 mg. of aspirin a day, at the least.
Depression is among the most common comorbidities (means an additional health issue that goes with the original disease; in our case rosacea) identified in the research, followed closely by anxiety. Multiple studies have found a higher than average prevalence of depression and anxiety in patients with rosacea. Unfortunately, doctors tend to underestimate the psychological impact of having rosacea, and ignore the level of despair and mental suffering it can bring. Reversing this trend, at least one study found no greater risk for rosacea among those who already had clinical depression, but the association may be bidirectional given that stress can trigger rosacea flare-ups. A National Rosacea Society survey of more than 400 rosacea patients found that 75% of them feel low self-esteem, 70% feel embarrassed, and 69% feel frustrated. In those with severe symptoms, 88% cited the disorder as adversely affecting their professional interactions and 51% had missed work because of their condition. Prevalence of anxiety about the condition was present in 41%, and 25% reported having depression related to their disease.
Cardiovascular Disease
Patients with rosacea have a higher incidence of hypertension and dyslipidemia (an abnormal amount of lipids (e.g. triglycerides, cholesterol and/or fat phospholipids) in the blood), which increases with severity of rosacea symptoms, than the general population. Rosacea patients also have higher rates of peripheral artery disease, heart failure, diabetes mellitus, and coronary artery disease — the latter even after controlling for hypertension and dyslipidemia. Recent data have suggested the risk for vascular events increases with tetracycline treatment. People with rosacea were found in research to have four times the risk for cardiovascular disease and reflux. Although several cardiovascular-related conditions have been very clearly associated with rosacea, existing evidence does not suggest an increased risk for heart attack, stroke, or other cardiovascular events in patients with rosacea. It is a good idea to check if your family has a general history of heart disease and if so, to mention this to your doctor and have extra screening if suffering from any symptoms related to cardiovascular disease. Having a higher Body Mass Index (BMI - so a high weight) can increase the risk of such conditions. It is also wise to have your blood pressure checked routinely, and doctors also recommend for rosacea patients of 45 years and older to have their blood work done now and then to check fasting lipid panel, fasting glucose, or hemoglobin A1c levels. If you have 2 or more risk factors, doctors recommend taking 81 mg. of aspirin a day, at the least.
Neurological Disorders
Researchers have identified an increased risk for rosacea patients to develop Parkinson Disease, dementia (particularly Alzheimer disease), and migraine, although risk levels vary. Two Danish cohort studies, for example, revealed a 71% greater risk for Parkinson disease and a 36% greater risk for dementia. Migraine is more often seen in female patients and involves vascular abnormality, just as rosacea does. Both conditions can also be triggered by stress or alcohol.
Cancer
The only cancers linked with rosacea are a weak association with thyroid cancer in women and glioma (brain cancer) in men, plus a stronger association with basal cell carcinoma (skin cancer). Skin cancer is the least surprising of the three, given that UV radiation from the sun not only can cause skin cancer, but also worsens rosacea for most patients.
Researchers have identified an increased risk for rosacea patients to develop Parkinson Disease, dementia (particularly Alzheimer disease), and migraine, although risk levels vary. Two Danish cohort studies, for example, revealed a 71% greater risk for Parkinson disease and a 36% greater risk for dementia. Migraine is more often seen in female patients and involves vascular abnormality, just as rosacea does. Both conditions can also be triggered by stress or alcohol.
Cancer
The only cancers linked with rosacea are a weak association with thyroid cancer in women and glioma (brain cancer) in men, plus a stronger association with basal cell carcinoma (skin cancer). Skin cancer is the least surprising of the three, given that UV radiation from the sun not only can cause skin cancer, but also worsens rosacea for most patients.
Gastrointestinal and Auto-immune diseaseThe gastrointestinal disorder with the highest prevalence among patients with rosacea is inflammatory bowel disease, which some researchers have suggested may be related to a shared pathogenesis from Helicobacter pylori or small intentional bacterial overgrowth (SIBO), both also more prevalent in rosacea. One small study found that 21.6% of patients with rosacea had H. pylori and 25% had small intentional bacterial overgrowth. Evidence also supports an association between rosacea and celiac disease, ulcerative colitis, rheumatoid arthritis, and allergies. For example, a small case-control study published in 20159 found higher odds of airborne and food allergies, plus other systemic diseases, in patients with rosacea. Although male patients show higher risk for glioma (brain cancer), the associations linking rosacea with rheumatoid arthritis, celiac disease, type 1 diabetes, migraines, multiple sclerosis, and hormone imbalances are stronger in females. Environmental risk factors that are under investigation currently for shared pathogenesis with rosacea and other comorbidities, are H pylori infections, small intentional bacterial overgrowth, and differences in gut microbiomes, which are also implicated in celiac disease, diabetes, depression, and cardiovascular disease. Other research into possible shared mechanisms compares rosacea with other autoimmune diseases, other genetic biomarkers, and similar inflammatory elements or pathways. The exact connections are complex, remain mostly unclear at this point, and probably involve mechanisms that underlie chronic inflammatory conditions in addition to metabolic, immune and endocrine changes.
It is a good idea for your doctor to screen you for these other health conditions, ideally before considering rosacea treatment options. Other health conditions with an overlap of symptoms that can be mixed up with rosacea (and it can turn out you suffer one of these instead of rosacea) are mastocytosis, lupus, carcinoids, thyroid disease, allergies, vasculitis and several other autoimmune-diseases. In this long blog post, I mentioned and described a host of other health conditions (mostly auto-immune ones) that can also cause a red flushed face, and that are not rosacea: "Other conditions that cause facial flushing, and mimic rosacea symptoms". Scientists do not know yet what the precise link is between having rosacea and having statistically higher risk of developing the above mentioned health conditions. Some scientists think that the explanation must be sought not so much in a genetic predisposition to develop some (or all) of these conditions, but that people who have a certain lifestyle and live in a certain environment, can as a result of this have an increased risk of developing both rosacea and the other mentioned health conditions. A higher risks does not mean that you will develop these conditions however. Being at risk for these conditions does not mean that you will go on to develop any of these disorders. Disease development is different for everyone; family history, personal history, age, gender, environment, lifestyle and other factors all play a role in disease development, yes or no. But scientists want to bring awareness of the possibility of this for you, who suffer most likely from rosacea if you read this.
Do I have rosacea? What to look for
How to treat rosacea redness, flushing and burning with medication - (The science behind my current medication)
April 2nd 2018,Did researchers find the trigger for autoimmune disease?
Researchers might have finally found the trigger for autoimmune disease. Given that rosacea has most likely (although not yet proven) an auto-immune element to it, this could be interesting for rosacea patients too. Scientists have identified a chain reaction that explains why our own bodies can turn against our own healthy cells. The reaction, discovered in 2017 after four years of research in mice, has been described as a "runaway train" where one error leads the body to develop a very efficient way of attacking itself. The study focused on B cells gone rogue. Normally these cells produce antibodies and program our bodies' immune cells to attack unwanted invaders (or foreign substances; think of viruses or bacteria). An autoimmune disease is a chronic inflammatory condition caused by a person’s own immune cells, which mistakenly believes the body is under threat and so responds by attacking the bodies' own healthy cells and tissues.
Scientists found an 'override switch' in mouse B cells that messed up this behaviour and caused autoimmune attacks. "Once your body's tolerance for its own tissues is lost, the chain reaction is like a runaway train," said one of the team, Michael Carroll from Boston Children's Hospital and Harvard Medical School. "The immune response against your own body's proteins, or antigens, looks exactly like it's responding to a foreign pathogen." These B-cells-gone-awry could in turn explain the biological phenomenon known as epitope spreading, where our bodies start to hunt down different antigens that shouldn't be on the immune system's 'kill list'. Epitope spreading has long been observed in the lab but scientists have been in the dark about how it happens, and why autoimmune diseases evolve over time to target more and more healthy organs and tissues. In this case the research looked at a mouse model of the lupus autoimmune disease, considered an archetypal or 'classic' type of autoimmune disease that many others are based on. Lupus is known as 'the great imitator' because the disease can have so many symptoms resembling other common conditions and because it affects many organs. When B cells sense a foreign body – or something healthy that appears to be a foreign body – they swing into action in clusters called germinal centres. Those centres are why your lymph nodes become swollen when you've got a cold coming on, for example. B cell clones actually battle each other inside these centres so the body can determine which antibody is best suited to fight the threat, and in the case of this study that meant one colour of protein winning out against the others. The problem comes when the body incorrectly identifies a normal protein as a threat. When that happens, the B cell selection process produces what are known as auto-antibodies that prove very effective at harming our own bodies. Over time, the B cells that initially produce the 'winning' autoantibodies begin to recruit other B cells to produce additional damaging autoantibodies – just as ripples spreading out when a single pebble is dropped into water. This has only been examined in mice so far, but the researchers now want to use this confetti model to look at how B cell production of autoantibodies is regulated and gets sped up. Autoreactive B cells are competing inside germinal centres to design an autoantibody, but the immune response then broadens to attack other tissues in the body, leading to epitope spreading at the speed of wildfire. Hence, why people with one auto immune disease so often develop more and different ones over time. Eventually, blocking the germinal centers in some way could put a break on the vicious cycle that autoimmune diseases create. It would effectively block the immune system's short term memory. Unfortunately, as always, that kind of treatment is still a long way off. And there is more new research on autoimmune diseases:
A team of researchers from Yale University has linked autoimmune reactions to a bacteria in the gut called Enterococcus gallinarumAn autoimmune response, they say, can be triggered when the bacterium spontaneously migrates from the gut to other organs in the body, such as the spleen, liver, and lymph nodes. During the study, the researchers genetically engineered mice to be susceptible to autoimmune diseases. They then analyzed the gut bacteria to identify those that caused inflammation or were involved in the production of antibodies known to promote autoimmune responses. The culprit was Enterococcus gallinarum. The results were confirmed when they compared cultured liver cells of healthy people versus those of people with an autoimmune disease and found traces of Enterococcus gallinarum in the latter group. The researchers weren’t just able to identify the source, they also developed effective ways to reduce autoimmune symptoms. By using antibiotics or a vaccine, the researchers dulled symptoms by suppressing the growth of Enterococcus gallinarum. The vaccine was delivered through injection in muscle to avoid targeting other bacteria that reside in the gut. It is hoped that this research can be developed into successful treatment options with an antibiotic and other approaches such as vaccination for certain autoimmune diseases, including autoimmune liver disease and systemic lupus.
April 1st 2018,
CRISPR
I read that after the information revolution, we are now heading towards the revolution of genetic engineering. Scientists are experimenting with CRISPR; programming plant- and human- and animal cells and doing DNA surgery. CRISPR allows scientists today already to cut and paste in DNA strands. Like a programmable scissor, that can recognize a certain spot on the genome of an organisms, and modify the genome at will. The technology is based on Dutch research about little parts of DNA in bacteria, called CRISPR. Bacteria suffer from viruses too, like us. When a virus hits them , it releases DNA into the bacteria, in order to create more viruses. But bacteria have their own defense system, CRISPR/cas, which allows them to recognize the DNA from viruses and to find it and then cut to pieces.
Emmanuella Charpentier came up with a similar system to cut and paste DNA from organisms (CRISPR cas9). DNA consists of 4 substances, given the letters C, G, A and T. The order of these substances dictates the genetic code of a cell. CRISPR can accurately read this info and change it. It allows DNA reprogramming through cutting and pasting in any cell, not just in virus DNA. She and her colleague Jennifer Doudna are up for a Nobel prize apparently, and won a lot of other prizes already for this discovery. They studied evolution, to change evolution. Rewriting our own genetical make-up. Reprogramming viruses, like an app would do; viruses are software anyway, like a memory stick, loaded with specific information, and once it attaches to a physical structure, that allows the virus to load its program onto the cell. That program is nowadays: print more viruses. But viruses could also be loaded with a different message, one that we as humans find interesting to program into the cell. For instance; make this protein, because it is a good drug for us, or load the program into a cancer cell and program it to die. Viruses can be reprogrammed and are like software; like an app. And viruses today are designed, from scratch, in order to make biological programs with new applications possible. All cancers have different DNA, but some people are already working on viruses that are adjusted to very specific tumour genetics. Special DNA printers can then print that DNA and put it in viruses. Every cancer patient can this way get a personalized cancer drug. Digital synthetic virus designs and it's already tested on dogs with cancer. An epi-pen for all of us, uploaded by the doctor and auto-inject. Personalized medicine. It's going to happen eventually. A medical netflix subscription with which you keep your body healthy. Soon we can print medication and change ourselves genetically (I can't wait for that, hopefully before my old age they can cut out my genetic illnesses, ruthlessly!). People are trying to write programs now that eradicate cancer cells. Science students could soon have opportunities that today only pharmaceutical companies have. 
Hopefully the technology can repair genetic diseases, now that so many illnesses have been mapped DNA-wise in the past decade. But between a discovery in the lab, and using that discovery to develop a new technology and usable medication, there are usually around 20 years... It is also very expensive, so scientists are told to only go after the largest diseases and disease groups. But hopefully soon all the DNA errors that switches on genetic diseases can be identified and put into switch blocks and be eradicated or changed. And to build new biological constructions with them. Some people are already making and selling CRISPR-kits, for geeks to use at home; bio hackers (instead of computer hackers). Genetic engineering, in order to experiment, for instance with trying to make muscle mass grow. Changing your skin- or hair colour, growing more or less hair. Or attempting to have humans grow wings. Ultimately all the knowledge should be shared and people should be able to create the same stuff as pharmaceutical companies, but at a much better price. There is already genetic experimenting done on human embryo's now.. At a very early age when they are just a couple of cells. The worry is that technology will be used to make designer babies. Of course you could wait for the moment that there are fights erupting about the patenting of (parts of) this CRISPR technology, which is going on right now. And many companies have started working on the technique and on the treatment of certain diseases, but out of fear that someone will steal their inventions or know-how, they do not share any of with with other companies or scientists. Which holds back the entire development pace. Not just a few companies (Editas, Caribou and Crispr therapeutics), but also especially big universities in the USA can gather enough money (hundreds of millions of dollars with each round) to have teams of hundreds of the best people around working on this technique now. Editas, Caribou and Crispr therapeutics can become the new Google and Apple of the future if the CRISPR technology turns out to be effective and profitable.
April 1st 2018,
Researchers discover why bacteria only cause acne in some people
Researchers discover why bacteria only cause acne in some people
Researchers under guidance of Richard Gallo from the University of California, San Diego, might have figured out why bacteria only causes acne in some people, and how to stop it. Pretty much all of our skin is covered in bacteria always, as a skin defense system against germs. Usually there is a balance and symbioses going on, and we don't get acne from it, but some people are more prone to such infections. Gallo and his colleagues showed that a usually harmless bacterium that lives on our skin starts triggering inflammation and breakouts when it finds itself trapped in airless, oily conditions, such as hair follicles. Everyone has hair follicles in their skin, but not all hair follicles are the same and created equal. Dr. Gallo and researchers now suspect that some people might have hair follicles that are more "suffocating" than others. The researchers specifically looked at a type of bacterium known as Propionibacterium acnes, which can cause acne breakouts. "Most of us have P. acnes on our face all the time, but it doesn't always cause breakouts. So the team tested the bacteria under a range of conditions on the skin of mice to try and figure out what was going on. They showed that when trapped in airless environments alongside hair and skin cells, P. acnes turned sebum - the oil found on our skin - into fatty acids that activate inflammation in nearby skin cells. Usually this inflammation is switched off by enzymes called histone deacetylases, but the fatty acids produced by the bacteria deactivated that brake, so inflammation continued unchecked - going on to cause red, itchy breakouts. So far, the research has only been done on mice, but the team is now looking to replicate their results in humans, and they're hopeful that the inflammation pathway involved will be the same."
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"For the first time, it shows how fatty acids derived from P. acnes act on skin cells to induce inflammation," Holger Brüggemann, an expert on skin bacterium from Aarhus University in Denmark, explained. New findings could also explain why teenagers are so prone to breakouts, because their sex hormones during puberty put their sebum production into overdrive, giving P. acnes more fuel. The bad news is that cleaning your face regularly isn't the answer, because the team showed that the bacteria clump together to form structures called biofilms, which effectively locks them onto your skin. And, when this type of bacterium isn't causing havoc inside suffocating hair follicles, P. acnes is actually beneficial to skin health, which explains why antibiotic treatments don't work for many people - and in some cases, can actually make things worse. But now that the team understands the root cause of the inflammation, they're confident they'll be able to come up with new treatments for acne. "We can either inhibit these fatty acids, or block their impact on the skin," Gallo told New Scientist. "We're working on how to do this ... If we get lucky, it could lead to new medications in two to five years."The researchers now want to investigate what it is specifically that makes some people's faces more susceptible to acne. In addition to having particularly suffocating hair follicles, they might also be genetically disposed to being more vulnerable to the inflammation triggered by P. acnes fatty acids. Or maybe the strains of bacteria they have on their skin make excessive amounts of fatty acids compared to other people's strains. "I think all of these aspects probably play a role," said Gallo. Once they've figured this out, they'll be a step closer to not only treating, but potentially preventing acne in the first place. Right now, doctors treat severe acne with either antibiotics, hormone regulators (such as the contraceptive pill), or isotretinoin - better known as Roaccutane. All of these come with side effects (some more severe than others), and worst of all, most of them don't offer long-term relief, or in some cases, they don't work at all.
March 15th 2018,New class of menopause drugs reduces severity of hot flushes in three days
A new class of experimental drugs reduces hot flushes in menopausal women by almost three-quarters in just three days. The treatment, tested by scientists at Imperial College London, also reduces the severity of hot flushes by over a third within three days of taking it. The research, funded by the Medical Research Council (MRC) and the National Institute for Health Research (NIHR), is a new in-depth analysis of data collected from a clinical trial initially published last year. This class of new drugs may provide women with a much-needed alternative to HRT, but it could also be an interesting new treatment on the horizon for people with vascular rosacea and facial flushing. Other medication aimed at reducing the severity of hot flashes (for instance clonidine, mirtazapine, other SSRI-antidepressants and certain beta blockers) all are prescribed by various dermatologists to try to curb facial flushing, a difficult to treat rosacea symptom. The original drug trial, which was a randomised, double-blind, placebo-controlled trial, involved 37 menopausal women aged between 40 and 62 years old – and who experienced seven or more hot flashes a day. Participants were randomly chosen to first receive either an 80mg daily dose of the drug, called MLE4901 (which was previously developed as a drug for schizophrenia) or a placebo over the course of a four-week period. They then switched to receive the other tablet for an additional four weeks. This ensured the women acted as their own controls during the study, and the effects of the drug were clear. The researchers found that the compound MLE4901 significantly reduced the average total number of flushes during the four-week treatment period, as well as their severity, compared to when the patients received the placebo for four weeks.
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The new experimental compounds are thought to work by blocking the action of a brain chemical called neurokinin B (NKB). Previous animal and human trials have shown increased levels of NKB may trigger hot flushes. The drug compound is thought to prevent NKB activating temperature control areas within the brain – which appears to halt hot flushes. The new data also revealed that the drug was as effective at improving daytime flush symptoms as it was at improving night time symptoms. Furthermore, the women reported a 82 percent decrease in the amount their hot flushes interrupted their sleep, and a 77 percent reduction in interruption to their concentration. Dr Julia Prague, first author of the study, explained: “As NKB has many targets of action within the brain the potential for this drug class to really improve many of the symptoms of the menopause, such as hot flushes, difficulty sleeping, weight gain, and poor concentration, is huge. To see the lives of our participants change so dramatically and so quickly was so exciting, and suggests great promise for the future of this new type of treatment.” The new analysis shows the compound has a significant effect within just three days explains Professor Waljit Dhillo, an NIHR Research Professor from the Department of Medicine at Imperial: “We already knew this compound could be a game-changer for menopausal women, and get rid of three-quarters of their hot flushes in four weeks. But this new analysis confirms the beneficial effect is obtained very quickly – within just three days.” Professor Dhillo explains this specific compound will not be taken further in trials, due to side effects that may affect liver function. However, two very similar drugs, which also block NKB but do not appear to carry these side effects have entered larger patient trials, with one such trial launched in the US last year. The research was funded by the Medical Research Council and the National Institute for Health Research. The study was supported by the Imperial NIHR/Wellcome Trust Clinical Research Facility. (source)
Update: due to side effects the research of this anti hot flash drug seems to have currently stalled, sadly enough... https://en.wikipedia.org/wiki/Pavinetant
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March 12th 2018,scientists summarize the treatment options for neurogenic rosacea
In this good research paper, scientists summarized the treatment options for neurogenic rosacea; rosacea subtype 1 with skin redness (erythema), skin burning and flushing. It states that this rosacea subtype requires a unique approach of management. In the paper, typical symptoms and triggers are mentioned for people with this type of rosacea, based on 14 test persons:
"Prominent symptoms included burning or stinging pain (100% [14 of 14]), erythema (skin redness) (100% [14 of 14]), and flushing (93% [13 of 14]), sometimes accompanied by facial edema (skin swelling) (50% [7 of 14]), telangiectasias (visible blood vessels in the skin) (50% [7 of 14]), pruritus (43% [6 of 14]), and papules (36% [5 of 14]). Important symptom triggers included heat (93% [13 of 14]), sunlight (93%[13 of 14]), hot showers (79% [11 of 14]), stress (71% [10 of 14]), exercise (64% [9 of 14]), and alcohol consumption (57% [8 of 14]). Use of makeup (50% [7 of 14]), eating spicy foods (43% [6 of 14]), touching skin (36% [5 of 14]), drinking hot beverages (29% [4 of 14]), cold weather (21% [3 of 13]), and humidity (14% [2 of 13]) were less reliable triggers. Notably, 71% of patients experienced relief from cooling via fans or cold compresses or ice applied to the face or held in the mouth (10 of 14).
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| Facial erythema is seen in most patients at baseline and uniformly during flares. Inflammatory papules and pustules and rhinophymatous change are unusual in this subset of patients. |
In the paper it is written that of the examined patients with neurogenic rosacea, a high percentage had neurologic (43% [6 of 14]) or neuropsychiatric (50% [7 of 14]) conditions, including complex regional pain syndrome, essential tremor, depression, and obsessive-compulsive disorder. Neurovascular disorders, including headaches (71% [10 of 14]) and Raynaud phenomenon (29% [4 of 14]), as well as rheumatologic disorders (36% [5 of 14]), including lupus, rheumatoid arthritis, fibromyalgia, mixed connective tissue disease, and psoriatic arthritis, were also common. Many patients had tried the following treatments with limited success:
*Topical metronidazole (0 of 12 were helped)
*Topical steroids (1 of 8)
*Oral antibiotics, usually tetracyclines (4 of 8).
Most patients benefited from treatments that tried to calm the burning pain down, for instance gabapentin (5 out of 11), duloxetine (4 of 6), pregabalin (1 of 4), tricyclic antidepressants (2 of 3), and memantine (2 of 2). Topically creams were only occasionally effective, for instance doxepin, glycopyrrolate, amitriptyline, capsaicin, and ketamine.
Effective were:
*Hydroxychloroquine (Plaquenil) (3 of 5)
*Beta blockers
*Clonidine
The researchers also added that this group of patients with strikingly prominent neurologic (nerve pain) symptoms, are an underrecognized subgroup of rosacea. By highlighting and formally naming this subgroup, they hope to increase awareness and recognition of these patients and aid the practicing dermatologist in their therapeutic management. The cause of rosacea is complex, poorly understood, and likely multiple causes and factors, including bad functioning blood vessels in the facial skin and with most likely an auto-immune aspect to it. Also the nerves in the skin are no longer functioning as they should with this rosacea type. There is an element of abnormal response to heat and an increase of inflammation in the skin. And the injury of the nerves in the skin of rosacea patients with this subtype 1, also leads to dysesthesias: an abnormal sensation in the skin, of pain, skin burning, wetness, itching, electric shock, and pins and needles. It is sometimes described as feeling like acid under the skin.
"Patients with prominent vasomotor symptoms, defined clinically by flushing and telangiectasias, may respond to vasoactive medications, including β-blockers, alpha-1 adrenergic blockers, and calcium channel blockers. In addition, laser- and light-based therapies seem to be more effective in this subset of patients. Patients with inflammatory features such as papules, pustules, or edema may respond, if symptoms are mild, to traditional topical therapies such as metronidazole, azelaic acid, or sulfur. Systemic antibiotics and antimalarial agents used for their anti-inflammatory effect may be useful for nonresponders. Finally, patients with dysesthesia out of proportion to flushing or inflammation can be difficult to treat and require a unique approach first used to treat disorders such as complex regional pain syndrome and neuropathic itch. In our experience, neuroleptic agents (eg, gab-apentin, pregabalin), tricyclic antidepressants, and pain-modifying antidepressants (eg, duloxetine) are the most effective. N-methyl-D-aspartic acid receptor antagonists (eg, memantine), systemic antibiotics, and other topically formulated medications (eg, ketamine, glycopyrrolate, capsaicin) may be helpful in certain cases. Because of the associated heightened sensitivity to heat and sunlight, laser- and light-based interventions should be used with caution. Because our understanding of this enigmatic subclass of rosacea is extremely limited, further research is clearly needed to better describe the underlying patho-physiologic characteristics and to identify additional effective treatment methods."
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September 12th 2017,
Secukinumab for rosacea
Stanford University has started clinical trials for Secukinumab, used to treat rosacea. It is an open label study to assess the effect of Secukinumab in moderate to severe papulopustular rosacea. However hopes are that it will also address rosacea redness and inflammation. Test participants receive injections of secukinumab. First impressions from one rosacea patient who is undergoing these tests were: "Redness was almost completely gone by Saturday afternoon. [one day post injection]. The doctor says full results are shown anywhere from 12 to 16 weeks."
Update from this rosacea patient, September 29th 2017:
"Secukinumab update:
So this thing has really worked immensely. My redness is gone and I'm going back to Stanford medical center to get my 5th dosage. I'd recommend everyone in this group if you can get there, to do so. So you can finally rid yourself of this disease."
Secukinumab is a "human IgG1κ monoclonal antibody" that binds to the protein interleukin (IL)-17A. It is injected once weekly for four weeks (or around 5 booster shots) and then once a month for 5 months. It works a bit like methotrexate; suppressing the immune response and inflammation. Secukinumab lowers the bodies immune response and is used to treat auto immune diseases like psoriasis and related inflammation in the joints (artritis psoriatica). In psoriasis the bodies immune system goes in overdrive, and multiplies the skin cells too quickly, causing plaques of skin, inflammation and scaling and ultimately a lot of skin cell shedding. By lowering the immune system response, the skin symptoms can be calmed down too. Rosacea does not have an issue usually with increased skin cell formation, but some scientists do think that rosacea can be an auto immune disease as well, having the bodies own immune system attacking normal tissue and as such creating inflammation and redness. I know of some severe rosacea sufferers who were given methotrexate and who had their skin issues (redness, flushing) calm down significantly. Side effects can be significant however, increased risk of infections (viral infections, nose and throat infections, sinus infections and other infections) and it even raises the risk of certain cancers. That is generally the downside of methotrexate. Luckily Secukinumab does not seem to come with an increased risk of cancer. Several studies show that secukinumab demonstrates "a highly favorable safety profile, especially compared with commonly used psoriasis treatments such as methotrexate and TNF-α blockers. More specifically, secukinumab carries no increased risks for end-organ toxicities, serious infection, multiple sclerosis, reactivation of latent tuberculosis or hepatitis B, leukemia/lymphoma, and nonmelanoma skin cancer."
So despite of secukinumab being somewhat comparable to methotrexate, a drug that lowers (auto)immune response and inflammation as well, it comes with far less severe side effect risks. On January 21, 2015, the FDA announced that it had approved secukinumab to treat adults with moderate-to-severe plaque psoriasis, followed later with the approval for the treatment of ankylosing spondylitis, and psoriatic arthritis. A 2016 study also showed that secukinumab seems to be effective in the treatment of multiple sclerosis. I am a bit hopeful for this new trial! I know that my dermatologist treated some very severe rosacea patients with methotrexate for a little while, and their skin really cleared up (also through suppressed immune response and inflammation), but that the increased risk of infections was too tricky. Since secukinumab does not have that side effect profile as much, it seems a great alternative.Open Label Study to Assess the Effect of Secukinumab in Moderate to Severe
Papulopustular Rosacea
This study is currently recruiting participants.
Verified July 2017 by Anne Chang, Stanford University
Sponsor:
Anne Chang
Information provided by (Responsible Party):
Anne Chang, Stanford University
ClinicalTrials.gov Identifier:
NCT03079531
First received: March 9, 2017
Last updated: July 11, 2017
Last verified: July 2017
Purpose
This is a study to determine whether secukinumab is a potential therapy for those with papulopustular rosacea. We will observe whether this drug decreases the size and/or amount and severity of the pustules of those who suffer from rosacea.
| Condition | Intervention | Phase |
|---|---|---|
| Papulopustular Rosacea | Drug: Secukinumab | Phase 1Phase 2 |
| Study Type: | Interventional |
| Study Design: | Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
| Official Title: | An Open Label Phase 1b Study of Secukinumab in Patients With Moderate to Severe Papulopustular Rosacea |
Further study details as provided by Anne Chang, Stanford University:
Primary Outcome Measures:
- number of papules/pustules on rosacea patients at week 16 vs 0 [ Time Frame: 16 weeks ]Comparison of number of papules/pustules at 16 weeks compared to 0 weeks
Secondary Outcome Measures:
- reduction in the number of papules and/or pustules in moderate to severe papulopustular rosacea at week 12 vs 0 [ Time Frame: 12 weeks ]Compare number of papules/pustules at 12 weeks compared to 0 weeks
- reduction of the overall severity of rosacea by global assessment [ Time Frame: 16 weeks ]comparing week 16 and 0, includes clinical and patient reported symptoms
- reduction of erythema in patients with moderate to severe papulopustular rosacea [ Time Frame: 16 weeks ]comparing week 16 to 0
- improved quality of life measures in patients with moderate to severe papulopustular rosacea [ Time Frame: 16 weeks ]by patient questionnaire
- assess adverse events ≥ grade 3 in patients taking secukinumab for moderate to severe papulopustular rosacea [ Time Frame: 16 weeks ]frequency and severity of adverse events will be recorded throughout the study by CTCAE version 4.0
- changes in immune infiltrate in papulopustular rosacea lesions after secukinumab use [ Time Frame: 16 weeks ]assess by immunohistochemistry at 16 weeks versus 0 weeks
| Estimated Enrollment: | 24 |
| Anticipated Study Start Date: | July 14, 2017 |
| Estimated Study Completion Date: | January 1, 2019 |
| Estimated Primary Completion Date: | July 1, 2018 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: secukinumab arm
This is an open label study without placebo and it is a single arm study
| Drug: Secukinumab
We will be giving secukinumab to patients with papulopustular rosacea
|
Rosacea is a common inflammatory skin disease affecting up to 10% of adults. Despite this, the etiology of rosacea is unclear, although there may be a genetic predisposition (Chang et al., 2015). Currently, there is no cure. Rosacea can lead to scarring, itching, burning, and is associated with anxiety and depression (Moustafa et al., 2015), significantly affecting quality of life.
Secukinumab is an antibody that binds to a protein (interleukin (IL)-17A) that is involved in inflammation. When IL-17A is bound to secukinumab, it cannot bind to its receptor, thereby inhibiting its ability to feed the inflammatory response. In clinical trials, secukinumab has been effective for moderate to severe psoriasis (Blauvelt et al., 2015). Recently, human data from all types of rosacea have shown Th1/Th17 polarization profile of the T-cell response, suggesting that anti-IL-17 therapy may be beneficial for rosacea (Buhl et al., 2015). Hence, secukinumab could be effective against rosacea. This proposal is a proof-of-concept study to use secukinumab in open label design for moderate to severe papulopustular rosacea.
Eligibility
| Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- 1) moderate to severe papulopustular rosacea defined clinically using the grading system of Wilkin et al. (2004) as having at least ten lesions (either papules or pustules) on face at time of enrollment 2) age 18 years or greater willing and able to understand and sign informed consent form
Exclusion Criteria:
- 1) known hypersensitivity to secukinumab 2) topical or oral anti-rosacea medication usage for 28 days prior to enrollment 3) active Crohn's disease, as secukinumab may exacerbate this disease 4) active infection including tuberculosis, hepatitis B or C, human immunodeficiency virus 5) participants with latent tuberculosis will need to have treatment initiated prior to starting study drug 6) pregnant or lactating 7) active and/or uncontrolled medical conditions that may interfere with study procedures or obscure rosacea assessment such as cutaneous lupus 8) use of retinoids within past 3 months of enrollment 9) use of antibiotics within 4 weeks of enrollment 10) use of light based or laser treatment to face within 8 weeks of enrollment 11) use of topical or systemic steroids within 4 weeks of enrollment 12) acne conglobate, acne fulminans, chloracne, severe acne requiring systemic treatment
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT03079531
Contacts
Locations
Sponsors and Collaborators
Anne Chang
Investigators
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on September 11, 2017
| Rosacea Skin Diseases Antibodies, Monoclonal Immunologic Factors Physiological Effects of Drugs |
ClinicalTrials.gov processed this record on September 11, 2017
August 20170,5% ketamine with 1% amitriptyline cream for rosacea skin
My dermatologist told about a cream that really seems promising for rosacea skin. Some patients reported very good success with a mix of 0,5% ketamine with 1% amitriptyline in a cream base. You use it topically and it apparently pales the skin. It also helps (more officially) with erythromelalgia, a health condition that also involves a deep red flushing and burned red skin of the legs, arms, chest etc. The cream has to be made by a compounding pharmacist. My doctor is looking for one right now, willing to make it, as it's not a commercial cream yet. Here is some more information on this cream:
Deansm wrote on December 2nd, 2016: "Cleared up my type 1 Rosacea (flushing red nose). I have had flushing and swelling (caused by the flushing) on my nose for around 7 years (no pustules or pustules). Tried antibiotics, Soolantra, metrogel etc, nothing worked, every treatment has had absolutely zero effect. Two months ago the GP I am seeing prescribed me an ointment containing Ketamine 0.5% and Amitriptyline 1%. Within 3 days of using it twice a day the flushing disappeared and my skin is white, the same as it was before Rosacea. It has been the same ever since for the last two months. I can eat, exercise, go out in the sun and nothing will bring on a flush. If anyone has this subtype and nothing has worked have a look into this, I have no side affects (the GP said it is very safe as the amount of active ingredients is too low and it's not absorbed systemically). I am not sure which or if both of the ingredients are working. I have since learned that topical Ketamine behaves as an anti-inflammatory by acting on Toll-like receptor (TLRs), which leads to down regulation of pro-inflammatory gene expression." [..] "The packaging has no branding, it was made in a compounding pharmacy. He said he has found it helpful going back years for patients with Erythromelalgia and it was worth trying for my Rosacea as nothing else worked."Hg24 wrote on December 3rd, 2016: "This is really interesting, Dean. I googled and found reference to a study about this topical for erythromelalgia. The ointment seems to be for the pain (versus redness). I have type 1 rosacea, too. Flushing and permanent redness. Dean, you mentioned that your skin color is back to normal (pre-rosacea). So did you also have permanent redness? Or just the redness that comes on temporarily when you flushed? I guess I'm wondering if the ointment returned your vessels to normal - constricted them back. I wonder if the ingredients work because they address nerve pain. Nerves can stimulate our flushing. Eg, nerves release acetylcholine, a chemical that tells our vessels to dialate."
Deansm wrote on December 3rd, 2016: "I'm from Wales, I don't see any reason why it could not be prescribed in the other UK countries (The only problem I can think of is Scotland/Wales/England having separate devolved NHS bodies and rules etc). It probably is completely up to the GP, how many treatments you have already tried etc.He told me the ointment reduced redness and flushing on patients with Erythromelalgia(no idea what this was). I never expected this to work as every other treatment he prescribed (Soolantra, Antibiotics, Metrogel) has either done nothing or even made my Rosacea worse. [..] My Rosacea started (I was 24) as a sudden huge flareup (huge flushing episode) on my nose when I went to bed one night. I had never blushed or flushed on my nose before that first flareup. Ever since every night without fail I would have a flareup when I went to bed. Through the day I had one or two flareups and my nose was sensitive to flushing but not as bad as in the night. After each flare up it would take around 2-3 hours for my skin to return normalish in colour but there was always a slight pink hue on my nose. The worse symptom of all is the nose swelling for around 7 hours when I sleep and waking up every morning with a swollen nose. The flushing has stopped now and that stopped the swelling. My nose still looks a bit swollen but it's slowly going down now(2 months so far)."
Deansm wrote on December 3rd, 2016: "I'm from Wales, I don't see any reason why it could not be prescribed in the other UK countries (The only problem I can think of is Scotland/Wales/England having separate devolved NHS bodies and rules etc). It probably is completely up to the GP, how many treatments you have already tried etc.He told me the ointment reduced redness and flushing on patients with Erythromelalgia(no idea what this was). I never expected this to work as every other treatment he prescribed (Soolantra, Antibiotics, Metrogel) has either done nothing or even made my Rosacea worse. [..] My Rosacea started (I was 24) as a sudden huge flareup (huge flushing episode) on my nose when I went to bed one night. I had never blushed or flushed on my nose before that first flareup. Ever since every night without fail I would have a flareup when I went to bed. Through the day I had one or two flareups and my nose was sensitive to flushing but not as bad as in the night. After each flare up it would take around 2-3 hours for my skin to return normalish in colour but there was always a slight pink hue on my nose. The worse symptom of all is the nose swelling for around 7 hours when I sleep and waking up every morning with a swollen nose. The flushing has stopped now and that stopped the swelling. My nose still looks a bit swollen but it's slowly going down now(2 months so far)."
Fiugs wrote on December 4th, 2016: "There is a topical with the brand name Epicept, although I think the compound's percentages are different than you describe,Deansm. https://www3.rcsb.org/ligand/NP1. Did your GP indicate if s/he thought this would be a short or long term solution? Just wondering because I got the impression that some topical analgesics lose their effectiveness after a while.... I say that only based on what my local pharmacist told me in relation to a lidocaine based gel I was inquiring about; he said it would stop working after a while. I will certainly ask my GP about this! Thanks Deansm and all the best. I also found this article, referring to a compound using the same percentages as Deansm has been given http://jamanetwork.com/journals/jamadermatology/fullarticle/403191
Deansm wrote on December 4th, 2016: "From looking at the link EpiCept Cream is much stronger (2% ketamine / 4% amitriptyline), The cream I am on is 1%ami and 0.5%ket and it stops the flushing (the lower dose it works the better). Since my doctor said he had success with the ointment on patients with Erythromelalgia I have been reading a lot on Erythromelalgia forums about the safety of this cream (it seems very safe at low dose). I am not sure which ingredient (or a combination of both) is stopping the flushing, but this is something I found about topical ketamine.. Also from reading various Erythromelalgia forum posts, the vasodilation, flushing, redness are very similar to Rosacea, only it happens on the feet and hands and sometimes the face in Erythromelalgia. The only real difference over type 1 Rosacea as far as symptoms is the addition of more pain, stinging. It is interesting hearing about the other treatments they use on those forums to stop flushing that might also work for flushing on people with Rosacea."
Brady Barrows wrote on December 4th, 2016: "What a wonderful find to substantiate this thread. Note what the article says: "Erythromelalgia is a clinical syndrome characterized by attacks in which the affected limbs become bright red, hot, and excruciatingly painful. The common trigger is heat exposure induced by exercise or increased ambient temperature. As the condition progresses, the limbs become permanently red, hot, and painful. The pain of erythromelalgia, commonly described as hot and burning in quality, is frequently disabling, and patients obtain relief by lowering skin temperature, for example, by applying cold objects to the affected area, exposing the affected extremities to cold surfaces, immersing the limb in ice water, or by elevating the affected extremity. Frequently, these measures damage the skin, further exacerbating the pain, and occasionally cause maceration. Pain associated with erythromelalgia may be difficult to treat. Because erythromelalgia is not a single disease but a syndrome, the response to various treatments may differ depending on the underlying condition and pathophysiology. Furthermore, treatment of the pain symptoms may have little if any effect on the other manifestations (ie, the redness and increased temperature of the affected limbs). According to various theories, erythromelalgia is a vascular disorder or neuropathic condition. In previous studies, we have shown that both systems are involved, but we do not know which one is affected first. It is plausible that the vascular and neuropathic components differ in each subject depending on the underlying cause." Hopefully in the future we will know more if this treatment for erythromelalgia will be a standard treatment for rosacea."
Arsenalista wrote on December 5th, 2016: "Looks like another guy has also great results with this stuff.. I was read about Erythromelalgia (first time hear about it) and it looks like something very similar to rosacea but more painful. One of my worst symptoms is a chronic burning feeling at all my face. Damn, have to get the prescription."
I wrote on December 6th, 2016: "A very interesting find! I'm very curious if more people with facial (rosacea) flushing and burning will find relief from this cream. It's also a big bonus if your pharmacist can just add the powdered medication to your regular moisturizer. It's a fascinating distinction between facial erythromelalgia and rosacea. I'm not completely sure how you can detect one from the other, (apart from EM typically at the least affecting the hands and feet - but people with rosacea can get Raynauds (me too), which mimic these symptoms a lot), as these cases mentioned here look and sound pretty much like rosacea.
"A 53-year-old man presented to an outside dermatologist with an erythematous facial eruption of 4 years' duration. The eruption was associated with burning and swelling, which the patient reported worsened with sun exposure. These symptoms were debilitating, preventing the patient from working and maintaining daily activities. Initially, the eruption was thought to be rosacea and actinic damage; however, it was unresponsive to standard therapies." "Upon further questioning, the patient reported skin burning not only with sun exposure, but also with heat exposure. Furthermore, he reported attempting cooling measures, such as the frequent use of ice packs, to relieve his symptoms. With these additional details, a clinical diagnosis of facial and auricular erythromelalgia was established. Further workup excluded potential causes of secondary erythromelalgia. Given that erythromelalgia is thought to involve both small fiber neuropathy as well as vasculopathy, we initiated therapy with aspirin, pentoxifylline, and gabapentin. Subsequently, nifedipine was added to this treatment regimen. At 5 months' follow-up, the patient reported 80% improvement (Fig 2, B) and was able to return to work and enjoy normal daily activities
With a picture:
People with FIBROMYALGIA also mention rosacea symptoms more often Someone with fibro emailed me that her rosacea disappeared once she started to take guaifenesin tablets (a decongestant). Anyway, shows how complex these skin conditions are, there might be a lot of overlap and different factors at play. So curious to hear who else here might have benefit from this cream that is suggested."
RaymondS wrote on April 18th, 2017: "Didn't harm me but didn't help either. And it was a hell of a process to get the stuff. Just proves what works for one doesn't always work for another. I will keep it and just use in one area to make sure that over time it works or doesn't. But unfortunately it did not cure me."
Fiugs replied on April 18th, 2017: "Sorry to hear it didn't work for you either. I gave up on mine quite some time ago as it really aggravated my skin. It seems that only one person on our forum - the original poster - got marked results with this. It's truly weird, isn't it, that our skins are all so different! Every day I grow more of the opinion that there is no such single condition as Rosacea, but rather it's a blanket term for a red, irritated and sensitive flushy face, that may or may not include P&Ps, the unique cure of which is probably only going to be determined by the cause(s)."
Vice wrote on February 23rd, 2017: "Nobody should be worried about ketmamine having an effect. I take ketamine in powedered form recreationally and in my eyes 'medicinally'. It has an anti depressant effect and is currently being reviewed and researched as a breakthrough anti depressant for treatment resistant patients. It's a wonder drug really. The hallucinations are more distortions and only occur with high doses. - I personally love them myself. I am also trying to get the cream ointment and am in the middle of the process to getting it in uk now but it's difficult. Obviously I know it won't have any effect on my mind but it's still crazy that a drug I used systemically to get high might also be a good treatment for Rosacea! Who'd have thought!"
Hey,
ReplyDeleteI am a young girl suffering from rosacea, I think I might be as young as you when your rosacea started.
I am impressed by your knowledge about rosacea and thus I am thinking you might be able to give me a realisitc validation about the following:
What do you think might be the (near and not so near) future of rosacea treatment? I don't want to start talking about even a cure but even treatment that is able to bring rosacea for most of us to remission would be great. Can I hope (or even count) for advances in treatment or should I (for my own sake) better accept the fact that I am having an ever progressing condition for the rest of my life?
Best wishes,
Mimi
Hi Mimi, thanks for your message. Sorry to read you suffer from rosacea too and at a young age..
ReplyDeleteI developed all this in 1999 and ever since, the only things that were developed, were based on existing medication. Mirvaso and Rhofade for instance use a chemical that constricts the blood vessels in the eye originally. Both seem to give rebound worsening of rosacea when used on the skin, unfortunately... On forums, we looked forward to their launch for almost a decade I think.
Laser and IPL does help a lot of people with rosacea, but have not yet been refined to the point where they no longer come with a risk of worsening the rosacea, so they are no true remedy yet either... All other medication that is used for rosacea has been on the market for a long time already, and none specifically created for rosacea.
I have become skeptical therefore about the short term outlook on something new that will really help us. It seems there is not enough funding and interest among scientists and pharmaceutical companies to get to the core of the problem and then to make fitting treatments. I am hopeful that gene therapy will in the next decades march on and be able to identify and cut out genetic illnesses in our DNA, but rosacea will not be among the first genetic diseases to be tackled.. It might actually come far behind other diseases like cancer and deadly auto immune diseases. So that won't be something to have hopes for in the near future either... I am pessimistic that we can expect anything that is a break through and that could cure rosacea, honestly. Also because rosacea is a complex condition, that does not have one single cause or trigger or treatment response. It has most likely links to the skin barrier, blood vessels of course, central nervous system, immune system, possibly even the digestive system... All that still needs to be thoroughly researched and all that goes painstakingly slow.
But we can benefit from new treatment options for other diseases that link a bit to rosacea. New medication for menopausal hot flashes could also help us who have rosacea facial flushing perhaps. Anti inflammatory medication for other skin diseases might help us too. Back in time, thinking about the future as a 19 year old, I expected things to have improved a lot by now, and it has been very disappointing in that respect, but hopefully there is some acceleration in research nowadays and more to expect soon!
I expect that the future of rosacea will have to do with figuring out what causes the inflammation in our blood vessels and skin, and finding an auto immune component to it, and that there will be new drugs developed that break up this inflammation chain, and help is in that sense.
Not sure this helps you... There are luckily some creams and pills and treatments we can try these days but I haven't found a cure yet :(
Best of wishes