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.
USPTO Backgrounds
USPTO Backgrounds