Related Articles Methods for extraction and ex-vivo experimentation with the most complex human commensal, Demodex spp. Exp Appl Acarol. 2019 Dec 13;: Authors: Clanner-Engelshofen BM, French LE, Reinholz M Abstract Demodex spp. mites are the most complex organisms of the human skin microbiome and were discovered more than 175 years ago, yet only little basic research is published about them. As they can be pathophysiologically relevant ectoparasites associated with rosacea, pityriasis folliculorum, and other inflammatory skin diseases, more research should be encouraged. Being a large microorganism or a tiny animal, there are no established basic methods to handle these mites. Here, we describe techniques enabling the extraction of Demodex mites from human skin, their analysis in different ex-vivo settings, the lysis of their exoskeleton, their preservation by freezing, and observation microscopically using specific fluorescent dyes or their inherent autofluorescence. These procedures should facilitate future Demodex research and fuel further the generation of knowledge. Furthermore it is intended to ultimatively enable the mite's cultivation in vitro and reveal its pathophysiological mechanisms. PMID: 31834574 [PubMed - as supplied by publisher] {url} = URL to article

image courtesy of Wikimedia Commons Acne Vulgaris is a completely different disease from rosacea, but many authoritative sources report that acne vulgaris can co-exist with rosacea.[1] In past literature, acne rosacea was used to describe adult acne. [2] However, rosacea is generally confined to the facial area while acne can be not only on the facial area but also on the trunk. Treatments for acne usually irritate or exacerbate rosacea and is one of the differentiating diagnostic marker for a rosacea diagnosis. [3] [1] "It should be noted, however, that it is possible for acne vulgaris and rosacea to appear at the same time in the same patient." Medscape [2] “It is interesting that the original term for rosacea was “acne rosacea”, which has more features in common with acne than currently realized. If the “acne” portion had been retained in the later works, rosacea might have received much greater investigative attention.” A Personal Critique on the State of Knowledge of Rosacea Albert M. Kligman, M.D., Ph.D. Department of Dermatology, University of Pennsylvania, Philadelphia, PA, U.S.A. [3] What is the difference between acne and rosacea?

There has been at least three pharmaceutical companies researching and testing a topical minocycline for rosacea. We await to see the results of these clinical trials and if these are effective. (1) FMX103 Topical Minocycline Foam, Foamix Ltd (2) BPX-04 Minocycline Topical Gel 1%, BioPharmX, Inc. (3) HY-01 Minocycline Gel 3%, Hovione  

image courtesy of Wikimedia Commons A genome-wide association study (GWAS) of rosacea symptom severity was conducted by Aponte et al [1] that concluded "All associations with rosacea were novel except for the HLA locus. Two of these loci (HERC-OCA2 and SLC45A2) and another precedented variant (rs1805007 in melanocortin 1 receptor) with an association P value just below the significance threshold (P = 1.3 × 10-7) have been previously associated with skin phenotypes and pigmentation, two of these loci are linked to immuno-inflammation phenotypes (IL13 and PSMB9-HLA-DMA) and one has been associated with both categories (IRF4). Genes within three loci (PSMB9-HLA-DMA, HERC-OCA2 and NRX3-DIO2) were differentially expressed in a previously published clinical rosacea transcriptomics study that compared lesional to non-lesional samples. The identified loci provide specificity of inflammatory mechanisms in rosacea, and identify potential pathways for therapeutic intervention."  "In genetics, a locus (plural loci) is a specific, fixed position on a chromosome where a particular gene or genetic marker is located." Wikipedia "With the completion of the Human Genome Project in 2003 and the International HapMap Project in 2005, researchers now have a set of research tools that make it possible to find the genetic contributions to common diseases." [2] "Genome wide association studies (GWAS) are a relatively new approach to analyzing genetic sequence and have quickly become a fundamental part of modern genetic studies. Their purpose is to determine alleles that correlate to different diseases and traits." [3] "Despite clear successes in identifying novel disease susceptibility genes and biological pathways and in translating these findings into clinical care, GWAS have not been without controversy. Prominent criticisms include concerns that GWAS will eventually implicate the entire genome in disease predisposition and that most association signals reflect variants and genes with no direct biological relevance to disease." [4] End Notes [1] Hum Mol Genet. 2018 Aug 1;27(15):2762-2772. doi: 10.1093/hmg/ddy184. Assessment of rosacea symptom severity by genome-wide association study and expression analysis highlights immuno-inflammatory and skin pigmentation genes. Aponte JL, Chiano MN, Yerges-Armstrong LM, Hinds DA, Tian C, Gupta A, Guo C, Fraser DJ, Freudenberg JM, Rajpal DK, Ehm MG, Waterworth DM. [2] Genome-Wide Association Studies Fact Sheet, NHGRI, NIH [3] Genome Wide Association Studies (GWAS), Genetics Generation [4] Nature Reviews Genetics, ISSN 1471-0064 (online) Benefits and limitations of genome-wide association studies Vivian Tam, Nikunj Patel, Michelle Turcotte, Yohan Bossé, Guillaume Paré & David Meyre  

Image of Demodex Folliculorum courtesy of National Geographic - by Darlyne A. Murawski There are substantial anecdotal reports that treatment for demodectic rosacea gets worse before it gets better. The logic behind this is that killing the demodex mites causes a die-off of the mites that takes weeks to accomplish since new eggs are being hatched each day and the "life cycle of demodex mites consists of five phases of development and lasts from 14 to 18 days". [1] Furthermore because the movement of the mites has been shown to be "at a speed of 8-16 mm/h" [2] they may leave the area being treated and return later while planting eggs along the route. During the initial treatment which may take weeks some of the mites are reported to be killed which may cause inflammation and worsen the skin. One explanation of this is the "Jarisch–Herxheimer reaction" (JHR) which has been "traditionally associated with antimicrobial treatment of syphilis." [3] The principle of JHR may indicate a reason why it gets worse before it gets better. One source comments on this by stating, "And while the JHR only technically relates to spirochetal infections (spiral-shaped bacteria) and antibiotics, the concept of symptom-onset or worsening after starting treatment with antimicrobials has been seen to apply more broadly in clinical practice. This is why you’ll often hear practitioners talk about a Herx-reaction, even if it isn’t scientifically accurate. But, what we call ‘die-off symptoms’ is certainly something we see commonly when clients begin addressing bacteria, parasites and yeast pathogens using natural antimicrobials." Furthermore, there are at least six types of bacteria that have been associated with demodex mites. [5] At least one virus has been associated with rosacea [6] and viruses have not been ruled out in demodectic rosacea. There are very little clinical studies done on virus and rosacea. Viruses are in bacteria and comprise more weight in the human body than bacteria by a factor of ten times. [7] More study should be done on why treatment for demodectic rosacea seems in many cases to get worse before it gets better. Nevertheless, reducing demodex density counts in rosacea improves the patient with rosacea. [8] End Notes [1] Demodex Update Subheading, The potential role of Demodex folliculorum mites and bacteria in the induction of rosacea, third paragraph  [2] Russian Study on Demodex Mites and Rosacea Illuminating, (2) The report confirms the size and movement of demodex, second paragraph [3] Jarisch–Herxheimer reaction, Wikipedia [4] Pathogen & Parasite Die-Off Symptoms: How to manage detox side-effects, Bella Lindemann, June 24, 2019 [5] Bacteria Associated with Rosacea and Demodex Mites [6] Candida Albicans [7] Human Microbiome, Brady Barrows  [8] Decreasing Demodex Density Count Improves Rosacea