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Glandular Rosacea is recognized as a rosacea variant. "In 2004 in an article appearing in the Journal of the American Academy of Dermatology, Crawford et al. proposed the concept of glandular rosacea to describe another phenotype distinct from the four subtypes introduced by the expert committee. Glandular rosacea occurs predominantly in males who characteristically have oily skin, large pores, a tendency to rhinophyma, and inflammatory lesions, including papules, pustules and nodulocystic lesions, that extend onto the lateral cheeks and neck." [1] Whether Glandular Rosacea should be classified as a phenotype, subtype or variant remains to be seen, but for now it is listed with the variants of rosacea to end the confusion (we also listed it previously as a proposed subtype). End Notes [1] Literature review highlights renewed interest in rosacea research Dermatology Times, Modern Medicine, Nov 1, 2006, Cheryl Guttman, page 2

Rosacea Variant: Granulomatous Rosacea [also known as Lupoid rosacea] This is the only variant as of this date recognized by the NRS 'expert committee' who first classified rosacea into subtypes and variants. This variant of rosacea is characterized by firm, yellow, brownish or redish, cutaneous papules or nodules. These lesions are less inflammatory and frequently sit upon relatively normal-appearing skin but sometimes it is diffusely red and thickened. Typically, they are monomorphic in each individual patient affecting the cheeks and the periorifical areas. For diagnosing this form of rosacea, other signs and symptoms of rosacea are not necessary. Diascopy with a glass spatula reveals the lupoid character of the infiltrations. Lupoid or granulomatous rosacea may lead to scarring of the skin. [1] "Granulomatous rosacea is a rare chronic inflammatory skin disease with an unknown origin. The role of Demodex follicularum in its pathogenesis is currently proved." [9] Granulomatous rosacea Image Dermatology Online Journal One source describes granulomatous rosacea: "A rare caseating granulomatous variant of rosacea (acne agminata/lupus miliaris disseminatus faciei) can manifest with inflammatory erythematous or flesh-colored papules distributed symmetrically across the upper part of the face, particularly around the eyes and the nose. The lesions tend to be discrete, and surrounding erythema is not a marked feature but may be present. This pattern of rosacea is sometimes associated with scarring and may be resistant to conventional treatment." [1] "...Although usually considered a non-pathogenic parasite in parasitological textbooks, Demodex folliculorum has been implicated as a causative agent for some dermatological conditions, such as rosacea-like eruptions and some types of blepharitis. Several anecdotal reports have demonstrated unequivocal tissue damage directly related to the presence of the parasite. However, this seems to be exceedingly rare, in contrast with the marked prevalence of this infestation. We have had the opportunity to observe one of such cases. A 38-year-old woman presented with rosacea-like papular lesions in her right cheek. Histopathological examination revealed granulomatous dermal inflammation with a well-preserved mite phagocytized by a multinucleated giant cell. This finding may be taken as an evidence for the pathogenicity of the parasite, inasmuch as it does not explain how such a common parasite is able to produce such a rare disease." It is associated with demodex. [2] "Histological investigation revealed follicular cysts and a chronic granulomatous perifolliculitis with many of Demodex folliculorum." [3] Another report had a similar finding. [4] A report by Neri, et. al., suggested that Idiopathic Facial Aseptic Granuloma (IFAG), or pyodermite froide du visage be "considered the possibility that IFAG might be included in the spectrum of granulomatous rosacea (GR)." [5] Other names considered are "Micropapular tuberculid", or "Rosacea-like tuberculid of Lewandowsky") [12] Treatment Dapsone [6] Isotretinoin (10-20 mg daily) [7] "The aetiopathogenetic role of Helicobacter pylori in rosacea remains controversial. We report a 27-year-old man with a 4-year history of intractable rosacea. Histopathology showed epithelioid granulomas. H. pylori infection was proven directly on gastroscopy and by serological testing. Treatment with clarithromycin, metronidazole and pantoprazole eradicated H. pylori. Skin changes were markedly improved by the end of this therapy and had resolved completely 2 months later. The patient has been followed up, and has remained free of symptoms for 3 years. We suggest that H. pylori may be involved in the aetiopathogenesis of granulomatous rosacea." [8] elmonxito says he is convinced that removing some of his infected teeth improved his granulomatous rosacea. [10] "a 66-year-old lung transplant recipient, who was successfully treated with oral metronidazole and ivermectin cream." [11] Reply to this Topic There is a reply to this topic button somewhere on the device you are reading this post. End Notes [1] rosacea.dermis.net [2] Granulomatous rosacea associated with Demodex folliculorum. Amichai B, Grunwald MH, Avinoach I, Halevy S. Int J Dermatol. 1992 Oct;31(10):718-9. [3] Tubero-pustular demodicosis Grossmann B, Jung K, Linse R. Hautarzt. 1999 Jul;50(7):491-4. [4] Demodex folliculorum and the histogenesis of granulomatous rosacea Grosshans EM, Kremer M, Maleville J. Hautarzt. 1974 Apr;25(4):166-77. [5] Should Idiopathic Facial Aseptic Granuloma Be Considered Granulomatous Rosacea? Report of Three Pediatric Cases. Neri I, Raone B, Dondi A, Misciali C, Patrizi A. Pediatr Dermatol. 2012 Feb 16. doi: 10.1111/j.1525-1470.2011.01689.x. [6] Hautarzt. 2013 Apr;64(4):226-8. doi: 10.1007/s00105-013-2556-7. Successful treatment of granulomatous rosacea with dapsone. Ehmann LM, Meller S, Homey B. Hautklinik des Universitätsklinikums Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Deutschland. [7] Hautarzt. 2013 Nov 1. Lupoid rosacea as a special form of rosacea : Review of pathogenesis and therapeutic options. Vanstreels L, Megahed M. Source Klinik für Dermatologie und Allergologie, Universitätsklinikum der RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Deutschland [8] Eur J Gastroenterol Hepatol. 2001 Nov;13(11):1379-83. Resolution of granulomatous rosacea after eradication of Helicobacter pylori with clarithromycin, metronidazole and pantoprazole. Mayr-Kanhäuser S1, Kränke B, Kaddu S, Müllegger RR. [9] J Med Case Rep. 2017; 11: 230. Published online 2017 Aug 20. doi: 10.1186/s13256-017-1401-5 PMCID: PMC5563383 Granulomatous rosacea: a case report A. Kelaticorresponding author and F. Z. Mernissi [10] Demodex follicularum connected to Granulomatous rosacea, post no 4 by elmonxito [11] Hautarzt. 2019 Sep 27;: [Granulomatous rosacea in a lung transplant recipient : A possible therapy option in a unique group of patients]. Ansorge C, Technau-Hafsi K [12] Lupoid Rosacea Other Sources A case of granulomatous rosacea: Sorting granulomatous rosacea from other granulomatous diseases that affect the face. Omar Khokhar MD, and Amor Khachemoune MD CWS Dermatology Online Journal 10 (1): 6 Granulomatous rosacea. Sánchez JL, Berlingeri-Ramos AC, Dueño DV. Am J Dermatopathol. 2008 Feb;30(1):6-9. J Cutan Med Surg. 2012 Dec 1;16(6):438-441. Isotretinoin for the Treatment of Granulomatous Rosacea: Case Report and Review of the Literature. Rallis E, Korfitis C.

Please read this notice about Subtypes Subtype 4: Ocular Ocular rosacea is common but often not recognized by the clinician.[1] It may precede, follow, or occur simultaneously with the skin changes typical of rosacea. In the absence of accompanying skin changes, ocular rosacea can be difficult to diagnose, and there is no test that will confirm the diagnosis. Patients usually have mild, nonspecific symptoms, such as burning or stinging of the eyes. A sensation of dryness is common, and tear secretion is frequently decreased. [2] Mild-to-moderate ocular rosacea (including blepharoconjunctivitis, chalazia, and hordeola) occurs frequently, whereas serious disease with the potential for visual loss, such as that which results from keratitis, occurs rarely. "Probably the first description of ocular rosacea was by the famous English dermatologist Willan in the earl 1800’s whose handwritten note on an illustration fo a patient with PPR documented the presence of ocular inflammation." [16] Ocular problems occur in at least 50 percent of patients with rosacea. [3] "Although considered a skin disease, rosacea may evolve the eyes in 58-72% of the patients, causing eyelid and ocular surface inflammation. About one third of the patients develop potentially sight-threatening corneal involvement. Untreated rosacea may cause varying degrees of ocular morbidity." [14] There may be a clinical diagnositic test now available for ocular rosacea. [4] One report said, "Patients with rosacea have thinner corneas, which could be attributed to the observed deteriorated tear function parameters." [12] For images of Ocular Rosacea click here: http://goo.gl/ESG4n Treatment Treating ocular rosacea (from the AAO) Topical Cyclosporine Proves Beneficial For Ocular Rosacea [6] Avermectin Milbemycin Eyewash for Ocular Rosacea [7] Might consider demodex mite treatment. [8] Terpinen-4-ol (T4O) Pass [11] One report states, "We suggest that a clinically acceptable dosage of PRP provides the ocular surface with the components necessary to restore normal cellular tensegrity and provides a foundation to eliminate the recurrence of the inflammation associated with DES [Dry eye syndrome]." [13] Cliradex [15] Diagnostic Test While there is no diagnostic test for Ocular Rosacea there may be indicators coming down the pipeline for such a test. One paper suggests, "The abundance of highly fucosylated N-glycans in the control samples and sulfated O-glycans in ocular rosacea patient samples may lead to the discovery of an objective diagnostic marker for the disease." [9] Another paper suggests, "The high abundance of oligosaccharides in the tear fluid of patients with rosacea may lead to an objective diagnostic marker for the disease." [10] "There is not yet a diagnostic test for rosacea. The diagnosis of ocular rosacea relies on observation of clinical features, which can be challenging in up to 90% of patients in whom accompanying roseatic skin changes may be subtle or inexistent." [14] Links [5] Dry Eye: Awareness, Diagnosis, and Management All of the ocular rosacea articles at rosacea news Ocular Rosacea: Dr. Eric Jones, MD Ocular Rosacea: Dr. Mark J. Mannis, MD Ocular Rosacea: Curse of the Celts and Celebs, Heather Potter, MD, University of Wisconsin, School of Medicine and Public Health End notes [1] Kligman AM. Ocular rosacea: current concepts and therapy. Arch Dermatol 1997;133:89-90.[CrossRef][iSI] [Medline] [2] Gudmundsen KJ, O'Donnell BF, Powell FC. Schirmer testing for dry eyes in patients with rosacea. J Am Acad Dermatol 1992;26:211-214.[iSI] [Medline] [3] Rosacea: A Common, Yet Commonly Overlooked, Condition B. WAYNE BLOUNT, M.D., M.P.H. and ALLEN L. PELLETIER, M.D. Am Fam Physician. 2002 Aug 1;66(3):435-441. [4] Glycomics Analyses of Tear Fluid for the Diagnostic Detection of Ocular Rosacea Hyun Joo An, Milady Ninonuevo, Jennifer Aguilan, Hao Liu,‡ Carlito B. Lebrilla, Lenio S. Alvarenga, and Mark J. Mannis J. Proteome Res., 2005, 4 (6), pp 1981–1987, October 6, 2005, American Chemical Society Trail of Tears May Lead to the First Diagnostic Test for Ocular Rosacea Ocular Rosacea Test Updated: 6/21/2006 9:16:46 AM Dental Care & Health Care Articles [5] Link list courtesy of David Pascoe [6] Topical Cyclosporine Proves Beneficial For Ocular Rosacea Skin and Allergy News, Medical Dermatology BRUCE JANCIN, Skin & Allergy News Digital Network [7] Patent applied for by Galderma David Pascoe's comment on the above patent [8] In vitro and in vivo killing of ocular Demodex by tea tree oil. Gao YY, Di Pascuale MA, Li W, Baradaran-Rafii A, Elizondo A, Kuo CL, Raju VK, Tseng SC. Ocular Surface Center, 7000 SW 97 Avenue, Suite 213, Miami, FL 33173, USA. Br J Ophthalmol. 2005 Nov;89(11):1468-73. [9] Glycomic analysis of tear and saliva in ocular rosacea patients: the search for a biomarker. Vieira AC, An HJ, Ozcan S, Kim JH, Lebrilla CB, Mannis MJ. Ocul Surf. 2012 Jul;10(3):184-92. Epub 2012 May 3. [10] Glycomics Analyses of Tear Fluid for the Diagnostic Detection of Ocular Rosacea Hyun Joo An, Milady Ninonuevo, Jennifer Aguilan,Hao Liu, Carlito B. Lebrilla, Lenio S. Alvarenga,and Mark J. Mannis J. Proteome Res., 2005, 4 (6), pp 1981–1987, DOI: 10.1021/pr0501620, Publication Date (Web): October 6, 2005 [11] In clinical trials as of August 2012: Demodex Blepharitis Treatment Study (DBTS) [12] Can J Ophthalmol. 2012 Dec;47(6):504-8. doi: 10.1016/j.jcjo.2012.07.009. Central corneal thickness in patients with mild to moderate rosacea. Onaran Z, Karabulut AA, Usta G, Ornek K. [13] Optometry. 2012 Mar 30;83(3):111-3. Dry-eye--is inflammation just the tip of the iceberg? Jarka ES, Kahrhoff M, Crane JB. [14] Arq Bras Oftalmol. 2012 Oct;75(5):363-9. Ocular rosacea: a review. Vieira AC, Höfling-Lima AL, Mannis MJ. [15] One report on Cliradex is from yoegan on 5th April 2013 10:01 PM Post #467 [16] Rosacea: Diagnosis and Management, By Frank Powell

Please read this notice about Subtypes Subtype 3 is now known as Phenotype Phymatous (Rhinophyma)

Please read this notice about Subtypes Subtype 2: Papulopustular (PPR) (characterized by persistent redness with bumps [papules] and pimples [pustules]) Usually the most responsive to treatment subtype. Usually, small, dome-shaped erythematous papules, some of which have tiny surmounting pustules, on the convexities of the central portion of the face, with background erythema typify papulopustular rosacea. for images of PPR click below: http://goo.gl/aNoPX

Please read this notice about Subtypes Subtype 1: Erythematotelangiectatic (ETR) (characterized by persistent redness, usually with the Butterfly or T -Zone) This is usually the most difficult to treat. Flushing, with persistent central facial erythema (erythematotelangiectatic rosacea), is probably the most common presentation of rosacea. Click below for images: http://goo.gl/68HpW image courtesy of the University College Dublin

Please read this notice about Subtypes Neurogenic Rosacea recognized by the RRDi as a Subtype of Rosacea since 2011, now recognizes Neurogenic Rosacea as a variant of rosacea. This post has been promoted to an article

Human steroidogenesis* Steroid Rosacea is recognized as a Rosacea Variant Steroids are sometimes used for rosacea and other skin conditions for treatment, usually in severe cases, for a limited time or short term therapy (scroll down to the subheading SHORT TERM STEROID TREATMENT). Steroids are not recommended for long term treatment of rosacea. If your doctor recommends a steroid treatment for your skin problem it should be explained to you what the benefits and risks or side effects associated with this treatment are. Usually the insert that comes from the product explains what these risks and side effects might be. Obviously, sometimes short term steroid treatment has been helpful to some who have had rosacea or other skin condition, or we wouldn't even hear of anyone being prescribed steroids. Topical Steroid Rosacea - image courtesy of Wikimedia Commons Steroid rosacea photos by DermNet NZ • Google images of Steroid Rosacea While some rosaceans have mixed the two, steroids and rosacea, it is not a good idea. And if you want some good advice, never mix the two. Do not use topical steroids on rosacea, period! Why is this such a problem that it is listed as a variant? Because rosaceans continue to use steroids or allow their physicians to treat them with steroids. An informed rosacean can decide whether the benefit of using steroids for rosacea is worth the risk, and your physician should explain the benefit/risk ratio to you. You have the choice to either accept the treatment or decline it. Dermatologists have been using topical corticosteroids since the 1950s treating intractable dermatoses. However, a report in 1988 says, "Disadvantages of corticosteroid activity include the possibility of adrenal suppression, epidermal and dermal thinning, and local effects such as purpura, striae, and steroid-induced rosacea and perioral dermatitis." [1] Various Names for Steroid Rosacea One paper calls it Facial corticosteroid addictive dermatitis (FCAD). [2] Another paper calls it Topical Steroid-Induced Facial Dermatosis [3] One paper designates this as Topical steroid dependent/damaged face (TSDF). [31] The names are a growing list. Another report called it "steroid dermatitis." [25] One paper calls it "Topical corticosteroid withdrawal ("steroid addiction")." [34] "Based on the patient’s history of the long-term topical corticosteroids and physical examination, we finally diagnosed this case as unilateral steroid-induced rosacea-like dermatitis (SIRD)." [36] "Topical steroid damaged face (TSDF) was a newly described phenomenon in 2008, which is characterized by a group of symptoms induced by the prolonged, unsupervised usage of TCs on the face, regardless of the potency." [37] History of Treating Skin Conditions with Steroids "...Corticosteroids were first introduced for topical use in dermatology in 1951. Since then uncontrolled use (abuse) has caused many different reactions, often with manifestations resembling those of rosacea..." [3] "...Dermocorticosteroids can be indicated in numerous inflammatory skin diseases (psoriasis, eczema ...). They are formally contraindicated in case of skin infections, diaper rash, acne and rosacea..." [4] "Never, never, never, ever prescribe steroids for rosacea." [5] Ironically, uninformed physicians sometimes prescribe steroids for rosacea or rosaceans may use over the counter non-prescription steroid topicals for rosacea and initially the rosacea may improve but after continuous use the rosacea gets worse. Hence the term, steroid-induced rosacea has developed due to uninformed rosaceans using long term topical steroids to treat rosacea or other skin conditions. This indicates that it is up to rosaceans to be informed and ask their physicians if they are keeping up with current treatment for rosacea. Reports still show that physicians prescribe steroids for acne rosacea, for example: "The first patient was treated with oral steroids, as well as doxycycline, to control his acne rosacea." (1998) [6] Here is a classic example of physicians treating rosacea with prednisolone, a steroid, in 1990: "Metronidazole was investigated in the basic dermatologic agent Elacutan W to improve the topical therapy of rosacea. The suitability of that basic dermatologic agent was verified for metronidazole, prednisolone and dexamethasone by stability tests (UV-spectroscopy, pH) and by in-vitro-liberation-measurements (membrane method). The drugs are stable for a period of 100 days." [7] And here is what these physicians should have read about prednisone in 1989: "A patient with malignant lymphoma repeatedly developed transient rosacea-like dermatitis several days after each interruption of continuous oral prednisone intake. We thought that the eruption was provoked by withdrawal of orally administered steroid, and thus we diagnosed the patient as having steroid-withdrawal rosacea-like dermatitis, one manifestation of steroid-withdrawal syndrome." [8] What is difficult to understand is that two variants of rosacea, Rosacea Fulminans, and Perioral Dermatitits are treated with Accutane and steroids. One report says that Corticosteroids and isotretinoin are regarded as the two main therapeutic agents for treating RF. [9] Periorol Dermatitis, a variant of rosacea, is sometimes the result of steroid use so rosaceans wonder what should they do if the physician prescribes steroids with all this conflicting data? Demodicosis may develop after the use of steroids according to the following two reports: "...the highest density of mites was found on the cheeks. A statistically significant increase in mites was found in all subgroups of rosacea, being most marked in those with steroid-induced rosacea...CONCLUSION: Increased mites may play a part in the pathogenesis of rosacea by provoking inflammatory or allergic reactions, by mechanical blockage of follicles, or by acting as vectors for microorganisms." [10] "...Demodex folliculorum were also more frequently detected in patients who had previously been treated with topical corticosteroids (even in 91.9%), what was often followed by epitheloid granulomas..." [11] However, one report in 2002 says the following: "...Recently, steroid components have been synthesized that aim to have adequate anti-inflammatory effects and minimal adverse effects. The newest topical corticosteroids used for the treatment of different dermatoses and allergic reactions of the respiratory tract (in particular asthma) are budesonide, mometasone furoate, prednicarbate, the di-esters 17,21-hydrocortisone aceponate and hydrocortisone-17-butyrate-21-propionate, methylprednisolone aceponate, alclometasone dipropionate, and carbothioates such as fluticasone propionate..." [12] As these new synthesized steroids are used, no doubt we will hear reports later of the long term effects for treating rosacea with these drugs. You as a rosacean have the right to ask questions about what treatment your doctor recommends. "...54% developed the steroid rosacea while being treated with the lowest-strength (class 7) topical corticosteroids. Even over-the-counter hydrocortisone preparations induced steroid rosacea in susceptible children. Susceptibility may be genetic as 20% of children had a first-degree relative with rosacea." [13] "...Initially, the mass was thought to be rhinophyma, but biopsy of the mass revealed noncaseating granulomata consistent with sarcoidosis. The mass resolved following several steroid injections..." [14] Apparently topical fluorinated steroid therapy resulted in an onset of smooth, shiny, erythematous papules on the face according to one report. [15] 1% hydrocortisone was applied to six patients. Three developed a rosacea-like eruption for the first time and one also had perioral dermatitis. [16] With Primary care physicians (PCPs), "When asked to rank the potency of 4 surveyed TCs [Topical Corticosteroids], 51.2% respondents were able to identify hydrocortisone acetate 1% cream as a low potent topical steroid." And with PCPs, "33.9% incorrectly responded that TCs can be used in all skin rashes, and 37.8% in acne vulgaris." [27] Tthe University of Bristol has found evidence that prolonged treatment of synthetic corticosteroid drugs increases adrenal gland inflammation in response to bacterial infection, an effect that in the long-term can damage adrenal function. [28] One report discusses the "Implications of Borderline Personality Disorder [with] Topical Steroid Dependence." [32] "Exposure to potent topical corticosteroids is associated with increased risk for osteoporosis and major fracture, according to an observational study in JAMA Dermatology." [33] "The long-term use of topical corticosteroids can result in rosacea-like dermatitis or facial perioral dermatitis." [35] Short Term Steroid Treatment for Rosacea Sometimes if your rosacea is severe your physician may prescribe short term steroid treatment, usually oral systemic steroid like Prednisone or in some cases a topical prescription steroid. Short term steroids are incredible to attenuate rosacea. [29] Treatment for Steroid Rosacea 0.03% tacrolimus and 595-nm pulsed dye laser [17] 1% pimecrolimus cream [18] FK506 (tacrolimus) may control the increase in IL-1alpha with glucocorticoid in KCs, suggesting FK506 to suppress harmful effects of glucocorticoids such as steroid rosacea. [19] Combination therapy of tetracyline and tacrolimus [20] However, one report of using Tacrolimus resulted in a "proliferation of Demodex due to local immunosuppression." [21] Caveat emptor! Another report concluded "Topical tacrolimus is becoming an important cause of RD [rosacea-like dermatitis] along with topical steroids." [24] A combination of oral antibiotics and topical tacrolimus is the treatment of choice for steroid-induced rosacea. [22] Treating Steroid Induced Rosacea, Linda Sy, MD [23] Calendula cream for steroid induced rosacea by May2012 Episofit A [26] Probiotics Topical 10% Tranexamic acid [31] Anecdotal Reports Henry Two Reports in one. M's report of what to do for steroid rosacea TrixP was diagnosed with dermatitis and treated with a steroid and developed steroid induced rosacea. reddy says, "My doctor gave me Daktakort cream which I have been using for the past 3 years but she told me if I kept using the cream it would make my skin very thin, only recently the cream has stopped working and when I use it now it makes my face even worse." Fallout2077 writes, "...however I stupidly continued to use this same steroid cream on and off for 3 years and then every single day for the next year. Whilst it did suppress the flakes and dryness, it made my face gradually become very sensitive, red and spotty and so i thought i had developed rosacea...." frank88 reports, "...I decided to cease the 1% cream on the 27th April about 20 days ago and my entire face has become very red, blotchy and inflammed with little pimples, all moreso in both the applications sites where I lightly applied the cream...." Reply to this Topic There is a reply to this topic button somewhere on the device you are reading this post. End Notes *Image courtesy of Wikimedia Commons [1] Clinical pharmacology and pharmacokinetic properties of topically applied corticosteroids. A review. Goa KL., Drugs. 1988;36 Suppl 5:51-61. [2] Facial corticosteroid addictive dermatitis in Guiyang City, China. Lu H, Xiao T, Lu B, Dong D, Yu D, Wei H, Chen HD. Clin Exp Dermatol. 2010 Aug;35(6):618-21. Epub 2009 Dec 8. [3] Steroid dermatitis resembling rosacea: aetiopathogenesis and treatment. Ljubojeviae S, Basta-Juzbasiae A, Lipozenèiae J. J Eur Acad Dermatol Venereol. 2002 Mar;16(2):121-6. [4] Local corticosteroid therapy in dermatology Chosidow O, Lebrun-Vignes B, Bourgault-Villada I. Presse Med. 1999 Nov 27;28(37):2050-6. [5] "Dr.Kligman (Dermatology-University of Philadelphia) & Dr. Plewig (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." Topical Steroids International Rosacea Foundation [6] Mooren's ulcer. Seino JY, Anderson SF. Optom Vis Sci. 1998 Nov;75(11):783-90. [7] Stability of metronidazole, prednisolone and dexamethasone in urea-containing Elacutan W dermatologic agent Heyde R, Dorsch S, Heidenreich S, Illig G. Dermatol Monatsschr. 1990;176(7):407-15. [8] Steroid-withdrawal rosacea-like dermatitis. Tomita Y, Tagami H. J Dermatol. 1989 Aug;16(4):335-7. [9] Rosacea fulminans in pregnancy. Lewis VJ, Holme SA, Wright A, Anstey AV. Br J Dermatol. 2004 Oct;151(4):917-9. [10] The Demodex mite population in rosacea. Bonnar E, Eustace P, Powell FC. J Am Acad Dermatol. 1993 Mar;28(3):443-8. [11] The possible role of skin surface lipid in rosacea with epitheloid granulomas. Basta-Juzbasić A, Marinović T, Dobrić I, Bolanca-Bumber S, Sencar J. Acta Med Croatica. 1992;46(2):119-23. [12] New and established topical corticosteroids in dermatology: clinical pharmacology and therapeutic use. Brazzini B, Pimpinelli N. Am J Clin Dermatol. 2002;3(1):47-58. [13] Steroid rosacea in prepubertal children. Weston WL, Morelli JG. Arch Pediatr Adolesc Med. 2000 Jan;154(1):62-4. [14] Sarcoidosis of the external nose mimicking rhinophyma. Case report and review of the literature. Goldenberg JD, Kotler HS, Shamsai R, Gruber B. Ann Otol Rhinol Laryngol. 1998 Jun;107(6):514-8. [15] Recent onset of smooth, shiny, erythematous papules on the face. Steroid rosacea secondary to topical fluorinated steroid therapy. Martin DL, Turner ML, Williams CM. Arch Dermatol. 1989 Jun;125(6):828, 831. [16] Complications of topical hydrocortisone. Guin JD., J Am Acad Dermatol. 1981 Apr;4(4):417-22. [17] Eur J Dermatol. 2016 Jun 1;26(3):312-4. doi: 10.1684/ejd.2016.2757. Recalcitrant steroid-induced rosacea successfully treated with 0.03% tacrolimus and 595-nm pulsed dye laser. Seok J, Choi SY, Li K, Kim BJ, Kim MN, Hong CK. [18] The use of 1% pimecrolimus cream for the treatment of steroid-induced rosacea. Chu CY., Br J Dermatol. 2005 Feb;152(2):396-9. [19] FK506 (tacrolimus) inhibition of intracellular production and enhancement of interleukin 1alpha through glucocorticoid application to chemically treated human keratinocytes. Horiuchi Y, Bae SJ, Katayama I., Skin Pharmacol Physiol. 2005 Sep-Oct;18(5):241-6. Rosacea: where are we now? Bikowski JB, Goldman MP. J Drugs Dermatol. 2004 May-Jun;3(3):251-61. [20] Combination therapy of tetracycline and tacrolimus resulting in rapid resolution of steroid-induced periocular rosacea. Pabby A, An KP, Laws RA., Cutis. 2003 Aug;72(2):141-2. [21] Induction of rosaceiform dermatitis during treatment of facial inflammatory dermatoses with tacrolimus ointment. Antille C, Saurat JH, Lübbe J. Arch Dermatol. 2004 Apr;140(4):457-60. [22] Steroid-induced rosacea: a clinical study of 200 patients. Bhat YJ, Manzoor S, Qayoom S. Indian J Dermatol. 2011 Jan;56(1):30-2. [23] Rosacea Support Treating Steroid Induced Rosacea December 4th, 2007, by David Pascoe [24] Tacrolimus-Induced Rosacea-Like Dermatitis: A Clinical Analysis of 16 Cases Associated with Tacrolimus Ointment Application. Teraki Y, Hitomi K, Sato Y, Izaki S. Dermatology. 2012 May 22. [25] ISRN Dermatol. 2013 Apr 21;2013:491376. doi: 10.1155/2013/491376. Print 2013. Steroid dermatitis resembling rosacea: a clinical evaluation of 75 patients. Hameed AF. [26] Georgian Med News. 2013 Oct;(223):31-5. Improvement of rosacea treatment based on the morphological and functional features of the skin. [Article in Russian] Tsiskarishvili NV, Katsitadze A, Tsiskarishvili Ts. Source: Tbilisi State Medical University, Department of Dermatology, Georgia. [27] Saudi Med J. 2017 Jun; 38(6): 662–665. doi: 10.15537/smj.2017.6.17586 PMCID: PMC5541192 Topical corticosteroids knowledge, attitudes, and practices of primary care physicians Sarah F. Alsukait, MBBS, Najd A. Alshamlan, MBBS, Zeina Z. Alhalees, MBBS, Sami N. Alsuwaidan, MD, and Abdulmajeed M. Alajlan, MD [28] Prolonged corticosteroid treatment increases adrenal gland inflammation, News Medical [29] Prednisone [30] Indian Dermatol Online J. 2020 Mar-Apr; 11(2): 208–211. Study of Clinical Profile of Patients Presenting with Topical Steroid-Induced Facial Dermatosis to a Tertiary Care Hospital Sonal Jain, Liza Mohapatra, Prasenjeet Mohanty, Swapna Jena, Binodini Behera [31] Indian Dermatol Online J. 2020 Nov-Dec; 11(6): 1024–1026. Topical 10% Tranexamic Acid for Recalcitrant Topical Steroid-Dependent Face Deepak Jakhar, Ishmeet Kaur, and Sachin Yadav [32] Indian J Psychol Med. 2020 Jul; 42(4): 396–398. Diagnostic and Therapeutic Implications of Borderline Personality Disorder on Topical Steroid Dependence: A Case Report Karthick Subramanian, Ashvini Vengadavaradan, Vigneshvar Chandrasekaran, Priyadarshini Manoharan, and Vikas Menon [33] NEJM, Journal Watch, MEDICAL NEWS | PHYSICIAN'S FIRST WATCH, January 21, 2021 Potent Topical Corticosteroids Tied to Increased Fracture Risk Amy Orciari Herman [34] J Dermatolog Treat. 2021 Jan 26;:1-24 Topical corticosteroid withdrawal ("steroid addiction"): An update of a systematic review. Hwang J, Lio PA Topical Steroid Addiction (TSA) and Topical Steroid Withdrawal (TSW) [35] Topical Steroid-Induced Perioral Dermatitis (TOP STRIPED): Case Report of a Man Who Developed Topical Steroid-Induced Rosacea-Like Dermatitis (TOP SIDE RED) [36] Yonago Acta Med. 2022 Feb; 65(1): 88–89. Infiltrative Erythemas and Nodules on a Unilateral Cheek Following Inappropriate Use of a Topical Steroid Ai Yoshida, Kazunari Sugita, Osamu Yamamoto [37] Clin Pract. 2022 Feb; 12(1): 140–146. Topical Steroid Damaged Face: A Cross-Sectional Study from Saudi Arabia Mahdi Al Dhafiri, Alaa Baqer Alali2 Zuhur Ali Alghanem, Zahraa Wasel Alsaleh, Eman Abdulrahman Boushel, Zahraa Baqer Alali, and Aeshah Adel Alnajjar Et Cetera Steroid-induced rosacea. Litt JZ. Case Western Reserve University School of Medicine, Cleveland, Ohio. Topical tacrolimus Protopic. Lazarous MC, Kerdel FA. Department of Dermatology and Cutaneous Medicine, University of Miami School of Medicine, Miami, FL 33136, USA. Potential future dermatological indications for tacrolimus ointment. Ruzicka T, Assmann T, Lebwohl M. Department of Dermatology, University of Dusseldorf, Moorenstr 5, 40225 Dusseldorf, Germsny Tacrolimus clinical studies for atopic dermatitis and other conditions. Bergman J, Rico MJ. Division of Pediatric and Adolescent Dermatology, Children's Hospital, San Diego, CA, USA. - 2001 Tacrolimus ointment for the treatment of steroid-induced rosacea: a preliminary report. Goldman D. - 2001 Rosacea in association with the progesterone-releasing intrauterine contraceptive device. Choudry K, Humphreys F, Menage J. Rosacea induced by beclomethasone dipropionate nasal spray. Egan CA, Rallis TM, Meadows KP, Krueger GG. Department of Dermatology, University of Utah School of Medicine, Salt Lake City 84132, USA. Practical aspects of local steroid treatment Gehring W, Gloor M. - 1989 Possible side effects of topical steroids. Morman MR. - 1981 Steroid rosacea in children. Franco HL, Weston WL. - 1979 Differential diagnosis of facial skin swellings (author's transl) Hornstein OP. - 1979 Perioral dermatitis (rosacea-like dermatitis)--adverse effects of externally applied steroid preparations Urabe H. - 1978 The treatment of steroid-induced rosacea and perioral dermatitis. Sneddon IB. - 1976 Perioral dermatitis and rosacea-like dermatitis: clinical features and treatment. Urabe H, Koda H. 1976 Steroid rosacea. Leyden JJ, Thew M, Kligman AM. Rosacea with steroid atrophy. Abell E, Borrie PF - 1969

Demodectic rosacea is as valid a variant as any other proposed variant for rosacea. Demodectic Rosacea (Variant) For more info click here.

One rosacea trigger that is always on every rosacea trigger list is stress. We all have noticed that when we are under stress our rosacea breaks out big time. Many anecdotal reports confirm this finding. It may be one rosacea trigger that everyone could agree with, but there is little research being done on this. You might find some useful information by reading this post on Psychology and Rosacea. One report suggests, "For example, inflammatory skin disorders; such as psoriasis, atopic dermatitis, rosacea and acne; are widely believed to be exacerbated by stress." [1] "Muller et al. reported that mental stress leads to an increase in skin sympathetic nerve activity (SSNA). SSNA is involved in vasodilatory activities and has been shown to elucidate intermittent vasodilatation on the skin [81]. SSNA hyperresponsiveness after mental stress was observed in the supraorbital skin of patients with rosacea. Such exaggerated sympathetic responses might trigger the symptoms of rosacea and also cause local inflammation and neurovascular dysregulation in these patients." [2] End Notes [1] Brain Behav Immun. 2013 Mar 18. pii: S0889-1591(13)00135-9. doi: 10.1016/j.bbi.2013.03.006. [Epub ahead of print] Nerve-derived Transmitters Including Peptides Influence Cutaneous Immunology. Madva EN, Granstein RD. [2] Int J Mol Sci. 2016 Sep; 17(9): 1562.Published online 2016 Sep 15. doi: 10.3390/ijms17091562, PMCID: PMC5037831Rosacea: Molecular Mechanisms and Management of a Chronic Cutaneous Inflammatory ConditionYu Ri Woo, Ji Hong Lim, Dae Ho Cho, and Hyun Jeong Park, Chris Jackson, Academic Editor

Propionibacterium acnes grown in thioglycollate medium image courtesy of Wikimedia Commons "Based on the theory that rosacea shares the same inflammatory features of acne, a recent study showed that, just as the combination of benzoyl peroxide 1 percent and clindamycin 5 percent gel is a powerful treatment modality for reducing Propionibacterium acnes levels, it also significantly reduces the papules and pustules of rosacea, according to Debra L. Breneman, M.D. ...."Benzaclin, once daily, was found to be well tolerated and effective in the reduction of papules and pustules in patients with rosacea," said Dr. Breneman. "This lends credence to the theory that P. acnes is a potential aggravating factor in rosacea. This gives dermatologists a very effective treatment for rosacea." [1] However a recent report states, "Our results suggest that P. acnes does not play a major role in the pathogenesis of rosacea." [2] End Notes [1] P. Acnes Possible Factor in Rosacea BenzaClin a significant Tx in lesion reduction Apr 1, 2003, By: Beth Kapes, Dermatology Times, Modern Medicine [2] No link between rosacea and Propionibacterium acnes. Jahns AC, Lundskog B, Dahlberg I, Tamayo NC, McDowell A, Patrick S, Alexeyev OA. APMIS. 2012 Nov;120(11):922-5. doi: 10.1111/j.1600-0463.2012.02920.x. Epub 2012 May 18.

See this list.

NOTE: Diet Triggers seem to be the more popular rosacea trigger to discuss. However, one must understand rosacea triggers in general before considering the list below. One must always remember that these proposed diet triggers are based upon purely anecdotal reports. You may be interested in what the role diet plays in rosacea? Rosacea Diet Trigger List Alcohol * [7] Animal Diet Avocados * Bananas * Broad-leaf beans and pods * Capsaicin + Carbohydrate [5] Cheese * Chili + Chocolate * Citrus fruits * Coconut Oil [3] Coffee + Curry + Eggplant * Figs * Foods high in histamine * Gluten [6] High Carbohydrate Diet ** Hot drinks * Lima beans * Liver * Marinated meats * Navy beans * Pea * Peppers + Raisins Red plums * Salicylates [4] Sour cream * Soy + Sour Cream Soy sauce * Spicy food * Spinach * Sugar ** Thermally hot foods * Tomatoes * Vanilla * Vinegar Vitamin B Complex Supplement [1] Vitamin E [2] Yogurt Sources: * National Rosacea Society Trigger List ** Rosacea 101—Rosacea Diet # Flushing Syndromes ## Dermis ^ Rosacea Support Group + Ken Landow, MD The source of the above list was complied based upon Rosacea 101: Includes the Rosacea Diet, iUniverse, 2007, by Brady Barrows with the author's permission. I have continued to add more diet triggers upon any anecdotal evidence discovered since the publication of my book. Chemical Triggers More info on Triggers End Notes [1] Actas Dermosifiliogr. 2011 Feb 4. Rosacea Triggered by a Vitamin B Complex Supplement. Martín JM, Pellicer Z, Bella R, Jordá E. Actas Dermosifiliogr. 2011 Feb 4. [2] There is one anecdotal report that Vitamin E is a rosacea trigger in at least one rosacea sufferer. This has not been substantiated by any other reports. For more info read cherylarose's post. [3] One anecdotal report by Mister88 [4] christine123 posted on September 4, 2012 #17 [5] Rosacea 101: Includes the Rosacea Diet [6] Julie Rangel Oliver and Stephanie Amarante in Rosacea (English), Facebook Jacqui C., It Works for Me, Category, Food & Beverages, NRS [7] What About Alcohol and Rosacea?

Here is a possible trigger list for topical irritants for rosacea: Acne Products ** Acetone * Alcohol * Alpha hydroxy acids ^ Anti-Aging ** Astringents ^ Azelaic acid ^ Benzoyl Peroxide ^ Beta-Hydroxy Acids ** Exfoliants ^ Fragrance + Hair Sprays * Hydro-alcoholic * Perfume + Retinoids ^ Skin Peels ^ Salicylic Acid ** Soap + Steroids * Sunscreen + Toners ^ Triclosan ^ Witch Hazel * Some environmental triggers: Hot baths * HIV + Humidity * Saunas * Simple overheating * Sun * Strong winds * Ultraviolet radiation ## Washcloths *+ Physiological Triggers Anger # Anxiety * Caffeine withdrawal * Chronic cough * Embarrassment # Exercise * Frequent flushing * Hot Flashes # “Lift and load” jobs * Menopause * Straining # Stress * Valsalva maneuver # Oral Drugs that may trigger rosacea: Amyl nitrite # Butyl nitrite # Bromocriptine # Calcium channel blockers # Chlorpropamide (Diabinese) with alcohol + Cholinergic drugs # Cyclosporine # Cyproterone acetate # Disulfiram (Antabuse) + Doxorubicin + Interferon + Nicotinic acid # Niacin + Nifedipine + Nitroglycerin + Morphine # Opiates # Oral triamcinolone # Prostaglandin E + Rifampin (Rifadin) # + Sildenafil citrate # Tamoxifen # Thyrotropin Releasing Hormone (TRH) # Topical steroids *257 Vasodilators * Vancomycin + * National Rosacea Society Trigger List ** Rosacea 101—Rosacea Diet # Flushing Syndromes ## Dermis ^ Rosacea Support Group + Ken Landow, MD Source for the above triggers: Rosacea 101 by Brady Barrows page 46 Diet Triggers More info on Triggers

Heat or cold exposure is just about on every rosacea trigger list. Even in the general population heat or cold usually produces a red face. For a rosacean this is not a good idea since it irritates rosacea further. "Ozkol et al. reported that frequently exposed to heat from using a tandoor oven exhibited a significantly higher incidence of rosacea than control subjects." [1] For a list of environmental exposure triggers click here. End Notes [1] Int J Mol Sci. 2016 Sep; 17(9): 1562.Published online 2016 Sep 15. doi: 10.3390/ijms17091562, PMCID: PMC5037831Rosacea: Molecular Mechanisms and Management of a Chronic Cutaneous Inflammatory ConditionYu Ri Woo, Ji Hong Lim, Dae Ho Cho, and Hyun Jeong Park, Chris Jackson, Academic Editor

According to the JAAD, May 2010, "UV radiation exposure does not appear to affect the prevalence of PPR." This is one of the few studies ever done on this theory about rosacea. Hopefully more studies will be done in the future. [1] Another report in 2013 says UV exposure may be the cause of "telangiectasias with actinic elastosis." [7] So the evidence isn't nailed down that this theory is the correct one. For years we have reports like the ones below that focus on sun or light damage being a culprit in the cause of rosacea. However, it is important to note that recently more reports on UV radiation exposure may have some link to rosacea. "A very important background feature is sun damage. Rosacea is always associated with solar elastosis and often with heliodermatosis. Fair-skinned patients with rosacea type I will often give a history of sun sensitivity." [2] "The general consensus among clinicians is that rosacea is a photoaggravated disorder." [3] An article in the June 1, 2004 Dermatolgy Times by Rebecca Bryant quotes Michael Detmar, M.D., as saying, "Bacteria are likely involved because what works to some extent as a treatment are antibiotics. Also there appears to be a relationship to photo damage. The nervous system may be involved, because exertion, emotions, and weather trigger the disease, in addition to other triggers such as heat, certain types of food, alcoholic beverages, various topical balms and cosmetics, and various drugs. We're clear that blood vessels are dilated but don't know if that comes first or later. A new area of research suggests that lymphatic vessels are involved." [4] One study suggests "that sun exposure has a different influence on each subtype of rosacea." [5] "The degree of sun exposure had significant correlation with the development and severity of the erythematotelangiectatic subtype (p<0.05), while it had no correlation with the papulopustular, ocular and phymatous subtypes." [5] One anecdotal report says rosacea was caused by being exposed to sunlight in an office with windows and concluded, "I am happy to say that its been about 3 months that I have been back to my original office without the windows....and the redness on my face is completely gone." [6] Another reports concluded, "The association of large telangiectasias with actinic elastosis may indicate a causative role of exposure to UV radiation." [7] Still another report says, "UV-B irradiation and microbial components increase vitamin D3 and TLR2 expression in keratinocytes leading to an increase of cathelicidin production." [8] However, on the flip side, one report says, "The majority of subjects with atopic eczema, acne vulgaris or seborrheic dermatitis experienced improvement after exposure to sunlight. Individuals with rosacea also experienced improvement more often than impairment from exposure to sunlight." [9] "Many chronic inflammatory cutaneous diseases, such as rosacea and psoriasis, are known to be associated with dermal remodeling after UV irradiation....the production of ROS and ER stressors after UV radiation provide a logical framework explaining UV radiation as a triggering factor for rosacea." [10] Actinic Folliculitis (AF) should be ruled out in a differential diagnosis. Ruling out Photosensitivity diseases from Rosacea EM Radiation a Rosacea Trigger? Florescent Lights and Rosacea End Notes [1] Papulopustular rosacea: prevalence and relationship to photodamage. McAleer MA, Fitzpatrick P, Powell FC. J Am Acad Dermatol. 2010 Jul;63(1):33-9. Epub 2010 May 11. [2] Rosacea: classification and treatment. T Jansen and G Plewig J R Soc Med. 1997 March; 90(3): 144–150. [3] Ultraviolet light and rosacea. Murphy G. Cutis. 2004 Sep;74(3 Suppl):13-6, 32-4. [4] Rosacea: turning all stones for source of pathology June 1, 2004, By: Rebecca Bryant Dermatology Times, Modern Medicine [5] Ann Dermatol. 2009 Aug;21(3):243-9. doi: 10.5021/ad.2009.21.3.243. Epub 2009 Aug 31. Clinical evaluation of 168 korean patients with rosacea: the sun exposure correlates with the erythematotelangiectatic subtype. Bae YI, Yun SJ, Lee JB, Kim SJ, Won YH, Lee SC. Ann Dermatol. 2009 Aug;21(3):243-9. Epub 2009 Aug 31. [6] Sara45, The Rosacea Forum, Sept. 17, 2012 [7] Ann Dermatol Venereol. 2013 Jan;140(1):21-9. doi: 10.1016/j.annder.2012.10.592. Epub 2012 Dec 21. A histological and immunohistological study of vascular and inflammatory changes in rosacea. Perrigouard C, Peltre B, Cribier B. [8] Duodecim. 2012;128(22):2327-35. New insights in the pathogenesis and treatment of rosacea. Palatsi R, Kelhälä HL, Hägg P. [9] Photodermatol. 1989 Apr;6(2):80-4. Epidemiological studies of the influence of sunlight on the skin. [10] Int J Mol Sci. 2016 Sep; 17(9): 1562.Published online 2016 Sep 15. doi: 10.3390/ijms17091562, PMCID: PMC5037831Rosacea: Molecular Mechanisms and Management of a Chronic Cutaneous Inflammatory ConditionYu Ri Woo, Ji Hong Lim, Dae Ho Cho, and Hyun Jeong Park, Chris Jackson, Academic Editor

Micrograph of Chlamydia pneumoniae in an epithelial cell image courtesy of Wikimedia Commons Chlamydophila pneumoniae has been implicated with a possible role in the etiology of rosacea and remains another theory to add to the long list. At least one report suggests Chlamydophila pneumoniaeas a cause of rosacea and states, “These preliminary data suggest the need for further investigation with clinical trials to study long-term tolerability and efficacy and also strongly implicate C pneumoniae in the pathogenesis of acne rosacea.” [1] There is some discussion on this at RF [2] and at the RRF Wiki. [3] You might want to know more about this subject by clicking here. End Notes [1] The role of Chlamydia pneumoniae in the etiology of acne rosacea: response to the use of oral azithromycin. Fernandez-Obregon A, Patton DL; Cutis. 2007 Feb;79(2):163-7 [2] The Rosacea Forum thread on CPn See also: Testing for Chlamydia Pneumoniae (Cpn) infection - Rosacea Forum's Unofficial Study [3] RRF Wiki

Another theory on the cause of rosacea is that irritable bowel syndrome is related to rosacea. "Rosacea may be a symptom of an unhealthy gastrointestinal system and healing the entire gastrointestinal system may be the basis for eliminating rosacea. Many people with rosacea also have been diagnosed with Irritable Bowel Syndrome (IBS), Crohn's Disease or some form of Colitis." [1] "Our meta-analysis confirmed a significant bi-directional association in occurrence of IBD and rosacea." [2] We need more citations on this theory but a possible clue could be found in a related subject, my SIBO and Rosacea post which has more citations and papers than IBS. However, in Googling this subject I ran across this interesting article written in 1896 by Dr. Leviseur: "There are a number of skin diseases which occur in connection with disturbance of the stomach and intestine. This fact is well supported by clinical evidence, but, viewed from the more elevated standpoint of theoretical science, it must be admitted that the true nature of this connection is far from being clearly understood….All writers agree that a large percentage of cases of acne rosacea is caused by indigestion…..These patients have factor ex ore, especially in the morning, sour eructations, constipation, and perhaps a distressing feeling of fulness after meals; in short, all the symptoms of a mild fermentative gastritis…..In severe cases lavage is indicated and has sometimes a surprisingly good effect on the skin eruption. It must not, however, be expected that the mechanical removal of the fermenting masses stops the fermentation; the latter will promptly start again with the very next food supply. Careful dieting is almost always necessary; the amount of carbohydrates should be limited; alcohol, tea pastry, the coarser vegetables and milk should be forbidden. Bismuth, carbonate of sodium, creosote, carbolic acid, thymol, and ichthyic may be employed. I have had good results from the use of fluid extract of ergot…..It would carry me too far if I were to consider the various drug eruptions which appear in connection with gastrointestinal disturbances, as for instance erythema after the use of quinine, antipyrin, turpentine, balsam of copaiba, sandalwood oil, arsenic, etc….." [3] Is inflammatory bowel disease (IBD) the same thing as Irritable Bowel Syndrome (IBS)? Answer Skin manifestations associated with irritable bowel syndrome Reply to this TopicThere is a reply to this topic button somewhere on the device you are reading this post. If you never heard about this topic and you learned about it here first, wouldn't it be a gracious act on your part to show your appreciation for this topic by registering with just your email address and show your appreciation with a post? And if registering is too much to ask, could you post your appreciation for this topic by finding the START NEW TOPIC button in our guest forum where you don't have to register? We know how many have viewed this topic because our forum software shows the number of views. However, most rosaceans don't engage or show their appreciation for our website and the RRDi would simply ask that you show your appreciation, please, simply by a post. End Notes [1] Dr. David Dahlman, a Chiropractic Physician with a degree in Nutrition [2] Clin Res Hepatol Gastroenterol. 2018 Oct 30; The relationship between inflammatory bowel disease and rosacea over the lifespan: A meta-analysis. Han J, Liu T, Zhang M, Wang A [3] Remarks of Some Skin Diseases Occurring in Connection with Gastro-Intestinal Disturbances by Fred. J. Leviseur, M.D. Medical record, A Weekly Journal of Medicine and Surgery Volume 50, No. 3, Whole No. 1341, New York, July 18, 1896, p 84, 85 edited by George Frederick Shrady, Thomas Lathrop Stedman Image courtesy of Wikimedia Commons

This post has been promoted to an article

SIBO refers to "Small bowel bacterial overgrowth syndrome (SBBOS), or small intestinal bacterial overgrowth (SIBO), also termed bacterial overgrowth; is a disorder of excessive bacterial growth in the small intestine." [1] It has also been called Dysbiosis (sometimes called dysbacteriosis). The presence of small intestinal bacterial overgrowth (SIBO) in patients with rosacea has been investigated and the results of this study says, "We found an increased prevalence of SIBO in patients with rosacea compared to controls (40/60 vs 3/60, respectively, p<0.001). Oro-cecal transit time resulted significantly delayed in patients with SIBO than in controls (p<0.01). After SIBO eradication we obtained a complete recovery of cutaneous lesions in 17/20 (85%) and a relevant improvement in 2/20 (10%) patients, while those treated with placebo remained unchanged (14/16) or even worsened (2/16), (p<0,001). These latter patients were subsequently switched to rifaximin therapy with complete resolution of rosacea in 14/16 and significant improvement in the remaining 2 cases. CONCLUSION: Our study shows the high prevalence of SIBO in patients with rosacea and emphasizes the clinical effectiveness of its eradication in inducing almost complete remission of cutaneous lesions." [2] Another report shows similar results. [3] You might notice that the article [Clin Gastroenterol Hepatol] says that "Patients positive for SIBO were randomized to receive rifaximin 1200 mg/day for 10 days or placebo...These latter patients were subsequently switched to rifaximin therapy with complete resolution of rosacea in 14/16 and significant improvement in the remaining 2 cases."[2] Wikipedia says that Rifaximin is "a semisynthetic, rifamycin-based non-systemic antibiotic, meaning that the drug will not pass the gastrointestinal wall into the circulation as is common for other types of orally administered antibiotics....It is currently sold in the U.S. under the brand name Xifaxan by Salix Pharmaceuticals. It's also sold in Europe under the name Spiraxin and Zaxine.." Another source says "Rifaximin is effective in treatment of SIBO in IBS and controlled trials are warranted." There is also evidence that SIBO occurs "in patients suffering from scleroderma" as well. [4] An EIR Report on SIBO says that according "to Dr. Leo Galland, a specialist in dysbiosis related illness, the best diet to aid in the treatment of SIBO is very similar to that used to treat yeast overgrowth. This being a diet free of simple sugars and grains/cereals and low in fruit and starchy vegetables depending on individual tolerance. This diet restricts the nutrition available for bacteria in the upper GI tract to proliferate and reduces the excess alcohols and organic acids that are produced as a result of bacterial fermentation." [5] This is similar to the Rosacea Diet, reducing sugar/carbohydrate. A report in 2013 concluded: "This study demonstrated that rosacea patients have a significantly higher SIBO prevalence than controls. Moreover, eradication of SIBO induced an almost complete regression of their cutaneous lesions and maintained this excellent result for at least 9 months. [6] "For example, rosacea has an association with SIBO (small intestine bacteria overgrowth). In one study, there was a higher number of patients with rosacea who tested positive for SIBO than the group without the skin disease. The researchers randomly assigned the patients with a positive SIBO breath test to either take a placebo or rifaximin (an antibiotic) therapy at 1200 mg/day for 10 days to clear the SIBO. Some patients also underwent the therapy despite having a negative breath test. Upon treating the SIBO, 20 of 28 patients had a clearance of cutaneous lesions, while there was either no change or worsening of the lesions in those who were on the placebo. The researchers then switched the patients taking the placebo to the antibiotic treatment, resulting in 17 of the 20 experiencing an eradication of SIBO. Out of that group, 15 also saw a complete resolution of their rosacea. The improvement of rosacea lasted for at least 9 months. There was no change in rosacea in 13 of the 16 patients who tested negative for SIBO. This study demonstrates that not only is there a strong association between SIBO and rosacea, but that treating the SIBO improved rosacea." [7] Certain foods common in diets of US adults with inflammatory bowel disease You may want to consider the Rosacea Diet. Anecdotal Rifaximin Treatment Reports philfaebuckie Etcetera IBS and Rosacea IBD and Rosacea HLA-DRA Locus and Rosacea Gastrointestinal Rosacea [GR], aka, Gut Rosacea Reply to this Topic There is a reply to this topic button somewhere on the device you are reading this post. If you never heard about this topic and you learned about it here first, wouldn't it be a gracious act on your part to show your appreciation for this topic by registering with just your email address and show your appreciation with a post? And if registering is too much to ask, could you post your appreciation for this topic by finding the START NEW TOPIC button in our guest forum where you don't have to register? We know how many have viewed this topic because our forum software shows the number of views. However, most rosaceans don't engage or show their appreciation for our website and the RRDi would simply ask that you show your appreciation, please, simply by a post. End Notes [1] Image courtesy of Wikimedia Commons, http://en.wikipedia....growth_syndrome [2] SMALL INTESTINAL BACTERIAL OVERGROWTH IN ROSACEA: CLINICAL EFFECTIVENESS OF ITS ERADICATION. United European Gastroenterology Week Clin Gastroenterol Hepatol. 2008 Jul;6(7):759-64. Epub 2008 May 5 Parodi A, Paolino S, Greco A, Drago F, Mansi C, Rebora A, Parodi AU, Savarino V [3] Journal of the American Academy of Dermatology Volume 68, Issue 5, Pages 875–876, May 2013 Rosacea and small intestinal bacterial overgrowth: Prevalence and response to rifaximin Leonard B. Weinstock, MD, Martin Steinhoff, MD, PhD [4] Small intestinal bacterial overgrowth in patients suffering from scleroderma: clinical effectiveness of its eradication. Parodi A, Sessarego M, Greco A, Bazzica M, Filaci G, Setti M, Savarino E, Indiveri F, Savarino V, Ghio M. Am J Gastroenterol. 2008 May;103(5):1257-62. Epub 2008 Apr 16. [5] Antibacterial Treatment, For The Treatment Of Bacterial Dysbiosis, Small Intestinal Bacterial Overgrowth (SIBO), Bacterial Overgrowth, Environmental Illness Report [6] Clin Gastroenterol Hepatol. Small intestinal bacterial overgrowth in rosacea: clinical effectiveness of its eradication By A. Parodi A et al. • ProHealth.com • April 12, 2013 [7] The Gut-Skin Axis: The Importance of Gut Health for Radiant Skin, Deanna Minich, Ph.D., Contributor, Huff Post Image courtesy of Wikimedia Commons

If you were around in August 2007, there were headlines such as, Scientists unmask the cause of rosacea, [1] and UCSD Researchers Discover Cause of Rosacea [2] not to mention all the other headlines which created quite a stir in all the online rosacea groups and brought a lot of hope for rosacea sufferers. These articles seemed to conclude that rosacea’s mystery is resolved and within time a treatment would be found to eradicate rosacea. These startling headlines were the result of a paper published by researchers at UCSD associated with Richard L Gallo, et.al, in a study published by Nature Medicine [3]. This paper concluded: “These findings confirm the role of cathelicidin in skin inflammatory responses and suggest an explanation for the pathogenesis of rosacea by demonstrating that an exacerbated innate immune response can reproduce elements of this disease.” If you will notice in the above statement that the findings suggest an explanation for the pathogenesis of rosacea. Gallo, et.al, never said they found the cause of rosacea. The newspapers came to the conclusion that now all the mystery of rosacea is over and we now have the cause nailed down. All we have to do is wait for the treatment. This is not exactly the truth. While the research of Gallo, et.al, at UCSD is remarkable and insightful, the jury is still out on what causes rosacea. And while the jury is still out, there is more news worth mentioning that may be related to cathelicidin, peptides or antigenic proteins. You might want to read this thread on Gallo's research. You may also view a Medscape video lecture by Dr. Gallo, New Insights Into the Science of Treating Rosacea, where he discusses the innate immunity and cathelicindin. An interesting read if you understand this subject well is an article published in Antimicrobial Agents and Chemotherapy, entitled, Degradation of Human Antimicrobial Peptide LL-37 by Staphylococcus aureus-Derived Proteinases. [4] What Does Cathelicidin Have To Do With Rosacea? Wikipedia in its article on Cathelcidin says, "Cathelicidin-related antimicrobial peptides are a family of polypeptides found in lysosomes of macrophages and polymorphonuclear leukocytes (PMNs), and keratinocytes." After reading the above, this is where we meager uneducated rosacea sufferers start to yawn, get lost, or say 'who cares?' So get on your thinking caps and follow with me. Cathelicidin is a peptide. Antimicrobial Peptides (AMPs), "also called host defense peptides (HDPs) are part of the innate immune response found among all classes of life." Wikipedia "Peptides (from Gr.: πεπτός, peptós "digested"; derived from πέσσειν, péssein "to digest") are biologically occurring short chains of amino acid monomers linked by peptide (amide) bonds." Wikipedia If you forgot what amino acid monomers are, amino acids are the building blocks of protein and make up the 'the second-largest component (water is the largest) of human muscles, cells and other tissues." Wikipedia "A monomer (/ˈmɒnəmər/ mon-ə-mər[1]) (mono-, "one" + -mer, "part") is a molecule that may bind chemically or supramolecularly to other molecules." Wikipedia So breaking this down, Cathelicidin is related to a family of anti-microbial (an antimicrobial is an agent that kills microorganisms or inhibits their growth) peptides (short chains of amino acids) found in lysomes (a membrane-bounded organelle [a specialized subunit within a cell that has a specific function] found in most animal cells) of macrophages (a type of white blood cell) and polymorphonuclear leukocytes (a category of white blood cells) and and keratinocytes (predominant cell type in the outermost layer of the skin). The nutshell version is that Cathelicidin is a killer of microscopic organisms that is at the cellular level found in white blood cells and also found in cells on the skin. In the article in Nature magazine [3] the paper mentions that in rosacea patients the cathelicidin levels were abnormally high suggesting that the redness is caused by an abnormal immune system response. The conclusion of the article says, "These findings confirm the role of cathelicidin in skin inflammatory responses and suggest an explanation for the pathogenesis of rosacea by demonstrating that an exacerbated innate immune response can reproduce elements of this disease." [3] (Italics added) "However, following injury or inflammatory skin diseases such as psoriasis and rosacea, expression of the cathelicidin antimicrobial peptide LL37 breaks tolerance to self-nucleic acids and triggers inflammation." [7] "Dysregulation of the innate immune response increases the secretion of antimicrobial peptides (AMP) and cytokines, via activation of toll-like receptor 2 (TLR-2). The main AMP is cathelicidin, which is cleaved by kallikrein 5 (KLK-5) into the active peptide LL-37. This is the fundamental mediator for activating and controlling numerous processes: release of cytokines and metalloproteinases (MMP) by leukocytes, mast cells, and keratinocytes, regulation of the expression of extracellular matrix components, and increased proliferation of endothelial cells, causing angiogenesis. MMP-2 and MMP-9 are elevated on the skin of patients, exerting inflammatory, angiogenic, and dermal framework disruption functions in addition to helping in the activation of KLK-5, retrofeeding the system. MMP-9 is directly stimulated by the mite Demodex folliculorum (Df)." [8] AMPs in Clinical Development There is much excitement with using AMPs and ACPs in treating cancer. "As shown here, different microbial infections and/or cancer-targeting peptides are in clinical trials, with approval for clinical application expected for the next few years (at least 10 in the next 5 years). Moreover, that number should tend to increase due to advances in the rational design of peptides, minimizing or eliminating cytotoxic effects. In addition, advances in the large-scale synthesis of peptides has made this process cheaper, thus making peptide-based therapies likely to become more accessible to patients." [5] Associated Diseases "In addition, the association between cardiovascular diseases and rosacea might also be explained by enhanced expression of the cathelicidin, which has been observed both in the course of atherosclerosis and rosacea." [6] Independent Rosacea ResearchCould a group of rosacea sufferers in a non profit organization like the RRDi collectively get together and sponsor their own research on rosacea? For example, if 10K members each donated a dollar, could it be possible that this money could be used to sponsor their own independent rosacea research on a cathlecidin? What do you think? If you want to do something about this read this post. Conclusion All this started due to Gallo, et al, in 2007 and we continue to watch for more developments. Etcetera Rosacea Theories Revisited. Other Cytokines to Consider Reply to this TopicThere is a reply to this topic button somewhere on the device you are reading this post. If you never heard about this topic and you learned about it here first, wouldn't it be a gracious act on your part to show your appreciation for this topic by registering with just your email address and show your appreciation with a post? And if registering is too much to ask, could you post your appreciation for this topic by finding the START NEW TOPIC button in our guest forum where you don't have to register? We know how many have viewed this topic because our forum software shows the number of views. However, most rosaceans don't engage or show their appreciation for our website and the RRDi would simply ask that you show your appreciation, please, simply by a post. End Notes [1] Scientists unmask the cause of rosacea August 06, 2007 | Alison Williams, Los Angeles Times Staff Writer [2] UCSD Researchers Discover Cause of Rosacea UCSD News Center [3] Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea Kenshi Yamasaki, Anna Di Nardo, Antonella Bardan, Masamoto Murakami, Takaaki Ohtake, Alvin Coda, Robert A Dorschner, Chrystelle Bonnart, Pascal Descargues, Alain Hovnanian, Vera B Morhenn & Richard L Gallo Nature Medicine 13, 975 – 980 (2007) Published online: 5 August 2007 | doi:10.1038/nm1616 [4] Antimicrob Agents Chemother. 2004 December; 48(12): 4673–4679. doi: 10.1128/AAC.48.12.4673-4679.2004 PMCID: PMC529204 Degradation of Human Antimicrobial Peptide LL-37 by Staphylococcus aureus-Derived Proteinases Magdalena Sieprawska-Lupa, Piotr Mydel, Katarzyna Krawczyk, Kinga Wójcik, Magdalena Puklo, Boguslaw Lupa, Piotr Suder, Jerzy Silberring, Matthew Reed, Jan Pohl, William Shafer, Fionnuala McAleese, Timothy Foster, Jim Travis, and Jan Potempa [5] Front Chem. 2017; 5: 5. Published online 2017 Feb 21. doi: 10.3389/fchem.2017.00005 PMCID: PMC5318463 Peptides with Dual Antimicrobial and Anticancer Activities Mário R. Felício, Osmar N. Silva, Sônia Gonçalves, Nuno C. Santos, and Octávio L. Franco [6] Int J Mol Sci. 2016 Sep; 17(9): 1562. Published online 2016 Sep 15. doi: 10.3390/ijms17091562, PMCID: PMC5037831 Rosacea: Molecular Mechanisms and Management of a Chronic Cutaneous Inflammatory Condition Yu Ri Woo, Ji Hong Lim, Dae Ho Cho, and Hyun Jeong Park [7] Cathelicidin promotes inflammation by enabling binding of self-RNA to cell surface scavenger receptors. Sci Rep. 2018 Mar 05;8(1):4032 Takahashi T, Kulkarni NN, Lee EY, Zhang LJ, Wong GCL, Gallo RL [8] An Bras Dermatol. 2020 Nov-Dec; 95(Suppl 1): 53–69.Consensus on the therapeutic management of rosacea – Brazilian Society of DermatologyClivia Maria Moraes de Oliveira, Luiz Mauricio Costa Almeida, Renan Rangel Bonamigo, Carla Wanderley Gayoso de Lima, Ediléia Bagatinf

"The nervous system may be involved, because exertion, emotions, and weather trigger the disease, in addition to other triggers such as heat, certain types of food, alcoholic beverages, various topical balms and cosmetics, and various drugs. We're clear that blood vessels are dilated but don't know if that comes first or later." [1] "Patients with rosacea have a significantly increased risk of neurologic disorders such as migraine, depression, complex regional pain syndrome, and glioma. Enhanced expression of matrix metalloproteinase (MMP) is observed in these neurologic disorders as well as in rosacea, which might explain the possible shared pathogenic mechanisms between these conditions." [2] "Recently, an increased interest has been shown in the potential associations between neurodegenerative diseases and rosacea. For example, a nationwide cohort study from Denmark explored the relationship between rosacea and neurodegenerative diseases such as Parkinson’s disease. MMPs are believed to be associated with the neurodegenerative diseases and an increased expression of MMP-1 and MMP-9 has also been observed in rosacea. In addition, another Danish study found that rosacea was significantly associated with dementia, especially Alzheimer disease. AMPs, MMP, and inflammatory cascades, which have a shared impact on both rosacea and Alzheimer disease, are considered to be involved in the underlying mechanism. Together, these findings suggest that a pathogenic link might therefore exist between rosacea and neurodegenerative diseases." [2] "We found a significantly higher prevalence and risk of incident migraine especially in female patients with rosacea. These data add to the accumulating evidence for a link between rosacea and the central nervous system." [3] "Currently, it is clear that the innate immune and the sensory and autonomic nervous systems are overstimulated with dysregulated interactions, leading to a chronic pathological inflammatory state." [4] "Thus, an activated nervous system in the skin correlates well with the early phase of rosacea, although it is still unclear whether neuronal activation precedes or follows the inflammatory infiltrate. The extent to which the autonomic and/or sensory nervous system is involved in the neuronal dysregulation during rosacea has received considerable attention, as modulation of α-adrenergic receptors or β-adrenergic blockers is helpful in some patients (Craige and Cohen, 2005; Shanler and Ondo, 2007; Gallo et al., 2010)." [5] "Both augmented innate immune response and neurovascular/neuroimmune dysregulation appear to work in concert in signaling into motion the underlying vasodilation and cascades of inflammation, which produce intermittent flares of diffuse facial erythema." [6] "According to Morrison (2012) in the study of the autonomic nervous system (using the vegetative index of Kerdo) the prevalence of parasympathetic tone of the autonomic nervous system has been found in Rosacea patients." [7] "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 documented that the nervous system is intimately linked with the vascular system in producing the typical signs and symptoms of rosacea, which suggests that both the flushing and inflammation of rosacea may be part of the same continuum." [8] Also see this post about Psychology and Rosacea. End Notes [1] Rosacea: turning all stones for source of pathology Publish date: Jun 1, 2004 By: Rebecca Bryant, Dermatology Times, Modern Medicine [2] Int J Mol Sci. 2016 Sep; 17(9): 1562.Published online 2016 Sep 15. doi: 10.3390/ijms17091562, PMCID: PMC5037831Rosacea: Molecular Mechanisms and Management of a Chronic Cutaneous Inflammatory ConditionYu Ri Woo, Ji Hong Lim, Dae Ho Cho, and Hyun Jeong Park, [3] Prevalence and risk of migraine in patients with rosacea: A population-based cohort study. J Am Acad Dermatol. 2016 Nov 3; Egeberg A, Ashina M, Gaist D, Gislason GH, Thyssen JP [4] Clin Cosmet Investig Dermatol. 2015; 8: 159–177. Published online 2015 Apr 7. doi: 10.2147/CCID.S58940 PMCID: PMC4396587 Update on the management of rosacea Allison P Weinkle, Vladyslava Doktor, and Jason Emer [5] J Investig Dermatol Symp Proc. Author manuscript; available in PMC 2013 Jul 8. Published in final edited form as: J Investig Dermatol Symp Proc. 2011 Dec; 15(1): 2–11. doi: 10.1038/jidsymp.2011.7 PMCID: PMC3704130 NIHMSID: NIHMS479650 Clinical, Cellular, and Molecular Aspects in the Pathophysiology of Rosacea Martin Steinhoff, Jörg Buddenkotte, Jerome Aubert, Mathias Sulk, Pawel Novak, Verena D. Schwab, Christian Mess, Ferda Cevikbas, Michel Rivier, Isabelle Carlavan, Sophie Déret, Carine Rosignoli, Dieter Metze, Thomas A. Luger, and Johannes J. Voegel [6] J Clin Aesthet Dermatol. 2012 Mar; 5(3): 26–36. PMCID: PMC3315876 Advances in Understanding and Managing Rosacea: Part 2 The Central Role, Evaluation, and Medical Management of Diffuse and Persistent Facial Erythema of Rosacea James Q. Del Rosso, DO, FAOCD [7] Georgian Med News. 2013 Jan;(214):23-8. [New possibilities in the treatment of early stages of rosacea]. Tsiskarishvili NV1, Katsitadze A, Tsiskarishvili Ts. [8] Causes of Rosacea: Neurovascular System, NRS

H. pylori reaches the epithelium of the stomach image courtesy of Wikimedia Commons H Pylori (Helicobacter Pylori) has been a controversy with rosacea for some time now. Some experts dismiss H Pylori’s role in rosacea and yet it remains a controversy since other rosacea experts continue to discuss H Pylori as a possible factor in rosacea. The reason why this is such a controversy is that treatment for H Pyori eradication improves rosacea is so many cases. For example, "This study was designed to examine the prevalence of gastric Helicobacter pylori (Hp) infection verified by 13C-UTB-test, CLO, Hp culture and serology (IgG) in patients with rosacea....The eradication of Hp leads to a dramatic improvement of symptoms of rosacea and reduction in related gastrointestinal symptoms, gastritis, hypergastrinemia and gastric acid secretion; and 3) Rosacea could be considered as one of the major extragastric symptoms of Hp infection probably mediated by Hp-related cytotoxins and cytokines." [20] Gastrointestinal Rosacea When treatment for rosacea improves by treating for gastrointestinal issues, i.e., eradicating H Pylori, it is called Gastrointestinal Rosacea [GR]. H Pylori A report published by Dovepress in May 2017 says about H Pylori, "There is not sufficient evidence regarding how determinant the role of H. pylori is." [16] Another report on this subject published in the J Eur Acad Dermatol Venereol also in May 2017 "found weak associations between rosacea and Helicobacter pylori infection as well as an effect of Helicobacter pylori therapy on rosacea symptoms." [15] A report in 2013 states, "There still proves to find a correlation of Hp infection with patients with rosacea but it can still be hypothesised as a cutaneous manifestation of an internal peptic ulcer disease." [11] A report in January 2010 states that “Helicobacter pylori infection is implicated in the pathogenesis of extradigestive diseases such as acne rosacea…” A report by Mc Leer, Lacey and Powell in 2009 listed H Pylori as a possible factor in the pathophysiology in rosacea. Another report in 2012 concluded: "We concluded that H. pylori has a significant role in rosacea patients who had dyspeptic symptoms. The PPR type is more influenced by H. pylori and this is regarded as being because of certain virulent strains that increase the inflammatory response in gastric mucosa and also in cutaneous lesions." [9] One report in 2003 suggests “some form of relationship between rosacea and H. pylori infection.” Two reports in 1996 suggested H Pylori’s role in rosacea with titles such as “Eradication of Helicobacter pylori as the only successful treatment in rosacea” and “Acne rosacea and Helicobacter pylori betrothed.” Rebora suggested in 1995 that the “role of H. pylori is more probable in erythrotic rosacea than in its papulopustular and granulomatous stages.” [1] These are just a few reports suggesting H Pylori as a factor in rosacea. When you consider the fact that H Pylori was ‘officially’ discovered in 1986 by Drs Marshall and Warren in Australia who both won the Nobel Prize in 2005 for this discovery and changed the textbooks about how bacteria can survive in the human stomach and its relation to ulcers and other gastric problems and the fact that this gram negative bacteria is considered an infection that half the world’s population is carrying with most being totally asymptomatic it is a wonder that anyone can even connect H Pylori with rosacea at all. Yet the reports on H Pylori and rosacea keep coming out despite the fact that many reports negate H Pylori’s role in rosacea. While there are many older reports suggesting H Pylori having some role in rosacea, newer reports dismiss this role. For instance, the late Dr. Kligman noted H Pylori’s controversial role in rosacea in his 2003 report. [2] A report released in 2002 mentions ‘promising recent reports of beneficial H. pylori eradication’ in many cutaneous skin diseases except rosacea. [3] A study published in May 2010 concluded, “There is no association between Helicobacter pylori infection and rosacea in current study.” [4] Nevertheless, there are reports of H Pylori associated with rosacea indicating that eradicating H Pylori clears rosacea and discuss the possible cutaneous pathology of H Pylori to an autoimmune mechanism. A report in 2009 says, a “few case reports have documented associations between Helicobacter pylori infection and rosacea.” [5] What is H Pylori and how does it relate to rosacea? H Pylori is a gram negative bacteria that is considered an infection and harmful to humans. According to one report, “more than 50% of the human population have long-term Helicobacter pylori infection.” [3] Wikipedia says that the diagnosis of H Pylori is done with different tests that are not failsafe and sometimes results in false positives. How anyone can know for sure that 50% of the human population is infected with H Pylori is quite suspect. The percentage of ‘infection’ of H Pylori, if indeed it is an infection, may be more or less than 50% . According to Wikipedia, “Helicobacter pylori is a Gram-negative, microaerophilic bacterium that can inhabit various areas of the stomach, particularly the antrum. It causes a chronic low-level inflammation of the stomach lining and is strongly linked to the development of duodenal and gastric ulcers and stomach cancer. Over 80% of individuals infected with the bacterium are asymptomatic.” So, if 80% of individuals are asymptomatic and they only discovered H Pylori in 1986 how do they know that H Pylori is a human pathogen? There is an amusing article, “So, What’s Your Problem with Gram-Negative Bacteria??,” that gets you thinking. Do you really think that medical science knows everything about H Pylori in a little over twenty years? Obviously sometimes H Pylori is a human pathogen and runs amuck causing us problems. But in 80% of individuals H Pylori is asymptomatic and obviously is in the stomach for some reason, possibly for some nefarious purpose such as an ulcer, but it is quite possible for some beneficial purpose as well. Could it be possible that a gram negative bacteria serves some useful purpose that as yet hasn’t been discovered? For instance, E. coli can help people and animals to digest food and help in providing vitamins but sometimes runs amuck causing some serious food poisoning. Could H Pylori have some beneficial yet undiscovered function for humans yet sometimes cause issues like E. coli does? Could H Pylori be asymptomatic because it is helping us for some reason yet undiscovered, and sometimes for some yet undiscovered reason turns into a monster that causes problems like ulcers and rosacea? SIBO has been associated with rosacea with gram negative bacteria associated with it such as H Pylori. One report says, “Gastric acid suppresses the growth of ingested bacteria, thereby limiting bacterial counts in the upper small intestine. Diminished acid production (hypochlorhydria) is a risk factor for SIBO, and can develop after colonization with Helicobacter pylori or as a consequence of aging. [6] Gram Negative Folliculitis, a rosacea mimic, is an acne condition caused by Gram-negative organisms which usually develops in patients who have received systemic antibiotics for prolonged periods. This is quite odd when you consider that eradicating H Pylori, a gram negative bacterium, clears rosacea in some cases. This certainly raises some questions about using long term antibiotic treatment for rosacea, doesn’t it? More info on the long term antibiotic risks you should consider. Since eradicating H Pylori involves the use of antibiotics it would be difficult to really know if the H Pylori is truly a factor in rosacea since antibiotics have been used for many years to successfully treat rosacea. If it were possible to eradicate H Pylori without using antibiotics and rosacea clears up, then, there would be some substantial evidence of H Pylori being a factor in rosacea According to Wikipedia, “The standard first-line therapy is a one week “triple therapy” consisting of a proton pump inhibitors such as omeprazole, Lansoprazole and the antibiotics clarithromycin and amoxicillin. Variations of the triple therapy have been developed over the years…” Proton pump inhibitors have been also listed as a systemic comorbidity in rosacea! Since antibiotics are usually used in the eradication of H Pylori you can see why it would be difficult to know whether the clearing of rosacea is due to the eradication of the H Pylori or simply because antibiotics have been used successfully to treat rosacea for over fifty years. Nevertheless, there are anecdotal reports that treatment for gastric problems has cleared rosacea. For instance, one anecdotal report suggests that after treating a patient with gastritis and evidence of GERD that the rosacea cleared. [7] According to Wikipedia, “In 1999, a review of existing studies found that, on average, 40% of GERD patients also had H Pylori infection. The eradication of H. pylori can lead to an increase in acid secretion, leading to the question of whether H. pylori-infected GERD patients are any different than non-infected GERD patients. A double-blind study, reported in 2004, found no clinically significant difference between these two types of patients with regard to the subjective or objective measures of disease severity.“ A few other anecdotal reports have suggested digestive issues related to their rosacea. [8] There may be other anecdotal reports suggesting H Pylori eradication clears rosacea which I plan on adding to this page. If you have thoughts on this subject I suggest you post them here. Bonnie [10] reports that in Dr. Jonathan V. Wright's NUTRITION & HEALING Newsletter, February 2010, Getting to the root of Rosacea - in your stomach, Dr. Wright is reported to have said: "It's sad that information about the very common connection between acne rosacea and low stomach acid has been lost. In 1948, an article about Rosacea in a major medical journal stated that "every Dermatologist knows" about this connection. In 2009, hardly any dermatolgists know about it. It's also important to note that 2/3 of individuals with Rosacea are actually infected with Helicobacter Pylori bacteria, a common cause of low stomach acid." This report cites no clinical papers on this subject. A report in 2006 concluded, "based upon these results, the relation between Helicobacter pylori and rosacea is supported, and infection should be investigated in these patients because an appreciable percentage of patients diagnosed with rosacea and Helicobacter pylori infection can benefit from eradication therapy, mainly in the papulopustular subtype." [12] "H. pylori appears contribute to several inflammatory skin diseases. Rosacea is the most common skin disease potentially associated with H. pylori. In one study, H. pylori was present in 81% of rosacea patients who also had gastric complaints, and almost all of those patients harbored cagA+ strains. A similar Egyptian study found that both cagA and the s1m1 allele of vacA were more prevalent in papular rosacea patients. The papular rosacea patients responded better to eradication therapy than the erythematous rosacea patients. A limited study of ocular rosacea patients reports that the seven ocular rosacea patients responded better to H. pylori eradication therapy than did rosacea patients without ocular symptoms." [13] "H. pylori has proven to be a more complex pathogen than early research indicated. Multiple surface carbohydrate structures, outer membrane proteins, and toxins interact to modify host cell signaling and the immune response.....Thirty years after its discovery, H. pylori remains an enigmatic pathogen with many secrets yet to be revealed." [13] "The prevalence of Helicobacter pylori infection was also found to be higher in patients with rosacea than in controls [70]. However, other studies have failed to demonstrate a relationship between H. pylori and rosacea [14]. "This meta-analysis found weak associations between rosacea and Helicobacter pylori infection as well as an effect of Helicobacter pylori therapy on rosacea symptoms, albeit that these did not reach statistical significance. Whether a pathogenic link between the two conditions exists, or whether Helicobacter pylori infection represents a proxy for other factors remains unknown." [15] "Although a possible pathogenetic link between H. pylori and rosacea is advocated by many authors, evidence is still interpreted differently by others." [17] "Of 167 patients, 150 received H. pylori eradication therapy, demonstrating a 92% (138/150) cure rate.....The present study concluded that H. pylori eradication leads to improvement of rosacea." [18] "Prevalence of H. pylori infection was significantly higher in patients with rosacea than control group, whereas SIBO prevalence was comparable between the two groups. Eradication of H. pylori infection led to a significant improvement of skin symptoms in rosacea patients." [29] "Some studies consider it as one of the recently identified human bacterial pathogens, and special attention is paid to the evidence suggesting that it is probably part of the composition of the human microbiome as a commensal (commensal from French to English is a table companion) or even a symbiont. The presented data discussing the presence or absence of the effect of H. pylori on human health suggest that there is an apparent ambiguity of the problem....On the other hand, the high prevalence of H. pylori in the population and its asymptomatic coexistence with humans in most of the world’s population indicates its persistence in the body as a representative of the microbiome and as a nonpathogenic microorganism." [22] H Pylori Causes Low Gastric Acid It is has been known for some time that H Pylori reduces gastric acid. You should read this post about Low Gastric Acid and Rosacea. Reply to this Topic There is a reply to this topic button somewhere on the device you are reading this post. If you never heard about this topic and you learned about it here first, wouldn't it be a gracious act on your part to show your appreciation for this topic by registering with just your email address and show your appreciation with a post? And if registering is too much to ask, could you post your appreciation for this topic by finding the START NEW TOPIC button in our guest forum where you don't have to register? We know how many have viewed this topic because our forum software shows the number of views. However, most rosaceans don't engage or show their appreciation for our website and the RRDi would simply ask that you show your appreciation, please, simply by a post. End Notes [1] Helicobacter pylori infection and autoimmune disease such as immune thrombocytopenic purpura Ohta M. Kansenshogaku Zasshi. 2010 Jan;84(1):1-8 The pathophysiology of rosacea. Mc Aleer MA, Lacey N, Powell FC G Ital Dermatol Venereol. 2009 Dec;144(6):663-71. Helicobacter pylori and rosacea. Zandi S, Shamsadini S, Zahedi MJ, Hyatbaksh M East Mediterr Health J. 2003 Jan-Mar;9(1-2):167-71. Eradication of Helicobacter pylori as the only successful treatment in rosacea Kolibásová K, Tóthová I, Baumgartner J, Filo V. Arch Dermatol. 1996 Nov;132(11):1393. Acne rosacea and Helicobacter pylori betrothed Wolf R. Int J Dermatol. 1996 Apr;35(4):302-3 May Helicobacter pylori be important for dermatologists? Rebora A, Drago F, Parodi A. Dermatology. 1995;191(1):6-8 [2] A Personal Critique on the State of Knowledge of Rosacea Albert M. Kligman, M.D., Ph.D. [3] Helicobacter pylori infection in skin diseases: a critical appraisal. Wedi B, Kapp A. Am J Clin Dermatol. 2002;3(4):273-82. [4] Risk factors associated with rosacea. Abram K, Silm H, Maaroos HI, Oona M. J Eur Acad Dermatol Venereol. 2010 May;24(5):565-71. Epub 2009 Oct 23. [5] Helicobacter pylori infection and dermatologic diseases. HERNANDO-HARDER AC, BOOKEN N, GOERDT S, SINGER MV, HARDER H. Eur J Dermatol. 2009 Sep-Oct;19(5):431-44. Epub 2009 Jun 15. [6] Small Intestinal Bacterial Overgrowth: A Comprehensive Review Andrew C. Dukowicz, MD, Brian E. Lacy, PhD, MD, and Gary M. Levine, MD Gastroenterology & Hepatology Volume 3, Issue 2 February 2007 [7]ice2meetyu’s report July 4, 2010 [8] Rosacea and digestive problems [9] Role of Helicobacter pylori in common rosacea subtypes: A genotypic comparative study of Egyptian patients. El-Khalawany M, Mahmoud A, Mosbeh AS, Abd Alsalam F, Ghonaim N, Abou-Bakr A. J Dermatol. 2012 Oct 5. doi: 10.1111/j.1346-8138.2012.01675.x [10] Bonnie's report at RSG [11] Kathmandu Univ Med J (KUMJ). 2012 Oct-Dec;10(40):49-52. The study of prevalence of helicobacter pylori in patients with acne rosacea. Bhattarai S, Agrawal A, Rijal A, Majhi S, Pradhan B, Dhakal SS. Department of Dermatology and Venereology, B.P.Koirala Institute of Health Sciences, Dharan, Nepal. [12] REV ESP ENFERM DIG (Madrid) Vol. 98. N.° 7, pp. 501-509, 2006 Effect of Helicobacter pylori eradication therapy in rosacea patients D. Boixeda de Miquel, M. Vázquez Romero, E. Vázquez Sequeiros, J. R. Foruny Olcina, P. Boixeda de Miquel1, A. López San Román, S. Alemán Villanueva and C. Martín de Argila de Prados [13] World J Gastroenterol. 2014 Sep 28; 20(36): 12781–12808. Published online 2014 Sep 28. doi: 10.3748/wjg.v20.i36.12781, PMCID: PMC4177463 Beyond the stomach: An updated view of Helicobacter pylori pathogenesis, diagnosis, and treatment Traci L Testerman and James Morris [14] Int J Mol Sci. 2016 Sep; 17(9): 1562.Published online 2016 Sep 15. doi: 10.3390/ijms17091562, PMCID: PMC5037831Rosacea: Molecular Mechanisms and Management of a Chronic Cutaneous Inflammatory ConditionYu Ri Woo, Ji Hong Lim, Dae Ho Cho, and Hyun Jeong Park, Chris Jackson, Academic Editor [15] Acad Dermatol Venereol 2017 May 23. doi: 10.1111/jdv.14352 Rosacea is associated with Helicobacter pylori: a systematic review and meta-analysis. Jørgensen AR, Egeberg A, Gideonsson R, et al. [16] Dovepress Rosacea and Helicobacter pylori: links and risks Elizabeth Lazaridou, Chrysovalantis Korfitis, Christina Kemanetzi, Elena Sotiriou, Zoe Apalla, Efstratios Vakirlis, Christina Fotiadou, Aimilios Lallas, Demetrios Ioannides [17] Rosacea and Helicobacter pylori: links and risks. Clin Cosmet Investig Dermatol. 2017;10:305-310 Lazaridou E, Korfitis C, Kemanetzi C, Sotiriou E, Apalla Z, Vakirlis E, Fotiadou C, Lallas A, Ioannides D [18] J Dermatol. 2017 Sep;44(9):1033-1037. doi: 10.1111/1346-8138.13878. Epub 2017 Apr 28. Effects of Helicobacter pylori treatment on rosacea: A single-arm clinical trial study. Saleh P, Naghavi-Behzad M, Herizchi H, Mokhtari F, Mirza-Aghazadeh-Attari M, Piri R. [19] United European Gastroenterol J. 2015 Feb;3(1):17-24. doi: 10.1177/2050640614559262. Helicobacter pylori infection but not small intestinal bacterial overgrowth may play a pathogenic role in rosacea. Gravina A1, Federico A1, Ruocco E2, Lo Schiavo A2, Masarone M3, Tuccillo C1, Peccerillo F2, Miranda A1, Romano L1, de Sio C1, de Sio I1, Persico M3, Ruocco V2, Riegler G1, Loguercio C1, Romano M1. 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"Angiogenesis is a physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over this, vasculogenesis is the term used for spontaneous bloodvessel formation, and intussusception is the term for new blood vessel formation by splitting off existing ones. Angiogenesis is a normal process in growth and development, as well as in wound healing. However, this is also a fundamental step in the transition of tumors from a dormant state to a malignant state. VEGF (Vascular Endothelial Growth Factor) has been demonstrated to be a major contributor to angiogenesis, increasing the number of capillaries in a given network." [1] "Vascular endothelial growth factor (VEGF), originally known as vascular permeability factor (VPF), is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis." Wikipedia "Vascular endothelial growth factor (VEGF ) is an important signaling protein involved in both vasculogenesis (the de novo formation of the embryonic circulatory system) and angiogenesis (the growth of blood vessels from pre-existing vasculature). As its name implies, VEGF activity has been mostly studied on cells of the vascular endothelium, although it does have effects on a number of other cell types (e.g. stimulation monocyte/macrophage migration, neurons, cancer cells, kidney epithelial cells). In vitro, VEGF has been shown to stimulate endothelial cell mitogenesis and cell migration. VEGF is also a vasodilator and increases microvascular permeability and was originally referred to as vascular permeability factor." [2] "Dr. Sandra Cremers, assistant professor of ophthalmology at Harvard Medical School, was awarded $25,000 for a study evaluating the role of angiogenesis (new blood vessel formation) in ocular rosacea. Dr. Cremers will investigate the levels of angiogenesis markers, such as vascular endothelial growth factor (VEGF ), in the conjunctiva and eyelids of patients with severe ocular rosacea, compared with normal subjects. She postulates that defining the role of angiogenesis in the development of ocular rosacea may bring focus to future research on this common rosacea subtype, and eventually lead to the development of an effective treatment." [3] Dr. Cremers is a volunteer RRDi MAC member. "Recently an increased of VEGF in Rosacea, a major mitogen for dermal microvascular endothelial cells is also reported." [4] "VEGF, IL-2, IL-8 may be directly related to the mechanism of the development of cardiovascular disease in rosacea patients" [5] "The principal subtype of rosacea includes erythematotelangiestatic rosacea, which is characterized by uncontrolled angiogenesis. Angiogenic growth factors such as fibroblast growth factors (FGF) and vascular endothelial growth factor (VEGF) are currently targets of intense effort to inhibit deregulated blood vessel formation in diseases such as cancer. Here we report a 33-years-old woman with erythematotelangestatic rosacea who responds to a daily treatment of topically applied dobesilate, an inhibitor of FGF, with an improvement in erythema and telangectasia after two weeks. Thus, dobesilate might be useful in the treatment of rosacea and other diseases that depend on pathologic angiogenesis." [6] "It should be also taken into account that, being FGF a necessary mediator of VEGF activity, dobesilate also inhibits this last signalling system, as it has been also recently described. The case report presented here is a representative example of five enrolled rosacea patients from a study directed to assess the long-term clinical benefit of dobesilate in rosacea. Taken together these data support a new therapeutic modality for a safe and efficient topical treatment of rosacea." [7] "The present findings indicate that +405C/G polymorphism of the VEGF gene increases the risk of rosacea." [8] "The Hippo signaling pathway plays a key role in regulating organ size and tissue homeostasis. Hippo and two of its main effectors, yes-associated protein (YAP) and WWTR1 (WW domain-containing transcription regulator 1, commonly listed as TAZ), play critical roles in angiogenesis.... Our findings suggest that YAP/TAZ inhibitors can attenuate angiogenesis associated with the pathogenesis of rosacea and that both YAP and TAZ are potential therapeutic targets for patients with rosacea." [10] Treatment "ART ameliorated rosacea-like dermatitis by regulating immune response and angiogenesis, indicating that it could represent an effective therapeutic option for patients with rosacea." [9] "Our results indicate that the blockade of YAP/TAZ contributes to anti-angiogenic responses in rosacea and VEGF-related angiogenesis. We suggest that YAP/TAZ can serve as a therapeutic target for rosacea and other inflammatory skin diseases associated with angiogenesis." [10] "Besides, aspirin administration decreased the microvessels density and the VEGF expression in rosacea-like skin. We further demonstrated that aspirin inhibited the activation of NF-κB signaling and the release of its downstream pro-inflammatory cytokines." [11] End Notes [1] http://en.wikipedia....ki/Angiogenesis [2] http://en.wikipedia.org/wiki/VEGF [3] http://www.rosacea.o...arded/index.php [4] New aspects of the pathogenesis of rosacea Sabine Fimmel, Mohamed Badawy Abdel-Naser, Heinz Kutzner, Albert M. Kligman, Christos C. Zouboulis Arch Dermatol Res, DOI 10.1007/s00403-007-0816-z, 5 June 2007, Revised 28 September 2007 / Accepted 19 November 2007, Springer - Verlag 2007 Full Text [5] RISK-FACTORS OF CARDIOVASCULAR DISEASE IN PATIENTS WITH ROSACEA [6] Eur J Med Res. 2005 Oct 18;10(10):454-6. Therapeutic response of rosacea to dobesilate. Cuevas P, Arrazola JM. [7] BMJ Case Rep. 2011; 2011: bcr0820114579. Published online 2011 Oct 19. doi: 10.1136/bcr.08.2011.4579 PMCID: PMC3207764 Long-term effectiveness of dobesilate in the treatment of papulopustular rosacea Pedro Cuevas, Javier Angulo, and Guillermo Giménez-Gallego [8] J Am Acad Dermatol. 2019 Jun 07;: Vascular endothelial growth factor gene polymorphisms in patients with rosacea: A case-control study. Hayran Y, Lay I, Mocan MC, Bozduman T, Ersoy-Evans S [9] Biomedicine & Pharmacotherapy, Volume 117, September 2019, 109181 Artemisinin, a potential option to inhibit inflammation and angiogenesis in rosacea XinYuana, Ji Li, Yangfan Li. Zhili Deng, Lei Zhou, Juan Long, Yan Tang. Zhihong Zuo, Yiya Zhang. Hongfu Xie [10] Int J Mol Sci. 2021 Jan; 22(2): 931. Inhibition of Hippo Signaling Improves Skin Lesions in a Rosacea-Like Mouse Model Jihyun Lee, Yujin Jung, Seo won Jeong, Ga Hee Jeong, Gue Tae Moon, and Miri Kim [11] Aspirin alleviates skin inflammation and angiogenesis in rosacea