A paper in 2017 continues to explain the quandary. "Many studies have shown higher density of the parasites in diseased inflammatory skin than in normal skin, but whether it is the cause or result of the inflammation remains unclear." [6]  A paper in 2018 may help to resolve this issue because for the first time it has been discovered that Demodex mites secrete bioactive molecules that reduced TLR2 expression in sebocytes. [7] So while the jury is still out on this subject, What do you think?  Which comes first, the demodex or the rosacea? Does it even matter? With your above statement I highlighted and giving my view on this topic which comes first, I am also stating the same thing that I think demodex came first well it is not experiment or evidence based but with the experience I have had. Human Permanent Ectoparasites; Recent Advances on Biology and Clinical Significance of Demodex Mites: Narrative Review Article With this journal which you quoted in your article , "Many studies have shown higher density of the parasites in diseased inflammatory skin than in normal skin, but whether it is the cause or result of the inflammation remains unclear." So I was elaborating this sentence that higher density might be the result of inflammation (inflammatory immune response) and then subsequently the cause of inflammation. So I explained this with the term “reciprocal correlation”. And let’s say if the higher density is the result of inflammation, so the altered cutaneous immune responses are the cause of persistent inflammation and that is what I was trying to state in my post but then I read the above journal in detail after your question and I found the confirmation of my  expression with these sentences of journal   “ Studies indicate increased number of D. folliculorum in immunocompromised patients”  and “It remains to be determined which kind of cellular immunity may foster mites’ proliferation” and my statement “the false immune response(altered immune response) might be the cause of increasing number of demodex”  state the same thing. Thank you for questions because what I was stating is experience based but after thoroughly reading the reference journals from your article I found the confirmation of the same thing.    

That is difficult to follow. In a paper by Powell, et al, it is stated that the mites "secrete bioactive molecules that reduced TLR2 expression in Sebocytes." The 'bioactive molecules' that the mites secrete keep the innate immune system from reacting to the mites when in normal numbers on normal skin, so my question is what causes the demodex to proliferate in greater numbers to what you say,  "cause inflammatory immune response and inflammatory immune response" ?   Could you better explain what you mean by "self-antigen presentation to immune cells rather than non-self which is false immune response? ?

In my view, normal skin also has demodex mites but less in number so they can't activate pro-inflammatory cytokines but when the number is more they activate it. so logically when the normal skin flora has demodex before rosacea has occured so demodex apparently came first and because demodex mites cause inflammatory immune response and inflammatory immune response is not just related to mites but self-antigen presentation to immune cells rather than non-self which is false immune response or we call it autoimmune response and attacks to healthy cells and so the false immune response might be the cause of increasing number of demodex .So demodex and rosacea have reciprocity with each other to increase its effects and outcomes.

While it has been reported that topical ivermectin has better results than topical metronidazole, there is a paper you should consider reading if you are considering taking oral ivermectin and metronidazole.  A paper published by the International Journal of Infectious Diseases that compared taking 200 micro-grams Ivermectin per Kilogram of body weight of oral ivermectin once a week in one group (1) of sixty rosacea patients with another group (2) of sixty rosacea patients who received a combined therapy of the same amount of ivermectin along with 250 mg of oral metronidazole three times a day. The results were that the second group improved better than the first group. For more information Some may concerned about taking ivermectin orally. It is interesting to note that ivermectin has been around since the late 1970s and half "of the 2015 Nobel Prize in Physiology or Medicine was awarded jointly to Campbell and Ōmura for discovering avermectin, 'the derivatives of which have radically lowered the incidence of river blindness and lymphatic filariasis, as well as showing efficacy against an expanding number of other parasitic diseases' " Wikipedia Ivermectin is "a dihydro derivative of avermectin—originating solely from a single microorganism isolated at the Kitasato Intitute, Tokyo, Japan from Japanese soil...originally introduced as a veterinary drug...has led many to describe it as a “wonder” drug....few drugs that can seriously lay claim to the title of ‘Wonder drug’, penicillin and aspirin being two that have perhaps had greatest beneficial impact on the health and wellbeing of Mankind....But ivermectin can also be considered alongside those worthy contenders, based on its versatility, safety and the beneficial impact that it has had, and continues to have, worldwide—especially on hundreds of millions of the world’s poorest people....Despite decades of searching around the world, the Japanese microorganism remains the only source of avermectin ever found. Originating from a single Japanese soil sample and the outcome of the innovative, international collaborative research partnership to find new antiparasitics, the extremely safe and more effective avermectin derivative, ivermectin, was initially introduced as a commercial product for Animal Health in 1981." [1] While there are no long term clinical studies done on ivermectin use with rosacea, there are papers showing the long term effects of oral ivermectin in school-age and pre-school children treated for helminths. [2] There are also papers written about the long term effects of treating humans with ivermectin on other parasites.  'Intriguingly, IVM has a diverse range of effects in many different organisms, far beyond the endoparasites and ectoparasites it was developed to control. For example, IVM has been shown to regulate glucose and cholesterol levels in diabetic mice, to suppress malignant cell proliferation in various cancers, to inhibit viral replication in several flaviviruses, and to reduce survival in major insect vectors of malaria and trypanosomiasis. Clearly, much remains to be learned about this versatile drug, but the promise of more sustainable strategies for current helminth-control programmes and novel applications to improve and democratise human health, are compelling arguments to pursue this cause." [3] With the craze of rosaceans using horse paste to treat rosacea topically, there is one report of oral horse paste treatment for Lyme disease in Facebook by a poster. [4] So there are a substantial number of humans globally who have taken oral ivermectin.  More information on oral ivermectin. ElaineA has a post worth reading on this subject, Oral Ivermectin, getting diagnosed and a prescription. End Notes [1] Proc Jpn Acad Ser B Phys Biol Sci. 2011 Feb 10; 87(2): 13–28. doi: 10.2183/pjab.87.13 PMCID: PMC3043740; PMID: 21321478 Ivermectin, ‘Wonder drug’ from Japan: the human use perspective Andy CRUMP and Satoshi ŌMURA [2] PLoS Negl Trop Dis. 2008 Sep; 2(9): e293. Published online 2008 Sep 10. doi: 10.1371/journal.pntd.0000293 PMCID: PMC2553482; PMID: 18820741 Impact of Long-Term Treatment with Ivermectin on the Prevalence and Intensity of Soil-Transmitted Helminth Infections Ana Lucia Moncayo,  Maritza Vaca,  Leila Amorim,  Alejandro Rodriguez,  Silvia Erazo,  Gisela Oviedo,  Isabel Quinzo,  Margarita Padilla,  Martha Chico,  Raquel Lovato,  Eduardo Gomez,  Mauricio L. Barreto,  and Philip J. Cooper   [3] Trends in Parasitology Volume 33, Issue 6, June 2017, Pages 463-472 Ivermectin – Old Drug, New Tricks? Roz Laing. Victoria Gillan. Eileen Devaney [4] Post number five in this thread

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