Demodex mites ivermectin effective treatment ?
From: “Linda Sy MD”
Date: Fri Dec 1, 2000 11:36 am
Subject: Re: [rosacea] Effective treatment ?
Hello Annie,
Welcome. I have just read your message with interest and am impressed with your enthusiasm to share your treatment with the group. You also seem to be committed to your research, what with all the work required, not to mention the liability. You cannot find a more intelligent group to test your treatment plan. Rosacea is an enigma to me and I am sure, to many colleagues. I for one, would be interested in the outcome of your informal study.
Demodex folliculorum has been mentioned as an aggravating factor to rosaceans for many decades and yet, I have not seen any formal double blind study done on this front. (This supports the wisdom of independent research funding by rosaceans). As you have presented, articles have been published, reporting individuals (a number of whom are immunocompromised) who responded to rx of demodex. The rx’s were not cures but nevertheless, afforded some form of control to otherwise refractory situations. I do not think your hypothesis is without merit. As a matter of fact, at the end of this message, I have copied an article reporting a case rx’d successfully with oral Ivermectin & topical Permethrin. Months ago, I sent a copy of this article to a group member with very resistant case of folliculitis.
However, I’m not sure that it is wise to have someone self- treat without the supervision of an attending physician. Luckily, here in the U.S., 5% Permethrin (Elimite Cream) is only available by prescription. I have given this topical medication to many patients for scabies but not for rosacea. Other than a few cases of contact or irritant dermatitis, I have not seen any serious side effects. However, my patients have only used it no more than 2-3 times at most. I don’t know what the side effects of long-term use are; considering the hypersensitivity, easier penetrability (hence, increased absorption) and vascular lability of inflamed rosacean skin. I personally believe demodex mites are incidental parasites that prey on compromised skin causing secondary symptoms, not unlike bacteria & fungi. They are not the primary cause of rosacea. Therefore, I suspect that not all rosaceans have demodex as a relevant factor.
If I may, I would like to offer some suggestions:
- Limit participants to those who were unresponsive to all the usual treatments.
- Ask participants to solicit the cooperation and supervision of their respective dermatologists. By that, I mean – if possible, get a KOH skin scraping (a common procedure in a derm’s office) to establish the presence of florid demodex population. There may be some resistance to this but I believe many physicians will have the interest of their patients at heart and the curiousity to find out if this works.(I know of some colleagues who have given this treatment for rosacea). Thus, if there is any acute reaction, a physician is available and responsible to take care of the problem.
- Participants try the Permethrin on a small area of face first, to determine if any immediate severe problem exists.
Here is the article which appeared in JAAD:
Treatment of rosacea-like demodicidosis with oral ivermectin and topical permethrin cream
JAAD, November 1999, part 1 . Volume 41 . Number 5 Christa Forstinger, MD Harald Kittler, MD Michael Binder, MD Vienna, Austria, and Boston, Massachusetts
A 32-year-old man presented with a chronic rosacea-like dermatitis of the facial skin and the eyelids. The skin disorder had been present for 4 years and was unresponsive to multiple previous treatment attempts. Skin scrapings and a histologic examination of a biopsy specimen from the affected area revealed the presence of numerous Demodex mites. The patient was treated with oral ivermectin and subsequent topical permethrin resulting in complete and rapid clearing of the folliculitis. We believe that this case supports the view that Demodex mites may be pathogenic when they are present in large numbers. Oral treatment with 200 µg/kg ivermectin with subsequent weekly topical permethrin showed impressive treatment efficacy in a case refractory to conventional treatment. (J Am Acad Dermatol 1999;41:775-7.)
Demodex folliculorum, a 0.3-mm long Acarus mite, is the most common ectoparasite of man. Because of its ubiquitous nature, infestation with this organism is recognized as a normal occurrence. However, there have been numerous clinical observations linking the presence of Demodex mites at extremely high-density colonization with various skin disorders. Demodex mites have been suggested as the causative agent in rosacea, perioral granulomatous dermatitis, blepharitis, and pustular folliculitis. Demodicidosis has been associated with AIDS and chemotherapy for malignant diseases.
We describe a patient with the clinical and histologic features of demodicidosis, in whom rapid and complete recovery was achieved by a single oral dose of the antiparasitic agent ivermectin and subsequent treatment with topical permethrin cream.
A 32-year-old white man was seen with a 4-year history of a slowly progressive and pruritic facial eruption. Apart from mild seborrheic dermatitis on the scalp, he had no history of skin disease.
Physical examination revealed a diffuse erythema localized on the cheeks, the nose, the forehead, and the glabella. There were scattered 2 to 3 mm erythematous papules and follicular papulopustules with eczematous lesions and scaling. Blepharitis and 3 external chalazions were noted on the upper eyelids (Fig 1, A and B).
The retroauricular region, neck, and chest were not affected. The rest of the physical examination was within normal limits. The patient noted moderate to severe pruritus in the affected regions.
Laboratory findings including routine blood counts and acute phase proteins revealed no abnormalities. Enzyme-linked immunosorbent assay for HIV was negative. A skin test for recall antigens was positive for several antigens.
A 10% potassium hydroxide preparation of skin scrapings from the cheek showed many Demodex mites but no yeast or fungal elements. Histopathologic examination of a biopsy specimen obtained from the left cheek revealed features of both rosacea and seborrheic dermatitis and enlarged hair follicles containing structures of D folliculorum (Fig 2). Because of the long list of previous unsuccessful treatment attempts the patient received a single oral dose of 200 µg/kg of ivermectin (Mectizan; Merck, Inc, Whitehouse Station, NJ). Topical treatment consisted of applications of a bland oil-in-water preparation and was applied for 1 month after treatment with ivermectin.
Within 2 weeks after initiation of treatment the patient noticed a remarkable reduction of pruritus; within 4 weeks there was noticeable reduction in the size and intensity of the inflammatory response (Fig 1, C and D). Skin scrapings were negative for Demodex mites.
To prevent reinfestation 5% permethrin cream was prescribed for once-weekly use and was initiated 4 weeks after ivermectin treatment. Subsequent examinations during the past year showed excellent control of the disease. Repeated scrapings remained negative for D folliculorum. The patient in this case report presented with an unusual long-lasting history of rosacea-like dermatitis of the face and eyelids. For 4 years his skin condition had been diagnosed as rosacea, seborrheic dermatitis, or an allergic dermatitis of unknown cause. As a consequence, treatment was attempted with topical and oral antibiotics including metronidazole, topical ketoconazole, etretinate, and topical corticosteroids. Finally, the patient decided to treat his skin condition with homeopathy and diet. This attempt was also without success.
Ivermectin is a semisynthetic product from Streptomyces avermitilis, a potent macrocyclic lactone disaccharide antiparasitic agent used to prevent and treat parasitic infestations in man and animals. The compound has activity against internal and external parasites and has been found effective against arthropods, insects, nematodes, filarioidea, platyhelminths, and protozoa. Ivermectin, initially applied extensively to control loiasis and bancroftian filariasis, is increasingly used for the treatment of scabies in immunocompetent and immunocompromised patients. In this case a single oral dose of 200 µg/kg ivermectin effectively led to substantial clinical improvement within 1 month. Repeated skin scrapings remained negative for Demodex mites. The 10-year history of the use of oral ivermectin to control onchocerciasis indicates that it is a safe drug. In our case, neither the patient nor the investigators noted any adverse reaction. Meinking et al recently reported that ivermectin showed no residual activity 2 months after a single dose. To prevent reinfestation with Demodex mites, 5% permethrin cream was prescribed for once-weekly use.
Linda Sy M.D.
Linda Sy Skin Care
http://www.lindasy.com
Voice:Toll-free 877-Lindasy (546-3279)
Outside US: 925-256-0178
FAX: 925-939-5207
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11 comments ↓
I will 53 years old this coing November and have suffered with rosacea for approximately 7-8 years. I first noticed it when I moved from Ohio to San Diego during the El Nino and put vitamin C treatments from a dermatologist on my skin. The treatment seemed to aggravate my “pimples”. Another dermatologist diagnosed me with rosacea and I began topical Metrogel that helped. I then started HgH injections (very low dosage) from another doctor and noticed that my Rosacea virtually disappeared. That was early on. Now, it seems the condition has worsened. I recently stopped the HgH injections (about a month ago) and my skin gets a lot of tiny blackheads and whiteheads, very noticable flushing and redness, and the occassional pustule and watery pimple. No matter how well I wash my face there are are clogged pores. I have always had remarkably good skin, smooth, translucent, and finely textured. I never had facials because I never really needed them so this is unnerving. What is really concerning me is my itchy, red eyes. It is hard to wear any kind of eye make-up. In reading your internet article, I’m wondering if I could be a candidtate for the Ivermectin, Permethrin treatment. Right now, I am taking Cefalexina 500mg. (I can’t remember the English name for this. It’s a pretty general antibiotic I got when I cut my finger and the doctor in the hospital prescribed it. I noticed my skin cleared up so I saw online that it was also used in Rosacea therapy). I just am not a big fan of ingesting 3-4 of these tablets a day. I still will sometimes flush and my pores are still clogged. I also noticed that before my menstrual periods my Rosacea is at it’s peak so I control it with this antibiotic and Metrogel. I also must say that about 5 years ago I was getting the telagen….lasered on my face but stopped with that because they always came back eventually. My skin condition isn’t much affected by the cleansers I use. I am done seeing conventional dermatologists that don’t think outside the box. Obviously, Metrogel isn’t enough. I think this has something to do with the immune system and possible mites. Any advice would be appreciated.
After experiencing acne/rosacea type symtoms for three months, I finally decided to go see a dermatologist to find out what was itching on my face.
KOH showed demodex mites I was treated with elimite and oral ivermectin, recurrence after 1 month. I am currently using the elimite cream bid for 14 days, 4 to go, with high hopes. My derm says if after treatment follow up appt. shows demodex on the KOH, then they will treat me again with oral ivermectin. THANKS!
Hi Anna,
Great that you found a derm who would support oral ivermectin, topical elimite for your rosacea symptoms. Hopefully your rosacea symptoms were also relieved at the same time as eliminating the demodex.
davidp.
Need info about demodex treatment for acne and hair loss
I’m elated to have come across this site, and even more surprised to see Dr. Linda Sy’s name on it.
I used a soap and shampoo from a chinese Dr. who also stated that Rosacea could be caused from these mites. I also feel like I have traveled the world looking for evey possible treatment to help.
I totally plan on seeing a Dermatologist as soon as I can to see if I could try this treatment plan
No one has anything to lose by trying this, but maybe every thing to GAIN especially our HAPPINESS back and to just be normal
Wish ME LUCK MAUREEN
Hi , Saw my Derma dr. last month would not let me try the oral Ivermectin and topical Permethrin. His words were oh we don’t use that.
I will look for someone else.
Maureen
Hi Anna,
I have had rosacea for many many years. Would you be willing to share who your Derma Dr. is? Here is my e-mail. maureenrosky@yahoo.com
Thanks
Hope to hear from you.
Maureen
I’m convinced topical Metronidazole works by disrupting Demodex Folliculorum (hair follicle mites).
http://www.rosacea.org/rr/2004/spring/article_2.php
Furthermore, topical Metronidazole will NOT work by disrupting Demodex Brevis (oil gland mites) because it can not penetrate down in to the sebaceous glands that they dwell in.
Demodex Folliculorum (hair follicle mites)
Treatment = topical Metronidazole
Demodex Brevis (old gland mites)
Treatment = systemic Accutane
Treatment for the infections (pimples) caused by the mites dragging and burrowing bacteria commonly found on human skin can be helped by antibiotics. Antibiotics for Rosacea or Acne is just curing the symptom, NOT the cause of the problem. MITES!
These mites become UN-commensal parasites when they reach large numbers.
Many things can lead to large numbers (otherwise known as an infestation – weaken immune system due to illness, stress, age, poor diet, etc.
http://skindisease.suite101.com/article.cfm/demodex_spp_face_mites
I forgot to include…
Demodex Folliculorum (hair follicle mites)
Treatment = topical Permethrin
Demodex Brevis (old gland mites)
Treatment = systemic Ivermectin
But good luck finding a Dermatologist who isn’t living in the dark-ages about the link between Demodex mites and Rosacea / Acne.
It blows my mind that the Demodex mites (found on 80-90% of all human beings and the other 10% are infants) are not even illustrated in medical texts:
http://en.wikipedia.org/wiki/Human_skin#Skin_layers
They are leaving out a proven component of human skin! MITES!
Hi there,
Please can someone tell me how long to leave the permethrin on for? I want to try the once weekly application but want to do it right!
Thanks!
Look at this study. Uses oral Ivermectin and very effective. However, this study used 2 doses instead of one. You do one dose and wait 3-4 days and then do another dose. The size of the dose depends on your weight.
Seems like it would be harmless to try. Thoughts? Any guinee pigs?
Method for treating rosacea using oral or topical ivermectin..
BACKGROUND OF THE INVENTION
This invention relates to a method for treatment of rosacea (acne rosacea) in humans employing orally-administered or topically-applied ivermectin. By reducing or eliminating Demodex folliculorum organisms from affected skin areas, this method reduces clinical signs of rosacea which are primarily due to allergic and vasomotor responses of the body to the organism in susceptible persons.
Rosacea, originally termed acne rosacea, is a chronic inflammatory skin condition affecting the face and eyelids of certain middle-aged adults. Clinical signs include erythema (redness), dryness, papules, pustules, and nodules either singly or in combination in the involved skin areas. Eyelid involvement may be manifested by mild conjunctival irritation or inflammation of the meibomian (oil) glands on the eyelid margin. Chronic eyelid irritation can result in loss of eyelashes. No visual impairment accompanies the eyelid irritation. Chronic involvement of the nose with rosacea in men can cause a bulbous enlargement known as rhinophyma. In the classic situation, the condition develops in adults between the ages of 30 and 50. While certain lesions of rosacea may mimic lesions of acne vulgaris, the processes are separate and distinct, the principal differences being the presence of comedones (whiteheads and blackheads) only in acne vulgaris and not in rosacea, the characteristic mid-facial localization and flushing of rosacea not seen in acne, and the potential for eyelid involvement in rosacea which never occurs in acne. In fact, the clinical observation has been made that persons who have classic acne vulgaris as teenagers rarely, if ever, develop full-blown rosacea as adults.
The etiology of rosacea has been a frequently-discussed topic in medical circles but little consensus has ever been reached. The prominent presence of erythema (redness) and flushing of the face of affected persons with aggravation from heat, sunshine, and alcohol has focused attention on this aspect of the disease. However, treatment with medications to block such vasomotor flushing have no effect on other aspects of the disease such as papules and pustules. Treatment with oral antibiotics has been shown to effectively block progression of rosacea through a poorly-understood anti-inflammatory mechanism, but studies have shown that thee medications do not act by killing either bacteria or Demodex folliculorum organisms in affected skin. Reaction to the presence or metabolic activity of Demodex mites in facial follicles has been discussed as a cause of rosacea, but previous studies where topical miticides have been used have shown inconsistent and marginal results. Dietary avoidance of spicy foods and alcohol which cause flushing provides at most temporary symptomatic relief from rosacea. An excellent review of current knowledge in treating rosacea was written by Jansen and Plewig in their chapter titled “Rosacea” in Clinical Dermatology (Philadelphia: Lippincott-Raven Publishers, 1997; chapter 10-7.)
Ivermectin (22,23-dihydroavermectin B1) is a safe and effective orally-administered antiparasitic drug that paralyzes and kills treated organisms by increasing cell permeability to chloride ions which in turn overpolarizes nerve and muscle cells. It is a broad-spectrum member of a family of lactone antibiotics known as avermectins which are produced by cultures of the bacterium Streptomyces avermitilis. It has been used orally in animals and humans to prevent and treat a variety of parasites including Strongyloides stercoralis and Onchocerca volvulus. Campbell wrote an informative review of the use of ivermectin in human parasitic diseases (“Ivermectin as an Antiparasitic Agent for Use in Humans,” Annual Review of Microbiology. 1991. 45: 445-74.) Studies have shown effectiveness in treating human infections with Sarcoptes scabei and head lice. Demodex folliculorum could logically be expected to be killed by ivermectin also since it, like Sarcoptes scabei, is classified among the members of the mite family. Related art specifying products or methods for treating rosacea has not claimed that any beneficial effects of the disclosed agents had anything to do with elimination of Demodex folliculorum from the skin of affected individuals. In U.S. Pat. No. 5,654,013, Taylor and Bass disclosed a method of reducing inflammation in rosacea involving lightly rubbing a block of crystalline sodium chloride over moistened skin in affected areas. No claim was made for any antibiotic effect on bacteria or ectoparasites in the skin. In U.S. Pat. No.3,867,522, Kligman discloses the abrasive use of sodium chloride crystals rubbed over affected skin in acne and related disorders, again with no intended antibiotic effect and with the goal of treatment being the lessening of the severity of the disease and not a permanent or even a temporary cure.
BRIEF SUMMARY OF THE INVENTION
The current invention involves treating rosacea by the oral or topical use of ivermectin. By effectively reducing or eliminating the population of Demodex mites in affected skin areas, this treatment achieves a more complete remission of clinical signs and symptoms of the disease than any previously described method.
DETAILED DESCRIPTION OF THE INVENTION
In the preferred embodiment of this invention, ivermectin is administered orally to a patient with active rosacea in a dose of about 200 micrograms per kilogram of body weight per dose. Because the target organism, Demodex folliculorum, is an ectoparasite in the mite family, an effective treatment must be capable of eradicating the entire life cycle of such a microscopic insect, including egg, larval, and adult stages. For this reason, this embodiment treats such rosacea patients with at least two doses timed so that between three and seven days separate the doses. Such spacing allows time for Demodex eggs to hatch into immature mites that are killed before they can mature into egg-producing adults. While two doses has been demonstrated to be quite effective, in unusual cases where absorption is impaired, as many as four doses at three- to seven-day intervals could be employed. After ivermectin carries out its miticidal activity on skin Demodex folliculorum organisms, inflammatory responses to them begin to diminish but remnants of the dead mites still elicit some flushing and lesion formation until the cleanup processes of the body remove them, a process requiring six to eight weeks. During this initial phase of ivermectin administration, conventional anti-rosacea medications such as oral tetracycline and topical metronidazole can be employed to suppress early flareups and to give early clinical response. No such medications are needed to treat manifestations of rosacea after six to eight weeks have elapsed. After prolonged intevals of freedom from rosacea symptoms, should classic signs begin to reappear, treatment can be repeated. Such retreatments should not be necessary more than one or two times per year.
In an alternative embodiment, ivermectin is formulated into a cosmetically-acceptible topical lotion, cream, or gel and applied to skin affected by rosacea. Because of the well-known barrier effect the skin presents to the penetration of topical medications, such a route of treatment with ivermectin would be anticipated to require once- or twice-daily applications for as long as four weeks to achieve sufficient follicle penetration and effective miticidal activity. A topical formulation that could achieve this effect would contain about 1-5% ivermectin and could be enhanced in penetration if the active agent were encapsulated inside microliposomes. Such a topical treatment would likely need to be repeated more frequently than the preferred oral embodiment, but a disease-free interval should be achieved by each course of therapy.
EXAMPLES
Three adult rosacea patients with varied clinical presentations and with varied disease durations are selected to illustrate the disclosed invention. These patients’ cases illustrate the effectiveness of ivermectin treatment on the different clinical manifestations of the disease.
Patient 1
This 44-year old Caucasian female had exhibited clinical evidence of rosacea for 1-2 years and had been treated with limited success with oral tetracycline, topical and oral metronidazole, and cortisone creams. Her facial skin exhibited mid-facial erythema and flushing with papule and pustule formation. In addition, her eyelids exhibited chronic blepharitis and repeated loss of eyelashes, which is quite typical of rosacea. She was treated with ivermectin, 200 micrograms per kilogram of body weight in each of two oral doses with an interval of four days between doses. Oral tetracycline was continued at a dose of 500 milligrams per day for the first 30 days after ivermectin was given and then was discontinued. After a mild initial flareup of mid-facial papules, the condition improved rapidly to the point that by 60 days no papules were present, all eyelashes were growing back, and she had no more flushing with heat or spicy foods. Symptoms had not returned after three months.
Patient 2
This 33-year old Caucasian female had the acute onset of papular and pustular rosacea involving nearly all of her cheeks and chin two months prior to her evaluation. Marked itching and redness were present, but no eye symptoms were noted. Ivermectin in two 200 microgram per kilogram oral doses given three days apart was administered along with a four-week course of oral tetracycline. The clinical signs abated quickly, with itching being gone after one week and papular lesions clearing by three weeks. At two months from the onset of treatment and one month after cessation of tetracycline, no clinical signs or symptoms of rosacea remained.
Patient 3
This 65-year old African-American female had suffered from severe papular and pustular rosacea of the mid-face and nose for 15 years. Tetracycline, in doses of 500-1000 mg per day had proven to be the only partially-effective medication for her. Oral ivermectin was administered in two 200 microgram per kilogram doses given four days apart and tetracycline was continued for one month in a dose of 500 mg per day. Followup at three months from the start of ivermectin therapy revealed only mild hyper-pigmentation at the sites of previous inflamed papules and pustules. The patient reported that no new lesions had been noted for six weeks prior to that 3-month evaluation.
While these examples illustrate the preferred embodiment of this invention, the treatment of rosacea using oral ivermectin, exposure of Demodex mites to ivermectin from any route of administration will result in the elimination of the organisms and secondary amelioration of the signs of inflammation that are typical of rosacea. Therefore, the topical use of ivermectin in any vehicle that allows it to adequately penetrate into skin follicles to reach the level occupied by Demodex folliculorum will be an effective treatment for rosacea and is considered to be entirely within the scope of this invention. Changes of dosages, dosing schedules, concentrations, vehicles, and frequency of repetition of ivermectin regimens are also not considered to be outside the scope of this invention.
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